Case Discussion 17 yo girl with congenital myopathy

Case Discussion 17 y/o girl with congenital myopathy Ri吳青芳 ╱ SC 陳毓仁 Brief History-1    82 (7y/o): exercise difficulty 86/10 (11y/o): scoliosis s/p Milwaukee brace at McKay Hospital 87/4 (12y/o): Progressive unsteady gait, dyspnea and consciousness loss Cerebellar tumor with brainstem compression s/p emergency tumor excision at McKay H. Tumor: vascular origin Post-op: failure to wean off ventilator Muscle biopsy: limb girdle myopathy Tracheostomy with ventilator Wheelchair-bound since then Brief History-2    88/9 (13y/o): 1st admission to NTUH for weaning Scoliosis at C-T spine Severe restrictive lung defect (FEV1 12.7%) CK: 657 IU/L Muscle biopsy: minimal histological change 89/2 (14y/o): Scoliosis correction at NCKU 92/3 (17y/o): Bil. Hamstring & Achilles tendon release at NCKU Then walked by side bar Brief History-3  92/9: 2nd admission to NTUH for abd. pain, poor appetite, episodes of desaturation occurred 92/10/31: Gastrostomy due to dysphagia (poor swallow function), silent aspiration & upper esophageal swelling 92/12/3: Gastrostomy revision due to wound discharge & leakage Hickmann catheter insertion   92.10.31 92.12.03 Pre-op Evaluation    Congenital myopathy (limb girdle myopathy?) mild muscle weakness over bilateral lower limbs scoliosis s/p operation mild oropharyngeal dysphagia with silent aspiration hypercapneic respiratory failure s/p tracheostomy severe restrictive lung defect (FEV1 12.7%) normal cardiac function (LVEF 83% in 88/11) unproved muscle biopsy Joint contracture s/p operation Cerebellar tumor s/p excision Anesthesia Method 92/12/3 Induction Sevoflurane 92/10/31 Fentanyl 10ml Esmeron 10mg (0.4mg/kg) Atropine 0.4mg Sevoflurane Tracheostomy Sevoflurane Esmeron 10mg (0.4mg/kg) Intubation Tracheostomy Maintenance Sevoflurane Niabex (cisatracurium) 4mg (0.16mg/kg) NM blockade reversal Atropine Enlon (edrophonium) Discussion Diseases of Skeletal Muscle Denervation atrophy  Muscular dystrophy  Myotonic dystrophy  Ion channel myopathy  Congenital myopathy  Inflammatory myopathy  Toxic myopathy  Disease of neuromucular junction  Robbins, Pathological basis of disease, 1999 Muscular dystrophy Muscular dystrophy is a heterogeneous group of hereditary noninflammatory but progressive muscle disorders without a central or peripheral nerve abnormality.  It’s clinically characterized by progressive muscle weakness and wasting.  Muscular dystrophy  Sex-linked MDs  Duchenne 10～30 per 100,000  Becker 3 per 100,000  Emery-Dreifuss 1 per 100,000 Autosomal dominant MDs  Fascioscapulohumeral  Distal, Ocular, Oculopharyngeal Classification   Autosomal recessive MDs  Congenital muscular dystrophy (CMD) 7~12 per 100,000  Pure CMD  Fukuyama CMD  Finnish-type CMD  Walker-Warburg Limb girdle muscular dystrophy, LGMD ( both AD & AR ) only accounts for 1.3% of patients with muscular dystrophy  Muscular dystrophy Congenital Limb girdle Duchenne, Becker Emery-Dreifuss Muscular dystrophy Clinical manifestations  Duchenne muscular dystrophy       Dystrophin gene mutation (at Xp21) No abnormality is noted in the patient at birth The symptoms appear at the age of 2~6 yr, and patients are usually wheelchair-bound by 10 yr. Rapidly progressive Not only skeletal muscle but also cardiac and smooth muscle Death occurs late in the second decade from respiratory complications in over 90% of cases Muscular dystrophy Clinical manifestations  Becker  Similar to Duchenne. Because they still have some functioning dystrophin, the symptoms may occur later and are more mild.  Emery-Dreifuss   Mutation of the X chromosome in the emerin gene Typically presents at the age of 4~5 years with contractures of the elbows, Achilles tendon (causing toe walking) and posterior cervical muscle. Cardiomyopathy usually presenting as heart block, result in sudden death Muscular dystrophy Clinical manifestations  Limb girdle muscular dystrophy (LGMD)   Originally it’s a diagnosis of exclusion, with symptoms of progressive proximal muscular dystrophy. Now it’s reclassified recording to genetic basis. At least 13 different types can be recognized now.  Autosomal dominant type  Autosomal recessive type One gene with different phenotypes, one phenotype with different genes Muscular dystrophy Anesthetic considerations  General principles     More sensitive to the myocardial depressant effects of potent inhaled anesthetics Succinylcholine is contraindicated because massive rhabdomyolysis, hyperkalemia, and cardiac arrest can occur Sensitive to nondepolarizing muscle relaxants, they may require a longer recovery time Vigorous respiratory therapy and ventilatory support may be necessary. Muscular dystrophy Anesthetic considerations  In Duchenne muscular dystrophy (1)       Obesity is most common Hypertrophy of the tongue, difficult intubation Deformities and contractures of the limb joints that will hinder vascular access and also positioning Spinal deformity may compress the upper respiratory tract Compromised respiratory function Heart, persistent sinus tachycardia, arrhythmias, nonspecific murmurs Muscular dystrophy Anesthetic considerations  In Duchenne muscular dystrophy (2)    The use of halothane, isoflurane, sevoflurane and succinylcholine in DMD child can result in acute rhabdomyolysis, hyperkalemia. The use of Vecuronium in DMD there can be up to sixfold delay in the recovery of muscle function. Atracurium is currently the drug of choice. The association of DMD with malignant hyperthermia is not proven. Prophylactic use of dantrolene in known DMD patients may be considered. Muscular dystrophy Anesthetic considerations  In Emery-Dreifuss muscular dystrophy     Cardiac involvement：atrial standstill is a pathognomonic finding, with a lack of atrial response to intracardiac electrical or mechanical stimulation. Neck stiffness Flexion contractures Muscle involvement：succinylcholine is contraindicated Myotonic dystrophy ( dytrophia myotonica, DM ) The most frequently inherited neuromuscular disease of adult life  It is a multisystem disease with major cardiac involvement  Core features of myotonic dystrophy are myotonia, muscle weakness, cataract, and cardiac conduction abnormalities  Myotonic dystrophy Classification  Type 1 (most common, 98%)   an expansion of CTG repeats in the DMPK gene on chromosome 19 Prevalence in West: 13.5 per 100,000 an expansion of CCTG repeats in the ZNF9 gene on chromosome 3  Type 2   Type 3 ? Myotonic dystrophy Clinical manifestations      Ptosis and weakness of the facial, jaw, and anterior neck muscles, distal weakness of the limbs progressing to proximal weakness Myotonia Cataracts Cardiac involvement is characterised by progressive conduction system abnormalities, supraventricular and ventricular arrhythmias and, less frequently, myocardial dysfunction and ischaemic heart disease. Type 1 and type 2 are similar Myotonic dystrophy Anesthetic considerations (1)      Heart: progressive conduction system abnormalities  Halothane will delay conduction in His-Purkinje system and should be avoided Mitral regurgitation is common Lung: restrictive lung disease, and diminished ventilatory responses to hypoxia and hypercapnia Thiopental and Etomidate are safe to use Propofol as an induction and maintenance agent is controversial Myotonic dystrophy Anesthetic considerations (2)     Particularly sensitive to succinylcholine, the development of myotonia may result in difficult intubation and ventilation Non-depolarizing MR usually have normal or prolonged response, and the reversal of MR may be needed. But the anticholinesterases may precipitate myotonia, presumably a result of increased sensitivity to Ach. Short-acting MR are recommended The response to a peripheral nerve stimulator must be carefully interpreted because muscle stimulation may trigger myotonia Cold is a potent trigger of myotonia episodes Congenital myopathy      Congenital myopathy is a term for any muscle disorder present at birth Unique morphological features on histochemical or ultrastructural examination of a muscle biopsy Present in early life or infancy with proximal or generalized hypotonia and weakness Often with dysmorphic features Relatively nonprogressive Congenital myopathy Classification       Nemaline (rod) myopathy (20%) incidence about 2 per 100,000 Central core disease (16%) Centronuclear (myotubular) myopathy (14%) Multi-minicore myopathy (10%) Fiber type disproportion or type 1 fiber predominance (21%) Miscellaneous congenital myopathies (19%)           Fingerprint body myopathy Reducing body myopathy Sarcotubular myopathy Hyaline body myopathy Trilaminar fiber myopathy Cap myopathy Zebra body myopathy Spheroid body myopathy Cytoplasmic body myopathy Desmin storage myopathies Nemaline (rod) myopathy Gomori trichrome (GT) stain, Skeletal muscle Facial & Axial weakness (severe)  High-arched narrow palate (severe)  Distal weakness & contractures  Deaths due to respiratory insufficiency  Central core myopathy Nicotinamide adenine dinucleotide (NADH) stain, Skeletal muscle Dominant inheritance: Often  History of malignant hyperthermia in family (Ryanodine receptor, RYR 1)  Proximal weakness  Relatively non-progressive  Centronuclear myopathy ↑H&E stain ← Trichrome stain Onset: infancy, early death (5 months)  EOM limitation, ptosis  Respiratory failure  Weakness non-progressive  Nemaline Myopathy Anesthetic considerations(1)    Facial dysmorphism: difficult intubation Inhalation induction, awake intubation or use of fiberoptic bronchoscope Restrictive pulmonary defect: due to myopathy and scoliosis, confirmed by spirometry, tracheal extubation after fully awake and responsive The question of which anesthetic agent may be used safely Stephen & Heard, 1983 Pre-op evaluation 18 y/o woman, severe restrictive lung Mary & Frederick, 1985 13 y/o girl, severe restrictive lung, minor facial dysmorphism Mary & Frederick, 1985 14 y/o girl, severe restrictive lung, narrow mandible, high-arched palate correction of scoliosis T. Asai, 1992 2 y/o boy, high-arched palate, pneumonia episode Op purpose repair of prognathic malocclusion correction of scoliosis ASD repair Intubation nasally deep halothane posterior arythenoid, stylet nitrous oxide, oxygen, halothane diazepam 2mg, fentanyl 200μg, pancuronium 2 mg Induction fentanyl 1μg/kg iv, thiopental 4mg/kg iv, nitrous oxide 66%, oxygen 34% nitrous oxide/ oxygen/ enflurane (1.0% ET conc.) + fentanyl + intermittent pancuronium (total dose 0.18mg/kg) single twitch every 10 sec thiopentone 5mg/kg, atropine 0.02mg/kg Maintenance fentanyl + halothane nitrous oxide, oxygen, isoflurane high-dose fentanyl + diazepam NM blockade monitor Muscle relaxant Succinylcholine Pancuronium atropine 0.02mg/kg, neostigmine 0.06mg/kg iv no no Pancuronium NM blockade reversal Nemaline Myopathy Anesthetic considerations(2)  Resistance to succinylcholine (1mg/kg) under normal pseudocholinesterase, no fasciculation, phase Ⅱ block or hyperkalemia Response to pancuronium (0.08mg/kg) and neostigmine were normal From Stephen and Heard,1983  Patients can be safely managed without use of muscle relaxant No reported association with malignant hyperthermia From Mary and Frederick, 1985  Muscle relaxant should be administered in cardiac surgery with high-dose fentanyl anesthesia, to control rigidity, to facilitate intubation and to prevent movement From T. Asai, 1992 Centronuclear Myopathy Anesthetic considerations(1) Allan&Terry, 1998 D. Breslin, 2000 Euro. J. of Anes., 2002 20y/o man easy choking with progressive deformity of jaw, ASA grade Ⅲ s/p tracheostomy Pre-op evaluation 32y/o woman restrictive lung & asthma, GERD, TMJ limited movement 53y/o man PEV1 70% Op purpose Arthroplasty of TMJ Tibial nail insertion Correction of deformity of maxilla and mandible Premedicatio n Induction Glycopyrrolate propofol Propofol, remifentanil Propofol, remifentanil Intubation Topical lidocaine & superior laryngeal nerve block→nasal fiberoptic Propofol, nitrous oxide, oxygen Surgical site: bupivacaine smoothly Pre-existing tracheostomy Propofol, remifentanil Maintenance Profopol, remifentanil infusion & 60% N2O Centronuclear Myopathy Anesthetic considerations(2)     Depolarizing muscle relaxant is avoided Volatile anesthetics were avoided because of the risk of developing MH. The combination of propofol and remifentanil infusions allowed smooth induction, easy intubation and ventilation, intra-op hemodynamic stability and early recovery and extubation with minimal residual effects. It is important to monitor NM function before the administration of muscle relaxants. From Allen & Terry, 1998, D.Breslin & J.Reid, 2000 In this case     Assess intubation difficulty tracheostomy already Pulmonary function test severe restrictive lung defect Risk of aspiration tracheostomy, atropine Anesthetic drug of choice Nondepolarizing MR: rocuronium, cisatracurium Sevoflurane reversal of block: atropine and edrophonium Conclusion  Pre-op evaluation Assess intubation difficulty Look for cardiac conduction abnormality Do pulmonary function test Risk of aspiration  Anesthetic drug Avoid SCC, volatile anesthetic Try low dose & short acting nondepolarizing muscle relaxants Thanks for your attention! Let’s go to OR!