Anaesthetic management in patients with Duchenne muscular dystrophy undergoing orthopaedic surgery: a review of 232 cases.

CONTEXT: Patients with Duchenne muscular dystrophy are at increased risk of some anaesthesia-related hazards such as rhabdomyolysis, fever and hyperkalaemia. OBJECTIVES: To evaluate the management of anaesthesia in patients with Duchenne muscular dystrophy, including preoperative evaluation, intraoperative performance, critical events and postoperative care. DESIGN: We performed a retrospective case review study of anaesthesia in patients with Duchenne muscular dystrophy covering the period between April 2000 and December 2008. PATIENTS: 91 Duchenne patients undergoing 232 general anaesthetics for orthopaedic surgical interventions. SETTING: University hospital. RESULTS: Anaesthesia was performed using propofol, opioids and, if required, a non-depolarising muscle relaxant. Eight difficult direct laryngoscopies were reported. All patients undergoing spinal fusion surgery received transfusion of homologous blood products and required postoperative invasive ventilatory support for an average of 19 h. There was no severe anaesthesia-related complication and no case of unexplained fever or rhabdomyolysis. CONCLUSION: This retrospective survey confirms clinical experience that total intravenous anaesthesia can be used safely in Duchenne patients without major concern. Further prospective studies are necessary to establish evidence-based clinical guidelines for daily practice.

Pharmacodynamic modelling of rocuronium in adolescents with Duchenne muscular dystrophy.

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Reversal of rocuronium-induced neuromuscular blockade by pyridostigmine in patients with Duchenne muscular dystrophy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Pyridostigmine 0.1 mg.kg(-1) effectively reversed a rocuronium-induced NMB in DMD patients.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Onset and duration of rocuronium-induced neuromuscular blockade in patients with Duchenne muscular dystrophy.

BACKGROUND: 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. METHODS: 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 RESULTS: 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). CONCLUSIONS: 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.