Spontaneous recovery of residual neuromuscular blockade after atracurium or vecuronium during isoflurane anaesthesia

With atracurium and vecuronium, spontaneous recovery of residual neuromuscular blockade monitored electromyographically during 0.5% isoflurane anaesthesia was studied in 60 patients undergoing plastic surgery. After thiopentone, in random order, either atracurium 0.5 mg kg-1 or vecuronium 0.1 mg kg-1 was administered and isoflurane added to N2O and O2 mixture. Following spontaneous recovery of both the single twitch amplitude (T1) to 75% of the control value and the train-of-four ratio (TOF ratio) to 75%, incremental doses of the relaxant were given to maintain the T1 at less than 10%. Before the end of surgery, the blockade was again permitted to recover spontaneously. During the initial spontaneous recovery, the mean recovery time of T1 from 25% to 75% (the recovery index) with atracurium was longer (P less than 0.001) than that with vecuronium (13.2 min and 10.1 min, respectively) but, during the second recovery, the mean recovery index was shorter (P less than 0.05) with atracurium than with vecuronium (16.1 min and 19.8 min, respectively). The recovery time from T1 75% to TOF ratio 75%, indicating the recovery rate of residual neuromuscular blockade, with atracurium was about 15 min after both the initial and the second recoveries. With vecuronium, the respective recovery times were significantly (P less than 0.001) longer (25.6 min and 38.5 min, respectively). It is concluded that with vecuronium there is slower spontaneous recovery of residual neuromuscular blockade than with atracurium.     

The neuromuscular effects of ORG9426 in patients receiving balanced anesthesia

In searching for a nondepolarizing muscle relaxant with intermediate duration but more rapid onset of action than the presently available compounds, the neuromuscular and circulatory effects of ORG9426 were investigated in two studies in humans receiving fentanyl, droperidol, thiopental, and nitrous oxide-oxygen anesthesia. Eighty patients, randomly assigned to one of four groups of 20 each, received 0.12, 0.16, 0.20, or 0.24 mg/kg ORG9426. In the first study, the doses (in milligrams per kilogram) of ORG9426 that caused 50% (ED50), 90% (ED90), or 95% (ED95) neuromuscular block were determined by the individual dose-response method; they were 0.170, 0.268, and 0.305 mg/kg, respectively. In the second study, after induction of anesthesia, patients received 0.6 mg/kg (about 2 x ED95) of ORG9426, either in a single bolus (group 1) or in two unequal (0.1 and 0.5 mg/kg) increments 4 min apart (group 2). After the administration of 0.6 mg/kg ORG9426, maximal neuromuscular block developed in 1.5 +/- 0.12 min in group 1 and in 1.2 +/- 0.14 min in group 2. Patients tracheas were intubated after development of the maximal neuromuscular effect of the intubating dose and after the recording of heart rate and systolic and diastolic blood pressure. There was no difference in the clinical duration of the intubating doses, which were 40.0 +/- 3.2 (15-73) min in group 1 and 39.3 +/- 2.4 (19-57) min in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)     

The neuromuscular effects of sevoflurane and isoflurane alone and in combination with vecuronium or atracurium in the rat

Sevoflurane was compared to isoflurane anesthesia alone and in combination with atracurium or vecuronium in 84 rats using the sciatic nerve—anterior tibialis muscle preparation. Both bolus injection and infusion rate techniques were used to evaluate these drug interactions. The ED₅₀ (dose which produced a 50% depression of twitch tension) of atracurium was 311 ± 31 and 360 ± 32µg·kg^–1 during 1.25MAC sevoflurane and isoflurane anesthesia respectively. The ED₅₀ of vecuronium was 190 ± 27 and 149 ± 14µg·kg^–1 during 1.25MAC sevoflurane and isoflurane anesthesia respectively. The mean infusion rates of atracurium and vecuronium required to maintain a 50% depression of twitch tension were 5.04 ± 0.7 and 2.02 ± 0.3mg·kg^–1·hr^–1. These infusion rates were 5.04 ± 0.7 and 2.02 ± 0.3mg·kg^–1·hr^–1 during 1.25MAC sevoflurane and 3.73 ± 0.3 and 1.81 ± 0.4mg·kg^–1·hr^–1 during 1.25MAC isoflurane anesthesia respectively. With both atracurium and vecuronium, the infusion rate required to maintain a 50% depression twitch of tension was inversely related to the concentrations of isoflurane and sevoflurane. The authors conclude that sevoflurane is similar in potency to that of isoflurane in augmenting a vecuronium or atracurium induced neuromuscular blockade in a dose-dependent manner.(Shin YS, Miller RD, Caldwell JE, et al.: The neuromuscular effects of sevoflurane and isoflurane alone and in combination with vecuronium or atracurium in the rat. J Anesth 6: 1–8, 1992)     

Acceleromyographic monitoring of neuromuscular block over the orbicularis oris muscle in anesthetized patients receiving vecuronium

Study ObjectiveTo evaluate the level of neuromuscular block acceleromyographically over the orbicularis oris muscle.DesignProspective, randomized, controlled study.SettingOperating room of a university-affiliated hospital.Patients36 adult, ASA physical status I and II women scheduled for mastectomy with air-oxygen-isoflurane-fentanyl anesthesia.InterventionsPatients were randomized to two groups. In the orbicularis oris group (n=18), the facial nerve was stimulated and movement of the orbicularis oris muscle was measured acceleromyographically. In the control group (n=18), adduction of the thumb was quantified mechanically.MeasurementsOnset and recovery of neuromuscular block caused by vecuronium 0.1 mg/kg were compared between the groups.Main ResultsTime to onset of neuromuscular block in the orbicularis oris group was significantly shorter than in the control group (176 ± 52 vs. 220 ± 34 sec, mean ± SD; P = 0.004). Times to return of the first, second, third, or fourth (T1, T2, T3, or T4) response of train-of four (TOF), and recovery of T1/control were comparable between the groups. Train-of-four ratio (T4/T1) in the orbicularis oris group was significantly higher than in the control group 50 to 120 minutes after vecuronium administration (P < 0.05).ConclusionDepth of neuromuscular block can be assessed acceleromyographically over the orbicularis oris muscle. Onset of neuromuscular block is quicker and recovery of TOF ratio is faster over the orbicularis oris muscle than at the thumb in patients receiving vecuronium.     

Assessment of neuromuscular and haemodynamic effects of cisatracurium and vecuronium under sevoflurane-remifentanil anaesthesia in elderly patients

BACKGROUND AND OBJECTIVE: Neuromuscular block times, quality of muscle relaxation for tracheal tube insertion, and the haemodynamic effects after cisatracurium and vecuronium under sevoflurane-remifentanil anaesthesia were compared in elderly patients. METHODS: The study was performed in 40 patients over 65 yr of age. Anaesthesia was induced with thiopental, and maintained with sevoflurane in N2O/O2 and remifentanil. Cisatracurium 0.15 mg kg(-1) or vecuronium 0.1 mg kg(-1) were administered after induction. Intubation was attempted when neuromuscular block was 95%. Onset time, clinical duration of action, recovery index, spontaneous recovery time and tracheal intubation conditions were assessed. Haemodynamic parameters were also monitored. RESULTS: The average ages of the patients were 72.5 +/- 5.1 and 73.6 +/- 6.3 in the cisatracurium and vecuronium groups, respectively. Onset time was significantly shorter after vecuronium, 158 +/- 34 s vs. 200 +/- 50s, respectively. Recovery index was significantly shorter after cisatracurium, 19.5 +/- 7.5 s vs. 33.7 +/- 18.6 s (P < 0.05). Clinical duration and spontaneous recovery time were similar in both groups as well as haemodynamic variables. CONCLUSIONS: In elderly patients, vecuronium has a faster onset time while cisatracurium has a shorter recovery index under sevoflurane-remifentanil anaesthesia.     

The haemodynamic effects of rocuronium and vecuronium are different under balanced anaesthesia

Background: Rocuronium has been reported to have minimal haemodynamic effects. However, this conclusion has been drawn primarily from investigations conducted under narcotic-based anaesthesia. This study was designed to evaluate the cardiovascular effects of rocuronium under isoflurane/N20/fentanyl anaesthesia and to compare rocuronium's haemodynamic effects to those of vecuronium and pancuronium.
Methods: Anaesthesia was induced with fentanyl 2 μg/kg, thiopentone 4 mg/kg, and suxamethonium 0.5 mg/kg in 75 ASA I or II patients. After tracheal intubation, anaesthesia was maintained with isoflurane 0.5% and N₂0 50% in oxygen. Five min after intubation (baseline), patients randomly received either vecuronium 100 μg/kg, rocuronium 600 μg/kg, rocuronium 900 μg/kg, rocuronium 1200 μg/kg, or pancuronium 140 μg/kg. One min after administration of muscle relaxant, mean arterial pressure (MAP) and heart rate (HR) were recorded and were subsequently measured at 1-min intervals for the next 4 min.
Results: HR decreased significantly ( P <0.05) at all times compared to baseline in patients receiving vecuronium. HR significantly ( P < 0.05) increased in those receiving rocuronium 1200 μg/kg or pancuronium. Patients who received vecuronium had a sigruficant ( P < 0.05) decrease in MAP at all times compared to baseline. Comparing results between groups, patients who received rocuronium or pancuronium had significantly ( P < 0.05) higher MAP compared to those administered vecuronium.
Conclusion: The haemodynamic effects of rocuronium and vecuronium are different under balanced anaesthesia. Rocuronium may attenuate the fall in MAP that often occurs under balanced anaesthesia without surgical stimulation.     

Effect of tetanus on subsequent neuromuscular monitoring in patients receiving vecuronium.

The current study evaluated the effects of tetanic stimulation on neuromuscular responses to serial train-of-four (TOF) and double-burst stimulation (DBS). For TOF monitoring (n = 13), a degree of neuromuscular blockade was achieved with an intravenous vecuronium infusion such that the ratio of fourth twitch (T4) to first twitch (T1), T4/T1, was stable at a value between 0.1 and 0.7. Four seconds after a 5-s, 50-Hz tetanic stimulus was delivered, TOF monitoring was resumed at 10-s intervals. Significant changes were noted for T1, T4, and T4/T1, with median increases of 38, 250, and 93%, respectively. The median times for T1, T4, and T4/T1 to return to within 10% of their pretetanic (baseline) values were 34, 43, and 34 s, respectively (P = nonsignificant [NS] among times to recovery). A 100-Hz tetanic stimulus induced 50, 300, and 178% median increases of T1, T4, and T4/T1, while corresponding values for recovery times were 53, 73, and 54 s. For DBS monitoring (n = 14), tetanic stimulation (50-Hz, 5-s) induced 38, 300, and 153% median increases of the DBS3,3 parameters (first response [D1], second response [D2], and their ratio [D2 not equal to D1], respectively). The posttetanic effects on D1, D2, and D2/D1 persisted for 43, 66, and 46 s, respectively. For DBS3,2, median posttetanic (50-Hz, 5-s) increases were 41, 275, and 176%, while corresponding times to recovery were 43, 43, and 43 s. Although the data indicate that the posttetanic percent increase was at least 10 times larger at greater degrees of blockade (T4/T1 = 0.1) than at lesser degrees (T4/T1 = 0.7), all T4/T1 and D2/D1 ratios returned to within 10% of baseline in 125 s or less after 5-s tetanic stimulation.     

The effects of prolonged isoflurane anaesthesia on cerebral blood flow and metabolism in the dog

To determine whether cerebral blood flow (CBF) changed with time under isoflurane anaesthesia, as has been reported for halothane, CBF and cerebral metabolic rate for oxygen (CMRO2) were studied in five dogs under prolonged isoflurane anaesthesia. CBF was measured with a modified sagittal sinus technique and CMRO2 was calculated as the product of CBF and the arteriovenous O2 difference. Maintaining this experimental dog model with 1% isoflurane in oxygen and nitrogen for 3 h in five dogs and for 4 h in three dogs did not cause any significant changes in CMRO2 or CBF. Cerebral metabolite levels were consistent with earlier reports from short-time studies and the EEG recordings showed a continuous sleep pattern with no pathological changes. It is concluded that there is no change in CBF or CMRO2 in our modified sagittal outflow model during 3-4 h of 1% isoflurane anaesthesia.     

Safety and efficacy of atracurium (BW33A) in surgical patients receiving balanced or isoflurane anesthesia

Atracurium was administered in a dose range of 0.027-0.4 mg/kg and dose-response curves were established for both balanced and isoflurane anesthetic techniques. With balanced anesthesia, ED50 and ED95 were 0.12 and 0.27 mg/kg, respectively, while with isoflurane they were 0.07 and 0.13 mg/kg and the least-squares regression line R2 values were 0.71 and 0.64, respectively. With balanced anesthesia there was a significant increase in systolic blood pressure at the 0.04 mg/kg dose (P = 0.02), while with isoflurane the systolic and diastolic blood pressures decreased at the 0.3 mg/kg dose (P less than 0.03). These changes were clinically insignificant. Atracurium is a potent nondepolarizing muscle relaxant which is potentiated by isoflurane. Its cardiovascular effects appear clinically nonsignificant. There is no evidence of histamine release.     

The influence of the duration of isoflurane anaesthesia on neuromuscular effects of mivacurium

Background: The pharmacodynamic profile of muscle relax-ants is usually changed by volatile anaesthetics. These changes seem to be time-dependent, even though few data are available to substantiate this.
Methods: We studied neuromuscular effects of a single dose of mivacurium (0.2 mg·kg^-1) during short and intermediate duration of isoflurane anaesthesia. Forty-five children 1–10 years of age were randomized to receive 1.5% end-tidal concentration of isoflurane in N₂O/O₂ for 10 or 30 min (groups Iso-10 and Iso-30, respectively) or to receive nitrous oxide in oxygen for 10 min (Group N₂O) before 0.2 mg · kg^-1 of mivacurium was given. Neuromuscular response was recorded by adductor pollicis electromyogram.
Results: The onset time of mivacurium was shorter in Group Iso-30, 1.7 (1.0–2.3) min than in Group Iso-10, 2.3 (1.7-3.3) rnin or Group N₂O, 2.3 (1.7-3.3) min (median with 10–90% percen-tiles) ( P <0.05). In Group Iso-30 the recovery time of the first EMG response was significantly longer than in groups Iso-10 and N₂O ( P <0.0001). Groups Iso-10 and N₂O did not differ from each other.
Conclusions: Our results indicate that the duration of a constant concentration of isoflurane anaesthesia influences significantly the pharmacodynamics of mivacurium. The duration of a volatile anaesthesia is critical when potentiation of NMB is evaluated or compared in neuromuscular studies.     

Effects of halothane and isoflurane anaesthesia on microcirculatory blood flow in musculocutaneous flaps

Hypoperfusion and necrosis in musculocutaneous flaps used forreconstruction of tissue defects is still a significant clinicalproblem. Although the causes of hypoperfusion are frequentlysurgical in nature, little is known about the effects of anaestheticmanagement on blood flow in flaps or the outcome of flap surgery.We compared in minipigs the effects of halothane and isofluraneanaesthesia in equipotent doses on microcirculatory blood flow(MBF) in the skin and muscle part of musculocutaneous flapsand also in intact (control) skin and muscle. Measurements weremade during stable normovolaemic conditions and during mildto moderate hypovolaemia (withdrawal of 5%, 10% and 15% of totalblood volume). Multi-channel laser Doppler flowmetry (LDF) wasused to measure MBF and electromagnetic flowmetry (EMF) fortotal flap blood flow. During normovolaemic conditions therewas no significant difference between the two groups in centralhaemodynamic or respiratory data. After 15% blood loss, however,there was a significant decrease in mean arterial pressure andcardiac output in the halothane group while there was no significantchange in the isoflurane group (P < 0.05). MBF in controlskin, control muscle and flap muscle remained approximately10–15% higher in the isoflurane than in the halothanegroup throughout the study. In the isoflurane group, MBF inflap skin was unchanged during normovolaemia and there was lessthan 10% decrease during hypovolaemia. In the halothane grouphypovolaemia caused a significant decrease in MBF in flap skin:27% decrease after 5% blood loss, 45% decrease after 10% bloodloss and 49% decrease after 15% blood loss compared with 5%,20% and 21%, respectively, in intact skin. We conclude thatduring normovolaemic conditions MBF was well maintained in musculocutaneousflaps in minipigs both with halothane and isoflurane anaesthesia;however, during mild to moderate hypovolemia MBF decreased markedlyin flap skin with halothane anaesthesia while it remained unchangedwith isoflurane.     

Augmentation of vecuronium-induced neuromuscular block during sevoflurane anaesthesia: comparison with balanced anaesthesia using propofol or midazolam

We have quantified the potentiating effects of 1.7% sevoflurane (n = 12) on vecuronium-induced neuromuscular block and compared the results with those obtained during balanced anaesthesia with propofol (n = 12) or midazolam (n = 12) in 36 patients. Neuromuscular function was monitored using an accelerograph and the train-of-four responses of the adductor pollicis muscle to ulnar nerve stimulation. Vecuronium 0.1 mg kg-1 was administered as an intubating dose, and maintenance doses of 0.02 mg kg-1 were administered on three occasions when T1/T0 had recovered to 25%. Thereafter, spontaneous recovery was monitored until complete. Times to 25% recovery of T1/T0 (DUR25) after an intubating dose of vecuronium did not differ between groups (mean 44.2 (SD 18.7) min for sevoflurane, 38.3 (7.5) min for propofol and 35.5 (9.5) min for midazolam). DUR25 values after each maintenance dose were 29.8 (9.5) min, 30.3 (10.4) min and 31.6 (10.7) min during sevoflurane anaesthesia, and were significantly longer than values for propofol (21.7 (6.0) min, 21.5 (5.8) min and 21.9 (5.8) min) and midazolam (20.0 (5.9) min, 19.3 (7.7) min and 19.8 (8.0) min) (P < 0.05) in each case). Recovery index25-75% and interval from T1/T0 = 25% to T4/T1 = 0.7 after the final dose of vecuronium were significantly prolonged by sevoflurane (28.3 (13.2) min and 42.7 (16.4) min) compared with propofol (17.6 (6.1) min and 26.6 (9.8) min) or midazolam (16.3 (9.4) min and 26.0 (10.2) min) (P < 0.05 in each case).      

Liver function after sevoflurane or isoflurane anaesthesia in neurosurgical patients

Purpose

Although both sevoflurane and isoflurane are thought to be less hepatotoxic than halothane or enflurane, recent case reports have described liver injury after sevoflurane or isoflurane anaesthesia. There are no studies comparing liver function after sevoflurane or isoflurane anaesthesia. The purpose of this study was to compare serum liver enzyme concentrations in patients receiving either sevoflurane or isoflurane anaesthesia prospectively.

Methods

Ninety patients scheduled for elective neurosurgery were studied. Serum concentrations of aspartame aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBil), alkaline phosphatase (ALP), γ- glutamyl transpeptidase (GTP), and lactate dehydrogenase (LDH) were measured before and, 1, 2, 3, 7, and 14 days after either sevoflurane (45 patients) or isoflurane (45 patients) anaesthesia.

Results

AST ALT and GTP increased peaking seven days after anaesthesia, especially in the isoflurane group. The numbers of patients with abnormal values in AST and ALT were not different in the isoflurane from that in the sevoflurane group. The increase in TBil peaked one day after anaesthesia in both groups.

Conclusion

Even in a small number of patients, isoflurane induced an elevation of serum levels of liver enzymes more frequently than did sevoflurane three to 14 days after anaesthesia.     

The effects of sevoflurane are similar to those of isoflurane on the neuromuscular block produced by vecuronium

We have examined the interactions of 1 MAC of isoflurane andsevoflurane (and 66% nitrous oxide in oxygen) with vecuronium,using the EMG response of the abductor digiti minimi to train-of-four(TOF) stimulation of the ulnar nerve. We constructed dose-responsecurves for vecuronium in 54 patients. The curves for both isofluraneand sevoflurane had a significant leftward shift compared withthat for fentanyl-nitrous oxide anaesthesia (P < 0.01). Whenthe amplitudes of the first response (T1) had recovered to 50%of control in another 32 patients, subsequently we comparedthe spontaneous recovery rate of the ratio of the fourth tothe first TOF response (T4:T1) at 3-min intervals during the15-min period, in the presence of two volatile anaestheticsor after discontinuation of administration of anaesthetic. Therate of recovery of T4:T1 was significantly greater when bothanaesthetics were discontinued. However, this rate was similarfor both anaesthetics, suggesting that the mechanism of actionof the two anaesthetics is similar. (Br. J. Anaesth. 1994; 72:465–467)     

Bradycardia in patients receiving atracurium or vecuronium in conditions of low vagal stimulation

Four groups of 20 patients each received either vecuronium or atracurium together with either glycopyrronium or saline, and underwent anaesthesia free of vagolytic drugs, and surgery devoid of vagal activity. Determinations of plasma histamine concentrations were made to examine the possible correlation between these levels and changes in heart rate and blood pressure as well as a possible relationship with skin reactions after the administration of the relaxants. Patients who received vecuronium without the anticholinergic drug, glycopyrronium, showed a greater tendency towards bradycardia (though not statistically significant) than those given atracurium. More cutaneous reactions were observed with patients who received atracurium than in those with vecuronium, but there was no correlation with plasma histamine concentrations of either relaxant group. There was no correlation either between histamine concentrations and heart rate or blood pressure associated with atracurium. The incidence of bradycardia with either relaxant is low if the anaesthetic technique and the surgery are devoid of vagal activity.     

The cardiovascular effects of vecuronium during halothane anaesthesia

In a double-blind, placebo-controlled, prospective randomized trial in 70 otherwise healthy patients undergoing elective surgery of the thyroid gland, the breast, the inguinal canal or the lower limbs, we studied the cardiovascular effects of vecuronium during halothane-nitrous oxide anaesthesia. Vecuronium was found to have no clinically significant influence on heart rate or mean arterial pressure, before or during surgery. Bradycardia was a rare event under the special conditions of the study design.