Assessment of the Efficacy of Personalized Physiology-guided Resuscitation in Patients With Cardiac Arrest: The PERSEUS Pilot Randomized Trial

BACKGROUND

Since 2000, resuscitation guidelines remain uniform across all cardiac arrest patients, focusing on the delivery of chest compressions to a standardized rate and depth and algorithmic vasopressor dosing. Although the concept of goal-directed hemodynamic optimization as a treatment strategy to improve clinical outcome in critically ill patients has been tested since the 1980s, no human study has established that prospectively targeting hemodynamics during CPR improves outcomes until now. Nevertheless, individualizing resuscitation to the appropriate hemodynamic and ventilatory goals rather than a standard Bone-size-fits-all treatment seems a promising new therapeutic strategy that can be applied during resuscitation attempts in highly monitored patients.

The PERSEUS protocol is a new approach to the resuscitation of highly monitored patients with cardiac arrest. It has been developed based on our experience and the observation that the most important determinant of survival is the optimization of all the available physiological parameters and the full exploitation of both the "cardiac pump" and "thoracic pump'.

Physiological and pathophysiological aspects of cardiac arrest Cardiac arrest interval Immediately after the abrupt loss of effective blood flow, the hypotension-induced baroreflex withdrawal with the net increase in the vascular resistance maintains an impaired antegrade and pulmonary blood flow. The systemic and pulmonary blood flow continue for at least 30-60 s, until the pressure gradient between the aorta and the right side of the heart, as well as between the pulmonary artery and the left atrium, has been completely dissipated, resulting in a rapid increase in the volume of the right ventricle and the extrapericardial component of the pulmonary veins. When arterial and systemic venous pressures reach equilibrium, the mean systemic filling pressure (Pmsf) is approximately 6-12 mmHg. The coronary blood flow declines to zero, but CPP remains positive because of the retrograde coronary flow. However, this diminishes the removal of norepinephrine from the interstitial spaces, which together with the formation of cardiac edema prolongs vasoconstriction and enhances myocardial hypoperfusion and hypoxia.

At the same time, cerebral perfusion decreases while the damage of fatty acids of the neuronal cell membrane by reactive oxygen species leads to a progressive increase in membrane permeability and severe derangements of intracellular electrolytes, resulting in cell swelling and brain edema formation. This, together with venous congestion, increases intracranial pressure (ICP) and damages the neuropil and synaptic structures and/or contacts.