Hyperthermia After Cardiac Arrest Indicates a Poor Neurologic Prognosis

Abstract & Commentary

Synopsis: Fever going over the threshold temperature of 37.0°C during the first 48 hours after restoration of spontaneous circulation was a strong independent predictor for unfavorable neurologic recovery within 6 months after cardiopulmonary resuscitation.

Source: Zeiner A, et al. Hyperthermia after cardiac arrest is associated with an unfavorable neurologic outcome. Arch Intern Med. 2001;161(16):2007-2012.

This study was conducted to evaluate the effect of body temperature course on neurologic outcome after cardiac arrest and successful restoration of spontaneous circulation. Subjects were 151 patients with a median age of 60 years who experienced a witnessed cardiac arrest of presumed cardiac cause with subsequent cardiopulmonary resuscitation (CPR) and return of spontaneous circulation. Patients were excluded if their cardiac arrest was associated with trauma, hypothermia, drowning, drug overdose, or a primary respiratory, neurologic, or metabolic cause. Patients were also excluded if they had a C-reactive protein level > 1.5 mg/dL on admission to the emergency department and if they had evidence of an infection or were taking antibiotics prior to the cardiac arrest.

Body temperature was recorded immediately after hospital admission using a tympanic thermometer and thereafter in the pulmonary artery. Cerebral function was graded as good (slight or moderate disability) or unfavorable (severe disability, vegetative state, or brain death) based on Glasgow overall performance categories. Most (78%) of the cardiac arrests occurred outside the hospital. The estimated median no-flow duration (collapse to initiation of CPR) was 5 minutes, and the estimated median low-flow duration (CPR to return of spontaneous circulation) was 14.5 minutes.

There were no significant differences (P = 0.39) in median temperature at admission in patients with a good (n = 89; 35.6°C) vs. unfavorable functional neurologic outcome (n = 62; 35.3°C). Within 4 hours after restoration of spontaneous circulation, the lowest recorded temperature in patients with a good functional recovery was higher (36.0°C) compared to patients with a poor functional recovery (35.2°C) (P < 0.001). Thereafter, body temperature trended upward until 36 hours after return of spontaneous circulation when it began a downward trend in patients with a good functional recovery. The maximum body temperature was lower (P < 0.001) in patients with a good vs. unfavorable recovery (37.7°C vs 38.3°C, respectively). Overall, patients with a good functional recovery spent less time (P = 0.002) with a temperature above 37.0°C. Logistic regression showed that fever going over the threshold temperature of 37.0°C was a strong independent predictor for unfavorable neurologic recovery. For each degree Celsius higher than 37.0°C, the association with an unfavorable neurologic recovery increased, with an odds ratio of 2.26 (95% confidence interval, 1.24-4.12).

Comment by Leslie A. Hoffman, RN, PhD

In this study, patients who had a good functional neurologic recovery, compared to those with an unfavorable recovery, were less likely to have experienced an out-of-hospital arrest (58 vs 60; P < 0.001) and had a shorter no-flow (0.0 min. vs 5.5 min; P < 0.001) and low-flow duration (5.0 min. vs 20.0 min; P < 0.001). They also received fewer counter shocks (2 vs 3; P = 02), had a higher arterial pH (7.34 vs 7.27; P = 0.003), and a lower lactate level (7.4 vs 10.8; P < 0.001) but did not differ in age (P = 0.74) or gender (P = 0.81). When these variables and the highest temperature observed during the first 48 hours after return of spontaneous circulation were entered into a logistic regression, the model showed that fever going over the threshold of 37.0°C was the strongest independent predictor for an unfavorable functional neurologic recovery. Of note, each degree Celsius higher than 37.0°C showed an increased association with the risk of severe disability, coma, or a persistent vegetative state, with an odds ratio of 2.26.

The study provided no data on the underlying cause of fever. Patients with an unfavorable neurologic recovery had a significantly higher rate of antibiotic treatment, but this therapy may have been instituted empirically. Temperature alterations may also have been due to cerebral injury induced during cardiac arrest. Regardless, fever seemed to be an independent contributor to a poor prognosis. Several prior studies have shown that moderate hyperthermia, when present during or after a period of cerebral ischemia or trauma, can exacerbate the degree of resulting neural injury, although the mechanisms are not well defined. Further, mild resuscitative hypothermia in patients who experience a cardiac arrest seems to mitigate neurologic damage. (Zeiner A, et al. Stroke. 2000;31:86-94). Given this persuasive evidence, it seems appropriate to aggressively treat fever in this patient population with the goal of maintaining temperature within normal limits in the immediate interval following successful CPR resuscitation.

Dr. Hoffman is Professor, Medical-Surgical Nursing, Chair, Department of Acute/Tertiary Care, University of Pittsburgh, School of Nursing.