PYTHON
PYTHON: Early versus On-Demand Nasoenteric Tube Feeding in Acute Pancreatitis
Bekker. N Engl J Med 2014; 371:1983-93. doi:10.1056/NEJMoa1404393
Clinical Question
- In patients with severe pancreatitis, does early enteral feeding compared with on-demand feeding reduce death or major infection?
Design
- Randomised-controlled superiority trial
- Two groups of patients in a 1:1 ratio
- Randomisation performed centrally and stratified for severity and treatment centre
- Treating clinicians non-blinded
- Outcome adjudicators blinded to patient group
- Sample size of 208 patients calculated to give 80% power to detect a reduction in primary outcome from 40% (on demand feeding) to 22% (early enteric feeding) based on previous data
Setting
- Six university medical centres and thirteen large teaching hospitals in the Netherlands
- August 2008 – June 2012
Population
- Inclusion: Adults who were predicted to have severe pancreatitis
- Pancreatitis was diagnosed based on two or more of:
- Typical abdominal pain
- Characteristic findings on cross-sectional abdominal imaging
- Serum lipase or amylase more than three times upper limit of normal
- Severity
- APACHE II ≥ 8
- Imrie or modified Glasgow score ≥ 3
- CRP over 150mg/l within 24 hours of admission
- Pancreatitis was diagnosed based on two or more of:
- Exclusion: Recurrent acute or chronic pancreatitis; Pancreatitis due to ERCP or malignancy; Home enteral or parenteral nutrition; Pregnancy; Assessed more than 24 hours after presentation; Presented more than 96 hours after symptom onset
- 867 patients screened, 208 enrolled and randomised, 205 analysed (3 incorrectly diagnosed)
Intervention
- “Early” group:
- Nasojejunal tube placed within 24 hours of randomisation and feeding commenced
- Tubes placed endoscopically or radiologically
- Feeding was started at 20ml/hr for the first 24 hours, then 45ml/hr from 24-48 hours, then 65ml/hr from 48-72 hours, and full feeding based on actual body weight after this
- If symptoms of delayed passage developed, the feeding rate was decreased by 50%, and gradually increased again the following day, but stopped if symptoms worsened
- When patients were able to tolerate an oral diet, tube feeding was gradually stopped and replaced
Control
- “On-demand” group:
- Oral diet was provided at 72 hours
- Supplementation by tube feeding after further 24 hours if unable to tolerate oral intake
- Prior to this received only IV fluids unless they requested oral food
Outcome
- Primary outcome:
- Composite outcome of death or major infection within 6 months showed no statistically significant difference
- Early group: 30%
- On-demand group: 27%
- Absolute risk increase: 3% (95% CI -9 to 15)
- NNH: 36
- p-value: 0.76
- Death within six months was not significant statistically difference (11% early vs 7% on-demand, p=0.33)
- Major infection within six months (pneumonia, bacteraemia, infected pancreatic necrosis) was not significant statistically difference (25% early vs 26% on-demand, p=0.87)
- Composite outcome of death or major infection within 6 months showed no statistically significant difference
- Secondary outcome:
- Days to full oral diet was significantly reduced in on-demand group (9 days early vs 6 days on-demand, p=0.001)
- Rate of NJ tube placement was significantly higher in early group (100% early vs 31% on-demand)
- No significant difference in:
- Necrotising pancreatitis (62%)
- Rate of ITU admission
- Frequency of gastrointestinal events
- Length of SIRS
- Post hoc analyses showed no significant primary outcome difference for:
- The most unwell patients (APACHE ≥ 13)
- Those who already had SIRS at randomisation
- BMI under 25 or ≥ 35
- Health care utilisation (except with regards tube placement)
Authors’ Conclusions
- Early enteral feeding in these patients did not improve outcomes when compared to delayed on-demand feeding at 72 hours
- This result disagrees with current guidelines which advise feeding to provide a protective effect on intestinal integrity and systemic nutritional status
- It was unusual for tube feeding to be required
Strengths
- Succeeded in randomising the treatment of a large number of patients with severe illness.
- Chosen outcomes are clinically important
- The statistical methods are valid and well-illustrated
- Long follow-up
- Low drop-out rate
- Interesting result with potential to change practice
Weaknesses
- May have been too small and underpowered
- Feeding may also been initiated too late or too gently in disease process
- Scoring systems poor at predicting eventual severity so cases of non-severe pancreatitis may have been included
- Unblinded treating clinicians
- NJ tubes used, when nasogastric tubes are easier to place and may be as effective
- Not able to inform management of other forms of pancreatitis
The Bottom Line
- Allowing patients with severe pancreatitis three to four days to initiate oral intake appears to be safe and effective
- This can reduce the discomfort, cost and complications associated with tube feeding in these patients
- Although well-conducted this was a relatively small trial, and future data may change this picture
External Links
- [Article] Early versus On-Demand Nasoenteric Tube Feeding in Acute Pancreatitis
- [Further reading] Research and Reviews 63 by LITFL
- [Further reading] Nutrition in severe pancreatitis: none at all (for 3 days) worked fine by PulmCCM
Metadata
Summary author: John Kiely
Summary date: 12 June 2015
Peer-review editor: @DuncanChambler