A porcine model of acute quadriplegic myopathy: a feasibility study

BACKGROUND: The mechanisms underlying acute quadriplegic myopathy (AQM) are poorly understood, partly as a result of the fact that patients are generally diagnosed at a late stage of the disease. Accordingly, there is a need for relevant experimental animal models aimed at identifying underlying mechanisms. METHODS: Pigs were mechanically ventilated and exposed to various combinations of agents, i.e. pharmacological neuromuscular blockade, corticosteroids and/or sepsis, for a period of 5 days. Electromyography and myofibrillar protein and mRNA expression were analysed using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), confocal microscopy, histochemistry and real-time polymerase chain reaction (PCR). RESULTS: A decreased compound muscle action potential, normal motor nerve conduction velocities, and intact sensory nerve function were observed. Messenger RNA expression, determined by real-time PCR, of the myofibrillar proteins myosin and actin decreased in spinal and cranial nerve innervated muscles, suggesting that the loss of myosin observed in AQM patients is not solely the result of myofibrillar protein degradation. CONCLUSION: The present porcine AQM model demonstrated findings largely in accordance with results previously reported in patients and offers a feasible approach to future mechanistic studies aimed at identifying underlying mechanisms and developing improved diagnostic tests and intervention strategies.     

Anaesthesia for a child with centronuclear myopathy

Centronuclear myopathy (CNM) is an inherited condition involving most muscle fibres in all the body mass, first described in 1966, which has a varying spectrum of presentations. Until recently it had not been associated with an increased risk of malignant hyperpyrexia. A seven-year-old male with CNM was admitted to our hospital for elective surgery. High dose propofol anaesthesia was used, supplemented with N₂O/O₂ from a new anaesthesia machine. The operation was successful with uncomplicated anaesthesia and recovery.     

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.     

Anesthetic considerations in myofibrillar myopathy

Myofibrillar myopathy (MFM) is a relatively newly recognized genetic disease that leads to progressive muscle deterioration. MFM has a varied phenotypic presentation and impacts cardiac, skeletal, and smooth muscles. Affected individuals are at increased risk of respiratory failure, significant cardiac conduction abnormalities, cardiomyopathy, and sudden cardiac death. In addition, significant skeletal muscle involvement is common, which may lead to contractures, respiratory insufficiency, and airway compromise as the disease progresses. This study is the first report of anesthetic management of a patient with MFM. We report multiple anesthetic encounters of a child with genetically confirmed BAG3‐myopathy, a subtype of MFM with severe childhood disease onset. A review of the anesthetic implications of the disease is provided, with specific exploration of possible susceptibility to malignant hyperthermia, rhabdomyolysis, and sensitivity to other anesthetic agents.     

The effect of neuromuscular blockade on the efficiency of facemask ventilation in patients difficult to facemask ventilate: a prospective trial

Facemask ventilation of the lungs can be an important rescue intervention in a ‘cannot intubate’ scenario. We assessed the effect of neuromuscular blockade on expiratory tidal volumes in patients with expected difficulty in mask ventilation. The lungs of patients with at least three predictors of difficulty in mask ventilation were ventilated using a facemask held with two hands, with mechanical ventilation set in a pressure‐controlled mode. Tidal volumes were recorded before and after the establishment of complete neuromuscular block. In 113 patients, median (IQR [range]) tidal volume increased from 350 (260–492 [80–850]) ml initially, by 48% to 517 (373–667 [100–1250]) ml 30 s after rocuronium administration, (p < 0.001). After the onset of the complete neuromuscular block, a median tidal volume of 600 (433–750 [250–1303]) ml was observed, corresponding to an increase of 71% from baseline values (p < 0.001), and 16% from values obtained 30 s after rocuronium administration, respectively; p = 0.003). No decrease in the tidal volume during the measurements was observed. We conclude that the administration of rocuronium at a dose of 0.6 mg.kg^?1 was able to improve facemask ventilation in all cases with a potentially clinically relevant increase in tidal volume. The early use of a neuromuscular blocking agent can be considered as a therapeutic option in case of difficulty with mask ventilation.     

Comparative fading responses induced by mivacurium,cisatracurium, and d-tubocurarine in the evoked muscular compound action potentials of the cat

PURPOSE: It has been suggested that the different degrees of fade induced by nondepolarizing neuromuscular blocking agents in repetitive muscular contractions may be due to the varying affinities or binding kinetics of presynaptic nicotinic receptors. We compared the degree of fade induced by mivacurium, cisatracurium, and d-tubocurarine in the cat muscular compound action potential (mCAP). METHODS: In 21 cats, mCAPs of the gastrocnemius muscle were evoked by paired (conditioning and test stimuli) and 2 Hz train-of-four (TOF) sciatic nerve stimulation. The interval between the paired stimuli was changed stepwise from 7 to 1000 ms. The ratios of the amplitude evoked by test stimulus to that evoked by the conditioning stimulus (M2/M1 ratios) and TOF ratios were measured. After baseline variables had been obtained, the cat received either mivacurium (0.08 mg x kg(-1), n = 7), cisatracurium (0.05 mg x kg(-1), n = 7), or d-tubocurarine (0.5 mg x kg(-1), n = 7). A series of M2/M1 ratios and TOF ratios were measured at various levels of partial block during recovery. RESULTS: At 10% of baseline amplitude, all agents significantly depressed the M2/M1 ratios (i.e., fade) at relatively longer intervals of paired stimuli (mivacurium, > or = 100 ms; cisatracurium. > or = 40 ms; and d-tubocurarine, > or = 20 ms), when compared with baseline. The order of activity to produce fade was mivacurium < cisatracurium < d-tubocurarine. A similar result was obtained in TOF ratios measured at various levels of neuromuscular block. CONCLUSION: Our results suggest that mivacurium shows a lesser degree of fade during partial neuromuscular block than cisatracurium and d-tubocurarine.     

Resistance to vecuronium in a term neonate

We report a case of resistance to curarization in a term neonate undergoing surgery. The dosage of vecuronium required to obtain satisfactory muscular blockade and cessation of spontaneous breathing efforts was more than 10-fold the normal one. The operation was delayed for 90 min The mechanism of this marked resistance is unknown, but some possible hypotheses are presented, focusing on the neonate's poor intrauterine growth and an abnormality in pharmacodynamics.     

Duration of action of an equipotent dose of vecuronium in infants and in children

During general anaesthesia without any volatile anaesthetic agents, ten infants and ten children received incremental doses of vecuronium to achieve a 95% neuromuscular block. Thereafter, the thenar electromyographic response was allowed to recover spontaneously. Total dose of vecuronium to establish a 95.0 ± 0.5% (mean ± SEM) neuromuscular block was 66% greater for children than for infants (73 ± 4 vs. 44 ± 4 μg·kg^?1, P < 0.0001). However, recovery index and time to complete recovery of the neuromuscular function were 88 and 89% longer, respectively, in infants than in children (P < 0.0001). These results of the effect of an equipotent dose of vecuronium in infants and in children confirm that vecuronium is a long acting neuromuscular blocking agent in infants.     

Mivacurium in children with Duchenne muscular dystrophy

The authors retrospectively reviewed their experience with mivacurium for neuromuscular blockade in seven children with Duchenne muscular dystrophy. Mivacurium was administered to seven children ranging in age from 8.3 to 14.4 years and in weight from 29 kg to 68 kg during either posterior spinal fusion or lower extremity release. An initial bolus dose of 0.2 mg·kg^?1 was followed by a continuous infusion. Neuromuscular blockade was monitored with a standard twitch monitor and the TOF (2 Hz for 2 s). Complete suppression of all four twitches occurred in 1.5 to 2.6 min. The continuous infusion was started with the return of the first twitch and adjusted to maintain one twitch. Time to recovery of the first twitch varied from 12 to 18 min. Continuous infusion requirements varied from 3 to 20 μg·kg^?1 with an average for the case of less than 10 μg·kg^?1 min^?1 in five of the seven patients. A moderate increase in sensitivity to mivacurium in this patient population is suggested by a decrease in infusion requirements and a prolonged effect following the initial dose.     

A retrospective observational study of neuromuscular monitoring practice in 30,430 cases from six Danish hospitals

Timely application of objective neuromuscular monitoring can avoid residual neuromuscular blockade. We assessed the frequency of objective neuromuscular monitoring with acceleromyography and the last recorded train-of-four ratio in a cohort of Danish patients. We extracted data from all patients receiving general anaesthesia from November 2014 to November 2016 at six hospitals in the Zealand Region of Denmark. Acceleromyography was available in all operating rooms and data were recorded automatically. The primary outcome measure was acceleromyography use in patients receiving neuromuscular blocking agents, divided into non-depolarising agents and succinylcholine only. The dataset included 76,743 cases, of which 30,430 received a neuromuscular blocking drug. Non-depolarising drugs were used in 16,525 (54%) and succinylcholine as the sole drug in 13,905 (46%) cases. Acceleromyography was used in 14,463 (88%) patients who received a non-depolarising neuromuscular blocking drug and in 4224 (30%) receiving succinylcholine alone. Acceleromyography use varied between the departments from 58% to 99% for non-depolarising drugs and from 3% to 79% for succinylcholine alone. The median (IQR [range]) of the last recorded train-of-four ratio before tracheal extubation was 0.97 (0.90–1.06 [0.01–2.20]) when non-depolarising drugs were used, and was less than 0.9 in 22% of cases. The OR for oxygen desaturation was higher with the use of succinylcholine [2.51 (95%CI 2.33–2.70) p < 0.001] and non-depolarising drugs [2.57 (95%CI 2.32–2.84) p < 0.001] as compared with cases where no neuromuscular blockade drug was used. In conclusion, acceleromyography was almost always used in cases where non-depolarising neuromuscular blocking drugs were used, but a train-of-four ratio of 0.9 was not always achieved. Monitoring was used in less than 30% of cases where succinylcholine was the sole drug used.     

Visceral myopathy causing chronic intestinal pseudoobstruction and intestinal failure in a child with Sanjad-Sakati syndrome

Sanjad-Sakati syndrome is a rare autosomal recessive disorder mainly occurring in the Arab Peninsula. This condition is associated with metabolic and septic complications starting in the neonatal period. Chronic intestinal pseudoobstruction owing to visceral myopathy is a rare disabling condition. We report a rare concurrence of Sanjad-Sakati syndrome and chronic intestinal pseudoobstruction in a Saudi child complicated by intestinal failure, sepsis, and early mortality.     

Anasthesia in myotubular (centronuclear) myopathy

A patient with a known history of myotubular myopathy presented for surgery for insertion of a tibial nail. Anasthesia was induced and maintained using an intravenous anasthetic technique. Neuromuscular function was assessed using mechanomyography, which showed a profound reduction in muscle contractility. In view of this, the use of muscle relaxants was avoided altogether. Nerve conduction was normal but electromyography showed small motor units, with generalised distribution, suggesting mild to moderately severe myopathy. The patient made a slow but uneventful recovery.     

Neuromuscular blocking agents and reversal agents

The neuromuscular junction consists of the motor nerve terminal, the synaptic cleft and post-synaptic nicotinic receptors on the motor end-plate of striated muscle. Neuromuscular blocking drugs are categorized into depolarizing and non-depolarizing agents. They are structurally related to acetylcholine (ACh), containing at least one positively charged quaternary ammonium radical that binds to the nicotinic receptor. Depolarizing agents (e.g. suxamethonium) act as agonists like ACh at the nicotinic receptor, but cause a more prolonged depolarization of the motor end-plate, thus rendering the ion channel insensitive to further action potentials. Non-depolarizing agents, in contrast, compete directly with ACh for nicotinic receptor binding sites and prevent neurotransmitter–receptor binding. These are either benzylisoquinoliniums (e.g. atracurium) or aminosteroids (e.g. rocuronium). Once recovery has commenced, neuromuscular block can be reversed with anticholinesterases (e.g. neostigmine). In contrast, the novel cyclodextrin sugammadex can be used to reverse any degree of neuromuscular block produced by rocuronium or vecuronium.     

Neuromuscular blocking agents and reversal agents

The neuromuscular junction consists of the motor nerve terminal, the synaptic cleft and post-synaptic nicotinic receptors on the motor end-plate of striated muscle. Neuromuscular blocking drugs are categorized into depolarizing and non-depolarizing agents. They are structurally related to acetylcholine (ACh), containing at least one positively charged quaternary ammonium radical that binds to the nicotinic receptor. Depolarizing agents (e.g. suxamethonium) act as agonists like ACh at the nicotinic receptor, but cause a more prolonged depolarization of the motor end-plate, thus rendering the ion channel insensitive to further action potentials. Non-depolarizing agents, in contrast, compete directly with ACh for nicotinic receptor binding sites and prevent neurotransmitter–receptor binding. These are either benzylisoquinoliniums (e.g. atracurium) or aminosteroids (e.g. rocuronium). Once recovery has commenced, neuromuscular block can be reversed with anticholinesterases (e.g. neostigmine). In contrast, the novel cyclodextrin sugammadex can be used to reverse any degree of neuromuscular block produced by rocuronium or vecuronium.     

Five Non-Depolarizing Muscle Relaxants in Precurarization

Five different non-depolarizing muscle relaxants and a control solution of saline were studied as precurarization agents. Two hundred and twenty-two surgical patients (ASA I-II) were allocated in a double-blind fashion to one of the following groups: d-tubocurarine 0.05 mg/kg, alcuronium 0.03 mg/kg, pancuronium 0.01 mg/kg, gallamine 0.25 mg/kg, ORG NC-45 (vecuronium) 0.01 mg/kg and saline solution 0.005 ml/kg. Pretreatment was performed 4 min before administering a 1.5 mg/kg bolus of succinylcholine (SCh). Fasciculations, intubation conditions, duration of neuromuscular blockade after SCh, serum potassium changes and postoperative myalgias (in 60 patients) were recorded. All the drugs studied prevented fasciculations significantly (P less than 0.05) more than in the control group. d-Tubocurarine and alcuronium were superior to the others in this respect. Intubation conditions were best in the control and pancuronium groups, but there was no significant difference between the pancuronium and d-tubocurarine or between the d-tubocurarine and alcuronium groups. Pancuronium pretreatment prolonged the SCh block significantly, whereas other agents shortened the duration of the SCh block. The antagonism of the SCh block apparently also affected intubation conditions, although intubation remained satisfactory. A statistically significant rise in serum potassium level was measured only in the control and pancuronium groups. In the control and pancuronium groups, four patients out of 10 had postoperative myalgias, whereas in the other groups only one or none out of 10 had them (0/10 vs. 4/10; 0.10 greater than P greater than 0.05). In conclusion, d-tubocurarine and alcuronium seem to have advantages over pancuronium, ORG NC-45 and gallamine for precurarization.     

Acute myopathy of intensive care in a child after heart transplantation

PURPOSE: Acute myopathy of intensive care has been described infrequently in children and never after organ transplantation. We report a case of acute myopathy of intensive care in a child after heart transplantation. CLINICAL FEATURES: An 11-yr-old girl, with no previous medical history, developed acute cardiomyopathy leading to cardiac shock. Family history revealed four cases of unidentified myopathy and/or cardiomyopathy. Preoperatively, while muscle biopsy was near normal, myocardial biopsy revealed non specific mitochondrial disorders. A few days after heart transplantation, she developed acute hypotonia and flaccid quadriplegia, consistent with the diagnosis of acute myopathy of intensive care. Nerve conduction studies were normal, electromyography showed myopathic changes and a new muscle biopsy from quadriceps femoris showed severe loss of myosin filaments and ATPase activity in type 2 fibres. A large laboratory screening failed to demonstrate a metabolic disease or a known myopathy. Muscle strength recovered progressively in three weeks allowing home discharge. A few months later, she was free of symptoms and muscle biopsy showed full histopathological recovery. CONCLUSION: Acute myopathy of intensive care can occur in children after heart transplantation. It should be suspected in the presence of muscle weakness and difficulty in weaning from ventilatory support. Electromyography confirmed a myogenic process and muscle biopsy allowed diagnosis. Full clinical and histopathological recovery usually occur within three weeks.