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

Purpose: 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 degrees C in patients with shockable out-of-hospital cardiac arrest (OHCA). Methods: ISOCRATE was a single-center randomized controlled trial comparing rewarming at 0.50 degrees C/h versus 0.25 degrees C/h in patients coma after shockable OHCA in 2016-2020. The primary outcome was serum IL6 level 24-48 h after reaching 33 degrees C. Secondary outcomes included the day-90 Cerebral Performance Category (CPC) and the 48-h serum neurofilament light-chain (NF-L) level. Results: 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 degrees C/h (52.0%; 95% CI 31.3-72.2%) and 13/25 patients at 0.50 degrees 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 degrees C/h and 0.50 degrees C/h groups (76.0 pg mL, [25.5-3074.0] vs. 192 pg mL, [33.6-4199.0]; P = 0.43; respectively). Conclusion: In our RCT, rewarming from 33 degrees C at 0.25 degrees C/h, compared to 0.50 degrees 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. Take-Home Message: Rewarming at a rate of 0.25 degrees C/h, compared to 0.50 degrees C, did not result in lower serum IL6 levels after achievement of hypothermia at 33 degrees 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 degrees C versus 0.50 degrees C did not decrease serum IL6 levels after hypothermia at 33 degrees C in patients comatose after shockable cardiac arrest.

Automated summary

Rewarming at 0.25 degrees C/h, compared to 0.50 degrees C/h, did not decrease serum IL6 levels after shockable cardiac arrest. Further studies are needed to determine the optimal TTM strategy.