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Accidental hypothermia–an update Paal, Peter; Gordon, Les; Strapazzon, Giacomo; Brodmann Maeder, Monika; Putzer, Gabriel; Walpoth, Beat; Wanscher, Michael; Brown, Doug; Holzer, Michael; Broessner, Gregor; Brugger, Hermann Sep 15, 2016

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REVIEW Open AccessAccidental hypothermia–an updateThe content of this review is endorsed by theInternational Commission for Mountain EmergencyMedicine (ICAR MEDCOM)1,2,3* 4,5 3,6 3,6,7 1and is the treatment of choice in the patient with unstable circulation or cardiac arrest.Paal et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine (2016) 24:111 DOI 10.1186/s13049-016-0303-7floor, West Smithfield, London EC1A 7BE, UKFull list of author information is available at the end of the articleUniversity Hospital, Anichstr. 35, 6020 Innsbruck, Austria2Barts Heart Centre, St Bartholomew’s Hospital, West Smithfield, Barts HealthNHS Trust, Queen Mary University of London, KGV Building, Office 10, 1st* Correspondence: peter.paal@icloud.com1Department of Anaesthesiology and Critical Care Medicine, InnsbruckKeywords: Cardiopulmonary bypass, Cardiopulmonary resuscitation, Emergency medicine, Extracorporeal membraneoxygenation, Hypothermia, ResuscitationPeter Paal , Les Gordon , Giacomo Strapazzon , Monika Brodmann Maeder , Gabriel Putzer ,Beat Walpoth8, Michael Wanscher9, Doug Brown3,10, Michael Holzer11, Gregor Broessner12 and Hermann Brugger1,6AbstractBackground: This paper provides an up-to-date review of the management and outcome of accidentalhypothermia patients with and without cardiac arrest.Methods: The authors reviewed the relevant literature in their specialist field. Summaries were merged, discussedand approved to produce this narrative review.Results: The hospital use of minimally-invasive rewarming for non-arrested, otherwise healthy, patients with primaryhypothermia and stable vital signs has the potential to substantially decrease morbidity and mortality for thesepatients. Extracorporeal life support (ECLS) has revolutionised the management of hypothermic cardiac arrest, withsurvival rates approaching 100 % in some cases. Hypothermic patients with risk factors for imminent cardiac arrest(temperature <28 °C, ventricular arrhythmia, systolic blood pressure <90 mmHg), and those who have already arrested,should be transferred directly to an ECLS-centre. Cardiac arrest patients should receive continuous cardiopulmonaryresuscitation (CPR) during transfer. If prolonged transport is required or terrain is difficult, mechanical CPR can behelpful. Delayed or intermittent CPR may be appropriate in hypothermic arrest when continuous CPR is impossible.Modern post-resuscitation care should be implemented following hypothermic arrest. Structured protocols should bein place to optimise pre-hospital triage, transport and treatment as well as in-hospital management, including detailedcriteria and protocols for the use of ECLS and post-resuscitation care.Conclusions: Based on new evidence, additional clinical experience and clearer management guidelines anddocumentation, the treatment of accidental hypothermia has been refined. ECLS has substantially improved survival© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Paal et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine  (2016) 24:111 Page 2 of 20Methodsimmediately cool the heart and blood in the carotid arte-ries and therefore the brain [48–50]. Finally, a small child-BackgroundThe management of accidental hypothermia has madesubstantial progress over the last two decades andhypothermic cardiac arrest (CA) patients who oftendo not survive with traditional rewarming methods(e.g. dialysis, pleural lavage) have become increasinglysalvageable with extracorporeal life support (ECLS).The aim of this review is to consider the substantialadvances made in the last decade in the managementand outcome of accidental hypothermia patients withand without CA. Based on new evidence, additionalclinical experience and clearer management guidelinesand documentation, the treatment of accidentalhypothermia has been refined. ECLS has substantiallyimproved survival and is the treatment of choice inthe patient with unstable circulation or CA.Accidental hypothermia: an update- part 1definitions, diagnosis, prehospital managementand triageIntroductionThe management of accidental hypothermia has madesubstantial progress over the last two decades andhypothermic CA patients who often do not survive withtraditional rewarming methods (e.g. dialysis, pleural lavage)have become increasingly salvageable with extracorporeallife support (ECLS) [1–8]. New recommendations regar-ding delayed or intermittent CPR may facilitate patienttransport [9].Although some pathophysiological mechanisms are simi-lar, accidental hypothermia should neither be compared toinduced hypothermia (as used in deep hypothermic circu-latory arrest (DHCA) for cardiovascular surgery) nor totherapeutic hypothermia (i.e. in targeted temperature man-agement as part of a post-resuscitation care bundle):i) accidental hypothermia happens unexpectedly and isuncontrolled; ii) it is often associated with exposure to coldenvironments and/or secondary to impaired thermoregu-lation e.g. alcohol, drug ingestion, trauma, extremes ofage or co-morbid illness [10]. The elderly are at increasedrisk due to decreased physiologic reserve, chronic diseaseand medications that impair compensatory responses.The current lowest temperatures from which successfulresuscitation and rewarming have been achieved are13.7 °C [11] for accidental and 9 °C [12] for inducedhypothermia. Successful resuscitation at even lower tem-peratures may be possible. This article gives a state-of-the-art review on accidental hypothermia management.An algorithm is provided in Fig. 1.A working panel of doctors with a special interest inaccidental hypothermia, including speakers at the IVthInternational Symposium on Hypothermia in Bozen/Bolzano (2014), addressed the current management ofaccidental hypothermia. Each doctor reviewed with indi-vidualized Pubmed searches the relevant literature in theirfield of expertise. Summaries were merged into this narra-tive review. Following discussion and approval, 279 rele-vant articles were included.Cooling: implications for drowning and avalanche rescueIn accidental hypothermia, cooling rates depend on manyfactors including cold acclimatisation, body size, age,insulation (clothing and subcutaneous fat), ability toshiver, body movement, temperature gradient, the amountof body surrounded by a cold medium (air, snow or water)and local conditions that increase cooling e.g. wind speed,rough water [13, 14]. The crucial factor in all hypothermiacases is whether critical brain hypoxia occurs before pro-tective brain-cooling takes place [15–18].In water incidents, management is as for hypothermia ondry land, including careful movement to avoid precipitatinga life-threatening arrhythmia [19] and keeping the casualtyin a horizontal position when pulled from the water tominimise the likelihood of rescue collapse [20]. Theseissues are discussed in greater detail later in this review. Ifan immersion victim (head out) is able to cling to floatingwreckage or the edge of an ice sheet, they will eventuallybecome hypothermic, although it may take up to one hourfor this to become a life-threatening problem [21–24].Submersion (head under water) duration is a directmeasure of anoxic injury [8, 25] so that 2.5–5 min pre-dicts a good outcome [8, 26–28], >10 min is associatedwith poor outcome [8, 26, 29, 30] and there is almostno chance of survival >25–30 min [8, 16, 26, 31, 32].Although hypothermia may reflect a prolonged submer-sion time and poor prognosis [33], early hypothermia is animportant reason why survival without neurologic damageis possible [34]. Instances of miraculous survival with goodrecovery after submersion have occurred, mainly in smallchildren submersed in icy water who rapidly becamehypothermic prior to hypoxia (Table 2) [8, 16, 35–41], butalso in adults [19, 42–44]. There are several reasons forimproved immediate survival in children after submersionbut from a hypothermia perspective, they cool morerapidly than adults during cold water submersion (<6 °C)[21, 45], especially infants, who have an inefficient shive-ring mechanism [46]. Children have less subcutaneous fat,which at any age leads to faster cooling [13, 19, 47], and ahigher surface area to body weight ratio [45]. Aspirationof very cold water into a child’s small body is believed tosized head will cool faster by conduction than a largeadult-sized head [48]. Case reports repeatedly demonstratePaal et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine  (2016) 24:111 Page 3 of 20a poor outcome after drowning, even after ECLS forrewarming [51–55] and use of targeted temperaturemanagement [56]. In drowning, there are currently nomethods to reliably predict early on who will survive orthe likely long-term neurocognitive outcome, so in theabsence of obvious indications of death e.g. rigor mortis[32], published guidance urges aggressive out-of-hospitaland in-hospital treatment in all cases [16, 35], particularlyin young hypothermic victims [57]. Immediate full CPR(not compression-only without ventilation) [58] afterdrowning [59, 60] and the early arrival of EMS (<9 min)are associated with increased survival to hospital admis-sion and survival to one month [8, 61–63]. However, out-comes are extremely poor if ALS takes >30 min to achieveROSC, even with hypothermia [31]. Retrospective analysisof a large number of drowning cases has produced auseful algorithm based on clinical signs and submersionduration to guide management and grade patientsFig. 1 Management in Accidental Hypothermia. (*) Decapitation; truncal trannot compressible) [128]. (†) SBP <90 mmHg is a reasonable prehospital estimsufficient circulation for a deeply hypothermic patient (e.g., <28 °C) has not bTable 1. (§) In remote areas, transport decisions should balance the risk of inccentre. (||) Warm environment, chemical, electrical, or forced air heating packsrefractory to medical management, consider rewarming with ECLS. (¶) If the dpotassium, a hospital en route towards the ECLS centre should be chosen. (**resuscitate, ECLS extracorporeal life support, HT hypothermia, MD medical doaccording to survival rate [32, 64, 65]. Understanding theimplications of submersion duration on outcome is usefulwhere decisions to rescue and care for a casualty pose arisk to the rescue services. This may contribute to thedecision to change from rescue to body retrieval [8, 25].Finally, although water temperature alone does not affectlong-term outcome [8, 26, 28, 29], recent guidance forSearch & Rescue teams has suggested that for victims whoare continuously submerged (i.e. not in a vehicle wherethere might be an air pocket), if water temperature iswarmer than 6 °C, survival/resuscitation is extremelyunlikely if submerged >30 min; if water temperature is≤6 °C, survival/resuscitation is extremely unlikely if sub-merged >90 min [34].The cooling rates in snow in avalanche victims vary sub-stantially. Although the fastest reported cooling rate in anavalanche victim is 9.4 °C/h [66], the accuracy of this figurehas been questioned because some cooling would besection; whole body decomposed or whole body frozen solid (chest wallate of cardiac instability but for in-hospital decisions, the minimumeen defined. (‡) Swiss staging of accidental hypothermia [73], see alsoreased transport time with the potential benefit of treatment in an ECLSor blankets, and warm IV fluids (38–42 °C). In case of cardiac instabilityecision is made to stop at an intermediate hospital to measure serum) See Table 3. CPR denotes cardiopulmonary resuscitation, DNR do-not-ctor, ROSC return of spontaneous circulation, SBP systolic blood pressureexpected to have occurred after extrication [67]. However,another case of 9 °C/h suggests that some patients coolvery rapidly [68]. In avalanche burial, survival decreasesdramatically after 35 min [17]. Beyond this inflection point,survival is only possible if the airway is patent and oxygensupport from the surrounding snow is sufficient. There aresome rare extreme examples of avalanche survival [17, 69].However, if an avalanche victim is found in cardiacarrest, the outcome is poor, even after ECLS for rewarm-ing [1, 4, 70]. An algorithm is available for avalancherescue [71]. Current guidance is that victims are unlikelyto survive if buried >60 min (or initial core temperatureis <30 °C) and in cardiac arrest with an obstructed airwayon extrication, or buried and in cardiac arrest on extrica-tion with an initial serum potassium > 8 mmol L−1 [8].The wider aspects of body cooling, avalanche rescue,drowning and resuscitation go beyond the remit of thisreview and are covered extensively elsewhere [17, 72]. Inhypothermia [88, 89], if the head is cold [90, 91] orPaal et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine  (2016) 24:111 Page 4 of 20all cases, rescuer safety is paramount [17, 25].StagingAccidental hypothermia is staged by core-temperaturemeasurement and clinical findings. A classification basedon the Swiss system (Hypothermia I–IV; HT I–IV) [73]provides useful guidance in the prehospital situation(Table 1) using level of consciousness, vital signs, and coretemperature (if available) to indicate hypothermia severity.A fifth stage (Hypothermia V) may be used to denotedeath due to irreversible hypothermia [74]. The multitudeof patient factors (e.g. age, gender, body composition,physical fitness, race, comorbidities, intoxication, multipletrauma and head injuries) [5] means that clinical findingsdo not consistently correlate with core-temperature [75].Table 1 Staging of accidental hypothermia [73]Stage Clinical findings Core temperature(°C) (if available)Hypothermia I(mild)Conscious, shiveringa 35–32 °CHypothermia II(moderate)Impaired consciousnessa;may or may not be shivering<32–28 °CHypothermia III(severe)Unconsciousa; vital signs present <28 °CHypothermia IV(severe)Apparent death; Vital signs absent VariablebaShivering and consciousness may be impaired by comorbid illness(i.e. trauma, CNS pathology, toxic ingestion, etc.) or drugs (i.e. sedatives,muscle relaxants, narcotics etc.) independent of core temperatureThe lowest temperature from which successful resuscitation and rewarming hasbeen achieved is currently 13.7 °C [11] for accidental hypothermia and 9 °C forinduced hypothermia [12]. This does not preclude resuscitation attempts at evenlower temperatures if clinical judgment suggests the possibility ofsuccessful resuscitationbThe risk of cardiac arrest increases below 32 °C, but as it is unlikely to be duesolely to hypothermia until the temperature is <28 °C, alternative causesshould be considered. Some patients still have vital signs <24 °C and thelowest reported temperature of a patient with vital signs is 17 °C [232, 233]hypothermia onset is rapid [92]. Oral temperature isaccurate in normothermia [93], but not in the cold [94]and is affected by other factors e.g. head and facetemperature [90, 91, 95] making it unreliable. Skin andexposed sites do not accurately reflect core temperaturedue to poor peripheral circulation and should not be used[94]. Non-invasive flux-method devices have been deve-Consequently, CA may occur just below ≈ 32°C or vitalsigns can be present into upper teens [76]. A stagingsystem is a valuable clinical tool to facilitate triage andemergency treatment. However, definitive assessmentof the severity of hypothermia requires accurate coretemperature measurement.Temperature measurementCore-temperature measurement is essential for diagno-sing hypothermia and assessing severity. The practicalprinciples are identical for pre- and in-hospital use.Temperature measurement sites in order of decreasinginvasiveness include pulmonary artery, oesophagus, blad-der, rectum, tympanic membrane, oral cavity, and skin.Pulmonary artery temperature reflects central bloodtemperature and is the gold standard [77], but is too inva-sive for routine use, and it may precipitate an arrhythmia.Oesophageal temperature closely correlates with pulmo-nary artery temperature [77] if the probe is placed in thelower third of the oesophagus [78], and is standard forpatients with a secured upper airway [77, 79]. Pre-hospitalmeasurement in the bladder or rectum is impractical. Thepatient has to be partially undressed, rectal probes mustbe inserted to a depth of ≥15 cm, values of both lagbehind core during rapid cooling and rewarming [80, 81]and may be falsely elevated if warmed peritoneal lavage isused [79]. For in-hospital measurement of core temperature,inserting a urinary catheter with a temperature probe is apractical method in hypothermic spontaneously-breathingpatients, as it allows for simultaneous core temperaturemeasurement andmonitoring of urine output.Epitympanic temperature is reliable in patients withspontaneous circulation, but may give falsely low valueswith unstable or absent circulation [10]. In a cold envi-ronment, epitympanic probes are only reliable afterstabilising for a few minutes [82, 83], if the ear canal isunobstructed and insulated from cold air [83–85]. Tym-panic temperature measurement should be by thermistoror thermocouple probes placed near the tympanic mem-brane, but currently there are no epitympanic thermome-ters with an insulation barrier available for out-of-hospitaluse. Infrared tympanic thermometers are inaccuratein a cold environment [81, 86, 87], in the presence ofloped [96] but validation studies in hypothermic patientsexposed to a cold environment are required.Paal et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine  (2016) 24:111 Page 5 of 20Prehospital insulation, rewarming, rescue collapse andafterdropShivering and active movement are very efficient mecha-nisms of heat production and are effective rewarming stra-tegies for patients who are fully conscious and able to move[97]. At rest, shivering increases heat production up to fivetimes but also increases oxygen-requirements [98]. Shive-ring ceases when energy stores are depleted (within hours),core-temperature drops below an individual’s threshold(Table 1), consciousness is impaired, or sometimes duringexogenous skin heating [99]. Multiple trauma, otherco-morbidities, intoxication, analgesia or sedation [100]may hasten cooling by impairing central and peripheralthermoregulation (i.e. shivering and vasoconstriction).When shivering ceases (HT II–IV), minimal rewarmingoccurs [101, 102] and in the absence of active rewarming,cooling rate increases [103].A warm, sweet, non-alcoholic drink will not provideenough heat to rewarm a patient with HT I but will supplycarbohydrate to fuel continued shivering [79, 104, 105].Heat redistribution within the body can cause a continuedfall in core temperature after removal from the cold stress–a phenomenon called afterdrop that may also occur duringrewarming. Experimental studies [106–108], have demon-strated a ~0.5–1 °C afterdrop during minimally invasiverewarming and slightly more during exercise-assistedrewarming. However, patients often rewarm faster inthe exercise group and no adverse outcomes have everbeen observed in either group. Some experts argue thathypothermic patients should neither stand nor walk for30 min after rescue-care commences due to concernsthat exercise may exacerbate afterdrop and cause harm[97]. In practice, patients who are awake and alert shouldnot be prevented from mobilising if this will help therescue [109, 110].Emergency medical services should have protocols andequipment for managing hypothermic patients [111, 112].The optimal prehospital transport and rewarming stra-tegies are unknown but some human studies have com-pared insulation methods [113–116]. Lack of adequateinsulation and heat during transport allows continuedcooling, thereby increasing the risk of CA. Insulation fromcold, wet, and wind as soon as possible is essential,particularly when removing an avalanche victim, as thecooling rate after extrication is faster than during burial[67]. Experimental evidence and experience indicate thatin a patient with spontaneous circulation, pre-hospitalpatient packaging should include a sealed impermeablevapour barrier [114, 117] (if the patient is wet) excludingthe face [118, 119], an external heat source, dry insulation(the thicker, the better), and a wind barrier that alsoreflects heat [114]. Bubble wrap is light-weight andwater-resistant so can form part of a packaging system.However, it is available in different thicknesses withdifferent insulation properties and is of limited use onits own [114, 120–122]. Removing wet clothes in-creases patient comfort but results in rapid cooling ifdone in a cold or windy environment [74, 115, 119] andis unnecessary if a vapour barrier is used [115, 119]. Exter-nal heat (e.g. chemical heat-packs, warm water bottles orforced air blankets) should be applied to the head [123],torso and neck areas [117] during transport. Heat mustnever be applied directly to skin because of the risk ofburns [117]. Ideally the outer packaging layer will providea wind barrier to minimise convective losses and a heatreflector will minimise radiation losses. With short trans-ports (e.g. <60 min), active warming may be only mini-mally helpful and expensive. For longer journeys (e.g.>60 min), active warming should be used for HT I–IIIpatients. Patients in CA (HT IV) being transportedfor ECLS-rewarming should ideally have their core-temperature monitored and heat delivery should betitrated to maintain the core body temperature. Pre-hospital rewarming or cooling of HT IV during trans-port should be avoided.Careful handling and avoidance of rough movementsare mandatory, especially in patients who have notarrested. Patients should ideally be transported horizon-tally by stretcher to decrease position-associated changesin venous return, which may increase the risk of post-rescue CA (rescue collapse), particularly if removed fromcold water [20].Triage and prognostication of accidental hypothermicpatients in cardiac arrestBrain oxygen-consumption decreases by ~6 % per 1 °Cfall in core temperature [8] and reaches 16 % at 15 °C[124] compared with normothermia. This improves thebrain’s tolerance for low- or no blood-flow states. At18 °C the brain tolerates CA for up to 10 times longerthan at 37 °C [8].Many factors affect outcome from hypothermic arrest:(1) hypoxia (the most important single factor) [125]; (2)patient considerations (e.g. age, co-morbidities, trauma);(3) speed of cooling; (4) environment (air, water, snow);(5) CA features (body temperature; whether hypoxiapreceded arrest; delay before instituting CPR, and CPRquality); (6) rescue considerations (e.g. adequate trainingto manage a low flow or no blood-flow state; speed ofhospital transfer); (7) proximity of appropriate hospitalfacilities; (8) whether hospital staff appreciate the specialrequirements of these cases. The best chance of fullrecovery from hypothermic CA occurs in the previously-well patient with witnessed CA, in which continuous CPRis implemented immediately, timely ECLS commencesand appropriate critical care support is available afterreturn of spontaneous circulation (ROSC). Trying toestimate the survivable duration of CA without CPR isPaal et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine  (2016) 24:111 Page 6 of 20fraught with uncertainty, but knowing the maximum timesrecommended for cardiovascular surgery when conditionsare optimal (~25 min for adults >60 years or ~40 min forneonates undergoing DHCA at ~18 °C) may provide astarting point [9].Avalanche victims who survived neurologically intact(i.e. Cerebral Performance Category (CPC) 1–2) [126]were found in ventricular fibrillation (VF) or pulselesselectrical activity (PEA) [2, 4, 127]. Survival chances arevery low in buried avalanche victims with unwitnessedasystole at extrication [2, 4] because hypoxia has gene-rally preceded CA leading to irreversible brain damageand death within minutes.Clinicians have looked for laboratory markers to guidemanagement decisions in difficult cases, but accuratelypredicting outcome in accidental hypothermia is noto-riously difficult. Consequently, the guiding principle isthat in the absence of signs incompatible with life, “Noone is dead until warm and dead”, regardless of bodytemperature [8, 128]. The decision to withhold ECLS-rewarming is usually best-taken at the receiving hospital.Reasons may include death by hypoxia before hypothermia,K+ > 12mmolL-1, and any condition that is unlikely tobe survivable in its own right e.g. major trauma, traumaticbrain injury, intracerebral haemorrhage or end stagedisease [8, 10]. Although no patient with hyperkalaemia>12 mmol/L has ever been successfully resuscitated, manypatients with a normal potassium also do not survive sothe utility of serum potassium for clinical decision-makingis limited. A retrospective review of avalanche victimswho underwent computer tomographic (CT) scanningin hospital suggests that admission serum potassiumconcentration was higher in patients with CT-verified brainanoxia compared to patients with a normal CT scan [129].Current European Resuscitation Council (ERC) guidelines[8] recommend a potassium threshold of 8 mmol L-1 foravalanche victims and 12 mmol L-1 for other causes of acci-dental hypothermia [8] because one adult avalanche victimwith a potassium of 6.4 mmol L-1 [130] and a child coolingoutdoors (14.2 °C) with a potassium of 11.7 mmol L-1 [131]both survived neurologically intact (Table 2).Oxygenation, anaesthesia induction and airwaymanagementIndications to secure the airway do not differ from recom-mendations in normothermic patients [8]. Intubation mayprovoke ventricular fibrillation (VF) in severe hypothermia[132, 133] but the risk is small [8, 134, 135]. There is littlepublished data about anaesthesia in these patients, but thelikely effects can be anticipated by extrapolating fromstudies done on animals, and in patients with inducedhypothermia for medical treatment. Most intravenousanaesthetic induction agents cause cardiovascular depres-sion so doses should be small. Ketamine may be safe inpre-existing hypothermia [136], but the sympathomimeticeffects could theoretically cause problems for an irritablehypothermic heart [99]. If succinylcholine is used for in-tubation, the potential for it to increase serum potassiumshould be considered [137]. Neuromuscular transmissiondecreases during hypothermia, even in the absence ofmuscle relaxants [138] and studies performed in animalsand humans during hypothermic cardiopulmonary bypass(CPB) have indicated that hypothermia <32 °C increasessensitivity to non-depolarising muscle relaxants [139].Hypothermia reduces the systemic clearance of CYP450-metabolised drugs (including propofol and ketamine) by anamount proportional to the fall in body temperature, in-creasing the likelihood of unanticipated toxicity [140, 141].During anaesthesia induction and intubation, continu-ous ECG monitoring, CPR-preparedness and placementof defibrillation-pads are recommended. Normocapniashould be maintained during airway management andthereafter [135], because hypercapnia and hypocapniacan induce arrhythmias [79]. Inspired oxygen can betitrated against pulse oximetry (if peripheral perfusionallows) or blood gas analysis (if available), as normoxia isbelieved to protect from arrhythmia [135]. During CPR,ventilation should be provided as in normothermic CApatients.Cardiopulmonary resuscitationPatients in hypothermic arrest often need prolongedCPR [3, 142–144]. High-quality CPR is the key to bestoutcome. During technically-challenging evacuationfrom difficult terrain, manual CPR may be impaired orimpossible [145–147]. Mechanical chest compressiondevices can deliver >50 % of baseline cerebral blood flowin normothermic animals [148], and therefore are likelyto provide sufficient oxygen delivery to vital organs indeeply hypothermic patients. They are of value duringtransport, and to maintain CPR whilst ECLS is beinginstituted [43, 149–161]. When mechanical CPR is notavailable and manual CPR is not feasible, intermittent>CPR has been suggested, based on three cases and ex-trapolation of clinical data from cardiovascular surgeryunder DHCA (Fig. 2) [9].Continuous monitoring of CPR efforts to optimize cere-bral blood flow is desirable. End-tidal CO2 (ETCO2) iscommonly used as a marker for CPR quality [162, 163]but is not a surrogate for cerebral oxygenation, and it isunclear how to interpret the readings in hypothermiawhen CO2 production is reduced. Near-infrared spectros-copy (NIRS) is increasingly used to monitor regional cere-bral oxygen saturation (rSO2) during CPR. NIRS may beused to predict ROSC [164, 165] and possibly favourableneurological outcome [166], though current evidenceis weak [167, 168]. In an experimental hypothermicCA model, rSO2 values closely correlated with invasivessseC corsewnsdmgPaal et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine  (2016) 24:111 Page 7 of 20Table 2 The most extreme reported accidental hypothermia caseLongest no flow time 42-year-old male, found in crevawhen patient was asystolic, 19 °Longest manual CPR 42-year-old male, found outdo23.2 °C, 6 h and 30 min CPR. RLongest mechanical CPR 42-year-old female, found uncohospital. Manual CPR started anMinimal temperature 24 °C. 80Longest total resuscitation 65-year-old female went missinparameters of cerebral oxygenation such as cerebral perfu-sion pressure and cerebral venous oxygen saturation dur-ing chest compressions [169]. To date, there is too littleclinical experience to recommend NIRS for routine use inhypothermic CA [170].During normothermic CA, vasopressors are adminis-tered to augment coronary perfusion pressure andmyocardial blood flow with the aim of increasingROSC and survival to neurologically-intact hospitaldischarge [171]. In hypo- (≤28 °C) and normothermicanimal [171–174] and normothermic human studies,dropped to 20.8 °C. Asystole. Resutime was 8 h 40 min [142].Lowest survived body coretemperature29-year-old female, fell into water45 min, CPR started after rescue, afull recovery [11].Longest persisting VF 42-year-old male, found outdoor,started at 130 min CPR and after25-year-old female, buried by and(17.0 °C) after extrication, 3 unsuc4th shock at 24.8 °C. Full recoveryLongest intermittent CPR 57-year-old female, witnessed cardistance to EMS vehicle of 1.1 kmfor 25 min, 5 h CPR, ECLS rewarmLongest submersion 2.5-year-old, submersion in cold wchild, submersion in icy water for afull recovery [212].Longest survival in an avalanche Female, core temperature <32 °Chand and feet, no injuries, 43 h aLongest time in an avalanche indoor Thirteen days entrapped in a houAustria [238].Lowest temperature with vital signs Male age 3 years. ECG showed veafter arrival at the hospital was 17Female age 37 years. Rectal tempHighest survived potassium in anavalanche victimAvalanche victim, 6.4 mmol L-1, surHighest survived potassium in an adult 34 year old female, 20 °C, cold enNeurologic outcome not reportedHighest potassium in an accidentallyhypothermic patient7 -year-old and, cold water subme11.7 mmol L-1 [131].Longest time in a crevasse 27 -year-old male, 8 days, good o70 year male, moderate fracturescold injuries to toes, otherwise goLargest number of simultaneous casesof accidental hypothermia withcardiac arrest15 healthy subjects age 15–45 yecirculatory arrest with a median tsubsequently evaluated with advaresuscitated [41]., 7 m under snow, no vital signs, CPR started only after 70 min in hospitalore temperature, ECLS rewarming, full recovery [211].. Developed asystole just after discovery, CPR started,armed with non-ECLS methods until ROSC. Full recovery [143].cious in her apartment. VF arrest during evacuation tothis was changed to mechanical CPR on arrival at hospital.in mechanical CPR while the patient was rewarmed noninvasively [153].and was found on a snow-covered riverbank. Initially 28 °C (rectal) butvasopressor administration was associated with im-proved ROSC [175–177], but not an increase insurvival-to-hospital discharge or better neurologicaloutcome [175, 178–180]. Larger doses of adrenalinemay be associated with unfavourable neurological out-come [181], and the peripheral vasoconstriction mayworsen concurrent frostbite [17, 182, 183]. Because theadrenaline question has not been resolved, internationalguidance differs. The ERC 2015 guidelines recommendwithholding adrenaline administration in hypothermic CA(HT IV) and limiting defibrillation to three attempts untilscitation was CPR (4 h 48 m) and ECLS (3 h 52 m). Total resuscitationfall gully, flooded by icy water but able to breathe. Lifeless for approx.t hospital admission 13.7 °C and K+ of 4.3 mmol L-1, ECLS rewarming,CPR started, repeated shocks, hospital transfer, 22 °C, ECLS rewarming38 shocks, successful shock at 30 °C, full recovery [234].avalanche in Tatra mountains, Poland. Witnessed VF cardiac arrestcessful shocks. CPR until ECMO rewarming (6 h, 45 min), and successful[235].diac arrest in French Alps at 2000 m altitude in a snowstorm; transport, 122 m difference in height; 1 min CPR alternating with 1 min walkinging, full recovery [69].ater for at least 66 min, 19 °C, ECLS rewarming, full recovery [38]. 7-year-oldt least 83 min, CPR for 64 min, 13.8 °C, K+ 11.3 mmol L-1, ECLS rewarming,, when found somnolent, disorientated. 1st- 2nd degree frost bites onnd 45 min [236, 237].se which in part collapsed after being hit by an avalanche, Heiligenblut,ry irregular rhythm 8–10/min. Rectal temperature recorded about 20 min°C [232].erature 17.2 °C. ECG showed atrial fibrillation 28–40/min with PVCs [233].vived; core temperature and neurological outcome are not reported [130].vironment exposure, asystole, 7.9 mmol L-1, ECLS rewarming, survived.[239].rsion, 11.3 mmol L-1 [212], and 31 month old child, cold water submersion,utcome, no temperature or other specific details reported [240]of skull, vertebral column, pelvis, and femur, 6 days, 33.5 °C,od outcome [241].ars were immersed in 2 °C salt water. Seven victims were recovered inemperature of 18.4 °C. They were rewarmed with ECMO and werenced neuroradiological and functional testing. All were successfullyonPaal et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine  (2016) 24:111 Page 8 of 20the core temperature is >30 °C [8]. By contrast, theAmerican Heart Association guidelines allow further de-fibrillation attempts concurrent with rewarming strategiesand state that it may be reasonable to consider adrenalineadministration during CA according to the standard ALSalgorithm [184, 185]. In HT III, adrenaline has reduced ef-fectiveness and accumulates, although whether this leadsto overdose after rewarming is not clear [186]. In HTIV, vasopressors should probably be restricted to weaningfrom ECLS. Although a few case reports have shown sus-Fig. 2 Delayed and intermittent CPR in in hypothermic patients when ctained ROSC after defibrillation at <28 °C [41, 131, 144,187–192], most attempts are unsuccessful. A maximumof three defibrillations appears reasonable <30 °C andthen waiting for rewarming to ≥30° before further at-tempts [8]. Given the on-going controversies, it is accept-able to use either approach until further data becomesavailable.The benefit of antiarrhythmic drugs in hypothermicCA is unclear. Many arrhythmias (e.g. bradycardia, atrio-ventricular blocks, atrial fibrillation, nodal rhythms andQRS prolongation with or without Osborn J-waves) areconsidered benign in accidental hypothermia, usually re-gress with patient rewarming and do not require furthertreatment provided the perfusion is deemed adequate.Pacing may be ineffective in these patients and is notcommonly recommended [8].Dispatching and transport decisionsPatients with haemodynamic instability or CA [10]should ideally be rapidly transported directly to an ECLShospital as outcome is better, with survival rates of up to100 %, compared with other rewarming techniques [41].The ECLS centre must be contacted early to allow timeto organise the team and operating facilities before thepatient arrives [160]. There are many examples provingthat in hypothermic arrest, good neurological recovery ispossible following many hours of CPR, even with pro-longed transport [1, 3, 132, 142–144, 187, 190, 193, 194].If rewarming in an ECLS centre is impossible, it maybe attempted in the nearest hospital if a dedicated teamis available [195]. If available, an emergency team withportable ECMO may be dispatched to a peripheralhospital [41].tinuous CPR is not possible during difficult rescue missions [9]ConclusionsCooling rates may vary widely according to the individualsituation. Insulation, hypothermia staging, and triage tothe appropriate hospital are key. Hypothermic patientswith risk factors for imminent cardiac arrest (temperature<28 °C, ventricular arrhythmia, systolic blood pressure<90 mmHg), and those who have already arrested, shouldbe transferred directly to an ECLS-centre. Cardiac arrestpatients should receive continuous cardiopulmonaryresuscitation (CPR) during transfer. Delayed or intermittentCPR may be appropriate in hypothermic arrest whencontinuous CPR is impossible. If prolonged transportis required or terrain is difficult, mechanical CPR can behelpful. Outcome is best if hypothermic cardiac arrest iswitnessed, high quality CPR performed continuously untilECLS rewarming is started.Accidental hypothermia: an update- part 2in-hospital managementIn-hospital management of hypothermic patientsRewarming methods can be classified as passive (protec-tion from further heat loss whilst the patient raises theirown body temperature), active external (delivery of heatto the surface of the body) and active internal (deliveryof heat to the interior of the body). Common rewarmingmethods, their effectiveness in the hospital setting, con-troversies and potential complications are presented inTable 3 [10]. Rewarming methods should be evaluatedTable 3 Rewarming techniques in accidental hypothermiaRewarming technique Rewarming rate Notes & controversies Rewarming complicationsPASSIVE REWARMING [79]Passive rewarming 0.5–4 °C hr-1 (dependent uponpatient’s thermoregulatoryfunction and metabolic reserves)[79, 242].Protect from further heat loss andallow patient to self-rewarm. Minimalcontroversy for mild hypothermia ifthe patient is able to self-rewarm.Negligible in isolated mild hypothermia.For colder patients and those withsecondary hypothermia or comorbid illness,there may be morbidity associated witha prolonged rewarming process if thepatient has poor tolerance for thehypothermia-induced organ dysfunction(i.e. hypotension, coagulopathy,arrhythmias, impaired cellular function etc.).Passive rewarmingwith active movement1–5 °C hr-1 Exercise has been shown to increaseafterdrop in physiology studies from~0.3 °C in controls to ~1 °C in exercisedsubjects, however the exercisedsubjects rewarmed more quickly [243].No reported complications. Some authorshighlight the theoretical risk that the slightlyincreased afterdrop could contribute tomorbidity and mortality. No adverse eventswere noted [243].ACTIVE EXTERNAL REWARMINGActive rewarminge.g. forced air surface[244] Arctic Sun®[245–247]0.5-4 °C hr-1 Protect from further heat loss, deliverexternal heat and (if required) warmedIV fluids. Minimal controversies.Similar to passive rewarming.ACTIVE INTERNAL REWARMINGBladder lavage Variable. Adds ~0.5–1 °C hr-1 Helpful if rewarming rate is slow. Minimalcontroversies. Rewarming is intermittent& slow because of small surface area.Poor control of infusate temperature[242, 248, 249].Negligible unless difficult catheterization.Gastric lavage Adds ~0.5–1 °C hr-1 Not commonly used due to risk vs.benefit ratio [249].Potential for aspiration, fluid & electrolyteshifts.Intravascular catheterrewarming e.g. Icy®catheter (CoolGuard®)[76, 250–252]Quattro® [253] Cool Line®[254] Innercool® [255]Device specific(adds ~0.5–2.5 °C hr-1)Uncertain indication for use, potentialfor benefit exists in colder and sickerco-morbid patients with stablecirculation.Potential for haemorrhage or thrombosis,potentially worsening hypotension inunstable patients.Thoracic [79, 256, 257]or Peritoneal lavage[79, 258]Adds ~1–2 °C hr-1 Not commonly used unless patient isunstable and ECLS rewarming is notavailable.Potential for haemorrhage, lung or boweltrauma, fluid & electrolyte shifts. Thoraciclavage has the potential to impair CPRquality.Continuous venovenoushaemofiltration[190, 242, 259–261]Adds ~1.5–3 °C hr-1 Not commonly used unless ECLSrewarming not available. Requiresadequate blood pressure.Heparinisation required.Problems rare. Local vascularcomplications. Air embolism. Hypotension.Haemodialysis[242, 262–266]Adds ~2–3 °C hr-1 Not commonly used, patient mustbe able to increase cardiac outputto perfuse the external circuit.Heparinisation required.Potential for hypotension, haemorrhage,thrombosis, haemolysis, etc.Veno-venous rewarming(usually with an ECMO~4–10 °C hr-1 Not commonly used. Provides nocirculatory or ventilatory support iniaccrircPotential for hypotension, haemorrhage,thrombosis, haemolysis, etc.waardPaal et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine  (2016) 24:111 Page 9 of 20circuit) [248] case of cardbe able to into provide cExtra-corporeal lifesupport~4–10 °C hr-1 Preferred repatients in c(VA-ECMO or CPB) use femoral rofor sternotomyarrest. Patient mustease cardiac outputuit perfusion.rming method foriac arrest. CPB canPotential for haemorrhage, thrombosis,haemolysis, etc. (as with all intravascularute avoiding need[1, 42]devices).cardiovascular surgery, and is easier to interpret becauseexists to guide the non-ECLS rewarming of hypothermicPaal et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine  (2016) 24:111 Page 10 of 20clinicians are familiar with interpreting arterial bloodgases at 37 °C. Evidence extrapolated from studies intherapeutic hypothermia suggests that it is generallyassociated with improved cerebral perfusion and neuro-logical outcome [198, 204–206]. In hypothermia, moreoxygen will be dissolved in the blood and PaO2 falls[198, 207]. PaO2 will increase when the blood sampleis rewarmed to 37 °C. To maintain the body PaO2 inthe normal range, PaO2 should be corrected forcurrent body temperature in hypothermic patientsbased on morbidity, mortality, patient comfort andresource-use efficiency. Attempts should not be made torewarm frostbitten extremities until core temperature is>34 °C [196]. During rewarming, all hypothermicpatients will have significant intravenous fluid re-quirements as vasoconstriction relaxes and colddiuresis-mediated dehydration is reversed. Avoidanceof hypovolaemia is also important in the presence offrostbite [197].Interpreting arterial blood gases in severe hypothermiaAcid-base disturbances in hypothermia are complex be-cause of changes in respiration, metabolic rate, plasmasolubility of CO2 and O2 and buffering capability ofthe blood [79, 198–200]. Initial cooling may be accompa-nied by hyperventilation and a respiratory alkalosis butsubsequently (e.g. ≤35 °C), a mixed acidosis often ensuesfrom a combination of falling metabolic rate and CO2 pro-duction [198], respiratory depression (partly to maintainCO2 constant in relation to metabolic production [199],increased lactate from shivering and reduced tissue perfu-sion, and impaired hepatic function [79]. In practice, somepatients will be acidotic and others alkalotic [201], reflec-ting the combined-effects of concurrent pathology, indi-vidual variation and factors associated with the patient’shypothermic events.Blood gas samples are analysed at 37 °C, but with math-ematical correction it is possible to express the results atactual body temperature. The difference has practicalsignificance because altering the temperature changes theinterpretation of the results and subsequent treatment[198]. For example, normocapnia at 37 °C will becomehypocapnia at 25 °C [198, 202]. One approach assumesthat 7.42 is the ideal pH at all temperatures so that man-agement is directed towards maintaining the arterial pHat that level (pH-stat strategy). A better approach inaccidental hypothermia appears to be to recognise thatpH and PaCO2 do alter with temperature (alpha-stat strat-egy) [200, 203]. This approach seems to be widely ac-cepted now in induced hypothermia, e.g. DHCA for[198, 208]. Other physiological changes in hypothermiaare listed in Table 4.CA. Until an effective circulation is re-established, someexperts recommend shielding the head from externalheat sources (such as warming blankets) to prevent thebrain temperature from rising too quickly. Regarding thechoice of heating modalities, each device should be con-sidered for its ability to assist with heat delivery againstthe potential to impair circulation. For example the use ofpleural lavage has the potential to impair chest compressionquality and may not be indicated if sufficient heat deliverycan be achieved through other means. Extracorporealdevices that do not support circulation (e.g. haemodia-lysis) are relatively contraindicated because they can nega-tively impact the circulation and are relatively ineffectivein the absence of native circulation to perfuse the externalcircuitry. The optimal rewarming rate is unknown. Theo-retically, the most ‘dangerous’ time for the patient is fromwhen the brain temperature rises >28 °C until ROSC isachieved. Current expert opinion suggests performinghigh-quality mechanical or manual CPR; rewarming asquickly as possible until ROSC is achieved; one or moreexternal heat delivery devices applied only around thetrunk to reduce the likelihood of afterdrop throughperipheral vasodilation (e.g. heating blanket under thepatient plus one or two heating blankets on the patient);warm bladder lavage through a 3-way catheter or if avail-able, warm peritoneal lavage. Intravenous infusions shouldbe warmed. Once the core temperature rises >28 °C,attempts at defibrillation may be considered for eachdegree of rewarming or with any change in observed heartrhythm. Given that studies have shown that prolongedCPR does not preclude survival [194], and that high qua-lity CPR is possible with a mechanical device, transfer toan ECLS centre is recommended.Extracorporeal life supportECLS using veno-arterial extracorporeal membrane oxy-genation (VA-ECMO) or cardiopulmonary bypass (CPB)are the rewarming treatments of choice and should beperformed in the presence of primary hypothermic CAor severe circulatory instability refractory to ALS due toHT III–IV. ECLS is safe and survival rates are higherthan rewarming by other methods. ECLS immediatelyNon-ECLS rewarmingIn a hypothermic patient with CA, non-ECLS rewarmingis only indicated if ECLS is not available for any reason.To be effective, rewarming by non-ECLS methods is reli-ant on the presence of a circulation so in a CA situation,rewarming is extremely slow, and until the heart is warmenough to restart, it is necessary to provide prolongedcontinuous CPR, which is very demanding. No evidencerestores the circulation, maintains tissue oxygenationand CO2 removal and provides fast and controllablePaal et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine  (2016) 24:111 Page 11 of 20Table 4 Main physiological effects of severe hypothermiaSystem Parameterrewarming. Reported survival rates are variable (23–100 %) reflecting the wide variety of factors includingenvironment (e.g. speed of cooling; hypoxic or non-hypoxic CA), patient factors (e.g. the presence ofCARDIOVASCULAR[79, 230, 267]• Initial vasoconstriction (effect blocked by ethanol).Vasoconstriction fails <24 °C [268].• Cardiac conduction is affected by cold and changes inpH and PaO2 [79]. Initial tachycardia due to shivering [subsides as temperature drops due to decreasedspontaneous depolarization of pacemaker cells leadinglinear fall in pulse rate (~50 % at 28 °C) [79]. Any ECGrhythm is possible. Commonly at <32 °C, sinus bradycaprolonged QTc. J waves (not pathognomonic forhypothermia) best seen in leads I & V6 [79, 269–272].Likelihood of VF is high <28 °C [267].• Cardiac output falls to 45 % at 25 °C [79].• After rewarming, mean arterial pressure, contractility,and cardiac output are decreased, especially if alcoholingested before cooling [273].CENTRALNERVOUS SYSTEM• Reflexes become increasingly sluggish as bodytemperature falls and become absent ≈ 28–30 °C [230,• Pupils become dilated and cease reacting to light at ≈• EEG shows burst suppression ≈ 22 °C and becomesisoelectric ≈ 18–20 °C [79, 275].RESPIRATORY • Tidal volume, respiratory rate, pulmonary compliance athoracic elasticity decrease [230]. The respiratory rate monly be five breaths per minute when the body tempe<30 °C [79]. Sensitivity to CO2 is attenuated, although tdrive is maintained to deeper levels of hypothermia [2reflex is obtunded, ciliary activity is reduced and secretmore viscous.• Oxygen consumption and carbon dioxide productionabout 50 % at 30 °C [230]RENAL &METABOLIC• Cold diuresis, partly due to the relative central hypervoresulting from peripheral vasoconstriction [79], but alsoa reduction in ADH release and resistance to its effectsAlcohol will further increase the diuresis.• Hyperglycaemia is common due to catecholamine-indglycogenolysis, decreased insulin release and inhibitioninsulin transport [79, 267].• Glomerular filtration rate falls as cardiac output and heblood flow fall [230]. At low temperatures, tubular capaH+ secretion is reduced, and hence there is a renal comof the acidosis [230].• Hypokalaemia commonly occurs with hypothermia [23HAEMATOLOGY • Haematocrit increases by about 2 % for every 1 °C decin temperature [250].COAGULATION • Platelet function and coagulation enzyme activity are redClinical implicationsconcurrent medical problems), causes of hypothermia(e.g. avalanche, water), issues arising during rescue, hos-pital selection criteria and facilities, and treatmentsavailable e.g. VA-ECMO vs. CPB [2, 6, 41, 209, 210].• Failed vasoconstriction means the patient becomespoikilothermic i.e. dependent on ambient temperature.79]tordia,• Bradycardia is atropine unresponsive [79].• A “relative” tachycardia inconsistent with patient’stemperature means something else is going one.g. occult trauma.• Be prepared for any rhythm but expect it to beresistant to treatment until the heart rewarms.• Normal rhythm resumes on rewarming.• Hypotension is the norm.• More prolonged depression of cardiac function afterrewarming274].28 °C [230].• The level of consciousness should be consistent withthe core temperature. A significant discrepancy suggestsan alternative diagnosis.• All the effects of hypothermia make it very hard todiagnose death by the usual criteria while the patientis still coldndayrature ishe hypoxic30]. Coughions are• An irregular respiratory pattern can be mistaken foragonal breathing leading to premature institution of CPR.• The likelihood of a chest infection is increased.fall by • Reduced CO2 production means it is easy to inadvertentlyhyperventilate hypothermic patients. Hyperoxia is alsopossible.laemiafrom[230].• Severely hypothermic patients are dehydrated.This becomes particularly important during rewarmingas the consequent opening up of the peripheralcirculation will lead to a rapid fall in BP.ucedof• Hyperglycaemia can exacerbate the diuresis.nce renalcity forponent• This makes the interpretation of acid-base more complex.0]. • If potassium replacement is given excess to the losses,hyperkalaemia may occur on rewarming [276, 277].• Severe initial hyperkalaemia is a marker of acidosisand cell death and is therefore a sign of poor prognosis [8]line • A normal haematocrit in a moderately or severelyhypothermic patient suggests pre-existing anaemiaor blood loss [230].uced [278]. • Coagulopathy is likely and increases with decreasing coretemperature. At temperatures below 33 °C coagulopathysignificantly increases mortality in patients withconcomitant trauma [279].Paal et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine  (2016) 24:111 Page 12 of 20The majority of patients with primary hypothermiawill maintain a perfusing rhythm until <28 °C. There-fore, the indication for ECLS in arrested patients withcore temperature 28–32 °C is more controversial since alarger proportion of these patients will have suffered CAfrom other causes and the chances of a good neuro-logical outcome are reduced. The use of ECLS for HTIII (<28 °C) patients (not in CA) may be considered inthe following situations [2] (1) failure to improve withexternal active and minimally invasive rewarmingmethods, as described above (Table 3) (2) life-threateningarrhythmia; (3) hypotension (systolic blood pressure<90 mmHg); (4) respiratory failure; (5) refractory acidosis.Older patients, or those with comorbidities, that limittheir tolerance for the low-flow state of HT III, may havebetter outcomes when managed with ECLS [209]. Younghealthy HT III patients should initially be rewarmed by ac-tive external methods and minimally invasive rewarming.For patients at risk of CA (i.e. core body temperature<28 °C, ventricular arrhythmia, systolic blood pressure<90 mmHg), rewarming should ideally take place in anECLS centre with the equipment and personnel availableon site until the patient has stabilized.In the past, most ECLS rewarming was performed usingCPB [211]. More recently, VA-ECMO has become thepreferred method due to its rapid availability, lower hepa-rinisation requirements and the possibility of prolongingcardiorespiratory support if required after rewarminge.g. continuing cardiac instability, arrhythmias and post-rewarming severe pulmonary oedema [6, 11, 212]. Inhypothermic CA victims, similar ROSC rates after CPBor VA-ECMO rewarming are reported though oneretrospective study reported better survival with VA-ECMO [6]. Multi-organ failure is not unusual and mayrequire prolonged VA-ECMO to maintain adequateperfusion and oxygenation until recovery of organfunction [6, 213, 214]. Veno-venous ECMO is inef-fective in circulatory arrest, but it can be used in ahaemodynamically-stable patient with respiratory fail-ure after rewarming with VA-ECMO.Cannulation of the femoral artery and vein is thequickest and easiest way to establish emergency access.Sternotomy is less desirable since it is time-consumingand CPR has to be interrupted. Ideally CPR shouldcontinue until ECLS-rewarming has started [161]. Depen-ding on the available type of rewarming (CPB vs. VA-ECMO), patients should be heparinised according to localECLS protocols. In hypothermic multi-trauma patients,using heparinised ECLS systems and a reduction ofthe systemic heparinisation should be considered. Newcompletely-heparinised VA-ECMO systems may be usedfor up to one week with minimal heparinisation. Thismakes ECLS rewarming also suitable for hypothermic CApatients with trauma and high risk of haemorrhage.General anaesthesia should be provided to prevent the pa-tient from waking or being aware during the procedure. It isgenerally advisable to start ECLS-rewarming with circuittemperatures approximately the same as the admissiontemperature of the patient, the idea being to avoid a largetemperature gradient when ECLS commences [215]. Flowsare increased gradually in an attempt to avoid the risk ofgas bubble formation and ischaemia/reperfusion-inducedcell damage. Gradually increasing flow to 2.2–2.5 L min-1m-2, a pressure >45 mmHg, a rewarming rate of 1 °C per10 min, maintaining a temperature gradient 5–10 °Cbetween the venous blood and the heat exchanger avoidsgas emboli and seems safe. Rewarming rates between 1 °C5 min-1 and 1 °C hour-1 are commonly used, but the opti-mal rate is unknown and thus not standardized. Whenusing femoral access, the presence of native cardiac func-tion will provide a counter flow in the ascending aorta andaortic arch. Ventilation must be started as soon as ECLShas been established to avoid perfusing the heart and thebrain with deoxygenated blood [216–219].ECLS should be continued until the patient has astable cardiac rhythm, adequate native perfusion andoxygenation, and a core temperature >32 °C. Inotropesor vasopressors may be used for weaning. Targetedtemperature management should be performed accord-ing to local protocols and post-resuscitation hyperther-mia should be avoided [41, 220, 221]. However, the maingoal is to optimize haemodynamic status and ensure ad-equate cerebral perfusion. Cardiac stunning or multi-organ failure are not unusual following prolonged CPR,ischaemia and subsequent ECLS reperfusion, and mayrequire post-resuscitation VA-ECMO until adequate car-diorespiratory recovery. In a recent study, severelyhypothermic patients (with and without CA) rewarmedwith VA-ECMO, bi-ventricular diastolic dysfunction per-sisted despite systolic function recovery [222].Termination of ECLS is considered if there is no ROSCat 32–35 °C [10, 223]. The decision to stop treatment mayalso be based on additional clinical information, such asuncontrollable haemorrhage, new information relating tothe cause of CA or signs of severe anoxic brain injury.Prolonged HT III and IV from any cause are relativelyrare, and although premature death due to CA may occur,successful resuscitation by ECLS rewarming is possible.The outcomes of all such cases are under-reported, yetmuch could be learned from them. Therefore, the Inter-national Hypothermia Registry [224] was created at theUniversity Hospital of Geneva, Switzerland, to collect casereports from across the world. If enough data can begathered, subsequent peer-review analysis will permit theestablishment of new consensus guidelines for the treat-ment of accidental hypothermia. All centres dealing withaccidental hypothermia patients can contribute to theRegistry.Paal et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine  (2016) 24:111 Page 13 of 20Hypothermia in childrenCooling in children is discussed briefly in the section onhypothermia and drowning. The stages, symptoms andsigns of hypothermia in children are broadly similar toadults. The most important clue to significant hypothermiain children is altered mental status. The presence or ab-sence of shivering is not a reliable marker of severity ofhypothermia [46]. Unlike adults, small children may stillhave signs of life with a core temperature in the mid-teens[192] and a normal cardiac rhythm may resume when thetemperature is 20 °C or less [192, 225]. Rewarming may befaster in children compared to adults given the largersurface-to-mass ratio and should follow the same principlesas for adults [131, 133, 192, 212, 226].Does a country benefit from an accidental hypothermiaalgorithm?In contrast to robust recommendations for the out-of-hospital management of hypothermic patients [10, 18, 227]algorithms for the in-hospital treatment are rare: Accordingto an expert meeting in Bern, Switzerland (2013), stra-tegies for the assessment and therapy of hypothermicpatients vary widely and although several hospitals havedeveloped algorithms, they face challenges with validation,implementation and publication of suggested guidelines[112, 228, 229]. Because hypothermic patients are notonly admitted to level I hospitals but also to smallerhospitals, recommendations should focus on a smallset of universally-available transport and treatmentoptions. Accidental Hypothermia centres and treatmentalgorithms should be developed within the present struc-tures of specialized departments capable of ECLS rewar-ming [112, 228, 230]. These algorithms include trainingof emergency medical services for recognition and treat-ment of severe hypothermia, the special requirements ofhypothermic CA, pre-hospital core temperature measure-ment, insulation, rewarming, adequate hospital-selectionfor patients potentially requiring ECLS-rewarming, asdescribed above [10, 231].A good model for co-ordinating hypothermia care hasbeen created in south-east Poland. Medical personnelin- and out-of-hospital have been trained in diagnosisand management of hypothermia, and ECLS rewarmingfacilities and intensive care treatment are available. Acoordinator, who is an accidental hypothermia specialist,is available 24/7 to assist in case a critically hypothermicpatient is reported [160, 229].ConclusionsThe hospital use of minimally-invasive rewarming fornon-arrested, otherwise healthy, patients with primaryhypothermia and stable vital signs has the potential tosubstantially decrease morbidity and mortality for thesepatients. ECLS has revolutionised the management ofhypothermic CA, with survival rates approaching 100 %in some cases. Hypothermic patients with risk factorsfor imminent CA (e.g. temperature <28 °C, ventriculararrhythmia, systolic blood pressure <90 mmHg), andthose who have already arrested, should be transferreddirectly to an ECLS-centre. Cardiac arrest patientsmust receive CPR during transfer. In difficult condi-tions mechanical or intermittent CPR should be consid-ered. ECLS has substantially improved survival and isthe treatment of choice in the patient with unstablecirculation or CA. Modern post-resuscitation careshould be implemented following hypothermic arrest.Structured protocols should be in place to optimisepre-hospital triage, transport and treatment as well asin-hospital management, including detailed criteria andprotocols for the use of ECLS and post-resuscitationcare.Based on new evidence, additional clinical experiencewith ECLS rewarming and clearer management guide-lines and documentation, the treatment of accidentalhypothermia has been refined.AbbreviationsALS: Advanced life support; CA: Cardiac arrest; CO2: Carbon dioxide;CPB: Cardiopulmonary bypass; CPC: Cerebral performance category;CPR: Cardiopulmonary resuscitation; DHCA: Deep hypothermic circulatory arrest;ECLS: Extracorporeal life support; ECMO: Extracorporeal membrane oxygenation;ETCO2: End tidal carbon dioxide; HT: Hypothermia; NIRS: Near infraredspectroscopy; O2: Oxygen; PaO2: Partial arterial oxygen pressure; ROSC: Return ofspontaneous circulation; rSO2: Regional oxygen saturation; VA: Veno-arterialAcknowledgementsNot applicable.FundingThis review was not supported by any external funds.Availability of data and supporting materialsThis review article does not contain any original human or animal data.If the Journal wants to see any specific literature we can sent it uponrequest.Authors’ contributionsPP and LG have equally contributed to this article and should be bothconsidered as first authors. Each author drafted one or more sections. Thesewere then extensively discussed by all the authors to produce the final version.PP conceived this review, invited the co-authors, drafted introduction, methods,the “Cardiopulmonary resuscitation” and “Dispatching and transport decisions”and Table 2 (most extreme accidental hypothermia cases), discussed andcritically revised the manuscript. LG drafted “Interpreting arterial blood gases insevere hypothermia”, “Anaesthesia,” “Hypothermia in children”, Hypothermiaand drowning and the “physiological effects table”, and substantially revisedand finalized the manuscript. GS drafted “Temperature measurement”, discussedand critically revised the manuscript. MBM drafted “Oxygenation, anaesthesiainduction and airway management” and “Does a country benefit from anaccidental hypothermia algorithm”, discussed and critically revised themanuscript. GP co-authored the “Cardiopulmonary resuscitation” and“Dispatching and transport decisions” drafts, discussed and critically revised themanuscript. BW and MW drafted “Extracorporeal Life Support”, discussed andcritically revised the manuscript. DB drafted “Non ECLS rewarming”, Table 3 onrewarming techniques, discussed and critically revised the manuscript. MHdiscussed and critically revised the manuscript. GB discussed and criticallyrevised the manuscript. HB drafted “Staging” and “Prehospital insulation,rewarming, rescue collapse and afterdrop”, and critically revised the manuscript.All authors read and approved the final manuscript.Paal et al. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine  (2016) 24:111 Page 14 of 20Competing interestsMichael Holzer received travel grants for scientific conferences and honorariafor lectures from Bard Medical, EmCools, Polimed Sp. z o.o. and Zoll Medical,Austria. He received honoraria for consulting from Zoll Medical, Austria andwas responsible for studies where the Department of Emergency Medicinereceived study grants from Velomedix and Philips. Peter Paal received travelgrants for scientific conferences and honoraria for lectures from Zoll Medical,Austria. The other authors declare that they have no competing interests.Consent for publicationIs not applicable.Ethics approval and consent to participateIs not applicable: This is a review article and does not contain any originalhuman or animal data, therefore an ethics committee approval and consentto participate statement does not apply to this manuscript.Author details1Department of Anaesthesiology and Critical Care Medicine, InnsbruckUniversity Hospital, Anichstr. 35, 6020 Innsbruck, Austria. 2Barts Heart Centre,St Bartholomew’s Hospital, West Smithfield, Barts Health NHS Trust, QueenMary University of London, KGV Building, Office 10, 1st floor, West Smithfield,London EC1A 7BE, UK. 3International Commission of Mountain EmergencyMedicine (ICAR MEDCOM), Kloten, Switzerland. 4Department of Anaesthesia,University hospitals, Morecambe Bay Trust, Lancaster, UK. 5LangdaleAmbleside Mountain Rescue Team, Ambleside, UK. 6Institute of MountainEmergency Medicine, EURAC research, Drususallee 1, Bozen/Bolzano, Italy.7Department of Emergency Medicine, Inselspital, Bern University Hospital,Bern, Switzerland. 8Department of Surgery, Cardiovascular Research, Serviceof Cardiovascular Surgery, University Hospital Geneva, Geneva, Switzerland.9Department of Cardiothoracic Anaesthesia and Intensive Care 4142,Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.10Department of Emergency Medicine, University of British Columbia,Vancouver, Canada. 11Department of Emergency Medicine, MedicalUniversity of Vienna, Vienna, Austria. 12Department of Neurology, NeurologicIntensive Care Unit, Medical University of Innsbruck, Innsbruck, Austria.Received: 8 June 2016 Accepted: 7 September 2016References1. 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