Anesth Analg 2002;94:123-124
© 2002 International Anesthesia Research Society
ANESTHETIC PHARMACOLOGY
Prolongation of Rapacuronium Neuromuscular Blockade by Clindamycin and Magnesium
Paul A. Sloan, MD, and
Mazhar Rasul, MB
University of Kentucky College of Medicine, Lexington, Kentucky
Address correspondence to Paul A. Sloan, MD, Department of Anesthesiology, University of Kentucky Hospital, 800 Rose Street, Lexington, KY 40536. Address e-mail to PaulSloan{at}prodigy.net
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Abstract
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Rapacuronium was developed as an ultra-short acting nondepolarizing neuromuscular blocker allowing tracheal intubation at 90 s, yet still permitting reversal at a mean of 14 min after administering an intubating dose (1). The duration of blockade is slightly prolonged by the use of inhaled anesthetics, aminoglycosides, clindamycin, magnesium, and pregnancy (2). In general, the effect of rapacuronium is only prolonged by a few minutes in parturients (3).
The purpose of this report is to record the first rapacuronium neuromuscular block significantly prolonged by concomitant clindamycin and magnesium when rapacuronium was used to facilitate general endotracheal anesthesia in a patient for emergency cesarean delivery.
IMPLICATIONS: We report a prolonged neuromuscular block with the nondepolarizing muscle relaxant rapacuronium in the presence of clindamycin. Even when using "short-acting" muscle relaxants, the anesthesiologist must routinely monitor the neuromuscular function.
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Case Report
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A 25-yr-old woman, G2P0, with a history of pregnancy-induced hypertension (PIH) required emergency cesarean delivery of a 29-wk-old fetus suffering with severe intrauterine growth retardation. Her medical history was unremarkable apart from penicillin allergy. She presented to the hospital without prior obstetrical care, receiving no medications apart from vitamins, and with a new diagnosis of pregnancy-induced hypertension. Treatment of her preeclampsia included IV magnesium sulfate 2 gm/h and inhalation of oxygen via a mask.
The patient weighed 60 kg and was 155 cm tall. Vital signs revealed an arterial blood pressure of 121/88 mm Hg, pulse of 96 bpm, and respiratory rate of 14 breaths/min. Fetal monitoring revealed repeated and prolonged late decelerations. Pertinent laboratory findings were a hematocrit of 38%, platelet count of 205,000 cells/mL3, and partial thromboplastin time of 35 s.
The patient was taken to the operating room for emergency cesarean section. General anesthesia was administered because there was inadequate time to perform regional anesthesia. Standard monitoring was used, including ulnar nerve stimulation for neuromuscular monitoring and temperature probe. Anesthesia was induced with thiopental 300 mg and lidocaine 80 mg, and tracheal intubation (rapid sequence) was facilitated by administration of rapacuronium 100 mg IV. This reduced dose (1.7 mg/kg) of rapacuronium was used because of the additive neuromuscular blocking effect of magnesium given to the patient. Anesthesia was maintained with desflurane 4%–6%, 50% nitrous oxide in oxygen, and fentanyl 50 µg after delivery of the baby. End-tidal CO2 was maintained at 34 mm Hg and esophageal temperature was 35.6°C. Magnesium sulfate at 2 gm/h was continued throughout the case.
Fifteen minutes after rapacuronium bolus, neuromuscular block was starting to lessen with 1 twitch visible on the ulnar nerve train-of-four (TOF). At the request of the surgeon clindamycin 900 mg was then given IV over 15 min to the patient. Surgery was completed uneventfully at 45 min postinduction. After clindamycin therapy there was no longer any muscle twitch visible with TOF stimulation, including tetany, of the ulnar nerve. Anesthesia was therefore continued with 50% nitrous oxide in oxygen, and midazolam 1 mg IV was given. TOF monitoring of the ulnar nerve showed 1 twitch returning at 80 min after rapacuronium induction bolus. At 90 min after the rapacuronium bolus, 2 twitches were noted on the ulnar nerve TOF monitor. Neostigmine (4 mg) reversal was then given, along with glycopyrrolate 0.8 mg, the TOF returned to 1.0 and the patient emerged from anesthesia uneventfully. Her trachea was extubated easily and her postoperative course was smooth.
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Discussion
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Rapacuronium bromide is a nondepolarizing neuromuscular blocking drug with a rapid onset (90 seconds) and with a short duration of action. The drug is metabolized to an active metabolite, Org 9488, that is more potent and longer acting than the parent compound (3). Nonetheless, the time to reversal of neuromuscular blockade is, on average, 12–16 minutes (1). It has a high clearance (0.6 L · h-1 · kg-1) and is generally devoid of cardiovascular side effects. The clinical duration of a rapacuronium block may be prolonged a few minutes with the use of volatile anesthestics (4) and in pregnant women (3). There is no case report, however, of a prolonged blockade with rapacuronium as occurred with our patient.
We report the first case of a significantly prolonged neuromuscular block from rapacuronium by clindamycin. At 15 minutes after rapacuronium bolus dose, some recovery of neuromuscular function was noted. This would suggest that neither the pregnant condition nor the use of IV magnesium infusion had significantly affected the rapacuronium block. As soon as clindamycin antibiotic was given, an evoked response to peripheral nerve stimulation was no longer detectable. This implies that the clindamycin was most responsible for the block prolongation. We could not find any case report of prolongation of rapacuronium motor block by either clindamycin or a clindamycin/magnesium sulfate combination. The use of routine neuromuscular monitoring is strongly encouraged even when "short-acting" nondepolarizing muscle relaxants are used as a single bolus.
IV aminoglycosides potentiate nondepolarizing neuromuscular-blocking drugs (5). At clinically relevant doses, the penicillins, cephalosporins, tetracyclines, and erythromycin are apparently devoid of effects at the neuromuscular junction (6). However, clindamycin, a macrolide antibiotic resembling erythromycin in antimicrobial activity, prolongs nondepolarizing muscle relaxants such as pancuronium (7), vecuronium (8), and it has also been found to produce profound neuromuscular blockade even when administered in the absence of any detectable neuromuscular block (9). Al Ahdal and Bevan (9) reported a profound neuromuscular block from an overdose of 2400 mg of clindamycin that was given to a patient who had fully recovered (TOF of 1.0) from succinylcholine. Our patient received a relatively large dose of clindamycin 15 mg/kg that prolonged our rapacuronium block by approximately 65 minutes. The mechanism of clindamycin-induced neuromuscular block is not fully understood; however, it appears to cause muscle relaxation predominantly by a direct action on muscle contractility, rather than by inhibition of neuromuscular transmission (9). It is unclear whether clindamycin would have prolonged the effect of succinylcholine if it had been used in our patient because the interaction, if any, between clindamycin and succinylcholine is unknown.
Magnesium increases the potency of both depolarizing and nondepolarizing muscle relaxants (10). For this reason, a reduced dose of rapacuronium 1.7 mg/kg was chosen to aid intubation rather than a typical dose of 2.5 mg/kg as studied by Abouleish et al. (3). Because the TOF showed return of neuromuscular function at 15 minutes postrapacuronium, we do not believe that the magnesium infusion significantly prolonged the block in our patient.
When general anesthesia is given for cesarean delivery, it is imperative that control of the airway with endotracheal intubation proceeds quickly. Succinylcholine has been the "gold standard" to aid rapid-sequence induction in obstetrics, yet it has many undesirable side effects such as cardiac dysrhythmias. Rapacuronium has been compared with succinylcholine for cesarean delivery and it has been found to provide similar and excellent intubating conditions (3).
In summary, clinical doses of clindamycin may significantly prolong the neuromuscular blockade of "short-acting" nondepolarizing muscle relaxants when used in the presence of inhaled anesthetics and magnesium. This requires vigilance and routine monitoring of the neuromuscular junction by the anesthesiologist.
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References
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Accepted for publication August 15, 2001.
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Abstract
Case Report
