Etomidate vs Ketamine RSI Adult Trauma

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Upchurch CP, et al. "Comparison of Etomidate and Ketamine for Induction During Rapid Sequence Intubation of Adult Trauma Patients". Ann Emerg Med. 2017. 69(1):24-33.
PubMedFull text

Clinical Question

In adult trauma patients receiving Rapid Sequence Intubation does the transient adrenal suppression induced by etomidate affect hospital mortality, ICU days, ventilator use, vasopressor use, and time to hospital discharge as compared to ketamine.

Bottom Line

In adult trauma patients, this trial demonstrated that the transient adrenal suppression induced by etomidate may not be clinically significant, but this needs to be evaluated in a prospective, head-to-head comparison.

Major Points

For Rapid Sequence Intubation (RSI) there are several viable for induction agents including etomidate, propofol, midazolam, and ketamine. Each agent carries a risk/benefit. Midazolam is a reversible amnesic and anticonvulsant, but may induce apnea and offers no analgesic properties. Propofol is an amnesic but may induce profound hypotension. Ketamine may increase blood pressure, bronchodilation, offer some analgesia, and dissociative amnesic but may increase intracranial pressure (ICP). Etomidate may decrease ICP but lead to myoclonic jerks, vomiting, and offers no analgesia. Also, etomidate is also associated with a transient adrenal suppression which may lead to adverse events in the critically ill. Because of this physicians may choose to use ketamine over etomidate, which also carries its own risks.

This pre-post study included 968 patients at a single Level I trauma center in the USA. It compared mortality and morbidity after trauma RSI comparing a practice change from etomidate to ketamine for induction. Comparing the two drugs there appears to be no difference in hospital mortality, ICU days, ventilator use, vasopressor use, and time to hospital discharge but this needs to be evaluated in a head-to-head comparison.

Guidelines

Eastern Association for the Surgery of Trauma (EAST) Emergency tracheal intubation immediately following traumatic injury, 2012[1]

An RSI drug regimen should be given to achieve the following clinical objectives:

  • Adequate sedation and neuromuscular blockade,
  • Maintenance of hemodynamic stability and CNS perfusion,
  • Maintenance of adequate oxygenation,
  • Prevention of increases in intracranial hypertension, and
  • Prevention of vomiting and aspiration.

Acute Cardiac Life Support suggest the following viable options for induction agents:

  • Etomidate 0.2-0.3 mg/kg IV
  • Ketamine 1-2 mg/kg IV
  • Methohexital 1-1.5 mg/kg IV
  • Propofol 1.5-2.5 mg/kg IV in adults
  • Propofol 2.5-3.5 mg/kg IV in children
  • Propofol 1-1.5 mg/kg IV in elderly patients
  • Thiopental 2-5 mg/kg IV

Design

  • Retrospective, Observational, single center
  • N= 968
    • Etomidate (n=526) (January 2011 to October 2012)
    • Ketamine (n=442) (March 2013 to December 2014)
  • Setting: Academic, tertiary care, Level I trauma center in USA
  • Enrollment: January 1, 2011 to December 31, 2014
  • Mean follow-up: 28 days
  • Analysis: Multivariable logistic regression
  • Primary outcome: All-cause hospital mortality

Population

Inclusion Criteria

  • ≥18 years old
  • Acute trauma
  • Intubated in ED

Exclusion Criteria

  • nil

Baseline Characteristics

Etomidate group shown

  • Age, median (IQR), y: 39.8 (26–57)
  • Sex, No. (%), female: 139 (26.4)
  • Race, No. (%)
    • White: 392 (74.5)
    • Black: 103 (19.6)
    • Other: 31 (5.9)
  • GCS score, median(IQR): 13 (7–15)
  • Systolic blood pressure, median(IQR), mmHg: 130 (107–150)
  • Diastolic blood pressure, median(IQR), mmHg: 80 (64–90)
  • Pulse rate, median (IQR), beats/min: 103 (83–119)
  • Respiratory rate, median(IQR), breaths/min: 20 (16–24)
  • Injury mechanisms, No.(%):
    • Any blunt mechanism: 441 (83.8)
      • Motor vehicle crash: 217 (41.3)
      • Fall: 88 (16.7)
      • Motorcycle crash: 52 (9.9)
      • Pedestrian vs motor vehicle: 32 (6.1)
      • Assault: 33 (6.3)
      • Crush: 11 (2.1)
      • Bicycle crash: 4 (0.8)
      • Other: 4 (0.8)
    • Any penetrating mechanism: 85 (16.2)
      • Gunshot wound: 61 (11.6)
      • Stab: 20 (3.8)
      • Impalement: 3 (0.6)
      • Other: 1 (0.2)
  • Specific injuries
    • Acute adrenal injury, No.(%): 29 (5.5)
    • Traumatic brain injury, No.(%): 178 (33.8)
  • Injury severity
    • ISS, median(IQR): 22 (13–33)
    • APACHE II score, median(IQR): 22 (17–27)
    • Presentation SBP <100 mm Hg, No.(%): 117 (22.2)
  • Elixhauser summary score, median(IQR): 5 (0.5–11)

Interventions

  • Before December 2012 (Pre):
    • Etomidate 0.3 mg/kg + succinylcholine
  • After December 2012 (Post):
    • Ketamine 1-2 mg/kg + succinylcholine

Outcomes

Comparisons are etomidate (n=526) vs. ketamine (n=442)

Primary Outcomes

Hospital Mortality
17.3% vs. 20.4% [unadjusted OR 1.22(0.88–1.69), adjusted OR 1.41(0.92–2.16)]

Secondary Outcomes

ICU Free Days (days alive and outside an ICU between RSI and 28 days)
24.5(13.3-27.2) vs. 24.8(11.2–27.0) [unadjusted OR 0.93(0.75–1.16), adjusted OR 0.80(0.63–1.00)]
Ventilator free days (days alive and free of invasive mechanical ventilation between RSI and 28 days), median(IRQ)
26.4(16.0–27.4) vs. 26.6(14.3–27.5) [unadjusted OR 1.07(0.86–1.33), adjusted OR 0.96(0.76–1.20)]
Vasopressor-free days (days alive and free of vasopressor support between RSI and 28 days), median(IRQ)
27(26–28) vs. 27(25–28) [unadjusted OR 0.86(0.68–1.08), adjusted OR 0.74(0.58–0.95)]
Units of packed RBCs transfused in first 48 hours, median(IRQ)
0(0–4) vs. 0(0–5) [unadjusted OR 1.19(0.94–1.51), adjusted OR 1.14(0.87–1.49)]
Hospital-acquired sepsis to day 28 (≥2 SIRS criteria with confirmed/suspected source of infection)
27.8% vs. 22.4% [unadjusted OR 0.75(0.56–1.01), adjusted OR 0.72(0.52–0.99)]
Time to hospital discharge, median(IRQ) days
7.5(2.8–15.7) vs. 6.7(2.5–13.9) [unadjusted OR 1.17(1.01–1.35), adjusted OR 1.10(0.95–1.27)]
Hazard of hospital death
N/A vs. N/A [unadjusted OR 1.26(0.94-1.69), adjusted OR 1.15(0.84-1.56)]
At least 1 dose of steroids between RSI and 28 days
15.2% vs 16.1% (absolute difference 0.9%; 95%CI –3.7% to 5.5%)

Subgroup Analysis

  • Patients with traumatic brain injury (intracranial hemorrhage, diffuse axonal injury, or shear injury identified by an attending radiologist on the first head computed tomography (CT) scan after presentation)
  • Glasgow Coma Scale (GCS) score <15 at presentation
  • penetrating trauma
  • “major trauma,” (Injury Severity Score (ISS) >15)
  • Systolic blood pressure less than 100 mm Hg at presentation

Not independently reported, stated to have no affect on outcomes.

Criticisms

  • Potentially under-powered to find a difference in mortality
  • Not randomized
  • Outcomes may have been missed:
    • patients who died before day 28 considered to have zero ICU-free, ventilator-free, and vasopressor-free days
    • patients discharged/transferred before day 28 assumed to have no additional ICU, ventilator, or vasopressor days after discharge/transfer
  • Practice change during the 4-year observation may have affected outcomes
  • Did not measure adrenal function to evaluate the clinical impact
  • Local culture and practices limit external validity from this single center study

Funding

Vanderbilt University School of Medicine Medical Scholars Program and the Vanderbilt University CTSA grant (TL1TR000447)

Further Reading

  1. Mayglothling J et al. Emergency tracheal intubation immediately following traumatic injury: an Eastern Association for the Surgery of Trauma practice management guideline. J Trauma Acute Care Surg 2012. 73:S333-40.