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Use of Gastric Acid Suppressants in the ICU

by Amy Butler, DVM, MS, DACVECC

Gastric ulceration, either as a result of the disease state or from administration of COX inhibitors, is a common problem in the ICU. Most of the patients we consult on are receiving some form of gastric acid suppressor therapy. This blog post touches on some of research and current recommendations for gastric acid suppression.

Physiology:

Control of gastric acid secretion is performed by a large number of hormones and second messenger systems, many of them intertwined and redundant. The best known are gastrin, acetylcholine, histamine and prostaglandins. Gastrin works by stimulating release of histamine from enterochromaffin-like cells, which then bind to the H2 receptor of the parietal cells. This upregulates the activity of the parietal cell proton pump (H+/K+ATP-ase pump), which secretes hydrogen. Chloride from nearby chloride channels combines with hydrogen to form hydrochloride acid.

Most acid reducing drugs target either the histamine receptors (such as famotidine), or the proton pump (omeprazole, pantoprazole). Since the proton pump is the final common step in acid secretion, it makes sense that inhibition of the pump is the most effective route to inhibiting acid secretion. However, most proton pump inhibitors (PPIs) take days to effectively lower acid secretion. In most of our patients, especially those with ongoing GI ulceration, we don’t have the luxury of time.

Current knowledge

In humans, effective acid reduction is defined as a gastric pH > 3 for ~75% of the day, and a gastric pH > 4 for ~67% of the day. Typically, oral PPIs take 3-5 days before maximal gastric acid suppression is achieved.  A study performed by Bersenas et al (AJVR 2005) compared ranitidine 2 mg/kg, IV, q 12h, famotidine 0.5 mg/kg, IV, q 12h, pantoprazole 1 mg/kg, IV, q24 h, and  omeprazole 1 mg/kg, PO, q24 h versus saline solution for 7 days. Ranitidine was not effective in suppressing gastric acid secretion. While famotidine, pantoprazole and omeprazole did significantly increase gastric pH compared to saline, it did not approach the human guidelines established above. The authors then compared famotidine 0.5 mg/kg, IV, q 8h and omeprazole as a suspension 1 mg/kg, PO, q 12h, and found that only omeprazole given twice daily approached the therapeutic efficacy for human disease. Another study by Tolbert et al, (JVIM 2011) comparing famotidine 1.0-1.3mg/kg PO q12h with omeprazole paste or tablets 1.5–2.6 mg/kg q 24h showed that omeprazole did achieve acid suppression while famotidine did not. Note that the dose of omeprazole is higher than the currently published recommended dose.

Due to the length of time required for PPI efficacy, the use of famotidine in conjunction with PPIs was studied.  Some clinicians purported to achieve more rapid control of gastric pH by using fast acting famotidine, while waiting for the effects of PPIs. Tolbert et al (JVIM 2015) investigated concurrent use of famotidine and pantoprazole versus pantoprazole alone. The mean pH did not differ between the two groups, and pantoprazole alone was just as effective in achieving target gastric pH. However, pH control typically took 4-7 days.

Effective use of gastroprotectants:

Many of our consultants are asked about the best protocol for gastric acid suppression. There are no hard and fast rules, but based on the literature we can make the following recommendations:

  • Adding famotidine to a PPI does not appear to be any more efficacious or faster in increasing gastric pH than a PPI alone.
  • Famotidine, even given q8h, is not as effective in increasing gastric pH compared to a PPI.
  • PPIs should be dosed 1 hour prior to meals so that their maximum concentration coincides with maximal acid stimuli from the GI tract. (this is from the human recommendations)
  • Omeprazole dosed 1mg/kg BID or at 2 mg/kg once daily appeared to be safe, and in the Bersenas study was the only protocol that achieved target gastric pH. I am currently using omeprazole or pantoprazole twice daily in my patients.
  • Regardless of the protocol used, maximal pH control typically takes several days.

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