DISSEMINATED MULTIFOCAL MUCORMYCOSIS TREATED WITH A COMBINATION ANTIFUNGAL REGIMEN

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Rhinocerebral mucormycosis is a fatal infection in poorly controlled diabetic patients with a history of diabetic ketoacidosis (DKA). DKA blunts neutrophil chemotaxis, phagocytosis and boosts serum iron, a mucor nutrient. It spreads to the brain via the hematogenous or contiguous spread [1]. We present a case of disseminated rhinocerebral mucormycosis in a diabetic patient on treatment with a combination antifungal regimen CASE PRESENTATION: A 22-year-old poorly controlled diabetic with a hemoglobin A1c of 14.1% was admitted to an outside hospital for a week of chest pain, dyspnea, fever, and dry cough with recently diagnosed coronavirus disease 2019. She was treated for DKA. Four days later, she developed a new-onset right-sided vision loss, ptosis, areflexic pupil, eye abduction loss, and bloody nasal mucus drainage. Computed tomography (CT) of the chest was normal. CT angiogram (CTA) of the head and neck showed occlusion of the right ophthalmic artery and the superior ophthalmic vein. Magnetic resonance imaging (MRI) showed subacute right frontal infarct and chronic sinusitis. An oral exam disclosed a large hard palate necrotic area, which on biopsy culture grew Rhizopus oryzae (Figure A-B). She was transferred to our facility for further surgical debridement. On arrival, she was placed on high-dose liposomal amphotericin (LAmB) and euglycemic control. A cerebral angiogram revealed right internal carotid artery occlusion. MRI showed right cavernous sinus thrombosis, right ophthalmic artery mycotic aneurysm, paranasal sinusitis with right sphenoid fungal sinusitis extending into gyri rectus, and watershed infarcts in the right middle and anterior cerebral artery territories (Figure C1). Neurosurgery deferred surgical debridement. Later caspofungin and deferasirox were added adjunctively for two weeks with surgical debridements and a week of hyperbaric oxygen, after which MRI findings improved (Figure C2). She is clinically improving on LAmB and caspofungin DISCUSSION: Combination regimens are ineffective in neutropenic or cancer patients [2,3]. LAmB and deferasirox with or without an echinocandin/posaconazole have been effective in diabetics with intracranial lesions [2]. Combination regimen efficacy has been observed in diabetic mice and anecdotal case reports [3,4]. This is due to prompt recovery of neutrophil function and loss of glucose-regulated protein78 mediated Rhizopus angioinvasion once acidosis and hyperglycemia are corrected [5] CONCLUSIONS: To improve diabetic patient outcomes, a timely diagnosis, prompt reversal of DKA and hyperglycemia, along with surgical debridement and antifungal therapy, are of immense importance. Combination antifungal therapy may benefit cases where complete surgical debridement is not achievable REFERENCE #1: Mallis A, Mastronikolis SN, Naxakis SS, Papadas AT. Rhinocerebral mucormycosis: an update. Eur Rev Med Pharmacol Sci. 2010;14(11):987-92 DISCLOSURES: No relevant relationships by Mohammed Alnijoumi, source=Web Response No relevant relationships by Phillip Beck, source=Web Response No relevant relationships by Paragkumar Patel, source=Web Response No relevant relationships by SACHIN PATIL, source=Web Response No relevant relationships by Deepthi Rao, source=Web Response No relevant relationships by Hariharan Regunath, source=Web Response No relevant relationships by Blaine Winterton, source=Web Response

WHEN IT'S NOT THE MEMBRANE LUNG'S FAULT

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is increasingly used in the management of respiratory failure failing to respond to conventional methods. This case highlights the importance of identifying and rectifying complications of ECMO. CASE PRESENTATION: We present a 56-year-old male who presented after being diagnosed with COVID-19. His past medical history included diabetes mellitus and hypertension. He was admitted to the intensive care unit for rapidly worsening hypoxic respiratory failure requiring mechanical ventilation. Despite trials of paralysis and prone positioning for severe acute respiratory distress syndrome (ARDS), the patient did not improve and was cannulated with a 21 French right internal jugular (IJ) and 25 French right femoral cannulas under fluoroscopic guidance for VV-ECMO.On initiation, flow was suboptimal despite revolutions per minute (RPM) as high as 5000 generating flows of 2.1 liters per minute (LPM). Post oxygenator pressures were 500-520 mmHg. Rectifying this problem was delayed by 12 hours. A new left IJ vein return cannula was placed and the prior return cannula removed which had a kink on its distal end that was not seen on imaging. Flows improved significantly after this change.The return cannula blood was noted to be dark red, which prompted evaluation of membrane lung function which was normal. A co-oximetry demonstrated significantly elevated methemoglobinemia of 15%. Medications were reviewed and none were noted to cause methemoglobinemia. Patient was treated with repeated doses of methylene blue.The patient developed multi-organ failure as well as refractory vasoplegic shock on multiple vasopressors. The family made the decision to transition patient's care to comfort care on day 5 of VV-ECMO. DISCUSSION: This case demonstrates the grave consequences of late identification and correction of flow limitation in VV-ECMO and how a kinked cannula led to severe hemolysis causing methemoglobinemia. In literature, cooxyhemoglobin correlated with increasing hemolysis, however there is indirect evidence that with increased hemolysis, increase oxygen radicals can lead to the formation of methemoglobin. Methemoglobinemia is a known cause of renal failure, as well as multi-organ failure. Monitoring levels of methemoglobin have both diagnostic and therapeutic advantages.This case also highlights a rather atypical cause of dark blood in return cannula, other than membrane lung dysfunction. Methemoglobin in classic teaching causes "chocolate-red" blood, with a low spO2 and a relatively high PaO2, as noted in our patient. CONCLUSIONS: It is important to be well versed with the possible complications of ECMO. Common differential diagnoses for flow limitation include hypovolemia, shock, increased abdominal/thoracic pressures, kinked cannula, thrombus formation or obstructed drainage from the return cannula. REFERENCE #1: Hemolysis in pediatric patients receiving centrifugal-pump extracorporeal membrane oxygenation: prevalence, risk factors, and outcomes. Lou S., MacLaren G., Best D., Delzoppo C., Butt W. Crit Care Med. 2014 May;42(5):1213-20. REFERENCE #2: Methemoglobinemia: A Diagnosis Not to Be Missed. Lata K., Janardhanan., R. AJM ONLINE CLINICAL COMMUNICATION TO THE EDITOR. 2015 Oct;128(10): E45-6. REFERENCE #3: The Complex Relationship of Extracorporeal Membrane Oxygenation and Acute Kidney Injury: Causation or Association? Kilburn D. J., Shekar K., Fraser J. F., Biomed Res Int. 2016 Feb. 2016;2016:1094296. DISCLOSURES: No relevant relationships by Anna Abbasi, source=Web Response No relevant relationships by Cliff Chen, source=Web Response No relevant relationships by Ethan Karle, source=Web Response No relevant relationships by Shyam Shankar, source=Web Response No relevant relationships by Blaine Winterton, source=Web Response