Objective.-To estimate the incidence of serious and fatal adverse drug reactions (ADR) in hospital patients.Data Sources.-Four electronic databases were searched from 1966 to 1996. Study Selection.-Of 153, we selected 39 prospective studies from US hospitals.Data Extraction.-Data extracted independently by 2 investigators were analyzed by a random-effects model. To obtain the overall incidence of ADRs in hospitalized patients, we combined the incidence of ADRs occurring while in the hospital plus the incidence of ADRs causing admission to hospital. We excluded errors in drug administration, noncompliance, overdose, drug abuse, therapeutic failures, and possible ADRs. Serious ADRs were defined as those that required hospitalization, were permanently disabling, or resulted in death.Data Synthesis.-The overall incidence of serious ADRs was 6.7% (95% confidence interval [CI], 5.2%-8.2%) and of fatal ADRs was 0.32% (95% CI, 0.23%-0.41%) of hospitalized patients. We estimated that in 1994 overall 2 216 000 (1 721 000-2 711 000) hospitalized patients had serious ADRs and 106 000 (76 000-137 000) had fatal ADRs, making these reactions between the fourth and sixth leading cause of death.Conclusions.-The incidence of serious and fatal ADRs in US hospitals was found to be extremely high. While our results must be viewed with circumspection because of heterogeneity among studies and small biases in the samples, these data nevertheless suggest that ADRs represent an important clinical issue.

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Objective: To assess the evidence and make evidence-based recommendations for acute interventions to reduce brain injury in adult patients who are comatose after successful cardiopulmonary resuscitation.Methods: Published literature from 1966 to August 29, 2016, was reviewed with evidencebased classification of relevant articles. Results and recommendations:For patients who are comatose in whom the initial cardiac rhythm is either pulseless ventricular tachycardia (VT) or ventricular fibrillation (VF) after out-of-hospital cardiac arrest (OHCA), therapeutic hypothermia (TH; 32-348C for 24 hours) is highly likely to be effective in improving functional neurologic outcome and survival compared with non-TH and should be offered (Level A). For patients who are comatose in whom the initial cardiac rhythm is either VT/VF or asystole/pulseless electrical activity (PEA) after OHCA, targeted temperature management (368C for 24 hours, followed by 8 hours of rewarming to 378C, and temperature maintenance below 37.58C until 72 hours) is likely as effective as TH and is an acceptable alternative (Level B). For patients who are comatose with an initial rhythm of PEA/asystole, TH possibly improves survival and functional neurologic outcome at discharge vs standard care and may be offered (Level C). Prehospital cooling as an adjunct to TH is highly likely to be ineffective in further improving neurologic outcome and survival and should not be offered (Level A). Other pharmacologic and nonpharmacologic strategies (applied with or without concomitant TH) are also reviewed. Neurology ® 2017;88:2141-2149 GLOSSARY AAN 5 American Academy of Neurology; AE 5 adverse event; CI 5 confidence interval; CPC 5 Cerebral Performance Category; CPR 5 cardiopulmonary resuscitation; ECMO 5 extracorporeal membrane oxygenation; HF 5 hemofiltration; IHCA 5 in-hospital cardiac arrest; OHCA 5 out-of-hospital cardiac arrest; PEA 5 pulseless electrical activity; RD 5 risk difference; ROSC 5 return of spontaneous circulation; TH 5 therapeutic hypothermia; TTM 5 targeted temperature management; VT 5 ventricular tachycardia; VF 5 ventricular fibrillation.Outcomes for patients after nontraumatic cardiac arrest are dismal. Only 6%-9.6% of all patients with out-of-hospital cardiac arrest (OHCA) survive to hospital discharge, 1,2 and an estimated 22.3% of patients with in-hospital cardiac arrest (IHCA) survive to hospital discharge.3 Brain injury related to cardiac arrest is a major determinant of mortality and disability.