Hypothermia in bleeding trauma: a friend or a foe?

Abstract

The induction of hypothermia for cellular protection is well established in several clinical settings. Its role in trauma patients, however, is controversial. This review discusses the benefits and complications of induced hypothermia--emphasizing the current state of knowledge and potential applications in bleeding patients. Extensive pre-clinical data suggest that in advanced stages of shock, rapid cooling can protect cells during ischemia and reperfusion, decrease organ damage, and improve survival. Yet hypothermia is a double edged sword; unless carefully managed, its induction can be associated with a number of complications. Appropriate patient selection requires a thorough understanding of the pre-clinical literature. Clinicians must also appreciate the enormous influence that temperature modulation exerts on various cellular mechanisms. This manuscript aims to provide a balanced view of the published literature on this topic. While many of the advantageous molecular and physiological effects of induced hypothermia have been outlined in animal models, rigorous clinical investigations are needed to translate these promising findings into clinical practice.

Figure 1

Aerobic metabolism in the cell guarantees adequate ATP for normal physiologic function and heat production (thermoregulation). ATP = Adenosine Tri-Phosphate. ADP = Adenosine Di-Phosphate.

Figure 2

Hemorrhage reduces availability of oxygen and substrates and stimulates a switch to anaerobic metabolism leading to decreased ATP synthesis and subsequent heat production. This cellular hypoxia also stabilizes HIF-1, which activates several inflammatory and apoptotic pathways leading to increased cell injury and death. ATP = Adenosine Tri-Phosphate. ADP = Adenosine Di-Phosphate. HIF-1 = Hypoxia-Induced Factor-1. iNOS- induced Nitric Oxide Synthase. NO = Nitric Oxide. PG = Prostaglandin. NF-kB = Nuclear Factor- kappa B. COX-2 = cyclo-oxygenase-2. IL = Interleukins. TNFα = Tumor Necrosis Factor alpha. G-CSF = Granulocytes Colony Stimulating Factor. STAT = Signal Transducers and Activators of Transcription.

Figure 3

The molecular changes associated with induced therapeutic hypothermia. Minimal metabolic activity due to inactivation of Na⁺/K⁺ ATPase pump conserves ATP in the cell and abolishes the need for oxygen and substrates during the circulatory arrest. Induced hypothermia also affects several molecular pathways altering the expression of many intermediates and leads to decreased inflammation, decreased neutrophils migration and decrease apoptosis. Production of ROS is blunted as well. TNFR = Tumor Necrosis Factor Receptor. Cyt-C = Cytochrome C. ROS = Reactive Oxygen Species. STAT = Signal Transducers and Activators of Transcription. HSP 70 = Heat Shock Protein. JNK = stress-activated protein c-jun Kinase.