Cardiovascular effects of dexmedotomidine for ITU sedation: UK results of a multi-centre study (St George's, University College, St Thomas's and Bristol Royal Infirmary Hospitals)

Introduction

A multi-centre study examining the safety and efficacy of the novel sedative agent dexmedetomidine, a highly selective alpha-2 agonist, possessing analgesic and sympatholytic properties.

Methods

One-hundred and nineteen post-operative patients who required sedation and ventilation for at least 6 h on the ITU were enrolled. Ninety-eight completed the randomised, placebo-controlled, double-blind study (81 cardiac and 17 general surgical) in four centres in the UK, but all patient data was used in the safety analysis. Within 1 h of return from theatre, the study drug was started with a loading dose of 1 μg/kg for 10 min, followed by a maintenance infusion of 0.2–0.7 μg/kg/h to maintain a Ramsay sedation score of ≥ 3 and was continued for 6 h after extubation (maximum duration 24 h). Rescue sedation and analgesia was provided with midazolam and morphine respectively. Heart rate, systolic, diastolic pressures and central venous pressures were recorded at 10 min intervals for the first 30 min and then hourly.

Results

Patient demographics were comparable as were Ramsay sedation scores between the two groups. The average dexmedetomidine infusion rate was 0.35 μg/kg/h whilst intubated and 0.15 μg/kg/h after extubation (range 0–0.7 μg/kg/h). Data was collated for the initial 6 h of the infusion and for the period pre- and post-extubation ± 4 h, hence, allowing for the variation in the duration of intubation in the data analysis. Once adequately sedated the patients receiving dexmedetomidine achieved greater cardiovascular stability as compared to the placebo group, with a significantly lower and less variable heart rate (P = 0.0001), this was clearly demonstrated in the period around extubation when mean heart rate in the dexmedetomidine group was 75 (SEM ± 2.0), versus 92 (± 2.9) in the placebo group. Diastolic blood pressure showed a similar trend with a reduction of 5 mmHg in the dexmedetomidine group, but no sustained significant differences in systolic arterial pressure or central venous pressures. Of the 66 patients who received dexmedetomidine, 16 had transient episodes of hypotension (MAP < 60 or > 30% reduction from pre-infusion BP) and/or bradycardia (HR < 50), mainly during the loading dose, of which three patients required temporary interruption of the infusion and three others required termination of the infusion.

Summary

Dexmedetomidine may improve cardiovascular stability.