a. Typically, neurons are the most sensitive to lack of O2 and will develop irreversible damage within 3 to 5 minutes; myocytes and hepatocytes on the other hand can survive 1 to 2 hours in the absence of O2; muscle cells may survive for several hours.
b. By decreasing metabolic rate, hypothermia can prolong the “safe” ischemic time. Neurons for example decrease their metabolic rate by approximately 7% for every 1°C decrease in temperature.
B. Although temperature has an impact on survivability of ischemic cells, time is the factor that most directly and importantly impacts the reversibility of ischemia—the safe ischemic time.
1. Independent of all other factors, the number of minutes that cardiac function is arrested, the amount of time that the hemoglobin concentration is below 6 g/dL to 7 g/dL, or the duration of apnea or asphyxia all directly correlate with morbidity and mortality.
2. The effect of duration of the arrest on survivability suggests that mortality increases by 8% to 10% for each minute for which there is no cardiac output.
C. From a physiologic perspective, the most vital factor in determining outcome is the timely restoration of normal cardiac, pulmonary, and hemostatic function. Drugs play a limited, but very important, role in the return of the above functions in certain circumstances.
III. Cardiac Arrest
A. Ventricular tachyarrhythmias account for many cardiac arrests (6% to 14% of the time no known structural lesions of the heart can be identified).
1. If no structural cause can be identified, individuals who have a prolonged QT interval are at increased risk of developing polymorphic ventricular tachycardia (torsades de pointes) especially if they receive certain drugs that are also known to prolong the QT.
a. Mutations in genes that code for ion channels that generate the cardiac action potential have been identified in patients with the long QT syndrome.
b. The ability of a drug to precipitate a malignant tachyarrhythmia is related not just to the drug itself but also to the dose, to drug interactions, to genetic factors, to the gender of the patient, and to the type and severity of preexisting cardiac disease.
B. Ventricular fibrillation is the cause for most of the other instances of sudden cardiac arrest (true incidence of the precipitating arrhythmia is not known because most sudden cardiac arrests occur out of hospital and typically several minutes pass before the rhythm can be assessed).
C. Independent of the etiology of the cardiac collapse, for resuscitation to be successful, CPR must be initiated as soon as possible.
1. The best outcomes are achieved if the heart is defibrillated within the first 4 minutes after the cardiac arrest, during the electrical phase.
2. In those patients with return of spontaneous circulation (ROSC), the enthusiasm for the ability of hypothermia to attenuate the neurologic injury has been tempered by a more recent well-performed study that did not demonstrate an improvement in neurologic outcome with hypothermia (33°C vs. 36°C).
3. Once patients enter the metabolic phase after 10 minutes of untreated cardiac arrest, the chances of meaningful recovery are slim.
D. Hemorrhagic Shock
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