Induction of Therapeutic Hypothermia Requires Modulation of Thermoregulatory Defenses

Abstract

Hypothermia has been linked to beneficial neurologic outcomes in different clinical situations and its therapeutic value is considered important. For example, in asphyctic neonates and in patients with out-of-hospital cardiac arrest (with ventricular fibrillation as the initial cardiac rhythm), rapid installation of hypothermia has been reported to add substantial therapeutic benefits over nonthermal standard treatments. Yet, in other groups of patients in which the application of therapeutic hypothermia may be applied with clinical benefits, the optimization of therapy remains less straightforward, as the body possesses vigorous defense mechanisms to protect it from inducing hypothermia, that is, especially in conscious patients and/or in those in which the hypothalamus remains intact, such as stroke patients or patients who suffer a myocardial infarction or spinal cord injury. This overview summarizes the body's primary reactions to hypothermia and the defense mechanisms available or evoked. Then, clinically applicable ways to overcome these forceful cold defenses of the body are described to ensure both an optimal induction process for therapeutic hypothermia and maximal subjective comfort for these conscious patients.

Therapeutic Hypothermia in Stroke and Traumatic Brain Injury

“…In conscious, non-intubated patients it can be difficult to induce TH without pharmacological interventions because the human body mounts vigorous thermoregulatory defenses. These thermoregulatory mechanisms substantially increase metabolic activity within the body, which may be harmful or at least counter productive as they impede the induction of TH (Busto et al, 1989a ; Bandschapp and Iaizzo, 2011 ).…”

“…The behavioral components of these responses (e.g., protection by clothes, shelter, shade, or air conditioning) are ultimately under our conscious control. In clinical settings these behavioral controls are often usurped by healthcare providers (Busto et al, 1989a ; Bandschapp and Iaizzo, 2011 ). The effects or responses governed by the autonomic nervous system are the primarily activated responses to cold include arteriovenous shunting or induced vasoconstriction and shivering.…”

“…Notably, in a hypothermic patient, the elicitation of forceful shivering can increase metabolic heat production several-fold, which exacerbates the patient’s condition. Therefore, one needs to consider modulating this response either with muscle paralysis and/or lowering the shivering threshold (Busto et al, 1989a ; Bandschapp and Iaizzo, 2011 ). Muscle paralysis is the most effective way to stop shivering, but increases risk of many adverse events (AEs) including inability to detect changes in the neurological exam, high risk of pneumonia, and prolonged ventilation.…”

“…Thus, using a pharmacological approach to lower the shivering threshold in awake patients may considerably reduce the need for heavy sedation, paralytics and, therefore, the need for ventilatory support (Guluma et al, 2006 ). Some pharmacological agents that are used to inhibit shivering include buspirone, meperidine, clonidine, magnesium, and dexmedetomidine (Xue and Huang, 1992 ; Karibe et al, 1994 ; Bandschapp and Iaizzo, 2011 ; Kallmünzer et al, 2011 ). Several reported pharmacological anti-shivering protocols have allowed investigators to achieve the target temperature (TT) without using heavy sedation or paralytics, often obviating the need for mechanical ventilation (Xue and Huang, 1992 ; Karibe et al, 1994 ; Bandschapp and Iaizzo, 2011 ; Kallmünzer et al, 2011 ).…”

Induction of Mild Hypothermia by Noninvasive Body Cooling in Healthy, Unanesthetized Subjects: Editorial Commentary on Bandschapp et al., 2011

“…In a recent study by Bandschapp and coworkers (Bandschapp et al, 2011a) and in previous studies from the same group (Bandschapp and Iaizzo, 2011a), these important questions were highlighted. In one of the studies (Bandschapp et al, 2011b), the efficacy of several topical cooling methods, and combinations thereof, was tested in healthy volunteers.…”