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Investigate Exertional Rhabdomyolysis (Or Not)

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Investigate Exertional Rhabdomyolysis (Or Not) HOW TO DO IT Pract Neurol: first published as 10.1136/practneurol-2018-002008 on 10 October 2018. Downloaded from How to do it: investigate exertional rhabdomyolysis (or not) Peter M Fernandes,1 Richard J Davenport2 1Centre for Clinical Brain ABSTRACT pain and dark urine. Neurological exam- Sciences, University of Rhabdomyolysis is the combination of symptoms ination was normal but his serum CK was Edinburgh, Edinburgh, UK 2Division of Clinical (myalgia, weakness and muscle swelling) and >300 000 IU/L and he required dialysis Neurosciences, University of a substantial rise in serum creatine kinase for acute kidney injury with myoglobin- Edinburgh, Western General (CK) >50 000 IU/L; there are many causes, uria. He was discharged after 1 week with Hospital, Edinburgh, UK but here we specifically address exertional improving kidney function and CK 2750 Correspondence to rhabdomyolysis. The consequences of this IU/L. Repeat blood tests after 3 months Peter M Fernandes, Centre condition can be severe, including acute kidney showed normal kidney function and CK for Clinical Brain Sciences, injury and requirement for higher level care with 334 IU/L, remaining elevated at 550 IU/L University of Edinburgh, Edinburgh EH16 4SA, UK; organ support. Most patients have ‘physiological’ at 1 year. He had developed exercise peterfernandes@ nhs. net exertional rhabdomyolysis with no underlying intolerance in his teenage years without disease; they do not need investigation seeking medical attention. Further inqui- Accepted 21 August 2018 and should be advised to return to normal ries revealed his sister, with whom he Published Online First 10 October 2018 activities in a graded fashion. Rarely, exertional had little contact for many years, had rhabdomyolysis may be the initial presentation of been diagnosed with McArdle’s disease underlying muscle disease, and we review how in childhood. Subsequent gene testing to identify this much smaller group of patients, demonstrated he was homozygous for who do require investigation. the c.148C>T (p.Arg50Ter) pathogenic mutation in myophosphorylase (PGYM). CASE 1 DEFINING RHABDOMYOLYSIS A 25-year-old male personal trainer ran a There is no universally agreed clinical defi- ‘fun run’ on a hot day wearing a heavy nition of rhabdomyolysis, but a working costume. He collapsed 9 km into the definition would encompass the twin run and was brought to hospital. He was features of symptomatic muscle involve- agitated and confused (Glasgow Coma ment and a substantial rise in serum CK, http://pn.bmj.com/ Scale score 10; E3, V3, M4), feverish usually >50 000 IU/L. Muscle symp- (40.5°C) and tachycardic (149 bpm) with toms include myalgia, weakness and/or muscle pain and weakness. He was cooled swelling. The presence of myoglobinuria and given intravenous fluids. Investiga- is not required and many laboratories do tions showed serum creatine kinase (CK) not routinely measure serum and urinary concentration was 3000 IU/L, rising to myoglobin. Nevertheless, patients should on October 2, 2021 by guest. Protected copyright. 105 000 IU/L at 24 hours, with an acute be asked about changes in urine color- kidney injury and myoglobinuria. He was ation, which may be the classical ‘Coca- discharged 3 days later with no neurolog- Cola’ of myoglobinuria. Urine should ical deficit and normal renal function; his be dipstick tested: haemoglobin without CK normalised after 3 weeks. He was an erythrocytes indicates myoglobinuria. athletic man who had completed several marathons, with no medical conditions or CAUSES OF RHABDOMYOLYSIS family history of neuromuscular disease. Rhabdomyolysis can be divided into non-exertional and exertional causes CASE 2 (box 1), although certain non-exertional © Author(s) (or their employer(s)) 2018. Re-use A 42-year-old male security supervisor causes are due to generalised muscle over- permitted under CC BY. attended a training course involving activity, such as alcohol withdrawal, status Published by BMJ. intense physical exertion. He became epilepticus or tetany. Some causes, such as To cite: Fernandes PM, dehydrated and took oral and topical statin medications, may be obvious but Davenport RJ. Pract Neurol ibuprofen. He attended the emergency others need more careful thought, as in 2019;19:43–48. department 3 days afterwards with flank case 2. A detailed history of the preceding Fernandes PM, Davenport RJ. Pract Neurol 2019;19:43–48. doi:10.1136/practneurol-2018-002008 43 HOW TO DO IT are common and are asymptomatic in up to half of Pract Neurol: first published as 10.1136/practneurol-2018-002008 on 10 October 2018. Downloaded from Box 1 Causes of rhabdomyolysis cases.2 Mean serum CK values 24 hours after mara- Non-exertional causes thons are 3322 IU/L for men (22× baseline) and 946 IU/L for women (9× baseline).3 The clinical signifi- ► Drug – Amphetamines, cocaine, cyclosporine, fibrates, cance of the serum CK concentration is unclear: 6000 IU/L has been cited as the minimum necessary for isoniazid, lithium, neuromuscular blocking agents, 4 propofol, quetiapine, statins, zidovudine. renal failure but case reports indicate acute kidney injury may occur with a serum CK of 5000 IU/L5 and ► Toxic – Alcohol, heavy metal poisoning, snake venom. other studies suggest no safe serum concentration of CK.6 Pragmatically, a rise in CK to >5000 U/L and/ ► Metabolic – Alcohol withdrawal, electrolyte abnormalities, or evidence of end-organ damage (eg, myoglobin- hypothyroidism, serotonin syndrome, status uria or decline in renal/liver function) is sufficient epilepticus. for a diagnosis of exertional rhabdomyolysis. Patients with exertional rhabdomyolysis may also experience ► Inflammatory – Dermatomyositis, polymyositis. fever, nausea and decreased/absent urine production. Supportive biochemical findings include hyperka- ► Infection – Coxsackie, Epstein-Barr virus, influenza, HIV, laemia, hyponatraemia, hyperphosphataemia, hyper- malaria, tetanus, other viruses. calcaemia or hypocalcaemia and metabolic acidosis. Most cases of exertional rhabdomyolysis are caused ► Local muscle damage – Crush injury, compartment syndrome, muscle by heat-related injuries, specifically heat stroke and ischaemia. heat injury. The WHO’s International Classification Exertional causes of Diseases, 10th Revision includes four overlap- ping categories relating to exertional heat conditions ► Heat-related injuries (table 1, case 1) – Heat stroke, heat injury. (table 1). These symptoms are worth enquiring about since rhabdomyolysis in the context of a clear-cut ► Metabolic myopathies – Glycogenolytic disorders. heat-related condition usually does not require further –F atty acid metabolism disorders. investigation. – Mitochondrial disorders. – Structural myopathies (eg, dystrophinopathies). CONSEQUENCES OF EXERTIONAL RHABDOMYOLYSIS Exertional rhabdomyolysis causes traumatic and meta- activity is required, particularly for certain metabolic bolic damage to myocytes, resulting in local muscle myopathies where events can be triggered by non-ex- injury and systemic effects from release of intracel- ertional muscle contraction, including emotional lular contents. Acute kidney injury from myoglobin 1 situations. toxicity is a feared complication, but other serious http://pn.bmj.com/ consequences include compartment syndrome, hyper- EXERCISE-INDUCED RHABDOMYOLYSIS kalaemia and disseminated intravascular coagulation. Exertional rhabdomyolysis is the combination of Patients with preceding heat exposure may experience muscle symptoms (myalgia, weakness and swelling) altered mental state, probably hyperthermia induced, and a substantial rise in serum CK (>50 000 IU/L) in which may be ameliorated by adequate hydration.7 The the setting of exercise. Serum CK rises after exercise consequences of untreated exertional rhabdomyolysis on October 2, 2021 by guest. Protected copyright. Table 1 Exercise-associated heat illnesses Heat cramps Exercise-associated muscle cramps are a mild form of exertional heat illness familiar to those who watch sports (except perhaps for darts aficionados) characterised by severe muscle pain and spasms/prolonged muscle contraction without other features. Heat syncope Exercise-associated transient loss of consciousness usually occurs after exercise cessation. The likely cause is a sudden reduction in venous return secondary to reduced skeletal muscle tone, and diversion of blood flow to extremities to lose heat. Recovery is rapid and complete (as in vasovagal syncope) and core body temperature is not elevated. Heat exhaustion Characterised by difficulty continuing with exercise with raised core body temperature but no significant or prolonged alteration of mental state. Heat stroke Combination of elevated core temperatures (above 40°C) and altered mental state. Other end organs may also be damaged, including muscles (raised serum CK), kidneys (acute kidney injury) and liver (elevated liver enzymes). Heat injury A description used by military physicians (but not recognised in ICD-10) to describe heat exhaustion and end-organ damage without mental state changes. CK, creatine kinase; ICD-10, International Classification of Diseases, 10th Revision. 44 Fernandes PM, Davenport RJ. Pract Neurol 2019;19:43–48. doi:10.1136/practneurol-2018-002008 HOW TO DO IT survived this stage it descended to the legs, skipping Pract Neurol: first published as 10.1136/practneurol-2018-002008 on 10 October 2018. Downloaded from Box 2 Features suggesting need for further 18 all the intervening parts of the body, and caused dire investigation injury
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