Mortality among patients due to adverse drug reactions that occur following hospitalisation: a meta-analysis

Abstract

Purpose: To estimate the prevalence of mortality among patients that develop adverse drug reactions during hospitalisation (ADR_In), to examine heterogeneity through subgroup analysis and to identify system-organ class (SOC) and their causative drugs.

Methods: Two investigators searched PubMed, Google Scholar and related bibliography for studies reporting ADR_In-related mortality data. The primary outcome was to compute overall prevalence of fatal ADR_In (95% CI) using double arcsine method. We explored the heterogeneity (I²) in its estimation based on study design, study population and data collection methods. The secondary outcomes were the pattern of fatal reactions and their causative drugs. PROSPERO register number-CRD42018090331.

Results: Out of 349 full text assessed, 48 studies satisfying the selection criteria were included. The fatal ADR_In prevalence was 0.11% (95% CI 0.06-0.18%; I² = 93%). The fatal ADR_In prevalence ranged from 0.03% (I² = 0%) in all ages to 0.27% (I² = 90%) in elderly population studies. Elderly studies varied for all study characteristics. Among study wards, a higher trend of prevalence was observed in 'internal medicine and ICU' (0.46%, I² = 51%) and 'neonatal/paediatric ward and ICU' (0.34%, I² = 58%) studies. The commonly involved SOC were 'gastrointestinal disorders' (28.79%), 'blood and lymphatic system disorders' (19.69%) and 'renal and urinary disorders' (13.64%). Most commonly observed causative drug-fatal ADR_In pairs were antithrombotics and nonsteroidal anti-inflammatory drugs induced gastrointestinal bleeding, and antineoplastic agents induced cytopenia.

Conclusion: ADR_In is an important cause of mortality. Age groups and study wards have important influence on prevalence of fatal ADR_In and its heterogeneity across studies. Few class drugs contribute to sizable proportion of ADR_In-related mortality.

Keywords: Adverse drug reactions; Antineoplastic agents; Antithrombotic agents; Drug safety; Hospital mortality; Nonsteroidal anti-inflammatory drugs; Pharmacoepidemiology.