A surgeon's assessment of inadequate neuromuscular antagonism in a case of prolonged neuromuscular blockade.

Evaluation of the degree of neuromuscular blockade by the surgeon using clinical criteria alone is unreliable. We report a case of prolonged neuromuscular blockade lasting 5.5 h, where an additional intra-operative dose of neuromuscular relaxant was given at the request of the surgical team. Possible causes of prolonged neuromuscular antagonism are discussed, as is the importance of neuromuscular assessment prior to the administration of additional neuromuscular blocking agents when receiving a surgeon request for additional neuromuscularblockade.

Introduction

We report a case of residual neuromuscular blockade lasting more than 5 h following an intravenous intubating dose of 50 mg of rocuronium, followed by 10 mg of the same neuromuscular blocking agent given an hour later. We have also discussed possible causes of prolonged neuromuscular antagonism in our patient, the importance of neuromuscular assessment, and the use of post-tetanic count when receiving a surgeon’s request for additional relaxation.

Case Report

An 82-year-old 74 kg woman presented for completion of a right extended hemicolectomy for colonic dysplasia. Her past medical history included long-standing hypertension, obesity, dyslipidemia, type 2 diabetes mellitus, and glaucoma. Her surgical history included bilateral eye procedures for glaucoma, left Achilles tendon repair, and a colonic resection for dysplasia 4 years ago. Outside hospital records describing her prior surgeries could not be obtained. She denied any anesthesia-related complications with her previous procedures, family history of anesthetic complications, or family history of neuromuscular disorders. Her medications at the time of surgery included aspirin, bimatoprost-timolol ophthalmic solution, calcium with vitamin D, dorzolamide ophthalmic solution, ezetimibe, glyburide, hydrochlorothiazide, insulin glargine, lisinopril, pravastatin, and prednisolone ophthalmic solution. The patient received 2 mg of intravenous midazolam pre-operatively, and induction was accomplished with 100 mcg of fentanyl, followed by 150 mg of propofol. Rocuronium 50 mg was then given to facilitate endotracheal intubation. The patient received 0.4 mg of hydromorphone shortly after induction as well as 3 g of ampicillin-sulbactam intravenously. Anesthesia was maintained throughout the case at 1MAC of end-tidal desflurane with 50/50 air and oxygen. Esophageal temperature was kept above 35°C throughout the case using active warming with a forced air warming device.

Our involvement in the case begins at 1.5 h after induction, at which point an anesthesia personnel change occurred. It was noted that 10 mg of rocuronium was given 15 min prior to hand-off communication due to the surgeon’s request for additional relaxation. Monitoring of neuromuscular function was not performed at that time and the surgeon’s assessment was made by tactile feel in the surgical field. Shortly after hand-off, a nerve stimulator (TOF-Watch, Bluestar Enterprises, Omaha NE) was attached over the facial nerve using electrocardiogram pads and it was set to 60 mA, revealing a train-of-four (TOF) count of 0 at the corrugator supercilii. At 1.75 h after induction, TOF count was still 0 and the post-tetanic count (PTC) was 0. The post-tetanic count was determined by 5 sec of 50 Hz tetanic stimulation followed 3 sec later by 1 Hz single stimulation. An additional nerve stimulator was attached over the ulnar nerve giving the same results.

Surgery was completed at approximately 2 h post-induction, and TOF count remained 0 with a PTC of 0. Desflurane was discontinued and an infusion of propofol 25-50 mcg/kg/min was started. A Mapleson F circuit was constructed and the patient was transferred to the post-anesthesia care unit (PACU) while delivering positive pressure ventilation using 100% oxygen. End-tidal desflurane was 0% prior to transportation. Consideration was made for a selective relaxant binding agent (SRBA) such as sugammadex, however, it is not currently available in the United States. On arrival to the PACU, she was hemodynamically stable with a skin temperature of 36.2°C. Laboratory studies were sent with results and reference values as shown in Table 1. The laboratory results were similar to pre-operative values except for serum potassium, which was 3.6 mmol/L pre-operatively. The patient received 40 mEq of intravenous potassium given at 10 mEq/h to correct the hypokalemia. Hepatic enzymes had been assessed within recent months and were found to be within normal limits.

Table 1

Post-operative laboratory results

Mechanical ventilation was initiated and propofol infusion was continued. TOF and PTC monitoring continued every 15 min. At 3.5 h after induction, TOF count was 0, PTC was 1, and no spontaneous respiratory effort was noted. At 4.5 h, TOF count was 1. At 5.5 h, TOF ratio was 90%. Since the TOF-Watch was not placed or calibrated at the beginning of surgery, and due to prolonged neuromuscular blockade, it was decided to give an acetylcholinesterase inhibitor prior to extubation. The patient was given 5 mg of neostigmine with 0.6 mg of glycopyrrolate and extubated without difficulty 10 min later. She demonstrated no signs of respiratory compromise and her recovery was otherwise uneventful.

Discussion

Evaluation of the degree of neuromuscular blockade by clinical criteria alone does not exclude clinically significant curarization.[1] Furthermore, surgical personnel do not routinely evaluate neuromuscular blockade with objective monitoring. Anesthesia personnel should take into consideration the assessment of neuromuscular blockade by the surgical team, but should not administer additional neuromuscular blocking agents based on this assessment alone. Prolonged neuromuscular blockade is rare, but not unique. Similar cases[2-4] have demonstrated that even a single intubating dose of an intermediate-acting neuromuscular blocking agent can cause prolonged neuromuscular blockade, which should mandate the need for neuromuscular assessment every time additional neuromuscular blocking agent is considered. Failure to objectively assess neuromuscular function may result in prolongation of a profound neuromuscular blockade, as was seen in our case. Many factors were considered in attempting to understand our patient’s prolonged blockade. Liver disease could decrease drug metabolism and increase the volume of distribution, which could prolong the duration of action. Renal failure prolongs the duration of action and the effect could range from insignificant[56] to an 84% increase in mean residence time[7] with a 0.6 mg/kg bolus dose.

Women are 30% more sensitive to rocuronium than men.[8] Variability in duration of action doubles in elderly patients receiving rocuronium versus cisatracurium.[9] Hypothermia is also known to prolong the duration of nondepolarizing neuromuscular blockers. Volatile anesthetics may slightly reduce neuromuscular transmission, even in the absence of neuromuscular blockade.[10] Volatile anesthetics prolong the duration of action of neuromuscular blockers and decrease the dose required for blockade.[10-12] Potentiation is greatest with desflurane, followed in order by sevoflurane, isoflurane, halothane, and propofol.[1314]

Antibiotics that are known to potentiate neuromuscular blockade include aminoglycosides, polymyxins, lincomycin, clindamycin, and tetracyclines. There is a long list of drugs that can augment blockade including lithium, local anesthetics, cardiac antidysrhythmics, diuretics, antiestrogens, and magnesium sulfate.

Metabolic and respiratory acidosis may increase neuromuscular blockade. Magnesium imbalance potentiates blockade as does hypokalemia and hypocalcemia.[15]

When assessing a profound neuromuscular blockade, the choice of muscle to monitor as well as the type of stimulation to deliver should be taken into account. The corrugator supercilii is useful as a guide to assess deep blockade when compared to the orbicularis oculi and adductor pollicis muscles.[16-18] Assessment of TOF at the corrugator supercilii better reflects abdominal muscle relaxation.[1619] Post-tetanic count can provide useful information about deep neuromuscular blockade.[20-22] A post-tetanic count of <3 demonstrates over 5-10 min of additional deep blockade with rocuronium, vecuronium, atracurium, or cisatracurium and over 30 min of additional deep blockade with pancuronium.[2324] It is important to note that tetanic stimulation may produce lasting antagonism of neuromuscular blockade at the site of testing, and tetanic stimulation should not be performed more often than every 6 min at a given site.[2025]

It is probable that a single factor cannot explain the prolonged neuromuscular blockade in our patient. These factors include female gender, increased age, mildly reduced renal function, hypokalemia, and the use of desflurane. However, there are many cases of patients with similar compromises who emerge from neuromuscular block without delay. The exact cause of our patient’s prolonged blockade remains unknown and helps to emphasize that neuromuscular assessment should be used for all patients despite the presence or absence of factors that prolong neuromuscular blockade. Figure 1 represents our algorithm to aid in clinical decision making when presented with a surgeon’s perception of inadequate neuromuscular antagonism, leading to a request for additional neuromuscular blocking agent. Given our patient’s presentation, it is very likely that she had profound neuromuscular blockade at the time when additional relaxation was requested. Qualitative confirmation of an appropriate surgical level of relaxation could have been achieved by following our proposed algorithm.

Figure 1

Algorithm for surgeon’s perception of inadequate neuromuscular antagonism

Conclusion

This case illustrates the need to assess neuromuscular function prior to the use of additional neuromuscular blocking agent and not to rely on a surgeon’s perception of inadequate blockade. Numerous factors can lead to prolonged effect of neuromuscular blocking agents including increased age, female gender, renal failure, electrolyte disturbances, and concomitant use of various medications. Train-of-four assessment combined with post-tetanic count can be used to provide objective evidence of profound blockade when the anesthesia provider is presented with perceived inadequate neuromuscular antagonism in the surgical field.