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Regarding sugammadex and residual neuromuscular blockade: I’m aware of two cases of residual neuromuscular blockade which occurred during the past year. Both cases involved obese patients who required emergency reintubation. Both cases were near misses for brain death. Both of these near misses would never have occurred if sugammadex had been used.
The first case was a 50-year-old, 120 kilogram male for an endoscopic retrograde cholangiopancreatography (ERCP). The procedure was to be done in the prone position, and required endotracheal intubation. The intubation was easily performed, and was facilitated with 60 mg of rocuronium for paralysis. The patient was turned prone, and the procedure commenced. After only 15 minutes of operating time, the gastroenterologist announced that the procedure was over. Electrical nerve stimulation of the train of four (TOF) at the facial nerve with a Life Tech Mini Stim showed one twitch. The anesthesiologist injected 5 mg of neostigmine and 1 mg of glycopyrrolate IV, and the patient was turned supine. After ten minutes, the TOF nerve stimulation of the facial nerve showed four equal twitches, and the sevoflurane anesthesia was discontinued. The patient was allowed to return to spontaneous breathing, and he opened his eyes. The trachea was extubated. Within the first two minutes, the patient had inadequate strength for spontaneous respiration. On 100% oxygen via mask, his oxygen saturation dropped from 100% to 80%. 120 mg of succinylcholine was injected IV, and an emergency reintubation was performed. The repeat intubation was more difficult than the original intubation, and required two looks before the trachea was visualized. The nadir oxygen saturation was 60%. The patient was kept asleep for thirty additional minutes, until nerve stimulation at the ulnar nerve showed both TOF and sustained tetany without fade. At that point the trachea was extubated. The patient had no brain damage, and he was discharged home ninety minutes later.
The second case was a 45-year-old, 120 kilogram male with obstructive sleep apnea for a uvulopalatopharyngoplasty (UPPP) and tonsillectomy. The endotracheal intubation was easily done, and was facilitated with 70 mg of rocuronium for paralysis. The surgery lasted 60 minutes. The anesthesiologist injected 5 mg of neostigmine and 1 mg of glycopyrrolate IV fifteen minutes prior to the end of surgery. At the conclusion of surgery, electrical nerve stimulation of the facial nerve with a Life Tech Mini Stim showed four equal twitches in the TOF, and the sevoflurane anesthesia was discontinued. The patient was allowed to return to spontaneous breathing, and opened his eyes. The trachea was extubated. Within the first minute, the patient was awake and breathing, but had jerky breathing pattern and was unable to ventilate himself effectively. On 100% oxygen via mask, his oxygen saturation dropped from 100% to 70%. 200 mg of propofol and 120 mg of succinylcholine were injected IV, and an emergency reintubation was performed. The repeat intubation was more difficult than the original intubation because of blood in the mouth and the oral surgery, and required two looks before the trachea was visualized. The nadir oxygen saturation was 49%. The patient was kept asleep for thirty additional minutes until nerve stimulation at the ulnar nerve showed both TOF and sustained tetany without fade. At that point the trachea was extubated. The patient had no brain damage. He was a planned admission to the hospital, and the remainder of his hospital course was uncomplicated.
Several teaching points are warranted:
- If succinylcholine been used for the intubations, the large intubating doses of rocuronium would have been avoided, and the inadequate reversal of the rocuronium intubating doses would likely not have occurred.
- If smaller doses of rocuronium been used for intubation, the inadequate reversal of the rocuronium intubating doses would likely not have occurred.
- These two cases were done prior to sugammadex availability. In the era of sugammadex, beginning now in 2016, these two near misses should never occur. Sugammadex is a modified γ-cyclodextrin which shows a high affinity for rocuronium and vecuronium. Sugammadex forms a tight inclusion complex with either rocuronium or vecuronium, resulting in rapid reversal of neuromuscular blockade. Sugammadex is able to reverse a moderate profound neuromuscular blockade with a dose of 2.0 mg/kg, and a profound neuromuscular blockade with a dose of 4.0 mg/kg.(1) In my experience, these doses of sugammadex completely reverse rocuronium paralysis within 30-40 seconds. Inadequate neuromuscular blockade reversal should never occur in the era of sugammadex. The past practice of administering neostigmine plus glycopyrrolate to reverse neuromuscular blockade, and then waiting up to ten minutes, is an inferior pharmacologic measure when compared to sugammadex. Reversal with neostigmine plus glycopyrrolate is slow, unreliable, and at times incomplete. While it’s true that a 200 mg ampoule of sugammadex costs approximately $100, that sum of money is trivial when compared to the cost of the lawsuit that would have occurred if either of the two case studies above had resulted in brain death due to delayed or unsuccessful reintubation. In my medical-legal consulting practice I see multiple cases of failed or delayed endotracheal intubations that result in brain death and multimillion-dollar closed malpractice claims.
- Residual neuromuscular blockade cannot always be reliably excluded by using qualitative monitoring such as a Life Tech MiniStim device to monitor TOF. The TOF is monitored by comparing the amplitude of the fourth (T4) to the first (T1) evoked mechanical response at the facial nerve or the ulnar nerve. The T4/T1 ratio, or the TOF ratio, coincides with symptoms of peripheral muscle weakness.At a TOF ratio less than 0.60, signs of muscle weakness and ptosis are easily observed. When TOF ratios recover to 0.70, the majority of patients are able to sustain head lift and eye opening. A very low TOF ratio between 0.1 and 0.5 is easily detected by a qualitative nerve stimulator. However, TOF ratios between 0.5 and 1.0 can be difficult to discern visually. Many clinicians are unable to detect fade when TOF ratios exceed 0.30 to 0.4.(1) Qualitative neuromuscular monitoring of the facial nerve twitch can be deceiving. Applying the peripheral nerve stimulator to the ulnar nerve at the adductor pollicis is the gold standard, and this site must be used for the pre-reversal assessment even when the ulnar nerve and thumb are not accessible intraoperatively. Recovery from neuromuscular paralysis should be present when a TOF count without fade has been confirmed at the adductor pollicis.(2) In a partially paralyzed patient, a visually undetectable fade of the TOF at the facial nerve may coincide with a visually detectable fade in TOF when the ulnar nerve is tested. When a patient’s arms are tucked during surgery, or when the ulnar nerve area is distant from the anesthesiologist’s location, it may be impossible to test ulnar nerve stimulation intraoperatively. Prior to extubation, when the ulnar nerve is accessible, ulnar nerve stimulation will convey a more accurate assay of the level of neuromuscular reversal.
- Immediate reversal of neuromuscular blockade induced by rocuronium is possible with a larger dose of sugammadex of 16 mg/kg. To facilitate intubation, a dose of succinylcholine (1 mg/kg) will cause a neuromuscular blockade of 4 – 5 minutes in duration. If an airway is found to be difficult or if the intubation is found to be impossible, the anesthesiologist has no way to return the patient to spontaneous breathing until these 4 – 5 minutes elapse. To facilitate intubation, a dose of rocuronium (0.5 – 1 mg/kg), if immediately reversed by sugammadex 16 mg/kg, will cause a shorter duration of paralysis than if succinylcholine were used. It remains to be seen whether this fact will lead to increased use of rocuronium rather than succinylcholine in difficult endotracheal intubations in which a potential early return to spontaneous ventilation is deemed prudent.
Healthcare systems are likely to promote selective or infrequent utilization of the new neuromuscular paralysis antidote sugammadex because of its cost. For your practice, and for mine, use the drug when you need it. You’re not personally paying the $100 price for the dose of sugammadex. If you have a serious patient complication because of inadequate neuromuscular reversal by the old drug neostigmine, the adverse patient outcome and the resulting lawsuit may cost you a whole lot more than that $100.
For the record, I have no financial interest or investment in sugammadex. I just know a good product when I see one.
- Murphy GS et al, Reversal (Antagonism) of Neuromuscular Blockade, Chapter 35, Miller’s Anesthesia, 8th Edition, 2015.
- Thilen SR, Qualitative Neuromuscular Monitoring: How to Optimize the Use of a Peripheral Nerve Stimulator to Reduce the Risk of Residual Neuromuscular Blockade, Curr Anesthesiol Rep. 2016;6:164-169.
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Published in September 2017: The second edition of THE DOCTOR AND MR. DYLAN, Dr. Novak’s debut novel, a medical-legal mystery which blends the science and practice of anesthesiology with unforgettable characters, a page-turning plot, and the legacy of Nobel Prize winner Bob Dylan.
In this debut thriller, tragedies strike an anesthesiologist as he tries to start a new life with his son.
Dr. Nico Antone, an anesthesiologist at Stanford University, is married to Alexandra, a high-powered real estate agent obsessed with money. Their son, Johnny, an 11th-grader with immense potential, struggles to get the grades he’ll need to attend an Ivy League college. After a screaming match with Alexandra, Nico moves himself and Johnny from Palo Alto, California, to his frozen childhood home of Hibbing, Minnesota. The move should help Johnny improve his grades and thus seem more attractive to universities, but Nico loves the freedom from his wife, too. Hibbing also happens to be the hometown of music icon Bob Dylan. Joining the hospital staff, Nico runs afoul of a grouchy nurse anesthetist calling himself Bobby Dylan, who plays Dylan songs twice a week in a bar called Heaven’s Door. As Nico and Johnny settle in, their lives turn around; they even start dating the gorgeous mother/daughter pair of Lena and Echo Johnson. However, when Johnny accidentally impregnates Echo, the lives of the Hibbing transplants start to implode. In true page-turner fashion, first-time novelist Novak gets started by killing soulless Alexandra, which accelerates the downfall of his underdog protagonist now accused of murder. Dialogue is pitch-perfect, and the insults hurled between Nico and his wife are as hilarious as they are hurtful: “Are you my husband, Nico? Or my dependent?” The author’s medical expertise proves central to the plot, and there are a few grisly moments, as when “dark blood percolated” from a patient’s nostrils “like coffee grounds.” Bob Dylan details add quirkiness to what might otherwise be a chilly revenge tale; we’re told, for instance, that Dylan taught “every singer with a less-than-perfect voice…how to sneer and twist off syllables.” Courtroom scenes toward the end crackle with energy, though one scene involving a snowmobile ties up a certain plot thread too neatly. By the end, Nico has rolled with a great many punches.
Nuanced characterization and crafty details help this debut soar.
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