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Short bowel syndrome: remedial features that influence outcome and the duration of parenteral nutrition
September 1997
Volume 131
s
Number 3
EDITORIALS
bowel syndrome: Remedial features that ............
me outcome and the duration of parenteral nutrition The pathophysiology of short bowel syndrome was described more than 100 years ago by Senn. 1 However, not unN the landmark experience of appl3fing total parenteral nutrition to children with severe SBS in the mid-1960s, by the University of Pennsylvania surgical research team, have opportunities for consistent long-term survival become available to this group of patients. 2 In this issue of The Journal of Pedia#ics, Kaufman et al.a report on their analysis of those variables that predict the duration of parenteral nutrition in these patients. Their data reaffirm the importance of small bowel length and, for the first time, identify the acquired problem of bacterial ovelyrowth as an additional independent variable that influences the duration of parenteral nutrition in this patient population. Furthermore, Kaufman et al. have identified
See related article, p. 356. the correlation of small bowel inflammation with bacterial overgrowth; the presence and severity of this inflammation directly influenced the ability to wean patients from parenteral nutrition. What is less clear from this report is whether a direct causal relationship among bacterial overgrowth, intestinal inJ Pediatr 1997;131:335-6 Copyright9 1997by Mosby-YearBook, Inc. 0022-3476/97/$5.00 + 0 9/18/80516
flammation, and the duration of parenteral nutrition has been proved. The pathophysiology of SBS has been thought to be influenced by the anatomic length and location of the remaining small bowel, the motility and absorptive function of that intestine, the presence or absence of an ileoeecal valve, and the presence or absence of the colon and its anal sphincter. The nutritional, medical, and surgical therapy for SBS has focused on ways to enhance mucosal absorptive function by increasing the area of the absorbing surface, decreasing the transit, and therefore increasing the interval of nutrient-mucosal exposure while concomitantly normalizing the systemic growth of the body as a whole. Kaufman's group has reconfirmed the importance of small bowel length and the presence of an ileocecal valve in determining which patients with SBS could be weaned from parenteral nutrition. The 42 of d9 children successfully weaned had small bowel lengths of 81 + 65 cm, 45% having the presence of an ileocecal valve; in the seven children not successfully weaned, the average length was only 31 -+30 cm and none had an ileocecal valve. More importantly, the new finding from this report was the documentation by endoscopy and culture technique of the role that bacterial overgrowth plays in SBS. The origin of bacterial overgrowth is
multifaceted, and key etiologic factors include intestinal stasis and an accumulation of intraluminal nutrient products. The stasis of luminal contents is a product of both the fundamental cause of SBS and a potential result of its treatment. SBS caused by gastroschisis, necrotlzing enterocolitis, ischemic bowel disease such as malrotation with volvulus, and extended Hirschsprung disease (these patients were excluded from the Kaufman series) inherently is characterized by alterations in normal gut motility with secondary intraluminal stasis. A bowel resection and a simple anastomosis may itself adversely alter intestinal motility and promote overgrowth. 4 Furthermore, the adaptive response, with a compensatory increase in luminal diameter, as well as focal obstruction and dilation, may contribute to stasis
and ineffective cleansing peristaltic activity. Small bowel motility depends on a functioning enteric nervous system, an activity that regulates the progression of the migrating motor complex, which serves as the gut "housekeeper," preventing bacterial overgrowth. 5 The second feature required for bacterial overgrowth, namely, intraluminal nutrient available to the bacteria, is a product
335
THE JOURNALOF PEDIATRICS SEPTEMBER1997
EDITORIALS
of the malabsorption of such nutrients, seen as a part of SBS regardless of the underlying cause. It is the metabolism of intraluminal substrate by the bacteria that produces the basis for auxiliary diagnostic tests for bacterial overgrowth, the elevated plasma d-lactate concentration and the abnormal breath hydrogen excretion. It is this same luminal substrate accumulation that may contribute to bacterial adhesion, internalization, and transmucosal passage, which itself may contribute to the enteritis reported by the authors to be associated with bacterial overgrowth. 6' 7 Kaufman et al.J have further demonstrated that the enteritis seen in this series of patients with SBS was more severe than that which would be attributable to bacterial overgrowth alone, speculating that an immune complex-mediated reaction to both the bacteria and the accumulating nutrients may be causal. Additional factors that may contribute to these inflammatory changes include toxic injury from luminal nutrients and their metabolites, such as short-chain fatty acids, bacterial or vital products, or endogenous digestive tract products such as bile salts. 7 Contributing to these inflammatory changes may be impairment in mucosal immune defense mediated by enteric nervous system dysfunction, which, as noted above, also contributes to the dysmotility seen in SBS. 5 The most important contribution of this study is the recognition of those factors that influence the ability to wean the patient with SBS from parenteral nutrition. Because the long-term consequence of SBS in this and other series is death from
336
liver failure, and because such failure is related to the need for prolonged parenteral nutrient intake, an understanding of those factors that potentiate weaning become increasingly important. This and other reports link intestinal length as that most important independent variable predicting both the ability of patients to be weaned from parenteral nutrition and the ultimate outcome. However, short of operative intestinal lengthening procedures, further gut adaptation, or ultimate length replacement by transplantation, that factor is largely fixed at the time of the initial diagnosis. The contribution of Kaufman et al.3 is the recognition of bacterial overgrowth as an additional independent variable that limits the ability to be weaned from parenteral nutrition. Fortunately, this "acquired" complication can be treated. Treatment may potentially be directed at the bacteria themselves by means of systemic or intraluminal cyclic antibiotics. Whether the use of selected nutrients or tropbic factors to enhance enterocyte function or intestinal barrier function is advantageous is currently speculative. However, both medical and surgical therapy can potentially be directed at dysmotility and its associated stasis resulting from dilation or obstruction, s Finally, the "acquired" inflammatory change is also amenable to both nutrient alteration and the use of antibiotic or antiinflammatory medications, or, in selected cases, to surgical treatment where stasis from either obstruction or dilation is present. This report emphasizes the complexity of management of children with severe SBS, and it underscores the need for a comprehensive medical and surgical at-
mamentarium for optimal treatment of these patients. Moritz ~. Ziegler,MD Departments of Surgery and Pediatrics Children 5 Hospital Medical Center University of Cincinnati Collegeof Medicine Cincinnat~ OH 45229-3039
REFERENCES 1. Senn N. An experimental contribution to intestinal surgery with special reference to the treatment of intestinal obstruction. II. Enterectomy. Ann Surg 1888;7:99115. 2. Wilmore DW, Dudrick SJ. Growth and development of an infant receiving all nutrients exclusively by vein. JAMA 1968; 203:860-4. 3. KaufmanSS, Loseke CA, Lupo JM, Youn~ RJ, Murray ND, Pinch LW, et al. Influence of bacterial overgrowth and intestinal inflammation on duration of parenteral nutrition in children with short bowel syndrome. J Pediatr 1997;131:356-61. 4. Hocking ~MP,Carlson RG, Courington KR, Bland KI. Altered motility and bacterial flora after functional end-to-end anastomosis. Surgery 1990;108:384-92. 5. Debas HT, Mulvihill SJ. Neuroendocrine design of the gut. Am J Surg 1991;161:2439. 6. Go LL, Ford HR, Watkins SC, Healey PJ, Albanese CT, Donhalek A, et al. Quantitative and morphologic analysis of bacterial translocation in neonates. Arch Surg 1994;129:1184-90. 7. Taylor SE Sondheimer JM, Sokol RJ, Silverman A, Wilson HI. Noninfectious colitis associated with short gut syndrome in infants, d Pediatr 1991;119:24-8. 8. Chaet MS, Farrell NiK, Ziegler MM, Warner BW. Intensive nutrition support and remedial surgical intervention for extreme short bowel syndrome. O Pediatr Gastroenterol Nutr 1994;19:295-8.
Volume 131
s
Number 3
EDITORIALS
bowel syndrome: Remedial features that ............
me outcome and the duration of parenteral nutrition The pathophysiology of short bowel syndrome was described more than 100 years ago by Senn. 1 However, not unN the landmark experience of appl3fing total parenteral nutrition to children with severe SBS in the mid-1960s, by the University of Pennsylvania surgical research team, have opportunities for consistent long-term survival become available to this group of patients. 2 In this issue of The Journal of Pedia#ics, Kaufman et al.a report on their analysis of those variables that predict the duration of parenteral nutrition in these patients. Their data reaffirm the importance of small bowel length and, for the first time, identify the acquired problem of bacterial ovelyrowth as an additional independent variable that influences the duration of parenteral nutrition in this patient population. Furthermore, Kaufman et al. have identified
See related article, p. 356. the correlation of small bowel inflammation with bacterial overgrowth; the presence and severity of this inflammation directly influenced the ability to wean patients from parenteral nutrition. What is less clear from this report is whether a direct causal relationship among bacterial overgrowth, intestinal inJ Pediatr 1997;131:335-6 Copyright9 1997by Mosby-YearBook, Inc. 0022-3476/97/$5.00 + 0 9/18/80516
flammation, and the duration of parenteral nutrition has been proved. The pathophysiology of SBS has been thought to be influenced by the anatomic length and location of the remaining small bowel, the motility and absorptive function of that intestine, the presence or absence of an ileoeecal valve, and the presence or absence of the colon and its anal sphincter. The nutritional, medical, and surgical therapy for SBS has focused on ways to enhance mucosal absorptive function by increasing the area of the absorbing surface, decreasing the transit, and therefore increasing the interval of nutrient-mucosal exposure while concomitantly normalizing the systemic growth of the body as a whole. Kaufman's group has reconfirmed the importance of small bowel length and the presence of an ileocecal valve in determining which patients with SBS could be weaned from parenteral nutrition. The 42 of d9 children successfully weaned had small bowel lengths of 81 + 65 cm, 45% having the presence of an ileocecal valve; in the seven children not successfully weaned, the average length was only 31 -+30 cm and none had an ileocecal valve. More importantly, the new finding from this report was the documentation by endoscopy and culture technique of the role that bacterial overgrowth plays in SBS. The origin of bacterial overgrowth is
multifaceted, and key etiologic factors include intestinal stasis and an accumulation of intraluminal nutrient products. The stasis of luminal contents is a product of both the fundamental cause of SBS and a potential result of its treatment. SBS caused by gastroschisis, necrotlzing enterocolitis, ischemic bowel disease such as malrotation with volvulus, and extended Hirschsprung disease (these patients were excluded from the Kaufman series) inherently is characterized by alterations in normal gut motility with secondary intraluminal stasis. A bowel resection and a simple anastomosis may itself adversely alter intestinal motility and promote overgrowth. 4 Furthermore, the adaptive response, with a compensatory increase in luminal diameter, as well as focal obstruction and dilation, may contribute to stasis
and ineffective cleansing peristaltic activity. Small bowel motility depends on a functioning enteric nervous system, an activity that regulates the progression of the migrating motor complex, which serves as the gut "housekeeper," preventing bacterial overgrowth. 5 The second feature required for bacterial overgrowth, namely, intraluminal nutrient available to the bacteria, is a product
335
THE JOURNALOF PEDIATRICS SEPTEMBER1997
EDITORIALS
of the malabsorption of such nutrients, seen as a part of SBS regardless of the underlying cause. It is the metabolism of intraluminal substrate by the bacteria that produces the basis for auxiliary diagnostic tests for bacterial overgrowth, the elevated plasma d-lactate concentration and the abnormal breath hydrogen excretion. It is this same luminal substrate accumulation that may contribute to bacterial adhesion, internalization, and transmucosal passage, which itself may contribute to the enteritis reported by the authors to be associated with bacterial overgrowth. 6' 7 Kaufman et al.J have further demonstrated that the enteritis seen in this series of patients with SBS was more severe than that which would be attributable to bacterial overgrowth alone, speculating that an immune complex-mediated reaction to both the bacteria and the accumulating nutrients may be causal. Additional factors that may contribute to these inflammatory changes include toxic injury from luminal nutrients and their metabolites, such as short-chain fatty acids, bacterial or vital products, or endogenous digestive tract products such as bile salts. 7 Contributing to these inflammatory changes may be impairment in mucosal immune defense mediated by enteric nervous system dysfunction, which, as noted above, also contributes to the dysmotility seen in SBS. 5 The most important contribution of this study is the recognition of those factors that influence the ability to wean the patient with SBS from parenteral nutrition. Because the long-term consequence of SBS in this and other series is death from
336
liver failure, and because such failure is related to the need for prolonged parenteral nutrient intake, an understanding of those factors that potentiate weaning become increasingly important. This and other reports link intestinal length as that most important independent variable predicting both the ability of patients to be weaned from parenteral nutrition and the ultimate outcome. However, short of operative intestinal lengthening procedures, further gut adaptation, or ultimate length replacement by transplantation, that factor is largely fixed at the time of the initial diagnosis. The contribution of Kaufman et al.3 is the recognition of bacterial overgrowth as an additional independent variable that limits the ability to be weaned from parenteral nutrition. Fortunately, this "acquired" complication can be treated. Treatment may potentially be directed at the bacteria themselves by means of systemic or intraluminal cyclic antibiotics. Whether the use of selected nutrients or tropbic factors to enhance enterocyte function or intestinal barrier function is advantageous is currently speculative. However, both medical and surgical therapy can potentially be directed at dysmotility and its associated stasis resulting from dilation or obstruction, s Finally, the "acquired" inflammatory change is also amenable to both nutrient alteration and the use of antibiotic or antiinflammatory medications, or, in selected cases, to surgical treatment where stasis from either obstruction or dilation is present. This report emphasizes the complexity of management of children with severe SBS, and it underscores the need for a comprehensive medical and surgical at-
mamentarium for optimal treatment of these patients. Moritz ~. Ziegler,MD Departments of Surgery and Pediatrics Children 5 Hospital Medical Center University of Cincinnati Collegeof Medicine Cincinnat~ OH 45229-3039
REFERENCES 1. Senn N. An experimental contribution to intestinal surgery with special reference to the treatment of intestinal obstruction. II. Enterectomy. Ann Surg 1888;7:99115. 2. Wilmore DW, Dudrick SJ. Growth and development of an infant receiving all nutrients exclusively by vein. JAMA 1968; 203:860-4. 3. KaufmanSS, Loseke CA, Lupo JM, Youn~ RJ, Murray ND, Pinch LW, et al. Influence of bacterial overgrowth and intestinal inflammation on duration of parenteral nutrition in children with short bowel syndrome. J Pediatr 1997;131:356-61. 4. Hocking ~MP,Carlson RG, Courington KR, Bland KI. Altered motility and bacterial flora after functional end-to-end anastomosis. Surgery 1990;108:384-92. 5. Debas HT, Mulvihill SJ. Neuroendocrine design of the gut. Am J Surg 1991;161:2439. 6. Go LL, Ford HR, Watkins SC, Healey PJ, Albanese CT, Donhalek A, et al. Quantitative and morphologic analysis of bacterial translocation in neonates. Arch Surg 1994;129:1184-90. 7. Taylor SE Sondheimer JM, Sokol RJ, Silverman A, Wilson HI. Noninfectious colitis associated with short gut syndrome in infants, d Pediatr 1991;119:24-8. 8. Chaet MS, Farrell NiK, Ziegler MM, Warner BW. Intensive nutrition support and remedial surgical intervention for extreme short bowel syndrome. O Pediatr Gastroenterol Nutr 1994;19:295-8.