Neuroprotection after Cardiac Arrest: Are There Any Therapeutic Targets?

Critical Care Update

August, 2023

Neuroprotection after Cardiac Arrest: Are There Any Therapeutic Targets?
Ricardo Diaz Milian MD FASE, Steven Minear MD MBA FASA
Mayo Clinic Florida, Department of Critical Care Medicine, Department of Anesthesiology and Perioperative Medicine.
Cleveland Clinic Florida, Department of Critical Care Medicine, Anesthesia Institute

Protecting a patient’s neurologic function after cardiac arrest is a critical goal for anesthesiologists. Anesthesiology teams work to stabilize these patients, administer critical care, and work with these high-risk patients later in the operating rooms. Ongoing efforts to identify physiologic parameters that are neuroprotective are of interest to anesthesiologists, who leverage these targets to benefit patients at risk of impaired brain perfusion. The current data are conflicting and murky: for example, the results of studies in the context of out-of-hospital cardiac arrest cannot be translated directly to anesthesia clinical contexts. However, evolving research refines clinical targets, and it inspires further investigation into best practices.
The TAME study1, recently published in the New England Journal of Medicine, looked at ventilation goals in out-of-hospital adults who presented with coma in intensive care units. Most enrolled patients had witnessed cardiac arrest with shockable rhythm and bystander resuscitation. Following two observational studies that signaled a benefit in neurological outcomes at 12 months, the researchers designed a well-powered (n= 1700) prospective, open-label, randomized trial in intensive care units in different countries. The trial intervention consisted of assigning patients to a mild hypercapnia group (arterial partial pressure of CO2 of 50-55 mm Hg), or normocapnia (arterial partial pressure of CO2 of 35-45 mmHg). The primary outcome was neurological outcomes as measured by the Glasgow Outcome Scale- Extended (GOS-E) at six months. Secondary outcomes included death, poor functional status, and quality of life. The investigators did not find any significant differences in the primary outcome (favorable outcome): 43.5% in the intervention group versus 44% in the control group (RR 0.98; 95% confidence interval, 0.87 to 1.11; p=0.76), or any of the secondary outcomes.
The results of this study echo other studies in which normal physiological parameters continue to show no difference in outcomes relative to investigational “therapeutic” parameters in the care of patients after cardiac arrest. Perhaps the most important recent example of this is the rebuttal of the utilization of therapeutic hypothermia after cardiac arrest.2 Prior to that trial, targeted hypothermia was utilized with the aim of improving neurological outcomes, based on societal guidelines and the lower quality of evidence available. Other physiological targets that have been explored and that have not yield beneficial outcomes include restrictive versus liberal oxygenation targets3, and high versus normal mean arterial pressure goals.4 Perhaps the initial neurological insult for these high-risk patients is not affected by special therapeutic targets during post-arrest care. Alternatively, research may have not elucidated that special mix of targets for these patient cohorts. To date, prevention of neurological injury remains the mainstay strategy to improve neurological outcomes. In the context of out-of-hospital cardiac arrests, this includes fast and appropriate resuscitation efforts including high-quality CPR, availability of defibrillator, advanced cardiac life support availability and training. In the context of perioperative and intraoperative care, this entails optimizing brain perfusion across a broad range of scenarios.

1. Eastwood G, Nichol AD, Hodgson C, et al. Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest. N Engl J Med 2023;389(1):45-57. DOI: 10.1056/NEJMoa2214552.
2. Dankiewicz J, Cronberg T, Lilja G, et al. Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest. N Engl J Med 2021;384(24):2283-2294. DOI: 10.1056/NEJMoa2100591.
3. Schmidt H, Kjaergaard J, Hassager C, et al. Oxygen Targets in Comatose Survivors of Cardiac Arrest. N Engl J Med 2022;387(16):1467-1476. DOI: 10.1056/NEJMoa2208686.
4. Kjaergaard J, Moller JE, Hassager C. Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest. Reply. N Engl J Med 2023;388(3):285-286. DOI: 10.1056/NEJMc2215179.