If ROSC occurs, blood flow returns to the ischemic neurons, and the brain is exposed to a natural inflammatory response and free oxygen radicals that were released systemically during the arrest.4 Both swelling and free oxygen radicals damage lipids, proteins and the DNA of neuron cells. All of this causes irreversible cell damage. Free oxygen radicals irreparably damage neuron membranes.2 This triggers a cascade of events that promotes injury to nearby cells, worsening the injury size. Additionally, ischemia causes a weakening of the cellular blood-brain barrier, which allows for additional fluid shifts from the bloodstream into intracellular and interstitial spaces. This worsens cerebral edema.4
While this occurs, cardiac tissues are also stressed and consuming oxygen at an accelerated rate as they, too, try to compensate for an extended period of ischemia. During this time ischemic cardiac cells are prone to triggering atrial and ventricular dysrhythmias. Transient post-cardiac arrest tachycardias are common and in general should not be treated, as they are typically benign. Sustained life-threatening tachydysrhythmias such as ventricular tachycardia or supraventricular tachycardia (SVT) require treatment.
A systemic inflammatory response is the body’s natural response to a major body insult and can be described as generalized inflammation and swelling. It is diagnosed by the presence of any two of the following:
- Temperature less than 96.8°F or greater than 100.4°F;
- Heart rate greater than 90 bpm;
- Respiratory rate greater than 20 or PaCO2 less than 32 mmHg;
- White blood cell count less than 4,500 l/mm3 or greater than 10,000 l/mm3.
This inflammatory response leads to a shifting of fluids into interstitial spaces and vasodilation, both of which may exacerbate hypotension. Additionally these fluid shifts increase the amount of fluid between cells and capillaries, which makes it more difficult for cells to receive oxygen and offload waste products, including carbon dioxide and lactic acid (Figure 1). As a result, already irritable organs are stressed even further and may show signs of dysfunction. Organs that are particularly sensitive to dysfunction include the liver, kidneys and brain.7
Finally, think of the cardiac arrest as a sign of an underlying issue that caused it. This could be a myocardial infarction, primary respiratory arrest, myocardial trauma, etc. As long as this trigger remains uncorrected, the patient is likely to go back into cardiac arrest. Thus, in addition to managing the cardiac arrest itself, the underlying cause must also be managed.
Actions and Effects
The goal of TH is to halt the physiologic events occurring during post-cardiac arrest syndrome and thereby minimize damage to the body’s organs, particularly the brain. This works because cooling tissues is believed to reduce metabolic demands, the production of free radicals and the volume of inflammatory cytokines.3 Cytokines are messenger chemicals responsible for the inflammation and fluid shifts that occur during an inflammatory response.
When the body is cooled from its baseline of 37°C (98.6°F) to 31°–34°C, the following occurs:2,4
- Neuronal metabolic rate decreases;
- Neuron membranes are stabilized;
- Minimal buildup of glutamine and dopamine;
- Reduced production of free oxygen radicals;
- Chemical pathways responsible for cellular apoptosis (cell death process) halt;
- Pro-inflammatory cytokines are reduced;
- The blood-brain barrier is preserved and enhanced;
- The function of mitochondria, the cell’s energy powerhouse, improves;
- Cellular survival pathways improve;
- Microthrombi formation is limited.
While the physiology limiting some of these events is understood, how cooling positively influences many of these cascades is not. While the mechanisms enhancing the cellular survival pathways are not known, it is well known that microthrombi develop in the arterioles during and following the hypotension and stagnant blood flow that occur during and following cardiac arrest. These impair circulation and cause tissues to become hypoxic. Hypothermia is known to impair the clotting cascade, and as a result fewer of these microthrombi develop.
Some of these actions are understood. With cooling there is a measurable decrease in cerebral edema because fewer cytokines are available to trigger swelling.2 Normally ischemic neurons work in overdrive to compensate for becoming ischemic. The result is a local increase in formation of free oxygen radicals. However, intracellular metabolism slows during TH, leading to a decreased oxygen demand and decreased neuron workload, which results in fewer free oxygen radicals being released. This allows ischemic and injured neurons time to heal and reduces overall damage. The result is limited central nervous system injury following cardiac arrest.4