Critical Care, Critical Care Alert, Sepsis, COVID-19, Airway

Critical Care Alert: Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis

Critical Care Alert

ARTICLE
Hughes CG, Mailloux PT, Devlin JW, Swan JT, Sanders RD, Anzueto A, et al. Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis. N Engl J Med. 2021; 384(15):1424-1436.

OBJECTIVE
To evaluate if dexmedetomidine leads to better short- and long-term outcomes compared with propofol specifically for mechanically ventilated patients with sepsis. 

BACKGROUND
Mechanical ventilation is common in patients with sepsis - in fact, over 20% of patients diagnosed with severe sepsis eventually require intubation. However, the use of sedative medications in some ventilated patients has demonstrated pronounced brain dysfunction and long-term cognitive impairment. The MIDEX trial was a non-inferiority RCT that compared the use of dexmedetomidine and propofol in a general ICU population requiring sedation.1 Results from this study showed that dexmedetomidine is non-inferior to propofol at maintaining light sedation and there was no difference in duration of days requiring mechanical ventilation, short-term mortality, or more adverse effects. However, translational research suggests that dexmedetomidine has superior immunomodulatory effects compared to GABA agonists as well as enhanced anti-inflammatory, bacterial clearance properties, and sleep quality that may make it a more favorable sedative agent in sepsis.2-3

POPULATION
Inclusion

  • Aged 18 or older
  • Required admission to MICU
  • Suspected/known infection
  • Mechanically ventilated with continuous sedation

Exclusion

  • Baseline severe cognitive impairment
  • Pregnant/breast-feeding
  • Deaf, blind, or unable to understand approved languages
  • Second- or third-degree heart block or persistent bradycardia requiring intervention
  • Allergy to Dexmedetomidine or propofol
  • Benzodiazepines were indicated
  • Anticipated to have immediate discontinuation of mechanical ventilation
  • Expected to have neuromuscular blockade for >48 hours

DESIGN
Overview

Double-blind randomized control trial at 13 medical centers in the United States of America where participants were given either propofol or dexmedetomidine

OUTCOMES MEASURED
Primary
Number of days alive without delirium or coma during the 14-day intervention period as measured by the CAM-ICU score

Secondary

  • Ventilator-free days at 28 days
  • Death at 90 days
  • Global cognition at 6 months using the age-adjusted TICS-T score

KEY RESULTS
No evidence that sedation with dexmedetomidine led to more days alive without acute brain dysfunction that propofol. There was no difference in ventilator free days at 28 days, death at 90 days, or global cognition at 6 months.

Strengths

  • Large RCT double-blinded study
  • Relevant question as may influence ED post-intubation management 
  • Improved demarcation of study groups (ie, those receiving dexmedetomidine received GABA concurrent infusions) compared to previous research
  • Utilization of well validated tools to assess cognition and delirium
  • Good long-term follow-up data on those eligible to determine delayed cognitive sequelae

 

Limitations

  • Slow enrollment resulting in an alteration of the sample size
  • Significant use of rescue medications, which may have blurred the comparison between dexmedetomidine and propofol
  • Unmasking of study group occurred in 14% of patients
  • Trial drug started 22 hours after patient met all inclusion criteria

EM TAKE-AWAYS

Despite the hope that the use of dexmedetomidine in sepsis may be superior in sepsis, this study shows no significant difference in outcomes. This reinforces the SCCM guideline that either dexmedetomidine or propofol are useful for continuous sedation. However, if either is to be utilized, this study highlights the difficulty in maintaining light sedation with low doses, and given the significant reliance on rescue medications, specific conclusions about the optimal ED sedative to initiate remain uncertain for adult patients with sepsis.


References

  1. Jakob SM, Ruokonen E, rounds RM, Sarapohia T, Garratt C, Pocock SJ, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012; 307(11):1151-1160.
  2. Venn RM, Bryant A, Hall GM, Grounds RM. Effects of dexmedetomidine on adrenocortical function, and the cardiovascular, endocrine and inflammatory responses in post-operative patients needing sedation in the intensive care unit. Br J Anaesth. 2001; 86(5):650-656.
  3. Wu XH, Cui F, Zhang C, Meng ZT, Wang DXW, Ma K, et al. Low-dose Dexmedetomidine Improves Sleep Quality Pattern in Elderly Patients after Noncardiac Surgery in the Intensive Care Unit: A Pilot Randomized Controlled Trial. Anesthesiology. 2016; 125(6):979-991.

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