Comparison of the intubation conditions provided by rapacuronium (ORG 9487) or succinylcholine in humans during anesthesia with fentanyl and propofol.

BACKGROUND: Currently, the only approved muscle relaxant with a rapid onset and short duration of action is succinylcholine, a drug with some undesirable effects. Rapacuronium is an investigational nondepolarizing relaxant that also has a rapid onset and short duration and consequently should be compared with succinylcholine in its ability to facilitate rapid tracheal intubation. METHODS: This prospective, randomized clinical trial involved 336 patients. Anesthesia was induced with fentanyl and propofol and either 1.5 mg/kg rapacuronium or 1.0 mg/kg succinylcholine. The goal was to accomplish tracheal intubation by 60 s after administration of the neuromuscular blocking drug. Endotracheal intubation was performed, and conditions were graded by a blinded investigator. Recovery of neuromuscular function was assessed by electromyography. RESULTS: Intubation conditions were evaluated in 236 patients. Intubation by 60 s after drug administration occurred in 100% of patients with rapacuronium and in 98% with succinylcholine. Intubation conditions were excellent or good in 87% of patients with rapacuronium and in 95% with succinylcholine (P < 0.05). The time (median and range) to the first recovery of the train-of-four response was 8.0 (2.8-20.0) min with rapacuronium and 5.7 (1.8-17.7) min with succinylcholine (P < 0.05). The overall incidence of adverse effects was similar with both drugs. CONCLUSIONS: A 1.5-mg/kg dose of rapacuronium effectively facilitates rapid tracheal intubation. It can be considered a valid alternative to 1.0 mg/kg succinylcholine for this purpose.

Preadmission strategies: reducing the length of preoperative stay.

Pursuing efficiency, the Ottawa Civic Hospital implemented a preadmission program which moved as much of the surgical admission procedure as possible to a single preadmission visit. The authors describe the process of researching, planning and implementing the program. They also report the savings it has represented for the hospital and the reaction from surgical patients.

Edrophonium requirements for reversal of deep neuromuscular block following infusion of mivacurium.

Mivacurium is a new non-depolarizing muscle relaxant consisting of three stereoisomers. The two active isomers (cis-trans and trans-trans) undergo rapid metabolism by plasma cholinesterase (t1/2 beta < 2 min). Due to its rapid elimination, the need for reversal of mivacurium-induced neuromuscular block is controversial, and to date there have been no studies evaluating reversal of deep blocks. The object of the current investigation was to establish the lowest effective dose of edrophonium required to reverse deep mivacurium-induced neuromuscular block. One hundred ASA Class I and II patients undergoing outpatient surgery in two teaching institutions were studied in this randomized, placebo-controlled double-blind trial. Under balanced propofol/nitrous oxide/alfentanil anaesthesia, a continuous infusion of mivacurium was adjusted to maintain between 5-10% of control T1 amplitude. Upon completion of surgery, neuromuscular block was reversed by injecting normal saline (Group PLAC), edrophonium 0.125 mg.kg-1 (Group EDR-1), 0.25 mg.kg-1 (Group EDR-2), or 0.50 mg.kg-1 (Group EDR-3), in addition to a corresponding dose of atropine. Spontaneous recovery, from a T1 response of < 10% to a TOF ratio > or = 0.7, required 13.5 +/- 2.6 min (PLAC Group). In comparison, patients in the EDR-1 group required 9.2 +/- 2.6 min (P < 0.01). Higher doses of edrophonium conferred no advantage. Four patients (4%) had not achieved a TOF ratio of > or = 70%, 20 min after reversal, and required additional edrophonium. Two patients (PLAC group), had dibucaine numbers and cholinesterase levels consistent with an EUEA genotype, whereas the two patients with delayed recovery in the EDR-1 group had characteristics of a normal genotype. We conclude that a very low dose of edrophonium (0.125 mg.kg-1) hastens reversal of deep mivacurium-induced neuromuscular block by approximately four minutes, and that edrophonium doses exceeding 0.125 mg.kg-1 provide no additional benefit. Heterozygous patients with atypical plasma cholinesterase levels, as well as certain individuals with normal dibucaine numbers and plasma cholinesterase activity, are at risk for prolonged neuromuscular block, but the block is easily reversed with edrophonium.

Cumulation and reversal with prolonged infusions of atracurium and vecuronium.

A randomized, double-blind study was undertaken to compare the tendencies for cumulation, and reversal characteristics of atracurium (ATR) and vecuronium (VEC) when administered by continuous infusion for long surgical procedures under balanced anaesthesia. Eligible subjects were between 50 and 75 yr of age and were free of neuromuscular disease. Patients in the ATR group (n = 25) received a loading dose of atracurium 0.25 mg.kg-1, followed by an infusion initially set at 5.0 micrograms.kg-1.min-1. In the VEC group (n = 25) patients received a loading dose of vecuronium 0.05 mg.kg-1, followed by an infusion at 1.0 microgram.kg-1.min-1. During surgery, the infusions of both ATR and VEC were titrated in increments or decrements of 12.5% to maintain first twitch (T1) suppression of 90-95%. Neuromuscular block was measured by recording the integrated evoked electromyographic response (EMG) of the first dorsal interosseous muscle in response to supramaximal TOF stimuli on the ulnar nerve. The durations of infusion were similar for the two groups (164 +/- 42 and 183 +/- 67 min for ATR and VEC, respectively). The infusion rates of ATR (mean +/- SD) remained between 4.0 +/- 0.7 and 5.0 +/- 1.0 microgram.kg-1.min-1 throughout the study period. In contrast, a progressive decrease (P less than 0.05) in the infusion rate of VEC, from 1.0 to 0.47 +/- 0.13 micrograms.kg-1.min-1, was observed during the study period. The number of adjustments required to maintain 90-95% T1 suppression decreased between the second and fourth hours of administration, but were similar at corresponding times when comparing the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal and fetal effects of intravenous patient-controlled fentanyl analgesia during labour in a thrombocytopenic parturient.

The use of intravenous (i.v.) patient-controlled fentanyl analgesia during labour in a parturient with unexplained thrombocytopenia (70 x 10(3).ml-1) is described. The patient self-administered boluses of 25 micrograms of fentanyl with a lock-out interval of ten min. In addition, a concurrent fentanyl infusion of 25 micrograms.hr-1 was given. Effective analgesia was achieved during labour and a total of 1025 micrograms of fentanyl was infused over 11 hr 55 min until delivery of a vigorous infant with Apgar scores of 9 after one and five min. Respiratory depression or undue sedation were not observed in the mother either during labour or in the post-partum period. At birth, maternal total plasma fentanyl concentration was 1.11 ng.ml-1, whereas neonatal umbilical total plasma fentanyl concentration was 0.43 ng.ml-1. Newborn plasma protein binding of fentanyl was lower compared to the mother (63% vs 89%). Thus, free fentanyl concentrations (0.16 ng.ml-1) were identical in the mother and newborn at delivery.

Pharmacokinetics and pharmacodynamics of atracurium in the elderly.

To evaluate the effect of aging on the distribution, clearance, and neuromuscular junction sensitivity to atracurium, the authors determined the pharmacokinetics and pharmacodynamics of atracurium in five healthy elderly subjects (74-76 yr) during halothane-nitrous oxide anesthesia and compared these values to those obtained previously in five healthy young adults (22-44 yr). A brief (6.0-13.0 min) infusion of atracurium was administered until twitch tension was suppressed by approximately 70%, and atracurium plasma concentration and twitch tension data were used to determine pharmacokinetic and pharmacodynamic parameters for each patient. Total clearance (Cltotal) was similar in elderly and young adults. However, clearance via the liver and/or kidney (Clorgan) was lower in elderly patients, whereas clearance due to Hofmann elimination and ester hydrolysis (Clnonorgan) was higher. Volume of distribution at steady state (Vss) was larger in elderly patients. The increase in Vss without an age-related increase in Cltotal resulted in a longer elimination half-life [21.8 (+)/- 3.3 vs. 15.7 (+)/- 2.5 min (mean (+)/- SD)] in elderly patients. The steady state plasma concentration of atracurium required to suppress twitch tension by 50% was similar in elderly and young adults. The authors conclude that the pharmacokinetics, but not the pharmacodynamics, of atracurium differ significantly between elderly and young adults. As a result, repeated doses will be required with similar frequency in young and elderly adults, but recovery from comparable levels of neuromuscular blockade may be slightly prolonged in elderly patients.

Comparison of the neuromuscular block induced by mivacurium, suxamethonium or atracurium during nitrous oxide-fentanyl anaesthesia.

We compared the neuromuscular and cardiovascular changes following administration of mivacurium 0.15, 0.20 and 0.25 mg kg-1, suxamethonium 1.0 mg kg-1 or atracurium 0.5 mg kg-1 i.v. in 41 (ASA physical status I or II) patients during nitrous oxide-fentanyl anaesthesia. Mean onset times for total ablation of twitch response for mivacurium 0.15, 0.20 and 0.25 mg kg-1, were 2.5, 2.4 and 2.7 min, respectively, similar to that for atracurium (2.5 min), but longer than for suxamethonium (1.1 min) (P less than 0.05). Mean times from administration of drug until twitch response recovered to 10% of control were shorter for each dose of mivacurium (15.6, 18.0 and 20.6 min, respectively) than for atracurium (40.0 min) and longer than for suxamethonium (7.7 min) (P less than 0.05). Mean infusion rate required to maintain twitch response at 5 +/- 4% control was 6.7 micrograms kg-1 min-1 for mivacurium and 6.3 micrograms kg-1 min-1 for atracurium. Following neostigmine 0.045 mg kg-1, mean times for twitch tension to recover from 10% to 90% of control were similar for mivacurium (9.7 min) and atracurium (10.5 min). Transient decreases in mean arterial pressure (greater than 20%) were observed in seven of 15 patients who received the two higher doses of mivacurium.

The relationship between adductor pollicis twitch tension and core, skin, and muscle temperature during nitrous oxide-isoflurane anesthesia in humans.

Temperature and volatile anesthetic agents influence neuromuscular transmission. Because mild hypothermia is common during general anesthesia, the authors sought to determine the relationship between the core temperature, adductor pollicis muscle temperature, and the twitch response of the adductor pollicis muscle, during isoflurane anesthesia in 15 patients undergoing elective surgery in which muscle relaxants were not required. Five patients were allowed to cool spontaneously, five were cooled actively, and normothermia was maintained actively in the remaining five. In the normothermic patients (core greater than 36.5 degrees C, muscle greater than 35.7 degrees C), the twitch response of the muscle remained unchanged from control values. In the patients who were cooled passively or actively, a muscle temperature threshold was observed (35.2 degrees C), below which twitch response of the muscle diminished by 10-15%/degrees C decrease in muscle temperature. To ensure that the adductor pollicis muscle temperature remained above 35.2 degrees C, the core temperature had to be maintained above 36 degrees C. A significant linear relationship (P less than 0.05) was found between the adductor pollicis muscle temperature and twitch tension below the threshold for each individual patient in the cooled groups (correlation coefficient range, 0.80-0.99). Thus, there is a temperature-related decrease in adductor pollicis twitch response during isoflurane anesthesia, and the temperature of this muscle should be maintained above 35-35.5 degrees C during studies of neuromuscular transmission. This can be achieved by maintaining core temperature above 36 degrees C.

The dose-response relationship of mivacurium chloride in humans during nitrous oxide-fentanyl or nitrous oxide-enflurane anesthesia.

The dose-response relationships of mivacurium chloride during N2O/fentanyl or N2O/enflurane anesthesia were compared in 70 patients intraoperatively. Responses were defined in terms of percentage changes in the evoked twitch tension of the adductor pollicis muscle, and dose-response curves were constructed following probit transformation of the responses. End-tidal concentrations of enflurane during the were study were 0.9-1.2%. When compared with the dose-response curve determined during N2O/fentanyl anesthesia the curve determined during N2O/enflurane anesthesia was displaced significantly to the left (P less than 0.05). As a result, the doses of mivacurium that depressed twitch tension by 50% (ED50) and 95% (ED95) were 39 and 67 micrograms/kg, respectively, during N2O/fentanyl anesthesia, and 27 and 52 micrograms/kg during N2O/enflurane anesthesia. Regression lines describing the relationship between the maximum depression of twitch tension (response) and the time interval between the injection of mivacurium and the return of twitch tension to 90% of the control value (duration) were constructed. The response-duration line for N2O/enflurane anesthesia was displaced significantly to the left of the line for N2O/fentanyl (P less than 0.05), indicating that enflurane anesthesia was associated with a prolongation of mivacurium-induced neuromuscular blockade. The neuromuscular blocking effect of mivacurium is both enhanced by and prolonged during N2O/enflurane compared with that during N2O/fentanyl anesthesia.