Effects of different adrenaline (epinephrine) doses on cerebral perfusion, cerebral oxygenation and cerebral metabolism during cardiopulmonary resuscitation in pigs – preliminary data

Aim of the study:

Adrenaline is routinely used in the treatment of cardiac arrest (CA). It is associated with higher rates of return of spontaneous circulation and improved short-term survival [1], but may have detrimental effects on neurologically intact survival [2 – 4]. Impairment of cerebral microcirculatory blood flow might be a possible explanation. It could be speculated that lower adrenaline doses, while still promoting vasoconstriction in central vessels, are less interfering with cerebral microvascular perfusion and oxygen delivery. We therefore investigated the effects of two different adrenaline doses (15 vs. 30 µg/kg) during advanced life support on cerebral perfusion, oxygenation and metabolism in a porcine CPR model [5,6].

Methods:

Fourteen pigs were anesthetized, intubated and instrumented. After 5 min of CA, pigs were randomized to either 15 or 30 µg/kg adrenaline and mechanically resuscitated (LUCAS2™, Stryker, Kalamazoo, Michigan). Adrenaline was administered every 5 min. Mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP) and cerebral regional oxygen saturation (rSO2) were recorded at ten-second intervals. Laser-doppler flow perfusion units, brain tissue oxygen tension (PbtO2), arterial and cerebral venous oxygen saturation (S_cvO₂) as well as cerebral microdialysis parameters, e.g. lactate/pyruvate ratio (L/P ratio) were measured at baseline, after CA, every 5 min during CPR and at the end of the experiment.

Results:

Each 30 compared to 15 µg/kg adrenalin bolus resulted in higher MAP and CPP peaks (Fig. 1). Average MAP was higher only after the first bolus whereas average CPP was higher in the 30 µg/kg adrenaline group throughout the experiment (Fig. 1). However, after 18 min of CPR there was no difference in cerebral cortical perfusion (25.1 ± 4.5 vs. 47.1 ± 13.1; p = 1), cerebral SO₂ (26 ± 2 vs. 27 ± 1; p = 0.898), P_btO₂ (2.6 ± 1.8 vs. 4.6 ± 3.0; p = 0.79), S_cvO₂ (26.2 ± 5 vs. 25 ± 4.5; p = 0.662) and L/P ratio (419 ± 180 vs. 260 ± 114; p = 1) between study groups.

Conclusion:

Despite higher MAP and CPP after repeated boluses of 30 compared to 15 µg/kg adrenaline during advanced life support, cerebral perfusion, cerebral oxygenation and cerebral metabolism were comparable in this porcine CPR model. This indicates that higher blood pressures do not translate into better brain perfusion and oxygen delivery and raises the question whether adrenaline with its pronounced vasoconstrictive effects on cerebral microvessels is the most suitable drug for the treatment of CA.

Fig. 1

References:

[1] Paradis NA, Martin GB, Rivers EP, et al. (1990) Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation. JAMA 263:1106 – 1113.

[2] Hagihara A, Hasegawa M, Abe T, Nagata T, Wakata Y, Miyazaki S. (2012) Prehospital adrenaline use and survival among patients with out-of-hospital cardiac arrest. JAMA 307:1161 – 8.

[3] Dumas F, Bougouin W, Geri G, et al. (2014) Is adrenaline during cardiac arrest associated with worse outcomes in resuscitated patients? J Am Coll Cardiol 64:2360 – 7.

[4] Loomba RS, Nijhawan K, Aggarwal S, Arora RR. (2015) Increased return of spontaneous circulation at the expense of neurologic outcomes: Is prehospital adrenaline for out-of-hospital cardiac arrest really worth it? J Crit Care 30:1376 – 81.

[5] Putzer G, Braun P, Strapazzon G et al. Monitoring of brain oxygenation during hypothermic CPR – A prospective porcine study. Resuscitation. 2016 Jul;104:1 – 5

[6] Putzer G, Braun P, Martini J et al. Effects of head-up vs. supine CPR on cerebral oxygenation and cerebral metabolism – a prospective, randomized porcine study. Resuscitation. 2018 Jul;128:51 – 55