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The Cooling to Help Injured Lungs (CHILL) trial is an open label, two group, parallel design multicenter, randomized phase IIB clinical trial assessing the efficacy and safety of targeted temperature management with combined external cooling and neuromuscular blockade to block shivering in patients with early moderate-severe acute respiratory distress syndrome (ARDS). This report provides the background and rationale for the clinical trial and outlines the methods using the Consolidated Standards of Reporting Trials guidelines. Key design challenges include: [1] protocolizing important co-interventions; [2] incorporation of patients with COVID-19 as the cause of ARDS; [3] inability to blind the investigators; and [4] ability to obtain timely informed consent from patients or legally authorized representatives early in the disease process. Results of the Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) trial informed the decision to mandate sedation and neuromuscular blockade only in the group assigned to therapeutic hypothermia and proceed without this mandate in the control group assigned to a usual temperature management protocol. Previous trials conducted in National Heart, Lung, and Blood Institute ARDS Clinical Trials (ARDSNet) and Prevention and Early Treatment of Acute Lung Injury (PETAL) Networks informed ventilator management, ventilation liberation and fluid management protocols. Since ARDS due to COVID-19 is a common cause of ARDS during pandemic surges and shares many features with ARDS from other causes, patients with ARDS due to COVID-19 are included. Finally, a stepwise approach to obtaining informed consent prior to documenting critical hypoxemia was adopted to facilitate enrollment and reduce the number of candidates excluded because eligibility time window expiration.
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OBJECTIVE: We describe a multicenter descriptive case series of six patients admitted with synthetic cannabinoid (SC) intoxication displaying similar symptoms and sequelae, all resulting in multiple organ failure. METHODS: Patients were included in this report if they presented with known SC use and experienced multiple organ failure between March 1, 2016, and July 19, 2016, to the intensive care units of three hospitals in Maryland. Patients were followed to either discharge or death, and complications related to SC were documented. RESULTS: All six patients presented with altered mental status and severe rhabdomyolysis, with a peak creatine phosphokinase ranging from 4000 to >320,000 units/L. The majority of patients (five of six) presented with acute kidney injury, with most (four of six) requiring continuous renal replacement therapy. Most patients experienced fever (five of six) and myocardial injury, as evidenced by a troponin elevation (three of six). Seizures occurred in half of patients (three of six patients). Two patients required emergent fasciotomies of the bilateral lower extremities for acute compartment syndrome. Two patients developed fulminant hepatic failure that necessitated liver transplant evaluation, one requiring Molecular Adsorbent Recirculating System (MARS) therapy as a bridge to successful transplant, while the patient without it did not survive. Delirium, severe rhabdomyolysis, acute kidney injury, and fever are common in patients with synthetic cannabinoid intoxication. CONCLUSIONS: Given the growing abuse of these substances, clinicians should consider their use in the differential of such patient presentations. To our knowledge, only a few published case reports discuss multiple organ failure associated with SC toxicity, and only two have described an associated acute liver failure. Our report describes the first case of SC-associated acute liver failure requiring organ transplantation. Clinicians should be aware of life-threatening complications and consider SC ingestion in the differential diagnosis of patients presenting with multiple organ failure.