Dexmedetomidine is as safe as midazolam for the long-term sedation of ICU patients, with a lower incidence of tachycardia and hypertension requiring interventional treatments.
MIAMI BEACH—The a2-agonist dexmedetomidine (DEX) maintains a stable cardiovascular profile during long-term sedation in critically ill patients without evidence of rebound or withdrawal following abrupt discontinuation, researchers reported at the Society of Critical Care Medicine’s 39th Critical Care Congress.
Using data from the Safety and Efficacy of Dexmedetomidine Compared With Midazolam (SEDCOM) trial—a prospective, double-blind, study conducted in 68 centers between March 2005 and August 2007—the investigators evaluated the cardiovascular profiles of 375 medical and surgical ICU patients randomized 2:1 to sedation with DEX or the a-aminobutyric acid receptor–agonist midazolam (MDZ). At enrollment, patients were expected to require more than 24 hours of mechanical ventilation with continuous IV sedation. For the current study, Richard R. Riker, MD, of the Neuroscience Institute and Critical Care Medicine, Maine Medical Center, Portland, Oregon, and colleagues investigated the overall hemodynamic, dose-dependent, and time-dependent effects, interventions, and cessation characteristics of the two medications.
Of the safety variables, hypertension was defined as a 30% or greater increase above baseline systolic blood pressure (SBP) or SBP greater than 180 mm Hg, hypotension as a 30% or greater decrease below baseline SBP or SBP less than 90 mm Hg, tachycardia as a 30% or greater increase above baseline heart rate (HR) or an HR of more than 120 beats per minute (BPM), and bradycardia as a 30% or greater decrease below baseline HR or an HR of less than 40 BPM.
Cardiovascular Results
Treatment-emergent adverse events (TEAEs) were not significantly different between study groups (DEX, 96.7%; MDZ, 95.9%) and were common among ICU patients. TEAEs related to study drug withdrawal in the 24 hours after stopping medication were similar for the two groups (DEX, 4.9%; MDZ, 8.2%). TEAEs 24 to 48 hours postdrug cessation also were similar (DEX, 2.9%; MDZ, 0.8%).
Patients treated with DEX had a greater incidence of bradycardia than patients treated with MDZ (42.2% to 18.9%), including five patients whose heart rates dropped below 40 BPM and 98 who experienced a 30% or greater decrease from baseline. Twelve DEX patients required intervention for bradycardia, including titration or interruption of study drug in six patients and use of atropine in six subjects. One MDZ patient received atropine for bradycardia intervention.
“All of the commonly used sedative medications for ICU patients have cardiovascular adverse effects,” Dr. Riker told Neurology Reviews. “In this study, the high incidence of bradycardia was related to the FDA-mandated definition, which included a heart rate less than 40 BPM, but also a 30% decrease from the baseline value,” he noted. “So if a patient’s baseline heart rate was 100 BPM and during the study it went down to 68 BPM, it was considered bradycardia, even though most clinicians would not consider a heart rate of 68 BPM to be bradycardia.”
Tachycardia incidence was higher in patients sedated with MDZ than in those given DEX (44.3% to 25.4%); however, the rates of intervention for tachycardia were the same for each group (9.8%). Hypotension rates also were similar for the two medications (DEX, 56.1%; MDZ, 55.7%) as were interventions for hypotension (DEX, 28.3%; MDZ, 27.0%). Hypertension rates were 43.4% for DEX and 44.3% for MDZ; rates of intervention for hypertension were 29.5% and 18.9%, respectively.
In addition, the researchers found no difference in initiation of antihypertensive, chronotropic, and sedative medications between the two groups after discontinuing the drugs. Mean heart rate and blood pressures during the 48-hour follow-up postdrug cessation were similar in patients treated with DEX and MDZ.
The Best Fit for Patients
“Our study provides physicians with a better idea of what to expect when they use DEX, and could help them select the best sedative fit based on patient characteristics,” Dr. Riker explained. “If it’s a patient you would not want to be hypertensive or tachycardic, DEX may be better than MDZ. If the patient is already significantly bradycardic, perhaps MDZ would be better than DEX.”
Data for the original SEDCOM trial, which was published in JAMA in February 2009, showed faster extubation rates and lower incidence of delirium with DEX, Dr. Riker noted.
—Rebecca K. Abma