Interactions between suxamethonium and mivacurium or atracurium

We have compared the dose-response relationships of suxamethonium, mivacurium and atracurium and examined the interactions of suxamethonium with mivacurium or atracurium in humans by isobolographic analysis. We studied 100 adult patients during fentanyl and thiopentone anaesthesia. Neuromuscular function was monitored using a Myograph 2000 (Biometer Co., Odense, Denmark). The dose-response curves were determined by probit analysis. Isobolographic and fractional analyses were used to assess quantitatively the combined effect of equipotent doses of suxamethonium, mivacurium and atracurium and to define the type of interaction between suxamethonium and mivacurium or atracurium. The ED50 values for suxamethonium, mivacurium and atracurium were 198.8 (95% confidence interval 190.7-206.9), 48.6 (45.4-51.8) and 202.1 (197.9-206.2) mg kg-1, respectively. Isobolographic and fractional analyses of the suxamethonium-mivacurium and suxamethonium-atracurium combinations demonstrated antagonistic interactions.     

Writing for a medical journal

Cisatracurium (51W89) is one of the ten stereoisomers of atracurium, accounting for about 15% of the racemate. The ED95 of cisatracurium was determined to be about 50 micrograms/kg (cation, molecular weight 929), while the ED95 of atracurium (besylate salt, molecular weight 1245) was 250 micrograms/kg. Thus, on a molar basis in adult patients, cisatracurium is about 3.5 times as potent as the racemic atracurium mixture. We compared atracurium with cisatracurium in healthy adult patients and found an almost identical pharmacodynamic profile. In children, an ED95 of about 40 micrograms/kg was determined, while a 1-min-longer onset of cisatracurium was found in geriatric than in young adult patients. The presence of chronic renal failure did not prolong the duration of action of cisatracurium. The recovery of neuromuscular transmission from a cisatracurium infusion of up to 145 h was investigated in intensive care unit patients. Their time from the end of infusion to a train-of-four ratio > 0.7 (68 +/- 18 min) was on average only some 70% longer than after an infusion of cisatracurium for 2 h in normal surgical patients. In another study, no signs of histamine release nor any clinically relevant cardiovascular effects of cisatracurium were found in doses up to eight times ED95.     

Comparative clinical pharmacology of rocuronium, cisatracurium, and their combination

BACKGROUND: The comparative clinical pharmacology of cisatracurium and rocuronium and their combinations has not been reported. In this study, the authors compared the relative potency and the clinical profile and characterized the interaction of both drugs. METHODS: Two hundred twenty adults classified as American Society of Anesthesiologists physical status I and anesthetized with propofol-fentanyl-nitrous oxide were studied. In part 1, the neuromuscular-blocking effects of cisatracurium and rocuronium were assessed after administration of bolus doses of 20-50 microg/kg and 100-300 microg/kg, respectively. In part 2, we compared the time course of 1xED50, 1, 1.5, and 2xED95 doses of both drugs (where ED50 and ED95 are, respectively, the doses producing 50% and 95% depression of the first twitch height [T1]). In part 3, equieffective combinations of both drugs were studied to characterize their interaction. RESULTS: The calculated ED50 values and their 95% confidence intervals were 111 (107-115) and 26.2 (25.8-26.5) microg/kg [corrected] for rocuronium and cisatracurium, respectively. Compared with equipotent doses of cisatracurium, rocuronium had a faster onset, and a faster spontaneous T1 and train-of-four recovery times that were significant except at maximum recovery with the 2xED95 dose. The interaction between rocuronium and cisatracurium was synergistic, and the time profile of the combination group was different from that of the single-dose groups. CONCLUSIONS: Cisatracurium is four to five times more potent than rocuronium. Rocuronium had a faster onset of action, a shorter clinical duration, and a faster spontaneous recovery rate compared with equipotent doses of cisatracurium.     

Haemodynamic effects of rocuronium during fentanyl anaesthesia: comparison with vecuronium

Haemodynamic variables were measured following administration of rocuronium 0.6 mg.kg-1 or vecuronium 0.08 mg.kg-1 (approximately equivalent to 2 x ED95 doses) in patients anaesthetized with fentanyl 50 micrograms.kg-1 and scheduled to undergo elective coronary artery bypass grafting. There were increases in stroke volume index (+15%) and cardiac index (+11%), and a decrease in pulmonary capillary wedge pressure (-25%) following administration of rocuronium (P < 0.05). The changes in heart rate (+7%), mean arterial pressure (-5%), systemic vascular resistance (-12%) and other measured or derived indices were insignificant. In comparison the administration of vecuronium was associated with decreases in heart rate (-7%), mean pulmonary artery pressure (-17%), central venous pressure (-15%) and the rate-pressure product (-9%) (P < 0.05). The changes in mean arterial pressure (-7%), cardiac index (-6%) and systemic vascular resistance (-8%) following vecuronium were insignificant. There were no differences in any of the variables between rocuronium and vecuronium. The absolute values of all variables were, however, within acceptable clinical limits. There was no evidence of histamine release in any patient. The present study shows that rocuronium 0.6 mg.kg-1 is associated with changes of only small magnitude in haemodynamic variables.     

An open-label study of the safety and tolerability of converting stable liver transplant recipients to neoral

STUDY OBJECTIVES: (1) To compare the dose-response relations of rocuronium and vecuronium in healthy adult patients anesthetized with nitrous oxide-oxygen-fentanyl-thiopental; and (2) to evaluate the time-course of action of two drugs following equipotent doses. DESIGN: Prospective, randomized, clinical comparison. SETTING: Operating room, Plastic Surgery Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College. PATIENTS: 60 ASA physical status I patients, aged 17-51 years, scheduled for elective plastic surgery. INTERVENTIONS: All patients were randomly assigned to either the rocuronium or vecuronium group. General anesthesia was induced with thiopental 4 to 6 mg/kg and fentanyl 2 to 4 micrograms/kg intravenously (i.v.), and maintained with 60% nitrous oxide (N2O) in oxygen. Further increments of thiopental or fentanyl were given as required. The dose-response relations of rocuronium and vecuronium were determined by the cumulative dose-response technique. MEASUREMENTS AND MAIN RESULTS: Neuromuscular function was assessed mechanomyographically with train-of-four (TOF) stimulation at the wrist every 12 seconds. The percentage depression of first twitch (T1) was used as the study parameter. The cumulative dose-response curve of vecuronium was shifted to the left in a parallel fashion compared with that of rocuronium. As assessed by linear regression, the potency ratio of vecuronium: rocuronium was 1:7.2. There were significant differences in the ED50, ED90, and ED95 between the two drugs. After i.v. administration of equipotent doses of both drugs (2 x ED90), the duration of peak effect, clinical duration, recovery index, and total duration were not significantly different between the two drugs. CONCLUSIONS: Compared with vecuronium, rocuronium is a low-potency, nondepolarizing relaxant, and its neuromuscular blocking potency is approximately 15% that of vecuronium in adult patients anesthetized with N2O and fentanyl. Following equipotent doses, the time-course of recovery for rocuronium is similar to that of vecuronium.     

Dose-response relationship of atracurium besylate in the halothane-anaesthetised pig

The dose response relationship for the intermediate-acting non-depolarising muscle relaxant, atracurium besylate in the pig was determined using evoked electromyography. An incremental dose technique was used in seven Large White/Landrace crossbred pigs anaesthetised with nitrous oxide and halothane. ED50 and ED95 were 510 +/- 87 micrograms kg-1 and 1150 +/- 270 micrograms kg-1, respectively. Although these values may represent an overestimate, they provide a reasonable guideline for the use of atracurium by veterinary anaesthetists.     

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.     

In vitro metabolic N- and C-oxidation of phenanthridine

In order to compare an acceleromyograph (TOF-Guard) with a mechanomyograph (Grass FT03), the dose-response relationship of rocuronium was simultaneously determined in both arms of 15 children aged 3-11 years during anaesthesia with thiopentone, alfentanil and nitrous oxide. Three subgroups of five children received rocuronium 120, 180 or 240 micrograms.kg-1 randomly. The effective doses to produce 50% and 95% depression of the first twitch of the train-of-four determined by acceleromyography were 206 and 337 micrograms.kg-1, respectively, while these values determined by mechanomyography were 151 and 331 micrograms.kg-1, respectively. The dose-response curve obtained by acceleromyography was steeper and shifted to the right compared with that obtained by mechanomyography (p < 0.0001). The difference between the effective dose producing 50% twitch depression determined by the two devices was highly significant (p < 0.0001). In 13 out of 15 children, the acceleromyograph control train-of-four ratio was significantly greater than unity. Although there was a good correlation (r = 0.85) between simultaneous pairs of measurements of neuromuscular block, the acceleromyograph exhibited a bias of -25% relative to the mechanomyograph with wide limits of agreement (-62 to +12%). We conclude that acceleromyographic and mechanomyographic measurements should not be used interchangeably when determining the potency of muscle relaxants.     

Potency and time course of action of rocuronium during desflurane and isoflurane anaesthesia

We have studied the potency and onset and duration of action of rocuronium in patients anaesthetized with 1 MAC of desflurane or isoflurane (in 66% nitrous oxide). Potency was estimated using the single bolus dose technique. Neuromuscular block was measured by stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. The ED50 and ED95 of rocuronium were estimated as 138 (95% confidence limits 117-162) micrograms kg-1 and 281 (241-328) micrograms kg-1, and 126 (105-151) micrograms kg-1 and 283 (236-339) micrograms kg-1 during desflurane and isoflurane anaesthesia, respectively. The mean times to onset of maximum block after rocuronium 0.6 mg kg-1 were 1.0 (SD 0.10) min and 1.1 (0.15) min, respectively, during anaesthesia with desflurane and isoflurane. The respective times to recovery of T1 (the first response in the train-of-four (TOF) stimulation) to 25% and 90% were 36 (8.3) min and 54 (15.4) min during desflurane anaesthesia and 31 (8.2) min and 45 (12.7) min during isoflurane anaesthesia. The times to recovery of the TOF ratio to 0.7 were 66 (13.4) min and 52 (16.3) min and the 25-75% recovery indices 14 (5.3) min and 10 (3.2) min, respectively, in the desflurane and isoflurane groups. There were no differences in the estimated potency or onset of action of rocuronium during desflurane and isoflurane anaesthesia. However, duration of action tended to be longer curing desflurane anaesthesia although only the differences in times to TOF ratio of 0.7 and the recovery indices were close to being significantly different (P = 0.0503 and 0.0560).     

The onset of rocuronium, but not of vecuronium or mivacurium, is modified by tourniquet inflation

A previous investigation showed that inflation of a tourniquet did not interrupt onset of vecuronium neuromuscular block. To test the hypothesis that this effect depended on potency, twitch tension was measured in an arm with a tourniquet inflated during onset and compared with a control arm in 30 patients under fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. Patients were randomly allocated to receive either vecuronium 0.1 mg/kg (n = 10), rocuronium 0.6 mg/kg (n = 10), or mivacurium 0.2 mg/kg (n = 10). The electromyographic response of the first dorsal interosseus to single twitch stimulation of the ulnar nerve every 10 s was recorded in both arms. When neuromuscular block was 20% (i.e., twitch tension was 80% of control), the tourniquet was inflated to a pressure of 300 mm Hg. It was deflated 5 min later. In the vecuronium and mivacurium groups, the tourniquet did not influence onset of block. In the rocuronium group, maximum neuromuscular block was (mean +/- SD) 79% +/- 10% in the tourniquet arm, compared with 96% +/- 4% in the perfused arm (P < 0.05). The maximum rate of onset was half that of the perfused arm. The difference in maximum neuromuscular block between arms was 17% +/- 7%, 5% +/- 5%, and 0% +/- 2% in the rocuronium, vecuronium, and mivacurium groups (P < 0.05). To explain that onset of block continues in spite of interruption of blood flow, drug molecules must gain access to the neuromuscular junction via routes other than the circulation. The results of this investigation are consistent with the hypothesis that there is redistribution of drug from extrajunctional to junctional areas during onset of action of muscle relaxants and this process is more important for the more potent drugs (vecuronium and mivacurium) than for rocuronium.     

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.     

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.     

The comparative study of LUMIWARD immunoassay system and CAP RAST system for determination of specific IgE antibody against mite in infantile atopic dermatitis

The neuromuscular blocking effects and the reversibility of cisatracurium 0.1 or 0.15 mg.kg-1 were compared with those of atracurium 0.5 mg.kg-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 micrograms.kg-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 mg.kg-1 and atracurium 0.5 mg.kg-1, respectively. After cisatracurium 0.1 mg.kg-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 mg.kg-1 and atracurium 0.5 mg.kg-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.     

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.     

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.     

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)     

The effect of priming with vecuronium and rocuronium on young and elderly patients

The priming principle consists of administering a subparalyzing dose of nondepolarizing neuromuscular blocking drug 3-6 min before giving a second dose for tracheal intubation. This study was performed to observe the effects of priming doses of vecuronium and rocuronium on pulmonary function tests and muscular weaknesses in young (25-35 yr of age) and elderly (65-73 yr of age) patients. Ten young and 10 elderly patients were each placed in vecuronium and rocuronium groups. Oxygen saturation and train-of-four (TOF) ratio were determined, and pulmonary function tests were performed. Then 20% of the 95% effective dose (ED95) of the muscle relaxants was given intravenously. All tests were performed again 4 min after vecuronium and 3 min after rocuronium. Other signs of muscular weaknesses were also recorded. Elderly patients showed more signs of muscle weakness in both groups. The TOF ratio was 0.77 and 0.79 in the elderly rocuronium and vecuronium groups, respectively, and 0.89 and 0.90 in the young rocuronium and vecuronium groups, respectively. Dynamic spirometry revealed decreases in forced expiratory volume in 1 s and forced vital capacity in both groups, and no significant changes in peak expiratory flow rate. The expiratory reserve volume was reduced more in the elderly groups. Oxygen saturation decreased in both groups. We conclude that oxygen saturation, pulmonary function, and muscle strength decrease more in the elderly than in their younger counterparts from priming doses of vecuronium or rocuronium. IMPLICATIONS: The priming principle consists of giving a subparalyzing dose of muscle relaxant 3-6 min before giving a second dose for tracheal intubation. We found that priming doses of vecuronium and rocuronium produced greater decreases in oxygen saturation and pulmonary function in the elderly (aged 65-73 yr) than their younger (aged 25-35 yr) counterparts. Priming may not be a safe approach in elderly patients.     

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.     

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.     

Serotonin syndrome due to an overdose of moclobemide and clomipramine. A potentially life-threatening association

The speeds of onset of pancuronium, atracurium and vecuronium are increased by prior administration of magnesium sulphate. A prospective, randomized, double-blind, controlled, clinical study was performed to examine the effects of prior i.v. administration of magnesium sulphate 60 mg kg-1 on the neuromuscular blocking effects of rocuronium 0.6 mg kg-1 during isoflurane anaesthesia. Neuromuscular function was measured electromyographically (Relaxograph) in 30 patients who received either magnesium sulphate 60 mg kg-1 or normal saline, 1-min before rocuronium 0.6 mg kg-1. Mean onset times were similar in the two groups (magnesium sulphate 71 (SD 20) s; normal saline 75 (23) s), but times to initial, 10% and 25% recovery from neuromuscular block were significantly longer in the magnesium sulphate group (42.1 (16.3), 49.0 (12.4) and 56.5 (13.2) min, respectively) than in the saline group (25.1 (9.1), 33.0 (11.1) and 35.6 (13.2) min, respectively) (P < 0.05 in all three cases). Administration of magnesium sulphate was not associated with adverse haemodynamic effects. Prior administration of magnesium sulphate, under the study conditions described, prolonged rocuronium-induced neuromuscular block but did not increase speed of onset.