Nutrition Support Blog: The GI tract and critical illness link
October 20, 2011
For more than 30 years, there has been substantial theorizing, discussion, and research about the role of GI tract integrity and flora in the outcomes of critical illness. Naturally, the world of nutrition support has had an avid interest in these research developments because of the potential role that feeding route (EN vs PN) and specific nutrients may play in gut integrity. An appreciation for the importance of enteral nutrients in maintaining the barrier function of the intestinal lumen has been a crucial part of the practice shift from PN to EN in critically ill patients.
However, research has revealed that the GI-critical illness link is complex and that we still have much to learn about the effect of interventions that alter GI tract flora in critically ill patients. We now know that humans do not translocate bacteria or endotoxin as readily as rat or mice models from short term PN with modest stress. Nevertheless, the host of studies of selective digestive decontamination (SDD) in various critically ill populations illuminates the potential role of enteric flora in bacteremia and sepsis during critical illness.1 We have also learned that even seemingly benign and routine interventions such as gastric acid suppression to prevent stress ulceration can influence GI tract flora.2 Certainly there is ongoing debate and research regarding SDD, with concerns for exacerbating problems of antibiotic resistance if SDD were more routinely used. The issue of antibiotic resistance with SDD has led to research with probiotic preparations as a possible way to decrease nosocomial infections in the ICU.3 However, the results were disappointing, with probiotics actually showing a trend towards worse outcome than SDD.
Overall, the results of investigations with probiotics to reduce nosocomial ICU infections have been variable and the studies have been limited by relatively small numbers of patients, different probiotic preparations and doses in different populations4. Additionally, the finding that certain probiotic strains provided via jejunal access in severe pancreatitis significantly increased mortality and appeared to cause ischemic insult to the GI tract has severely curtailed wholesale enthusiasm for providing probiotics to critically ill patients.5 Some physicians have theorized that probiotics can contribute to small bowel overgrowth in critically ill patients and actually promote infectious complications and antibiotic resistance.6 Certainly there are a number of case reports of individuals that have become bacteremic and even septic from the very strain of probiotic administered via the feeding tube. It may be that only certain strains, or a certain dose, or only in certain specific conditions do probiotics present a risk, but the problem for clinicians is that we just don’t have those answers yet.
It is important to remember that we do not have adequately powered studies demonstrating a clear benefit from probiotic preparations in the ICU. Also, the ICU population often has compromised immune function, receives medications that suppress gastric acid (increasing the viability of probiotics), opiates that slow GI motility (promoting bacterial proliferation) and a potential compromised luminal barrier function. We know that seemingly benign substances such as blue food coloring appear to be absorbed into the systemic circulation from the GI tract in septic patients, and then can act as a mitochondrial toxin.7 If we would not dare add some blue food color to our ICU patients feeding, perhaps we should pause and ask about the wisdom of providing large numbers of viable organisms that have been selectively cultured to resist acid, proliferate in the GI tract and often produce lactic acid in the same patient population without adequate studies.
Likewise, we should probably be asking more research questions even before we routinely begin adding prebiotics to the feedings of our critically ill patients. Considering what we know about the role of GI flora in nosocomial infections, it would be valuable to see adequate research specifically in critically ill patients, before modified carbohydrates that can enhance GI flora are added to commercial feedings. Certainly we know that our clinical impressions about what “seems fine” in practice can be misleading or just plain wrong. We need to remember that in the study of probiotics in severe pancreatitis that at the interim analysis the study was allowed to proceed and that nearly 300 patients were then enrolled and only after careful analysis, they realized that patients were harmed.
There may well be a valuable role for prebiotic and/or probiotic preparations in the ICU, but further research is required before we will understand what products (at what dose and in what patients) may be beneficial or lead to problems.
1. Silvestri L, van Saene HK, Zandstra DF, et al. Impact of selective decontamination of the digestive tract on multiple organ dysfunction syndrome: systematic review of randomized controlled trials. Crit Care Med. 2010;38(5):1370-6.
2. Bavishi C, Dupont HL. Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection. Aliment Pharmacol Ther. 2011 Oct 17. doi: 10.1111/j.1365-2036.2011.04874.x. [Epub ahead of print]
3. Oudhuis GJ, Bergmans DC, Dormans T, et al. Probiotics versus antibiotic decontamination of the digestive tract: infection and mortality. Intensive Care Med. 2011;37(1):110-7.
4. Oudhuis GJ, Bergmans DC, Verbon A. Probiotics for prevention of nosocomial infections: efficacy and adverse effects. Curr Opin Crit Care. 2011;17(5):487-92.
5. Besselink MG, van Santvoort HC, Buskens E, et al.; Dutch Acute Pancreatitis Study Group. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomized, double-blind, placebo-controlled trial. Lancet. 2008;23;371(9613):651-9.
6. Petros A, Taylor N, van Saene HK, et al. Gut overgrowth harms the critically ill. Intensive Care Med. 2011;37(9):1560.
7. Lucarelli MR, Shirk MB, Julian MW, Crouser ED. Toxicity of Food Drug and Cosmetic Blue No. 1 dye in critically ill patients. Chest. 2004 Feb;125(2):793-5.
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