Pathophysiology 21 (2014) 111–118
Management of short bowel syndrome Jason P. Sulkowski, Peter C. Minneci ∗ Center for Surgical Outcomes Research, The Research Institute at Nationwide Children’s Hospital and Department of Surgery, Nationwide Children’s Hospital, Columbus, OH, United States
Abstract Most intestinal failure in children is due to short bowel syndrome (SBS) where congenital or acquired lesions have led to an extensive loss of intestinal mass. The vast majority of morbidity and mortality of patients with SBS is due to complications secondary to their long term dependence on parenteral nutrition. In response to SBS, the intestine undergoes a process of remodeling termed adaptation. Principles guiding the medical management of SBS include providing adequate parenteral nutrition, fluids and electrolytes for growth and normal development, promoting small bowel adaptation, and preventing and treating complications related to the patient’s underlying disease and their parenteral nutrition. Catheter associated blood stream infection (CABSI) is major source of morbidity and mortality in patients with intestinal failure from SBS. Intestinal failure associated liver disease (IFALD)is another major source of morbidity and mortality in patients with SBS. IFALD is the most consistent negative predictor of outcome including death and continued parenteral nutrition dependence. Enteral nutrition is critical for intestinal adaptation and preventing IFALD. Patients with SBS who develop dilated dysmotile segments may benefit from autologous intestinal reconstruction surgery (AIRS) with the goal of decreasing stasis and disordered motility through intestinal narrowing and lengthening. Patients with SBS should be referred for transplantation if they have failed intestinal rehabilitation including AIRS, have no reasonable chance for enteral feeding tolerance, develop irreversible IFALD, have recurrent sepsis, or have exhausted their central venous access sites. With improvements in medical and surgical care, overall survival of patients with SBS now exceeds 90%. © 2013 Elsevier Ireland Ltd. All rights reserved. Keywords: Short bowel syndrome; intestinal failure; intestinal failure associated liver disease; IFALD; autologous intestinal reconstructive surgery
1. Introduction Intestinal failure refers to all states where the intestine has inadequate absorptive capacity to meet the nutritional, fluid and electrolyte needs to sustain the life and growth requirements of a child [1,2]. Intestinal failure leads to chronic dependence on parenteral nutrition to maintain adequate growth, hydration, and micronutrient balance. There are three major categories of intestinal failure including short bowel syndrome with the loss of intestinal length leading to decreased absorptive capacity, malabsorptive states, such as microvillus inclusion disease, and motility disorders, such as intestinal pseudo-obstruction [1]. ∗ Corresponding author at: Center for Surgical Outcomes Research, The Research Institute at Nationwide Children’s Hospital, 700 Childrens Drive, JW4914, Columbus, OH 43205, United States. Tel.: +1 614 722 3066; fax: +1 614 722 3903. E-mail address: [email protected] (P.C. Minneci).
0928-4680/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.pathophys.2013.11.013
Most intestinal failure in children is due to short bowel syndrome (SBS) where congenital or acquired lesions have led to an extensive loss of intestinal mass (Table 1) [2–4]. The earliest descriptions of SBS describe midgut volvulus and small bowel atresia as the most common causes of SBS. However, more recently, necrotizing enterocolitis (NEC) has become the most common cause of intestinal failure due to SBS [5–7]. NEC is expected to continue as a predominant cause of SBS as more neonates at high risk for developing NEC survive including extremely premature infants and infant with complex congenital cardiac anomalies [8]. The reported incidence of SBS varies based on the presence of prematurity and low birth weight. In one report form Canada, the overall incidence of SBS was 24.5 cases per 100,000 live births; however, the incidence in premature infants (30 mequiv./L and to maintain a urine sodium to potassium ratio of 1:1 [2]. 3.2. Enteral nutrition considerations in SBS Enteral nutrition is critical for intestinal adaptation and preventing IFALD. Because luminal substrates and nutrients are essential for adaptation, attempts should be made to establish enteral nutrition no matter how small an amount [33]. Once intestinal function has returned, attempts at enteral feeding should be initiated regardless of length of remaining bowel. Enteral feedings lead to intestinal growth, enhancement of enterocyte enzyme activity, and bowel motility [33].
113
In addition, tolerance of any amount of enteral feeding can dramatically decrease the risk profile of patients with SBS. Initial enteral feedings in patients with SBS are usually administered continuously to maximize the function of the residual intestinal mucosa by allowing for a relatively uniform saturation of intestinal mucosa. Use of breast milk or elemental formulas, which are more easily absorbed, can decrease duration of parenteral nutrition dependence in neonates with SBS [18]. Feeding advancement is limited to keep stool or stoma output to 3%) can lead to an osmotic diarrhea which can counteract its benefits. Patients with SBS with high stool or stoma output limiting enteral intake and no mechanical or intestinal cause may benefit from the use of loperamide to decrease stool output. Patients with SBS who have poor motility will develop vomiting, abdominal distention, or high gastric residuals; these patients may have improved enteral tolerance with the use pro-motility agents including erythromycin, azithromycin, or augmentin. Small bowel bacterial overgrowth can occur in up to 50% of patients with SBS [16]. As part of adaptation, segments of bowel may dilate and develop disordered motility leading to stasis with the potential for bacterial overgrowth. Consequently, bacterial overgrowth leads to inflammation with mucosal injury that may allow for bacterial translocation or gastrointestinal bleeding. Bacterial overgrowth can also worsen absorption through the deconjugation of bile acids and can produce toxic by-products such as d-lactic acid which can lead to ataxia, mental status changes, and acidosis [16,36]. Clinically, small bowel bacterial overgrowth can present as new feeding difficulties, worsening of motility, abdominal distention or pain, or gastrointestinal bleeding. Treatment is empirically initiated in the appropriate clinical setting with a dilated segment of bowel and consists of cycles of enteral antibiotics with anaerobic spectrum, such as metronidazole or augmentin if there are also motility issues, for 7–10 days of therapy following 7–10 days off therapy [2]. Recurrent episodes of bacterial overgrowth are an indication for surgical intervention to narrow of the dilated segment of intestine.
114
J.P. Sulkowski, P.C. Minneci / Pathophysiology 21 (2014) 111–118
4. Vascular access and catheter associated blood stream infection Patients with SBS require long term central venous access to receive their parenteral nutrition. This traditionally required surgically placed tunneled cuffed central venous catheters (Broviac or Hickmann catheters); however, many centers are now using peripherally inserted central catheters (PICCs) for long term parenteral nutrition. Use of percutaneous placement techniques and peripheral lines can decrease loss of central venous access [37]. Advantages of PICCs are that they can be placed without general anesthesia, they do not require ligating a central vein, and they may carry a lower risk of thrombosis of the central veins. In one recent report, the incidence of PICC related catheter associated blood stream infection (CABSI) was 5.3 per 1000 catheter days and PICC related venous thrombosis was 2.0 per 1000 catheter days. These rates are similar or lower than reported rates with surgical central lines, therefore, the authors recommend using PICCs for central access in patients with intestinal failure until 1 year of age when a tunneled central catheter should be placed [38]. In long term intestinal failure patients, central venous access can be exhausted over time secondary to thrombosis or occlusion. In these cases, alternative sites such as transhepatic, translumbar, or internal mammary venous lines may need to be considered. Referral for transplantation becomes the only option when central venous access can no longer be obtained accounting for up to 50% of transplant referrals [39,40]. Catheter associated blood stream infection (CABSI) is major source of morbidity and mortality in patients with intestinal failure from SBS. CABSI rates in patients with intestinal failure range from 4 to 10 infections per 1000 catheter days [1,41]. Circumstances leading to higher rates of CABSI in this population include a long duration of time with the catheter with a willingness to treat through infections to maintain central access instead of removing the catheter, long term infusion of high concentration dextrose solutions, and the presence of dilated intestinal segments with the potential for bacterial overgrowth. Risk factors for developing CABSI in patients with SBS include prematurity, low birth weight, and shorter length of remaining intestine. In patients with SBS, fever, lethargy or ileus should raise concerns for CABSI. These patients should have blood cultures drawn and be treated empirically with broad spectrum antibiotics for 48 h. The catheter should be removed if the blood cultures are repeatedly positive for 3 days, there are signs of systemic instability, or if fungus is isolated in the cultures. Several methods to reduce CABSI have been reported including using checklists for insertion and dressing changes, using chlorhexidine based cleansing solutions, and using ethanol locks [42–44]. In particular, 70% ethanol locks have been reported to decreased CABSI in intestinal failure patients from 9.9 cases per 1000 catheter days to 2.1 cases per 1000 catheter days [42].
5. Intestinal failure associated liver disease Intestinal failure associated liver disease (IFALD) is another major source of morbidity and mortality in patients with SBS. IFALD is the most consistent negative predictor of outcome including death and continued parenteral nutrition dependence [5,45–47]. It occurs in up to 60% of children with SBS with 16.6% progressing to end stage liver disease [48,49]. The mechanism of IFALD is thought to be multifactorial with contributions from episodes of infection/sepsis, bowel stasis, altered enterohepatic bile acid circulation, susceptibility of the neonatal liver to cholestatic injury, and parenteral nutrition toxicity, particularly from the lipid infusions [15,48–52]. Clinically, IFALD presents with increased serum transaminases and direct hyperbilirubinemia. Histologically, there is cholestasis, bile duct proliferation, periportal inflammation and fibrosis [53]. Of note, the level of cholestasis may not reflect the presence and degree of liver damage [54]. If not reversed, ongoing liver injury leads to cirrhosis with coagulopathy and eventually thrombocytopenia and portal hypertension. However, the histopathologic changes and cholestasis can be reversed if enteral nutrition can be initiated and advanced [18]. Several parenteral nutrition strategies that focus on cycling parenteral nutrition and limiting or changing lipid emulsions have been developed to try to prevent IFALD. One strategy is to cycle parenteral nutrition to provide the total caloric amount over less than 24 h. Cycling of parenteral nutrition allows for disconnection of the central venous catheter, improves visceral protein stores, and can reduce the incidence of hyperinsulinemia. Cycling is recommended when the expected duration of parenteral nutrition is expected to be longer than 30 days [55,56]. In one small study of patients with SBS secondary to gastroschisis, patients who had cycling of parenteral nutrition were three times less likely to develop IFALD compared to patients who received continuous parenteral nutrition [57]. Lipid limitation is another strategy that is now commonly being applied. The lipid emulsions used in the United States are soybean and/or safflower oil based which are rich in omega-6 fatty acids, including arachidonic acid, which lead to the production of pro-inflammatory cytokines. The proinflammatory properties of these lipid emulsions may play a role in IFALD. In order to prevent or delay the development of IFALD, many groups are now limiting lipid administration to 1 g/kg/day or lower [58–61]. This strategy limits the hepatotoxicity of parenteral nutrition and has been associated with a decreased incidence of IFALD [59,60]. However, lipid limitation should be used cautiously in neonates as extended periods of limitation may lead to growth retardation and the decrease in calories must be compensated for by increasing the amount of dextrose in the parenteral nutrition. Another area of investigation to prevent IFALD involves using fish oil based lipid emulsions that are rich in omega-3 fatty acids which have anti-inflammatory properties. Studies
J.P. Sulkowski, P.C. Minneci / Pathophysiology 21 (2014) 111–118
of omegaven, a fish oil based lipid emulsion rich in omega-3 fatty acids, demonstrated higher and faster rates of reversal of cholestasis compared to historical controls that received soybean oil based lipid emulsions [62–65]. Other groups have reported chemical reversal of IFALD with the use of lipid emulsions rich in omega-3 fatty acids [62,63]. There is an ongoing clinical trial evaluating omegaven; however, for now, omegaven is only available for compassionate use in the U.S. for patients with significant cholestatic disease with little chance of enteral feeding advancement in hopes of allowing for reversal of cholestasis to permit more time for intestinal adaptation.
6. Surgical therapy for SBS 6.1. Initial surgical management Initial surgical management of patients at risk for SBS requires conservation of every centimeter of intestine possible. In patients with NEC or volvulus, this may involve an initial abdominal exploration with resection of only frankly necrotic areas of bowel with planned serial ‘second look’ operations to evaluate marginal areas of intestine for viability. It may also involve using temporary abdominal silos which allow for constant visualization of the remaining bowel. At the end of initial surgical management, most patients with SBS from NEC will have a stoma and mucous fistula created. The child can be started on enteral nutrition once bowel function has returned and they have recovered from their episode of NEC. The stoma and mucous fistula are usually reversed to restore bowel continuity once the neonate has grown and recovered from their underlying medical conditions. Whenever possible, early stoma closure is recommended because it can hasten the ability to wean the patient from parenteral nutrition [18]. In patients with SBS, placement of a surgical gastrostomy tube during the stoma closure procedure is recommended to allow for long term enteral access for tube feedings. In children with SBS with poor gastric motility, the gastrostomy tube can later be converted to a gastro-jejunal tube which allows for post-pyloric feedings while draining the poorly motile stomach. 6.2. Autologous intestinal reconstruction surgery (AIRS) As intestinal adaptation occurs, the small bowel may dilate and loose its normal peristaltic activity. The increased diameter of the dilated segment prevents proper and complete approximation of the bowel walls which can lead to disorganized antegrade progression of luminal contents [66–68]. These dilated dysmotile segments can become sites of stasis and bacterial overgrowth [66]. Patients with SBS who develop dilated dysmotile segments may benefit from autologous intestinal reconstruction surgery (AIRS). The goals of AIRS are to correct stasis and disordered motility through intestinal narrowing and lengthening [66].
115
These procedures should be considered in patients with SBS with dilated intestinal segments that have reached a plateau in enteral tolerance despite maximal medical management. There are three relatively common AIRS procedures that can be considered in patients with SBS. The oldest and simplest procedure is a tapering enteroplasty in which the dilated intestine is narrowed by excising a wedge of its anti-mesenteric border. The tapering enteroplasty improves motility by narrowing the intestinal lumen, but is does so at the expense of excising a segment of viable intestine. This procedure should be reserved for children who are thought to have enough intestinal length to successfully wean from parenteral nutrition once the dysmotility and stasis have improved. The other two AIRS procedures, the longitudinal intestinal lengthening and tapering (LILT) and the serial transverse enteroplasty (STEP), combine the benefit of tapering with bowel lengthening and preservation of all viable intestinal tissue. Both the LILT and the STEP procedures have been reported to improve enteral autonomy in patients with SBS. The LILT procedure was developed in 1980 by Bianchi and is often referred to as the “Bianchi procedure”. During LILT, the dilated segment of bowel is longitudinally divided along its length into two smaller equal diameter segments which are then anastomosed end-to-end to increase the length of the intestine. This requires a difficult and meticulous dissection of the mesentery supplying the dilated segment into two separate leaves, one to supply each half of the dilated segment when it is divided. The overall effect of the LILT is to double the length of the dilated segment and to halve its diameter. In patients with SBS undergoing a LILT procedure, overall reported rates of survival are 30–100% with rates of successfully weaning from parenteral nutrition ranging from 28 to 100% [68]. Recurrent dilation of the bowel can occur after a LILT. Disadvantages of the LILT include its technical difficulty, the need for the dilated segment of intestine to be uniformly dilated, and it can only be performed once. The STEP procedure was first reported in 2003 [69,70]. The STEP uses sequential alternating lateral stapling of the dilated intestinal segment along its long axis to narrow the lumen to approximately 2 cm and increase its length [69,70]. Advantages of the STEP procedure are that it is easily reproducible, can be used to create a uniform bowel diameter without uniform dilation preoperatively, carries minimal risk of intestinal ischemia, and can be performed primarily, repeated or performed in patients who have recurrent dilation of their bowel after a LILT procedure. The STEP has been shown to decrease dependence on parenteral nutrition in patients with SBS [71–73]. It has also been used as a primary procedure in neonates with dilated atresia and marginal length and to treat problematic bacterial overgrowth including d-lactic acidosis [69,74–77]. A recent report of the International STEP Registry on 97 patients reported a mortality rate of 11% with 47% of patients reaching enteral autonomy; the median time to enteral autonomy post-STEP procedure was 21 months [78]. Recurrent dilation of the bowel can occur after a STEP procedure if
116
J.P. Sulkowski, P.C. Minneci / Pathophysiology 21 (2014) 111–118
Table 2 Factors affecting outcomes in patients with short bowel syndrome [5,6,15,18,45,81–83]. Factors associated with improved outcomes
Factors associated with worse outcomes
Residual bowel length >35 cm Older infant/child at initial bowel loss Jejunal resection Presence of terminal ileum/ileocecal valve Presence of colon Earlier re-establishment of bowel continuity
Residual bowel length
Management of short bowel syndrome Jason P. Sulkowski, Peter C. Minneci ∗ Center for Surgical Outcomes Research, The Research Institute at Nationwide Children’s Hospital and Department of Surgery, Nationwide Children’s Hospital, Columbus, OH, United States
Abstract Most intestinal failure in children is due to short bowel syndrome (SBS) where congenital or acquired lesions have led to an extensive loss of intestinal mass. The vast majority of morbidity and mortality of patients with SBS is due to complications secondary to their long term dependence on parenteral nutrition. In response to SBS, the intestine undergoes a process of remodeling termed adaptation. Principles guiding the medical management of SBS include providing adequate parenteral nutrition, fluids and electrolytes for growth and normal development, promoting small bowel adaptation, and preventing and treating complications related to the patient’s underlying disease and their parenteral nutrition. Catheter associated blood stream infection (CABSI) is major source of morbidity and mortality in patients with intestinal failure from SBS. Intestinal failure associated liver disease (IFALD)is another major source of morbidity and mortality in patients with SBS. IFALD is the most consistent negative predictor of outcome including death and continued parenteral nutrition dependence. Enteral nutrition is critical for intestinal adaptation and preventing IFALD. Patients with SBS who develop dilated dysmotile segments may benefit from autologous intestinal reconstruction surgery (AIRS) with the goal of decreasing stasis and disordered motility through intestinal narrowing and lengthening. Patients with SBS should be referred for transplantation if they have failed intestinal rehabilitation including AIRS, have no reasonable chance for enteral feeding tolerance, develop irreversible IFALD, have recurrent sepsis, or have exhausted their central venous access sites. With improvements in medical and surgical care, overall survival of patients with SBS now exceeds 90%. © 2013 Elsevier Ireland Ltd. All rights reserved. Keywords: Short bowel syndrome; intestinal failure; intestinal failure associated liver disease; IFALD; autologous intestinal reconstructive surgery
1. Introduction Intestinal failure refers to all states where the intestine has inadequate absorptive capacity to meet the nutritional, fluid and electrolyte needs to sustain the life and growth requirements of a child [1,2]. Intestinal failure leads to chronic dependence on parenteral nutrition to maintain adequate growth, hydration, and micronutrient balance. There are three major categories of intestinal failure including short bowel syndrome with the loss of intestinal length leading to decreased absorptive capacity, malabsorptive states, such as microvillus inclusion disease, and motility disorders, such as intestinal pseudo-obstruction [1]. ∗ Corresponding author at: Center for Surgical Outcomes Research, The Research Institute at Nationwide Children’s Hospital, 700 Childrens Drive, JW4914, Columbus, OH 43205, United States. Tel.: +1 614 722 3066; fax: +1 614 722 3903. E-mail address: [email protected] (P.C. Minneci).
0928-4680/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.pathophys.2013.11.013
Most intestinal failure in children is due to short bowel syndrome (SBS) where congenital or acquired lesions have led to an extensive loss of intestinal mass (Table 1) [2–4]. The earliest descriptions of SBS describe midgut volvulus and small bowel atresia as the most common causes of SBS. However, more recently, necrotizing enterocolitis (NEC) has become the most common cause of intestinal failure due to SBS [5–7]. NEC is expected to continue as a predominant cause of SBS as more neonates at high risk for developing NEC survive including extremely premature infants and infant with complex congenital cardiac anomalies [8]. The reported incidence of SBS varies based on the presence of prematurity and low birth weight. In one report form Canada, the overall incidence of SBS was 24.5 cases per 100,000 live births; however, the incidence in premature infants (30 mequiv./L and to maintain a urine sodium to potassium ratio of 1:1 [2]. 3.2. Enteral nutrition considerations in SBS Enteral nutrition is critical for intestinal adaptation and preventing IFALD. Because luminal substrates and nutrients are essential for adaptation, attempts should be made to establish enteral nutrition no matter how small an amount [33]. Once intestinal function has returned, attempts at enteral feeding should be initiated regardless of length of remaining bowel. Enteral feedings lead to intestinal growth, enhancement of enterocyte enzyme activity, and bowel motility [33].
113
In addition, tolerance of any amount of enteral feeding can dramatically decrease the risk profile of patients with SBS. Initial enteral feedings in patients with SBS are usually administered continuously to maximize the function of the residual intestinal mucosa by allowing for a relatively uniform saturation of intestinal mucosa. Use of breast milk or elemental formulas, which are more easily absorbed, can decrease duration of parenteral nutrition dependence in neonates with SBS [18]. Feeding advancement is limited to keep stool or stoma output to 3%) can lead to an osmotic diarrhea which can counteract its benefits. Patients with SBS with high stool or stoma output limiting enteral intake and no mechanical or intestinal cause may benefit from the use of loperamide to decrease stool output. Patients with SBS who have poor motility will develop vomiting, abdominal distention, or high gastric residuals; these patients may have improved enteral tolerance with the use pro-motility agents including erythromycin, azithromycin, or augmentin. Small bowel bacterial overgrowth can occur in up to 50% of patients with SBS [16]. As part of adaptation, segments of bowel may dilate and develop disordered motility leading to stasis with the potential for bacterial overgrowth. Consequently, bacterial overgrowth leads to inflammation with mucosal injury that may allow for bacterial translocation or gastrointestinal bleeding. Bacterial overgrowth can also worsen absorption through the deconjugation of bile acids and can produce toxic by-products such as d-lactic acid which can lead to ataxia, mental status changes, and acidosis [16,36]. Clinically, small bowel bacterial overgrowth can present as new feeding difficulties, worsening of motility, abdominal distention or pain, or gastrointestinal bleeding. Treatment is empirically initiated in the appropriate clinical setting with a dilated segment of bowel and consists of cycles of enteral antibiotics with anaerobic spectrum, such as metronidazole or augmentin if there are also motility issues, for 7–10 days of therapy following 7–10 days off therapy [2]. Recurrent episodes of bacterial overgrowth are an indication for surgical intervention to narrow of the dilated segment of intestine.
114
J.P. Sulkowski, P.C. Minneci / Pathophysiology 21 (2014) 111–118
4. Vascular access and catheter associated blood stream infection Patients with SBS require long term central venous access to receive their parenteral nutrition. This traditionally required surgically placed tunneled cuffed central venous catheters (Broviac or Hickmann catheters); however, many centers are now using peripherally inserted central catheters (PICCs) for long term parenteral nutrition. Use of percutaneous placement techniques and peripheral lines can decrease loss of central venous access [37]. Advantages of PICCs are that they can be placed without general anesthesia, they do not require ligating a central vein, and they may carry a lower risk of thrombosis of the central veins. In one recent report, the incidence of PICC related catheter associated blood stream infection (CABSI) was 5.3 per 1000 catheter days and PICC related venous thrombosis was 2.0 per 1000 catheter days. These rates are similar or lower than reported rates with surgical central lines, therefore, the authors recommend using PICCs for central access in patients with intestinal failure until 1 year of age when a tunneled central catheter should be placed [38]. In long term intestinal failure patients, central venous access can be exhausted over time secondary to thrombosis or occlusion. In these cases, alternative sites such as transhepatic, translumbar, or internal mammary venous lines may need to be considered. Referral for transplantation becomes the only option when central venous access can no longer be obtained accounting for up to 50% of transplant referrals [39,40]. Catheter associated blood stream infection (CABSI) is major source of morbidity and mortality in patients with intestinal failure from SBS. CABSI rates in patients with intestinal failure range from 4 to 10 infections per 1000 catheter days [1,41]. Circumstances leading to higher rates of CABSI in this population include a long duration of time with the catheter with a willingness to treat through infections to maintain central access instead of removing the catheter, long term infusion of high concentration dextrose solutions, and the presence of dilated intestinal segments with the potential for bacterial overgrowth. Risk factors for developing CABSI in patients with SBS include prematurity, low birth weight, and shorter length of remaining intestine. In patients with SBS, fever, lethargy or ileus should raise concerns for CABSI. These patients should have blood cultures drawn and be treated empirically with broad spectrum antibiotics for 48 h. The catheter should be removed if the blood cultures are repeatedly positive for 3 days, there are signs of systemic instability, or if fungus is isolated in the cultures. Several methods to reduce CABSI have been reported including using checklists for insertion and dressing changes, using chlorhexidine based cleansing solutions, and using ethanol locks [42–44]. In particular, 70% ethanol locks have been reported to decreased CABSI in intestinal failure patients from 9.9 cases per 1000 catheter days to 2.1 cases per 1000 catheter days [42].
5. Intestinal failure associated liver disease Intestinal failure associated liver disease (IFALD) is another major source of morbidity and mortality in patients with SBS. IFALD is the most consistent negative predictor of outcome including death and continued parenteral nutrition dependence [5,45–47]. It occurs in up to 60% of children with SBS with 16.6% progressing to end stage liver disease [48,49]. The mechanism of IFALD is thought to be multifactorial with contributions from episodes of infection/sepsis, bowel stasis, altered enterohepatic bile acid circulation, susceptibility of the neonatal liver to cholestatic injury, and parenteral nutrition toxicity, particularly from the lipid infusions [15,48–52]. Clinically, IFALD presents with increased serum transaminases and direct hyperbilirubinemia. Histologically, there is cholestasis, bile duct proliferation, periportal inflammation and fibrosis [53]. Of note, the level of cholestasis may not reflect the presence and degree of liver damage [54]. If not reversed, ongoing liver injury leads to cirrhosis with coagulopathy and eventually thrombocytopenia and portal hypertension. However, the histopathologic changes and cholestasis can be reversed if enteral nutrition can be initiated and advanced [18]. Several parenteral nutrition strategies that focus on cycling parenteral nutrition and limiting or changing lipid emulsions have been developed to try to prevent IFALD. One strategy is to cycle parenteral nutrition to provide the total caloric amount over less than 24 h. Cycling of parenteral nutrition allows for disconnection of the central venous catheter, improves visceral protein stores, and can reduce the incidence of hyperinsulinemia. Cycling is recommended when the expected duration of parenteral nutrition is expected to be longer than 30 days [55,56]. In one small study of patients with SBS secondary to gastroschisis, patients who had cycling of parenteral nutrition were three times less likely to develop IFALD compared to patients who received continuous parenteral nutrition [57]. Lipid limitation is another strategy that is now commonly being applied. The lipid emulsions used in the United States are soybean and/or safflower oil based which are rich in omega-6 fatty acids, including arachidonic acid, which lead to the production of pro-inflammatory cytokines. The proinflammatory properties of these lipid emulsions may play a role in IFALD. In order to prevent or delay the development of IFALD, many groups are now limiting lipid administration to 1 g/kg/day or lower [58–61]. This strategy limits the hepatotoxicity of parenteral nutrition and has been associated with a decreased incidence of IFALD [59,60]. However, lipid limitation should be used cautiously in neonates as extended periods of limitation may lead to growth retardation and the decrease in calories must be compensated for by increasing the amount of dextrose in the parenteral nutrition. Another area of investigation to prevent IFALD involves using fish oil based lipid emulsions that are rich in omega-3 fatty acids which have anti-inflammatory properties. Studies
J.P. Sulkowski, P.C. Minneci / Pathophysiology 21 (2014) 111–118
of omegaven, a fish oil based lipid emulsion rich in omega-3 fatty acids, demonstrated higher and faster rates of reversal of cholestasis compared to historical controls that received soybean oil based lipid emulsions [62–65]. Other groups have reported chemical reversal of IFALD with the use of lipid emulsions rich in omega-3 fatty acids [62,63]. There is an ongoing clinical trial evaluating omegaven; however, for now, omegaven is only available for compassionate use in the U.S. for patients with significant cholestatic disease with little chance of enteral feeding advancement in hopes of allowing for reversal of cholestasis to permit more time for intestinal adaptation.
6. Surgical therapy for SBS 6.1. Initial surgical management Initial surgical management of patients at risk for SBS requires conservation of every centimeter of intestine possible. In patients with NEC or volvulus, this may involve an initial abdominal exploration with resection of only frankly necrotic areas of bowel with planned serial ‘second look’ operations to evaluate marginal areas of intestine for viability. It may also involve using temporary abdominal silos which allow for constant visualization of the remaining bowel. At the end of initial surgical management, most patients with SBS from NEC will have a stoma and mucous fistula created. The child can be started on enteral nutrition once bowel function has returned and they have recovered from their episode of NEC. The stoma and mucous fistula are usually reversed to restore bowel continuity once the neonate has grown and recovered from their underlying medical conditions. Whenever possible, early stoma closure is recommended because it can hasten the ability to wean the patient from parenteral nutrition [18]. In patients with SBS, placement of a surgical gastrostomy tube during the stoma closure procedure is recommended to allow for long term enteral access for tube feedings. In children with SBS with poor gastric motility, the gastrostomy tube can later be converted to a gastro-jejunal tube which allows for post-pyloric feedings while draining the poorly motile stomach. 6.2. Autologous intestinal reconstruction surgery (AIRS) As intestinal adaptation occurs, the small bowel may dilate and loose its normal peristaltic activity. The increased diameter of the dilated segment prevents proper and complete approximation of the bowel walls which can lead to disorganized antegrade progression of luminal contents [66–68]. These dilated dysmotile segments can become sites of stasis and bacterial overgrowth [66]. Patients with SBS who develop dilated dysmotile segments may benefit from autologous intestinal reconstruction surgery (AIRS). The goals of AIRS are to correct stasis and disordered motility through intestinal narrowing and lengthening [66].
115
These procedures should be considered in patients with SBS with dilated intestinal segments that have reached a plateau in enteral tolerance despite maximal medical management. There are three relatively common AIRS procedures that can be considered in patients with SBS. The oldest and simplest procedure is a tapering enteroplasty in which the dilated intestine is narrowed by excising a wedge of its anti-mesenteric border. The tapering enteroplasty improves motility by narrowing the intestinal lumen, but is does so at the expense of excising a segment of viable intestine. This procedure should be reserved for children who are thought to have enough intestinal length to successfully wean from parenteral nutrition once the dysmotility and stasis have improved. The other two AIRS procedures, the longitudinal intestinal lengthening and tapering (LILT) and the serial transverse enteroplasty (STEP), combine the benefit of tapering with bowel lengthening and preservation of all viable intestinal tissue. Both the LILT and the STEP procedures have been reported to improve enteral autonomy in patients with SBS. The LILT procedure was developed in 1980 by Bianchi and is often referred to as the “Bianchi procedure”. During LILT, the dilated segment of bowel is longitudinally divided along its length into two smaller equal diameter segments which are then anastomosed end-to-end to increase the length of the intestine. This requires a difficult and meticulous dissection of the mesentery supplying the dilated segment into two separate leaves, one to supply each half of the dilated segment when it is divided. The overall effect of the LILT is to double the length of the dilated segment and to halve its diameter. In patients with SBS undergoing a LILT procedure, overall reported rates of survival are 30–100% with rates of successfully weaning from parenteral nutrition ranging from 28 to 100% [68]. Recurrent dilation of the bowel can occur after a LILT. Disadvantages of the LILT include its technical difficulty, the need for the dilated segment of intestine to be uniformly dilated, and it can only be performed once. The STEP procedure was first reported in 2003 [69,70]. The STEP uses sequential alternating lateral stapling of the dilated intestinal segment along its long axis to narrow the lumen to approximately 2 cm and increase its length [69,70]. Advantages of the STEP procedure are that it is easily reproducible, can be used to create a uniform bowel diameter without uniform dilation preoperatively, carries minimal risk of intestinal ischemia, and can be performed primarily, repeated or performed in patients who have recurrent dilation of their bowel after a LILT procedure. The STEP has been shown to decrease dependence on parenteral nutrition in patients with SBS [71–73]. It has also been used as a primary procedure in neonates with dilated atresia and marginal length and to treat problematic bacterial overgrowth including d-lactic acidosis [69,74–77]. A recent report of the International STEP Registry on 97 patients reported a mortality rate of 11% with 47% of patients reaching enteral autonomy; the median time to enteral autonomy post-STEP procedure was 21 months [78]. Recurrent dilation of the bowel can occur after a STEP procedure if
116
J.P. Sulkowski, P.C. Minneci / Pathophysiology 21 (2014) 111–118
Table 2 Factors affecting outcomes in patients with short bowel syndrome [5,6,15,18,45,81–83]. Factors associated with improved outcomes
Factors associated with worse outcomes
Residual bowel length >35 cm Older infant/child at initial bowel loss Jejunal resection Presence of terminal ileum/ileocecal valve Presence of colon Earlier re-establishment of bowel continuity
Residual bowel length
