MEGA-DOSE ROC?

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The Pre-brief

Today if you look at any airway manual you see a range for dosing rocuronium for RSI as 0.6mg/kg to 1.2mg/kg.  But is this the right dose?  Through an editorial examining the dosing of rocuronium, we’ll ask, could we still be underdosing roc?

What is Rocuronium?

Rocuronium has been part of the airway arsenal for decades. It is a non-depolarizing neuromuscular blocker derived from the South American curare plant.   Rocuronium checks all the boxes for an ideal paralytic in RSI;

The duration of rocuronium is longer than its competitors, which was underscored by the recent publication by Pappal et al in Annals of Emergency Medicine. We will be reviewing this paper soon!  There are no contraindications other than a documented reaction to rocuronium.  

 

The Argument for Standard Dose Roc

We see from the early anesthesia literature that there is a dose-correlated response with time to paralysis and time to “ideal intubating conditions.”  So for example, a blinded study comparing a placebo to 0.4, 0.8 and 1.2mg/kg rocuronium compared qualitative outcomes like “jaw relaxed versus jaw very tight” as well as movement of limbs as “vigorous to none.”  While not exactly the outcomes we look for in RSI of critically-ill patients, these studies do demonstrate a dose-dependent improvement in “perfect” intubating conditions and successful intubation at 70 seconds from the push of rocuronium.  

Follow this with the notorious succinylcholine versus rocuronium studies.  While none of these studies looked at doses greater than 1.2mg/kg, they very consistently show faster ideal intubating conditions with higher doses of rocuronium.  Importantly, you could argue that only at 1.2mg/kg does rocuronium even compete with succinylcholine.  This also supports the argument that all dosing should be accurately weight-based, not an empiric “60mg or 100mg” in order to reliably obtain ideal intubating conditions.

What is the right High-Dose?

Also popular is the argument for “high-dose” rocuronium, often cited as 1.6mg/kg, but more accurately stated in the literature as anything equal to or greater than (≥) 1.2mg/kg.  The argument for a higher dose comes from two NEAR registry studies, a national retrospective airway database.  The first from 2018, quoted an OR for first pass success of 2.2 for a ‘high-dose’ rocuronium when compared to ‘standard dose’ or 0.6mg/kg.  Under more scrutiny however, this high dose still had a mean of 1.2mg/kg – not quite the 1.6mg/kg sometimes reflected in popular commentary. While this does reaffirm that 1.2mg/kg should be the standard dose, it doesn’t necessarily support greater doses.  A more recent  NEAR study from 2021 used regression modeling comparing first pass success at doses of <1.0, 1.0 – 1.1, 1.2 – 1.3 and >1.4mg/kg with over 2,000 intubations in the highest dose group. These doses correlated to first pass success of 88.4%, 88.1%, 89.7%, and 92.2%.  When compared to the 1.0 – 1.1 group, the 1.4mg/kg dose had an odds of first pass success of 1.5, further supporting higher doses.

Latest Evidence

While this data is encouraging, it is limited by all the pitfalls of retrospectivity.  Unfortunately, there exists no prospective data in critically-ill intubations looking at higher doses of rocuronium.  However, we’ll end this editorial with a follow up study from the OR study mentioned above, one in which you could say a MEGA-dose of rocuronium was used.  

This study randomized patients to 0.4, 0.8, 1.2, 1.6 and 2.0mg/kg rocuronium and looked at the quality of intubation at 40 seconds from time roc was pushed.  Again utilizing a qualitative method grading intubation conditions, the study demonstrated a dose-dependent correlation with ‘perfect’ intubation conditions.  This also demonstrated higher success rates at the pre-set time of 70 seconds.  Furthermore, extrapolated from their data set, they found a dose of 2.38mg/kg (!!!) would have led to a 95% probability of perfect intubation conditions.  This study also reiterated that there was no substantial difference in hemodynamic effect at the different doses. Not surprisingly, there was a dose-dependent increase in the duration of paralysis, nearly 2 hours in the 2.0mg/kg dose. 

It was noted by the authors, the long duration of paralysis would be a problem with short cases and that prolonged neuromuscular block could compromise patient safety if an airway could not be secured. This commentary, while valid, is less of a concern in emergent airway management. Caveats could be imagined in the patient population that will require neuro checks such as in head trauma or strokes.

Conclusion

So while we don’t have the studies we want to take higher doses of rocuronium standard of care, we also don’t have data to refute utilizing higher doses.  There appears to be no negative effects other than a longer duration of action at higher doses, which needs to be considered.  At a minimum, we should be dosing all RSI at 1.2mg/kg with, ideally an accurate weight.  

Editors Comments:

Terren does a great job highlighting the value of high-dose rocuronium in regards to rapid onset and first-pass success. The recent publication by Pappal et al demonstrated that when we use rocuronium, we may be allowing our patients to wake up while they are still under the effect of the paralytic. With the longer duration of action of high-dose rocuronium, it is more important to remember to start appropriate sedation immediately. You never want your initial induction agent to wear off and the patient may still be paralyzed. 

  • Haywood

I can’t remember the last time I used a dose of rocuronium under 1.2 mg/kg given the improvement in intubating conditions (especially time to relaxation), but I’m curious as to what the ceiling of benefit is. As Terren and Steve pointed out, adequate analgosedation is a must, and post-intubation medications need to be part of your pre-intubation checklist. Duration of rocuronium effect will be longer not only with higher doses, but also with hepatic and renal dysfunction.

  • Suiba

The Debrief

  • Data definitively supports a dose of 1.2mg/kg rocuronium in RSI
  • There is some limited data to support higher doses, as high as 2.0mg/kg without significant side effects

References

  1. Kirkegaard-Nielsen H, Caldwell JE, Berry PD. Rapid tracheal intubation with rocuronium: a probability approach to determining dose. Anesthesiology. 1999 Jul;91(1):131-6. doi: 10.1097/00000542-199907000-00021. PMID: 10422938.
  2. Curley GF. Rapid sequence induction with rocuronium – a challenge to the gold standard. Crit Care. 2011;15(5):190. doi: 10.1186/cc10418. Epub 2011 Sep 23. PMID: 22112346; PMCID: PMC3334740.
  3. April MD, Arana A, Pallin DJ, Schauer SG, Fantegrossi A, Fernandez J, Maddry JK, Summers SM, Antonacci MA, Brown CA 3rd; NEAR Investigators. Emergency Department Intubation Success With Succinylcholine Versus Rocuronium: A National Emergency Airway Registry Study. Ann Emerg Med. 2018 Dec;72(6):645-653. doi: 10.1016/j.annemergmed.2018.03.042. Epub 2018 May 7. PMID: 29747958.
  4. 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 Apr 10. doi: 10.1007/s43678-021-00119-6. Epub ahead of print. PMID: 33837951.
  5. Heier T, Caldwell JE. Rapid tracheal intubation with large-dose rocuronium: a probability-based approach. Anesth Analg. 2000 Jan;90(1):175-9. doi: 10.1097/00000539-200001000-00036. PMID: 10625000.
  6. Pappal RD, Roberts BW, Mohr NM, Ablordeppey E, Wessman BT, Drewry AM, Winkler W, Yan Y, Kollef MH, Avidan MS, Fuller BM. 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 May;77(5):532-544. doi: 10.1016/j.annemergmed.2020.10.012. Epub 2021 Jan 21. PMID: 33485698.

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