TOPIC№2: Purulent-inflammatory diseases of abdominal cavity.

(Acute Appendicitis, cholecystitis, pancreatitis, Peritonitis in Infancy).

Plan:

1.                Acute Appendicitis.

2.                Cholecystitis.

3.                Pancreatitis.

4.                Peritonitis in Infancy.

1. Acute Appendicitis

Introduction. Appendicitis is the second most common acute abdominal inflammatory problem in childhood. It is also the most common disease process requiring surgery in childhood. Diagnosis in children can be elusive because as many as 30-45% of patients present with atypical symptoms. Perforated appendicitis is more common in children than in adults, and is associated with increased morbidity. It can mask the typical symptoms of acute appendicitis and delay the diagnosis. Knowledge of the typical pathophysiologic sequence of appendicitis will be useful in making the clinical diagnosis in only 70 -75 % of the children with appendicitis. This is because an accurate history and sequential examination of a child is not possible in many instances. However the goal in the clinical care of acute appendicitis is to make the diagnosis before perforation occurs. The progression of acute appendicitis to perforation is more rapid in the younger child, sometimes occurring within 6-12 hours. The risk of perforation within 24 hours of symptom onset is less than 30%; after 48 hours, the risk of perforation increases to greater than 70%. The perforation rate and the false negative appendectomy rate may be reduced through enhanced understanding of the natural history of appendicitis and its variable presentation in children.

History of the procedure. The first report of an appendectomy came from Amyan, a surgeon of the English army. Amyan performed an appendectomy in 1735 without anesthesia to remove a perforated appendix. Reginald H. Fitz, an anatomopathologist at Harvard who advocated early surgical intervention, first described appendicitis in 1886. Because he was not a surgeon, his advice was ignored for a time. Then, at the end of the 19th century, the English surgeon H. Hancock successfully performed the first appendectomy in a patient with acute appendicitis. Some years after this, the American C. McBurney published a series of reports that constituted the basis of the subsequent diagnostic and therapeutic management of acute appendicitis. Currently, appendectomy, either open or laparoscopic, remains the treatment for noncomplicated appendicitis.

Relevant anatomy. The appendix is a wormlike extension of the cecum, and its average length is 8-10 cm (ranging from 2-20 cm). This organ appears during the fifth month of gestation, and its wall has an inner mucosal layer, 2 muscular layers, and a serosa. Several lymphoid follicles are scattered in its mucosa. The number of follicles increases when individuals are aged 8-20 years.

The inner muscular layer is circular, and the outer layer is longitudinal and derives from the taenia coli. Taenia coli converge on the posteromedial area of the cecum. This site is the appendiceal base. The appendix runs into a serosal sheet of the peritoneum called the mesoappendix. Within the mesoappendix courses the appendicular artery, which is derived from the ileocolic artery. Sometimes, an accessory appendicular artery (deriving from the posterior cecal artery) may be found. The vasculature of the appendix must be addressed to avoid intraoperative hemorrhages. The course of the appendix and the position of its tip may vary widely, accounting for the nonspecific signs and symptoms of appendicitis.

Inconstancy of position:

Retrocecal – 74 %;

Pelvic – 21 %;

Subcaecal – 1 – 5 %;

Postileal – 5%;

Preileal – 1%;

Paracecal – 2%;

In left iliac fossa or in the hypochondrium – very occasionally.

 

Pathophysiology

Early stage of appendicitis. Obstruction of the appendiceal lumen leads to mucosal edema, mucosal ulceration, diapedesis of bacteria, distention of the appendix due to accumulated fluid, and increasing intraluminal pressure. This stimulates the visceral afferent nerve fibers and the patient perceives visceral periumbilical or epigastric pain. This mild pain usually lasts 4-6 hours.

Suppurative appendicitis. Increasing intraluminal pressures eventually exceed capillary perfusion pressure, which is associated with obstructed lymphatic and venous drainage and allows bacterial and inflammatory fluid invasion of the tense appendiceal wall. Transmural spread of bacteria causes acute suppurative appendicitis. When the inflamed serosa of the appendix comes in contact with the parietal peritoneum, patients typically experience the classic shift of pain to the right lower quadrant (RLQ), which is continuous and more severe than the early visceral pain.

 

Gangrenous appendicitis. Intramural venous and arterial thromboses ensue, resulting in gangrenous appendicitis.

 

Perforated appendicitis. Persisting tissue ischemia results in appendiceal infarction and perforation. Perforation can cause localized or generalized peritonitis.

 

Phlegmonous appendicitis or abscess. An inflamed or perforated appendix can be walled off by the adjacent greater omentum or small bowel loops and phlegmonous appendicitis or focal abscess occurs.

The bacterial flora of appenditis is derived from organisms that normally inhabit in the human colon. The most important pathogen is Bacteroides fragilis, a gram-negative, strict anaerobe. The second most important pathogene is Escherichia coli, a gram-negative, facultative anaerobe. Other anaerobic species, including Streptococcus, Pseudomonas, Klebsiella and Clostridium, also appear.

Histologic findings. In the early stages of the disease, the appendix grossly appears edematous with dilation of the serosal vessels. Microscopy demonstrates neutrophil infiltrate of the mucosal and muscularis layers extending into the lumen. As time passes, the appendiceal wall grossly appears thickened, the lumen appears dilated, and a serosal exudate (fibrinous or fibrinopurulent) may be observed as granular roughening. At this stage, mucosal necrosis may be observed microscopically.

At later stages, the appendix grossly shows marked signs of mucosal necrosis extending into the external layers of the appendiceal wall that can become gangrenous. Sometimes the appendix may be found in a collection of pus. At this stage, microscopy may demonstrate multiple microabscesses of the appendiceal wall and severe necrosis of all layers.

Frequency. The incidence of acute appendicitis is around 7% of the population in the United States and in European countries. In Asian and African countries, the incidence is probably lower because of the dietary habits of the inhabitants of these geographic areas.

In the last few years, a decrease in frequency of appendicitis in Western countries has been reported, which may be related to changes in dietary fiber intake. In fact, the higher incidence of appendicitis is believed to be related to poor fiber intake in such countries.

Mortality/Morbidity. At the time of diagnosis, the rate of perforation varies from 17 – 40% with a higher frequency occurring in younger age groups. The mortality rate for children with appendicitis ranges from 0.1-1%. Perforation increases the complication rate.

Age. Appendicitis occurs in all age groups. The mean age in the pediatric population is 6-10 years. Appendicitis is rare in the neonate, and the diagnosis in this age group is typically made after perforation. Younger children have a higher rate of perforation, with reported rates of 50-85%.

Sex. Male-to-female ratio is approximately 2:1.

Clinical manifestations

History. It is important to understand the typical clinical manifestations of appendicitis in order to make an early and accurate diagnosis prior to perforation. The classic history of anorexia and periumbilical pain, followed by right lower quadrant pain and vomiting, is observed in fewer than 60% of cases.

The initial symptom is poorly defined periumbilical pain, often associated with anorexia. Acute onset of severe pain is typically present with acute ischemic conditions, such as volvulus, testicular torsion, ovarian torsion, or intussusception. In appendicitis, nausea and vomiting develop shortly after onset of pain. In most cases of appendicitis, abdominal pain precedes vomiting.

After a few hours, the pain shifts to the right lower quadrant due to inflammation of the parietal peritoneum. This pain is more intense, continuous, and more localized than the initial pain. This shift of pain rarely occurs in other abdominal conditions.

The majority of children with appendicitis either are afebrile or have a low-grade fever. High fever is not a common presenting feature unless perforation has occurred. In one study, vomiting and fever are more frequent in children with appendicitis than in children with other causes of abdominal pain.

Appendicitis causes acute abdominal pain in up to 8 % of children who undergo emergency evaluation of such pain. Neonatal and prenatal appendicitis have occurred.

The incidence of appendicitis increases during viral epidemics and outbreaks of amebiasis and bacterial gastroenteritis. Extended breast-feeding seems to significantly decrease the risk of appendicitis, and there appears to be a genetic predisposition for this infection.

Appendicitis pain typically begins as a vague periumbilical discomfort followed by parietal peritoneum inflammation localized to the right lower quadrant. This classic migration of pain does not occur in one third of pediatric cases. The classic location of the appendix, known as McBurney’s point, is one third of the distance from the right anterior superior iliac spine to the umbilicus. Nausea and vomiting with fever are common.

Ieonates, the clinical features of appendicitis are nonspecific and include irritability or lethargy, abdominal distention, vomiting, a palpable abdominal mass and cellulitis of the abdominal wall. In infants and children up to two years of age, symptoms include vomiting, pain, diarrhea and fever. Diagnosis is more difficult in this age group because the symptoms are nonspecific. In children two to five years of age, symptoms include vomiting, abdominal pain, fever and anorexia. Tenderness of the right lower quadrant is more common in this age group than it is in younger children, who usually have diffuse tenderness. The incidence of appendicitis increases in children six to 12 years of age and in adolescents 13 years or older, with symptoms that include vomiting and abdominal pain that worsens with movement or cough. Tenderness in the right lower quadrant is common.

Physical. Children vary in their ability to cooperate with the physical examination. It is important to tailor the physical examination with respect to the child’s age and developmental stage.

A child with acute appendicitis walks slowly, often humped forward protecting the right side. The facial expression reflects discomfort and apprechension. The right hip frequently is held in slight flexion. Fever, tachycardia, and signs of dehydration usually are minimal in the first 12 to 24 hours but quickly increase in the later stages.

Before examination of the abdomen, the child should be made as comfortable, as possible, with the hands folded on the chest and perhaps a pillow placed beneath the knees to flex the hips.If asked to point one finger where it hurst most, the child invariably will identify the tender point. The examiner should then begin the palpation in other less sensitive areas of abdomen. Gentleness and warm hands are important.

A careful physical examination, not limited to the abdomen, must be performed in any patient with suspected appendicitis. GI, genitourinary, and pulmonary systems must be studied. Perform a rectal examination in any patient with an unclear clinical picture, and perform a pelvic examination in all women with abdominal pain.

Observation of the child’s interaction and gait prior to the examination can be extremely helpful.

Localization of the pain depends on the position of the appendix. Typically, maximal tenderness can be found at McBurney point in the right lower quadrant. Additional signs such as cough sign (sharp pain in the right lower quadrant after a voluntary cough, ie, Dunphy sign), rebound tenderness related to peritoneal irritation elicited by deep palpation with quick release (ie, Blumberg sign), and guarding may or may not be present. Rovsing sign is pain in the right lower quadrant in response to left-sided palpation and strongly suggests peritoneal irritation.

 

A rectal examination should be done last and may reveal impacted stool, right-sided tenderness, or a mass.

Patients with appendicitis may not have the reported classic clinical picture 37-45% of the time, especially when the appendix is located in an unusual place. In such cases, imaging studies may be important but not always available. Patients with this condition usually have accessory signs that may be helpful for diagnosis.

Atypical clinical presentation

Atypical clinical presentation related to the position of the appendix. The incidence of atypical clinical presentation of appendicitis ranges from 30 – 45%. The relationship of the base of the appendix to the cecum is generally constant. However, the position of the distal end of the appendix is variable. It may be found in a medial, lateral, or caudal position with respect to the cecum, or may be retrocecal. Two thirds of appendices are retrocecal in location; only one third extend in an inferomedial direction.

Retrocecal or retroileal appendix. A child with acute retrocecal or retroileal appendicitis (appendix deep to distal ileal bowel loops) may walk with exaggerated lumbar lordosis and have a slightly flexed right hip as a result of right psoas muscle spasm. Pain with extension of the right hip with the patient in left lateral decubitus position (psoas sign) and with internal rotation of the thigh (obturator sign) may be found with retrocecal appendicitis. If present, this indicates peritonitis. Absence of bowel sounds or high-pitched, tinkling bowel sounds may indicate bowel obstruction associated with retroiliac appendicitis in children less than six years of age.

The appendix may extend across the midline. When inflamed, the clinical symptoms may mimic those of inflammatory processes involving other organs in the left pelvis, such as the small bowel, sigmoid colon, or left adnexa in female patients.

Appendix in the right paracolic gutter. Location of the inflamed appendix in the right paracolic gutter typically results in flank pain mimicking acute pyelonephritis or ureteral calculus.. In addition, symptoms resembling those of gastroenteritis may result from colonic irritation.

Pelvic appendix. Appendicitis in this location may result in pain on rectal examination. Location of the inflamed appendix in the vicinity of the urinary bladder may produce symptoms of urinary frequency resembling those of cystitis.

Appendicitis in the presence of other illnesses may result in an atypical clinical presentation. The typical clinical signs and symptoms of appendicitis may be masked or misinterpreted in neutropenic or immunocompromised patients, such as those with leukemia ; diabetes mellitus; or Crohn’s disease. This may result in delayed diagnosis and its accompanying adverse influence on patient outcome.

Diagnosis

Lab Studies. Laboratory findings may increase the suspicion for appendicitis but are not diagnostic. A minimum laboratory evaluation for patients with possible appendicitis includes a Complete blood cell count (CBC) with differential and urinalysis.

The White blood cell (WBC) count is elevated in approximately 70-90% of patients with acute appendicitis but also is elevated in many other abdominal conditions. The predictive value of the WBC count is limited. Because at least 10% of patients with appendicitis have a WBC count within the reference range, appendicitis cannot be excluded based on a WBC count within the reference range. It is important to interpret the WBC count with respect to the clinical presentation. If the WBC count exceeds 15,000 cells/mm³, the patient is more likely to have a perforation. However, one study found no difference in the WBC count between children with simple appendicitis and those with a perforated appendicitis.

Urinalysis is useful for detecting urinary tract disease, such as infection or renal stones.

Irritation of the bladder or ureter by an inflamed appendix may result in a few WBCs in the urine, but the presence of over 20 WBCs suggests a urinary tract infection.

Causes of hematuria include renal stones, urinary tract infection, Henoch-Schőnlein purpura (HSP), or hemolytic uremic syndrome (HUS).

Normal findings on urinalysis are of limited diagnostic value for appendicitis. Grossly abnormal urinalysis findings may suggest another cause of abdominal pain.

Electrolytes and renal function tests are more helpful in the management than in the diagnosis of appendicitis. Indications for assessing electrolytes include a significant history of vomiting or clinical suspicion of dehydration.

Additional studies:

Liver function tests, serum amylase, and serum lipase may be helpful when the etiology of the abdominal pain is unclear.

Urinary levels of human chorionic gonadotropin-beta subunit (hCG-beta) are useful in sexually active adolescent females to exclude ectopic pregnancy.

Imaging Studies:

Computed tomography (CT). Abdominal CT has become the most important imaging study in the evaluation of patients with atypical presentations of appendicitis. Several studies have shown a decrease iegative laparotomy rate and appendiceal perforation rate when abdominal CT is used in selected patients with suspected appendicitis. Advantages of CT scanning include superior sensitivity and accuracy compared with other imaging techniques, ready availability, noninvasiveness, and potential to reveal alternative diagnoses. Disadvantages include radiation exposure, potential for anaphylactoid reaction if intravenous (IV) contrast is used, lengthy acquisition time if oral contrast is used, and patient discomfort if rectal contrast is used. A variety of CT techniques have been studied.

Ultrasonography. In 1986, Puylaert described a graded compression technique for evaluation of the appendix using transabdominal ultrasonography. A 5-MHz transducer is used, applying gentle but firm pressure in the RLQ to displace intervening bowel gas and to decrease the distance between the transducer and the appendix, thereby improving image quality. An outer diameter of greater than 6 mm, noncompressibility, lack of peristalsis, or presence of a periappendiceal fluid collection characterizes an inflamed appendix. The normal appendix is not visualized in most cases. A posterolateral approach is suggested to evaluate the retrocecal area. Scattered case reports endorse transvaginal ultrasonography for women with low pelvic tenderness if the appendix is not visualized on transabdominal sonography.

Numerous studies have documented a sensitivity of 85-90% and a specificity of 92-96%. Some studies using graded compression ultrasonography in children reported sensitivities of 85-95% and specificities ranging from 47-96%.

Advantages include noninvasiveness, short acquisition time, lack of radiation exposure, and potential for diagnosis of other causes of abdominal pain, particularly in the subset of females of childbearing age. Many authorities feel that ultrasonography should be the initial imaging test in pregnant women and in pediatric patients because radiation exposure is particularly undesirable in those groups.

The principal disadvantage is that ultrasonographic examination is operator dependent. Because nonvisualization is interpreted as a noninflamed appendix, technical expertise and commitment to a thorough examination are essential in obtaining maximum sensitivity.

If graded compression ultrasonography of the right lower quadrant is positive for appendicitis, appendectomy should be performed. If negative, this finding is not sufficiently sensitive to rule out the possibility of appendicitis. Consideration should be given to further observation and focused helical CT with rectal contrast.

Abdominal radiography. Kidneys-ureters-bladder (KUB) view used typically. Visualization of an appendicolith in a patient with symptoms consistent with appendicitis is highly suggestive of appendicitis, but this occurs in fewer than 10% of cases. The consensus in the literature is that plain radiography is insensitive, nonspecific, and not cost-effective.

Barium enema. A single contrast study can be performed on an unprepared bowel. Nonfilling or incomplete filling of the appendix coupled with pressure effect or spasm in the cecum suggests appendicitis.

Advantages of barium enema are its wide availability, use of simple equipment, and potential for diagnosis of other diseases (eg, Crohn disease, colon cancer, ischemic colitis) that may mimic appendicitis.

Disadvantages include its high incidence of nondiagnostic examination, radiation exposure, insufficient sensitivity, and invasiveness. These disadvantages make barium enema a poor screening examination for use by emergency physicians. Barium enema has essentially no role in the diagnosis of acute appendicitis in the era of ultrasonography and CT.

Diagnostic Procedures

Diagnostic laparoscopy may be useful in selected cases (eg, infants, elderly patients, female patients) to confirm the diagnosis. If findings are positive, such procedures should be followed by definitive surgical treatment at the time of laparoscopy.

Differential diagnosis

Possible conditions that can mimic appendicitis include:

Gastroenteritis – usually causes pain, diarrhoea and vomiting. The pain does not usually shift from centrally to the right lower part of the abdomen.

Mesenteric adenitis – this is swollen glands in the abdomen and produces symptoms that are often identical to appendicitis in children. They usually have a sore throat, cough, earache or cold.

Distal ileitis – this is inflammation of the last part of the small bowel. It is usually be caused by Crohn’s disease, an infection called Yersinia, or TB .

Caecal cancer – usually in the elderly a cancer that is perforating may mimic appendicitis

Meckel’s diverticulitis – this is inflammation in a congenital outgrowth of the small bowel. It is present in around 2% of the population and usually causes no trouble so that a person does not know of its existence. The pain is often a little less localised than with appendicitis, but the diagnosis is often made at operation.

Salpingitis – this is inflammation of the tube in a woman and if the right tube is affected appendicitis is often difficult to separate from this condition. Often the woman has a vaginal discharge as well as pain.

Ruptured ectopic pregnancy – this causes pain on the right if the right tube is affected. The woman has usually missed the last period, and may have bleeding from the vagina at the time of the pain.

Right ovarian cyst – if this ruptures it can cause pain in the right side and mimic early appendicitis. If the cyst twists this is called torsion of an ovarian cyst and this leads to throbbing pain in the right lower abdomen. It is often of sudden onset and is associated with vomiting when the pain starts.

Urinary tract infection – there is often pain on passing water and the doctor can test the urine to look for signs of infection to exclude this.

Complications of appendicitis:

·    Perforation

·    Peritonitis

·    Abdominal sepsis

·    Dehiscence

Treatment

Medical therapy. Appendectomy remains the only curative treatment for appendicitis.

Although many controversies exist over the nonoperative management of acute appendicitis, antibiotics have an important role in the treatment of patients with this condition. Antibiotics considered for patients with appendicitis must offer full aerobic and anaerobic coverage. Duration of the administration is closely related to the stage of appendicitis at the time of the diagnosis, considering either intraoperative findings or postoperative evolution. According to several studies, antibiotic prophylaxis should be administered before every appendectomy. When the patient becomes afebrile and the WBC count normalizes, antibiotic treatment may be stopped. Cefotetan and cefoxitin seem to be the best choices of antibiotics.

Surgical therapy. Thousands of classic appendectomies (open procedure) have been performed in the last 2 centuries. Mortality and morbidity have gradually decreased, especially in the last few decades because of antibiotics, early diagnosis, and improvements in anesthesiologic and surgical techniques.

Since 1987, many surgeons have begun to treat appendicitis laparoscopically. This procedure has now been improved and standardized.

Laparoscopy has some advantages, including decreased postoperative pain, better aesthetic result, a shorter time to return to usual activities, and lower incidence of wound infections or dehiscence. This procedure is cost effective but may require more operative time compared with open appendectomy.

Preoperative details. Preparation of patients undergoing appendectomy is similar for both open and laparoscopic procedures.

Because they may mask the underlying disease, do not administer analgesics and antipyretics to patients with suspected appendicitis who have not been evaluated by the surgeon.

Perform complete routine laboratory and radiologic studies before intervention.

Venous access must be obtained in all patients diagnosed with appendicitis. Venous access allows administration of isotonic fluids and broad-spectrum intravenous antibiotics prior to the operation.

Patients presenting with perforated appendicitis may be volume depleted and require aggressive fluid resuscitation. The combination of cefotaxim, clindamycin, and amycacin is administered to treat infection from aerobic and anaerobic organisms. Alternative regimens include ampicillin and sulbactam, cefoxitin, cefotetan, piperacillin and tazobactam, ticarcillin and clavulanate, and imipenem and cilastatin.

Prior to the start of the surgical procedure, the anesthesiologist performs endotracheal intubation to administer volatile anesthetics and to assist respiration.

The abdomen is washed, antiseptically prepared, and then draped.

Contraindications: Patients with appendicitis always need urgent referral and prompt treatment. No contraindications to appendectomy are known for patients with suspected appendicitis except in the case of a patient with a long history of symptoms and signs of a large phlegmon. If a periappendiceal abscess or phlegmon exists secondary to appendiceal perforation or rupture, some physicians may choose a conservative approach with broad-spectrum antibiotics and percutaneous drainage followed by appendectomy later.

Nontoxic patients with a localized walled-off abscess may be candidates for initial medical management with antibiotics, followed by an elective appendectomy.

Certain contraindications exist for laparoscopic appendectomy. These contraindications are extensive adhesions, radiation or immunosuppressive therapy, severe portal hypertension, and coagulopathies. Laparoscopic appendectomy is contraindicated in the first trimester of pregnancy.

Rarely, an appendiceal mucocele may occur. It is a collection of mucus within the appendiceal lumen. Occasionally, patients may present with a low-grade carcinoma of the appendix or cecum. In such cases, the surgeon must avoid perforation during dissection because it may cause seeding of the peritoneum with viable cells, leading to pseudomyxoma peritonei.

Intraoperative details

Open appendectomy

Prior to incision, the surgeon should carefully perform a physical examination of the abdomen to detect any mass and to determine the site of the incision.

Open appendectomy requires a transverse incision in the RLQ over the McBurney point (ie, two thirds of the way between the umbilicus and the anterior superior iliac spine). The vertical incisions (ie, the Battle pararectal) are rarely performed because of the tendency for dehiscence and herniation.

The abdominal wall fascia (ie, Scarpa fascia) and the underlying muscular layers are sharply dissected or split in the direction of their fibers to gain access to the peritoneum. If necessary (eg, because of concomitant pelvic pathologies), the incision may be extended medially, dissecting some fibers of the oblique muscle and retracting the lateral part of the rectus abdominis. The peritoneum is opened transversely and entered. Note the character of any peritoneal fluid to help confirm the diagnosis and then suction it from the field; if purulent, collect and culture the fluid.

Retractors are gently placed into the peritoneum. The cecum is identified and medially retracted. It is then exteriorized by a moist gauze sponge or Babcock clamp, and the taenia coli are followed to their convergence. The convergence of teniae coli is detected at the base of the appendix, beneath the Bauhin valve (ie, the ileocecal valve), and the appendix is then viewed. If the appendix is hidden, it can be detected medially by retracting the cecum and laterally by extending the peritoneal incision.

After exteriorization of the appendix, the mesoappendix is held between clamps, divided, and ligated. The appendix is clamped proximally about 5 mm above the cecum to avoid contamination of the peritoneal cavity and is cut above the clamp by a scalpel. Fecaliths within the lumen of the appendix may be detected. The appendix must be ligated to prevent bleeding and leakage from the lumen. The residual mucosa of the appendix is gently cauterized to avoid future mucocele. The appendix may be inverted into the cecum with the use of a pursestring suture or z-stitch. Although performed by several surgeons, the appendiceal stump inversion is not mandatory.

 

The cecum is placed back into the abdomen. The abdomen is irrigated. When evidence of free perforation exists, peritoneal lavage with several liters of warm saline is recommended. After the lavage, the irrigation fluid must be completely aspirated to avoid the possibility of spreading infection to other areas of the peritoneal cavity. The use of a drain is not commonly required in patients with acute appendicitis, but obvious abscess with gross contamination requires drainage.

The wound closure begins by closing the peritoneum with a running suture. Then, the fibers of the muscular and fascial layers are reapproximated and closed with a continuous or interrupted absorbable suture. Lastly, the skin is closed with subcutaneous sutures or staples. In cases of perforated appendicitis, some surgeons leave the wound open, allowing for secondary closure or a delayed primary closure until the fourth or fifth day after operation. Other surgeons prefer immediate closure in these cases.

Laparoscopic appendectomy

The surgeon typically stands on the left of the patient, and the assistant stands on the right. The anesthesiologist and the anesthesia equipment are placed at the patient’s head, and the video monitor and instrument table are placed at the feet.

Although some variations are possible, 3 cannulae are placed during the procedure. Two of them have a fixed position (ie, umbilical and suprapubic). The third is placed in the right periumbilical region, and its position may vary greatly depending on the patient’s anatomy.

According to the preferences of the surgeon, a short umbilical incision is made to allow the placement of a Hasson cannula or Veress needle that is secured with 2 absorbable sutures.

Pneumoperitoneum (10-14 mm Hg) is established and maintained by insufflating carbon dioxide. Through the access, a laparoscope is inserted to view the entire abdomen cavity.

A 12-mm trocar is inserted above the pubic symphysis to allow the introduction of instruments (eg, incisors, forceps, stapler). Another 5-mm trocar is placed in the right periumbilical region, usually between the right costal margin and the umbilicus, to allow the insertion of an atraumatic grasper to expose the appendix. The appendix is grasped and retracted upward to expose the mesoappendix. The mesoappendix is divided using a dissector inserted through the suprapubic trocar. Then, a linear Endostapler, Endoclip, or suture ligature is passed through the suprapubic cannula to ligate the mesoappendix. The mesoappendix is transected using a scissor or electrocautery. To avoid perforation of the appendix and iatrogenic peritonitis, the tip of the appendix should not be grasped.

The appendix may now be transected with a linear Endostapler, or, alternately, the base of the appendix may be suture ligated in a similar manner to that in an open procedure. The appendix is now free and may be removed through the umbilical or the suprapubic cannula using a laparoscopic pouch to prevent wound contamination. Peritoneal irrigation is performed with antibiotic or saline solution. Completely aspirate the irrigant. The cannulae are then removed and the pneumoperitoneum is reduced.

The fascial layers at the cannula sites are closed with absorbable suture, while the cutaneous incisions are closed with interrupted subcuticular sutures or sterile adhesive strips.

Postoperative complications

After an appendectomy there is a 10% risk of infection in the wound, which can usually be treated by the GP prescribing antibiotics. Occasionally it will require a small operation in hospital. A small number of patients can get an abscess in the abdomen, especially if the appendix had perforated. These cause diarrhoea and make the patient unwell often a few days after the operation. It may be necessary to have another operation but they can usually be treated with a drain placed into the abdomen using a scanner to guide the placement and the prescription of antibiotics.

Fifteen to 20% of appendectomies are performed in cases for which test results are later determined to be falsely positive, as appendicitis is difficult to diagnose in infants and toddlers.

Postoperative care

Length of stay. Hospital stay averages two to three days after the operation if the appendix was not perforated and there were no complications.

A longer stay of five to seven days is required for treatment of a perforated appendix. Bowel functioormally returns after two to four days, but intravenous antibiotics are required for at least four to five days and sometimes longer, depending upon the child’s fever and white blood cell count. When the appendix is perforated, the chance for an infection of the incision site are about five to ten percent and the chance that an abscess (pus collection) will develop inside the abdomen is less than five percent. If a wound infection develops, the would will be opened partially and dressing changes begun. If there is an abscess inside the abdomen it is usually possible to drain it by insertion of a needle without the need for re-operation. These complications may delay discharge if they occur.

Diet. If the appendix did not rupture and a nasogastric tube is not needed, clear liquids by mouth are usually started the first day after the operation. The diet is then advanced to normal if the child tolerates the clear liquids (no vomiting or nausea).

Children with perforation of the appendix are started on clear liquids once the child has passed gas or stool from the rectum. Again, as long as the child is tolerating the clear liquids, diet is advanced.

Activity. After appendectomy, children may usually return to school within a week of discharge from the hospital, although they may find that they tire quickly. Vigorous activities and contact sports should be limited for at least three weeks. When the appendectomy is done using a laparoscope, children may resume their usual physical activities as soon as they feel ready–there are no activity constraints.

Prognosis is excellent. In fact, no mortality has been reported in patients with a nonperforated appendix. The mortality rate is less than 1.0% if appendiceal perforation exists. An intermediate mortality rate (1-4%) is reported in infants because of the high frequency of perforation caused by delayed diagnosis related to the difficulties in distinguishing appendicitis from other conditions in the differential diagnosis.

Conclusion. Historically, the diagnosis of appendicitis has been made based on clinical findings. Diagnostic imaging has been used primarily to evaluate patients who have an atypical clinical presentation. Over the past several years, improvements in imaging technology have contributed to an increase in diagnostic accuracy in these patients. Early and accurate diagnosis of appendicitis can decrease patient morbidity and hospital costs by reducing the delay in diagnosis of appendicitis and its associated complications, as well as by avoiding inpatient observation prior to surgery in patients who present with atypical symptoms.

 

2.Cholecystitis.

Figure. Normal biliary tract anatomy. The main right and left hepatic ducts join to form the common hepatic duct, which joins with the cystic duct to form the common bile duct. The common bile duct courses caudally in the hepatoduodenal ligament along with the hepatic artery and portal vein to the level of the pancreatic head.

 

Cholelithiasis

The prevalence of gallstones in children varies according to geography and age. Ultrasound studies provide the following estimates: 0.5% of neonates in Germany (7), 0.13% to 0.2% of infants and children in Italy (8), and less than 0.13% of children in Japan (9). Most studies show a bimodal distribution with a small peak in infancy and a steadily rising incidence from early adolescence onward (10). In early childhood, boys are affected at least as often as girls, but a clear female predisposition emerges during adolescence. In Western children, there has been a consistent increase in both the prevalence of gallstones and the frequency of cholecystectomy for cholelithiasis since the mid-1970s (11,12,13,14,15). This may reflect improved detection from the widespread use of diagnostic ultrasonography and/or a genuine increase in the incidence of cholelithiasis.

Gallstone Composition

There are four major types of gallstone in adults (16), and an additional variety has been characterized in children (17) (Table 93-1). Mixed cholesterol stones develop as a result of cholesterol supersaturation of bile; they are the most common variety in adults and are also found in adolescent girls. Noncholesterol components of these calculi include calcium salts (bilirubinate, carbonate, phosphate, fatty acids) and proteins. In young children, black pigment stones are most frequent. They are formed from the supersaturation of bile with calcium bilirubinate, the calcium salt of unconjugated bilirubin. Black pigment stones are typical of hemolytic disorders and are also found in association with total parenteral nutrition (TPN) (18). Brown pigment stones develop from biliary stasis and bacterial infection, and occur more often in the bile ducts than in the gallbladder. Calcium carbonate stones were previously considered rare and reported largely in association with milky bile (19), but they are now known to be more common (17).

Biliary sludge is sonographically echogenic but, unlike a gallstone, does not cast an acoustic shadow (20). It consists of mucin, calcium bilirubinate, and cholesterol crystals. Gallbladder sludge may complicate TPN/fasting, pregnancy, sickle cell disease, treatment with Ceftriaxone or Octreotide, and bone marrow transplantation. Spontaneous resolution or progression to gallstone formation is possible. Sludge itself may cause biliary complications.

 

Etiology

The predominant factors in gallstone formation are biliary stasis, excess bilrubin pigment, and lithogenic bile. Numerous predisposing conditions have been identified.

Hemolytic disorders such as sickle cell anemia, hereditary spherocytosis, and thalassemia major create excess bilirubin pigment. The prevalence of pigment gallstones in affected children increases with age (21,22,23). In sickle cell disease, cholelithiasis is present in approximately 10% to 15% of children younger than 10 years of age, but in 40% or more of older children (21,24). Other hemolytic disorders, such as hemolytic uremic syndrome, ABO or rhesus incompatibility, and cardiac valve replacement, may also be complicated by pigment stones.

The association between TPN and biliary sludge/cholelithiasis is well established (25). Fasting and TPN promote biliary stasis by impairing both the enterohepatic circulation of bile acids and cholecystokinin-induced gallbladder contraction (26). Limited data suggest that TPN-associated calculi are either pigment stones with a high calcium bilirubinate content (18,27) or calcium carbonate stones (17). Premature infants are particularly susceptible to this complication (28).

Ileal resection/disease is a risk factor for cholelithiasis (27,29). Even a limited ileal resection (less than 50 cm) in the neonate, particularly when associated with a period of parenteral nutrition, predisposes to gallstones (30). Symptomatic gallstones occur in 10% to 20% of children with short bowel syndrome (31). Children with Crohn‘ s disease affecting the terminal ileum are also at risk of cholelithiasis. Pathogenesis is probably related to disturbances of the enterohepatic circulation of bile salts (10).

In adolescents, gallstones are typically composed of cholesterol and associated with an adult pattern of risk factors (i.e., female gender, obesity, pregnancy, and a positive family history) (13,32). Estrogens increase cholesterol secretion and progesterone slows gallbladder emptying (33). Biliary stasis from mechanical obstruction (e.g., choledochal cyst or cystic duct anomalies) or functional impairment of gallbladder emptying is an additional risk factor. An excessive bilirubin load in the presence of an immature bilirubin excretion mechanism may predispose to pigment stone formation. Thus, polycythemia, multiple blood transfusions, and phototherapy (which stimulates biliary excretion of unconjugated bilirubin) have been implicated as etiologic factors in the newborn.

Many other conditions have been associated with an increased incidence of cholelithiasis in children (10). Examples include cystic fibrosis, Down syndrome, childhood cancer, bone marrow transplantation, cardiac transplantation, spinal surgery, dystrophia myotonica, and chronic intestinal pseudoobstruction.

The contribution of each etiologic factor in different series of children with cholelithiasis will vary with institutional referral patterns, age distribution, method of detection of gallstones, and the era under study (11,14,15,32). In prepubertal children, black pigment stones often predominate, but from adolescence onward cholesterol stones become increasingly frequent.

Clinical Features

The presenting features of cholelithiasis are age dependent. Most reported cases of fetal gallstones resolve spontaneously (34).

Reports of infants with gallstones have increased in more recent years. Premature babies are at greatest risk because of poor gallbladder contractility in response to enteral feeding (35), repeated blood transfusions, furosemide therapy, reduced bile acid output (36), ileal resection, and systemic or biliary infection (37,38). Gallstones are often asymptomatic in this age group, but may cause poor feeding or vomiting. Complications such as acute cholecystitis, choledocholithiasis with obstructive jaundice, and/or cholangitis are uncommon, and biliary perforation is rare (37,38).

Older children with symptomatic gallstones tend to complain of abdominal pain localized to the right upper quadrant or epigastrium, associated with nausea and vomiting. Some present with obstructive jaundice or pancreatitis.

Fatty food intolerance, biliary colic, and acute or chronic cholecystitis are well described in most adolescent patients with symptomatic stones. In acute cholecystitis, there may be fever, right upper quadrant tenderness, and occasionally a palpable mass. Jaundice and/or pancreatitis may complicate a common duct stone.

Diagnosis

Cholelithiasis is readily diagnosed by ultrasound scan (US) in a fasted patient. Gallstones are usually mobile, may be solitary or multiple, and cast an acoustic shadow. Stone size rather than calcium content determines the presence or absence of acoustic shadowing (39). Gallbladder wall thickness, the diameter of the common bile duct, the liver, and the remaining biliary tree should also be assessed. Between 20% and 50% of gallstones in children are radiopaque. Radioisotope studies with ^99mTc diisopropyl iminodiacetic acid (DISIDA) is a sensitive and specific investigation for acute cholecystitis; nonvisualization of the gallbladder in an otherwise patent biliary system usually indicates acute cholecystitis.

Figure. CT. Cholelithiasis. A densely calcified calcium bilirubinate stone {arrow) is present in the dependent part of the gallbladder. The striated renal parenchyma is the result of pyelonephritis.

 

Magnetic resonance cholangiography (MRC) and endoscopic ultrasound are helpful in the diagnosis of choledochlithiasis. Endoscopic retrograde cholangiography (ERC) is more invasive, but has the additional advantage that it may be therapeutic.

Management of Cholelithiasis

Gallstones in infants occasionally resolve spontaneously as a result of dissolution and/or passage through the biliary tree (38,39,40,41). Early surgery can be deferred in the asymptomatic infant with gallbladder calculi, provided there is no other evidence of biliary tract disease. Acute calculous cholecystitis generally requires cholecystectomy, although ieonates a brief period of conservative management may be worthwhile (42).

Management of asymptomatic gallbladder calculi in older children is controversial. There is a good argument for elective cholecystectomy in selected children with hemolytic disorders. For other children, a conservative policy has been recommended (43). However, cholecystectomy in experienced centers is generally safe, the chance of spontaneous resolution of gallstones in older children is low, and a child with cholelithiasis is at risk of complications for life.

Gallbladder sludge frequently resolves spontaneously once the precipitant is removed. Thus, biliary sludge associated with TPN usually disappears after enteral feeding has been resumed. For infants who remain dependent on TPN, cholecystokinin and/or ursodeoxycholic acid can be helpful in clearing sludge (44) and rendering the bile less hepatotoxic.

Dissolution therapy for gallstones in children is of little value. Despite prolonged treatment, low dissolution rates and high recurrence rates have been observed in adults with cholesterol stones. Calcified and pigment stones and calculi within a nonfunctioning gallbladder are not amenable to treatment. Extracorporeal shock wave lithotripsy has rarely been used for gallstones in children (45).

Surgery

Cholecystectomy is the standard treatment for symptomatic or complicated gallbladder stones. Rarely, in a severely ill child, cholecystostomy may be a safer initial option.

In the hemolytic disorders, asymptomatic gallstones deserve special consideration.

Cholecystectomy is indicated for hereditary spherocytosis patients with asymptomatic calculi undergoing splenectomy for hematologic indications (22). Cholecystotomy and stone extraction is associated with an unacceptable incidence of recurrent calculi (46). Prophylactic cholecystectomy at the time of splenectomy is not indicated in children without gallstones (47).

Opinion is divided about patients with sickle cell anemia, but many authors favor elective cholecystectomy for asymptomatic gallstones. This is for several reasons: the increasing risk of complications with age (48), the increased morbidity of emergency surgery for gallstone complications (49), and the difficulty of distinguishing cholecystitis from a sickle cell abdominal crisis (50). Laparoscopic cholecystectomy is probably advantageous (51) and, using this approach, a selective preoperative transfusion policy is appropriate (52).

Cholecystectomy is recommended for thalassemia major children with asymptomatic cholelithiasis undergoing splenectomy (53).

Cholecystectomy

Before surgery, routine blood tests and a recent biliary tract ultrasound scan should be available. Awareness of normal variants of biliary anatomy is important. Minicholecystectomy via a small right upper quadrant incision and laparoscopic cholecystectomy are both associated with minimal morbidity. However, the latter is associated with a reduced stress response and analgesic requirement, more rapid recovery, earlier discharge, and improved cosmesis (54). In adults, there is a slightly higher incidence of common bile duct injury with laparoscopic compared with open cholecystectomy (0.2% to 0.5% vs. 0.1% to 0.2%) (55).

The technique of laparoscopic cholecystectomy has been well described (10,56). An operative cholangiogram can be used to clarify anatomy and/or identify a common bile duct stone, but the latter is unlikely if the caliber of the common duct is normal and there is no history of jaundice, pancreatitis, or abnormal liver function. Cholangiography can be carried out with a Kumar clamp and sclerotherapy needle (57).

 

Holcomb et al. recorded no major complications and no conversions in 100 laparoscopic cholecystectomies (the smallest patient was 10 kg) (56). Prasad et al. described a cystic duct stump leak diagnosed by ERC and treated successfully by external drainage, antibiotics, and endoscopic insertion of a nasobiliary catheter (58).

Choledocholithiasis

Common bile duct stones are uncommon, but are relatively more frequent in children with sickle cell disease (59) and in infants (15,38). Obstructive jaundice, cholangitis, and/or pancreatitis are typical presenting features in symptomatic cases. Although US (conventional or endoscopic), MRC (Fig. 93-2), and computed tomography (CT) may be helpful in diagnosis, endoscopic retrograde cholangiopancreatography (ERCP) offers the possibility of both diagnosis and treatment. ERCP and sphincterotomy with stone retrieval can be performed before or after laparoscopic cholecystectomy (60,61). Early ERCP is recommended for common duct stones associated with obstructive jaundice (bilirubin greater than 100 (Вµmol/L) and/or cholangitis, but not for most cases of gallstone pancreatitis because the stone usually passes spontaneously. Laparoscopic cholecystectomy with intraoperative cholangiography is usually undertaken a few weeks after the episode of gallstone pancreatitis (56).

Choledocholithiasis can be treated by open exploration of the common bile duct, laparoscopic common duct exploration (56), or ERCP, sphincterotomy, and stone extraction. In some centers, percutaneous techniques are used (62). In small infants, cholecystotomy and irrigation may be successful. An initial short period of observation may be worthwhile if the infant is well without evidence of sepsis or progressive obstruction because some stones will pass spontaneously (37,40).

Acquired Disorders of the Gallbladder

If the gallbladder is suspended by a peritoneal fold from the under surface of the liver, it is at risk of torsion. Presentation is with acute abdominal pain and vomiting, and a mobile tender mass may be palpable in the right hypochondrium (63). Cholecystectomy is curative.

Severe acute distention of the gallbladder (acute hydrops) may progress to acalculous cholecystitis if infection, ischemia, or chemical inflammation supervene. This is seen most often in children who are critically ill for other reasons (Table 93-2) (64,65). A multifactorial etiology is likely, involving dehydration, biliary stasis, infection, and gallbladder ischemia. In Kawasaki disease, vasculitis is the probable cause. In tropical countries, Salmonella typhi infection and ascariasis should be considered (66). Clinical features include abdominal pain, vomiting, fever, localized tenderness, and, in 50% of cases, a palpable right upper quadrant mass. Laboratory investigations reveal a leukocytosis, raised inflammatory markers, hyperbilirubinemia, and mild hyperamylasemia. Ultrasound shows a markedly distended gallbladder. Initial management is with antibiotics and intravenous fluids. Cholecystectomy is indicated if there is progressive clinical deterioration, a persistent tender mass, and/or increasing gallbladder distension on US. Tube cholecystostomy is an option if the gallbladder is viable.

An aggressive variant of chronic calculous cholecystitis is xanthogranulomatous cholecystitis, in which there is dense inflammation of the gallbladder wall extending into adjacent tissues (67). It may be confused with malignancy. On cut section, the gallbladder wall has multiple yellow nodules containing foamy histiocytes.

Impaired gallbladder contractility (dyskinesia) in the absence of cholelithiasis is a rare cause of chronic abdominal pain in children (68). US shows a normal gallbladder, and the diagnosis rests on demonstrating impaired gallbladder contraction in response to an injection of cholecystokinin during a DISIDA scan. Treatment is by cholecystectomy.

Polypoid lesions of the gallbladder are rare in childhood. They may occur as a manifestation of metachromatic leukodystrophy, Peutz-Jeghers syndrome, or pancreaticobiliary malunion. Other, idiopathic polyps have a variable histology (adenoma, gastric heterotopia, cholesterol polyp, and epithelial hyperplasia) (69). Cholecystectomy is recommended for idiopathic polyps if there are biliary symptoms or if the polyp is greater than or equal to 1 cm in size.

 

3. Acute Pancreatitis

Incidence

Acute pancreatitis is an uncommon disease in children but has higher morbidity and mortality than in adults.

Etiology

The vast majority of cases of pancreatitis in children are from blunt abdominal injury In the pediatric population, nearly 40% of cases of traumatic pancreatitis are attributable to bicycle-related injury. After trauma, the most common causes of pan­creatitis in children are drug therapy (corticosteroids, azathioprine, thiazides, furo-semide, tetracyclines, and valproic acid), viral infection (Epstein-Barr, Coxsackie, enterovirus, and mumps), and bacterial infection. Cystic fibrosis, biliary disease, vasculitic diseases (systemic lupus, Henoch-Schonlein purpura), and type I and V hyperlipidemias are also associated with acute pancreatitis in the pediatric popula­tion.

Clinical Presentation

Children present with vague abdominal pain which is exacerbated by eating. The classic symptom of pain radiating to the back is rarely observed in the pediatric population. Nausea and vomiting may be present. Rarely, patients may present with a small bowel obstruction or young women may present with salpingitis secondary to pancreatitis.

Diagnosis

Serum amylase, trypsinogen, and lipase levels are useful to establish the diagno­sis of acute pancreatitis. An elevated serum amylase is the usual biochemical abnor­mality associated with acute pancreatitis. Because amylase production occurs from other nonpancreatic sources (i.e., salivary gland), elevated serum amylase is rela­tively nonspecific. Calculation of the amylase clearance may be helpful and is nor­mally less than 5%. Trypsinogen and lipase are produced almost exclusively by the pancreas; elevated serum levels are more specific for pancreatitis.

Computed tomography (CT) is the best radiographic study to image the pan­creas in cases of severe or complicated pancreatitis. Abdominal CT is often obtained as part of the trauma evaluation.

Fisure .CT. Acute diffuse pancreatitis. Mild acute pancreatitis in a 2-year-old girl with Crohn disease. Portal venous phase CT shows global enlargement of the pancreas {arrows) with normal glandular enhancement throughout. This patient’s symptoms improved substantially within 48 hours.

 

Figure .CT. Acute focal pancreatitis in two patients. A: A 9-year-old girl with elevated amylase and lipase levels. Parenchymal phase CT scan shows an enlarged, heterogeneously enhancing pancreatic head {arrows). Also note fluid in the anterior pararenal space {open arrow) and root of the small bowel mesentery {arrowhead). B: A 13-year-old boy with abdominal pain, vomiting, and elevated amylase levels. Portal venous phase CT shows heterogeneous enhancement of the pancreatic tail {arrow). Also note fluid in the left pararenal space and left paracolic gutter.

 

Ultrasound is sometimes useful, but often only provides limited visualization of the pancreas due to its retroperitoneal location and interposed bowel gas which further limits the study.

 

Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive test that can accurately delineate pancreatic ductal anatomy. ERCP causes pancreatitis in 5-10% of cases and is gen­erally avoided during the early phases of acute pancreatitis.

Treatment

Medical management is the mainstay of treatment for pancreatitis. Volume resuscitation is essential to counter retroperitoneal third space fluid losses. Nasogastric decompression is recommended to avoid gastric distention and patients are initially maintained NPO with nasogastric decompression. Pain management is essential. Meperidine is preferred because it does not cause sphincter of Oddi contraction like morphine does. Hyper-alimentation may be necessary if the course of pancreatitis is prolonged. Enteral feeding distal to the ligament of Treitz via duodenal feeding tube is the preferred method of providing nutrition in refractory cases. The majority of cases of pancreatitis are self-limited and resolve spontaneously with supportive therapy.

In severe cases (i.e., necrotizing pancreatitis, infected pancreatic necrosis), surgi­cal intervention may be necessary for irrigation and/or debridement of the pancreas. The morality rate in this scenario approaches 15%.

 

Peritonitis

 

Peritoneum is multilayered membrane which lines the abdominal cavity, and supports and covers the organs within it. The part of the membrane that lines the abdominal cavity is called the parietal peritoneum. The portion that covers the internal organs, or viscera, is known as the visceral peritoneum and forms the outer layer (serosa) of most of the intestinal tract. The supportive peritoneum forms sheets of greatly modified membranes called mesenteries. These tissues hold the organs of the digestive tract in position and convey nerves, blood vessels, and lymphatic ducts to the viscera. The space between the visceral and parietal membranes contains a watery fluid that permits the abdominal organs to slide freely against the abdominal wall.

Peritonitis is defined as inflammation of the peritoneum. Peritonitis is often caused by introduction of an infection into the otherwise sterile peritoneal environment through perforation of the bowel, such as a ruptured appendix or colonic diverticulum. The disease may also be caused by introduction of a chemically irritating material, such as gastric acid from a perforated ulcer or bile from a perforated gall bladder or a lacerated liver. In women, localized peritonitis most often occurs in the pelvis from an infected fallopian tube or a ruptured ovarian cyst.

Inflammation and/or infection of the peritoneal cavity are commonly encountered problems in the practice of clinical medicine today. In general, the term peritonitis refers to a constellation of signs and symptoms, which includes abdominal pain and tenderness on palpation, abdominal wall muscle rigidity, and systemic signs of inflammation. Patients may present with an acute or insidious onset of symptoms, limited and mild disease, or systemic and severe disease with septic shock. The peritoneum reacts to a variety of pathologic stimuli with a fairly  uniform inflammatory response.

Classification.

Depending on the underlying pathology, the resultant peritonitis may be infectious or sterile (ie, chemical or mechanical).

Peritoneal infections are classified as primary (ie, spontaneous), secondary (ie, related to a pathologic process in a visceral organ), or tertiary.

Spontaneous peritonitis is caused by an infection in the blood that occurs when irritant fluid accumulates in the space between the layers of the peritoneum. This is most commonly one of the complications of cirrhosis. However, it is also sometimes related to peptic ulcer disease, appendicitis or diverticulitis.

Secondary peritonitis is a chronic or acute inflammation caused by bacteria entering the peritoneum following perforation of the gastrointestinal tract (for example, ruptured appendix). The irritant can be gastric juice, small bowel contents or faeces from the colon.

Tertiary peritonitis is persistent or recurrent infection after adequate initial therapy.

The intra-abdominal infection may be localized or generalized, with or without abscess formation.

Microbiology includes a mixture of aerobic and anaerobic organisms. The most commonly isolated aerobic organism is Escherichia coli, and the most commonly observed anaerobic organism is Bacteroides fragilis. A synergistic relationship exists between these organisms. In patients who receive prolonged antibiotic therapy, yeast colonies (eg, candidal species) or a variety of nosocomial pathogens may be recovered from peritoneal fluids.

Skin flora may be responsible for abscesses following a penetrating abdominal injury. Neisseria gonorrhoeae and chlamydial species are the most common organisms involved in pelvic abscesses in females as part of pelvic inflammatory disease.

The type and density of aerobic and anaerobic bacteria isolated from intra-abdominal fluid depend upon the nature of the microflora associated with the diseased or injured organ.

Microbial flora of the GI tract shifts from small numbers of aerobic streptococci, including enterococci and facultative gram-negative bacilli in the stomach and proximal small bowel, to larger numbers of these species with an excess of anaerobic gram-negative bacilli (particularly Bacteroides species) and anaerobic gram-positive flora (streptococci and clostridia) in the terminal ileum and colon. Differences in microorganisms observed from the upper to the lower portion of the GI tract partially account for differences in septic complications associated with injuries or diseases to the upper and lower gut. Sepsis occurring after upper GI perforations or leaks causes less morbidity and mortality than sepsis after leaks from colonic insults.

Clinical features.

Initial diagnosis is based on symptoms and a physical examination. Abdomen will be tender, and often distended. Children with peritonitis will often feel the need to protect their abdominal area from touch. Ieonates abdominal distention usually accompanied by erythema and edema of abdominal wall ad scrotum.

Many patients have a significant septic response, volume depletion, and catabolic state. This syndrome may include high cardiac output, tachycardia, low urine output, and low peripheral oxygen extraction. Initially, respiratory alkalosis due to hyperventilation may occur. If left untreated, this progresses to metabolic acidosis. Sequential multiple organ failure is highly suggestive of intra-abdominal sepsis.

Once an initial diagnosis and assessment of the probably causes has been made, tests are carried out.

Tests for spontaneous and secondary peritonitis include:

·                    Culture of peritoneal fluid (which is found in the peritoneal cavity and acts as a lubricant between the layers of the peritoneum) – a bacteriological laboratory test to identify infectious organisms in the fluid.

·                    Chemical examination or laboratory analysis of peritoneal fluid.

·                    Blood culture to determine the presence of microorganisms in the blood.

Other possible tests for peritonitis, especially spontaneous peritonitis, include:

·                    An abdominal X-ray to rule out other possible reasons for symptoms such as abdominal pain.

Surgery to open and examine the interior of the abdomen (exploratory laparotomy).

Treatment.

The main goal of treating peritonitis is to cure the infection. The treatment method used depends on the source of the infection and the type of peritonitis present.

Spontaneous peritonitis: The most common treatment is by injection of antibiotics into the peritoneum to control the infection, together with drainage of the area. Surgery is only used to repair a perforation, such as in the rare case when peritonitis is caused by a rupture of an intra-abdominal organ, such as in the case of appendicitis.

Secondary peritonitis often requires surgical treatment to remove or repair the source of the infection, such as an abscess or an infected bowel. This is accompanied by bed rest, and intravenous antibiotics. Broad spectrum antibiotics (include cefoxitin 80 to 160 mg/kg/day in divided doses, or amikacin 15 mg/kg/day in divided doses plus clindamycin 20 to 40 mg/kg/day in divided doses) are used to combat the infection until lab results indicate which treatment method is safest and best for the patient.

The sooner treatment is begun, the better your chances of recovery from any type of peritonitis.

In the case of spontaneous peritonitis, chances of full recovery are guarded due to the underlying cause (such as serious liver disease). Complications may include:

·                    Abscess development

·                    Bowel obstruction caused by scar tissue

·                    Acute renal failure

·                    Damage to the brain and nervous system due to complications of septic shock.

People with secondary peritonitis may recover completely if treatment begins soon enough; however, the disorder can be lethal in some cases. Complications may include:

·                    Septic shock (cardiovascular collapse following serious infection in the blood) as a result of insufficient blood flow to vital organs and the heart.

·                    Abscess development

·                    Development of fibrous intraperitoneal scar tissue (intraperitoneal adhesions) i.e. within the peritoneal cavity.

In women with PID for whom the diagnosis is not certain, laparoscopy is an option, but exploration may be needed to rule out appendicitis or to treat a tubo-ovarian abscess or salpingitis.

Treatment of peritonitis primarily involves treatment of the underlying disease. General therapy includes antibiotics, nasogastric intubation and suction, respiratory care, and fluid and electrolyte replacement. The most effective antibiotic regimen to give before results of cultures are available is debatable. Third-generation cephalosporins are effective and probably safest.

Surgical management

The management of secondary peritonitis involves:

o   Elimination of the source of infection

o   Reduction of bacterial contamination of the peritoneal cavity

o   Prevention of persistent or recurrent intra-abdominal infections

Source control achieved by closure or exteriorisation of perforation. Bacterial contamination reduced by aspiration of faecal matter and pus. 

Recurrent infection prevented by the used of:

o        Drains

o        Planned re-operations

o        Leaving the wound open (laparostomy)

Peritoneal lavage often used but benefit is unproven

·                    Simple swabbing of pus from peritoneal cavity may be of same value

·                    Has been suggested that lavage may spread infection or damage peritoneal surface

·                    No benefit of adding antibiotics to lavage fluid

·                    No benefit of adding Chlorhexidine or Betadine to lavage fluid

·                    If used, lavage with large volume of crystalloid solution probably has best outcome

 

Abdominal Abscess

Intra-abdominal abscesses are localized collections of pus that are confined in the peritoneal cavity by an inflammatory barrier. This barrier may include the omentum, inflammatory adhesions, or contiguous viscera. The abscesses usually contain a mixture of aerobic and anaerobic bacteria from the GI tract.

Pathophysiology. Bacteria in the peritoneal cavity, in particular those arising from the large intestine, stimulate an influx of acute inflammatory cells. The omentum and viscera tend to localize the site of infection, producing a phlegmon. The resulting hypoxia in the area facilitates growth of anaerobes and impairs bactericidal activity of granulocytes. The phagocytic activity of these cells degrades cellular and bacterial debris, creating a hypertonic milieu that expands and enlarges the abscess cavity in response to osmotic forces. If untreated, the process continues until bacteriemia develops, which then progresses to generalized sepsis with shock.

Clinical.

Intra-abdominal abscesses are highly variable in presentation. Persistent abdominal pain, focal tenderness, spiking fever, prolonged ileus, leukocytosis, or intermittent polymicrobial bacteriemia suggest an intra-abdominal abscess in patients with predisposing primary intra-abdominal disease or following abdominal surgery. If a deeply seated abscess is present, many of these classic features may be absent. The only initial clues may be persistent fever, mild liver dysfunction, persistent GI dysfunction, or nonlocalizing debilitating illness.

The diagnosis of an intra-abdominal abscess in the postoperative period may be difficult because postoperative analgesics and incisional pain frequently mask abdominal findings. In addition, antibiotic administration may mask abdominal tenderness, fever, and leukocytosis.

In patients with subphrenic abscesses, irritation of contiguous structures may produce shoulder pain, hiccup, or unexplained pulmonary manifestations such as pleural effusion, basal atelectasis, or pneumonia. With pelvic abscesses, frequent urination, diarrhea, or tenesmus may occur.

Relevant Anatomy. The 6 functional compartments within the peritoneal cavity include the (1) pelvis, (2) right paracolic gutter, (3) left paracolic gutter, (4) infradiaphragmatic spaces, (5) lesser sac, and (6) interloop potential spaces of the small intestine.

The paracolic gutters slope into the subhepatic and subdiaphragmatic spaces superiorly and over the pelvic brim inferiorly. In a supine patient, the peritoneal fluid tends to collect under the diaphragm, under the liver, and in the pelvis. More localized abscesses tend to develop anatomically in relation to the affected viscus. For example, abscesses in the lesser sac may develop secondary to severe pancreatitis, or periappendiceal abscesses from a perforated appendix may develop in the right lower quadrant. Small bowel interloop abscesses may develop anywhere from the ligament of Treitz to the ileum. An understanding of these anatomic considerations is important for recognizing and draining these abscesses.

Lab Studies.

Hematologic parameters suggesting infection (eg, leukocytosis, anemia, abnormal platelet counts, abnormal liver function) frequently are present, although patients who are debilitated often fail to mount reactive leukocytosis or fever.

Blood cultures indicating persistent polymicrobial bacteremias strongly implicate the presence of an intra-abdominal abscess. Because more than 90% of intra-abdominal abscesses contain anaerobic organisms, particularly B fragilis, postoperative Bacteroides species bacteremia suggests intra-abdominal sepsis.

Imaging Studies.

Plain abdominal radiographs, though rarely diagnostic, frequently indicate the need for further investigation.

Abnormalities on plain abdominal films may include a localized ileus, extraluminal gas, air-fluid levels, mottled soft tissue masses, absence of psoas outlines, or displacement of viscera.

In subphrenic or even subhepatic abscesses, the chest radiograph may show pleural effusion, elevated hemidiaphragm, basilar infiltrates, or atelectasis.

In experienced hands, ultrasonography has an accuracy rate greater than 90% for diagnosing intra-abdominal abscesses.

Ultrasonography is readily available, portable, and inexpensive. The findings can be quite specific when correlated with the clinical picture.

A drawback is that marked obesity, bowel gas, intervening viscera, surgical dressings, open wounds, and stomas can create problems with definition. In addition, the quality of the procedure is operator-dependent. These disadvantages may limit efficacy in postoperative patients.

CT scan has greater than 95% accuracy and is the best diagnostic imaging method. The presence of ileus, dressings, drains, or stomas does not interfere with reliability.

Identify any occult abscesses using serial images obtained from the diaphragm to the pelvis.

The appearance of an air bubble within a fluid collection or a low-attenuation extraluminal mass is diagnostic of an intra-abdominal collection.

CT scans can document inflammatory edema in the adjacent fat (obliteration of fat plane) and hyperemia in the abscess wall (enhancement).

Drawbacks include nonportability, relative difficulty in diagnosing intraloop abscesses, and, possibly, poor patient cooperation.

Recent intra-abdominal surgery also may pose a diagnostic problem in patients in whom intra-abdominal abscesses are suspected. CT scan is not recommended for use in the diagnosis of such abscesses until approximately the eighth postoperative day. By that time, postoperative tissue edema is reduced, and nonsuppurative fluids (eg, hematoma, seroma, intraoperative irrigation fluid) should be reabsorbed. In most postoperative patients, signs of intra-abdominal abscesses do not develop within the first 4-5 days.

Treatment.

Medical therapy. Antibiotic therapy involves the administration of parenteral empirical antibiotics. Begin therapy prior to abscess drainage, and conclude therapy when all systemic signs of sepsis resolve. Because abscess fluid usually contains a mixture of aerobic and anaerobic organisms, direct initial empiric therapy against both sets of microbes. This may be accomplished with antibiotic combination therapy or with broad-spectrum, single-agent therapy. Specific therapy then is guided by the results of cultures retrieved from the abscess.

In patients who are immunosuppressed, candidal species may play an important pathogenic role, and treatment with amphotericin B or fluconasol  may be indicated.

Surgical therapy.

Drainage of pus is mandatory and is the first line of defense against progressive sepsis. Percutaneous CT-guided catheter drainage has become the standard treatment for most intra-abdominal abscesses. It avoids possibly difficult laparotomy, requires anesthesia, prevents the possibility of wound complications from open surgery, and may reduce the length of hospitalization. It also obviates the possibility of contamination of other areas within the peritoneal cavity. CT-guided drainage delineates the abscess cavity and may provide safe access for percutaneous drainage. When performed by experienced hands, it also prevents the possibility of injury to adjacent viscera or blood vessels.

After surgical drainage, clinical improvement should occur within 48-72 hours. Lack of improvement within this time frame mandates a repeat CT scan to check for additional abscesses.

Criteria for removal of percutaneous catheters include resolution of sepsis signs, minimal drainage from the catheter, and resolution of the abscess cavity as demonstrated by a sonogram or CT scan. Persistent drainage usually reflects the presence of an enteric fistula, and a CT scan with contrast should be performed. Frequently, this fistula can be documented by sonography.

Complications of percutaneous drainage include bleeding or inadvertent puncture of the GI tract.

Surgical intervention.

Open surgical drainage is mandatory if percutaneous drainage fails or if collections are not amenable to catheter drainage. The surgical approach may be either extraperitoneal or transperitoneal.

With accurate preoperative localization, direct surgical drainage may be possible through an extraperitoneal approach. This technique reduces the risk of bowel injury, spread of contamination, and bleeding. It also allows for a faster return of bowel function.

The transperitoneal approach is made safer by the judicious use of preoperative antibiotics. Although contamination of otherwise uninfected sites remains a major concern, this complication is particularly reduced if the organisms involved are sensitive to the chosen drugs. . Transperitoneal exploration is indicated for multiple abscesses not amenable to CT-guided drainage, such as interloop collections or an enteric fistula feeding the abscess.

Pelvic abscesses often are palpable as tender fluctuant masses impinging on the vagina or rectum. Draining these abscesses transvaginally or transrectally is best to avoid the transabdominal approach.

During the course of a laparotomy, the surgeon must use digital or direct exploration to be certain that all loculations are broken down and that all debris, such as hematomas or necrotic tissue, is evacuated.

Improved clinical findings within 3 days after treatment indicate successful drainage. Failure to improve may indicate inadequate drainage or another source of sepsis. If left untreated, the septic state inevitably produces multiple organ failure.

 

SPECIFIC TYPES OF ACUTE PERITONITIS

 

Meconium Peritonitis

Clinical Presentation. Abdominal distension.

Etiology/Pathophysiology. The most common causes of meconium peritonitis are ischemic lesions of the small bowel associated with mechanical obstruction (atresia, volvulus, intussusception, congenital bands, Meckel diverticulum and internal hernia). These likely account for 50% of the cases of meconium peritonitis. Meconium peritonitis may also be caused by viral infections (cytomegalovirus, or parvovirus B19). Meconium ileus accounts for less than 25% of cases of meconium peritonitis.

Meconium is a sterile mixture and consists of desquamated epithelial cells, vernix, lanugo hair, and intestinal secretions containing cholesterol and mucopolysaccharides. When meconium spills into the peritoneum it acts as an irritant and an inflammatory serosal reaction. A secondary inflammatory response results in the production of fluid (ascites), fibrosis, calcification and sometimes cyst formation.

There are 3 types of meconium peritonitis:

1. Fibroadhesive – an intense adhesive peritoneal reaction with no active leak of bowel contents.

2. Cystic – a localized cavity formed by adjacent loops of bowel.

3. Generalized – no adhesions or calcifications, seen in cases where the bowel perforation occurs just before birth.

The sonographic findings vary depending on several factors: the etiology, the time interval since perforation and the degree of inflammatory response. It may be seen as early as 13 weeks gestation. In the typical case, diffuse hyperechoic punctate echoes with or without acoustic shadowing may be seen in the abdominal cavity, on the hepatic surface and in the scrotal sac. In addition, depending upon the etiology, ascites, polyhydramnios or fetal bowel distention may be present. Polyhydramnios, reported in approximately 50% of patients, may be caused by by peristaltic deficiency associated with decreased swallowing activity. If the inflammatory response remains localized a meconium pseudocyst may occur. This appears sonographically as a cystic heterogeneous mass with an irregular, calcified wall.

The prognosis depends upon the etiology. Bowel perforations may heal and the ascites and bowel dilatation may resolve, leaving only peritoneal calcifications as the only sonographic sign of meconium peritonitis. While cystic fibrosis is universally seen in cases of meconium ileus, it is seen in only 7-40% of cases of meconium peritonitis

In the absence of an intra-abdominal mass such as a meconium pseudocyst, the major differential diagnostic possibilities for bright echoes within the abdomen is “hyperechogenic bowel”. In this condition, the bowel appears as bright as bone. This is ofteormal, particularly in the third trimester, but has been described to be associated with cystic fibrosis and chromosomal abnormalities. It should be remembered that the use of high frequency transducers will cause the fetal bowel wall to be hyperechogenic and simulate this appearance.

 

Perforated abdominal esophagus may develop from iatrogenic perforations (eg, from an esophagoscope, balloon dilator, or bougie) above or below the diaphragm. Forceful vomiting with a full stomach may cause esophageal rupture (Boerhaave’s syndrome), which is the most serious type of emetic injury. Pain in the left upper quadrant, left chest, or shoulder after any of these occurrences should alert the physician to order an immediate barium or meglumine diatrizoate (Gastrografin) swallow. If a perforation is noted, immediate operation is necessary because the mortality from peritonitis or empyema increases rapidly with delay.

Perforated gastric or duodenal ulcer tends to cause the most serious cases of peritonitis; the mortality rate is nearly 20%. There may be a history of peptic ulcer disease, but in children 33% of cases, the first symptom is a sudden attack of severe epigastric pain. A patient examined shortly after onset may be relatively free of pain and show only mild tenderness and diminished or absent peristalsis. However, within a few hours, vomiting, tenderness, and spasm, either in the epigastrium or over the whole abdomen, develop.

An upright abdominal x-ray taken 6 h after perforation shows air under one or both sides of the diaphragm in about 50% of cases; as time passes, this sign becomes more common. If the diagnosis is in doubt, meglumine diatrizoate (Gastrografin) passed into the stomach through an inlying nasogastric tube will demonstrate the perforation. (Meglumine diatrizoate does not irritate the peritoneum as does standard barium.) The earlier an operation is performed, the greater the chance of success. The decision to use simple closure of the perforation or a definitive operation for the ulcer disease (vagotomy with gastric resection or pyloroplasty) depends on the patient’s history (eg, of ulcer disease) and condition.

Perforated intestine may arise from strangulating obstruction and perforated Meckel’s diverticulum. The diagnosis of peritonitis must be based on clinical symptoms of severe abdominal pain, tenderness, and absent peristalsis. X-rays are of little value, save for free air under the diaphragm, because abnormal findings may be absent. Gangrene and perforation can occur within 6 h, so exploration must be performed expeditiously.

Perforated appendix can occur at any age but is the most common cause of peritonitis in children and young adults. In children, because of a poorly developed omentum, peritonitis is likely to be generalized; in adults, local peritonitis and abscess formation are more common. Tenderness in the right lower quadrant or over the entire abdomen indicates the extent of inflammation.

Before operation, a high fever in children should be reduced if possible. Antibiotics are mandatory in appropriate dosage adjustment for age and size. A nasogastric tube is inserted and urine output measured. Fluid status is maintained by adequate IV fluid and electrolyte replacement. In late cases, a patient’s condition may not improve for several hours. If an abscess or an inflammatory mass has formed, operation may be limited to drainage of the abscess; whenever possible, the appendix should be removed as well.

Perforated colon is caused by obstruction, diverticulitis, inflammatory disease, and toxic megacolon. Sometimes perforation occurs spontaneously. In the presence of colonic obstruction, perforation of the cecum can occur; this catastrophe is imminent if the cecum is >= 13 cm in diameter. Perforated diverticulitis of the sigmoid or right colon is the most common cause of peritonitis from a perforated colon. Patients receiving prednisone are apt to have such perforations, which may be essentially silent anywhere in the colon. Other immunosuppressive drugs (eg, cytotoxins) can also increase the danger of perforation. Other diseases that lead to perforation are ulcerative colitis, Crohn’s disease, and any cause of toxic megacolon. Colonic resection is usually always indicated when peritonitis is caused by any of these diseases.

Acute necrotizing enterocolitis affects newborns; in about 25% of cases, laparotomy is necessary because of bowel perforation and peritonitis.

Perforated gallbladder or biliary tree can cause peritonitis. Acute cholecystitis can lead to perforation of the gallbladder, which usually leads to a local abscess but occasionally to generalized peritonitis. Operation should include cholecystectomy. The most common cause of bile peritonitis arising from the bile ducts is iatrogenic damage during cholecystectomy.

Primary acute peritonitis produces generalized abdominal pain, fever, and ileus with vomiting and either diarrhea or constipation. Pneumococcal peritonitis, although uncommon, is the most frequent cause of this condition, which occurs chiefly in young girls: Bacterial entry via the vagina seems to be one source. However, 25% of cases occur in males, so septicemia must be another source. Other organisms (eg, streptococci, staphylococci) can produce primary acute peritonitis; most cases are associated with septicemia. If the disease is suspected, an abdominal tap may be performed. If pneumococci, staphylococci, or streptococci are found, appropriate IV antibiotic therapy can be started at once. If no fluid can be found or if the smear shows a mixture of gram-positive cocci and gram-negative bacilli, a laparotomy is necessary.

Pancreatitis can cause an exudate that at first is retroperitoneal but soon involves the peritoneal cavity. It is a chemical peritonitis, initially with a high level of amylase in the exudate; later, contamination with organisms from the GI tract may occur. If the diagnosis seems certain and trauma was not a factor, laparotomy usually is avoided and reserved for the complications of pancreatic necrosis, abscess, or pseudocyst. However, failure to improve may be an indication for earlier operation.

 

Complications of peritonitis can include the following:

·                    Sepsis – an infection throughout the blood and body that can potentially cause multiple organ failure 

·                    Abnormal clotting of the blood (generally due to significant spread of infection) 

·                    Formation of fibrous tissue in the peritoneum 

·                    Respiratory distress syndrome– a severe infection of the lungs

·                    Some forms of chronic peritonitis do not respond to treatment 

The prognosis for peritonitis depends primarily on the type of the condition. For example, the outlook for those with secondary peritonitis tends to be poor (10% to 40% mortality rate), especially among individuals with compromised immune systems, and those who have had symptoms for longer than 48 hours before treatment. While the long-term outlook for individuals with primary peritonitis related to liver disease also tends to be poor, the prognosis for primary peritonitis among children is generally very good after treatment with antibiotics.

 

Necrotizing enterocolitis (NEC)

 

Necrotizing enterocolitis (NEC) is the most common gastrointestinal medical and/or surgical emergency occurring ieonates. With mortality rates approaching 50% in infants who weigh less than 1500 g, NEC represents a significant clinical problem. Although, it is more common in premature infants, it can also be observed in term babies.

Etiology/Pathophysiology.

Hypoxic-ischemic injury. Mesenteric ischemia has been postulated for many years to be the common denominator in the pathogenesis of NEC. Analogies have been made with “diving reflex” in aquatic animals (reflex circulatory shunting to selectively perfuse the brain and heart at the expense of other “nonvital” organs) leading to selective splanchnic ischemia. The premature infant is exposed to numerous perinatal stresses, such as hypotension, hypothermia, hypoxia, feeding, anemia, and umbilical vessel catheterization, which have been postulated to play a role in pathogenesis of ischemic injury to the neonatal intestine. The mechanism of intestinal injury may be related to reduced or absent intrinsic ability of the neonatal intestine to regulate blood flow and oxygenation. Since oxygen extraction and mucosal blood flow appear to be near maximal during feeding alone, the newborn intestine may be unable to maintain oxygen uptake in the presence of superimposed cardiovascular stress. Oxygen-derived free radicals have also been proposed as mediators of mucosal injury in NEC.

Enteral alimentation. A great of controversy has been generated about the relationship of feeding to the pathogenesis of NEC. Enteral alimentation is thought to play a major role since 90% to 95% of all infants who develop NEC have been enterally fed. Incompletely digested formula can provide a substrate for bacterial proliferation. Feeding may also increase the risk for intestinal tissue hypoxia by increasing intestinal oxygen demand during nutrient absorption. In the setting of an immature immune system, possible gastrointestinal dysmotility/stasis, immature mesenteric vascular regulatory capacity, ischemic, hypoxic, or infectious stresses, and the increased metabolic demand imposed on the intestine during nutrient absorption may lead to tissue hypoxia, subsequent mucosal injury, bacterial invasion, and necrotizing enterocolitis.

A beneficial effect of breast milk against the development of NEC has been suggested. Potential protective factors in human milk include enhanced growth of lactobacilli, an antistaphylococcal agent, immunoglobulins, complement components, lysozyme, lactoperoxidase, lactoferrin, macrophages, and lymphocytes. NEC does occur in infants fed human milk, indicating that additional factors, which can override the protective effects of fresh breast milk, must be involved in the development of NEC.

Infectious disease. Bacterial proliferation is undoubtedly another factor in the pathogenesis of NEC, but whether bacteria are primary initiators of the disease is unknown. The occurance of NEC in epidemic forms suggests a direct role for microorganisms in the pathogenesis. Multiple organisms, including bacteria and viruses, have been suggested as candidates, with considerable interest centered on clostridial species, which produce potent exotoxins. The mere presence of bacteria in the gut is not necessarily synonymous with mucosal invasion, although the premature infant may have an immature barrier to infectious agents. A possible role for immunoglobulins in the prevention of NEC has also been implicated. Excess levels of exotoxin and/or increased sensitivity to exotoxin might initiate the damage seen in infants with NEC.

In most cases, NEC occurs sporadically. However, NEC also occurs in temporal and geographic clusters or outbreaks (epidemic NEC). Superimposed on their baseline rate, several centers have reported alternating periods of endemic and epidemic NEC. Differential etiologic factors may be involved in endemic and epidemic NEC.

Histologic Findings. Inspecting the affected bowel reveals mucosal ischemia, progressing to cell death and sloughing. Necrosis can be limited to the mucosal layer, observed radiographically as pneumatosis, or it can affect the full wall, resulting in perforation with subsequent peritonitis. Necrotic and/or perforated intestine must be resected.

Frequency varies without correlation with season or geographic location. Outbreaks of NEC seem to follow an epidemic pattern withiurseries, suggesting an infectious etiology even though a specific causative organism is unknown. Over the past 25 years is a relatively stable incidence, ranging from 0.3-2.4 cases per 1000 live births. Because more premature babies are surviving, expecting an increase in the overall incidence of NEC is reasonable.

Mortality/Morbidity. The mortality rate ranges from 10-44% in infants weighing less than 1500 g, compared to 0-20% mortality rate for babies weighing more than 2500 g. Extremely premature infants (1000 g) are particularly vulnerable, with reported mortality rates of 40-100%. One study compared mortality rates for term versus preterm infants and reported rates of 4.7% for term infants and 11.9% for premature babies.

Race. Some studies indicate higher frequency in black babies than in white babies, but other studies show no difference based on race.

Sex. Most studies indicate that male and female babies are affected equally. However, the higher incidence of neonatal sepsis and meningitis reported for male infants suggests otherwise.

Age. NEC clearly predominates in premature infants, with incidence inversely related to birth weight and gestational age. Although specific numbers range from 4% to more than 40%, infants weighing less than 1000 g at birth have the highest attack rates. This rate drops dramatically to 3.8 per 1000 live births for infants weighing 1501-2500 g at birth. Similarly, rates decrease profoundly for infants born after 35-36 weeks’ postconceptional age.

Average age at onset in premature infants seems to be related to postconceptional age, with babies born earlier developing NEC at a later chronologic age. One study reported the average age of onset as 20.2 days for babies born less than 30 weeks’ estimated gestational age (EGA), 13.8 days for babies born at 31-33 weeks’ EGA, and 5.4 days for babies born after 34 weeks’ gestation.

Term infants develop NEC much earlier, with the average age of onset occurring within the first week of life or sometimes occurring within the first 1-2 days of life.

 

Clinical features.

History. NEC is more common in preterm infants. Epidemiologic studies demonstrate that antecedent history is usually the same for term as well as preterm babies. However, demographics, risk factors, typical patient characteristics, and clinical course differ significantly.

Term baby. Typically the term baby is much younger than the afflicted preterm baby, with published series reporting median age of onset from 1-3 days of life.  The affected term neonate is usually systemically ill with other conditions, such as birth asphyxia, respiratory distress, congenital heart disease, metabolic abnormalities, or has a history of abnormal fetal growth pattern.

Maternal risk factors that reduce fetal gut flow, such as placental insufficiency from chronic disease or maternal cocaine abuse, can increase the baby’s risk.

Premature baby. Premature babies are at risk for several weeks, with the age of onset inversely related to gestational age at birth.

Patients are typically advancing on enteral feedings or may have achieved full-volume feeds when symptoms develop.

Presenting symptoms may include subtle signs of feeding intolerance that progress over several days, subtle systemic signs that may be reported enigmatically by the nursing staff as “acting different,” and fulminant systemic collapse. Symptoms of feeding intolerance can include abdominal distention/tenderness, delayed gastric emptying as evidenced by gastric residuals, and vomiting (occasionally).

Systemic symptoms can progress insidiously to include increased apnea and bradycardia, lethargy, and temperature instability representing the primary manifestation(s). Patients with fulminant NEC present with profound apnea, rapid cardiovascular and hemodynamic collapse, and shock.

The baby’s feeding history can help increase the index of suspicion for early NEC. Babies who are breastfed have a lower incidence of NEC than formula-fed babies. Rapid advancement of formula feeding has been associated with an increased risk of NEC.

Physical. The pertinent physical findings in patients who develop NEC can be primarily gastrointestinal, primarily systemic, indolent, fulminant, or any combination of these. A high index of clinical suspicion is essential to minimize potentially significant morbidity or mortality.

Gastrointestinal signs can include any or all of the following:

¨    Increased abdominal girth

¨    Visible intestinal loops

¨    Obvious abdominal distention and decreased bowel sounds

¨    Change in stool pattern

¨    Hematochezia

¨    A palpable abdominal mass

¨    Erythema of the abdominal wall

 

Systemic signs can include any of the following:

¨    Respiratory failure

¨    Decreased peripheral perfusion

¨    Circulatory collapse

¨    With insidious onset, the severity of derangement may be mild, whereas patients with fulminant disease can present with severe clinical abnormalities.

Table 3.1Sudden Compared with Insidious Onset

 

Lab Studies. Initial presentation usually includes subtle signs of feeding intolerance, such as gastric residuals, abdominal distention, and/or grossly bloody stools. Abdominal imaging studies are crucial at this stage. Laboratory studies are pursued if the abdominal studies are worrisome or the baby is manifesting any systemic signs.

Complete blood cell count (CBC)  with manual differential to look for signs of infection, anemia, and thrombocytopenia is usually repeated at least every 6 hours if the patient continues to deteriorate.

White blood cell count. Marked elevation may be worrisome (<20,000 depending on whether treatment includes systemic steroids for lung disease), but leukopenia (<5000) is even more concerning. Although elevated mature and/or immature neutrophil counts may not be good indicators of neonatal sepsis after the first 3 days of life, moderate neutropenia (absolute neutrophil count [ANC] <1500) strongly suggests evolving sepsis.

Red blood cell count. Premature infants are prone to anemia from iatrogenic blood draws as well as anemia of prematurity; however, blood loss from hematochezia and/or a developing consumptive coagulopathy can manifest as an acute decrease in hematocrit.

Platelet count. Platelets are an acute phase reactant, and thrombocytosis can represent physiologic stress to an infant, but acute NEC is more commonly associated with thrombocytopenia (<100,000). Thrombocytopenia may become more profound and alarming in severe cases that become complicated with consumption coagulopathy. Consumption coagulopathy is characterized by prolonged prothrombin time (PT), prolonged activated partial thromboplastin time (aPTT), and decreasing fibrinogen and increasing fibrin degradation products concentrations

Blood culture. Drawing a blood culture is recommended before beginning antibiotics in any patient presenting with any signs/symptoms of sepsis or NEC. Although blood cultures do not grow any organisms in most cases of NEC, sepsis is one of the major conditions that mimic NEC and it should be considered in the differential diagnosis. Therefore, identification of a specific organism can aid and guide further therapy.

Serum electrolytes can show some characteristic abnormalities. Obtain a panel of basic electrolytes during the initial evaluation, followed serially at least every 6 hours depending on the acuity of the patient’s condition.

Ø    Serum sodium. Hyponatremia is a worrisome sign that can suggest the initial stages of a developing capillary leak. Depending on the baby’s age and feeding regimen, baseline sodium levels may be low-normal or subnormal, but an acute decrease (<130 mEq/dL) is alarming and heightened vigilance is warranted.

Ø    Metabolic acidosis. Low serum bicarbonate (<20) in a baby with a previously normal acid-base status also is concerning.

Arterial blood gasses. Depending on presentation acuity and the baby’s respiratory status, an arterial blood gas can reveal whether the baby needs respiratory support and the developing acid-base status.

Acute acidosis with baseline carbon dioxide pressure is worrisome (as is apnea). Metabolic acidosis results from decreased cardiac output (as in cardiovascular collapse and shock), leading to poor perfusion of peripheral tissues and lactic acidosis.

 

Imaging Studies. 

The mainstay of diagnostic imaging is abdominal radiography. An anteroposterior (AP) abdominal radiograph and a left lateral decubitus radiograph (left side down) are essential for initially evaluating any baby with abdominal signs. Perform these abdominal radiographs serially at 6-hour or greater intervals, depending on presentation acuity and the preferences of the attending medical team, including any involved surgeons.

Ø Characteristic findings on an AP abdominal radiograph include an abnormal gas pattern, dilated loops, and thickened bowel walls (suggesting edema/inflammation). Serial radiographs help assess disease progression. A fixed and dilated loop that persists over several examinations is especially worrisome.

Ø Radiographs can sometimes reveal scarce or absent intestinal gas, which is more worrisome than diffuse distention that changes over time.

Ø Pneumatosis intestinalis is a radiologic sign pathognomonic of NEC. It appears as a characteristic train-track lucency configuration within the bowel wall. Intramural air bubbles represent extravasated air from within the intestinal lumen.

Ø Abdominal free air is ominous and usually requires emergency surgical intervention. The presence of abdominal free air can be difficult to discern on a flat radiograph, which is why decubitus radiographs are recommended at every evaluation. The football sign is characteristic of intraperitoneal air on a flat plate and manifests as a subtle oblong lucency over the liver shadow. It represents the air bubble that has risen to the most anterior aspect of the abdomen in a baby lying in a supine position and can be demonstrated by left lateral decubitus imaging.

Ø Portal gas is a subtle and transient finding that was originally thought to be ominous when detected but is now considered less ominous. Portal gas, which is not usually captured in serial radiographs, appears as linear branching areas of decreased density over the liver shadow and represents air present in the portal venous system. Portal gas is much more dramatically observed on ultrasonography.

Ø Ascites is a late finding that usually develops some time after perforation when peritonitis is present. Ascites is observed on an AP radiograph as centralized bowel loops that appear to be floating on a background of density. It is better appreciated on ultrasonography.

Ø Left side down (left lateral) decubitus radiography allows the detection of intraperitoneal air, which rises above the liver shadow (right side up) and can be visualized easier than on other views. Obtain this view with every AP examination until progressive disease is no longer a concern.

Abdominal ultrasonography is a relatively new technology for evaluating suspected NEC ieonates. With abdominal ultrasonography, a skilled physician can identify a larger amount of diagnostic information faster and with less risk to the baby than with the current standard evaluation methods.

Advantages: available at bedside; noninvasive imagery of intra-abdominal structures.

Disadvantages: limited availability at some medical centers; requires extensive training to discern subtle ultrasonographic appearance of some pathologies. 

ü Abdominal air (easily observed on ultrasonography and in grossly distended patients) can interfere with assessing intra-abdominal structures.

ü Ultrasonography can be used to identify areas of loculation and/or abscess consistent with a walled-off perforation when patients with indolent NEC have scarce gas or a fixed area of radiographic density.

ü Ultrasonography is excellent for distinguishing fluid from air, so ascites can be identified and quantified. Serial examinations can be used to monitor the progression of ascites as a marker for the disease course.

ü Portal air can be easily observed as bubbles present in the venous system. This finding has been termed informally the “champagne sign” because of its similar appearance to a champagne flute.

ü Recent data suggest that ultrasonographic assessment of major splanchnic vasculature can help in the differential diagnosis of NEC from other more benign and emergent disorders.

ü Doppler study of the splanchnic arteries early in the course of NEC can help distinguish developing NEC from benign feeding intolerance in a mildly symptomatic baby.

 

Procedures. 

Upper GI (with or without) small bowel follow-through. This procedure is a definitive way to diagnose the presence or absence of intestinal volvulus. Always consider intestinal volvulus if bilious vomiting is present, especially in the term infant. Because the presence of volvulus is a surgical emergency, it is an important diagnosis to exclude in a neonate with abdominal symptoms.

Perform before contrast enema because the presence of contrast in the colon can obscure pertinent findings.

Contrast enema. This procedure is a definitive way to diagnose a distal obstruction.

Always use a water-soluble contrast agent because of the risk of perforation. Contrast enemas are contraindicated in the presence of perforation. Consider carefully the clinical risks and benefits before undertaking this evaluation in the unstable and/or acutely ill infant.

Contrast enema findings are important for the differential diagnosis of intestinal abnormalities because distal obstructions, such as meconium plug, small left colon syndrome, and Hirschsprung disease, may cause symptoms in the baby without fulminant systemic collapse.

Abdominal decompression. Decompression is essential at the first sign of abdominal pathology. If possible, use a large-bore catheter with multiple side holes to prevent vacuum attachment to the stomach mucosa.  Set the catheter for low continuous suction and monitor output.

If copious amounts of gastric/intestinal secretions are removed, consider IV replacement with a physiologically similar solution, such as lactated Ringer solution.

Paracentesis. Ascites can develop during fulminant NEC and can compromise respiratory function. Remove ascites using intermittent paracentesis. Ultrasonographic guidance can facilitate paracentesis.

After completing the procedure, significant fluid shifts between the intravascular and extravascular spaces are possible, so avoid removing large amounts of fluid at one time.

Place an intra-abdominal drain as an alternative to laparotomy if the baby is not a surgical candidate.

Treatment.

Medical Care. Diagnosis of NEC is based on clinical suspicion supported by findings on radiologic as well as laboratory studies. Treatment of NEC depends on the degree of bowel involvement and severity of its presentation.

Antimicrobial agents – Although no definitive infectious etiology is known to cause NEC, clinical consensus finds that antibiotic treatment is appropriate for the threat of sepsis. Broad-spectrum parenteral therapy is initiated at the onset of symptoms after collecting blood, spinal fluid, and urine for culture. Antibacterial coverage for gram-positive and gram-negative organisms is essential, with the addition of anaerobic coverage for infants older than 1 week who show radiologic disease progression. Antifungal therapy should be considered for premature infants with a history of recent or prolonged antibacterial therapy or for babies who continue to deteriorate clinically and/or hematologically despite adequate antibacterial coverage.

Although any combination of drugs can be employed, one frequently used regimen includes vancomycin, cefotaxime, and clindamycin or metronidazole. This combination provides broad gram-positive coverage (including staphylococcal species), excellent gram-negative coverage (with the exception of pseudomonads), and anaerobic coverage.

Antifungal agents — Their mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide, which is toxic to the fungal cell.
If antifungal therapy is warranted, fluconazole can be initiated. Fluconazole is less toxic than amphotericin B, which is substituted if no clinical response to fluconazole occurs or if evidence of microbiological resistance is present.

Vasopressors. Babies with serious illness may progress to shock and require pharmacologic blood pressure support.

Volume expanders. Patients with severe illness may experience fluid shifts to the extracellular space, resulting in intravascular depletion requiring expansion.

Albumin (5% and 25%) — Used to increase intravascular oncotic pressure in hypovolemia and helps mobilize fluids from the interstitial to the intravascular space. Concentration can be either 5% (5 g/100 mL) or 25% (25 g/100 mL), depending on the desired effect. Typical dose: 0.5-1 g/kg.

Sodium chloride 0.9% (Normal saline, NS, Isotonic saline). Can be used as a volume expander and be as effective as albumin in acute hypovolemia. Pediatric dose: 10-20 mL/kg IV infused over 30 min.

Fresh frozen plasma is used as a volume expander, especially helpful for patients with concomitant coagulopathy. Pediatric dose: 10-15 mL/kg IV infused over 1 h

 

Surgical Care. Any patient requiring surgical intervention and many of those patients not progressing to surgery require protracted courses of parenteral nutrition and intravenous antibiotics. The dead bowel tissue is removed and a colostomy or ileostomy is performed. The bowel is then reconnected several weeks or months later when the infection and inflammation have healed.

If the patient is extremely small and sick, he/she may not have the stability to tolerate laparotomy. If free air develops in such a patient, consider inserting a peritoneal drain under local anesthesia in the nursery. Two retrospective reviews of the use of peritoneal drains as initial therapy for perforated bowel concluded that, while most patients ultimately require open laparotomy, initial peritoneal drainage may allow systemic stabilization and recovery in the smallest, sickest infants until they become better surgical candidates.

Indications for surgery are commonly accepted to be as follows:

v    Highly specific indications

Ø  Pneumoperitoneum

Ø  Positive paracentesis

Ø  Fixed loop on serial radiographs

Ø  Erythema on the abdominal wall

Ø  Abdominal mass

Ø  Portal venous gas

v    Nonspecific supportive findings

Ø    Abdominal tenderness

Ø    Persistent thrombocytopenia (<100,000/mm3)

Ø    Progressive neutropenia

Ø    Clinical deterioration

Ø    Severe GI bleeding

Diet.

When NEC is suspected, enteral feedings are withheld and parenteral nutrition is initiated. Centrally delivered formulations with maximal nutritional components are preferred. Enteral feedings can be restarted 10-14 days after findings on abdominal radiographs normalize in the case of nonsurgical NEC. Reinitiating enteral feeds in postsurgical babies may take longer and may also depend on issues such as the extent of surgical resection, timing of reanastomosis, and preference of the consulting surgical team.

Because of the high incidence of postsurgical strictures, some clinicians prefer to evaluate intestinal patency via contrast studies prior to initiating enteral feeds. When feeds are restarted, formulas containing casein hydrolysates, medium-chain triglycerides, and safflower/sunflower oils (Pregestimil/Nutramigen) may be better tolerated and absorbed than standard infant formulas.

Further inpatient care.

Prolonged parenteral nutrition is essential to optimize the baby’s nutrition while the gastrointestinal tract is allowed enough time for recovery and return to normal functioning. Central venous access is essential to facilitate parenteral delivery of adequate calories and nutrients to the recovering premature baby to minimize catabolism and promote growth.

Prolonged central venous access may be associated with an increased incidence of nosocomial infection, predominately with skin flora such as coagulase-negative Staphylococcus species. A high degree of clinical suspicion must be maintained to detect the subtle signs of such infection as early as possible.

Parenteral administration of lipid formulations via central venous catheters is also associated with an increased incidence of catheter-related sepsis.

Lipids coat the catheter’s interior, allowing ingress of skin flora through the catheter lumen. A high degree of clinical suspicion is required for early detection of such an infection.

If line infection is suspected, obtain a blood culture through the central line. Antibiotics effective against skin flora (eg, vancomycin) should be administered through the line. Obtain another central line blood culture if the results of the first culture are positive. Persistently positive line cultures require removing the central line.

Prolonged parenteral nutrition may be associated with cholestasis and direct hyperbilirubinemia. This condition resolves gradually following initiation of enteral feeds.

Prolonged broad-spectrum antibacterial therapy increases the premature infant’s risk for fungal sepsis.

Almost all premature infants demonstrate fungal colonization of the intestinal tract. Antibacterial therapy inhibits normal gut flora and allows fungal overgrowth caused by the absence of normal bacterial inhibition. Although prophylactic antifungal therapy reduces the incidence of fungal colonization in premature infants, it does not reduce the incidence of fungal sepsis. Therefore, it is not a recommended standard practice in the management of the preterm neonates.

As with other systemic infections in this patient population, clinical signs of fungal sepsis can be subtle and nonspecific. Delay in detection and treatment of fungal sepsis can allow the formation of fungal balls intraocularly, in the kidney, and/or in the heart. This complication carries a high mortality rate and morbidity including blindness, obstructive renal failure, and endocarditis. A high index of suspicion for fungal infection must be maintained when a baby on broad-spectrum antibacterials develops signs of systemic infection.

Further outpatient care

If a baby goes home with a colostomy, parents need thorough instruction regarding the baby’s care. Having the parent(s) room with the baby at the hospital for several days prior to discharge is advisable so that they can learn and demonstrate adequate caregiving skills.

Babies who have undergone intestinal resection may experience short-gut syndrome. These babies require vigilant nutritional regimens to maintain adequate calories and vitamins for optimum growth and healing.

 

Complications. Approximately 75% of all patients survive. Of those patients who survive, 50% develop a long-term complication. The 2 most common complications are intestinal stricture and short-gut syndrome.

Intestinal strictures. This complication can develop in infants with or without a preceding perforation. Incidence is 25-33%. Although the most likely location for acute disease is the terminal ileum, strictures most commonly involve the left side of the colon.

Symptoms of feeding intolerance and bowel obstruction typically occur 2-3 weeks after recovery from the initial event. The presence and location of the obstruction is diagnosed using barium enema; surgical resection of the affected area is required.

Short-gut syndrome. This is a malabsorption syndrome resulting from removal of excessive or critical portions of small bowel necessary for absorption essential nutrients from intestinal lumen.

Symptoms are most profound in babies who either have lost most of their small bowel or have lost a smaller portion that includes the ileocecal valve.

Loss of small bowel can result in malabsorption of nutrients as well as fluids and electrolytes.

The neonatal gut will grow and adapt over time, but long-term studies suggest that this growth may take as long as 2 years to occur. During that time, maintenance of an anabolic and complete nutritional state is essential for the growth and development of the baby. This is achieved by parenteral provision of adequate vitamins, minerals, and calories; appropriate management of gastric acid hypersecretion; and monitoring for bacterial overgrowth. The addition of appropriate enteral feedings during this time is important for gut nourishment and remodeling.