Normal body temperature changes during the course of the day and is regulated by the thermoregulatory center in the anterior hypothalamus. The normal temperature at 6 AM is 37.2°C and at 4 PM is 37.7°C. Rectal temperatures are normally higher than oral temperatures because of mouth breathing. To obtain core temperature, readings should be obtained in the esophagus or tympanic membrane. During a fever, the setpoint in the hypothalamus is shifted upward. During hyperthermia, the setpoint is unchanged, but the rest of the body overcompensates to remove heat. At the other end of the spectrum, hypothermia is defined as core temperature less than 35°C. This chapter discusses the therapeutic and pathologic implications of hypothermia and hyperthermia.
THERAPEUTIC AND PATHOLOGIC HYPOTHERMIA
Therapeutic hypothermia (TH) is part of targeted temperature management (TTM). It is currently advocated as part of the postresuscitation care that includes optimization of oxygen supplementation and blood pressure and treatment of acute coronary syndromes. The consequences of anoxia are secondary to loss of adenosine triphosphate (ATP) and glucose, loss of cellular integrity, mitochondrial damage, and loss of calcium homeostasis.1 Increased calcium and glutamate perpetuates necrosis or apoptosis. In addition, restoration of perfusion leads to reperfusion injury caused by reactive oxygen species that further exacerbates endothelial dysfunction, vasomotor dysregulation, and edema.2 Hypothermia reduces release of excitatory amino acids and free radicals and improves oxygen supply and demand mismatch with reduction of cerebral metabolic rate of oxygen, blood volume, and pressure.2
Therapeutic hypothermia is indicated for patients who received return of spontaneous circulation (ROSC) after cardiac arrest from ventricular tachycardia or ventricular fibrillation (Class I) or ROSC after cardiac arrest from nonshockable rhythm (Class IIb).2 These patients must be comatose, which was initially defined by the Glasgow Coma Scale but has been broadened to include patients who are not answering verbal commands.2 Contraindications include sepsis, surgery within 14 days, and bleeding diathesis.
The temperature goals have evolved but every hour of delay of initiation increases the mortality rate by 20%.3 Therefore, it is advocated that TH is initiated within 6 hours. Initially, the temperature goal is 32°C to 34°C for 24 hours as per the 2010 guidelines.3-5 By 2015, the guidelines suggest 32° to 36°C because one randomized control trial suggested no survival or neurologic benefit between 32° and 36°C. (Class I; Level of Evidence: B).3-5 In 2017, The American Academy of Neurology (AAN) further stratified the recommendations. AAN recommendations are based on the following levels of evidence. Level A Recommendation is established effectiveness, ineffectiveness, or harmful and requires two Class I studies.6 Level B Recommendation is probably effective, ineffective, or harmful and requires one or more than one Class I study or two Class II studies.6 Level C Recommendation is possibly effective, ineffective, or harmful with at ≥ 1 Class II study or more than two Class III studies.6 Class I study is a prospective randomized controlled clinical trial (RCT) with (a) cleared defined outcomes, (b) exclusion/inclusion criteria, (c) adequate accounts for dropouts and crossovers, and (d) relevant baseline characteristics.6 Class II is a prospective matched group cohort study or RCT which lacks one of a-d criteria.6 Class III are other controlled trials in a representative population.6 Class IV are case studies, case reports, or expert opinion.6 For comatose patients with initial rhythm of pulseless ventricular tachycardia or ventricular fibrillation, AAN favors a TH goal of 32-34°C for 24 hours (Level A) over of 36°C for 24 hours (Level B) due to better evidence.6 36°C is considered in high risk of bleeding, and is followed by 8 hours of rewarming to 37°C and maintenance below 37.5°C until 72 hours.6 TH is weakly recommended for comatose patients with initial rhythm of PEA or asystole since it possibly improves neurologic outcomes and survival6 (Level C).
Cooling is achieved via ice bags, cooling blankets, and temperature-regulated surface devices. Shivering occurs between 35° and 37°C, increases the metabolic rate, and delays achieving the temperature goal.2 Nonpharmacologic approaches to prevent shivering include warm blankets on the face, hands, or feet. Magnesium sulfate is sometimes given to increase the shivering threshold.7 Patients often are placed on analgesics or sedation with or without a neuromuscular blocking agent.
After ROSC is achieved, hypotension may result from vasodilation from inflammation and cardiac dysfunction. During the initiation of TH, tachycardia and hypertension are expected because of cutaneous vasoconstriction. However, after cooling is initiated, bradycardia with a prolonged PR interval is noted. Further cooling can lead to junctional rhythm, sinus bradycardia, or ventricular escape rhythms. Despite prolonged QTc, there is no higher risk of torsade de pointes.2 If significant hemodynamic instability is the result of TH, temperature can be increased up to 35°C at a rate of 0.25°C per hour.2 Mean arterial pressure (MAP) should be maintained at greater than 80 mmHg.
Increased insulin resistance and decreased insulin secretion can cause hyperglycemia, but administration of insulin can cause a precipitous drop in glucose level. Therefore, the glucose goal is greater than 200 mg/mL.
Hypokalemia can result inward potassium influx and diuretic effect of TH. Potassium should be kept at above 3.5 mEq/L but repletion held 4 hours before rewarming because it causes reversal of influx.
Rewarming occurs 12 to 24 hours after cooling at a rate of 0.25°C every hour until the patient is normothermic (37°C). The patient is maintained normothermic for 48 hours. Neurologic prognostication is performed at least 72 hours after ROSC in patients who have not used TH and 4.5 to 5 days after TH.3,8
The Hypothermia after Cardiac Arrest Study Group conducted a multicenter trial with blinded assessment of the outcome of patients with cardiac arrest after ventricular fibrillation who were randomly assigned to undergo TH (32–34°C for 24 hours) compared with normothermia showed that 55% of the hypothermia group had favorable neurologic outcome compared with 39% in the normothermic group. The mortality rate at 6 months was 41% in the hypothermic group compared with 55% in the normothermic group.9 A randomized controlled trial by Bernard and coworkers had similar results: 49% of patients in hypothermia had a good outcome (ie, discharged home or to a rehabilitation facility) compared with 26% of patients in normothermia.10 After adjustment for age and time from collapse to ROSC, the odds ratio of a good outcome with hypothermia compared with normothermia was 5.25 (5% confidence interval [CI], 1.47–18.76; P = 0.011).10 TH is used for both out-of-hospital and in-hospital cardiac arrest. Another study by Chan and colleagues showed that in-hospital cardiac arrest in patients who had TH had lower in-hospital survival rates (27.4% vs 29.2%; relative risk [RR], 0.88; 95% CI, 0.80–0.97; risk difference, -3.6%; 95% CI, 6.3–0.9%; P = 0.01).11
Heat is lost because of radiation (55–65%), conduction and convection (15%), and respiration and evaporation, although conduction and convection are the most common causes of accidental hypothermia.12,13 The stages of accidental hypothermia, clinical symptoms, core temperature, and treatment are shown in Table 34-1.14