Some complimentary combination of, first, mitochondrial damage and, second, endothelial activation, causes a release of reactive oxygen species (ROS), which initiates and/or exacerbates a pathophysiological inflammatory response.
Third, reperfusion initiates an immune, inflammatory response resulting in the circulation of pro-inflammatory cytokines such as TNFα, IL-6 and IL-8 as well as complement activation (such as TCC and C3bc).
The severity of PCAS is highly dependent on many variables including: the underlying cause of the arrest, the length of the ischemic period, the quality of CPR received, and a patient's physiologic reserve.
The symptoms of PCAS are related to the effect of ischemia-reperfusion injury on individual systems, though there is significant co-morbidity between all organs' responses.
Increasingly severe injury can lead to long term consequences such as cognitive dysfunction, persistent vegetative state and finally brain death.
[8] This myocardial dysfunction may present as prolonged cardiogenic shock, highly variable blood pressures, reduced cardiac output and/or dysrhythmias.
[9] Unlike brain tissue, evidence suggests that the myocardial injury is generally transient and can mostly recover within 72 hours,[10] though full recovery may take months.
While ischemia is not the mechanism of injury, evidence suggests[clarification needed] that the lack of perfusion through the pulmonary vasculature during an arrest reduces the alveolar–arterial gradient which creates dead space.
It is unclear if the development of AKI worsens PCAS overall prognosis, but it does not seem to be a major contributor to death or poor neurological outcome at this time.
Accumulation of lactate and carbon dioxide during the ischemic period largely accounts for the metabolic acidosis seen in PCAS patients, though strong ion gaps and phosphate also plays a role.
[17] Finally, though electrolytes can present variably, PCAS patients most often demonstrate hypokalemia, hypocalcemia and hypomagnesaemia[8] Acute kidney injury is not the leading cause of death after cardiac arrest.
However, evidence suggests that the kidney damage after a cardiac arrest should be highly considered in the prognosis of the patients' health outcome.
The ischemia-reperfusion injury promotes damage-associated molecular patterns (DAMPs) which encourage pro-inflammatory cytokine circulation, which then induces a pro-coagulopathic state.
However late PCAS generally presents with hypofibrinolysis, due to increased PAI-1 levels, resulting in a risk of multiorgan dysfunction.
[24] While most commonly applied as a post-ROSC intervention, there are some studies and EMS systems that start the cooling process in the initial intra-arrest stage.
[27] TTM is an important therapy in PCAS because it directly targets the systemic nature of the pathophysiological inflammatory and metabolic processes.
PCAS outcomes are generally better under certain conditions including: fewer patient comorbidities, initial shockable rhythms, rapid CPR responses, and treatment at a high-volume cardiac arrest center.
[33] Common long term complications of cardiac arrest and subsequent PCAS include: anxiety, depression, PTSD, fatigue, post–intensive care syndrome, muscle weakness, persistent chest pain, myoclonus, seizures, movement disorders and risk of re-arrest.
As of 2022,[37] research on PCAS includes, non-exclusively, work on early resolution of ischemia through pre-hospital extracorporeal membrane oxygenation,[38] and wide distribution of defibrillators and CPR-trained bystanders, continued investigation of TTM,[39] use of immunosuppressive drugs such as steroids[40] and tocilizumab,[41] the use of cytoprotective perfusates,[42] and the use cerebral tissue oxygen extraction fraction.