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Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, VA, USA
Keywords
DiarrhoeaConstipation Clostridia difficile ProbioticsAntibiotic associated diarrhea (AAD)Diarrhea
Diarrhea is a common problem in the ICU [1]. Diarrhea is best defined as ≥3 loose stools per day [2, 3]. The incidence of diarrhea in the ICU varies widely according to the definition used [1]. However, approximately 20–30 % of ICU patients will develop clinically relevant diarrhea [4, 5]. In the ICU diarrhea is best classified as infectious or non-infectious, due to different therapeutic approaches. Multiple risk factors contribute to the causation of both infections and non-infectious diarrhea.
The risk factors for “non-infectious” diarrhoea include previous/concurrent antibiotic use, hypoalbuminemia, change in tube feed formula, high volume tube feeds, high osmolarity tube feeds, ICU/hospital LOS, previous starvation (NPO) and medications (containing sorbitol) [4–8]. The use of third generation cephalosporins has been strongly associated with both “non-infectious” diarrhea as well as C. difficile colitis [4, 9–11].
Infectious Diarrhea
Clostridium difficile is the primary cause of infectious nosocomial diarrhea in developed countries (see Chap. 16). Risk factors include broad spectrum antibiotics, acid suppressive therapy and direct/indirect contact with infected/colonized patients. C. difficile must be excluded in all ICU patients who develop diarrhea. In addition, Pseudomonas aeruginosa has been reported to be a cause outbreaks of diarrhea associated with the use of antibiotics in ICU patients [4]. Other enteric pathogens that can cause diarrhea include salmonella, C. Perfringens type A and Staphylococcus aureus [9]. Although Candida species have been considered culprit pathogens associated with infectious diarrhea, there is no convincing data to support this association [12].
“Non-Infectious” Diarrhea
Antibiotic Associated Diarrhea (AAD)
Bartlett defines AAD as diarrhea of unknown etiology that occurs in patients who are using antibiotics; in 10–20 % of these cases, Clostridium difficile infection is found [9, 10]. The pathophysiological explanation for AAD is that antibiotics reduce the concentration of anaerobic bacteria normally present in the intestine; this decreases carbohydrate (dietary fiber) fermentation and causes an osmotic diarrhea (see below) [9].
Enteral Feeding-Associated Diarrhoea
Enteral feeding is frequently “blamed” as the cause of diarrhea resulting in the interruption of tube feeds. However, many studies have found no association between the risk of nosocomial diarrhea and enteral tube feeds [4, 7]. Interestingly, in a recent meta-analysis comparing the complications of parenteral and enteral nutrition, enteral feeding was not found to increase the risk of diarrhea [13]. Furthermore, many experimental and clinical studies have demonstrated that, in comparison with parenteral nutrition, enteral nutrition can actually reduce the incidence of diarrhea via a better preservation of the gastrointestinal mucosal structure and function [1].
Energy-dense formulae have a high osmolality result in significant fluid shifts into the stomach and proximal small bowel. The resulting excessive intraluminal volume may accelerate small intestinal transit resulting in a greater fluid load in the large bowel and subsequent diarrhea. In addition, high enteral feed volumes increase the risk of diarrhoea [5].
Management of “Non-Infectious” Diarrhoea
Bolus feeding of a low osmolarity enteral formula is preferred. If patients’ develop diarrhoea DO NOT STOP the feed, rather reduce the rate.
Dietary fiber are carbohydrates that cannot be digested by endogenous digestive enzymes and undergo fermentation by the colonic bacteria. Short-chain fatty acids, products of carbohydrate fermentation in the colon, play an important role in salt and water absorption in the colon. Furthermore, short-chain fatty acids, such as butyrate, are an important fuel for colonocytes. Consequently, dietary fibers have been added to enteral nutrition formulas to normalize bowel function. Experimental studies have shown that enteral feeding with fiber results in better colonic mucosal trophicity and in a lower rate of bacterial translocation than does enteral feeding without fiber [14]. The clinical use of dietary fibre in patients receiving tube feed is controversial, with contradictory findings [15–18]. However, a recent meta-analysis which included hospitalized patients receiving enteral nutrition demonstrated that the incidence of diarrhoea was reduced with fibre administration (OR 0.68, 95 % CI: 0.48–0.96) [19]. This effect was attenuated when ICU patients were analyzed as a distinct group. Meta-regression showed a more pronounced effect when the baseline incidence of diarrhoea was high.
Soluble fibers are a better substrate for colonic bacterial fermentation than insoluble fiber. However, until recently, water-soluble fiber supplements were used rarely in enteral formulas because of their high viscosity.
Recently, new fiber processing techniques have been used to produce highly water-soluble and low-viscosity dietary fibers for use in enteral formulas. A multi-fibre-enriched enteral formula and/or the enteral administration of a fiber mixture should be considered in patients with diarrhoea [19, 20].
The use of opioids including loperamide can induce a paralytic ileus. These drugs are best avoided. However, they can be considered as a “last resort” in patients in whom an infectious diarrhea has been excluded.
The Use of Probiotics and Prebiotics
The gut flora is profoundly disturbed during critical illness and this can profoundly alter gut function. Ingestion of specific fibre-fermenting lactic acid bacteria (probiotics) and fermentable fibre (prebiotics) is known reduce intestinal colonization with potentially pathogenic gram negative bacteria, to reduce bacterial translocation, to reduce pro-inflammatory cytokine induction and upregulate immune function The use of probiotics and prebiotics is however controversial [21, 22].
Four meta-analyses have demonstrated that probiotics significantly reduce the risk of AAD including C. difficile associated diarrhoea and were beneficial in patients with C. difficile colitis [23–26]. The most recent meta-analysis demonstrated that probiotics reduced the incidence of C. difficile associated diarrhoea by 66 % [25]. A recent Cochrane review reported similar findings and concluded that “based on this systematic review and meta-analysis moderate quality evidence suggests that probiotics are both safe and effective for preventing Clostridium difficile-associated diarrhea” [26].
Selinger et al. performed a small RCT which demonstrated that the use of the probiotic VSL#3 significantly reduced the incidence of AAD (0 % vs 11.4 %, p = 0.006) [27]. VSL#3 contains Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus delbrueckii subsp. Bulgaricus and Streptococcus thermophilus.
Hickson et al. randomized 135 patients over the age of 65 to receive a drink containing Lactobacillus casei, L. bulgaricus, and Streptococcus thermophilus twice a day during a course of antibiotics and for 1 week after the course finished [28]. The placebo group received a sterile milkshake. Twelve percent of the probiotic group developed AAD compared with 34 % in the placebo group (p = 0.007).
A more recent large (n = 2,941) multicentre, randomized, double-blind, placebo-controlled trial of inpatients aged 65 years and older who were exposed to one or more antibiotics did not confirm these findings [29]. In this study patients were randomized to either a multi-strain preparation of lactobacilli and bifidobacteria for 21 days or placebo. AAD (including CDD) occurred in 10.8 % of patients receiving probiotics vs 10.4 % in the placebo group (RR 1.04; 95 % CI 0.94–1.28; p = 0.71).
Petrov et al. performed a meta-analysis evaluating the impact of the use of probiotics in ICU patients [30]. Twenty-three randomized controlled trials were included in this analysis. Probiotics were associated with reduced infectious complications (RR 0.82; 95 % CI 0.69–0.99; p = 0.03) and VAP (RR 0.75; 95 % CI 0.59–0.97; p = 0.03). When only high quality studies were included, probiotics had no effect on the risk of infections. Probiotics had no effect on hospital mortality, intensive care unit or hospital length of stay.
Gu et al. performed a meta-analysis evaluating the role of probiotics in preventing ventilator associated pneumonia (VAP) [31]. In this study probiotics did reduce the incidence of VAP (OR, 0.82; 95 % CI, 0.55–1.24; p = 0.35). However, in trauma patients these authors demonstrated that probiotics were associated with a reduction in the incidence of nosocomial infections (RR, 0.65; 95 % CI, 0.45–0.94, P = 0.02) and VAP (RR, 0.59; 95 % CI, 0.42–0.81, P = 0.001) [32].
The Dutch Acute Pancreatitis Study randomized 298 patients with severe pancreatitis to receive a probiotic preparation (containing multiple species of Lactobacilli and Bifidobacterium) or placebo administered enterally twice daily for 28 days [33]. There was no difference in the rate of infections complications between groups, however the group of patients receiving the probiotic had a significantly higher incidence of multi-system organ failure and a higher mortality (16 % vs 6 %, p = 0.01). Nine patients in the probiotic group developed non-occlusive mesenteric ischemia while none of the patients in the placebo group developed this complication. The cause of the increased occurrence of bowel ischemia in the probiotic group is unclear. It should be noted that the formulation containing high concentrations of multiple probiotic species and prebiotics was infused directly into the jejunum; this unusual trial design may have affected the outcome of the study.Related posts:
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