Serious Adverse Events in Adult ICU Patients: A Substudy of the PATIENCE Cohort

INTRODUCTION: Prokinetic agents are used to enhance upper gastrointestinal motility, but adverse events related to these agents are poorly described. We aimed to provide detailed epidemiological data on predefined serious adverse events (SAEs) in a cohort of adult intensive care unit (ICU) patients with and without prokinetic treatment. We hypothesised that all predefined SAEs would occur in both patients treated and those not treated with prokinetic agents, and that a higher number of SAEs would occur among patients treated with prokinetic agents for more than three consecutive days. METHODS: This substudy of the inception cohort study "Prokinetic agents in adult intensive care unit patients" included acutely admitted adult ICU patients. The prokinetic agents assessed (exposures) were erythromycin, metoclopramide, domperidone, and prucalopride. The primary outcome was the proportion of patients experiencing at least one episode of five pre-specified SAEs during ICU stay (cardiac arrhythmias, cardiac arrest, vomiting with aspiration, diarrhoea, extrapyramidal symptoms). Secondary outcomes were (1) proportion of patients experiencing each SAE, (2) the proportion of patients experiencing any of the SAEs after prokinetic treatment stratified by longest consecutive treatment duration, (3) time from index ICU admission to first SAE and (4) time from prokinetic initiation to first SAE. All analyses were descriptive, summarising SAE proportions and timing overall and according to prokinetic exposure. RESULTS: Among 1440 adult ICU patients, 710 SAEs occurred in 354 patients (24.6%), most commonly cardiac arrhythmias (199/1440, 13.8%). Across the exposure groups, the proportion of patients experiencing one or more SAEs ranged from 23.0% to 42.5%. Among patients treated with prokinetic agents for > 3 consecutive days, 14/59 (23.7%) experienced a SAE, which was similar to the proportion observed among patients not receiving prokinetic agents (291/1.253, 23.2%). Most SAEs occurred on median Day 2 after ICU admission and on median Day 3 after prokinetic initiation. CONCLUSION: One in four adult ICU patients experienced at least one SAE, with cardiac arrhythmias being the most frequent. Among patients receiving prokinetic agents, the proportion experiencing one or more SAEs ranged from 23.0% to 42.5% across treatment groups. The findings from this study may help inform the design of a future clinical trial. EDITORIAL COMMENT: This analysis presents reported serious adverse event observed in an ICU trial cohort assessing gastrointestinal prokinetic drug effects. Serious adverse events were reported frequently in both the drug treatment groups and the comparison (no prokinetic drug) group. Types of serious adverse events reported are presented.