Meta Analysis Nutrition support in acute pancreatitis: a systematic review of the literature.
This review may be edited
Summary
Posted By:	Gordon S Doig
E-Mail:	Gordon.Doig@EvidenceBased.net
Posted Date:	10 October 2006
Title:	Nutrition support in acute pancreatitis: a systematic review of the literature.
Authors:	McClave SA, Chang WK, Dhaliwal R, Heyland DK.
Reference:	JPEN J Parenter Enteral Nutr. 2006 Mar-Apr;30(2):143-56.
Link:	Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract:	BACKGROUND: Failure to use the gastrointestinal (GI) tract in patients with acute pancreatitis may exacerbate the stress response and disease severity, leading to greater incidence of complications and prolonged hospitalization. The objectives of this study were to determine the optimum route for nutrition support, whether nutrition therapy is better than no artificial nutrition support, whether specific additives to enteral or parenteral therapy can further enhance their efficacy, and whether methodologic differences in delivery of enteral nutrition (EN) influence tolerance. METHODS: A computerized search was performed of MEDLINE, Cochrane database, EMBASE, and reference lists of pertinent review articles for prospective randomized trials in adult patients with acute pancreatitis that evaluated interventions with nutrition therapy. Primary outcome data and surrogate endpoint parameters (for nutrition indices, stress markers, and measures of the inflammatory/immune response) were extracted in duplicate independently. Where appropriate, meta-analysis was performed by random-effects model. RESULTS: From 119 articles screened, 27 randomized controlled trials were included and analyzed. In patients admitted for acute pancreatitis, meta-analysis of 7 trials showed that use of EN was associated with a significant reduction in infectious morbidity (risk ratio [RR] = 0.46; 95% confidence interval [CI], 0.29 - 0.74; p = .001) and hospital length of stay (LOS; weighted mean difference [WMD] = -3.94; 95% CI, -5.86 to -2.02; p < .0001), a trend toward reduced organ failure (RR = 0.59; 95% CI, 0.28-1.27; p = .18), with no effect on mortality (RR = 0.88; 95% CI, 0.43-1.79; p = .72) when compared with use of parenteral nutrition (PN). Results from individual studies suggest that EN in comparison to PN reduces oxidative stress, hastens resolution of the disease process, and costs less. Insufficient data exist to determine whether EN improves outcome over standard therapy (no artificial nutrition support) in patients admitted for acute pancreatitis. However, in those patients requiring surgery for complications of acute pancreatitis, meta-analysis of 2 trials indicates that provision of EN postoperatively may reduce mortality (RR = 0.26; 95% CI, 0.06 - 1.09; p = .06) compared with standard therapy. PN provided early within 24 hours of admission was shown to worsen outcome, whereas PN provided later after full-volume resuscitation appeared to improve outcome when compared with standard therapy. In early individual studies, specific supplements added to EN, such as arginine, glutamine, omega-3 polyunsaturated fatty acids, and probiotics, may be associated with a positive impact on patient outcome in acute pancreatitis, compared with EN alone without the supplements, but studies are too few to make strong treatment recommendations. Supplementation of PN with parenteral glutamine was shown to reduce oxidative stress and improve patient outcome (reduced duration of nutrition therapy and decreased hospital LOS) compared with PN alone in patients with acute pancreatis. A wide range of tolerance to EN exists, irrespective of known influences such as mode (continuous vs bolus) and level of infusion within the GI tract (gastric vs postpyloric). CONCLUSIONS: Patients with acute severe pancreatitis should begin EN early because such therapy modulates the stress response, promotes more rapid resolution of the disease process, and results in better outcome. In this sense, EN is the preferred route and has eclipsed PN as the new "gold standard" of nutrition therapy. When PN is used, it should be initiated after 5 days. The favorable effect of both EN and PN on patient outcome may be further enhanced by supplementation with modulators of inflammation and systemic immunity. Individual variability allows for a wide range of tolerance to EN, even in severe pancreatitis.
Are the Results Valid?
1. Did the overview address a focused clinical question?
	No. The authors pose a series of clinical questions: Does nutrition therapy by either route (EN or PN) improve outcome compared with "standard therapy" (STD), where no artificial nutrition support is provided? Can recommendations for nutrition therapy in the patient newly admitted for severe acute pancreatitis be extrapolated for use in the postoperative setting in the patient requiring surgical intervention for complications of pancreatitis? Do alterations in the composition of nutrition therapy influence outcome? Does the method of enteral delivery affect tolerance? The paper could have retained more focus by reporting the results of any one of these questions. Because the authors chose to address so many questions in one paper, little information is often presented on the results of each question.
2. Were the criteria used to select articles for inclusion appropriate?
	Yes, the authors intended to exclude studies that were retrospective, prospective trials that failed to properly randomize patients, reviews in which the data were duplicated in other papers, or reports in which there was contamination by patients with a disease process other than pancreatitis.
3. Is it unlikely that important, relevant studies were missed?
	Yes. The search strategy was comprehensive and included Medline, EMBASE and the Cochrane Database. Reference lists from retrieved articles and personal databases were also searched.
4. Was the validity of the included studies appraised?
	The authors conducted a methodological appraisal AND they report that "trials that failed to properly randomize patients" were not to be included. Unfortunately, trials with major flaws were still included in this meta-analysis. More specifically, the authors included the trial by Windsor et al (Ref 10) which is not 'properly randomised' since it allocated patients to receive treatment based on odd/even hospital MRN. Since the allocation process was not concealed, researchers recruiting patients would know which treatment was to be received before they had judged eligibility or obtained consent.
5. Were assessments of studies reproducible?
	Although it is reported that 2 investigators extracted data from each trial we are not provided with a measure of agreement on the assessment of methodological quality.
6. Were the results similar from study to study?
	There is heterogeneity (I2=65.3%) in the meta-analysis of hospital LoS for early EN vs PN (Fig 2). Due to heterogeneity, these results should be interpreted with extreme caution. There is evidence of moderate heterogeneity (I2=32.4%) in the meta-analysis of organ failure (Fig 3). These results should be interpreted with caution.
What are the Results?
1. What are the overall results of the overview?
	On the primary and initial question of early EN vs PN the authors report no difference in Mortality (RR 0.88 95%CI 0.28-1.27). The authors do report a reduction in Infectious Morbidity (RR 0.46 95% CI 0.29 to 0.74). Due to heterogeneity, we suggest caution in interpreting the meta-analyses of hospital LoS and organ failure. No definitive results were obtained by meta-analyses conducted to answer any other questions addressed by the authors. We express concern with regards to interpreting the results of a meta-analysis conducted on only two trials. We believe at least three trials are required to obtain a meaningful estimate of heterogeneity.
2. How precise were the results?
	See 95% CIs above.
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care
	This is a very interesting and thorough review however it does combine trials conducted in ward patients with pancreatitis with trials conducted in ICU patients. It is possible that due to different stages/severity of pancreatitis in each group, the overall results of pooled trials are not informative in either.
2. Were all clinically important outcomes considered?
	No. The primary decision regarding EN vs PN was driven by Infections Morbidity but there was no indication of the clinical importance of these 'infections'. Were these infections major ICU infections or just positive surveillance cultures?
3. Are the benefits worth the harms and costs?
	Uncertain. In reality we do not have a definitive answer to any of the questions presented in this review. The process would benefit from an in-depth analysis of each question.
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