Intravenous esomeprazole pharmacodynamics in critically ill patients

Abstract

Objective:

A widely held belief contends that food-induced proton pump activation is important for optimal proton pump inhibitor–induced inhibition of gastric acid secretion. This study was undertaken to assess intragastric acid control with intravenous (IV) esomeprazole in critically ill patients.

Research design and methods:

This open-label, single-arm, exploratory trial was conducted at five university or regional hospital intensive care units in the US. Adult patients admitted to an intensive care unit who required mechanical ventilation and had at least one additional risk factor for stress-induced ulcer received twice-daily IV esomeprazole 40 mg for 48 hours and could continue for another 24 hours if no prepyloric enteral feedings were planned.

Clinical trial registration:

Trial registration: ClinicalTrials.gov identifier: NCT00428701.

Main outcome measures:

The primary efficacy variable was the linear-interpolated percentage of time intragastric pH was ≥4 during 24–48 hours. Secondary efficacy variables included the interpolated percentage of time intragastric pH was ≥4 during 0–24, 0–48, and 48–72 hours, the percentage of gastric aspirates collected with pH ≥4 during 0–24, 24–48, 0–48, and 48–72 hours, and time to stable pH ≥4. Safety was assessed based on adverse events (AEs), physical examinations, vital signs, laboratory tests, and electrocardiograms.

Results:

Forty-five patients were enrolled (one was excluded because of previous partial gastrectomy). Interpolated mean percentage time pH ≥4 was 88.8%, 80.7%, and 83.5% for 24–48, 0–24, and 0–48 hours, respectively. For 0–72 hours, ≥78% of gastric aspirates had pH ≥4. Median time to stable pH was 1 hour (95% confidence interval: 0.67, 2.00). Treatment was well tolerated, with no evidence of gastrointestinal bleeding. A total of 75 AEs occurred in 34 patients, none considered treatment related.

Conclusions:

In this noncontrolled exploratory study, twice-daily IV esomeprazole 40 mg rapidly decreased intragastric acidity and effectively maintained pH ≥4 during 0–72 hours in fasting, critically ill, mechanically ventilated patients at high risk for stress ulcers.

Keywords::

• Drug administration routes
• Esomeprazole
• Intensive care units
• pH
• Ulcer

Transparency

Declaration of funding

Funding by AstraZeneca LP, Wilmington, DE.

Declaration of financial/other relationships

D.C.M. has disclosed that he is a stockholder in Johnson & Johnson; has worked as an advisor to AstraZeneca, TAP, Wyeth, Santarus, and Nycomed; that he has received grants from AstraZeneca, and TAP; and that he sits on an advisory board for Santarus. G.J.F. has disclosed that he has received grant support from AstraZeneca. K.M.O. has disclosed that he has received grant support from AstraZeneca, Astellas, Carmel Pharma, and Takeda; and that he is on a speakers’ bureau for AstraZeneca. J.T.M. and M.B.S. have disclosed that they are employees of AstraZeneca. S.G.S. has disclosed that he is an employee and stockholder of AstraZeneca.

Acknowledgments

The authors thank the study investigators and Anny S. Wu, PharmD, Lisa M. Klumpp, PhD, and Judy Fallon, PharmD, from Scientific Connexions (Newtown, PA) for medical writing support (funded by AstraZeneca LP, Wilmington, DE).

Data from this manuscript have been presented at the Digestive Disease Week annual meeting in San Diego May 17–28, 2008, and at the American Thoracic Society annual meeting in Toronto, Canada, May 16–21, 2008.