Mivacurium infusion requirement and spontaneous recovery of neuromuscular transmission in children anaesthetized with nitrous oxide and fentanyl,halothane, isoflurane or sevoflurane

BACKGROUND: Forty children, aged 3-11 years, ASA I or II, were allocated at random to receive N2O/O2-fentanyl or 1 MAC halothane, isoflurane or sevoflurane-N2O/O2 anaesthesia. Mivacurium was used for muscle relaxation. METHODS: Electromyographic response of the adductor pollicis to train-of-four (TOF) stimulation, 2 Hz for 2 s, applied to the ulnar nerve at 10-s intervals was recorded using the Relaxograph (Datex, Helsinki, Finland). An intubating dose of mivacurium, 0.2 mg.kg-1 was given, and when T1 returned to 5%, muscle relaxation was maintained by continuous infusion of mivacurium, adjusted manually to maintain a stable 90-99% block. RESULTS: Halothane, isoflurane and sevoflurane groups had lower infusion requirements for mivacurium than the N2O-fentanyl group (P=0.000083). Mivacurium requirement was 18.8 +/- 6.8, 10.8 +/- 4.2, 6.9 +/- 3.9 and 9.6 +/- 5.6 microg.kg-1.min-1 for children receiving N2O/O2-fentanyl, halothane, isoflurane and sevoflurane anaesthesia, respectively. CONCLUSIONS: Spontaneous recovery from T1=10% to TOF ratio=0.7 was insignificantly prolonged from 6.3 to 12.5 min in the fentanyl group to 7-16.5 min in children anaesthetized with inhalational anaesthetics.     

Effects of sevoflurane, isoflurane, enflurane, and halothane on left ventricular diastolic performance in dogs

The effects of volatile anesthetics on active (ventricular relaxation) and passive (chamber stiffness) indices of diastolic function and on left ventricular filling rates in dogs were studied to determine how these agents affect left ventricular diastolic performance. Thirty-five mongrel dogs were randomly assigned to receive sevoflurane, isoflurane, enflurane, or halothane. Left ventricular pressure waveforms, phonocardiograms, and echocardiograms were recorded after administering the anesthetics at concentrations of 0% (control), 1%, 2%, and 3%. Ventricular relaxation was defined as the time constant of the decline in left ventricular pressure. Chamber stiffness was derived from the ventricular pressure-volume relationship during passive filling. Rapid filling rate, slow filling rate, and atrial filling rate were obtained from echocardiograms and phonocardiograms. No change in the time constant or in chamber stiffness was observed at any concentration of sevoflurane or isoflurane. However, the highest studied concentration of enflurane and halothane produced a significant increase in the time constant and in chamber stiffness. Rapid filling rate as well as atrial filling rate decreased significantly with the volatile anesthetics, especially with enflurane and halothane. Sevoflurane and isoflurane did not alter ventricular relaxation or chamber stiffness, but did affect diastolic function as manifested by their alteration of filling rates. In contrast, enflurane and halothane each prolonged ventricular relaxation and increased chamber stiffness. With the administration of the volatile anesthetics, the rapid filling rate decreased with the deterioration of diastolic function; in addition, atrial filling rates decreased and did not compensate for the reduction in early ventricular filling.     

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.     

A comparison of the pharmacodynamics of rocuronium and vecuronium during halothane anaesthesia

Thirty healthy patients were randomised to receive either a single bolus dose of rocuronium 0.6 mg.kg-1 or vecuronium 0.1 mg.kg-1 during halothane anaesthesia. Onset time, duration 25, duration 75 and train-of-four 70 were measured. The onset of neuromuscular blockade following rocuronium was more rapid than vecuronium (p = 0.0001). All other pharmacodynamic parameters were similar. During the first minute following injection of the neuromuscular blocking agent, the heart rate increased by 36% in the rocuronium group but remained stable in those patients who received vecuronium (p = 0.0008). No adverse effects were noted in either group.     

Dose–response and time-course of the effect of rocuronium bromide during sevoflurane anaesthesia

To evaluate the influence of sevoflurane on the dose–response relationship and on the time-course of the effect of rocuronium, 60 adult patients undergoing elective plastic surgery were randomly allocated to either the control or the sevoflurane group. Anaesthesia was maintained with 60% nitrous oxide in oxygen and thiopentone in the control group and with 60% nitrous oxide in oxygen and an end-tidal concentration of 1.75% sevoflurane in the sevoflurane group. Neuromuscular function was assessed mechanomyographically with train-of-four stimulation at the wrist every 12 s and the percentage depression of the first twitch of the train-of-four was used as the study parameter. The dose–response relationship of rocuronium in the two groups was determined by the cumulative dose–response technique. The dose–response curve of rocuronium in the sevoflurane group was shifted to the left compared to the control group, indicating a potentiation of rocuronium-induced neuromuscular block. The effective doses of rocuronium required to produce 50%, 90% and 95% twitch depression in the sevoflurane group were decreased by 30.5%, 26.7% and 25.2%, respectively, compared to the control group. Following the administration of a total dose of rocuronium of 400 μgkg⁻¹, the duration of action of, and the recovery from, rocuronium were both significantly prolonged by sevoflurane. There were significant differences in the duration of peak effect, clinical duration, recovery index and the total duration of action between the control and the sevoflurane groups.     

Blood/gas partition coefficients of halothane,isoflurane and sevoflurane in horse blood

Background. Blood/gas partition coefficients (_b/g) for volatileagents in horse blood are reported for halothane but not forisoflurane and sevoflurane. We measured the _b/g of halothane,isoflurane and sevoflurane in the blood of fasted horses. Thecorrelation with age, weight and some haematological and biochemicalvariables was studied. The temperature correction factor forisoflurane solubility was calculated. Methods. Twenty-four horses were randomly allocated to halothane(n=8), isoflurane (n=8) or sevoflurane (n=8). Blood sampleswere taken after 10 h’ fasting. Calculation of _b/g wasbased on the measurement of anaesthetic partial pressures inblood at 37 °C, which was achieved with tonometer equilibrationand headspace gas chromatography. Results. Mean _b/g was 1.66 (SD 0.06) for halothane, 0.92 (0.04)for isoflurane, and 0.47 (0.03) for sevoflurane. The _b/g valueswere all significantly lower than in humans (P<0.001). Nocorrelation was found between _b/g and weight, age, haematocrit,plasma triglycerides, cholesterol or total bilirubin. The changein isoflurane solubility per 1 °C temperature increase was–2.63 (0.13)%. Conclusion. The _b/g values of halothane, isoflurane and sevofluranein fasted horses are significantly lower than those reportedin humans. The _b/g for halothane in this study agrees with valuesreported in the literature but a positive correlation with plasmatriglycerides could not be confirmed. Knowledge of _b/g can refinemodels of anaesthetic uptake. Br J Anaesth 2003; 91: 276–8     

Effects of halothane, isoflurane and sevoflurane on calcium-related contraction in porcine coronary arteries

Background: Volatile anaesthetics have a direct inhibitory effect upon epicardial coronary arterial smooth muscles (1–4). The site and mode of their action at the cellular level need to be clarified, which was the purpose of our study. The present investigation attempted to answer the question in what way volatile anaesthetics influence Ca²⁺-related contraction in isolated porcine epicardial coronary to understand their intracellular mechanism. Methods: Isolated helical strips of porcine epicardial coronary artery without endothelium were suspended for isotonic contraction recordings in Krebs-Ringer's solution. 9.4×10^-2 MK+, 2.5×10^-1 M Ca²⁺-induced shortening of the strips was regarded as the reference value (100%). After incubation in Ca²⁺-free solution with 10^-3 M ethlene glycol bis (β-aminoethyl ether)-N, N-tetraacetic acid (EGTA) for 60 minutes, the muscle strips were exposed to increasing Ca²⁺ concentrations (10^-4-10^-2) either in the presence or absence of 1.5 or 2.5 minimum alveolar concentration (MAC) halothane, isoflurane or sevoflurane, with 9.4×10^-2 M K⁺ bath solution. Results: All three drug groups produced apparent biphasic effects with a cumulative increase of Ca²⁺ concentration compared with control groups. An initial increase at low Ca²⁺ concentration was followed by a decrease of Ca²⁺-activated contractions. Isoflurane affected Ca²⁺-induced contraction significantly more than halothane and sevoflurane. Conclusions: The results imply that volatile anaesthetics influence Ca²⁺-dependent activity of coronary smooth muscle by complex mechanisms, which involve promotion of intracellular Ca²⁺ release and other mechanisms that alter sensitivity to calcium.     

The influence of isoflurane on a continuous infusion of mivacurium

Sixty surgical patients were studied to evaluate the neuromuscular effects of mivacurium 0.l5 mg.kg^-1 (2 × ED₉₅)for tracheal intubation. After intubation the patients were randomly allocated to receive alfentanil with either propofol (starting with 9mg.kg^-1 h^-1, reducing to 6mg.kg^-1 h^-1 after 20min) or isoflurane (0.5% end-tidal). In addition, all the patients were given a continuous infusion of mivacurium 10 μg.kg^-1 min^-1 after tracheal intubation which was adjusted to maintain 90% depression of T₁. Following mivacurium 0.15 mg.kg^-1 T₁ decreased below 25% in all but four patients. Mean (SD) percentage maximum block attainedwas 92.9% (12.5) after 309 (89)s. Tracheal intubation was completed 232 (155) s after administration of the relaxant and intubating conditions were graded as‘excellent’ or‘good’ in 56 patients. Although the mean (SD) mivacurium infusion rate for maintaining T₁ at 10% was higher in the propofol group, 4.8 (2.1) compared with 4.4 (2.0) μg.kg^-1 min^-1 in the isoflurane group, this was not significantly different (p > 0.05). The mean (SD) recovery index was prolonged in the isoflurane patients, 757 (508)s, compared to those receiving propofol, 466 (219)s (p < 0.05).     

Comparison of the effects of isoflurane and halothane on intraocular pressure

Intraocular pressure (IOP) was measured in four groups of patients receiving isoflurane or halothane in consecutively increasing or decreasing concentrations (1.0, 2.0 and 3.0 MAC in 70% nitrous oxide). IOP decreased significantly in all groups irrespective of whether the higher or the lower concentration of the volatile agent was used first. There were no further significant changes in IOP whether the concentrations were increased or decreased, suggesting no dose-relation. Maximum reductions in IOP were slightly greater in those receiving the higher concentrations of the volatile agents first (64 and 66% with isoflurane and halothane, respectively) in comparison to those receiving the lower concentrations first (54 and 46%, respectively).     

The Bispectral Index in children: comparing isoflurane and halothane

Background. The Bispectral Index (BIS) has been calibrated forseveral general anaesthetic agents including isoflurane. Halothaneis still used in paediatric anaesthesia. Compared with othervolatile anaesthetics, halothane has a different receptor affinityand differing effects on the EEG. There are limited data evaluatingthe BIS with halothane. We set out to compare the BIS usinghalothane and isoflurane at a clinically relevant equipotentconcentration (1 MAC) and at a reproducible measure of anaestheticeffect (awakening). Methods. Forty children aged between 2 and 15 yr were enrolledin a masked randomized trial—20 in each group. Anaesthesiawas induced with sevoflurane or propofol. Either halothane orisoflurane were given to obtain an end-tidal concentration of1 MAC for 15 min. The BIS was then recorded. The BIS was alsorecorded at awakening. Values (mean (SD)) were compared witha t test. Results. At 1 MAC the BIS for halothane was significantly greaterthan isoflurane (56.5 (8.1) vs 35.9 (8.5), P<0.0001). Atawakening there was no significant difference (BIS halothane;81.1 (11.9), BIS isoflurane; 82.5 (16.4)). The difference inmeans at awakening was 1.4 (95% CI –8.2 to 11.1). Conclusions. At equipotent concentrations of halothane and isofluraneBIS valves were significantly greater with halothane. At awakeningthe BIS values were equivalent for each agent. This findingis consistent with the BIS being more affected by the agentused at higher concentrations of anaesthetic. The BIS must beinterpreted with caution when using halothane. Br J Anaesth 2004; 92: 14–17     

The effect of halothane on mivacurium infusion requirements in adult surgical patients

Background: The extent of interaction between volatile anaesthetics and neuromuscular blocking agents depends both on the inhalational anaesthetic and the muscle relaxant. Halothane has the weakest potentiating effect on neuromuscular blocking drugs and previous studies of the interaction between halothane and mivacurium have been contradictory. We were interested in determining the effect of different levels of halothane-nitrous oxide anaesthesia on infusion requirements of mivacurium. Methods: Sixty adult surgical patients were studied. Anaesthesia was induced with thiopentone and fentanyl and intubation facilitated with mivacurium 0.15 mg kg^-1. The patients were randomly assigned to one of four study groups. The control group received nitrous oxide in oxygen (2: 1) supplemented with fentanyl, while in the other groups halothane was administered at different end-tidal concentrations: 0.19% (Group 2), 0.37% (Group 3), 0.74% (Group 4), corresponding to 0.25, 0.5 and 1.0 MAC of halothane. Neuromuscular block was kept at 95% with a closed-loop feedback infusion of mivacurium and monitored with electromyography. Plasma cholinesterase concentrations and dibucaine numbers were determined. Results: Mivacurium infusion requirements (mean±SD) were 7.5±3.1 μg kg^-1 min^-1 with nitrous oxide-fentanyl anaesthesia. In the groups receiving 0.25, 0.5 or 1.0 MAC of halothane the steady-state infusion rates of mivacurium were reduced to 6.3±2.8, 5.6±1.4 and 5.7±2.5 μg-kg^-1min^-1 (P < 0.05), respectively. There was a linear relationship between mivacurium infusion requirements and plasma cholinesterase activity. Conclusion: Halothane anaesthesia reduces mivacurium infusion requirements by 15–25% compared to nitrous oxide-fentanyl anaesthesia. Interindividual differences in the extent of this interaction are great.     

Recovery characteristics of sevoflurane or halothane for day-case anaesthesia in children aged 1-3 years

BACKGROUND: Our objective was to compare the recovery characteristics of sevoflurane and halothane for short day-case anaesthesia in a specifically limited age group of children 1-3 yr. METHODS: Eighty unpremedicated children undergoing day-case adenoidectomy were randomly assigned to receive inhalational induction with either sevoflurane 8% or halothane 5% and nitrous oxide in oxygen (70/30) via a face mask. Tracheal intubation was performed without a muscle relaxant. Anaesthesia was continued with the volatile anaesthetic, adjusted to maintain heart rate and blood pressure within +/-20% of initial values. Recovery was evaluated using a modified Aldrete score, a Pain/Discomfort scale and by measuring recovery end-points. A postoperative questionnaire was used to determine the well-being of the child at home until 24 h after discharge. RESULTS: Emergence and interaction occurred significantly earlier after sevoflurane than halothane but discharge times were similar. More children in the sevoflurane group achieved full Aldrete scores within the first 30 min after anaesthesia, although this group suffered more discomfort during the first 10 min. The amount of postoperative analgesic administered was higher and the first dose given earlier in the sevoflurane group. Postoperative vomiting was more common with halothane, but side-effects in the two groups were otherwise similar in the recovery room and at home. CONCLUSIONS: In children 1-3 yr, sevoflurane provided more rapid early recovery but not discharge after anaesthesia of <30-min duration. Apart from more vomiting with halothane and more discomfort during the first 10 min after awakening with sevoflurane, the quality of recovery was similar with the two anaesthestics.     

Different effects of halothane, isoflurane and sevoflurane on sarcoplasmic reticulum of vascular smooth muscle in dog mesenteric artery

Background: The direct effect of halothane on vascular smooth muscle is mediated in part via its effects on the sarcoplasmic reticulum (SR). Little information is available concerning the effects of other volatile anesthetics including isoflurane and sevoflurane, whose vascular effects differ from those of halothane. The aim of the present study was to compare the effects of halothane, isoflurane and sevoflurane on the SR by testing the contraction induced by caffeine in vascular smooth muscle. Methods: Rings without endothelium from isolated canine mesenteric artery were mounted in physiological saline solution (PSS) for isometric tension recording. After complete depletion of Ca²⁺ from the SR by adding 35 mM caffeine, the rings were exposed to normal Ca²⁺ containing PSS (Ca²⁺ loading), to Ca²⁺-free PSS for 10 min, and then to 15 mM caffeine to induce contraction. Anesthetics were administered during Ca²⁺ loading, the Ca²⁺-free phase and simultaneously with caffeine administration. Results: Halothane (0.5-2%) attenuated the caffeine-induced contraction of canine mesenteric artery when administered during Ca²⁺ loading in the SR (P<0.001), whereas isoflurane and sevoflurane (1–4%) failed to affect the contraction. When given simultaneously with caffeine, halothane (1–2%) potentiated the caffeine-induced contraction (P<0.05), but isoflurane and sevoflurane had no effect. When given before caffeine administration, halothane (0.5-2%), isoflurane (24%) and sevoflurane (4%) all potentiated the caffeine-induced contraction (P<0.05). Conclusion: It has been shown that halothane not only potentiates caffeine- induced Ca²⁺ release from the SR, but also induces contraction by releasing Ca²⁺ from the SR. We conclude that halothane decreases Ca²⁺ accumulation in the SR while exerting facilitative and additive effects on caffeine-induced Ca²⁺ release from the SR when applied before caffeine administration and simultaneously with caffeine, respectively, whereas isoflurane and sevoflurane lack both the ability to decrease Ca²⁺ accumulation and an additive effect on caffeine-induced Ca²⁺ release from the SR, but are able to facilitate Ca²⁺ release by caffeine.     

A review of recovery from sevoflurane anaesthesia: comparisons with isoflurane and propofol including meta-analysis

BACKGROUND: Sevoflurane has a lower blood:gas partition coefficient than isoflurane and thus should be associated with a more rapid recovery from anaesthesia. METHODS: A review and meta-analysis were employed to examine the recovery profiles of adult patients following anaesthesia, comparing sevoflurane to isoflurane and sevoflurane to propofol. RESULTS: There were significant differences in times to several recovery events that favoured sevoflurane to isoflurane anaesthesia, including time to emergence, response to commands, extubation, and orientation. Likewise, there were significant differences in times to the same recovery events following anaesthesia with sevoflurane versus propofol. There were no differences in time to recovery room discharge when comparing sevoflurane to isoflurane or propofol. CONCLUSION: The observed differences between sevoflurane and isoflurane or propofol anaesthesia support the postulate that the use of sevoflurane is associated with a more rapid recovery from anaesthesia than either isoflurane or propofol.     

A comparison of antagonism of rocuronium-induced neuromuscular blockade during sevoflurane and isoflurane anaesthesia

Volatile anaesthetic agents potentiate neuromuscular blocking agents and retard their rate of reversal. We hypothesised that there was a difference in the rate of reversal of rocuronium-induced neuromuscular blockade based on the selection of inhalation agent. Thirty-eight patients undergoing elective surgical procedures received either sevoflurane or isoflurane, by random allocation. Neuromuscular blockade was induced using rocuronium 0.6 mg.kg-1 followed by continuous intravenous infusion to maintain 90% suppression of the single twitch response. Upon completion of surgery, the rocuronium infusion was discontinued, neostigmine 50 microg.kg-1 and glycopyrrolate 10 microg.kg-1 were administered. Times from reversal to T1 = 25, 50 and 60% and train-of-four ratio = 0.6 were recorded. The mean (SD) times to train-of-four ratio = 0.6 in the isoflurane and sevoflurane groups were 327 (132) and 351 (127) s, respectively. The mean (SD) times to single twitch response T1 = 25, 50 and 60% in the isoflurane group were 81 (33), 161 (59) and 245 (84) s, respectively, and in the sevoflurane group were 95 (35), 203 (88) and 252 (127) s, respectively. It is concluded that reversal of rocuronium-induced neuromuscular blockade is similar during isoflurane and sevoflurane anaesthesia.