Therapeutic Hypothermia Essay

Title: Therapeutic Hypothermia

Author: Padmaja Durga, Additional Professor, Department of Anesthesiology and Intensive Care, Nizam’s Institute of Medical Sciences, Hyderabad, A.P., India.
Abstract:
Therapeutic hypothermia has been advocated for neuroprotection in cardiac arrest-induced encephalopathy, neonatal hypoxic-ischemic encephalopathy, traumatic brain injury, stroke, hepatic encephalopathy, and spinal cord injury, and as an adjunct to aneurysm surgery. In this review, we address physiological mechanism of hypothermia to mitigate neurological injury, the trials that have been performed for each of these indications, the strength of the evidence to support treatment with mild/moderate hypothermia. Evidence is strongest for prehospital cardiac arrest and neonatal hypoxic-ischemic encephalopathy. For traumatic brain injury, a recent meta-analysis suggests that cooling may increase the likelihood of a good outcome, but does not change mortality rates. For many of the other indications, such as stroke and spinal cord injury, trials are ongoing, but the data is insufficient to recommend routine use of hypothermia at this time. Although induced hypothermia appears to be a highly promising
treatment, it should be emphasized that it is associated with a number of potentially serious side effects, which may negate some or all of its potential benefits. Prevention and/or early treatment of these complications are the key to successful use of hypothermia in clinical practice.
Key words: Therapeutic Hypothermia, mechanism, clinical application, evidence, cooling methods, practical aspects.

Section Headings
Introduction
Definition
Mechanisms underlying neuroprotective effects of Hypothermia
Potential clinical applications of hypothermia
Physiological, Metabolic and cellular effects of hypothermia
Practical Aspects of TH
Conclusion

Introduction

Hypothermia has been used for medicinal purposes since ancient times. It has been used to provide neuroprotection in survivors of cardiac arrest, neonatal hypoxic encephalopathy, traumatic brain injury, stroke, and various other disorders. The concept has experienced periodic re-emergence in the medical literature. Until recently, evidence for therapeutic hypothermia (TH) has lacked sufficient strength to propel it into common practice. Large clinical trials in the recent past have demonstrated improved survival and neurological outcomes with induction of TH. The clinical use of TH is likely to increase in the near future; thus, all clinicians should have knowledge regarding the clinical applications of TH.
Definition
Therapeutic hypothermia is defined as a core temperature ≤ 35°C induced by artificial cooling, which is used to prevent or attenuate various forms of neurological injury. One should distinguish between controlled therapeutic hypothermia and uncontrolled (i.e., spontaneous, accidental) hypothermia.
Mechanisms underlying neuroprotective effects of Hypothermia
Cerebral ischemia and subsequent reperfusion injury cause enormous biochemical, structural, and functional insults, which in a complex interrelated process leads to progressive cell destruction, neuronal apoptosis, and death. Hypothermia has been shown to attenuate or ameliorate many of these deleterious temperature-sensitive mechanisms, thereby contributing to protection of the brain. [1, 2] (table 1). Many of the mechanisms underlying hypothermia’s effects have been derived from animal experiments, although many were subsequently confirmed in clinical studies.

Current and Potential Clinical Applications of Therapeutic Hypothermia
Cardiopulmonary resuscitation (CPR)
Rationale: Neurological injury and cardiovascular instability are the major determinants of survival after cardiac arrest.[3] For protection of the brain and other organs, hypothermia is a helpful therapeutic approach in patients who remain comatose (usually defined as a lack of meaningful response to verbal commands) after return of spontaneous circulation (ROSC).
Trials and Evidence: Two landmark randomized controlled clinical trials published in early in 2002, reported significant improvements in good neurological outcome in patients with out of hospital cardiac arrest (OHCA) treated with mild hypothermia though there was no difference in survival.[4, 5] Subsequently other randomized clinical trials and studies with historical controls have shown the beneficial effects of hypothermia for comatose survivors of ventricular fibrillation(VF) cardiac arrest.[6-8] Much less data is available for other categories of patients such as those with asystole or pulseless electrical activity (PEA) upon arrival of the ambulance.
Although there was no statistically significant improvement, the trend was toward good outcome.[9, 10]. (Table
2)
The Cochrane systematic review concluded that, with conventional cooling methods, patients in the hypothermia group were more likely to reach cerebral performance categories score (CPC) of one or two (risk ratio (RR), 1.55; 95% Confidence interval (CI )1.22 to 1.96) and were more likely to survive to hospital discharge (RR 1.35; 95% CI 1.10 to 1.65) compared to standard post-resuscitation care. Across all studies there was no significant difference in reported adverse events between hypothermia and control. Class-I evidence supports the use of hypothermia in patients unresponsive to verbal commands following CPR with. witnessed arrest, brief interval (15 min) until arrival of ambulance, VF, or VT upon arrival of ambulance, ROSC within 60 min and no refractory cardiac shock or persistent hypoxia.[11] There is class-III evidence supporting use of hypothermia in patients with asystole and PEA. Controversies exist regarding the most efficient method of cooling.[8, 12], timing, duration and target temperature. The clinical predictors of survival in patients treated with TH following cardiac arrest were VF on presentation (OR 14.9 p=0.002), pre-cardiac arrest aspirin use (OR 9.7 p=0.02), ROSC