Nimbex Is Dead. Long Live Sugammadex

I've been a lifelong fan of cisatracurium (Nimbex). It has been my neuromuscular blocker of choice ever since residency. Why do I love it so much? Let me count the ways.

I've found that Nimbex is very predictable in its metabolism. I've been burned badly before when I used another agent like rocuronium on a patient with renal insufficiency and the patient had incomplete reversal at the end of the case that necessitated reintubation. Not good for the patient or your reputation as an anesthesiologist.

Thanks to its Hoffman elimination, I don't have to worry about a patient's kidney or liver function. The drug just metabolizes at a very steady and predictable manner. This is particularly important when a patient may have an unknown issue with their renal or hepatic functions and suddenly you're wondering why the patient isn't waking up. Nimbex is also very easy to reverse. Neostigmine easily takes care of the drug and the patient emerges quickly. 

Sure you can't use Nimbex for rapid sequence induction but that's okay. Most cases don't require RSI anyway. Due to Nimbex's property of predictable reversal, I've stuck with it long after many of my colleagues switched to roc. But now that's all changed thanks to the miracle of sugammadex.

Sugammadex (Bridion) is a drug invented specifically to reverse the paralysis induced by rocuronium. But it also works with other aminosteroid compounds like vecuronium. I feel it has revolutionized NMB reversal the way propofol transformed the induction of anesthesia.

First of all, Bridion works very fast. I'm always amazed by how quickly a patient starts moving after it is given, even if there is still a fair amount of inhalational agents on board.

Rocuronium no longer needs to be carefully titrated in order for it to be reversible at the end of the case. This is especially relevant in procedures that finish rapidly like in ENT. Those cases always present the conundrum of the need for deep paralysis followed by a quick emergence. There's no greater predicament for the anesthesiologist than staring down at a patient with zero muscle twitches and an impatient surgeon wanting to get his next case started ASAP. Prior to sugammadex there was no way to reverse a deeply paralyzed patient effectively.

One can give roc to anybody with sugammadex. Before, I was always leery of using Bridion in dialysis patients because there was always a small chance that the reversal agent would wear off before the body has cleared the NMB. I have yet to see that happen. It's just as easy to wake up a patient with renal failure as a patient with normal kidney functions.

With all these advantages, rocuronium and sugammadex have become the combo of choice in our department. Nimbex use has practically disappeared. Bridion is in such high demand that our pharmacy is complaining about the high cost of the drug. Whereas one 200 mg vial of sugammadex costs about $100, one vial of neostigmine costs $10, and that can be used with multiple patients. Our sugammadex costs are now disrupting our pharmacy's budget because people are using it so often. In addition, the anesthesiologists frequently use more than one vial per patient as some are now becoming too lazy to titrate their NMBs properly.

Are there costs that are saved because we use so much sugammadex? One has to consider the cost benefit analysis for a weak patient in PACU that requires reintubation. What are the costs of prolonged OR use because the patient took a longer time than anticipated to wake up? What is the cost of the psychological trauma in a patient who is gasping for breath because he is too weak to breathe? Or the patient who is too weak to protect his own airway when extubated too early and she aspirates, requiring hospitalization for pneumonia? All these should be taken into consideration when calculating the cost of using sugammadex.

Are there downsides to sugammadex? I've already mentioned the exorbitant price of the drug. That hopefully will come down in a few years when the drug goes off patent and generics flood the market.

Worse than that though is that I think sugammadex makes anesthesiologists lazy and they lose an essential skill. It's a real art to titrate paralytic agents properly so it can be reversed quickly at the end of a case. It's not something that can be taught in a book since each patient is unique in their ability to metabolize NMBs and every surgical case is different. With sugammadex, it doesn't matter at all. This is particularly detrimental to the anesthesia residents. It is just as easy to wake up a patient with zero twitches as one with four twitches. There is no learning there. Just give more sugammadex! But they didn't learn anything about the art of controlling anesthesia.

This is all part of the long standing trend of making anesthesia ever faster and easier to use. From halothane to desflurane. Pentathol to propofol. Pancuronium to rocuronium. If we're not careful, anesthesia could become too easy to administer. There are plenty of people who would love to get anesthesiologists out of their procedure rooms. From gastroenterologists to cardiologists, having one less physician in the room would be a dream come true. If anybody ever makes reversal agent for propofol, anesthesiologists would soon be unemployed.

My Experience With Propofol Frenzy

The Mayo Clinic Proceedings recently had an informative article on a condition called propofol frenzy. This is a state where propofol has an unintentional effect of causing increased agitation rather than the expected sedation. I wish this article had arrived a few months earlier because I was flummoxed by a patient with the exact same problems.

I had a female patient describe to me how she always goes into "seizures" after getting propofol for endoscopic procedures. I was skeptical of her description and explained to her that propofol actually attenuates seizures and is used to break seizure activity. I should also mention that she says she's allergic to benzodiazepines. Her old anesthesia record didn't document any complications from previous sedations so I assured her I would use as little propofol as possible to get through her procedure.

The endoscopy proceeded without incident and was quickly completed. Postop, she was extremely lethargic, much more than would be expected from a small brief interaction with propofol. After about 20 minutes she started to thrash her head. Then she began trying to get out of bed and then falling hard back onto the mattress. It took four people to hold her down and keep her from injuring herself. The entire time she was not aware enough to answer questions. When we brought her husband in, he said that is pretty much what happens every time.

Finally after about one hour she started to calm down and became responsive to commands. After two hours she was calm but felt too groggy to go home. We finally decided to admit her because of her symptoms. The admitting team even ordered a Neurology consult to rule out seizures. Of course they found nothing.

The Mayo article notes there is no known cause why propofol causes a paradoxic reaction in some people. Maybe it deactivates GABA receptors in some whereas propofol normally activates GABA. But nobody knows for sure. It's not related to the quantity of propofol given. The seizure like activity is not attenuated by adding more drugs like benzos or narcotics.

The only recommendations are to anticipate the symptoms if a patient tells you they get seizures with propofol and to avoid propofol if possible. Perhaps attempt sedation with dexmedetomidine, benzodiazepines, or narcotics if propofol frenzy is a possibility. And always listen to your patients.

Fastest Way To Wake Up A Patient

One thing that anesthesiology residency doesn't teach you is how to quickly and efficiently wake up a patient from general anesthesia. Sure, we all get grilled on the SAFEST method for emergence and extubation. However, in the real world, safe emergence is a given. Therefore to a surgeon what differentiates one anesthesiologist from another is how quickly the patient is transferred to recovery after a case is over. If the patient is still asleep after the surgeon has written the postop orders and finished talking to the patient's family, then you, my friend, are a slow anesthesiologist.

I've noticed this lack of exactitude results in two different philosophies (and possibly three which I will get to later) on how best to quickly wake up a patient. When I come in to the OR in the morning, I do my anesthesia machine check and I can easily see what the anesthesiologist who last used it was thinking about how to awaken the patient.  The machine usually has the last ventilatory setting of the previous patient still in place. From this, I can deduce two methods that are generally followed by anesthesiologists at the end of a case.

One is the slow and go idea for emergence. The vent settings on the machine will show a respiratory rate of about five with tidal volumes below five hundred. I presume the anesthesiologist is attempting to revive the patient's spontaneous respiration by allowing the patient's pCO2 levels to rise quickly. Once the patient is breathing on his own then the endotracheal tube can be removed.

The other method is the fast and furious approach. The vent setting will have the respiratory rate set in the high teens with large tidal volumes. The anesthesiologist was apparently trying to wake up the patient by swiftly blowing off the inhalational agents accumulated in the blood stream and lungs.  Once the patient is conscious, then the ETT can be safely taken out.

I don't think there has been a study on which process for emergence is better. There are just too many variables and either one works satisfactorily.  During residency I had attendings who advocated one or the other technique and the patients did just fine either way. Again the goal of residency training is safety first. But now in the real job market there is no real consensus on the best and fastest plan for emergence. So some unfortunate anesthesiologists get labeled as "slow."

So finally let me tell you about one colleague's practice for achieving fast emergence. I don't advocate his methods but it sure gets the job done. During surgery he gives absolutely no narcotics. He doesn't believe in preemptive analgesia. He thinks any narcotics given during the case will slow down emergence, which is true. His patients wake up in blinding pain from surgery whereupon he gives liberal doses of pain meds. Unfortunately the narcs rarely work rapidly enough before the patient is transferred to recovery. You can imagine the anesthesiologist is not one of the recovery room nurses' favorites when they are confronted with a miserable postop patient. But he gets the room turned over quickly and is thus well liked by the surgeons. Try it if you dare.