Train-of-four Response Research Articles

Randomised controlled trial comparing cisatracurium and vecuronium infusions in a paediatric intensive care unit

To evaluate and compare the efficacy, infusion rate and recovery profile of vecuronium and cisatracurium continuous infusion in critically ill children requiring mechanical ventilation. Prospective, randomised, double-blind, single-centre study in critically ill children in a paediatric intensive care unit in a tertiary children's hospital. Thirty-seven children from 3 months to 16 years old (median 4.1 year) were randomised to receive either drug; those already receiving more than 6 h of neuromuscular blocking drugs were excluded. The Train-of-Four (TOF) Watch maintained neuromuscular blockade to at least one twitch in the TOF response. Recovery time was measured from cessation of infusion until spontaneous TOF ratio recovery of 70%. The cisatracurium infusion rate in nineteen children averaged 3.9+/-1.3 microg kg(-1) min(-1) with a median duration of 63 h (IQR 23-88). The vecuronium infusion rate in 18 children averaged mean 2.6+/-1.3 microg kg(-1) min(-1) with a median duration of 40 h (IQR 27-72). Median time to recovery was significantly shorter with cisatracurium (52 min, 35-73) than with vecuronium (123 min, 80-480). Prolonged recovery of neuromuscular function (>24 h) occurred in one child (6%) on vecuronium. Recovery of neuromuscular function after discontinuation of neuromuscular blocking drug infusion in children is significantly faster with cisatracurium than vecuronium. Neuromuscular monitoring was not sufficient to eliminate prolonged recovery in children on vecuronium infusions.

Duration of vecuronium-induced neuromuscular block can be predicted by change of skin temperature over the thenar muscles.

The purpose of this study was to clarify the relationship between skin temperature over the thenar muscles and the duration of action of vecuronium measured acceleromyographically at the thumb in anesthetized patients. In 15 patients undergoing elective open abdominal surgery under propofol, fentanyl, and nitrous oxide anesthesia, train-of-four (TOF) stimuli were delivered over the ulnar nerve at 2 Hz every 15 s, and the degree of neuromuscular block was measured acceleromyographically at the thumb. Each patient received an intubating dose of vecuronium 0.1 mg x kg(-1), followed by maintenance doses of 0.02 mg x kg(-1) administered repeatedly whenever the first twitch of TOF responses had recovered to 25% of control. The interval between maintenance doses was defined as the clinical duration (DUR25). The median values of skin temperature (ST) over the ipsilateral thenar muscles and esophageal temperature (ET) were recorded during the action of the first and all subsequent maintenance doses. The relationships between change in temperature and change in DUR25 were analyzed. Whereas ET showed only minor changes (median, -0.3 degrees C), ST fluctuated markedly between +0.9 degrees and -6.3 degrees C (median, -1.4 degrees C). Increase and decrease were also seen in a series of DUR25s, as expected from the changes in ST. The median values of DUR25 produced by the first and last maintenance vecuronium doses were 21.5 and 32.3 min, respectively. A negative linear correlation was found between the change in DUR25 and that in ST, demonstrating that DUR25 increased by 20% of baseline with each 1 degrees C decrease in ST. Our results show that peripheral ST decreases considerably during open abdominal surgery without reduction in core temperature, and the decrease contributes to the potentiation of neuromuscular block in the periphery during propofol, fentanyl, and nitrous oxide anesthesia.

Acceleromyography of the orbicularis oculi muscle I: significance of the electrode position.

This study aimed to establish the best position of the stimulating electrodes for facial nerve stimulation during acceleromyographic monitoring from the orbital part of the orbicularis oculi muscle. In 59 anaesthetised patients, an acceleration transducer was positioned over the middle of the eyebrow. In 47 patients, supramaximal train-of-four (TOF) stimulation was established for four electrode pairs with different positions along the facial nerve and behind the ear. The electrode pair with the lowest, the intermediate, and the highest supramaximal stimulating current based on first response (T1) in TOF was found in each patient. A possible response from direct muscle stimulation was evaluated during complete vecuronium block. In 12 patients, supramaximal stimulation was established using a stimulation sequence different from the one used in the first part of the study. The best positions for the stimulating electrodes were either with both electrodes just lateral to the eye, or with one electrode lateral to the eye and one in front of the ear. In most patients, supramaximal stimulation was obtained at these positions at 20-60 mA. However, in 10-21% of the patients, supramaximal stimulation could not be obtained. During complete block, 1-4 responses with a twitch height of 3-11% were recorded in 80% of the patients. The best placements of the stimulation electrodes are either just lateral to the eye or along the zygomatic arch. However, supramaximal stimulation may often not be obtainable, and activation of other facial muscles may be a confounding factor that may impede correct evaluation of the degree of neuromuscular block.

Predicting recovery from deep neuromuscular block by rocuronium in children and adults

Study Objective: To compare the response to motor nerve stimulation at a rate of 1 Hz after 50 Hz tetanus [posttetanic count (PTC)] and 2 Hz for 2 seconds [train-of-four (TOF)] in children and adults during spontaneous recovery from blockade caused by rocuronium. Design: Prospective, clinical, observational, multicenter study. Setting: Operating rooms of two university hospitals. Patients: 22 children (ASA physical status I and II) aged 2 to 5 years, scheduled to undergo dental treatment and 20 adults aged 18 to 60 years, scheduled to undergo elective general or orthopedic surgery during general anesthesia with tracheal intubation. Measurements: Neuromuscular blockade was evaluated with accelerometry of the thumb, using PTC and TOF stimulation of the ulnar nerve, in patients who received rocuronium 1 mg · kg −1. Main Results: The first response to posttetanic and TOF nerve stimulation appeared earlier in children than in adults. The time from injection of rocuronium to appearance of the fourth response to TOF ranged from 27 to 62 minutes in children and from 37 to 94 minutes in adults. The average interval between the appearance of a posttetanic response and the first detectable response to TOF stimulation (T1) was also shorter in children, 7 minutes, than in adults, 16 minutes. The relationship between PTC and the time interval between a given PTC and the first detectable TOF response in both children and adults was exponential (R = −0.64 and R = −0.81, respectively). Conclusions: Children recover faster than adults from neuromuscular blockade after administration of 1 mg · kg −1 rocuronium. The relationship between PTC and time to first response to TOF is exponential both in children and adults during recovery from neuromuscular blockade caused by rocuronium.

The interpretation of train-of-four monitoring in intensive care: what about the muscle site and the current intensity?

To investigate the effect of current intensity and choice of the stimulated muscle group on train-of-four (TOF) interpretation in the intensive care unit (ICU). Intervention study in a surgical intensive care unit. 13 ventilated patients requiring prolonged muscle relaxation. Prior to blockade TOF responses of left and right orbicularis oculi, adductor pollicis, and plantar flexors were recorded by setting the current intensity at 20, 40, 60, and 80 mA. The minimal current intensity (MCI) providing a supramaximal response was then identified for each muscle. Cisatracurium was then infused aiming to continuously observe a TOF at 2/4 on the left orbicularis oculi at 40 mA. The responses to TOF on all the muscle sites were further recorded at 40, 60, and 80 mA when the endpoint was reached for the first time, and after a 48-h infusion. After cessation of infusion the delay to observe 4/4 responses at TOF was recorded at each site at 40 mA or at MCI if MCI was above 40 mA. MCI did not differ between muscle groups. When the fixed endpoint was reached for the first time on left orbicularis oculi, the TOF response at 40 mA on right orbicularis oculi differed significantly. In contrast, no difference was observed between left and right sides at 40 mA at the other sites, nor at any sites at 60 and 80 mA. The TOF response on orbicularis oculi (left and right sides together) was different at 40 mA, compared to 60 and 80 mA. TOF responses at orbicularis oculi at 60 or 80 mA significantly differed from responses on adductor pollicis or plantar flexor, orbicularis oculi being less sensitive to cisatracurium than adductor pollicis or plantar flexor. After a 48-h infusion the same differences in sensitivities were observed between the muscle groups. At any current intensity the recovery was slower at adductor pollicis than at orbicularis oculi or plantar flexor. For a good TOF interpretation in the ICU the current intensity should be tested before onset of blockade. The orbicularis oculi is less sensitive to cisatracurium than adductor pollicis and plantar flexor both at onset and after a prolonged infusion. The recovery from relaxation is faster on orbicularis oculi and plantar flexor than on adductor pollicis.

Monitoring and reversal of neuromuscular block

Methods of monitoring and reversing neuromuscular blocking agents to avoid residual neuromuscular block are described. Studies have shown that if a long-acting neuromuscular blocking agent is used during anesthesia, the frequency of residual block, regardless of the method of neuromuscular monitoring, will be at least 20%. In the past 20-25 years, anesthesiologists have come to use some form of nerve stimulation to monitor the degree of residual neuromuscular block; there are various patterns of stimulation, including train-of-four (TOF) stimulation and double-burst stimulation (DBS). For both TOF stimulation and DBS, the response to the stimuli in a series fades such that the last response can be expressed as a ratio of the first. The fade to DBS is the same as that to TOF stimulation. Clinicians can clinically detect a fade in TOF response when the TOF ratio is <0.5. Fade to DBS is easier to detect than that to TOF stimulation, but, as the block recovers, the anesthesiologist's ability to detect fade decreases. Although anesthesiologists have accepted a TOF ratio of at least 0.7 as the standard, studies of vecuronium neuromuscular block have shown an impaired ventilatory response to hypoxemia and the possibility of increased risk of aspiration until the TOF ratio recovered to 0.9. The use of pancuronium and a persistent TOF ratio of 0.7 in the postanesthesia care unit was shown to be associated with a threefold greater occurrence of postoperative pulmonary complications compared with vecuronium or atracurium. Spontaneous recovery from neuromuscular block occurs through redistribution, metabolism, or buffered diffusion, but recovery can be accelerated by administration of anticholinesterase agents, such as neostigmine and edrophonium. Studies suggest that even intermediate-duration agents should be reversed. Rapacuronium is a new investigational drug with similar onset characteristics to succinylcholine and, if reversed early, similar recovery characteristics. Postoperative residual neuromuscular block is frequent, dangerous, and difficult to recognize clinically. The action of neuromuscular blocking agents should always be reversed unless there is unequivocal evidence of adequate function.

Monitoring and reversal of neuromuscular block.

Methods of monitoring and reversing neuromuscular blocking agents to avoid residual neuromuscular block are described. Studies have shown that if a long-acting neuromuscular blocking agent is used during anesthesia, the frequency of residual block, regardless of the method of neuromuscular monitoring, will be at least 20%. In the past 20-25 years, anesthesiologists have come to use some form of nerve stimulation to monitor the degree of residual neuromuscular block; there are various patterns of stimulation, including train-of-four (TOF) stimulation and double-burst stimulation (DBS). For both TOF stimulation and DBS, the response to the stimuli in a series fades such that the last response can be expressed as a ratio of the first. The fade to DBS is the same as that to TOF stimulation. Clinicians can clinically detect a fade in TOF response when the TOF ratio is <0.5. Fade to DBS is easier to detect than that to TOF stimulation, but, as the block recovers, the anesthesiologist's ability to detect fade decreases. Although anesthesiologists have accepted a TOF ratio of at least 0.7 as the standard, studies of vecuronium neuromuscular block have shown an impaired ventilatory response to hypoxemia and the possibility of increased risk of aspiration until the TOF ratio recovered to 0.9. The use of pancuronium and a persistent TOF ratio of 0.7 in the postanesthesia care unit was shown to be associated with a threefold greater occurrence of postoperative pulmonary complications compared with vecuronium or atracurium. Spontaneous recovery from neuromuscular block occurs through redistribution, metabolism, or buffered diffusion, but recovery can be accelerated by administration of anticholinesterase agents, such as neostigmine and edrophonium. Studies suggest that even intermediate-duration agents should be reversed. Rapacuronium is a new investigational drug with similar onset characteristics to succinylcholine and, if reversed early, similar recovery characteristics. Postoperative residual neuromuscular block is frequent, dangerous, and difficult to recognize clinically. The action of neuromuscular blocking agents should always be reversed unless there is unequivocal evidence of adequate function.

Twitch augmentation and train-of-four fade during onset of neuromuscular block after subclinical doses of suxamethonium

We have studied the train-of-four (TOF) response mechanomyographically during onset of neuromuscular block produced by subclinical doses of suxamethonium in order to follow the augmentation of the first twitch of the TOF (T1) and TOF fade compared with control TOF responses before the drug was given. In the groups given suxamethonium 0.05, 0.1, 0.2 and 0.3 mg kg-1, the increments in T1 after administration of the drug were observed before twitch depression occurred; these were mean 22.3 (SEM 8.1)%, 19.2 (3.3)%, 10.8 (2.0)% and 4.2 (2.2)%, respectively. This effect was more marked with the lower doses (P < 0.05). The degree of TOF fade was moderate during onset of neuromuscular block and depended on the dose of drug. The results of this study suggest that low doses of suxamethonium produced transient increase in muscle tension and twitch depression with significant TOF fade. We conclude that suxamethonium was associated with presynaptic effects as a consequence of brief stimulation of acetylcholine release followed by progressive diminution at the neuromuscular junction.

Sequestration of vecuronium bromide during extremity surgery involving use of a pneumatic tourniquet

We hypothesized that sequestration of a neuromuscular blocking agent could occur during surgery involving use of an extremity tourniquet and cause changes in neuromuscular function after tourniquet release. Sixteen patients scheduled for total knee replacement were randomized to one of two groups. In Group I, 10 patients were administered 0.1 mg/kg of vecuronium 5 minutes prior to inflation of a pneumatic tourniquet; in Group II, 6 patients were administered 0.1 mg/kg of vecuronium after inflation of the tourniquet. The twitch (T1) and train-of-four (TOF) were analyzed before and after release of the tourniquet, as was the rate of recovery of T1 and TOF. Serial vecuronium plasma levels were drawn during the study. The T1 and TOF responses and the T1 and TOF recovery rates were not significantly different between groups at tourniquet deflation. In Group I, after release of the tourniquet, T1 and TOF recovery rate decreased significantly over a 10-min period (10% +/- 3 to 4% +/- 4 and 0.12 +/- 0.06 to 0.06 +/- 0.04, mean +/- SD, respectively); in Group II, T1 and TOF recovery rate increased significantly over a 10-min period following deflation of the tourniquet (10% +/- 6 to 14% +/- 7 and 0.10 +/- 0.03 to 0.18 +/- 0.02, respectively). Changes in pharmacodynamics were temporally associated with transient but statistically significant changes in vecuronium plasma levels. Overall pharmacokinetics during the study period were comparable between groups. After administration of neostigmine 30-40 micrograms/kg i.v. all subjects in both groups showed complete TOF recovery within 15 min. Sequestration of a bolus dose of vecuronium, by a pneumatic tourniquet, causes transient changes in pharmacokinetics and pharmacodynamics. These changes are of limited clinical importance and do not affect reversibility of neuromuscular block.

Residual Postoperative Paralysis

Based on a train-of-four (TOF) ratio greater than 0.70 as the standard of acceptable clinical recovery, undetected postoperative residual paralysis occurs frequently in postanesthesia care units. In most published studies, detailed information regarding anesthetic management is not provided. The authors reexamined the incidence of postoperative weakness after the administration of long- and short-acting neuromuscular blockers because few, if any, such comparative studies are available. Ninety-one adult patients were studied. In group 1 (mivacurium, n = 35), anesthesia was induced with propofol/ fentanyl and maintained with nitrous oxide, desflurane, and opioid supplementation. The response of the adductor pollicis to ulnar nerve stimulation was estimated by palpating the thumb. Mivacurium (0.20 mg/kg) was administered for tracheal intubation, and an infusion was adjusted to maintain the TOF count at 1. When surgery was completed, the infusion was discontinued. When a second twitch could be detected, 7.0 micrograms/kg atropine and then 0.5 mg/kg edrophonium were administered. At 5 and 10 min, the mechanical TOF response was measured. Additional measurements were recorded if possible. Patients were tracheally extubated and discharged from the operating room when they could respond to verbal commands and no TOF fade was palpable. In group 2 (pancuronium-desflurane anesthesia, n = 29), the protocol was identical to that of group 1, except that 0.07 mg/kg pancuronium was administered for tracheal intubation. Additional increments (0.5 to 1 mg) were given as needed. Antagonism was accomplished with 0.05 mg/kg neostigmine and 0.01 mg/kg glycopyrrolate. In group 3 (pancuronium propofol-opioid, n = 27), the protocol was identical to that of group 2, except that anesthesia was maintained with nitrous oxide and a propofol-alfentanil infusion. In all groups, patients were assessed until a TOF ratio of 0.90 or more was achieved. All of the patients in group 1 had TOF ratios greater than 0.80 on arrival in the postanesthesia care unit. Twenty of 35 patients had TOF ratios 0.90 or more while they were still in the operating room. Thirty-three of 35 patients had TOF ratios 0.90 or more within 30 min of reversal, and this value was reached in all patients by 45 min. Recovery parameters in groups 2 and 3 did not differ from each other. Hence data from these groups were pooled. Fifty-four of 56 patients who received pancuronium had TOF values of 0.70 or more, the remaining two patients had values of 0.6 to 0.7. In contrast to the mivacurium group, however, only four patients achieved a TOF ratio of 0.90 or greater while still in the operating room. Finally, eight of these patients did not achieve this degree of recovery within 90 min of reversal. These results suggest that if nondepolarizing neuromuscular blockers are administered using tactile evaluation of the TOF count as a guide, critical episodes of postoperative weakness in the postanesthesia care unit should occur infrequently even with long-acting relaxants. Nevertheless, if full recovery is defined as return to a TOF ratio of 0.90 or more, then short-acting agents would appear to offer a wider margin of safety.

Sensitivity to Mivacurium in a Patient with Mitochondrial Myopathy

Sensitivity to Mivacurium in a Patient with Mitochondrial Myopathy

An effect of magnesium on neuromuscular function in parturients

Study Objective: To determine the effects of magnesium sulfate on neuromuscular transmission in parturients. Design: Open-label, clinical study. Setting: Preeclamptic patients at a university-affiliated hospital. Patients: 12 pregnant patients, ages 18 to 40 years, with preedampsia or entering preterm labor. Interventions: Patients were treated with magnesium sulfate. Train-of-four (TOF) recordings of the adductor pollicis muscle were obtained before, and 30 minutes after the magnesium sulfate infusion. Measurements and Main Results: Each contractile response in the control TOF showed an increase in the tension developed in response to supramaximal stimulation. The TOF responses after magnesium sulfate did not demonstrate this phenomenon, but rather developed fade. The T 4 T 1 ratios ranged from 0.72 to 0.92. Conclusions: In this patient population, clinically relevant infusions of magnesium sulfate produced significant changes in neuromuscular transmission as manifested by loss of treppe phenomenon and diminished TOF response to ulnar nerve stimulation.

Enzymatic Versus Pharmacologic Antagonism of Profound Mivacurium-induced Neuromuscular Blockade

Mivacurium, a nondepolarizing muscle relaxant, is hydrolyzed by butyrylcholinesterase. The use of butyrylcholinesterase for antagonism of profound mivacurium-induced blockade has not been studied in humans. In part 1 of this two-part study, the authors examined the relationship between the posttetanic count (PTC) and recovery from profound mivacurium-induced blockade. In part 2, an attempt was made to antagonize a quantified level of profound mivacurium-induced blockade using either butyrylcholinesterase, edrophonium, or neostigmine. Eighty-seven ASA physical status 1 or 2 adult patients were given 0.15 mg.kg-1 mivacurium during fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. They were randomly assigned to eight groups. Neuromuscular function was monitored by recording the mechanomyographic response of the adductor pollicis to PTC and train-of-four (TOF) stimulation in all patients except those in group 1 where the TOF was the only pattern used. In part 1, neuromuscular function was allowed to recover spontaneously in ten patients (group 1; control-TOF) until TOF ratio (the amplitude of the fourth evoked response as a fraction of the first evoked response T4/T1) had reached 0.75. The temporal relationship between PTC and the first reaction to TOF stimulation was determined in another 31 patients, and neuromuscular function in 10 of these patients was allowed to recover spontaneously until TOF ratio had reached 0.75. The temporal relationship between PTC and the first reaction to TOF stimulation was determined in another 21 patients, and neuromuscular function in 10 of these patients was allowed to recover spontaneously, until TOF ratio had reached 0.75 (group 2; control-PTC). In part 2, the antagonism of mivacurium-induced profound (PTC > or = 1; groups 3-6) and 90% block (groups 7-8) of twitch height were investigated in another 56 patients. Groups 3 and 7 received neostigmine 0.06 mg.kg-1 whereas groups 4 and 8 received edrophonium 1 mg.kg-1, respectively. Groups 5 and 6 received exogenous human butyrylcholinesterase equivalent to activity present in 25 or 70 ml.kg-1 of human plasma, respectively. Neither butyrylcholinesterase nor edrophonium shortened the times from first PTC response to TOF = 0.75 compared to group 2. Neostigmine resulted in prolongation of recovery time. There was a linear relationship (r = -0.80; P = 0.00001) between PTC and time of onset of TOF response. There appears to be no clinical advantage in attempting to antagonize profound mivacurium-induced neuromuscular blockade.

Optimal stimulating current for train-of-four stimulation in conscious subjects

The purpose of this study was to determine the optimal stimulating current for train-of-four (TOF) monitoring with regard to the return of TOF response and the discomfort associated with TOF. Two variables were examined at 60, 50, 40, 30, and 20 mA: (1) times from administration of vecuronium 80 micrograms.kg-1 to returns of responses to TOF determined accelographically in 75 anaesthetised patients and (2) discomfort associated with TOF in 15 awake volunteers using visual analogue scale (VAS). Times to return of the first response to stimulation at 60, 50, 40, and 30 mA were not different (29.1 +/- 11.2, 30.1 +/- 12.0, 31.9 +/- 12.6, and 35.4 +/- 14.2 min, respectively, mean +/- SD). However, time to the return of the first response elicited at 20 mA (53.7 +/- 21.6) was longer than at higher currents (P < 0.05). Similarly, with regard to the second, third, and fourth responses, the time to the return at 20 mA was longer than at the other currents (P < 0.05). The VAS associated with TOF at 60, 50, 40, 30, and 20 mA were 7.3 +/- 1.9, 6.7 +/- 1.8, 6.0 +/- 2.0, 4.1 +/- 2.1, and 2.7 +/- 2.3, respectively. The VAS at 30 mA was less than at 60 and 50 mA (P < 0.05), and at 20 mA was less than at 60, 50, and 40 mA (P < 0.05). In conclusion it is suggested that, when testing conscious patients, 30 mA is the optimal stimulating current for TOF monitoring because it represents the best compromise of neuromuscular monitoring and patient discomfort.

Comparison of the Infusion Requirements and Recovery Profiles of Vecuronium and Cisatracurium 51W89 in Intensive Care Unit Patients

The selection and administration of neuromuscular blocking (NMB) drugs in intensive care unit (ICU) patients remain controversial.We compared the dose-response and recovery pharmacodynamics of a new intermediate-acting NMB drug, cisatracurium besylate, to the intermediate-acting NMB drug, vecuronium (VEC), in a prospective, randomized, double-blind, multicenter study in critically ill adults. After informed consent, 58 mechanically ventilated ICU patients from five medical centers were randomized to receive either cisatracurium or VEC. Fifty-four of the 58 patients received NMB drugs before entering this study but demonstrated at least partial recovery (>or=to one twitch) in the train-of-four (TOF) response before initiation of the NMB study drug. NMB drug infusion was titrated by peripheral nerve stimulation to maintain at least one twitch in the TOF response. NMB drugs were infused for 1-5 days. After discontinuation of NMB drug infusion, recovery of neuromuscular transmission was monitored with an accelerometer. NMB drug infusion for 28 cisatracurium patients averaged 2.6 +/- 0.2 (mean +/- SEM) micro gram centered dot kg-1 centered dot min-1 with a mean duration of 80 +/- 7 h. After discontinuing cisatracurium administration, recovery to 70% TOF ratio averaged 68 +/- 13 min. The mean infusion rate for 30 VEC patients was 0.9 +/- 0.1 micro gram centered dot kg-1 centered dot min-1 with a mean duration of 66 +/- 12 h. Neuromuscular recovery after VEC averaged 387 +/- 163 min, which was significantly longer (P = 0.02) than that after cisatracurium. Prolonged recovery of neuromuscular function after discontinuation of NMB drug infusion (identified by the primary investigator at each medical center) was reported in two cisatracurium patients and 13 VEC patients (P = 0.002), and occurred despite the routine use of neuromuscular twitch monitoring. Seven VEC and one cisatracurium patients died during the infusion of study drug or within 48 h after discontinuation of the NMB drug infusion. In summary, we found recovery of neuromuscular function after discontinuation of NMB drug infusion in ICU patients is significantly faster with cisatracurium than with VEC. In addition, routine neuromuscular monitoring was not sufficient to eliminate prolonged recovery and myopathy in ICU patients. (Anesth Analg 1995;81:3-12)

Comparison of the Infusion Requirements and Recovery Profiles of Vecuronium and Cisatracurium 51W89 in Intensive Care Unit Patients

The selection and administration of neuromuscular blocking (NMB) drugs in intensive care unit (ICU) patients remain controversial. We compared the dose-response and recovery pharmacodynamics of a new intermediate-acting NMB drug, cisatracurium besylate, to the intermediate-acting NMB drug, vecuronium (VEC), in a prospective, randomized, double-blind, multicenter study in critically ill adults. After informed consent, 58 mechanically ventilated ICU patients from five medical centers were randomized to receive either cisatracurium or VEC. Fifty-four of the 58 patients received NMB drugs before entering this study but demonstrated at least partial recovery (> or = one twitch) in the train-of-four (TOF) response before initiation of the NMB study drug. NMB drug infusion was titrated by peripheral nerve stimulation to maintain at least one twitch in the TOF response. NMB drugs were infused for 1-5 days. After discontinuation of NMB drug infusion, recovery of neuromuscular transmission was monitored with an accelerometer. NMB drug infusion for 28 cisatracurium patients averaged 2.6 +/- 0.2 (mean +/- SEM) micrograms.kg-1.min-1 with a mean duration of 80 +/- 7 h. After discontinuing cisatracurium administration, recovery to 70% TOF ratio averaged 68 +/- 13 min. The mean infusion rate for 30 VEC patients was 0.9 +/- 0.1 micrograms.kg-1.min-1 with a mean duration of 66 +/- 12 h. Neuromuscular recovery after VEC averaged 387 +/- 163 min, which was significantly longer (P = 0.02) than that after cisatracurium. Prolonged recovery of neuromuscular function after discontinuation of NMB drug infusion (identified by the primary investigator at each medical center) was reported in two cisatracurium patients and 13 VEC patients (P = 0.002), and occurred despite the routine use of neuromuscular twitch monitoring. Seven VEC and one cisatracurium patients died during the infusion of study drug or within 48 h after discontinuation of the NMB drug infusion. In summary, we found recovery of neuromuscular function after discontinuation of NMB drug infusion in ICU patients is significantly faster with cisatracurium than with VEC. In addition, routine neuromuscular monitoring was not sufficient to eliminate prolonged recovery and myopathy in ICU patients.

Neuromuscular and haemodynamic effects of mivacurium in elderly and young adult patients

We have studied the neuromuscular effects of mivacurium and changes in heart rate and arterial pressure in 40 elderly (aged 70 yr) and 20 young adult (aged 18-40 yr) patients anaesthetized with thiopentone, fentanyl, nitrous oxide in oxygen and halothane. Neuromuscular block was monitored by train-of-four (TOF) stimulation of the ulnar nerve and recording of the force of contraction of the adductor pollicis muscle using a force displacement transducer and a neuromuscular function analyser (Myograph 2000, Biometer Ltd). Twenty elderly and 10 young adults received single doses of mivacurium 0.15 mg kg-1 and spontaneous recovery was recorded. The other 20 elderly and 10 adults received the same dose but an infusion was started at T1 (first response in TOF) of 10% and the block maintained at this level. Haemodynamic effects were studied after administration of mivacurium over 15 or 5 s in elderly (n = 10 each) and over 5 s in adult (n = 10) patients. Onset of maximum block occurred at a mean time of 122 (SD 32) and 125 (49) s in elderly and young adults, respectively. Recovery of T1 to 25% occurred in 22.0 (5.7) and 17.2 (4.4) min, and T1 to 90% in 32.8 (6.9) and 24.4 (5.8) min in elderly and adult subjects, respectively. Recovery of the TOF ratio to 0.7 occurred in 32.8 (7.1) and 26.0 (15.0) min in the elderly and young subjects, respectively (all P < 0.05 between young and elderly).(ABSTRACT TRUNCATED AT 250 WORDS)

RETRACTED: Effect of tetanic stimulation on subsequent train-of-four responses at various levels of vecuronium-induced neuromuscular block

Tetanic stimulation influences subsequent neuromuscular responses. In addition, the tetanus-induced changes in neuromuscular responses differ according to the level of neuromuscular block at which tetanic stimulation is delivered. We studied the tetanus-induced effect on subsequent train-of-four (TOF) responses at various levels of vecuronium-induced neuromuscular block in 45 anaesthetized patients. Tetanic stimulation was applied when a twitch height of T1 returned to 25%, 50% and 75% of its control twitch height (T0) (groups 1, 2 and 3, respectively) after administration of vecuronium 0.1 mg kg-1. Maximum post-tetanic percentage increases in TOF responses in groups 1, 2 and 3 were 257 (SD 119)%, 107 (75)% and 68 (54)% for T1/T0 (P < 0.001 for group 1 vs 2; P < 0.001 for group 1 vs 3) and 535 (259)%, 421 (213)% and 292 (171)% for T4/T1 (P < 0.01 for group 1 vs 3), respectively. Durations of post-tetanic increases in TOF responses in groups 1, 2, and 3 were 52 (19) s, 37 (14) s and 32 (13) s for T1/T0 (P < 0.05 for group 1 vs 2; P < 0.01 for group 1 vs 3) and 53 (17) s, 46 (15) s and 35 (12) s for T4/T1 (P < 0.05 for group 1 vs 3), respectively. These data suggest that the tetanus-induced effect on subsequent TOF is more apparent and lasts longer at greater degrees than at lesser degrees of neuromuscular block.

The Effect of Hypothermia on Adductor Pollicis Twitch Tension During Continuous Infusion of Vecuronium in Isoflurane-Anesthetized Humans

The effect of total body cooling on force of contraction of the adductor pollicis was determined during a constant rate infusion of vecuronium. Anesthesia was induced with thiopental and maintained with isoflurane/nitrous oxide in eight volunteers (study group) and seven surgical patients (control group). After train-of-four (TOF) stimulation of the ulnar nerve, we measured the amplitude of the first response (T1) in the train and the ratio of the fourth-to-first response (TOF ratio). Vecuronium was then administered as an intravenous (i.v.) bolus, 25 micrograms/kg, followed by continuous i.v. infusion, 25 micrograms.kg-1 x h-1; central body (core) temperature was maintained stable for 60 min, at the end of which T1 and TOF responses were constant. In the study group, core temperature was then reduced (using circulating-water blankets) by a mean of 2.6 degrees C, decreasing the T1 and TOF ratio, respectively, by 19% and 18% per degrees C reduction in adductor pollicis temperature. Normothermia was maintained in the control group for a mean of 111 min, with no significant change in T1 and TOF responses. We conclude that, during a constant-rate infusion of vecuronium, the magnitude of neuromuscular block increases significantly when adductor pollicis temperature decreases secondary to core cooling.

Pharmacodynamic effects of three doses of ORG 9426 used for endotracheal intubation in humans

Study Objective: To determine the pharmacodynamic characteristics of three incremental doses of ORG 9426 used for endotracheal intubation in patients. Design: Double-blind, randomized administration of one of three doses of intravenous ORG 9426. Setting: Inpatients requiring surgery at Georgetown University Medical Center. Patients: Thirty-six patients, ages 18 to 65, ASA physical status I, II, and III, scheduled for general surgery. Interventions: After Georgetown University Institutional Review Board approval and patient consent, patients were premeditated with midazolam or droperidol. Anesthesia was induced with thiopental sodium and fentanyl. Anesthesia was maintained with 60% nitrous oxide in oxygen. The ulnar nerve was stimulated supramaximally with a 2 Hz train-of four (TOF) every 20 seconds. Thumb contractions were measured with a force transducer. When TOF and anesthesia were stable, 2, 2.5, or 3 times the ED 95 of ORG 9426 (570 μg/kg 710 μg/kg or 850 μg/kg) was administered randomly. Tracheal intubation was attempted at maximal depression of the first TOF response (T 1). Measurements and Main Results: The following parameters were measured: time interval from the injection of ORG 9426 to 90% depression of T 1 (T 1 90% block), maximal T 1 depression (onset time), intubating conditions, clinical duration (time for return of T 1 to 25% of control), heart rate (HR), blood pressure (BP), and any adverse clinical experience. ORG 9426 provided adequate intubating conditions in all patients but two, independent of the dose used. Its onset time was rapid, but increasing the dose did not shorten the onset. T 1 90% block was achieved rapidly (75 ± 25 seconds to 78 ± 18 seconds, means ± SD). The clinical duration of ORG 9426 was relatively short and lengthened with increasing doses (from 36 ± 18 minutes at 570 μg/kg to 42 ±10 minutes at 850 μg/kg. Spontaneous twitch recovery from 10% to 25% was similar in all dosage groups (5 ± 1 minutes to 6 ± 4 minutes). No clinically significant changes in HR and BP and no adverse clinical experiences were noted in any group. Conclusion: These findings warrant further clinical evaluation of ORG 9426 for induction and maintenance of muscle relaxation in humans.