title: A systematic review of adult admissions to ICUs related to adverse drug events.
abstract: Adverse drug events (ADE) may lead to hospital admission, and in some cases admission to an ICU is mandatory. We conducted a systematic review dealing with the incidence of ADE requiring ICU admission in adult patients, the reference population being all ICU admissions. Medline, Embase and Web of Science databases were screened from January 1982 to July 2014, using appropriate key words. Only original articles in English reporting the incidence of ADE requiring ICU admission in adult patients among total ICU admissions were included. Article eligibility was assessed by two independent reviewers, a third being involved in cases of disagreement. All reported characteristics (type of ICU, characteristics of patients, incidence of ADE, severity and preventability, drugs involved, causality) in the selected articles were collected for the review. The quality of studies was independently assessed by two reviewers with a specific score that we developed. A meta-analysis was conducted. Inclusion criteria were fulfilled by 11 studies out of the 4,311 identified in the initial literature search. The median (interquartile) quality score was 0.61 (0.44; 0.69). The reported incidences of ADE requiring ICU admission in adult patients ranged from 0.37 to 27.4%, with an associated mortality rate ranging from 2 to 28.1% and a mean length of stay ranging from 2.3 to 6.4 days. Preventable events accounted for 17.5 to 85.7% of the events. Costs and mechanisms at the root of ADE were investigated in only two and five studies, respectively. The forest plot examining the incidence of ADE requiring ICU admission in adult patients was associated with high heterogeneity (I (2) statistic > 98%), and the shape of the corresponding funnel plot was asymmetric. Heterogeneity across studies concerned many features, including studied populations, events considered, causality assessment methods, definitions of preventability and severity. Despite the heterogeneity of the reports, our review indicates that ICU admission due to ADE is a significant issue that should deserve further interest. The review led us to propose a list of items devoted to the reporting of future studies on ADE requiring ICU admissions.
authors.affiliation: Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, F-75013, Paris, France. pa.jolivot@gmail.com.|Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, UMR_S 1136, F-75013, Paris, France. pa.jolivot@gmail.com.|AP-HP, Hôpital Saint-Antoine, Service de Pharmacie, F-75012, Paris, France. pa.jolivot@gmail.com.
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Jolivot
authors.affiliation: Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, F-75013, Paris, France. patrick.hindlet@sat.aphp.fr.|Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, UMR_S 1136, F-75013, Paris, France. patrick.hindlet@sat.aphp.fr.|AP-HP, Hôpital Saint-Antoine, Service de Pharmacie, F-75012, Paris, France. patrick.hindlet@sat.aphp.fr.|Univ Paris-Sud, Faculté de Pharmacie, F-92296, Chatenay-Malabry, France. patrick.hindlet@sat.aphp.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hindlet
authors.affiliation: AP-HP, Hôpital Saint-Antoine, Service de Réanimation, F-75012, Paris, France. claire.pichereau@sat.aphp.fr.
authors.forename: Claire
authors.initials: C
authors.lastname: Pichereau
authors.affiliation: Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, F-75013, Paris, France. christine.fernandez@sat.aphp.fr.|Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, UMR_S 1136, F-75013, Paris, France. christine.fernandez@sat.aphp.fr.|AP-HP, Hôpital Saint-Antoine, Service de Pharmacie, F-75012, Paris, France. christine.fernandez@sat.aphp.fr.|Univ Paris-Sud, Faculté de Pharmacie, F-92296, Chatenay-Malabry, France. christine.fernandez@sat.aphp.fr.
authors.forename: Christine
authors.initials: C
authors.lastname: Fernandez
authors.affiliation: Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, F-75013, Paris, France. eric.maury@sat.aphp.fr.|Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, UMR_S 1136, F-75013, Paris, France. eric.maury@sat.aphp.fr.|AP-HP, Hôpital Saint-Antoine, Service de Réanimation, F-75012, Paris, France. eric.maury@sat.aphp.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Maury
authors.affiliation: Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, F-75013, Paris, France. bertrand.guidet@sat.aphp.fr.|Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, UMR_S 1136, F-75013, Paris, France. bertrand.guidet@sat.aphp.fr.|AP-HP, Hôpital Saint-Antoine, Service de Réanimation, F-75012, Paris, France. bertrand.guidet@sat.aphp.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Guidet
authors.affiliation: Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, F-75013, Paris, France. gilles.hejblum@inserm.fr.|Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, UMR_S 1136, F-75013, Paris, France. gilles.hejblum@inserm.fr.|AP-HP, Hôpital Saint-Antoine, Unité de Santé Publique, F-75012, Paris, France. gilles.hejblum@inserm.fr.
authors.forename: Gilles
authors.initials: G
authors.lastname: Hejblum
mesh_terms: D000328:Adult; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis* / Q000453:epidemiology* / Q000628:therapy; D006801:Humans; D007362:Intensive Care Units / Q000639:trends*; D010343:Patient Admission / Q000639:trends*