This morning, Dr. Matthew Leveno, director of the Parkland Medical ICU and youngest winner of the housestaff teaching award, gave an incredible grand rounds presentation about the history, pathophysiology, diagnosis, and management of severe alcohol withdrawal. Take a look below for some important information.
Alcohol abuse is a common problem globally, and it is estimated to result in 2.5 million deaths annually. Of the drugs of abuse, alcohol is the most common, with an estimated 18.3 million individuals dependent on it in the United States. Alcohol abuse has a prevalence of 22.4% in a hospitalised general medical population. In one analysis, alcohol-related admissions accounted for 9% of admissions to a population of mixed medical intensive care unit (ICU) and surgical ICU patients; in addition these patients accounted for 13% of total ICU costs. One population with a particularly high rate of alcohol abuse are trauma patients, with estimates of prevalence ranging from 31% to 70% across centers.
Alcohol-related complications in the ICU affect nearly every organ system (Table 1). Alcohol abuse in patients is associated with increased length of stay, outpatient pneumonia and an almost three times higher incidence of healthcare-associated infections.
Clinical Manifestations and Diagnosis
The gold standard for the diagnosis of alcohol withdrawal syndrome (AWS) is the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. It requires that a patient’s alcohol usage is heavy and prolonged, there is a cessation in alcohol intake and also that there is no other general condition that better accounts for the diagnosis.
AWS has four clinical stages: (1) autonomic hyperactivity, (2) hallucinations, (3) neuronal excitation and (4) delirium tremens (Table 2). Patients generally start the withdrawal process at 5 h, with hallucinations at 24 h, and delirium at 48 h; it is rare for this to persist for more than 120 h.
AWS is the result of a disruption of the delicate neurochemical balance that is controlled via inhibitory and excitatory neurotransmitters. The principal inhibitory neurotransmitter is gamma aminobutyric acid (GABA), which exerts its effect on the GABA-A neuroreceptor. A principal excitatory transmitter is glutamate, which affects the N-methyl-D-aspartate neuroreceptor. With chronic alcohol exposure, the brain has a tolerance to the effects of the alcohol due to down-regulation of the GABA-A receptor over time. This down-regulation may occur by modification of the GABA-A receptor in the alpha 1 subunit to make the receptor less susceptible to the effects of alcohol exposure.
The severity of the symptoms of AWS should direct the appropriate pharmacotherapeutic interventions. The patient’s comorbidities, other active diagnoses as well as exposure to any other drug of abuse should also be factored into the development of their treatment plan.
Benzodiazepines have historically been the mainstay pharmacologic intervention of AWS; they are generally considered to be the ‘gold standard’ treatment. It has been shown that sedative-hypnotic agents such as benzodiazepines, in comparison with other agents, reduce mortality and control the symptoms of AWS. All benzodiazepines have the same mechanism of action on the GABA receptor. Several agents have been used for AWS including chlordiazepoxide, lorazepam, valium, oxazepam and midazolam. Lorazepam is suggested as the benzodiazepine of choice for AWS due to its intermediate half-life, which balances a smooth withdrawal, with the potential for delayed metabolism in those with impaired hepatic function such as geriatric or cirrhotic patients.
Benzodiazepines were traditionally administered to AWS patients in a fixed dose regimen. There has now been over two decades of experience accumulated with the use of on demand or ‘symptom-triggered’ dosing of benzodiazepines for AWS treatment. This method of symptom-triggered dosing relies on the Clinical Institute Withdrawal Assessment for Alcohol [CIWA-A or CIWA-Ar (revised)]. In studies, the symptom-triggered dosing method results in both a decrease in the amount of benzodiazepines administered and a shortened duration of withdrawal symptom. While the symptom-triggered approach has these advantages, there is quite limited experience of the use of this approach in critical care settings, and it has not shown the same benefit across all studies.
The alpha-2-agonist, clonidine, has traditionally been used to blunt the sympathomimetic effects of AWS. This has been done outside critical care settings. While intravenous clonidine is available in Europe, it is not currently available for use in the United States. This has resulted in intensivists to turn to dexmedetomidine, a drug derived from clonidine. Dexmedetomidine is not FDA-approved for AWS, but rather for procedural conscious sedation and sedation for mechanical ventilation
Beta-blockers have been used as an adjunctive agent in AWS. Given the sympathetic outflow associated with autonomic hyperactivity, betablockers are a direct antagonist. This medication can be administered either orally or intravenously, and it serves to normalise tachycardia and hypertension in non-agitated patients that are otherwise comfortable. In a randomised trial by Gottlieb, atenolol in patients with AWS served to make a more rapid resolution of their vital sign abnormalities and clinical signs such as tremor. Betablockers serve an important role as part of a multimodal pharmacological plan, but they should never be used without a GABA agent.
Haloperidol is a phenothiazine that is commonly prescribed in ICUs for acute agitation. It has the benefit of haemodynamic neutrality, and the possible complications of an elevation in the QTc interval and tardive dyskinesia. While haloperidol is an adjunctive agent in AWS setting, it is particularly useful for the symptoms related to delirium. Most frequently, it is used in patients with underlying psychiatric disorders.
AWS continues to challenge clinicians in critical care settings. Keys to good outcomes in this area include early recognition of the disorder and rapid implementation of appropriate pharmacologic treatment. The range of symptoms represents a spectrum; the pharmacologic strategy needs to match the severity that the patient is experiencing. While some patients have a good therapeutic response to a single benzodiazepine agent, more severe cases may require a multimodality therapy. The current protocol used at our institution is presented in Table 3. With a stepwise protocol-driven plan, intubation and mechanical ventilation can be avoided except in the more severe cases, contributing to better outcomes in terms of length of stay and VAP.
Modified from: DeMuro JP. Alcohol withdrawal syndromes in the critically ill. OA Alcohol 2013 Feb 01;1(1):1. Under the terms of the Creative Commons Attribution License (CC-BY).
In 2011, the definition of acute respiratory distress syndrome (ARDS) was updated by the European Society of Intensive Care Medicine with endorsement from the American Thoracic Society and the Society of Critical Care Medicine. Referred to as the “Berlin Definition” because the panel had met in Berlin, Germany. Check out the table below from JAMA outlining the definition of ARDS!
- Remove clothing
- Dry patient
- Cover with blankets / space blanket
- Provide warm sugary drinks
- Forced Air Rewarmer (eg: Bair Hugger) ‐ to trunk only to reduce core temperature afterdrop.
- Arctic Sun (for moderate / severe).
- Warmed fluids (D5 NS @ 40-42 C) – Initially 250-500mL bolus, repeat based on clinical
- Warm, humidified oxygen. By facemask or consider CPAP – by ETT if intubated.
- Peritoneal Lavage – 2 liters of diasylate @ 40 – 45 C, remove after 20-30 minutes. Rewarming rate of 1-3 C / hr.
- Body cavity lavage – Through Foley or NGT / OGT. 500mL boluses or continuous Consider risk of fluid / electrolyte shifts.
- Closed Thoracic Lavage – 2 large bore (38-40 fr) chest tubes in each hemithorax (one at mid clavicular line @ 2nd / 3rd interspace, second at post. axillary line @ 5th / 6th interspace). Infuse warmed (40-42 C) saline and drain though posterior tube.
- Thoracotomy with Mediastinal Lavage – 1-2 liters of warmed NS to mediastinum, remove after 1-2 minutes. May utilize cardiac massage and internal defibrillation. Highly Invasive, requires disposition to OR.
- Continuous Venovenous Rewarming (CVVR) – 2-3 C / hr.
- Continuous Arteriovenous Rewarming (CAVR) – 3-4 C / hr. Requires adequate MAP. Can be performed in ED with proper equipment.
- Hemodialysis – 3-4 C / hr. Requires adequate MAP. Possible to correct electrolyte and toxic abnormalities. Requires dialysis staff.
- Cardiopulmonary Bypass – Most rapid rewarming (8-10 C / hr). Provides full cardiopulmonary support for hemodynamically unstable patients.
Created by Jack Gervais MD, Matt Sholl, MD, and Jeff Holmes MD at Maine Medical Center
As the big winter chill continues, so does our series on cold-weather medicine!
Frostbite is a freezing, cold thermal injury, which occurs when tissues are exposed to temperatures below their freezing point (typically −0.55°C, but can occur as high as 2°C) for a sustained period of time .
Immediate and general care for those admitted with frostbite
On arrival to a hospital setting, it is vitally important to fully reassess the patient. Underlying unstable comorbidities, trauma or hypothermia must be assessed and managed before frostbitten extremities are treated. Moderate or severe hypothermia should be corrected to bring core temperature above 35°C before initiating frostbite warming [14,17] (recommendation grade 1C).
A detailed history should include time the injury occurred, either early (<24 h) or late (>24 h) as this will dictate some treatment options. History of the conditions surrounding the injury (i.e. temperature, wind chill, wet/dry exposure, duration and use or not use of thermal protection) can also be helpful. Any pre-hospital treatment and time of rewarming, if applicable, should be noted .
Remove jewellery from affected digits early as significant swelling can be expected post thaw, and vascular compromise may occur with tight rings, etc. . Examination of the frostbitten tissue after rewarming can predict depth of injury more accurately than examination before thawing. There may be different depths of injury even on digits of the same extremity, so careful examination and documentation in either diagram form or with photographs are useful. Clinical photography obviates the need for repeated removal of dressings for each consultant examination, reducing pain and risk of infection. Loss of sensation after rewarming is a poor prognostic indicator, and the converse is also true.
There exist a number of frostbite classifications to assess the severity and predict likely outcome. Cauchy et al. have suggested a useful classification consisting of four grades and three key descriptors (Table 2) . At 24 h post insult after rewarming, a grade can be attributed according to the level of any visible lesion. Then, at day two, a technetium99 triple-phase bone scan should be performed on the more severe injuries (see Imaging section) and a further assessment of any blisters undertaken. Injuries receiving grade 1 classification require no hospitalisation and full recovery is likely. Grades 2 through 4 injuries require hospitalisation and full investigation as they are associated with an increased risk of amputation and long-term sequelae .
Rehydration can be oral or intravenous, and depending upon severity and ability of the patient to tolerate oral fluids. High altitude increases the risk of dehydration. If the patient is also hypothermic, dehydration may be compounded by cold diuresis due to suppression of antidiuretic hormone, requiring correction with warmed intravenous fluids (recommendation grade 1C).
Rewarming is beneficial if there remains a partially or fully frozen part and is ideally accomplished using a whirlpool bath set at 38°C with added antiseptic solution (povidone iodine or chlorhexidine). The Wilderness Medical Society and State of Alaska Cold Injury Guidelines recommend a temperature of 37°C–39°C, which decreases the pain experienced by the patient whilst only slightly slowing rewarming time [14,15]. The time period for optimal rewarming varies from 15–30 min up to 1 h . Rewarming should continue until a red/purple colour appears and the extremity tissue becomes pliable . Active motion during the rewarming process is beneficial, but care should be taken to prevent the extremity from touching the sides of the whirlpool. It is important to provide good analgesic cover and is likely to include narcotic medication (recommendation grade 1B).
Blisters and dressings
It is important to note the type of any blisters that form; they can be clear/cloudy or haemorrhagic in nature. There is current debate as to whether blisters should be de-roofed as this may desiccate the underlying tissue, but there is little comparative data to settle this argument. The recommended practice is that of selective drainage of clear/cloudy blisters by needle aspiration (especially if bullae restrict movement) and to leave haemorrhagic blisters alone . However, we would suggest that all blisters are debrided in the hospital (not in the field) because we believe it assists with wound care. Severe injuries require detailed assessment, and it may be that this appraisal and debriding of blisters may be best performed under a general anaesthetic (recommendation grade 2C).
Topical aloe vera cream or gel (a potent anti-prostaglandin agent) should then be applied to thawed tissue before dressings are applied  (recommendation grade 2C). Splinting, elevating and wrapping the affected part in a loose, protective dressing with padding between affected patient’s digits are ideal (recommendation grade 1C).
The role of prophylactic antibiotics is not proven but should be considered in more severe injuries (grades 3 and 4) and, in particular, when associated with significant oedema or malnutrition (homeless, chronic alcohol abuse or return from extreme altitude). Systemic antibiotics are required in the presence of proven infection, trauma or cellulitis (recommendation grade 1C).
The need for tetanus toxoid administration should be determined by following standard guidelines, as frostbite injuries are not inherently tetanus-prone wounds (recommendation grade 1C).
Analgesia and NSAIDs
Rewarming the extremities can become extremely painful, so use of non-steroidal anti-inflammatory drugs or opiates should be administered. Oral ibuprofen 12 mg/kg divided over two daily doses provides systemic anti-prostaglandin activity that limits the cascade of inflammatory damage. This dose can be increased to a maximum of 2,400 mg/day if the patient is experiencing pain and can be continued until wounds are healed or amputation occurs. A dose of 400 mg BID is a practical regime on which to start most patients, and this can then be increased to 600 mg QDS as pain dictates. If aspirin has not been given in the field (providing no contraindications), 300 mg once a day can be given  (recommendation grade 2C).
Iloprost is a prostacyclin analogue with vasodilatory properties that mimic the effects of a sympathectomy . It may also affect platelet aggregation and therefore decrease microvascular occlusion. Unfortunately, intravenous iloprost is not currently available in the USA.
In 1994, Groechenig published his experience in treating four cases of severe frostbite with iloprost . The results were promising, with no patients requiring amputation; however, since these initial findings were published, the focus has shifted towards rTPA, with no further data published on iloprost use until a recent paper by Cauchy et al . In a randomized controlled trial designed to compare the efficacy of iloprost and rTPA, 47 patients were included with a total of 407 digits at risk. All patients underwent identical initial treatment and rewarming and then were randomized into three arms: buflomedil, iloprost or iloprost and IV rTPA. The risk of amputation on the buflomedil arm was the greatest with 39.9% of at-risk digits requiring amputation. In the iloprost and iloprost/rTPA arms, the amputation rates were 0% and 3.1%, respectively .
The administration of iloprost is via an IV infusion. The dose used is 0.5 up to a maximum of 2 ng/kg/min , incrementally increased every 30 min by 0.5 ng/kg/min until the patient develops unacceptable or intolerable side effects (headache and hypotension). The rate is then reduced by 0.5 ng/kg/min. The infusion is continued for 6 h/day for 5–8 days at the previously determined maximal rate a patient can tolerate.
The advantages of iloprost compared to rTPA are that it does not require radiological intervention during administration and can be managed on a general or vascular ward. Iloprost can be used when there is a history of trauma or when the exposure occurred over 24 h ago, unlike rTPA where trauma is a contraindication and efficacy is reduced beyond 24 h. Figure 3b gives a stepwise approach to iloprost administration (recommendation grade 1B).
Death from exposure to cold has been recognised for thousands of years but hypothermia as a clinical condition was not generally recognised until the mid-20th century and then only in extreme conditions such as immersion in cold water or snow. In the UK, hypothermia in less extreme conditions was not generally recognised until the 1960s. Recognition of hypothermia required the temperature to be measured and this did not become a clinical tool until the late 1800s and it was not used routinely until the early 1900s. Although John Hunter and James Curry did some physiological experiments in the 1700s, detailed physiological experiments were not done until the early 20th century and the use of therapeutic hypothermia for malignancy and in anaesthesia in the 1930s and 1940s provided more impetus for investigating the physiology of hypothermia in humans and familiarising the medical profession with measuring core temperatures.
In the literature of the Heroic Age of Antarctic exploration (1895–1922) it is striking that there is no mention of hypothermia. The word itself was never used and the only medical reference to anyone suffering from hypothermia is a brief mention in Marshall’s medical report on Shackleton’s first expedition. He wrote that “on the southern journey … our temperatures were subnormal”.1 Wild says that when Marshall “took … our temperatures, his clinical thermo was not marked low enough to take any except mine. The other three were therefore below 94.2° which spells death at home”.2 This equates to 34.6 °C and presumably was an oral or axillary temperature and so was only mild hypothermia but this comment indicates that it was known that people could die if their temperature became too low.
The only medical description of hypothermia in the medical reports of the expeditions is a brief description by Gourdon (who went on the two French expeditions) of what he calls “congelation generale” which he describes as being rare.3
And yet hypothermia almost certainly occurred. On Scott’s second expedition, Atkinson got lost in bad weather. Scott wrote: “He was badly frostbitten … and though a good deal confused, as men always are on such occasions, he was otherwise well… His tale is confused, but … the fact that he did not [hit land as he intended], but attempted to wander straight on, is clear evidence of the mental condition caused by that situation. There can be no doubt that in a blizzard a man has not only to safeguard the circulation in his limbs, but must struggle with a sluggishness of brain and an absence of reasoning power which is far more likely to undo him… It is a rambling tale to-night and a half thawed brain”.4 Not only does this seem to describe hypothermia but Scott recognised the behaviour of a cold person.
The aim of this paper is to describe the history of hypothermia, exploring why it was accepted that people could die of cold and yet hypothermia does not seem to have been recognised as a disease.
2. Types of hypothermia
Three types of accidental hypothermia are recognised. Acute hypothermia (often called immersion hypothermia) is caused by sudden exposure to cold such as immersion in cold water or a person caught in a snow avalanche. Exhaustion hypothermia is caused by exposure to cold in association with lack of food and exhaustion such that heat can no longer be generated. Chronic hypothermia comes on over days or weeks and mainly affects the elderly. Mixed forms also occur, e.g. the exhausted soldier who collapses into snow.
3. History of hypothermia
All three forms of hypothermia appear to have been recognised since ancient times. In 492 BC Mardonios, a Persian general, was sailing against the Greeks when he encountered bad weather, losing about 300 ships and 20,000 men. Herodotus, said that “… some were seized by these [sea monsters] and so perished, while others were dashed against the rocks; and some of them did not know how to swim and perished for that cause, others again by reason of cold”.5
Hippocrates is often quoted as describing hypothermia. For example: “cold causes fits, tetanus, gangrene and feverish shivering fits … Cold is bad for the bones, teeth, nerves, brain and the spinal cord…”.6
This is capable of several interpretations and it must be uncertain whether Hippocrates was describing hypothermia, but death from cold has been known for over 2000 years. This was particularly recognised by the military. In 218BC Hannibal lost 20,000 men crossing the Alps and cold injuries were described in many other military campaigns including, for example, the American War of Independence, The American Civil War and the Crimean War,7 and 8 though many of the early descriptions of cold injury did not differentiate between frostbite and hypothermia.
Perhaps the best-known example of the disruption of a military campaign by cold was Napoleon’s retreat from Moscow in 1812. In this campaign the hypothermia was superimposed on hunger, exhaustion and disease. Many would have had frostbite. The best-known descriptions of cold injury are by Napoleon’s surgeon, Larrey9 but perhaps the best descriptions of hypothermia are by Moricheau-Beaupré, another French doctor.10 He describes the fate of the soldiers: “some, pale and depressed by inanition swooned away and died, stretched on the snow. Others … were seized by shivering to which quickly succeeded languor and propensity to sleep. They were seen walking insensible and ignorant where they went: scarcely could you succeed in making them understand a few words … In a word, when no longer able to continue walking, having neither power nor will, they fell on their knees. The muscles of the trunk were the last to lose the power of contraction. Many of those unfortunates remained some time in that posture contending against death. Once fallen, it was impossible for them with their utmost efforts to rise again … Their pulse was small and imperceptible; respiration, infrequent and scarcely perceptible in some, was attended in others by complaints and groans. Sometimes the eye was open, fixed, dull, wild, and the brain was seized by quiet delirium…”.10 Later in his book he describes a condition that he calls “general asphyxia from cold” in similar words.11
The fact that the elderly are prone to cold has also been recognised for thousands of years. One of the Hippocratic aphorisms says: “Old men have little warmth … for this reason, fevers are not so acute in old people for then the body is cold”.12
This was also described in the Old Testament: “Now King David was old and stricken in years; and they covered him with clothes, but he gat no heat. Wherefore his servants said unto him, Let there be sought for my lord the king a young virgin: and let her stand before the king, and let her cherish him, and let her lie in thy bosom, that my lord the king may get heat. So they sought for a fair damsel … and brought her to the king. And the damsel was very fair, and cherished the king, and ministered to him: but the king knew her not”.13
It has long been known that the drunkard staggering home who collapsed in the snow would probably die and deaths from exposure to cold were collected in official statistics. In the USA, in 1860, exposure to cold made up 0.7% of violent deaths and in Scotland there were 58 deaths from cold in1876 (1.94% of violent deaths).14
It was also recognised that hypothermia could mimic death. Moricheau-Beaupré says that “General asphyxia … presents the image of perfect death; but persons found senseless and deeply benumbed have been recalled to life after twenty-four or forty-eight hours”11 and this is also shown by a book title: Observations on apparent death from drowning, hanging, suffocation by noxious vapours, fainting-fits, intoxication, lightning, exposure to cold etc etc. In it, Curry states that in “apparent death occasioned by excessive cold … animation [has been] brought about after having been suspended for several hours…”. 15
Hypothermia could not be diagnosed before temperature measurement was a clinical tool. An example was a man of 45, described in 1859, who went out in a snow storm and when he returned, was shivering, cold and confused, with a poor attention span and a weak pulse of 60 per minute. He had not been drinking and a diagnosis was made of delirium tremens caused by cold and wet, from which he recovered.16
4. Measurement of temperature
Although the first thermometer for clinical use was made in 1612, it was not a practical tool until Fahrenheit invented the mercury thermometer in 1714. There were some pioneers who measured temperature in diseases17 but there are descriptions of thermometers being a foot long and it requiring 20 min to take a temperature. Also there were problems with ensuring accuracy.18 Two events in the second half of the 19th century made the thermometer a useful clinical tool.
The first was the invention in 1866 of a small thermometer that only required 5 min to obtain a temperature.17 The second was the publication in 1868 of Wunderlich’s Das Verhalten der Eigenwanne in Krankheiten (translated into English in 1871) which presented data on nearly 25,000 patients and analysed temperature variations in 32 diseases. 19 This defined the role of the thermometer as a diagnostic aid but the interest was mostly in fever and the way it varied. However, Wunderlich recognised the problems of a low temperature: “temperatures much below 36 °C [96.8 °F] are ‘collapse’ temperatures. Below 33.5 °C [92.3 °F], deep, fatal algide collapse; 33.5–35 °C [95 °F], algide collapse with great danger, still with possibility of recovery; 35–36 °C, moderate collapse, in itself without danger”. 19 He was primarily talking of low temperatures in disease though he recognised that “extreme degrees of ‘external cold’ are the most certain means of abstracting warmth from the body; it may go so far as to render death inevitable”. 20
Measuring axillary temperatures was the usual method until the late 1890s when antiseptics were better, allowing oral temperatures to be taken.17
The word hypothermia seems to have originated in the late 19th century. The first use in the British Medical Journal seems to have been in 1880 describing hypothermia in typhoid21 and most of the early references to hypothermia relate diseases such as typhoid,22 cholera,23 pneumonia,24 diphtheria25 and spinal cord injury.26
Low body temperature due to exposure to cold was described very early in the history of clinical thermometry. In 1875 Reincke described 17 men exposed to extreme cold while intoxicated. Of five with temperatures below 30 °C [86 °F], only two survived, one with a temperature of 24 °C [75.2 °F].27 The first review of hypothermia I have found was in 1900 but it does not differentiate between medical causes and accidental hypothermia.28
Accidental hypothermia is not mentioned in Osler’s textbook of medicine of 1907,29 perhaps the standard medical textbook of the time.
The history of hypothermia is complicated not only by the different names it has been called but also because “hypothermia” has had different meanings, being used to describe “a persistent subjective coldness of the hands and feet” and “a local feeling of chilliness”30 and cold intolerance.31
Moricheau-Beaupré recommended: “we must not … transport the body into a heated place, or immediately apply to it warm substances; too strong re-action might exhaust the remaining vitality”11 and “Not withstanding the greatest probability of ill-success, we must always afford the assistance described … We begin by placing the body asphyxiated in a place where there is no current of air, and the temperature is a little above that of the atmosphere; it is quickly stripped of clothes and laid on a mattress or horse-bed. Frictions with some exciting tincture are made on the precordial region and navel, and warm clothes are subsequently applied. Afterwards we proceed to the use of snow, iced water, and water successively less cold, in the same order and degree as in local asphyxia [i.e., frostbite]. This first operation should last almost a quarter of an hour; in the second place, water a little warmed and afterwards lukewarm, and hot water.
When respiration and circulation are sensibly restored, and the muscles lose something of their stiffness, and a little heat is manifested, then the body is quickly wiped with dry linen; dry frictions are made with flannel, and the patient is placed in bed, wrapped up in a woollen blanket.” Later other stimulants might be used, e.g. tickling the nostrils with a feather, frictions on the palm or sole with strong vinegar and in severe cases “some success might perhaps be obtained from the employment of the voltaic pile” (i.e., electrical stimulation with a battery).
As soon as they can swallow they could be given an infusion of tea or elderflowers “with the addition of some drops of ammonia, or a little brandy – or cinnamon wine, sweetened – by spoonfuls”.32
Curry’s15 recommended treatment was very similar though earlier he had said that “the best mode of counteracting the cold, was to apply a bladder, with hot water, to the pit of the stomach”.33The problems of rapid re-warming of hypothermic casualties were obviously recognised but not addressed appropriately by physicians at that time. Alcohol was thought to be helpful because it caused the casualty to feel warm but in 1805 Curry said that “spirituous liquors … are, I believe uniformly hurtful, when taken under severe and continued cold”.34
Moricheau-Beaupré recognised that soldiers who got drunk on the retreat from Moscow, died.35 He thought this was because they fell asleep in the snow but by the late 19th century it was realised that the peripheral vasodilation caused heat loss and worsened the hypothermia.36 and 37 Also as vasodilatation causes a feeling of warmth, people take less care in protecting themselves against the cold. Despite this, brandy was still regarded as a treatment for cold and as late as 1915 rum was being issued to soldiers in wet and cold weather.38
6. Physiological experiments and modern appreciation of hypothermia
Physiologists started to investigate the effects of cooling animals in the 18th century. The best known was John Hunter who starting experiments in 1766 to try to discover whether animals exposed to extreme cold could recover when their temperature was raised again.39
The first experiments on humans also started at the end of the 18th century. Curry developed an interest in the subject after a ship floundered at the mouth of the river Mersey in 1790 and it took 23 h for the 14-man crew to be rescued, by which time three were dead. He did a series of experiments on individuals who were immersed in cold water and then variously exposed to cold still air, cold wind and placed in a warm bath.33 In his first experiment a man had a resting sublingual temperature 98 °F [36.7 °C]. One and a half minutes after being immersed in a tank of salt water at 44 °F [6.7 °C], his temperature had fallen to 87 °F [30.6 °C]. It then rose to 93½ °F [34.2 °C] after 12 min. When he came out and was dried, his temperature fell to 87 °F [30.6 °C]. These were not, of course, core temperatures. Curry also noted a slowing of the pulse and respiration.
Detailed experimentation in animals and men really started in the first half of the 20th century,40, 41, 42, 43 and 44 but very little clinical literature was produced. An exception was a paper by Britton from Canada which described the physiology of hypothermia in animals and man and put it into a clinical context. He concluded that humans were potentially able to withstand lower temperatures than previously recognised.45
In the late 1930s and 1940s hypothermia developed a major clinical importance which led to more research. The first reason was the use of therapeutic hypothermia. Cold had been used for the treatment of fever and other conditions46 but hypothermia was used in the late 1930s for the treatment of malignancy,47 and 48 intractable pain, morphine addiction, leukaemia, and schizophrenia.49 and 50
Although Herodotus had recognised death from cold in 450 BC, immersion deaths were usually described as drowning. Thus all who died in the Titanic disaster were recorded as having drowned although most, undoubtedly, died of hypothermia.51 In the Second World War, many crew of torpedoed ships and of aircraft shot down over the sea were immersed in cold water and died. Many were wearing life-jackets and it was recognised that they died of hypothermia. This was the stimulus for more investigation of hypothermia and led to the Nazi hypothermia experiments in concentration camps52 and to investigations in the USA53 and UK.
In the late 1940s and 1950s, a bigger incentive for researching the physiology of hypothermia and rewarming was the development of cardiac and vascular surgery. Hypothermia reduces oxygen consumption and so allowed the circulation to be cut off during a surgical procedure without causing hypoxic damage.54, 55 and 56 More recent use of hypothermia has been to aid recovery after cardiac arrest57 and neonatal hypoxic encephalopathy.58
Although accidental hypothermia in extreme conditions was well described by the middle of the 20th century, it was not fully appreciated that it also occurred in less extreme conditions such as those experienced by hill walkers in a temperate climate. Individual cases are not particularly common and the exhaustion hypothermia was poorly recognised in civilians, at least in the UK, until a report in 1966 described 23 incidents which produced 25 deaths and 23 survivors (five of whom had been unconscious).59
Following a number of case reports in the early 1960s, particularly during a very cold winter in the UK in 1963, chronic hypothermia in the elderly became better recognised. This occurs gradually over days or weeks to people who were indoors with poor heating. Occasionally there are associated medical problems and medications predisposing to hypothermia. A report for the Ministry of Health led to this being better defined and recognised.60
Death from cold has been recognised for hundreds of years but the clinical syndrome of hypothermia could not be defined until temperature measurement was simple and normal temperatures defined in the late 19th century. Even then, temperatures were not measured routinely. There was a circular problem that hypothermia was not diagnosed because temperatures were not measured routinely and they were not measured routinely because the condition had not been recognised.
In addition, the diagnosis of hypothermia requires measurement of the core temperature in, for example, the rectum or oesophagus or tympanic thermometry. This requires a low-reading thermometer (for rectal measurement) or electrical methods and the technology and familiarity in the use of these needed to wait for therapeutic hypothermia in the 1940s and 1950s. The measurement of core temperature is somewhat invasive and not a routine but is done on those suspected to be at risk of hypothermia. Hypothermia was known to be associated with extreme conditions but until hypothermia in less extreme conditions was defined, there was no reason to suspect it.
This past Friday Dr. Ruggiero, Assistant Professor in the Division of Pulmonary and Critical Care at UT Southwestern, gave grand rounds and talked about chronic critical illness. She referred to the “ProVent” score which is a prognostic model for 1-year mortality in patients ventilated for 21 days or more. This was a prospective cohort study and identified 4 independent predictors of 1-year mortality with 1 point assigned to each variable:
1. Vasopressor requirement
3. Age greater than or equal to 50 years
4. Platelets < 150,000
A score of 0 is associated with 15% mortality compared to a score of 3 and 97% mortality. Click on the link below to review this 2008 study!