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Pilot Feasibility Study of Therapeutic Hypothermia for Moderate to Severe Acute Respiratory Distress Syndrome*

Slack, Donald F. MD1; Corwin, Douglas S. MD1; Shah, Nirav G. MD1; Shanholtz, Carl B. MD1; Verceles, Avelino C. MD, MS1; Netzer, Giora MD, MS1; Jones, Kevin M. MD, MPH2; Brown, Clayton H. PhD3; Terrin, Michael L. MD, MPH3; Hasday, Jeffrey D. MD1,4

doi: 10.1097/CCM.0000000000002338
Clinical Investigations

Objectives: Prior studies suggest hypothermia may be beneficial in acute respiratory distress syndrome, but cooling causes shivering and increases metabolism. The objective of this study was to assess the feasibility of performing a randomized clinical trial of hypothermia in patients with acute respiratory distress syndrome receiving treatment with neuromuscular blockade because they cannot shiver.

Design: Retrospective study and pilot, prospective, open-label, feasibility study.

Setting: Medical ICU.

Patients: Retrospective review of 58 patients with acute respiratory distress syndrome based on Berlin criteria and Pao2/Fio2 less than 150 who received neuromuscular blockade. Prospective hypothermia treatment in eight acute respiratory distress syndrome patients with Pao2/Fio2 less than 150 receiving neuromuscular blockade.

Intervention: Cooling to 34–36°C for 48 hours.

Measurements and Main Results: Core temperature, hemodynamics, serum glucose and electrolytes, and P/F were sequentially measured, and medians (interquartile ranges) presented, 28-day ventilator-free days, and hospital mortality were calculated in historical controls and eight cooled patients. Average patient core temperature was 36.7°C (36–37.3°C), and fever occurred during neuromuscular blockade in 30 of 58 retrospective patients. In the prospectively cooled patients, core temperature reached target range less than or equal to 4 hours of initiating cooling, remained less than 36°C for 92% of the 48 hours cooling period without adverse events, and was lower than the controls (34.35°C [34–34.8°C]; p < 0.0001). Compared with historical controls, the cooled patients tended to have lower hospital mortality (75% vs 53.4%; p = 0.26), more ventilator-free days (9 [0–21.5] vs 0 [0–12]; p = 0.16), and higher day 3 P/F (255 [160–270] vs 171 [120–214]; p = 0.024).

Conclusions: Neuromuscular blockade alone does not cause hypothermia but allowed acute respiratory distress syndrome patients to be effectively cooled. Results support conducting a randomized clinical trial of hypothermia in acute respiratory distress syndrome and the feasibility of studying acute respiratory distress syndrome patients receiving neuromuscular blockade.

1Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD.

2Program in Trauma, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD.

3Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD.

4Medicine and Research Services, Baltimore Veterans Affairs Medical Care System, Baltimore, MD.

*See also p. 1244.

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Supported, in part, by National Institutes of Health grant R01HL69057 and Veterans Administration grant IBX002143A (to Dr. Hasday).

Dr. Shah received funding from Bristol Myers Squibb (consulting), Silverman, LLC (expert witness), and from Pfizer (speakers bureau). Dr. Hasday received support for article research from the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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