Posted by: Chris Cole | June 3, 2014

PPI’s in Upper GI Bleeding

I thought it might be useful to take a brief look at the evidence surrounding the use of intravenous proton-pump inhibitors (PPIs) in patients presenting to ED with upper GI bleeding (UGIB).

The current situation:

  • We routinely give an IV bolus of PPI (pantoprazole 80 mg) + ongoing infusion (8 mg / hr) for 72 hrs (or until discharge)
  • If we don’t do it, the gastroenterology team will ask for it
  • If we still don’t do it, they’ll order/start it
  • The rational pathophysiologic basis for this is that reduced stomach acid = less irritation of delicate bleeding tissues = a good thing

As with many interventions, however, what sounds like it should be true, what we want to be true, and what actually is true can be very different things. So what sayeth the evidence?

The folks at NNT ( http://www.thennt.com ) think it’s all a load of rubbish:  http://www.thennt.com/nnt/proton-pump-inhibitors-for-acute-upper-gi-bleeding/

The guys at LITFL thought it was pretty reasonable standard practice back in 2010:  http://lifeinthefastlane.com/ebm-upper-gi-haemorrhage/

…but have since linked to a few articles by others suggesting that maybe PPI’s aren’t all they were cracked up to be in UGIB after all.

A quick look at the most informative papers I came across (there are others but these are the Greatest Hits):

 

N Engl J Med. 2000 Aug 3;343(5):310-6.

Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers.

  • This paper is the “NINDS stroke tPA trial” of the UGIB world & why we started using PPIs in UGIB
  • DBRCT
  • n = 120 + 120
  • Rx with PPI bolus + infusion x 72hrs after endoscopic haemostasis vs placebo
  • Primary endpoint re-bleeding within 30 days: 6.7% vs 22.5% (Rx vs placebo)
  • No difference in mortality, or number requiring surgery
  • No difference in re-bleeding while in hospital
  • No difference in length of stay
  • No difference in ulcer healing at 8 weeks (in fact there was a trend toward better healing in placebo group)

 

 

Health Technol Assess. 2007 Dec;11(51):iii-iv, 1-164.

Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding.

 

  • Included all papers up to 2006
  • PPI after endoscopy reduces re-bleeding
  • No impact on mortality
  • PPI before endoscopy reduces “stigmata of recent haemorrhage” at endoscopy (fails to move me)
  • PPI before endoscopy has no impact on clinically relevant outcomes

 

  • 6 x RCTs included
  • n = 2,223
  • Might reduce the number of patients with stigmata of recent haemorrhage at endoscopy (how exciting)
  • Reduced need for injection during endoscopy (probably a good thing, but…)
  • No evidence for reduction in mortality, re-bleeding or need for surgery

 

So, while your mileage may vary depending on which RCT or systematic review you choose to hang your hat on (and to be fair they do all have their methodologic foibles which are not worth delving into in great detail here), given the currently available evidence, it is difficult to dispute that:

 

  • Giving IV PPI probably makes endoscopy easier for the endoscopist (less blood, better view, less injecting)
  • Giving IV PPI might or might not reduce re-bleeding (but the relevance of this is highly questionable)
  • Giving IV PPI doesn’t save people from needing surgery
  • Giving IV PPI has no impact on long-term (> 2 months) ulcer healing
  • Giving IV PPI has no impact on mortality (and this is consistent across all RCTs to date)

 

But, I hear you ask, if you’re going to acquiesce and give IV PPIs in ED for UGIB, how should you do it? Do we really need to tie up a dedicated IV line for an ongoing PPI infusion? Well, probably not, as is turns out:

 

Am J Gastroenterol. 2008 Dec;103(12):3011-8. doi: 10.1111/j.1572-0241.2008.02149.x.

High- versus low-dose proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding: a multicentre, randomized study.

 

  • DBRCT
  • n = 238 + 236
  • Either got PPI 80 mg bolus + 8mg/hr infusion x 72hrs…      or a 40 mg bolus once daily x 3 days
  • No difference in re-bleeding (11.8% vs 8.1%)
  • No difference in transfusion requirements (1.7 vs 1.5 units PRBCs)
  • Shorter length of stay for low-dose bolus group (37% vs 47% <5 days)
  • No difference in mortality

 

Take Home Message

  • PPIs for UGIB in ED probably make no significant difference to patient outcomes
  • Improving the endoscopist’s view (the only benefit) is a fairly soft indication for giving a drug, but not entirely unreasonable
  • If you’re going to give a PPI, a single IV bolus is fine… There is no need to tie up an IV line for an infusion

 

Chris Cole – April 2014

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