Understanding the role of neuromuscular blocking agents in EMS

Neuromuscular blocking agents (NMBAs) have been used since the 1940s and are referred to by a number of different names, such as muscle relaxants or paralytics [1]. While NMBAs can be used during surgery or to improve ventilator synchrony, the most applicable use of NMBAs for prehospital providers is in advanced airway management, with increased industry discussion regarding two drugs for this role: succinylcholine and rocuronium.

Why do we need NMBAs?

The value of NMBAs in improving intubation success is well established. A recent meta-analysis described a decrease in the frequency of difficult intubations from 56.3% to 4.7% when NMBAs were used [2]. In drug-assisted airway management, according to the NAEMSP, an NMBA is often combined with a sedative in rapid sequence intubation (RSI) – a specific airway sequence used in unfasted patients to minimize aspiration while improving intubating conditions [3].

Recently, the concept of delayed sequence intubation (DSI) is also receiving attention in the literature. DSI emphasizes physiological consequences of intubation not just first pass success. The result is a delayed approach that includes additional preoxygenation and optimizing hemodynamics prior to intubation, which decreases hypoxia and hypotension, without decreasing first pass success rate [4]. Additionally, NMBAs can be used in a rapid sequence airway, a process identical to RSI but which results in the insertion of a supraglottic airway instead of an endotracheal tube [3].

How do NMBAs work?

NMBAs work at the neuromuscular junction. In order for muscle to be stimulated, acetylcholine (ACh) is released from the motor nerve terminal, crosses the synaptic cleft and binds to nicotinic receptors, which results in the depolarization and subsequent contraction of the muscle. NMBA drugs are categorized based on if they are depolarizing or non-depolarizing – whether or not the muscle is stimulated first or just blocked. The cycle is complete when acetylcholinesterase breaks down ACh into acetyl and choline so it can be reused [5]. Put simply, NMBAs block outgoing nerve impulses only. It is important to remember that a conscious patient who only received an NMBA can still see, hear and feel everything – they just can’t move!

Succinylcholine (Sux)

Sux is the only widely-available depolarizing NMBA. Historically, it has been the drug of choice for RSI, owing to its short duration, and remains the fastest onset of all of the NMBA options [5]. While these two properties make it an ideal agent for intubation, it is not without the potential for significant side effects. With sux, the onset of paralysis is marked by fasciculations (brief, irregular muscle contractions), which may lead to myalgias. One of the primary concerns is the risk of hyperkalemia; this limits its usage in patients with burns, crush injuries and spinal cord injury with flaccid paralysis [3].

Rocuronium (Roc)

Roc is a relatively new offering in the lineup of non-depolarizing NMBAs. Historically, because of the slower onset and longer duration of action, non-depolarizing NMBAs like pancuronium, vecuronium and cis-atracurium have been used to facilitate ventilation more often than for intubation. Rocuronium has a much lower risk of histamine release than other non-depolarizing drugs (such as cis-atracurium) but has been rarely associated with histamine release and the potential for anaphylaxis [5]. One advantage to rocuronium is the availability of reversal agents. Anticholinesterase inhibitors such as neostigmine, have been historically used to reverse the neuromuscular blockade; however, the time to reversal is approximately 12 minutes. Newer agents such as suggamadex can reverse NMBAs in two minutes, making it a much more practical option [1].

Which drug is better?

Research is clear that NMBAs improve first pass success rate in intubation [2]. However, which NMBA should be used is less clear. Even though a number of studies have recently compared sux and roc, the results have been mixed:

• In favour of roc, Dao et al recommended its use for intubating head injury patients, describing it as safer than sux [6].
• A number of recent studies suggested the efficacy of the two drugs were more equal. Rocuronium (0.9mg/kg) was found to produced similar intubating conditions as 1mg/kg of sux in hospital and no difference in first pass success or incidence of hypoxia when used for prehospital intubations [7,8]. In children, roc and sux produced similar intubating conditions with roc having fewer side effects and more stable vital signs [9,10].
• Roc also has detractors. A randomized control trial of over 1,200 pre-hospital intubations examined first pass success rates between roc and sux (74.6% vs 79.4%), which failed to demonstrate non-inferiority between roc and sux (11). In a population of in-hospital acute myocardial infarct patients, the use of rocuronium was associated with higher mortality (42.4% versus 33.6%; P<0.001) than sux (12)

Which NMBA drug should EMS use?

The answer to that question is difficult to answer with the current research, so it should be decided based on individual patient needs. Remember, there is no such thing as a good drug or a bad drug – there are only drugs. What makes them “good” or “bad” is your understanding of the drug and how it is used. Generally speaking, if you value rapid onset and short duration of paralysis, sux may be a good fit for you. If you are concerned about side effects, roc may be the best choice.

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REFERENCES

1. Hristovska AM, Duch P, Allingstrup M, Afshari A. Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults. Cochrane Database Syst Rev. 2017 Aug 14;8(8):CD012763. doi: 10.1002/14651858.CD012763. PMID: 28806470; PMCID: PMC6483345
2. Lundstrøm, L. H., Duez, C. H. V., Nørskov, A. K., Rosenstock, C. V., Thomsen, J. L., Møller, A. M., ... & Wetterslev, J. (2018). Effects of avoidance or use of neuromuscular blocking agents on outcomes in tracheal intubation: a Cochrane systematic review. British journal of anaesthesia, 120(6), 1381-1393.
3. Jarvis JL, Lyng JW, Miller BL, Perlmutter MC, Abraham H, Sahni R. Prehospital Drug Assisted Airway Management: An NAEMSP Position Statement and Resource Document. Prehosp Emerg Care. 2022;26(sup1):42-53. doi: 10.1080/10903127.2021.1990447. PMID: 35001829.
4. Bandyopadhyay, A., Kumar, P., Jafra, A., Thakur, H., Yaddanapudi, L.N. and Jain, K., 2023. Peri-intubation hypoxia after delayed versus rapid sequence intubation in critically injured patients on arrival to trauma triage: a randomized controlled trial. Anesthesia & Analgesia, 136(5), pp.913-919.
5. Farooq, K. & Hunter, J. M. (2021). Neuromuscular blocking agents and reversal agents. Anaesthesia & Intensive Care Medicine, 22(6), 380–384. https://doi.org/10.1016/j.mpaic.2021.04.010
6. Dao AQ, Mohapatra S, Kuza C, Moon TS. Traumatic brain injury and RSI is rocuronium or succinylcholine preferred? Curr Opin Anaesthesiol. 2023 Apr 1;36(2):163-167. doi: 10.1097/ACO.0000000000001225. Epub 2022 Dec 6. PMID: 36729846.
7. Bhunia P, Mandal A, Chatterjee S, Mayur N. A comparative study to evaluate the optimum intubating dose of rocuronium bromide versus succinylcholine chloride as an ideal intubating muscle-relaxing agent. Asian Journal of Medical Sciences. 2024 Feb 1;15(2):196-201.
8. Ramsey, J. et al. (2023) ‘Comparison of Intubating Conditions with Succinylcholine Versus Rocuronium in the Prehospital Setting’, Prehospital Emergency Care, 28(4), pp. 537–544. doi: 10.1080/10903127.2023.2285399.
9. Patel, M. and Chandak, V., 2023. Comparison of Intubating Conditions of Two Doses of Rocuronium Bromide with Succinylcholine in Children-Protocol for a Randomised Control Trial. JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH, 17(2), pp.UK01-UK03.
10. Kumar A, Kumar A, Bharti AK, Choudhary A, Hussain M, Dhiraj S. A Randomized Double-Blind Comparative Study of the Intubating Conditions and Hemodynamic Effects of Rocuronium and Succinylcholine in Pediatric Patients. Cureus. 2023 Sep 4;15(9):e44631. doi: 10.7759/cureus.44631. PMID: 37799234; PMCID: PMC10548308.
11. Guihard, B., Chollet-Xemard, C., and Lakhnati, P. (2019). Effect of rocuronium vs succinylcholine on endotracheal intubation success rate among patients undergoin out-of-hospital rapid sequence intubation. A randomized clinical trial. JAMA. 2019;322(23):2303-2312. doi:10.1001/jama.2019.18254
12. 12 Schenck C, Banna S, Heck C, Ali T, Miller PE. Rocuronium Versus Succinylcholine in Patients With Acute Myocardial Infarction Requiring Mechanical Ventilation. J Am Heart Assoc. 2023 May 16;12(10):e8468. doi: 10.1161/JAHA.123.029775. Epub 2023 May 9. PMID: 37158165; PMCID: PMC10227322