Neurons are exceptionally vulnerable to hypoxia and anoxia (Casas et al). In cardiac arrest without chest compressions (i.e. if cerebral perfusion ceases), irreversible neuronal cell death starts within 5–6 minutes. Biological death usually occurs within minutes thereafter; survival is highly unlikely after 8–10 minutes of no-flow (i.e. cardiac arrest without any circulation). These estimates should be viewed as approximations due to the following:
- Registry data indicate that survival is possible with longer periods of no-flow (Rawshani et al, Lippert et al, Gräsner et al). This could be due to uncertainty in the recording of no-flow and low-flow times in registries. The uncertainty is often obvious when interrogating witnesses, bystanders and health care professionals.
- The person may have some circulation despite circulatory collapse (e.g., with sustained ventricular tachycardia).
- Experimental and clinical understanding of hypoxic neuronal cell death stems largely from studies in stroke, which differs pathophysiologically from cardiac arrest. In stroke, neuronal cell death begins in the central ischemic zone, where the ischemia is most pronounced and extends towards the penumbra zone (the outermost and less ischemic area), which may receive oxygen from collateral vessels. In cardiac arrest, there is no cerebral perfusion, with an equal degree of hypoxia in all neurons.
There is one fundamental difference between neurons and myocardium in the setting of hypoxia. Myocardium ceases contracting immediately when becoming hypoxic, a phenomenon referred to as myocardial stunning. This is a protective mechanism since the cessation of contractions leads to a marked reduction in cell metabolism and thus prolongs survival. Myocardial stunning starts to normalize within minutes after the hypoxia is relieved. However, full recovery of contractility may take hours to days. It is generally stated that myocardium resists 20 minutes of severe hypoxia before cell death begins. It appears that neurons are unable to transition into a similar state with downregulated metabolism, which is presumed to explain why neuronal cell death begins within 5–6 minutes (Lipton et al).
Survival in cardiac arrest is highly dependent on the initial rhythm (first recorded rhythm). The initial rhythm is a marker of several crucial events and factors:
- Cause of cardiac arrest:
- Shockable rhythms (ventricular fibrillation, pulseless ventricular tachycardia) are mostly due to acute myocardial ischemia or myocardial infarction, and in these cases, the likelihood of ROSC is higher as compared to other etiologies and presentations.
- Asystole and pulseless electrical activity (PEA) often have other etiologists, but are also seen in ischemia or infarction when no-flow or low-flow time is prolonged. Survival is several times lower, regardless of etiology, if the initial rhythm is asystole or PEA. Most current protocols for ECMO exclude patients presenting with asystole or PEA.
- Duration of cardiac arrest: In cases where cardiac arrest is caused by myocardial ischemia, myocardial infarction, or primary arrhythmias, shockable rhythm indicates that the duration of cardiac arrest is relatively short (or there is high-quality CPR). The longer the duration of cardiac arrest, the greater the likelihood of a shockable rhythm degenerating into asystole or PEA.
Neurological function after cardiac arrest
Neurological function after ROSC can be assessed using several different scoring systems. To date, the most used systems are the cerebral performance category (CPC) Score and modified Ranking Score (mRS).
Cerebral Performance Category score (CPC Score)
Cerebral function among survivors can be assessed using the qualitative CPC (Cerebral Performance Category) score. The scale is depicted in Table 1.
CPC 1 | No neurological disability. Good cerebral function without any significant issues managing daily living, work, etc. |
CPC 2 | Moderate neurological disability. Sufficient cerebral function to manage daily living. Working may require work place adaptations. |
CPC 3 | Severe neurological disability. Activity of daily living requires support from others. Disabilities range from difficulties walking to being paralyzed and cognitively severely impaired. |
CPC 4 | Coma or vegetative state Vegetative patients may appear awake but do not respond to cerebral stimuli. Spontaneous eye opening and circadian rhythm may be present, but there is no other interactions. |
CPC 5 | Brain death |
Modified Ranking Score
The modified Ranking Score (mRS) was introduced in 1957 by John Ranking and the modification was made in 1988 to study stroke/TIA patients (van Swieten et al). The interrater variability is generally good for the modified Ranking Score, and it is therefore often used in cardiac arrest trials.
The modified Ranking Score is a 6 point disability scale, ranging from 0 to 5 points (Table 2). A patient can only obtain one score during an assessment.
Question | Score if answer is Yes |
---|---|
No residual symptoms. | 0 |
No significant disability. Able to carry out all usual activities, despite some symptoms. | 1 |
Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. | 2 |
Moderate disability. Requires some help, but able to walk unassisted. | 3 |
Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. | 4 |
Severe disability. Requires constant nursing care and attention, bedridden, incontinent. | 5 |
Dead | 6 |
Simple predictors of 30-day survival
Survival after cardiac arrest is commonly assessed at hospital admission, hospital discharge and at 30 days. The absolute majority of deaths occur within one or a few days, after which survival is high unless there is severe comorbidity. Survival at 30 days correlates strongly with long-term survival. As mentioned above, the initial rhythm is a strong predictor of survival:
- Survival to 30 days is 34% if the initial rhythm is ventricular fibrillation (VF) or pulseless ventricular tachycardia.
- Survival to 30 days is 1.5% in asystole.
- Survival to 30 days is 5.7% in PEA.
- Overall survival is 11%.
Survival also depends on age, location of cardiac arrest (survival is roughly 2-fold higher when cardiac arrest occurs in public places, where there are more witnesses and bystanders), when there is a witness (witnessed cardiac arrest has 2- to 3-fold increased survival), no-flow time, CPR time (low-flow time), ambulance (EMS) response time, and cause of cardiac arrest.
Among those who survive, 90% have good neurological function (CPC score 1 or 2). The remaining 10% have moderate to severe neurological injuries. The small proportion with moderate to severe injuries is due to the high mortality after ROSC when CPC score is 3 or higher; only a small percentage of those cases survive. This is explained by the fact that ROSC can often be achieved even after fatal brain injuries have manifested because the myocardium endures longer periods of hypoxia.
Approximately 50% of patients achieving ROSC and transferred to the ICU are discharged alive from the hospital (Carr et al, Elliot et al, McCarthy et al). Of those who regain consciousness, 70% do the first day and 90% within 2 days. Spontaneous breathing, motor activity, pupil reaction, and spontaneous eye movements are good predictors of regaining consciousness.
References
Casas et al. NOx4-dependent neuronal autotoxicity and BBB breakdown explain the superior sensitivity of the brain to ischemic damage. PNAS. 2017.
Carr BG, Kahn JM, Merchant RM, et al. Inter-hospital variability in post-cardiac arrest mortality. Resuscitation 2009; 80:30 —4. 27.
Elliott VJ, Rodgers DL, Brett SJ. Systematic review of quality of life and other patient-centred outcomes after cardiac arrest survival. Resuscitation 2011; 82:247—56. 29.
McCarthy JJ, Carr Basson C, et al. Out-of-hospital cardiac arrest resuscitation systems of care: a scientific statement from the American Heart Association. Circulation 2018; 137:e645—60.
Lipton P. Ischemic Cell Death in Brain Neurons. Physiological Reviews 1999; 79: 1431–568.