Serious Cardiovascular Adverse Events Reported with Intravenous Sedatives: A Retrospective Analysis of the MedWatch Adverse Event Reporting System

Abstract

Background Serious cardiovascular adverse events (SCAEs) associated with intravenous sedatives remain poorly characterized. Objective The objective of this study was to compare SCAE incidence, types, and mortality between intravenous benzodiazepines (i.e., diazepam, lorazepam, and midazolam), dexmedetomidine, and propofol in the USA over 8 years regardless of the clinical setting where it was administered. Methods The Food and Drug Administration’s MedWatch Adverse Event Reporting System was searched between 2004 and 2011 using the Evidex ® platform from Advera Health Analytics, Inc. to identify all reports that included one or more of ten different SCAEs (package insert incidence ≥ 1%) and where an intravenous benzodiazepine, dexmedetomidine, or propofol was the primary suspected drug. Results Among the 2326 Food and Drug Administration’s MedWatch Adverse Event Reporting System cases reported, 394 (16.9%) were related to a SCAE. The presence of a SCAE (vs. a non-SCAE) is associated with higher mortality (34 vs. 8%, p < 0.001). The percentage of cases with one or more SCAE, the case mortality rate (%), and the incidence of each SCAE (per 10 6 days of sedative exposure), respectively, were benzodiazepines (14, 26, 13) [diazepam (13, 23, 31); lorazepam (15, 43, 14); midazolam (14, 20, 11)]; dexmedetomidine (40, 15, 13); and propofol (17, 39, 7). Propofol (vs. either a benzodiazepine or dexmedetomidine) was associated with more total SCAEs (268 vs. 126, p < 0.001) but a lower incidence (per 10 6 days of sedative exposure) of SCAE (7 vs. 13, p = 0.0001) and cardiac arrest [6.3 (benzodiazepine) vs. 6.7 (dexmedetomidine) vs. 1.4 (propofol), p < 0.0001]. Conclusions Serious cardiac adverse events account for nearly one-fifth of intravenous sedative Food and Drug Administration’s MedWatch Adverse Event Reporting System reports. These SCAEs appear to be associated with greater mortality than non-cardiac serious adverse events. Serious cardiac events may be more prevalent with either benzodiazepines or dexmedetomidine than propofol. Electronic supplementary material The online version of this article (10.1007/s40801-019-00161-y) contains supplementary material, which is available to authorized users.

Comparative Safety Profiles of Sedatives Commonly Used in Clinical Practice: A 10-Year Nationwide Pharmacovigilance Study in Korea

“…However, the significant increase in the risk for serious AEs was not observed for fentanyl (p > 0.05), which is another primary sedative in a comparable therapeutic place to propofol (Table 4), suggesting a truly high risk of propofol for serious sedative-induced AEs such as cardiovascular events. In fact, similar to our current study, a previous study conducted by Duprey and colleagues reported an increased risk of serious cardiovascular AEs associated with propofol compared to other sedatives [30].…”

“…In our current study, serious events accounted for 3.3% (n = 3132) of the total sedativeinduced AEs, suggesting a substantially lower reporting rate of serious events compared to that in the United States (16.9%) [30]. This might be associated with the reporting pattern of ADEs in Korea [31].…”

“…Compared to alfentanil with the lowest relative frequency of sedative-related serious AEs reported in our study (Table 1), the risk of developing serious AEs was 52-, 35-, 31-, and 27-fold higher for etomidate, dexmedetomidine, ketamine, and propofol, respectively (Table 4); only fentanyl and sufentanil showed a comparable risk of developing sedative-induced serious AEs to alfentanil (p > 0.05). Although the risk of etomidate, dexmedetomidine, and ketamine for developing serious AEs, including cardiovascular and/or respiratory toxicities, might be truly higher than that of other sedatives assessed in this study [30,41], their frequent use as an adjunct therapy to other primary sedatives such as fentanyl, propofol, and benzodiazepines might contribute to the significantly increased risk for serious AEs as shown in this study (Table 4). Of our great concern was the high risk of propofol for serious AEs considering the prevalent use of propofol for sedation in patients undergoing invasive procedures such as endoscopy and hospitalized in an ICU [29].…”

“…Of our great concern was the high risk of propofol for serious AEs considering the prevalent use of propofol for sedation in patients undergoing invasive procedures such as endoscopy and hospitalized in an ICU [29]. Previous studies suggested propofol as a relatively safe sedative, used alone or in combination with other adjunctive sedatives, with a lower incidence of AEs for invasive procedures and critical care [8,30,42]. Consequently, propofol has been commonly used with or without anesthesiologist involvement in various settings of clinical practice, including outpatient endoscopic procedures in primary care clinics in Korea [21,22,43].…”

A survival after cardiac arrest during CT scan: The critical imaging findings

“…Midazolam is the sedative of choice for radiographic studies because of its rapid onset of action and short elimination half-life [12] . However, this sedative could be the reason for cardiac arrest in a small proportion of cases [13] .…”