boxed-textPetrov MS et al. (2006) A randomized controlled trial of enteral versus parenteral feeding in patients with predicted severe acute pancreatitis shows a significant reduction in mortality and in infected pancreatic complications with total enteral nutrition. Dig Surg 23: 336–345

Synopsis

Background

Total enteral nutrition (TEN) and total parenteral nutrition (TPN) have shown efficacy for the prevention of infectious complications in patients with severe acute pancreatitis.

Objectives

To compare TEN with TPN in patients with predicted severe acute pancreatitis.

Design and intervention

This single-center, randomized, controlled trial included patients with predicted severe acute pancreatitis within 72 h of the onset of symptoms. Acute pancreatitis was defined as upper abdominal pain with a serum amylase concentration ≥3 times the upper limit of normal. Predictive severe acute pancreatitis was defined as an Acute Physiology And Chronic Health Evaluation (APACHE) II score of ≥8 or a C-reactive protein serum level of >150 mg/l. Eligible patients were randomly allocated to TEN or TPN for ≥7 days. A central venous catheter was used to deliver TPN, and TEN was delivered via a nasojejunal feeding tube that was placed radiographically distal to the ligament of Treitz. Nutritional support started ≤24 h after enrollment and supplied daily 30 kcal/kg, and 1.5 g of protein per kg. All patients received analgesia, intravenous fluids, and antibiotic prophylaxis with ofloxacin plus metronidazole. C-reactive protein serum levels and the APACHE II score were measured to monitor inflammatory response at baseline, and on day 4 and day 7 after feeding was started. All complications were recorded.

Outcome measures

The primary end point was the incidence of pancreatic infectious complications. Secondary end points included mortality, frequency of organ failure, and requirement for surgical intervention because of infection.

Results

In total, 69 patients were included the final analysis: 35 patients (mean age 51 years [range 42–67 years]) received TEN and 34 patients (mean age 52 years [41–70 years]) received TPN. Pancreatic infectious complications were significantly lower in the TEN group compared with the TPN group: 7 patients versus 16 patients, P = 0.02. The need for surgical intervention because of infection was significantly lower in the TEN group than the TPN group: 8 patients versus 25 patients, P <0.01. Extrapancreatic infections were significantly less frequent in the TEN group compared with the TPN group: 4 patients versus 11 patients, P = 0.04. Noninfectious complications were significantly higher in the TEN group than the TPN group: 15 patients versus 6 patients, P = 0.04. Multiple organ failure was significantly lower in the TEN group compared with the TPN group: 7 patients versus 17 patients, P = 0.02. The overall mortality rate for the study population was 20%. Mortality rate was significantly higher in the TPN group than the TEN group: 12 deaths (35%) versus 2 deaths (6%), P = 0.003.

Conclusion

TEN is a safe and effective prophylactic therapy for infectious complications of severe acute pancreatitis, and seems to be superior to TPN.

Commentary

The results of the Petrov et al. study were not unexpected. Several sufficiently powered, randomized, clinical comparisons between TEN and TPN, and a subsequent meta-analysis,1 have shown conclusively that TEN is superior to TPN in patients with acute pancreatitis, particularly with regard to infectious complications, need for surgery, and cost. The novel observation in the Petrov et al. study was the significantly lower mortality in TEN patients. This is an extremely important finding as there have been no substantial advances in the management of acute pancreatitis in the last 20 years. Despite initial optimism about platelet-activating antagonist infusions, such as lexipafant, these agents have failed to show any significant effect on outcome in the clinical setting.

Why should TEN improve mortality? I believe that it is not because it is more effective than TPN at meeting nutritional needs, but rather because of its benefits in maintaining intestinal health and function.2 Our own randomized study showed that TPN was far more effective than TEN at satisfying nutritional goals; TEN, on average, delivered only 50% of estimated protein and energy requirements.3 Despite fears, however, that TEN might stimulate the pancreas and, therefore, exacerbate the disease (which is caused by premature activation of trypsinogen with the acinar cells), the benefits of TEN far outweigh the risks. TEN stabilizes mucosal barriers preventing bacterial overgrowth and reducing systemic inflammatory responses, which are factors that promote the development of multiple organ failure—the most common cause of mortality in patients with severe acute pancreatitis.2

The Petrov et al. study also puts into perspective two recent clinical investigations that concluded that it is not necessary to feed patients distal to the ligament of Treitz because disease outcome is the same in patients who receive simple nasogastric feeding.4,5 Nasogastric feeding has many advantages: in contrast to nasojejunal feeding, it does not require expertise to implement and can be started earlier. The findings of these two studies were remarkable as many clinicians are hesitant about using nasogastric feeding for ventilated patients in intensive care units who have poor gastric emptying, which is worsened in acute pancreatitis by extrinsic compression of the upper gastrointestinal tract by the inflammatory mass. The mortality rates reported in both of these studies were alarming as they were extremely high, ranging from 25–30%; these findings raise concern that no benefit was achieved by either form of management. More acceptable mortality rates are below 10%, as attained in the study by Petrov et al. and in that published by Kalfarentzos et al., which was conducted in patients with severe necrotizing pancreatitis who were also fed well beyond the ligament of Treitz.6 These dramatic variations in mortality are difficult to explain as one might have expected mortality rates to be lower in the more recent studies because of the judicious use of antibiotics and the avoidance of early surgery. Clearly, there is a need for large-scale clinical trials that are powered to examine subgroup differences. The results of the Petrov et al. study provide great optimism that TEN might prove to be the first modern therapy that can reduce the unacceptably high mortality rates associated with this often devastating disease.