A Retrospective Review of High versus Standard Dose Dexmedetomidine for Sedation in Critically Ill Patients

Abstract

Introduction: Studies have demonstrated safety and efficacy of dexmedetomidine infusions at doses up to 1.5 mcg/kg/hr. Data evaluating doses greater than 1.5 mcg/kg/hr is limited; however, up to 2.5 mcg/kg/hr has been utilized. It is uncertain whether higher doses provide additional benefit but may result in more adverse events. The purpose of this study was to compare the safety and efficacy of dexmedetomidine at high doses (greater than 1.5 mcg/kg/hr) versus standard doses (0.2 to 1.5 mcg/kg/hr). Methods:A retrospective cohort study was conducted in critically ill, mechanically ventilated patients receiving dexmedetomidine for at least 24 hours. Standard dose dexmedetomidine (SD-DEX) was defined as less than or equal to 1.5 mcg/kg/ hr and high dose (HD-DEX) as greater than 1.5 mcg/kg/hr. Patients were assigned to SD-DEX group if maximum dose of dexmedetomidine received was between 0.2 and 1.5 mcg/kg/hr. Conversely, patients were assigned to HD-DEX group if maximum dose of dexmedetomidine received was greater than 1.5 mcg/kg/hr. Composite incidence of bradycardia or hypotension and proportion of time within target sedation were assessed.Results: A total of 799 patients were screened for inclusion with 120 included: 69 in the HD-DEX group and 51 in the SD-DEX group. Composite incidence of bradycardia or hypotension was not statistically different. A significantly larger proportion of time was spent within target sedation in the SD-DEX group. More patients in the HD-DEX group required sedatives and antipsychotics than the SD-DEX group and tended to receive higher daily doses of concomitant medications. Conclusion:Dexmedetomidine doses greater than 1.5 mcg/kg/hr may be as safe as standard doses; however, no additional benefit in maintaining target sedation level was found.

Standard- versus High-Dose Dexmedetomidine for Sedation in the Intensive Care Unit

“…A study by Rodriguez et al analyzed 120 patients who received dexmedetomidine for at least 24 hours. 8 They found that patients who received a maximum dexmedetomidine dose ≤1.5 mcg/kg/hour (n = 51), spent more time within the goal RASS range of −2 to +1 than patients who had a high dose As expected, we also found that patients who received higher doses of dexmedetomidine were more likely to require an additional sedative agent. This is in agreement with both Jones et al and Rodriguez et al who both reported higher use of additional sedative agents in the high dose group (53.5% vs 26.8%; P = .003 and 87% vs 67%; P = .008, respectively).…”

“…This is in agreement with both Jones et al and Rodriguez et al who both reported higher use of additional sedative agents in the high dose group (53.5% vs 26.8%; P = .003 and 87% vs 67%; P = .008, respectively). 8,9 These findings show that adjunct sedation is often needed despite increased doses of dexmedetomidine. This may in part be explained by the pharmacodynamic properties of dexmedetomidine, which has historically not been considered to be deeply sedating, and thus requirement for additional sedation may be expected despite use of higher doses.…”

“…Finally, dividing the groups into greater than and <1 mcg/kg/hour does not allow for direct comparison between the present study and previous studies who utilized cutoffs of 0.7 and 1.5 mcg/ kg/hour. [8][9][10] We selected our institution-defined maximum as our cutoff to limit selection bias in the post-protocol group, though the pre-protocol group is still susceptible to this limitation.…”

“…[5][6][7] Two retrospective studies both found patients in the lower dose groups spent more time within a goal Richmond Agitation Sedation Scale (RASS) range compared to patients who received higher doses. 8,9 A third retrospective study in trauma patients found an increase in adverse events in patients who received doses >0.7 mcg/kg/hour including a prolonged duration of mechanical ventilation and ICU length of stay. 10 Several previous studies did not find a benefit with higher doses of dexmedetomidine when compared to lower doses, however the retrospective design of these studies may put them at risk of selection bias on who required higher doses.…”

“…5-7 Two retrospective studies both found patients in the lower dose groups spent more time within a goal Richmond Agitation Sedation Scale (RASS) range compared to patients who received higher doses. 8,9 A third retrospective study in trauma patients found an increase in adverse events in patients who received doses >0.7 mcg/kg/hour including a prolonged duration of mechanical ventilation and ICU length of stay. 10…”