Intravenous esomeprazole pharmacodynamics in critically ill patients

David C. Metz, Gerard J. Fulda, Keith M. Olsen, John T. Monyak, Steven G. Simonson, M. B. Sostek

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Objective: A widely held belief contends that food-induced proton pump activation is important for optimal proton pump inhibitorinduced 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 40mg for 48 hours and could continue for another 24 hours if no prepyloric enteral feedings were planned. Clinical trial registration: D9612L00107; ClinicalTrials.gov Identifier NCT00428701. Main outcome measures: The primary efficacy variable was the linear-interpolated percentage of time intragastric pH was 4 during 2448 hours. Secondary efficacy variables included the interpolated percentage of time intragastric pH was 4 during 024, 048, and 4872 hours, the percentage of gastric aspirates collected with pH 4 during 024, 2448, 048, and 4872 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 2448, 024, and 048 hours, respectively. For 072 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 40mg rapidly decreased intragastric acidity and effectively maintained pH 4 during 072 hours in fasting, critically ill, mechanically ventilated patients at high risk for stress ulcers.

Original languageEnglish (US)
Pages (from-to)1141-1148
Number of pages8
JournalCurrent Medical Research and Opinion
Volume26
Issue number5
DOIs
Publication statusPublished - May 1 2010

    Fingerprint

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Metz, D. C., Fulda, G. J., Olsen, K. M., Monyak, J. T., Simonson, S. G., & Sostek, M. B. (2010). Intravenous esomeprazole pharmacodynamics in critically ill patients. Current Medical Research and Opinion, 26(5), 1141-1148. https://doi.org/10.1185/03007991003694308