Pneumatosis intestinalis in non-neonatal pediatric patients.

OBJECTIVES: To describe fully pneumatosis intestinalis (PI) in non-neonatal pediatric patients and to characterize those patients with higher risk of poor outcome, including need for surgery and death. METHODS: A retrospective chart review was conducted of all patients 30 days of age and older with PI in a tertiary care children's hospital during an 8-year period. Underlying medical condition, presenting signs and symptoms, radiologic grade of pneumatosis, and events that immediately preceded the onset of PI were reviewed, and their correlation with outcome was assessed. RESULTS: Thirty-seven episodes of PI occurred in 32 patients. Seventy-eight percent of patients were male, and the median age was 29 months. Major patient diagnostic groups identified with PI included healthy children (22%), patients with organ and bone marrow transplant (22%), patients with decompensated congenital heart disease (12.5%), motility disorders (12.5%), gastroschisis (9%), and short bowel syndrome (6%). The most common events that immediately preceded the onset of PI were noninfectious colitis (32%), acute enteric infection or toxin (27%), bowel ischemia (20%), and gastrointestinal dysmotility (17%). Resolution of PI with medical management occurred in 78% of episodes (good outcome). Twenty-two percent of episodes resulted in a poor outcome: patient death (8%) or surgery (14%). The presence of portal venous gas and low mean serum bicarbonate concentration were the only clinical factors that correlated significantly with poor outcome. Only 25% of patients with pneumoperitoneum required surgery. Poor outcome was seen most commonly in 2 patient diagnostic groups: transplant patients (43% of patients) and decompensated cardiac disease (50% of patients). The event that preceded PI also had an impact on outcome. PI preceded by ischemia or graft versus host disease colitis was associated with poor outcome in 50% and 75% of cases, respectively. CONCLUSIONS: PI is a radiologic sign that occurs in a variety of settings in non-neonates. PI preceded by bowel ischemia or graft versus host disease colitis has the worst prognosis, and the presence of portal venous gas and acidosis correlate with poor outcome. Not all patients with pneumoperitoneum require surgical intervention. Overall, outcome of PI in non-neonatal patients was better than that reported in neonates with necrotizing enterocolitis.pneumatosis intestinalis, necrotizing enterocolitis, non-neonatal.

Infection and cholestasis in neonates with intestinal resection and long-term parenteral nutrition.

OBJECTIVES: This retrospective study was conducted to determine the incidence of cholestasis and liver failure in patients with intestinal resection in the neonatal period who subsequently become dependent on parenteral nutrition support and to assess the significance of associated clinical factors--gestational age, birth weight and length; length of bowel resected; presence of ileocecal valve; enteral feeding history; and infection--to the incidence and severity of cholestasis. METHODS: Retrospective chart review of all patients in a single institution from May 1984 to February 1997 with neonatal small intestinal resection dependent on parenteral nutrition for at least 3 months. RESULTS: Forty-two patients fitting the inclusion criteria were the subjects of this review. Cholestasis developed in 28 (67%) while they were receiving parenteral nutrition (direct serum bilirubin more than 2 mg/dl). In 21, the elevated direct bilirubin normalized while patients continued to receive parenteral nutrition. Seven patients progressed to liver failure. In 14 patients, serum direct bilirubin nerve rose above 2 mg/dl. The cholestatic patients did not differ from the noncholestatic in gestational age, birth weight, and length; primary diagnosis; length of bowel resected; or presence of ileocecal valve. The duration of dependence on parenteral nutrition was longer in noncholestatic (33.2 +/- 9 months) than in cholestatic patients progressing to liver failure (19.4 +/- 3 months) or in cholestatic patients who recovered (16.1 +/- 1.9 months) (p < 0.05). Invasive fungal or bacterial infections occurred in all but one noncholestatic patient. The number of infections per patient was similar in all groups. The mean age (days) at first infection was significantly younger in cholestatic patients progressing to liver failure (28.5 +/- 5) and cholestatic patients who recovered (48.2 +/- 14.2) than in noncholestatic patients (167 +/- 43.2) (p < 0.01). Infection preceded the onset of cholestasis in all but 3 patients by an average of 13.5 days. Infecting organisms and site of first infection were similar in all patients. CONCLUSIONS: Cholestasis is common in infants with neonatal intestinal resection. Liver failure develops in 16.6%. Bacterial infection early in life characterized the cholestatic patients, and cholestasis developed shortly after the first infection in 90% of patients.

Predicting the duration of dependence on parenteral nutrition after neonatal intestinal resection.

OBJECTIVE: To determine whether there are clinical or physical factors that could be used to predict the duration of dependence on parenteral nutrition (PN) in infants who have undergone resection of small intestine in the neonatal period. STUDY DESIGN: Medical records of 44 patients who had small intestinal resection as neonates from 1985 to 1996 and who were dependent on PN for at least 3 months were reviewed. Statistical evaluation of patient variables and their impact on duration of dependence on PN were determined by using the Cox Proportional Hazard model. RESULTS: Twenty-seven patients became independent of PN before the age of 36 months. Seven patients between 40 and 129 months of age are permanently dependent on PN. Outcome could not be determined in 10 patients, four of whom died of hepatic failure while still receiving PN and six of whom are still receiving PN but are younger than 36 months of age. Small bowel length after initial surgery and the percent of daily energy intake received by the enteral route at 12 weeks' adjusted age were significantly related to the duration of dependence on PN. Gestational age, presence of the ileocecal valve, and development of cholestasis were not significantly related. With the use of the Cox Proportional Hazards survival model, a formula was generated to allow estimation of the duration of dependence on PN. CONCLUSIONS: The duration of dependence on PN can be predicted at an early age in neonatal short bowel syndrome by using two patient variables: the length of residual small bowel after initial surgery and the percent of daily energy intake tolerated through the enteral route.

Outcome after exploratory laparoscopy for unexplained abdominal pain in childhood.

BACKGROUND: Abdominal pain in childhood is common yet frustrating when unexplained. OBJECTIVE: To describe the clinical features and outcome of 8 children (6 girls and 2 boys; mean[+/- SD] age, 13 +/- 2 years) with unexplained abdominal pain who underwent exploratory laparoscopy. SETTING: All 8 patients were examined at an academic pediatric gastroenterology center and referred for exploratory laparoscopy because of unexplained abdominal pain. Laparoscopy was offered after family agreement to pursue behavioral management if the pain and disability did not improve. RESULTS: In all 8 children, laparoscopy detected an anomaly at a site corresponding to that of the abdominal pain. Findings were adhesions in 7 children (3 colonic, 2 ileocecal, 1 gastric, and 1 appendiceal) and ovarian torsion in 1 child. At a mean follow-up of 12.6 months, the abdominal pain had completely resolved in 6 children, notably improved in 1 child, and continued unchanged in 1 child. Disability completely resolved in 2 of 3 children. CONCLUSIONS: In children with unexplained abdominal pain that is acute in onset, well described, and suggestive of peritoneal involvement, exploratory laparoscopy (1) successfully ends the cycle of abdominal pain in most cases; and (2) commonly identifies abnormalities, usually adhesions. However, whether laparoscopy, the placebo effect, or both promote the healing process is unclear. Further study is needed to develop criteria for referral for laparoscopic evaluation of unexplained abdominal pain.

Outcome of syndromic paucity of interlobular bile ducts (Alagille syndrome) with onset of cholestasis in infancy.

OBJECTIVE: To determine the outcome, in index patients followed at an American Center, of syndromic paucity of interlobular bile ducts (sPILBD; Alagille syndrome), with onset of cholestasis in infancy. DESIGN: Cohort. SETTING: Regional referral center for infants and children with liver disease. RESULTS: During the past 10 years, 26 unrelated children with sPILBD were identified. Fifteen (58%) are alive without liver transplantation at a median age of 12.1 years. Three (11%) died, all before 2 years of age. Eight patients (31%) underwent liver transplantation at a median age of 6.5 years; all eight are alive a median 5.4 years after transplantation. The most common factors contributing to the decision for transplantation were bone fractures, pruritus, and severe xanthoma. The predicted probability of reaching 19 years of age without transplantation is about 50%; however, with transplantation, the predicted probability of long-term survival is 87%. Of 26 patients 4 (15%) have had significant central nervous system disease, and two of them have died of intracranial hemorrhage. Of the four patients who underwent cholecystoportostomy or portoenterostomy, three required liver transplantation. CONCLUSIONS: Children with sPILBD identified in infancy because of cholestasis have a 50% probability of long-term survival without liver transplantation, a worse prognosis than other follow-up studies have reported. In selected patients, liver transplantation provides the opportunity for long-term survival with improved quality of life. Patients with sPILBD are at risk of having intracranial hemorrhage.

Anastomotic ulceration: a late complication of ileocolonic anastomosis.

Symptomatic ulceration developed at a previous ileocolonic anastomosis in six children. In the neonatal period all patients had had necrotizing enterocolitis that required resection of the terminal ileum, ileocecal valve, and proximal portion of the colon. Gross or occult rectal bleeding, with or without pain and diarrhea, began 5 1/2 years after successful resection and ileocolonic anastomosis. The cause of the ulcers is unknown. They appear inflammatory, both grossly and histologically, but have been uniformly unresponsive to antiinflammatory medications, antibiotics, and immunosuppressive medication. Surgical revision of the anastomosis and ulcer resection in five patients have resulted in rapid recurrence in four. Thirteen similar cases have been reported in the English-language literature. We conclude that ulceration is a long-term complication of neonatal resection of the terminal ileum and ascending colon with ileocolonic anastomosis.

An analysis of the adequacy of preparation for end-stage renal disease care in Michigan. Michigan Renal Plan Task Force.

The Michigan Renal Plan Task Force has been charged with the development of a comprehensive plan to optimize the management of renal disease in Michigan. To assess the preparedness of new patients with end-stage renal disease (ESRD) patients in Michigan, surveys were sent to all outpatient ESRD facilities in the state concerning all new ESRD outpatients starting treatment during the first quarter of 1994. Responses were received from 69% of these facilities, covering 439 patients; 73% of patients were admitted to the hospital at the initiation of dialysis, and 69% required a temporary dialysis catheter. The median time to first outpatient dialysis was 10 days. Hospital admittance and use of temporary catheters were associated with a lower serum albumin at 1 month of follow-up. Temporary dialysis catheter usage was highest (85%) in rural areas, and lowest (59%) in suburban centers. Fifty-four percent of patients had a 1 month serum albumin of < or = 3.5 g/dl. At 1 month, nearly 60% of patients had a plasma hemoglobin of < or = 10.0 g/dl. These results suggest that better patient preparation for ESRD is needed to reduce the need for hospital admittance, to reduce the use of temporary catheters with their associated risks, and to improve the nutritional and psychosocial rehabilitation of these patients.

Gastroesophageal reflux in children. Clinical presentation and diagnostic evaluation.

Gastroesophageal reflux in infants and children is common. It is distinguished from the disorder in the adult population by the large number of thriving infants with functional reflux and by the large proportion of older infants and children with secondary pathologic reflux, in whom vomiting and reflux are symptoms of another condition. Evaluation of the child with suspected reflux starts with a thorough history and physical examination. Diagnostic testing must be tailored to the suspected diagnosis.

Gastroesophageal reflux with drifting onset in infants: a phenomenon unique to sleep.

We have characterized the gastroesophageal reflux (GER) episodes which occurred during sleep in 28 infants with pathologic gastroesophageal reflux and 10 symptomatic age-matched controls without gastroesophageal reflux. We describe three kinds of episodes during the sleeping period-awake episodes which occur completely during electroencephalogram (EEG)-defined wakefulness associated with clinical evidence of the waking state (62 episodes), episodes occurring during EEG-defined sleep which have a rapid drop in pH at their onset (119 episodes), and episodes occurring during EEG-defined sleep in which the esophageal pH drifts down slowly over a period up to 30 min (113 episodes). Only 9 of the 10 control subjects experienced any reflux episodes during monitoring. The total number of episodes of reflux in controls (34) was less than the total number in reflux subjects (260). Controls did, however, experience all three types of reflux episode. Awake episodes all had a rapid drop in pH at their onset and were characterized by a short acid clearance time (2.0 +/- 0.3 min in reflux patients and 1.0 +/- 0.2 min in controls). The sleep episodes with rapid onset had longer mean acid clearance time than the awake episodes, significantly so in GER subjects (20.1 +/- 6.8 min in reflux subjects and 2.6 + 1.3 min in controls). Body movement was noted at the onset of 93.4% of rapid-onset sleep episodes in reflux subjects and 88.9% in controls. Body movement was also common at the termination of rapid-onset sleep episodes (77.8% of rapid-onset episodes in reflux subjects and 80.0% in controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Electroencephalogram patterns during sleep reflux in infants.

Twenty-four infants, 3-35 months of age, with histories of apnea or chronic lung disease underwent nighttime polysomnography and esophageal pH monitoring. Fifteen infants had pathological levels of gastroesophageal reflux on esophageal pH monitoring, and 9 had normal study results (symptomatic controls). Partition of sleep stages, sleep efficiency, and frequency of arousals to electroencephalographic stage 0 were the same in both groups. During sleeping reflux episodes, defined as reflux starting during sleep stages 1-5 or reflux episodes consisting of greater than 50% of sleep stages 1-5, there was a 50% decrease in the amount of stage 0 electroencephalogram pattern compared with nonreflux sleep, and a compensatory increase in the non-rapid eye movement sleep stages. Reflux onsets in patients with pathological reflux were evenly divided between stages 0, 1/2, and 5. Onset of reflux occurred rarely during sleep stages 3 and 4. Slight body movement accompanied the onset of 62.5% of sleep reflux episodes in symptomatic controls and 64.7% in patients with pathological gastroesophageal reflux. Arousals to stage 0 electroencephalogram occurred with equal frequency in sleep reflux episodes of symptomatic controls and patients, and frequency did not increase over the observed value for nonreflux time. There were no differences between the sleep patterns of infants with and without pathological gastroesophageal reflux; nor were there decreases in arousals from sleep in infants with pathological reflux. However, reflux occurring during sleep in all infants studied was characterized by a significant decrease in stage 0 (waking) electroencephalogram.

Liver involvement in Alpers disease.

Alpers disease consists of diffuse cerebral degeneration manifested as developmental delay, seizures, vomiting, and progressive neuromuscular deterioration, with liver disease and death. We report the clinical course of the liver disease, histologic progression of the hepatic lesions, and etiologic investigations in five patients (four girls, three kinships). All had grown and developed normally until seen at 6 to 36 months of age (mean 20 months), with vomiting (n = 5), progressive hypotonia (n = 3), or seizures (n = 2). All had been given anticonvulsants, including valproic acid in three. Liver disease was noted at a mean age of 35 months (range 9 to 67 months), with hepatomegaly (two patients), abnormal hepatic synthetic function (three) or transaminase values (three), and cirrhosis in one. Patients survived for a mean of 4.6 weeks (range 1 to 8 weeks) after the identification of liver disease; all died of hepatic failure. Results of evaluation for infectious and metabolic causes of liver disease and causes of degenerative neuromuscular disease were negative in all patients. Premortem liver biopsy specimens (n = 3) demonstrated an early lesion consisting of lobular disarray, microvesicular steatosis, periportal acute and chronic inflammation, and individual hepatocyte necrosis. Autopsy findings (n = 5) consisted of macrovesicular steatosis, massive hepatocyte dropout, and proliferation of bile ductular elements, with almost complete replacement of hepatocytes by proliferating bile ductular elements in two patients. Brain showed characteristic neuronal degeneration. We conclude that Alpers disease can be a cause of rapidly progressive liver failure in early childhood. Although the cause of this autosomal recessive disease is not known, it does not appear to be related to peroxisomal dysfunction.

Noninfectious colitis associated with short gut syndrome in infants.

We describe noninfectious bloody diarrhea in 13 of 16 infants referred for management of short bowel syndrome and parenteral nutrition during a 33-month period. The condition was characterized by bloody, watery stools associated with carbohydrate malabsorption. Colitis occurred at a mean age of 4.2 months during periods of advancing enteral feedings of a hydrolyzed protein- or amino acid-containing formula. Sigmoidoscopy performed in nine patients revealed edema, patchy erythema, loss of normal vascular pattern, and mucosal friability without ulcerations or pseudomembranes. Colonic biopsy specimens demonstrated edema and mixed hypercellularity of the lamina propria, with prominent eosinophilia. Rectal bleeding ceased if formula feedings were decreased or withheld. Of multiple medications administered, sulfasalazine seemed to improve rectal bleeding most effectively in our patients and allowed for more rapid reintroduction of enteral feedings.

Safety, efficacy, and tolerance of intestinal lavage in pediatric patients undergoing diagnostic colonoscopy.

In an open-label prospective study the safety, efficacy, and patient tolerance of an enterally administered isotonic intestinal lavage solution containing polyethylene glycol-3350 was evaluated in 20 pediatric patients (ages 1 1/2 to 19 years) undergoing diagnostic colonoscopy. After an oral dose of metoclopramide, lavage solution was administered by mouth or nasogastric tube at a rate of 40 ml/kg per hour until stools were clear. Emesis occurred in 4 patients, nausea in 11, and abdominal distension in 5. Clear stools were produced in a mean (+/- SE) time of 2.6 +/- 0.3 hours. The volume of lavage solution delivered, which ranged from 15.6 to 183.3 ml/kg, varied inversely with the weight (and age) of the patient. Preparation of the colon was considered optimal in 11 patients, satisfactory in 7, and suboptimal in 2. Small but significant decreases in urine osmolality, blood urea nitrogen, serum glucose, and potassium values were noted at the termination of perfusion. Postperfusion serum glucose concentration in the smallest patient (11.4 kg) was 61 mg/dL (3.4 mmol/L). Mean (+/- SEM) change in weight after perfusion was 0.14 +/- 0.05 kg (range -0.2 to +0.6 kg). Of 20 patients, 11 required or requested nasogastric administration of the lavage solution because of its unpleasant taste. We conclude that whole intestinal perfusion with a balanced electrolyte solution containing polyethylene glycol is safe, acceptable, and efficacious in children.

The glomerulopathy of homozygous sickle hemoglobin (SS) disease: morphology and pathogenesis.

This morphologic and morphometric study of native-kidney biopsies of six homozygous sickle hemoglobin (SS) nephrotics defines a distinctive glomerulopathy of focal sclerosis developing in maximally hypertrophied glomeruli. In each biopsy, two patterns of segmental glomerulosclerosis were observed: a "collapsing" pattern and an "expansive" pattern. Morphologic analysis comparing group mean glomerular (Bowman's capsular) diameters indicates that glomeruli in SS are routinely markedly enlarged whether nephrotic (group SSN, 233.6 mu +/- SE of 25.3 [N = 6]) or not (control group SSC, 243.5 mu +/- SE of 12.5 [N = 5]). These values are significantly larger when compared with those of matched normal controls (group NC, 158.0 mu +/- SE of 12.7 [N = 6]) or to matched patients with idiopathic focal glomerulosclerosis (group IFS, 188.2 mu +/- SE of 17.9 [N = 6]). Furthermore, based on a previous study, it is most likely that glomerular enlargement in SS represents the maximal hypertrophy attainable in humans. Correlating observations of renal homografts in two sickle hemoglobin patients that developed segmental sclerosis of only the collapsing pattern soon after transplantation, it is proposed that in homozygous sickle hemoglobin nephrotics the collapsing pattern of segmental glomerulosclerosis represents an initial but progressive obliteration of the glomerular capillary bed by red blood cell sickling which cannot be compensated by further glomerular hypertrophy. Hemodynamic glomerular injury then supervenes from the sustained or increasing hyperfiltration in a diminishing capillary bed, manifesting morphologically as the expansive pattern of sclerosis.

Mannitol-induced acute renal failure.

Mannitol is widely used to reduce intracranial pressure and is protective against ischemic and nephrotoxic acute renal failure. However, the capacity of this seemingly innocuous agent to produce acute renal failure is not well recognized. We report herein the clinical course of 8 cases of mannitol-induced acute renal failure. In addition, we reviewed all previously reported cases of mannitol-induced renal failure. In the present series, acute oliguric renal failure developed within 3.5 +/- 1.1 (mean +/- SD) days after receiving daily and total mannitol doses of 189 +/- 64 g and 626 +/- 270 g, respectively, over 3.5 +/- 1.5 days. The peak serum creatinine was 5.7 +/- 2.7 mg/dl and peak osmolal gap was 74 +/- 39 mOsm/kg water. Renal tubular epithelial cells containing vacuoles were seen in the urinary sediments of 6 patients. Renal function improved rapidly upon discontinuation of mannitol and/or removal of mannitol by hemodialysis. In those previously reported cases in which the baseline renal function was normal, acute renal failure developed after receiving total mannitol doses of 1171 +/- 376 g. The peak osmolal gap was 107 +/- 17. In contrast, in those with underlying renal compromise, renal function worsened after a total mannitol dose of 295 +/- 143 g. The pathogenesis of mannitol-induced renal failure is not yet established but may be associated with renal vasoconstriction produced by high concentrations of mannitol. This may be averted in clinical practice by monitoring the osmolal gap, rather than serum osmolality alone, when using mannitol infusions for the treatment of intracranial hypertension.

Clearance of spontaneous gastroesophageal reflux in awake and sleeping infants.

Thirty infants less than 12 mo old (19 with pathologic gastroesophageal reflux and 11 symptomatic controls) underwent continuous monitoring of distal esophageal pH with simultaneous pharyngeal and multiple-site esophageal manometry to compare acid clearance times of awake and asleep reflux episodes. While awake, acid clearance times of the two groups were equivalent. While asleep, mean acid clearance time increased in subjects with pathologic reflux greater than 500% while remaining essentially unchanged in symptomatic controls. No difference in minimum pH attained during sleep reflux, in percentage of swallows resulting in esophageal peristalsis, or in the frequency of secondary peristaltic waves was found to explain the difference in sleeping acid clearance times in the two groups. However, there was a significant difference between the groups with respect to swallowing rate (p less than 0.01). During sleeping reflux episodes, subjects with pathologic reflux swallowed 0.5 +/- 0.1 times per minute (mean +/- SEM), whereas controls who refluxed swallowed 3.5 +/- 1.3 times per minute. During awake reflux episodes the swallowing rates were equivalent in the two groups, 4.1 +/- 0.4 and 4.7 +/- 0.7 per minute, respectively. We conclude that low swallowing rate during sleeping reflux episodes is primary to the delayed clearance of sleeping reflux in these infants.