European Journal of Clinical Pharmacology

, Volume 74, Issue 6, pp 819–832 | Cite as

Mortality among patients due to adverse drug reactions that lead to hospitalization: a meta-analysis

  • Tejas K. PatelEmail author
  • Parvati B. Patel
Pharmacoepidemiology and Prescription



The aim of this study was to estimate the prevalence of mortality among patients due to adverse drug reactions that lead to hospitalisation (fatal ADRAd), to explore the heterogeneity in its estimation through subgroup analysis of study characteristics, and to identify system-organ classes involved and causative drugs for fatal ADRAd.


We identified prospective ADRAd-related studies via screening of the PubMed and Google Scholar databases with appropriate key terms. We estimated the prevalence of fatal ADRAd using a double arcsine method and explored heterogeneity using the following study characteristics: age groups, wards, study region, ADR definitions, ADR identification methods, study duration and sample size. We examined patterns of fatal ADRAd and causative drugs.


Among 312 full-text articles assessed, 49 studies satisfied the selection criteria and were included in the analysis. The mean prevalence of fatal ADRAd was 0.20% (95% CI: 0.13–0.27%; I2 = 93%). The age groups and study wards were the important heterogeneity modifiers. The mean fatal ADRAd prevalence varied from 0.01% in paediatric patients to 0.44% in the elderly. Subgroup analysis showed a higher prevalence of fatal ADRAd in intensive care units, emergency departments, multispecialty wards and whole hospitals. Computer-based monitoring systems in combination with other methods detected higher mortality. Intracranial haemorrhage, renal failure and gastrointestinal bleeding accounted for more than 50% of fatal ADRAdcases. Warfarin, aspirin, renin–angiotensin system (RAS) inhibitors and digoxin accounted for 60% of fatal ADRAd.


ADRAd is an important cause of mortality. Strategies targeting the safer use of warfarin, aspirin, RAS inhibitors and digoxin could reduce the large number of fatal ADRAdcases.


Adverse drug reaction Hospital Prevalence Causative drugs Fatal reaction Meta-analysis 


Compliance with ethical standards

Conflict of interest

The authors each declare that they do not have a conflict of interest.

Sponsor(s) of the research

This study has no sponsors.

Supplementary material

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Supplementary Figure 1 Risk of bias summary (PNG 40 kb)
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Supplementary Figure 2 Funnel plot (JPEG 45 kb)
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Supplementary Figure 3 Meta-analytic summary of prevalence of fatal ADRAd according to age (JPEG 960 kb)
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Supplementary Figure 4 Meta-analytic summary of subgroup analysis of prevalence of fatal ADRAd according to study wards (JPEG 1154 kb)
228_2018_2441_MOESM5_ESM.pdf (473 kb)
ESM 1 (PDF 473 kb)
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ESM 2 (PDF 208 kb)
228_2018_2441_MOESM7_ESM.pdf (190 kb)
ESM 3 (PDF 190 kb)
228_2018_2441_MOESM8_ESM.pdf (783 kb)
ESM 4 (PDF 783 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PharmacologyGMERS Medical CollegeVadodaraIndia

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