In this episode, I’ll discuss a Monte Carlo analysis I performed to assess the risk of anesthetic awareness when giving rocuronium before ketamine (rocketamine) in rapid sequence intubation.
Recently, Dr. Josh Farkas at pulmcrit.org wrote an excellent post discussing whether in certain scenarios rocuronium should be administered before ketamine in rapid sequence intubation. This is the reverse of the more common RSI practice of giving the sedative followed by the paralytic.
In his post, Josh uses the example of a morbidly obese patient with hypoxic respiratory failure and an oxygen saturation of 96% despite maximal preoxygenation efforts. Such a patient has a very short “safe apnea time” of perhaps 2 minutes, beyond which if their airway is not secure they will likely suffer anoxic injury.
With the traditional approach of giving ketamine before rocuronium, Josh estimates a 1 minute “sedation lag time” where the ketamine will kick in before the rocuronium. This is problematic because the patient may become apneic from a fast ketamine push 1 minute before the intubating conditions are rendered ideal by rocuronium. In this scenario, 50% of the safe apnea time is used up waiting for the rocuronium to work, leaving the physician with a very narrow window of time to place the airway without a risk of anoxic injury.
By reversing the usual order and giving rocuronium first, Josh points out that this sedation lag time should be minimized, assuming an onset of 50-60 seconds for rocuronium, an onset of 30-40 seconds for ketamine, and a few seconds to complete the administration of each drug.
As some comments in Josh’s post point out, these onset times for rocuronium and ketamine are only averages – there are standard deviations that may make a difference in the calculation of the sedation lag time.
The major risk that comes from giving rocuronium before ketamine is the risk of “anesthetic awareness.” That is, the risk the rocuronium kicks in before the ketamine does and the patient is paralyzed but not yet sedated.
To determine the risk of anesthetic awareness from pushing rocuronium before ketamine, I performed a Monte Carlo analysis using 5000 simulated patients.
In one of the most commonly cited papers comparing the onset of rocuronium to succinylcholine, the average onset of paralysis from rocuronium 1.2 mg/kg IV was 55 seconds with a standard deviation of 14 seconds.
In a separate study, the onset of ketamine 2mg/kg IV was 46.05 seconds with a standard deviation of 1.93 seconds.
To assess the risk of anesthetic awareness, I simulated the onset times for ketamine and rocuronium 5000 times using Microsoft Excel to create random values with a normal distribution around each mean onset time.
I assumed that each medication would be given sequentially and that administration would take 20 seconds for each medication. I then calculated the sedation lag time and anesthetic awareness time for each simulated patient receiving rocuronium first and again receiving ketamine first.
When ketamine was given first, the average sedation lag time was 49 seconds. In a patient with a 2 minute safe apnea time, this represents 41% of the safe apnea time used up waiting for medications to work.
One out of 5000 simulated patients had a 3.9 second period of anesthetic awareness. However, this simulated value had rocuronium taking effect at 4 seconds after administration.
When rocuronium was given first, the sedation lag time was 15.1 seconds in simulated patients without an episode of anesthetic awareness. In a patient with a 2 minute safe apnea time, this represents 13% of the safe apnea time used up waiting for medications to work.
25.3% of simulated patients had some duration of anesthetic awareness. 15.4% of simulated patients had an anesthetic awareness time greater than 5 seconds, 8.9% had an anesthetic awareness time greater than 10 seconds, 2.2% had an anesthetic awareness time greater than 20 seconds, and 0.4% had an anesthetic awareness time greater than 30 seconds.
The validity of this analysis is limited because I used onset times from two different patient populations, neither of which were critically ill. Perfusion of muscles (which is poor to begin with) is worse in critically ill patients with shock, and this would extend the onset of rocuronium. In turn, the risk of anesthetic awareness with rocuronium first would be lower and the sedation lag time would be higher with ketamine first.
Two-thirds of the simulated patients that experienced anesthetic awareness would not have if the administration time of ketamine were shortened to 10 seconds. Such a rapid administration time of ketamine has a greater chance of causing apnea.
If ketamine and rocuronium were mixed in the same syringe, the risk of anesthetic awareness would be 2.2%. Unfortunately, no published data examines the stability of rocuronium and ketamine in the same syringe. There are two textbooks which state that ketamine and rocuronium may be mixed in the same syringe however they provide no citation for this claim (click through the images to the book):
The risk of anesthetic awareness when giving rocuronium before ketamine for RSI is not completely answered due to the limitations of this analysis. However, the risk is likely to be significant enough that using rocuronium before ketamine should not be routinely done. In patients with a very short estimated safe apnea time, the risk of anesthetic awareness may be less than the risk of anoxic injury and giving rocuronium first may represent the best therapeutic option for such a patient. A compatibility in syringe study of rocuronium and ketamine would be very helpful.
Do you mix ketamine and rocuronium in the same syringe? Please share and if you do mix reply w/ supporting reference if you have it!
— Pharmacy Joe ?? (@PharmacyJoe) May 1, 2017
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If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.