Neuromuscular interaction between cisatracurium and mivacurium, atracurium, vecuronium or rocuronium administered in combination

We compared the dose–response relationships of cisatracurium, mivacurium, atracurium, vecuronium and rocuronium and examined the interactions of cisatracurium with mivacurium, atracurium, vecuronium and rocuronium in humans by isobolographic and fractional analyses. We studied 180 adult patients during nitrous oxide–fentanyl–propofol anaesthesia. Neuromuscular block was monitored using mechanomyography to detect the twitch response of the ulnar nerve at the wrist. The dose–response curves were determined by probit analysis. The calculated ED₅₀ values and their 95% confidence intervals were 40.9 (38.1–43.7), 49.8 (47.0–52.6), 187.2 (175.1–199.3), 36.6 (34.7–38.5) and 136.4 (129.2–143.6) μg.kg⁻¹ for cisatracurium, mivacurium, atracurium, vecuronium and rocuronium, respectively. Corresponding ED₉₅ values were 57.6 (53.5–61.7), 91.8 (88.1–95.5), 253.1 (238.9–267.3), 52.9 (49.1–56.7) and 288.7 (276.2–301.2) μg.kg⁻¹, respectively. The interaction between cisatracurium and mivacurium, vecuronium or rocuronium was found to be synergistic, but the interaction between cisatracurium and atracurium was found to be additive. Synergy between cisatracurium and vecuronium or rocuronium was greater than between cisatracurium and mivacurium.     

Comparison of rocuronium and suxamethonium for use during rapid sequence induction of anaesthesia

This study was designed to compare the tracheal intubating conditions during a rapid sequence induction of anaesthesia using rocuronium 0.6 ( n  = 61) or 1.0 mg.kg⁻¹ ( n  = 130) or suxamethonium 1.0 mg.kg⁻¹ ( n  = 127) as the neuromuscular blocking drugs. Anaesthesia was induced with fentanyl 1–2 μg.kg⁻¹ and thiopentone 5 mg.kg⁻¹ (median dose) and intubating conditions were assessed 60 s after the administration of the neuromuscular blocking drug by an observer unaware of which drug had been given. Intubating conditions were graded on a three-point scale as excellent, good or poor, the first two being considered clinically acceptable. The study was carried out in two parts. At the end of the first part a comparison between the two doses of rocuronium was carried out when at least 50 patients had been enrolled in each group. The results showed the intubating conditions to be significantly superior with the 1.0 mg.kg⁻¹ dose of rocuronium (p < 0.01). Final comparison between the 1.0 mg.kg⁻¹ doses of rocuronium and suxamethonium showed no significant difference in the incidence of acceptable intubations (96 and 97%, respectively). The incidence of excellent grade of intubations was, however, significantly higher with suxamethonium (80% vs. 65%; p = 0.02). It is concluded that rocuronium 1.0 mg.kg⁻¹ can be used as an alternative to suxamethonium 1.0 mg.kg⁻¹ as part of a rapid sequence induction provided there is no anticipated difficulty in intubation. The clinical duration of this dose of rocuronium is, however, 50–60 min.     

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.     

Prediction of infusion rates of rocuronium using the bolus test dose technique

Twenty-four patients were given a loading dose of rocuronium 1.0 mg.kg⁻¹ intravenously followed by boluses of 20 mg ( n  = 19) and 10 mg ( n  = 24) after return of T1 of the train-of-four to 5% of control. Neuromuscular function was assessed using a Relaxograph. The time was recorded for the return of T1 to 5% after the administration of the boluses and subsequently an infusion of rocuronium was started. The aim was to maintain T1 between 3% and 7% of control for at least 40 min without a change of infusion rate. The correlations between the duration of the test doses and the infusion rates were −0.94 (10 mg) and −0.86 (20 mg). The predictive accuracy of the 10 mg bolus was assessed in a further 10 patients. At the termination of the infusion three patients had a T1% that was outside the desired range of 3–7%. A 10 mg bolus that lasts 6 min indicates a need for an infusion of at least 60 mg.h⁻¹, 8 min (50 mg.h⁻¹), 10 min (40 mg.h⁻¹), 15 min (30 mg.h⁻¹), 24 min (20 mg.h⁻¹) and 34 min (15 mg.h⁻¹).     

A comparison of a prototype electromyograph vs. a mechanomyograph and an acceleromyograph for assessment of neuromuscular blockade

The extent of neuromuscular blockade during anaesthesia is frequently measured using a train-of-four stimulus. Various monitors have been used to quantify the train-of-four, including mechanomyography, acceleromyography and electromyography. Mechanomyography is often considered to be the laboratory gold standard of measurement, but is not commercially available and has rarely been used in clinical practice. Acceleromyography is currently the most commonly used monitor in the clinical setting, whereas electromyography is not widely available. We compared a prototype electromyograph with a newly constructed mechanomyograph and a commercially available acceleromyograph monitor in 43 anesthetised patients. The mean difference (bias; 95% limits of agreement) in train-of-four ratios was 4.7 (−25.2 to 34.6) for mechanomyography vs. electromyography; 14.9 (−13.0 to 42.8) for acceleromyography vs. electromyography; and 9.8 (−31.8 to 51.3) for acceleromyography vs. mechanomyography. The mean difference (95% limits of agreement) in train-of-four ratios between opposite arms when using electromyography was −0.7 (−20.7 to 19.3). There were significantly more acceleromyography train-of-four values > 1.0 (23%) compared with electromyography or mechanomography (2–4%; p < 0.0001). Electromyography most closely resembled mechanomyographic assessment of neuromuscular blockade, whereas acceleromyography frequently produced train-of-four ratio values > 1.0, complicating the interpretation of acceleromyography results in the clinical setting.     

Pre-operative forced-air warming as a method of anxiolysis

We tested the hypothesis that pre-operative forced-air warming is as effective for anxiolysis as intravenous midazolam, using a blinded, placebo controlled factorial design. One hundred and twenty patients were randomly assigned to cotton blanket and saline injection ( n  =   30), forced-air warmer and saline injection ( n  =   30), midazolam 30 μg.kg⁻¹ and cotton blanket ( n  =   30), and forced-air warmer and midazolam 30 μg.kg⁻¹ ( n  =   30). Patients completed visual analogue scales for anxiety and thermal comfort, and the State-Trait Anxiety Inventory, at baseline and after 20 min. The estimated effect of midazolam on visual analogue scores for anxiety was −10 (95% CI −3 to −18; p = 0.007) and on state anxiety was −5 (95% CI −7 to −4; p = 0.03). Warming had no influence on visual analogue scores for anxiety (p = 0.50) or state anxiety (p = 0.33), but its estimated effect on thermal comfort was +23 (95% CI 19–27; p < 0.0001). There was no interaction between midazolam and warming. Pre-operative warming was not equivalent to midazolam for anxiolysis and cannot be recommended solely for this purpose.     

Ketamine or alfentanil administration prior to propofol anaesthesia: the effects on ProSeal™ laryngeal mask airway insertion conditions and haemodynamic changes in children

This study was designed to compare the effects of ketamine and alfentanil administered prior to induction of anaesthesia with propofol, on the haemodynamic changes and ProSeal laryngeal mask airway^® (PLMA) insertion conditions in children. Eighty children, aged between 3–132 months, were randomly allocated to receive either alfentanil 20 μg.kg⁻¹ (alfentanil group) or ketamine 0.5 mg.kg⁻¹ (ketamine group) before induction of anaesthesia. Ninety seconds following the administration of propofol 4 mg.kg⁻¹, a PLMA was inserted. In the ketamine group, heart rate and mean arterial pressure were higher during the study period compared with the alfentanil group (p < 0.05). The time for the return of spontaneous ventilation was prolonged in the alfentanil group (p = 0.004). In conclusion, we found that the administration of ketamine 0.5 mg.kg⁻¹ with propofol 4 mg.kg⁻¹ preserved haemodynamic stability, and reduced the time to the return of spontaneous ventilation, compared with alfentanil 20 μg.kg⁻¹ during PLMA placement. In addition, the conditions for insertion of the PLMA with ketamine were similar to those found with alfentanil.     

The optimum bolus dose of remifentanil to facilitate laryngeal mask airway insertion with a single standard dose of propofol at induction in children

The purpose of this study was to determine the optimal bolus dose of remifentanil required for the successful insertion of the laryngeal mask airway during propofol induction in children without a neuromuscular blocking agent. Twenty-six paediatric patients, aged 3–10 years, requiring anaesthesia for short ambulatory surgery were recruited. A predetermined bolus dose of remifentanil was injected over 30 s, followed by propofol 2.5 mg.kg⁻¹ over 10 s. The bolus dose of remifentanil was determined by a modified Dixon's up-and-down method, starting from 0.5 μg.kg⁻¹ (0.1 μg.kg⁻¹ as a step size). Laryngeal mask insertion was attempted 90 s after the end of remifentanil injection and the response of patients was classified as either 'movement' or 'no movement'. The bolus dose of remifentanil at which there was a 50% probability of successful laryngeal mask insertion (ED₅₀) during induction with 2.5 mg.kg⁻¹ propofol was 0.56 (0.07) μg.kg⁻¹ in children without a neuromuscular blocking agent. From probit analysis, the ED₅₀ and ED₉₅ of remifentanil were 0.52 μg.kg⁻¹ (95% confidence limits, 0.42–0.62 μg.kg⁻¹) and 0.71 μg.kg⁻¹ (95% confidence limits, 0.61–1.40 μg.kg⁻¹), respectively.     

A comparison of the neuromuscular blocking effects and reversibility of cisatracurium and atracurium

The neuromuscular blocking effects and the reversibility of cisatracurium 0.1 or 0.15 mgkg⁻¹ were compared with those of atracurium 0.5 mgkg⁻¹ during anaesthesia with propofol, nitrous oxide and isoflurane. Neuromuscular block was monitored using train-of-four stimulation while recording the mechanomyographic response of the adductor pollicis muscle. The block was either allowed to recover spontaneously or was antagonised with neostigmine 50 μgkg⁻¹ at 10% or 25% recovery of the first twitch of the train-of-four. The median times to maximum block were 2.7, 2.2 and 1.5 min following cisatracurium 0.1 and 0.15 mgkg⁻¹ and atracurium 0.5 mgkg⁻¹, respectively. After cisatracurium 0.1 mgkg⁻¹ had been given, the median time to recovery of the train-of-four ratio to 0.8 ('adequate recovery') was 74 min during spontaneous recovery, 48 min after reversal with neostigmine when the first twitch of the train-of-four had returned to 10% of control and 50 min after reversal when the first twitch of the train-of-four had returned to 25% of control. These times for cisatracurium 0.15 mgkg⁻¹ and atracurium 0.5 mgkg⁻¹ were 90, 66 and 57 min and 75, 56 and 54 min, respectively. Administration of neostigmine significantly shortened the time to adequate recovery for both drugs but there were no significant differences in the case of either neuromuscular blocking drug between the groups of patients given neostigmine at 10 or 25% recovery of the first twitch of the train-of-four.     

Onset of neuromuscular blockade and intubating conditions one minute after the administration of rocuronium in children

In a blinded randomized study intubating conditions were compared at one min following intravenous induction with propofol and either suxamethonium 1.0 mg·kg⁻¹, or rocuronium 0.6 mg·kg⁻¹. Onset time to maximal twitch depression, % block at one minute and clinical duration (time to 25% recovery) were measured. Sixty children undergoing elective tonsillectomy were recruited. Onset time [42 s ( SD 11 s)] and clinical duration [3.3 min ( SD 1.0 min)] in the suxamethonium group was significantly ( P <0.001) less than in the rocuronium group [92 s (41 s)] and [24.2 min (6.6 min)] respectively. The median twitch height at one minute for suxamethonium was 0% (range 0–8%) and significantly greater ( P <0.001) at 5% (range 0–22%) for rocuronium. Despite this there was no difference in the intubating conditions at one minute with 25 excellent/5 good in the suxamethonium group and 27 excellent/3 good in the rocuronium group. We conclude that rocuronium 0.6 mg·kg⁻¹ gives optimal intubating conditions at one minute in children.     

Neuromuscular interactions between mivacurium and esmolol in rabbits

We compared the dose–response relationship and the neuromuscular blocking effects of mivacurium during infusions of esmolol in 40 anaesthetised rabbits. Train-of-four stimuli were applied every 10 s to the common peroneal nerve and the force of contraction of the tibialis anterior muscle was measured. Plasma cholinesterase activity decreased by 13% after esmolol infusion. The ED₉₅ of mivacurium increased significantly from 29 (4.8) μgkg⁻¹ with placebo to 61 (9.8) μgkg⁻¹ during esmolol 100 μgkg⁻¹.min⁻¹, 49 (8.2) μgkg⁻¹ during esmolol 300 μgkg⁻¹.min⁻¹ and 54 (7.3) μgkg⁻¹ during esmolol 500 μgkg⁻¹.min⁻¹, respectively (p < 0.001). The duration of neuromuscular block with mivacurium 0.16 mgkg⁻¹ was prolonged by 30% with esmolol due to diminished plasma cholinesterase activity (p < 0.05). Heart rate and mean arterial blood pressure decreased by 15% with esmolol (p < 0.05). The results of this study show that, in rabbits, esmolol decreased plasma cholinesterase activity, antagonised the neuromuscular blocking potency of mivacurium and prolonged its neuromuscular blocking effect.     

A portable self-learning fuzzy logic control system for muscle relaxation

We have assessed the practicality and performance of the Vital Signs Paragraph neuromuscular blockade monitor as part of a 'self-learning' fuzzy logic control feedback system used to administer atracurium to a required depth of neuromuscular blockade. Fifteen patients undergoing surgery expected to last longer than 90 min entered the study. A Vital Signs Paragraph was used to measure the degree of neuromuscular blockade and control it such that the first twitch of the train-of-four was kept at 10% of its baseline value. The controller instructed a Graseby Medical 3400 infusion pump to administer an atracurium infusion to maintain this level of blockade. Five patients (33%) were withdrawn from the study due to inadequate piezo-electric sensor function. In the remaining 10 patients, the system achieved stable control of neuromuscular blockade with a mean (range) error for the first twitch of the train-of-four of −0.45 (−1.06 to 0.13)%. The mean atracurium infusion rate ranged from 0.13 to 0.67 mg.kg⁻¹.h⁻¹. These results compare reasonably well with previous results using the Datex Relaxograph, whilst the system itself was portable and easy to use. However, the reliability of the system was limited due to variability in the sensitivity of piezoelectric sensors.     

Efficacy of ondansetron and metoclopramide for preventing postoperative emesis following strabismus surgery in children

A double-blind, randomised, placebo-controlled trial was conducted to compare the efficacy of metoclopramide with the 5-HT₃ antagonist, ondansetron, for the prevention of postoperative emesis in children undergoing elective strabismus surgery. None of the children received any premedication and a similar anaesthetic technique was used for all. Ondansetron 0.15 mg.kg⁻¹, metoclopramide 0.25 mg.kg⁻¹ or saline placebo were administered following intravenous catheter placement. Episodes of emesis were recorded for the first 24 h for the intervals of 0–2, 2–6 and 6–24 h. The incidence of emesis in the first 24 h was observed to be 71.7% in the placebo group, 34.4% in the ondansetron group (p < 0.001) and 61.4% in the metoclopramide group (p = NS). The severity of vomiting was less in the ondansetron group as compared with metoclopramide (p < 0.01) and placebo (p < 0.001). Recovery room scores were comparable in all the groups. No serious side-effects were observed in the ondansetron group. We conclude that prophylactic ondansetron is effective and superior to metoclopramide in the prevention of postoperative emesis in children following elective strabismus surgery.     

Optimal remifentanil dosage for providing excellent intubating conditions when co-administered with a single standard dose of propofol

This dose–response study aimed to determine the dose of remifentanil combined with propofol 2.5 mg.kg⁻¹ which provided excellent intubation conditions in 95% of patients. Ninety premedicated female ASA 1 and 2 patients were randomly allocated to five remifentanil dose groups (1, 2, 3, 4 or 5 μg.kg⁻¹). Induction of anaesthesia was performed with a blinded dose of remifentanil infused over 60 s simultaneously co-administered with propofol 2.5 mg.kg⁻¹ infused over 45 s. Tracheal intubation was attempted 150 s after the beginning of induction. Intubating conditions were assessed with the Copenhagen score. A probit analysis was performed to calculate the intubating efficient doses (IED) of remifentanil in 95% of patients (IED₉₅). Our data revealed that the IED₉₅ of remifentanil was 4.0 (95% CI: 3.4–5.6) μg.kg⁻¹, which was associated with a maximum decrease in heart rate and mean arterial pressure of < 30%, a finding which also applied to the other groups.     

The effect of clonidine on sevoflurane requirements for anaesthesia and hypnosis

We evaluated the effects of clonidine given orally on sevoflurane requirements for anaesthesia and hypnosis. Patients received either clonidine (5 μg.kg⁻¹) by mouth ( n  =21) 90 min before surgery or no premedication ( n  =21) by random allocation. MAC was calculated using repeated tetanic nerve stimulation with end-tidal sevoflurane concentration increased or decreased by 0.3 vol.% depending on the previous response. MAC awake was calculated according to the response to verbal command. The mean (SD) MAC in the clonidine-treated patients was 1.53 (0.20)% compared with 1.83 (0.15)% in the control group (p <0.001). Similarly, MAC awake was reduced in the clonidine group (0.50 (0.08)% compared with 0.60 (0.07)% in the control group) (p <0.001). We conclude that clonidine 5 μg.kg⁻¹ orally administered pre-operatively reduces sevoflurane requirements for anaesthesia and hypnosis.     

The use of low-dose mivacurium to facilitate insertion of the laryngeal mask airway

Ninety patients were assigned randomly in a double-blind manner to receive 0.9% sodium chloride, mivacurium 0.04 mg.kg⁻¹ or mivacurium 0.08 mg.kg⁻¹ intravenously, followed by propofol 2.5 mg.kg⁻¹. A laryngeal mask airway (LMA) was inserted 90 s later. The LMA was positioned correctly during the first attempt in 87% of patients and this was not significantly altered by the use of mivacurium. However, mivacurium decreased the incidence of swallowing, coughing, movement and laryngospasm (p < 0.05). LMA insertion was graded as easy in 88% of patients who had mivacurium, compared with 50% in patients who had propofol alone (p < 0.05). The conditions during LMA insertion were similar after 0.04 or 0.08 mg.kg⁻¹ of mivacurium. Patients were apnoeic for a mean (SD) time of 0.67 (0.72) min after propofol alone, compared with 1.72 (1.06) min and 3.05 (1.36) min in patients who also received mivacurium 0.04 and 0.08 mg.kg⁻¹, respectively (p < 0.01). Patients who received mivacurium had a lower incidence of postoperative sore throat (24–30% vs. 53%) (p < 0.05). In conclusion, low-dose mivacurium facilitates LMA insertion and decreases the incidence of postoperative sore throat.     

The minimum effective doses of pethidine and doxapram in the treatment of post-anaesthetic shivering

This study was designed to find the minimum effective doses of doxapram and pethidine to stop post-anaesthetic shivering. Two hundred and twenty healthy patients who shivered following routine surgery were allocated randomly to receive one of 10 doses of doxapram (0.18, 0.23, 0.29, 0.35, 0.41, 0.47, 0.7, 0.93, 1.17 and 1.4 mg.kg⁻¹), one of five doses of pethidine (0.12, 0.18, 0.23, 0.29 and 0.35 mg.kg⁻¹) or saline. Probit analysis demonstrated that the number of patients who stopped shivering with doxapram was independent of the amount of drug given in this dose range. The lowest dose of doxapram (0.18 mg.kg⁻¹) was significantly more effective than placebo (p < 0.01). For pethidine there was a dose-dependent effect on shivering to a maximum of 95% of patients successfully treated with 0.35 mg.kg⁻¹. We conclude that 0.35 mg.kg⁻¹ of pethidine is the minimum dose required to treat post-anaesthetic shivering effectively. We also conclude that 0.18 mg.kg⁻¹of doxapram is as effective as 1.4 mg.kg⁻¹ in the treatment of post-anaesthetic shivering. Further study is required to find the minimum effective dose of doxapram.     

Significance of the injection timing of ephedrine to reduce the onset time of rocuronium

We postulated that the onset time of rocuronium can be accelerated effectively if it is administered at the time when the effect of ephedrine on cardiac output has reached its maximum. Seventy-five male, anaesthetised, patients were randomly allocated to three groups. Ephedrine 70 μg.kg⁻¹ was administered at 4 min (Early) or 30 s (Late) before administering rocuronium. The control group received saline at 4 min and at 30 s before rocuronium. The onset time of rocuronium in the Early group was significantly shorter than in the Control group, but there was no difference in the onset time between the Late and Control groups. There were no significant differences in the intubating conditions of the three groups. Ephedrine 70 μg.kg⁻¹ can reduce the onset time of rocuronium effectively if rocuronium is administered at 4 min following the ephedrine injection, when the effect of ephedrine on cardiac output is expected to reach its maximum.     

Co-induction and laryngeal mask insertion# A comparison of thiopentone versus propofol

Conditions for insertion of the laryngeal mask airway were assessed in 70 unpremedicated patients comparing the co-induction with midazolam-alfentanil-thiopentone and midazolam–alfentanil–propofol. Following pre-induction doses of midazolam 0.04 mg.kg⁻¹ and alfentanil 10 μg.kg⁻¹, patients received equipotent doses of either thiopentone or propofol. Whilst jaw relaxation and ease of laryngeal mask insertion were similar between the two groups, patients receiving propofol were less likely to have undesired responses requiring additional boluses of induction agent (p < 0.05). We conclude that, using these doses, propofol is superior to thiopentone for laryngeal mask airway insertion when using a co-induction technique.     

Comparison of computer-controlled administration of propofol with two manually controlled infusion techniques

Ninety women were studied in order to compare dose requirements and quality of anaesthesia between target-controlled infusion and two manually controlled infusion schemes for propofol administration: group I received target-controlled infusion for induction (4 μg.ml⁻¹ target blood concentration, increased by 2 μg.ml⁻¹ after 3 min if consciousness not lost), groups II and III received an induction bolus of propofol at infusion rates of 1200 or 600 ml.h⁻¹, respectively, until loss of consciousness. Anaesthesia was maintained with propofol target-controlled infusion in group I or by constant rate infusion in the other two groups. Computer simulations were used to calculate blood and effect-site propofol concentrations. Mean induction times (SD) were 78 (65) s in group I versus 51 (10) s and 62 (12) s in groups II and III, respectively (p < 0.05 between groups II and III). Mean induction doses were: 1.31 (0.44), 2.74 (0.56) and 1.77 (0.43) mg.kg⁻¹ and mean maintenance doses were 13.4 (3.55), 9.32 (1.71) and 9.97 (1.53) mg.kg⁻¹.h⁻¹ in groups I, II and III, respectively (p < 0.05 between all groups). There was a lower incidence of apnoea in group I than in groups II and III. There were no significant differences between the groups in other objective parameters of anaesthetic quality studied. Computer simulations showed an 'overshoot' in propofol blood and effect-site concentration with manual induction and significantly higher maintenance levels with target-controlled infusion.