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

Abstract

Objectives Prior studies suggest hypothermia may be beneficial in ARDS, but cooling causes shivering and increases metabolism. The objective of this study was to assess the feasibility of performing a randomized clinical trial (RCT) of hypothermia in patients with ARDS receiving treatment with neuromuscular blockade (NMB) because they cannot shiver. Design Retrospective study and pilot prospective open-label feasibility study. Setting Medical Intensive Care Unit. Patients Retrospective review of 58 patients with ARDS based on Berlin criteria and PaO2:FiO2 (P:F)<150 who received NMB. Prospective hypothermia treatment in 8 ARDS patients with (P:F)<150 receiving NMB. Intervention Cooling to 34°–36°C for 48h. Measurements and Main Results Core temperature, hemodynamics, serum glucose and electrolytes, and P:F, were sequentially measured and medians (interquartile ranges) presented, and 28-day ventilator-free days (VFDs), and hospital mortaltiy were calculated in historical controls and 8 cooled patients. Average patient core temperature was 36.7(36–37.3)°C and fever occurred during NMB in 30/58 retrospective patients. In the prospectively cooled patients core temperature reached target range ≤4h of initiating cooling, remained <36°C for 92% of the 48h cooling period without adverse events, and was lower than the controls (34.35(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 VFDs (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 NMB alone does not cause hypothermia, but allowed ARDS patients to be effectively cooled. Results support conducting an RCT of hypothermia in ARDS and the feasibility of studying ARDS patients receiving NMB.

A Survey of Academic Intensivists' Use of Neuromuscular Blockade in Subjects With ARDS

“…Our Cooling to Help Injured Lungs (CHILL) pilot study supported the feasibility of this strategy. 18 However, successful completion of such a clinical trial depends on the continued practice of using NMB to manage patients with ARDS. Although NMB has been used as ancillary therapy to facilitate mechanical ventilation for the past 4 decades, 19 there is little data available about the current patterns of NMB administration in patients with ARDS; specifically, the frequency of NMB use in patients with ARDS, the duration of administration, and the clinical reasoning for its use.…”

A temperature-dependent conformational shift in p38α MAPK substrate–binding region associated with changes in substrate phosphorylation profile

“…Unregulated temperature deviations occur when normal thermoregulation fails or thermoregulatory effector mechanisms are overwhelmed by intentional or accidental environmental exposures. The biological effects of hypothermia have been harnessed to improve neurologic outcome after cardiac arrest (1,2) and more recently to reduce acute lung injury (3,4). Hyperthermia has proven to be effective as adjuvant treatment against some forms of cancer (5), but it may worsen organ injury, including acute lung injury (6,7).…”

Hypothermic total liquid ventilation after experimental aspiration-associated acute respiratory distress syndrome

“…This could open perspective for the treatment of pure ARDS, beyond the management of the post-cardiac arrest syndrome. For instance, a recent clinical study reported possible benefits with 48 h of cooling at 34–36 °C in 8 ARDS patients receiving neuromuscular blockade agents [ 27 ]. In neonates, a retrospective analysis also suggested consideration of therapeutic hypothermic as an adjunctive therapy during meconial aspiration syndrome [ 28 ].…”