Background and objective: Non-depolarizing neuromuscular blocking agents have a shorter duration of action on the diaphragm than on skeletal muscles. It was to be tested if this also held true for rapacuronium, a shortacting, amidosteroid non-depolarizing neuromuscular blocker, lately withdrawn from the market, using a novel technique for stimulating the diaphragm and assessing its function.

Methods: Anaesthesia was induced with propofol 2 mg kg−1 and remifentanil 1 μg kg−1, and the trachea was intubated after topical anaesthesia. Rapacuronium was given at a dose of 1.5 mg kg−1. The diaphragm was stimulated by cervical magnetic stimulation of the phrenic nerves (2 Tesla, single coil) and airway pressure responses were measured at the endotracheal tube connector. The neuromuscular effects at the adductor pollicis and orbicularis oculi muscles were measured by acceleromyography.

Results: Fifteen males and five females (ASA I and II; 27 ± 8 yr; 73 ± 13 kg; mean ± SD) were recruited. Median maximal relaxation was less (P < 0.01) for the diaphragm (89%) than for the adductor pollicis or orbicularis oculi muscles (each 100%). The time to 25% recovery was shorter for the diaphragm than for adductor pollicis or orbicularis oculi (7.5 ± 3.1 versus 14.1 ± 3.7 and 15.1 ± 3.5 min, respectively, P < 0.01). Recovery from 25 to 75% was identical for the diaphragm and adductor pollicis (9.4 ± 2.9 versus 9.1 ± 3.5 min), but longer for orbicularis oculi (13.4 ± 4.2 min, P < 0.01). The median recovery time to TOF0.8 was shorter for the diaphragm (23.9 min) than for the adductor pollicis or orbicularis oculi muscles (31.5 and 28.4 min, respectively; P < 0.05).

Conclusions: As with other non-depolarizing muscle relaxants, the duration of the clinical effect of rapacuronium was shorter for the diaphragm than for skeletal muscle. The recovery index was identical for the diaphragm and adductor pollicis.

Background and objective: The aim was to examine the course of intraocular pressure after relaxation with different doses of cisatracurium.

Methods: The investigation was carried out as a prospective, randomized double-blind study in a crossover design in 30 postoperative patients with stable haemodynamic and respiratory function (ASA I and II). To exclude any disrupting factors, patients remained intubated and continuously sedated. Twenty patients received an intubation dose (2 × ED95) of cisatracurium (0.1 mg kg−1) compared with atracurium (0.5 mg kg−1). In a second series, 10 patients were given an effective dose, ED95 (0.05 mg kg−1), and a repeat dose (0.02 mg kg−1) of cisatracurium. The intraocular pressure was determined before (T0) as well as 1 (T1), 5 (T5), 10 (T10), 15 (T15), 20 (T20) and 45 (T45) min after bolus administration.

Results: Intraocular pressure decreased after an intubation dose of either cisatracurium or atracurium, and reached a minimum after 10 min (6.7 ± 2.2 and 7.9 ± 2.1 mmHg, respectively). There was no significant difference between either muscle relaxant (P = 0.27). When lower doses of cisatracurium (0.05 and 0.02 mg kg−1) were applied, the intraocular pressure also decreased, albeit to a lesser extent and with a delayed onset (8.4 ± 1.9 mmHg after 10 min, 9.9 ± 3.4 mmHg after 15 min). There was no significant difference between dosages (P = 0.44).

Conclusions: Cisatracurium is a useful drug in patients when a decrease of intraocular pressure is wanted and where muscle relaxation is necessary and acceptable.

Background and objective: The aim was to compare the effects of two different priming doses and priming intervals with the standard intubating dose of rocuronium on the onset time and intubation conditions.

Methods: After induction of anaesthesia, 75 patients were randomly assigned to one of five groups. Patients in Group 1 received a priming dose of rocuronium 0.06 mg kg−1 followed 2 min later by rocuronium 0.54 mg kg−1, Group 2 received a priming dose of 0.10 mg kg−1 followed 2 min later by a rocuronium injection of 0.50 mg kg−1. Group 3 was given a priming dose of 0.06 mg kg−1 followed 3 min later by administration 0.54 mg kg−1, where Group 4 received a priming dose of 0.10 mg kg−1 followed 3 min later by injection of 0.50 mg kg−1. Group 5 received a placebo injection followed 3 min later by rocuronium 0.60 mg kg−1.

Results: Priming with a 3 min priming interval shortened the onset time of rocuronium irrespective of the dosage of (P < 0.001). Clinical duration of action was significantly longer after priming in Group 4 than in Group 5. Clinically acceptable intubation conditions were obtained in all patients.

Conclusions: Priming with a 3 min priming interval was effective when rapid tracheal intubation with rocuronium was necessary. However, priming with rocuronium should be used carefully with special attention given to the possibility of hypoxia and aspiration of gastric contents in awake patients.

Laudanosine is a metabolite of the neuromuscular-blocking drugs atracurium and cisatracurium with potentially toxic systemic effects. It crosses the blood-brain barrier and may cause excitement and seizure activity. Its interest in recent years has increased because of the recognized interaction with γ-aminobutyric acid, opioid and nicotinic acetylcholine receptors. It has been shown to produce analgesia in animals. In the cardiovascular system, high plasma concentrations produce hypotension and bradycardia. In hepatic failure, its elimination halflife is prolonged but only moderate accumulation occurs in adults, whereas in infants and children plasma concentration are greater. In patients undergoing liver transplantation, laudanosine concentrations are increased during preanhepatic, anhepatic and postanhepatic stages. Patients with renal failure have higher plasma concentrations and a longer mean elimination half-life. In pregnancy, laudanosine crosses the placental barrier. The mean transplacental transfer is 14% of maternal blood concentrations. Except for prolonged administration of atracurium in intensive care units, laudanosine accumulation and related toxicity seem unlikely to be achieved in clinical practice. When cisatracurium is used, plasma concentrations of laudanosine are lower. Further studies are needed, especially around the interactions with γ-aminobutyric acid, opioid and nicotinic acetylcholine receptors.

Background and objective: The addition of alfentanil or atracurium to lidocaine solution for intravenous regional anaesthesia of the arm may have advantages with respect to improved muscle relaxation and better analgesia. The study investigates these possibilities.

Methods: We investigated 33 patients. Plain lidocaine solution was administered to Group 1 (n = 11). Alfentanil (0.5 mg) and atracurium (3 mg) were added to the lidocaine solution in Groups 2 (n = 11) and 3 (n = 11), respectively. The onset of sensory and motor block, intra- and postoperative pain scores, and the duration of postoperative analgesia were evaluated.

Results: There was a significant difference in the speed of the onset of sensory block in the hand, but not at the tourniquet site. The onset of the motor block, intra- and postoperative pain scores, and the duration of postoperative analgesia were similar in all groups.

Conclusions: No clinical benefits of adding alfentanil or atracurium to lidocaine solution for intravenous regional anaesthesia of the arm could be shown.

Background and objective: Monitoring of neuromuscular blockade still often relies on clinical judgement. Moreover, there are substantial national differences in the use of agents to 'reverse' their effects. We investigated the recovery characteristics and incidence of postoperative residual curarization after cisatracurium and rocuronium infusions for long duration interventions without systematic antagonism.

Methods: In 30 patients undergoing major surgery, we measured infusion dose requirements for rocuronium and cisatracurium during propofol anaesthesia. Infusions were discontinued at the beginning of surgical closure; spontaneous recovery of neuromuscular function was awaited in both groups. Neostigmine (50 μg kg−1) was administered only when a patient started to wake without a train-of-four ratio (TOF) of 0.9.

Results: In the cisatracurium and rocuronium groups, four (27%) and one (7%) patients, respectively, had a TOF ratio ≥0.9 at the end of surgery. The TOF ratio in each group at that time was 51 ± 32% for cisatracurium and 47 ± 31% for rocuronium (P = 0.78). Six patients (40%) in the cisatracurium group and seven (47%) in the rocuronium group required neostigmine. The TOF ratio at the time of reversal was 63 ± 7% for cisatracurium and 40 ± 19% for rocuronium (P = 0.01). The time interval between the end of surgery and a TOF ratio of 0.9 was 10 ± 9 min for cisatracurium and 18 ± 13 min for rocuronium (P = n.s.).

Conclusions: Patients receiving a cisatracurium or rocuronium infusion have a high incidence of postoperative residual curarization when the block is not antagonized. When ‘reversal’ is not attempted, cisatracurium seems to be safer than rocuronium.

Background and objective Inflammatory liver dysfunction in rats leads to a prolonged vecuronium-induced neuromuscular blockade due to insufficient metabolism. A coexisting resistance against the drug partly counteracts this prolongation. The present study investigates the pharmacodynamics of atracurium whose metabolism does not depend on liver function.

Methods Male Sprague–Dawley rats (n = 14; 290 ± 30 g) were randomly allocated to either a group in which liver inflammation was induced by intravenous injection of 60 mg kg−1 heat-killed Corynebacterium parvum or to a control group. On day 5 after injection, liver function was assessed using the aminopyrine breath test. Under propofol anaesthesia, duration of action of atracurium (4.8 mg kg−1) was measured by evoked mechanomyography (stimulation of the sciatic nerve; contraction of the gastrocnemius muscle). Nitric oxide concentrations, as variables for the severity of the inflammation, were assessed by measurement of nitrite/nitrate plasma concentrations.

Results In C. parvum-injected rats, nitrite/nitrate plasma concentrations were increased (972 ± 597 vs. 25 ± 7 μmol L−1), the aminopyrine turnover was depressed (1.7 ± 0.4% vs. 3.5 ± 0.5%), and the atracurium-induced neuromuscular blockade was shortened (372 ± 128 s vs. 1081 ± 234 s).

Conclusions A systemic inflammatory response syndrome with liver dysfunction results in decreased sensitivity to atracurium. Further investigations are needed regarding a possible up-regulation of acetylcholine receptors or an increased protein binding of atracurium during sepsis to clarify reasons behind this phenomenon.

Mitochondrial myopathies are rare complex multisystem disorders, which can present several potential anaesthetic problems. A 49-year-old man with mitochondrial myopathy was anaesthetized successfully for cataract extraction using propofol and alfentanil infusions. Vecuronium sensitivity was apparent, with a prolonged duration of action, despite dosage reduction

The aim of this study was to elucidate the influence of four neuromuscular blocking substances on coronary vascular tone using the model of isolated porcine coronary artery segments. We studied the effects of four muscle relaxants, atracurium, pancuronium, rocuronium, and vecuronium (0.1, 1, and 10 μg mL−1 each), on the contractile response to three vasoconstrictors: acetylcholine, histamine, and serotonin. None of the neuromuscular blocking agents under investigation exerted a significant influence on the vasoconstricting effects of these mediators except for pancuronium, which dose-dependently attenuated acetylcholine-mediated contractions (−10.8% attenuation for 10 μg mL−1 pancuronium, P < 0.05). There was no difference between vessels with intact endothelium and denuded preparations. It is concluded that high-dose pancuronium exerts an antimuscarinic effect in vascular smooth muscle. The other neuromuscular agents studied do not alter vascular reactivity of isolated porcine coronary arteries.

Nimodipine, a calcium channel blocking drug, is used in the treatment of cerebral arterial spasm after subarachnoid haemorrhage due to bleeding from an intracranial aneurysm. The purpose of this study was to evaluate the effects of nimodipine on neuromuscular blockade after vecuronium had been given to facilitate tracheal intubation and maintenance of muscle paralysis in patients undergoing clipping of intracranial aneurysm. Twenty patients were divided into two groups: a control group (n = 10) who received no calcium channel blocking drug, and a nimodipine group (n = 10) consisting of patients treated with nimodipine at clinically used doses of 0.03 mg kg−1 h−1 pre- and perioperatively. Anaesthesia was induced with atropine 10 μg kg−1, dehydrobenzperidol 5 mg, fentanyl 5 μg kg−1, thiopental 5 mg kg−1 and maintained with a mixture of N2O and isoflurane (0.5–1% inspired concentration) in O2, and additional doses of fentanyl 2.5 μg kg−1. Neuromuscular responses were monitored by acceleromyograpy. The first twitch of the train-of-four response (T1) was considered as twitch height.After a stabilization period, an intubating dose of vecuronium 0.1 mg kg−1 was administered. The onset of action, the time of first appearance of T−1 and clinical duration of action were recorded. Then, maintenance doses of vecuronium 0.03 mg kg−1were administered twice more when T1 had recovered to 25% of control twitch height. The study ended when the recordings of the 3rd 25% T1 recovery had been obtained. There were no statistical differences in the onset time (120±44 s in the control group, 141±33 s in the nimodipine group), in the first appearance time of T1 (28±6 min in the control group, 30±8 min in the nimodipine group), and in the times for 25% recovery in T1 (41±11, 32±2, 40±13 min in the control group, respectively, and 44±16, 36±15, 38±15 min in nimodipine group, respectively) between the groups studied. The time between the injection of the intubating dose of vecuronium and the third recovery of T1–25% of control was not significantly different between the control group (113±34 min) and the nimodipine group (117±42 min). This study indicates that nimodipine does not have any significant effect on the time course of action of vecuronium including the onset time and its clinical duration of action after the initial and the two maintenance doses in these patients.