Gastrointestinal By Elizabeth

Perforation After Pediatric Transplantation

A. Beierle, Linda A. Nicolette, Deborah F. Billmire, Charles William H. Weintraub, and Stephen P. Dunn Philadelphia, Pennsylvania

Purpose:

The aim of this review was to determine the incidence of gastrointestinal perforation after pediatric liver transplantation and to identify risk factors and clinical indicators that may lead to an earlier diagnosis. Methods: A retrospective chart review of all children who presented with gastrointestinal perforation after liver transplantation at our institution between January 1, 1987 and August I,1996 was performed.

Results: One hundred fifty-seven orthotopic liver transplants were performed in 128 children. Fifty-eight reexplorations, excluding those for retransplantation, were performed in 38 children. Ten perforations occurred in six children (incidence, 6.4%). Two children required multiple reexplorations because of several episodes of perforation. The sites of perforation were duodenum (n = I), jejunum (n = 8), and ileum (n = I). A single-layer closure was used to repair five perforations, two-layer closures in four, and resection with primary anastomosis in another. The type of repair did not affect the occurrence of subsequent perforations. All the children were less than 18 months old. Four children had undergone prior laparotomy. All children had choledochoenteric anastomoses, but only one had a perforation associated with it. One child sustained bowel injury during the dissection for the

A

DVANCES IN OPERATIVE TECHNIQUES and immunosuppression over the last decade have allowed liver transplantation to become an accepted therapy for children with end-stage liver disease. Complications after liver transplantation in children remain common and are often attributed to the patient’s poor general health and nutritional status in the preoperative period. Gastrointestinal perforation is a potentially devastating complication after transplantation. An inherent lack of effective communication from the pediatric

From the Department of Pediatric Surgery, St Christopher’s Hospital for Children, Temple University School of Medicine, Philadelphia, PA. Presented at the 28th Annual Meeting of the American Pediatric Surgical Association, Naples, Florida, May 18-21, 1997. Address reprint requests to Stephen R Dunn, MD, Department oj Pediatric Surgery, St Christopher’s Hospital for Children, Erie Ave at Front St, Philadelphia, PA 19134-1095. Copyright o I998 by WB. Saunders Company 0022.3468/98/3302-0017$03.00/O

240

Orthotopic

Liver

D. Vinocur,

liver transplant, but none of the perforations occurred at this site. Bowel function had returned before perforation in five children. Five children were receiving systemic antibiotics at the time of their perforation, and none had been dosed with pulse steroids for rejection. All of the children had significant changes in their temperature. Acute leukopenia developed in one child. A leukocytosis developed in the rest of the children. Abdominal radiographs demonstrated pneumoperitoneum in only one child. All children had positive culture findings from their abdominal drains. Cytomegalovirus developed in one child. Although the diagnosis of gastrointestinal perforation after pediatric liver transplant remains difficult, positive drain culture findings and significant alterations in temperature and leukocyte counts suggest its presence. Pneumoperitoneum is rarely present. Conclusion:A high index of suspicion and timely laparotomy, especially in children less than 2 years of age, may be the only way to rapidly diagnose and treat this potentially devastating complication of liver transplant. J Pediatr Surg 33:240-242. Copyright o 1998 by W.B. Saunders Company. INDEX WORDS: gastrointestinal

Orthotopic perforation.

liver

transplant,

complications,

patient and the magnitude of immunosuppression that is necessary after orthotopic liver transplantation may mask the common clinical signs and symptoms of perforation, making the diagnosis of a perforated viscus difficult. This review examines the incidence of gastrointestinal perforation after pediatric liver transplantation and attempts to identify risk factors and clinical findings that may lead to earlier diagnosis and intervention, and hence, better outcomes. MATERIALS

AND

METHODS

A retrospective chart review was conducted examining data from January 1, 1987 to August 1, 1996. All children who had gastrointestinal perforation after orthotopic liver transplantation at our institution were included. The records were examined for details of the perforation, patients’ clinical status, laboratory and radiographic studies, methods of repair, and outcomes. RESULTS

One hundred fifty-seven orthotopic liver transplants were performed in 128 children over this period. ThirtyJournal

of Pediatric

Surgery,

Vol33,

No 2 (February),

1998: pp 240-242

GI PERFORATION

IN LIVER TRANSPLANTATION

eight children underwent 58 reexplorations after their liver transplant. Reexploration for the purpose of retransplantation were excluded from this review. Ten gastrointestinal perforations occurred in six children, for an incidence of perforation after transplant of 6.4%. Two children required multiple laparotomies because of several episodes of perforation. The most common etiology for liver failure in these children was cholestasis secondary to hyperalimentation (n = 3). Other causes of hepatic failure were biliary atresia (n = l), acute hepatic necrosis (n = l), and idiopathic hepatic failure (n = 1). The age of the children ranged from 20 days to 16 months. Their weights ranged from 3.98 kg to 11.7 kg. The sites of perforation were varied (duodenum, n = 1; jejunum, n = 8; ileum, n = 1). The time between transplant and exploration for perforation ranged from 4 to 26 days. All children had choledochoenteric anastomosis for the transplant biliary reconstruction, but only one child had a perforation associated with the Roux-en-Y limb. Four of the children had undergone laparotomies before their transplant. One child sustained an inadvertent enterotomy at the time of transplantation, but the subsequent bowel perforation did not occur at this site. None of the children were receiving pulse steroids for rejection before their perforation. Systemic antibiotics were being administered to five of the children. Persistent ileus was present in only one child. All six children had significant changes in their temperature (five > 38°C and one < 36°C). Acute leukopenia developed in one child, and a leukocytosis developed in the other five. Only one child demonstrated pneumoperitoneum on abdominal radiographic studies. Abdominal ultrasonography demonstrated a small fluid collection near the allograft in two cases, neither of which were significant at laparotomy. Jackson Pratt drains were cultured on a daily basis per transplant protocol. All of the children had positive culture results from their abdominal drains with Enterococcus (most common), gram-negative organisms, or yeast. Often these data were not available before reexploration. One child had cytomegalovirus infection. The methods used to repair the perforations were varied. A single-layer closure was used in five perforations, two-layer closures in four, and resection with reanastamosis in another. The occurrence of subsequent bowel perforations was independent of the repair. All of the children survived their reexplorations, however, three of them died later. DISCUSSION

Acute gastrointestinal perforation after organ transplantation is a well-documented phenomenon.Q The incidence of this complication after pediatric liver transplantation has been reported to be as high as 14%.3 The etiology remains obscure and is most likely multifactorial. Previous laparotomy has been cited as a contributing

factor to bowel complications after orthotopic liver transplant.4 Common sense suggests that prior surgery in the right upper quadrant coupled with portal hypertension would make the recipient hepatectomy more challenging. Also, isolating a segment of intestine from dense adhesions to construct a Roux-en-Y choledochoenterostomy would also predispose the gastrointestinal tract to injury. However, attributing all intestinal perforations to a previous laparotomy would be naive because two children with perforations in our review had unviolated peritoneal cavities at the time of transplantation. In fact, intestinal perforation is known to occur after organ transplantation without a prerequisite laparotomy as seen when this complication occurs after kidney, heart, and lung transplantations-10 Finally, the construction of the Roux-en-Y limb does not appear to be a major factor in subsequent gastrointestinal perforation, because only one child had a perforation related to the Roux limb, when the majority of the children undergoing transplantation at our program undergo choledochoenteric biliary reconstruction. Cytomegalovirus (CMV) has also been reported to be a causative factor in bowel perforation after liver transplantation.“,i2 The postulated mechanism is that of primary intestinal infection with subsequent ulceration and perforation. In this review, only one child with bowel perforation had an associated CMV infection. None of the other children with intestinal perforation had documented CMV infection, and conversely, many other children in whom CMV infection developed did not have gastrointestinal perforations. Steroids have been implicated as a contributing factor to gastrointestinal complications after transplantation.13-15The primary problems caused by steroid administration are gastric ulceration, bleeding, and perforation. None of our bowel perforations occurred in the stomach or colon. Our protocol for steroid administration is similar to the dosages given to adults on a per-weight basis, and none of these children were receiving additional steroids as a treatment for rejection. Many of the classic signs and symptoms that normally herald an intraabdominal catastrophe are absent or masked in these cases.For example, the classicradiological finding of a hollow viscus perforation, that is, pneumoperitoneum, was seen in only a single case in this review. In addition, only one of the children had a persistent ileus when they underwent reexploration for potential bowel perforation. Acute changes in temperature and leukocyte count were documented in all episodes of perforation. The single consistent laboratory finding was the positive drain cultures obtained from the abdominal drains, although the usefulness of these data is debatable because of the inherent time lag required for culturing the fluid. Finally, the administration of antibiotics did not prevent bowel perforation and may have masked the presence of intraabdominal sepsis.

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BEIERLE

The diagnosis of gastrointestinal perforation after liver transplantation in children remains difficult. All of the perforations in our series occurred in children under 18 months of age. One must maintain a high index of

ET AL

suspicion, especially in young children, and be willing to perform timely laparotomy in the face of soft clinical and laboratory signs to diagnose and treat this potentially life-threatening complication.

REFERENCES 1. Beath S, Pearmain G, Kelly D, et al: Liver transplantation in babies and children with extrahepatic biliary atresia. J Pediatr Surg 28:1044-1047, 1993 2. Bilik R, Yellen M, Superina RA: Surgical complications in children after liver transplantation. J Pediatr Surg 27:1371-1375, 1992 3. Yamanaka .I, Lynch SV, Ong TH, et al: Posttransplant gastrointestinal perforation in pediatric liver transplantation. J Pediatr Surg 29:635-638, 1994 4. Shaked A, Vargas J, Csete ME, et al: Diagnosis and treatment of bowel perforation following pediatric orthotopic liver transplantation. Arch Surg 128:994-999, 1993 5. Demling RH, Salvatierra 0, Belzer FO: Intestinal necrosis and perforation after renal transplantation. Arch Surg 110:251-253, 1975 6. Faro RS, Corry RJ: Management of surgical gastrointestinal complications in renal transplant recipients. Arch Surg 114:310-312, 1979 7. Benoit G, Moukarzel M, Verdelli G, et al: Gastrointestinal complications in renal transplantation. Transpl Int 6:45-49, 1993 8. Merrell SW, Ames SA, Nelson EW, et al: Major abdominal

complications following cardiac transplantation. Arch Surg 124:889894,1989 9. Steed DL, Brown B, Reilly JJ, et al: General surgical complications in heart and heart-lung transplantation. Surgery 98:739-745, 1985 10. Beaver TM, Fullerton DA, Zamora MR, et al: Colon perforation after lung transplantation. Ann Thorac Surg 62:839-843, 1996 11. Mayoral JL, Loeffler CM, Fasola CG, et al: Diagnosis and treatment of cytomegalovirus disease in transplant patients based on gastrointestinal tract manifestations. Arch Surg 126:202-206, 1991 12. Hinnant K, Rotterdam H, Bell E, et al: Cytomegalovirus infection of the alimentary tract: A clinico-pathologic correlation. Am J Gastroenterol81:944-950, 1986 13. Dayton MT, Kleckner SC, Brown KD: Peptic ulcer perforation associated with steroid use. Arch Surg 122:376-380, 1987 14. ReMine SG, McIlrath DC: Bowel perforation in steroid-treated patients. Ann Surg 192:581-586, 1980 15. Warshaw AL, Welch JP, Ottinger LW Acute perforation of the colon associated with chronic corticosteroid therapy. Am J Surg 131~442446, 1976

Discussion M.R. Langham (Gainesville, FL): First, having been a fellow at St Christopher’s Hospital in the early part of this series, I recall several of the six perforations. Since I’ve moved to Gainesville I started “on a roll” there with a couple, but in about 80 transplants over the last few years, we’ve not had one in the last 4 years. I was wondering with the increased experience at St Christopher’s, if you’ve had a decline in this complication. We have had one death in Gainesville that I think was related to delay in diagnosis. You didn’t give us any mortality figures with these perforations. Can you tell us how devastating a complication this really is? E.A. Beierle (response): As far as the decline in perforation, we’ve also noted the same thing at St Christopher’s. I don’t know if it is related to experience, or if it’s more related to the fact that previously a complete adhesiolysis was performed in children who had previous laparotomy, and that’s no longer done. Regarding mortality, one child died of cytomegalovir-us pneumonia and another of uncontrolled sepsis from multiple perforations. J.-M. Laberge (Montreal, Canada): Could you speculate as to how these perforations occur? Do you think they are delayed cautery injuries, or what causes them? E.A. Beierle (response): That’s basically what we were trying to figure out. They are probably related, as I said earlier, to complete adhesiolysis. Four of the six had undergone laparotomies for necrotizing enterocolitis,

followed by ileostomy takedown. Their bowel was probably inherently not as healthy as most of the children that undergo transplant. J.P: Vacanti (Boston, MA): How many perforations occurred in the Roux-en-Y limb of a child who had a Kasai operation? E.A. Beierle (response): Only one of the ten perforations was associated with the Roux limb, and that was not in a child with a Kasai. M. Fallat (Louisville, KY): Do you have an idea of what the average time interval was between when you suspected something was wrong with these children and when the operation took place? E.A. Beierle (response): The highest index of suspicion was for a child who looked septic for no other reason, didn’t have an infiltrate seen on chest x-ray, and nothing was obvious. Within 12 hours he was taken to the operating room. Dr Dunn has a very aggressive attitude toward reexploration in these children. M. Fallat (Louisville, KY): Is there a central registry for children after transplantation so that we will have an idea of what the global incidence of this and other complications is? E.A. Beierle (response): I don’t know the answer to that. Because there are just smatterings of reports in the literature, it would be useful to gather and compare data to decide if any indices are actually helpful.