In the last decade, there have been significant improvements in the management of pediatric intestinal failure (IF). Recently reported long-term survival rates from tertiary care pediatric centers range from 73% to 90%, and there are contemporary data that suggest a survival benefit when children with IF are treated in dedicated, multidisciplinary intestinal rehabilitation programs (1–3).
Historically, the length of residual small bowel after initial surgery has been closely associated with overall patient outcome, including survival (2,4,5). Despite this correlation, the literature on pediatric ultrashort bowel syndrome (USBS) is scarce and long-term outcomes data in this group from the most recent era of multidisciplinary IF management are limited. These data could have direct relevance to patient care, because in an earlier era it was widely thought that neonates with extreme intestinal loss were not candidates for survival. Therefore, we sought to measure the outcomes and chronic morbidities associated with USBS. We hypothesized that children with USBS referred to an intestinal rehabilitation program would demonstrate long-term survival, similar to the recent trend observed in children with IF and longer remnant bowel lengths.
A prospective database from the Seattle Children's Hospital Intestinal Failure Program (SCH-IFP) was used to evaluate the outcomes of consecutive patients enrolled in the program with USBS. We defined USBS as ≤10 cm of small bowel at time of referral. This definition was based on previous studies defining very short bowel syndrome as remnant bowel length of <10% of expected small bowel length (6). Data were reviewed from the inception of the program in January 2005 to December 2011.
For patients who had their initial surgical resection performed at our institution, small bowel lengths were determined using an intraoperative measuring device placed in a longitudinal plane along the antimesenteric border of the small bowel by the attending surgeon. All measurements were initiated at the ligament of Treitz so that the duodenum was not included in the remnant bowel length. For patients who underwent surgical resection at other institutions, the measurement of remaining small bowel length as reported by the attending surgeon or referral gastroenterologist was used to connote remnant length. Surgical procedures included any additional procedure performed at our institution from the time of patient referral to the SCH-IFP and did not include the primary bowel resection. Emergency department (ED) visit data included any ED encounter, whether it led to home discharge or inpatient admission. Central line–associated bloodstream infections (CLABSIs) were reported based on the Centers for Disease Control and Prevention National Healthcare Safety Network definition for laboratory-confirmed bloodstream infections; the full definition can be found in Reference 7. Appropriate data points are presented as median (range).
Of 80 children enrolled in the SCH-IFP since 2005, we identified 5 patients who met our definition of USBS. The relevant demographic and referral characteristics of the present cohort are summarized in Table 1. All children in this cohort are alive and between 3.5 to 5.5 years of age.
All patients had a remnant small bowel length ≤10 cm, and the median bowel length was 6 (1–10) cm. Etiologies of short bowel syndrome included 1 child each with gastroschisis, necrotizing enterocolitis, and intestinal atresia, and 2 patients with midgut volvulus. Children were referred at a median age of 2.7 (0.6–3.8) months, and duration of outpatient follow-up was 54 (43–62) months. One patient underwent isolated intestinal transplantation at 3 years of age, and 1 patient is actively listed for intestinal transplantation. Of the remaining children, 1 is advancing on enteral nutrition, 1 has severe neurologic comorbidity and it was felt that transplantation would not improve the length or quality of life, and 1 child's social situation precludes transplant listing (Table 1).
The nutritional support characteristics of our cohort are summarized in Table 1. The transplanted child is fully enterally fed. The other patients remain dependent on varying amounts of parenteral nutrition (PN). Four of the 5 patients were referred with parenteral nutrition–associated liver disease (PNALD) with a conjugated bilirubin of 5.1 (0.0–14.2) mg/dL at presentation. These four children were treated with omega-3 fatty acid supplementation. All 3 patients who underwent liver biopsy had histologic evidence of PNALD with portal fibrosis. Currently, no patient in the present cohort has biochemical evidence of liver disease.
From a morbidity standpoint, the patients have required extensive inpatient and outpatient hospital care, including 18 (15–32) ED visits, 113 (89–217) days of inpatient care at our institution, and 11 (7–14) additional surgical procedures since referral (Table 2). The majority of these operations were related to central venous access. No bowel lengthening procedures have been performed in this group. Patients have had 6 (5–9) CLABSIs treated at our institution. Additional outpatient data are presented in Table 2.
There are extensive data in the literature on the association between residual intestinal length and overall survival in children with IF (2,4–5). However, USBS is rare and there are few studies that specifically address the outcomes of children with the shortest bowel lengths. A decade-old case series of children with <20 cm of bowel reported a mortality of 50% (8). A more recent series of 4 children with <25 cm of bowel reported 100% survival and emphasized the benefits of management with omega-3 fatty acid supplementation (9). These are the only 2 series in the literature, other than individual case reports, to examine the outcomes of children with USBS (10–15). Although data for this select group of children are included as part of more comprehensive IF cohort studies, the clinical and ethical complexities specific to children with USBS may be overlooked in these reports.
An expanding body of literature has shown that children with IF benefit from treatment at multidisciplinary intestinal rehabilitation centers (3,16–21). Several management strategies used in such programs likely contribute to this benefit. Early introduction and gradual advancement of enteral feeding is a characteristic staple of management through intestinal rehabilitation programs, including ours. This practice aids in the process of intestinal adaptation and is likely useful in reversing PNALD (22–24). Omega-3 fatty acid supplementation and lipid-restricted PN regimens have been shown to be effective in the treatment of PNALD associated with IF (10,25–28). Our program routinely uses Omegaven in patients with PNALD and minimal potential for enteral feeding advancement. Two children in our cohort are receiving Omegaven, and the other 2 PN-dependent children are receiving soy-based lipid-restricted regimens (Table 1). The use of ethanol locks in central venous lines is a strategy used by a growing number of intestinal rehabilitation programs to decrease the risk of central venous line infections and, as such, some of the morbidity associated with long-term PN dependence (29). Our data indicate that children with USBS experience multiple CLABSIs and therefore likely benefit from aggressive ethanol lock prophylaxis. Antibiotic protocols to manage intestinal bacterial overgrowth are administered on the basis that bacterial overgrowth impairs bowel function and motility in IF patients (30). This may be especially relevant in children with extremely short bowel remnants that may be predisposed to dilation and dysmotility. All of these strategies, when implemented appropriately as part of intestinal rehabilitation, likely contribute to the long-term survival of children with USBS and IF in general.
From a surgical standpoint, early reestablishment of intestinal continuity in patients with short bowel lengths has been recommended as a means to maximize the intestinal absorptive surface (31). In the present cohort, only 2 of the patients in our USBS cohort had ostomies after their initial operation; both patients underwent procedures to reestablish continuity early in their disease course. No child in the present series underwent a bowel-lengthening procedure. Although we use bowel lengthening in select patients as part of their intestinal rehabilitation, we have been reluctant to offer these procedures to children with USBS. In the presence of USBS, the gain in bowel length from a lengthening procedure is highly unlikely to lead to enteral autonomy. Given the extremely short lengths of bowel present in the present cohort, we believe the risks associated with a bowel-lengthening procedure outweigh the benefits.
The present data demonstrate a long-term survival of 100%, with all of these children approaching school age despite the fact that most of them remain dependent on PN. These data are encouraging and highlight distinct improvements in the care of children with severe IF. Although these data are limited, it appears that the survival trends previously observed in all of the children with IF may be reflected in patients with USBS. At the same time, however, these survival data should be interpreted cautiously. Due to the retrospective nature of the present study, we cannot estimate the number of children in our 5-state catchment area with USBS that either died before referral to our institution or were simply not referred to us for intestinal rehabilitation. We also do not have an adequate control group to compare these outcomes because there is no robust historical cohort of children with extremely short bowel remnants who survived before the current era. Most importantly, the number of patients in the present series is small and represents <10% of our program's patient population. Nonetheless, infants with USBS who survived long enough to be referred to our program experienced long-term survival that would likely not have been possible in the absence of contemporary IF management strategies.
Despite this fact, patients with USBS are not without chronic morbidity. The children spend prolonged durations on the hospital inpatient wards and continue to experience multiple central line infections as they remain PN dependent. They undergo many additional surgical procedures, most often related to their central venous access needs. Outpatient clinic visits are frequent, often once to twice every month, and visits to the ED and specialty clinics are numerous (Table 2). Clearly, the survival benefit in this group comes at the expense of aggressive medical and surgical care for many years that is unlikely to be found outside of specialized intestinal rehabilitation centers. In addition, it is important to note that intestinal rehabilitation in children with USBS may be unlikely to achieve complete independence from PN. Many of these children still require intestinal transplantation to effectively attain enteral autonomy. On the basis of these data, intestinal rehabilitation in this population seems to serve as a long-standing bridge to intestinal transplantation without the urgency that progressive liver disease posed in the recent past. Moreover, we have observed that many of our patients can ultimately be listed for isolated intestinal transplantation alone as intestinal rehabilitation has served to effectively ameliorate progressive liver disease and obviate the need for liver transplantation.
In conclusion, USBS patients are rare, but they are at high risk for experiencing the worst complications associated with IF. From our experience, these children can now survive long term and likely benefit from management at multidisciplinary IF programs similar to their peers with longer bowel lengths. Multi-institutional studies evaluating a more sizable and diverse USBS patient population are needed to corroborate these findings. Moreover, additional research is needed to define and treat the specific co-morbidities associated with long-term survival in the USBS population. The information gained from the present study can be used to inform care decisions made in critically ill neonates who have lost substantial bowel length and also to counsel families of young infants with prospective USBS.
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