Impact of rewarming rate on interleukin-6 levels in patients with shockable cardiac arrest receiving targeted temperature management at 33 °C: the ISOCRATE pilot randomized controlled trial

• Published in: Critical care (London, England) Vol. 25; no. 1; p. 434
• Main Authors: Lascarrou, Jean-Baptiste, Guichard, Elie, Reignier, Jean, Le Gouge, Amélie, Pouplet, Caroline, Martin, Stéphanie, Lacherade, Jean-Claude, Colin, Gwenhael
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 17.12.2021; BioMed Central; BMC
• Subjects: Anesthesia; Body temperature; Cardiac arrest; Cardiopulmonary Resuscitation; Care and treatment; Coma; Complications and side effects; Critical care; Cytokines; Decision making; Drug withdrawal; Granulocytes; Health aspects; Heart attacks; Humans; Hypothermia; Hypothermia, Induced; Interleukin-6; Methods; Mortality; Narcotics; Out-of-Hospital Cardiac Arrest - therapy; Patient outcomes; Patients; Pilot Projects; Psychologists; Rewarming; Targeted temperature management; Therapeutic hypothermia; France; Therapeutic hypothermia; Cardiac arrest; Targeted temperature management
• ISSN: 1364-8535; 1466-609X; 1364-8535; 1366-609X
• DOI: 10.1186/s13054-021-03842-9

While targeted temperature management (TTM) has been recommended in patients with shockable cardiac arrest (CA) and suggested in patients with non-shockable rhythms, few data exist regarding the impact of the rewarming rate on systemic inflammation. We compared serum levels of the proinflammatory cytokine interleukin-6 (IL6) measured with two rewarming rates after TTM at 33 °C in patients with shockable out-of-hospital cardiac arrest (OHCA). ISOCRATE was a single-center randomized controlled trial comparing rewarming at 0.50 °C/h versus 0.25 °C/h in patients coma after shockable OHCA in 2016-2020. The primary outcome was serum IL6 level 24-48 h after reaching 33 °C. Secondary outcomes included the day-90 Cerebral Performance Category (CPC) and the 48-h serum neurofilament light-chain (NF-L) level. We randomized 50 patients. The median IL6 area-under-the-curve was similar between the two groups (12,389 [7256-37,200] vs. 8859 [6825-18,088] pg/mL h; P = 0.55). No significant difference was noted in proportions of patients with favorable day-90 CPC scores (13/25 patients at 0.25 °C/h (52.0%; 95% CI 31.3-72.2%) and 13/25 patients at 0.50 °C/h (52.0%; 95% CI 31.3-72.2%; P = 0.99)). Median NF-L levels were not significantly different between the 0.25 °C/h and 0.50 °C/h groups (76.0 pg mL, [25.5-3074.0] vs. 192 pg mL, [33.6-4199.0]; P = 0.43; respectively). In our RCT, rewarming from 33 °C at 0.25 °C/h, compared to 0.50 °C/h, did not decrease the serum IL6 level after shockable CA. Further RCTs are needed to better define the optimal TTM strategy for patients with CA. Trial registration ClinicalTrials.gov, NCT02555254 . Registered September 14, 2015. Rewarming at a rate of 0.25 °C/h, compared to 0.50 °C, did not result in lower serum IL6 levels after achievement of hypothermia at 33 °C in patients who remained comatose after shockable cardiac arrest. No associations were found between the slower rewarming rate and day-90 functional outcomes or mortality. 140-character Tweet: Rewarming at 0.25 °C versus 0.50 °C did not decrease serum IL6 levels after hypothermia at 33 °C in patients comatose after shockable cardiac arrest.