Physiologic Response to Hypothermia

In response to cold, the hypothalamus increases heat conservation by reducing blood flow to peripheral tissues through sympathetically-mediated vasoconstriction. The hypothalamus also stimulates heat production through shivering and increased thyroid, catecholamine, and adrenal activity. The initial phase of cooling increases metabolism, ventilation, heart rate, cardiac output, and mean arterial pressure. The threshold for shivering is 1° C lower than that of vasoconstriction and is considered a last resort by the body to maintain temperature.

Alterations of the central nervous system, comorbid illness (ie trauma, spinal shock), drugs (ie sedatives, muscle relaxants, or opioids), fatigue, and glycogen depletion may impair these mechanisms. Continued cooling will eventually decrease tissue metabolism and inhibit neural activity. Primary effects of cooling can be seen during anesthesia or at lower core temperatures (<32° C) when shivering ceases and ventilation, metabolism, and cardiac output begin to decline.

Laboratory Work-up of Hypothermia

Previously healthy patients with mild accidental hypothermia may not require a work-up. In moderate to severe hypothermia, laboratory evaluation should be undertaken to identify potential complications and comorbidities, including lactic acidosis, rhabdomyolysis, bleeding diathesis, and infection. Standard investigation should include fingerstick glucose assessment, serum electrolytes and kidney function tests, arterial blood gas, and complete blood cell count.

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Acute hypothermia can result in hyperglycemia due to catecholamine-induced glycogenolysis and because insulin is ineffective below 30° C.1 Chronic or secondary hypothermia may present with hypoglycemia, which may suggest pancreatitis or diabetic ketoacidosis if persistent during rewarming.1

Hypokalemia commonly occurs with hypothermia; if replacement is given in excess of losses then hyperkalemia may occur on rewarming.6 Baseline hyperkalemia is a prognostic indicator: levels of >10 mmol/L are associated with very low likelihood of recovery.4 Rewarming can be accompanied by rapid, unpredictable changes in electrolytes and frequent reassessment (approximately every 4 hours) is prudent in moderate-severe hypothermia.1

Generally, hyperventilation is an initial response to body temperature cooling leading to a respiratory alkalosis, but over time mixed acidosis is precipitated by falling metabolic rate and CO2 production, respiratory depression and increasing lactate.6 Sodium bicarbonate should be given if pH is less than 7.25. White blood cell and platelet counts are usually decreased due to splenic sequestration.1 Hematocrit is elevated due to hemoconcentration from cold diuresis and increases 2% for each decrease of 1° C; therefore, low-normal hematocrit is abnormal in severe hypothermia and may be indicative of traumatic blood loss.1,4 Elevated lipase levels may indicate hypothermia-induced pancreatitis.1

Moderate-to-severe hypothermia results in a bleeding diathesis similar to disseminated intravascular coagulation. At temperatures <33° C, this coagulopathy significantly increases mortality in patients with concomitant trauma5; the synergistic effects of hypothermia, acidosis and coagulopathy are referred to as the trauma triad of death. The laboratory will report deceptively “normal” results of prothrombin and partial thromboplastin times because these tests are always performed at 37° C. Treatment of the coagulopathy consists of rewarming and administration of clotting factors is ineffective.1

A similar laboratory error can be seen with analysis of the arterial blood gas sample, which also operates at 37° C. As fluid is heated, the arterial blood gas may report a falsely elevated O2 and CO2 level and a lower pH in patients who are hypothermic.4 Oxygenation should be monitored continuously; be aware that the response time of pulse oximeters placed on the finger is slowed by hypothermia. Probes placed on the ears or forehead appear to be less influenced by decreased body temperature and the associated peripheral vasoconstriction.1

Hypothermia causes slowed impulse conduction through potassium channels leading to characteristic ECG changes: prolongation of all intervals: RR, PR, QRS and QTc. As such, hypothermia obscures normal premonitory ECG changes commonly associated with hyperkalemia.1,4 There may also be elevation of the J point (if the ST segment is unaltered), producing a characteristic Osborn J wave.1

Studies suggest the finding is most prominent in precordial leads V2 to V5 and the height of the J wave is roughly proportional to the degree of hypothermia1,4; they may also be seen in leads I and V6in moderate hypothermia.6 Available software for ECG interpretation is unable to recognize J waves, and often misinterprets them as ischemic changes or ST elevations.1

Although suggestive of hypothermia, J waves are not pathognomonic and may be a normal variant or can be found in other conditions: subarachnoid hemorrhage, sepsis, myocardial ischemia, and brain injury.1 Chest radiography may reveal aspiration pneumonia, vascular congestion, or pulmonary edema. Additional studies should be obtained based on clinical assessment: toxicology screen in patients with depressed mood or psychiatric history; serum cortisol and thyroid function studies in a patient with moderate or severe hypothermia who fails to rewarm despite aggressive interventions.1

Pre-Hospital Transport and Treatment

Management of the hypothermic patient begins with careful handling of the patient, preventing further heat loss, and passive and active external rewarming appropriate to the degree of hypothermia. Experimental evidence and experience indicates that pre-hospital patient packaging should include a full-body shell of total insulation for the patient.6

The basic principles of rewarming a hypothermic victim are to conserve the heat they have and replace the body fuel they are burning up to generate that heat. If a person is shivering, they have the ability to rewarm themselves at a rate of 2° C per hour. Patients in cardiac arrest, prehospital cardiac instability (systolic blood pressure <90 mm Hg, ventricular arrhythmia) or those with core temperatures <28° C should be transported to a center capable of providing extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass unless co-existing conditions mandate transport to a closer facility.2 These therapies provide better outcome, with survival rates of up to 100% compared with other rewarming techniques.5

Cardiac arrest patients should receive continuous cardiopulmonary resuscitation (CPR) during transfer if possible; mechanical CPR can be helpful. Delayed or intermittent CPR may be appropriate in hypothermic arrest to facilitate transport when continuous CPR is impossible.6 If the patient’s core temperature is <20°C, alternate 5 minutes of CPR and <10 minutes without CPR; if <28° C or unknown, alternate 5 minutes of CPR and <5 minutes without CPR.6 There are many cases of hypothermic cardiac arrest where good neurologic recovery is possible following many hours of CPR, even with prolonged transport.6 In cardiac arrest, core temperature should be monitored and heat delivery should be titrated to maintain the patient’s core body temperature but prehospital rewarming or cooling during transport should be avoided.6

The hypothermic heart is very sensitive to movement and rough handling may precipitate arrhythmias, including ventricular fibrillation. Personnel should gently maintain and extricate the patient while immobilized in a horizontal position and avoid jostling the patient during transport, physical examination, or the performance of essential procedures.

It is thought deterioration, or rescue collapse, may be precipitated by hypovolemia, hypotension, decreased brain-blood flow, and increased metabolic byproducts and catecholamines. An important factor for deterioration is thought to be core body temperature after drop, a decrease in temperature with associated clinical deterioration after rewarming has been initiated. As peripheral tissues are warmed, especially when the extremities and trunk are warmed simultaneously, vasodilation allows the cold, acidic pooled blood in the vasoconstricted extremities to circulate back into the body core.1 Additionally, the use of peripheral muscles should be avoided as core body temperature drops with exertion.1 Vasodilation caused by movement also contributes to the precipitous hypotension, inadequate coronary perfusion, and ventricular fibrillation that sometimes occurs during rewarming.1 This can be avoided by concentrated rewarming of the core and delayed warming of the periphery of the body.

Rewarming Techniques

Optimal rewarming techniques depend on patient status, the capability of providers, and availability of in-hospital care and warming devices. Regardless of the level of hypothermia or the rewarming method to be used, rewarming should begin as soon as possible with patients removed from the cold exposure as gently as possible, dried and provided with as much insulation as practical. The degree of hypothermia determines the techniques implemented (Table 2).

TABLE 2. Rewarming Techniques1,6

Passive external rewarmingTreatment of choice for mild hypothermiaSupplemental method, when feasible, in patients undergoing aggressive rewarming for moderate to severe hypothermiaWet clothing is removed
Patient is covered with blankets or other types of insulation
Recommended rewarming rate of 0.5 to 2° C/hr
Active external rewarmingTreatment for moderate to severe hypothermia (<32° C) Used for mild hypothermia in patients who are unstable, lack physiologic reserve, or fail to respond to passive external rewarmingCombination of warm blankets or baths, heating pads, radiant heat, or forced warm air applied Recommended rewarming rate 0.5-4° C/hr
Active internal (core) rewarmingTreatment for severe hypothermia (<28° C)
Used for patients with moderate hypothermia who fail to respond to less aggressive measures
May be combined with active external rewarming
Intravenous catheter warmed crystalloid (45° C)Warm humidified oxygen
Irrigation of the peritoneum, thorax (via the pleural space) with warmed isotonic crystalloid
Extracorporeal blood rewarming

In passive external rewarming, which has a rewarming rate of 1 to 5° C per hour for mild hypothermia, protection from further heat loss combines with the patient’s intrinsic heat production to produce rewarming.6 Passive external rewarming requires the patient to have physiologic reserve sufficient enough to generate heat and may be unsuccessful in the setting of glycogen depletion, multiple trauma, malnourishment, intoxication, major comorbidities, sepsis, hypovolemia, and especially in elderly patients.1 When shivering ceases (hypothermia II–IV), minimal rewarming occurs and in the absence of active rewarming, cooling rate increases.6

Active rewarming measures is indicated if the rewarming rate is lower than 0.5° C per hour or if dysrhythmias are present.1 In patients who fail to rewarm, ensure that appropriately aggressive rewarming techniques are in progress and that reversible or secondary causes are addressed. During active external rewarming, it is recommended to rewarm the trunk before the extremities. Heat should be applied in proximity to major arteries.1 Use caution, as the combination of decreased sensation and reduced blood flow predisposes the hypothermic patient to surface burns with heating pads; forced warm air systems are preferable. 1 Full-body immersion in warm water is not recommended because of concerns for core temperature after drop and the risk of cardiovascular collapse.4 For moderate to severe hypothermia (hypothermia II-III) in spontaneously perfusing patients, active external rewarming may be combined with minimally-invasive active internal-core rewarming techniques: heated IV fluids and warm humidified oxygen.

Slow rewarming methods include IV fluid heated to 45°C (heated, humidified O2 by mask or 0.7° C/h), warmed blankets (0.9° C/h), and heated, humidified oxygen via endotracheal tube (1.2° C/h).4 If intact, a patient’s endogenous physiologic mechanisms (other than shivering) provide similar rates of rewarming.4 For colder patients and those with secondary hypothermia or comorbid illness, there may be morbidity associated with a prolonged rewarming process if the patient has poor tolerance for the hypothermia-induced organ dysfunction.6 Rewarming rates faster than 2° C/hour was noted to reduce mortality when compared with slower rates.4

Moderate rewarming methods provide heat at approximately 3° C/h through warmed gastric lavage (2.8° C/h), IV solutions heated to 65° C (2.9° C/h), and peritoneal lavage with 45° C fluid at 4 L/h (3° C/h).4 A trial using fluids heated to 65 °C (vs standard 45° C) demonstrated more efficacy in treating severe hypothermia.4 Thoracic or peritoneal lavage are not commonly used unless the patient is unstable and ECLS rewarming is not available.6

Rapid rewarming methods include thoracic lavage at 500 mL/min (6.1° C/h), cardiopulmonary bypass (18° C/h), thoracic lavage at 2 L/min (19.7° C/h), ECMO (1-4o C/h).4 According to case reports, thoracic lavage has restored spontaneous circulation within 2 hours and is a reasonable alternative rewarming technique when ECMO or cardiopulmonary bypass is not available.2 Endovascular warming devices are an effective and less invasive alternative to ECLS in patients who are not in cardiac arrest.1

ECLS using venoarterial-ECMO or cardiopulmonary bypass is the preferred rewarming method for patients with potentially salvageable severe hypothermia in cardiac arrest (hypothermia IV), and may be considered for patients with core temperatures less than 28o C (hypothermia III) with severe circulatory instability or life-threatening arrhythmia, respiratory failure, refractory acidosis, for those who do not rewarm with standard active external and internal-core rewarming techniques, and those with completely frozen extremities or severe rhabdomyolysis with hyperkalemia.1,4,6 Older patients, or those with comorbidities that limit their tolerance for the low-flow state of hypothermia III, may have better outcomes when managed with ECLS, which immediately restores circulation, maintains tissue oxygenation and CO2 removal, and provides fast and controllable rewarming.6 For patients with hypothermia IV who are not treated with ECLS survival is likely to be less than 37%.2

ECLS is safe and efficient, yielding rates of survival without neurologic impairment of 47% to 63%.2,6 Venoarterial-ECMO is preferred due to its rapid availability, lower anticoagulant requirements and the possibility of prolonging cardiorespiratory support.2,6 During rewarming core body temperature should be monitored closely to assess the adequacy of therapy and to prevent iatrogenic hyperthermia, ideally with esophageal temperature in intubated patients.1 Desperate cases of severe hypothermia may warrant consideration of direct cardiac rewarming via open emergency department thoracotomy with open cardiac massage with warmed saline solution.4

Termination of ECLS may be considered if there is no return of circulation at 32 to 35° C; however, several biomarkers may inform whether to continue resuscitation. These include, extreme hyperkalemia at levels greater than 12 mEq/L (case reports suggest lower cutoffs should not be used); fibrinogen levels less than 50 mg/dL, elevated ammonia, blood lactate, serum sodium, and/or serum creatinine levels.1,4