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Previous research on anesthesia-related mortality in the United States was limited to data from individual hospitals. The purpose of this study was to examine the epidemiologic patterns of anesthesia-related deaths at the national level.The authors searched the International Classification of Diseases, 10th Revision manuals for codes specifically related to anesthesia/anesthetics. These codes were used to identify anesthesia-related deaths from the US multiple-cause-of-death data files for the years 1999–2005. Rates from anesthesia-related deaths were calculated based on population and hospital surgical discharge data.The authors identified 46 anesthesia/anesthetic codes, including complications of anesthesia during pregnancy, labor, and puerperium (O29.0–O29.9, O74.0–74.9, O89.0–O89.9), overdose of anesthetics (T41.0–T41.4), adverse effects of anesthetics in therapeutic use (Y45.0, Y47.1, Y48.0–Y48.4, Y55.1), and other complications of anesthesia (T88.2–T88.5, Y65.3). Of the 2,211 recorded anesthesia-related deaths in the United States during 1999–2005, 46.6% were attributable to overdose of anesthetics; 42.5% were attributable to adverse effects of anesthetics in therapeutic use; 3.6% were attributable to complications of anesthesia during pregnancy, labor, and puerperium; and 7.3% were attributable to other complications of anesthesia. Anesthesia complications were the underlying cause in 241 (10.9%) of the 2,211 deaths. The estimated rates from anesthesia-related deaths were 1.1 per million population per year (1.45 for males and 0.77 for females) and 8.2 per million hospital surgical discharges (11.7 for men and 6.5 for women). The highest death rates were found in persons aged 85 yr and older.Each year in the United States, anesthesia/anesthetics are reported as the underlying cause in approximately 34 deaths and contributing factors in another 281 deaths, with excess mortality risk in the elderly and men.