Pathogenesis, diagnosis and treatment of hyperglycemic and hypoglycemic coma
in patients with diabetes mellitus.
1. Diabetic coma:
1) diabetic ketoacidisis (DKA);
2) nonketonic hyperglycemic-hyperosmolar coma (NKHHC);
3) lactoacidosis (LA).
2. Hypoglycemic coma (HC).
Diabetic ketoacidisis (DKA)
DKA is the most frequent endocrine emergency seen by the primary care physician. Mortality rates from 6 – 10 % have been reported. All the abnormalities associated with DKA can be traced to an absolute or relative insulin lack, which develops over the period of several hours or days.
Diabetic ketoacidosis (DKA) results from absolute or relative deficiency of circulating insulin and the combined effects of increased levels of the counterregulatory hormones: catecholamines, glucagon, cortisol and growth hormone.
Absolute insulin deficiency occurs in the following conditions:
· undiagnosed type 1 diabetes mellitus (T1DM); DKA is reported be the first presentation in about 25% of cases especially in those less than 5 years old.
· patients on treatment who miss their insulin doses, especially the long-acting component of a basal-bolus regimen. It is estimated that 75% of DKA episodes are associated with insulin omission or treatment error.
· patients who use insulin pump if insulin delivery fails.
Relative insulin deficiency, on the other hand, occurs when the concentrations of counterregulatory hormones increase in response to stress in conditions such as:
· sepsis,
· trauma, or
· gastrointestinal illness with diarrhea and vomiting.
Major components of the pathogenesis of diabetic ketoacidosis are reductions in effective concentrations of circulating insulin and concomitant elevations of counterregulatory hormones (catecholamines, glucagon, growth hormone and cortisol).
These hormonal alterations bring about three major metabolic events:
(1) hyperglycemia resulting from accelerated gluconeogenesis and decreased glucose utilization,
(2) increased proteolysis and decreased protein synthesis and
(3) increased lipolysis, ketone production and lipid oxidation as alternative source of energy.
The combination of low serum insulin and high counterregulatory hormone concentrations results in an accelerated catabolic state with increased glucose production by the liver and kidney (via glycogenolysis and gluconeogenesis), impaired peripheral glucose utilization resulting in hyperglycemia and hyperosmolality, and increased lipolysis and ketogenesis, causing ketonemia and metabolic acidosis. The blood levels of ketone bodies increases, especially of beta-hydroxybutyrate; the ratio between acetoacetate and beta-hydroxybutyrate increases to about 1 :10 (pict.).
Hyperglycemia and hyperketonemia cause osmotic diuresis, dehydration, and electrolyte loss. This stimulates stress hormone production, which induces insulin resistance and leads to a vicious circle, worsening the hyperglycemia and hyperketonemia. Fatal dehydration and metabolic acidosis will ensue if management is not initiated. Poor tissue perfusion or sepsis may lead to lactic acidosis which can aggravate the ketoacidosis. At presentation, the magnitude of specific deficits of fluid and electrolytes in an individual patient varies depending upon the extent to which the patient was able to maintain intake of fluid and electrolytes, and the content of food and fluids consumed before coming to medical attention and the duration and severity of illness.
Precipitating factors:
1) newly diagnosed diabetes (presenting manifestation);
2) inadequate administration of exogenous insulin;
3) increased requirements for insulin caused by the presence of an underlying stressful condition:
– an intercurrent infection (pneumonia, cholecyctite);
– a vascular disorder (myocardial infarction, stroke);
– an endocrine disorder(hyperthyroidism, pheochromocytoma);
– trauma;
– pregnancy;
– surgery.
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Factors Most Often Associated with the Development of Diabetic Ketoacidosis |
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Factor |
Approximate frequency (%) |
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Infection |
35 |
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Omission of insulin or inadequate insulin |
30 |
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Initial presentation of diabetes mellitus |
20 |
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Medical illness |
10 |
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Unknown |
5 |
Clinical presentation
Diabetic ketosis
It is status which is characterized by increased level of ketones in blood, without clinical signs of dehydration and can be corrected by diet (fat restriction) and regular insulin injection.
DKA develops over a period of days or weeks.
Signs and symptoms
1. Polydipsia, polyurea and weakness are the most common presenting complaints.
2. Anorexia, nausea, vomiting, and abdominal pain may be present and mimic an abdominal emergency.
3. Ileus and gastric dilatation may occur and predispose to aspiration.
4. Kussmaul breathing (deep, sighing respiration) is present as respiratory compensation for the metabolic acidosis and is obvious when the pH is less than 7.2.
5. Symptoms of central-nervous-system involvement include headaches, drowsiness, lassitude, stupor and coma (only 10 % patients are unconscious).
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Physical examination
1. Hypotermia is common in DKA. A fever should be taken as strong evidence of infection.
2. Hyperpnea or Kussmaul respiration are present and related to degree of acidosis, acetone may be detected on the breath (musty (fruity) odor to the breath).
3. Tachycardia frequently is present, but blood pressure is usually normal unless profound dehydration is present.
4. Poor skin tugor may be prominent depending on the degree of hydration.
5. Hyporeflexia (associated with low serum potassium) can be elicited.
6. Signs consistent with a “surgical abdomen” but which follow severe ketonemia can confuse the clinical picture.
7. In extreme cases of DKA one can see hypotonia, stupor, coma, incoordination of ocular movements, fied dilated pupils, and finally death.
8. Other signs from a precipitating illlness can be present.
Although usually straightforward, the diagnosis of diabetic ketoacidosis is occasionally missed in unusual situations, such as when it is the initial presentation of diabetes in infants or elderly patients or when patients present with sepsis or infarction of the brain, bowel or myocardium. These presentations can distract the physician from the underlying diagnosis of diabetic ketoacidosis.
The laboratory tests needed to confirm the presence of diabetic ketoacidosis and to screen for precipitating events.
Laboratory findings
1. The hallmark of DKA is the finding of:
– hyperglycemia;
– ketonemia;
– metabolic acidosis (plasma pH and bicarbonates are decreased).
– measurement of blood ß-OHB concentration, if available, is useful to confirm ketoacidosis and may be used to monitor the response to treatment
– A presumptive bedside diagnosis is justified if the urine is strongly positive for both glucose and ketones.
2. Different changes of electrolyte levels in the blood can be observed and does not reflect the actual total body deficits.
3. Serum amylase and transaminases can be elevated.
4. Leucocytosis occurs frequently in DKA and therefore cannot be used as a sole indication of infectious process.
5. Obtain appropriate specimens for culture (blood, urine, throat), if there is evidence of infection.
The biochemical criteria for DKA include the following triad:
• Hyperglycemia (blood glucose >11 mmol/L [200 mg/dL])
• Venous pH <7.3 and/or bicarbonate <15 mmol/L
• Ketonemia and ketonuria
Although DKA is defined by the biochemical triad of ketonemia, hyperglycemia and acidemia, several exceptions do exist which may provide a diagnostic dilemma for the physician in the emergency room. Examples of such are:
• “Euglycemic ketoacidosis’’: Partially treated children and children who have consumed little or no carbohydrate may present rarely with mildly increased blood glucose concentrations.
• Absent or mild metabolic acidosis, ketonemia and ketonuria: This may occur in the Hyperglycemic Hyperosmolar State (HHS) or if the patient experiences severe vomiting which may lead to alkalosis which can mask the present acidosis.
• Hyperglycemic hyperosmolar state (HHS), also referred to as hyperosmolar nonketotic coma, may occur in young patients withT2DM, but rarely in T1DM subjects.
It is important to recognize that overlap between the characteristic features of HHS and DKA may occur. Some patients with HHS, especially when there is very severe dehydration, have mild or moderate acidosis. Conversely, some children with T1DM may have features of HHS (severe hyperglycemia) if high carbohydrate containing beverages have been used to quench thirst and replace urinary losses prior to diagnosis.
• Other diagnostic difficulties may be faced in the very young age such as the following:
◦ Polyuria, polydipsia and weight loss which are characteristic features of diabetes are difficult to demonstrate in the very young.
◦ up to 70% of the young have DKA as a first presentation, hence, at presentation, duration of DKA is usually longer, dehydration and acidosis are more severe, as young children have relatively higher basal metabolic rate, and a relatively large surface area relative to body mass.
• Measurement of blood ß-hydroxybutyrate (ß -OHB) concentration, may not be available in all labs, besides, urine Ketone testing can be misleading due the following reasons:
◦ The used method does not detect the major ketone body B-hydroxybutyrate. (sodium nitroprusside only measures acetoacetate and acetone). Serum ß-OHB concentrations, may be increased to levels consistent with DKA when a urine ketone test is negative or shows only trace or small ketonuria
◦ The readings are qualitative depending on color comparisons
◦ High doses of Vitamin C may cause false-negative results, while some drugs may, on the other hand, give false-positive results.
Clinical types of DKA:
– abdominal;
– vascular collapse;
– cerebral (encephalopathic);
– renal;
– mixed.
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Grade the severity of DKA: |
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Mild DKA |
venous pH <7.3 or bicarbonate <15 mmol/L |
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Moderate DKA |
pH <7.2, bicarbonate <10 mmol/L |
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Severe DKA |
pH <7.1, bicarbonate <5 mmol/L |
Treatment
The management of patients may be difficult because of problems in achieving of normal glucose control. Because there is good evidence that hyperglycemia conveys risks for all of the common long-term complications of DM, which are the major cases of excess morbidity and mortality in diabetics.
Patients with type 1 DM usually start treatment at the hospital. They require close monitoring during efforts to develop an appropriate insulin treatment regimen, and the patients or their care givers require detailed education in their responsibilities and proficiency in them before home management is safe.
Most patients with type 2 DM who are not acutely ill can be safety started on the insulin (if they need it) on an outpatient basis with adequate patient education and close physician follow-up.
An efforts to maintain persistently normal serum glucose fluctuations in diabetics entail significant risk of causing frequent or severe hypoglycemic episodes, particularly in type 1 DM patients. Treatment regimens differ in the priorities assigned to keeping the risks for hypoglycemia minimal and to keeping serum glucose fluctuations in a normal to near-normal range.
The therapeutic goals for diabetic ketoacidosis consist of improving circulatory volume and tissue perfusion, reducing blood glucose and serum osmolality toward normal levels, clearing ketones from serum and urine at a steady rate, correcting electrolyte imbalances and acid base status, identifying precipitating factors.
The goals of therapy include:
1. Rehydratation.
2. Reduction of hyperglycemia.
3. Correction of: a) acid-base and b) electrolyte imbalance.
4. Investigation of precipitating factors, treatment of complications.
The most important factor to emphasize is the frequent monitoring of the patient both clinically and chemically. Initially, laboratory data should be obtained every 1 – 3 hours and less frequently once clinical improvement is noted.
Monitoring should include the following:
• Hourly (or more frequently as indicated) vital signs (heart rate, respiratory rate, blood pressure)
• Hourly (or more frequently as indicated) neurological observations for warning signs and symptoms of cerebral edema. The latter include:
◦ headache
◦ recurrence of vomiting
◦ change ieurological status (restlessness, irritability, increased drowsiness, incontinence) or specific neurologic signs (e.g., cranial nerve palsies, abnormal pupillary responses)
◦ inappropriate slowing of heart rate
◦ rising blood pressure
◦ decreased oxygen saturation
• Amount of administered insulin
• Hourly (or more frequently as indicated) accurate fluid input (including all oral fluid) and output.
• Capillary blood glucose should be measured hourly (but must be cross-checked against laboratory venous glucose, as capillary methods may be inaccurate in the presence of poor peripheral circulation and acidosis).
If the patient is in shock, stupor or coma;
• Secure the airway and empty the stomach by continuous nasogastric suction to prevent
pulmonary aspiration, in case there is deterioration in conscious level.
• A peripheral intravenous (IV) catheter should be placed for convenient and painless repetitive blood sampling. An arterial catheter may be necessary in some critically ill patients managed in an intensive care unit.
• Perform continuous electrocardiographic monitoring to assess T-waves for evidence of
hyper- or hypokalemia
• Give oxygen to patients with severe circulatory impairment or shock
• Give antibiotics to febrile patients after obtaining appropriate cultures of body fluids
• Catheterize the bladder if the child is unconscious or unable to void on demand (e.g., infants and very ill young children).
Frequent assessment of potassium status is vital. A lead II electrocardiogram (ECG) can be provide a rapid assessment of hyperkalemia (peaked T waves) and hypokalemia (flat T waves and presence of U waves). Hyporeflexia and ileus are clinical indications of potassium deficiency.
Careful observation of neurological status is vital to detect the infrequent but devastating presence of cerebral edema.
Additional calculations that may be informative:
· ◦ Anion gap = serum sodium(Na) – {serum chloride (Cl) + serum bicarbonate (HCO3)} : normal is 12 ± 2 (mmol/L). In DKA, the anion gap is typically 20–30 mmol/L; an anion gap >35 mmol/L suggests concomitant lactic acidosis.
· ◦ Corrected sodium = measured Na + 2([plasma glucose -5.6]/5.6) (mmol/L) The measured serum sodium concentration is an unreliable index of the degree of ECF contraction as glucose, largely restricted to the extracellular space, causes osmotic movement of water into the extracellular space thereby causing dilutional hyponatremia.
· ◦ Therefore, it is important to calculate the corrected sodium (using the above formula) and monitor its changes throughout the course of therapy. As the plasma glucose concentration decreases after administering fluid and insulin, the measured serum sodium concentration should increase (positive sodium load), but it is important to appreciate that this does not indicate a worsening of the hypertonic state. A failure of measured serum sodium levels to rise or a further decline in serum sodium levels with therapy is thought to be a potentially ominous sign of impending cerebral edema
· ◦ Effective osmolality (mOsm/kg)= 2x(Na + K) + glucose (mmol/L) The effective osmolality (formula above) is frequently in the range of 300–350 mOsm/Kg.
Rehydration (Fluid Replacement)
The severity of fluid and sodium deficits is determined primarily by the duration of hyperglycemia, the level of renal function and the patient’s fluid intake. Patients with DKA have a deficit in extracellular fluid (ECF) volume that usually is in the range 5–10%. Clinical estimates of the volume deficit are subjective and inaccurate, therefore, in moderate DKA use 5–7%and in severe DKA 7–10% dehydration.
The average fluid deficit in adults with DKA is 3 to
Dehydration can be estimated by clinical examination and by calculating total serum osmolality and the corrected serum sodium concentration. Total serum osmolality is calculated using the following equation:
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Total serum osmolality (mOsm per kg of water) |
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2 × measured serum sodium (mEq per L) |
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The measured serum sodium concentration can be corrected for the changes related to hyperglycemia by adding 1.6 mEq per L (1.6 mmol per L) to the measured sodium value for every 100 mg per dL (5.6 mmol per L) of glucose over the normal baseline of 100 mg per dL. Corrected serum sodium concentrations of greater than 140 mEq per L (140 mmol per L) and calculated total osmolalities of greater than 330 mOsm per kg of water are associated with large fluid deficits. Calculated total osmolalities are correlated with mental status, in that stupor and coma typically occur with an osmolality of greater than 330 mOsm per kg of water.
A rapid infusion of 0,9 % sodium chloride (e.g., 1 l/h for the first 1 to 2 hours) is given and then reduced to about 0,5 – 0,3 l/h if the blood pressure is stable and the urine follow is adequate. After the initial infusion, intravenous fluid therapy must be adjusted individually on the basis of urine output, clinical assessments of hydration and circulation, determination of plasma electrolytes and glucose. When serum glucose level is about 11 – 13 mmoll/ (approximately 250 mg per dL )l administration of 5 % glucose with insulin can be performed (1 to 2 unites of insulin on each 100 ml of 5 % glucose solution). The addition of glucose to the intravenous solution is necessary for correction of tissue lipolysis and acidosis. This allows continued insulin administration until ketonemia is controlled and also helps to avoid iatrogenic hypoglycemia.
Another important aspect of rehydration therapy in patients with diabetic ketoacidosis is the replacement of ongoing urinary losses.
Insulin treatment
Modern management of diabetic ketoacidosis has emphasized the use of lower doses of insulin.
This has been shown to be the most efficacious treatment in both children and adults with diabetic ketoacidosis. The current recommendation is to give low-dose (short-acting regular) insulin after the diagnosis of diabetic ketoacidosis has been confirmed by laboratory tests and fluid replacement has been initiated. Start insulin infusion 1–2 hours after starting fluid replacement therapy; i.e. after the patient has received initial volume expansion.
It is prudent to withhold insulin therapy until the serum potassium concentration has been determined. In the rare patient who presents with hypokalemia, insulin therapy may worsen the hypokalemia and precipitate life-threatening cardiac arrhythmias.
E.g., initial intravenous administration of 10 to 20 units of regular insulin followed by continuous intravenous infusion of 0,1 unit/kg/hour in 0,9 % sodium chloride infusion. (50 units of insulin can be added to a 500 ml bottle of 0,9 % sodium chloride solution to give 1 insulin unite/10 ml of solution.) The dose of insulin should usually remain at 0.1unit/kg/hour at least until resolution of DKA (pH >7.30, bicarbonate >15 mmol/L and/or closure of the anion gap), which invariably takes longer thaormalization of blood glucose concentrations (when the blood glucose level is approximately 11 – 13 mmoll/L (250 mg per dL)). If the patient demonstrates marked sensitivity to insulin (e.g., some young children with DKA, patients with HHS), the dose may be decreased to 0.05 unit/kg/hour, or less, provided that metabolic acidosis continues to resolve.
In circumstances where continuous IV administration is not possible, hourly or 2-hourly subcutaneous (SC) or intramuscular (IM) administration of a short- or rapid-acting insulin analog (insulin lispro or insulin aspart) in dose is 0.3 unit per kg is safe and may be as effective as IV regular insulin infusion, but should not be used in subjects whose peripheral circulation is impaired.
If the blood glucose concentration does not fall by 2.8 to 3.9 mmol per L (50 to 70 mg per dL) in the first hour, the intravenous infusion rate should be doubled or additional intravenous 10-unit boluses of insulin should be given every hour. Either of these treatments should be continued until the blood glucose level falls by 2.8 to 3.9 mmol per L (50 to 70 mg per dL). Low-dose insulin therapy typically produces a linear fall in the glucose concentration of 2.8 to 3.9 mmol per L (50 to 70 mg per dL). If biochemical parameters of DKA (pH, anion gap) do not improve, reassess the patient, review insulin therapy, and consider other possible causes of impaired response to insulin; e.g., infection, errors in insulin preparation.
More rapid correction of hyperglycemia should be avoided because it may increase the risk of cerebral edema. This dreaded treatment complication occurs in approximately 1 percent of children with diabetic ketoacidosis. Cerebral edema is associated with a mortality rate of up to 70 percent.
But if there is a tendency for decreasing the level of glycemia we have to decrease the dose of insulin in two times.
The fall of blood glucose should not exceed 5,5 mmol (100 mg) per hour or when the serum glucose concentration reaches 11-13 mmol/l, hourly insulin dosage can be reduced to 0.05 unit per kg per hour or insulin can be given subcutaneously (if plasma and urine persistently negative for ketones). Blood glucose level should be maintained at about 11 mmol/l during intravenous therapy.
To prevent an unduly rapid decrease in plasma glucose concentration and hypoglycemia, 5% glucose should be added to the IV fluid (e.g., 5% glucose in 0.45% saline) when the plasma glucose falls to approximately 14-17 mmol/l (250–300 mg/dL), or sooner if the rate of fall is precipitous.
Improvement usually is noted in 8 – 24 hours. Following stabilization of the clinical condition, patients are placed in insulin regimen consisting of five injections of regular insulin.
Treatment of electrolyte disorders.
Intracellular potassium is depleted because of the following factors:
· increased plasma osmolality drags water and potassium out of cells
· glycogenolysis and proteolysis secondary to insulin deficiency cause potassium efflux from cells
· Potassium is lost from the body from vomiting and as a consequence of osmotic diuresis.
· Volume depletion causes secondary hyperaldosteronism, which promotes urinary potassium excretion.
Despite potassium depletion, at presentation, serum potassium levels may be normal, increased or decreased. Renal dysfunction, by enhancing hyperglycemia and reducing potassium excretion, contributes to hyperkalemia. Administration of insulin and the correction of acidosis will drive potassium back into the cells, decreasing serum levels. The serum potassium concentration may decrease abruptly, predisposing the patient to cardiac arrhythmias.
As a rule, potassium should never be given until the state of renal function is known and until the serum potassium concentration is available.
Although the typical potassium deficit in diabetic ketoacidosis is 500 to 700 mEq (500 to 700 mmol), most patients are hyperkalemic at the time of diagnosis because of the effects of insulinopenia, hyperosmolality and acidemia. During rehydration and insulin therapies for diabetic ketoacidosis, the serum potassium concentration typically declines rapidly as potassium reenters the intracellular compartment.
The initiation of K replacement (20 to 40 mmol/h) usually can be deferred for 2 hours, using hourly serum measurements as a guide.Potassium would be to infuse at a rate of ml of 1,5 g/h during 3 – 5 hours.
The goal is to maintain the serum potassium concentration in the range of 4 to 5 mEq per L (4 to 5 mmol/L).
Correction of metabolic acidosis.
The metabolic acidosis occurs due to insulin deficiency and dehydration. So ketone bodies are themselves metabolized to bicarbonate once proper therapy is begun (fluids, electrolytes, insulin) and exogenous administration of bicarbonate can overcorrect to alkalosis.
The use of bicarbonate can be recommended only in the following cases:
– if life-threatening hyperkalemia;
– when severe lactic acidosis complicates DKA;
– with severe acidosis (pH<6.9), especially when complicated by shock that is not responsive to appropriate fluid resuscitative measures in an attempt to improve cardiac output. 100 mmol sodium bicarbonate (two ampules) in 400 ml sterile water (an isotonic solution) with 20 mEq KCI administered at a rate of 200 ml/h for 2 h until the venous pH is >7.0. If the pH is still <7.0 after this is infused, we recommend repeating infusion every 2 h until pH reaches >7.0.
Phosphate correction
Phosphate is lost as a result of osmotic diuresis in DKA. Plasma phosphate levels fall after starting treatment by insulin, which promotes entry of phosphate into cells. Prospective studies have not shown clinical benefit from phosphate replacement. Severe hypophosphatemia in conjunction with unexplained weakness should be treated. Administration of phosphate may induce hypocalcemia. Potassium phosphate salts may be safely used as an alternative to or combined with potassium chloride or acetate, provided that careful monitoring of serum calcium is performed to avoid hypocalcemia
Other therapeutic consideration:
– since infection is one of the leading precipitating events of DKA, it should be looked for and, if found, treated appropriately;
– vascular thrombosis (it is secondary to severe dehydration, high serum viscosity, and low cardiac output) – heparin (5000 unites 4 times a day);
– vascular collapse can be treated by mesatone (1 – 2 ml); glucocorticoides (dexametasone 4 mg two times a day). You must remember that development of vascular collapse after initiation of therapy should suggest the presence of gram-negative sepsis or silent myocardial infarction;
– cerebral edema (It is a rare and frequently fatal complication. Some physicians believe that rapid osmotic reduction of plasma glucose should be avoided to minimize rapid osmotic changes. Some patients have premonitory symptoms (e.g., sudden headache, rapid decrease in the level of consciousness), but in others acute respiratory arrest is the initial manifestation. If cerebral edema is diagnosed, therapeutic maneuvers might include the use of : mannitol (1 – 2 g/kg intravenous over 20 min), dexametasone (0,25 – 0,50 mg/kg/day divided q 4 – 6 h). But they are usually ineffective after the onset of respiratory arrest.
Introduction of oral fluids and transition to SC insulin injections
In patients who are unable to eat, 5 percent dextrose in hypotonic saline solution is continued at a rate of 100 to 200 mL per hour. Blood glucose levels are monitored every four hours, and regular insulin is given subcutaneously every four hours using a sliding scale. When patients are able to eat, multidose subcutaneous therapy with both regular (short-acting) and intermediate-acting insulin may be given.
Oral fluids should be introduced only when the clinical condition has become stable, however mild acidosis/ketosis may still be present. When oral fluid is tolerated, IV fluid should be reduced and change to SC insulin is planned. To prevent rebound hyperglycemia the first SC injection should be given 15–30 minutes (with rapid acting insulin) or 1–2 hours (with regular insulin) before stopping the insulin infusion to allow sufficient time for the insulin to be absorbed. With intermediate- or long-acting insulin, the overlap should be longer and the IV insulin gradually lowered. For example, for patients on a basal-bolus insulin regimen, the first dose of basal insulin may be administered in the evening and the insulin infusion is stopped the next morning. After transitioning to SC insulin, frequent blood glucose monitoring is required to avoid marked hyperglycemia and hypoglycemia.
Immediate Posthyperglycemic Care
In patients with newly diagnosed diabetes, an initial total insulin dosage of 0.6 to 0.7 unit per kg per day is usually adequate to achieve metabolic control. A typical regimen is two thirds of the total daily dosage before breakfast and one third of the total daily dosage before dinner, with the insulin doses consisting of two-thirds NPH (intermediate-acting) insulin and one-third regular (short-acting) insulin.
Patients with known diabetes can typically be given the dosage they were receiving before the onset of diabetic ketoacidosis.
Morbidity and mortality from DKA
Cerebral edema accounts for 60% to 90% of all DKA deaths. Ten % to 25% of survivors of cerebral edema have significant residual morbidity. Other rare causes of morbidity and mortality include:
• Hypokalemia
• Hyperkalemia
• Severe hypophosphatemia
• Hypoglycemia
• Other central nervous system complications (disseminated intravascular coagulation, dural sinus thrombosis, basilar artery thrombosis)
• Peripheral venous thrombosis
• Sepsis
• Rhinocerebral or pulmonary mucormycosis
• Aspiration pneumonia
• Pulmonary edema
• Pneumothorax, pneumomediastinum and subcutaneous emphysema
• Rhabdomyolysis
• Acute renal failure
• Acute pancreatitis
Adult respiratory distress syndrome (ARDS) is a rare but potentially fatal complication of the treatment of diabetic ketoacidosis. Excessive crystalloid infusion favors the development of pulmonary edema, even in the presence of normal cardiac function. Patients with an increased alveolar to arterial oxygen gradient (AaO2) and patients with pulmonary rales on physical examination may be at increased risk for ARDS. Monitoring of oxygen saturation with pulse oximetry may assist in the management of such patients.
Hyperchloremic metabolic acidosis with a normal anion gap typically persists after the resolution of ketonemia. This acidosis has no adverse clinical effects and is gradually corrected over the subsequent 24 to 48 hours by enhanced renal acid excretion. The severity of hyperchloremia can be aggravated by excessive chloride administration in hydration fluids.
Cerebral edema is responsible for the majority of deaths related to, and significant neurologic morbidity persists in many of the survivors. The incidence of cerebral edema is 0.5–0.9% and the mortality rate is 21–24%.The pathogenesis of both its initiation and progression is unclear and incompletely understood, although a number of mechanisms have been proposed. These include cerebral ischemia and hypoxia, fluid shifts caused by inequalities in osmolarity between the extravascular and intravascular intracranial compartments, increased cerebral blood flow, and altered membrane ion transport. Factors that have been associated with an increased risk of cerebral edema include:
1. Epidemiological factors
a. Newly diagnosed cases
b. Young age: < 5 years old
c. Longer duration of symptoms
d. Prolonged illness
e. Extended history of poor metabolic control
2. Features at presentation
a. Severe acidosis (initial pH < 7.1)
b. Greater hypocapnia after adjusting for degree of acidosis
c. High Blood urea nitrogen
d. Severe dehydration
e. Abnormal mental status
3. Therapeutic interventions
a. Rapid rehydration (> 50cc/ kg in first 4 hrs)
b. Bicarbonate therapy for correction of acidosis
c. Insulin administration in the first hour of therapy
4. Changes in biochemical values during treatment
a. Severe Hypernatremia
b. Persistent hyponatremia
c. An attenuated rise in measured serum sodium concentrations during therapy
d. Non closure of the anion gap
Warning signs and symptoms of cerebral edema include:
· Headache & slowing of heart rate
· Change ieurological status (restlessness, irritability, increased drowsiness, incontinence)
· Specific neurological signs (e.g., cranial nerve palsies)
· Rising blood pressure
· Decreased oxygen saturation
Clinically significant cerebral edema usually develops 4–12 hours after treatment has started, but can occur before treatment has begun or, rarely, may develop as late as 24–48 hours after the start of treatment.
Symptoms and signs are variable. A method of clinical diagnosis based on bedside evaluation of neurological state is shown below :
Diagnostic criteria
· Abnormal motor or verbal response to pain
· Decorticate or decerebrate posture
· Cranial nerve palsy (especially III, IV, and VI)
· Abnormal neurogenic respiratory pattern (e.g., grunting, tachypnea, Cheyne-Stokes respiration, apneusis)
Major criteria
· Altered mentation/fluctuating level of consciousness
· Sustained heart rate deceleration (decrease more than 20 beats per minute) not attributable to improved intravascular volume or sleep state
· Age-inappropriate incontinence
Minor criteria
· Vomiting
· Headache
· Lethargy or not easily arousable
· Diastolic blood pressure >
· Age <5 years
One diagnostic criterion, two major criteria, or one major and two minor criteria have a sensitivity of 92% and a false positive rate of only 4%. A chart with the reference ranges for blood pressure and heart rate, which vary depending on height, weight, and gender, should be readily available, either in the patient’s chart or at the bedside.
Treatment of cerebral edema
· Start as early as you suspect the condition, do not delay treatment until radiographic evidence
· Transfer to the ICU (if not already there)
· Restrict IV fluids to 2/3 maintenance and replace deficit over 72 hr rather than 24 hr
· Give mannitol 0.5-1 g/kg IV (2.5 ml/kg of 20% solution) over 20 minutes and repeat after 6 hours, if there is no initial response in 30 minutes to 2 hours
· Hypertonic saline (3%), 5-10 mL/kg over 30 minutes, may be an alternative to mannitol or a second line of therapy if there is no initial response to mannitol
· Elevate the head of the bed
· Intubation may be necessary for the patient with impending respiratory failure, but aggressive hyperventilation (to a pCO2 <2.9 kPa [22 mm Hg]) has been associated with poor outcome and is not recommended.
· After treatment for cerebral edema has been started, a cranial CT scan should be obtained to rule out other possible intracerebral causes of neurologic deterioration (10% of cases), especially thrombosis or hemorrhage, which may benefit from specific therapy.
Prevention of recurrent DKA
Home measurement of blood ß –OHB concentrations, when compared to urine ketone testing, decreases diabetes-related hospital visits (both emergency department visits and hospitalizations) by the early identification and treatment of ketosis. Blood ß -OHB measurements may be especially valuable to prevent DKA in patients who use a pump because interrupted insulin delivery rapidly leads to ketosis. There may be dissociation between urine ketone (sodium nitroprusside only measures acetoacetate and acetone) and serum ß -OHB concentrations, which may be increased to levels consistent with DKA when a urine ketone test is negative or shows only trace or small ketonuria. A psychiatric social worker or clinical psychologist should be consulted to identify the psychosocial reason(s) contributing to development of DKA. Insulin omission can be prevented by schemes that provide education, psychosocial evaluation and treatment combined with adult supervision of insulin administration. Diabetes education of the child and his/her family is the cornerstone to prevent DKA occurrence and recurrence.
NonketoTic hyperglycemic–hyperosmolar coma (NKHHC or HNC)
HNC is a syndrome characterized by impaired consciousness, sometimes accompanied by seizures, extreme dehydration, , and extreme hyperglycemia that is not accompanied by ketoacidosis.
The syndrome usually occurs in patients with type II DM, who are treated with a diet or oral hypoglycemic agents, sometimes it is a complication of previously undiagnosed or medically neglected DM (type II).
In contrast to ketoacidosis, mortality in patients with HNC has been very high (50 %) in most series. Mortality has been associated with convulsions, deep vein thrombosis, pulmonary embolus, pancreatitis and renal failure. Death is usually due to an associated severe medical condition and not to the hyperosmolality.
The pathophysiology of HNC is similar to that of ketoacidosis, except that ketoacids do not accumulate in the blood. The reason of this phenomenon is unclear. Initially it was thought that patients with HNC produced enough insulin to prevent lipolysis and ketogenesis but not enough to prevent hyperglycemia. The concept was invalidated by finding similar inappropriately low plasma insulin concentrations in patients with the two syndromes. The finding of lower plasma free fatty acids, as well as cortisol and growth-hormone concentrations, in patients with ketoacidosis has raised the possibility that the absence of ketosis may be the result of decreased cortisol and growth-hormone effects on lipolysis. Suppression of lipolysis by hyperosmolality also has been proposed.
HNC usually develops after a period of symptomatic hyperglycemia in which fluid intake is inadequate to prevent extreme dehydration from the hyperglycemia-induced osmotic diuresis.
Predisposing factors.
1. HNC seems to occur spontaneously in about 5 – 7 % of patients.
2. In 90 % of patients some degree of renal insufficiency seems to coexist.
3. Infection (e.g., pneumonia, urinary tract infection, gram-negative sepsis) is underlying frequent precipitating cause.
4. Use of certain drugs has been associated with this condition:
– steroids increase glucogenesis and antagonize the action of insulin;
– potassium-wasting diuretics (hypokalemia decreases insulin secretion), e.g., thiazides, furosemide;
– other drugs, e.g., propranolol, azathioprine, diazoxide.
5. Other medical conditions such as cerebrovascular accident, subdural hematoma, acute pancreatitis, and severe burns have been associated with HNC.
6. Use of concentrated glucose solutions, such as used in peripheral hyperalimentation or renal dialysis, has been associated with HNC.
7. HNC can be induced by peritoneal or hemodialysis, tube feeding.
8. Endocrine disorders such as acromegaly, Cushing disease, and thyrotoxicosis have also been associated with HNC.
Clinical presentation
Signs and symptoms.
1. Polyuria, polydipsia, weight loss, weakness and progressive changes in state of consciousness from mental cloudiness to coma (present in 50 % of patients) occur over a number of days to weeks.
2. Because other underlying conditions (such as cerebrovascular accident and subdural hematoma) can coexist, other causes of coma should be kept in mind, especially in the elderly.
3. Neurologic changes: drowsiness and lethargy, delirium, coma, focal or generalized seizures, visual changes or disturbances, hemiparesis, sensory deficits.
Physical examination.
1. Severe dehydration is invariably present.
2. Various neurologic deficits (such as coma, transient hemiparesis, hyperreflexia, and generalized areflexia) are commonly present. Altered states of consciousness from lethargy to coma are observed.
3. Findings associated with coexisting medical problems (e.g., renal disease, cardiovascular disease) may be evident.
Laboratory findings.
1. Extreme hyperglycemia (blood glucose levels from 30 mmoll/l and over are common.
2. A markedly elevated serum osmolality is present, usually in excess of 350 mOsm/l. (
3. The initial plasma bicarbonate averaged.
4. Serum ketones are usually not detectable, and patients are not acidic.
5. Serum sodium may be high (if severe degree of dehydration is present), normal, or high (when the marked shift of water from the intracellular to the extracellular space due to the marked hyperglycemia is present).
Serum potassium levels may be high (secondary to the effects of hyperosmolality as it draws potassium from the cells), normal, or low (from marked urinary losses from the osmotic diuresis). But potassium deficiency exists.
Differential diagnoses
Any condition that can cause altered mental status should be considered, including the following:
– Central nervous system infection
– Hypoglycemia
– Hyponatremia
– Severe dehydration
– Uremia
– Hyperammonemia
– Intoxication (eg, with ethanol, narcotics, other drugs)
– Sepsis
– Change in mental status or level of consciousness
– Postictal state
– Arrhythmia
– Hypotension
– Other causes of dehydration
– Acute blood loss (gastrointestinal or other)
– Polyuria
– Excessive diuretic use
– Diabetes Insipidus
– Diabetic Ketoacidosis
– Myocardial Infarction
– Pulmonary Embolism
Treatment
This condition is a medical emergency and the patient should be placed in an intensive care unit.
Many of the management techniques recommended for a patient with DKA are applicable here as well.
The goals of therapy include:
– rehydration;
– reduction of hyperglycemia;
– electrolytes replacement;
– investigation of precipitating factors, treatment of complications.
Diabetes Care January 2004 vol. 27 no. suppl 1 s94-s102
Rehydration.
The average fluid deficit is
Treatment is starting by infusion 1 to
0,45 % sodium chloride is used at a rate of 150 to 500 ml/hour depending on the state of hydration, previous clinical response and the balance between fluid input and output. The aim of this phase of intravenous fluid therapy is not to attempt to rapidly correct the total fluid deficit or the hyperosmolality, but rather to maintain stable circulation and renal function and to progressively replenish water and sodium at rates that do not threaten or cause acute fluid overload.
At a serum osmolality below 320 mOsm/kg, the IV fluids may again be switched to 0.9% isotonic saline. When the blood glucose concentration, initially checked hourly, reaches 300 (or, as some prefer, 250) mg/dL, change the infusion to 5% dextrose in 0.9% isotonic saline again. This helps prevent a precipitous fall of glucose, which may be associated with cerebral edema.
Generally, half of the loss is replaced in the first 12 hours and the rest in the subsequent 24 hours.
Insulin therapy.
All patients with HHS require IV insulin therapy; however, immediate treatment with insulin is contraindicated in the initial management of patients with HHS. The osmotic pressure that glucose exerts within the vascular space contributes to the maintenance of circulating volume in these severely dehydrated patients. Institution of insulin therapy drives glucose, potassium, and water into cells. This results in circulatory collapse if fluid has not been replaced first.
After the kidneys show evidence of being perfused, initiating insulin therapy is safe. This is accomplished most effectively in the ICU, where cardiovascular and respiratory support is available if needed. Infuse insulin separately from other fluids, and do not interrupt or suspend the infusion of insulin once therapy is started.
Insulin treatment in HNC is started by 10 to 20 unites of regular insulin intravenously as a bolus dose prior to starting the insulin infusion and then giving intravenously regular insulin in a dose of 0,05 – 0,10 unites/kg/hour (many authorities routinely use the same insulin treatment regimens as for treating DKA, other authorities recommend smaller doses of insulin, because they believe that patients with type 2 DM are offer very sensitive to insulin, but this view is not universally accepted, and many obese type 2 diabetics with HNC require larger insulin doses to induce a progressive decrease in their marked hyperglycemia. It is important to remember that because of insulin therapy causes blood glucose levels to fall, water shifts into the cells and existing hypotension and oliguria can further aggravated. Thus, initially some advocate delaying insulin therapy while infusioormal saline until vital signs have improved.
The following steps may be used as a guideline for insulin infusion:
Begin a continuous insulin infusion of 0.1 U/kg/h
Monitor blood glucose by means of bedside testing every hour; if glucose levels are stable for 3 hours, decrease the frequency of testing to every 2 hours
Set the target blood glucose level at 250-300 mg/dL (14-16 mmol/l); this target level may be adjusted downward after the patient is stabilized
For a blood glucose concentration lower than 250 mg/dL (14 mmol/l), decrease the insulin infusion rate by 0.5 U/h
For a blood glucose concentration of 250-300 mg/dL (14-16 mmol/l), do not change the insulin infusion rate.
For a blood glucose concentration of 301-350 mg/dL (16-20 mmol/l), increase the insulin infusion rate by 0.5 U/h
For a blood glucose concentration higher than 350 mg/dL (20 mmol/l), increase the insulin infusion rate by 1 U/h
Do not discontinue the insulin drip
If the blood glucose concentration decreases by more than 100 mg/dL (5,5 mmol/l) between consecutive readings, wait to increase the insulin infusion rate
When the plasma glucose reaches the range 11 to 13 mmoll/l, 5 % glucose should be added to the intravenous fluids to avoid the risk of hypoglycemia. Following recovery the acute episode, patients are usually switched to adjusted doses of subcutaneous regular insulin at 4 to 6-hour intervals. When they are able to eat, this is changed to a 1 or 2 injection regimen.
Treatment of electrolyte disorders.
Profound potassium depletioecessitates careful replacement. With rehydration, the potassium concentration is diluted. With the institution of insulin therapy, potassium is driven into cells, exacerbating hypokalemia. A precipitous drop in the potassium concentration may lead to cardiac arrhythmia.
Potassium may be added to the infusion fluid and should be started at a level of 5 mEq/L or less. Hypokalemia at the onset of rehydration requires up to 60 mEq/L to correct the serum potassium concentration. Check the potassium level at least every 4 hours until the blood glucose concentration is stabilized.
Phosphate, magnesium, and calcium are not replaced routinely, but a patient who is symptomatic with tetany requires replacement therapy.
.
Lactic acidosis (LA)
Lactic acidosis is a physiological condition characterized by low pH in body tissues and blood (acidosis) accompanied by the buildup of lactate, especially D-lactate, and is considered a distinct form of metabolic acidosis. DM is one of the major causes of LA, a serious condition characterized by excessive accumulation of lactic acid and metabolic acidosis.
Lactic acid exists in 2 optical isomeric forms, L-lactate and D-lactate.
L-lactate is the most commonly measured level, as it is the only form produced in human metabolism. Its excess represents increased anaerobic metabolism due to tissue hypoperfusion.
D-lactate is a byproduct of bacterial metabolism and may accumulate in patients with short-gut syndrome or in those with a history of gastric bypass or small-bowel resection.[
There are primarily 2 types of lactic acidosis by Cohen and Woods:
Type A Lactic Acidosis
Most cases of lactic acidosis are due to reduced oxygen delivery as a result of reduced tissue perfusion from shock or cardiopulmonary arrest. Other conditions such as acute pulmonary edema, can cause severe hypoxemia leading to reduced O2 delivery. Other causes are carbon monoxide poisoning and severe anemia. Other causes of type A lactic acidosis which may not necessarily involve generalized tissue hypoxia are severe seizure, severe exercize and hypothermic shivering. All of which result in localized skeletal muscle hypoxia leading to increased lactic acid production.
In cases of underutilization of lactate, liver disease, gluconeogenesis inhibition, thiamine deficiency, and uncoupled oxidative phosphorylation can be responsible.
The clinical signs usually indicate reduced tissue perfusion and include severe hypotension, tachypnea, oliguria or anuria, peripheral vasoconstriction and deteriorating mental status. Sepsis, particularly in critically ill patients is a very important cause of lactic acidosis and is often associated with fever (>
Type B is lactic acidosis occurring wheo clinical evidence of poor tissue perfusion or oxygenation exists. However, in many cases of type B lactic acidosis, occult tissue hypoperfusion is now recognized to accompany the primary etiology.
Type B is divided into 3 subtypes based on underlying etiology.
Type B1 occurs in association with systemic disease, such as renal and hepatic failure, diabetes and malignancy.
Type B2 is caused by several classes of drugs and toxins, including biguanides, alcohols, iron, isoniazid, zidovudine, and salicylates.
Type B3 is due to inborn errors of metabolism.
Typical picture includes acute onset after nausea and vomiting, altered state of consciousness and hyperventilation. Laboratory findings are variable depending on underlying cause.
The several different causes of lactic acidosis include:
· Genetic conditions
o Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)
o Diabetes mellitus and deafness
o Glucose-6-phosphatase deficiency
o Fructose 1,6-diphosphatase deficiency
o Pyruvate dehydrogenase deficiency
o Pyruvate carboxylase deficiency
· Drugs
o Phenformin
o Metformin
o Isoniazid toxicity
o Nucleoside reverse transcriptase inhibitors
o Potassium cyanide (cyanide poisoning)
· Other
o Hypoxia and hypoperfusion
o Hemorrhage
o Ethanol toxicity
o Sepsis
o Shock
o Hepatic disease
o Diabetic ketoacidosis
o Muscular exercise
o Regional hypoperfusion (bowel ischemia, marked cellulitis…)
o Non-Hodgkin’s and Burkitt lymphomas
The hallmark of LA is the presence of tissue hypoxemia, which leads to enhanced anaerobic glycolysis and to increased lactic acid formation.
Piruvic acid is converted into lactic acid by lactic dehydrogenase (LDH) in the presence of reduced nicotinamide adenine dinucleotide (NADH), which, in turn, is converted into NAD. The reaction is reversible and involves LDH in both directions. The conversion of acetoacetic acid into beta-hydroxybutyric acid also requires the oxydation of NADH. LA results from decreased availability of NAD caused by lack of oxygen. Likewise, the deficiency of NAD impairs the conversion of beta-hydroxybutyric into acetoacetic acid. Thus, LA predisposes to accumulation of beta-hydroxybutyric acid, which does not react with acetest tablet, so, the reaction for ketone bodies may be negative or slightly positive. The normal blood lactic acid concentration is 1mmol/l, and the pyruvic to lactic ratio is 10:1. An increase in lactic acid without concomitant rise in pyruvate leads to LA of clinical importance.
Predisposing factors
1. Heart and pulmonary failure (which leads to hypoxia).
2. Alcohol intoxication.
3. Ketoacidosis (it is important to have a very high index of suspection with respect to presence of LA).
4. Sepsis
5. Usage of bigyanides, pheformin therapy. The incidence of metformin-associated lactic acidosis (MALA) is rare, estimated at 2–9 patients per 100,000 patients receiving metformin per year; MALA accounts for approximately 1% of total patients admitted to intensive care units.
Clinical presentation
Signs and symptoms.
1. Kussmaul breathing (deep, sighing respiration) is present as respiratory compensation for the metabolic acidosis and is obvious when the pH is less than 7.2.
2. Symptoms of central-nervous-system involvement include headaches, drowsiness, lassitude.
3. Anorexia, nausea, vomiting, and abdominal pain may be present.
4. Myalgia is common.
Physical examination.
1. Acrocyanosis is common.
2. Tachycardia frequently is present, blood pressure is decreased.
3. Poor skin tugor and dry skin may be prominent.
4. Hypothermia is common in LA (because sepsis accounts for most cases of lactic acidosis, fever (>
5. Alteration in sensorium
6. Peripheral vasoconstriction
7. Oliguria
8. Hyperpnea or Kussmaul respiration are present and related to degree of acidosis.
9. Deteriorating mental status
4. Findings associated with coexisting medical problems (e.g., renal disease, cardiovascular disease) may be evident.
Laboratory findings
1. Blood glucose level is not high
2. Glucosurea is absent.
3. Blood lactic acid is high.
The use of lactate as an index of tissue perfusion has several limitations. The presence of liver disease causes a decreased ability to clear lactate during periods of increased production. Various causes of type B lactate acidosis may produce hyperlactemia and lactate acidosis in the absence of tissue perfusion. For significant increase in blood lactate to occur, lactate must be released into the systemic circulation and the rate of production must exceed hepatic, renal, and skeletal muscle uptake. Therefore, regional hypoperfusion of tissues may be present despite normal blood lactate concentrations.
Lactic acid levels can also lag several hours after the oxygen delivery critical threshold (DO2 crit) has been crossed. Indeed, patients may be accruing a significant amount of oxygen debt before lactate levels start to increase. It has been demonstrated that mixed venous saturation can fall below 50% before serum hyperlactatemia is evident.
Treatment
· LA is treated by correcting the underlying cause.
· In severe cases, bicarbonate therapy should be used.
The starting dose of sodium bicarbonate (NaHCO3–) is one third to one half of the calculated extracellular bicarbonate (HCO3–) deficit, as illustrated by the following formula:
HCO3 deficit (in mEq) = 0.5 × (Wt in kg) × (Desired HCO3 – Measured HCO3)
Metabolic alkalosis can ensue after bicarbonate administration if the correction is complete rather than partial. This result can be avoided by titration of the bicarbonate dose to modest therapeutic end points (eg, arterial pH of 7.20). In severe hypoxemia, sodium bicarbonate should be administered by slow infusion to minimize any increase in central venous carbon dioxide tension (PvCO2). Minute ventilation must be increased in order to expel carbon dioxide (CO2) generated by bicarbonate administration. Because of increased CO2 production, sodium bicarbonate may precipitate ventilatory failure and, as such, must be given with caution.
· LA can be treated with low dose insulin regimens with 5 % glucose solution infusion.
· Volume expanders and oxygen therapy are helpful treatment as well.
· The use of intermittent hemodialysis may be protective, and it is recommended by many intensivists
· Thiamine deficiency may be associated with cardiovascular compromise and lactic acidosis. The response to thiamine repletion (given as 50-100 mg intravenously [IV] followed by 50 mg/d orally [
Comparison of DCA, HNC and LA.
|
|
DKA |
HNC |
LA |
|
Age |
Below 40 |
Above 40 |
Above 40 |
|
Type of DM |
Type I |
Type II |
Type II |
|
Predisposing factor |
Insulin deficiency |
Dehydration |
Hypoxia |
|
Prodromes |
Several days duration or less than 1 day |
Several days duration |
Less than 1 day |
|
Underlying renal, cardiovascular or pulmonary disease |
About 15 % |
About 85 % |
About 90 % |
|
General |
More acidic and less dehydrated, hyperventilation |
More dehydrated and less acidic, no hyperventilation |
More acidic and less dehydrated, hyperventilation |
|
Neurologic symptoms and signs |
Rare |
Very common |
Very common |
|
Laboratory findings – blood glucose |
High (about 20 – 30 mmoll/l) |
Very high (about 40 – 50 mmoll/l) |
Normal or about 10 – 11 mmoll/l |
|
– plasma ketones |
+ |
– |
– |
|
– serum sodium |
|
|
|
|
– serum potassium |
|
|
|
|
– serum bicarbonate |
Low |
|
Low |
|
– blood pH |
Less than 7,35 |
|
Less than 7,35 |
|
– serum osmolality |
Less than 330 mOsm/l |
Over 350 mOsm/l |
|
|
– free fatty acids |
↑ |
↓ or normal |
|
|
Complications: – Thrombosis – Mortality |
Rare 1 – 10 % |
Frequent 20 – 50 % |
Very rare About 90 % |
|
Diabetes treatment after recovery |
Always insulin |
Diet alone or oral agents, sometimes insulin |
Diet alone or oral agents, sometimes insulin |
Hypoglycemia
It is a syndrome characterized by symptoms of sympathetic nervous system stimulation or central nervous system dysfunction that are provoked by an abnormally low plasma glucose level. The modern definition of hypoglycemia is plasma glucose <70 mg/dl.
At plasma glucose below this threshold (60–65 mg/dl), the brain becomes neuroglycopenic and promotes secretion of counterregulatory hormones, primarily the adrenomedullary adrenaline and the neurotransmitter norepinephrine (along with glucagons, the “rapid” responses), which have relevant cardiovascular effects. This occurs in the absence of the warning symptoms of hypoglycemia, which normally occur at lower plasma glucose (60 mg/dl). If (even mild) hypoglycemia episodes recur often over time (e.g., once a day), the brain adapts to hypoglycemia with symptom responses at a lower-than-usual plasma glucose concentration. This shifting of brain glucose thresholds to higher levels (i.e., it takes a lower plasma glucose to activate symptom responses) is dangerous because it masks most of the mild hypoglycemia episodes until blood glucose decreases to 50 mg/dl. In turn, failure to sense symptoms of hypoglycemia in an early phase (hypoglycemia unawareness) increases the risk of prolonging duration and increasing frequency of hypoglycemia. These events perpetrate a deleterious vicious circle leading to an increase in severe hypoglycemia with brain dysfunction. The response of adrenaline (and norepinephrine) in individuals with hypoglycemia unawareness is lower than in aware subjects, a finding that might be of cardiovascular protection.
Causes:
1. complication of treatment of diabetes mellitus with insulin or oral medications,
2. excessive insulin produced in the body (hyperinsulinemia),
3. inborn error of metabolism,
4. medications and poisons,
5. alcohol,
6. hormone deficiencies,
7. prolonged starvation,
8. alterations of metabolism associated with infection, and organ failure.
Thereare 3 categories of clinical hypoglycemia: (1) fasting, (2) reactive or postprandial, and (3) drug-related.
Fasting hypoglycemia is defined as the inability to maintain glucose homeostasis in the postabsorptive, or fasting, state.
Causes of fasting hypoglycemia include certain medications, alcoholic beverages, critical illnesses, hormonal deficiencies, some kinds of tumors, and certain conditions occurring in infancy and childhood.
Medications. Medications, including some used to treat diabetes, are the most common cause of hypoglycemia. Other medications that can cause hypoglycemia include
· salicylates, including aspirin, when taken in large doses
· sulfa medications, which are used to treat bacterial infections
· pentamidine, which treats a serious kind of pneumonia
· quinine, which is used to treat malaria
If using any of these medications causes a person’s blood glucose level to fall, the doctor may advise stopping the medication or changing the dose.
Alcoholic beverages. Drinking alcoholic beverages, especially binge drinking, can cause hypoglycemia. The body’s breakdown of alcohol interferes with the liver’s efforts to raise blood glucose. Hypoglycemia caused by excessive drinking can be serious and even fatal.
Critical illnesses. Some illnesses that affect the liver, heart, or kidneys can cause hypoglycemia. Sepsis, which is an overwhelming infection, and starvation are other causes of hypoglycemia. In these cases, treating the illness or other underlying cause will correct the hypoglycemia.
Hormonal deficiencies. Hormonal deficiencies may cause hypoglycemia in very young children, but rarely in adults. Shortages of cortisol, growth hormone, glucagon, or epinephrine can lead to fasting hypoglycemia. Laboratory tests for hormone levels will determine a diagnosis and treatment. Hormone replacement therapy may be advised.
Tumors. Insulinomas are insulin-producing tumors in the pancreas. Insulinomas can cause hypoglycemia by raising insulin levels too high in relation to the blood glucose level. These tumors are rare and do not normally spread to other parts of the body. Laboratory tests can pinpoint the exact cause. Treatment involves both short-term steps to correct the hypoglycemia and medical or surgical measures to remove the tumor.
Conditions occurring in infancy and childhood. Children rarely develop hypoglycemia. If they do, causes may include the following:
· Brief intolerance to fasting, often during an illness that disturbs regular eating patterns. Children usually outgrow this tendency by age 10.
· Hyperinsulinism, which is the overproduction of insulin. This condition can result in temporary hypoglycemia iewborns, which is common in infants of mothers with diabetes. Persistent hyperinsulinism in infants or children is a complex disorder that requires prompt evaluation and treatment by a specialist.
· Enzyme deficiencies that affect carbohydrate metabolism. These deficiencies can interfere with the body’s ability to process natural sugars, such as fructose and galactose, glycogen, or other metabolites.
· Hormonal deficiencies such as lack of pituitary or adrenal hormones.
Reactive (postprandial) hypoglycemia occurs after ingesting food. The 3 sub-types of reactive (postprandial) hypoglycemia are: (1) alimentary; (2) associated with type 2 (noninsulin-dependent) diabetes mellitus; and (3) idiopathic. The causes of most cases of reactive hypoglycemia are still open to debate. Some researchers suggest that certain people may be more sensitive to the body’s normal release of the hormone epinephrine, which causes many of the symptoms of hypoglycemia. Others believe deficiencies in glucagon secretion might lead to reactive hypoglycemia. A few causes of reactive hypoglycemia are certain, but they are uncommon.
Patients who have undergone gastrointestinal surgery (eg, subtotal gastrectomy) experience reactive hypoglycemia within 2 to 3 hours after eating. Gastric—or stomach—surgery can cause reactive hypoglycemia because of the rapid passage of food into the small intestine. Rare enzyme deficiencies diagnosed early in life, such as hereditary fructose intolerance, also may cause reactive hypoglycemia.
Patients with relatively mild noninsulin-dependent diabetes mellitus experience reactive hypoglycemia 3 to 5 hours after a meal.The reactive hypoglycemia may be related to the late and extended second phase of insulin secretion that is characteristic of type 2 diabetes mellitus. Idiopathic reactive hypoglycemia is a common cause of nonspecific symptoms such as depression and mood swings.
Drug-related hypoglycemia is related to accidental or intentional administration of a drug (eg, insulin, sulfonylureas) that may occur in the both the fasting and postprandial states.
Clinical presentation
Signs and symptoms.
Two distinct patterns are distinguished:
1) adrenergic symptoms (they are attributed to increased sympathetic activity and epinephrine release): sweating, nervousness, tremulousness, faintness, palpitation, and sometimes hunger;
2) cerebral nervous system manifestations: confusion, inappropriate behavior (which can be mistaken for inebriation); personality change, emotional lability, ataxia, incoordination, sometimes mistaken for “drunkenness”, difficulty speaking, slurred speech; visual disturbances (staring, “glassy” look, blurred vision, double vision, flashes of light in the field of vision), stupor, coma or seizures generalized or focal. (Improvement in the cerebral nervous system manifestations will be with a rise in blood glucose.);
3) Glucagon manifestations: hunger, borborygmus, nausea, vomiting, abdominal discomfort, headache.
A common symptom of hypoglycemia is the early morning headache, which is usually present when the patient awakes.
Patients should be familiar with the symptoms of the hypoglycemia but some of them are not heralded by symptoms.
Physical examination.
1. The skin is cold, moist.
2. Hyperreflexia can be elicited.
3. Hypoglycemic coma is commonly associated with abnormally low body temperature
4. Patient may be unconsciousness.
Diagnosis of hypoglycemia depends upon the demonstration of Whipple’s triad and includes a low plasma glucose concentration, presence of hypoglycemic symptoms, and relief of symptoms when the plasma glucose levels return to normal after ingesting food (eg, carbohydrates). All 3 criteria should be met, as some patients may have subnormal serum glucose levels and be asymptomatic, while other patients may have normal serum glucose levels but experience symptoms similar to those associated with hypoglycemia.
Patients with symptomatic fasting hypoglycemia require a thorough evaluation. It is important to consider a variety of disorders that cause symptomatic fasting hypoglycemia with and without hyperinsulinism. Conditions such as a pancreatic beta-cell tumor (eg, insulinoma) and surreptitious administration of insulin or sulfonylureas, which causes inappropriate fasting hyperinsulinism, are the most common causes of fasting hypoglycemia. Usually, these patients appear healthy between hypoglycemic episodes. The possibility of autoimmune disease (eg, antibodies to insulin) that is associated with hyperinsulinemic hypoglycemia should also be ruled out.
By contrast, patients with symptomatic fasting hypoglycemia without hyperinsulinism experience hypoglycemia associated with an illness. Usually, the clinical signs and symptoms of the major illness dominate. Some common causes of symptomatic fasting hypoglycemia without hyperinsulinism include severe hepatic dysfunction, chronic renal insufficiency, and hypercortisolism.
Factitious hypoglycemia is often diagnosed when the physician is attempting to rule out insulinoma. Whipple’s triad is not of diagnostic value in detecting factitious hypoglycemia because the symptoms of Whipple’s triad are the same among patients with hyperinsulinism and patients with factitious hypoglycemia. It is difficult to differentiate factitious hypoglycemia from insulinoma because of similar clinical and biochemical findings.
Once the diagnosis of hyperinsulinemic hypoglycemia is confirmed, the next step is to differentiate the hypoglycemia due to endogenous hypersecretion of insulin from hypoglycemia due to exogenous use of insulin or oral hypoglycemic drugs. It is more difficult to diagnose insulin-induced factitious hypoglycemia in diabetic patients; approximately one third of the patients with insulin-induced factitious hypoglycemia are diabetic.
Previously, diagnosis of factitious hypoglycemia relied upon circumstantial evidence such as the patient’s unauthorized possession of insulieedles and syringes. The radioimmunoassay for human C-peptide, a clinical marker of endogenous insulin secretion, can be used in the diagnosis of factitious hypoglycemia.
hypoglycemia in diabetes
Iatrogenic hypoglycemia in patients with diabetes – is defined as all episodes of an abnormally low plasma glucose concentrati on that expose the individual to potential harm. A single threshold value for plasma glucose concentration that defines hypoglycemia in diabetes cannot be assigned because glycemic thresholds for symptoms of hypoglycemia (among other responses) shift to lower plasma glucose concentrations after recent antecedent hypoglycemia and to higher plasma glucose concentrations in patients with poorly controlled diabetes and infrequent hypoglycemia.
Precipitating factors
– irregular ingestion of food;
– extreme activity;
– alcohol ingestion;
– drug interaction;
– liver or renal disease;
– hypopituitarism and adrenal insufficiency.
Risk factors for hypoglycemia in diabetics include:
1) endogenous insulin deficiency, which also predicts a deficient glucagon response;
2) a history of hypoglycemia, hypoglycemia unawareness, or both;
3) aggressive glycemic therapy per se as evidenced by lower glycemic goals, lower HbA1c levels, or both;
4) recent moderate or intensive exercise;
5) sleep;
6) renal failure.
Iatrogenic hypoglycemia is more frequent in patients with profound endogenous insulin deficiency type 1 diabetes and advanced type 2 diabetes and its incidence increases with the duration of diabetes. It is caused by treatment with a sulfonylurea, glinide, or insulin and occurs about two to three times more frequently in type 1 diabetes than in type 2 diabetes. However, because type 2 diabetes is much more prevalent than type 1 diabetes, most episodes of hypoglycemia, including severe hypoglycemia, occur in people with type 2 diabetes There is no doubt that hypoglycemia can be fatal. Although profound and prolonged hypoglycemia can cause brain death, most episodes of fatal hypoglycemia are probably the result of other mechanisms, such as ventricular arrhythmias
In people with diabetes, hypoglycemia is the result of the interplay of relative or absolute insulin excess and compromised physiological defenses against falling plasma glucose concentrations. Insulin excess from time to time is the result of the pharmacokinetic imperfections of all insulin preparations and insulin secretagogues used to treat diabetes in the context of an array of factors such as food intake, exercise, drug (including alcohol) interactions, altered sensitivity to insulin, and insulin clearance. Compromised physiological defenses against falling plasma glucose concentrations are the result of the pathophysiology of glucose counterregulation—the mechanisms that normally prevent or rapidly correct hypoglycemia—at least in type 1 and advanced type 2 diabetes. That pathophysiology includes impairment of all three key defenses against falling plasma glucose levels in the endogenous insulin deficient state: 1) insulin levels do not decrease, 2) glucagon levels do not increase, and 3) the increase in epinephrine levels is typically attenuated (i.e., the glycemic threshold for epinephrine secretion is shifted to a lower plasma glucose concentration). In the setting of absent insulin and glucagon responses, the attenuated epinephrine response causes the syndrome of defective glucose counterregulation. The attenuated sympathoadrenal (sympathetic neural as well as adrenomedullary) response also causes the clinical syndrome of hypoglycemia unawareness, i.e., loss of the warning symptoms that previously allowed the patient to recognize developing hypoglycemia and take corrective action. While the absent insulin and glucagon responses are persistent defects, it is now recognized that the reduced sympathoadrenal response to a given level of hypoglycemia is a dynamic process typically induced by recent antecedent iatrogenic hypoglycemia. The concept of hypoglycemia-associated autonomic failure in type 1 diabetes and advanced type 2 diabetes posits that recent antecedent hypoglycemia causes both defective glucose counterregulation (by reducing the epinephrine response in the setting of absent insulin and glucagon responses) and hypoglycemia unawareness (by reducing the sympathoadrenal and the resulting symptomatic responses) and thus a vicious cycle of recurrent hypoglycemia. That concept has been extended recently to include exercise- and sleep-related hypoglycemia-associated autonomic failure. Thus, hypoglycemia unawareness is reversible in most affected patients, and the reduced epinephrine component of defective glucose counterregulation is variably improved, by as little as 2–3 weeks of scrupulous avoidance of iatrogenic hypoglycemia. Importantly, antecedent plasma glucose levels as high as 70 mg/dl (3.9 mmol/l) cause reduced sympathoadrenal responses to subsequent hypoglycemia.
Iatrogenic hypoglycemia often has a profound impact on the lives of people with diabetes (as well as on their physiological defenses against subsequent hypoglycemia). The experience of an episode can range from unrecognized to extremely uncomfortable and disrupting. As a group, people with diabetes fear hypoglycemia more than they fear the long-term complications of diabetes. The degree of cognitive-motor dysfunction, particularly slowing of cognitive and motor processing speed, during an episode depends on the magnitude of hypoglycemia. The psychological reactions can be quite frightening and can extend beyond the patient to include family, friends, and coworkers. If neuroglycopenia occurs while the individual is performing a critical task, such as driving, the individual and others are placed at risk of injury and death. The rational fear of hypoglycemia can lead to worsening of metabolic control as well as tension with, and a restriction of personal freedoms and responsibilities by, anxious and over-protective loved ones, colleagues, or employers.
Hypoglycemia unawareness and hypoglycemia-associated autonomic failure
Acute hypoglycemia in patients with di- abetes can lead to confusion, loss of consciousness, seizures, and even death, but how a particular patient responds to a drop in glucose appears to depend on how frequently that patient experiences hypoglycemia. Recurrent hypoglycemia has been shown to reduce the glucose level that precipitates the counterregulatory response necessary to restore euglycemia during a subsequent episode of hypoglycemia. As a result, patients with frequent hypoglycemia do not experience the symptoms from the adrenergic re- sponse to a fall in glucose until the blood glucose reaches lower and lower levels. For some individuals, the level that triggers the response is below the glucose level associ- atedwithneuroglycopenia.The fi rstsignof hypoglycemia in these patients is confusion, and they often must rely on the assis- tance of others to recognize and treat low blood glucose. Such individuals are said to have developed hypoglycemia unaware- ness. Defective glucose counterregulation (the result of loss of a decrease in insulin production and an increase in glucagon re- lease along with an attenuated increase in epinephrine) and hypoglycemia unaware- ness (the result of an attenuated increase in sympathoadrenal activity) are the compo- nents of hypoglycemia-associated autonomic failure (HAAF) in patients with diabetes. HAAF is a form off unctional sympathoadrenal failure that is most often caused by recent antecedent iatrogenic hypoglycemia and is at least partly reversible by scrupulous avoidance of hypoglycemia. Indeed, HAAF has been shown to be maintained by recurrent or greater increased risk of severe hypoglycemia during intensive glycemic therapy. It is important to distinguish HAAF from classical autonomic neuro- pathy, which may occur as one form of diabetic neuropathy. Impaired sympathoadrenal activation is generally confined to the response to hypoglycemia, and auto- nomic activities in organs such asthe heart, gastrointestinal tract, and bladder appear to be unaffected. Clinically, HAAF can be viewed as both adaptive and maladaptive. On the one hand, patients with hypoglycemia unawareness and type 1 diabetes appear to perform better on tests of cognitive function during hypoglycemia than do patients who are able to detect hypoglycemia normally. In addition, the time necessary for full cognitive recovery after restoration of euglycemia appears to be faster in patients who have hypoglycemia unawareness than in patients with normal detection of hypoglycemia. The HAAF habituation of the sympathoadre- nal response to recurrent hypoglycemic stress in humans may be analogous to the phenomenon of habituation of the hypothalamic-pituitary-adrenocortical response to recurrent restraint stress in rats. Rats subjected to recurrent moderate hypoglycemia had less brain cell death and less mortality during or following marked hypoglyce- mia than those not subjected to recurrent hypoglycemia. On the other hand, HAAF is clearly maladaptive since defective glucose coun- terregulation and hypoglycemia un- awareness substantially increase the risk of severe hypoglycemia with its morbidity and potential mortality. A particu- larly low plasma glucose concentra- tion might trigger a robust, potentially fatal sympathoadrenal discharge. Life- threatening episodes of hypoglycemia need not be frequent to be devastating.
Classification
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1. Severe hypoglycemia. |
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An event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Plasma glucose measurements may not be available during such an event, but neurological recovery attributable to the restoration of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration. |
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2. Documented symptomatic hypoglycemia |
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An event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration ≤70 mg/dl (3.9 mmol/liter). |
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3. Asymptomatic hypoglycemia. |
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An event not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose concentration ≤70 mg/dl (3.9 mmol/liter). |
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4. Probable symptomatic hypoglycemia. |
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An event during which symptoms typical of hypoglycemia are not accompanied by a plasma glucose determination (but that was presumably caused by a plasma glucose concentration ≤ 70 mg/dl [3.9 mmol/liter]). |
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5. Relative hypoglycemia |
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An event during which the person with diabetes reports any of the typical symptoms of hypoglycemia and interprets those as indicative of hypoglycemia, with a measured plasma glucose concentration > 70 mg/dl (3.9 mmol/liter) but approaching that level.
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Laboratory findings
Low level of blood glucose
Treatment
Insulin–treated patients are advised to carry sugar lumps, candy, or glucose tablets at all time.
If the symptoms of hypoglycemia develop, the patients have to drink a glass of fruit juice or water with 3 tbsp. of table sugar added or to eat candy, and to teach their family members to give such treatment if they suddenly exhibit confusion or inappropriate behavior:
1) Glucagon 0,5 – 1 unit (0,5 – 1 ml) s/c, i/m or i/v. If the patient does not respond to 1 unit of glucagon within 25 minutes, further injections are unlikely to be effective, and are not recommended;
Pict. Glucagon
2) an i/v injection of 20 or 100 ml of 40 % glucose, followed by a continuous infusion of 5 % glucose (10 % glucose may be needed) until it clearly can be stopped safely;
3) glucocorticoids and adrenaline are helpful as well.
Treatment of factitious hypoglycemia, whether it is insulin- or sulfonylurea-induced, takes place in 2 stages. The first stage involves relieving the neuroglycopenic symptoms by restoring the low plasma glucose to within the normal range.The second stage involves correcting the underlying cause of the hypoglycemia.
If the patient is unconscious, the initial stage involves immediate return of the patient’s blood glucose to normal or slightly above normal (5 to 10 mmol/L). However, it is important to ensure that the glucose levels remain stable by intravenous infusion of glucose until all of the causative drug has been absorbed and degraded metabolically. Typically, this requires a minimum of 36 hours. Continuous monitoring is necessary to determine how much glucose should be administered.
Treatment of sulfonylurea-induced hypoglycemia with intravenous glucose does not correct the hyperinsulinemia.In these patients, a hypertonic glucose bolus may aggravate the situation by exposing the patient to the sudden hyperglycemia. This may further stimulate the sulfonylurea-primed pancreas to release more insulin.
Drugs that block the release of insulin may be required in patients with sulfonylurea-induced hypoglycemia if it is difficult to maintain blood glucose levels by intravenous glucose alone. These drugs include diazoxide, a specific antidote to sulfonylurea–induced hypoglycemia,and octreotide, a semisynthetic long–acting analog of somatostatin. Diazoxide, an antihypertensive drug, has potent hyperglycemic action when it is administered orally. Diazoxide antagonizes the hypoglycemic effect of sulfonylureas by specifically inhibiting the release of insulin from the beta cells. Intravenous administration of octreotide is capable of inhibiting glucose-stimulated beta cells.
Additional treatment is recommended to counteract hypoglycemic coma. Intravenous hydrocortisone should be administered immediately once therapy is started. If the patient does not regain consciousness within 15 to 20 minutes after restoration of normoglycemia, then intravenous dexamethasone and mannitol should be administered.
The second stage, the more difficult stage, requires managing the patient and preventing further hypoglycemia attacks. The medical literature cites numerous reports of patients who not only deny their illness but who are unwilling to undergo psychiatric treatment. The patient’s acknowledgment of the diagnosis does not guarantee that the patient will deal with the problem.
The medical literature poorly describes the long-term treatment of patients with factitious hypoglycemia and its outcomes. One study followed 10 patients with insulin-induced factitious hypoglycemia for several years.Three patients returned to good health, 2 patients committed suicide, 4 patients continued to experience medical problems, and 1 patient was lost to follow-up. The researchers concluded that the long-term outcome for these patients is unpredictable.
Principles of prevention of hypoglycemia
The glycemic target established for any given patient should depend on the patient ’ s age, life expec- tancy, comorbidities, preferences, and an assessment of how hypoglycemia might impact his or her life. This patient-centered approach requires that clinicians spend time developing an individualized treatment plan with each patient.
For very young children, the risks of severe hypoglycemia on brain development may require a strategy that attempts to avoid hypoglycemia at all costs.
For healthy adults with diabetes, a reasonable glycemic goal might be the lowest HbA 1c that does not cause severe hypoglycemia, preserves awareness of hypoglycemia, and results in an acceptable number of documented episodes of symptomatic hypoglycemia. With current therapies, a strategy that completely avoids hypogly- cemia may not be possible in patients with type 1 diabetes who strive to minimize theirrisksofdevelopingthe microvascular complications of the disease.
However, glycemic goals might reasonably be re- laxed in patients with long-standing type 1 diabetes and advanced complications or in those who are free of complications but have a limited life expectancy because of another disease process. In such patients, the glycemic goal could be to achieve glu- cose levels suf fi ciently low to prevent symptoms of hyperglycemia.
For patients with type 2 diabetes, the risk of hypoglycemia depends on the medications used (96).Earlyinthe course of the disease, most patients are treated with lifestylechanges and metformin, nei- ther of which causes hypoglycemia. Therefore, an HbA 1c of , 7% is appropri- ate for many patients with recent-onset type 2 diabetes. As the disease progresses, it is likely that medications that increase theriskofhypoglycemiawillbeadded. This, plus the presence of complications or comorbidities that limit life expec- tancy, means that glycemic goals may need to be less aggressive. While the bene fi ts of achieving an HbA 1c of , 7% may continue to beadvocated forpatientswith type 2 diabetes at risk for microvascular complications and with suf fi cient life ex- pectancy, less aggressive targets may be appropriate in those with known cardio- vascular disease, extensive comorbidities, or limited life expectancy.
Older individuals with gait imbalance and frailty may experience a life-changing injury if they fall during a hypoglycemia episode, so avoiding hypoglycemia is paramount in such patients. Patients with cognitive dysfunction may have dif fi culty adhering to a complicated treat- ment strategy designed to achieve a low HbA 1c (48). Such patients will bene fi t from a simpli fi cation of the treatment strategy with a goal to prevent hypoglyce- mia as much as possible. Furthermore, the bene fi ts of aggressive glycemic ther- apy in those affected are unclear Effective approaches known to decrease the risk of iatrogenic hypoglycemia include patient education, dietary and exercise modifications, medication adjustment, careful glucose monitoring by the patient, and conscientious surveillance by the clinician.
Patient education:
· Discuss hypoglycemia risk factors and remediation regularly with patients taking insulin or sulfonylurea/glinides
· Educate patients and domestic companions/caregivers on how to recognize and treat hypoglycemic episodes
· Educate patients on pharmacokinetics of medications
· Consider enrolling patients with frequent hypoglycemia in a blood glucose awareness training program
Dietary intervention:
· Encourage patients on long-acting secretagogues and fixed insulin regimens to follow predictable meal plan; patients on flexible insulin regimens should couple insulin injections with meal times
· Patients on any hypoglycemia-inducing medication should carry carbohydrates at all times for hypoglycemia treatment
Exercise management:
· Patients should carefully monitor glucose before and after exercise, and take preemptive actions to prevent or minimize postexertional hypoglycemia
· Patients should eat pre-exercise snacks if blood glucose levels indicate declining glucose
· Patients should carry readily absorbable carbohydrates when starting any exercise, including house or yard work
· For patients with well controlled diabetes and history of exercise-related hypoglycemia, may be appropriate to adjust insulin doses on exercise days
Medication adjustment:
· Review blood glucose patterns to determine if medication adjustments are needed. Adjustments may include substitution of rapid-acting insulin (lispro, aspart, glulisine) for regular, or basal insulin glargine or detemir for NPH
· Sulfonylureas have greatest hypoglycemia risk; consider substitution with another class for troublesome hypoglycemia
· Adjust treatment regimen to avoid frequent hypoglycemia/hypoglycemia unawareness
Glucose monitoring:
· Patients on insulin, sulfonylureas, glinides: check blood glucose when hypoglycemia symptoms are present to confirm need for ingestion of carbohydrates and collect information for reporting to healthcare provider for adjustment of treatment regimen
· Patients on basal-bolus insulin: check blood glucose before each meal; figure value into calculation of rapid-acting insulin dose
Clinical surveillance:
· Patients on insulin, insulin secretagogues: assess hypoglycemia risk at all visits
· Consider having patient complete hypoglycemia questionnaire and review responses together
· Ask patients to keep a glucose log, including date, time, and circumstances surrounding hypoglycemic episodes, and review at each visit
References.
А.
1. Davidson’s Principles and Practice of Medicine (1st Edition) / Edited by N. R. Colledge, B. R. Walker, S. H. Ralston. – Philadelphia
2. Harrison’s Principles of Internal Medicine (18th edition) / D. Longo, A. Fauci, D. Kasper, S. Hauser, J. Jameson, J. Loscalzo,. – New York : McGraw-Hill Education – Europe , 2011. – 4012 p.
3. Kumar and Clark’s Clinical Medicine (8th Revised edition) (With student consult Online Access) / P. KumarM. L. Clark . –
B. Additional
1. Greenspan’s Basic and Clinical Endocrinology ( 9th Revised edition) / David G. Gardner, Dolores M. Shoback. –
2. Oxford Textbook of Endocrinology and Diabetes2nd Revised edition / John A. H. WassPaul StewartStephanie A. AmielMelanie J. Davies. –
3. Web-sites:
a) http://emedicine.medscape.com/endocrinology
c) http://care.diabetesjournals.org/
Management of Hyperglycemia in Type 2 Diabetes (2012)
