Despite strong evidence of the benefits of neuromuscular blockade monitoring and the addition of such monitoring in guidelines in other countries,1 the American Society of Anesthesiologists (ASA) House of Delegates voted against adding it to the ASA Standards for Basic Anesthesia Monitoring in October 2015. Introduction of universal quantitative neuromuscular monitoring in the operating rooms at the University of Iowa met similar resistance before being embraced.2 Part of such resistance may actually be due to the lack of routine monitoring since providers do not have the opportunity to actually observe, in detail, patient-specific onset and recovery after the use of nondepolarizing neuromuscular blocking drugs. This report presents 2 examples of prolonged or unexpected responses to rocuronium, documented by continuous quantitative monitoring, in otherwise completely healthy individuals.
Both patients signed written consent for publication of this report.
The patient was a 39-year-old female, ASA class 1E, weighing 64 kg (body mass index 26 kg/m2) who presented for urgent laparoscopic salpingostomy and salpingectomy for ectopic pregnancy. Her only current medications were folate and a multivitamin, and she had no significant medical history. Transvaginal ultrasound revealed a tubal pregnancy consistent with gestational age by known conception date of 6 6/7 weeks. Preoperative laboratory values were normal, including serum concentrations of sodium, potassium, calcium, and albumin; magnesium concentration was not measured.
Standard monitors were applied. The anesthesia team felt the patient had a full stomach but might have a very short surgery. They planned to perform endotracheal intubation with intense opioid effect rather than neuromuscular blockade, then administer rocuronium only as needed to facilitate laparoscopy. However, the staff anesthesiologist (P.A.L.) did not clarify for the trainee the timing of the first dose of the muscle relaxant. The trainee administered intravenously midazolam 2 mg, lidocaine 100 mg, and rocuronium 5 mg (0.08 mg/kg). The anesthesiologist thought the error was minor and did not intervene. The patient appeared to rest quietly, but postoperatively, she volunteered that she was unable to communicate her sudden difficulty breathing. She then received 100 mg propofol, 150 µg remifentanil, and 25 mg ketamine, and her trachea was intubated without additional administration of rocuronium.
After endotracheal intubation, electromyographic (EMG) neuromuscular blockade monitoring (Datex-Ohmeda ElectroSensor; Datex-Ohmeda Inc, Madison, WI) was implemented, with a continuous graphical display as previously illustrated.2 Both by monitor recording and by manual palpation, the stimuli elicited only a weak response. Due to a known potential for problems with the monitoring system and the lack of a baseline recording,2 the electrodes were replaced. At approximately 17 minutes after the first 5 mg dose of rocuronium, a reproducible, high-quality EMG waveform was obtained, with a train-of-four (TOF) ratio of approximately 0.1. Over the next 22 minutes, the patient’s TOF ratio progressively increased to >0.8; the esophageal temperature decreased from 36.3°C to 36.2°C during this time. The patient received a second 5 mg dose of rocuronium, which caused a decrease of the TOF ratio to 0 (2 twitches). No further rocuronium was administered. The TOF ratio recovered to 0.91, 67 minutes after the second dose; the temperature decreased from 36.2°C to 35.4°C during this time. No neostigmine was given, and tracheal extubation was uneventful. Anesthesia was maintained with propofol, remifentanil, and an end-tidal isoflurane concentration of 0.6% to 0.7% during the entire time EMG was monitored.
The patient was a 54-year-old female ASA class 2 (93 kg, body mass index 34 kg/m2, ideal body weight [IBW] = 57 kg) scheduled to undergo resection of an acoustic neuroma. She did not take any chronic medications and had no significant medical history other than hearing loss. Her perioperative laboratory studies, including serum concentrations of electrolytes, and renal function studies were all normal. After placement of routine monitors, including the EMG neuromuscular blockade monitor, anesthesia was induced with propofol and fentanyl and maintained with desflurane and supplemental doses of fentanyl. End-tidal desflurane concentrations were 6.5% to 7.9% from 58 minutes until 438 minutes after rocuronium, and usually 4.4% to 6.1% during other times when surgical stimulation was less intense. The lowest recorded rectal temperature was 34.8°C early in the case, later rising to 35.8°C. The patient’s TOF ratio before administration of rocuronium was 1.0. After induction of anesthesia, 40 mg rocuronium (0.4 mg/kg: 0.7 mg/kg IBW) was administered to facilitate endotracheal intubation. All twitches disappeared within 2 minutes. One twitch could be elicited 30 minutes after administration of rocuronium, and 4 twitches (with a TOF ratio of 0.2) were elicited 55 minutes after initial dosing. No additional rocuronium was given. Spontaneous recovery of neuromuscular function was extremely prolonged (Figure). At 9.5 hours after rocuronium administration, her TOF ratio was recorded at 0.87 to 0.89; 1.25 mg neostigmine was given, with her TOF ratio increasing to 0.96 after 5 minutes. Another 1.25 mg neostigmine was given, and after another 5 minutes, the TOF ratio was 1.00 to 1.03. End-tidal desflurane concentrations did not change during this time (4.4%), and the patient’s temperature was also stable (35.8°C). Emergence from anesthesia and tracheal extubation was uneventful.
While the ED95 of rocuronium is generally considered to be approximately 0.3 mg/kg, patients with unusual sensitivity to nondepolarizing neuromuscular-blocking drugs in general,3 and rocuronium specifically, have been reported previously.4–6 We describe 2 such cases. What makes this report novel is the minute-by-minute documentation of the course of each patient’s paralysis and the fact that neither patient had any known comorbidities. Without continuous quantitative monitoring, it is unlikely that these unusual responses would have been recognized by the care providers.
The first patient had a pronounced response to a small dose (0.08 mg/kg) of rocuronium, reinforcing published warnings against doses >10% of ED95 in awake patients.7 A repeat dose confirmed the sensitivity to rocuronium. The second patient demonstrated an extremely prolonged recovery after a routine “intubating dose” of drug (0.7 mg/kg IBW). These results cannot be explained by concurrent medications, renal, hepatic, or electrolyte abnormalities, or extreme age. Only a limited contribution might be expected from the early pregnancy8 in the first patient and modest obesity,9 hypothermia,10 and fluctuating desflurane concentrations11 in the second. “Unmasking” of previously undiagnosed myasthenia by nondepolarizing agents has been described.12 However, neither patient had any symptoms consistent with myasthenia, and both had documented TOF ratios of 0.9 or higher in the absence of drug effect (after spontaneous recovery in the first patient and before drug administration in the second). In the second patient, extensive evaluation by a specialist in neurology resulted in no findings consistent with myasthenia.
The Figure is interesting because the observed recovery pattern, in particular the long “plateau period,” does not seem consistent with the expected clearance of rocuronium (even prolonged clearance). However, high-quality EMG data were obtained throughout the case, and neostigmine administration resulted in an abrupt increase in the TOF ratio. This pattern may represent some unusual and unexplained interaction between administered desflurane and rocuronium,13 but further discussion of mechanism would be purely speculative. There are many variables associated with TOF fade, and no other carefully documented comparative information over a comparable time course to allow a more thorough explanation.
Clinicians are clearly aware of the evidence supporting quantitative monitoring, but they seem resistant to its actual use. Similarly, 78% of American anesthesia practitioners affirm that residual paralysis is a public health problem, but 88% quietly exempt themselves, reporting the statistically implausible belief that they have never seen a case.14 We believe that this situation exists because of lack of personal experience with monitored cases such as those reported here (a variation of “out of sight, out of mind”). Without any monitoring at all, both patients (who had spontaneously recovered to TOF ratios of >0.8 by the end of their procedures) would probably have been extubated uneventfully (although the first patient might have been given a much larger dose of rocuronium, with resultant adverse consequences that may or may not have been recognized as relaxant related2). Even with continuous qualitative monitoring, only the unusual responses in the first patient might have been recognized (based on loss of the third and fourth twitches). Four “equal twitches” would have been visible in the second patient within 120 minutes after rocuronium (when her TOF ratio surpassed 0.415). Extensive experience with quantitative monitoring at the University of Iowa suggests that patients such as these (although perhaps with less extreme responses) are more common than many practitioners recognize.
Continuous quantitative neuromuscular monitoring provides insights into the response of our patients to nondepolarizing drugs that is not available otherwise. While there is good evidence that its use can improve patient outcomes, part of its documented benefit on patient outcome may be attributable to improved understanding by care providers of the action of muscle relaxants. E
Name: Paul A. Leonard, MD, PhD.
Contribution: This author helped take care of one of the patients and write and edit the manuscript.
Name: Michael M. Todd, MD.
Contribution: This author helped take care of one of the patients and write and edit the manuscript.
This manuscript was handled by:Hans-Joachim Priebe, MD, FRCA, FCAI.
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