Non-quantal acetylcholine release is increased after nitric oxide synthase inhibition.
(33/520)
After anticholinesterase treatment, depolarization of the postsynaptic muscle membrane by about 5 mV develops due to non-quantally released acetylcholine from the motor nerve terminal and can be revealed as hyperpolarization by the addition of curare (H-effect). The H-effect increases significantly to 8.7 mV after inhibition of NO-synthase by L-nitroarginine methylester (L-NAME) whilst no changes in the amplitude and frequency of quantal miniature endplate potentials are observed. (+info)
Neuromuscular effects of mivacurium in 2- to 12-yr-old children with burn injury.
(34/520)
BACKGROUND: Burned patients are usually resistant to the neuromuscular effects of nondepolarizing relaxants, mostly because of receptor changes. The magnitude of the resistance is related to burn size and time after burn. Mivacurium is a muscle relaxant, degraded by plasma cholinesterase, whose enzyme activity is decreased in burns. The present study tested the hypothesis that burn-induced depressed plasma cholinesterase activity counteracts the receptor-mediated resistance, resulting in a lack of resistance to mivacurium. METHODS: Burned patients (n = 23), aged 2-12 yr, subclassified into burns of 10-30% or > 30% of body surface, were studied at < or = 6 days and again at 1-12 weeks after burn if possible. Thirteen additional patients served as controls. Neuromuscular variables monitored included onset and recovery following bolus dose, continuous infusion rates required to maintain 95 +/- 4% paralysis, and recovery rates following infusion. RESULTS: The onset times of maximal twitch suppression were not different between burns and controls, but recovery to 25% of baseline twitch height was prolonged in patients with > 30% burn irrespective of time after injury. The continuous infusion rates to maintain twitch suppression at 95 +/- 4% were not different between groups. The recovery indices, including train-of-four to > 75%, 25-75%, or 5-95% in burned patients, were similar or prolonged compared with controls. The prolonged recovery in burned patients was inversely related to plasma cholinesterase activity (R2 = 0.86, r = -0.93, P < 0.001), and the decreased plasma cholinesterase activity was related to burn size and time after burn. CONCLUSIONS: A normal mivacurium dosage (0.2 mg/kg) effects good relaxation conditions in burned patients, with an onset time similar to that in controls. This finding contrasts with the response seen with other nondepolarizing drugs, higher doses of which are required to effect paralysis. The decreased metabolism of mivacurium, resulting from depressed plasma cholinesterase activity, probably counteracts the receptor-mediated potential for resistance. Because succinylcholine is contraindicated in burned patients, larger doses of nondepolarizing agents are advocated to effect rapid onset of paralysis. This generalization does not hold for mivacurium. diatrics; plasma cholinesterase; relaxant resistance; succinylcholine, alternative to.) (+info)
Temperature-dependent pharmacokinetics and pharmacodynamics of vecuronium.
(35/520)
BACKGROUND: The authors evaluated the influence of temperature on the pharmacokinetics and pharmacodynamics of vecuronium because mild core hypothermia doubles its duration of action. METHODS: Anesthesia was induced with alfentanil and propofol and maintained with nitrous oxide and isoflurane in 12 healthy volunteers. Train-of-four stimuli were applied to the ulnar nerve, and the mechanical response of the adductor pollicis was measured. Volunteers were actively cooled or warmed until their distal esophageal temperatures were in one of four ranges: < 35.0 degrees C, 35.0-35.9 degrees C, 36.0-36.9 degrees C, and > or = 37.0 degrees C. With temperature stabilized, vecuronium was infused at 5 microg x kg(-1) x min(-1) until the first response of each train-of-four had decreased by 70%. Arterial blood (for vecuronium analysis) was sampled at intervals until the first response recovered to at least 90% of its prevecuronium level. Vecuronium, 20 microg x kg(-1) x min(-1), was then infused for 10 min, and arterial blood was sampled at intervals for up to 7 h. Population-based nonlinear mixed-effects modeling was used to examine the effect of physical characteristics and core temperature on vecuronium pharmacokinetics and pharmacodynamics. RESULTS: Decreasing core temperature over 38.0-34.0 degrees C decreases the plasma clearance of vecuronium (11.3% per degrees C), decreases the rate constant for drug equilibration between plasma and effect site (0.023 min(-1) per degrees C), and increases the slope of the concentration-response relationship (0.43 per degrees C). CONCLUSIONS: Our results show that reduced clearance and rate of effect site equilibration explain the increased duration of action of vecuronium with reducing core temperature. Tissue sensitivity to vecuronium is not influenced by core temperature. (+info)
Cisatracurium neuromuscular block at the adductor pollicis and the laryngeal adductor muscles in humans.
(36/520)
We have compared the dose-response relationship (n = 30) and time course of neuromuscular block (n = 20) of cisatracurium at the laryngeal adductor and the adductor pollicis muscles. ED95 values for cisatracurium were 66.8 (95% confidence interval 61.3-72.3) micrograms kg-1 at the larynx and 45.2 (42.1-48.3) micrograms kg-1 at the adductor pollicis muscle (P < 0.0001). After administration of cisatracurium 0.1 mg kg-1, onset time was 2.7 (2.2-3.2) min at the larynx and 3.9 (3.0-4.8) min at the adductor pollicis (P < 0.0001). Time to 95% recovery of the first twitch of the TOF was 26.9 (20.1-33.7) min and 45.6 (39.7-51.5) min, respectively (P < 0.0001). We found that the laryngeal adductors were more resistant to the action of cisatracurium than the adductor pollicis muscle, but onset and recovery were faster at the larynx. (+info)
Augmentation of vecuronium-induced neuromuscular block during sevoflurane anaesthesia: comparison with balanced anaesthesia using propofol or midazolam.
(37/520)
We have quantified the potentiating effects of 1.7% sevoflurane (n = 12) on vecuronium-induced neuromuscular block and compared the results with those obtained during balanced anaesthesia with propofol (n = 12) or midazolam (n = 12) in 36 patients. Neuromuscular function was monitored using an accelerograph and the train-of-four responses of the adductor pollicis muscle to ulnar nerve stimulation. Vecuronium 0.1 mg kg-1 was administered as an intubating dose, and maintenance doses of 0.02 mg kg-1 were administered on three occasions when T1/T0 had recovered to 25%. Thereafter, spontaneous recovery was monitored until complete. Times to 25% recovery of T1/T0 (DUR25) after an intubating dose of vecuronium did not differ between groups (mean 44.2 (SD 18.7) min for sevoflurane, 38.3 (7.5) min for propofol and 35.5 (9.5) min for midazolam). DUR25 values after each maintenance dose were 29.8 (9.5) min, 30.3 (10.4) min and 31.6 (10.7) min during sevoflurane anaesthesia, and were significantly longer than values for propofol (21.7 (6.0) min, 21.5 (5.8) min and 21.9 (5.8) min) and midazolam (20.0 (5.9) min, 19.3 (7.7) min and 19.8 (8.0) min) (P < 0.05) in each case). Recovery index25-75% and interval from T1/T0 = 25% to T4/T1 = 0.7 after the final dose of vecuronium were significantly prolonged by sevoflurane (28.3 (13.2) min and 42.7 (16.4) min) compared with propofol (17.6 (6.1) min and 26.6 (9.8) min) or midazolam (16.3 (9.4) min and 26.0 (10.2) min) (P < 0.05 in each case). (+info)
Response to vecuronium in a patient with facioscapulohumeral muscular dystrophy.
(38/520)
Increased sensitivity to vecuronium has been noted in patients with Duchenne muscular dystrophy. We report the response to vecuronium in a patient with facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant disorder with an incidence of 10-20 cases per million. In this patient, sensitivity to an initial dose of vecuronium (0.02 + 0.08 mg kg-1) was normal, but recovery was faster and the effect of incremental doses of vecuronium (0.02 mg kg-1) was less than expected. Onset time and 25% recovery of T1/T0 after the intubating dose of vecuronium were 240 s and 22 min, respectively. Recovery index (spontaneous recovery of T1/T0 from 25% to 75%) was 9 min. (+info)
Haemodynamic effects of rapacuronium in adults with coronary artery or valvular disease.
(39/520)
We have assessed the haemodynamic effects of rapacuronium (Org 9487) in adults undergoing cardiac surgery and compared these with vecuronium and placebo. We studied 56 adult patients undergoing coronary artery bypass grafting or valve replacement surgery using a fentanyl-based anaesthetic technique. A pulmonary artery flotation catheter was inserted before induction of anaesthesia. After induction, tracheal intubation and stabilization of haemodynamic measurements, subjects were allocated randomly to receive rapacuronium 1.5 mg kg-1 vecuronium 0.1 mg kg-1 or saline placebo. Haemodynamic measurements were made before drug administration and 1, 3, 5 and 10, and if possible, 15 min after administration. Rapacuronium was associated with statistically significant increases in heart rate (17%) and cardiac index (15%) and decreases in mean arterial pressure (11%) and systemic vascular resistance (18%), whereas vecuronium and placebo were associated with significant decreases in heart rate only (14-15%) (P < 0.05). No cutaneous signs of histamine release were observed. Clinically, the results were within acceptable limits. Our results suggest that administration of rapacuronium may be associated with significant changes in heart rate and arterial pressure in patients undergoing coronary artery bypass grafting. (+info)
Antagonism of rapacuronium using edrophonium or neostigmine: pharmacodynamics and pharmacokinetics.
(40/520)
We have studied the pharmacodynamics and pharmacokinetics of rapacuronium (Org 9487) in 70 healthy patients. Neuromuscular transmission was monitored using TOF stimulation of the ulnar nerve and mechanomyography of the adductor pollicis muscle. Half of the patients were given a single dose of rapacuronium 1.5 mg kg-1 and the remainder rapacuronium 1.5 mg kg-1 with three incremental doses of 0.5 mg kg-1, each given when T1/T0 had recovered to 25%. In all patients, neuromuscular block was antagonized using neostigmine 0.05 mg kg-1 or edrophonium 1.0 mg kg-1 (allocated randomly), 2 min after the final dose of rapacuronium. All patients developed complete block after rapacuronium 1.5 mg kg-1. Mean onset time was 66 (SD 24) s. In patients who received an antagonist 2 min after the first dose of rapacuronium, time to recovery of T1/T0 to 25% was similar after neostigmine (9.8 (3.8) min) and edrophonium (10.3 (4.3) min): in patients who received incremental doses of rapacuronium, spontaneous recovery of T1/T0 to 25% after the first dose was 18.9 (4.7) min. In those who received an antagonist 2 min after the first dose of rapacuronium, times to recovery of T4/T1 to 0.7 were also similar after neostigmine (23.7 (7.7) min) and edrophonium (29.1 (10.7) min). After three incremental doses of rapacuronium, there was a longer time to recovery of T1/T0 = 25% after neostigmine compared with edrophonium (5.1 (1.0) vs 3.3 (1.3) min; P < 0.05) but more rapid recovery to T1/T0 = 75% (10.1 (2.9) vs 16.8 (10.1) min; P < 0.05) and T4/T1 = 0.7 (19.8 (6.3) vs 35.1 (10.4) min; P < 0.05). A three-compartment pharmacokinetic model was justified. Typical values for clearance and initial volume of distribution (V1) were 4.4 ml kg-1 min-1 and 94.8 ml kg-1, respectively. In females, clearance was decreased by 38.5% compared with males and V1 was decreased by 25% in patients aged more than 65 yr. (+info)