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Three Part Question

In [adults with severe acute pancreatitis] is [nasogastric feeding better than conventional routes] in decreasing [mortality and septic complications]?

Clinical Scenario

A 58-year-old man comes to the emergency department complaining of upper abdominal pain, nausea and vomiting during the past 8 h. He has a history of alcohol excess. He is sweaty and pale. His blood pressure is 85/45 mm Hg and blood sugar 250 mg/dl. The upper quadrants of the abdomen are very painful to the touch. Abdominal ultrasound and blood tests analysis confirms a heterogenous pancreas with raised serum amylase, lipase, lactate dehydrogenase and transaminases. His white blood count is 22 000/mm3. The patient is admitted with the diagnosis of severe acute pancreatitis and a nasogastric tube is placed in passive drainage. On admission to high dependency you suggest feeding via the enteral route, but the local protocol suggests total parenteral nutrition (TPN). You wonder whether TPN, with its known associated complications is really needed in this case.

Search Strategy

A computerised literature search of the Cochrane and MEDLINE databases was conducted. The bibliographies of all selected articles found, which included information on nasogastric tube feeding in severe acute pancreatitis, were reviewed in an attempt to find other relevant articles. Limits to language (English, Spanish, Portuguese and French), age (adult) and human patients were applied.
MEDLINE search: ‘nasogastric tube’ (All Fields) AND ‘acute pancreatitis’ (All Fields) AND (‘humans’ (MeSH Terms) AND (English (lang) OR French (lang) OR Spanish (lang) OR Portuguese (lang)) AND (‘adult’ (MeSH Terms:noexp) OR ‘middle aged’ (MeSH Terms) OR (‘middle aged’ (MeSH Terms) OR ‘aged’ (MeSH Terms)) OR ‘aged’ (MeSH Terms) OR ‘aged, 80 and over’ (MeSH Terms)) AND (‘1996/01/01’ (PDAT): ‘2011/08/02’ (PDAT))) Cochrane search: (nasogastric feeding) (search all text) AND (acute pancreatitis) (search all text).

Search Outcome

MEDLINE search results:
8 papers found; 1 was considered relevant and critically appraised

Cochrane search results:
25 papers found; 3 were considered relevant and critically appraised

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Eckerwall et al 2006 Sweden	50 patients (>18 years) admitted with the clinical diagnosis of acute pancreatitis. Inclusion criteria: onset of abdominal pain within 48h and amylase ≥3 times upper normal value and APACHE II score≥8 and/or CRP≥150mg/L and/or peripancreatic liquid shown on CT. 26 patients were randomized to the total parenteral nutrition group (TPN) and 24 in the enteric group, administered via a nasogastric tube (EN). One dropout of each group. Nutritional support was started within 24 hours from admission observation period of 10 days and follow-up of 3 months	RCT 1b	Intestinal permeability	No significant difference (baseline PEG: TPN 1,2% vs 1,6% EN p>0,3; day3 PEG: TPN 0,6% vs 2% EN, p=0,003; day7 PEG: 1,1% TPN vs 2% EN, p>0.3)	Only 46% patients were defined as severe, according to the Atlanta classification, so the authors compare patients with different stages of the disease The amount of EN administered was 66% of the estimated energy target, wich is in the upper range of what has been achieved in other studies comparing EN with TPN The EN formula did not contain fibers and glutamine, substances which have been suggested to be beneficial for the epithelial cells Sample size estimates have not been performed
			Systemic inflammatory response	No significant difference
			Complications	More complications in EN (70% vs 40%TPN;p=0,05: Pulmonary complications (pleural effusions; atelectasis); septic complications (acute fluid collection; infected pancreatic necrosis; 3 pseudocyst after 3 months.
Kumar et al 2006 India	48 patients (>18 years, Atlanta score≥8 or CT severity score≥7) 17 dropouts 15 patients randomized to nasogastric group (NG) and 16 to nasojejunal group (NJ) Nutritional support was started between 48 and 72 hours after admission 2 phases of observation: -7 days observation (enteral nutrition) - untill discharge/ surgery/ death (oral nutrition)	RCT 1b	Mortality	No significant differences (28,6% NJ vs 31,3% NG, p=0,76)	Sample size estimate has not been performed Single blinded: the observer who measured the outcome knew the patients allocation, although considered outcomes were objective, with few possibility of bias
			Infection rate	No significant differences (42,9%NJ vs 43,8% NG, p=0,46)
			Organ failure	No significant differences (78,6% NJ vs 93,8% NG, p=0,35)
Petrov et al 2008 Russia	93 patients (from 1 cohort study and 3 RCT) with predicted severe pancreatitis (based on APACHEII score) one dropout Groups: Nasogastric feeding vs nasojejunal (RCT from UK and India) or parenteral (RCT form UK) or none (cohort study form UK) Nutritional support was started between 24 to 72 hours from admission	SR* 1a *a meta- analysis was also made, restricted to the studies of nasogastric vs nasojejunal feeding Papers included: * Eatock, 2000 UK (cohort st) * Eatock 2005 UK (RCT) * Kumar 2006 India (RCT) * Eckerwall 2006 Sweden (RCT)	Tolerance	Full tolerance was achieved in 79,3% of patients. Non-significant increased risk of diarrhea compared to nasojejunal route (RR=1,42; p=0,54)	In the RCT from Sweden polymeric nutrition was used, while the other authors used semi- elemental. In this study the percentages of complications were lower (although there was no heterogeneity between the study results, for all comparisons) Some data on clinical outcomes were missing in the RCT from UK In the RCT from India there was a delay between the begining of nasogastric (7,8±6,5 days) and nasojejunal nutrition (5,7±4,7 days) All trials were insufficiently powered (for 80% power and alpha value equal to 0,05 at least 153 patients were needed in each arm)
			Mortality	Non-significant reduction in the risk when compared to nasojejunal route (RR=0,77; 95% CI: 0,37 to 1,62; p=0,50)
Jiang et al, 2007 China	131 patients (3 RCTs) ≥ 18 years. Predicted severe acute pancreatitis based onAPACHEII and/or Ranson and/or Balthazar computer tomography criteria. 6 dropouts 67 patients randomized to nasogastric enteric group (NG) and 64 to conventional route group (CR), which included total parenteral or nasojejunal nutrition. Nutritional support timing not stated	SR 1a Papers included: *Eatock 2005 Scotland (RCT) *Kumar 2006 India (RCT) * Eckerwall 2006 Sweden (RCT)	Mortality	NG 14,9% vs CR 18,8% with no significant difference (RR=0,76, 95% CI= 0,37 and 1,55, p=0,45)	We do not know when the nutritional support has begun Neither the allocation concealment was clear nor an intention to treat method was used in the RCT from India RCT from Scotland included a potential selection bias due to the severity criteria set at APACHE II >6, when the others RCT used 8 as a cuttof value Sample size estimates have not been performed
			Infectious complications	No significant differences on reported sepsis and infected pancreatic necrosis (RR=1,41, 95% CI= 0,62 and 3,23, p=0,41) or rate for surgery (RR=0,66, 95% CI= 0,12 and 3,69, p=0,64)

Comment(s)

Acute pancreatitis is an increasing disease with a wide range of severity. Severe pancreatitis can be predicted by Ranson or Atlanta scores and is usually complicated by systemic inflammatory response syndrome (SYRS) and infectious complications. SYRS can lead to hypermetabolism and therefore to a catabolic status, resulting in rapid onset malnutrition and a high risk of development of sepsis and multi-organ failure. Until recently, TPN and gastrointestinal rest was advised in severe pancreatitis. The aim was to provide an adequate caloric intake and reduce pancreatic exocrine secretion. It quickly became apparent that the mechanism of bacterial translocation through the intestinal wall could decisively contribute to the emergence of SYRS. Fasting can easily cause mucosal atrophy and facilitate the bacteria translocation, conversely enteral feeding may be protective. The studies described in this BET indicate that enteral feeding is safe and should be recommended.

Clinical Bottom Line

Early enteral feeding should be started in patients with acute pancreatitis.

Level of Evidence

Level 3 - Small numbers of small studies or great heterogeneity or very different population.

References

1. Eckerwall GE, Axelsson JB, Andersson RG, et al. Early nasogastric feeding in predicted severe acute pancreatitis. A clinical, randomized study Annals of Surgery 2006; 244 (6): 959-967.
2. Kumar A, Singh N, Prakash S, et al. Early enteral nutrition in severe acute pancreatitis: a prospective randomized controlled trial comparing nasojejunal and nasogastric routes. Journal of Clinical Gastroenterology 2006; 40 (5) May/June: 431-434.
3. Petrov MS, Correia MI, Windsor JA, et al. Nasogastric tube feeding in predicted severe acute pancreatitis. A systematic review of the literature to determine safety and tolerance Journal of the Pancreas 2008; 9(4): 440-448.
4. Jiang K, Chen XZ, Xia Q, et al. Early nasogastric enteral nutrition for severe acute pancreatitis: a systematic review. World Journal of Gastroenterology 2007; 13 (39): 5253-5260.