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).