Why We Do What We Do: Proton Pump Inhibitors

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38 y f comes to the ER complaining of dizziness and shortness of breath. On further history, you find out she has black tarry stools. On exam, you identify melena. Her hemoglobin level returns at 7.8 when it usually runs around 12. You admit the patient and start the patient on a nexium drip. The GI fellow is called who tells you the patient is stable and will be fine for endoscopy tomorrow. She also instructs you to keep the drip going and she will re-evaluate the patient in the morning. You admit the patient to a subacute setting and make sure that the patient has a type and screen sent in the event you need to cross match blood….

A resident recently asked me the mechanism by which Proton Pump Inhibitors (PPIs) aid us in the treatment of gastric ulcers. I decided it was a good opportunity to comb through some of the evidence…

Some of our colleagues in the late 70’s recognized a correlation between a pH of 6 and clot formation. A pH level in vitro above 6 seems crucial for developing and stabilizing clot (1). This in vitro inference seemed logical to apply to the clinical setting where medicines raising the gastric pH could be used to create and stabilize clots and therefore reduce the rate of bleeding. It can then be deduced that a reduction in gastric bleeding should also reduce the rates of mortality at 30 days, the incidence of rebleeding and the need for surgery. A lot of studies including some published in the last 2 years support this conclusion. However, the most recent Cochrane review published by Sreedharan et al. (2010) challenge this view in their meta-analysis. Check it out below and look a little lower for a discussion of some of their conclusions if you don’t have the time:

Cochrane Review PPI

The review identified no statistical difference in terms of mortality, rebleeding and surgery when comparing patients with UGI bleed on a PPI to patients not receiving a PPI. It did identify a reduction in amount of blood in the stomach at the time of endoscopy as well as the incidence of active bleeding at index endoscopy. It also reduces the need for rescoping the patient. Interestingly, Lau et al. is the only study that examined the use of high dose PPI that is now the standard of care. Lau et al (2007) noted that giving Omeprazole 80mg bolus followed by 8mg infusion per hour actually resolved bleeding signs and symptoms and the need for endoscopic therapy. Sreedharan et al. noted that there needs to be further studies using large dose PPI as it may prove to reduce the need for endoscopy or prove to be helpful when no endoscopy is readily available.

At the end of the day we need more evidence for high dose PPI as there is only one real study. The one true study we have suggests it may have benefit in reducing the need for endoscopy. PPI’s do not hurt in the setting of GI bleed and may indeed help, therefore, using PPI’s are a good idea.

1. Green FW Jr, Kaplan MM, Curtis LE, Levine PH. Effect of acid and pepsin on blood coagulation and platelet aggregation. Gastroenterology 1978; 74:34-43.
2. Sreedharan et al., Proton Pump Inhibitor treatment initiated prior to endoscopic diagnosis in upper gestational bleeding (review), Cochrane Database of Systematic Reviews 2010; 7:1-68.
3. Lau et al., Omeprazole before Endoscopy in Patients with Gastrointestinal Bleeding. NEJM 2007; 356 (16): 1631-40.

– Dr. Michael Meguerdichian

One Comment

  • pik

    And interestingly enough, the NNT review of the exact same paper came up with the idea that there was no benefit. Essentially, the # of pts. in the PPI grp also had fewer intervenable lesions on endoscopy, which was taken as evidence of causation. Since there was no harm either, it’s only a cost issue.

    Let’s go a little further. There is talk of using octreotide, not only in known cirrhotics who may have varices (by their medlist, on Nadolol or Pindolol) but in undifferentiated GI bleed. Might even help shunt blood away from certain sectors of a bleeding stomach, right?

    Guess what effect IV octreotide has on the pH of the stomach. If you said roughly the same as IV PPI, you get a banana! So why not give one meh expensive drug that kills 2 birds if you’re gonna do it at all? (Answer: GI won’t like it if I don’t give their med.)

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