A randomised preclinical trial of adrenaline use during cardiac arrest in mice

Background: Adrenaline is routinely administered during cardiac arrest resuscitation. Using a novel murine model of cardiac arrest, this study evaluates the effects of adrenaline use on survival and end-organ injury. Methods: A total of 58 mice, including cardiac arrest (CA) and sham (SHAM) groups received intravenous potassium chloride either as a bolus (CA) or slow infusion (SHAM), inducing ECG-confirmed asystole (in CA only) for 4-minutes prior to intravenous adrenaline (+ADR;250 ul, 32 ug/ml) or saline (-ADR;250 ul) and manual chest compressions (300 BPM) for 4-minutes. Mice with return of spontaneous circulation (ROSC) were assessed at 24- or 72-h timepoints. Results: Among animals that underwent CA, rates of ROSC (n = 21 (95 %) vs n = 14 (82 %), P = 0.18) and survival to the planned endpoint (n = 11 (50 %) vs n = 12 (71 %), P= 0.19) were similar when comparing those treated with (CA+ADR) and without (CA-ADR) adrenaline. However, in CA animals that initially achieved ROSC, subsequent mortality was approximately 3-fold greater with adrenaline treatment (48 % vs 14 %, P = 0.042). Among SHAM animals, adrenaline use had no impact on survival rates or other endpoints. Greater myocardial injury occurred in CA +ADR vs CA-ADR, with increased Hs-Troponin levels measured at 24- (26.0 +/- 0.9 vs 9.4 +/- 5.3 ng/mL, P = 0.015) and 72-h (20.9 +/- 8.3 vs 5.0 +/- 2.4 ng/mL, P = 0.012), associated with increased expression of pro-inflammatory and fibrotic genes within cardiac and renal tissue. Conclusion: Adrenaline did not improve ROSC or overall survival but following successful ROSC, its use resulted in 3-fold greater mortality rates. Adrenaline was also associated with increased myocardial injury, end-organ inflammation, and fibrosis. These findings underscore the need for further preclinical evaluation of alternate pharmacologic adjuncts for cardiopulmonary resuscitation that improve survival and limit end-organ injury.

Automated summary

This study evaluated the effects of adrenaline use during cardiac arrest resuscitation, and found that it did not improve survival rates. In fact, following successful return of spontaneous circulation, the use of adrenaline led to significantly higher mortality rates. Additionally, adrenaline was associated with increased myocardial injury, organ inflammation, and fibrosis. These findings highlight the need for further research on alternative pharmacologic adjuncts for cardiopulmonary resuscitation to improve survival and reduce organ injury.