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February - 2021

   

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Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis

C Hughes, P Mailloux, J Devlin et al for the MENDS2 Study Investigators NEJM, 2021, online Feb

Comment

How does dexmedetomidine compare to propofol as a primary sedative agent for adult patients with septic shock. In particular, are the anti-inflammatory and bacterial clearance properties of dexmedetomidine associated with improved outcomes in sepsis. Given this, the MENDS2 trial (Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients with Acute Respiratory Failure) to test whether dexmedetomidine leads to better short-term and long-term outcomes than propofol in mechanically ventilated adults with sepsis.

In this multicenter, double-blind trial, 432 mechanically ventilated adults with sepsis were randomised to receive dexmedetomidine (0.2-1.5 μg/kg/hr) or propofol (5-50 μg/kg/min), adjusted achieve target sedation RASS goals.

  • Dexmedetomidine was delivered at a median dose of 0.27 μg/kg/hr, propofol 10.21 μg/kg/min, with median duration 3.0 days and median RASS score −2.0.
  • Primary end point was days alive without delirium or coma during the 14-day intervention period - there was no difference dex vs propofol (adj median, 10.7 vs. 10.8 days; OR, 0.96; 95% CI, 0.74 to 1.26)
  • Secondary end points were no difference  ventilator feee days, death at 90 days, or TICS-T score at 6 months.
  • Safety end points were similar in the two groups.

Overall, among mechanically ventilated adults with sepsis receiving light-sedation, outcomes did not differ between patients receiving dexmedetomidine or propofol with respect to days alive without acute brain, dysfunction, ventilator-free days, death at 90 days, or cognition at 6 months

 

 

Abstract

BACKGROUND

Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown.

METHODS

In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation–Sedation Scale (RASS, on which scores range from −5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months.

RESULTS

Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses — 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was −2.0 (interquartile range, −3.0 to −1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups.

CONCLUSIONS

Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol.

February


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