When better is the enemy of good: the optimal heart rate during therapeutic cooling.

November 2014 • Volume 42 • Number 11 One of the most fundamental rules in medicine is “Primum Non Nocere”—to first, do no harm. However, unfortunately, sometimes our quest to “improve” physiologic variables in our patients can lead to harm; this is when “better” becomes the enemy of good. Recent examples of such unintended consequences include use of intensive insulin therapy to induce strict normoglycemia in critically ill patients, linked to increased risk of death (1, 2); the use of starches to improve hemodynamics and increase efficacy of resuscitation in patients with severe sepsis, linked to increased risk of renal failure and death (2, 3); excessive oxygenation in patients with out-of-hospital cardiac arrest (OHCA), linked to higher mortality (4); aggressive treatment of intracranial arterial stenosis with elective stent placement in addition to drug therapy, linked to increased risk of stroke and higher mortality (5); use of long-acting β-blockers to reduce cardiac risk in the perioperative setting, linked to increased risk of stroke and higher mortality (6); and quite possibly use of long-acting antihypertensives in the acute phase of neurological injury, linked to increased mortality when “overshoot” (accidental hypotension) occurs (7). This list could easily be expanded. A recurrent theme in many of these interventions is an overzealous attempt to restore (perceived) physiological or reference values. Often it is the “overshoot” of efforts to restore “normal” values that is harmful, where the intervention itself may be neutral or even beneficial; but sometimes the concept of “normal” may change under pathophysiologic conditions, and trying to achieve “normal” values may itself be harmful. We should always keep in mind that for any given intervention, risks may outweigh benefits and that our efforts to restore numbers to normal or supranormal could backfire. These observations come to mind when reading the article by Stær-Jensen et al (8) published in this issue of Critical Care Medicine. The authors, who work in a large tertiary referral center for patients with OHCA, performed a retrospective cohort study in 111 of their patients to determine whether there was a link between bradycardia developing during therapeutic hypothermia (TH) and neurological outcome. The result may come as a surprise to some: the authors found that bradycardia during TH was associated with favorable neurologic outcome at hospital discharge. They conclude that bradycardia during TH should not be aggressively treated in most patients (8). The authors also established a dose-response relationship between bradycardia and favorable outcome, that is, the lower the heart rate, the greater the likelihood of favorable outcome. Although the study is limited by its retrospective design, finding such a dose-response relationship makes it more plausible that the observed link is genuine. These findings suggest that in many cases our desire for the heart rate to be “normal” under hypothermic conditions may be misguided and that attempts to “fix” the heart rate may be yet another example of better being the enemy of good. To better understand the results of this study, it is useful to take a brief look at the physiological links between temperature and heart rate. Hypothermia has multiple direct and indirect effects on heart rhythm and myocardial function. A mild drop in temperature to levels just below normal (±36.0°C) initially leads to an increase in plasma levels of norepinephrine and activation of the sympathetic nerve system. This induces constriction of peripheral vessels (particularly in the skin) and a shift of blood from peripheral (small) veins to deeper veins in the core compartment of the body, leading to an increase in venous return to the heart (9). This hypothermia-induced rise in venous return initially leads to mild sinus tachycardia and is one of the factors contributing to so-called cold diuresis (the others being a decrease in antidiuretic hormone [ADH] and renal ADH receptor levels, tubular dysfunction, and activation of atrial natriuretic peptide) (9). Cold diuresis can lead to hypovolemia, which can sustain and increase tachycardia (9). The initial increase in heart rate is reversed as core temperature decreases further, below 35.5°C. Heart rate begins to drop progressively as core temperature decreases, and soon sinus bradycardia ensues; at 32°C, the normal heart rate will be 35–45 beats/min (although there is wide interpatient variability). This is caused by a hypothermia-induced decrease in the rate of spontaneous depolarization of cardiac pacemaker cells, including those of the sinus node, combined with decreased Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0000000000000600 *See also p. 2401.