LOCAL POTENTIAL ANESTHESIA. GENERAL ANESTHESIA. CARDIOPULMONARY RESUSCITATION. LOCAL ANESTHETICS, THEIR PROPERTIES, SIDE EFFECTS. EQUIPMENT FOR LOCAL ANESTHESIA

Dental anesthesia

Dental anesthesia (or dental anaesthesia) is a field of anesthesia that includes not only local anesthetics but sedation and general anesthesia.

Local anesthetic agents in dentistry

The most commonly used local anesthetic is lidocaine (also called xylocaine or lignocaine), a modern replacement for novocaine and procaine. Its half-life in the body is about 1.5–2 hours. Other local anesthetic agents in current use include articaine (also called septocaine or ubistesin), marcaine (a long-acting anesthetic), and mepivacaine. A combination of these may be used depending on the situation. Also, most agents come in two forms: with and without epinephrine or other vasoconstrictor that allow the agent to last longer and also controls bleeding in the tissue during procedures. Usually the case is classified using the ASA Physical Status Classification System before any anesthesia is given.

Types of local anesthesia in dentistry

• Nerve block — a common form of local dental anesthesia; blocks the reception of pain in one region of the mouth at a time.

• Infiltration given inferior to the root the tooth involved in the dental work; used usually for minor procedures such as restorations.

• Palatal block given into the hard palate using pressure anethesia; useful in anesthetizing the palate side of the maxillary teeth.

• Intraosseous an injection of local anesthetic given directly into the osseous (bone) structure of the tooth for more involved dental procedures such as surgery or endodontic therapy (root canals).

• Intrapulpal an injection of local anesthetic given directly into the pulp of the tooth to completely desensitize the tooth.

• Pressure anesthesia — pressure with a cotton swab in the area to distract the nerve sensation of pain when the needle enters certain areas such as palatal tissue.

• Electrical nerve blocks— a technology that involves using electrical current to block the reception or generation of pain signals; the pain control can be transient.

• Acupuncture or accupressure An alternative to chemical or electrical blocks, but is rarely used.

Most common local anesthetic procedure

The Inferior alveolar nerve anaesthesia or block or IANB (sometimes referred to wrongly as the mandibular block) probably is anesthetized more often than any other nerve in the body. An injection blocks sensation in the inferior alveolar nerve, which runs from the angle of the mandible down the medial aspect of the mandible, innervating the mandibular teeth, lower lip, chin, and parts of the tongue, which is effective for dental work in the mandibular arch. To anesthetize this nerve, the licensed dental professional inserts the needle somewhat posterior to the most distal mandibular molar on one side of the mouth. The lingual nerve is also anesthetized through diffusion of the agent to produce a numb tongue as well as anesthetizing the floor of the mouth tissue, including that around the tongue side or lingual of the teeth.

Several nondental nerves are usually anesthetized during an inferior alveolar block. The mental nerve, which supplies cutaneous innervation to the anterior lip and chin, is a distal branch of the inferior alveolar nerve. When the inferior alveolar nerve is blocked, the mental nerve is blocked also, resulting in a numb lip and chin. Nerves lying near the point where the inferior alveolar nerve enters the mandible often are also anesthetized during inferior alveolar anesthesia, such as affecting hearing (auriculotemporal nerve).

The facial nerve lies some distance from the inferior alveolar nerve within the submandibular salivary gland, but in rare cases anesthetic can be injected far enough posteriorly to anesthetize that nerve. The result is a transient facial paralysis, with the injected side of the face having temporary loss of the use of the muscles of facial expression that include the inability to close the eyelid and the drooping of the labial commissure on the affected side for a few hours, which disappears when the anesthesia wears off.

In contrast, the superior alveolar nerves are not usually anesthetized directly because they are difficult to approach with a needle. For this reason, the maxillary arch is usually anesthetized locally for dental work by inserting the needle beneath the oral mucosa surrounding the teeth so as to anesthetize the smaller branches.

Dental syringe

A dental syringe is a syringe used by licensed dental professionals for the injection of a local anesthetic. It consists of a breech-loading syringe fitted with a sealed cartridge containing anesthetic solution.

Other anesthetics used in dentistry

• Topical anesthetics benzocaine, eugenol, and forms of xylocaine are used topically to numb various areas before injections or other minor procedures

• Nitrous oxide (N₂O), also known as “laughing gas”, easily crosses the alveoli of the lung and is dissolved into the passing blood, where it travels to the brain, leaving a dissociated and euphoric feeling in most cases. Nitrous oxide is used in combination with oxygen. Often (especially with children) a sweet-smelling fruity scent similar to an auto^{[clarificatioeeded]} scent is used with the gas to inspire deep inhalation.

• General anesthesia drugs such as midazolam, ketamine, propofol and fentanyl are used to put a person in a twilight sleep or render them completely unconscious and unaware of pain. Dentists who have completed a training program in anesthesiology may also administer general IV and inhalation anesthetic agents.

• Nebotamine, a drug with similar effects to ketamine, is injected into the anterior lingual glands blocking action potentials from sending signals to the myelinated nerve. The potency of the anesthetic is directly related to its lipid solubility, since 90% of the nerve cell membrane is composed of lipid.

• Midazolam (Versed), a drug that represses memories of the procedure, is usually given two hours prior to the procedure in combination with Tylenol in general anesthesia so the person will go home with no memories of being in surgery.

• Sevoflurane gas in combination with nitrous oxide and oxygen is often used during general anesthesia followed by the use of isoflurane gas to maintain anesthesia during the procedure. In children sweet fruity scents are often used with the gases to inspire deep inhalation. Scents come in cherry, apple, bubblegum, watermelon, etc.

• Propofol, a drug with similar effects to Sodium Pentathol, is often used through intravenous infusion through an IV during general anesthesia after gasses are initiated.

• Morphine is often used to control pain during the dental surgery under general anesthesia. The morphine is usually administered through IV.

• Ketorolac is often administered through IV to suppress both pain and inflammation while under general anesthesia.

Other drugs used in combination with general anesthesia in dentistry

• Decadron a steroid is often administered through IV to suppress inflammation and swelling resulting during the surgery while under general anesthesia.

• Ondansetron brand named Zofran is often administered to prevent nausea during the surgery which may result from the blood draining into the stomach while under general anesthesia, or it is given after the procedure for postoperative nausea which may result from the anesthesia itself which was administered.

Local anaesthetic is a type of painkilling medication that is used to numb areas of the body during some surgical procedures.

The word “anaesthetic” comes from the Greek word meaning the absence or loss of sensation.

Local anaesthetic is different from general anaesthetic which is used for larger operations when a persoeeds to be unconscious. You stay awake when you have a local anaesthetic.

How does local anaesthetic work?

Local anaesthetic causes a complete loss of feeling to a specific area of your body without making you lose consciousness. It works by blocking the nerves from the affected part of your body so that pain signals cannot reach your brain. You will not be able to feel any pain during the procedure but you may still feel some pressure or movement.

It only takes a few minutes to lose feeling in the area where local anaesthetic is given. The doctor will make sure that the area is fully numb before starting the procedure. It can take a few hours for local anaesthetic to wear off and for full feeling to return. You should be careful not to damage the area during this time. You may be offered painkillers if it’s thought that you’ll be in pain after the anaesthetic has worn off.

When is local anaesthetic used?

Local anaesthetic is often used by dentists, surgeons and GPs when carrying out minor operations on small areas of the body. For example, local anaesthetic is often used during:

• the removal of a tooth or a filling

• minor skin surgery, such as the removal of moles, warts and verrucas

• some types of eye surgery, such as the removal of cataracts (cloudy areas in the lens of the eye)

• some types of biopsies, such as a needle biopsy, where a tissue sample is removed for examination under a microscope

Local anaesthetic is also sometimes used during more major surgical procedures, such as certain types of brain surgery.

For example, it may be used when a brain tumour is located in the area of the brain that controls speech. As the tumour is being removed, you will need to remain conscious so that you can respond to the surgeon’s instructions. This helps them ensure that your speech is harmed as little as possible during the procedure.

Some creams and ointments that are available over the counter from pharmacists contain local anaesthetic. For example, gels for mouth ulcers sometimes contain small amounts of benzocaine, which numbs the area around the ulcer.

Epidural anaesthetic

Epidural anaesthetic is sometimes used during childbirth to ease the pain of labour or after surgery that has been carried out under general anaesthetic.

An epidural is a type of local anaesthetic that works by blocking the nerve roots from the spinal cord. If a woman decides to have an epidural during childbirth, anaesthetic will be injected into the area below the spinal cord (epidural space). This numbs the lower part of the body so that she does not feel any pain while giving birth.

Regional anaesthetic

This is also known as peripheral nerve block anaesthetic. A nerve block is an injection of local anaesthetic near a nerve to block pain during and after surgery. This may be used for an operation on a hand, arm or leg so that it can be carried out without the need for a general anaesthetic.

An ultrasound scan is often used to pinpoint the correct nerve, and the injection should not be painful.

The block usually takes full effect in about 30 minutes and it may be used in combination with general anaesthetic.

A screen is used during any operation that follows so that you do not see the surgery taking place.

Side effects

There may be temporary side effects after local anaesthetic is used, but there should be no long-lasting problems.

Side effects can include:

• a numb tongue

• dizziness

• blurred vision

• twitching muscles

If you have any of these symptoms, tell the doctor who administered the local anaesthetic. In rare cases, these symptoms can progress to more serious complications such as seizures (fits) or cardiac arrest (when the heart stops pumping blood around the body).

Local anesthesia is the temporary loss of sensation or pain in one part of the body produced by a topically applied or injected agent without depressing the level of consciousness.

Dental anesthetics fall into two groups:  esters (procaine, benzocaine) and amides (lidocaine, mepivacaine, prilocaine and articaine).  Esters are no longer used as injectable anesthetics, however benzocaine is used as a topical anesthetic.  Amides are the most commonly used injectable anesthetics with lidocaine also used as a topical anesthetic.

Topical anesthetics are effective to a depth of 2-3 mm and are effective in reducing the discomfort of the initial penetration of the needle into the mucosa.  It’s disadvantages are the taste may be disagreeable to patient and the length of application time may increase apprehension of approaching procedure in the pediatric patient.  Topical anesthetics are available in gel, liquid, ointment, patch and pressurized spray forms.  When applying topical anesthetics to the soft tissue use the smallest effective amount to avoid anesthetizing the pharyngeal tissues.

The most common topical anesthetics used in dentistry are those with benzocaine or lidocaine.

Benzocaine

Ethyl aminobenzoate (benzocaine) is an ester local anesthetic.  It is available in up to 20% concentrations.  It is poorly absorbed into cardiovascular system.  It remains at the site of application longer, providing a prolonged duration of action.  Localized allergic reactions may occur following prolonged or repeated use and it is reported to inhibit the antibacterial action of sulfonamides.

Not known to produce systemic toxicity in adults but can produce local allergic reactions.  However, the Food and Drug Administration announced in April 2011 that “Topical benzocaine sprays, gels and liquids used as anesthesia during medical procedures and for analgesia from tooth and gum pain may cause methemoglobinemia, a rare but serious and potentially fatal condition.  Children younger than 2 years appear to be at particular risk.  In the most severe cases, methemoglobinemia can result in death.  Patients who develop methemoglobinemia may experience signs and symptoms such as pale, gray or blue colored skin, lips and nail beds; headache; lightheadedness; shortness of breath; fatigue; and rapid heart rate.

Most of the cases reported were in children younger than 2 years who were treated with topical benzocaine gels for the relief of teeth pain.  The signs and symptoms can occur after a single application or multiple applications and can begin within minutes and hours of application.

Lidocaine

Lidocaine is available as a solution or ointment up to 5% and as a spray up to 10% concentration.  It has a low incidence of allergic reactions but is absorbed systemically and can combine with an injected amide local anesthetic to increase the risk of overdose.  A metered spray is suggested if an aerosol preparation is selected.

Systemic absorption of a lidocaine topical anesthetic must be considered when calculating the total amount of anesthetic administered.

Local anesthetics create a chemical roadblock between the source of pain and the brain by interfering with the ability of a nerve to transmit electrical signals or action potentials.  The local anesthetic blocks the operation of a specialized gate called the sodium potential.  When the sodium channel of a nerve is blocked, the nerve signals cannot be transmitted.  The only location at which the local anesthetic molecules have access to the nerve membrane is at the nodes of Ranvier, where there is an abundance of sodium channels.  The interruption of a nerve signal in a myelinated nerve (such as a dental nerve) occurs wheerve depolarization (the nerve signal) is blocked at three consecutive nodes of Ranvier.

Local anesthetics are vasodilators and are eventually absorbed into the circulation.  They have systemic effects that are directly related to their blood plasma level.  Overdose with local anesthetics can result in CNS depression, convulsions, elevated heart rate, and blood pressure.

Vasoconstrictors (epinephrine and levonordefrin) are added to local anesthetics to counteract the vasodilatory action, slowing the removal of the anesthetic from the area of the nerve and thus prolonging its action.  Different anesthetics have different rates of onset of symptoms and duration of action.  The more acidic a local anesthetic solution is the slower the onset of action.  The more closely the equilibrium pH for a given anesthetic approximates physiologic pH the more rapid the onset of anesthetic action.  The better the local anesthetic molecule binds to the protein in the nerve’s sodium channel, the longer the duration of anesthesia.

Amide local anesthetics available for dental usage include lidocaine, mepivacaine, articaine, prilocaine and bupivacaine.  They differ from each other in their duration of action (Table 1) and the maximum dosage that may be safely administered to patients (Table 2).

Table 1 demonstrates the variation in duration of action of injectable local anesthetics in minutes. There is variation in duration between anesthetics, pulp and soft tissue, and maxillary infiltration and mandibular blocks.

In the mandibular block, the duration of action of pulpal anesthesia for bupivacaine (240 minutes) is greater than lidocaine (85 minutes) and articaine (90 minutes) and is also greater in soft tissue (440 minutes) compared to lidocaine and articaine (190 minutes).  There are no procedures in pediatric dentistry that warrant 4 hours of pulpal anesthesia and over 7 hours of soft tissue anesthesia.  The prolonged time of duration of action increases the likelihood of self-inflicted, post-operative soft tissue injury and therefore the use of bupivacaine is not recommended in pediatric patients and those patients with special needs.

Another difference among injectable anesthetic agents is the maximum recommended doses.  This is extremely relevant in pediatric dentistry where there is a wide variation in weight between patients and thus not all patients should receive equal amounts of local anesthetic for the same procedure.  Table 2 summarizes the maximum recommended doses of local anesthetic agents.

Referring to Table 2, one can calculate the maximum recommended dosage and amount of local anesthetic agent for patients of specific weight and type of anesthetic.  For example:

To calculate the maximum amount of lidocaine 2% with 1:100,000 epinephrine and the number of carpules that can be safely administered to a 30 pound patient, the clinician would perform the following calculations.

Thus for a 30 pound child one can safely administer 1.67 carpules of lidocaine 2% with 1:100,000 epinephrine.

To calculate the maximum amount of Mepivacaine 3% plain and the number of carpules that can be administered to a 30 pound patient the clinician would perform the following calculations.

Note that the difference between the number of carpules of lidocaine 2% and mepivacaine 3% that can be administered to a 30 pound child is due to the difference in the number of mg of anesthetic solution in a 1.8cc carpule of anesthesia; lidocaine contains 54 mg and mepivacaine contains 60 mg.

The maximum amount of local anesthetic agent needs to be reduced if the patient is receiving a supplementary dose of enteral or parenteral sedative agent for behavior management.  The action of the sedative has an additive depressive effect on the central nervous and cardiovascular systems can initiate overdose consequences (see Complications of Local Anesthesia).

Before administrating any drug to a patient, the clinician must evaluate the health of the patient to determine whether the patient can tolerate the drug and minimize possible complications resulting from the drug interacting with the patient’s organ systems or with medication the patient is taking.  Local anesthetic actions include depressant effects on the central nervous system and cardiovascular system.  Because local anesthetics undergo bio-transformation in the liver (amides) and blood (esters) and are excreted in the kidneys the status of these organ systems should be evaluated.  A patient’s psychological acceptance of a local anesthetic needs to be assessed as many patients view the “shot” as the most traumatic aspect of the dental procedure.

While a comprehensive medical history is recommended for all dental patients, the following questions are most pertinent for those patients who are to receive local anesthesia.

• Has the patient ever received a local/topical anesthetic for medical or dental care?

• If so, were there any adverse reactions?

• Is the patient having any pain at this time?

• How severe?

• How long?

• Any swelling?

• Is the patient nervous about receiving dental treatment?

• Why are they nervous?

• Has the patient had any bad dental experiences?

• Has the patient been in a hospital during the past two years?

• Has the patient taken any medicine or drugs during the past two years?

• Has the patient been under the care of a physician during the past two years?

• Is the patient allergic to any foods or drugs?

• Does the patient have any bleeding problems that require special treatment?

• Has the patient ever have any of the following conditions or treatment?

• Heart failure

• Heart attack or heart disease

• Angina pectoris

• Hypertension

• Heart murmur, rheumatic fever

• Congenital heart problems

• Artificial heart valve

• Heart pacemaker

• Implanted cardioverter/defibrillator

• Heart operation

• Has the patient ever have any of the following conditions or treatment?

• Anemia (methemoglobinemia)

• Stroke

• Kidney trouble

• Hay fever, sinus trouble, allergies or hives

• Thyroid disease

• Pain in jaw joints

• HIV/AIDS

• Hepatitis A, B, C

• Epilepsy or seizures

• Fainting, dizzy spells, nervousness

• Psychiatric treatment

• Does the patient bruise easily?

• Is the patient pregnant?

• Does the patient have any disease, condition or problem not mentioned?

As the confines of this course limit a full discussion of the effects of local anesthetics on the body and with other drugs the following tables summarize the more common interactions.

 

 

• Armamentarium

• Next

The armamentarium necessary to administer local anesthesia is the carpule, needle and syringe.  Although clinicians may feel extremely comfortable with these items, a discussion of their characteristics is warranted.

• Carpule

The carpule (also referred to as the cartridge) contains the anesthetic solution.

• In the U.S. it contains 1.8 ml of anesthetic solution.  This amount may vary in other countries.

• Its components consist of a cylindrical glass tube, rubber stopper, aluminum cap and diaphragm.

• The glass cylinder is surrounded by thin plastic label that describes the contents and protects the patient if the carpule cracks.

• The stopper is located at the end of the cartridge that receives the syringe harpoon.  It is no longer color coded to the type of anesthetic used so the practitioner should double-check the contents of the carpule before administrating the anesthetic solution to the patient.  The stopper is slightly indented from the lip of the glass cylinder and the carpule should not be used if it is flush.

• The aluminum cap is located at the opposite end from the plunger.  It holds the diaphragm in place and is silver colored on all carpules.

• The diaphragm is a semi-permeable membrane made of latex rubber through which the needle perforates. (For patients with latex allergies, anesthetic carpules with non-latex stoppers are available.)

• The contents of the carpule are local anesthetic, vasopressor drug, preservatives for the vasopressor, sodium chloride and distilled water.

• The local anesthetic interrupts the nerve impulses preventing them from reaching the brain.

• The vasopressor drug is used to reduce dispersion of the local anesthetic into the circulation and increases its duration of action.  It lowers the pH of the carpule solution which may lead to discomfort during injection.

• The vasopressor drug contains sodium bisulfite as an antioxidant.  Patients may be allergic to bisulfite.  Local anesthetics without vasopressor do not contain bisulfites and may be used as an alternative for these patients.

• Sodium chloride is added to the anesthetic solution to make it isotonic with the body tissues.

• Distilled water is added to provide the proper volume of solution in the carpule.

Clinicians should be aware of possible problems with the carpules:

Bubble in the carpule – A small bubble may just be nitrogen gas used in the manufacturing process and is of no concern.  A large bubble that extrudes the plunger beyond the rim of the carpule is indicative of freezing and should not be used.

Burning on injection – This may be just a normal response to the pH of the drug especially those containing vasopressor.  However it can also be indicative of disinfecting solution leaking into the carpule or overheating of the anesthetic solution from a defective carpule warmer.

Leakage of solution – Leakage of solution during injection can result from improper alignment of the diaphragm and needle.

Broken carpule – A crack in the glass container may be a result of damage during shipping. It can also result from excessive force during engagement of the harpoon, a bent harpoon, or a bent needle leading to excessive pressure on the carpule during injection.

• Needles

• Next

Bevel – The point or tip of the needle.  The greater the angle of the bevel with the long axis of the needle, the greater the degree of deflection as the needle passes through the soft tissues.  For most injections the bevel of the needle is oriented toward bone.

Shank or shaft – Is identified by the length of the shank and the diameter of the needle lumen (gauge).  The higher the gauge the smaller the internal diameter.  The most common gauges are 25, 27, and 30 gauge.  Malamed recommends using the smallest gauge (largest diameter) needle available which allows for easier aspiration, less deflection of the needle as it perforates the soft tissue, and less chance of breakage at the hub.  The needle comes in three lengths, long short and ultrashort.  The decision as to the length is dependent on the type of injection (block or infiltration) size of patient and thickness of tissue.  The needle should not be inserted to the hub as retrieval during breakage is difficult so a long or short needle should be used for block anesthesia.  The advantage of the ultrashort needle is less deflection of the needle.  It may be used for infiltrations.

Hub – The hub is the plastic or metal piece through which the needle attaches to the syringe.  The interior surface of a plastic hub is not pre-threaded.  Therefore, attachment requires that the needle must be pushed onto the syringe while being screwed on.  Metal hub needles are usually pre-threaded.  The syringe end of the needle perforates the rubber diaphragm of the carpule when attached to the syringe.

Recommendations for needle utilization are:

• Sterile needles should be used.

• If multiple injections are to be administered, needles should be changed after three or four insertions in a patient.

• Needles must never be used on more than one patient.

• Needles should not be inserted into tissue to their hub to allow for easy retrieval if the needle breaks.

• To change a needle’s direction while it is still in tissues, withdraw the needle almost completely then change direction.

• Never force a needle against resistance (bone) as it can increase the chance of breakage.

• Do not bend needles except for intrapulpal injections.

• Needles should remain capped until used and then recapped immediately after injection.

• Needles should be discarded and destroyed after use.

 

• Syringe (carpule holder)

• The American Dental Association has established criteria for acceptance of local anesthetic syringes.

• They must be durable to withstand repeated sterilization without damage.

• Disposable syringes should be packaged in a sterile container.

• They should be capable of accepting a wide variety of cartridges and needles of different manufacturers.

• They should be inexpensive, self contained, lightweight, and simple to use with one hand.

• They should provide for effective aspiration and be constructed so that blood may be easily observed in the cartridge.

Syringe durability can be enhanced by following a routine of proper care and handling.

• After each use, thoroughly wash and rinse the syringe of any local anesthetic solution, saliva and other foreign matter.

• Autoclave the syringe as other surgical instruments.

• After every five autoclavings, dismantle the syringe and lightly lubricate all threaded joints and where the piston contacts the thumb ring and guide bearing.

• Clean the harpoon with a brush after each use.

• After extended use the harpoon will decrease in sharpness and fail to remain embedded within the cartridge stopper. Replace the piston and harpoon as necessary.

Even with proper maintenance problems may still arise.

• Bent harpoon – An off center puncture of the rubber plunger may cause breakage of the anesthetic cartridge or leakage of the anesthetic solution.

• Dull harpoon – A dull harpoon may cause disengagement from the rubber plunger during aspiration.

Side Effects of Dental Anesthesia

Dental work often involves the extraction of teeth or cutting into the oral tissue. Because this can be painful dentists typically use anesthetics to diminish the pain at the time of the operation. Most dentists use local anesthesia, which is the injection of agents that temporarily numb the nerves. Some dentists also use nitrous oxide, an inhaled gas that diminishes consciousness reducing pain during the operation.

Hematoma

Toothpaste company Colgate indicates that one potential side effect of dental anesthesia is the development of hematomas. Many dental anesthetics are given via injection. If the needle punctures or nicks a vessel blood can seep and collect below the surface of the skin or the gum tissue. This can lead to swelling. Although painful, hematomas are not considered dangerous.

Paresthesia

Local anesthetics for dental procedures are designed to numb the nearby tissue. Because it takes time for these to wear off, you may experience temporary paralysis or numbness in your mouth or face. This can cause your eyelids or part of the face to droop. It can also make speech or eating difficult. You are also advised to be careful when moving your mouth because it is easy to inadvertently bite the cheeks or tongue.

CNS Toxicity

According to the Mayo Clinic, in some cases the compounds used for dental anesthesia rapidly travel to the bloodstream and are absorbed by the body. This primarily affects the brain, leading to toxicity of the central nervous system (CNS). CNS toxicity can cause unusual excitability and irritability coupled with a rapid heartbeat and difficulty breathing. It can also cause increased sweating and paleness, as well as the sensation of being hot or cold. Patients can also develop double vision, confusion and in extreme situations, convulsions or seizures.

Nitrous Oxide Side Effects

According to the journal Medical Toxicology, nitrous oxide can cause a number of side effects. If too much is used, it can cause hypoxia, which is a subnormal amount of oxygen in the blood. One sign of hypoxia is dizziness resulting from low oxygen flow to the brain. It can also cause air filled portions of the body to expand, so it should not be used if you have bowel obstructions, sinus or middle ear problems or a collapsed lung. Finally, nitrous oxide impairs your body’s ability to use vitamin B12, which is needed for cell replication. As a result it can cause anemia and low white blood cell counts to develop.

 

Pharmacology of Outpatient Anesthesia Medications Intravenous sedation has a long history of use in oral surgery practice. Oral surgeons have been the historical leaders in the development of office-based ambulatory anesthesia practice. The development of newer intravenous agents and techniques have led to the increased acceptance of these practices as being safe and cost effective. Currently, the vast majority (> 70%) of surgical procedures are performed on an ambulatory basis, and at least 20% of surgical procedures are performed with office-based sedation or general anesthesia. While it is neither possible nor the intention of the authors to present the full scope of anesthetic medications including emergency medications in this chapter, we will review the pharmacology of many agents used in office-based sedation and general anesthesia practice. Where applicable the use of these agents in oral surgical practice is highlighted.

Pharmacodynamics and Pharmacokinetics Pharmacodynamics Pharmacodynamics is the study of the pharmacologic actions and clinical effects of a drug in the body.1 The clinical response of most anesthetic and sedative medications derives from their actions in the central nervous system (CNS). At a cellular level the most frequent mechanism by which drugs exert their pharmacologic effects is through interactions with specific protein receptors embedded in cell membranes, which then initiate a specific set of intracellular actions. These protein receptors can be characterized as ion channels or transmembrane receptors. Ion channels allow the passage of specific ions into or out of the cell, including chloride, potassium, sodium, and calcium. Alterations in the intracellular concentration of these ions initiate characteristic cellular effects such as depolarization of a cell membrane or movement of storage vesicles. Opening of ion channels may be triggered by either changes in membrane voltage or binding by a specific ligand. Voltage-sensitive ion channels open and close depending on cell membrane voltage, whereas a ligand-gated ion channel undergoes conformational changes when a drug or natural ligand binds to it, altering ion channel opening and closing. The -aminobutyric acid (GABA) receptor is an example of a ligand-gated chloride ion receptor. Transmembrane receptors are also ligand regulated and typically rely on second messenger systems to carry out the pharmacodynamic effect.When a specific ligand binds to the extracellular portion of these transmembrane receptors, a conformational change in the domain of the receptor exposed towards the cytoplasm activates either a specific enzyme or a second messenger system. Second messenger systems, such as G proteins and cyclic adenosine monophosphate, are complex cascades of signaling proteins that, once triggered, will produce the intended effect. An example of an enzyme-activated system is insulin, which binds to its specific receptor, activating an intracellular enzyme called tyrosine kinase, resulting in increased glucose uptake. Muscarinic acetylcholine (ACh) receptors also use a second messenger cascade involving intracellular calcium. Some lipid-soluble drugs do not engage membrane receptors, but instead exert their pharmacodynamic effect intracellularly via receptors found in the cytoplasm. Hormones and steroid medications cross the cell membrane and bind to cytoplasmic receptors, which then alter cellular functions such as gene transcription. A small number of medications may also alter enzyme activity outside of cells, such as anticholinesterase drugs that block the activity of acetylcholinesterase. Drugs are commonly classified as either agonists or antagonists for a specific receptor. Agonist drugs function to exert the normal property associated with receptor activation. GABA A agonists like benzodiazepines activate GABA receptors, allowing an influx of chloride, hyperpolarizing the cell, and reducing neuronal activity, thus promoting the normal activity associated with GABA activation. Antagonist drugs exert the opposite effect of the natural ligand or agonist drug activity. Competitive antagonists bind at the normal ligand-binding site but exert no pharmacologic effect. Instead the antagonist “takes up space” at the binding site, thus blocking agonist drug activity. The higher the concentration of antagonist, the greater the blocking effect. Agonist activity returns once the antagonist concentration decreases or if additional agonist is administered to overcome the antagonist concentration. Nondepolarizing neuromuscular blockers are competitive antagonists for the acetylcholine receptor. Noncompetitive antagonists do not bind at the ligand site but instead attach to a different location on the receptor, altering the configuration of the binding site and preventing normal ligand binding. Administration of an additional agonist does not affect noncompetitive antagonist activity, as they do not compete for the same binding site. Many pesticides are an example of noncompetitive antagonist agents.

Pharmacokinetics Pharmacokinetics is the study of the factors that affect the plasma concentration of a drug in the body, encompassing the processes of absorption, distribution, metabolism, and elimination.1 Commonly identified by the route of administration, such as per oral (PO), intravenous (IV), intramuscular (IM), or inhalation, absorption describes the point of entry of the drug into the body. Orally administered agents undergo first-pass metabolism; PO medications are absorbed by the intestinal mucosa and carried via the portal circulation to the liver where they undergo partial metabolism prior to entrance into the central circulation. This process potentially reduces the plasma concentration of drug that reaches the effector site, such as the CNS. Since the degree of gastrointestinal absorption and first-pass metabolism is unpredictable, PO sedative drugs can have less reliable clinical effects. Most anesthetic agents used in oral surgical practice are delivered intravenously, intramuscularly, or by inhalation. In contrast to oral agents these routes of administration do not undergo firstpass metabolism. Both intravenous and inhalation administration provide direct entry into the central circulation, reaching peak plasma concentration very quickly following drug administration. Inhalation pharmacokinetics will be discussed in the following section “Inhalation Anesthetics.” Distribution describes the movement of the drug between body compartments. The main factors influencing distribution include the allocation of blood flow to a specific compartment, the concentration gradient of the drug between compartments, the chemical structure of the drug, and plasma protein binding of the drug. Following administration the majority of the drug initially redistributes to the vessel-rich compartments. This vessel-rich group includes the brain, heart, kidney, and liver, representing 10% of total body mass but 75% of cardiac output.

Since the major site of anesthetic agent activity is the brain, early distribution to the CNS results in early anesthetic effects. The transfer of the drug from the central circulation to the brain is also determined by the concentration gradient between the two compartments. A lower concentration in one compartment favors the transfer from a region of higher concentration. Following initial intravenous administration the initial drug concentration in the brain is low relative to the plasma concentration; thus, the drug will rapidly transfer into the brain based on this differential concentration gradient. As the plasma concentration falls by continued redistribution to other vessel-rich organs, and later to less vessel-rich organs such as skeletal muscle (approximately 20% of cardiac output), anesthetic drug not bound to receptors in the brain will transfer back into the central circulation for further redistribution to other tissue sites. As the brain concentration of sedative agent falls, the clinical effects of sedation also decrease. Characteristics of the drug itself affect its distribution throughout the body. Lipophilic drugs readily cross the bloodbrain barrier and cellular membranes, and generally exert their effects rapidly. Likewise lipophilic drugs can quickly exit the CNS, shortening the duration of their effects. Hydrophilic medications either cross very slowly or must be transported by specific mechanisms. The size or molecular weight of the drug molecules influences movement across capillary walls; smaller molecules will cross more readily. The degree to which the drug binds to plasma proteins such as albumin and 1- acid glycoprotein will affect the amount of free drug available to cross into the brain. Most sedative agents are highly plasmaprotein bound. For example, initial doses of diazepam are 98% bound to plasma protein and unavailable to cross into the CNS. As the free drug plasma concentration decreases through further redistribution, and later metabolism and elimination, plasma–protein-bound drug is released back into the plasma as free drug and is able to cross the blood-brain barrier. In this way drug bound to plasma protein may be thought of as a reservoir of drug that may contribute to prolonged sedative effects. Once plasma-protein binding sites have been filled, an additional consequence is that further administration of small quantities of drug can have profound effects as the majority of the additional administered agent will be free drug that is able to cross the blood-brain barrier. Careful titration of intravenous agents, especially after initial administration and filling of protein binding sites, is important to avoid oversedation due to this mechanism.

Hypoproteinemia secondary to advanced age or severe liver failure can also dramatically increase the concentration of free drug, and dose reduction may be required. As redistribution continues, a fraction of the plasma concentration is delivered to the liver, the primary organ of drug metabolism, undergoing transformation from a lipid-soluble entity to a water-soluble form. There are four main pathways of hepatic metabolism: oxidation, reduction, hydrolysis, and conjugation. Phase I reactions include the first three pathways, converting the drug into a water-soluble metabolite or intermediate form. Phase II reactions involve most forms of conjugation, in which an additional group is added onto the metabolite in order to increase its polarity. Subsequent elimination via the kidney, the main excretory organ, requires hydrophilicity to avoid reabsorption of the excreted drug. Water-soluble drugs and metabolites are eliminated chiefly by the kidney, but also via the bile, lungs, skin, and other organs. Phase I hepatic reactions, including the cytochrome P-450 (CYP-450) group of enzymes which carry out the oxidation and reduction reactions, occur in the hepatic smooth endoplasmic reticulum (hepatic microsomal enzymes). The CYP- 450 group of enzymes has been characterized into several isoforms, including CYP- 3A4, CYP-2D6, and CYP-1A2. The conjugation reaction of glucuronidation is also conducted by the hepatic microsomal enzymes. The hepatic microsomal enzymes are unique in that certain chemicals and drugs, including those used in anesthesia, can stimulate their activity. This is termed enzyme induction and generally requires chronic exposure of the drug to the enzyme system for at least several days or weeks. An isolated exposure to anesthetic agents is unlikely to induce hepatic enzyme activity.

However, if the patient’s daily medications induce hepatic enzymes, then increased metabolism of additional medications is possible. Induction is isoform specific; a coadministered drug will only be affected by enzyme induction if both drugs are metabolized by the same enzyme system. Hepatic microsomal enzymes can also be inhibited by certain drugs, thus reducing metabolism of drugs by a specific enzyme system. For example, patients taking cimetidine for treatment of gastric ulcers may experience prolonged residual CNS effects from diazepam, as cimetidine inhibits the hepatic enzymes that normally metabolize diazepam. Various tables have been published which list drugs that are substrates, inducers, and inhibitors of the various cytochrome enzyme systems. Nonhepatic forms of metabolism are important for certain anesthetic medications, and are useful in patients with significant liver or kidney disease. Drugs susceptible to Hofmann elimination spontaneously degrade at body pH and temperature. Ester hydrolysis by nonspecific and specific (eg, pseudocholinesterase) esterases is also less dependent on renal and hepatic functions. Redistribution, metabolism, and elimination reduce the plasma concentration of the drug, increasing the transfer of drug from tissue sites (eg, brain) back into the central circulation for further redistribution, metabolism, and elimination. Different mathematical models involving these processes have been developed that describe the offset of activity of anesthetic agents. The fall of 50% of the plasma concentration of the drug secondary to redistribution is termed the alpha half-life. The removal of 50% of the drug from the body due to metabolism and/or elimination is termed the beta half-life, or elimination half-life. Offset of clinical effects and awakening from a bolus of an IV anesthetic agent is more dependent on redistribution of the drug away from the brain and is therefore better approximated by the alpha half-life than the beta half-life. In some cases residual CNS effects can be predicted by a long elimination half-life. The beta half-life has more use for orally administered agents and particularly describes central compartment concentration in a one-compartment model. The pharmacokinetics of a continuous infusion of intravenous anesthetic agents may be better described by the context-sensitive half-time. This value represents the time necessary for the plasma drug concentration to decrease by 50% after discontinuing a continuous infusion, depending on how long the anesthetic agent has been administered.2 Figure 5-1 describes the context-sensitive half-time for a number of common anesthetic agents. Currently computercontrolled pumps administer continuous infusions based on a specific amount of drug per time, but the newest infusion pumps can be programmed to calculate and provide target plasma concentrations of an agent to a specified anesthetic or analgesic level. In the future these pumps will likely be integrated with concurrent electroencephalogram consciousness monitoring to individualize anesthetic drug delivery.

Benzodiazepines Benzodiazepines are the most commonly used sedative and anxiolytic medications in oral surgery. Their relatively high margin of safety as compared to other sedativehypnotic medications, in addition to the availability of an effective reversal agent, makes their use attractive during operator-anesthetist procedures in an outpatient setting. Benzodiazepines are composed of a benzene and diazepine ring fused together.3 Agonist agents contain a 5-aryl substitution which is not present on the antagonist reversal agent (Figure 5-2). This structure binds to inhibitory GABA receptors found throughout the brain, particularly in the cerebral cortex. Binding to the GABA A subunit increases the frequency of poreopening in the chloride-gated channel, thus increasing inward chloride flow, hyperpolarizing cell membranes, and reducing neuronal transmission. Characteristics shared by benzodiazepines include sedation, anxiolysis, anterograde amnesia, muscle-relaxing properties, and anticonvulsant activity. Indeed, any intravenous benzodiazepine agonist may be used to suppress acute seizure activity. These drugs do not produce analgesia. Benzodiazepines are commonly used for preoperative sedation both immediately prior to the procedure and as a sleep adjunct the night before surgery. In clinical practice they are also used for conscious sedation, and at higher doses can produce deep sedation and even general anesthesia. In a nervous patient anxiolysis from benzodiazepines can produce noticeable reduction in blood pressure and heart rate, but these medications have little direct effect on cardiovascular parameters. Given alone in slowly titrated doses, benzodiazepines also have minimal effects on ventilation. Large bolus doses will, however, induce unconsciousness and apnea. Additionally, even smaller doses when given in combination with an opioid can synergistically enhance opioidinduced respiratory depression. Benzodiazepines are metabolized by hepatic enzymes into hydrophilic forms. These metabolites are then excreted by the kidney in urine. Side effects of benzodiazepines are few, but paradoxical excitement, in which patients may become overly disinhibited and disoriented, is a possible complication. Flumazenil is useful in the reversal of paradoxical excitement and benzodiazepine- related respiratory depression.

Diazepam Diazepam is lipid soluble and is carried in an organic solvent such as propylene glycol or a soybean oil emulsion. Intravenous injection can be painful, although injecting into a larger vein or pre-administration of lidocaine or an opioid can reduce discomfort. Intramuscular injection is painful and absorption can be unpredictable. Diazepam is still used for intravenous conscious sedation, given in 2.5 to 5 mg increments every few minutes. Onset of sedation occurs in several minutes and recovery from clinical sedation by diazepam is similar compared to midazolam. However, the much longer elimination time of diazepam may contribute to lingering sedative effects. Diazepam can also be given orally (5 to 10 mg) for preoperative anxiolysis and mild sedation. This highly lipid-soluble drug accumulates in fat tissues with slow reentry of very small quantities into the central circulation, leading to an elimination halflife of 24 to 96 hours. Diazepam is also metabolized into two pharmacologically active metabolites, desmethyldiazepam and oxazepam, each with long elimination half-lives as well. The active metabolites and parent drug are partially eliminated in bile and can result inreemergence of sedation several hours after completion of the procedure, due to enterohepatic metabolism. Upon ingestion of a fat-rich meal, bile is released into the gut, and active drug components in the bile are reabsorbed by the intestinal mucosa and undergo first-pass metabolism. These still active drugs are then re-introduced into the central circulation and into the CNS, resulting in possible resedation.

Midazolam Midazolam has an imidazole ring attached to its diazepine ring. The imidazole ring is open, rendering the compound water soluble at pH less than 4, but the ring closes at physiologic pH producing the lipid-soluble benzodiazepine. Midazolam can therefore be delivered in an aqueous solution, rather than propylene glycol, resulting in less pain on intravenous and intramuscular injection. 4 It is 2 to 3 times as potent at diazepam, with a faster onset, much faster elimination, and shorter duration of lingering effects. Its active metabolites are not thought to produce significant sedative effects. Respiratory depression is more of a concern with midazolam than diazepam after bolus intravenous administration. Midazolam is currently more popular than diazepam for intravenous sedation for short oral surgical procedures. For conscious sedation 0.05 to 0.15 mg/kg IV in divided doses is titrated to effect, typically given in 1 or 2 mg boluses every few minutes. Peak effect is seen in approximately 5 minutes. Dosage should be adjusted downward when given concurrently with other medications such as opioids or propofol. An intramuscular injection of 0.5 mg/kg to a maximum of 10 to 15 mg depending on patient age is also possible. As an alternative midazolam may be given orally at 0.5 to 1 mg/kg (maximum 15 mg), usually mixed into a flavored syrup or in a commercially available premixed product; this route may be better accepted by pediatric patients.5 Clinical effect from PO administration will be seen after 15 to 20 minutes in the pediatric patient.

Lorazepam Lorazepam is a long-acting benzodiazepine with a slow onset. Its use for PO and IV sedation is therefore limited but is an option for oral preoperative anxiolysis, particularly the night before surgery or for long operative appointments. Dosage for an adult is 0.05 mg/kg, not to exceed 4 mg total.

Triazolam Triazolam is only available in an oral formulation as 0.125 mg and 0.25 mg tablets. This sleep adjunct can be used off-label for anxiolysis and sedation at a dose of 0.25 to 0.5 mg for an adult. It is a very short-acting benzodiazepine and its effects are observed in 30 to 45 minutes with clinically effective sedation lasting from 30 to 90 minutes.

Flumazenil Flumazenil is a highly specific competitive antagonist for the benzodiazepine receptor and is used as a reversal agent for benzodiazepine agonists.6 It will reverse benzodiazepine sedation, excessive disinhibition, and the additive ventilatory depression related to benzodiazepines when combined with opioids. Flumazenil is given 0.2 mg IV initially, followed by 0.1 mg at 1-minute intervals as necessary, to a total of 1 mg. In emergency situations, 0.5 to 1 mg or more may be administered in a bolus dose. Reversal effects may take several minutes to manifest. The effect of flumazenil will last 30 to 60 minutes and may require redosing since agonist drug activity may outlast the reversal effects. Flumazenil should not be administered to epileptic patients using benzodiazepines for seizure control and should be used cautiously with other epileptic patients.

Opioids Opioid medications are used in oral surgery primarily for analgesia and mild sedation or euphoria. It is important to note that narcotic medications do not produce amnesia or classic sedation, nor do they induce loss of consciousness or sensation of touch at clinically relevant doses. Patients given opioid medications alone will retain awareness and memory. Instead, opioids are often used in combination with sedative-hypnotic medications such as benzodiazepines and barbiturates to provide analgesia and augment the desired level of anesthesia. While the term opiate refers to any drug derived from opium, opioid medications include all substances, natural and synthetic, which bind to the opioid receptors. 7 Common opioid medications are shown in Figure 5-3. Endogenous opioids such as endorphins and enkephalins, and administered opioid medications like morphine, bind to opioid receptors located in presynaptic and postsynaptic neurons throughout the CNS as well as in peripheral afferent nerves. Agonist activity at these receptors either modifies or decreases neuronal transmission of pain signals. Several subtypes of opioid receptors (eg, μ, κ, δ) with differential effects have been identified. The μ and κ receptors are predominantly responsible for analgesia, and most clinically used opioids are agonists for the μ receptor. A subset of opioids, termed agonist-antagonist opioids, are agonists at κ receptors and antagonists at μ receptors. Thus agonist-antagonist opioids are contraindicated for patients on long-term opioids, such as those using these agents for chronic pain or those on methadone maintenance for treatment of opioid substance abuse. Respiratory depression is the most common and pronounced side effect of μ receptor agonists as used in anesthetic practice. This effect can be significantly exacerbated with concurrent administration of other medications such as benzodiazepines, barbiturates, propofol, and other opioids. Respiratory depression is dose dependent, resulting from a decrease inthe respiratory response to arterial carbon dioxide (CO2) levels in the brainstem respiratory centers. Decreased respiratory rate and arterial hypoxemia may result without supplemental oxygen (O2) and appropriate monitoring (eg, pulse oximetry). Opioids are often titrated incrementally to balance the analgesic effect against respiratory depression. Bradycardia as a direct effect is more apparent with high doses of opioids and is due to centrally mediated vagal response. This effect is common with opioids such as morphine, fentanyl, and the synthetic derivatives, but less common with meperidine. A mild decrease or stabilization of the heart rate may be desirable in patients with cardiovascular disease. Most opioids are metabolized by hepatic enzymes and excreted into the urine and bile. The exception is remifentanil, which is metabolized by plasma esterases. Opioids suppress the cough reflex and are a common ingredient in cough medicines. These antitussive effects can be beneficial during sedation, especially when used in patients with hyperreactive airways (eg, smokers). However, several opioids can cause the release of histamine and caution should be used when histamine-triggering opioids are administered to an asthmatic patient. Other manifestations of histamine release include a decrease in blood pressure secondary to vasodilation, and pruritus and erythema, especially at the site of injection. Other adverse effects such as nausea and vomiting, constipation, urinary retention, and biliary tract spasm may increase patient discomfort postoperatively, particularly with repeated oral or neuraxial administration. These reactions are frequently misinterpreted by the patient and other health care providers as an “allergic” reaction.

Morphine Morphine is the standard agent by which other opioids are compared. It has poor lipid solubility and therefore has a slow onset. Peak effect following IV administration occurs in 15 to 30 minutes and the analgesic effect lasts approximately 4 hours. Because of its slow onset and longer duration of activity, it is commonly used in anesthesia for postoperative pain management rather than intravenous sedation. Morphine is normally given in 1 to 2 mg IV increments for postoperative analgesia. Morphine has several notable characteristics. Histamine release from morphine can result in skin flushing and a decrease in blood pressure and may be of concern in an asthmatic patient. Morphine is metabolized by hepatic enzymes into two metabolites that are subsequently eliminated by the kidney. One of these metabolites, morphine-6-glucuronide, is more potent than morphine itself, and prolonged opioid effects in patients with renal failure can be significant.

Meperidine Meperidine is a synthetic opioid with a relatively rapid onset time and duration of action between 2 and 3 hours. It is used for both intravenous sedation and postoperative pain control. Meperidine is usually given in 12.5 to 25 mg IV increments titrated to effect. The drug has several identifying characteristics. Like morphine, it also has an active metabolite, normeperidine, which is half the potency of meperidine. When mixed with monoamine oxidase inhibitors, meperidine administration may produce a dangerous excitatory hyperthermic reaction. With repeated dosing, particularly in renally compromised patients, accumulation of normeperidine may lead to seizures.Meperidine is also associated with the release of histamine; thus, appropriate precautions should be taken. Unlike the other opioids it is not associated with bradycardia; its structure resembles atropine and it possesses mild anticholinergic effects such as a mild increase in heart rate (offset by direct vagal stimulation) and xerostomia.Meperidine is commonly used to reduce shivering postoperatively, an action likely associated with partial agonist activity at the κ receptor.

Fentanyl Fentanyl is a synthetic opioid, and its high lipid solubility leads to its high potency, rapid onset (1 min), and shorter duration of action (10 to 20 min). Withsuch characteristics fentanyl is a frequent choice for intravenous conscious sedation for short office-based procedures. It is typically given in 25 to 50 μg increments towards a total dose of approximately 1 to 2 μg/kg. It is also given during induction of general anesthesia, both for analgesia and attenuation of airway reflexes during intubation. Fentanyl does not induce histamine release and is therefore not associated with vasodilatory or bronchospastic effects. However, at higher doses, it can cause more pronounced bradycardia than morphine. Fentanyl is a potent respiratory depressant. At high doses and with rapid bolus administration, fentanyl and other synthetic derivatives have been associated with chest wall and glottic rigidity, making ventilation impossible; there are reports that even lower doses (eg, 100 μg) can trigger this centrally mediated effect. Fentanyl-associated chest wall rigidity is treated with either naloxone or succinylcholine (SCh), and positive pressure O2 and other resuscitation equipment should be immediately available. The incidence of fentanyl rigidity is reduced by a preceding dose of a benzodiazepine or other hypnotic drug.

Remifentanil, Sufentanil, and Alfentanil Remifentanil, sufentanil, and alfentanil are synthetic fentanyl derivatives used primarily for analgesia during general anesthesia. Remifentanil in particular is associated with a rapid onset and extremely short duration of action, resulting in a significantly shorter recovery time. Metabolized by nonspecific plasma esterases, its clearance is very rapid and independent of both hepatic and renal functions. It has a very short context-sensitive half-time of 4 minutes with virtually no cumulative effect, even following hours of continuous infusion. These features make remifentanil ideal for use in a titratable continuous infusion. Of note is the fact that because the actions of this medication are so shortlived, postoperative pain will not be addressed by intraoperative remifentanil, and alternative pain control with another narcotic such as a nonsteroidal antiinflammatory drug (NSAID) or local anesthesia should be considered towards the end of the procedure. Remifentanil is used in a total intravenous infusion anesthetic technique to maintain anesthesia during dental surgery, often in combination with propofol. For analgesia during general anesthesia it is used at 0.25 to 1 μg/kg or 0.5 to 2 μg/kg/min. During sedation the dose ranges from 0.05 to 0.10 μg/kg/min. Remifentanil, like fentanyl, can cause chest wall rigidity and caution should be used during bolus administration. It is also a highly potent respiratory depressant, and even at lower doses, apnea may be pronounced. If spontaneous ventilation is desired the remifentanil infusion is usually titrated to maintain an adequate respiratory rate. None of these synthetic derivatives cause the release of histamine. Sufentanil and alfentanil are shorteracting agents than fentanyl but not as rapid in offset as remifentanil. These agents are commonly used as a continuous infusion adjunct for intubated general anesthesia during cardiac or prolonged surgery, particularly when residual opioid effects are desirable postoperatively. They are not as commonly used for office-based oral surgical anesthesia.

Nalbuphine Nalbuphine is the most frequently used intravenous agonist-antagonist opioid. It has a relatively short onset and duration of action of 2 to 4 hours at sedation doses of 5 to 10 mg for the adult patient. Although nalbuphine and other agonist-antagonist opioids do possess a ceiling effect for respiratory depression at higher doses, at equianalgesic and clinically relevant sedation doses, the respiratory depressant effects are similar to μ agonist opioids. Nalbuphine does not release histamine. Unlike all the other agents noted above which are US Drug Enforcement Agency Schedule II controlled substances, nalbuphine is not currently a scheduled controlled substance and does not require state and federal documentation of use.

Naloxone Naloxone is a pure opioid antagonist that is active at all opioid receptor subtypes. It will reverse both the ventilatory depressive and analgesic effects of opioids. It can also be used to reverse chest wall or glottic rigidity from fentanyl and its derivatives. In patients taking opioids chronically (eg, chronic pain management, illicit opioid users, methadone therapy for opioid abuse), naloxone must be used with caution as the antagonist effect may precipitate acute opioid withdrawal and acute congestive heart failure may result. The initial dose is 0.4 to 2 mg IV for acute reversal. Naloxone can also be titrated in 0.04 mg increments when gradual adjustment of mild respiratory depression is required. Because the duration of naloxone activity is 30 to 45 minutes, reemergence of respiratory depression may occur and additional dosing may be needed.

Barbiturates Barbiturates are sedative-hypnotic medications that have long been employed as induction agents of general anesthesia. Barbiturates produce sedation, loss of consciousness, and amnesia. These drugs do not provide analgesia and may actually reduce pain threshold at lower doses. Several barbiturates such as IV pentobarbital and oral phenobarbital are commonly used as anticonvulsants for both prevention and treatment of seizures. High doses of any intravenous barbiturate can also suppress acute seizure activity. Barbiturates are derivatives of barbituric acid (Figure 5-4). The characteristics of the individual barbiturate are determined by the side chains attached to the barbiturate ring (Figure 5-5). For example, sulfur substitution on the no. 2 carbon in thiobarbiturates increases the lipid solubility of these drugs and hence decreases onset of action and duration of activity. The methyl group attached to the nitrogen atom of the ring in methohexital results in a more rapid onset for this oxybarbiturate and increased susceptibility to cleavage, producing a shorter duration than other oxybarbiturates. Barbiturates act on GABA receptors at a specific binding site (different from benzodiazepines), causing the chloride channel to remain open for a longer duration. The increased negative inward flow hyperpolarizes the membrane, decreasing neuronal transmission. Awakening from intravenous barbiturates is dependent on redistribution from the brain. These medications are metabolized by hepatic enzymes without the formation of active metabolites and are then cleared renally. Because these drugs are highly protein-bound, hypoproteinemia secondary to liver failure or malnutrition increases the plasma concentration of free drug. Chronic use of barbiturates can cause induction of liver enzymes. Barbiturates are also contraindicated in patients with acute intermittent porphyria as they may precipitate an attack. Barbiturates are associated with a dose-dependent decrease in respiratory rate and tidal volume with apnea observed at higher doses. Centrally mediated peripheral vasodilation leads to a transient drop of 10 to 30% in systemic blood pressure, particularly when a full induction dose is administered. This is partially attenuated by a compensatory increase in heart rate as baroreceptor reflexes remain intact. Hypotension is more evident in the elderly or medically compromised, hypovolemic patients. Thiopental can cause histamine release, which is clinically insignificant with methohexital. Intra-arterial injection of barbiturates causes painful spasm of the vessel from precipitation of barbiturate crystals, which damage the endothelium and may result in occlusion of the artery. At worst, decreased distal perfusion may result in tissue necrosis of a limb or nerve damage and must be addressed immediately. The intravenous catheter should be left in place, IV cardiac lidocaine or procaine (without epinephrine) administered, and the patient should be transported to an emergency department where medications or regional blockade may be given to relieve the spasm and reduce the occlusion. Although also uncommon, venous irritation and thrombosis secondary to crystal formation is also possible with concentrations of barbiturates above 1% methohexital and 2.5% thiopental. These medications are stored in powder form and reconstituted in saline prior to use as sodium salts. The alkalinity of the solutions prevents bacterial growth and ensures a longer refrigerated shelf life of up to 2 weeks for thiopental and 6 weeks for methohexital.

Thiopental Thiopental is an ultrashort-acting barbiturate that is commonly used at 3 to 5 mg/kg IV to induce loss of consciousness for general anesthesia prior to endotracheal intubation. It is associated with a longer recovery than methohexital due to its decreased plasma clearance and is generally not used as a continuous infusion to maintain anesthesia due to significant storage in multiple drug compartments. A 2.5% solution of thiopental is lessexpensive than other induction agents, but when rapid recovery is desired during outpatient anesthesia, other agents such as methohexital and propofol have proven more popular. Thiopental can release histamine, which is a concern in asthmatic patients.

Methohexital Methohexital is an ultrashort-acting barbiturate that is commonly employed for outpatient oral surgical procedures, primarily for its more rapid recovery compared to thiopental and its lower cost compared to propofol. As an oxybarbiturate, methohexital is less lipid soluble than thiopental but is associated with a more rapid awakening because of its increased hepatic clearance.8 Psychomotor function returns more quickly with methohexital than thiopental, allowing for earlier discharge following an outpatient procedure. Methohexital is reconstituted into a 1% solution and given at 1.5 to 2 mg/kg IV for induction of general anesthesia. With these doses blood pressure may drop by up to 35% and heart rate increases up to 40% of baseline. In a common deep sedation technique used in oral surgical practice, 10 to 30 mg increments of methohexital are periodically administered after obtaining baseline conscious sedation with a benzodiazepine and opioid to produce a state of deep sedation for local anesthetic administration and other stimulating portions of dentoalveolar surgery. Methohexital is associated with involuntary movements such as myoclonus and hiccuping. These excitatory phenomena are dose dependent and may be reduced by prior administration of opioids. Low doses of methohexital can activate seizure foci and should be used cautiously, if at all, for epileptic patients. Shivering upon awakening is also common following methohexital anesthesia. Methohexital exhibits clinically insignificant histamine release.

Pentobarbital Pentobarbital is an intravenous shortacting barbiturate with a duration of action of 2 to 4 hours. It is generally used for conscious sedation in doses of 100 to 300 mg, combined with opioids and possibly benzodiazepines, for longer operative procedures. Cardiovascular effects are more modest than the ultrashort-acting agents.

Nonbarbiturate Induction Agents Other medications are available for sedation and induction of general anesthesia. These include propofol, etomidate, and ketamine, all of which can produce unconsciousness but with several differing characteristics from barbiturate medications.

Propofol Propofol has become one of the most popular sedative-hypnotic drugs used for ambulatory surgery. Propofol, 2,6– diisopropylphenol (Figure 5-6), is highly lipid soluble and available as a milky white 1% suspension in soybean oil, glycerol, and egg phosphatide. Like benzodiazepines and barbiturates, propofol is thought to interact with the GABA receptor, causing increased chloride conductance and hyperpolarization of neurons. At higher doses propofol can produce amnesia and loss of consciousness. It is also an anticonvulsant, although spontaneous excitatory movements may be noted following administration.9 Depending on the dose and technique, propofol is used for all levels of sedation and general anesthesia. For induction of general anesthesia a bolus of 1.5 to 2.5 mg/kg IV produces unconsciousness within 30 seconds. In the intermittent bolus technique frequently used for deep sedation in oral surgery, small increments of propofol (10 to 30 mg) are periodically administered after a baseline conscious sedation with a benzodiazepine and opioid is obtained, in order to produce a state of deep sedation for local anesthetic administration and other stimulating portions of dentoalveolar surgery. Propofol can also be used as a continuous intravenous infusion. 10 The dosages for conscious sedation range from 25 to 100 μg/kg/min, deep sedation from 75 to 150 μg/kg/min, and general anesthesia from 100 to 300 μg/kg/min depending on the use of intubation. The overlap of dose ranges, from conscious sedation to general anesthesia, highlights the lower margin of safety of this drug, especially if the intended level of sedation is conscious sedation. US Food and Drug Administration labeling prohibits use of propofol by those involved in the conduct of the surgical or diagnostic procedure. Propofol is extensively metabolized by hepatic enzymes. In addition, extensive redistribution and other mechanisms of metabolism and elimination most likely occur, as the rate of propofol clearance from the plasma exceeds hepatic blood flow. This rapid plasma clearance may account for the decreased cumulative effect of this drug in the body, contributing to rapid awakening. The context-sensitive half-time for this drug is short, reaching a maximum of 40 minutes even after 2 to 6 hours of continuous infusion. Contextsensitive half-times are even shorter with brief infusions. Propofol decreases systemic blood pressure by as much as 20 to 40% from baseline through centrally mediated vasodilation. Propofol also blocks sympathetic tone and allows parasympathetic vagal responses to predominate, thereby blunting the reflex tachycardia that wouldnormally be associated with such a drop in blood pressure. Hypotension may therefore be very significant following bolus administration of propofol, particularly in the elderly, medically compromised, and hypovolemic patients. Propofol also leads to dose-dependent respiratory depression and can produce apnea at higher doses. It is not associated with histamine release and has bronchodilatory properties. Recovery from anesthesia with propofol has several unique characteristics. Compared to other induction agents propofol is associated with a more rapid awakening and recovery, with less residual CNS effects. Many patients also experience mild euphoria on awakening, which enhances reported satisfaction with the anesthesia postoperatively. Even at subhypnotic doses propofol is associated with decreased postoperative nausea and vomiting.9 All these features make propofol an attractive choice for outpatient procedures where decreased time to discharge is desirable. Even with an available generic formulation the higher cost compared to barbiturates is still apparent. The increased cost can overshadow the advantages of using propofol infusions, especially if the surgical time is long (> 2 h), or if quick discharge is not required. Several considerations should be taken when using propofol. The solution can cause significant pain on injection, especially in smaller vessels. This may be attenuated with pre-administration of opioids or 1% cardiac lidocaine. Unlike barbiturates, however, it does not cause vasospasm when inadvertently injected into an artery. Anaphylaxis is rare but has been reported in patients with a history of allergic reactions to other medications, especially neuromuscular blocking drugs. A history of egg allergy does not necessarily preclude the use of propofol, as the egg protein contained in the suspension is lecithin, whereas most egg allergies consist of a reaction to egg albumin. The original proprietary agent, Diprivan, uses ethylenediaminetetraacetic acid as an antibacterial agent, whereas the generic version contains a sulfite. Although this generic agent should not be used in patients with known sulfite sensitivity, it appears that allergic reactions and bronchospasm are very unlikely, although not completely unheard of, in other patients including asthmatics. Both drug suspensions are pH neutral and can support bacterial growth; therefore, the observation of sterile technique and discarding of an opened vial or filled syringe after 6 hours are recommended. Cracked glass containers or discolored contents should be discarded, as sepsis is a possibility.

Etomidate Like midazolam, etomidate contains an imidazole structure (Figure 5-7). It is water soluble but available in a 0.2% solution in propylene glycol. In the same way as the other induction medications, etomidate interacts at the GABA receptor. Etomidate is used primarily as an induction agent for general anesthesia at 0.2 to 0.4 mg/kg IV. Its main advantage over barbiturates and propofol is cardiovascular stability. Although systemic blood pressure can decrease by up to 15% with etomidate, changes in heart rate are minimal. It also does not depress myocardial contractility. Etomidate is usually reserved for patients with unstable cardiac disease because it is more expensive than other induction agents. Spontaneous respiration may be maintained. Respiratory depression is less pronounced with etomidate compared to barbiturates, although apnea is still possible with higher doses. Etomidate is metabolized by both hepatic enzymes and plasma esterases. This rapid clearance leads to awakening and recovery that is faster than with thiopental but slower than with methohexital or propofol. Myoclonus is common in over 50% of patients and may be partially prevented with pre-administration of a benzodiazepine or opioid. Many patients experience pain on injection secondary to the propylene glycol. Etomidate has been associated with adrenocortical suppression but this is less profound when only a single induction dose is administered.

Ketamine Ketamine is a phencyclidine derivative (Figure 5-8) that induces a state of “dissociative anesthesia.” This is characterized as a “dissociation” between the thalamocortical and limbic systems, producing a cataleptic state during which the patient may appear awake but does not respond to commands.11 The eyes may be open and nystagmic. Ketamine does produce anterograde amnesia, and unlike other induction agents, it can produce intense analgesia. Unlike other hypnotic agents ketamine does not interact with GABA receptors. The exact mechanism of action is unclear but ketamine is a nonselective antagonist of supraspinal N-methyl-Daspartate receptors,which involve the excitatory neurotransmitter glutamate. Inhibition of these receptors decreases neuronal signaling and is likely responsible for some analgesic effects. Ketamine may also interact with pain receptors in the spinal cord as well as opioid receptors, which may also account for analgesia.12 Ketamine is highly lipid soluble and redistributes quickly, which accounts forits rapid onset of action and relatively short duration. It is metabolized by hepatic enzymes and has an active metabolite, norketamine. Ketamine does have a significant abuse potential and chronic use can lead to enzyme induction. The cardiovascular effects of ketamine reflect its indirect activation of the sympathetic nervous system. Ketamine causes an increase iorepinephrine by inhibiting reuptake at postganglionic sympathetic neurons. Sympathetic stimulation increases heart rate and systemic blood pressure. Ketamine should therefore be used with caution in patients with uncontrolled hypertension or in whom tachycardia should be avoided. However, ketamine may be chosen for induction of general anesthesia at 1 to 2 mg/kg IV when cardiovascular stimulatory effects are desired, as in emergent trauma surgery. Practitioners should note that ketamine is actually a direct myocardial depressant, an effect normally masked by the indirect sympathetic stimulation. In severely compromised patients, however, catecholamine stores may be exhausted and hypotension secondary to myocardial depression can become significant. Respiratory depression is not significant with ketamine, although apnea will occur with rapid bolus administration. Upper airway reflexes remain largely but not reliably intact; aspiration is still possible, especially as ketamine increases salivary secretions and postoperative nausea and vomiting. Ketamine does not cause histamine release and is a potent bronchodilator secondary to sympathetic activation as well as direct bronchial smooth muscle relaxation. In oral surgical practice a primary indication for ketamine is intramuscular injection for uncooperative adult patients, such as the mentally challenged or those with severe psychiatric illness, or for children who will not tolerate IV placement. The intramuscular dose for induction of general anesthesia is 3 to 7 mg/kg, whereas 2 to 3 mg/kg is usually sufficient to obtain adequate control for IV placement. A water-soluble benzodiazepine like midazolam is commonly added to reduce the possibility of uncomfortable dreaming associated with ketamine. An anticholinergic medication like glycopyrrolate is also given to reduce the production of salivary secretions secondary to ketamine. Glycopyrrolate may be preferred over atropine or scopolamine for its superior antisialagogue effects, less pronounced cardiac effects, and poor CNS penetration. The other main use in oral surgical practice is in an IV deep-sedation technique. Conscious sedation is first achieved with a benzodiazepine, followed by subanesthetic doses of 10 to 30 mg of ketamine until a state that is similar to deep sedation is achieved. Although ketamine is quite analgesic some surgeons also add an opioid in the baseline sedation. Alternatively, if a standard deep-sedation technique with methohexital has been applied (see “Methohexital,” above) and large doses of the barbiturate become necessary to achieve adequate sedation, or unwanted patient movement persists despite high methohexital doses, the addition of small boluses of ketamine can often enhance the quality of sedation. “Emergence delirium” can occur during awakening. The patient may experience visual and auditory hallucinations that can be perceived as either pleasant (euphoria) or unpleasant (dysphoria), lasting for up to several hours. Delirium occurrence is less common in children and with doses less than 2 mg/kg IV. It may be attenuated with prior or concurrent administration of benzodiazepines, which should be routine when intravenous sedation techniques are used.

Inhalation Anesthetics Inhalation anesthetics include nitrous oxide (N2O) as well as the potent volatile halogenated agents, such as halothane, isoflurane, sevoflurane, and desflurane. N2O alone is commonly used in dental offices for anxiolysis and mild sedation, but it is also used in combination with other medications to induce and maintain both sedation and general anesthesia. The halogenated agents are extremely potent and are used for induction and maintenance of general anesthesia. The pharmacokinetics of these anesthetic agents differ from those of intravenous medications. These drugs are inhaled and cross from the alveoli into the pulmonary vasculature, entering the general circulation. They are able to cross the blood-brain barrier and exert anesthetic effects within the brain. Except for halothane most of these agents are minimally metabolized and are subsequently excreted unchanged back into the alveoli. Once exhaled these gases are deposited into the anesthesia circuit and eventually scavenged. Plasma concentrations of the inhaled anesthetics are dependent on the concentration of the gas within the alveoli, solubility characteristics of the individual gases, and cardiac output.13,14 Cardiac output influences the rate of uptake from the alveoli. Main factors affecting alveolar gas concentration include the inspired concentration of gas, alveolar ventilation, and the total gas flow rate. Administering a higher concentration of gas will increase intra-alveolar concentration, whereas altering the total gas inflow or alveolarventilation (respiratory rate, tidal volume) will affect how quickly the concentration of gas within the alveoli changes. Each agent varies in its solubility in blood and other tissues such as the brain and fat, and these characteristics determine the ease with which the gas crosses into the different tissues. Of these, the blood:gas solubility coefficient (Table 5-1) is the most useful in describing the onset and offset of action of an anesthetic gas. The blood:gas solubility coefficient expresses the extent to which the anesthetic gas molecules from the alveolar spaces will dissolve into plasma before the plasma solution becomes saturated. Conceptually, a lower coefficient means that the gas is less soluble in blood and will saturate the plasma compartment quickly. Additional “overflow” molecules will then be free to move into other highly vascular tissues such as the brain, where the CNS anesthetic effect takes place. A lower blood:gas coefficient therefore translates into faster onset of action at the brain. Once the gas is discontinued and the alveolar and plasma concentrations decrease, the gas molecules move down their concentration gradient from the tissues back into the blood stream and then into the alveoli. Gases with lower blood:gas coefficients will likewise “offload” from the blood stream into alveoli more quickly and can translate into a faster offset of action. Unlike intravenous medications these inhaled drugs are not administered in doses of mg/kg. The equivalent of the effective dose (ED50) of inhaled anesthetic agent is the minimum alveolar concentration (MAC). The MAC value of any given agent is the inhaled concentration (volume %) of that agent required to prevent movement in 50% of patients to a surgical stimulus. MAC values for different agents are given in Table 5-1.MAC values provide a useful dosage guide for anesthetic gases. In adults a level of 1.3 MAC will prevent movement in 95% of patients, whereas 1.5 MAC (MAC-BAR) will block an adrenergic response in 95% of patients. Below 0.3 MAC (MAC-Awake), patient awareness is more likely. MAC values are additive; for example, if 0.5 MAC of N2O and 1.0 MAC of isoflurane are given simultaneously, the total MAC of anesthetic agent administered to the patient is 1.5 MAC. It should be noted that MAC values are general guidelines, and individual anesthetic requirements can be influenced by a variety of factors such as age or medical status. Neonates have the lowest MAC requirement, whereas children have the highest requirement. MAC requirements subsequently decrease in the elderly patient. MAC values are typically listed for adult (30- to 35-year-old) patients at 1 atm pressure and 20°C. The exact mechanism of action of inhaled anesthetic agents at the CNS is still controversial. Earlier theories have suggested that anesthetic molecules insert into and disrupt the lipid bilayer of neuronal cell membranes, thus interfering with the cellular function. More current theories suggest that anesthetic molecules may instead directly interact with cellular proteins, possibly with membrane ion channels or even specific receptors. Whereas N2O has mild or minimal sympathomimetic effects, all of the halogenated agents produce generalized cardiovascular depressant effects. The potent volatile agents block peripheral vasoconstriction thus lowering mean arterial blood pressure. At lower doses below 1 MAC the baroreceptor sympathetic reflex is activated, which leads to a compensatory increase in heart rate. The exception is halothane, which in addition to directly depressing myocardial contractility, blocks the baroreceptor reflex. This resulting decrease in cardiac output can lead to a precipitous drop in systemic blood pressure with higher doses of halothane. Halothane also has the highest association with cardiac dysrhythmias. Halothane induction commonly suppresses sinoatrial node activity, leading to the development of junctional rhythms. It also sensitizes the myocardium to catecholamine-relatedventricular dysrhythmias (Figure 5-9), particularly under conditions of hypercarbia. 15 Isoflurane, sevoflurane, and desflurane are not significantly associated with an increased incidence of epinephrineassociated dysrhythmias. Epinephrine contained in local anesthetic solutions should be limited to a maximum dose of 1 to 2 μg/kg during halothane anesthesia whereas up to 3 to 4.5 μg/kg is considered safe with the other three agents. Under halothane anesthesia, administration of 1.0 to 1.5 mg/kg cardiac lidocaine IV immediately prior to intubation reduces the incidence of ventricular dysrhythmias during this stimulating period when endogenous epinephrine release may occur. Hypoxia and hypercarbia also lower the threshold for dysrhythmias and should be especially avoided with halothane anesthesia. Treatment of the presenting dysrhythmia should be managed as required, including hyperventilation, deepening of anesthetic level and, if indicated, discontinuation of halothane with administration of an alternative anesthetic agent. At usual doses N2O does not appreciably affect respiration. However, the halogenated agents produce a characteristic “rapid and shallow” spontaneous breathing pattern. A decrease in tidal volume is accompanied by an increase in the frequency of breaths, but the faster respiratory rate does not fully compensate for the smaller tidal volumes. Therefore, minute ventilation is reduced and arterial CO2 levels will be elevated in patients spontaneously breathing while under general anesthesia with these agents. The halogenated agents also cause a dosedependent decrease in airway resistance and produce bronchodilation. Hypoxic pulmonary vasoconstriction is attenuated at 0.1 MAC for all volatile agents. Although hepatic blood flow decreases with these agents, hepatic damage, if any, resulting from hypoxia is usually subclinical and transient.Hepatotoxicity is more of a concern with halothane administration. Renal blood flow and urine output are reduced secondary to the decreased mean arterial pressure. The release of fluoride from the halogenated gases does not appear to cause clinically significant damage to renal tissues. With sevoflurane, fresh gas flows should be at least 2 L/min to minimize compound A accumulation in the CO2 absorber which can lead to very rare hepatic or renal damage. Malignant hyperthermia (MH) is another rare but very dangerous reaction triggered by the halogenated agents as well as SCh. N2O, nondepolarizing neuromuscular blockers, opioids, benzodiazepines, and other intravenous anesthetic agents do not trigger MH. Exposure to these medications causes an abnormal receptor in skeletal muscle cells to release excessive intracellular calcium, leading to uncontrolled muscle contractions. As a result CO2 production increases quickly and exhaled CO2 rises sharply. Initial signs include tachycardia and tachypnea, along with muscle stiffness. Metabolic acidosis and hyperkalemia develop next and cardiac arrest is a possibility. Increasing body temperature is a relatively late sign. The halogenated agent must be discontinued at once and 100% O2 given, preferably through a different circuit and machine. Dantrolene at 2.5 to 10 mg/kg IV must be given as soon as possible. Cooling measures including cooled IV fluids should be instituted. Emergency help must be obtained immediately and the patient will require medical management and monitoring for at least 24 hours following the episode. Reemergence of the reaction is common, requiring re-administration of dantrolene, and acute renal failure is the most common morbidity secondary to myoglobinemia. A mortality rate of 10% is associated with an acute MH episode, even with immediate proper management.

Nitrous Oxide N2O is commonly administered in dental offices for anxiolysis and mild sedation. It is a colorless and odorless gas, available in blue cylinders. In the dental setting it is commonly administered with a nasal hood and appropriate scavenger system. Concentration ratios of N2O:O2 range up to 70:30 on most N2O and anesthesia machines.High levels of N2O:O2 alone can produce sedation and significant analgesia. Unexpected respiratory depression or airway obstruction can occur when N2O is added to other sedative agents. N2O in O2 is likely the most commonly used sedative agent in dental offices and enjoys the unique advantage of not requiring an escort after completion of the procedure provided adequate recovery time has elapsed. The drug can be titrated, usually starting at 20% N2O and gradually increasing to 50% as needed. Doses above that level are associated with increased nausea and dysphoria, although the brief application of doses higher than 50% is useful during local anesthetic administration and other short stimulating surgical episodes. At the conclusion of N2O sedation, 3 to 5 minutes of 100% O2 is administered to prevent diffusion hypoxia; if room air O2 is given instead, the rapidly exiting N2O candilute the O2 concentration in the alveoli to hypoxic levels during recovery. With a low blood:gas solubility coefficient of 0.47, N2O has a very quick onset and recovery.While N2O lacks the potency of the halogenated agents at a MAC value of 105, it also lacks the respiratory and cardiovascular side effects. During general anesthesia it is often administered to an intubated patient in combination with other medications such as halogenated gases and opioids. Using this combination can reduce the dose required of each drug if given singly and will lessen the incidence of potential side effects. N2O is also inexpensive and can reduce the total cost of administered drugs. There are a few contraindications for the use of N2O. It can enter closed spaces faster thaitrogen can exit, leading to distention of the closed space.13 In oral surgical practice the implication of this property is to avoid N2O use in patients with current otitis media and sinus infections and with emphysema (blebs). Other contraindications of N2O use include current respiratory disease and a history of severe postoperative nausea. Several precautions should be exercised when using N2O. It has been implicated in producing sexual hallucinations in some patients, predominantly young women. An additional person such as an assistant should always be present when this gas is being administered. Patients with preexisting psychiatric disorders may experience exacerbated symptoms while undergoing N2O sedation. Because low levels of N2O in room air have been demonstrated to increase spontaneous abortion rates in pregnant anesthesia providers, proper scavenging is essential to minimize room air levels so that surgical personnel are not at increased risk. Frequent recreational use of N2O has been reported to lead to peripheral neuropathy and other deleterious effects. As with all anesthetic agents anesthesia providers must never use these drugs for personal use and should be alert to potential misuse by other providers of these drugs.

Potent Inhalation Agents The halogenated inhalation agents commonly in use today in the United States include halothane, isoflurane, sevoflurane, and desflurane. As seen in Figure 5-10, all are derivatives of ether except for halothane. Unlike the original anesthetic gas, diethyl ether, these agents are halogenated and nonflammable. The newer halogenated agents, sevoflurane and desflurane, are unique in that all of the side chain halogen atoms are fluorine. The gases are stored and released by gas-specific vaporizers that control the concentration (volume %) allowed into the anesthesia circuits and into the patient. They must also be scavenged effectively so that room air levels do not affect health care personnel.

Halothane Halothane has a sweet nonpungent odor that does not irritate the airway mucosa to the extent of isoflurane and desflurane, and is therefore useful for inhalation induction of general anesthesia. Halothane is very potent, with a MAC value at 0.75 but a relatively high blood:gas solubility of 2.54. Therefore, halothane will have a slow onset of inhalation induction unless high doses are used. Recovery from anesthesia will be slower than with other agents with lower solubility coefficients. Halothane is the oldest and most inexpensive of currently available potent gases but presents with the most deleterious side effects. As noted above, halothane is associated with significant cardiovascular changes and dysrhythmias. These should be monitored closely during induction and epinephrine administration, such as with local anesthesia, when dysrythmias are more commonly encountered. Unlike the other agents, at least 15% of the halothane molecules are metabolized by the liver, and hepatotoxicity is more significant with halothane, especially after repeated and prolonged administration. Halothane hepatitis is very rare but can result in hepatic necrosis and death. Of all the halogenated agents it also appears to be the most potent trigger for MH.

Isoflurane Isoflurane is more pungent than halothane and is not a good choice for inhalation induction. It has an intermediate potency (MAC 1.2) and blood:gas partition coefficient (1.46). This agent is a common choice for maintenance of anesthesia, as recovery time is in the intermediate range and shorter than halothane. Isoflurane is also much more cost-effective for longer periods of anesthesia compared to two other popular agents, sevofluraneand desflurane; its cost per bottle is significantly lower and the total amount used is less due to the lower MAC. Isoflurane may be associated with an increase in coronary steal phenomena, leading some practitioners to avoid using this anesthetic in patients with significant atherosclerotic cardiac disease. Otherwise, contraindications for using isoflurane are few.

Sevoflurane Sevoflurane is nonpungent and a common choice for inhalation induction. It has an intermediate potency (MAC 2.0), and at higher doses, induction will be rapid. Recovery from sevoflurane following a short anesthetic (< 1 h) is more rapid than either isoflurane or halothane due to the lower blood:gas solubility coefficient (0.69). For longer procedures, however, the advantage of faster recovery is offset by the much greater cost of sevoflurane compared to isoflurane. The recovery time is also not significantly improved compared to isoflurane, as both gases similarly redistribute into fat during longer anesthesia periods, and offset of these gases from fat storage is not different. All of the side chain halogen atoms in sevoflurane are fluorine, contributing to its low blood:gas solubility and recovery profile. Unlike earlier inhaled agents the small amount of inorganic fluorine released during sevoflurane use has not been associated with renal damage.16 Sevoflurane and CO2 absorbers (soda lime, barium lime) produce a degradation product called compound A, an olefin, which is nephrotoxic in rats but has not been associated with significant permanent renal damage in humans. Regardless, sevoflurane is not usually the agent of choice for patients with renal disease. Even in healthy patients many practitioners recommend limiting sevoflurane use to less than 2 hours and maintaining a total gas flow of at least 2 L/min, to reduce the production of compound A.

Desflurane Desflurane is extremely pungent and can be so irritating to nonanesthetized airways that it may precipitate coughing and laryngospasm. It is to be avoided for inhalation inductions. During initial administration of desflurane, tachycardia can also occur until deeper levels of anesthesia are realized. Desflurane is delivered from specially heated vaporizers as its vapor pressure is close to atmospheric pressure. It also possesses only fluorine substitutions which, like sevoflurane, confer a low blood:gas solubility. In fact, desflurane has the lowest blood:gas solubility coefficient (0.43) of any inhalation agent, lower than even N2O. This confers a quick onset and offset, and recovery can be very rapid following a short anesthetic with desflurane. Like sevoflurane, desflurane is more expensive than the other gases, and considering its higher MAC value (6.0),much more of the gas will be used per minute, resulting in a significantly higher cost if desflurane is used for a longer procedure.

Perioperative Analgesic Medications Opioid medications, which have been discussed previously, are the classic intraoperative and postoperative analgesic medications. In the operating room opioids are often given concurrently with other anesthetic agents in a balanced technique to supplement intraoperative analgesia. An opioid with a long duration of action like morphine or hydromorphone is commonly administered by the practitioner prior to the end of the procedure, in anticipation of postoperative pain. During the initial phase of postoperative care these medications may be given either by the nursing staff or patient, administered via computer-aided patient-controlled analgesia pumps. Another option is ketorolac tromethamine, currently the only available intravenous NSAID medication in the United States. This agent can provide effective analgesia for many dentoalveolar procedures at IV and IM doses of 30 to 60 mg or 0.5 to 1.0 mg/kg. Onset time is 10 to 15 minutes, with an analgesic duration of approximately 6 hours. Ketorolac 30 mg IM is the analgesic equivalent of 10 mg of parenteral morphine and does not produce opioid-related respiratory depression, nausea, or sedation.3 NSAID use does have several cautions, however. Because of possible NSAID-induced inhibition of platelet aggregation, the drug is normally administered after bleeding has been controlled, and should be avoided for surgeries associated with postoperative hemorrhage. Patients with bleeding-related disorders (gastrointestinal ulcers, inflammatory bowel disease, blood dyscrasias, liver failure, etc) should not be given ketorolac. Life-threatening bronchospasm can also occur with NSAIDs, particularly in those with a history of asthma or aspirin allergy. Because NSAIDs block prostaglandin production, patients who depend on renal prostaglandins for adequate renal function should be administered ketorolac cautiously. Patients with congestive heart failure, hypovolemia, or cirrhosis, and those taking angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, may require renal perfusion to maintain adequate renal perfusion, and NSAID administration can result in acute fluid retention. This drug is also associated with a higher cost than other analgesic medications. The most commonly used agents for postoperative pain control in oral surgery are likely the local anesthetics. Long-acting local anesthetics, like bupivacaine and etidocaine, provide several hours of analgesia for inferior alveolar nerve block anesthesia as well as soft tissue anesthesia in the maxilla. Lidocaine with epinephrine given intraoperatively can also provide adequate analgesic duration until postoperative oral NSAIDs or opioid/acetaminophen combinations can achieve reliable plasma levels for generally predictable postoperative pain control.

Neuromuscular-Blocking Medications Skeletal muscle relaxation is often required during surgery when patient movementinterferes with procedures involving anesthesia or surgery. For example, paralysis may be required to facilitate tracheal intubation, relax abdominal wall muscles for access during gastrointestinal surgery, or completely inhibit patient movement during ocular surgery.Whereas relaxation can be achieved with deeper anesthetic levels or appropriate peripheral neural blockade, neuromuscular-blocking agents are commonly used to provide the necessary amount and duration of relaxation. The potential of these drugs during anesthesia and surgery was not recognized until the middle of the twentieth century. Many of the current neuromuscularblocking agents used are derivatives of curare, one of the oldest paralyzing agents, used by ancient hunters to paralyze prey. All are competitive antagonists that bind to the nicotinic ACh receptors located at the postsynaptic membrane of the neuromuscular junction of skeletal muscle, thus interfering with proper contraction of the muscle. Neuromuscular-blocking agents can be classified as either depolarizing or nondepolarizing, and within the latter group can be divided based on structure, speed of onset, duration of action, and metabolism.

Succinylcholine SCh, two joined ACh molecules, was introduced for surgical muscle relaxation in the 1950s and is the only depolarizing agent used today. Once SCh binds to the ACh receptor, the postsynaptic membrane depolarizes, an action potential is generated, and the muscle contracts. Subsequent muscle contractions are delayed until SCh dissociates from the receptor and is metabolized by pseudocholinesterase. SCh has the fastest onset (30–60 s) and shortest duration (5–10 min) of the neuromuscular- blocking agents and is typically used to treat laryngospasm not relieved with positive pressure (20 to 40 mg, or 0.1 to 0.2 mg/kg). It is also given to facilitate tracheal intubation (1 to 1.5 mg/kg IV) or when emergent tracheal intubation is required to treat laryngospasm. It is no longer used to maintain intraoperative paralysis. SCh has several notable side effects. Tachycardia can result upon initial administration but sinus bradycardia may develop, especially with repeated administration. Widespread muscle contractions can result in postoperative myalgia, which can at times be prevented by prior administration of a small dose of a nondepolarizing muscle blocker. The contractions may increase intraocular and intragastric pressure and can also cause a transient elevation in plasma potassium levels by 0.5 mEq/L. Plasma potassium levels may rise even higher than 0.5 mEq/L in patients with certaieuromuscular disorders, stroke, spinal cord injury, or significant burn injury. SCh is therefore contraindicated in these patients, along with patients in renal failure. SCh is a trigger for MH (see section on malignant hyperthermia). Its use should also be avoided in patients with pseudocholinesterase abnormalities, as the recovery from this drug will be prolonged.

Nondepolarizing Agents All of the remaining neuromuscular blocking agents are nondepolarizing and do not initiate muscle contraction upon administration. The chemical structures of these drugs fall into two classes: benzylisoquinolines and aminosteroids.13 Characteristics of currently available nondepolarizing muscle relaxants are outlined in Table 5-2. Although it is not as rapid in onset as SCh, rocuronium has the fastest onset of the nondepolarizing agents, with paralysis occurring at approximately 1 minute with higher doses. It is often chosen for facilitating intubation when SCh cannot be used, particularly in an emergent situation. Onset time for most other agents is approximately 3 minutes. Drug selection for maintenance of muscle relaxation is often based upon the anticipated need for continued paralysis. Pancuronium has the longest duration, whereas mivacurium has the shortest. With any of these agents paralysis will last longer than that produced with SCh and controlled ventilation must be provided. Return of skeletal muscle function is usually monitored by a nerve stimulator, and the degree of paralysis is gauged by the number of twitches produced by stimulation of specific muscles, such as adductor pollicis and orbicularis orbis. Paralysis may need to be reversed by an anticholinesterase to ensure adequate recovery of airway and respiratory muscle function prior to extubation. Adverse effects may also affect the choice of neuromuscular-blocking agent and can be categorized by structure. The benzylisoquinoline compounds may trigger histamine release thus causing flushing and peripheral vasodilation. Aminosteroid structures may block vagal activity, causing a noticeable increase in heart rate. Histamine release may be undesirable in asthmatic patients. Increased heart rate can be problematic in patients with cardiovascular disease. Most of the nondepolarizing agents are metabolized by the liver and excreted by the kidney. Three of these are less dependent on hepatic or renal function. Mivacurium, like SCh, is metabolized by pseudocholinesterase and is affected by its deficiency. Atracurium and cisatracurium are removed by Hofmann elimination, whereby the drug spontaneously degrades at body pH and temperature.

Anticholinesterases Anticholinesterases, or anti-acetylcholinesterases, block the action of acetylcholinesterase, the enzyme that breaks down ACh. In anesthesia, anticholinesterases such as neostigmine, edrophonium, and pyridostigmine are used to reverse the effects of nondepolarizing muscle relaxants once partial muscle function has returned and paralysis is no longer necessary, usually at the conclusion of surgery. By increasingthe amount of ACh available at the neuromuscular junction, more of the neurotransmitter can bind to nicotinic ACh receptors, overcoming the competitive inhibition of the neuromuscular blocker and aiding in the return of muscle function. Increased ACh will also bind to muscarinic ACh receptors at the heart, lungs, salivary glands, and smooth muscle. This can lead to undesirable side effects including bradycardia, bronchospasm, abdominal cramping, and excessive salivation.17 To prevent these effects anticholinergic medications such as atropine or glycopyrrolate, which block muscarinic but not nicotinic ACh receptors, are given together with anticholinesterases. The anticholinesterase and anticholinergic medications are paired according to similar time of onset and duration. Glycopyrrolate is generally administered with neostigmine, whereas atropine is more commonly used with edrophonium. Doses of these agents are listed in Table 5-3.

Anticholinergic Medications ACh is a neurotransmitter that binds to two types of receptors. Nicotinic receptors are located at autonomic ganglia and the neuromuscular junctions of skeletal muscle. Muscarinic receptors are found at postganglionic sites of the parasympathetic nervous system at the heart, salivary glands, and smooth muscle. AnticholinerAnticholinergic medications specifically block muscarinic receptors but do not affect nicotinic receptors. Clinical uses in anesthesia of atropine, glycopyrrolate, and scopolamine are defined by their varied effect at the muscarinic receptor sites of different organs (Table 5-4). Atropine has the fastest onset of increasing heart rate by blocking vagal nerve receptors at the heart and is used to treat emergent bradycardia. Both atropine and glycopyrrolate are used to counteract bradycardia secondary to anticholinesterase use during reversal of muscle relaxation. All three anticholinergic medications decrease salivary secretions. Glycopyrrolate is a quaternary ammonium compound, which cannot cross the blood-brain barrier. Atropine and scopolamine, both tertiary amines, can cross the blood-brain barrier and cause sedation. Scopolamine is also used for management of nausea and prevention of motion sickness. Central anticholinergic syndrome is a concern with higher doses of centrally acting anticholinergic medications, manifesting as restlessness and confusion. It may be reversed by physostigmine, ananticholinesterase that can cross the blood-brain barrier.

Antiemetic Medications Postoperative nausea and vomiting (PONV) is one of the most common complaints following surgery. Certain groups of patients (female, obese, previous history of nausea and vomiting) appear to be more susceptible. Certain surgeries (ear, ocular, tonsillar, gynecologic) are likewise associated with increased PONV. Nausea and vomiting after oral surgery is not uncommon. Swallowed blood and secretions stimulate the gag reflex and are potent gastric irritants. Drugs used during sedation and anesthesia, such as N2O, opioids, and ketamine, may trigger nausea postoperatively. Other “nonchemical” triggers of nausea include smell, gastric distention, motion, and even stress. Chemical triggers in the bloodstream come into contact with an area in the medulla lacking an intact blood-brain barrier called the chemoreceptor trigger zone (CTZ).18 The CTZ (Figure 5-11) contains receptors for serotonin, histamine, muscarinic ACh, and dopamine. Opioids, toxins, and chemotherapy agents, as well as input from the middle ear, also stimulate this area. Stimulation of the CTZ will activate vomiting. Many antiemetic medications act by blocking these receptors at the CTZ.Medications that block the dopamine receptor include phenothiazines (eg, prochlorperazine), and butyrophenones (eg, droperidol). They effectively reduce PONV but are associated with adverse effects such as sedation and extrapyramidal reactions. 5-HT3 antagonists including ondansetron and dolasetron are expensive, but produce less sedation and other adverse effects than the dopamine antagonists. Antihistamines such as promethazine (which also possesses a phenothiazine structure) and diphenhydramine can cause significant sedation. Anticholinergic medications (eg, scopolamine) are rarely used for PONV, although the antihistamines promethazine and diphenhydramine also possess anticholinergic effects. Recently, dexamethasone has been shown to decrease the incidence of PONV when given shortly after induction of general anesthesia. A minimum adult dose of 8 mg IV appears to be required for this effect to be realized.19 Selection of anesthetic agents may help prevent PONV. Propofol appears to have antiemetic effects as well, particularly when administered for maintenance of anesthesia. Additional antiemetic treatment may be unnecessary following the use of propofol infusions, even in patients with a previous history of PONV. Avoidance of knowausea triggering agents such as N2O, ketamine, and longer-acting opioid medications may also reduce PONV.

Pharmacology of inhalation and intravenous sedation

INTRODUCTION A sound understanding of the principles of the phamacology of the individual sedation agents is essential to the safe practice of sedation. It is important from the outset to specify exactly what is meant by a sedation agent, as there can be considerable overlap between drugs which produce both sedation and general anaesthesia. A drug used for sedation should: 1. Depress the central nervous system (CNS) to an extent that allows operative treatment to be carried out with minimal physiological and psychological stress 2. Modify the patient’s state of mind such that communication is maintained and the patient will respond to spoken command 3. Carry a margin of safety wide enough to render the unintended loss of consciousness and loss of protective reflexes unlikely. Current sedation practice should only use agents and techniques which satisfy the above criteria. Additionally, the agents themselves should have a: 1. Simple method of administration 2. Rapid onset 3. Predictable action and duration 4. Rapid recovery 5. Rapid metabolism and excretion 6. Low incidence of side effects. Sedation agents are usually administered via the inhalation, intravenous or oral routes. The route of administration affects the timing of drug action, although ultimately all drugs arrive at their target cells in the brain via the bloodstream. Inhalation agents have the advantage of being readily absorbed by the lungs to provide a rapid onset of sedation, followed by rapid elimination and recovery. Intravenous agents 4 Pharmacology of inhalation and intravenous sedation  are predictably absorbed but once administered cannot be removed from the bloodstream. The therapeutic action of intravenous agents is terminated by re-distribution, metabolism and excretion. Oral sedatives have a less certain absorption due to variability of gastric emptying and they therefore produce unpredictable levels of sedation. This chapter will primarily address the pharmacology of sedation agents currently used in inhalation and intravenous techniques. The pharmacology of the oral sedatives not included in this chapter, will be covered in INHALATION SEDATION AGENTS Inhalation agents produce sedation by their action on various areas of the brain. They reach the brain by entering the lungs, crossing the alveolar membrane into the pulmonary veins, returning with the blood to the left side of the heart and then passing into the systemic arterial circulation. Thus the two main components of inhalation sedation are, the entry of the inspired gas into the lungs and distribution of the agent by the circulation to the tissues.

Basic pharmacology of inhalation sedatives Gas solubility and partial pressure During the induction of inhalation sedation, each breath of sedation agent raises the partial pressure of the gas in the alveoli. As the alveolar partial pressure rises, the gas is forced across the alveolar membrane into the bloodstream, where it is carried to the site of action in the brain. The gas passes down a pressure gradient from areas of high partial pressure to areas of low partial pressure (Figure 4.1). The level of sedation is proportional to the partial pressure of the agent at the site of action. After termination of gas administration the reverse process occurs. The partial pressure in the alveoli falls and the gas passes in the opposite direction out of the brain, into the circulation and then into the lungs. The rate at which a gas passes down its pressure gradient is determined by its solubility. The solubility of a sedation agent (i.e. the blood-gas partition coefficient) determines how quickly the partial pressure in the blood and, ultimately the brain, will rise or fall. The higher the partition coefficient, the greater the alveolar concentration of the agent needs to be to produce a rise in partial pressure in the blood and ultimately the tissues. For the purposes of sedation, a gas with a low partition coefficient is preferred. Small concentrations of gas will produce a rapid rise in partial pressure and a fast onset of sedation.

 

Figure 4.1 Movement of nitrous oxide gas down the partial pressure gradient during induction and recovery from inhalational sedation

Similarly, after cessation of gas administration there will be a rapid fall in partial pressure and a fast recovery. It is the inspired concentration of sedation agent which will determine the final level of sedation. The speed of induction of sedation is influenced by the rate of increase in gas concentration, as well as the minute volume and cardiac output of the patient. Any increase in minute volume, such as can be caused by asking the patient to take deep breaths, will increase the speed of onset of sedation. Conversely, an increase in cardiac output will reduce the speed of induction of sedation. With a high cardiac output there is an increased volume of blood passing through the lungs. The sedation agent present in the lungs will be taken up into this larger volume of blood and the actual concentration of gas transported per unit volume of blood will be lower. Thus, less sedation agent will reach the brain and there will be a slower onset of sedation. The speed of recovery after termination of gas administration is similarly affected by the same factors.

Potency of inhalation sedation agents All sedation agents will produce general anaesthesia if used in high enough doses. The key to modern sedation practice is to ensure that the agents used have a wide enough margin of safety to render the unintended loss of consciousness unlikely. This means that there should be a considerable difference in the dose required to produce a state of sedation and the dose needed to induce general anaesthesia. For inhalation anaesthetic agents the potency is expressed in terms of a minimum alveolar concentration (MAC). The MAC of an agent is the inspired concentration which will, at equilibrium, abolish the response to a standard surgical stimulus in 50% of patients. Although the inspired concentration is measured as a percentage, the MAC is usually expressed as a number. Equilibrium is achieved when the tissue concentration of the gas equals the inspired concentration. MAC is a useful index of potency and is used to compare different anaesthetic gases. Gases used for sedation should preferably have a moderate or high MAC and a low solubility. This will ensure a broad margin of safety between the incremental doses used to produce sedation and the final concentration required to induce anaesthesia. It would be very easy, using an agent with a small MAC for sedation, to accidentally overdose and anaesthetise a patient.

 Types of inhalation sedation agents Nitrous oxide Nitrous oxide is the only inhalation agent currently in routine use for conscious sedation in dental practice. It was discovered by Joseph Priestly in 1772 and first used as an anaesthetic agent for dental exodontia by Horace Wells in 1844. Nitrous oxide has been used as the basic constituent of gaseous anaesthesia for the subsequent 160 years, demonstrating its acceptability and usefulness. In the 1930s, nitrous oxide was used for sedation purposes in the Scandinavian countries, particularly Denmark. However, it was not until the 1960s, when Harold Langa pioneered the modern practice of relative analgesia that nitrous oxide came into widespread use as an inhalation sedation agent in dentistry.

Presentation: Nitrous oxide is a colourless, faintly sweetsmelling gas with a specific gravity of 1.53. It is stored in light blue cylinders in liquid form at a pressure of 750 pounds per square inch (43.5 bar). The gas is sold by weight and each cylinder is stamped with its empty weight. As the contents of the cylinder are liquid, the pressure inside, as measured by the pressure gauge on the inhalational sedation machine, will remain constant until nearly all the liquid has evaporated. The value shown on the gauge does not decrease in a linear fashion and tends to fall rapidly immediately before the cylinder becomes empty (Figure 4.2). Thus, the only reliable means of assessing the amount of nitrous oxide in a cylinder is to weigh the cylinder and compare the value with the weight of the empty cylinder. It can also be tapped with a metal instrument by those with musical ears; the pitch of the note falls as the gas is used. In addition, after prolonged use, the evaporation of the liquid nitrous oxide causes ice crystallisation on the cylinder at the level of the liquid within, thereby providing a third indication as to the nitrous oxide volume remaining in the cylinder.

 

Figure 4.2 The pressure in the nitrous oxide cylinder remains constant and tends to fall rapidly immediately before the cylinder becomes empty. 

Blood/gas solubility: Nitrous oxide has a low blood-gas partition coefficient of 0.47, so it is relatively insoluble and produces rapid induction of sedation. A further consequence of the poor solubility is that, when administration is discontinued, nitrous oxide dissolved in the blood is rapidly eliminated via the lungs. During the first few minutes of this elimination, large volumes of nitrous oxide pour out of the blood and into the lungs. This can actually displace oxygen from the alveoli causing a condition known as diffusion hypoxia. This occurs because the volume of nitrous oxide in the alveoli is so high that the patient effectively ‘breathes’ 100% nitrous oxide. For this reason the patient should receive 100% oxygen for a period of at least 2–3 minutes after the termination of nitrous oxide sedation. In reality, the risk of diffusion hypoxia is minimal due to the high level of oxygen delivered by dedicated inhalation sedation machines.

Potency: Nitrous oxide has a theoretical minimum alveolar concentration (MAC) of about 110. The high MAC means that nitrous oxide is a weak anaesthetic which is readily titrated to produce sedation. Because the MAC is over 80, it is theoretically impossible to produce anaesthesia using nitrous oxide alone, at normal atmospheric pressure, in a patient who is adequately oxygenated. However, caution should be exercised when using inhaled concentrations of nitrous oxide over 50%, because even at this relatively low percentage, some patients may enter a stage of light anaesthesia.

Sedation: Nitrous oxide is a good, but mild sedation agent producing both a depressant and euphoriant effect on the CNS.  It is also a fairly potent analgesic. A 50% inhaled concentration of nitrous oxide has been equated to that of parenteral morphine injection at a standard dose (10mg in a 70kg adult). It can be used to good effect to facilitate simple dentistry in patients who are averse to local analgesia and it decreases the pain of injections in those who require supplemental local anaesthesia. Nitrous oxide has few side effects in therapeutic use. It causes minor cardio-respiratory depression, and produces no useful amnesia.

Occupational hazards of nitrous oxide: The main problems associated with the use of nitrous oxide relate not to the patient but to the staff providing sedation, and the potential hazards of chronic exposure to nitrous oxide gas have recently been recognised. It has been shown that regular exposure of healthcare personnel to nitrous oxide can cause specific illnesses, the most common effects being haematological disorders and reproductive problems (Figure 4.3).

Figure 4.3 Hazards of chronic exposure to nitrous oxide.  It is well known that nitrous oxide causes the oxidation of vitamin B12 and affects the functioning of the enzyme methionine synthetase. This in turn impairs haematopoesis and can give rise to pernicious anaemia in staff exposed to nitrous oxide for prolonged periods (Figure 4.4). Dental clinicians who have abused nitrous oxide have been shown to have the debilitating neurological signs of pernicious anaemia. It has been shown that where unscavenged nitrous oxide has been used, there may be an increase in the rate of miscarriages in female dental surgeons, dental nurses and, perhaps surprisingly, in the wives of male dental surgeons who have been exposed to nitrous oxide gas. Dental nurses assisting with nitrous oxide sedation, where scavenging is not provided, are also twice as likely to suffer a miscarriage as other dental nurses.  

Figure 4.4 Biochemical effect of chronic nitrous oxide exposure

Chronic exposure to nitrous oxide has also been shown to be associated with decreased female and male fertility. Other chronic effects of nitrous oxide exposure are much rarer but are said to include hepatic and renal disease, malignancy and cytotoxicity. It should be noted that it is the cumulative effect of the gas which is the major concern and that the effects of the nitrous oxide very much depend on: 1. The pattern of exposure 2. Tissue sensitivity 3. Vitamin B12 intake and body stores 4. Extent to which methionine synthetase is deactivated. The subject of nitrous oxide pollution has become a worldwide health and safety issue, particularly as it is described as a ‘greenhouse gas’ and appears to contribute to the damage of the ozone layer. Regulations have therefore been put in place to define the maximum acceptable occupational exposure of personnel to nitrous oxide. In the UK, exposure should not average more than 100 ppm over an 8-hour period under the current health and safety regulations. Since the initial studies into the effects of chronic exposure in healthcare personnel working with nitrous oxide, the risks have been reduced considerably by the introduction of efficient scavenging and ventilation systems. If exhaled nitrous oxide is actively removed there will be less pollution of the atmosphere where healthcare personnel are working. Better training and understanding ofthe technique has also led to more efficient and effective provision of inhalation sedation.

Sevoflurane Sevoflurane is receiving much attention in the field of sedation research as a possible agent for use in dentistry. It is a sweet-smelling, non-flammable, volatile anaesthetic agent used for induction and maintenance of general anaesthesia. Sevoflurane is a potent agent with a MAC value of under 2, leaving it with a narrow margin of safety. Its use in sedatioecessitates the use of a specialised vapouriser to ensure levels are kept to a subanaesthetic level of 0.3%. Other volatile anaesthetic agents such as halothane and isoflurane have also been tested for use in inhalational sedation. Unfortunately they are even more potent drugs than sevoflurane, with low MAC values (the MAC of halothane is 0.76). This again reduces the margin of safety and makes the induction of general anaesthesia more likely. These drugs are not currently suitable for providing sedation in dental practice and do not comply with the basic definitions of safe sedation, however research into the use of sevoflurane is promising.

Oxygen Oxygen is not a sedation agent, however, inhalation sedation agents are always delivered in an oxygen-rich mixture containing a minimum of 30% oxygen by volume. Oxygen is stored as a gas in black cylinders with white shoulders, at an initial pressure of 2000 pounds per square inch (137 bar). Because it is a gas under pressure, the gauge on the inhalational sedation machine will give an accurate representation of the amount of oxygen contained in the cylinder. The oxygen supply used for inhalational sedation should be separate from, and additional to, the supply kept for use in the management of emergencies. Oxygen will sustain and enhance combustion and therefore no naked flames should be allowed in an area where oxygen is being used.

INTRAVENOUS SEDATION AGENTS Intravenous sedation agents are injected directly into the bloodstream where they are carried in the plasma to the tissues. The plasma level of the sedative attained during injection causes the agent to diffuse down its concentration gradient and across the lipid membranes to the site of action in the brain. The factors which influence the plasma level of the drug are Pharmacology of inhalation and intravenous sedation 65 therefore instrumental in determining the onset of action and recovery from the effect of the sedation agent.

BASIC PHARMACOLOGY OF INTRAVENOUS SEDATIVES Induction of sedation Upon intravenous injection the plasma level of a sedation drug will rise rapidly. The agent will pass through the venous system to the right side of the heart and then via the pulmonary circulation to the left side of the heart. Once in the arterial system it will reach the brain but it will only start to have its effect once diffusion across the lipid membranes has occurred. The effect of sedation will normally commence in one armbrain circulation time, approximately 35 seconds. The final plasma concentration of the sedation agent will depend on the total dose of drug, the rate of the injection, the cardiac output and the circulating blood volume. The greater the dose of drug injected and the faster the rate of injection then the higher the plasma concentration. In contrast, the higher the cardiac output and/or the blood volume, the lower the plasma concentration.

Recovery from sedation Recovery from sedation occurs by two processes. The first is the redistribution of the sedation agent from the CNS into the body fat. The initial peak plasma concentration forces the sedation agent into tissues which are well-perfused such as the brain, heart, liver and kidneys. With time, an increasing amount of the sedation agent is taken into adipose tissue. Although solubility in fat is lower than in well-perfused tissues, the high mass of the body fat and the lipid solubility of sedation agents does promote redistribution to the fat stores. Ultimately the plasma concentration of drug falls and the blood-brain concentration gradient is reversed. This forces the sedation agent out of the brain and back into the bloodstream. The second process involves the uptake and metabolism of the sedation agent in the liver and elimination via the kidneys. This results in the final reduction in plasma concentration leading to complete recovery of the patient. The relative importance of redistribution and elimination depends on the individual sedation agent but in general, redistribution is responsible for the initial recovery from sedation (the alpha half-life; T1/2α), followed by elimination of the remaining drug (the beta half-life; T1/2β). Virtually all 66 Clinical Sedation in Dentistry intravenous agents have two half-lives. Only those with very rapid metabolism do not demonstrate a bi-phasic curve. In considering different drugs, however, it is the elimination half-life which can be used to compare the pharmacokinetic effects of different sedation agents.

Types of intravenous sedation agents Benzodiazepines It was not until the 1960s that agents were developed specifically for conscious sedation. At this time a group of tranquilising drugs known as the benzodiazepines were discovered in Switzerland by researchers at Hoffman-La Roche. Since then the benzodiazepines have become the mainstay of modern sedation practice in the United Kingdom. The first benzodiazepine to come on the market was diazepam (Valium®). Since then, other drugs including midazolam and temazepam have been developed which are used in the field of dental sedation.

Pharmacokinetics: To understand the mechanism of action of the benzodiazepines, it is necessary to appreciate the normal passage of information through sensory neurones to the CNS. A system made up of ‘GABA’ (gamma-amino-butyric-acid) receptors is responsible for filtering or damping down sensory input to the brain. GABA is an inhibitory chemical which is released from sensory nerve endings as electrical nerve stimuli pass from neurone to neurone over synapses. Once released, GABA attaches itself to receptors on the cell membrane of the post-synaptic neurone. The post-synaptic membrane becomes more permeable to chloride ions which has the effect of stabilising the neurone and increasing the threshold for firing (Figure 4.5). During this refractory period no further electrical stimuli can be transmitted across the synapse. In this way the numbers of sensory messages which travel the whole distance of the neurones (from their origin to the areas of the brain where they are perceived) are reduced or ‘filtered’. For every stimulus to the senses (touch, taste, smell, hearing, sight), very many more electrical stimuli are initiated than are necessary for the subject to perceive the stimulus and react to it. Benzodiazepines act throughout the CNS via the GABA network. Specific benzodiazepine receptors are located close to GABA receptors oeuronal membranes within the brain and spinal cord. All benzodiazepines (which, like all sedatives, are CNS depressants) have a similar shape, with a ring structure (benzene ring) on the same position of the diazepine part of each molecule. It is this common core shape which enables them to attach to the benzodiazepine receptors.

Figure 4.5 Mechanism of action of gamma-aminobutyric acid (GABA).

The effect of having a benzodiazepine in place on a receptor, is to prolong the time it takes for re-polarisation after a neurone has been depolarised by an electrical impulse. This further reduces the number of stimuli reaching the higher centres and produces pharmacological sedation, anxiolysis, amnesia, muscle relaxation and anticonvulsant effects. Benzodiazepines act essentially by mimicking the normal physiological filter system of the body and they may do so positively or negatively. There is a range of benzodiazepines which vary from those having the desired effects (agonists), to those having the entirely opposite effect (inverse agonists). In the centre of the spectrum is a group of drugs which have an affinity for the benzodiazepine receptor but which are, to all intents and purposes, pharmacologically inactive (antagonists).

Clinical effects: The clinical effects of the agonist benzodiazepines include: • Induction of a state of conscious sedation with acute detachment for 20–30 minutes and a state of relaxation for a further hour or so • Production of anterograde amnesia (loss of memory in the period immediately following the introduction of the drug) • Muscle relaxation • Anticonvulsant action • Minimal cardiovascular and respiratory depression when intravenous benzodiazepines are titrated slowly to a defined end point of conscious sedation in healthy patients. (Titration refers to the process of adding small increments of a sedative whilst observing the clinical response until it is deemed adequate) Benzodiazepines do not produce any clinically useful analgesia, although the sedation itself may alter the patient’s response to pain.

Side effects: Although intravenous benzodiazepines are generally very safe sedation agents, they do have some disadvantages, including: • Respiratory depression • Cardiovascular depression • Over-sedation in older people and children • Tolerance • Sexual fantasy. The most significant side effect is respiratory depression. Some degree of respiratory depression occurs in all patients sedated with the benzodiazepines but this usually only becomes clinically significant in patients with impaired respiratory function or in those who have taken other CNS depressants or where the drug is administered too rapidly or in a bolus dose .

Pre-existing respiratory disease: A patient with pre-existing respiratory disease will already have a degree of respiratory compromise and will be especially at risk from the respiratory depressant effects of the benzodiazepines. Synergistic effect: There is a synergistic relationship between the benzodiazepines and certain other CNS depressants, such as the opiates or alcohol. In a synergistic relationship, the effect of two drugs is greater than the sum total of the individual drugs and this is particularly noticeable with the opiates, when required doses may be 25% or less than if a single drug had been administered. The risk, therefore, of overdose in combined drug techniques is significantly higher than when a single agent is used.

Inappropriate drug administration: Excessively rapid intravenous injection of the benzodiazepines can cause significant respiratory depression which may result in apnoea. This can be avoided by slow incremental injection of the drug. If apnoea does occur, then assisted ventilation will be required. It is also thought that the laryngeal reflexes may be momentarily obtunded immediately following injection of a benzodiazepine. Although this state is short-lived, the dental clinician should always ensure that the patient’s airway is well protected when performing dental treatment on sedated patients. Because of the risk of apnoea, it has been suggested by some authorities that supplemental oxygen be used in all patients. However, this is not universally practised and it is questionable as to whether it is really indicated in fit, young healthy patients. There is little doubt, however, that supplemental oxygen does result in the maintenance of better oxygen saturation and it should, therefore, be considered in cases where appropriate, particularly in older or medically compromised patients. Pharmacology of inhalation and intravenous sedation 69 The benzodiazepines also produce minor cardiovascular side effects in healthy patients. They cause a reduction in vascular resistance which results in a fall in blood pressure. This is compensated by an increase in heart rate, and the cardiac output and usually blood pressure are thus unaffected. Older patients are particularly susceptible to the effects of the benzodiazepines. It is relatively easy to overdose an older patient and cause significant respiratory depression. Intravenous benzodiazepines should be administered slowly and in very small increments to older people. The total dose required to produce sedation will be much smaller than in a younger adult of the equivalent weight. The use of intravenous benzodiazepines for children under the age of 16 years in a primary care setting should be considered carefully. Children may react more unpredictably to intravenous benzodiazepines and can easily become over-sedated. Occasionally they may show signs of disinhibition and become extremely distraught, a reaction more common in the teenage years. Extreme care needs to be undertaken with such patients, as the temptation to keep adding further increments can easily result in an unconscious patient. Treating children under intravenous benzodiazepine sedation requires that the dental clinician is appropriately trained in the use of this technique and is fully competent in the provision of paediatric basic life support. Patients who are already taking oral benzodiazepines for anxiolysis or insomnia may be tolerant to the effect of intravenous benzodiazepines. Those who have become dependant on long-term benzodiazepine therapy may also have their dependence reactivated by acute intravenous administration. There have also been reported incidents of sexual fantasy occurring under intravenous benzodiazepine sedation but this only seems to occur when higher than recommended doses of the drug are administered. Diazepam Diazepam was the first benzodiazepine to be used in intravenous sedation practice (see Figure 4.6). It is almost insoluble in water and so it is either dissolved in an organic solvent, propylene glycol (Valium®), or it is emulsified into a suspension in soya bean oil (Diazemuls®). The organic solvent formulation caused a high incidence of vein damage, ranging from pain to frank thrombophlebitis and even skin ulceration, so this preparation is no longer used. Diazemuls® is a non-irritant preparation which overcomes the problem of venous damage. Diazepam is metabolised in the liver and eliminated via the kidneys. It has a long elimination half-life (T1/2β) of 43 hours(+/−13 hours) although its distribution half-life (T1/2α) is in the region of 40 minutes. An active metabolite, n-desmethyldiazepam, is produced, which can cause rebound sedation up to 72 hours after the initial administration of diazepam. Diazemuls® is presented in a 2ml ampoule in a concentration of 5mg/ml for intravenous injection. It is a reliable hypnosedative which should be given slowly, titrating the dose against the response obtained. The standard dose lies in the range 0.1-0.2mg/kg. Unfortunately the long recovery period and possibility of rebound sedation mean that diazepam in any form, is not the ideal drug for sedation for short dental procedures and its use has largely been superseded by the more modern and more rapidly metabolised midazolam.

Midazolam Midazolam was introduced into clinical practice in 1983 although it had been synthesised several years previously (see Figure 4.7). It is currently the agent of choice for intravenous sedation in dentistry, however there are newer agents on the horizon. It is an imadazobenzodiazepine which is water soluble with a pH of less than 4.0 and which is a non-irritant to veins. Once injected into the bloodstream, at physiological pH, it becomes lipid soluble and is readily able to penetrate the blood-brain barrier. It has an elimination half-life of 1.9 hours (+/−0.9 hours) so that complete recovery is quicker than that with diazepam. Midazolam is more rapidly acting, at least 2.5 times as potent and has more predictable amnesic properties, than diazepam. It is rapidly metabolised in the liver but there is also some extra-hepatic metabolism in the bowel. Midazolam producesan active metabolite called alpha-hydroxymidazolam. This has a short half-life of 1.25 hours (+/−0.25 hours) which is less than that of the parent compound and thus does not produce true rebound sedation. It does, however, explain the clinically observable phenomenon of a slower initial recovery from midazolam sedation than would be expected, on the basis of the pharmacokinetics of the drug, without reference to its active metabolite. Midazolam is available in two formulations: a concentration of 5mg/ml in a 2ml ampoule, or a concentration of 2mg/ml in a 5ml ampoule. Both presentations contain the same quantity of midazolam but the 5ml ampoule presentation, being less concentrated, is easier to titrate and is more acceptable for use in dental practice. The dose of midazolam is titrated according to the patient’s response but most patients require a dose usually in the range of 0.07–0.1mg/kg.

Flumazenil (benzodiazepine antagonist) The discovery of the benzodiazepine antagonist, flumazenil, in 1978, was a major advance in the practice of intravenous sedation. It was the first drug to effectively and completely reverse the effects of almost all benzodiazepines. Flumazenil is a true benzodiazepine but it has virtually no intrinsic therapeutic activity (the administration of huge doses of flumazenil may result in very slight epileptiform activity). It shares the same basic chemical form as other benzodiazepines but it lacks the ring structure attached to the diazepine part of the molecule (Figure 4.8). It is this slight alteration in structure which prevents flumazenil from having any genuine therapeutic activity. Flumazenil has a greater affinity for the benzodiazepine receptor than virtually all the known active drugs and it is therefore an effective antagonist. It will reverse (at least on a temporary basis) the sedative, cardiovascular and respiratory depressant effects of both diazepam and midazolam – in fact the vast majority of all commercially available enzodiazepines. Flumazenil is presented in 5ml ampoules containing 500mcg/ml for intravenous injection. It is administered by giving 200mcg and then waiting for 1 minute. A further 100mcg is then given every minute until the patient appears fully recovered. In an acute emergency there is no reason why higher initial doses of up to 500mcg should not be given immediately as a bolus. Flumazenil is currently only recommended for use in emergency situations and not as a means of hastening recovery. If flumazenil were used for routine reversal, there is a theoretical risk that that the benzodiazepine sedation may recur once the effect of the flumazenil had worn off. This is because flumazenil has a shorter elimination half-life (53 minutes, +/−13 minutes) than the active benzodiazepines. For healthy patients this is a theoretical concept with little basis in clinical practice and the greatest objections to using flumazenil routinely are its cost and the rather sudden and unpleasant ‘wakening’ which it produces. In patients who use benzodiazpines on a long-term basis, it may be significantly more problematic. The characteristics of all three benzodiazepines considered can be seen in Table 4.1.

Other intravenous sedation agents Although the benzodiazepines are the mainstay of modern sedation practice, they do not fulfil all the requirements of theideal sedation drug. The main problem is the relatively long period of recovery that is required before a patient can be discharged home and return to normal daily activities. To date there is only one drug which appears to have serious potential as the sedation agent of the future. Propofol (2, 6-diisopropylphenol) is a potent intravenous hypnotic agent which is widely used for the induction and maintenance of anaesthesia and for sedation in the intensive care unit. Propofol is an oil at room temperature and insoluble in aqueous solution. Present formulations consist of 1% or 2% (w/v) propofol, 10% soya bean oil, 2.25% glycerol, and 1.2% egg phosphatide. It is presented as an aqueous white emulsion at a concentration of 10mg/ml in 20ml ampoules. It has the advantage of undergoing rapid elimination and recovery with an elimination half-life of 30–40 minutes. It has a distribution half-life of 2–4 minutes and duration of clinical effect is short because propofol is rapidly distributed into peripheral tissues, and its effects wear off considerably within half an hour of injection. This, together with its rapid effect (within minutes of injection) and the moderate amnesia it induces, makes it an ideal drug for intravenous sedation. Propofol (Diprivan®) appears to act by enhancing the GABA neurotransmitter system. For maintenance of general anaesthesia, propofol is administered as a continuous infusion. Following completion of the operative procedure, the infusion is stopped and the patient regains consciousness within a few minutes. Propofol may be administered in sub-anaesthetic doses either by a technique using a target-controlled infusion, a patientcontrolled target infusion or by intermittent bolus administration. The propofol target-controlled infusion (TCI) system consists of an infusion pump containing software simulating the best pharmacokinetic model for propofol (Figures 4.9 and 4.10). The patient’s age and weight are programmed into the software and the desired target blood propofol concentration is selected. On commencing the infusion, a precisely calculated bolus dose is delivered to generate the selected target blood propofol concentration, followed by a continuous propofol infusion calculated to maintain that concentration. The target concentration can be increased or decreased depending on the patient’s response. If a higher target concentration is selected, the pump will automatically deliver an additional bolus of propofol, followed by an increased infusion rate to maintain the increased target concentration. If a lower target concentration is selected, the pump will cease infusing propofol until it predicts that the blood propofol level has fallen to the new value, whereupon a lower infusion rate is delivered.

 

Figure 4.9 Infusion pump used for the delivery of propofol sedation.

Figure 4.10 Button used by patient to administer propofol.

Once treatment is complete, the infusion is switched off and the patient normally will be fully recovered and fit to be discharged home within 10–15 minutes. Target-controlled infusion techniques have been described for sedation for a variety of diagnostic and therapeutic procedures, including dental surgery. Clinical trials using propofol in differing ways for dental sedation have been promising. Incremental doses of propofol 76 Clinical Sedation in Dentistry are administered initially until a satisfactory level of sedation is achieved, usually at a total dose of around 0.5mg/kg. The desired level of sedation is maintained by delivering a continuous infusion of around 1.5mg/kg/hr. The infusion rate can be adjusted to vary the level of sedation as required. Clinical trials using propofol, administered through a patient-controlled infusion pump (similar to those used for post-operative analgesia), have also been very promising. In many ways, propofol approaches the requirements of an ideal sedation agent. However, it does have a number of disadvantages. The margin of safety between sedation and anaesthesia is far narrower than that of the benzodiazepines. Special equipment is also needed as the administration of propofol is by continuous infusion, requiring the use of a special infusion pump. Injection of propofol can also be painful and it should preferably be delivered into larger veins or following pre-injection with a local anaesthetic. The use of propofol for dental sedation is essentially still at the experimental stage and as such it can only be recommended for use in a hospital environment. Its continued development may see it eventually become more commonly used in sedation practice, since it has certainly gained wide acceptance in its use as an induction agent for general anaesthesia, but at the present time it cannot be recommended as a drug suitable for a safe operatorsedation technique.

PREMEDICATION Premedication refers to a drug treatment given to a patient prior to a surgical or invasive medical procedure, to obtain anxiolysis. These drugs are typically sedatives. However, premedications can also be used on occasion for other reasons, such as reducing salivary and bronchial secretions, lessening the response to painful stimuli and reducing the risk of vomiting, particularly prior to general anaesthesia. When considering the management of anxious patients under conscious sedation, premedication is used for producing pre-operative anxiolysis and is generally given by the oral route. Such premedication may be indicated in the following cases: • To reduce anxiety the night before the appointment • To reduce anxiety in the 1–2 hours period before treatment • For patients who are needle phobic, but require intravenous sedation for treatment.

Drugs used for pre-operative anxiolysis Several agents can be used for premedication but the benzodiazepines are the most commonly used. Diazepam Until recently, diazepam was the most commonly and widely used of all sedatives for premedication. It is available in tablets of 2mg, 5mg and 10mg and is fairly reliably absorbed from the gut, its effects becoming apparent after about 30 minutes. The correct dosage for each individual is not easy to calculate, since several factors influence its action. In particular, it does appear to bear a relationship to the age of a patient, much higher (relative) dosages being required in children and adolescents. As with intravenous administration, the converse is true in the 5 Premedication and oral sedation 78 Clinical Sedation in Dentistry elderly and infirm. As a rough guide, a dose between 0.1mg and 0.25mg/kg of body weight will produce adequate anxiolysis and should be given 1 hour before surgery and after a light snack. Administration of a single dose of oral diazepam, does give the operator the opportunity to form a baseline assessment, on which further action may be taken. Too high a dosage will cause sleep, whilst inadequate dosage will result in an alert and still anxious patient. Potential side effects include dizziness, increased pain awareness, ataxia (difficulty maintaining posture) and occasional respiratory depression. Prolonged post-operative drowsiness has also been reported. Caution is necessary in administering diazepam to patients with obvious psychoses, neuromuscular disorders, or respiratory, liver or kidney disease. Alcohol intake must be prohibited for a period of 24 hours before and after administration. Patients should not drive or operate machinery for 24 hours post-medication. As with intravenous diazepam, there is also some risk of some re-sedation after 2–3 days due to the production of active metabolites. Oral diazepam has been found particularly useful in the treatment of patients with cerebral palsy, coupling it with intravenous midazolam as the main sedation agent.

Temazepam Temazepam is now one of the most commonly used oral premedication agents. It was originally marketed as a hypnotic for inducing sleep but its shorter half-life (circa 4 hours) makes it ideal for use as an anxyolitic. An anxious, otherwise healthy adult of normal weight should be given a dose of 10mg and the effect assessed after 30 minutes. The dose may be doubled for severely anxious patients.

ORAL SEDATION Oral sedation, in contrast to oral premedication, is a technique where an oral drug is administered to produce a state of conscious sedation, where the patient will allow treatment to be carried out and differs from premedication, which is designed to produce mild anxiolysis only. Oral sedation offers a non-threatening approach to sedation as it does not require an injection to administer. It may be considered more versatile than inhalation sedation, since it does not require the same amount of patient co-operation in the initial stages. The ideal oral sedative would clearly fit the general criteria for sedation and would, therefore: Premedication and oral sedation 79 1. Alleviate fear and anxiety 2. Not suppress protective reflexes 3. Be easy to administer 4. Be quickly effective 5. Be free of side effects 6. Be predictable in duration and action 7. Be quickly metabolised and excreted 8. Not produce active metabolites 9. Have an active half-life of approximately 45–60 minutes. It is difficult to find any drug that fits all the above criteria, and some of the features mentioned above are much easier to control in inhalation and intravenous sedation than they are with oral sedation. This is because of the variation in predictability that inevitably occurs in relation to: 1. An individual’s degree of anxiety 2. The pattern of absorption of the drug 3. The rate of metabolism of the drug. This leads to considerable individual variation in response, which means that the outcome of many oral sedatives is less predictable than agents (even of the same chemical formulation) which are given parenterally. Oral sedation should only be considered where intravenous or inhalation sedation are not appropriate or have been unsuccessful.

Drugs used for oral sedation Temazepam As well as its use as a premedication agent, temazepam can be used to produce oral sedation in adults when used in higher doses such as 30–40mg. When used in this way, the patient’s vital signs must be monitored throughout the period of sedation and treatment. Midazolam Midazolam is a potentially useful drug for providing oral sedation for the dental patient, however it is not licensed for this route of administration and its use must be fully justified following consideration of other management options. It is available in the oral form as an elixir in certain countries. The injectable form can be prepared by local hospital pharmacy units for use orally. It can also be mixed with fruit cordial or syrup to make it more palatable for providing oral sedation. 80 Clinical Sedation in Dentistry Taken orally, midazolam has an onset time of approximately 20–30 minutes. Some of the drug will be absorbed in the gastrointestinal tract and liver (‘first pass metabolism’) and as a result of this only a proportion of the drug reaches the circulation. The effects will therefore vary on an individual basis depending on the degree of first pass metabolism which takes place. Similarly, recovery times are variable and it is essential to keep the patient in recovery until they fully meet the desired discharge criteria. It is advisable when using oral midazolam to place an intravenous cannula so that, in the case of an emergency, flumazenil or other emergency drugs can be easily administered. SUMMARY The techniques of oral premedication and oral sedation have been presented. It should be emphasised that they are two separate therapeutic techniques and require appropriate knowledge and training to be competent in their use.

INTRODUCTION Inhalation sedation is the safest form of sedation, due principally to the nature of nitrous oxide, which is almost universally used in this technique. The term ‘inhalation sedation’ describes the induction of a state of conscious sedation by administering sub-anaesthetic concentrations of gaseous anaesthetic agents. Its most common application is in children’s dentistry, where it has been used successfully for many decades, but its use in adult dentistry is increasing. The favourable pharmacological properties of nitrous oxide make it the agent of choice for most inhalation sedation techniques. Since its discovery in the eighteenth century, nitrous oxide has been the basic constituent of gaseous general anaesthesia, although it was not until the 1960s that it was more widely used in inhalation sedation. Harold Langa of the United States introduced the concept of ‘relative analgesia’, a specific type of inhalation sedation. This sedation uses variable mixtures of nitrous oxide and oxygen to induce a state of psycho-pharmacological sedation that was previously classified as stage 1 of anaesthesia. The staging of anaesthesia was described in 1937 when Arthur Guedel detailed the physical level, or depth, of patients’ anaesthesia with ether. Langa later developed the concept of planes of sedation within stage 1 of anaesthesia. Though the stages are still found in most standard anaesthesia textbooks, they are unrecognisable from Guedel’s, with the use of modern, rapidly effective agents. Relative analgesia has now become the standard technique for inhalation sedation in dentistry. Other methods of inhalation sedation do exist, such as the use of fixed concentrations of nitrous oxide and oxygen (Entonox®) but these are not commonly used in dentistry.

INHALATION SEDATION IN DENTISTRY The aims of inhalation sedation are to alleviate fear by producing anxiolysis, to reduce pain by inducing analgesia, and to improve patient co-operation so that dental treatment can be performed. Inhalation sedation embodies a triad of elements: 1. The administration of low to moderate titrated concentrations of nitrous oxide in oxygen to patients who remain conscious 2. The use of a specifically designed machine with a number of safety features, including the ability to deliver a minimum of 30% oxygen and a fail-safe device that cuts off the delivery of nitrous oxide if the oxygen supply fails 3. The use of semi-hypnotic suggestion to reassure and encourage the patient throughout the period of sedation and treatment. The success of inhalation sedation relies on a balanced combination of pharmacology and behaviour management. Nitrous oxide (N2O) will produce a degree of pharmacological sedation on its own but this is unpredictable and should be supplemented and reinforced with psychological reassurance. The pharmacological properties of nitrous oxide produce physiological changes which enhance the patient’s susceptibility to suggestion. The use of semi-hypnotic suggestion to positively reinforce feelings of relaxation and well-being, will increase the extent of the anxiolysis and co-operation. In contrast to intravenous sedation, which produces pharmacological sedation regardless of any element of suggestion, inhalation sedation induces a state of psycho-pharmacological sedation.

Planes of analgesia The clinical effects of sedation with nitrous oxide can be divided into three broad categories. These form part of the stages of anaesthesia (Figure 6.1). The first stage of anaesthesia, the analgesic stage, is subdivided into three ‘planes of analgesia’: Plane I Moderate sedation and analgesia, obtained at concentrations of 5–25% nitrous oxide. Plane II Dissociation sedation and analgesia, occurring at concentrations of 20–55% nitrous oxide. Plane III Total analgesia, obtained with concentrations of nitrous oxide usually well above 50%. In general terms, most clinically useful sedation is produced in Plane I and sometimes in Plane II, although some patients find the dissociation effects disorientating. It is these planes that are

Figure 6.1 Guedel’s stages of anaesthesia.

Stage 1 is subdivided into three planes of analgesia. encompassed by the definition of relative analgesia (inhalation sedation). Plane III is a transition zone between the state of conscious sedation and true general anaesthesia and thus it is termed total analgesia rather than relative analgesia. There is considerable overlap between the planes and a large variation in susceptibility of individual patients to the effects of nitrous oxide. Whilst one person may be adequately sedated with 10% nitrous oxide, another individual may require in excess of 50% nitrous oxide to achieve the same degree of sedation. Each plane of analgesia is accompanied by specific clinical signs:

Plane I (N2O concentrations of 5–25%) • relaxation and a general sense of well-being • paraesthesia, a tingling feeling in the fingers, toes and cheeks • a feeling of suffusing warmth is common • alert and readily responds to questioning • slight reduction in spontaneous movements • decreased reaction to painful stimuli • pulse, blood pressure, respiration rate, reflexes and pupil reactions will all be normal. As the nitrous oxide concentration is increased to the 20–55% range there will be a gradual transition from Plane I to Plane II.

Plane II (N2O concentrations of 20–55%) • marked relaxation and sleepiness • a feeling of detachment from the environment • senses will be altered • possible dreaming 84 Clinical Sedation in Dentistry • widespread paraesthesia, moderate analgesia • reduction in the gag reflex • delayed response to questioning • vital signs and the laryngeal reflexes should be unaffected. When the nitrous oxide concentration goes above 50%, there will normally be a transition into Plane III.

Plane III (N2O concentrations above 50%) • marked sleepiness and a ‘glazed’ appearance • complete analgesia • nausea and dizziness are common • patient may vomit • unresponsive to questioning • may lose consciousness and enter Stage 2 of general anaesthesia. If any of these signs occur, the nitrous oxide level should be reduced. There is usually a gradual transition between planes and not all patients show all of the clinical signs. However, the planes of analgesia are a useful guide to what to expect when sedating a patient with nitrous oxide. Specific signs such as nausea, dizziness and a glazed appearance provide a warning that the level of sedation is too high and the percentage of nitrous oxide should be reduced. However, there is considerable variation in individual response and it should be remembered that the success of the technique is probably more dependent on the operator’s ability to infuse hypnotic suggestion, than it is to the effect of nitrous oxide.

Indications and contraindications for inhalation sedation Indications • Management of dental anxiety (children and adults) • Management of needle phobia • Management of gag reflex • Management of medically compromised patients. Inhalation sedation is particularly useful for anxious children. Children must be able to understand the purpose and mechanisms (in appropriate terminology) of inhalation sedation, so the minimum age for treating children under inhalation sedation is approximately three years. This is usually the lowest age at which the child has an appropriate degree of understanding to enable sufficient co-operation for treatment. Principles and practice of inhalation sedation 85 Older children scheduled for orthodontic extractions may also benefit from inhalation sedation. Such children may not be particularly frightened of routine treatment but multiple extractions of permanent teeth or surgical procedures, such as the exposure of canines, can be somewhat traumatic. Sedation can help to make the procedure more acceptable and the time pass more quickly. Another key indication for inhalation sedation is the treatment of adults who have a general (as opposed to dental) phobia of needles or injections. Such individuals find it impossible to accept venepuncture and venous cannulation. They can benefit considerably from inhalation sedation, either as the sole form of sedation or in combination with intravenous sedation. In many cases, the level of sedation and analgesia achieved with inhalation sedation is sufficient for the patient to receive a local anaesthetic injection into the mucosa with minimal discomfort and simple operative dentistry can then be performed. However, for patients with a severe anxiety or phobia of dentistry, it may be necessary to supplement inhalation sedation with an intravenous technique. In these individuals the inhalation sedation is used to induce a level of sedation sufficient to enable venous cannulation. Once the cannula is successfully located, the intravenous sedative can be administered and the delivery of nitrous oxide terminated. Inhalation sedation is also used for a number of special categories of patients who are at risk from the respiratory depressive effects of intravenous agents. These include patients with sickle cell anaemia or asthma, who benefit from the guaranteed level of oxygenation (at least 30% and usually significantly more) used in inhalation sedation. For the few patients with a proven allergy to intravenous sedatives, the only alternative sedation technique may be inhalation sedation.

Contraindications Many of the contraindications to inhalation sedation are relative or temporary and include: • upper respiratory tract infections • large tonsils or adenoids • serious respiratory disease • mouth breathers • very young children • moderate to severe learning difficulties • severe psychiatric disorders • pregnant women • upper anterior apicectomy. 86 Clinical Sedation in Dentistry Very few of the indications and contraindications for inhalation sedation are absolute. In many cases it is necessary to carefully balance the risk of giving the patient sedation against the risk of general anaesthesia, which is often the only option for many anxious dental patients. Each patient should be individually assessed, although only those who fit the above selection criteria and who meet the general standards discussed in Chapter 3, should be treated in dental practice. There may be others, however, who can be referred for treatment under inhalation sedation in a hospital setting, where any complications can be dealt with more easily.

Advantages and disadvantages of inhalation sedation Advantages • Non-invasive technique with no requirement for venepuncture/ cannulation • Nitrous oxide is relatively inert so that there are no metabolic demands • The low solubility of nitrous oxide ensures a rapid onset and recovery • The level of sedation can easily be altered or discontinued • Little effect on the cardiovascular and respiratory systems • Some analgesia produced.

Disadvantages • The drug is administered continuously via a nose mask close to the operative site • The mask may be objectionable to the patient • The level of sedation relies heavily on psychological reassurance • The technique requires a certain level of compliance in terms of breathing through the nose • It is not suitable for very young children and patients with learning difficulties.

Patient preparation for inhalation sedation Assessment and treatment planning for patients for inhalation sedation should follow the format described earlier in Chapter 3. The main difference is that most patients presenting for inhalation sedation are children. Inhalation sedation should be seen as part of an overall behaviour management strategy and the aim of the assessment appointment should be to select those patients who need some form of extra support to help them through treatment. When assessing children for Principles and practice of inhalation sedation 87 inhalation sedation it is important to involve both the child and the parent. The type and extent of dental treatment needed should be taken into account when considering sedation. Although most routine operative dentistry can be performed under inhalation sedation, the nature of the treatment must be matched against the age of the patient and their predicted level of co-operation. One or two extractions in a four-year-old could, quite reasonably, be performed under inhalation sedation. However, if the same patient required the extraction of multiple grossly carious teeth it might be kinder to refer the patient for a short general anaesthetic. Similarly, a 13-year-old could willingly accept the extraction of four premolars under inhalation sedation, but if they required the exposure of a deeply buried canine, general anaesthesia may be preferable. Assessment of the medical status of a patient scheduled for inhalation sedation is identical to that described in Chapter 3. Particular attention should be paid to respiratory disease, as this can affect ventilation and gas exchange. The patient should be examined to check patency of the nasal air passages. A baseline pulse and respiration rate should be recorded but, for healthy patients, it is unnecessary to take the weight and blood pressure.

 Pre-operative instructions A full explanation of the procedure should be given to the patient–and the parent where the patient is a child. For children it is important to explain the procedure using simple terminology. Children should be told that they will be given some ‘happy air’ or ‘magic wind’ to breath, which will make them feel ‘warm’, ‘tingly’ and ‘sleepy’. Once they feel comfortable then their tooth will be ‘washed’ to make it ‘tingly’. It will then be ‘wiggled out’ or ‘mended’. The truth should always be told, although the use of careful semantics is extremely important. Children should be reassured that they will be able to talk to the dentist while they are sedated. Clearly the level of explanation should be individually pitched according to the age and level of understanding of the child. The parent, guardian or patient (if over the age of 16 years) should be asked to sign a written consent to both the sedation and dental treatment. Full spoken and written instructions about pre- and postoperative care should be given to the parent or to the patient (if over 16 years old) including the need for • A light meal 2 hours before the appointment • Children to be accompanied by a responsible adult • Transport home in car or taxi 88 Clinical Sedation in Dentistry • Children should not ride bikes, drive vehicles or operate machinery for the rest of the day • Children should be supervised by an adult for the rest of the day. Adults who are undergoing inhalation sedation, as the sole method of sedation, do not need to be accompanied. Once they are deemed fit for discharge, adults can go home alone, although it is inadvisable for them to drive.

Equipment for inhalation sedation Machines have been designed specifically for providing inhalation sedation in the dental surgery. They may be either free-standing units or piped gas units. Various makes are available in the UK including the Quantiflex MDM®, Digital MDM Mixer® (Electronic), and Porter MXR Flowmeters. They allow a variable percentage of nitrous oxide and oxygen to be delivered to the patient via a nose mask. The gas flow is continuous but the rate can be individually adjusted to match the patient’s minute volume.

Free-standing units Free-standing units carry their own gas supply: two cylinders of nitrous oxide and two cylinders of oxygen (Figure 6.2). One cylinder of each gas is in active use and the second cylinder is a reserve supply which must always be kept full and should be labelled accordingly. The cylinders are attached to the machine with a specific pin-index connection which prevents attachment of the wrong gas cylinders. Gas leaving the cylinders goes through a pressure-reducing valve before passing into a flow control head.

Piped gas unit Piped units consist of a pipeline system which supplies the nitrous oxide and oxygen from remote cylinders held in appropriate storage units (Figure 6.3).

Sedation unit head Both free-standing and piped systems house the same head units, depending on the manufacturer (Figure 6.4). The flow rate of each gas can be visualised in two flow meters on the control head, each calibrated in one litre increments up to 10 litres per minute. The nitrous oxide and oxygen are mixed in the flow control head. A flow control knob regulates the rate at which the gas mixture is delivered to the patient, and mixture

Figure 6.2 Free-standing inhalation sedation machine.

Figure 6.3 Piped inhalation sedation system.  

Figure 6.4 Quantiflex MDM®, flow control head, showing nitrous oxide and oxygen flow meters, mixture control dial, flow control knob and oxygen flush button. control dials determine the relative percentage of nitrous oxide and oxygen being delivered to the patient. On the Quantiflex MDM head the mixture control dial actually indicates the percentage of oxygen being administered and is marked in 10% increments, from 100% down to 30% (the minimum level). As the oxygen concentration is changed, the balance of the gas mixture is automatically made to 100% with nitrous oxide. On the Porter system there are separate control dials for nitrous oxide and oxygen. The control head also contains an air entrainment valve which opens automatically to let air in if there is any negative pressure in the breathing circuit. So if the gas flow rate is inadvertently set too low for a particular patient, the air entrainment valve will open, so that the patient can breathe room air in addition to the delivered gas volume.

Reservoir bag After leaving the flow control head the gas mixture enters a reservoir bag, which should be latex free (Figure 6.5). The reservoir bag has three main purposes: • It allows the flow rate to be accurately adjusted to match the patient’s minute volume. If the bag empties whilst the patient breathes, then the flow rate is set too low for that patient’s minute volume.

Figure 6.5 The reservoir bag is situated just below the flow control head. 

In contrast, if the bag is continuously over-inflated, then the flow rate is set too high. Ideally the reservoir bag should stay about three-quarters full, deflating slightly as the patient inspires and refilling as the patient expires. • As an adjunct to clinical monitoring. Regular observation of movement of the bag during treatment allows the respiration rate and depth to be monitored. • For manual positive pressure ventilation in the event of an emergency. This can only be effective if the valves on the mask and in the breathing system are first closed.

Gas delivery system The gas mixture is administered to the patient via a gas delivery hose attached to the input port of a suitable nasal mask. There are various sizes of rubber nose masks available and it is important to select one which provides the best seal with the patient’s face (Figure 6.6). A poorly fitting mask will allow gas to escape, which decreases the efficiency of the sedation and leads to pollution of the dental surgery.

Figure 6.6 Inhalation sedation nose mask, showing the inner and outer units. The patient inhales fresh gas from the mask and then exhales waste gas back into the mask. Exhaled gas passes through the output port in the mask to a scavenging hose. A one-way valve in the scavenging hose or mask system prevents waste gas from being re-inhaled. The exhaled gas is actively removed by a customised scavenging system. Safety features of inhalation sedation equipment:

1. Minimum oxygen delivery: The machine is constructed so that the minimum oxygen delivery is 30% of total gas volume, regardless of the total volume of gases flowing. This will ensure the patient always receives a gas mixture with a higher percentage of oxygen than is present iormal room air (>21%), virtually eliminating the risk of inducing full anaesthesia.

2. Automatic gas cut-out : An automatic cut-out of all gas delivery occurs if the oxygen supply fails or if the oxygen delivery falls below 30%. This would only occur if the oxygen cylinder ran out of gas or if there was blockage or leakage in the high pressure system. This feature also ensures that 100% nitrous oxide caever be delivered to the patient.

3. Colour coding : All components associated with nitrous oxide are coloured blue, and oxygen white. This includes the flow-meter gauge, the tubing from the cylinder and/or the gas outlet to the pressure-reducing valve.

4. Pin index system: On the free-standing unit this system ensures that oxygen and nitrous oxide cylinders cannot be interchanged. On the piped unit the sizes of the oxygen and nitrous oxide wall outlets differ.

5. Gas pressure dials: The pressure dials enable the operator to ensure sufficient gas supplies are available before and during treatment. Figure 6.6 Inhalation sedatioose mask, showing the inner and outer units. Principles and practice of inhalation sedation 93 6.

Audible alarm: An alarm should be audible to indicate when oxygen levels are falling. 7. Scavenging : Active scavenging units must be available to reduce pollution of the surgery with nitrous oxide.

Equipment checks The inhalation sedation machine and associated apparatus should always be thoroughly checked before use:

Gas levels: For the free-standing unit, each oxygen cylinder must be separately switched on and the pressure dial checked. One cylinder at least should be completely full and any cylinders showing low readings should be changed. The flow rate should be turned on to maximum and the dial re-checked to ensure that there is no decrease in pressure. If such a decrease occurs, it would indicate that either the quantity of gas in the cylinder is low or there is an obstruction in the high pressure part of the system. The full cylinder should then be switched off and labelled as full. Cylinders of nitrous oxide need to be weighed to confirm the quantity of gas. Nitrous oxide is stored as a liquid under pressure and the pressure dial will not accurately indicate the amount of liquid in the cylinder. The ability of the cylinders to deliver a sufficient flow of gas should also be tested. It is more practical when the unit is first set up to ensure the full and in-use labels are appropriately placed and these are always checked when cylinders are replaced.

Leaks in system: A check should be made for leaks in the system by occluding the nose mask with one hand, allowing the reservoir bag to fill up and then squeezing it hard. The bag should not deflate unless gas is forced through the nose mask past the occluding hand. Any other deflation of the bag indicates a leakage.

Automatic gas cut-out: For the free-standing unit the effectiveness of the safety cut-out should be tested by switching on both the oxygen and nitrous oxide, setting the mixture control dial to 50% oxygen/50% nitrous oxide and the flow rate to 8 litres/minute. When the oxygen cylinder is turned off, the nitrous oxide should automatically cut-out within a few seconds. For the piped system, to cut off the oxygen supply, the wall outlet supply should be disconnected.

Oxygen flush button: The oxygen flush button should be tested to ensure a flow of gas is produced when it is activated. Gas tubing and one-way valves: The gas tubing should be inspected for tears or perishing and the one-way valve in the expiratory limb or mask of the breathing system should be in place. Gas supply activated: For the free-standing unit the correct cylinders should be switched on and their valves opened fully. 94 Clinical Sedation in Dentistry For the piped system ensure the gas hosing is connected to the wall outlets.

Inhalation sedation technique Pre-operative checks Before escorting the patient to the surgery, a checklist (Figure 6.7) should be completed and signed and should include: • Patient’s name and date of birth • Date of procedure • Operating dentist and assisting dental nurse • Equipment present and checked including • Dental equipment • Sedation equipment • Emergency equipment • Patient checks • Patient knows what is planned • Consent obtained • Medical history up to date • Patient has not fasted for longer than 2 hours • No alcohol has been consumed in the previous 24 hours • Escort available • Transport home available.

Patient management The patient should then be brought into the surgery by the dental nurse and settled in the dental chair. The procedure for inhalation sedation is explained and the patient is shown the nasal mask (Figure 6.8). The patient is encouraged to try it on so that an appropriate size can be selected. It is important to tell the patient about the positive feelings they will have during sedation. They should be reassured that they will be able to talk to the dentist during treatment. It is better to recline the patient into a supine position before starting the sedation, as this makes the technique easier and minimises the risk of fainting. Once the patient is comfortable, 100% oxygen is allowed to flow through the system at approximately 4 litres/minute for children and 6 litres/minute for adults. The patient is then asked to place the nose mask to allow the patient to feel in control and part of the process. The clinician then ensures the mask fits well to avoid gas leaks (Figure 6.9). The patient is asked to try and keep his/her mouth closed and to breathe slowly and regularly. Constant reassurance should be given. By observing the movement

of the reservoir  

bag and asking patients if they feel comfortable, the flow rate should be adjusted until a comfortable minute volume is achieved. The administration of nitrous oxide can then be slowly introduced. Ten percent nitrous oxide is added by turning the mixture control dial to 90% oxygen. Patients should be told that dizziness or feeling lightheaded is normal, as is a warm tingling in the feet and hands. They may also start to feel a little Figure 6.8 The nose mask is shown to the patient and the procedure explained. Figure 6.9 The nose mask is comfortably positioned on the patient’s nose. It is important to check for a good seal around the mask to prevent leakage. Principles and practice of inhalation sedation 97 detached from their surroundings and experience changes in hearing and vision. At this stage it is extremely important to reassure patients by continuous conversation and encouragement, stressing that the feelings will be positive and pleasant. The flow is maintained for one full minute and then the concentration of nitrous oxide is increased by a further 10%, to 20% (80% oxygen) for a full minute. Thereafter the level of nitrous oxide can be increased in 5% or 10% increments to 30% (70% oxygen), the dose being carefully titrated according to the patient’s response. If further sedation is required, it is essential that the nitrous oxide is increased by 5% increments until the end point is reached. Throughout the titration period it is mandatory to use hypnotic suggestion in the form of story telling or positive affirmation to distract and relax the patient. The operator should speak in low volumes with a monotone voice. An adequate level of sedation is achieved when there is general relaxation, the patient is less fidgety and less talkative, there is tingling or paraesthesia of the fingers, toes and possibly the lips and a slowed response to questioning is noted. When these signs are evident the patient should be asked if they would be happy to start treatment. A positive response is a good indication that the end point has been achieved. The average concentration of nitrous oxide that is used has been reported at 30%, however concentrations between 20% and 40%, commonly allow for a state of detached sedation and analgesia without any loss of consciousness or danger of obtunded laryngeal reflexes. If after a period of relaxation patients become restless and apprehensive, or if they start to complain of nausea or dizziness, this is usually an indication that the level of nitrous oxide is too high and the patient is becoming over-sedated. The percentage of nitrous oxide should be reduced in 5% stages, the patient reassured and a more appropriate level of sedation maintained until the operative procedure is complete. If at any time the patient becomes glazed and unresponsive to questioning, he or she is probably entering the early stages of anaesthesia and the immediate response should be to reduce the nitrous oxide level and provide 100% oxygen. Once an appropriate level of sedation has been achieved local anaesthesia can be administered. The analgesic effect of nitrous oxide can make local anaesthetic injections less uncomfortable, but it is still good practice to also use a topical anaesthetic. Administration of nitrous oxide and oxygen should continue throughout the operative period and treatment should be accompanied by ongoing reassurance and encouragement. The degree of sedation may fall slightly during treatment as 98 Clinical Sedation in Dentistry there may be a degree of mouth breathing, effectively diluting the gas mixture. This can be rectified by encouraging the patient to breathe through his/her nose or by ceasing dental treatment temporarily and asking the patient to close the mouth and breathe nasally for a few minutes. Oo account should a dental prop ever be used to keep the patient’s mouth open during routine treatment. If a patient cannot maintain an open mouth, it is a sign that they are too deeply sedated. Monitoring It is essential to monitor the clinical status of the patient throughout the period of nitrous oxide sedation. Clinical monitoring of respiration rate and depth, pulse, colour, level of sedation and responsiveness are mandatory. However, in a healthy patient, it is not necessary to supplement clinical observation with electro-mechanical monitoring. Pulse oximetry and blood pressure measurement during relative analgesia are only indicated in the care of medically compromised patients, especially those with cardiac insufficiency. It is useful to have them available, however, in case of complications. Recovery When dental treatment is complete, the nitrous oxide flow is stopped and 100% oxygen is administered for approximately two to three minutes until the patient feels that the sedation has worn off. The aim of this is primarily to prevent ‘diffusion hypoxia’, a condition which results from the rapid outflow of nitrous oxide across the alveolar membrane when the incoming gas flow is stopped. This can dilute the percentage of alveolar oxygen available for uptake by up to 50%, although the risk of severe, life-threatening diffusion hypoxia is very low. The administration of 100% oxygen counteracts the potential desaturation caused by diffusion hypoxia. Finally, the patient is asked to remove the face-mask and is slowly brought back to the upright position. Discharge After a period of about 10–15 minutes the patient is usually fit to be discharged. The dental clinician should check that the patient is coherent, standing steady and can walk unaided. Children should be discharged into the care of an adult, with written post-operative instructions (see Figure 6.10). Adult patients can be allowed home unaccompanied once the dental clinician has confirmed their fitness to be discharged. Sedation records The inhalation sedation procedure carried out must be fully documented in the patient’s records and should include details of the percentage of oxygen and nitrous oxide delivered, the flow rate of the gases, the level of patient co-operation and the fact that 100% oxygen was administered prior to discharge. A record sheet detailing the required information is illustrated in Figure 6.11. Safety and complications of inhalation sedation Inhalation sedation with nitrous oxide and oxygen has an excellent safety record. To date there have beeo recorded cases of significant morbidity or mortality occurring from this form of sedation in the United Kingdom. Provided that the dental clinician and assisting dental nurse are adequately trained, patients are carefully selected and the correct equipment with specific safety features is used, then inhalation sedation is a very safe and effective technique. The principal complications associated with inhalation sedation can be divided into acute and chronic effects. Acute effects Acute effects are associated with the patient and include: • Over-sedation • Diffusion hypoxia• Undue hypersensitivity to nitrous oxide • Medical emergencies (see Chapter 8). Chronic effects Chronic effects are associated with chronic exposure of dental personnel to nitrous oxide and have been considered in Chapter 4. Available data do not support the notion that exposure to trace amounts of nitrous oxide is associated with biochemical changes. Although no cause and effect relationship has been firmly established, exposure to the gas should be minimised. Reducing nitrous oxide pollution: To keep nitrous oxide pollution to a minimum in the dental surgery there are a number of recommendations to follow: • Active scavenging – Active gas scavenging is a statutory requirement during the provision of inhalation sedation with nitrous oxide in the UK. The recognised definition of an active dental scavenging breathing system is an air flow rate of 45 litres/min at the nasal hood, which allows the removal of waste gas by the application of low power suction to the expiratory limb of the breathing circuit. • Passive scavenging – Further ways to reduce trace levels of nitrous oxide include opening a window or door and using floor-level active fan ventilation to the exterior of the building. • Appropriate technique – Appropriate patient selection, good seal of nasal mask, minimise patient talking during treatment. There is a legal requirement for dental surgeons to comply with health and safety regulations. All steps should be taken to minimise unnecessary staff exposure to nitrous oxide. Pregnant women and those trying to conceive should not be allowed to work in a surgery where nitrous oxide is being used. It is imperative that a clinic protocol is written and adhered to concerning the issue of safe usage oitrous oxide/oxygen inhalation sedation. Despite all the precautions required and the skill needed in using inhalation sedation, it is a technique which is tried and tested and one which most patients find helpful in managing mild anxiety. Its use is likely to remain more popular in children but, as with oral sedatives, relative analgesia offers most patients a non-threatening approach to sedation.  Principles and practice of intravenous sedation

INTRODUCTION Intravenous sedation is the technique of choice for most adult dental patients requiring conscious sedation. The administration of sedation agents via the intravenous (IV) route normally produces a predictable and reliable pharmacological effect. Intravenous sedation is more potent and quicker-acting than inhalation or oral sedation and is particularly effective for very anxious or phobic dental patients and for difficult surgical procedures. It produces true pharmacological sedation rather than the psycho-pharmacological sedation that is achieved with inhalation techniques. The practice of IV sedation is technique-sensitive; it requires the ability to perform IV cannulation which, even for the experienced dental sedationist, can be a difficult technique to master. The dental clinician also has to be able to determine an appropriate end point for sedation and drug administration. The level of sedatioeeds to be sufficient to enable the patient to accept operative dentistry, but not so great as to present the risk of over-sedation. The aim of this chapter is to provide the theoretical basis from which sound clinical principles and skilled practical techniques can be developed, to ensure the safe practice of IV midazolam sedation. The material can only provide a didactic background to good practice. It is essential that supervised hands-on training and competency is achieved before applying these clinical techniques to patients. 7 Principles and practice of intravenous sedation 104 Clinical Sedation in Dentistry

INTRAVENOUS SEDATION AGENTS Indications and contraindications for intravenous sedation Indications • Suitable for most adult dental patients • Counteracts moderate to severe dental anxiety • Traumatic surgical procedures • Gag reflex and swallow reflex are present • Mild medical conditions which may be aggravated by the stress of dental treatment, e.g. mild hypertension or asthma • Mild intellectual or physical disability, e.g. mild learning disability, cerebral palsy. Intravenous sedation has an important role in the management of patients with severe systemic disease or moderate to severe disability, especially if it avoids the need for general anaesthesia. However, these patients do present a significant risk and IV sedation should only be undertaken in a specialist hospital environment. Contraindications • History of allergy to benzodiazepines • Impaired renal or hepatic systems • Pregnancy and breast feeding • Severe psychiatric disease • Drug dependency.

Other considerations For people with severe needle phobia who are unable to accept any type of injection, inhalation or oral sedation may be an acceptable alternative. For these patients it is sometimes necessary to combine two techniques. Inhalation sedation (or even hypnosis) may be employed initially to relax the patient enough to allow venous cannulation; once the cannula has been inserted, the IV sedative can be administered and the inhalation element of the sedation switched off. The use of IV techniques is also, to some extent, limited in patients with poor veins. This includes patients with excessive sub-cutaneous fat, whose veins are not visible, and the elderly who frequently have friable veins which are prone to damage during cannulation. The use of IV sedation in children (under 16 years of age) should be approached with caution. Not only do children Principles and practice of intravenous sedation 105 dislike needles but IV sedation agents can have an unpredictable effect. Children can lose their controlling inhibitions and become uncooperative so that, in the event of a complication, their condition can deteriorate very rapidly. Even slight over-sedation can result in significant respiratory depression and airway obstruction. Intravenous sedation in those under the age of 16 years should be undertaken only in very special circumstances and only by those appropriately trained and experienced in paediatric sedation.

Drug choice for intravenous sedation Intravenous sedation agents should not only have the ability to depress the central nervous system to produce a state of conscious sedation, but they should also have a margin of safety wide enough to render the unintended loss of consciousness unlikely. Modern IV sedation techniques depend almost exclusively on the benzodiazepines. Both midazolam and diazepam are suitable IV sedatives, although the pharmacokinetics of midazolam make this the preferred choice for dental sedation and the recommended drug of choice in the UK. Midazolam is presented in two concentrations: 2mg/ml in a 5ml ampoule and 5mg/ml in a 2ml ampoule. Although both presentations contain the same amount of midazolam, the 2mg/ml (5ml vials) formulation is less concentrated and easier to titrate because of the smaller volume required for the equivalent dose. New IV agents are currently undergoing clinical trials to evaluate their application to dental sedation. The most promising new agent is propofol, a short-acting anaesthetic drug administered via a continuous infusion or using patientcontrolled sedation techniques. It has an extremely rapid recovery period which is advantageous for ambulatory patients. It is not yet licensed for use in dental sedation in the UK, but it has been the subject of some extensive trials and its properties do offer several potential benefits, particularly with reference to patient-controlled sedation.

Clinical effects of sedation with intravenous midazolam • Conscious sedation with acute detachment (lack of awareness of one’s surroundings) for a period of 20–30 minutes after administration, followed by a period of relaxation which may last for a further hour or more • Anterograde amnesia, i.e. loss of memory following administration of the drug 106 Clinical Sedation in Dentistry • Muscle relaxation (useful for those with cerebral palsy) • Anticonvulsant action • Slight cardiovascular and respiratory depression.

Advantages and disadvantages Advantages • Reasonably wide margin of safety between the end point of sedation and loss of consciousness or anaesthesia (although it is easy to induce sleep with moderate over-dosage) • A satisfactory level of sedation is attained pharmacologically rather than psychologically • Recovery occurs within a reasonable period and the patient can usually be discharged home less than two hours following completion of treatment. Disadvantages • May alter a patient’s perception and response to pain but it does not produce any clinically useful analgesia • For a short period after injection the laryngeal reflexes may be obtunded. Over-dosage may result in profound respiratory depression, particularly in patients with impaired respiratory function or in those who have taken other depressants, such as alcohol • Excessively rapid IV injection can also cause significant respiratory depression and even apnoea • May occasionally produce disinhibition, so instead of becoming more relaxed, the patient becomes more anxious and difficult to manage.

Planning for intravenous sedation Careful planning is essential before undertaking IV sedation in dental practice. Chapter 3 has already dealt with the selection and assessment of patients for sedation. The following section will specify the personnel and equipment required to practice IV sedation both safely and effectively. 1. Personnel Dental clinicians should not undertake sedation unless they have been appropriately trained. In the UK, this means that dentists should have received relevant postgraduate training. This involves completing a recognised course which provides both didactic and clinical training in recognised conscious sedation techniques. It is acceptable for an appropriately trained dental clinician to sedate the patient and provide dental treatment simultaneously. The dental clinician must Principles and practice of intravenous sedation 107 be assisted by a dental nurse or other person who is appropriately trained in the field of conscious sedation. They must have knowledge of the sedation drugs and specialised equipment being used, be capable of monitoring the clinical condition of the patient and understand the relevance of blood pressure and oxygen saturation readings. It is also essential that all staff are trained to assist in the event of an emergency. The assisting dental nurse must be specifically trained in sedation and resuscitation techniques, as this is not part of the core training for dental nurses. The gold standard for training is the Certificate in Dental Sedation Nursing. 2. Equipment Dental surgery: The suitability of the dental surgery where sedation is provided needs to be assessed. Easy access and space for patients, staff and for the management of emergencies is required. There should be the facility to store sedation agents and other drugs in a locked drugs cupboard. The dental chair must have a fast-recline mechanism so that in an emergency the patient can be quickly laid supine. There should be a high-volume aspirator available (with emergency back-up) which can be used to clear the oropharynx. Monitoring equipment: It is essential to monitor the patient’s clinical condition during sedation. The following equipment is required: • Pulse oximeter: it is mandatory to continuously measure oxygen saturation and heart rate throughout the sedation procedure • Manual or automatic sphygmomanometer to monitor baseline blood pressure before sedation, during sedation and prior to the patient being discharged. Emergency equipment and drugs: Appropriate emergency equipment and drugs must also be available (detailed in Chapter 8). It is particularly important to have the facility to provide supplemental oxygen via a nasal cannula or a facemask and an additional device with which to give positive pressure ventilation. The emergency equipment required for sedation is identical to that which should be stocked in any dental practice; the only additional item required for undertaking benzodiazepine sedation is the reversal agent, flumazenil (trade name Anexate®). This is presented as a clear liquid in 500mcg ampoules. Recovery facility: Ideally there should be a separate recovery area where the patient can sit quietly and privately following sedation. A pulse oximeter and blood pressure monitor must 108 Clinical Sedation in Dentistry be available as well as oxygen and suction apparatus. An alternative is to allow the patient to recover in the dental chair but this utilises the chair for several hours and may not be possible in a busy dental practice. Specific sedation equipment: To administer IV sedation, the following equipment is required (Figure 7.1): • 2 × disposable 5ml graduated syringes • 2 × 21 gauge hypodermic needles (preferably blunt) • Tourniquet • Surgical wipes • Adhesive tape (or proprietary dressings) • Indwelling teflonated 22-gauge cannula.

 Figure 7.1 Equipment required for the administration of intravenous sedation agents.  A teflonated cannula provides more secure access and is unlikely to become dislodged or blocked during limb movement. A 22-gauge cannula is the ideal size for administering IV sedatives. It readily allows the administration of modest volumes of drugs but is small enough not to cause too much discomfort on insertion.

Technique of intravenous sedation Pre-procedural checks The patient scheduled for IV sedation should have undergone thorough pre-operative assessment as described in Chapter 3. Principles and practice of intravenous sedation 109 The availability of appropriate personnel and equipment should be checked before the start of each sedation session. It is helpful to use a pre-procedural checklist, such as that illustrated in Figure 7.2, to ensure that all the necessary criteria required to practise sedation safely are confirmed before the start of the session. Each item on the list should be checked and the appropriate box ticked. Equipment should not only be available but also in good working order. Gas cylinders, and particularly oxygen supplies, must be checked to ensure that they contain a sufficient volume of gas and are not low or empty. The expiry date on all drugs should be checked to ensure that they are still valid. All the equipment required for the session should be prepared and placed discreetly out of the patient’s line of vision. Before the patient is brought into the surgery, the following information should be confirmed: • Presence of suitable escort • Appropriate transport home (car/taxi) • Written consent obtained • Medical history updated • Routine medication taken • Time of last meal and drink (minimum fasting time 2 hours) • If alcohol been taken (if consumed within the previous 24 hours then treatment should be postponed). The patient can then be escorted to the surgery and seated in the dental chair. It is important to keep waiting time to a minimum, as delays only increase the fear of an already anxious patient. The procedure for sedation and the dental treatment to be performed on that visit should be briefly re-explained to the patient. Before any sedation procedure is commenced the blood pressure should be taken and a pulse oximeter probe attached to the patient’s finger or ear lobe. Once seated comfortably the chair can be reclined in preparation for venepuncture.

Venepuncture and intravenous cannulation Establishing secure IV access is essential to the success of IV sedation. An indwelling cannula, which is present throughout the period of sedation and recovery, is mandatory for safe sedation practice. It is not acceptable to simply inject an IV sedation agent using a syringe and needle, which is then removed once the drug has been administered. Venous access is required not only for the administration of the sedation agent but also, in the event of an emergency, for the administration of a reversal agent or other emergency drug. Untoward occurrences can occur at any time during the treatment

Figure 7.2 Pre-operative checklist for intravenous sedation including information about the emergency equipment, intravenous sedation equipment and patient details. appointment, so it is essential that once venous access has been established the cannula should remain in situ until the patient is discharged. Teflon® is minimally irritant to veins and, due to its low adhesive surface, the cannula rarely blocks during short procedures. In addition it can bend during limb movement and once in place it will rarely become dislodged. There are two main sites of venous access for the purposes of dental sedation, the dorsum of the hand and the antecubital fossa.

Dorsum of the hand: The dorsum of the hand has a variable network of veins which drain into the cephalic and basilic veins of the forearm (Figure 7.3 and Chapter 2, Figure 2.5). These veins provide the first choice for establishing venous access as they are accessible, superficial, clearly visible in most patients, stabilised by underlying bones of the hand, and are distant from vital structures. The disadvantage of the dorsal veins of the hand, is that they are poorly tethered and tend to move during the insertion of a cannula if the skin is not held sufficiently taught. The dorsal veins of the hand are also subject to peripheral vasoconstriction in cold weather and in patients who are very anxious. Vasoconstriction can usually be reversed by warming the hand in a bowl of warm water prior to venepuncture. The back of the hand can also be somewhat painful to puncture and consideration should be given to the use of a topical local anaesthetic agent such as EMLA® or AMETOP®, particularly in patients who are anxious about the cannulation procedure.

Antecubital fossa: The second choice for venous access is in the larger veins of the antecubital fossa. (Chapter 2, Figure 2.6) The two main veins of the forearm, the cephalic and basilic veins, pass the lateral and medial aspects of the antecubital fossa respectively. A further vein (the median vein) originates in the deep tissue of the forearm and divides to join the cephalic.

 

Figure 7.3 Dorsum of the hand, showing the network of superficial veins between diastolic and systolic pressure.

Hot towels can also be applied to the skin to encourage vasodilatation. Adequate preparation of the vein is the key to successful venepuncture and only when the vein is sufficiently full should penetration be attempted. 3. The skin should be cleaned with water or a suitable antiseptic, such as isopropyl alcohol. The latter tends to cause pain on injection unless it has completely evaporated and there is no scientific evidence that the use of alcohol is of any real benefit. 4. The skin is then tensed and the cannula inserted at an angle of around 10–15° (Figure 7.4). It is passed through the skin and into the underlying vein for a distance of around 1cm. Skillful phlebotomists view venepuncture as a two-stage process, initially penetrating the skin and subsequently the vein. A small flashback of blood indicates correct localisation of the cannula in the lumen of the vein (Figure 7.5). If no flashback is seen, then the cannula is still in the subcutaneous tissues and needs to be carefully advanced forward or laterally through the vein wall.

 

Figure 7.4 Insertion of the cannula. The skin is held taught and the cannula angled at 10–15 degrees to enter the vein.

 

Figure 7.5 A small flashback of blood confirms that the cannula is in the lumen of the vein.

Once a flashback of blood is visible, the teflon part of the cannula is advanced up to its hub, leaving the insertioeedle static. It is better to move the teflonated section forward rather than the needle backwards as this runs a greater risk of the cannula becoming extra-venous (Figure 7.6). 5. The needle is removed completely and a cap is removed from it so that it can be placed on the aperture of the cannula. To avoid blood spilling onto the patient, pressure should then be applied just proximal to the vein where the cannula is situated. 6. Finally, the extra-venous section of the cannula is fixed securely in place, using non-allergenic surgical tape or proprietary dressing (Figure 7.7). 7. The correct positioning and patency of the cannula may be tested by administering 2–3ml of 0.9 % saline intravenously (Figure 7.8). If the cannula is sited in the lumen of the vein, the saline will pass easily into the generalcirculation. In contrast, if the the cannula tube may be used.

 

Figure 7.6 As the needle is withdrawn a further flashback of blood is seen within

Figure 7.7 The cannula is fixed in place.

Special fixing plasters or micropore tape cannula has come out of the vein and is in the sub-cutaneous tissues, the saline will pool and a small lump will appear under the skin (tissuing). If this happens the cannula should be removed and reinserted at another site. The patient may feel a cold sensation moving up the arm when saline is administered into a correctly positioned cannula. If, however, there is a complaint of pain radiating down the arm, the injection must be stopped as this indicates accidental arterial cannulation.

 

 

Figure 7.8 The position of the cannula is checked by injecting 2ml of 0.9% saline.

Titration of sedation agent The syringe containing the prepared drug (midazolam 10mg in 5ml) is attached to the delivery port of the cannula (Figure 7.9). The patient is warned that they will begin to feel relaxed and sleepy over the next 10 minutes. The first increment of 1mg (0.5ml) midazolam is injected slowly over 15 seconds, followed by a pause for 1 minute. Further doses of 1mg are delivered, with an interval of 1 minute between increments, until the level of sedation is judged to be adequate. The aim of IV sedation, is to titrate incremental doses of drug according to the patient’s response. The dental clinician should keep talking to the patient whilst carefully watching for the effects of sedation as well as any adverse reactions, especially respiratory depression. The sedation end point is reached when several specific signs of sedation are apparent. These signs include:

 

Figure 7.9 Titration of the sedation agent, midazolam at a rate of 1mg/min. 

1. Slurring and slowing of speech 2. Relaxed demeanour 3. Delayed response to commands 4. Willingness to undergo treatment 5. Positive Eve’s sign 6. Verill’s sign. Eve’s sign is a test of motor co-ordination. The patient is requested to touch the tip of their nose with their finger. A sedated patient will be unable to accurately perform this simple task and usually touches the top lip (Figure 7.10). Verill’s sign occurs when there is ptosis or drooping of the upper eyelid, to an extent that it lies approximately half way across the pupil. These signs of sedation are not exclusive and often only two or three are present in an individual. They do, however, give some objective indication of an adequate level of sedation. The essential criterion for conscious sedation is that communication is maintained with the patient and there are responses to the clinician’s commands. Determining an appropriate end point for sedation is often difficult but depends on the ability of the dental clinician to recognise specific signs and to maintain a rapport with the patient. There is considerable variation in the dose required to produce adequate sedation between individual patients, and even between different sessions for the same patient. Factors such as the extent of dental fear, concurrent drug therapy, the amount of sleep the previous night and the level of stress at home, are so variable that it is impossible to predict how much drug will be required for a specific patient on a certain day.

Figure 7.10 Inability to touch the tip of the nose with the forefinger indicates loss of motor co-ordination and is known as Eve’s sign.

This is why careful titration of the dose of sedation agent, in response to specific signs, is so important for the practice of safe sedation. If drug dose was to be based on weight only, theumerous patients would become either over- or under-sedated. When the patient is judged to be appropriately sedated, the syringe containing the sedation drug is removed and the cannula flushed through with 2–3ml of 0.9% saline. No further increments of drug are given when a standardised technique is adopted.

Clinical and electromechanical monitoring The clinical condition of the patient must be continuously monitored throughout the sedation session. This involves the use of both clinical and electromechanical techniques.

Clinical monitoring • Patency of the patient’s airway • Pattern of respiration • Pulse • Skin colour • Level of consciousness.

Clinical Sedation in Dentistry The oximeter works by measuring and comparing the absorption of two different wavelengths of red and infrared light by the arterial blood. The colour of the blood changes according to the degree of oxygen saturation and this in turn affects the absorption spectrum. By calculating the relative absorption of the two wavelengths the oximeter can precisely calculate oxygen saturation.

Management of oxygen desaturation Oxygen saturation is an excellent monitor of both respiratory and cardiovascular function. Patients undergoing sedation should always have an oxygen saturation well above 90%. If the saturation drops below this level it is an indication of inhibited.

Electromechanical monitoring • Pulse oximetry • Blood pressure. Pulse oximetry Pulse oximetry is a technique which measures the patient’s arterial oxygen saturation and pulse rate from a probe attached to the finger or ear lobe (Figure 7.11). This should be recorded prior to commencing drug titration and throughout treatment and recovery.

Figure 7.11 The pulse oximeter measures the patient’s arterial oxygen saturation and heart rate using a finger or ear lobe probe.

The oximeter works by measuring and comparing the absorption of two different wavelengths of red and infrared light by the arterial blood. The colour of the blood changes according to the degree of oxygen saturation and this in turn affects the absorption spectrum. By calculating the relative absorption of the two wavelengths the oximeter can precisely calculate oxygen saturation.

Management of oxygen desaturation Oxygen saturation is an excellent monitor of both respiratory and cardiovascular function. Patients undergoing sedation should always have an oxygen saturation well above 90%. If the saturation drops below this level it is an indication of inhibited respiratory or cardiovascular activity.

Figure 7.12 Nasal oxygen is administered via a nasal cannula.

The cause should be promptly investigated and corrected. The most common causes of oxygen desaturation during sedation are slight respiratory depression, breath holding or over-sedation. The problem is usually rectified by asking the patient to take a few deep breaths. If the saturation remains below 90%, supplemental oxygen should be administered via a nasal cannula at a rate of 2–4 litres/minute (Figure 7.12). If the patient’s saturation still does not rise, then the most likely cause is over-sedation. In such cases the sedation should be reversed with flumazenil. The pulse oximeter is essentially an early warning device. It will indicate an initial problem which, with swift intervention, can be corrected before the situation becomes more serious. It should be remembered that the pulse oximeter is not infallible. Correct functioning of the equipment can be affected by excessive movement, pigmented skin, nail varnish and fluorescent or bright lights. Aberrant values should always be confirmed by clinical observation of the patient. Pulse oximeter alarm Pulse oximeters have an audible alarm which is activated when the saturation or pulse rate drops below a specific threshold. For routine IV sedation, the alarm should be set to sound if the saturation drops below 90% or the pulse goes below 50 or above 120. Bradycardia may indicate a vasovagal attack, vagal stimulation or hypoxia. Tachycardia usually results from

Clinical Sedation in Dentistry inadequate analgesia and pain control. Any values outside the accepted range, should result in immediate cessation of dental treatment followed by investigation and prompt rectification of the cause.

Blood pressure monitoring Blood pressure monitoring throughout sedation is recommended. The blood pressure should be taken immediately before IV sedation is administered, to provide a baseline value, at regular intervals during sedation and before the patient is discharged. Most hypertensive patients will have been picked up at the assessment appointment and referred for medical opinion. Some elevation of blood pressure is to be expected in anxious dental patients but if values are excessive (higher than 160/95) then sedation should be postponed until a later date. Blood pressure measuring need only be repeated during treatment if there is a concern over the clinical condition of the patient or in the event of an emergency. Blood pressure can be taken using either a manual sphygmomanometer or an automatic blood pressure machine (Figure 7.13). It should be remembered that simple observation of the patient’s clinical status is the most important type of monitoring. Although pulse oximetry is mandatory, it should not detract the dental surgeon and the dental nurse from continuously assessing the patient’s clinical condition.

Figure 7.13 The patient’s blood pressure is most easily monitored before, during and after treatment using an electromechanical blood pressure machine.

Dental treatment The administration of local analgesia and start of operative dentistry can begin as soon as the patient has reached the appropriate level of sedation. A simple way to assess the end point of sedation is to ask the patient if he/she is comfortable for treatment to begin. Approximately 30–40 minutes of operating time is usually available following a single administration, and treatment should be planned so that it can be readily completed in this time. It is good practice to undertake traumatic procedures, such as bone removal and cavity preparation, at the beginning of the session whilst the patient is in a state of acute detachment. After 30–40 minutes the effect of sedation starts to wear off and co-operation may be reduced. This is the time to concentrate on simple procedures such as suturing or carving restorations. Intravenous sedation using a single benzodiazepine produces no analgesia, so it is essential to provide effective pain control during dental procedures. This should include the use of both topical analgesia and sufficient quantities of local anaesthetic. Sedated patients will still respond to pain, although their response will be reduced. The muscle relaxant effect of sedation makes it difficult for patients to keep their mouths open during treatment. A mouth prop can improve access for the dental surgeon and make treatment more comfortable for the patient. It must never be an excuse, however, for failing to maintain conversation with patients and checking that their responses to instructions remain intact. During sedation, the gag reflex is significantly diminished, and immediately following drug administration the laryngeal reflexes may also be reduced. The airway must be protected from any obstruction and this is best achieved by high volume aspiration. When small instruments are used, a rubber dam or a butterfly sponge must be inserted to protect against foreign bodies accidentally falling into the airway. Great care should be exercised when extracting teeth in the sedated patient. Use good suction to prevent segments of crowns, roots or amalgam entering the pharynx.

Recovery At the end of the dental procedure the patient is slowly returned to the upright position over a period of several minutes. They are then transferred to the recovery area and placed in a comfortable chair or trolley. Patients should not be moved from the dental chair until they can walk with

minimal assistance. Whilst in the recovery area the patient should be under the direct supervision of the dental team or their escort (Figure 7.14).

Figure 7.14 Following treatment the patient is escorted to the recovery area where monitoring continues until discharge.

At least one hour should have elapsed since the last increment of drug was administered before patients can be assessed for discharge. Discharge criteria include: • Ability to walk in a straight line unassisted • Speech no longer slurred • Oxygen saturation back to baseline • Blood pressure restored to near baseline • Presence of suitable escort. When the dental clinician determines that patients are ready to leave they should be discharged into the care of their escort who must be given full spoken and written instructions about their post-operative care (Figure 7.15). The following advice should be provided: • Rest quietly at home for the rest of the day • For the next 24 hours, they should refrain from • Driving • Drinking alcohol • Operating machinery or domestic appliances • Signing legal documents • Making Internet transactions. The venous cannula should remain in situ until just before the patient is discharged. It should be taken out by carefully removing the surgical tape or dressing and withdrawing the cannula (Figure 7.16). Firm pressure is then maintained with a Figure 7.14 Following treatment the patient is escorted to the recovery area where monitoring continues until discharge. Figure 7.15 Written post-operative instructions are given to the patient and their escort prior to discharge.

 

Figure 7.16 The cannula is removed just before the patient is discharged. Cotton wool roll on the venepuncture site for several minutes to prevent haematoma formation.

If significant bleeding occurs when the cannula is removed it can also be helpful to elevate the arm for a period of two to three minutes. The patient should always be advised that there may be bruising at the cannulation site for several days after treatment.

Sedation records Every sedation episode should be carefully documented in the patient notes. It can be helpful to use a printed sheet to record details of the sedation provided (Figure 7.17). The following should be recorded prior to drug administration: • Operating dentist and assisting dental nurse(s) • Intravenous drug used • Drug expiry date and batch number • Time of first and final increment • Total dose administered • Size of the venous cannula • Site of cannulation. Although the patient is continuously monitored during sedation it is good practice to record the monitoring data at 5 minute intervals: • Oxygen saturation • Blood pressure • Heart rate • Respiration rate. The more advanced pulse oximeters will do this automatically and provide a printout of the results. The dental treatment provided should also be documented in the normal way. At the end of the session a note should be made about the level of sedation, operating conditions and any difficulties encountered. This information will be useful when the patient re-attends for the next sedation appointment. Finally, information about the recovery and discharge of the patient should be recorded including: • Oxygen saturation • Blood pressure • Ability to walk unassisted • Availability of escort • Removal of cannula • Post-operative instructions issued to patient and escort. The record sheet should be attached to the patient notes, along with the consent form, so that there is a complete record of the treatment appointment. The sheet should be signed by the dental clinician and assisting dental nurse.

Complications of intravenous sedation The complications of sedation are discussed fully in Chapter 8 and are better avoided than confronted. Good preparation is the key to reducing the incidence of complications. Intravenous sedation is very safe, provided that it is practised on carefully selected patients, in proper facilities, by appropriately trained dental clinicians. The incidence of mortality associated with IV sedation in dentistry in the UK is extremely small. Potentially serious complications such as drug interactions, over-sedation, unconsciousness and respiratory depression are largely avoidable by careful patient selection and the use of a sound and appropriate sedation technique. Nevertheless, IV sedation does give rise to significant minor morbidity such as haematoma at the cannulation site, and post-operative dizziness, nausea and headache. These minor sequelae are difficult to avoid completely and are, for the most part, accepted side effects of either the sedation technique or the sedation agent. Patients should be warned of the possibility of such problems and dental surgeons should continually review their techniques to minimise the risk of any complication.

Cardiopulmonary resuscitation

CPR being performed on a medical-training manikin

Cardiopulmonary resuscitation (CPR) is an emergency procedure, performed in an effort to manually preserve intact brain function until further measures are taken to restore spontaneous blood circulation and breathing in a person in cardiac arrest. It is indicated in those who are unresponsive with no breathing or abnormal breathing, for example, agonal respirations.

CPR involves chest compressions at least 5 cm (2 in) deep and at a rate of at least 100 per minute in an effort to create artificial circulation by manually pumping blood through the heart. In addition, the rescuer may provide breaths by either exhaling into the subject’s mouth or nose or utilizing a device that pushes air into the subject’s lungs. This process of externally providing ventilation is termed artificial respiration. Current recommendations place emphasis on high-quality chest compressions over artificial respiration; a simplified CPR method involving chest compressions only is recommended for untrained rescuers.

CPR alone is unlikely to restart the heart; its main purpose is to restore partial flow of oxygenated blood to the brain and heart. The objective is to delay tissue death and to extend the brief window of opportunity for a successful resuscitation without permanent brain damage. Administration of an electric shock to the subject’s heart, termed defibrillation, is usually needed in order to restore a viable or “perfusing” heart rhythm. Defibrillation is only effective for certain heart rhythms, namely ventricular fibrillation or pulseless ventricular tachycardia, rather than asystole or pulseless electrical activity. CPR may succeed in inducing a heart rhythm which may be shockable. CPR is generally continued until the patient has a return of spontaneous circulation (ROSC) or is declared dead.

Medical uses

CPR is indicated for any person who is unresponsive with no breathing, or who is only breathing in occasional agonal gasps, as it is most likely that they are in cardiac arrest. If a person still has a pulse, but is not breathing (respiratory arrest), artificial respirations may be more appropriate, but due to the difficulty people have in accurately assessing the presence or absence of a pulse, CPR guidelines recommend that lay persons should not be instructed to check the pulse, while giving health care professionals the option to check a pulse. In those with cardiac arrest due to trauma CPR is considered futile in the pulseless case, but still recommended for correctible causes of arrest.

Methods

CPR training: CPR is being administered while a second rescuer prepares for defibrillation.

In 2010, the American Heart Association and International Liaison Committee on Resuscitation updated their CPR guidelines. The importance of high quality CPR (sufficient rate and depth without excessively ventilating) was emphasized. The order of interventions was changed for all age groups except newborns from airway, breathing, chest compressions (ABC) to chest compressions, airway, breathing (CAB). An exception to this recommendation is for those who are believed to be in a respiratory arrest (drowning, etc.). The most important aspect of CPR are: few interruptions of chest compressions, a sufficient speed and depth of compressions, completely relaxing pressure between compressions, and not ventilating too much.

Standard

A universal compression to ventilation ratio of 30:2 is recommended. With children, if at least 2 rescuers are present a ratio of 15:2 is preferred. Iewborns a rate of 3:1 is recommended unless a cardiac cause is known in which case a 15:2 ratio is reasonable. If an advanced airway such as an endotracheal tube or laryngeal mask airway is in place delivery of respirations should occur without pauses in compressions at a rate of 8–10 per minute. The recommended order of interventions is chest compressions, airway, breathing or CAB in most situations, with a compression rate of at least 100 per minute in all groups. Recommended compression depth in adults and children is about 5 cm (2 inches) and in infants it is 4 cm (1.5 inches. As of 2010 the Resuscitation Council (UK) still recommends ABC for children. As it can be difficult to determine the presence or absence of a pulse the pulse check has been removed for lay providers and should not be performed for more than 10 seconds by health care providers. In adults rescuers should use two hands for the chest compressions, while in children they should use one, and with infants two fingers (index and middle fingers).

Compression only

Compression-only (hands-only or cardiocerebral resuscitation) CPR is a technique that involves chest compressions without artificial respiration. It is recommended as the method of choice for the untrained rescuer or those who are not proficient as it is easier to perform and instructions are easier to give over the phone. In adults with out-of-hospital cardiac arrest, compression-only CPR by the lay public has a higher success rate than standard CPR. The exceptions are cases of drownings, drug overdose, and arrest in children. Children who receive compression-only CPR have the same outcomes as those who received no CPR. The method of delivering chest compressions remains the same, as does the rate (at least 100 per minute). It is hoped that the use of compression-only delivery will increase the chances of the lay public delivering CPR. As per the American Heart Association, the beat of the Bee Gees song “Stayin’ Alive” provides an ideal rhythm in terms of beats per minute to use for hands-only CPR. One can also hum Queen‘s “Another One Bites The Dust“, which is exactly 100 beats-per-minute and contains a memorable repeating drum pattern. For those with non cardiac arrest and people less than 20 years of age, standard CPR is superior to compression-only CPR.

Pregnancy

During pregnancy when a woman is lying on her back, the uterus may compress the inferior vena cava and thus decrease venous return. It is recommended for this reason that the uterus be pushed to the woman’s left and if this is not effective either roll the person 30° or for healthcare professionals to consider emergency Caesarean section.

Other

Interposed abdominal compressions may be beneficial in the hospital environment. There is however no evidence of benefit pre hospital or in children. Internal cardiac massage is manual squeezing of the heart carried out through a surgical incision into the chest cavity. This may be carried out if the chest is already open for cardiac surgery.

Effectiveness

Used alone, CPR will result in few complete recoveries, and those who do survive often develop serious complications. Estimates vary, but many organizations stress that CPR does not “bring anyone back,” it simply preserves the body for defibrillation and advanced life support. However, in the case of “non-shockable” rhythms such as Pulseless Electrical Activity (PEA), defibrillation is not indicated, and the importance of CPR rises. On average, only 5–10% of people who receive CPR survive. The purpose of CPR is not to “start” the heart, but rather to circulate oxygenated blood, and keep the brain alive until advanced care (especially defibrillation) can be initiated. As many of these patients may have a pulse that is impalpable by the layperson rescuer, the current consensus is to perform CPR on a patient who is not breathing.

Studies have shown that immediate CPR followed by defibrillation within 3–5 minutes of sudden VF cardiac arrest improves survival. In cities such as Seattle where CPR training is widespread and defibrillation by EMS personnel follows quickly, the survival rate is about 30 percent. In cities such as New York, without those advantages, the survival rate is only 1–2 percent.

In most cases, there is a higher proportion of patients who achieve a Return of Spontaneous Circulation (ROSC), where their heart starts to beat on its own again, than ultimately survive to be discharged from hospital (see table above). This is due to medical staff either being ultimately unable to address the cause of the arrhythmia or cardiac arrest, or in some instances due to other co-morbidities, due to the patient being gravely ill in more than one way.

Compression-only CPR is less effective in children than in adults, as cardiac arrest in children is more likely to have a non-cardiac cause. In a 2010 prospective study of cardiac arrest in children (age 1–17), for arrests with a non-cardiac cause, provision by bystanders of conventional CPR with rescue breathing yielded a favorable neurological outcome at one month more often than did compression-only CPR (OR 5.54; 95% confidence interval 2.52–16.99). For arrests with a cardiac cause in this cohort, there was no difference between the two techniques (OR 1.20; 95% confidence interval 0.55–2.66). This is consistent with American Heart Association guidelines for parents.

Pathophysiology

CPR is used on people in cardiac arrest in order to oxygenate the blood and maintain a cardiac output to keep vital organs alive. Blood circulation and oxygenation are required to transport oxygen to the tissues. The brain may sustain damage after blood flow has been stopped for about four minutes and irreversible damage after about seven minutes. Typically if blood flow ceases for one to two hours, the cells of the body die. Because of that CPR is generally only effective if performed within seven minutes of the stoppage of blood flow.^[29] The heart also rapidly loses the ability to maintain a normal rhythm. Low body temperatures, as sometimes seen in near-drownings, prolong the time the brain survives. Following cardiac arrest, effective CPR enables enough oxygen to reach the brain to delay brain death, and allows the heart to remain responsive to defibrillation attempts.

Complications

Whilst CPR is a last resort intervention, without which a patient without a pulse will certainly die, the physical nature of how CPR is performed does lead to complications that may need to be rectified. Common complications due to CPR include rib fractures, sternal fractures, bleeding in the anterior mediastinum, heart contusion, hemopericardium, upper airway complications, damage to the abdominal viscus – lacerations of the liver and spleen, fat emboli, pulmonary complications – pneumothorax, hemothorax, lung contusions.

The most common injuries sustained from CPR are rib fractures, with literature suggesting an incidence between 13 % and 97 %, and sternal fractures, with an incidence between 1 % to 43 %. Whilst these iatrogenic injuries can require further intervention (assuming the patient survives the cardiac arrest), only 0.5% of them are life threatening in their own right.

The type and frequency of injury can be affected by factors such as gender and age. For instance, women have a higher risk of sternal fractures than men, and risk for rib fractures increases significantly with age. Children and infants have a low risk of rib fractures during CPR, with an incidence less than 2%, although when they do occur, they are usually anterior and multiple.

Where CPR is performed in error by a bystander, on a patient who is not in cardiac arrest, only around 2% suffer injury as a result (although 12% experienced discomfort).

Adjunct devices

While several adjunctive devices are available none other than defibrillation as of 2010 have consistently been found to be better than standard CPR for out of hospital cardiac arrest. These devices can be split into three broad groups – timing devices, those that assist the rescuer to achieve the correct technique, especially depth and speed of compressions, and those which take over the process completely.

Timing devices

They can feature a metronome (an item carried by many ambulance crews) in order to assist the rescuer in getting the correct rate. Some units can also give timing reminders for performing compressions, breathing and changing operators.

Manual assist devices

Mechanical devices have not been found to have greater benefit than harm and thus are not currently recommended for widespread use.

Audible and visual prompting may improve the quality of CPR and prevent the decrease of compression rate and depth that naturally occurs with fatigue, and to address this potential improvement, a number of devices have been developed to help improve CPR technique.

These items can be devices to placed on top of the chest, with the rescuers hands going over the device, and a display or audio feedback giving information on depth, force or rate, or in a wearable format such as a glove. Several published evaluations show that these devices can improve the performance of chest compressions.

As well as use during actual CPR on a cardiac arrest victim, which relies on the rescuer carrying the device with them, these devices can also be used as part of training programs to improve basic skills in performing correct chest compressions.

Automatic devices

There are also some automated devices available which take over the chest compressions for the rescuer. These have several advantages: they allow rescuers to focus on performing other interventions; they do not fatigue and begin to perform less effective compressions, as humans do; and they are able to perform effective compressions in limited-space environments such as air ambulances, where manual compressions are difficult. These devices use either pneumatic (high-pressure gas) or electrical power sources to drive a compressing pad on to the chest of the patient. One such device, known as the LUCAS, was developed at the University Hospital of Lund, is powered by the compressed oxygen supplies already standard in ambulances and hospitals, and has undergone numerous clinical trials, showing a marked improvement in coronary perfusion pressure and return of spontaneous circulation.

In August 2013, a 41 year old woman living in a towear Melbourne in Australia was treated with the LUCAS device for 53 minutes while a stent was placed in an artery near her heart, clearing a 100% blockage. She was considered to be clinically dead for 40 minutes. She left hospital a week later.

Artificial ventilation can be done with multiple devices: bag mask gives way valve ball with oxygen-enriched air (which is in the bag) through a facial mask filing (but not external tubes, does not open the airway). This uses an oropharyngeal airway, called Bergman, tube May or Guedel airway (these do not prevent mouth to mouth contact if there were no masks or masks with air balloons) or Maselli: oropharyngeal Maselli respirator (avoiding contagion in both directions) and is necessary to facilitate air pass to place the tongue in place and prevent it from falling back and relax in by the unconscious, as well as whether the person has a voluminous tongue, such as in cases of Angioedema. It also has a nozzle for the rescuer with a protective mask mode, which prevents any mouth to mouth contact. Another system called the AutoPulse is electrically powered and uses a large band around the patients chest which contracts in rhythm in order to deliver chest compressions. This is also backed by clinical studies showing increased successful return of spontaneous circulation.

Prevalence

Chance of receiving CPR

Various studies suggest that in out-of-home cardiac arrest, bystanders, lay persons or family members attempt CPR in between 14% and 45% of the time, with a median of 32%. This indicates that around a third of out-of-home arrests have a CPR attempt made on them. However, the effectiveness of this CPR is variable, and the studies suggest only around half of bystander CPR is performed correctly. A recent study has shown that members of the public who have received CPR training in the past lack the skills and confidence needed to save lives. These experts believe that better training is needed to improve the willingness to respond to cardiac arrest.

There is a clear correlation between age and the chance of CPR being commenced, with younger people being far more likely to have CPR attempted on them prior to the arrival of emergency medical services. It was also found that CPR was more commonly given by a bystander in public than when an arrest occurred in the patient’s home, although health care professionals are responsible for more than half of out-of-hospital resuscitation attempts. This is supported by further research, which suggests that people with no connection to the victim are more likely to perform CPR than a member of their family.

There is also a correlation between the cause of arrest and the likelihood of bystander CPR being initiated. Lay persons are most likely to give CPR to younger cardiac arrest victims in a public place when it has a medical cause; victims in arrest from trauma, exsanguination or intoxication are less likely to receive CPR.

Finally, it has been claimed that there is a higher chance of CPR being performed if the bystander is told to only perform the chest compression element of the resuscitation.

Chance of receiving CPR in time

CPR is only likely to be effective if commenced within 6 minutes after the blood flow stops, because permanent brain cell damage occurs when fresh blood infuses the cells after that time, since the cells of the brain become dormant in as little as 4–6 minutes in an oxygen deprived environment and the cells are unable to survive the reintroduction of oxygen in a traditional resuscitation. Research using cardioplegic blood infusion resulted in a 79.4% survival rate with cardiac arrest intervals of 72±43 minutes, traditional methods achieve a 15% survival rate in this scenario, by comparison. New research is currently needed to determine what role CPR, electroshock, and new advanced gradual resuscitation techniques will have with this new knowledge. A notable exception is cardiac arrest occurring in conjunction with exposure to very cold temperatures. Hypothermia seems to protect by slowing down metabolic and physiologic processes, greatly decreasing the tissues’ need for oxygen. There are cases where CPR, defibrillation, and advanced warming techniques have revived victims after substantial periods of hypothermia.

Society and culture

Portrayed effectiveness

CPR is often severely misrepresented in movies and television as being highly effective in resuscitating a person who is not breathing and has no circulation. A 1996 study published in the New England Journal of Medicine showed that CPR success rates in television shows was 75% for immediate circulation, and 67% survival to discharge. This gives members of the public an unrealistic expectation of a successful outcome. When educated on the actual survival rates, the proportion of patients over 60 years of age desiring CPR should they suffer a cardiac arrest drops from 41% to 22%.

Stage CPR

Chest compressions are capable of causing significant local blunt trauma, including bruising or fracture of the sternum or ribs. Performing CPR on a healthy person may or may not disrupt normal heart rhythm, but regardless the technique should not be performed on a healthy person because of the risk of trauma.

The portrayal of CPR technique on television and film often is purposely incorrect. Actors simulating the performance of CPR may bend their elbows while appearing to compress, to prevent force from reaching the chest of the actor portraying the victim. Other techniques, such as substituting a mannequin torso for the “victim” in some shots, may also be used to avoid harming actors.

Self-CPR hoax

A form of “self-CPR” termed “Cough CPR” was the subject of a hoax chain e-mail entitled “How to Survive a Heart Attack When Alone” which wrongly cited “ViaHealth Rochester General Hospital” as the source of the technique. Rochester General Hospital has denied any connection with the technique.

“Cough CPR” cannot be used outside the hospital because the first symptom of cardiac arrest is unconsciousness in which case coughing is impossible, although myocardial infarction (heart attack) may occur to give rise to the cardiac arrest, so a patient may not be immediately unconscious. Further, the vast majority of people suffering chest pain from a heart attack will not be in cardiac arrest and CPR is not needed. In these cases attempting “cough CPR” will increase the workload on the heart and may be harmful. When coughing is used on trained and monitored patients in hospitals, it has only been shown to be effective for 90 seconds.

The American Heart Association (AHA) and other resuscitation bodies do not endorse “Cough CPR”, which it terms a misnomer as it is not a form of resuscitation. The AHA does recognize a limited legitimate use of the coughing technique: “This coughing technique to maintain blood flow during brief arrhythmias has been useful in the hospital, particularly during cardiac catheterization. In such cases the patients ECG is monitored continuously, and a physician is present.”

CPR learned from movies and television

In at least one case, it has been claimed that CPR allegedly learned from a movie was used to save a person’s life. In April 2011, it was claimed that nine-year-old Tristin Saghin saved his sister’s life by administering CPR on her after she fell into a swimming pool, using only the knowledge of CPR that he had gleaned from a motion picture, Black Hawk Down.

Hands-Only CPR portrayed as more palatable version

Less than 1/3 of those people who experience a cardiac arrest at home, work or in a public location have CPR performed on them. Most bystanders are worried that they might do something wrong. On October 28, 2009 The American Heart Association and the Ad Council launched a Hands Only CPR public service announcement and website as a means to address this issue. In July 2011, new content was added to the website including a digital app that helps a user learn how to perform Hands-Only CPR.

History

In the 19th century, Doctor H. R. Silvester described a method (The Silvester Method) of artificial respiration in which the patient is laid on their back, and their arms are raised above their head to aid inhalation and then pressed against their chest to aid exhalation.^[83] The procedure is repeated sixteen times per minute. This type of artificial respiration is occasionally seen in films made in the early part of the 20th century.

A second technique, called the Holger Nielsen technique, described in the first edition of the Boy Scout Handbook in the United States in 1911, described a form of artificial respiration where the person was laid face down, with their head to the side, resting on the palms of both hands. Upward pressure applied at the patient’s elbows raised the upper body while pressure on their back forced air into the lungs, essentially the Silvester Method with the patient flipped over. This form is seen well into the 1950s (it is used in an episode of Lassie during the mid-1950s), and was often used, sometimes for comedic effect, in theatrical cartoons of the time. This method would continue to be shown, for historical purposes, side-by-side with modern CPR in the Boy Scout Handbook until its ninth edition in 1979. The technique was later banned from first-aid manuals in the U.K.

Similar techniques were described in early 20th century ju-jutsu and judo books, as being used as far back as early 17th century. A New York Times correspondent reported those techniques being used successfully in Japan in 1910. In ju-jutsu (and later on, judo), those techniques were called Kappo or Kutasu.

However, it was not until the middle of the 20th century that the wider medical community started to recognize and promote artificial respiration combined with chest compressions as a key part of resuscitation following cardiac arrest. The combination was first seen in a 1962 training video called “The Pulse of Life” created by James Jude, Guy Knickerbocker and Peter Safar. Jude and Knickerbocker, along with William Kouwenhoven and Joseph S. Redding had recently discovered the method of external chest compressions, whereas Safar had worked with Redding and James Elam to prove the effectiveness of artificial respiration. It was at Johns Hopkins University where the technique of CPR was originally developed. The first effort at testing the technique was performed on a dog by Redding, Safar and JW Perason. Soon afterward, the technique was used to save the life of a child.^[88] Their combined findings were presented at the annual Maryland Medical Society meeting on September 16, 1960 in Ocean City, and gained rapid and widespread acceptance over the following decade, helped by the video and speaking tour they undertook. Peter Safar wrote the book ABC of Resuscitation in 1957. In the U.S., it was first promoted as a technique for the public to learn in the 1970s.

Artificial respiration was combined with chest compressions based on the assumption that active ventilation is necessary to keep circulating blood oxygenated, and the combination was accepted without comparing its effectiveness with chest compressions alone. However, research over the past decade has shown that assumption to be in error, resulting in the AHA‘s acknowledgment of the effectiveness of chest compressions alone.