Evaluation of intense neuromuscular blockade caused by rocuronium using posttetanic count in male and female patients

STUDY OBJECTIVE: To establish the relationship between train-of-four (TOF) nerve stimulation and the number of posttetanic twitches (posttetanic count [PTC]) during neuromuscular blockade caused by rocuronium in males and females. DESIGN: Prospective, observational, clinical comparison. SETTING: Operating room of a university hospital. PATIENTS: 60 ASA physical status I and II patients (30 women and 30 men), aged 18 to 60 years, who were scheduled for elective orthopedic surgery and ear, nose, throat surgery with a planned duration of 2 hours. INTERVENTIONS; During fentanyl, propofol, and nitrous oxide (N(2)O) anesthesia, neuromuscular blockade was evaluated with accelerometry of the thumb using TOF and posttetanic twitch stimulation (PTTS) of the ulnar nerve in patients who received rocuronium 1 mg.kg(-1). MEASUREMENTS AND MAIN RESULTS: The first responses to PTTS were seen at mean times of 34.9 and 37.7 minutes after rocuronium injection in male and female patients, respectively (NS). The average interval between the appearance of a posttetanic response and the first response to TOF stimulation (T1) was not significantly different between male and female patients (15.4 +/- 4.8 min (SD) vs. 15.9 +/- 4.9 min, respectively). There was a significant negative correlation between PTC and the time to first response to TOF nerve stimulation (r = -0.83; p = 0.0001). Gender did not have a statistically significant effect on this relation (F = 0.9; p = 0.34). The intervals from administration of rocuronium to the first appearances of T1 and T2 were not significantly different between the two groups, but the intervals to the first appearances of T3 and T4 were significantly longer in female patients. CONCLUSIONS: Even though the times from initial administration of rocuronium 1 mg.kg(-1) to the first appearances of T3 and T4 are significantly longer in female patients, the intervals to the first detectable responses to PTTS and TOF are not significantly different between females and males. Gender has no significant effect on the relation between PTC and the time to T1.     

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 x 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 x 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.     

Predicting recovery from deep neuromuscular block by rocuronium in the elderly

STUDY OBJECTIVE:To determine the influence of aging on the relationship between posttetanic count (PTC) and train-of-four (TOF) response during intense neuromuscular blockade caused by rocuronium. DESIGN: Prospective, observational, clinical comparison study. SETTING: Operating room of a university hospital. PATIENTS: 42 ASA physical status I and II patients, 20 of whom were elderly (ages 65 to 80 yrs) and 22 younger control patients (ages 18 to 40 yrs), who were scheduled for elective orthopedic surgery and ear, nose, and throat surgery with a planned duration of 2 hours. INTERVENTIONS: Neuromuscular blockade was evaluated with accelerometry of the thumb, using posttetanic twitch (PTT) and TOF stimulation of the ulnar nerve, in patients who received rocuronium 1 mg x kg(-1). MEASUREMENTS AND MAIN RESULTS: The first responses to posttetanic nerve stimulation were seen at mean times of 38.5 and 35.2 minutes after the injection of rocuronium in the elderly and in the young, respectively (NS). The average interval between the appearance of a posttetanic response and the first response to TOF stimulation (T1) was longer in the elderly than the young (22.3 +/- 8.1 (SD) vs.14.8 +/- 4.2 min, p < 0.05). There was a significant correlation between PTC and the time to first response to TOF nerve stimulation both in the elderly and in the young (r = -0.73, p < 0.0001 and r = -0.87, p < 0.0001, respectively). CONCLUSIONS: Posttetanic twitch stimulation is a useful method of monitoring intense neuromuscular blockade caused by rocuronium in both age groups. The interval between the earliest appearance of a posttetanic response and the first response to TOF stimulation (T1) is greater in the elderly than in the young.     

Early and late reversal of rocuronium and vecuronium with neostigmine in adults and children.

We investigated the influence of the timing of neostigmine administration on recovery from rocuronium or vecuronium neuromuscular blockade. Eighty adults and 80 children were randomized to receive 0.45 mg/kg rocuronium or 0.075 mg/kg vecuronium during propofol/fentanyl/N2O anesthesia. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation and adductor pollicis electromyography. Further randomization was made to control (no neostigmine) or reversal with 0.07 mg/kg neostigmine/0.01 mg/kg glycopyrrolate given 5 min after relaxant, or first twitch (T1) recovery of 1%, 10%, or 25%. Another eight adults and eight children received 1.5 mg/kg succinylcholine. At each age, spontaneous recovery of T1 and TOF was similar after rocuronium and vecuronium administration but was more rapid in children (P < 0.05). Spontaneous recovery to TOF0.7 after rocuronium and vecuronium administration in adults was 45.7 +/- 11.5 min and 52.5 +/- 15.6 min; in children, it was 28.8 +/- 7.8 min and 34.6 +/- 9.0 min. Neostigmine accelerated recovery in all reversal groups (P < 0.05) by approximately 40%, but the times from relaxant administration to TOF0.7 were similar and independent of the timing of neostigmine administration. Recovery to T1 90% after succinylcholine was similar in adults (9.4 +/- 5.0 min) and children (8.4 +/- 1.1 min) and was shorter than recovery to TOF0.7 in any reversal group after rocuronium or vecuronium administration. Recovery from rocuronium and vecuronium blockade after neostigmine administration was more rapid in children than in adults. Return of neuromuscular function after reversal was not influenced by the timing of neostigmine administration. These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Implications: These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Although spontaneous and neostigmine-assisted recovery is more rapid in children than in adults, in neither is return of function as rapid as after succinylcholine administration.     

Relationship between posttetanic count and response to carinal stimulation during vecuronium-induced neuromuscular blockade

The correlation between degree of peripheral neuromuscular blockade and response to carinal stimulation was evaluated in two groups of 25 patients: one group was anaesthetized with thiopental, N2O and halothane, and the other group received thiopental, N2O and fentanyl. The degree of peripheral blockade was evaluated using train-of-four (TOF) and posttetanic twitch (PTC) stimulation of the ulnar nerve. The degree of diaphragmatic paralysis was evaluated indirectly by stimulating the carina and observing the corresponding muscular response, which was graded as severe, mild or absent. During halothane anaesthesia a PTC of 0 always indicated that no response to carinal stimulation could be elicited. On the appearance of the first response to posttetanic twitch stimulation (PTC = 1), 2% of the patients showed a mild response to carinal stimulation. At the first response to TOF stimulation, 48% of the patients reacted with a mild response. During thiopental, N2O, fentanyl anaesthesia one of 25 patients showed a mild response to carinal stimulation at a PTC of 0. When PTC was 1, 20% of the patients reacted mildly to the stimulation. At the first response to TOF stimulation, 92% showed a response to carinal stimulation; 24% of these responses were severe, necessitating intervention. It is concluded that the TOF response elicited peripherally is a late sign of neuromuscular recovery of the diaphragm, and that the method of counting posttetanic twitches is superior to the TOF response in evaluating early recovery of this muscle. Further, to ensure total diaphragmatic paralysis, the neuromuscular blockade of the peripheral muscles should be so intense that no response to posttetanic twitch stimulation (PTC = 0) can be elicited.     

Enzymatic Versus Pharmacologic Antagonism of Profound Mivacurium-induced Neuromuscular Blockade

Background: 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.

Methods: Eighty-seven ASA physical status 1 or 2 adult patients were given 0.15 mg *symbol* kg sup -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 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 greater or equal to 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 *symbol* kg sup -1 whereas groups 4 and 8 received edrophonium 1 mg *symbol* kg sup -1, respectively. Groups 5 and 6 received exogenous human butyrylcholinesterase equivalent to activity present in 25 or 70 ml *symbol* kg sup -1 of human plasma, respectively.

Results: 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.     

Reversal of rocuronium with edrophonium during propofol versus sevoflurane anesthesia

BACKGROUND: The use of volatile anesthetics for maintenance of anesthesia can enhance the action of non-depolarizing muscle relaxants and interfere with the reversal of neuromuscular blockade. In this study, we studied the antagonism of rocuronium with edrophonium-atropine during propofol- versus sevoflurane-based anesthesia. METHODS: Following induction of anesthesia with propofol (2-2.5 mg kg(-1), i.v.) and fentanyl (1-2 microg kg(-1) i.v.), rocuronium 0.6 mg kg(-1) i.v. was administered to facilitate tracheal intubation. Patients were then randomized to receive either a propofol infusion (100 microg kg(-1) min(-1)) or sevoflurane (1.0%, end-tidal) in combination with nitrous oxide 66% for maintenance of anesthesia. Neuromuscular blockade was monitored using electromyography at the wrist, and reversed with edrophonium 1.0 mg kg(-1) and atropine 0.015 mg kg(-1) when the first twitch hight (T1) of the train-of-four (TOF) stimulation recovered to 25% of the baseline value. Anesthetic maintenance with propofol or sevoflurane was continued following reversal until a TOF ratio of 0.7 was attained. RESULTS: The clinical duration of action (i.e., time to 25% T1 recovery) was similar during both propofol- (39.3+/-14.6 min) and sevoflurane-based (48.1+/-19.7 min) anesthesia. However, the reversal time from 25% T1 to TOF ratio of 0.7 was significantly longer with sevoflurane [Median 2.8 (range 0.5-18.8) min] compared with propofol [1.5 (0.75-3) min] (P<0.05). CONCLUSIONS: We conclude that the clinical duration of action after a single dose of rocuronium, 0.6 mg kg(-1) i.v., was similar during both propofol- and sevoflurane-based anesthesia. However, the reversal of rocuronium-induced residual blockade was slower and more variable in the presence of sevoflurane.     

The neuromuscular effects of desflurane, alone and combined with pancuronium or succinylcholine in humans

The neuromuscular effects of desflurane administered alone were studied in ten healthy human volunteers aged 20-27 yr. Also, the dose-response relationships of pancuronium and succinylcholine in surgical patients during anesthesia with desflurane (n = 13) were compared to those during isoflurane anesthesia (n = 14). In the volunteers, we measured the mechanical response of the adductor pollicis muscle to stimulation of the ulnar nerve in a train-of-four (TOF) sequence at 2 Hz and at tetanic frequencies of 50, 100, and 200 Hz, each administered for 5 s. Amplitudes of the first response (T1) in each TOF sequence and the ratios of the fourth TOF response (T4) to the first were similar at 3, 6, and 9% desflurane and decreased significantly only at 12% (P less than 0.05). Desflurane concentrations of 3-12% caused tetanic fade (greater than 10% decrement in amplitude) at 50, 100, and 200 Hz. The addition of N2O and the duration of anesthetic exposure did not alter desflurane's neuromuscular effects. The only neuromuscular variable influenced by CO2 was T1 amplitude, which decreased as arterial CO2 tension (PaCO2) increased. The doses of pancuronium that depressed T1 amplitude by 50% (ED50) were similar during anesthesia with 1.25 MAC desflurane, 10.5 +/- 2.8 micrograms/kg (mean +/- SD) and 1.25 MAC isoflurane, 12.3 +/- 5.0 micrograms/kg. The ED50 doses of succinylcholine were similar during anesthesia with desflurane 132 +/- 76 micrograms/kg and isoflurane 123 +/- 36 micrograms/kg. We conclude that desflurane significantly depresses neuromuscular function and augments the action of pancuronium and succinylcholine to a degree similar to that of isoflurane.     

Spontaneous recovery profile of rapacuronium during desflurane, sevoflurane, or propofol anesthesia for outpatient laparoscopy

We evaluated the spontaneous recovery characteristics of rapacuronium during desflurane-, sevoflurane-, or propofol-based anesthesia in 51 consenting women undergoing laparoscopic tubal ligation procedures. After the induction of the anesthesia with standardized doses of propofol and fentanyl, 1.5 mg/kg IV rapacuronium was administered to facilitate tracheal intubation. Patients were randomized to receive either 1 minimum alveolar anesthetic concentration of desflurane, 1 minimum alveolar concentration of sevoflurane, or 100 microg. kg(-1). min(-1) propofol infusion in combination with 66% nitrous oxide in oxygen for maintenance of anesthesia. Neuromuscular blockade was monitored at the wrist by using electromyography. The degree of maximum blockade and the times for first twitch recovery (T(1)) to 5%, 25%, 50%, 75%, and 90%, as well as the recovery index, were similar in all three anesthetic groups. However, recovery times for the train-of-four ratio to achieve 0.7 and 0.8 were significantly longer with desflurane (44.4 +/- 18.9 and 53.5 +/- 22.4 min) and sevoflurane (44.8 +/- 15.1 and 53.2 +/- 15.8 min) compared with propofol (31.8 +/- 5.3 and 36.5 +/- 6.5 min). Eight patients (16%) required a maintenance dose of 0.5 mg/kg rapacuronium and reversal of rapacuronium residual block occurred in three (6%) patients. We conclude that spontaneous recovery after an intubating dose of 1.5 mg/kg rapacuronium was significantly prolonged by both desflurane and sevoflurane compared with propofol-based anesthesia. Routine monitoring of neuromuscular activity is recommended even when a single bolus dose of rapacuronium is administered during ambulatory anesthesia. IMPLICATIONS: When administered for laparoscopic surgery, the duration of action of an intubating dose of rapacuronium was prolonged 40%-50% by desflurane and sevoflurane, respectively, (versus propofol). Monitoring recovery of neuromuscular blockade produced by rapacuronium is particularly important when desflurane or sevoflurane is administered to ensure that an adequate recovery (train-of-four > or = 0.8) is achieved by the end of anesthesia.     

Possible augmentation of neuromuscular blockade by propofol during recovery from rocuronium

Propofol is a widely used drug in anesthesia practice, and its pharmacological characteristics are well known. However, propofol is not known for neuromuscular effects. As part of clinical neuromuscular monitoring, the neuromuscular responses to train-of-four (TOF) stimulation were monitored and recorded. We observed, in two cases of balanced anesthesia maintained by desflurane and fentanyl, that administration of a small dose of propofol during almost complete recovery from rocuronium in two patients resulted in marked decreases of both T1 (first twitch response of the TOF) and the TOF ratio. This neuromuscular block dissipated in both patients without any subsequent neuromuscular effects. These two observations provide visual confirmation of the possible impact of propofol on recovery from a rocuronium neuromuscular blockade.     

Posttetanic potentiation and fade in the response to tetanic and train-of-four stimulation during succinylcholine-induced block

We designed this study to confirm anecdotal observations that neuromuscular block after a single administration of succinylcholine is characterized by fade to train-of-four (TOF) or tetanic stimulation, as well as posttetanic potentiation. This prospective, randomized, 2-center observational study involved 100 patients. Patients were allocated to 1 of 5 groups and received 0.1, 0.3, 0.5, 0.75, or 1.0 mg/kg succinylcholine during propofol/fentanyl/nitrous oxide anesthesia. Neuromuscular function was monitored by TOF using mechanomyography. At 10%-20% spontaneous recovery of the first twitch of TOF, the mode of stimulation was changed from TOF to 1-Hz single-twitch stimulation followed by a tetanic stimulus (50 Hz) for 5 s. Three seconds later, the single twitch (1 Hz) was applied again for approximately 30 s followed by TOF stimulation until full recovery of the TOF response. Succinylcholine-induced neuromuscular block had the following characteristics: 1) twitch augmentation before twitch depression, which was seen more frequently in patients given smaller doses (0.1 and 0.3 mg/kg) than in those given larger doses (0.5-1.0 mg/kg); 2) TOF fade during onset and recovery of the block; 3) tetanic fade; and 4) and posttetanic potentiation. Posttetanic potentiation was related to the pretetanic twitch height but was not related to the dose of succinylcholine administered. Some characteristics of Phase II block were detectable during onset and recovery from doses of succinylcholine as small as 0.30 mg/kg. Posttetanic potentiation and fade in response to train-of-four and tetanic stimuli are characteristics of neuromuscular block after bolus administration of different doses of succinylcholine. IMPLICATIONS: Posttetanic potentiation and fade in response to train-of-four and tetanic stimuli are characteristics of neuromuscular block after bolus administration of different doses of succinylcholine. We also conclude that some characteristics of a Phase II block are evident from an initial dose (i.e., as small as 0.3 mg/kg) of succinylcholine.     

Comparative effects of desflurane and isoflurane on vecuronium-induced neuromuscular blockade.

STUDY OBJECTIVE: To evaluate the neuromuscular effects of a nondepolarizing muscle relaxant (vecuronium) during anesthesia with equipotent concentrations of either desflurane or isoflurane. DESIGN: Randomized open study comparing effects of desflurane and isoflurane on vecuronium-induced neuromuscular blockade. SETTING: University-affiliated medical center. PATIENTS: Forty-five healthy adults undergoing elective surgical procedures randomly assigned to receive either desflurane, nitrous oxide (N2O), and vecuronium or isoflurane, N2O, and vecuronium for maintenance of general anesthesia. INTERVENTIONS: Following a standardized induction sequence, patients receiving either desflurane and N2O or isoflurane and N2O were administered bolus doses of vecuronium equal to 0.01, 0.02, or 0.03 mg/kg intravenously (IV) during the maintenance period. Neuromuscular transmission was measured using a Relaxograph monitor. MEASUREMENTS AND MAIN RESULTS: Vecuronium produced similar depression of neuromuscular function at equipotent (50% of the minimum alveolar concentration) end-tidal concentrations of isoflurane 0.6% and desflurane 3.0%. Following administration of vecuronium 0.01 to 0.03 mg/kg IV, onset times (3.4 +/- 0.4 minutes to 3.2 +/- 0.4 minutes and 3.2 +/- 0.5 minutes to 3.0 +/- 0.6 minutes), maximum T1 twitch depression (80% +/- 10% to 95% +/- 9% and 81% +/- 9% to 97% +/- 10%), clinical duration of blockade (12 +/- 5 minutes to 20 +/- 8 minutes and 10 +/- 5 minutes to 19 +/- 17 minutes), and T1 recovery times (10 +/- 3 minutes to 12 +/- 6 minutes and 10 +/- 3 minutes to 12 +/- 4 minutes) were similar in the isoflurane and desflurane treatment groups, respectively (means +/- SD). CONCLUSION: Vecuronium has similar neuromuscular effects when administered in the presence of desflurane 3% and isoflurane 0.6%.     

Reversal of intense neuromuscular blockade following infusion of atracurium

In order to evaluate reversal time from very intense neuromuscular blockade caused by a continuous infusion of atracurium, the time course of neostigmine induced reversal from different levels of neuromuscular blockade was evaluated using the post-tetanic count (PTC) and the train-of-four (TOF) in 30 patients anesthetized with nitrous oxide, fentanyl, and thiopental. Reversal time (time from administration of neostigmine at different PTC levels to a TOF ratio of 0.7) was found to depend upon the degree of blockade at the time of reversal. Median reversal time from a PTC of 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, and greater than 13 (but less than 10% twitch height) to a TOF ratio of 0.7 was 31, 23, 19, 18, 14, and 13 min, respectively. Spontaneous recovery from PTC level of 1-2, when atracurium infusion was stopped, to a PTC level at which antagonism was induced and reversal time were both correlated to the square root of the PTC. Total recovery time (spontaneous recovery plus reversal time) was not shortened by an early injection of neostigmine. It is concluded that neostigmine administration during intense neuromuscular blockade following atracurium infusion does not shorten total recovery time and offers no clinical advantages.     

Sevoflurane and isoflurane, but not propofol, decrease mivacurium requirements over time

PURPOSE: Volatile anesthetic agents potentiate neuromuscular blockade, but the magnitude of potentiation appears to be time dependent. The time course of this interaction was studied by measuring mivacurium infusion rates during sevoflurane, isoflurane and propofol anesthesia. METHODS: After informed consent, anesthesia was induced in 48 ASA physical status I-II adults with propofol, fentanyl and mivacurium 0.25 mg.kg(-1) and maintained with N(2)O (60%) and one of the three agents chosen at random: sevoflurane 1.9%; isoflurane 1.2%; or propofol 100-150 microgram.kg(-1).min(-1). Train-of-four stimulation was applied every 15 sec to the ulnar nerve. Neuromuscular blockade was monitored with accelerometry. At 5% recovery of the first twitch (T1), a mivacurium infusion was started and adjusted every five minutes to maintain 90-95% T1 depression. RESULTS: The time to 5% T1 recovery after the initial dose was similar in all groups (13-15 min). Fifteen minutes after the start of the infusion mivacurium requirements were greater (P < 0.05) in the propofol group (7.5 +/- 1.7 microgram.kg(-1).min(-1); mean +/- SD) than in either isoflurane (4.7 +/- 1.6 microgram.kg(-1).min(-1)) or sevoflurane (4.5 +/- 1.5 microgram.kg(-1).min(-1)) group. Then, the rate remained stable for propofol (6.2 +/- 1.4 microgram.kg(-1).min(-1) after 90 min of infusion) while it decreased with isoflurane to 2.9 +/- 1.6 microgram.kg(-1).min(-1) at 90 min (P < 0.05 vs propofol) and to 1.4 +/- 1.0 microgram.kg(-1).min(-1) in the sevoflurane group (P < 0.05 vs propofol and isoflurane). CONCLUSION: Sevoflurane and isoflurane do not prolong the effect of a bolus dose of mivacurium, but potentiation increases with time from 30-105 min of exposure. This interaction is greater with sevoflurane than isoflurane.     

The prolonged duration of rocuronium in Chinese patients

We compared the potency and duration of action of rocuronium in Chinese and Caucasian patients during general anesthesia. Thirty-six women (18 Caucasian and 18 Chinese) and 36 children (18 Caucasian and 18 Chinese) were evaluated during the administration of propofol/fentanyl anesthesia. Patients in each age group were randomized into three subgroups to receive single doses of 0.06, 0. 12, or 0.18 mg/kg rocuronium (adults) or 0.12, 0.18, or 0.24 mg/kg rocuronium (children). Neuromuscular blockade was assessed by electromyography of the adductor pollicis after train-of-four (TOF) stimulation of the ulnar nerve. Dose response curves were constructed when maximum neuromuscular depression of the first twitch of the train (T(1)) was obtained. A second bolus dose of rocuronium was then administered to a total dose of 0.6 mg/kg. The times of spontaneous recovery to T(1) 10%, 25%, and 90% of control and to TOF 0.25, 0.50, and 0.70 were recorded. For both adults and children, recovery occurred later in Chinese than in Caucasian patients (P<0.05 for T(1) of 10%, 25%, 75%, and 90% and TOF to 0.7). The 50% effective dose was smaller in Chinese adults (125+/-63 vs. 159+/-66 microg/kg) and Chinese children (171+/-43 vs. 191+/-46 microg/kg) than in Caucasian adults and children, but the difference was not statistically significant. In adults, time to 25% T(1) recovery was 43+/-13 min in Chinese patients and 33+/-10 min in Caucasian patients (P<0.05). The corresponding values were more rapid for children: 30+/-10 and 24+/-6 min (P<0.05). We conclude that the recovery from rocuronium neuromuscular blockade was longer in Chinese compared with Caucasian patients and in adults compared with children.     

Effect of maintenance bolus on the recovery profile of a short-acting nondepolarizing muscle relaxant

STUDY OBJECTIVE: To evaluate the effect of different maintenance boluses of a short-acting nondepolarizing neuromuscular blocking drug on its spontaneous recovery profile during anesthesia. DESIGN: Prospective, randomized, double-blind, dose-ranging study. SETTING: University-based medical center. PATIENTS: 69 ASA physical status I and II consenting adult outpatients undergoing general anesthesia with an anticipated duration of at least 2 hours. INTERVENTIONS: Patients were randomized to one of three study groups. Following induction of anesthesia with propofol and fentanyl, rapacuronium 1.5 mg x kg(-1) intravenously (i.v.), was administered to facilitate tracheal intubation. Anesthesia was maintained with desflurane 4% end-tidal in combination with nitrous oxide 67% in oxygen. When the first twitch (T(1)) in the train-of-four (TOF) returned to 25% of its baseline value, a maintenance dose of rapacuronium 0.25 mg x kg(-1) i.v. (Group 1), 0.5 mg. kg(-1) i.v. (Group 2), or 0.75 mg. kg(-1) i.v. (Group 3) was administered. The time course of neuromuscular block was monitored at the wrist using standard electromyography. MEASUREMENTS AND MAIN RESULTS: The times for recovery of the T(1) to 25% of the baseline value following different maintenance doses of rapacuronium were only 6.3 +/- 2.2, 7.5 +/- 2.3, and 9.6 +/- 2.5 minutes, in Groups 1, 2 and 3, respectively. However, the times for the TOF ratio to return to 0.7 were 44 +/- 15, 53 +/- 20, and 66 +/- 30 minutes in Groups 1, 2, and 3, respectively. Although recovery times were significantly longer after rapacuronium 0.75 mg x kg(-1) i.v. (Group 3), there were no significant differences in any of the recovery variables between Groups 1 and 2. CONCLUSIONS: Spontaneous recovery of the T(1) to 25% of the baseline value occurred 6 to 10 minutes after a maintenance bolus dose of rapacuronium 0.25 to 0.75 mg x kg(-1) i.v. However, recovery to a TOF>0.7 required 44 to 66 minutes during desflurane anesthesia.     

Duration and recovery profile of cisatracurium after succinylcholine during propofol or isoflurane anesthesia

Study Objective: To determine the duration and recovery profile of maintenance doses of cisatracurium besylate following succinylcholine, and during propofol or isoflurane anesthesia.

Design: Randomized, open-label study.

Setting: Operating suite of a university-affiliated medical center.

Patients: Forty ASA physical status I and II adult patients having elective surgery with general anesthesia lasting longer than 90 minutes.

Interventions: Following a standardized induction sequence, a baseline electromyogram (EMG) was obtained. An intubating dose of intravenous (IV) succinylcholine 1.0 mg/kg was administered. Ventilation was maintained with a face mask until the first twitch (T₁) of the evoked train-of-four (TOF) reached 10% of control when tracheal intubation was performed. Spontaneous recovery from neuromuscular blockade was allowed to occur until the first twitch returned to 25% of control. Patients then were randomized to receive cisatracurium as follows. Group 1: 0.025 mg/kg [0.5 × 95% effective dose (ED₉₅)]; Group 2: 0.05 mg/kg (ED₉₅); Group 3: 0.05 mg/kg (ED₉₅); and Group 4: 0.1 mg/kg (2×ED₉₅). Anesthesia for Groups 1 and 2 were maintained with isoflurane 1% to 2%, 66% nitrous oxide (N₂O) in oxygen (O₂), and in Groups 3 and 4, anesthesia was maintained with propofol 80 to 160 μg/kg/min, 66% N₂O in O₂. The TOF-evoked EMG was recorded at 10-second intervals. The time for the evoked EMG to spontaneously return to 25%, 50%, and 75% of the original baseline was recorded.

Measurements and Main Results: There were 10 patients in each of the four groups. The duration of action of cisatracurium 0.05 mg/kg (ED₉₅) after an intubating dose of succinylcholine is 24.5 ± 10 minutes and 21.3 ± 9 minutes during anesthesia maintained with isoflurane and propofol, respectively. Doubling the dose of cisatracurium resulted in approximately twice the duration of action (40.2 ± 7 min) during propofol anesthesia. Following a dose of cisatracurium 0.025 mg/kg (0.5×ED₉₅), the T₁ of the EMG-evoked response did not decrease below 25% in 7 of 10 patients.

Conclusion: Following succinylcholine, the duration of action of a single dose of cisatracurium 0.05 mg/kg is 20 to 25 minutes during anesthesia maintained with propofol or isoflurane. The duration and recovery profile of cisatracurium is dose dependent during propofol and isoflurane anesthetics. Cisatracurium 0.025 mg/kg is an inadequate maintenance dose following recovery from succinylcholine and it fails to provide adequate surgical relaxation.     

Cisatracurium-induced neuromuscular blockade in anticonvulsant treated neurosurgical patients

Patients treated with the anticonvulsants phenytoin or carbamazepine are resistant to steroidal neuromuscular blocking agents. We studied the effect of cisatracurium on onset, duration, and speed of recovery from neuromuscular blockade (NMB) in acutely anticonvulsant treated patients ([< 2 weeks] [AA]), chronically anticonvulsant treated patients ([> 2 weeks] [CA]) and patients not on anticonvulsants ([controls] [C]). After Internal Review Board approval, 10 AA, 14 CA, and 14 C neurosurgical patients were studied. Anesthetic induction was midazolam, fentanyl, and thiopental, and maintenance was fentanyl and 0.5 MAC isoflurane in O2. The evoked compound electromyogram of the hypothenar eminence was monitored (TOF supramaximal stimulus at 2 Hz every 20 seconds). Baseline TOF was established, then cisatracurium (0.2 mg/kg) was administered IV. Onset (time to maximal paralysis), duration [time to recovery of first twitch (T1) to 25% of baseline] and speed of recovery (time of recovery from 10%-25% of baseline) were recorded. Data were analyzed using ANOVA. Onset (C = 4 +/- 2, AA = 3 +/- 1, CA = 3 +/- 1.5 minutes) and duration (C = 69 +/- 13, AA = 64 +/- 19, CA = 59 +/- 19 minutes) were not different among the groups (P > .7). Speed of recovery was significantly faster in both AA (6 +/- 2 minutes) and CA (6 +/- 3 minutes) than in C (12 +/- 9 minutes) patients (P < .05). (Data = mean +/- SD). Onset and duration of cisatracurium-induced neuromuscular relaxation was not affected by acute or chronic anticonvulsant treatment, but speed of recovery was significantly faster. Frequent NMB monitoring is necessary to detect the greater speed of recovery in anticonvulsant-treated patients during cisatracurium muscle relaxation.     

Onset and duration of action of rocuronium--from tracheal intubation, through intense block to complete recovery

BACKGROUND: The primary objective of this study was to establish the relation between the post tetanic count (PTC) and the time to reappearance of the first response (T1) in train-of-four (TOF) nerve stimulation following rocuronium 0.6 mg/kg, 0.9 mg/kg, and 1.2 mg/kg. The secondary objective was to evaluate the intubation conditions after 1 min. METHODS: One hundred and eight patients were randomised to one of three doses of rocuronium: 0.6, 0.9 or 1.2 mg/kg. Tracheal intubation was performed at 60 s by a blinded investigator. During propofol, fentanyl, midazolam anaesthesia the neuromuscular block was monitored by mechanography using TOF stimulation every 12 s. At 6 min intervals, a tetanic stimulation (50 Hz) was applied for 5 s preceded and followed by a 30 s period of 1 Hz stimulation until the reappearance of T1. RESULTS: There was a significant difference in recovery following the high dose and the two lower doses. The relation between time (min) to reappearance of T1 (t) and PTC can be expressed as follows: t(0.6 and 0.9 mg/kg)(min)=18.8-6.46 PTC and t(1.2 mg/kg)(min)=26.1-9.12 PCT. T1 was seen at a mean PTC level of 8 or 9 in all three groups. The intubation conditions were graded as excellent or good in all patients except in two patients following the 0.6 mg/kg dose of rocuronium. CONCLUSION: The PTC method can be used to predict the time to first response to TOF nerve stimulation during intense rocuronium induced neuromuscular blockade. The relation between PTC and the time to T1 was prolonged after 1.2 mg/kg compared with 0.6 mg/kg and 0.9 mg/kg. No further improvement in intubation conditions at 60 s was evident by increasing the rocuronium dose from 0.9 mg/kg to 1.2 mg/kg.     

Neostigmine antagonism of rocuronium block during anesthesia with sevoflurance, isoflurane or propofol

PURPOSE: To examine the influence of continuing administration of sevoflurane or isoflurane during reversal of rocuronium induced neuromuscular block with neostigmine. METHODS: One hundred and twenty patients, divided into three equal groups, were randomly allocated to maintenance of anesthesia with sevoflurane, isoflurane or propofol. Neuromuscular block was induced with rocuronium and monitored using train-of-four (TOF) stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. Neostigmine was administered when the first response in TOF had recovered to 25%. At this time the volatile agent administration was stopped or propofol dosage reduced in half the patients in each group (n = 20 in each group). The times to attain TOF ratio of 0.8, and the number of patients attaining this end point within 15 min were recorded. RESULTS: The times (mean +/- SD) to recovery of the TOF ratio to 0.8 were 12.0 +/- 5.5 and 6.8 +/- 2.3 min in the sevoflurane continued and sevoflurane stopped groups, 9.0 +/- 8.3 and 5.5 +/- 3.0 min in the isoflurane continued and isoflurane stopped groups, and 5.2 +/- 2.8 and 4.7 +/- 1.5 min in the propofol continued and propofol stopped groups (P < 0.5-01). Only 9 and 15 patients in the sevoflurane and isoflurane continued groups respectively had attained a TOF ratio of 0.8 within 15 min (P < 0.001 for sevoflurane). CONCLUSIONS: The continued administration of sevoflurane, and to a smaller extent isoflurane, results in delay in attaining adequate antagonism of rocuronium induced neuromuscular block.