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Charleston, SC

jimmy@pharmacyfridaypeals.com

Airway Series: Induction Medications

Introduction

  1. Rapid sequence intubation (RSI) is a process whereby an induction agent and a neuromuscular blocking agent are given in rapid succession to facilitate endotracheal intubation
  2. The selection of a specific sedative depends on multiple factors: the clinical scenario, which includes patient factors (includes cardiorespiratory and neurologic status, allergies, comorbidity) and the clinician’s experience/training and institutional factors, as well as the characteristics of the sedative
  3. Etomidate remains the most commonly used induction agent, however, it is not without its own pharmacologic considerations
  4. The use of ketamine is continuing to rise especially due to its unique pharmacologic profile and its niche is becoming prevalent in situations where the risk of hypotension is significant

Pharmacology

 EtomidateKetaminePropofol
Dose0.3 mg/kg IV  1-2 mg/kg 1.5-2 mg/kg
AdministrationIV pushIV PushIV push
Formulation20 mg/ 10 ml vialPrefilled 50 mg/5 ml Syringe1000 mg/100 ml vial
PK/PDOnset: ~20 seconds   Duration: 4-10 minutes   Metabolism: Hydrolysis of the ethylester side   Renal Excretion: 75%Onset: ~ IV 30 seconds                 IM 3-4 minutes   Duration: 5-10 minutes   Metabolism: N- demethylation   Renal Excretion: 91%Onset: ~10-50 seconds   Duration: 3-10 minutes   Metabolism: CYP2B6   Renal Excretion: 88%
Adverse EffectsInjection site pain, nausea, vomiting, myoclonusHypertension, tachycardia, emergency phenomenon Hypotension, bradycardia
Drug Interactions No major reactionsNo major reactionsNo major reactions
CompatibilityIncompatible with vitamin c and vecuroniumIncompatible with furosemide, insulin, phenytoin, and sodium bicarbonateIncompatible with methylprednisolone, phenytoin, and metoclopramide
    
CommentsThere is hypothetical concerns about adrenal insufficiency with a single dose. Hemodynamically neutralRapid IV push my cause apnea, Option for delayed sequence intubation. Increase BP and HRLarge dose rapid doses can cause large drops in HR and BP. Option for increase ICP


DrugHemodynamic EffectComments
Etomidate↔ BP, ↔ CO, ↔ HR,  ↓ cortisol , ↔ ICPProlonged inhibition of steroid synthesis in the critically ill; withdrawn from number of countries
Ketamine↑BP, ↑ HR, ↑ CO, ↔ cortisol, ↑↓ ICP↔  or ↑ CPP and ↔ ICP with standard anesthetic management
Propofol↓ BP, ↔ HR,↓ CO, ↔ cortisol, ↓ ICPHemodynamic compromise marked in elderly, ASA 3 or more or hypovolemic patients with ‘standard’ induction dose

 ProsCons
KetamineKetmaine has some bronchodilatory properties and can be useful if intubating for asthma angioedema, airway narrowing from anaphylaxis, infection or malignant processes are the typical examplesThe dose should be greatly reduced in shock states- most notably hypovolemic shock as it is a direct myocardial depressant   There are some case reports of cardiac arrest when full induction doses of ketamine are pushed in these patients.  In those patients I will push 10mg at a time until dissociation occurs (usually around 0.2-0.3 mg/kg in my experience).
EtomidateMost commonly used unless there circumstance where the patient will not be paralyzed such as difficult airways such as angioedema, airway narrowing from anaphylaxis, infection or malignant processesVery short duration of action is important- 3 to 5 minutes   Etomidate with rocuronium can be a recipe for paralysis without sedation unless you are right on top of providing post intubation sedation
PropofolDue to vasodilatory and anti-epileptic properties, propofol is most useful in hypertensive head bleeds and patients with status epilepticus those with enough BP to work with but titrate 10 mg at a timeHypotension and bradycardia should be noted, especially in trauma patients


  Overview of Evidence
Author, year Design/ sample sizeIntervention & ComparisonOutcome
Dietrich, 2018Retrospective review/ n=83Propofol  vs Non-propofol (etomidate or midazolam)↑ post-intubation hypotension with propofol OR 3.64 (95% CI 1.16- 13.24)   Similar rates of hypotension were seen among patients who received ≤2 mg/kg and those receiving >2 mg/kg   No significant differences between groups in hospital length of stay or mortality
Lyons, 2015Cohort study/ n=261Etomidate+ Succinylcholine  (Group 1)      vs Fentanyl+ ketamine+ rocuronium  (Group 2)Significantly better laryngeal views with fentanyl/ketamine/rocuronium group   100% first attempt intubation with fentanyl/ketamine/rocuronium group   ↑ post-intubation MAP+ HR  with etomidate + succinylcholine 
Bruder, 2015Cochrane ReviewEtomidate  Midazolam  Propofol  KetamineThere was no difference in mortality, hospital LOS, duration of ventilation, and duration of vasopressors   Etomidate associated with ↑ ACTH and ↓ in cortisol level
Tekwani K, 2010RCT/ n=122Etomidate 0.3 mg/kg  vs midazolam 0.1 mg/kgNo significant differences in median hospital LOS (9.5 vs 7.3 days), ICU LOS (4.2 vs 3.1 days), In-hospital mortality ( 26% vs 43%) or ventilator days
Jabre P,  2009RCT/ n=469Etomidate 0.3 mg/kg vs Ketamine 2 mg/kgNo difference in intubating condition, SOFA score, 28 day mortality, Vent free days, vasopressor support, or GCS
White, 1982RCT/ n= 80Ketamine1.5 mg/kg   Thiopental 4 mg/kg   Midazolam 0.3 mg/kg   Midazolam 0.15 mg/kg + ketamine 0.75 mg/kgThiopental ↓ MAP by 11%, ketamine increased MAP by 10%, while neither midazolam nor the midazolam-ketamine combination significantly changed MAP   Midazolam effectively attenuated both the cardiostimulatory responses and unpleasant emergence reactions associated with ketamine

References

  1. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved September 6, 2018, from http://www.micromedexsolutions.com/
  2. Dietrich SK.. Am Surg. 2018 Sep 1;84(9):1504-1508.
  3. White PF. Anesthesiology. 1982 Oct;57(4):279-84.
  4. Jabre P. Lancet. 2009 Jul 25;374(9686):293-300.
  5. Tekwani KL. Ann Emerg Med. 2010 Nov;56(5):481-9
  6. Lyon RM anaesthesia. Crit Care. 2015 Apr 1;19:134.
  7. Bruder EA.  . Cochrane Database Syst Rev. 2015 Jan 8;1:CD010225.
  8. Mace SE. Emerg Med Clin North Am. 2008 Nov;26(4):1043-68

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