Canadian Journal of Anesthesia 47:342-346 (2000)
© Canadian Anesthesiologists' Society, 2000
Brief Report
Acute myopathy of intensive care in a child after heart transplantation
Philippe Chetaille, MD*,
Olivier Paut, MD
,
Alain Fraisse, MD*,
Bernard Kreitmann, MD
,
Jean Camboulives, MD and
Jean-François Pellissier, MD
* From the Departments of Pediatric Cardiology,
Pediatric Anesthesiology and Intensive Care,
Pediatric Cardio- Thoracic Surgery, and
Pathology and Neuropathology, La Timone Children's Hospital, Marseille, France.
Address correspondence to: Dr. Olivier Paut, Département d'Anesthésie-Réanimation Pédiatrique, CHU Timone- enfants, Boulevard Jean Moulin, 13385 Marseille cedex 5, France.Phone: 33-4-91-38-68-37; Fax: 33-4-91-47-81-70; E-mail: opaut{at}ap-hm.fr
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Abstract
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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.
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Introduction
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ACUTE Myopathy of Intensive Care (AMIC) has been documented in patients treated for status asthmaticus1,2 and other severe pulmonary disorders, sepsis and burns.3 It is usually associated with the use of intravenous corticosteroids (CS) and non depolarizing neuromuscular blocking agents.4,5 It has been reported rarely in transplant recipients3,5,6 and only one case, formally documented with muscle biopsy, has been reported in children.7 No pediatric cases have been reported after cardiac surgery or organ transplantation.
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Case report
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An 11-yr-old girl, with no previous medical history, was admitted in cardiac failure. She was born from related parents (first cousins) and two of her brothers died from non documented cardiomyopathy. Two others have advanced myopathy and cardiomyopathy, but their muscle biopsies did not reveal any structural or metabolic abnormality. She had a severe hypokinetic and dilated cardiomyopathy with normal coronary anatomy. Muscle biopsy (MB) showed subtle abnormalities and there was no degenerative or metabolic abnormality (Tables I,II
). Myocardial biopsy showed mitochondrial disorders and slight interstitial fibrosis without myocarditis. Details of laboratory screening for muscle and heart disease are reported in Table II.
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TABLE I Time course of main pathological findings seen on the three consecutive muscle biopsies. AMIC: Acute Myopathy of Intensive Care
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TABLE II Etiologic muscle and laboratory studies. All following studies were normal. (on the three muscle biopsies for pathology screenings).
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She developed refractory heart failure despite furosemide, dobutamine and enoximone, leading to biventricular circulatory assistance for 82 hr, until orthotopic heart transplantation was performed. She developed transient acute renal failure (creatinine 142 µmol•l–1 , BUN 22 mg•l–1), liver function was slightly impaired (PT 49%, Factor V 49%). Rocuronium was given in ICU (0.7 mg•kg–1, followed by a continuous infusion 0.5 mg•kg–1•hr–1 over 18 hr), while cistracurium (0.17 mg•kg–1•hr–1 over seven hours) was given during transplantation. Postoperatively, she received methylprednisolone, rabbit antithymocyte globulin, cyclosporine A, and was sedated with fentanyl and midazolam. Renal and liver functions recovered rapidly. Weaning from ventilator was performed on second postoperative day (D2) but the trachea was rapidly reintubated for respiratory fatigue (with respiratory rate at 70 bpm). There was no signs of rejection on myocardial biopsy and echocardiography. On D7 muscle weakness was present with poor motion and rare eyelid blinking. Successful weaning from mechanical ventilation was possible on D14. Clinical examination showed diffuse, proximal and distal muscle weakness, amyotrophy with no deep tendon reflexes leading to flaccid quadriplegia and facial diplegia with poor swallowing. No fasciculation was noted. Laboratory screening was negative (Table II
). Sensory and motor nerve conduction studies were normal, while detection electromyography showed rich and reduced amplitude of nerve action potentials during voluntary contraction with no spontaneous activity suggesting a myogenic process. On D21, a second MB showed severe abnormalities consistent with the diagnosis of AMIC (Figures 1,2, Table I).
Prednisolone was progressively tapered to a maintenance regimen (8 mg•day–1). Muscle weakness improved and she was discharged from ICU on D19 and home on D33. Muscle biopsy performed six months after transplantation, showed recovery of muscle architecture and enzymatic activity (Table I). The child at this time was free of symptoms, until now, more than two years after.
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Discussion
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This child, formerly free of cardiac symptoms, developed a severe cardiomyopathy. Screening for muscle disease was performed before transplantation: muscle specimen showed only slight heterogenity in fibres size. After transplantation, she developed a severe muscle fatigue related to a myogenic process. Diagnosis of AMIC was confirmed by histopathology and electron microscopy showing loss of myosin ATPase activity of type 2 fibres, secondary to myosin loss, while fast and slow myosin heavy chain (MHC) showed a normal immunoreactivity. At recovery, MB showed repolymerisation of myosin, with normal enzymatic activities and rearrangement of thick filaments of myosin in the sarcomeres. However, while this patient developed typical AMIC, her history may also suggest an underlying muscle disorder but, despite complete muscular and metabolic screenings no diagnosis has been made..
Acute Myopathy of Intensive Care must be differentiated from other causes of muscle weakness occurring in ICU. Electrodiagnosis is essential since it permits distinction of myopathy from critical illness polyneuropathy.5 The diagnosis of AMIC is made by histopathology. Different types of lesions are described. Non specific modifications are a selective atrophy of type 2 fibres or necrotizing and vacuolar lesions. The most specific lesions consist in a loss of thick filaments of myosin without necrosis or fibres vacuolisation: type 2 fibres lose their myosin ATPase activity because of myosin depolymerisation, supported by a normal immunoreactivity of MHC. Muscle usually recovers its normal function as its ultrastructure and enzymatic activities normalize within a few weeks.5,6
Non depolarizing muscle relaxants, corticosteroids and sepsis are thought to be the main etiopathogenic factors associated with AMIC.8 Administration of high doses of CS to a vulnerable patient is the main precipitating factor. Non depolarizing muscle relaxants produce biochemical modifications of acetylcholine receptors followed by a denervation amyotrophy,9 but no correlation exists between the outbreak of myopathy and non depolarizing muscle relaxant administration.10 With the loss of thick filaments, AMIC seems to be a particular entity even if its etiology is not well known.5 In animals, disassembly of myosin monomers is thought to lead to loss of thick filaments, presumably due to an effect at the level of cellular protein regulation.5 These models give the predominant role in pathogenesis to CS. Other factors such as terminal motoneurone axonopathy could act as potentiating factors. A causal relationship between cumulating doses, length of administration of CS and non depolarizing muscle relaxants and development of AMIC has been demonstrated.5 However, predicting factors of AMIC for an individual are lacking.4
Rare pediatric cases of AMIC, and none of them after organ transplantation have been previously reported. The only pediatric case documented with biopsy occurred in a 13-yr-old girl suffering from myasthenia gravis, treated with CS, who developed a myopathy with loss of myosin.7 It is noteworthy that both cases of pediatric AMIC, occurred in children having a known or suspected neuromuscular disorder. The precipitating role of an underlying muscle disease and its incidence in pediatric intensive care need to be addressed by further studies.
We conclude that AMIC can occur in the postransplantation period in children since predisposing factors such high dose of CS for immunosuppression and muscle relaxants can be given. AMIC must be suspected in a child presenting hypotonia and muscle weakness, with myopathic changes on electromyography. The diagnosis is then confirmed by muscle biopsy. Recovery occurs within weeks, with full histopathologic restitution.
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Acknowledgments
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The authors thank Dr, F. Wernert for patient referral, Dr. J.P. Azoulay for electrophysiologic exploration and Dr. V. Pakis for muscle DNA studies.
Accepted for publication December 11, 1999.
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References
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Abstract
Introduction
). (Gomori trichrome stain ; X = 100)
type 2B fibre; 
type 2C fibre) while ATPase activity is normal in type 1 fibres and intrafusal fibres (
).