Imad F. Btaiche

Pediatric Short Bowel Syndrome: Redefining Predictors of Success

Objective:To determine predictors of survival and of weaning off parenteral nutrition (PN) in pediatric short bowel syndrome (SBS) patients. Summary Background Data:Pediatric SBS carries extensive morbidity and high mortality, but factors believed to predict survival or weaning from PN have been based on limited studies. This study reviews outcomes of a large number of SBS infants and identifies predictors of success. Methods:Multivariate Cox proportional hazards analysis was conducted on 80 pediatric SBS patients. Primary outcome was survival; secondary outcome was ability to wean off PN. Nonsignificant covariates were eliminated. P < 0.05 was considered significant. Results:Over a mean of 5.1 years of follow-up, survival was 58 of 80 (72.5%) and 51 weaned off PN (63.8%). Cholestasis (conjugated bilirubin ≥2.5 mg/dL) was the strongest predictor of mortality (relative risk [RR] 22.7, P = 0.005). Although absolute small bowel length was only slightly predictive, percentage of normal bowel length (for a given infants gestational age) was strongly predictive of mortality (if <10% of normal length, RR of death was 5.7, P = 0.003) and of weaning PN (if ≥10% of normal, RR of weaning PN was 11.8, P = 0.001). Presence of the ileocecal valve (ICV) also strongly predicted weaning PN (RR 3.9, P < 0.0005); however, ICV was not predictive of survival. Conclusions:Cholestasis and age-adjusted small bowel length are the major predictors of mortality in pediatric SBS. Age-adjusted small bowel length and ICV are the major predictors of weaning from PN. These data permit better prediction of outcomes of pediatric SBS, which may help to direct future management of these challenging patients.

Review of the Refeeding Syndrome

Refeeding syndrome describes a constellation of metabolic disturbances that occur as a result of reinstitution of nutrition to patients who are starved or severely malnourished. Patients can develop fluid and electrolyte disorders, especially hypophosphatemia, along with neurologic, pulmonary, cardiac, neuromuscular, and hematologic complications. We reviewed literature on refeeding syndrome and the associated electrolyte abnormalities, fluid disturbances, and associated complications. In addition to assessing scientific literature, we also considered clinical experience and judgment in developing recommendations for prevention and treatment of refeeding syndrome. The most important steps are to identify patients at risk for developing refeeding syndrome, institute nutrition support cautiously, and correct and supplement electrolyte and vitamin deficiencies to avoid refeeding syndrome. We provide suggestions for the prevention of refeeding syndrome and suggestions for treatment of electrolyte disturbances and complications in patients who develop refeeding syndrome, according to evidence in the literature, the pathophysiology of refeeding syndrome, and clinical experience and judgment.

Relationship Between Hyperglycemia and Infection in Critically Ill Patients

Hyperglycemia is a common problem encountered in hospitalized patients, especially in critically ill patients and those with diabetes mellitus. Uncontrolled hyperglycemia may be associated with complications such as fluid and electrolyte disturbances and increased infection risk. Studies have demonstrated impairment of host defenses, including decreased polymorphonuclear leukocyte mobilization, chemotaxis, and phagocytic activity related to hyperglycemia. Until 2001, hyperglycemia (blood glucose concentrations up to 220 mg/dl) had been tolerated in critically ill patients not only because high blood glucose concentrations were believed to be a normal physiologic reaction in stressed patients and excess glucose is necessary to support the energy needs of glucose‐dependent organs, but also because the true significance of short‐term hyperglycemia was not known. Recent clinical data show that the use of intensive insulin therapy to maintain tight blood glucose concentrations between 80 and 110 mg/dl decreases morbidity and mortality in critically ill surgical patients. Intensive insulin therapy minimizes derangements in normal host defense mechanisms and modulates release of inflammatory mediators. The principal benefit of intensive insulin therapy is a decrease in infection‐related complications and mortality. Further research will define which patient populations will benefit most from intensive insulin therapy and firmly establish the blood glucose concentration at which benefits will be realized.

Parenteral nutrition-associated liver complications in children.

Parenteral nutrition is a life‐saving therapy for patients with intestinal failure. It may be associated with transient elevations of liver enzyme concentrations, which return to normal after parenteral nutrition is discontinued. Prolonged parenteral nutrition is associated with complications affecting the hepatobiliary system, such as cholelithiasis, cholestasis, and steatosis. The most common of these is parenteral nutrition‐associated cholestasis (PNAC), which may occur in children and may progress to liver failure. The pathophysiology of PNAC is poorly understood, and the etiology is multifactorial. Risk factors include prematurity, long duration of parenteral nutrition, sepsis, lack of bowel motility, and short bowel syndrome. Possible etiologies include excessive caloric administration, parenteral nutrition components, and nutritional deficiencies. Several measures can be undertaken to prevent PNAC, such as avoiding overfeeding, providing a balanced source of energy, weaning parenteral nutrition, starting enteral feeding, and avoiding sepsis.

Critical Illness, Gastrointestinal Complications, and Medication Therapy during Enteral Feeding in Critically Ill Adult Patients

Critically ill patients who are subjected to high stress or with severe injury can rapidly break down their body protein and energy stores. Unless adequate nutrition is provided, malnutrition and protein wasting may occur, which can negatively affect patient outcome. Enteral nutrition (EN) is the mainstay of nutrition support therapy in patients with a functional gastrointestinal (GI) tract who cannot take adequate oral nutrition. EN in critically ill patients provides the benefits of maintaining gut functionality, integrity, and immunity as well as decreasing infectious complications. However, the ability to provide timely and adequate EN to critically ill patients is often hindered by GI motility disorders and complications associated with EN. This paper reviews the GI complications and intolerances associated with EN in critically ill patients and provides recommendations for their prevention and treatment. It also addresses the role of commonly used medications in the intensive care unit and their impact on GI motility and EN delivery.

Amino Acid Requirements in Critically Ill Patients with Acute Kidney Injury Treated with Continuous Renal Replacement Therapy

Acute kidney injury in critically ill patients is often a complication of an underlying condition such as organ failure, sepsis, or drug therapy. In these patients, stress‐induced hypercatabolism results in loss of body cell mass. Unless nutrition support is provided, malnutrition and negative nitrogen balance may ensue. Because of metabolic, fluid, and electrolyte abnormalities, optimization of nutrition to patients with acute kidney injury presents a challenge to the clinician. In patients treated with conventional intermittent hemodialysis, achieving adequate amino acid intake can be limited by azotemia and fluid restriction. With the use of continuous renal replacement therapy (CRRT), however, better control of azotemia and liberalization of fluid intake allow amino acid intake to be maximized to support the patients metabolic needs. High amino acid doses up to 2.5 g/kg/day in patients treated with CRRT improved nitrogen balance. However, to our knowledge, no studies have correlated increased amino acid intake with improved outcomes in critically ill patients with acute kidney injury. Data from large, prospective, randomized, controlled trials are needed to optimize the dosing of amino acids in critically ill patients with acute kidney injury who are treated with CRRT and to study the safety of high doses and their effects on patient morbidity and survival.

Dosing and Monitoring of Trace Elements in Long-Term Home Parenteral Nutrition Patients

BACKGROUND Trace elements (TEs) dosing and monitoring in home parenteral nutrition (PN) patients vary with their underlying conditions. METHODS This retrospective observational study evaluated parenteral TE dosing, serum TE concentrations and monitoring, and dose-concentration relationships between TE doses and serum TE concentrations in 26 adult and adolescent home PN patients. RESULTS There was a total of 40,493 PN days. Average parenteral zinc doses of 9.1 mg/d and 7.6 mg/d resulted in the majority of serum zinc concentrations (90%) within normal range in patients with and without short bowel syndrome (SBS), respectively. Selenium at about 70 mcg/d resulted in about 60% of serum selenium concentrations within normal range, with 38% of values below normal in patients with and without SBS alike. Copper at 1 mg/d resulted in 22.5% of serum copper concentrations above the normal range. The majority of serum manganese (94.6%) and chromium (96%) concentrations were elevated. Serum TE concentrations were infrequently monitored. Significant relationships existed between doses and serum concentrations for zinc (P < .0001), manganese (P = .012), and chromium (P < .0001) but not for selenium or copper. CONCLUSIONS TE doses in home PN should be individualized and adjusted based on regular monitoring of TE status. In long-term home PN patients, higher zinc and selenium doses may be necessary to maintain their normal serum concentrations. Lower copper doses and restrictions of manganese and chromium supplementation may be needed to avoid their accumulation. Relationships between TE doses and serum TE concentrations vary for each TE and underlying clinical conditions.

Effects of lipid administration on liver apoptotic signals in a mouse model of total parenteral nutrition (TPN)

Lipids are an important component of total parenteral nutrition (TPN), contributing the largest caloric load per volume of solution and providing essential fatty acids necessary for survival. However, lipids are known to be causative factors in oxidative stress, which are expressed via the Bcl-2 family of proteins and/or Fas-mediated apoptosis in several tissues. Interestingly, we have recently observed an increase in hepatocyte apoptosis with administration of TPN. To address the mechanism of this apoptosis, we investigated the effects of parenteral lipid administration on apoptotic signaling in a mouse model. C57BL/6J male mice received physiologic saline and standard chow (control) or standard TPN solution with (TPN+L) or without lipid (TPN-L) emulsion. After 7 days of infusion, apoptosis increased in the TPN+L at a significantly higher rate compared with control and TPN-L groups ( p <0.05). Both TPN, with and without lipids, suppressed the pro-apoptotic signals Bid and Bcl-xs ( p <0.05). In contrast, TPN with lipid increased the expression of Fas and both the pro-apoptotic factor Bad and the anti-apoptotic factor Bcl-xl ( p <0.05). These changes may contribute to TPN-induced hepatocyte injury (apoptosis) or suppress the ability of liver hepatocytes to regenerate.

Ursodiol in Patients with Parenteral Nutrition–Associated Cholestasis

Objective: To review the role of ursodeoxycholic acid (ursodiol) in treating parenteral nutrition–associated cholestasis (PNAC). Data Sources: A MEDLINE (1950–May 2007) search was performed using the key terms parenteral nutrition, cholestasis, ursodeoxycholic acid, and ursodiol. Study Selection and Data Extraction: All English-language articles that evaluated the safety and efficacy of ursodiol for PNAC were included in this review. Data Synthesis: The benefits of exogenous ursodiol administration in the treatment of cholestasis can be explained by its alteration of effects on bile composition and flow and provision of cytoprotective, membrane stabilizing, and immunomodulatory effects. Two animal studies, 2 case reports, and 6 human studies (2 prospective and 3 retrospective pediatric studies, 1 adult prospective study) evaluated the efficacy of ursodiol in patients with PNAC. Ursodiol 10–30 mg/kg/day in children and 10–15 mg/kg/day in adults administered in 2–3 doses improved the biochemical and clinical signs and symptoms of PNAC. However, short-term improvement in biochemical parameters may not necessarily predict the outcome of PNAC patients. At recommended doses, ursodiol may not be effective in patients with short bowel syndrome or in those with resected terminal ileum because of reduced ursodiol absorption. Studies supporting the efficacy of ursodiol in treatment of PNAC are limited by small sample size, absence of randomization and controls, short duration, and lack of accountancy to confounding variables. Large, prospective, randomized, placebo-controlled, long-term follow-up studies evaluating the efficacy and optimal dosing and duration of ursodiol therapy for PNAC are not yet available. Conclusions: Ursodiol may improve the biochemical signs and clinical symptoms of PNAC. However, optimal dosing, timing, duration of therapy, and long-term effects on PNAC outcome and prognosis require further studies

The effects of needleless connectors on catheter-related bloodstream infections

Needleless connectors, including the standard split septum and the luer-activated mechanical valve connectors, have been introduced into clinical practice to eliminate the risk of needlestick injuries by avoiding the use of needles when accessing the intravascular catheters. Negative and positive displacement mechanical valves have been associated with increased rates of catheter-related bloodstream infections as compared with split septum connectors. Based on available data, split septum connectors should be preferentially used instead of mechanical valves. Adequate disinfection by scrubbing the access port preferably with chlorhexidine is recommended to minimize the risk of catheter microbial contamination along with proper infection control practices. Large prospective randomized clinical trials are needed to evaluate further the possible causes and effects of different types of mechanical valve needleless connectors on bloodstream infections.