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

Abstract

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.

Conflict of interest statement

Copyright form disclosure: Dr.Shah received funding from BMS (consulting), Silverman, Silverman, 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.

Figures

Figure 1

A. CONSORT flow diagram of retrospective chart review for patients with ARDS receiving NMB. B. Mean of all temperature measurements during NMB in controls and during hypothermia treatment period in cooled patients. Medians (indicated) were compared by Wilocoxon Rank-Sum test and p value is displayed. C. Temporal distribution of core temperature during NMB in controls and during the hypothermia treatment period in cooled patient. The difference in the means of all temperatures in the two groups was compared using a mixed model repeated measures (MMRM) analysis (39) and the p value is displayed. D. Box plots of 28-day VFDs for the cooled patients, all 58 controls, and the 16 matched controls. The 25th percentile values for VFDs was 0 for all three groups. Median values for VFDs for all 58 controls and the matched controls was 0. The 75th percentile values for VFD for the matched controls was 0. The p-values for each comparison are indicated.