Physiological Impact of Hypothermia: The Good, the Bad, and the Ugly

Abstract

Hypothermia is defined as a core body temperature of < 35°C, and as body temperature is reduced the impact on physiological processes can be beneficial or detrimental. The beneficial effect of hypothermia enables circulation of cooled experimental animals to be interrupted for 1-2 h without creating harmful effects, while tolerance of circulation arrest in normothermia is between 4 and 5 min. This striking difference has attracted so many investigators, experimental as well as clinical, to this field, and this discovery was fundamental for introducing therapeutic hypothermia in modern clinical medicine in the 1950's. Together with the introduction of cardiopulmonary bypass, therapeutic hypothermia has been the cornerstone in the development of modern cardiac surgery. Therapeutic hypothermia also has an undisputed role as a protective agent in organ transplantation and as a therapeutic adjuvant for cerebral protection in neonatal encephalopathy. However, the introduction of therapeutic hypothermia for organ protection during neurosurgical procedures or as a scavenger after brain and spinal trauma has been less successful. In general, the best neuroprotection seems to be obtained by avoiding hyperthermia in injured patients. Accidental hypothermia occurs when endogenous temperature control mechanisms are incapable of maintaining core body temperature within physiologic limits and core temperature becomes dependent on ambient temperature. During hypothermia spontaneous circulation is considerably reduced and with deep and/or prolonged cooling, circulatory failure may occur, which may limit safe survival of the cooled patient. Challenges that limit safe rewarming of accidental hypothermia patients include cardiac arrhythmias, uncontrolled bleeding, and "rewarming shock".

Heart-brain axis: Association of congenital heart abnormality and brain diseases

“…For the surgical treatment of complex heart abnormalities, due to the complicated operation, the large trauma to the patient, the long cardiopulmonary bypass time, and the need to maintain a long-term deep hypothermia state, the damage to the brain is relatively severe. One-third of children with complex congenital (116)(117)(118). Studies have reported that the incidence of epilepsy after surgery for children with congenital heart abnormalities is 4% to 10%, and the incidence of epilepsy after surgery for complex congenital heart abnormalities is even higher (113).…”

“…Deep hypothermic circulatory arrest is commonly used in open heart surgery for complex congenital heart abnormalities. In the state of deep hypothermic circulatory arrest, the energy metabolism of the brain is depleted, causing brain damage through mechanisms such as calcium overload and excitatory amino acid toxicity ( 116 – 118 ). Studies have reported that the incidence of epilepsy after surgery for children with congenital heart abnormalities is 4% to 10%, and the incidence of epilepsy after surgery for complex congenital heart abnormalities is even higher ( 113 ).…”

Physiological Changes in Subjects Exposed to Accidental Hypothermia: An Update

“…Our aim is to update the readers on physiological changes occurring in various organ systems, as a knowledge basis for rewarming victims of AH and HCA. Although the topic recently was reviewed by one of us, the different emphasis should make this paper be considered as complementary ( 22 ).…”

Hypothermia evoked by stimulation of medial preoptic nucleus protects the brain in a mouse model of ischaemia

“…However, currently used hypothermia triggered by peripheral cold sensors is ineffective in lowering the core body temperature ( T core ) to the desired level 13 , 15 . The cooling process also evokes vigorous counteractive shivering thermogenesis that is difficult to tolerate in awake patients 16 , 17 , and produces harmful side effects to the heart, lungs, and brain 9 . A better method to induce therapeutic hypothermia is urgently needed.…”

“…The molecular cascades that set in after cerebral ischaemia are complex [2][3][4][5] , which hamper the development of neuroprotective therapies. Hypothermia at mild to moderate levels (31-34 °C) during or following cerebral ischaemia is powerful neuroprotective [6][7][8][9][10][11][12] . Hypothermia can simultaneously inhibit multiple mechanisms of brain cell death and slow down metabolic processes to limit tissue damage 10,13,14 , providing additive or synergistic beneficial clinical effects for stroke patients.…”