Ketamine and Rocuronium: The New Etomidate and Succinylcholine?

Authors: Kathy Staats, MD (Resident Physician, University of Texas at Austin Dell School of Medicine) and Janna Welch, MD (Assistant Program Director, Emergency Medicine Residency University of Texas at Austin Dell School of Medicine) // Edited by: Alex Koyfman, MD (@EMHighAK) & Justin Bright, MD (@JBright2021)

Introduction

Rapid Sequence Intubation (RSI) is one of the most critically important skills for an Emergency Medicine physician to be able to perform quickly and accurately.  All airway management in the emergency department is performed on the unstable patient, often with unknown co-morbidities and a full stomach.  In recent years, standard medication choices for induction were etomidate and succinylcholine.  While other medications were proposed and tried, several were avoided for hypothetical side effects that have not borne out in recent research. Arguably, the modern combination of ketamine and rocuronium has less significant complications, and provides a superior alternative to etomidate and succinylcholine.

Sedation: Ketamine or Etomidate?

Ketamine and etomidate are both known for their hemodynamically neutral profiles.  Obviously, this is of key importance in crashing trauma or medical patients found in the emergency department.  If both are good options, why did we avoid ketamine for so long?  Concerns for increased intracranial pressure made us avoid the drug in head-injured and potential stroke patients.

 Ketamine has not been shown to increase ICP in recent studies.  The original studies concluding an increase in ICP were done on small numbers of patients, and the patients were given far greater doses of ketamine than are provided during your standard RSI.  Therefore, they did not bear out in clinical practice. In fact, due to ketamine’s blockade of reuptake of catecholamines, it maintains both MAP and CPP, preventing hypoxic and hypotensive episodes, which are more common and devastating dangers to head injury patients.

 Ketamine is less likely to cause post-intubation hypotension. While etomidate has demonstrated adrenal suppression with just one dose in multiple studies, ketamine has not shown any such complications.  An increase in mortality, lower cortisol levels, more ventilator days and longer ICU stays are associated with prolonged IV etomidate usage.  No study has demonstrated an increase in mortality with single dose etomidate.  However, single dose etomidate has shown maximal adrenal suppression at 4 to 6 hours post administration. Adrenal suppression can result in hypotension, and post-intubation hypotension does correlate with increased in-hospital mortality. With critically ill patients, maintaining their bodies’ stress responses should be prioritized.

 Ketamine and etomidate have been compared in meta-analyses, and multi-center trials, and have been shown to have equal efficacy.  While studies from a few years ago show increased mortality with ketamine, the most recent papers show that ketamine is a great alternative to etomidate, particularly in septic patients who benefit from catecholamine support.  Additionally, ketamine has analgesic and dissociative qualities that are important qualities in a sedative medication.

Paralysis: Rocuronium versus Succinylcholine?

At face value, rocuronium and succinylcholine have multiple pros and cons that make choosing between them a difficult decision in the emergent airway.  Most emergency physicians have a one-size-fits-all paralytic agent they prefer in almost all intubations.  With studies a few years back ultimately saying, “Roc sucks and Succ rocks!,”  this go-to agent is frequently succinylcholine. It is known as being fastest onset, easiest to use paralytic in our armamentarium. However, more recent studies have shown our prior knowledge about succinylcholine versus rocuronium efficacy was based on studies where patients were given sub-optimal doses of rocuronium, making those comparison studies nil.

 In the ED, no significant difference has been found in onset of action between rocuronium and succinylcholine.  Just like ketamine in the section above, the dosing of rocuronium in comparison studies vs. succinylcholine was not what was recommended for ED practice.  Once dosing of rocuronium was increased to 1.2 mg/kg, time to onset of action was almost equivalent.  Additionally, there was no difference in oxygen desaturations, intubation conditions, or failed first intubation attempts between groups receiving the two medications.

 Succinylcholine causes potentially life-threatening potassium increases and has multiple contraindications.  Getting a complete medical history is difficult or impossible with the obtunded patient. While uncommon, succinylcholine has the potential to cause life-threatening transient hyperkalemia in patients that have end-stage renal disease, malignant hyperthermia, ocular surgery, myasthenia gravis, muscular dystrophies, paraplegia, and a myriad of other chronic medical conditions.  When deciding between a drug with many possible complications, and one with few, the choice is easy.

 Rapid clearance of succinylcholine is detrimental to patients requiring an airway in the ER.  The onset of succinylcholine is 60 seconds and duration of action is 10 minutes.  Rocuronium’s onset is nearly as fast at 75 seconds but its action lasts an average of 33 minutes.  The rapid-on, rapid-off action of succinylcholine has always been considered as a strength. If a physician was unable to intubate the patient, paralysis would wear off quickly and the patient would be able to protect their airway while the physician prepared for the second attempt.  Short duration of action is a plus for the controlled intubation setting of an operating room.  However, in the ED, all patients requiring intubation are unstable and likely require an immediate definitive airway.  Even if they come out of their short acting succinylcholine, the patient is not going to be breathing any better than they were when the provider decided to intubate in the first place.  Rocuronium as a paralytic agent is unlikely to require repeat dosage in the middle of a difficult airway procedure. Additionally, side effects of succinylcholine are dose-dependent, and chances are increased with each subsequent dose of that medication.

Summary

• The risks of increased ICP with ketamine, and a clinically significant delay in medication onset with rocuronium have not borne out in recent literature
• Potential adrenal suppression with etomidate and the multiple contraindications of succinylcholine make the ketamine and rocuronium combination arguably a safer choice
• Recent studies have shown no difference in usage of ketamine versus etomidate, and rocuronium versus succinylcholine in intubation conditions and first pass success in the Emergency Department
• Ultimately, the ketamine and rocuronium combination has equal efficacy and a superior safety profile in comparison to etomidate and succinylcholine. Ketamine and rocuronium should become the first-line choices for RSI in critically ill patients.

References / Further Reading:

1. Bruder EA, Ball IM, Ridi S, Pickett W, Hohl C. Single induction dose of etomidate versus other induction agents for endotracheal intubation in critically ill patients. Cochrane Database of Systematic Reviews 2015, Issue 1. Art No.: CD010225.
2. Dong, Jing et al. “Pharmacological Interventions for Acceleration of the Onset Time of Rocuronium: A Meta-Analysis.” Ed. Marco Gemma.PLoS ONE9.12 (2014): e114231. PMC. Web. 28 Mar. 2015.
3. Jabre, Patricia, Xavier Combes, Frederic Lapostolle, Mohamed Dhaouadi, Agnes Ricard-Hibon, et al. “Etomidate versus Ketamine for Rapid Sequence Intubation in Acutely Ill Patients: A Multicentre Randomised Controlled Trial.” The Lancet 374.9686 (2009): 293-300.
4. Marsch, Stephan C., Luzius Steiner, Evelyne Bucher, Hans Pargger, Martin Schumann, Timothy Aebi, Patrick R. Hunziker, and Martin Siegemund. “Succinylcholine versus Rocuronium for Rapid Sequence Intubation in Intensive Care: A Prospective, Randomized Controlled Trial.” Critical Care 15.4 (2011): R199.
5. Perry JJ, Lee JS, Sillberg VAH, Wells GA. Rocuronium versus succinylcholine for rapid sequence induction intubation.Cochrane Database of Systematic Reviews2008, Issue 2. Art. No.: CD002788.
6. Scherzer, Daniel, Mark Leder, and Joseph D. Tobias. “Pro-Con Debate: Etomidate or Ketamine for Rapid Sequence Intubation in Pediatric Patients.” The Journal of Pediatric Pharmacology and Therapeutics 17.2 (2012): 142-49.
7. Sluga, Mathias, Wolfgang Ummenhofer, Wolfgang Studer, Martin Siegemund, and Stephan C. Marsch. “Rocuronium Versus Succinylcholine for Rapid Sequence Induction of Anesthesia and Endotracheal Intubation: A Prospective, Randomized Trial in Emergent Cases.” Anesthesia & Analgesia 101.5 (2005): 1356-361.
8. Stollings, J. L., D. A. Diedrich, L. J. Oyen, and D. R. Brown. “Rapid-Sequence Intubation: A Review of the Process and Considerations When Choosing Medications.” Annals of Pharmacotherapy 48.1 (2014): 62-76.
9. Heffner AC, Swords D, Kline JA, Jones AE. “The frequency and significance of postintubation hypotension during emergency airway management”. Journal of Critical Care 2012 27 (4): 417.e9-13
10. http://www.emdocs.net/roc-rocks-sux-sucks-rocuronium-agent-choice-rsi/
11. http://www.emdocs.net/neuro-intubation-highlights/