Dexmedetomidine overdose in the perioperative setting

OBJECTIVE: To report 3 cases of accidental dexmedetomidine overdose in the perioperative setting and review the pathophysiology of alpha(2)-agonist overdose. CASE SUMMARIES: Three patients accidentally received overdoses of dexmedetomidine, one intraoperatively (192 mug over 20 min) and 2 postoperatively (4 and 2 rather than 0.4 and 0.2 mug/kg/h; 0.5 mug/kg/min rather than 0.5 mug/kg/h). Hemodynamic parameters remained stable for all 3 patients. The most notable sign was oversedation diagnosed either clinically or using a bispectral index monitor; Naranjo criteria suggest possible or probable association of the reactions with dexmedetomidine. In all 3 cases, oversedation resolved within one hour of drug discontinuation. There were no other sequelae, and the remainder of each patient's hospital course was unremarkable. DISCUSSION: As of this writing, dexmedetomidine dosing in excess of the label recommendation has been reported, but accidental dexmedetomidine overdose in clinical practice has not been described. Excessive levels of sedation were the only significant finding in all 3 patients. Dexmedetomidine's short redistribution half-life of 6 minutes should lead to rapid resolution of oversedation induced by overdoses if the overall duration of infusion is short ( 8 h). While the patients reported here were hemodynamically stable, dexmedetomidine may engender significant hemodynamic changes either because of sympatholysis at normal doses or vasoconstriction at higher than recommended doses. The absence of a significant hypertensive response to high dexmedetomidine concentrations suggests that dexmedetomidine-induced hypertension may be multifactorial, not simply related to plasma drug concentrations. CONCLUSIONS: Practitioners presented with dexmedetomidine overdose should be prepared to manage oversedation. While hemodynamic alterations may be seen with dexmedetomidine use, hypertension from high dexmedetomidine plasma concentrations is not a consistent response. Practitioners using dexmedetomidine should carefully note that dosing for this agent is described by the manufacturer in mug/kg/h, not mug/kg/min.