Time Course Of Neuromuscular Block Research Articles

Dexamethasone decreases the duration of rocuronium-induced neuromuscular block

Several drugs influence the time course of neuromuscular block during general anaesthesia. To evaluate the effect of a single dose of dexamethasone 8 mg on the time course of a rocuronium-induced neuromuscular block. A randomised controlled, unblinded, monocentre trial. Kreiskrankenhaus Dormagen, Dormagen, Germany. One hundred and eight adult patients scheduled for elective gynaecological laparoscopic surgery allocated to three groups. Patients received dexamethasone 8 mg intravenously 2 to 3 h prior to surgery (Group A), during induction of anaesthesia (Group B) or after recovery of the neuromuscular block (Group C, control). The time course of the neuromuscular block of rocuronium 0.3 mg kg was assessed using acceleromyography. The primary end point was the time from start of injection of rocuronium until recovery to a train-of-four ratio of 0.9. The clinical duration was decreased in Group A (15.8 ± 4.5 min) compared with Group B (18.7 ± 5.8 min; P = 0.031). The recovery index was reduced in Group A (6.8 ± 1.8 min) compared with Group B (8.1 ± 2.6 min; P = 0.018) and Group C (8.3 ± 2.8 min; P = 0.01). The recovery to a train-of-four ratio of 0.9 was shorter in Group A (30.4 ± 6.9 min) than in Groups B (36.3 ± 10.7 min; P = 0.031) and C (36.8 ± 11.3 min; P = 0.02). A single dose of dexamethasone 8 mg attenuated rocuronium-induced block by 15 to 20% if administered 2 to 3 h prior to induction of anaesthesia. However, the administration of dexamethasone during induction of anaesthesia did not influence the time course of the neuromuscular block. ClinicalTrial.gov Identifier: NCT01782820.

Pharmacodynamic modelling of rocuronium in adolescents with Duchenne muscular dystrophy

Studies with rocuronium showed a delayed onset and prolonged recovery in patients with Duchenne muscular dystrophy (DMD). The objective of this study was to identify the pharmacokinetic and/or pharmacodynamic origin of these alterations. Twenty-five male patients (15 with DMD, 10 controls, aged 10-18 years) were studied. Patients were anaesthetized with propofol and sufentanil. Neuromuscular transmission was monitored by acceleromyography. Patients received a single intravenous dose of 0.3 mg kg(-1) rocuronium. In five patients of the DMD group, pharmacokinetic modelling was performed from arterial rocuronium concentrations. The time course of neuromuscular block was analysed with a sigmoid E(max) model including an effect compartment. The pharmacokinetics of rocuronium in DMD patients were Vc 63 +/- 14 ml kg(-1), Cl 3.0 +/- 1.0 ml min(-1) kg(-1), half-lives 2.0 +/- 0.6, 20 +/- 10 and 129 +/- 98 min, SE. For both the DMD and the control group, the time course of neuromuscular block could be described by a sigmoid E(max) model using the estimated pharmacokinetic parameters of the DMD group. In patients with DMD, the equilibration between the central and effect compartment was significantly slower (T(1/2)ke0: 9.7 +/- 0.3 vs. 1.3 +/- 0.1 min) and the EC(50) was significantly smaller (512 +/- 20 vs. 1170 +/- 64 ng ml(-1)), whereas the ED(50) was 0.16 +/- 0.02 mg kg(-1) in both groups. The pharmacodynamics of rocuronium were significantly altered in patients with DMD, whereas the pharmacokinetics seemed to be similar to those in healthy adults. Patients with DMD were more sensitive with respect to effect site concentration but not with respect to dose.

Influence of a continuous prednisolone medication on the time course of neuromuscular block of atracurium in patients with chronic inflammatory bowel disease

BackgroundCorticosteroids interact with neuromuscular blocking agents. However, experimental data are contradictory: enhancement and attenuation of the neuromuscular block has been observed. This study tested the influence of long-term medication with prednisolone on atracurium-induced neuromuscular block. MethodsSixty patients with chronic inflammatory bowel disease undergoing elective abdominal surgery were investigated. Thirty patients received a long-term medication with prednisolone (Group A) and 30 were without corticoid medication (Group B). Additionally, another 30 patients without inflammatory bowel disease and without corticoid medication served as control (Group C). The following parameters of an atracurium-induced neuromuscular block (0.25 mg kg−1) were measured: onset time, maximum block, recovery to 25% first twitch height, recovery index (time from 25% until 75% recovery of first twitch), duration to recovery to a train-of-four (TOF) rate of 0.7 and 0.9. ResultsThe groups did not differ with regard to onset time, maximum block, and recovery index. The duration to 25% twitch height was significantly lower in Group A [18.1 (0–30.7) min] compared with Group B [23.5 (0–36.7) min; P<0.05]. Duration to a TOF rate of 0.7 and 0.9, respectively, were significantly reduced in Group A [36.1 (7.9) and 40.9 (9.0 min)] compared with Group B [47.9 (7.6) and 53.4 (9.2) min; P<0.001]. ConclusionsLong-term medication with prednisolone resulted in a shorter duration of an atracurium-induced neuromuscular block in patients with Crohn's disease or ulcerative colitis. The presence of the inflammatory bowel disease did not influence the time course of the neuromuscular block.

Rocuronium 0.3 mg·kg−1 (ED95) induces a normal peak effect but an altered time course of neuromuscular block in patients with Duchenne's muscular dystrophy

In patients with Duchenne's muscular dystrophy (DMD) recovery from neuromuscular block is delayed. It has been assumed that this is because of a higher potency of muscle relaxants in this patient cohort. We determined the peak effect, and the time course of action of rocuronium 0.3 mg x kg(-1) (ED(95)) in DMD patients. Twenty-four patients (12 with DMD and 12 controls; aged 10-18 years) were studied. All patients were anesthetized with propofol and fentanyl/remifentanil. Neuromuscular transmission was monitored by acceleromyography. After induction all patients received a single dose of rocuronium 0.3 mg x kg(-1). The complete time course of action as onset, peak effect and spontaneous recovery was recorded. The onset time (s) to maximum block was significantly (P < 0.01) prolonged in DMD patients (median: 315; range: 120-465) compared with controls (195, 75-270). The peak effect (% twitch depression relative to baseline) was not different between the groups (DMD: 59-100; controls: 28-100). In the DMD group, recovery was significantly (P < 0.01) delayed compared with controls at all recorded time points. The clinical duration (min) was 40.3 (22-89) in the DMD group vs 9.8 (6-17) in the control group (P < 0.01). The similar peak effect in both groups does not confirm the thesis of rocuronium having a higher potency in DMD patients. The documented very long recovery after the ED(95) of rocuronium emphasizes the need for careful assessment of neuromuscular function in DMD patients.

Pharmacokinetic Aspects of the Onset of Action of Neuromuscular Blocking Agents

In order to understand the factors governing the onset of neuromuscular block, it is important to know the processes following administration of a neuromuscular blocking agent (NMBA), eventually resulting in neuromuscular block. With respect to the processes involved in the time course of neuromuscular block, four steps can be discerned:

Effect of maintenance bolus on the recovery profile of a short-acting nondepolarizing muscle relaxant

Study objective To evaluate the effect of different maintenance boluses of a short-acting nondepolarizing neuromuscular blocking drug on its spontaneous recovery profile during anesthesia. Design Prospective, randomized, double-blind, dose-ranging study. Setting University-based medical center. Patients 69 ASA physical status I and II consenting adult outpatients undergoing general anesthesia with an anticipated duration of at least 2 hours. Interventions Patients were randomized to one of three study groups. Following induction of anesthesia with propofol and fentanyl, rapacuronium 1.5 mg · kg –1 intravenously (IV), was administered to facilitate tracheal intubation. Anesthesia was maintained with desflurane 4% end-tidal in combination with nitrous oxide 67% in oxygen. When the first twitch (T 1) in the train-of-four (TOF) returned to 25% of its baseline value, a maintenance dose of rapacuronium 0.25 mg · kg –1 IV (Group 1), 0.5 mg · kg –1 IV (Group 2), or 0.75 mg · kg –1 IV (Group 3) was administered. The time course of neuromuscular block was monitored at the wrist using standard electromyography. Measurements and main results The times for recovery of the T 1 to 25% of the baseline value following different maintenance doses of rapacuronium were only 6.3 ± 2.2, 7.5 ± 2.3, and 9.6 ± 2.5 minutes, in Groups 1, 2 and 3, respectively. However, the times for the TOF ratio to return to 0.7 were 44 ± 15, 53 ± 20, and 66 ± 30 minutes in Groups 1, 2, and 3, respectively. Although recovery times were significantly longer after rapacuronium 0.75 mg · kg –1 IV (Group 3), there were no significant differences in any of the recovery variables between Groups 1 and 2. Conclusions Spontaneous recovery of the T 1 to 25% of the baseline value occurred 6 to 10 minutes after a maintenance bolus dose of rapacuronium 0.25 to 0.75 mg · kg –1 IV. However, recovery to a TOF >0.7 required 44 to 66 minutes during desflurane anesthesia.

Cisatracurium neuromuscular block at the adductor pollicis and the laryngeal adductor muscles in humans

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.

Administration of atropine and onset of neuromuscular block produced by atracurium in infants.

In this prospective study we tested the hypothesis that atropine administration, which is known to increase heart rate and cardiac output in infants, will result in a faster onset of neuromuscular block with atracurium. Thirty infants scheduled for elective surgery had anaesthesia induced with nitrous oxide and halothane. Fifteen patients were given atropine and 15 patients acted as controls. All the infants were given atracurium 0.5 mg.kg-1, and neuromuscular block was recorded with the Datex 221 neuromuscular transmission monitor. Although atropine caused an increase in heart rate compared to the control group (median 164 [range 151-182] vs 120 [98-160]min-1 P < 0.0001), there was not a statistically significant difference in the onset of neuromuscular block between the two groups. We conclude that onset of neuromuscular block after atracurium is determined mainly by noncirculatory factors and less by the circulation time to the muscle. The effect of atropine on the time course of neuromuscular block might be different with faster acting neuromuscular blockers.

Pharmacokinetics and pharmacokinetic-dynamic modelling of rocuronium in infants and children

We have determined the pharmacokinetics and pharmacokinetic-pharmacodynamic relationship of rocuronium in infants and children. We studied infants (n = 5, 0.1-0.8 yr) and children (n = 5, 2.3-8 yr), ASA II, in the ICU while undergoing artificial ventilation under i.v. anaesthesia with an arterial cannula in situ and the EMG of the adductor pollicis muscle was monitored. Rocuronium 0.06 (infants) and 0.09 (children) mg kg-1 min-1 was given i.v. over +/- 5 min until 85% neuromuscular block was obtained. Arterial blood samples were obtained over 240 min. Plasma concentrations were measured by HPLC. Pharmacokinetic-dynamic variables were calculated using the Sheiner model and the Hill equation. Statistical analysis was performed using the Mann-Whitney U test (P < 0.05). The mean administered dose was 0.32 (SD 0.08) mg kg-1 and 0.4 (0.1) mg kg-1 for infants and children, respectively. Infants differed from children in plasma clearance (4.2 (0.4) vs 6.7 (1.1) ml min-1 kg-1), distribution volume at steady state (231 (32) vs 165 (44) ml kg-1), mean residence time (56 (10) vs 26 (9) min), concentration in the effect compartment at 50% block (1.2 (0.4) vs 1.7 (0.4) mg litre-1) and the slope of the concentration-effect relationship (5.7 (1.3) vs 3.9 (0.5)). Calculated mean ED90 values were 0.26 and 0.34 mg kg-1 for infants and children, respectively. The time course of neuromuscular block after equipotent doses did not differ.

A Comparison of Cisatracurium and Atracurium

Cisatracurium is a new nondepolarizing muscle relaxant.In patients randomized to receive either cisatracurium (n = 40) or atracurium (n = 20) we compared the time course of neuromuscular block. The initial bolus dose of cisatracurium was 0.1 mg/kg, that of atracurium 0.5 mg/kg. Neuromuscular block, maintained with an infusion of either drug, was reversed with neostigmine 45 micro g/kg and atropine 20 micro g/kg in one half of the patients. Neuromuscular transmission was assessed by recording the mechanical twitch response to train-of-four nerve stimulation. Onset times were 3.1 +/- 1.0 min with cisatracurium and 2.3 +/- 1.1 min with atracurium (P = 0.008). The infusion rates for a 95% +/- 4% neuromuscular block were 1.5 +/- 0.4 micro g [centered dot] kg-1 [centered dot] min-1 for cisatracurium and 6.6 +/- 1.7 micro g [centered dot] kg-1 [centered dot] min-1 for atracurium, 3.3 times those of cisatracurium when referenced to the active cations. After the infusion, the spontaneous recovery intervals 25%-75% of 18 +/- 11 min and 18 +/- 8 min for cisatracurium and atracurium (P = 0.896) were shortened to 5 +/- 2 min and 4 +/- 3 min (P = 0.921) after neostigmine. While attributing different onset times also to differences in the initial doses, we conclude that time profiles for neuromuscular block of both muscle relaxants, when given in equipotent doses, are not different. (Anesth Analg 1996;83:1072-5)

Effect of isoflurane and sevoflurane on the magnitude and time course of neuromuscular block produced by vecuronium, pancuronium and atracurium

We have compared the ability of equipotent concentrations of isoflurane and sevoflurane to enhance the effect of non-depolarizing neuromuscular blocking drugs. Ninety ASA I and II patients of both sexes, aged 18-50 yr, were stratified into three blocker groups (Vec, Pan and Atr), to undergo neuromuscular block with vecuronium (n = 30), pancuronium (n = 30) or atracurium (n = 30), respectively. Within each group, patients were allocated randomly to one of three anaesthetic subgroups to undergo maintenance of anaesthesia with: (1) alfentanil-nitrous oxide-oxygen (n = 10); (2) alfentanil-nitrous oxide-oxygen-isoflurane (n = 10); or (3) alfentanil-nitrous oxide-oxygen-sevoflurane (n = 10) anaesthesia. During maintenance of anaesthesia, end-tidal concentrations of isoflurane, sevoflurane and nitrous oxide were 0.95, 1.70 and 70%, respectively. Both the evoked integrated electromyogram and mechanomyogram of the adductor pollicis brevis muscle were measured simultaneously. In the Vec and Pan groups, a total dose of 40 micrograms kg-1 of vecuronium or pancuronium, respectively, was given, and in the Atr group a total dose of atracurium 100 micrograms kg-1. Each blocker was given in four equal doses and administered cumulatively. We showed that 0.95% isoflurane and 1.70% sevoflurane (corresponding to 0.8 MAC of each inhalation anaesthetic, omitting the MAC contribution of nitrous oxide) augmented and prolonged the neuromuscular block produced by vecuronium, pancuronium and atracurium to a similar degree.

Ventilation and neuromuscular blocking drugs.

Ventilatory failure after administration of neuromuscular blocking agents is an important factor in anaesthesia-related perioperative morbidity and mortality. Improved knowledge and new monitoring methods may avoid ventilatory failure caused by incomplete recovery of neuromuscular function in the postoperative period. Central respiratory muscles are less sensitive than, and their time course of neuromuscular block is different from those of, pharyngeal muscles and those of the upper airway. Differences in potency and time course of neuromuscular block may lead to incorrect assessment of ventilatory function during onset and recovery. Even if recovery of the mechanical adductor pollicis train-of-four (TOF) response to a ratio of 0.70 has previously been associated with adequate ventilatory capacity, it is now shown that hypoxic ventilatory responses may be markedly reduced despite adequate respiratory force at a TOF ratio of 0.70. Hence, partial paralysis may interfere with ventilatory regulation in hypoxaemia. Consequently, monitoring neuromuscular function by peripheral nerve stimulation in one muscle yields limited information about total ventilatory capacity, especially the function of the upper airway and ventilatory regulation. Therefore, neuromuscular monitoring should be used with caution during recovery and should always be combined with bedside clinical tests if possible.

α-Conotoxin GI produces tetanic fade at the rat neuromuscular junction

The ability of the marine snail toxin, α-conotoxin GI, to produce blockade of singly evoked twitches and to produce tetanic and train-of-four fade has been determined in the isolated rat hemidiaphragm preparation. Results were compared to those obtained with a reversible (vecuronium) and an irreversible (α-bungarotoxin) nicotinic acetylcholine antagonist and have been interpreted in terms of relative effects on post- and prejunctional nicotinic acetylcholine receptors at the neuromuscular junction. α-Conotoxin GI (0.5–2 μM) produced a concentration-dependent, readily reversible, decrease in the peak amplitude of single twitches and 50 Hz tetani, and an increase in tetanic and train-of-four fade. α-Conotoxin GI was consistently 2–3-fold more potent than vecuronium with respect to all of the measured tension parameters. Both α-conotoxin GI and vecuronium were approximately 2-fold more potent in producing tetanic fade and in blocking tetanic contractions than in blocking single twitches. In contrast to both α-conotoxin GI and vecuronium, α-bungarotoxin (0.13 μM) reduced the peak amplitude of both single twitches and 50 Hz tetani to the same extent without the appearance of a large degree of tetanic or train-of-four fade. Based on a comparison of the in vitro time course of neuromuscular block and of the relative effects of vecuronium, α-conotoxin GI and α-bungarotoxin on twitches, tetani and trains-of-four, we conclude that α-conotoxin GI has both pre- and postjunctional activity at the neuromuscular junction. In this respect, α-conotoxin GI resembles the clinically used competitive neuromuscular blocking drugs rather than the irreversible snake α-neurotoxins.