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Background: Studies in volunteers suggest that train-of-four (TOF) ratios >0.9 are needed to retain normal function of muscles involved in upper airway patency, swallowing, and vital capacity breathing. We determined if sex-related differences exist in the relationship between adductor pollicis (AP) TOF ratio and measures of neuromuscular function commonly used to assess recovery from neuromuscular block., Methods: In 10 males and 10 females, three steady-state levels of neuromuscular block were achieved with mivacurium infusions. TOF ratio was measured with acceleromyography at the AP. Hand grip strength and the ability to clench the teeth, raise the head >5 s, swallow, protrude the tongue, and open the eyes were tested at each stable block level and reconciled to uncorrected and normalized (pre-paralysis values) TOF measures. These relationships were compared between sexes., Results: The ability to clench teeth and head raise >5 s was lost at a significantly greater TOF ratio in males than females. The percentage decrease in handgrip strength with decreasing TOF ratio was proportionally greater in males than females. Forty per cent of the males were unable to clench the teeth at an uncorrected TOF ratio >0.9. When TOF ratios were normalized, clinical functions showed no decrement at TOF ratio >0.9 in any volunteer., Conclusions: Sex-related differences exist in the relationship between AP TOF ratio and clinical measures of muscle function used to assess recovery from neuromuscular block. Normalization of AP TOF ratios is recommended because a non-normalized TOF ratio of 0.9 does not guarantee adequate reversal of neuromuscular block.

Background: Because tactile evaluation is the most common form of clinical neuromuscular monitoring, this study examines the relative efficacy of antagonizing residual block at different levels of recovery of the tactile train-of-four (TOF) response., Methods: Anesthesia was induced in 64 adults with 2-5 microg/kg fentanyl and 1-3 mg/kg propofol and maintained with fentanyl, propofol, and nitrous oxide. The tactile response of the adductor pollicis to TOF stimulation was evaluated at one arm, and the mechanomyographic response was recorded at the other. Patients received 0.15 mg/kg cisatracurium and were randomized to receive 0.07 mg/kg neostigmine on reappearance of the first (group I), second (group II), third (group III), or fourth (group IV) tactile TOF response (16 patients per group). Times from administration of neostigmine until the TOF ratio recovered to 0.7 (R0.7), 0.8 (R0.8), and 0.9 (R0.9) were measured., Results: Data are presented as median with range in parentheses. R0.7 was 10.3 (5.9-23.4), 7.6 (3.2-14.1), 5.0 (2.0-18.4), and 4.1 (2.4-11.0) min in groups I, II, III, and IV, respectively (P < 0.05, group I > II, III, and IV, group II > IV). R0.8 was 16.6 (8.9-30.7), 9.8 (5.3-25.0), 8.3 (3.8-27.1), and 7.5 (3.0-74.5) min in groups I, II, III, and IV, respectively (P < 0.05, group I > II, III, and IV, group II > IV). R0.9 was 22.2 (13.9-44.0), 20.2 (6.5-70.5), 17.1 (8.3-46.2), and 16.5 (6.5-143.3) min in groups I, II, III, and IV, respectively (no intergroup differences). Ten minutes after neostigmine, a TOF ratio of 0.7 or greater was achieved in 50, 75, 88, and 93% of patients in groups I, II, III, and IV, respectively (P < 0.05 group I > II, III, and IV). At 30 min, a TOF ratio of 0.9 or less was observed in 21, 13, 13, and 7% of patients in groups I, II, III, and IV respectively (no intergroup differences)., Conclusions: To achieve rapid (within 10 min) reversal to a TOF ratio of 0.7 in more than 87% of patients, three or four tactile responses should be present at the time of neostigmine administration. It was not possible within 30 min to achieve a TOF ratio of 0.9 in all patients, regardless of the number of tactile responses present at neostigmine administration.

Background: It is not known if the information on neuromuscular function obtained from the hand is interchangeable with that of the foot. In the present study the agreement of thumb mechanomyography with acceleromyography of the big toe was studied., Methods: Ten healthy patients scheduled for oral surgery were studied. Anaesthesia was induced with fentanyl 2 micrograms kg-1 and propofol 2 mg kg-1, and maintained with propofol 100-175 micrograms kg-1 min-1, nitrous oxide 60-70%, and fentanyl 1-2 micrograms kg-1 h-1. Vecuronium 0.1 mg kg-1 was used for muscle relaxation. Mechanomyography (MMG) of the thumb (Myograph 2000) and acceleromyography (AMG) of the big toe (TOF-Guard) were recorded simultaneously in all patients, and onset, period of no-twitch response, duration of action, and spontaneous recovery time obtained from both muscle groups. The agreement between methods was tested by calculation of bias and limits of agreement., Results: The onset time and duration of action were significantly shorter (87 s vs 154 s, and 35 min vs 38 min, respectively), and the spontaneous recovery time significantly longer in the thumb than in the big toe (32 min vs 19 min). Period of no-twitch response was not significantly different in the two muscle groups. Limits of agreement (thumb big toe) were -21 to -113 s, -7 to 1 min, and -9 to 35 min, for onset time, duration of action, and spontaneous recovery time, respectively., Conclusions: We conclude that clinically acceptable agreement between thumb mechanomyography and big toe acceleromyography was found for the period of no-twitch response, suggesting that the timing of supplemental doses of vecuronium can be guided by AMG at the big toe. However, the spontaneous recovery time agreement (to TOF ratio = 0.75) between the thumb and the big toe was poor.

To investigate the effect of mild hypothermia on the neuromuscular junction sensitivity to vecuronium, we determined the pharmacodynamics (concentration-effect relationship) of vecuronium in 10 patients (ASA physical class I or II; age range, 21-46 yr; weight range, 54-104 kg), during isoflurane-nitrous oxide-fentanyl anesthesia. Five were cooled to a mean temperature of 34.4 degrees C and five were maintained normothermic at a mean temperature of 36.8 degrees C. Neuromuscular function was monitored by measuring the evoked mechanical response of the adductor pollicis muscle after supramaximal train-of-four stimulation of the ulnar nerve at the wrist. Vecuronium, 3 micrograms.kg-1.min-1, was infused for 10 min, venous blood sampled for 60 min, and twitch tension and plasma concentration data were used to determine pharmacodynamic variables in each patient. Results for the hypothermic and normothermic groups were compared by Mann-Whitney U-test. There were no differences in any pharmacodynamic variable between the hypothermic and normothermic patients. For the hypothermic and normothermic patients, respectively, steady-state plasma concentrations of vecuronium producing 50% neuromuscular block (Css50) were 73 +/- 13 ng/mL (mean +/- SD) and 79 +/- 31 ng/mL; the rate constants for equilibration of vecuronium between the plasma and the neuromuscular junction (Keo) were 0.27 +/- 0.14 per min-1 and 0.26 +/- 0.11 per min, and the power functions representing the slope of the concentration-effect relationship (gamma) were 5.7 +/- 1.9 and 4.4 +/- 1.8.(ABSTRACT TRUNCATED AT 250 WORDS)

We compared the duration of action and recovery times for vecuronium in normothermic and mildly hypothermic patients. Ten patients were actively cooled to a central body temperature near 34.5 degrees C, and ten were maintained at a normothermic central temperature (greater than 36.5 degrees C); temperature was measured in the distal esophagus. Vecuronium 0.1 mg/kg was administered as an intravenous (iv) bolus to all patients, and the evoked mechanical response to train-of-four stimulation was recorded. Five hypothermic and five normothermic patients were allowed to recover spontaneously. In the remaining five in each group, neostigmine (40 micrograms/kg) and atropine (20 micrograms/kg) was administered when the first twitch (T1) height spontaneously recovered to 10% of control (T1 = 10% of the pre-vecuronium twitch tension). Vecuronium's duration of action (from injection of drug until T1 = 10%) was 28 +/- 4 and 62 +/- 8 min during normothermia and hypothermia, respectively (P less than 0.05). The corresponding values for spontaneous recovery from T1 = 10% to TOF ratio greater than 75% were 37 +/- 15 and 80 +/- 24 min (P less than 0.05), and for neostigmine-induced recovery were 10 +/- 3 and 16 +/- 11 min (difference not significant). We conclude that mild hypothermia increases the duration of action of and time for spontaneous recovery from vecuronium-induced neuromuscular blockade.

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.

This study aimed to determine whether: 1) the method of cooling the hand (i.e. central [total body] vs. local surface [hand only]) influences the relationship between the adductor pollicis temperature and twitch tension; and 2) decreased evoked twitch response during hypothermia is due to reduced muscle temperature and/or the anesthetic drug used. First, the effect of local surface cooling on adductor pollicis twitch tension during isoflurane anesthesia was determined in 15 patients, while central body temperature was not allowed to decrease. Adductor pollicis temperature and twitch tension decreased in a linear manner (P less than 0.05). However, the magnitude of the decreased response was only 43% of that observed during central cooling in the authors' previous study under otherwise similar experimental conditions. Second, the effect of central cooling on adductor pollicis twitch tension during nitrous oxide/fentanyl anesthesia was determined in five patients. The twitch tension did not decrease until the adductor pollicis temperature decreased below 35.2 degrees C. Below this temperature, twitch tension decreased 16%/degrees C reduction in muscle temperature. These results are similar to those obtained in the authors' previous study in patients anesthetized with nitrous oxide/isoflurane anesthesia. The authors conclude that both central and local surface cooling of the adductor pollicis muscle reduces twitch tension and that the decrease in adductor pollicis twitch tension is the same during nitrous oxide/isoflurane and nitrous oxide/fentanyl anesthesia.

To evaluate the effect of aging on the distribution, clearance, and neuromuscular junction sensitivity to atracurium, the authors determined the pharmacokinetics and pharmacodynamics of atracurium in five healthy elderly subjects (74-76 yr) during halothane-nitrous oxide anesthesia and compared these values to those obtained previously in five healthy young adults (22-44 yr). A brief (6.0-13.0 min) infusion of atracurium was administered until twitch tension was suppressed by approximately 70%, and atracurium plasma concentration and twitch tension data were used to determine pharmacokinetic and pharmacodynamic parameters for each patient. Total clearance (Cltotal) was similar in elderly and young adults. However, clearance via the liver and/or kidney (Clorgan) was lower in elderly patients, whereas clearance due to Hofmann elimination and ester hydrolysis (Clnonorgan) was higher. Volume of distribution at steady state (Vss) was larger in elderly patients. The increase in Vss without an age-related increase in Cltotal resulted in a longer elimination half-life [21.8 (+)/- 3.3 vs. 15.7 (+)/- 2.5 min (mean (+)/- SD)] in elderly patients. The steady state plasma concentration of atracurium required to suppress twitch tension by 50% was similar in elderly and young adults. The authors conclude that the pharmacokinetics, but not the pharmacodynamics, of atracurium differ significantly between elderly and young adults. As a result, repeated doses will be required with similar frequency in young and elderly adults, but recovery from comparable levels of neuromuscular blockade may be slightly prolonged in elderly patients.