Onset and duration of neuromuscular blockade following high-dose vecuronium administration

To determine the onset time and duration of high doses of vecuronium, 40 ASA Physical Status 1 and 2 patients were randomly assigned to receive either 100, 200, 300, or 400 micrograms/kg of vecuronium bromide for muscle relaxation during elective general surgery. Neuromuscular blockade was continuously quantitated by recording the electromyographic response to stimulation of the ulnar nerve train-of-four. The rate of onset of neuromuscular blockade, endotracheal intubating conditions, duration of neuromuscular blockade, and hemodynamic effects of vecuronium at each dose were evaluated and compared. The time from vecuronium administration to complete abolition of twitch tension (T1 = 0%) decreased from 208 +/- 41 to 106 +/- 35 s as the vecuronium dose was increased from 100 to 400 micrograms/kg (P less than 0.01). Corresponding times to endotracheal intubation (T1 less than 20%) also decreased from 183 +/- 24 to 96 +/- 31 s with increasing doses (P less than 0.01). Recovery time (T1 = 25%) increased from 37 +/- 13 to 138 +/- 24 min with increasing doses (P less than 0.01). No significant hemodynamic differences between the four groups were observed. Endotracheal intubating conditions were good or excellent in all patients. High doses of vecuronium may, therefore, be a useful alternative to succinylcholine when a rapid onset of neuromuscular blockade is required.     

Prolonged paralysis following mivacurium administration

Mivacurium is a benzylisoquinolone, choline-like, non-depolarizing muscle relaxant. Its onset of action is similar to that of atracurium but its duration of action is shorter (approximately 10-15 minutes). Mivacurium is metabolized by plasma cholinesterases at approximately 70% of the rate of metabolism of suxamethonium. Deficiency or abnormality of plasma cholinesterase may cause the duration of action of both suxamethonium and mivacurium to be greatly prolonged. We describe a case of prolonged mivacurium paralysis after day surgery. Laboratory investigations showed a genetic tendency toward abnormal cholinesterase levels, but markedly depressed cholinesterase activity was suggestive of additional acquired causes. This patient had a history of liver disease, malnutrition and anticholinesterase use, which we believe were the most significant factors involved.     

Prolonged neuromuscular blockade following vecuronium infusion

Administration of vecuronium by infusion is an increasingly common technique, both in the operating room and in the intensive care unit (ICU), for patients requiring prolonged neuromuscular blockade and mechanical ventilation. The major advantage of vecuronium over older neuromuscular blocking agents is its rapid excretion and intermediate duration of action. Prior to the current case report, the longest reported continuous paralysis after the cessation of a vecuronium infusion was 90 hours. A case of an 81-year-old patient with renal failure and subclinical chronic cirrhosis of the liver, who remained paralyzed for 13 days following a vecuronium infusion, is described. Intensive monitoring of neuromuscular function is recommended whenever muscle relaxants are administered by continuous infusion.     

Nicorandil accelerates recovery of neuromuscular block caused by vecuronium

PURPOSE: To examine the effect of nicorandil, a K ATP channel agonist, on neuromuscular block caused by vecuronium in patients anesthetized with nitrous oxide, oxygen, isoflurane, and fentanyl. METHODS: Sixty adult patients were allocated to four groups of 15: nicorandil-post-tetanic count (N-PTC), nicorandil-train-of-four (N-TOF), control-post-tetanic count (C-PTC) or control-train-of-four (C-TOF) group. In the N-PTC and N-TOF groups, 0.1 mg kg nicorandil was given as a bolus followed by an infusion at 1 microg x kg(-1) x min(-1). Two minutes after the bolus, 0.1 mg x kg(-1) vecuronium was administered. In the C-PTC or C-TOF group normal saline was given instead of nicorandil. PTC and TOF responses were measured mechanically using a force displacement transducer. RESULTS: Time from the administration of vecuronium to the onset of neuromuscular block in the N-PTC or N-TOF group did not differ from that in the C-PTC or C-TOF group (241 +/- 33 vs 225 +/- 32 sec, mean +/- SD). Times from vecuronium injection to the return of PTC in the N-PTC and C-PTC groups, and those of T1, T2, T3, and T4 (first, second, third, and fourth stimulation of TOF) in the N-TOF and C-TOF groups did not differ. Recoveries of PTC in the N-PTC and C-PTC groups followed similar time course. T1/control twitch height and TOF ratio (T4/T1) in the N-TOF group were higher than those in the C-TOF group 80-120 min and 100-120 min after administration of vecuronium, respectively. CONCLUSION: Nicorandil accelerates recovery of neuromuscular block caused by vecuronium.     

Different F-wave recovery after neuromuscular blockade with pancuronium and mivacurium

We performed this study to assess the recovery period after neuromuscular blockade by electromyographic F-wave analysis, a method that supplies more information about more proximal parts of the motor system than conventionally used methods, e.g., mechanomyography (MMG). In 20 neurosurgical ASA physical status I or II patients anesthesia was induced and maintained with IV fentanyl and midazolam. Patients were randomly assigned to receive either 0.25 mg/kg mivacurium (MV group, n = 10) or 0.1 mg/kg pancuronium (PC group, n = 10) intraoperatively. MMG monitoring of the adductor pollicis muscle was performed continuously. F waves were recorded at the abductor pollicis muscle of the contralateral hand at train-of-four (TOF) ratios of 0.1, 0.25, 0.5, 0.7, 0.75, 0.8, 0.85, 0.9, and 0.95. Recovery of F-wave amplitudes after neuromuscular blockade with pancuronium was significantly slower compared with mivacurium (P = 0.004) during the clinically important recovery period defined by MMG TOF ratios from 0.7 to 0.95. This electrophysiologic finding suggests a differential recovery of the motor system after administration of pancuronium and mivacurium not detected by MMG.     

Neuromuscular blockade following high-dose vecuronium administration

To determine the onset time, duration of action and recovery time of high-dose vecuronium, 70 patients were assigned to receive either 100, 150, 200 or 300 micrograms.kg-1 of vecuronium for muscle relaxation during elective surgery. Neuromuscular blockade was continuously quantitated by recording the EMG response to stimulation of the ulnar nerve. The onset time from the time of vecuronium administration to maximum blockade decreased from 4.6 +/- 1.1 to 2.4 +/- 0.5 min when the vecuronium doses increased from 100 to 300 micrograms.kg-1. Significant differences were observed in the onset time between the 100 micrograms.kg-1 dose and the other dose groups. Endotracheal intubating conditions were excellent in all patients except 3 in the 100 micrograms.kg-1 dose group. The duration of action from the time of injection to 25% recovery increased from 32 +/- 9 to 138 +/- 48 min in a dose dependent manner. The duration of action after increment doses of 40 or 50 micrograms.kg-1 up to 25% recovery of T1 did not vary significantly within the same dose group. With an initial dose of 150 micrograms.kg-1 and subsequent increment doses of 50 micrograms.kg-1 or less, the duration of action remained constant. The recovery time from 25 to 75% recovery was within 11 minutes when antagonists were administered. High-dose vecuronium may, therefore, be a useful alternative to SCC, when a rapid onset is required and to pancuronium, when a rapid recovery from neuromuscular blockade is requested.     

Localized hypothermia influences assessment of recovery from vecuronium neuromuscular blockade

The purpose of this study was to determine the extent to which localized hypothermia of a monitored extremity alters the assessment of recovery from vecuronium- induced neuromuscular blockade. Bilateral integrated evoked electromyographic (IEMG) responses were measured in the ulnar distribution of 14 anaesthetized patients who had differing upper extremity temperatures as measured at the adductor pollicis to determine whether localized hypothermia alters the clinical assessment of spontaneous recovery from vecuronium- induced neuromuscular blockade. All patients received general anaesthesia with thiopentone, N₂O/ O₂ and opioid; 11/14 patients received isoflurane for blood pressure control. Bilateral adductor pollicis, oesophageal and ambient temperatures, and IEMG evoked response (t₁) expressed as percent unparalyzed control were recorded during the anaesthetic. The difference in evoked response between the warmer and the colder upper extremity was calculated at 25%, 50% and 75% spontaneous recovery from neuromuscular blockade in the warm extremity. Differences in temperature between extremities ranged from 0.2–11° C. The difference in IEMG- evoked response between extremities was proportional to the difference in temperature, and there was a direct correlation (r = 0.78) between IEMG response and extremity temperature; IEMG response was absent when extremity temperature was less than 25° C. We concluded that localized hypothermia in the monitored extremity decreases the IEMG- evoked response to vecuronium neuromuscular blockade; the greater the temperature decrease, the less the evoked response. Thus, the administration of nondepolarizing relaxants may be inappropriately influenced by monitoring neuromuscular blockade in a cold extremity, especially if its temperature is <25° C.     

Accelerated onset of vecuronium neuromuscular block with pulmonary arterial administration

The purpose of this study was to determine the onset times of vecuronium neuromuscular block administered into either the central circulation or a peripheral vein. One hundred and twenty adult patients with a pulmonary artery (PA) catheter were randomly divided into one of three groups with respect to the routes of vecuronium administration (n = 40 in each group). Anaesthesia was induced with midazolam 2.5 mg iv and fentanyl 10–50 μg · kg^{? 1} iv and maintained with intermittent doses of fentanyl 50 μg iv and nitrous oxide 60–70% in oxygen. After immobilization of the forearm in a splint, the ulnar nerve was stimulated supramaximally every 12 sec. The resulting force of the evoked thumb twitch was recorded (Myograph 2000, Biometer, Denmark). The times from the injection to the first depression of twitch response (latent onset) in patients given vecuronium 0.08 mg · kg^{? 1} into the pulmonary artery, the right atrium, and a peripheral vein on the hand were 58.0 ± 19.5, 71.5 ± 17.1, and 82.4 ± 18.0 sec (mean ± SD), respectively. The latent onset of neuromuscular block occurred sooner in patients given vecuronium into the central vein than when administered into a vein on the hand (P < 0.01). In comparing the patients given vecuronium into the central vein, the onset times to 95% twitch depression (onset) were 152.3 ± 40.7 and 168.2 ± 35.5 sec. The onset of block was found to be faster when vecuronium was administered into the pulmonary artery than into the right atrium (P < 0.01). These findings suggest that the administration of vecuronium into the pulmonary artery is one approach to accelerate neuromuscular blockade in patients with a PA catheter.     

Unmasked residual neuromuscular block after administration of vecuronium for days

IMPLICATIONS: Significant neuromuscular block may be present in patients who have received vecuronium for days.     

Hypocarbia and spontaneous recovery from vecuronium neuromuscular blockade in anesthetized patients

The effect of hypocarbia on the recovery from the neuromuscular blockade produced by vecuronium was studied in 20 anesthetized patients. Vecuronium was administered until twitch tension was reduced to between 0-15% of control. Neuromuscular function was then allowed to spontaneously recover during continued normocarbia (end-tidal PCO2 5.5 kPa [41 mm Hg]) in half the patients, and in the other half of the patients hyperventilation producing hypocarbia (mean end-tidal PCO2 of 3.1 +/- 0.4 kPa SD [23 +/- 3 mm Hg] at the completion of twitch force recovery) was initiated at the beginning of spontaneous recovery from neuromuscular blockade. The mean vecuronium recovery index (time for spontaneous recovery from 25-75% of control twitch tension) was slightly but not significantly shorter in the hyperventilated patients (8.4 +/- 1.8 min SD) than in the normally ventilated patients (10.4 +/- 3.4 min SD). We conclude the vecuronium recovery index in anesthetized patients is not significantly changed by hyperventilation with hypocarbia when induced at the beginning of recovery from neuromuscular blockade.     

Edrophonium requirements for reversal of deep neuromuscular block following infusion of mivacurium

Mivacurium is a new non-depolarizing muscle relaxant consisting of three stereoisomers. The two active isomers (cis-trans andtrans-trans) undergo rapid metabolism by plasma cholinesterase (t_1/2 β<2 min). Due to its rapid elimination, the need for reversal of mivacurium-induced neuromuscular block is controversial, and to date there have been no studies evaluating reversal of deep blocks. The object of the current investigation was to establish the lowest effective dose of edrophonium required to reverse deep mivacurium-induced neuromuscular block. One hundred ASA Class I and II patients undergoing outpatient surgery in two teaching institutions were studied in this randomized, placebo-controlled double-blind trial. Under balanced propofol/nitrous oxide/alfentanil anaesthesia, a continuous infusion of mivacurium was adjusted to maintain between 5– 10% of control T₁ amplitude. Upon completion of surgery, neuromuscular block was reversed by injecting normal saline (Group PLAC), edrophonium 0.125 mg · kg^{? 1} (Group EDR- 1), 0.25 mg · kg^{? 1} (Group EDR- 2), or 0.50 mg · kg^{? 1} (Group EDR- 3), in addition to a corresponding dose of atropine. 4Spontaneous recovery, from a T₁ response of<10% to a TOF ratio ≥0.7, required 13.5 ± 2.6 min (PLAC Group). In comparison, patients in the EDR- 1 group required 9.2 ± 2.6 min (P < 0.01). Higher doses of edrophonium conferred no advantage. Four patients (4%) had not achieved a TOF ratio of ≥ 70%, 20 min after reversal, and required additional edrophonium. Two patients (PLAC group), had dibucaine numbers and cholinesterase levels consistent with an E^UE^A genotype, whereas the two patients with delayed recovery in the EDR- 1 group had characteristics of a normal genotype. We conclude that a very low dose of edrophonium (0.125 mg · kg^{? 1}) hastens reversal of deep mivacurium-induced neuromuscular block by approximately four minutes, and that edrophonium doses exceeding 0.125 mg · kg^{? 1} provide no additional benefit. Heterozygous patients with atypical plasma cholinesterase levels, as well as certain individuals with normal dibucaine numbers and plasma cholinesterase activity, are at risk for prolonged neuromuscular block, but the block is easily reversed with edrophonium.     

Neostigmine requirements for reversal of neuromuscular blockade following an infusion of mivacurium

Purpose

To study the efficacy of neostigmine compared with placebo for the antagonism of neuromuscular blockade at the end of a mivacunum infusion, and to determine its optimal dose.

Methods

One hundred adult patients undergoing an elective surgical procedure received a standardized anaesthetic with 20–30 mg·kg^?1 alfentanil, a propofol infusion and nitrous oxide. Muscle relaxation was maintained at 90–95% T1 depression with 0.2 mg·kg^?1 mivacunum followed by an infusion. Neuromuscular blockade was measured with an integrated evoked electromyogram in response to train-of-four (TOF) stimuli at the ulnar nerve every 20 sec. Patients were randomized into four groups. At the end of surgery, the mivacunum infusion was stopped and patients received. immediately, in a double-blind manner, neostigmine (10, 20. or 40 mg·kg^?1) or placebo according to a random number table. The Tl and TOF ratio were recorded until adequate recovery of neuromuscular function (TOF ratio > 0.70). During the reversal penod, non-invasive blood pressure and heart rate were recorded every minute. The incidence of postoperative nausea and vomiting (PONV) was recorded in the recovery room.

Results

Data from 94 patients who completed the protocol were analysed. Compared with placebo, neostigmine 10 gmg·kg did not reduce the time to TOF > 0.70 (17.0 ± 5.1 vs 14.6 ± 4.2 mm respectively). However the time was decreased with neostigmine 20μg·kg and 40 μ·?^?1 (P < 0.001), but with no difference between these last two groups (11.4 ± 3.0 and 11.4 ± 3.5 min respectively). Changes in systolic blood pressure and heart rate were not different between the four groups. Very few PONV events were observed in all groups (global incidence 7.4%).

Conclusion

Recovery of neuromuscular blockade following a mivacunum infusion is accelerated by neostigmine. A dose of neostigmine 20μ·kg^?1 appears optimal with no further reduction in recovery time obtained from a larger dose.     

Delayed recovery of vecuronium neuromuscular block in diabetic patients during sevoflurane anesthesia

PURPOSE: To study recovery from vecuronium-induced neuromuscular block in diabetic patients during total iv or sevoflurane anesthesia. METHODS: 30 diabetic patients were assigned to diabetes mellitus (DM)-total iv anesthesia (TIVA); (n = 15) or DM-sevoflurane (S) groups (n = 15). Thirty healthy patients were divided into control-TIVA (n = 15) or control-S groups (n = 15). In the DM-TIVA or control-TIVA groups and DM-S or control-S groups, anesthesia was maintained with propofol and fentanyl, and nitrous oxide-oxygen-sevoflurane 1.7%, respectively. After receiving vecuronium 0.1 mg.kg(-1)iv, recovery of the train-of-four (TOF) was compared among the four groups. RESULTS: Times to the return of T2, T3, or T4 in the DM-TIVA and DM-S groups were longer than in the control-TIVA and control-S groups (46.9 +/- 13.8 vs 32.2 +/- 10.7 and 32.6 +/- 8.7 min for T2, P < 0.05). T1/control in the DM-S group was less than in the control-TIVA and DM-TIVA groups 50 to 120 and 70 to 120 min after receiving vecuronium, respectively (P < 0.05). T1/control in the control-S group was less than in the control-TIVA group 80 to 120 min after receiving vecuronium (P < 0.05). TOF ratio in the DM-S group was less than in the control-TIVA, DM-TIVA, and control-S groups, 60 to 120, 80 to 120, and 80 to 120 min after receiving vecuronium, respectively (P < 0.05). CONCLUSION: In diabetic patients receiving vecuronium, recovery of T1/control and TOF ratio are delayed during sevoflurane anesthesia, but not in association with total iv anesthesia.