Exposure to extreme cold results in a series of predictable changes in human physiology, which can be broadly described as "everything stops working". From the coagulation cascade to the the nephron to the interactions of haemoglobin with oxygen, all things become slower and more disorganised. Ultimately, the borders of survival can be found somewhere around 13.7°C, which was the temperature of the coldest survivor (unreliable accounts suggest it may be as low as 9°C for children). Beyond this point, the defrosted organism tends to be permanently damaged by their experience.

Question 1 from the second paper of 2000 asked the candidates to list the clinical effects of severe accidental hypothermia. The defining feature of this question was the accidental nature of the injury: the college were not interested in the pathophysiology of carefully maintained therapeutic hypothermia. Then, extreme hypothermia was ignored by the college for almost twenty years, ultimately reappearing in Question 7 from the second paper of 2019, where the examiners were mainly interested in the consequences of hypothermia for the management of cardiac arrest.

Among the primary exam revision sections, there is already a chapter on the physiology of hypothermia which was probably too extensive for a last minute cram. The time-poor CICM Second Part candidate may safely ignore those details. A summary is all that is required for answering Question 1, and it is offered in a table below.  If one were to read only one peer-reviewed article, it should be the 2012 NEJM review by Brown et al. The hypothermia enthusiast may also derive some amusement from reading K.C. Wong's 1983 article,  or these two thorough reviews by Kees H. Polderman.

Definition and staging of hypothermia

Primary hypothermia is the process an otherwise healthy person being heat-depleted by exposure to some extreme cold environment. In contrast, secondary hypothermia can occur accidentally at a relatively normal temperature, and reuires the person to be in some way susceptible. Table 1 from Brown et al (2012) lists about thirty different conditions which may predispose a person to hypothermia. The notables include alcohol intoxication, hypoadrenalism, hypothyroidism, malnutrition and impaired shivering (e.g by quadriplegia or stroke).

A definition of the stages of hypothermia offered in the college model answer is as follows:

  • Mild hypothermia: 32-35 degrees
  • Moderate hypothermia: 28-32 degrees
  • Severe hypothermia: under 28 degrees

This staging system is well known, but requires the measurement of core temperature, which may not be possible in the prehospital environment. There, the Swiss system is probably going to be more useful (Durrer et al, 2003). The Swiss system classifies hypothermia according to clinical features rather than temeperature:

  • HT 1: Clear consciousness with shivering
  • HT 2: Impaired consciousness without shivering
  • HT 3: Unconsciousness
  • HT 4: Apparent death
  • HT 5: Irreversible hypothermia

The first three HT grades correlate roughly with the mild-moderate-severe temperature range; HT 4 spans the interval of 24-28 degrees and is defined as "apparent" death because historically people retrieved from frozen lakes with this sort of temperature have been asystolic, and yet went on to make reasonable neurological recoveries. The "real" death in HT 5 is associated with a temperature below 13.7 degrees, which is the lowest temperature ever survived by anybody (perhaps referring to this case report of a seven year old Swedish girl who fell into the winter sea).

Physiological consequence of hypothermia

Hypothermia results in a series of predictable physiological derangements in the human organism.The nature and severity of these derangements depends on the depth of hypothermia. A number of excellent free resources are available for this topic. K.C. Wong's 1983 article on this issue is one such resource, and I will refer to it constantly. Additionally, Kees H. Polderman has written two brilliant reviews on the topic of low temperature physiology; I am not sure whether he is the all-knowing guru of hypothermia, but he certainly has his articles available as free full-text, which earns massive brownie points with me.

The Physiological Consequences of Hypothermia

Endocrine and metabolic consequences

  • Decreased metabolism and oxygen consumption

  • Decreased carbohydrate metabolism and hyperglycaemia

  • Decreased drug metabolism and clearance

  • Essentially unchanged electrolytes

Haematological consequences

  • Increased hematocrit and blood viscosity

  • Neutropenia and thrombocytopenia

  • Coagulopathy and platelet dysfunction

Respiratory consequences

  • Decreased respiratory rate and medullary sensitivity to CO2

Acid-base changes: alkalosis and hypocapnea

  • Rise of pH with falling body temperature

  • Fall of PCO2 with falling body temperature

  • Increased oxygen solubility and O2-haemoglobin affinity

Cardiovascular consequences

  • Decreased cardiac output and bradycardia

  • QT prolongation and the J wave

  • Arrhythmias - classically AF and VF

  • Resistance to defibrillation

  • Vasoconstriction

Renal consequences

  • "Cold diuresis" due to decreased vasopressin synthesis

Central nervous system effects

  • Confusion and decreased level of consciousness

  • Shivering

  • Increased seizure threshold

Immunological consequences

  • Decreased granulocyte and monocyte activity

These effects can be represented on a large confusing diagram.

physiological effects of hypothermia at divverent temperatures

Clinical features of hypothermia

In their comments to Question 7 from the second paper of 2019, the cranky CICM examiners complained that many of the candidates "listed things that were not clinical signs e.g. ECG changes and ETCO2". These days of course the intensivist has an absolute orgy of data available at the bedside, including potentially core temperature, mixed venous oxygen saturation, cardiac output and EEG; but the examiners wanted to reach back to a simpler time. For this, an excellent review by Rosin et al (1964) was highly informative. A slightly more modern take by Aslam et al (2006) is also available for free.

Clinical examination findings

  • Observation
    • Mottled appearance
    • Cyanosis
    • Pallor
    • No shivering
    • Cold oedematous skin
  • Respiratory findings
    • Apnoea, hypoventilation or Cheyne-Stokes respiration
    • Creps on auscultation, suggestive of pulmonary oedema
  • Cardiovascular findings
    • Sinus bradycardia, AF or asystole
    • Hypotension
    • Weak thready pulse, or altogther impalpable peripheral pulses
    • Poor capillary refill
  • Neurological findings
    • Coma (unresponsiveness below 32°C)
    • Increased muscle tone
    • Sluggish deep tendon reflexes
    • Extensor plantar responses
    • Loss of cranial nerve reflexes (with fixed mid-dilated pupils)
  • Gastrointestinal findings
    • Absent bowel sounds
    • Abdominal tenderness (hypothermia-induced pancreatitis)
  • Renal findings
    • Decreased urine output

Resuscitation of the severely hypothermic patient

The ARC ALS2 manual is perhaps the best reference point for resuscitation of hypothermia. They offer a list of important differences in the initial management of a hypothermic patient in cardiac arrest. In addition to this resource, Chris Nickson's LITFL page on hypothermia is an excellent overview of resuscitation from hypothermia, including all the relevant techniques.

Issues in prehospital management  and cardiopulmonary resuscitation

  • When checking for pulse, one should be patient. Profound bradycardia and the decrease in cardiac contractility associated with severe hypothermia may result in a feeble slow pulse, which can be easily missed.
  • Resuscitation should be attempted on all patients in whom there is no evidence of lethal traumatic injury, fatal illness, or prolonged asphyxia.
  • Realistically, one should attempt CPR in all patients, unless the chest is actually incompressible because they are frozen solid.
  • Use the same ventilation and chest compression rates as for a normothermic patient.
  • CPR should continue until the patient has rewarmed to at least 35 degrees.
  • A special low-reading thermometer is required to measure the correct core temperature.
  • Defibrillation is unlikely to be effective below 28°C.
  • Drug metabolism has been slowed significantly; one should not use any resuscitation drugs until the temperature is at least 30°C.
  • Between 30°C and 35°C drug metabolism is still slowed, and adrenaline should be given at half the usual rate, i.e. every 4 cycles.
  • Some attempts should be made to prevent the patient from getting any colder; for example, having just fished them out of a body of water, the rescuers should make some attempt to dry the patient, so that they do not lose any more heat by evaporation.

The phenomena of afterdrop and rescue collapse

  • Afterdrop is the mythical phenomenon of continued core cooling after rescue. It is supposed to happen when circulation is restored following a prolonged period of poor or absent perfusion. Suddenly, cold blood from the peripheries returns to the heart, thereby dropping the core temperature. Apparently, it has been documented in artificial cooling experiments and inferred from discrepancies between rectal and core temperatures. Brown et al (2012) mention that it has never been reported in the era of accurate oesophageal temperature measurement and active rewarming.
  • Rescue collapse is the very real non-mythical possibility that the previously stable hypothermic  patient will suddenly arrest when you fiddle with them. This tends to happen as they rewarm (and develop circulatory collapse from vasodilation). The other possibiluty is cardiac arrhythmia: pProcedures at this early stage (with a temperature around 24-28°C) could possibly trigger VF. The patient is more likely to be asystolic anyway. Fear of VF should not deter rescuers from intubating the patient.

Issues in emergency hospital management

  • Rewarming is the priority.
  • It is important to remember that the heart is irritable, and tickling it with CVC guidewires may precipitate "rescue collapse".
  • With CPR in progress and a very low body temperature one may consider starting VA ECMO in the emergency department.
  • The ideal gold standard method of measuring core temperature is with a PA catheter
  • The next best measurement can be taken from the lower third of the oesophagus

Options for rewarming

  • Passive rewarming:
    • The conscious patient should be rewarmed passively (i.e. allowed to shiver).
    • Removing wet clothes can prevent the loss of heat
    • A reflective blanket can help the retention of heat
  • Active surface warming
    • Warm blankets
    • Chemical heat packs
    • Forced air surface warming (eg. Bair Hugger)
    • Arteriovenous anastomosis reheating (essentially, putting their hands into some warm water)
  • Minimally invasive core warming
    • Heated humidified air in the ETT
    • Warm intravenous fluids (but this is limited by the volume you would be comfortable infusing)
  • Invasive body cavity warming
    • Thoracic lavage: warm fluid administered via chest tubes into the pleural cavity; in via a midaxillary tube, out via a midclavicular tube.
    • Similarly, you can lavage the peritoneal cavity and the bladder
  • Extracorporeal circuit rewarming
    • Could use a dialysis circuit, but .. why would you.
    • ECMO has the strongest evidence in this context; it is the preferred method.


Wong, K. C. "Physiology and pharmacology of hypothermia." Western Journal of Medicine 138.2 (1983): 227.

Guly, Henry. "History of accidental hypothermia." Resuscitation 82.1 (2011): 122-125.

Polderman, Kees H. "Application of therapeutic hypothermia in the intensive care unit." Intensive care medicine 30.5 (2004): 757-769.

Polderman, Kees H. "Mechanisms of action, physiological effects, and complications of hypothermia." Critical care medicine 37.7 (2009): S186-S202.

Silfvast, Tom, and Ville Pettilä. "Outcome from severe accidental hypothermia in Southern Finland—a 10-year review." Resuscitation 59.3 (2003): 285-290.

Brown, Douglas JA, et al. "Accidental hypothermia." New England Journal of Medicine 367.20 (2012): 1930-1938.

Durrer, Bruno, Hermann Brugger, and David Syme. "The medical on-site treatment of hypothermia: ICAR-MEDCOM recommendation." High altitude medicine & biology 4.1 (2003): 99-103.

Romlin, Birgitta S., et al. "Excellent outcome with extracorporeal membrane oxygenation after accidental profound hypothermia (13.8° C) and drowning." Critical care medicine 43.11 (2015): e521-e525.

van der Voort, Peter, and Durk Zandstra. "Hospital Rewarming of Hypothermic Victims." Drowning. Springer Berlin Heidelberg, 2014. 881-891.

Wong, K. C. "Physiology and pharmacology of hypothermia." Western Journal of Medicine 138.2 (1983): 227.

Guly, Henry. "History of accidental hypothermia." Resuscitation 82.1 (2011): 122-125.

Polderman, Kees H. "Application of therapeutic hypothermia in the intensive care unit." Intensive care medicine 30.5 (2004): 757-769.

Polderman, Kees H. "Mechanisms of action, physiological effects, and complications of hypothermia." Critical care medicine 37.7 (2009): S186-S202.

Sessler, Daniel I. "Complications and treatment of mild hypothermia."Anesthesiology 95.2 (2001): 531-543.

Westenskow, Dwayne R., et al. "Physiologic Effects of Deep Hypothermia and Microwave Rewarming Possible Application for Neonatal Cardiac Surgery."Anesthesia & Analgesia 58.4 (1979): 297-301.

Westenskow, Dwayne R., et al. "Physiologic Effects of Deep Hypothermia and Microwave Rewarming Possible Application for Neonatal Cardiac Surgery."Anesthesia & Analgesia 58.4 (1979): 297-301.

van den Broek, Marcel PH, et al. "Effects of hypothermia on pharmacokinetics and pharmacodynamics: a systematic review of preclinical and clinical studies."Clinical pharmacokinetics 49.5 (2010): 277-294.

Otis, A. B., and James Jude. "Effect of body temperature on pulmonary gas exchange." American Journal of Physiology--Legacy Content 188.2 (1957): 355-359.

Bickford, A. F., and R. F. Mottram. "Glucose metabolism during induced hypothermia in rabbits." Clinical science 19 (1960): 345.

Melhuish, Tracey. "Linking hypothermia and hyperglycemia." Nursing Management 40.12 (2009): 42-45.

Müllner, Marcus, et al. "Blood glucose concentration after cardiopulmonary resuscitation influences functional neurological recovery in human cardiac arrest survivors." Journal of Cerebral Blood Flow & Metabolism 17.4 (1997): 430-436.

Tortorici, Michael A., Patrick M. Kochanek, and Samuel M. Poloyac. "Effects of hypothermia on drug disposition, metabolism, and response: A focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system."Critical care medicine 35.9 (2007): 2196-2204.

Michelsen, Luis G., et al. "The pharmacokinetics of remifentanil in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass."Anesthesia & Analgesia 93.5 (2001): 1100-1105.

Osborn JJ: Experimental hypothermia: Respiratory and blood pH changes in relation to cardiac function. Am J Physiol 1953; 175:389-398

Severinghaus JW, Stupfel M, Bradley AF: Alveolar dead space and arterial to end tidal carbon dioxide differences during hypothermia in dog and man. J Appl Physiol 1957; 10:349-355

Rittenhouse, Edward A., et al. "Deep hypothermia in cardiovascular surgery."The Annals of thoracic surgery 17.1 (1974): 63-98.

Spurr, G. B., and GEORGE BARLOW. "Influence of prolonged hypothermia and hyperthermia on myocardial sodium, potassium and chloride.Circulation Research 7.2 (1959): 210-218.

Chen, R. Y., and S. Chien. "Hemodynamic functions and blood viscosity in surface hypothermia." American Journal of Physiology-Heart and Circulatory Physiology 235.2 (1978): H136-H143.

Nose, H. "Transvascular fluid shift and redistribution of blood in hypothermia."The Japanese journal of physiology 32.5 (1982): 831.

Villalobos TJ, Adelson E, Riley PA Jr, et al: A cause of thrombocytopenia and leukopenia that occurs in dogs during deep hypothermia. J Clin Invest 1958; 37:1-7

Chen, R. Y., A. E. Wicks, and S. Chien. "Hemoconcentration induced by surface hypothermia in infants." The Journal of thoracic and cardiovascular surgery 80.2 (1980): 236.

Chen, R. Y., and S. Chien. "Plasma volume, red cell volume, and thoracic duct lymph flow in hypothermia." American Journal of Physiology-Heart and Circulatory Physiology 233.5 (1977): H605-H612.

Martini, Wenjun Zhou. "Coagulopathy by hypothermia and acidosis: mechanisms of thrombin generation and fibrinogen availability." The Journal of Trauma and Acute Care Surgery 67.1 (2009): 202-209.

Martini, Wenjun Znou. "The effects of hypothermia on fibrinogen metabolism and coagulation function in swine." Metabolism 56.2 (2007): 214-221.

Martini, Wenjun Z., et al. "Independent contributions of hypothermia and acidosis to coagulopathy in swine.The Journal of Trauma and Acute Care Surgery 58.5 (2005): 1002-1010.

Polderman, Kees H. "Hypothermia and coagulation." Critical Care 16.Suppl 2 (2012): A20.

Michelson AD, MacGregor H, Barnard MR, Kestin AS, Rohrer MJ, Valeri CR: Hypothermia-induced reversible platelet dysfunction. Thromb Haemost 1994, 71:633-640.

Ashwood, E. R., G. Kost, and M. Kenny. "Temperature correction of blood-gas and pH measurements." Clinical chemistry 29.11 (1983): 1877-1885.

Bacher, Andreas. "Effects of body temperature on blood gases." Applied Physiology in Intensive Care Medicine. Springer Berlin Heidelberg, 2006. 33-36.

Bradley, A. F., M. Stupfel, and J. W. Severinghaus. "Effect of temperature on PCO2 and PO2 of blood in vitro." Journal of applied physiology 9.2 (1956): 201-204.

Morrison, Laurie J., et al. "Strategies for Improving Survival After In-Hospital Cardiac Arrest in the United States: 2013 Consensus Recommendations A Consensus Statement From the American Heart Association." Circulation127.14 (2013): 1538-1563.

AIBIKI, MAYUKI, et al. "Effect of moderate hypothermia on systemic and internal jugular plasma IL-6 levels after traumatic brain injury in humans."Journal of neurotrauma 16.3 (1999): 225-232.

Salman, H., et al. "Hypothermia affects the phagocytic activity of rat peritoneal macrophages." Acta physiologica scandinavica 168.3 (2000): 431-436.

KUHN, LESLIE A., and JOHN K. TURNER. "Alterations in pulmonary and peripheral vascular resistance in immersion hypothermia." Circulation research7.3 (1959): 366-374.

Morgan, MARY L., et al. "Mechanism of cold diuresis in the rat." American Journal of Physiology-Renal Physiology 244.2 (1983): F210-F216.

Zager, Richard A., et al. "Degree and time sequence of hypothermic protection against experimental ischemic acute renal failure." Circulation research 65.5 (1989): 1263-1269.

Gollan, Frank. "Physiology of deep hypothermia by total body perfusion." Annals of the New York Academy of Sciences 80.2 (1959): 301-314.

Adolph, E. F., and J. Goldstein. "Survival of rats and mice without oxygen in deep hypothermia." Journal of Applied Physiology 14.4 (1959): 599-604.

Donald, David E., and Frederick WL Kerr. "The response of dogs to perfusion and arrest of circulation at near zero cerebral temperatures." Journal of Surgical Research 4.6 (1964): 243-252.

Gilbert, Mads; Gilbert M; Busund R; Skagseth A; Nilsen P; Solbo J (2000). "Resuscitation from accidental hypothermia of 13.7°C with circulatory arrest". The Lancet 355 (9201): 375–376.

Davis, Michael D., et al. "AARC Clinical Practice Guideline: Blood Gas Analysis and Hemoximetry: 2013." Respiratory care 58.10 (2013): 1694-1703.

Angelakos, E. T., and A. H. Hegnauer. "Pharmacological agents for the control of spontaneous ventricular fibrillation under progressive hypothermia." Journal of Pharmacology and Experimental Therapeutics 127.2 (1959): 137-145.

Bjørnstad, H., Pal M. Tande, and Helge Refsum. "Cardiac electrophysiology during hypothermia. Implications for medical treatment." Arctic medical research 50 (1991): 71.

Khan, Jamal Nasir, Neeraj Prasad, and James Michael Glancy. "QTc prolongation during therapeutic hypothermia: are we giving it the attention it deserves?."Europace 12.2 (2010): 266-270.

Riaz, Asim, et al. "Safety of therapeutic Hypothermia in post VF/VT Cardiac Arrest patients." The Irish Medical Journal 106.5 (2013).

Hoek, Terry L. Vanden, et al. "Part 12: Cardiac Arrest in Special Situations 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care." Circulation 122.18 suppl 3 (2010): S829-S861.

Boddicker, Kimberly A., et al. "Hypothermia improves defibrillation success and resuscitation outcomes from ventricular fibrillation." Circulation 111.24 (2005): 3195-3201.

Thomas, Richard, and Chris J. Cahill. "Successful defibrillation in profound hypothermia (core body temperature 25.6 C).Resuscitation 47.3 (2000): 317-320.

Mallet, M. L. "Pathophysiology of accidental hypothermia." Qjm 95.12 (2002): 775-785.

BUCKLEY, JOSEPH J., OTTO K. BOSCH, and MARVIN B. BACANER. "Prevention of ventricular fibrillation during hypothermia with bretylium tosylate."Anesthesia & Analgesia 50.4 (1971): 587-593.

Bjørnstad, Hanne, et al. "Effect of bretylium tosylate on ventricular fibrillation threshold during hypothermia in dogs." The American journal of emergency medicine 12.4 (1994): 407-412.

Somerville, Walter. "The Effect of hypothermia on atrial fibrillation and other arrhythmias." British heart journal 22.4 (1960): 515.

Strohmer, Bernhard, and Maximilian Pichler. "Atrial fibrillation and prominent J (Osborn) waves in critical hypothermia." International journal of cardiology 96.2 (2004): 291-293.

Fleming, Peter R., and Frank H. Muir. "Electrocardiographic changes in induced hypothermia in man." British heart journal 19.1 (1957): 59.

Lundgren, Johan, et al. "Hyperthermia aggravates and hypothermia ameliorates epileptic brain damage." Experimental brain research 99.1 (1994): 43-55.

Schmitt, F. C., et al. "Anticonvulsant properties of hypothermia in experimental status epilepticus." Neurobiology of disease 23.3 (2006): 689-696.

Rosin, A. J., and A. N. Exton-Smith. "Clinical features of accidental hypothermia, with some observations on thyroid function.British medical journal 1.5374 (1964): 16.

Aslam, Ahmed Faraz, et al. "Hypothermia: evaluation, electrocardiographic manifestations, and management." The American journal of medicine 119.4 (2006): 297-301.