(May 11, 2022)

Neuromuscular blockade is an essential component of rapid sequence intubation. Rocuronium is becoming the most commonly used non-depolarizing neuromuscular blocking agent (N-NMBA) in the emergency department due to its ability to create excellent intubating conditions compared to other NMBAs, and its superior safety profile over succinylcholine for a variety of clinical conditions when the latter is contraindicated (NMBA table). 

• Studies have shown that there are no significant differences in intubation conditions when using rocuronium at a dose ≥1.2 mg/kg compared to succinylcholine 1.5 mg/kg for RSI. (2, 5, 9).

• While rocuronium is a valid alternative for continuous neuromuscular blockade of critically ill patients with early ARDS (Acute Respiratory Distress Syndrome) and severe asthma, it should be used with caution in rigorously selected cases (6).  

• Non-depolarizing NMBAs can be reversed with sugammadex at any point, or with neostigmine when significant recovery has been achieved (40% approx)(18). 

  • In the ED, NMBA reversal is not an option in the vast majority of cases and is not included in most Emergency Medicine difficult airway algorithms. 

• ⚠ The only contraindication is a prior anaphylactic reaction to rocuronium (18).
  
  

Adult dose for rapid sequence intubation (15, 18)

1.5 mg/kg IV

• Time to intubation level paralysis: 60 sec

• Duration of paralysis: 40-60 min

Adult dose for rapid sequence intubation (15, 18)

• 1.5 mg/kg IV

  • Time to intubation level paralysis: 60 sec.

  • Duration of paralysis: 40-60 min.

  • The classic dose of 1.2 mg/kg for RSI (ED95 x4) has been suggested to be increased to 1.5 mg/kg in the emergency setting to prevent underdosing critically ill patients (15). Providing an accurate dose of 1.2 mg/kg is considered good practice and is widely accepted.

  • It is recommended to administer a saline flush of 20 ml after rocuronium administration, as it may reduce onset time (7).
    
    

Adult dose for paralysis, continuous infusion (11, 16, 19)

• 0.3-1.2 mg/kg/hr IV

  • Starting dose usually of 0.3 mg/kg/hr IV.

  • For deep neuromuscular blockade maintenance requires 0.75 mg/kg/hr IV.

  • Significant prolonged recovery times are associated with critically ill patients with multiple organ failure (TOF) exposed to deep levels of paralysis with rocuronium, consider alternative strategies (20).

• US-FDA labeled (19)

  • Routine tracheal intubation

  • Rapid sequence intubation

  • Muscle paralysis, during surgery or mechanical ventilation

• Off-label

  • Not described

• Rocuronium 0.6mg/kg to <1.2mg/kg vs succinylcholine: succinylcholine is associated with superior intubation conditions in achieving excellent and clinically acceptable intubating conditions (5).

• Rocuronium >1.2mg/kg vs succinylcholine: no differences observed in intubation conditions for both agents (2, 5, 9).

• Over the past 20 years, there has been a notable trend in the United States, Canada, and Australia of an increased number of emergency intubations performed using rocuronium, accompanied by a decrease in the usage of succinylcholine for both adult and pediatric patients (4, 8).

• This relatively new tendency does not change the fact that succinylcholine has excellent results for emergency intubation paralysis and success rates, and that many experts still recommend it as the first line NMBA for this setting. 

• EMDrugs' position is to use non-depolarizing NMBA as the first-line paralytic class for emergency intubation, with rocuronium being the preferred choice. This recommendation is based on safety considerations and the excellent level of paralysis achieved when administered in the appropriate doses and timing. It is crucial to emphasize the proper dosing of 1.2-1.5 mg/kg IV (total body weight in obese individuals).

• Rocuronium is classified as an extremely high risk medication due to its potential to cause muscle paralysis and apnea. It is considered a high alert medication according to the Institute for Safe Medication Practices (10). 

• Long-acting neuromuscular blocking agents have been associated with an increased risk of awareness with paralysis in mechanically ventilated patients (more details will be discussed in the next section).

• It is contraindicated only in patients with a reported or documented allergy or hypersensitivity to rocuronium (19,  18).

• For more comprehensive information on reported adverse reactions and warnings, please refer to the label information  (19). 

• In the ED, awareness with paralysis is reported to occur in 2.6% of mechanically ventilated patients (17). 

• Long-acting NMBA are associated with an increased risk of awareness with paralysis, which may have serious long-term psychological consequences for critically ill patients who undergo painful procedures, experience extreme discomfort and have stressful memories (17). 

• Psychological consequences include post traumatic stress disorder, phobias, depression, and other related conditions.

• The use of rocuronium in the ED has significantly increased in recent years. Prior research has shown that compared to patients receiving succinylcholine, paralyzed patients receiving rocuronium typically receive lower doses of analgesia and sedation, often with a delay. Since sedation depth cannot be reliably monitored clinically during periods of neuromuscular blockade, the literature suggests that clinicians should be aware that the use of rocuronium may increase patient-centered complications during this vulnerable period of care (17).

• Effective Dose 95 (ED95)

  • The definition of Effective Dose 95 (ED95) for a neuromuscular blocking agent differs from that of other drugs or molecules. In anesthesia and emergency medicine, it is defined as the dose at which a NMBA produces a 95% decrease in muscle contraction (14). For instance, the ED95, measured in mg/kg, represents the dose required to achieve a 95% neuromuscular blockade.

  • For other molecules, the pharmacologic term of Effective Dose, as an example ED95, is defined as the dose required to achieve a desired effect in 95% of the population. 

• Rocuronium ED95: 0.3mg/kg (12, 14).
  Experts recommend using 2 to 4 times the ED95 of a neuromuscular blocking agent to achieve a rapid and optimal level of paralysis for intubation. In the anesthesia setting, it is usually recommended to use 2 times the ED95, while in the emergency department setting, 4 times the ED95 is advised (14, 18). 

  • Rocuronium ED95 x2 = 0.6 mg/kg (frequently used in the operating room for elective surgeries).

  • Rocuronium ED95 x4 = 1.2 mg/kg (recommended dose for emergency department intubation).

• Recent studies suggest that using a dose of 1.5mg/kg is a safer option than 1.2 mg/kg to reduce the risk of underdosing (15).
  
  

• Duration of effect (12)

  • 2x ED95: 30-40 minutes

  • 3-4 times ED95: 30-85 minutes

Pregnancy risk classification

• US FDA pregnancy category: not assigned

• AU TGA pregnancy category: B2

Lactation

• It is unknown if rocuronium is excreted into human milk

• Very low risk for breastfeeding and the infant (21)

  • Due to its moderately elevated molecular weight and rapid elimination half-life (approximately 15 minutes), it is highly unlikely that significant quantities of rocuronium will pass into breast milk (3).

  • Breastfed infants have not shown any problems after anesthesia periods ranging from 1.5 to 5 hours with the use of rocuronium, along with additional drugs such as propofol, remifentanil, and xenon (1).

1. Stuttmann R, Schäfer C, Hilbert P, Meyer MR, Maurer HH. The breastfeeding mother and xenon anesthesia: four case reports. Breastfeeding and xenon anesthesia. BMC Anesthesiol. 2010;10:1. Published 2010 Feb 19. doi:10.1186/1471-2253-10-1
   BMC (Open Access)

2. Patanwala AE, Stahle SA, Sakles JC, Erstad BL. Comparison of succinylcholine and rocuronium for first-attempt intubation success in the emergency department. Acad Emerg Med. 2011;18(1):10-14. doi:10.1111/j.1553-2712.2010.00954.x
   Wiley (Open Access)

3. Dalal PG, Bosak J, Berlin C. Safety of the breast-feeding infant after maternal anesthesia. Paediatr Anaesth. 2014;24(4):359-371. doi:10.1111/pan.12331
   Pubmed

4. Brown CA 3rd, Bair AE, Pallin DJ, Walls RM; NEAR III Investigators. Techniques, success, and adverse events of emergency department adult intubations [published correction appears in Ann Emerg Med. 2017 May;69(5):540]. Ann Emerg Med. 2015;65(4):363-370.e1. doi:10.1016/j.annemergmed.2014.10.036
   Pubmed

5. Tran DT, Newton EK, Mount VA, Lee JS, Wells GA, Perry JJ. Rocuronium versus succinylcholine for rapid sequence induction intubation. Cochrane Database Syst Rev. 2015;2015(10):CD002788. Published 2015 Oct 29. doi:10.1002/14651858.CD002788.pub3
   Cochrane (Open Access)

6. Murray MJ, DeBlock H, Erstad B, et al. Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient. Crit Care Med. 2016;44(11):2079-2103. doi:10.1097/CCM.0000000000002027
   Pubmed

7. Ishigaki S, Masui K, Kazama T. Saline Flush After Rocuronium Bolus Reduces Onset Time and Prolongs Duration of Effect: A Randomized Clinical Trial [published correction appears in Anesth Analg. 2018 Jun;126(6):2153]. Anesth Analg. 2016;122(3):706-711. doi:10.1213/ANE.0000000000001094
   Pubmed

8. Pallin DJ, Dwyer RC, Walls RM, Brown CA 3rd; NEAR III Investigators. Techniques and Trends, Success Rates, and Adverse Events in Emergency Department Pediatric Intubations: A Report From the National Emergency Airway Registry. Ann Emerg Med. 2016;67(5):610-615.e1. doi:10.1016/j.annemergmed.2015.12.006
   Pubmed

9. April MD, Arana A, Pallin DJ, et al. Emergency Department Intubation Success With Succinylcholine Versus Rocuronium: A National Emergency Airway Registry Study. Ann Emerg Med. 2018;72(6):645-653. doi:10.1016/j.annemergmed.2018.03.042
   Pubmed

10. Institute for Safe Medication Practices (ISMP). ISMP List of High-Alert Medications in Acute Care Settings. ISMP; 2018. Accessed May 9, 2023.
    ISMP, ISMP List of High-Alert Medications 2018 (Open Access)

11. Couto M, Nunes C, Vide S, Amorim P, Mendes J. Rocuronium Continuous Infusion for Profound Neuromuscular Blockade: A Systematic Review and Meta-analysis. Clin Neuropharmacol. 2019;42(6):203-210. doi:10.1097/WNF.0000000000000366
    Pubmed

12. Hugh C, Hemmings JR, Talmage DE. Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application, 2nd Edition. Philadelphia, PA: Elsevier, Inc; 2019.
    Elsevier

13. Renew JR, Ratzlaff R, Hernandez-Torres V, Brull SJ, Prielipp RC. Neuromuscular blockade management in the critically Ill patient. J Intensive Care. 2020;8:37. Published 2020 May 24. doi:10.1186/s40560-020-00455-2
    Pubmed Central (Open Access)

14. Gropper MD. Miller’s Anesthesia. 9th edition. Philadelphia, PA: Elsevier; 2020.
    Elsevier

15. Levin NM, Fix ML, April MD, Arana AA, Brown CA 3rd; NEAR Investigators. The association of rocuronium dosing and first-attempt intubation success in adult emergency department patients. CJEM. 2021;23(4):518-527. doi:10.1007/s43678-021-00119-6
    Springer (Open Access)

16. Couto M, Couto JG, Nunes CS, Vide S, Amorim P, Mendes J. Systematic Review on Rocuronium Continuous Infusion for Deep Neuromuscular Blockade. Curr Rev Clin Exp Pharmacol. 2021;16(1):64-72. doi:10.2174/1574884714666191120144331
    Pubmed

17. Pappal RD, Roberts BW, Mohr NM, et al. The ED-AWARENESS Study: A Prospective, Observational Cohort Study of Awareness With Paralysis in Mechanically Ventilated Patients Admitted From the Emergency Department. Ann Emerg Med. 2021;77(5):532-544. doi:10.1016/j.annemergmed.2020.10.012
    Annals of Emergency Medicine (Open Access)

18. Brown CA, Sackles JC, Mick NW, Mosier JM, Braude DA. The Walls Manual of Emergency Airway Management. 6th edition. Philadelphia, PA. Wolters Kluwer; 2022.
    Wolters Kluwer

19. NIH-NLM (National Institutes of Health - National Library of Medicine). DailyMed. Label: Rocuronium - rocuronium bromide injection, solution. Updated in October 2021. Accessed April 12, 2023.
    DailyMed 2021 - Rocuronium

20. APILAM (Association for promotion of and cultural and scientific research into breastfeeding). e-lactancia. Rocuronium. Updated August 6, 2022. Accessed May 9, 2023.
    E-lactancia (Open Access)