To observe the occurrence of cardiovascular adverse events in patients undergoing mechanical ventilation with dexmedetomidine sedation, and to evaluate its safety in intensive care unit (ICU).

A prospective randomized controlled trial was conducted. Adult critical patients undergoing mechanical ventilation over 48 hours admitted to ICU of Zigong First People's Hospital in Sichuan Province were enrolled. The patients were divided into dexmedetomidine group (Dex group) and midazolam group (Mid group) according to the randomise number generated by computer. The patients in both groups were given slow intravenous infusion of 0.05 mg/kg midazolam and 1-2 μg/kg fentanyl to induce anesthesia before tracheal intubation, followed by 0.06 mg·kg^-1·h^-1 midazolam and 20-50 μg·kg^-1·h^-1 fentanyl or 0.1-0.2 μg·kg^-1·h^-1 sufentanil for continuous intravenous pumping to maintain analgesia and sedation; on the next day, the patients in Dex group was given dexmedetomidine (with the initial dose of 0.4 μg·kg^-1·h^-1, and maintenance dose of 0.1-0.7 μg·kg^-1·h^-1), and midazolam was stopped half an hour later; the original sedation and analgesia plan remained unchanged in Mid group. The goal of sedation was to maintain a Richmond agitation-sedation scale (RASS) score of -2 to 1 or a Ramsay sedation score of 3 to 4; patients were given midazolam if obvious agitation occurred, in combination with propofol for sedation if necessary; wake-up test was performed every day. Observation endpoints included patients discharged from ICU, death or mechanical ventilation over 28 days. Occurrence of cardiovascular adverse events during sedation such as hypertension, hypotension, bradycardia, tachycardia and arrhythmia, dose of sedatives and analgesics, duration of mechanical ventilation, length of ICU stay and 28-day mortality were observed in two groups.

A total of 383 patients were enrolled, with 190 patients in Dex group and 193 in Mid group. There was no statistically significant difference in general data such as gender, age, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and predicted mortality between two groups. Doses of midazolam, propofol and fentanyl in Dex group were reduced as compared with those of Mid group, while the dose of sufentanil was similar in two groups. The Ramsay score and RASS score of Dex group were significantly reduced as compared with those of Mid group (3.34±0.63 vs. 3.95±0.86, -1.33±0.87 vs. -1.98±1.27, both P < 0.01). Bradycardia was prominent in Dex group, which was observed in more than half of patients at the beginning of the treatment (1-2 hours), but the patients requiring isoprenaline treatment for heart rate lower than 50 bpm were less than that of Mid group (3.7% vs. 5.2%,χ² = 0.506, P = 0.477). The incidences of hypotension (45.3% vs. 68.4%), tachycardia (16.3% vs. 33.7%) and arrhythmia (14.7% vs. 31.1%) in Dex group were significantly lower than those of Mid group (all P < 0.01), and no other cardiovascular adverse events such as cardiac arrest, sinus arrest, hyperglycemia or hypoglycemia were observed in two groups. There was no statistically significant difference in duration of mechanical ventilation between Dex group and Mid group [days: 5 (2, 28) vs. 4 (2, 56), Z = -1.917, P = 0.055], but compared with Mid group, the length of ICU stay in Dex group was significantly prolonged [days: 9 (2, 67) vs. 6 (2, 57), Z = -4.302, P = 0.000], and the 28-day mortality in Dex group was significantly reduced (22.6% vs. 44.6%, χ² = 20.610, P = 0.000).

Long time dexmedetomidine sedation is safe in critical patients undergoing mechanical ventilation, which can significantly reduce cardiovascular adverse events except bradycardia, and lower the 28-day mortality.

Mechanical ventilation; Dexmedetomidine; Midazolam; Sedation; Adverse event; Safety