Introduction
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 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
Etomidate remains the most commonly used induction agent, however, it is not without its own pharmacologic considerations 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
Key Points
- RSI pairs an induction agent with a neuromuscular blocker; the induction agent is chosen by patient factors, clinician experience, and the drug’s pharmacologic profile.
- Etomidate is the most commonly used induction agent and is hemodynamically neutral, though a single dose raises a hypothetical concern for adrenal suppression.
- Ketamine is increasingly favored when the risk of hypotension is significant, as it tends to raise blood pressure and heart rate.
- Propofol can cause marked drops in blood pressure and heart rate, so it is reserved for more hemodynamically stable patients and situations such as elevated intracranial pressure.
Clinical Detail
| Parameter | Etomidate | Ketamine | Propofol |
|---|---|---|---|
| Dose | 0.3 mg/kg IV | 1-2 mg/kg | 1.5-2 mg/kg |
| Administration | IV push | IV push | IV push |
| Formulation | 20 mg/10 mL vial | Prefilled 50 mg/5 mL syringe | 1000 mg/100 mL vial |
| PK/PD | Onset: ~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 Effects | Injection site pain, nausea, vomiting, myoclonus | Hypertension, tachycardia, emergence phenomenon | Hypotension, bradycardia |
| Drug Interactions | No major reactions | No major reactions | No major reactions |
| Compatibility | Incompatible with vitamin C and vecuronium | Incompatible with furosemide, insulin, phenytoin, and sodium bicarbonate | Incompatible with methylprednisolone, phenytoin, and metoclopramide |
| Comments | There is hypothetical concern about adrenal insufficiency with a single dose. Hemodynamically neutral. | Rapid IV push may cause apnea. Option for delayed sequence intubation. Increases BP and HR. | Large rapid doses can cause large drops in HR and BP. Option for increased ICP. |
| Drug | Hemodynamic Effect | Comments |
|---|---|---|
| Etomidate | ↔ BP, ↔ CO, ↔ HR, ↓ cortisol, ↔ ICP | Prolonged inhibition of steroid synthesis in the critically ill; withdrawn from a number of countries |
| Ketamine | ↑ BP, ↑ HR, ↑ CO, ↔ cortisol, ↑↓ ICP | ↔ or ↑ CPP and ↔ ICP with standard anesthetic management |
| Propofol | ↓ BP, ↔ HR, ↓ CO, ↔ cortisol, ↓ ICP | Hemodynamic compromise marked in elderly, ASA 3 or more, or hypovolemic patients with ‘standard’ induction dose |
Evidence
| Author, Year | Design / Sample Size | Intervention & Comparison | Outcome |
|---|---|---|---|
| Dietrich, 2018 | Retrospective review / n=83 | Propofol vs non-propofol (etomidate or midazolam) | ↑ post-intubation hypotension with propofol OR 3.64 (95% CI 1.16-13.24). Similar rates of hypotension 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, 2015 | Cohort study / n=261 | Etomidate + 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, 2015 | Cochrane Review | Etomidate, Midazolam, Propofol, Ketamine | There was no difference in mortality, hospital LOS, duration of ventilation, and duration of vasopressors. Etomidate associated with ↑ ACTH and ↓ in cortisol level. |
| Tekwani K, 2010 | RCT / n=122 | Etomidate 0.3 mg/kg vs midazolam 0.1 mg/kg | No 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, 2009 | RCT / n=469 | Etomidate 0.3 mg/kg vs ketamine 2 mg/kg | No difference in intubating condition, SOFA score, 28-day mortality, vent-free days, vasopressor support, or GCS. |
| White, 1982 | RCT / n=80 | Ketamine 1.5 mg/kg vs thiopental 4 mg/kg vs midazolam 0.3 mg/kg vs midazolam 0.15 mg/kg + ketamine 0.75 mg/kg | Thiopental ↓ 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. |
Conclusions
- Rapid sequence intubation pairs an induction agent with a neuromuscular blocking agent given in rapid succession, and the induction agent should be selected on the basis of patient factors, clinician experience, and the drug’s own pharmacologic profile.
- Etomidate remains the most commonly used induction agent and is hemodynamically neutral, though a single dose carries a hypothetical concern for adrenal suppression.
- Ketamine is increasingly favored when the risk of hypotension is significant, because it tends to raise blood pressure and heart rate rather than lower them.
- Propofol can produce marked drops in blood pressure and heart rate, so it is reserved for more hemodynamically stable patients and situations such as elevated intracranial pressure.
References
Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved September 6, 2018, from http://www.micromedexsolutions.com/
Dietrich SK.. Am Surg. 2018 Sep 1;84(9):1504-1508.
White PF. Anesthesiology. 1982 Oct;57(4):279-84.
Jabre P. Lancet. 2009 Jul 25;374(9686):293-300.
Tekwani KL. Ann Emerg Med. 2010 Nov;56(5):481-9
Lyon RM anaesthesia. Crit Care. 2015 Apr 1;19:134.
Bruder EA. . Cochrane Database Syst Rev. 2015 Jan 8;1:CD010225.
Mace SE. Emerg Med Clin North Am. 2008 Nov;26(4):1043-68
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