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) micrograms.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) micrograms.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.     

Isobolographic and dose-response analysis of the interaction between pipecuronium and vecuronium

We have studied the neuromuscular effects of pipecuronium, vecuronium and their combination in 130 ASA group I or II patients. Patients were anaesthetized with 0.8% halothane and 60% nitrous oxide in oxygen. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to train-of-four stimulation of the ulnar nerve (2 Hz at 10-s intervals). The dose-response curves were determined by probit analysis. The calculated doses producing 50% depression of the first twitch height were 15.6, 16.9 and 15.0 micrograms kg-1 for the pipecuronium, vecuronium and pipecuronium-vecuronium combination groups, respectively. Isobolographic and algebraic (fractional) analyses were used to assess quantitatively the combined neuromuscular effect of pipecuronium and vecuronium and to define the type of interaction between these drugs. The interaction between pipecuronium and vecuronium was found to be additive.     

Novel approaches to the study of autoregulation of alternative complement pathway

Forty patients without eye disease, undergoing elective nonophthalmic surgery, were studied in a double-blind, randomised, placebo-controlled study evaluating the efficacy of mivacurium pretreatment in attenuating the rise in intra-ocular pressure in response to suxamethonium administration, laryngoscopy and intubation. The patients were randomly allocated to receive either mivacurium 0.02 mg.kg-1 or normal saline as pretreatment 3 min before a rapid sequence induction technique using alfentanil, propofol and suxamethonium. Suxamethonium induced a significant increase in intra-ocular pressure in the control group but not in the mivacurium pretreatment group (mean (SEM) increase = 3.5 (1.2) mmHg vs. 0.4 (0.8) mmHg, p < 0.05). There was a decrease in intra-ocular pressure in both groups after laryngoscopy and intubation with no significant difference between the two groups. These results show that mivacurium pretreatment is effective in preventing the increase in intra-ocular pressure after suxamethonium administration.     

Comparison of [123I]beta-CIT and [123I]IPCIT as single-photon emission tomography radiotracers for the dopamine transporter in nonhuman primates

The aim of our randomized controlled study was to compare the neuromuscular characteristics of mivacurium and atracurium by evaluating the intubation conditions, intubation times, onset times and the duration of action of these two muscle relaxants using two different dosing principles. Forty-eight patients were included in this study. All patients were premedicated orally with 0.2 mg/kg diazepam. Anaesthesia was induced with 2.0 mg/kg propofol and 0.02 mg/kg alfentanil and maintained with 6 mg/kg/h propofol and 60% nitrous oxide in oxygen. Neuromuscular monitoring was carried out with supramaximal TOF-stimulation (2 HZ) of the ulnar nerve every 10 seconds and recording of the mechanomyogram (MMG) (Myograph 2000, Biometer) at the adductor pollicis muscle. The patients of group 1 (n = 12) received an intubation dose of 0.15 mg/kg mivacurium (2 x ED95) and the patients of group 2 (n = 12) received a priming dose of 0.015 mg/kg mivacurium (20% of ED95) followed by an intubation dose of only 0.07 mg/kg mivacurium (ED95) two minutes later. The patients of group 3 (n = 12) were intubated with 0.46 mg/kg atracurium (2 x ED95) and the patients of group 4 (n = 12) received a priming dose of 0.046 mg/kg atracurium (20% of ED95) and an intubation dose of 0.23 mg/kg atracurium (ED95) four minutes later. The patients were intubated under normocapnic conditions and following stabilisation of the palmar skin temperature after a 90% neuromuscular block (T1) had occurred. The intubation conditions were measured semiquantitatively using an intubation score.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postoperative allergic complications: the role of the anesthetist in conducting the immuno-allergic investigation

When peri-anaesthesia anaphylactic and/or anaphylactoid reactions occur, anaesthetist is the first investigator: the quality of immuno-allergological investigations depends on these initial investigational procedures. We have used sample kits for several years in order to make easier the immediate investigation. From retrospective analysis of the allergic complications which happened in 1997, the importance of these sample kits as well as the anaesthetist's part in the immuno-allergological management are examined. Nine observations were itemized (0.047%): 3 generalized erythema observations (grade I), in which atracurium was incriminated twice, and propacetamol once; 2 observations of grade II, in which vecuronium (elevated tryptase) and atracurium were incriminated; 4 anaphylactic shocks, in which three neuromuscular blocking drugs (suxamethonium, vecuronium and pancuronium), and one antibiotic (cloxacilline) were incriminated. The use of sample kits allowed an early diagnosis approach, confirmed by skin tests. Diagnosis should be thought closely between anaesthetists and immunologists for investigations.     

Esophageal cyst--a rare cause of backache

BACKGROUND: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. METHODS: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg.kg-1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg.kg-1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg.kg-1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. RESULTS: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). CONCLUSION: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Viruses and virus-like particles identified in ostrich gut contents

Several postsynaptic nondepolarizing muscle relaxants are used today mainly for maintenance of muscular relaxation in surgical operations. They possess a highly selective effect on the cholinoceptors (CC) of the skeletal muscle postsynaptic membrane. Aminosteroid derivatives are important among them. The first to be suggested was pancuronium, and later pipecurium and the monoquaternary aminosteroid derivatives vecoronium and rocuronium. Highly selective muscle relaxants are atracurium and its isomers, cisatracurium in particular, as well as some atracurium derivatives: mivacurium and doxacurium. Tercuronium also has a highly selective effect on the CC of the skeletal muscles.     

Comparison of neuromuscular effects, efficacy and safety of rocuronium and atracurium in ambulatory anaesthesia

PURPOSE: To compare the neuromuscular effects, efficacy, and safety of equi-effective doses of rocuronium and atracurium in ambulatory female patients undergoing surgery. METHODS: Forty-one patients undergoing laparoscopic gynaecological surgery were randomized to receive 2 X ED90 rocuronium (0.6 mg.kg-1; n = 20) or atracurium (0.5 mg.kg-1; n = 21) during intravenous propofol/alfentanil anaesthesia with N2O/O2 ventilation. Neuromuscular block was measured with a mechanomyogram eliciting a train-of-four (TOF) response at the wrist. Intubation conditions 60 sec after administration of muscle relaxant and immediate cardiovascular disturbances or adverse events during the hospital stay were noted by blinded observers. RESULTS: Compared with atracurium, rocuronium was associated with a shorter onset time (59.0 +/- 22.2 vs 98.6 +/- 41.4 sec; P < 0.001) and clinical duration of action (33.3 +/- 7.1 vs 44.7 +/- 7.2 min; P < 0.001), but longer spontaneous recovery index (9.6 +/- 2.41 vs 6.9 +/- 1.89 min; P = 0.023) and a similar time to spontaneous recovery to TOF 70%; 53 +/- 6.31 vs 59.2 +/- 7.59 min; P = 0.139). Tracheal intubation was accomplished in < 90 sec in all patients receiving rocuronium but in only 14 of 21 patients receiving atracurium. The incidence of adverse events and the cardiovascular profiles for the two drugs were similar, although one patient receiving atracurium experienced transient flushing of the head and neck. CONCLUSION: Rocuronium has minimal side effects, provides conditions more suitable for rapid tracheal intubation, and is associated with a shorter clinical duration than atracurium. Once begun, the spontaneous recovery profile of rocuronium is slightly slower than that of atracurium.     

Prolonged mivacurium infusion in young and elderly adults

PURPOSE: This study was designed to evaluate pharmacodynamically and pharmacokinetically if the cis-cis isomer of mivacurium contributed to neuromuscular block during prolonged infusions lasting more than four hours in young adult and elderly (> 60 yr) patients. METHODS: The mechanomyogramic neuromuscular response of the adductor pollicis was recorded in 32 adults 18-59 yr. and 19 elderly (> 60 yr.) patients during N2O:O2:opioid anaesthesia. The mivacurium infusion rate was adjusted to maintain single twitch depression at 95 +/- 4% of control. Blood samples were taken every 30 min to determine the plasma concentration of cis-cis isomer of mivacurium. At the end of the surgical procedure, patients were allowed to recover spontaneously to at least 25% of control twitch response. RESULTS: The mean mivacurium infusion requirement to maintain 97 +/- 1 (mean +/- SD)% depression of the twitch response was 6.0 +/- 0.4 micrograms.kg-1.min-1 in young adults, and 4.3 +/- 0.3 micrograms.kg-1.min-1 in elderly patients (P < 0.001). The infusion requirement in patients with low plasma cholinesterase activity was the lowest 2.4 +/- 1.2 micrograms.kg-1.min-1. Plasma cis-cis isomer concentrations reached peak levels within one-two hours and remained relatively constant throughout the duration of infusion even in patients with low cholinesterase activity. There was no relationship between duration of infusion, plasma concentrations of cis-cis isomer and the early recovery indices of mivacurium (up to 25%). Neuromuscular transmission recovered adequately with or without antagonism in all patients. CONCLUSION: When the mivacurium infusion was titrated to maintain 95 +/- 4% twitch depression, the plasma concentration of the cis-cis isomer did not increase during prolonged infusions (four hours) and neuromuscular transmission recovers satisfactorily.     

Resistance to atracurium in rats with experimental inflammation: role of protein binding

The influence of altered protein binding on the neuromuscular effect of atracurium has been studied in rats with experimental inflammation induced by subcutaneous injection of turpentine oil. Doses of atracurium ranging from 0.45 to 1.5 mg.kg-1 were administered to control (n = 30) and to experimental inflammation induced rats (n = 30). Neuromuscular transmission was monitored by recording the twitch tension of the tibialis-anterior muscle elicited by stimulation of the sciatic nerve. Three effect parameters were recorded: (i) intensity of the effect, measured as percentage depression of baseline twitch tension, (ii) duration of drug action (min) and (iii) recovery time (min). The dose-intensity of the effect relationship was modelled using a sigmoid Emax model. The ED50 (effective dose eliciting 50% of the maximum effect) was significantly increased (P < 0.01) in the inflammation group as compared to the control group (0.94 vs. 0.68 mg.kg-1). This change was reflected in a shift of the dose-response curve to the right in the pretreated rats. For equipotent doses ED95 (defined as the effective dose eliciting 95% of maximum effect), no differences were found in recovery time and duration of action between the two groups of rats. Mucoproteins levels (index of alpha 1-acid glycoprotein (AAG) and protein binding were significantly increased in rats with experimental inflammation as compared to control rats. Based on these results, altered serum protein binding of atracurium appears to be responsible, at least in part, for the resistance to atracurium.     

Down''s syndrome is strongly associated with coeliac disease

BACKGROUND: Investigations recording recovery times of muscle relaxants have used initial or final baseline of a neuromuscular trace, or both, as a reference for data analysis. We evaluated the use of final baseline of EMG traces as a reliable reference to calculate recovery times. METHODS: We analyzed EMG traces from 82 children who had full spontaneous neuromuscular recovery following a single dose of mivacurium. Times from administration of mivacurium to 25, 50, 75, and 90% EMG recoveries were measured using both initial and final baselines as a reference. EMG traces with final baseline of 100 +/- 10% of the initial baseline were regarded as optimal. Recovery times from all other traces were compared to the times obtained from these optimal traces. Poor final baseline was defined as that of < 80% of initial baseline. Inter-group comparisons were made using Kruskal-Wallis test followed by Mann-Whitney U tests. RESULTS: EMG recovery times were similar for optimal traces whether the reference was the initial or the final baseline of the EMG trace. If the final baseline was used as the reference, then traces with poor final EMG baseline also showed similar neuromuscular recovery times. If the initial baseline was used as the reference for EMG traces with poor final baseline, then neuromuscular recovery times became 24-55% longer (P < 0.05). CONCLUSIONS: We conclude that the final baseline of an EMG trace can be used as a reference for calculations of neuromuscular recovery times following a bolus injection of mivacurium.     

Pharmacokinetics and pharmacodynamics of mivacurium stereoisomers in beagle dogs using twitch height and train-of-four response

Mivacurium, a non-depolarizing neuromuscular blocking agent, consists of three isomers; trans-trans (57%), cis-trans (36%) and cis-cis (7%). The purpose of this study was to characterize the pharmacokinetics and pharmacodynamics of mivacurium after various inputs. Four beagle dogs weighing between 7.95 and 9.89 kg were anesthetized with isofluorane (5%) and received a bolus dose (0.010-0.020 mg kg(-1)) and two constant rate infusions (1.0-1.5 microg kg(-1) min(-1)) of mivacurium via the saphenous vein. Single twitch height (TH) and train-of-four (TOF) were evaluated every 15 and 30 s, respectively. Arterial blood samples were collected, processed and analysed for mivacurium using a stereospecific HPLC-fluorescence method. The disposition of mivacurium isomers was best described by a two compartment model. Mean Cl for the cis-trans, trans-trans and cis-cis isomers were 19.98, 13.53 and 3.47 mL min(-1) kg(-1) respectively and the corresponding mean Vdss were 0.29, 0.24 and 1.00 L kg(-1). The measurement of onset showed dose dependence as evidenced by a rapid onset at the higher doses. TOF measurements were more sensitive to the onset of action and required a longer period of time to recover to baseline values as compared with TH measurements.     

Vitamins C and E prolong time to arterial thrombosis in rats

BACKGROUND: Patients on chronic anticonvulsant drugs are relatively resistant to certain nondepolarizing neuromuscular blockers such as pancuronium, vecuronium, pipecuronium, doxacurium, or metocurine, but not resistant to mivacurium and atracurium. This study investigated the influence of chronic carbamazepine therapy on the neuromuscular block induced by the new muscle relaxant rocuronium. METHODS: Twenty-two otherwise healthy individuals scheduled for neurosurgical operations were studied: 11 of them were on chronic treatment with carbamazepine; the others served as control subjects. The median duration of carbamazepine therapy was 9 weeks (range, 4-312 weeks). After premedication with oral diazepam, anesthesia was induced with fentanyl and thiopental and maintained with nitrous oxide/oxygen and 0.5% inspired isoflurane. Rocuronium, 0.6 mg/kg (2 x ED95), was given for intubation. The ulnar nerve was stimulated, and the evoked electromyogram recorded using a Datex NMT monitor. RESULTS: Based on the response to the first of four stimuli, neither the lag time nor the onset-time differed between the two groups. However, the intervals of recovery to 10%, 25%, 50%, and 75% of the baseline response and the recovery index (RI, 25%-75%) were significantly shorter in patients on chronic carbamazepine therapy. CONCLUSIONS: The authors conclude that the duration of the rocuronium-induced neuromuscular block is significantly shortened by preceding chronic carbamazepine therapy.     

Perinatal cocaine decreases the expression of prodynorphin mRNA in nucleus accumbens shell in the adult rat

Postpartum patients have decreased plasma cholinesterase activity, which may slow the metabolism of mivacurium. We compared the duration of a mivacurium neuromuscular block in 11 women undergoing postpartum tubal ligation 36-99 h after delivery with that in 11 control women undergoing gynecological surgery. Anesthesia was induced with propofol and fentanyl and maintained with propofol and nitrous oxide. Neuromuscular block was monitored by electromyography, and the ulnar nerve was stimulated transcutaneously using a train-of-four pattern. Patients received a bolus dose of mivacurium 0.15 mg/kg. The median (range) duration of neuromuscular block until 25% recovery of the first twitch response was longer in the postpartum group, 19.4 (15.6-25.2) min, compared with the control group, 16.3 (11.0-23.4) min (P = 0.04). The median (range) plasma cholinesterase activity was decreased in the postpartum group, 4.0 (0.1-5.5) kU/L, compared with the control group, 7.1 (6.2-10.0) kU/L (P < 0.001). The duration of neuromuscular block was inversely correlated with cholinesterase activity (Kendall rank correlation tau = -0.43, P = 0.005). The slight prolongation of neuromuscular block should not be significant clinically. Implications: Postpartum patients have decreased amounts of the plasma cholinesterase enzyme. This would slow the metabolism of the muscle relaxant mivacurium. However, the duration of muscle paralysis is only prolonged by approximately 3 min, which would not normally cause any significant problems.     

Pharmacokinetics of mivacurium isomers and their metabolites in healthy volunteers after intravenous bolus administration

BACKGROUND: Previous studies report the pharmacokinetics of mivacurium isomers after an infusion using venous blood sampling. Although the extent of the mivacurium arterial-venous gradient is not known, the sampling site is likely to influence mivacurium pharmacokinetic parameters because the drug is rapidly metabolized as it traverses the circulation. The objectives of this study were (1) to determine the pharmacokinetics of mivacurium isomers in healthy persons after intravenous bolus administration using intensive arterial blood sampling, and (2) to characterize the formation and elimination of mivacurium metabolites in human plasma. METHODS: Eight persons classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled to undergo elective surgery under balanced anesthesia received 0.15 mg/kg mivacurium chloride as an intravenous bolus. Arterial blood samples were collected every 10 s during the first 2 min and at frequent intervals for 4 h thereafter. Plasma concentrations of mivacurium isomers and their metabolites were determined by two stereoselective high-performance liquid chromatographic methods coupled with fluorometric detection and noncompartmental pharmacokinetic parameters. RESULTS: Mean elimination half-lives of the trans-trans, cis-trans, and cis-cis isomers were 2.4, 2, and 28.5 min, respectively, with corresponding mean plasma clearances of 29.2, 45.7, and 6.7 ml.min 1.kg-1. The volumes of distribution at steady state of the trans-trans, cis-trans, and cis-cis isomers were 0.047, 0.054, and 0.189 l/kg, respectively. Plasma concentrations of monoester and alcohol metabolites peaked 25 s (median) after mivacurium injection, with half-lives in the range of 90 min, except for the cis alcohol metabolite, which was only negligibly and transiently formed. CONCLUSIONS: Substantial hydrolysis of mivacurium isomers by cholinesterases was confirmed by the rapid appearance of mivacurium metabolites in plasma. The intensive arterial sampling proved to be critical for the trans-trans and cis-trans isomers because the area under the curve between 0 and 2 min accounted for 75% and 86% of the total, respectively.     

The effects of age on onset and recovery from atracurium, rocuronium and vecuronium blockade

Elderly patients may show an age-related decline in physiologic functions, which may be responsible for the prolonged duration of some neuromuscular blocking agents. Previous studies have yielded conflicting results as to the effects of these drugs in the elderly. METHODS: After obtaining informed consent and approval of the Ethics Committee, we compared onset and recovery times of single IV doses of atracurium, rocuronium, and vecuronium given to 108 patients divided into three groups according to age (18-50, 51-64, > or = 65 years). Following oxazepam premedication and fentanyl and thiopentone induction, patients were randomly allocated to receive atracurium, rocuronium or vecuronium (0.5, 0.6, or 0.1 mg/kg, respectively) in < or = 0.8 vol.% enflurane (end-tidal)-nitrous oxide anaesthesia. Muscular relaxation was assessed by electromyographic (EMG) recording of the adductor pollicis muscle after supramaximal single-twitch stimulation of the ulnar nerve every 10 s. Onset time and recovery to 25%, 75% and 90% of twitch control values (DUR25, 75, 90) were recorded. Creatinine clearance predicted from serum creatinine (Ccr) was correlated with recovery from neuromuscular block. RESULTS: Onset time was not different among groups or relaxants. The results showed a prolonged duration of action for atracurium (DUR75, DUR90), rocuronium (DUR25, DUR75), and vecuronium (DUR25) in the elderly. A number of patients did not reach DUR75 or DUR90. There was a significant relationship between age and failure to return to control values during recovery from neuromuscular block, especially after atracurium and rocuronium. Ccr showed a negative correlation with age for all relaxants, but a negative significant correlation between Ccr and recovery was found only for rocuronium. CONCLUSIONS: This study suggests that onset time for atracurium, rocuronium and vecuronium is not age-dependent. Recovery was prolonged in the elderly for all three relaxants. This effect appears to be secondary to changes in body composition and function accompanying the aging process. Neither atracurium nor vecuronium depends significantly on the kidney for elimination, but the negative correlation between Ccr and rocuronium suggests an appreciable role for the kidney in the elimination of this relaxant. The long recovery times observed in this study could also be related to enflurane anaesthesia. We suggest that failure of EMG responses to return to baseline values during recovery from neuromuscular block may be related to age, especially for atracurium and rocuronium.     

Basal concentrations of various steroids in the nonobese diabetic (NOD) mouse and effect of immobilization stress

Psychiatric patients receiving phenothiazine, tricyclic antidepressant and antiparkinsonian drugs for prolonged periods, occasionally develop mydriasis and angle closure glaucoma. Suxamethonium, usually given to modify the convulsion of electroconvulsive therapy (ECT) increases intraocular pressure (IOP) by about 7-8 mmHg, the increase being maximal and having returned to baseline 2 min and 6 mins after injection, respectively. We studied the effects on IOP of an electrically induced convulsion following induction of anesthesia using methohexitone 1 mg.kg(-1) and suxamethonium 0.5 mg.kg(-1) in 21 consecutive cooperative psychiatric patients, all receiving antipsychotropic drugs. IOP was recorded sequentially from before induction of anesthesia to after resumption of spontaneous respiration. Their mean IOP was 15.3 (SD 3.7) mmHg prior to induction of anesthesia, 13.5 (SD 3.5) mmHg after loss of eyelash reflex following injection of methohexitone, 16.1 (SD 2.4) mmHg after cessation of muscle fasciculations induced by suxamethonium, 19.2 (SD 5.6) mmHg after cessation of convulsion and 15.5 (SD 4.4) mmHg following resumption of regular spontaneous respiration. The successive stepwise changes in the mean IOP were all statistically significant (p < 0.001 each change compared with the preceding pressure; paired 't' tests). These data reveal that the reduction in IOP produced by methohexitone is reversed by the increase in IOP produced by suxamethonium. Collated with the time course of the effects of barbiturates and suxamethomium on IOP, the increase in IOP observed following the induced convulsion was not greater than that expected after suxamethonium alone, suggesting that the induced convulsion during ECT does not pose an ocular hazard to psychiatric patients receiving medications which have iatrogenic glaucomatous potential.     

Pneumoperitoneum complicating mechanical ventilation in congenital myotonic dystrophy

We have studied the train-of-four (TOF) response mechanomyographically during onset of neuromuscular block produced by subclinical doses of suxamethonium in order to follow the augmentation of the first twitch of the TOF (T1) and TOF fade compared with control TOF responses before the drug was given. In the groups given suxamethonium 0.05, 0.1, 0.2 and 0.3 mg kg-1, the increments in T1 after administration of the drug were observed before twitch depression occurred; these were mean 22.3 (SEM 8.1)%, 19.2 (3.3)%, 10.8 (2.0)% and 4.2 (2.2)%, respectively. This effect was more marked with the lower doses (P < 0.05). The degree of TOF fade was moderate during onset of neuromuscular block and depended on the dose of drug. The results of this study suggest that low doses of suxamethonium produced transient increase in muscle tension and twitch depression with significant TOF fade. We conclude that suxamethonium was associated with presynaptic effects as a consequence of brief stimulation of acetylcholine release followed by progressive diminution at the neuromuscular junction.     

Reduced neuromuscular blocking potency of atracurium in patients with purulent intrathoracic diseases

OBJECTIVE: Based on personal observations the neuromuscular blocking potency of atracurium was supposed to be diminished in purulent intrathoracic diseases. This hypothesis was tested in a prospective clinical trial. METHODS: 52 adult patients undergoing general anaesthesia (methohexitone, sufentanil, flunitrazepam, N2O, enflurane) for elective thoracic surgery were investigated. After the intubation dose of 0.6 mg/kg atracurium was applied continuously to maintain a 90% suppression of the evoked compound electromyogram. According to the intraoperatively established diagnosis patients were allocated to three categories: 1) non-malignant tumor as the control group (n = 15), 2) lung cancer (n = 22), 3) purulent intrathoracic process without tumor (n = 15). The groups were compared regarding onset time, DUR 10% and maintenance dose of atracurium. RESULTS: Patients with lung cancer did not differ significantly from the controls regarding efficiency of atracurium. In contrast, patients with a purulent intrathoracic process showed a significantly longer onset time (6.3 +/- 2.5 vs. 2.9 +/- 0.8 min, p < 0.001), and a significantly shorter DUR 10% (23 +/- 6 vs. 36 +/- 10 min, p < 0.001) compared to the control group. Mean infusion rate of atracurium to maintain a 90% suppression of the evoked compound electromyogram was significantly higher in patients with a purulent process compared to the controls (10.5 +/- 3.2 vs. 6.0 +/- 1.2 micrograms/kg.min, p < 0.001). CONCLUSION: Our results support the hypothesis that patients with a purulent intrathoracic disease show a clear reduction in neuromuscular blocking potency of atracurium.     

Potentiation of mivacurium by rocuronium is age- and time-dependent: a study in children, adolescents, and young and elderly adults

Potentiation occurs when the steroidal muscle relaxant, rocuronium, is coadministered with the benzylisoquinolinium relaxant, mivacurium. The effect of time and age on this interaction was evaluated in four predetermined groups: children, adolescents, young adults, and elderly adults (15 per group) by monitoring the ulnar nerve-evoked force of contraction of the adductor pollicis (twitch response). During recovery from paralysis induced by 800 micrograms/kg of rocuronium, an infusion of mivacurium was started and maintained for at least 90 minutes to retain the twitch response at 1% to 9% of baseline tension (95 +/- 4% paralysis). Rocuronium at 600 micrograms/kg induced greater than 95% paralysis in 57 of the 60 patients within 2.2 +/- 0.4 (mean +/- SE) minutes. The period of recovery from rocuronium-induced paralysis to 5% of baseline twitch height was longest in the elderly (30.1 +/- 2.9 minutes) and shortest in the adolescents (16.5 +/- 2.4 minutes). The mivacurium infusion requirements to maintain 95 +/- 4% paralysis was highest in children and progressively increased with time. In young and elderly adults, the infusion rates remained lower than that of children and did not change with time. The incidence of satisfactory spontaneous recovery within 20 minutes (train-of-four ratio > 75%) was the highest in children, followed by adolescents and young adults, and was least in the elderly. The residual neuromuscular effect of rocuronium on the subsequent mivacurium infusion was most pronounced in the elderly, followed by young adults, then adolescents, and was least in children.