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Coexistant hyperthermic processes and mechanical cardiovascular compromise can confound diagnosis.

23 M previously well, no toxic habits with remote appendectomy, presented 4/4/20 1 week after acknowledged sick contact with dyspnea and sharp back pain when supine and reported fever that resolved 2 days prior. On exam BP 133/103, HR 128 sinus, RR 32/min, Temp 97.1oF and no rub, diastolic murmur or pulse asymmetry were noted. Hb 20 g/dL, WBC 17k/L (2.5% lymphocytes), Cr 1.0 mg/dL and lactate 4.1 mmol/L, CO2 16mmol/L, CK 38,391 U/L, CKMB 75.8 U/L, troponin 0.353 ng/mL, BNP 13,900 pg/mL , LD 2238 U/L, AST 599 U/L, SaO2 > 95%, TSH normal. EKG sinus tachycardia low voltage, no alternans but diffuse concave up ST elevation and PR depression (Fig 1a). POCUS documented LVEF > 50%, moderate pericardial effusion with RV collapse reverified with synchronous EKG recording as early diastolic in timing (Fig1b). CT chest with contrast excluded aortic dissection and documented bilateral lower lobe ground glass consolidation. Hydroxychloroquine (HC) started 400 mg BID for presumed COVID pneumonia. Pericardial drainage was achieved surgically (400cc straw colored fluid, negative microbiology and cytology). Estimated blood loss 10cc. Operative vecuronium muscle relaxation and sevoflurane inhalational anesthesia was administered. Intraoperatively end tidal CO2 (ETCO2) rose from 36 to 50 mmHg but fell (46 mmHg) with increase Tidal volume (TV) from 500 to 700cc and respiratory rate (RR) from 12 to 28/min. Core temperature peaked at 100.5oF. Postop BP 169/85, HR 125/min (Fig1c). ABG pH 7.23, PCO2 38 mmHg , PO2 67 mmHg, HCO3 15.7 mmol/L, lactate 8.0 mmol/L, Hb 18.7 g/ dL, K 5.2 mmol/L, Cr 2.7 mg/dL. Within an hour of extubation, the patient was re-intubated for respiratory distress with succinylcholine neuromuscular blockade on this occasion. Normal post re-intubation CXR. Thereafter, despite 5.5l crystalloid resuscitation and norepinephrine SBP did not rise above 60 mmHg. POCUS verified no pericardial fluid re-accumulation. Temperature 109oF prompted cooling measures and reduction to 107oF. EKG (Fig 1d) sinus tachycardia 180 BPM with new marked QRS widening (>200ms) suggestive of hyperkalemia degenerated to VF unresponsive to defibrillation. POCUS confirmed absent cardiac activity after 45 min chest compression, resuscitative measures terminated. Viral testing negative for influenza, RSV, HIV, and COVID.

Bilateral ground glass consolidation on CT (97% sensitivity for COVID detection(1)) together with lymphopenic leukocytosis, elevated ferritin, AST, LD, hypoxia and prior admitted sick exposure during COVID-19 pandemic make COVID-19 the most likely the cause of pneumonia, MH and pericarditis despite PCR negativity (65% nasopharyngeal sensitivity(2)). Persistent deterioration following pericardial drainage would only be expected with aortic dissection(3), tension pneumothorax or operative vascular misadventure (all excluded). Massive PE is unlikely with, normal coagulation parameters, young age, male gender, negative CT and brief immobility. HC induced G6PD deficiency hemolysis unlikely without significant Hb decline(4).

The low-grade intraoperative fever was consistent with COVID pneumonia/pericarditis. Rising lactate was ascribed to COVID-induced vasoplegia. CK rise credibly resulted from cardiomyocyte release of pericarditis however, fractionation later suggested a largely (99%) skeletal origin. Intraoperative hypercarbia was noted but, proved ventilation responsive. Hyperkalemic QRS widening coincided with only modest serum K 5.2 mmol/L. MH is nevertheless supported by intense skeletal myolysis at admission, persistent hypotension after surgical tamponade relief and worsening metabolic hyperactivity (rising lactate, hyperkalemic EKG changes, worsening tachycardia, metabolic acidosis, refractory hypotension) with sevoflurane and marked hyperthermia after succinylcholine.

MH is an intense hypermetabolic state with skeletal muscle rigidity, ventilation refractory hypercarbia, acidemia (hypotension), hyperkalemia and hyperthermia triggered by intense exercise, fever, halogenated anesthetics or succinylcholine. Prior uneventful anesthesia does not exclude MH. MH is the result of an autosomal dominant ryanodine receptor mutation resulting in excess intracellular calcium release. Hyperthermia is a late finding in MH. Upon MH recognition the offending halogenated agent should be replaced with high fresh gas flow and urgent dantrolene administration (ryanodine receptor blocking reversing agent). Bicarbonate and other hyperkalemia interventions may be required. Subsequent genetic counselling and testing is warranted for family members(5 ).

Febrile illness with massive skeletal myolysis in the absence of toxic habits should prompt consideration of MH. Furthermore, persistent hypotension (hyperkalemic acidemia) and hyperthermia after endotracheal intubation or successful surgical intervention, should prompt consideration of MH, regardless of concurrent infection.

(1) Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases Tao Ai*, Zhenlu Yang*, Hongyan Hou, Chenao Zhan, Chong Chen, Wenzhi Lv, Qian Tao, Ziyong Sun, Liming Xia Published Online:Feb 26
(2) Detection of SARS-CoV-2 in Different Types of Clinical Specimens Wenling Wang, PhD1; Yanli Xu, MD2; Ruqin Gao, MD3; Roujian Lu, MPH1; Kai Han, BS2; Guizhen Wu, MD1; Wenjie Tan, MD, PhD1 JAMA. Published online March 11, 2020. doi:10.1001/jama.2020.3786

(3) Cardiac tamponade complicating proximal aortic dissection. Is pericardiocentesis harmful?
Isselbacher EM, Cigarroa JE, Eagle KA. Circulation. 1994 Nov; 90(5):2375-8.

(4) Mohammad S, Clowse MEB, Eudy AM, and Criscione-Schreiber LG. Hydroxychloroquine is not associated with hemolytic anemia in glucose-6-phosphate dehydrogenase (G6PD) deficient patients [published online May 26, 2017]. Arthritis Care Res. doi:10.1002/acr.23296.

(5) Rosenberg H, Pollock N, Schiemann A, Bulger T, Stowell K. Malignant hyperthermia: a review. Orphanet J Rare Dis. 2015;10:93. Published 2015 Aug 4 doi:10.1186/s13023-015-0310-1