We present a case of exceptionally long critical avalanche burial with severe accidental hypothermia and severe frostbite.
The combination of severe accidental hypothermia and frostbite is rare, and studies on both injuries as well as recommendations for concurrent treatment are lacking. It is widely accepted that moderate and severe hypothermia should be treated effectively before frostbite injury [8], and frozen tissue should be thawed as soon as circulation and core temperature have stabilized [8, 10, 11]. However, the pathophysiological interactions between hypothermia and frostbite are largely unknown, and it is unclear to what extent hypothermia treatment must be completed before frostbite treatment can be commenced. It is also not evident which drugs at what dosage can be administered for frostbite treatment [10]. Cold exposure leads to peripheral vasoconstriction [12], in hypothermia due to lowering core temperature < 35°C to protect the core body organs from further heat loss and in frostbite due to direct cold exposure of mainly unprotected skin. In frostbite, heat loss below the tissue freezing point (-0.5°C) causes ice crystal formation in superficial and deep tissue [8]. Environmental temperature, wind chill factor, length of exposure, clothing, concomitant factors such as alcohol and drug abuse and psychiatric disorders influence the severity of frostbite lesions [13]. During skin cooling, the “hunting reaction”, an adaptive response with cycles of vasoconstriction followed by vasodilation, can be observed [14]. Cold exposure can damage neurons in the skin with loss of cutaneous sensations and decreasing or vanishing pain, with the risk of prolonging further cold exposure. Blood viscosity can increase, and blood flow to the affected tissue can be shunted away to maintain core temperature with possible future tissue cooling when cold exposure continues [10]. During tissue freezing, due to extra and intracellular ice crystal formation, the osmotic gradient changes, which causes electrolyte shifts, pH alterations, intracellular dehydration, and hyperosmolality, harming the cellular integrity of the affected tissue [15–17].
Human data about the efficacy of drugs in hypothermia are limited and based mainly on prehospital studies [5]. Hypothermia may alter the pharmacokinetic and/or pharmacodynamic parameters of drugs, resulting in therapy failure or toxicity [18]. Altered clearance seems to be the most important pharmacokinetic effect for drugs with a narrow therapeutic index [18]. Changes in the volume of distribution (VD) occur during cooling as well as during rewarming [18]. The vasoconstriction and blood redistribution from the extremities, intestine and solid intraabdominal organs to the heart and brain decreases VD with the risk of toxicity with the usually recommended drug dosages. On the other hand, vasodilation during rewarming increases VD with the risk of therapy failure [18]. Due to scarce data, experts suggest for the cardiac arrest situation to withhold adrenaline and other CPR drugs until the patient is rewarmed to a core temperature ≥ 30°C, to double intervals between drug doses until 35°C and thereafter to use a standard drug protocol [5]. In the case hypothermia is associated with frostbite, treatment with epinephrine may be harmful because of further vasoconstriction in the extremities [19]. Additionally, other vasoconstrictive agents, such as norepinephrine, can impair perfusion in the extremities. During rewarming, vasodilation in hypothermic patients occurs, and cardiocirculatory instability with the need for fluid replacement therapy to prevent shock is frequent [11].
On the other hand, in patients with frostbite, vasodilation and perfusion are optimised with iloprost [20] and sympathicolysis due to regional anaesthesia, and thrombolytics and other drugs better reach the frostbitten area after thawing.
Thrombolytics can be administered intravenously or intraarterially with similar limb salvage rates of 77.3% and 76.4%, respectively [21]. However, the intraarterial route can be challenging and makes sense only for severe frostbite treatment in 1–2 extremities, whereas intravenous administration can be easier to perform and is the first choice for frostbite on 3–4 extremities [22]. Each hour of delay of thrombolysis after thawing the severe frostbitten area results in a 28.1% decrease in limb/digit salvage [23].
Thrombolysis has a risk of bleeding [24], resulting in complications such as compartment syndrome, and requires changes in frostbite management in 8.4% of cases [25]. Especially in patients with concomitant traumatic injuries, hypothermia-induced coagulopathy with elevated bleeding risk should also be considered. On the other hand, the procoagulant effect with increased clot extension and formation during freezing requires treatment with fibrinolytics and unfractionated heparin (UF) or low-molecular weight heparins (LMWH) and iloprost [20]. In our case, we decided for LMWH for several advantages: easier route for administration (subcutaneous vs intravenous), more predictable anticoagulant effect without need of close laboratory tests, and less likelihood for immune-mediated thrombopenia with thrombus formation [26]. High-quality evidence for severe frostbite treatment is lacking. It is possible that the combination of iloprost and anticoagulation with LMWH augmented the digit salvage rate [24]. Cauchy et al. described a lower risk of digit loss in the iloprost group than in the iloprost and alteplase groups [27]. However, in the combination group, there were more severely frostbitten digits [27]. A randomised controlled noninferiority study to compare alteplase to iloprost efficacy is ongoing [28]. Unlike the strong correlation between treatment delay and limb/digit loss using thrombolytics in severe frostbite with no benefit after 24 h, iloprost benefit was evident even in delayed treatment up to 5 days [27, 29]. Due to these results and the low complication rate [24], iloprost seems to be an important pillar in frostbite treatment in hypothermic patients, especially when the time to reach normothermia and normalisation of coagulation is prolonged. For wound healing improvement [30] and its anti-inflammatory effects, dexamethasone was administered.
In our case, the severe frostbite on the right hand of the avalanche victim, just rewarmed to normal core temperature, was treated by all available means, i.e., intraarterial thrombolysis, LMWH, platelet anti-aggregation and vasodilation with intravenous administration of synthetic prostaglandin I2 analogon iloprost, vasodilation through sympaticolysis using continuous axillary block, anti-inflammatory and analgesic acting ibuprofen and opioids. We assume that this aggressive therapeutic approach may have saved the hand from extensive tissue loss. In an almost identical case, a young healthy avalanche victim lost all fingers of the left hand after nine hours of critical burial with the hand exposed to outside at low temperatures [4].
The first measured core temperature on site was 23.1°C using an epitympanic probe. The low initial epitympanic core temperature measured during the out-of-hospital phase contrasts with clinical signs of the patient, responsiveness, and the presence of vital functions [31]. It is known that epitympanic measurements may give too low values at low ambient temperatures if the ear probe is not well insulated against the outside [32, 33]. In our case, there was a difference of 1.7°C between the epitympanically measured temperature and the bladder temperature (Fig. 3).
Rhabdomyolysis is a well-known and common problem after long immobilisation [34]. However, in our case, there are other causes contributing to the important crush syndrome of the patient: the compression of the snow, the continuous muscle activity of the right leg and right arm during burial and the hypothermia itself [35, 36]. Early treatment is the key for a good clinical outcome with different therapeutic options, including CRRT [34].
In conclusion, the combination of critical avalanche burial and severe frostbite is very rare, and treatment is challenging. This case represents successful management of severe accidental hypothermia, hypothermia-associated rhabdomyolysis and severe frostbite in an avalanche victim with good neurological recovery and no tissue loss.