The duration of action of mivacurium is prolonged if preceded by atracurium or vecuronium

We studied 45 patients (ASA I-II) during propofol-alfentanil-N₂O-O₂ anaesthesia to determine if recovery from neuromuscular block induced by mivacurium is influenced differently by prior injection of atracurium or vecuronium. Neuromuscular function was monitored by adductor pollicis EMG. Patients were randomized to receive two dosesof either mivacurium (150 and 70 μg kg^-1), atracurium (350 and 75 μg kg^-1) or vecuronium (70 and 15 μg kg^-1) followed by a final dose of mivacurium 70 μg kg^-1. The second and third doses of the muscle relaxants were administered at 25–30% recovery of the E₁ (first EMG response in the train-of-four series). Following the final dose of mivacurium, the EMG response recovered to 25 and 95% in 10.4±3.9 and 19.7±5.7 min (mean±SD), respectively, if mivacurium was the only muscle relaxant. Respective times were 100% longer if mivacurium had been preceded by atracurium (23.8 ± 3.3 and 39.8±6.9 mm) or vecuronium (22.6±3.5 and 44.1 ±7.9 min) ( P =0.000l). The 25–75% recovery times in the three groups were 4.9±1.0, 8.7±2.4 and 10.5±2.5 min, respectively ( P =0.0001). Our results indicate that there is no benefit in giving mivacurium at the end of surgery after peroperative use of atracurium or vecuronium.     

Quantifying the interaction of vecuronium with enflurane using closed-loop feedback control of vecuronium infusion

The influence of different levels of enflurane anaesthesia on infusion requirements of vecuronium was studied in 40 adult surgical patients. Ninety percent neuromuscular block was maintained by computer controlled infusion of vecuronium. During the first 90 min study period all patients received fentanyl-nitrous oxide-oxygen (2:1) anaesthesia. For the following 90 min the patients were randomly assigned to receive enflurane at different end-tidal concentrations: group I, control, fentanyl-nitrous oxide anaesthesia; group II, enflurane 0.3%-nitrous oxide; group III, enflurane 0.6%-nitrous oxide; group IV, enflurane 0.9%-nitrous oxide. Every patient served as his/her own control and the changes of vecuronium infusion requirements were determined individually. When the administration of enflurane was started, vecuronium infusion requirements decreased progressively until 90 min. In group II the infusion rate lowered from 80±28 to 56±20 μg . kg^-1 . h ^-1, in group III from 61 ±29 to 34±17 μg . kg^-1 . h^-1 and in group IV from 65±20 to 30± 14 μg . kg^-1 . h^-1. In the control group the infusion rate decreased during the three hour study period from 69± 17 (first 90 min period) to 59± 16 μg . kg^-1 . h^-1 (second 90 min period). Enflurane reduces the dose requirements of vecuronium administered by continuous infusion in a dose- and time-dependent manner.     

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.     

Lack of effect of flumazenil on the reversal of propofol anaesthesia

Propofol, like the benzodiazepines, activates the GABA_A receptor-chloride ionophore complex; they potentiate one another. Since neither pharmacodynamic nor pharmacokinetic data concerning drug interaction between flumazenil and propofol is available, and especially considering the relationship of binding sites, flumazenil, the antagonist of benzodiazepines, was investigated to determine its effect upon recovery from propofol anaesthesia. Forty women receiving dilatation and curettage procedures were included in this double-blind test. After 50 μg fentanyl, propofol 2 mg · kg^-1 was injected for induction and followed by infusion at the rate of 15 mg · kg^-1 · hr^-1. After the operation, patients were given normal saline (Group A) or flumazenil 10 μg · kg^-1 (Group B) randomly.
Recovery time in Group A was 15.2±5.1 min and Group B 15.8±4.8 min. Propofol concentrations at the end of infusion were 4.17±1.33 μg ·ml^-1 (Group A) and 4.03±1.45 μg · ml^-1 (Group B); these then declined to 1.22±0.17 μg · ml^-1 (Group A) and 1.18±0.15 μg · ml^-1 (Group B) when patients were able to open their eyes on command. No significant differences were found between the groups based on propofol concentrations and recovery time, nor did haemodynamic changes differ between them after administration of reversal agents. It was concluded that flumazenil 10 μg · ml^-1 does not influence recovery from propofol anaesthesia.     

Mivacurium chloride—a comparative profile

Mivacurium is a new nondepolarizing muscle relaxant of the benzylisoquinoline type. Its short duration of action is due to rapid breakdown by plasma cholinesterase. The dose of mivacurium which produces 95% inhibition of twitch response (ED₉₅) is between 60 and 80 μg/kg. Thus, mivacurium is 0.8 times and four times as potent as vecuronium and atracurium, respectively. With 2–3×ED₉₅, tracheal intubation can be accomplished within 2.5 min of intravenous injection. The ensuing DUR25% (time from injection to 25% recovery of control twitch tension) is twice as long as with suxamethonium and about half as long as with equipotent doses of atracurium or vecuronium. For muscle relaxation during long surgical procedures, mivacurium has been used as a continuous infusion. The average 6-min recovery index after infusion of mivacurium is particularly favourable for flexible control of muscle paralysis, whereas the recovery indices after infusion of atracurium or vecuronium are 15–30 min. In conclusion, mivacurium will close the pharmacodynamic gap between suxamethonium and the nondepolarizing muscle relaxants of intermediate duration of action. It will probably also be a suitable alternative to suxamethonium in elective cases.     

Quantification of train-of-four responses during recovery of block from non-depolarising muscle relaxants

Train-of-four (TOF) responses were assessed in 70 patients (seven groups of ten patients each) during recovery of neuromuscular block from atracurium (226 or 452 μg/kg), vecuronium (40 or 80 μg/kg), pancuronium (60 or 120 μg/kg) and tubocurarine (450 μg/kg) in order to quantify the height of T₁ (first response in the TOF sequence) at which T₂, T₃ and T₄ (2nd, 3rd and 4th response in TOF sequence) reappear. Patients were anaesthetised with thiopentone, nitrous oxide in oxygen and fentanyl. There were small but significant differences between relaxants. The clinically useful parameter, i.e. the 4th response in the TOF sequence, appeared at approximately 30% height of the first response (T₁) rather than at 25% as generally believed. It is suggested that the third response in the TOF sequence, which reappeared at an average height of T₁ of about 25%, be used for administration of further supplements of muscle relaxants since abdominal muscle relaxation becomes inadequate at this stage.     

The effect of epidural bupivacaine on vecuronium–induced neuromuscular blockade in children

The efTect of epidural bupivacaine on potency and duration of action of vecuronium–induced neuromuscular blockade (NMB) was evaluated in 30 general surgical paediatric patients (ASA I–II) of three to ten years of age. Premedication was midazolam 0.5 μg kg^-1 orally (max 15 mg). In addition to general anaesthesia, 15 of the children received a lumbar epidural block with 0.5% bupivacaine 2.5 mg kg^-1. Anaesthesia was induced and maintained with N₂O:o₂ (2:1), propofol and alfentanil. NMB was monitored by adductor pollicis EMG with the train–of–four stimulus every 20 sec. Thirty minutes following the epidural bupivacaine injection (mean plasma concentration 0.86 μg ml^-1) or induction of anaesthesia a cumulative dose–response curve of vecuronium was established to achieve a 95% depression of the twitch response. Thereafter, NMB was allowed to recover spontaneously. ED doses of vecuronium were 19–22% greater in the control group than in the epidural group. ED^ doses were 33.8 (s.e.mean 1.3) μg kg"¹ and 28.4 (2.2) μg kg"', respectively ( P <0.05). There were no differences in recovery times from NMB between control and epidural group, the recovery index (time of twitch height to recover from 25 to 75%) being 6.4 (0.4) min and 7.0 (0.9) min, respectively. However, a negative correlation was found between bupivacaine plasma concentration and an ED₅₀ dose of vecuronium ( P =0.01). Our results indicate that vecuronium is slightly more potent in children with bupivacaine epidural block than in children without it.     

Effective dose of granisetron in the reduction of nausea and vomiting after breast surgery

Background: Prophylactic use of granisetron, a selective Shydroxytryptamine type 3 receptor antagonist, reduces the incidence of nausea and vomiting after breast surgery. This study was undertaken to determine the minimum effective dose of granisetron in the reduction of postoperative nausea and vomiting (PONV) in patients undergoing general anaesthesia for breast surgery.
Methods: In a randomized, double-blind manner, 120 female patients aged 42–66 years were assigned to receive either placebo (saline) or granisetron in a dose of 20 μg · kg^-1, 40 μg · kg^-1 and 80 μg · kg^-1 i.v. immediately before the induction of anaesthesia. A standard general anaesthetic technique was employed throughout. The POW and safety assessments were performed continuously during the first 24 h after anaesthesia.
Results: There were no significant differences among the groups with regard to patient demographics, surgical procedures, anaesthetics administered and analgesics given. The incidence of PONV was 47%, 43%, 17% and 17% after administration of placebo and granisetron 20 μg -kg^-1, 40 μg kg^-1 and 80 μg kg^-1, respectively. Granisetron 40 μg kg^-1 was as effective as 80 μ g - kg^-1 and both resulted in significant reductions of the incidence of PONV compared with placebo and granisetron 20 μg kg^-1 ( P < 0.05). No differences in the incidence of adverse events were observed among the groups.
Conclusion: Granisetron 40 μg · kg^-1 appears to be the minimum effective dose for reducing POW in patients undergoing general anaesthesia for breast surgery.     

Granisetron prevents nausea and vomiting during spinal anaesthesia for caesarean section

Background: Nausea and vomiting during spinal anaesthesia for caesarean section are common and unpleasant complications. This study was undertaken to evaluate the efficacy of granisetron, a selective 5-hydroxytryptamine type 3 receptor antagonist, for prophylactic treatment of nausea and vomiting in parturients undergoing nonemergent caesarean section under spinal anaesthesia.
Methods: In a randomized, double-blind, placebo-controlled trial, 100 patients, 21–38 years, received either placebo (saline) or granisetron at 3 different doses (20 μg · kg^-1, 40 μg · kg^-1 or 80 μg · kg^-1) (n=25 for each) intravenously immediately after clamping of the foetal umbilical cord. Nausea, vomiting and safety assessments were performed during spinal anaesthesia for caesarean section.
Results: The treatment groups were similar with regard to maternal characteristics and operative management. The incidence of nausea and vomiting was 64%, 52%, 14% and 12% after administration of placebo and granisetron in a dose of 20 μg · kg^-1, 40 μg · kg^-1 and 80 μg · kg^-1, respectively ( P <0.05; overall Fisher's exact probability test). No clinically important adverse effects were observed in any group.
Conclusions: Prophylactic use of granisetron in a minimum dose of 40 μg · kg^-1 is effective for preventing nausea and vomiting during spinal anaesthesia for caesarean section.
© Acta Anaesthesiologiat Scandinavica 42 (1998)     

Propofol sedation and gastric emptying in volunteers

Background : The purpose of this study was to evaluate the effects of light propofol sedation on gastric emptying and orocecal transit time (OCT).
Methods : Ten healthy male volunteers were studied on 2 occasions separated by at least 1 week and were randomly allocated to receive either propofol sedation or i.v. saline as a control. During propofol sedation the volunteers were sedated to grade 2–3 on a 5-grade scale. This was achieved by a propofol infusion of 5 mg kg^-1 h^-1 initially, which was then titrated down to a dose of 2.4±0.7 mg kg^-1 h^-1 Paracetamol absorption was used as an indirect measure of the rate of gastric emptying and OCT was determined by use of the hydrogen breath test after ingestion of raffinose. Student's t -test for paired samples was used and the results are presented as means± SD.
Results: During propofol sedation the maximum concentration of paracetamol (C_max) was 115±26.8μl/L, time to peak concentration (T_max) 50±38.8 min, and the area under the curve during the first 60 min (AUC₆₀4793±1538 μmolXmin/L, versus C_max 99±20.8, T_max 69±41.9 and AUC₆₀ 3897±1310 during saline infusion. These differences were not statistically significant. OCT was significantly shorter during the control study, 180±32.4 min, than during propofol sedation, 217±64.9 min (P<0.05).
Conclusion : This study in volunteers has shown that gastric emptying of liquids seems uninfluenced by light propofol sedation. OCT was slightly prolonged during light propofol sedation.     

Effect of succinylcholine on subsequently administered mivacurium in children

The interaction between mivacurium and succinylcholine when mivacurium was administered during the early recovery from succinylcholine block was studied in 30 children 2-12 years of age anaesthetized with propofolalfentanil-N₂O-O₂. Neuromuscular response was monitored by adductor pollicis EMG. Fifteen patients received 200 μg. kg^-1 of mivacurium (Group M), and another fifteen received 1500 μg. kg^-1 of succinylcholine followed by 200 μg. kg^-1 of mivacurium when the first EMG response recovered to 5% of calibration value (Group SchM). Plasma cholinesterase (pChE) activity was normal in each patient. The recovery times following mivacurium did not differ between the two groups. Times required for recovery of the first EMG response from 25 to 75% of full EMG recovery were 3.6±1.0 (mean±SD) and 4.0±0.7 min for the Groups M and SchM, respectively. The time from administration of mivacurium to the recovery of train-of-four ratio 0.70 was 13.2±3.3 min for the Group M and 13.6±3.1 min for the Group SchM (NS). Thus, in patients with normal pChE activity preceding administration of succinylcholine did not influence the recovery of neuromuscular function from subsequent mivacurium.     

Synergism between mivacurium and pancuronium in adults

Mivacurium could be a useful agent as a final dose of a muscle relaxant following pancuronium if only additivily exists between these agents. We examined the interaction between mivacurium and pancuronium in 70 patients (ASA I-II) during propofol-alfentanil-N₂O-C₂ anaesthesia. Neuromuscular function was monitored by adductor pollicis EMG.
Firstly we established dose-response curves for mivacurium and pancuronium. Thereafter, 20 patients received a combination of 0.5 times the ED₅₀ doses of mivacurium and pancuronium (cMP) determined in the first part of this study. Patients were randomized to receive the cMP to the same IV-line (n=10) or to two separate IV-lines in opposite hands (n=10).
ED₅₀ values for mivacurium and pancuronium were 57.7 and 37.1 μg kg^-1, respectively. Maximal neuromuscular block following the cMP was 91.8 ±5.0% (mean±SD). This was highly significantly different from the estimated 50% NMB if only additivity exists between mivacurium and pancuronium ( P =0.0001). After the cMP, the 25 75% recovery rime was 9.4± 1.3 min and the time to train-of-four ratio of 0.70 was 35.8±5.4 min. There was no statistical difference in any recorded neuromuscular parameter between the two subgroups receiving mivacurium and pancuronium to the same or to opposite hands ( P >040).
We conclude that a significant synergism exists between mivacurium and pancuronium which may indicate that mivacurium does not produce a short-acting NMB if given after pancuronium. We do not recommend using mivacurium together with pancuronium.     

Differential effects of dobutamine, dopamine, and noradrenaline on splanchnic haemodynamics and oxygenation in the pig

Supranormal oxygen (O₂) transport may benefit critically ill patients. Catecholamines are clinically employed for this purpose. However, their effects on splanchnic haemodynamics and oxygenation are not well defined. The effects of dobutamine (DOBU), dopamine (DOPA), and noradrenaline (NA) on splanchnic blood flows (electromagnetic flow probes), O₂ deliveries and uptakes (catheterisation of portal and hepatic veins) were studied in nine anaesthetised (ketamine/flunitrazepam), ventilated, paralysed, and laparotomised pigs. All three catecholamines (DOPA at 15 μg·kg^-1 · min^-1, DOBU at 13 μg · kg^-1 · min^-1, NA at 0.4 μg · kg^-1 · min^-1) significantly ( P <0.05) increased cardiac output and systemic O₂ delivery. Only DOPA increased small intestinal and total hepatic blood flows, and O₂ deliveries, and decreased O₂ extractions. The same parameters did not change during DOBU. During NA, total hepatic blood flow and O₂ delivery decreased, and hepatic O₂ extraction increased. During all three catecholamines, small intestinal and total hepatic O₂ uptakes did not change significantly. Whereas hepatic arterial blood flow decreased during both DOPA and NE, portal venous flow increased during DOPA. These data suggest that in the experimental model used splanchnic O₂ supply and O₂ reserve capacity appear improved by DOPA, unaffected by DOBU, and impaired by NA.     

Dose-response relationship for mivacurium inpatients with phenotypically abnormal plasma cholinesterase activity

During thiopentone-fentanyl-nitrous oxide anaesthesia and using a cumulative design, we studied the dose-response relationship of mivacurium in 8 patients: 7 patients phenotypically homozygous for the atypical plasma cholinesterase gene and 1 patient homozygous for the silent gene. The estimated mean ED₅₀ and ED₉₅ were 15 and 20 μg. kg. bw^-1 in patients homozygous for the atypical gene, and 13 and 16 μg. kg. bw^-1 in the patient homozygous for the silent gene, respectively. The results indicate that mivacurium is 4-5 times more potent in patients homozygous for the atypical or the silent gene than in patients with normal plasma cholinesterase activity and phenotype.     

Multiple Dose Kinetics of Ketobemidone in Surgical Patients

Twelve patients scheduled for major abdominal surgery were selected for a study of the kinetics of ketobemidone during the day of surgery and in a follow-up study 3–5 days after surgery. In six patients ketobemidone was administered as ketobemidone plain and in the other six, it was given as Ketogin®, a combination formula containing a spasmolytic substance in addition to ketobemidone. Plasma samples were collected for approximately 24 h following induction of anesthesia, during which time multiple doses of ketobemidone were administered. A single-dose study was performed 3–5 days after surgery using the same drug. No significant differences were found between the two formulations of ketobemidone. Plasma clearance did not change significantly between the two periods of study, being 18.0±4.4 ml · kg^-1 · min^-1 peroperatively and 21.7±7.6 ml · kg^-1 · min^-1 postoperatively. Peroperative V_{d area} was significantly larger than post-operative V_{d area}, 5.84±2.621 · kg^-1 and 3.63±0.381 ·; kg^-1, respectively. T1/2 terminal decreased from 3.84±1.6 h peroperatively to 2.06±0.44 h postoperatively.     

Succinylcholine-induced fasciculations in denevated rat muscles as measured using 31P-NMR spectroscopy

Background : We have previously demonstrated by ³¹P nuclear magnetic resonance (NMR) that succinylcholine (SCh) induces metabolic changes in denervated muscle. To specify those changes, we attempted to inhibit them using two different kinds of drugs, dantrolene and vecuronium.
Methods : Three weeks after unilateral sciatic nerve section, 75 male Wistar rats were randomly assigned to one of the following 5 groups: (1) non-pretreated normal muscle group; (2) non-pretreated denervated muscle group; (3) denervated muscle group pretreated with a low dose of vecuronium (0.02 mg · kg^-1); (4) denervated muscle group pretreated with a high dose of vecuronium (0.2 mg · kg^-1); (5) denervated muscle group pretreated with dantrolene (2 mg · kg^-1). The change of the inorganic phosphate/phosphocreatine (Pi/PCr) ratio of each muscle was measured by ³¹P-NMR before and after SCh (1 mg · kg^-1) administration and the corresponding peak amplitude of the electromyograms (EMG) was determined.
Results : The high dose of vecuronium totally inhibited SCh-induced fasciculation on EMG (100%2%). In this group, though the Pi/PCr ratio significantly increased 10 min after SCh, the peak after 5 min disappeared. The inhibition with dantrolene was about the same order of magnitude as with the low dose of vecuronium (35%:21%). However, the increase in the Pi/PCr only lasted about 10 min, in contrast to the other drugs.
Conclusion : Our findings indicate that the Pi/PCr increases 5 and 10 min after SCh, respectively, as a result of two different processes. The first peak is caused by an excessive energy consumption in response to excessive muscle contraction. This in turn triggers the second peak, caused by breakdown of glycogen, initiated by an increased Ca²⁺ concentration.     

Comparison of propofol/alfentanil anaesthesia with isoflurane/N2O/fentanyl anaesthesia for renal transplantation

Total intavenous anaesthesia (TIVA) with propofol and alfentanil was compared with balanced anaesthesia (BA) in 30 uraemic patients undergoing renal transplantation. TIVA (n=15) was induced with propofol and alfentanil and maintained with propofol and alfentanil infusions, which were started immediately after induction. Thereafter the infusion rates were adjusted as needed. Ventilation was with oxygen in air. BA (n= 15) was induced with thiopentone and fentanyl and maintained with isoflurane/N20/fentanyl. Vecuronium was used for muscle relaxation in both groups. Mean infusion rates for propofol and alfentanil were 10 1.8 mg kg^-1 h^-1 and 70 9 μg kg^-1 h^-1, respectively. To control hypertension during TIVA, larger amounts of propofol and alfentanil were needed and slower recovery was observed than in previous studies in ASA 1–2 patients. Also, significantly more vecuronium was needed during TIVA than during BA ( P < 0.05). The recovery parameters were similar in both groups, except for the occurrence of nausea, which was less after TIVA. In conclusion, TIVA had no clinical advantages over BA.     

Contradictory effects of dopamine at 32°C in pigs anesthetized with ketamine

Background: In critically ill patients who were surface cooled to 332C, we have observed that dopamine sometimes causes a substantial decrease in blood pressure. The present study was designed to compare the effects of dopamine in normothermia to those seen after surface cooling to 32C.
Methods: Seven pigs with a mean body weight of 21 kg were anesthetized with ketamine and muscle relaxation was induced with pancuronium. They were mechanically ventilated and given dopamine infusions (5 and 12 μg · kg^-1 min^-1) in normothermia and after surface cooling by cold water immersion to a central blood temperature of 320C (range 31.6–32.6C).
Results: In normothermia, dopamine at a dose of 5 μg · kg^-1 min^-1 increased mean arterial blood pressure (MAP) by 16% ( P < 0.01) and cardiac output (CO) by 9% ( P =0.051); at 12 μg kg^-1 min^-1 dopamine increased MAP by 26% ( P < 0.01) and CO by 18% ( P < 0.01). In hypothermia, MAP and CO did not change at an administration rate of 5 μg kg^-l · min^-1; at 12 μg · kg^-1 min^-1 CO was unchanged but MAP was significantly reduced by 15% ( P < 0.01).
Conclusion: Dopamine increased CO and MAP in normothermia but not at 32C, where there was even a significant reduction of MAP in this porcine model.     

Influence of premedication with diazepam or morphine on the induction dose of eltanolone

Background : This study examined the influence of premedication with morphine or diazepam on the dose of eltanolone, a steroidal intravenous anaesthetic agent, required to induce anaesthesia.
Methods : Two hundred and sixteen patients, aged 18 to 65 years, were randomly assigned to receive premedication with diazepam 10 mg orally, morphine 10 mg intramuscularly, or placebo. The double-dummy technique was used to maintain blinding. Eltanolone 0.16-0.75 mg·kg^-1 was given intravenously over 20 s. At the commencement of injection patients were instructed to begin counting; if the patient ceased counting within 120 s and failed to respond to commands to continue, anaesthesia was considered to have been induced. The dose required to anaesthetise 50% of patients (ED₅₀) was determined by logistic regression.
Results : The ED₅₀ (95% confidence interval) of eltanolone in patients who received placebo premedication was 0.31 (0.27-0.34) mg · kg^-1. It was reduced slightly and nonsignificantly by premedication with diazepam, to 0.27 (0.24-0.30) mg · kg^-1, or morphine, to 0.26 (0.23-0.29) mg · kg^-1. Involuntary movement occurred in 65% of placebo premedicated patients. Its incidence was not significantly reduced by diazepam (57%), but was significantly ( P <0.001) reduced by morphine (37%). Morphine premedication was, however, associated with a significant ( P <0.01) increase in the incidence of apnoea (21%) compared to placebo premedicated patients (4%).
Conclusion : Premedication with diazepam or morphine had little influence on the dose of eltanolone required to induce anaesthesia.     

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.