Augmentation of the rocuronium-induced neuromuscular block by the acutely administered phenytoin.

BACKGROUND: The effects of an acute administration of phenytoin on the magnitude of the rocuronium-induced neuromuscular block were evaluated. METHODS: Twenty patients (classified as American Society of Anesthesiologists physical status I or II) scheduled for craniotomy were studied: 15 received phenytoin during operation (10 mg/kg), and the others served as controls. Anesthesia was induced with thiopental and fentanyl and maintained with nitrous oxide (65%) in oxygen and end-tidal isoflurane (1%). The ulnar nerve was stimulated supramaximally and the evoked electromyography was recorded using a neuromuscular transmission monitor. Continuous infusion of rocuronium maintained the neuromuscular block with first twitch (T1) between 10 and 15% for 45 min before the start of an infusion of either phenytoin or NaCl 0.9%. Twitch recordings continued for 60 min thereafter. Arterial blood samples were collected at the predefined time points (four measurements before and four after the start of the infusion) to determine the concentrations of phenytoin and rocuronium and the percentage of rocuronium bound to plasma proteins. RESULTS: The first twitch produced by an infusion of rocuronium remained constant during the 15 min before and the 60 min after the start of the saline infusion. After the phenytoin infusion, the twitch decreased progressively, but the plasma concentrations and the protein-bound fraction of rocuronium did not change. CONCLUSION: Phenytoin acutely augments the neuromuscular block produced by rocuronium without altering its plasma concentration or its binding to plasma proteins.

Rocuronium-induced neuromuscular block is affected by chronic carbamazepine therapy.

BACKGROUND: Patients on chronic anticonvulsant drugs are relatively resistant to certain nondepolarizing neuromuscular blockers such as pancuronium, vecuronium, pipecuronium, doxacurium, or metocurine, but not resistant to mivacurium and atracurium. This study investigated the influence of chronic carbamazepine therapy on the neuromuscular block induced by the new muscle relaxant rocuronium. METHODS: Twenty-two otherwise healthy individuals scheduled for neurosurgical operations were studied: 11 of them were on chronic treatment with carbamazepine; the others served as control subjects. The median duration of carbamazepine therapy was 9 weeks (range, 4-312 weeks). After premedication with oral diazepam, anesthesia was induced with fentanyl and thiopental and maintained with nitrous oxide/oxygen and 0.5% inspired isoflurane. Rocuronium, 0.6 mg/kg (2 x ED95), was given for intubation. The ulnar nerve was stimulated, and the evoked electromyogram recorded using a Datex NMT monitor. RESULTS: Based on the response to the first of four stimuli, neither the lag time nor the onset-time differed between the two groups. However, the intervals of recovery to 10%, 25%, 50%, and 75% of the baseline response and the recovery index (RI, 25%-75%) were significantly shorter in patients on chronic carbamazepine therapy. CONCLUSIONS: The authors conclude that the duration of the rocuronium-induced neuromuscular block is significantly shortened by preceding chronic carbamazepine therapy.

Atracurium-induced neuromuscular block is not affected by chronic anticonvulsant therapy with carbamazepine.

BACKGROUND: Patients on chronic anticonvulsant therapy are relatively resistant to some nondepolarizing neuromuscular blockers. Because of the controversial reports on atracurium, the purpose of the present study was to determine the effect of long-term carbamazepine treatment on the neuromuscular block produced by this muscle relaxant. METHODS: Eighteen otherwise healthy individuals scheduled for neurosurgical interventions were studied. Eight patients had received carbamazepine for an average of 41 weeks (range 4-156 weeks) prior to surgery. Ten patients without carbamazepine exposure served as controls. After premedication with oral diazepam, anaesthesia was induced with fentanyl and thiopental and maintained with nitrous oxide and isoflurane in oxygen. Atracurium was given for neuromuscular blockade and the evoked electromyogram (EMG) was recorded with a Datex Monitor NMT. RESULTS: The lag time, the onset time, the duration 10%, 25%, 50%, 75% and the interval 25-75% did not differ between the groups. CONCLUSION: Our results with atracurium differ from previous data demonstrating an influence of carbamazepine therapy on the pharmacokinetics and/or pharmacodynamics of other non-depolarizing muscle relaxants. As documented in this study, atracurium produces adequate neuromuscular block in patients chronically exposed to carbamazepine. Chronic carbamazepine therapy does not influence the onset time and duration of action of atracurium-induced neuromuscular block.

Chronic carbamazepine therapy does not influence mivacurium-induced neuromuscular block.

Patients receiving anticonvulsant drugs chronically are relatively resistant to some non-depolarizing neuromuscular blocking drugs. We investigated the influence of chronic carbamazepine therapy on neuromuscular block induced by mivacurium in 20 otherwise healthy individuals undergoing neurosurgical operations, 10 of whom were receiving chronic treatment with carbamazepine and the other 10 served as controls. The median duration of carbamazepine therapy was 22 weeks (range 4-182 weeks). After premedication with oral diazepam, anaesthesia was induced with fentanyl and thiopentone and maintained with 0.5% isoflurane and nitrous oxide in oxygen. The ulnar nerve was stimulated and the evoked electromyogram recorded using a Datex NMT monitor. Mivacurium 0.15 mg kg-1 (2 x ED95) was given as a bolus i.v. Based on the response to the first of four stimuli, lag time, onset-time, times to recovery to 10%, 25%, 50% and 75% of baseline responses and recovery index (RI 25-75%) did not differ between the two groups. We conclude that mivacurium-induced neuromuscular block was not influenced by preceding chronic carbamazepine therapy.

Pharmacodynamics of mivacurium in severely burned patients.

The pharmacodynamics of mivacurium, a new short-acting non-depolarizing muscle relaxant, were studied in nine severely burned patients with concomitant inhalation injury. Complete neuromuscular blockade was achieved within 1.3 min (controls 3.0 min) following the usually recommended intubating dose (0.15 mg/kg/BW 2 x ED95) of mivacurium. The clinical duration of neuromuscular blockade and the recovery times were slightly prolonged, due to significantly reduced serum cholinesterase activity (clinical duration 24.6 min vs. 15.3 min). This pharmacodynamic profile makes mivacurium preferable for intermittent on-demand neuromuscular blockade in the severely burned patient.