Intravenous esomeprazole pharmacodynamics in critically ill patients.
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.


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.


BACKGROUND
D9612L00107; ClinicalTrials.gov Identifier NCT00428701.


METHODS
The primary efficacy variable was the linear-interpolated percentage of time intragastric pH was > or =4 during 24-48 hours. Secondary efficacy variables included the interpolated percentage of time intragastric pH was > or =4 during 0-24, 0-48, and 48-72 hours, the percentage of gastric aspirates collected with pH > or =4 during 0-24, 24-48, 0-48, and 48-72 hours, and time to stable pH > or =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 > or =4 was 88.8%, 80.7%, and 83.5% for 24-48, 0-24, and 0-48 hours, respectively. For 0-72 hours, > or =78% of gastric aspirates had pH > or =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.
Metz
David C
DC
Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, USA. david.metz@uphs.upenn.edu
Fulda
Gerard J
GJ
Olsen
Keith M
KM
Monyak
John T
JT
Simonson
Steven G
SG
Sostek
M B
MB
D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016638:Critical Illness; D064098:Esomeprazole / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D016896:Treatment Outcome
D000897:Anti-Ulcer Agents; D064098:Esomeprazole