Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome

Fowler III, Alpha A; Kim, Christin; Lepler, Lawrence; Malhotra, Rajiv; Debesa, Orlando; Natarajan, Ramesh; Fisher, Bernard J; Syed, Aamer; DeWilde, Christine; Priday, Anna; Kasirajan, Vigneshwar

A chest X-ray revealed diffuse bilateral opacities (Figure 1) . Arterial blood gas testing revealed severe hypoxemia while receiving 100% oxygen by nonrebreather mask. Antibiotics were initiated and she was admitted to intensive care unit (ICU) with a diagnosis of community acquired pneumonia. She denied GI symptoms, rash or arthralgia. She denied any history of thromboembolic disease, chest or leg pain or swelling. Her only medication was oral contraceptive for migraines associated with her menstrual cycle. Non-invasive positive pressure ventilation failed to support hypoxemic respiratory failure and intubation was required on hospital day 3. An echocardiogram revealed normal cardiac function. Respiratory cultures were negative, but a molecular detection viral respiratory panel was positive for enterovirus/rhinovirus (FilmArray, BioFire Diagnostics, LLC, Salt Lake City, Utah). Despite high PEEP and low tidal volume ventilation, hypoxemia (PaO2/FiO2 = 75) and hypercapnia remained severe. Chest imaging on hospital day 3 revealed dense bilateral opacities with central air bronchograms (Figure 2 ). Due to failure of conventional ventilatory strategies, veno-venous extracorporeal membrane oxygenation (ECMO) was initiated on hospital day 3. Low tidal volume assist-control, pressure-control ventilatory strategy was continued. Vancomycin, piperacillin-tazobactam and levofloxacin started at ICU admission were continued. High-dose intravenous vitamin C (200 mg/kg per 24 h) was initiated on ECMO day 1 with the total daily vitamin C dosage divided equally into four doses and infused every 6 h. AP chest X-ray imaging on ECMO day 2 following institution of vitamin C infusion revealed significant improvement in bilateral lung opacities (Figure 3) . Given the patient's hemodynamic instability and vasopressor requirements, the critical care physician staff and nursing staff were very careful to keep the patient's intake and output fluid balance even, being careful not to volume load a patient who was suffering from permeability pulmonary edema. Bronchoscopy on ECMO day 3 was negative for bacterial or fungal respiratory pathogens. Histoplasma, Blastomyces, Aspergillus, and Legionella antigen studies were negative. Furosemide was used to achieve a daily negative fluid balance. Daily chest imaging with AP chest X-rays documented continued resolution of bilateral opacities. Importantly, lung gas exchange significantly improved following institution of vitamin C infusions. Chest imaging on ECMO day 6 revealed significant further reduction in lung opacities. ECMO decannulation and extubation from Fowler â…¢ AA et al . Intravenous vitamin C to treat ARDS ventilation occurred on ECMO day 7 (Figure 4 ). Vitamin C dosing was continued while the patient remained on ECMO. Vitamin C dosing was reduced by half (100 mg/kg per 24 h) for one day following decannulation from ECMO then reduced by half again (50 mg/kg per 24 h) for an additional day. Post-extubation the patient required 4 L/min nasal oxygen for 48 h and then was discharged home on room air. She was discharged home on hospital day 12. Although we did not quantify the plasma ascorbic acid levels in the patient we report here, we have previously reported that critically ill patients with severe sepsis treated with the identical vitamin C infusion protocol achieved plasma ascorbic acid levels of 3.2 mmol, values which are 60 fold higher than normal plasma ascorbic acid levels [18] .