Out of the cold: management of hypothermia and frostbite
========================================================

* Jay Biem
* Niels Koehncke
* Dale Classen
* James Dosman

**Case** 

In mid-January a 70-year-old man was brought by ambulance to the emergency department. He had been found lying on a sidewalk in a confused state. An acquaintance said the patient drank alcohol heavily. On examination the patient was drowsy, but he responded to voice commands by opening his eyes. His limbs were cold, blanched and pulseless. Muscle tone was increased, but the patient was not shivering. Reflexes were absent. His blood pressure was 90/52 mm Hg, pulse 50 and respiratory rate 8. His rectal temperature was 31°C. Crackles were heard at the right lung base. Bowel sounds were absent. The hemoglobin level was 182 g/L, and the leukocyte count was 12 х 106/L. On room air, the arterial blood pH was 7.25, partial pressure of carbon dioxide 52 mm Hg and partial pressure of oxygen 60 mm Hg. The anion gap was 18 mmol/L, the glucose level 12 mmol/L, the creatinine level 210 μmol/L, the creatine kinase level 1200 U/L and the ethanol level 21 mmol/L. The platelet count, international normalized ratio, partial thromboplastin time, aspartate aminotransferase level and amylase level were normal. An electrocardiogram showed sinus bradycradia and J waves. A chest radiograph showed a consolidation in the right lower lobe.

What is the severity of the patient's hypothermia and frostbite? How should he be managed acutely? What rewarming techniques should be used? How should the frostbite be treated?

Although cold-induced injuries and hypothermia are usually accidental, they can result from social (e.g., homelessness, inadequate home heating),1,2,3 occupational,4,5,6,7 recreational,8,9,10,11 iatrogenic12,13 and even criminal causes.14 It is difficult to obtain data on the incidence of cold-induced injuries and hypothermia. Hospital data are the “tip of the iceberg,” representing only the most severe cases. According to Statistics Canada, there were 411 deaths from hypothermia, frostbite and other cold-induced injuries during 1992–1996.15 Several case series in western Canada of patients admitted to hospital with frostbite identified the main associated factors to be alcohol consumption, psychiatric illness, and motor vehicle accident or breakdown.16,17,18 

There are many types of cold-induced injury. In this article, we review the pathophysiology of the most common forms — hypothermia and frostbite — and provide strategies for the diagnosis and management of these conditions.

## Pathophysiology

At temperatures below –10°C, wind speed increases the risk of cold-induced injuries.19 Environment Canada now reports a wind chill index in temperature equivalents. With a wind chill index of –25, there is a risk of frostbite, and with a wind chill index of –45, exposed skin will freeze in minutes ([www.msc.ec.gc.ca/education/windchill](http://www.msc.ec.gc.ca/education/windchill)). Humidity and skin moisture increase the rate of skin cooling through evaporation.20 Hypothermia develops faster with submersion in water than with exposure to cold air. Clothing with wind resistance and an insulating layer is protective.

### Underlying conditions that increase susceptibility to cold

Many underlying conditions increase a person's susceptibility to cold (Box 1). Infants have a high ratio of body surface area to mass, and elderly people have a decreased capacity for metabolic heat production and vasoconstriction.21 The amount of muscle and fat a person has may be more important than his or her age in defending against hypothermia.22 Less body fat decreases tissue insulation. Malnutrition and exertion decrease the fuel available for heat generation.23 Alcohol and sedative drugs dull mental awareness of cold and impair the judgement necessary to seek shelter or put on warm clothing. In addition, alcohol inhibits shivering, perhaps by causing hypoglycemia,24 and causes cutaneous vasodilatation, which counteracts the thermoregulatory response.25 The opioid meperidine and the α-adrenergic blocker clonidine also inhibit shivering.26 Neuroleptic drugs may predispose to hypothermia through antagonism of the serotonin receptor.27 Endocrine conditions such as hypothyroidism, adrenal insufficiency and hypoglycemia are accompanied by decreased metabolic heat production. People with diabetes mellitus may have peripheral or autonomic neuropathy. Peripheral neuropathy impairs the cold-induced nociception that might trigger retreat from cold. Both peripheral neuropathy and spinal cord damage may impair cutaneous vasoconstriction.28 Autonomic neuropathy impairs reflex peripheral vasoconstriction.29 Central nervous system degeneration, trauma or neoplasms may affect the hypothalamic thermoregulatory centre. Falls may be accompanied by hypothermia because of immobility and conductive heat loss.30 Hip fractures are more common during cold weather because of a greater risk of slipping or slower reaction times.31 Infection is common and can either be a precipitant or a complication of hypothermia.32

![Figure1](http://www.cmaj.ca/https://www.cmaj.ca/content/cmaj/168/3/305/F1.medium.gif)

[Figure1](http://www.cmaj.ca/content/168/3/305/F1)

Box 1. 

### Clinical manifestations

Cold-induced injury leads to clinical manifestations related to thermoregulation, cellular dysfunction, ischemia and edema (Fig. 1).33

![Figure2](http://www.cmaj.ca/https://www.cmaj.ca/content/cmaj/168/3/305/F2.medium.gif)

[Figure2](http://www.cmaj.ca/content/168/3/305/F2)

**Fig. 1: Cold-induced injuries such as hypothermia and frostbite lead to thermoregulatory response (e.g., shivering and increased sympathetic activity), cellular and tissue effects (e.g., membrane damage, electrolyte imbalance, endothelial injury and thrombosis) and systemic effects (e.g., shock, arrhythmia and neuromuscular dysfunction).** Photo: Chesley Sheppard

#### Thermoregulatory response

The preoptic hypothalamus controls heat conservation, triggers sympathetic activity and is activated by cold stimulation of cutaneous thermoreceptors. Sympathetic activity causes peripheral and visceral vasoconstriction, hypertension, tachycardia, ileus, and bladder atony.

#### Cellular and tissue effects

Cold damages tissues through cellular injury and vascular impairment.34 Cellular injury may be due to intracellular water crystallization, temperature-induced protein changes and membrane damage.35 Slow cooling crystallizes extracellular water, which decreases interstitial water in the liquid phase and draws water out of cells. This effect alters intracellular electrolyte concentrations, which modifies cellular protein structure.36

Vasoconstriction, endothelial injury and thromboembolism contribute to vascular insufficiency and ischemia. Inflammatory mediators such as prostaglandins may have a role as well.37 Vasoconstriction causes hypoperfusion and stasis. Endothelial injury causes thrombosis and loss of vascular integrity. Thromboembolism, from stasis and endothelial injury, may also be promoted by hemoconcentration and hyperviscosity. However, cold-induced inhibition of coagulation-cascade enzymes38 and platelet dysfunction can also cause bleeding.39

As tissues thaw, marked edema occurs because of melting of water crystals, cellular damage, loss of endothelial integrity and thrombosis. Hemorrhage may occur as well. Over time, necrosis and gangrene become apparent.

#### Systemic effects

Fluid sequestration in damaged tissues may cause volume depletion. Despite a decreased glomerular filtration rate, “cold diuresis” may occur, believed to be due to a defect in distal tubular sodium and water reabsorption, cold-induced glycosuria or inhibition of antidiuretic hormone.40 Acidemia may be caused by a combined lactic and respiratory acidosis.41

Although hypertension and tachycardia occur initially, hypothermia directly decreases cardiac contractility, which, along with volume depletion from fluid sequestration in tissues, decreases cardiac output and blood pressure and may progress to shock. Shock may also occur after rewarming, owing to capillary leakage of fluids and plasma proteins or disturbed calcium and phosphate homeostasis.42 Edema and ischemia cause muscles to stiffen. Ischemia may lead to rhabdomyolysis. Cognitive performance decreases,43 and nerve conduction slows. Patients may appear dead in cases of severe hypothermia.44

## Diagnosis

### Hypothermia

Hypothermia, defined as a core body temperature of less than 35°C, has multi-systemic clinical features (Table 1).33,45,46 It may be difficult to detect because clinical thermometers are inaccurate below 35°C.47 The presentation may be subtle in older patients32 and in patients suspected of alcohol intoxication. Although cutoff points vary, hypothermia can be classified as mild (core body temperature > 32°C and < 35°C), moderate (core temperature 28°C–32°C) or severe (core temperature < 28°C).33

View this table:
[Table1](http://www.cmaj.ca/content/168/3/305/T1)

Table 1. 

### Frostbite

Frostbite, one of the many types of local cold-induced injury (Table 2), most commonly affects the extremities.17 Although frostbite has been classified by degree,48 it may be more usefully classified as superficial or deep.49 Superficial frostbite affects the skin and subcutaneous tissues; deep frostbite also affects bones, joints and tendons. With the superficial form, rewarmed skin has clear blisters, whereas with deep frostbite the rewarmed skin has hemorrhagic blisters. Favourable prognostic factors include retained sensation, normal skin colour and clear rather than cloudy fluid in the blisters, if present. Poor prognostic features include nonblanching cyanosis, firm skin and dark, fluid-filled blisters. However, no prognostic features are entirely predictive,36 and weeks may pass before the demarcation appears between viable and nonviable tissues.50 To define the extent of ultimate tissue loss, some authors advocate triple-phase bone scanning51 or MRI scanning.52 Although such techniques may permit earlier surgical management, controlled clinical trials are lacking.

View this table:
[Table2](http://www.cmaj.ca/content/168/3/305/T2)

Table 2. 

## Management

Management demands attention to hypothermia and local cold-induced injury as well as to coexisting intoxication, trauma, infection and central nervous system disease.

### Hypothermia

Moderate to severe hypothermia is a medical emergency necessitating maintenance of airway, breathing and circulation. The core body temperature is monitored by means of an esophageal or rectal probe.

Because of the risk of arrhythmia, patients should have cardiac monitoring (needle electrodes may be necessary) and should be transferred gently. Venous access lines and arterial pressure monitoring should be established for fluid resuscitation in case of shock, which can be present initially or develop later with rewarming.41 Pulseless electrical activity may be caused by severe vasoconstriction and volume depletion. Cardiac life support for hypothermia is unique for several reasons. First, careful monitoring of the carotid pulse is needed because bradycardia is common and shivering artifact may simulate ventricular fibrillation. Second, a frozen thorax makes chest compression difficult. Although some have suggested withholding chest compressions, fearing precipitation of ventricular fibrillation,53 we believe it is reasonable to follow current guidelines for advanced cardiac life support,54 arguing for maintenance of cerebral blood flow. Third, ventricular fibrillation may not respond to electroshock or drugs until the patient is rewarmed. Fourth, if feasible, the best treatment may be cardiopulmonary bypass.46,55 On the electrocardiogram, positive deflections following the QRS complex (J, or Osborn, waves) are a clue to hypothermia, but they also may be confused for ST-segment elevation of myocardial infarction. Although J waves are more prominent with severe hypothermia, they do not reliably predict prognosis.56 Arrhythmias such as atrial fibrillation and junctional bradycardia are associated with poor prognosis,57 and asystole and ventricular fibrillation occur with severe hypothermia.

Blood work should include a complete blood count, measurement of electrolyte, glucose, creatinine and creatine kinase levels, and determination of the coagulation profile (international normalized ratio and partial thromboplastin time). Arterial blood gas analysis assesses ventilation and acid–base balance. Elevations in liver enzyme and amylase levels indicate hepatic dysfunction and pancreatitis respectively. Urinalysis and cultures of urine and blood should be done to identify infection, which can be both a precipitant and a complication of hypothermia. Measurement of serum ethanol levels detects alcohol intoxication, which is a common precipitant of hypothermia.

A chest radiograph may reveal signs of aspiration pneumonia. Other radiographs may be needed to exclude trauma (e.g., head injury, hip or spine fracture).

#### Rewarming techniques

There is a paucity of controlled trials of rewarming techniques in accidental hypothermia.58,59 Some evidence of the relative effectiveness of these techniques comes from studies of intraoperative hypothermia,60,61 experimental hypothermia,62,63 case series64 and case reports.65 Rewarming may be passive or active. Passive rewarming involves the use of blankets to cover the body and head; depending on shivering thermogenesis the warming rate may be 0.5°C–2°C per hour with this technique.

Active rewarming can be external or internal. Active external warming includes the use of heating blankets or a heated forced-air system. In a randomized trial involving 100 patients with minor trauma, of whom 80 had hypothermia, heating blankets warmed at a rate of 0.8°C per hour, as compared with a temperature drop of 0.4°C per hour with the use of wool blankets.58 In another randomized trial, involving 16 adult patients with moderate or severe accidental hypothermia, rewarming rates were 1°C per hour faster with a forced-air system than with cotton blankets.59 Warm baths are not recommended because they make monitoring difficult.33

Active internal rewarming techniques can be simple or invasive. Simple techniques may be initiated immediately and include the use of warmed intravenous fluids (heated to 43°C by microwave or heat infusion pump)66 and warmed oxygen,67 which together warm at a rate of 1°C–2°C per hour. Invasive techniques warm faster. For example, heated irrigation techniques warm at a rate of 1°C–4°C per hour and include peritoneal exchange,68 thoracostomy lavage64 and the use of esophageal warming tubes.60 Extracorporeal rewarming of blood warms at a rate of 1°C–2°C per 5 minutes and includes continuous arteriovenous or venovenous rewarming (a pulse must be present), heated hemodialysis (useful in cases of renal failure or hyperkalemia) and cardiopulmonary bypass (in cases of cardiac arrest).46

For mild hypothermia (core body temperature > 32°C), passive external rewarming is usually sufficient. However, active external rewarming may be required if patients are unable to generate heat through shivering (e.g., they are too exhausted or are elderly).

For moderate hypothermia (core temperature 28°C–32°C), active external rewarming should be applied to the trunk rather than the extremities because an “afterdrop” in core temperature may occur when blood supply to the cold periphery is recirculated to the core. External heat may also decrease the stimulus for shivering thermogenesis. For patients in whom shock occurs after rewarming,41 volume expansion with warmed intravenous fluids is required.69

For severe hypothermia (core temperature < 28°C), or for circulatory arrest, invasive internal rewarming techniques are recommended. Walpoth and associates46 described 32 hypothermic patients with circulatory arrest who underwent cardiopulmonary bypass; about half survived and had no significant long-term sequelae.

### Frostbite

In the pre-hospital care of frostbite, nonadherent wet clothing should be removed. Local rewarming should begin only if refreezing will not occur in transit. Rubbing affected areas worsens tissue damage. In hospital, rapid rewarming of a frostbitten extremity in a bath of water between 40°C and 42°C for 15 to 30 minutes may minimize tissue loss.70 Narcotics and tetanus toxoid should be given as required. Splinting and elevation of the affected part may reduce edema and promote tissue perfusion.

Management of frostbite blisters is controversial. Some advocate their removal because of the high concentrations of prostaglandin F2α and thromboxane A2 in the exudate.71 However, removal of blisters is associated with a risk of desiccation of exposed tissue. If the blisters do not interfere with range of motion, it may be reasonable to leave them intact. If they are large and need to be removed, or if they rupture, the area underneath should be débrided and covered with a topical antimicrobial and gauze.

Hospital stays for patients with deep frostbite are often prolonged because of immobility and because of the slow evolution of the injury. Escharotomy may be needed in cases of vascular impairment. Mummification and auto-amputation may occur. Surgical amputation may be required many weeks after the injury.

## The case revisited

Our patient had moderate hypothermia and deep frostbite. Mechanical ventilation was started, and he was given warmed oxygen and intravenous fluids and covered with a forced hot-air blanket. A nasogastric tube and Foley catheter were inserted. The patient was given antibiotics for pneumonia as well as thiamine. He was gently transported to the intensive care unit, where he was monitored for 24 hours. During this time he became more alert, and ventilatory support was no longer needed. His blood work and electrocardiogram findings returned to normal. Within 24 hours his feet and hands had large bullae (Fig. 2), which ruptured spontaneously over the next few days. During his second month in hospital, he had amputation of his left midfoot and right toes (Fig. 3). Social services arranged for the patient to live in a supervised group home after discharge.

![Figure3](http://www.cmaj.ca/https://www.cmaj.ca/content/cmaj/168/3/305/F3.medium.gif)

[Figure3](http://www.cmaj.ca/content/168/3/305/F3)

**Fig. 3: Surgical amputation of left midfoot and right toes 2 months after presentation with deep frostbite.** 


![Figure4](http://www.cmaj.ca/https://www.cmaj.ca/content/cmaj/168/3/305/F4.medium.gif)

[Figure4](http://www.cmaj.ca/content/168/3/305/F4)

**Fig. 2: Large bullae on hands and feet of man with moderate hypothermia and deep frostbite.** 


![Figure5](http://www.cmaj.ca/https://www.cmaj.ca/content/cmaj/168/3/305/F5.medium.gif)

[Figure5](http://www.cmaj.ca/content/168/3/305/F5)

**Fig. 2: Large bullae on hands and feet of man with moderate hypothermia and deep frostbite.** 


### Additional resources

*   Danzl DF. Accidental hypothermia. In: Marx JA, editor. *Rosen's emergency medicine*. St. Louis: Mosby; 2001. p. 1979-96.

*   Wind chill: charts and calculator. Ottawa: Environment Canada. Available: [www.msc.ec.gc.ca/education/windchill/charts\_tables\_e.cfm](http://www.msc.ec.gc.ca/education/windchill/charts_tables_e.cfm) (accessed 2002 Dec 11).

## Footnotes

*   This article has been peer reviewed.
    
    *Contributors:* Dr. Biem wrote and edited the article. Dr. Classen wrote the section on local cold-induced injury. Drs. Koehncke and Dosman retrieved literature and edited article drafts. All of the authors approved the final version of the article.
    
    *Acknowledgement:* Dr. Biem is supported by a Canadian Institutes of Health Research (CIHR) Regional Partnership Scholarship.
    
    *Competing interests:* None declared.

## References

1.  1. Hwang SW, Lebow JM, Bierrer MF, O'Connel JJ, Orav EJ, Brennan TA. Risk factors for death in homeless adults in Boston. Arch Intern Med 1998; 158:1454-60.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1001/archinte.158.13.1454&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=9665356&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000075095500011&link_type=ISI) 

2.  2. Hislop LJ, Wyatt JP, McNaughton GW, Ireland AJ, Rainer TH, Olverman G, et al. Urban hypothermia in the west of Scotland. West of Scotland Accident and Emergency Trainees Research Group. BMJ 1995;311:725.
    
    [FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYm1qIjtzOjU6InJlc2lkIjtzOjEyOiIzMTEvNzAwNy83MjUiO3M6NDoiYXRvbSI7czoyMDoiL2NtYWovMTY4LzMvMzA1LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

3.  3. Tanaka M, Tokudome S. Accidental hypothermia and death from cold in urban areas. Int J Biometereol 1991;34:242-6.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1007/BF01041837&link_type=DOI) 

4.  4. Brown WD. Heat and cold in farm workers. Occup Med 1991;6:371-89.
    
    

5.  5. Langley R. Physical hazards of animal handlers. Occup Med 1999;14:181-94.
    
    

6.  6. Hassi J, Gardner L, Hendricks S, Bell J. Occupational injuries in the mining industry and their association with statewide cold ambient temperatures in the USA. Am J Ind Med 2000;38:49-58.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1002/1097-0274(200007)38:1<49::AID-AJIM6>3.0.CO;2-3&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=10861766&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000087449200006&link_type=ISI) 

7.  7. Campbell DS. Health hazards in the meatpacking industry. Occup Med 1999; 14:351-72.
    
    

8.  8. Sallis R, Chassay CM. Recognizing and treating common cold-induced injury in outdoor sports. Med Sci Sports Exerc 1999;31:1367-73.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1097/00005768-199910000-00002&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=10527306&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000083055400002&link_type=ISI) 

9.  9. Nissen ER, Melchert PJ, Lewis EJ. A case of bullous frostbite following recreational snowmobiling. Cutis 1999;63:21-3.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=9951589&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000078230200004&link_type=ISI) 

10. 10. Weiss EA. Medical considerations for wilderness and adventure travelers. Med Clin North Am 1999;83:885-902.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=10453255&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 

11. 11. Provic P. Health aspects of Antarctic tourism. J Travel Med 1998;5:210-2.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1111/j.1708-8305.1998.tb00509.x&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=9876197&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 

12. 12. Arndt K. Inadvertent hypothermia in the OR. AORN J 1999;70:208-14.
    
    

13. 13. Rudolph R, Boyd CR. Massive transfusion: complications and their management. South Med J 1990;83:1065-70.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=2205922&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1990DZ43600021&link_type=ISI) 

14. 14. Saskatoon fires two convicted policemen. *Globe and Mail* [Toronto] 2001 Sept 21;A17.
    
    

15. 15. Factoids. In: *Wind chill fact sheet*. Ottawa: Environment Canada. Available: [www.msc.ec.gc.ca/education/windchill/fact\_quiz\_e.cfm](http://www.msc.ec.gc.ca/education/windchill/fact_quiz_e.cfm) (accessed 2003 Jan 7).
    
    

16. 16. Miller BJ, Chasmar LR. Frostbite in Saskatoon: a review of 10 winters. Can J Surg 1980;5:423-6.
    
    

17. 17. Urschel JD. Frostbite: predisposing factors and predictors of poor outcome. *J* Trauma1990;30:340-2.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1097/00005373-199003000-00015&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=2313755&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 

18. 18. Valnicek SM, Chasmar LR, Clapson JB. Frostbite in the Prairies: a 12-year review. Plast Reconstr Surg 1993;92:633-41.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=8356126&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1993LU79300012&link_type=ISI) 

19. 19. Danielsson U. Windchill and the risk of tissue freezing. J Appl Physiol 1996; 81:2666-73.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamFwIjtzOjU6InJlc2lkIjtzOjk6IjgxLzYvMjY2NiI7czo0OiJhdG9tIjtzOjIwOiIvY21hai8xNjgvMy8zMDUuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

20. 20. Holmer I. Work in the cold. Review of methods for assessment of cold exposure. Arch Occup Environ Health 1993;65:147-55.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1007/BF00381150&link_type=DOI) 

21. 21. Young AJ, Lee DT. Aging and human cold tolerance. Exp Aging Res 1997;23:45-67.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1080/03610739708254026&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=9049612&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1997WK11100004&link_type=ISI) 

22. 22. Kenney WL. Thermoregulation at rest and during exercise in healthy older adults. Exerc Sport Sci Rev 1997;25:41-76.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=9213088&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 

23. 23. Young AJ, Castellani JW, O'Brien C, Shippee RL, Tikuisis P, Meyer LG, et al. Exertional fatigue, sleep loss, and negative energy balance increase susceptibility to hypothermia. J Appl Physiol 1998;85:1210-7.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamFwIjtzOjU6InJlc2lkIjtzOjk6Ijg1LzQvMTIxMCI7czo0OiJhdG9tIjtzOjIwOiIvY21hai8xNjgvMy8zMDUuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

24. 24. Freund BJ, O'Brien C, Young AJ. Alcohol ingestion and temperature regulation during cold exposure. J Wilderness Med 1994;5:88-98.
    
    

25. 25. Kalant H, Le AD. Effects of ethanol on thermoregulation. Pharmacol Ther 1983;23:313-64.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1016/0163-7258(83)90018-9&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=6144116&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1983SP04600001&link_type=ISI) 

26. 26. Alfonsi P. Postanaesthetic shivering: epidemiology, pathophysiology, and approaches to prevention and management. Drugs 2001;61:2193-205.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.2165/00003495-200161150-00004&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=11772130&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000173217400004&link_type=ISI) 

27. 27. Schwaninger M, Weisbrod M, Schwab S, Schroder M, Hacke W. Hypothermia induced by atypical neuroleptics. Clin Neuropharmacol 1998;21:344-6.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=9844790&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 

28. 28. Sawka MN, Latzka WA, Pandolf KB. Temperature regulation during upper body exercise: able-bodied and spinal cord injured. Med Sci Sports Exerc 1989;21:S132-40.
    
    

29. 29. Scott AR, Bennett T, Macdonald IA. Diabetes mellitus and thermoregulation. Can J Physiol Pharmacol 1987;65:1365-76.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1139/y87-215&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=3304596&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1987J388000040&link_type=ISI) 

30. 30. McCallum AL. Update on trauma care in Canada. 5. Trauma and hypothermia. Can J Surg 1990;33:457-60.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=2253122&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 

31. 31. Levy AR, Bensimon DR, Mayo NE, Leighton HG. Inclement weather and the risk of hip fracture. Epidemiology 1998;9:172-7.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=9504286&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000072096000012&link_type=ISI) 

32. 32. Danzl DF, Pozos RS, Auerback PS, Glazer S, Goetz W, Johnson E, et al. Multicenter hypothermia survey. Ann Emerg Med 1987;16:1042-55.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1016/S0196-0644(87)80757-6&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=3631669&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1987J833900022&link_type=ISI) 

33. 33. Danzl DF, Pozos RS. Accidental hypothermia. N Engl J Med 1994;331:1756-60.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1056/NEJM199412293312607&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=7984198&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1994PZ26600007&link_type=ISI) 

34. 34. Su CW, Lohman R, Gottlieb LJ. Frostbite of the upper extremity. Hand Clin 2000;16:235-47.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=10791170&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000086653500008&link_type=ISI) 

35. 35. Heggers JP, Robson MC, Manavalen K, Weingarten MD, Carethers JM, Boertman JA, et al. Experimental and clinical observations on frostbite. Ann Emerg Med 1987;16:1056-62.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1016/S0196-0644(87)80758-8&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=3631670&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 

36. 36. Bracker MD. Environmental and thermal injury. Clin Sports Med 1992;11:419-36.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=1591794&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1992HQ69100012&link_type=ISI) 

37. 37. Murphy JV, Banwell PE, Roberts AH, McGrouther DA. Frostbite: pathogenesis and treatment. J Trauma 2000;48:171-8.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=10647591&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000084857400039&link_type=ISI) 

38. 38. Rohrer MJ, Natale AM. Effect of hypothermia on the coagulation cascade. Crit Care Med 1992;20:1402-5.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1097/00003246-199210000-00007&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=1395660&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1992JT93700007&link_type=ISI) 

39. 39. Valeri CR, Feingold H, Cassidy G, Ragno G, Khuri S, Altschule MD. Hypothermia induced reversible platelet dysfunction. Ann Surg 1987;205:175-81.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=3813688&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1987G090300012&link_type=ISI) 

40. 40. Broman M, Kallskog O, Nygren K, Wolgast M. The role of antidiuretic hormone in cold-induced diuresis in the anesthetized rat. Acta Physiol Scand 1998;162:475-80.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1046/j.1365-201X.1998.0314f.x&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=9597114&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000073257800006&link_type=ISI) 

41. 41. Delaney KA, Howland MA, Vassallo S, Goldfrank LR. Assessment of acid–base disturbances in hypothermia and their physiologic consequences. Ann Emerg Med 1989;18:72-82.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1016/S0196-0644(89)80319-1&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=2642674&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1989R744100015&link_type=ISI) 

42. 42. Tveita T. Rewarming from hypothermia. New aspects on the pathophysiology of rewarming shock. Int J Circumpolar Health 2000;59:260-6.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=11209678&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 

43. 43. Palinkas LA. Mental and cognitive performance in the cold. Int J Circumpolar Health 2001;60:430-9.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=11590885&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 

44. 44. Canadian Neurocritical Group. Guidelines for the diagnosis of brain death. Can J Neurol Sci 1999;26:64-6.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=10068812&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000078515900013&link_type=ISI) 

45. 45. Giesbrecht GG. Cold stress, near drowning and accidental hypothermia: a review. Aviat Space Environ Med 2000;7:733-52.
    
    

46. 46. Walpoth BH, Walpoth-Aslan BN, Mattle HP, Radanov BP, Schroth G, Schaeffer L et al. Outcome of survivors of accidental deep hypothermia and circulatory arrest treated with extracorporeal blood warming*. N Engl J Med* 1997;337:1500-5.
    
    

47. 47. Reuler JB. Hypothermia: pathophysiology, clinical settings and management. Ann Intern Med 1978;89:519-27.
    
    

48. 48. Reamy BV. Frostbite: review and current concepts. J Am Board Fam Pract 1998; 11:34-40.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NToiamFiZnAiO3M6NToicmVzaWQiO3M6NzoiMTEvMS8zNCI7czo0OiJhdG9tIjtzOjIwOiIvY21hai8xNjgvMy8zMDUuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

49. 49. Vogel JE, Dellon AL. Frostbite injuries of the hand. Clin Plast Surg 1989;16:565-76.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=2673636&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1989AJ03900014&link_type=ISI) 

50. 50. Goodwin CW, Pruitt BA. Cold injury. In: Moore EE. *Early care of the injured patient*. 4th ed. Toronto: BC Decker; 1990. p. 307-14.
    
    

51. 51. Greenwald D, Cooper B, Gottlieb BL. An algorithm for early aggressive treatment of frostbite with limb salvage directed by triple phase bone scanning. Plast Reconst Surg 1998;102:1069-74.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1097/00006534-199809040-00023&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=9734425&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000075711300023&link_type=ISI) 

52. 52. Barker JR, Haws MJ, Brown RE, Kucan JO, Moore WD. Magnetic resonance imaging of severe frostbite injuries. Ann Plast Surg 1997;38:275-9.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=9088467&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1997WP08500015&link_type=ISI) 

53. 53. Goodenberger D. Cold-induced illness. In: Ahya SN, Schaiff RA, editors. *Washington manual of medical therapeutics*. 30th ed. Philadelphia: Lippincott Williams & Wilkins; 2000. p. 541-3.
    
    

54. 54. Hazinski MF, Cummins RO, Field JM, editors. *2000 handbook of emergency cardiovascular care for healthcare providers*. Dallas: American Heart Association; 2000. p. 22.
    
    

55. 55. Gilbert M, Busund R, Skagseth A, Nilsen PA, Solbo JP. Resuscitation from accidental hypothermia of 13.7°C with circulatory arrest Lancet 2000;255:375-6.
    
    

56. 56. Vassallo SU, Delaney KA, Hoffman RS, Slater W, Goldfrank LR. A prospective evaluation of the electrocardiographic manifestations of hypothermia. Acad Emerg Med 1999;6:1121-6.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1111/j.1553-2712.1999.tb00114.x&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=10569384&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000083676200009&link_type=ISI) 

57. 57. Graham CA, McNaughton GW, Wyatt JP. The electrocardiogram in hypothermia. Wilderness Environ Med 2001;12:232-5.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=11769917&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 

58. 58. Kober A, Scheck T, Fulesdi B, Lieba F, Vlach W, Friedman A. Effectiveness of resistive compared to passive warming in treating hypothermia associated with minor trauma: a randomized controlled trial. Mayo Clin Proc 2001;76:369-75.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.4065/76.4.369&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=11322352&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000167898600006&link_type=ISI) 

59. 59. Steele MT, Nelson MJ, Sessler DI, Fraker L, Bunney B, Watson WA, et al. Forced air speeds rewarming in accidental hypothermia. Ann Emerg Med 1996;27:479-84.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1016/S0196-0644(96)70237-8&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=8604866&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1996UD07800024&link_type=ISI) 

60. 60. Rasmussen YH, Kekersfeldt G, Drenck NE. Forced-air surface warming versus oesophageal heat exchanger in the prevention of perioperative hypothermia. Acta Anaesthesiol Scand 1998;42:348-52.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1111/j.1399-6576.1998.tb04928.x&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=9542564&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 

61. 61. Borms SF, Engelen SL, Himpe DG, Suy MR, Theunissen WJ. Bair hugger forced-air warming maintains normothermia more effectively than thermo-lite insulation. J Clin Anesth 1994;6:303-7.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1016/0952-8180(94)90077-9&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=7946366&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1994PC22200006&link_type=ISI) 

62. 62. Otto RJ, Metzler MH. Rewarming from experimental hypothermia: comparison of heated aerosol inhalation, peritoneal lavage, and pleural lavage. Crit Care Med 1988;16:869-75.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=3402231&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1988P878700010&link_type=ISI) 

63. 63. Greif R, Rajek A, Laciny S, Bastanmehr H, Sessler DI. Resistive heating is more effective than metallic-foil insulation in an experimental model of accidental hypothermia: a randomized controlled trial. Ann Emerg Med 2000;35:337-45.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1016/S0196-0644(00)70051-5&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=10736119&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000086250500002&link_type=ISI) 

64. 64. Hall KN, Syverud SA. Closed thoracic cavity lavage in the treatment of severe hypothermia in human beings. Ann Emerg Med 1990;19:204-6.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1016/S0196-0644(05)81810-4&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=2301800&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1990CM07900017&link_type=ISI) 

65. 65. Iversen RJ, Atkin SH, Jaker MA, Quadrel MA, Tortell BJ, Odom JW. Successful CPR in a severely hypothermic patient using continuous thoracostomy lavage. Ann Emerg Med 1990;19:1335-7.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1016/S0196-0644(05)82300-5&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=2240735&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1990EG05900021&link_type=ISI) 

66. 66. Shields CP, Sixsmith DM. Treatment of moderate-to-severe hypothermia in an urban setting. Ann Ermerg Med 1990;19:1093-7.
    
    

67. 67. Weinberg AD. The role of inhalational rewarming in the early management of hypothermia. Resuscitation 1998;36:101-4.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1016/S0300-9572(98)00004-5&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=9571725&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000073102000003&link_type=ISI) 

68. 68. Troelsen S, Rybro L, Knudsen F. Profound accidental hypothermia treated with peritoneal dialysis. Scand J Urol Nephrol 1986;20:221-4.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.3109/00365598609024499&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=3787199&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 

69. 69. Ledingham IA, Mone JG. Treatment of accidental hypothermia: a prospective study. BMJ 1980;280:1102-5.
    
    

70. 70. Britt LD, Dascombe WH, Rodriguez A. New horizons in management of hypothermia and frostbite injury. Surg Clin North Am 1991;71:345-70.
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=2003255&link_type=MED&atom=%2Fcmaj%2F168%2F3%2F305.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1991GC73600014&link_type=ISI) 

71. 71. Robson MC, Heggers JP. Evaluation of hand frostbite blister fluid as a clue to pathogenesis. *J Hand Surg [Am]* 1981;6:43-7.