Clinical problem-solving: Short bowel syndrome in an infant

Abstract

The present case report describes the clinical problems encountered over a five-month period in an infant born with jejunal atresia, extensive midgut volvulus and a microcolon. After an initial surgical resection, the patient had no remaining ileum and his ileocecal valve was also removed. The patient had 35 cm of jejunum, which was successfully lengthened to 60 cm using enteral nutrition and two bowel-lengthening procedures (serial transverse enteropathy procedures). Bouts of cholestatic liver disease, sepsis and small bowel bacterial overgrowth were vigorously treated. The patient was discharged at 5.5 months of age and is now 40 months of age. He is at the 50th percentile for both height and weight, and is developing normally. The outcome for infants with short bowel syndrome has improved significantly in the past few years due to intestinal rehabilitation programs, which integrate nutritional, surgical and pharmacological approaches tailored to individual needs.

A 2870 g male infant with a prenatal diagnosis of intestinal obstruction was delivered uneventfully after 36 weeks of gestation, during which polyhydramnios was noted. Ultrasound of the abdomen confirmed the upper small intestinal obstruction.

In a recent survey of 18 congenital malformation registries in Europe, the rate of prenatal ultrasonographic detection of intestinal obstruction was 52% for duodenal obstruction, 40% for the small bowel and 29% for the colon (1).

A few hours after birth, the surgeon noted a short jejunal atretic segment, a microcolon and extensive midgut volvulus, likely triggered by the fixed point offered by a proximal loop of dilated jejunum. Extensive resection was necessary and included the ileocecal valve. A serial transverse enteroplasty procedure (STEP) lengthened the remnant bowel from 35 cm to 40 cm and included a decrease in the calibre of an exceedingly distended remnant proximal jejunum.

Upper gastrointestinal tract atresia, which occurs in one in 3000 live births, is associated with congenital anomalies affecting other organs in one-third of cases; therefore, other potential malformations should be assessed. Intestinal atresia and malrotation with midgut volvulus are, collectively, the major causes prenatally (Table 1). This involves the jejunum in 60% of cases, and often leads to short bowel syndrome. Intestinal failure occurs when <25% of the small bowel expected for gestational age is available for absorption (2). Its functional integrity and capacity to adapt, which is greater for the ileum than for the jejunum, are important factors. The STEP is also a key prognostic factor that provides patients with adequate time to reach their full adaptive potential and hastens enteral autonomy, thereby preventing parenteral nutrition (PN)-associated liver disease (PNALD) (3). Preservation of the ileocecal valve and/or colon are no longer believed to affect outcomes (4,5).

TABLE 1.

Most common causes of short bowel syndrome

Cause	%
Prenatal
Atresia (unique or multiple)	10
Malrotation with midgut volvulus	10
Abdominal wall defects (gastroschisis>omphalocele)	12.5
Neonatal
Necrotizing enterocolitis	35
Complications of meconium ileus (peritonitis, volvulus, atresia)	20

Adapted from reference 16

During the four weeks following surgery, the patient was on PN. Intestinal obstruction persisted, as evidenced by the large amount of fluid draining from the nasogastric tube. The infant underwent an additional resection of 20 cm of jejunum followed by jejunocolic reanastomosis and a Bishop-Koop temporary ileostomy, as well as a second STEP operation that lengthened the remnant small bowel from 46 cm to 60 cm. Intestinal obstruction was lifted and enteral nutrition (EN) was initiated. However, one month following the second operation, evidence of PNALD was observed, with progressive elevation of conjugated bilirubin, gamma-glutamyltransferase and transaminase levels. It resolved over a period of four months with oral ursodeoxycholic acid and 1 g/kg/day of the intravenous fish oil emulsion Omegaven (>50% ω3 fatty acids; Fresenius Kabi, Germany) and reduction of Intralipid (50% ω6 fatty acids; Fresenius Kabi, Germany) from 2 g/kg/day to 1 g/kg/day.

PNALD is a common (>50%) complication of prolonged PN. Table 2 summarizes its multiple assumed etiologies and risk factors. The long period of intestinal obstruction fostered small bowel intestinal bacterial overgrowth and may have contributed to the early onset of cholestasis after only six weeks of PN. The disease can rapidly lead to life-threatening liver failure and precipitate the decision to transplant. Cycling of PN and early EN are known to reduce the incidence and severity of PNALD (6). Ursodeoxycholic acid does not reverse the disease, but does improve biochemical markers (7). Omegaven, on the other hand, represents a breakthrough not only for its management but also for its prevention of PNALD (8). It is often administered in a 1:1 ratio with Intralipid early after the onset of cholestasis in cases in which PN is expected to be required for several months.

TABLE 2.

Etiology of parenteral nutrition-associated liver disease

Prematurity and low birth weight

Duration of parenteral nutrition

Lack of enteral feeding

Reduced enterohepatic circulation

Length of bowel remnant

Recurrent sepsis

Amounts of glucose and lipids perfused

Hydro and lipid peroxides in parenteral nutrition solutions

ω-6 lipid emulsions (soybean)

Phytosterols in soy-based lipid emulsions

Deficiency of essential fatty acids

Adapted from reference 17

At 2.5 months of age, the patient became febrile with tachycardia, lethargy and metabolic acidosis. The capillary pH was 7.06 (normal range 7.30 to 7.40), with a significant anion gap and a normal lactate level. The sepsis workup revealed the presence of Klebsiella pneumoniae in blood cultures and in cultures of the peripherally inserted central catheter line. The infection was treated for 16 days with piperacillin/tazobactam (Tazocin, Pfizer, USA).

D-lactic acidosis is a rare complication and is associated with bacterial overgrowth of lactobacilli strains producing D-lactic acid rather than other short-chain fatty acids and hydrogen (9). It is best treated with antibiotics and a reduced intake of mono- and disaccharides. Catheter-related infections from the infected peripherally inserted central catheter line supported by a culture from a peripheral vein are frequent complications of prolonged PN. As mentioned previously, repeated bouts of sepsis likely increase the risk of PNALD and compromise intestinal adaptation. In our group, increased attention is devoted to the prevention of repeated central line-associated blood stream infections and of intestinal bacterial overgrowth secondary to dilation and dysmotility (10). Standardized protocols for catheter insertion, antimicrobial catheters and ethanol locks are used in our program.

The persistence of a dilated and dysmotile short segment of proximal jejunum greatly limited the infant’s tolerance for EN despite the administration of prokinetic agents. EN could not be increased above 20 mL/kg/day to 40 mL/kg/day. Further surgery was necessary at 3.5 months of age, and consisted of tapering the dilated jejunum and closing the Bishop-Koop ileostomy. One month later, the infant developed bacterial overgrowth, which was treated for 10 days using metronidazole. Removal of the intestinal obstruction was associated with good tolerance for EN and led to discontinuation of PN at five months of age.

Because segments of poorly peristaltic, dilated bowel compromise enteral tolerance and often lead to bacterial overgrowth, prokinetic agents, such as cisapride and erythromycin, may be helpful (11). Ideally, >10⁵ Gram-negative fecal bacteria per millilitre of duodenal fluid should be observed. In practice, a response to a one-week therapeutic trial with a wide-spectrum antibiotic will establish the diagnosis.

Following the bout of bacterial overgrowth and over the ensuing two months, there was good tolerance for EN, which provided the infant with up to 45 kcal/kg/day. PN was progressively decreased and oral feeding was initiated with Neocate 24 kcal/30 mL (Nutricia, Canada). He was discharged at 5.5 months of age with a weight of 7280 g (25th to 50th percentile) and a height of 63.3 cm (10th percentile).

A major role of the management team is to use surgical, nutritional and pharmacological approaches to enhance adaptation (Figure 1). There is conclusive evidence that luminal nutrients, particularly fat, enhance the process, which continues for as long as five years and prevents the development of mucosal atrophy and a loss of epithelial barrier function associated with exclusive PN. Ideally, EN should be started as early as possible postoperatively. We favour the use of breast milk, which is known to decrease the duration of PN, or a free amino acid formula, at least initially, to decrease the chance of secondary allergy. Initiating oral feeding skills is very important to prevent feeding aversion, a significant problem in our experience.

Figure 1).

This diagram places in perspective the effect of enteral nutrition on intestinal adaptation and its hypothetical enhancement by non-nutrient molecules, such as glucagon-like peptide-2, now under study. Adapted from reference 18

The patient is now 42 months of age and developing normally. Both height and weight are now at the 50th percentile on the WHO charts. His blood cell count and chemistries are normal. He consumes a normal diet, with the exception of lactose-free milk, and produces two or three well-formed stools per day.

The overall survival of infants with short bowel syndrome currently ranges from 70% to 89% (12–14), and can reach 95% in infants weaned early from PN. The prognosis for long-term growth of those who, similar to our patient, have been successfully weaned early from PN is very good. However, it is not unusual for infants to experience a drop in weight percentile during the months following complete weaning from PN. Extremely low birth weight (<1000 g) infants are at particular risk for growth failure. In view of the high prevalence of metabolic bone disease in infants on PN for prolonged periods, monitoring of bone density is recommended.

Commentary

The three basic principles that should govern the management of infants with intestinal failure are presented in Table 3.

TABLE 3.

Guiding principles for the management of intestinal failure secondary to short bowel syndrome

Re-establish bowel continuity and function Surgical correction of remaining and/or acquired abnormalities Lengthening of remnant bowel using serial transverse enteropathy Optimize intestinal adaptation Early enteral nutrition Human milk and/or a free amino acid formula Consider a pharmacological agent, such as glucagon-like peptide-2, which was recently approved by the Food and Drug Administration Prevent irreversible parenteral nutrition-associated liver disease Early weaning from parenteral nutrition Prevention and vigorous treatment of bloodstream infections and of small bowel overgrowth The judicious use of Omegaven (Fresenius Kabi, Germany)

Intestinal failure in infants is a challenging problem that requires a multidisciplinary approach, best provided by intestinal rehabilitation programs through the integration of nutrition, pharmacological and surgical approaches tailored to individual needs. These programs account for shorter lengths of stay, shorter duration of PN, a lower incidence of PNALD, better growth parameters and a much-improved survival (14,15).

Intestinal failure is a devastating diagnosis for parents. They need ongoing psychological support and education. Early on, parents need to be alerted to a realistic prognosis: What are the chances that the intestinal failure will be reversible? How long will it take? What are the complications to be expected? Is home care an option and when? What are the treatment options if intestinal failure proves to be permanent?