rocuronium and Muscular-Dystrophy--Duchenne

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.

Topics: Adolescent; Androstanols; Child; Health; Humans; Male; Models, Biological; Muscular Dystrophy, Duchenne; Rocuronium

In patients with Duchenne muscular dystrophy (DMD) the response to nondepolarizing muscle relaxants is scarcely documented and conflicting. The current study was conducted to determine the time to peak effect and the time for complete spontaneous recovery after a single dose of 0.6 mg/kg of rocuronium in patients with DMD.. Twenty-four patients (12 with DMD, 12 controls, aged 10-16 yr) 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 0.6 mg/kg of rocuronium. The complete time course of onset and spontaneous recovery were recorded. Significant (P < 0.01) increase in the onset times to 95% neuromuscular block was observed in DMD patients (median, 203 s; range, 90-420 s) compared with controls (median, 90 s; range, 60-195 s). The time between rocuronium administration and recovery of first twitch of the train-of-four to 90% was significantly (P < 0.01) prolonged in DMD compared with controls (median, 132 min; range, 61-209 min versus 39 min; 22-55 min). The recovery index was also significantly prolonged in the DMD group compared with controls (median, 28 min, range, 15-70 min versus 8 min; 3-14 min).. The most striking and surprising result of this study is the delayed onset of blockade in DMD after a standard dose of rocuronium. This effect should be kept in mind in situations when a rapid airway protection is necessary in DMD patients. The documented very long recovery from rocuronium-induced block emphasizes the need for careful assessment of neuromuscular function in DMD patients.

Topics: Adolescent; Androstanols; Anesthesia Recovery Period; Child; Electric Stimulation; Humans; Kinetics; Male; Muscular Dystrophy, Duchenne; Myography; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Preanesthetic Medication; Rocuronium; Synaptic Transmission; Ulnar Nerve

Anesthetic management of patients with Duchenne muscular dystrophy (DMD) is complicated because these patients are more sensitive to nondepolarizing neuromuscular blocking agents (NMBAs) and are vulnerable to postoperative complications, such as postoperative residual curarization and respiratory failure. Sugammadex is a new reversal agent for aminosteroidal NMBAs, but its safety in children is controversial.. An 11-year-old boy with DMD underwent general anesthesia for a percutaneous nephrolithotomy. We used rocuronium bromide and sugammadex to reverse the deep neuromuscular block. Reversal of neuromuscular block was done 15 minutes after administration of 2 mg/kg of sugammadex. The patient's recovery from anesthesia was uneventful, and he was discharged to the postoperative recovery ward.. A delayed recovery was achieved, but no adverse events were observed, such as recurarization or hypersensitivity to sugammadex. We report safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block in a child with DMD.

Topics: Androstanols; Anesthesia, General; Child; gamma-Cyclodextrins; Humans; Male; Muscular Dystrophy, Duchenne; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex

We report a case of thoracoscopic pulmonary resection for pneumothorax in a patient with Becker muscular dystrophy The sensitivity of nondepolarizing muscle relaxant in a patient with muscle dystrophy is reportedly higher than in a patient without muscle disease, and the duration of the effect is known to be prolonged. In a 26-year-old man (height 160 cm, weight 39 kg) with Becker muscular dystrophy, general anesthesia was induced with target controlled infusion of propofol (3.0 microg x ml(-1)) and 0.4 microg x kg(-1) of min(-1) of remifentanil. A small amount of rocuronium was also administered additionally until TOF ratio reached to 0%. Total amount of rocuronium was 20 mg (0.5 mg x kg(-1)) for intubation with a double-lumen tracheal tube. The duration of surgery was 68 min. We confirmed 84% recovery of TOF ratio 90 min after injection of rocuronium, and extubated the patient without reversal of rocuronium. We found that the maximum concentration in the plasma or effective site (Cp/Ce) of rocuronium was reached at the time of intubation.

Topics: Adult; Androstanols; Anesthesia, General; Anesthetics, Intravenous; Humans; Male; Muscular Dystrophy, Duchenne; Neuromuscular Nondepolarizing Agents; Pneumonectomy; Pneumothorax; Propofol; Rocuronium; Thoracoscopy

We experienced anesthetic management of a patient with Becker muscular dystrophy. He had advanced dilated cardiomyopathy and high serum CK in the preoperative examinations. Anesthesia was planned to avoid triggering malignant hyperthermia or rhabdomyolysis and hemodynamic changes. Propofol, remifentanil and a minimum dose of rocuronium bromide were used for anesthetic induction and maintainance. Arterial pressure, cardiac output and stroke volume variation were monitored by Flotrac sensor. There were no adverse events observed during the anesthetic management. In conclusion, total intravenous anesthesia with the administration of rocuronium and circulatory monitoring by Flotrac sensor could be safe and efficient for anesthetic management of patients with Becker muscular dystrophy.

Topics: Androstanols; Anesthesia, General; Anesthesia, Intravenous; Cardiomyopathy, Dilated; Humans; Intervertebral Disc Displacement; Intraoperative Complications; Male; Malignant Hyperthermia; Middle Aged; Monitoring, Intraoperative; Muscular Dystrophy, Duchenne; Rhabdomyolysis; Rocuronium

A case is reported in which a child with Duchenne muscular dystrophy received a dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block. Sugammadex is the first selective relaxant binding agent and reverses rocuronium- and vecuronium-induced neuromuscular block. A fast and efficient recovery from profound neuromuscular block was achieved, and no adverse events or other safety concerns were observed.

Topics: Androstanols; Anesthesia, General; Child; gamma-Cyclodextrins; Humans; Humeral Fractures; Male; Muscular Dystrophy, Duchenne; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex; Treatment Outcome

The aim of this study was to investigate the effect and safety of pyridostigmine for the reversal of a neuromuscular block (NMB) in patients with Duchenne muscular dystrophy (DMD). In patients with DMD recovery from a rocuronium-induced NMB is markedly delayed.. Fourteen DMD patients (aged between 11 and 19 years) scheduled for elective scoliosis repair were studied. Following tracheal intubation without muscle relaxant, all patients received a single dose of rocuronium 0.6 mg.kg(-1). NMB was monitored by acceleromyography at the adductor pollicis muscle. When the first twitch height (T1) of the train-of-four (TOF) had recovered to 25% seven patients received either pyridostigmine 0.1 mg.kg(-1) (the anticholinergic drug with a long duration of action) or saline in a blinded manner. The times to attain TOF ratio of 0.9 were recorded. For comparison the Mann-Whitney U-test was used.. Recovery to TOF ratio of 0.9 was significantly (P < 0.05) accelerated by pyridostigmine [84 (median), 57-141(range)] compared with controls (148, 84-243 min). The recovery time (time between T1 of 25% and TOF of 90%) was also significantly (P < 0.01) shortened by pyridostigmine (15, 8-49 vs 76, 43-144 min, respectively). Time to recovery of T(1) to 90% was not different between the groups (108, 63-134 vs 169. 61-208 min, respectively).. Pyridostigmine 0.1 mg.kg(-1) effectively reversed a rocuronium-induced NMB in DMD patients.

Topics: Adolescent; Adult; Androstanols; Child; Cholinesterase Inhibitors; Electromyography; Humans; Male; Muscular Dystrophy, Duchenne; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Pyridostigmine Bromide; Rocuronium; Time Factors; Transcutaneous Electric Nerve Stimulation

Topics: Androstanols; Anesthesia, Inhalation; Anesthetics, Combined; Anesthetics, Dissociative; Anesthetics, Intravenous; Child, Preschool; Fentanyl; Humans; Ketamine; Male; Muscular Dystrophy, Duchenne; Neuromuscular Nondepolarizing Agents; Rocuronium; Tetralogy of Fallot

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.

Topics: Adolescent; Androstanols; Anesthesia Recovery Period; Anesthesia, Intravenous; Anesthetics, Combined; Case-Control Studies; Child; Dose-Response Relationship, Drug; Fentanyl; Humans; Male; Muscular Dystrophy, Duchenne; Myography; Neuromuscular Blockade; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Piperidines; Propofol; Remifentanil; Rocuronium; Time Factors