Search

The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for prevention and treatment of frostbite. We present a review of pertinent pathophysiology. We then discuss primary and secondary prevention measures and therapeutic management. Recommendations are made regarding each treatment and its role in management. These recommendations are graded on the basis of the quality of supporting evidence and balance between the benefits and risks or burdens for each modality according to methodology stipulated by the American College of Chest Physicians. This is an updated version of the guidelines published in 2014.

Background Acute mountain sickness is a common occurrence for travel to high altitudes. Although previous studies of ibuprofen have shown efficacy for the prevention of acute mountain sickness, recommendations have been limited, as ibuprofen has not been compared directly with acetazolamide until this study. Methods Before their ascent to 3810 m on White Mountain in California, adult volunteers were randomized to ibuprofen (600 mg, 3 times daily, started 4 hours before the ascent), or to acetazolamide (125 mg, twice daily, started the night before the ascent). The main outcome measure was acute mountain sickness incidence, using the Lake Louise Questionnaire (LLQ), with a score of >3 with headache. Sleep quality and headache severity were measured with the Groningen Sleep Quality Survey (GSQS). This trial was registered at ClinicalTrials.gov: NCT03154645 Results Ninety-two participants completed the study: 45 (49%) on ibuprofen and 47 (51%) on acetazolamide. The total incidence of acute mountain sickness was 56.5%, with the incidence for the ibuprofen group being 11% greater than that for acetazolamide, surpassing the predetermined 26% noninferiority margin (62.2% vs 51.1%; 95% confidence interval [CI], –11.1 to 33.5). No difference was found in the total LLQ scores or subgroup symptoms between drugs (P = .8). The GSQS correlated with LLQ sleep (r = 0.77; 95% CI, 0.67–0.84)=%. The acetazolamide group had higher peripheral capillary oxygen saturation than the ibuprofen group (88.5% vs 85.6%; P = .001). Conclusion Ibuprofen was slightly inferior to acetazolamide for acute mountain sickness prevention and should not be recommended over acetazolamide for rapid ascent. Average symptoms and severity were similar between drugs, suggesting prevention of disease.

Severe frostbite occurs frequently at extreme altitude in the Himalayas, often resulting in amputations. Recent advances in treatment of frostbite injuries with either intravenous or intra-arterial tissue plasminogen activator, or with iloprost, have improved outcomes in frostbite injuries, but only if the patient has access to these within 24 to 48 h postinjury, and ideally even sooner. Frostbitten Himalayan climbers are seldom able to reach medical care in this time frame. We wished to see if delayed iloprost use (up to 72 h) would help reduce tissue loss in grade 3 to 4 frostbite. In a series of 5 consecutive climbers with severe frostbite in whom we used iloprost, 4 of whom received treatment between 48 and 72 h from injury, 2 had excellent results with minimal tissue loss, and 2 had good results with tissue loss less than expected. The 1 patient with a poor outcome likely experienced a freeze-thaw-refreeze injury. This small series suggests that iloprost can be beneficial for severe frostbite, even after the standard 48-h window and perhaps for up to 72 h.

Brodmann Maeder, Monika, Hermann Brugger, Matiram Pun, Giacomo Strapazzon, Tomas Dal Cappello, Marco Maggiorini, Peter Hackett, Peter Baärtsch, Erik R. Swenson, Ken Zafren (STAR Core Group), and the STAR Delphi Expert Group. The STARdata reporting guidelines for clinical high altitude research. High AltMedBiol. 19:7–14, 2018. Aims: The goal of the STAR (STrengthening Altitude Research) initiative was to produce a uniform set of key elements for research and reporting in clinical high-altitude (HA) medicine. The STAR initiative was inspired by research on treatment of cardiac arrest, in which the establishment of the Utstein Style, a uniform data reporting protocol, substantially contributed to improving data reporting and subsequently the quality of scientific evidence. Materials and Methods: The STAR core group used the Delphi method, in which a group of experts reaches a consensus over multiple rounds using a formal method. We selected experts in the field of clinical HA medicine based on their scientific credentials and identified an initial set of parameters for evaluation by the experts. Results: Of 51 experts in HA research who were identified initially, 21 experts completed both rounds. The experts identified 42 key parameters in 5 categories (setting, individual factors, acute mountain sickness and HA cerebral edema, HA pulmonary edema, and treatment) that were considered essential for research and reporting in clinical HA research. An additional 47 supplemental parameters were identified that should be reported depending on the nature of the research. Conclusions: The STAR initiative, using the Delphi method, identified a set of key parameters essential for research and reporting in clinical HA medicine.

Background The development of trio binning as an approach for assembling diploid genomes has enabled the creation of fully haplotype-resolved reference genomes. Unlike other methods of assembly for diploid genomes, this approach is enhanced, rather than hindered, by the heterozygosity of the individual sequenced. To maximize heterozygosity and simultaneously assemble reference genomes for 2 species, we applied trio binning to an interspecies F1 hybrid of yak (Bos grunniens) and cattle (Bos taurus), 2 species that diverged nearly 5 million years ago. The genomes of both of these species are composed of acrocentric autosomes. Results We produced the most continuous haplotype-resolved assemblies for a diploid animal yet reported. Both the maternal (yak) and paternal (cattle) assemblies have the largest 2 chromosomes in single haplotigs, and more than one-third of the autosomes similarly lack gaps. The maximum length haplotig produced was 153 Mb without any scaffolding or gap-filling steps and represents the longest haplotig reported for any species. The assemblies are also more complete and accurate than those reported for most other vertebrates, with 97% of mammalian universal single-copy orthologs present. Conclusions The high heterozygosity inherent to interspecies crosses maximizes the effectiveness of the trio binning method. The interspecies trio binning approach we describe is likely to provide the highest-quality assemblies for any pair of species that can interbreed to produce hybrid offspring that develop to sufficient cell numbers for DNA extraction.

BackgroundAssemblies of diploid genomes are generally unphased, pseudo-haploid representations that do not correctly reconstruct the two parental haplotypes present in the individual sequenced. Instead, the assembly alternates between parental haplotypes and may contain duplications in regions where the parental haplotypes are sufficiently different. Trio binning is an approach to genome assembly that uses short reads from both parents to classify long reads from the offspring according to maternal or paternal haplotype origin, and is thus helped rather than impeded by heterozygosity. Using this approach, it is possible to derive two assemblies from an individual, accurately representing both parental contributions in their entirety with higher continuity and accuracy than is possible with other methods.ResultsWe used trio binning to assemble reference genomes for two species from a single individual using an interspecies cross of yak (Bos grunniens) and cattle (Bos taurus). The high heterozygosity inherent to interspecies hybrids allowed us to confidently assign >99% of long reads from the F1 offspring to parental bins using unique k-mers from parental short reads. Both the maternal (yak) and paternal (cattle) assemblies contain over one third of the acrocentric chromosomes, including the two largest chromosomes, in single haplotigs.ConclusionsThese haplotigs are the first vertebrate chromosome arms to be assembled gap-free and fully phased, and the first time assemblies for two species have been created from a single individual. Both assemblies are the most continuous currently available for non-model vertebrates.

Background: Acetazolamide is the most common medication used for prevention of acute mountain sickness (AMS), usually administered the day or night before ascent. The objective of this stu...

To provide guidance to clinicians, the Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for the out-of-hospital evaluation and treatment of victims of accidental hypothermia. The guidelines present the main diagnostic and therapeutic modalities and provide recommendations for the management of hypothermic patients. The panel graded the recommendations based on the quality of supporting evidence and a balance between benefits and risks/burdens according to the criteria published by the American College of Chest Physicians. The guidelines also provide suggested general approaches to the evaluation and treatment of accidental hypothermia that incorporate specific recommendations. This is the 2019 update of the Wilderness Medical Society Practice Guidelines for the Out-of-Hospital Evaluation and Treatment of Accidental Hypothermia: 2014 Update.

Background: Genetic testing for pedigree accuracy is critical for managing genetic diversity in North American (NA) yak (Bos grunniens), a population expanded mostly from imported zoological park specimens. DNA testing also enhances species conservation by identifying recentB. taurusF1 hybrid ancestors (within three generations). Biallelic single nucleotide polymorphisms (SNPs) can accomplish either task, but increases the marker count and costs necessary to achieve both. Our aim was to identify novel, multifunctional, triallelic yak SNPs (tySNPs), with each having two alleles for yak parentage testing, and a third allele for identifying recent cattle introgression. Methods: Genome sequences were aligned to the cattle UMD3.1 assembly and SNPs were screened for 1) heterozygosity in a NA and a Chinese yak, 2) a third allele at high frequency in cattle, and 3) flanking sequences conserved in both species. Subsequently, tySNPs were filtered for unique alignment to the haplotype-resolved F1 yak assembly. Allele frequencies were estimated in a subset of 87 tySNPs by genotyping 170 NA yak.Results: We identified 610 autosomal tySNPs, distributed in 441 clusters with 5 Mb average genome spacing. The average NA yak minor allele frequency was high (0.296), while average introgressed cattle alleles were low (0.004). In simulations with tySNPs, 28 were sufficient for globally-unique animal identification (PI=5.81x10-12), 87 were able to exclude 19 random bulls from parentage at the 99% level without using the dam’s genotype (PE=5.3x10-4), and 87 were able to detect F1 hybridization events after three generations of yak backcrosses (1/16thB. taurusgermplasm).Conclusions: Identifying animals, determining parentage and detecting recent hybridization events was efficient with as few as 87 tySNPs. A similar triallelic approach could be used with other bottleneckedBosspecies that hybridize with cattle, such as NA plains bison (B. bison).

To provide guidance to clinicians about best preventive and therapeutic practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. Recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to prevention and management of each form of acute altitude illness that incorporate these recommendations. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in 2010 and subsequently updated as the WMS Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness in 2014.

The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for the prevention and treatment of frostbite. We present a review of pertinent pathophysiology. We then discuss primary and secondary prevention measures and therapeutic management. Recommendations are made regarding each treatment and its role in management. These recommendations are graded on the basis of the quality of supporting evidence and balance between the benefits and risks or burdens for each modality according to methodology stipulated by the American College of Chest Physicians. This is an updated version of the original guidelines published in Wilderness & Environmental Medicine 2011;22(2):156–166.

To provide guidance to clinicians about best practices, the Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for prevention and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. These guidelines present the main prophylactic and therapeutic modalities for each disorder and provide recommendations about their role in disease management. Recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to prevention and management of each disorder that incorporate these recommendations. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in WildernessEnvironmental Medicine 2010;21(2):146-155.

how humans and other organisms sense and respond to hypoxia is a rapidly growing research field, with more than 18,000 MEDLINE citations on hypoxia since the last Journal of Applied Physiology Highlighted Topic in this area in 2015, and more than 80,000 since this series first appeared. Reflecting

Background Inhaled budesonide has been suggested as a novel prevention for acute mountain sickness. However, efficacy has not been compared with the standard acute mountain sickness prevention medication acetazolamide. Methods This double-blind, randomized, placebo-controlled trial compared inhaled budesonide versus oral acetazolamide versus placebo, starting the morning of ascent from 1240 m (4100 ft) to 3810 m (12,570 ft) over 4 hours. The primary outcome was acute mountain sickness incidence (headache and Lake Louise Questionnaire ≥3 and another symptom). Results A total of 103 participants were enrolled and completed the study; 33 (32%) received budesonide, 35 (34%) acetazolamide, and 35 (34%) placebo. Demographics were not different between the groups ( P > .09). Acute mountain sickness prevalence was 73%, with severe acute mountain sickness of 47%. Fewer participants in the acetazolamide group (n = 15, 43%) developed acute mountain sickness compared with both budesonide (n = 24, 73%) (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.3-10.1) and placebo (n = 22, 63%) (OR 0.5, 95% CI 0.2-1.2). Severe acute mountain sickness was reduced with acetazolamide (n = 11, 31%) compared with both budesonide (n = 18, 55%) (OR 2.6, 95% CI 1-7.2) and placebo (n = 19, 54%) (OR 0.4, 95% CI 0.1-1), with a number needed to treat of 4. Conclusion Budesonide was ineffective for the prevention of acute mountain sickness, and acetazolamide was preventive of severe acute mountain sickness taken just before rapid ascent.

High altitude illness encompasses a spectrum of clinical entities to include: acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. These illnesses occur as a result of a hypobaric hypoxic environment. Although a mild case of acute mountain sickness may be self-limited, high altitude cerebral edema and high altitude pulmonary edema represent critical emergencies that require timely intervention. This article reviews recent advances in the prevention and treatment of high altitude illness, including new pharmacologic strategies for prophylaxis and revised treatment guidelines.

We observed patients with chronic mountain sickness (CMS) in our clinic who developed progressive neurological deterioration (encephalopathy) and we wished to investigate this. We studied nine such CMS patients, and compared them to 21 CMS patients without encephalopathy, and to 15 healthy control subjects without CMS. All 45 subjects lived permanently at 3200–4000 m. Measurements at 2260 m included CMS symptom score, multi-slice CT, perfusion CT, pulse oximetry (SpO2%), and hemoglobin concentration (Hb). One patient had MRI imaging but not CT; 5 had CSF pressure measurements. CMS subjects had lower SpO2, higher Hb, higher brain blood density, lower mean cerebral blood flow (CBF), and significant cerebral circulatory delay compared to controls. The nine CMS subjects with neurological deterioration showed diffuse cerebral edema on imaging and more deranged cerebral hemodynamics. CSF pressure was elevated in those with edema. We conclude that cerebral edema, a previously unrecognized complication, may develop in CMS patients and cause encephalopathy. Contributing factors appear to be exaggerated polycythemia and hypoxemia, and lower and sluggish CBF compared to CMS patients without cerebral edema; but what triggers this complication is unknown. Recognition and treatment of this serious complication will help reduce morbidity and mortality from CMS.

Luks, Andrew M., Colin Grissom, Luanne Freer, and Peter Hackett. Medication use among mount Everest climbers: practice and attitudes. High Alt Med Biol. 17:315-322, 2016.-The lay public, media, and medical experts have expressed concern about the ethics of climbers using medications to improve performance and increase the odds of summit success while climbing at high altitude, but the true incidence of this practice remains unclear. We conducted an anonymous survey of climbers who have attempted to climb Mt. Everest to gather information about medication use and attitudes toward medication and supplemental oxygen use while climbing the mountain. One hundred eighty-seven individuals completed the survey, providing information about medication and oxygen use for 262 expeditions to Mt. Everest between 1963 and 2015, the majority of which occurred after the year 2000. The majority of respondents were male (82%) and from English-speaking countries (75%). Medications were used on 43% of climbs, with acetazolamide being the most commonly used medication. Reported use of dexamethasone, nifedipine, sildenafil, or tadalafil was uncommon as was use of multiple medications at the same time. The majority of respondents indicated that it was acceptable for climbers to use medications and supplemental oxygen to prevent altitude illness while climbing Mt. Everest. Opinions were more mixed regarding whether summiting without the use of medications or oxygen carried the same value as reaching the summit using those interventions. Our data suggest that less than one-half of Mt. Everest climbers use medications during their expedition, with the primary medication used being acetazolamide, for prevention of altitude illness. Given the limitations of the study design and preliminary nature of these data, further research is warranted to further clarify these issues.

Allergies and adverse reactions to sulfonamide medications are quite common. Two distinct categories of drugs are classified as sulfonamides: antibiotics and nonantibiotics. The two groups differ in their chemical structure, use, and the rate at which adverse reactions occur. Cross-reactivity between the two groups has been implied in the past, but is suspect. Acetazolamide, from the nonantibiotic group, is routinely used in the prevention and treatment of high altitude issues and may not need to be avoided in individuals with a history of sulfonamide allergy. This review addresses the differences between the groups and the propensity for intergroup and intragroup adverse reactions based on the available literature. We also examine the different clinical presentations of allergy and adverse reactions, from simple cutaneous reactions with no sequelae through Stevens-Johnson syndrome and anaphylaxis, with risk for significant morbidity and mortality. We offer a systematic approach to determine whether acetazolamide is a safe option for those with a history of allergy to sulfonamides.

To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the prevention and treatment of acute mountain sickness (AMS), high altitude cerebral edema (HACE), and high altitude pulmonary edema (HAPE). These guidelines present the main prophylactic and therapeutic modalities for each disorder and provide recommendations for their roles in disease management. Recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to the prevention and management of each disorder that incorporate these recommendations.

To determine the efficacy of 2 different sources of Ginkgo biloba extract (GBE) in reducing the incidence and severity of acute mountain sickness (AMS) following rapid ascent to high altitude.Two randomized, double-blind, placebo-controlled cohort studies were conducted in which participants were treated with GBE (240 mg x d(-1)) or placebo prior to and including the day of ascent from 1600 m to 4300 m (ascent in 2 hours by car). Acute mountain sickness was diagnosed if the Environmental Symptom Questionnaire III acute mountain sickness-cerebral (AMS-C) score wasor =0.7 and the Lake Louise Symptom (LLS) score wasor =3 and the participant reported a headache. Symptom severity was also determined by these scores.Results were conflicting: Ginkgo biloba reduced the incidence and severity of AMS compared to placebo in the first but not the second study. In the first study, GBE reduced AMS incidence (7/21) vs placebo (13/19) (P = .027, number needed to treat = 3), and it also reduced severity (AMS-C = 0.77 +/- 0.26 vs 1.59 +/- 0.27, P = .029). In the second study, GBE did not reduce incidence or severity of AMS (GBE 4/15 vs placebo 10/22, P = .247; AMS-C = 0.48 +/- 0.13 vs 0.58 +/- 0.11, P = .272). The primary difference between the 2 studies was the source of GBE.The source and composition of GBE products may determine the effectiveness of GBE for prophylaxis of AMS.

Previous studies have shown low-dose acetazolamide to be effective in preventing AMS in persons already at high altitude and then moving higher, a relatively low risk situation. We wished to evaluate prophylactic administration of low-dose acetazolamide for reducing the incidence and severity of AMS in a high-risk setting: rapid ascent from 1600 to 4300 m. We performed a double-blind, randomized, placebo-controlled study with human subjects (n=44) exposed to 4300 m for 24 h. Subjects were treated for 3 days prior to ascent to 4300 m and during day 1 at altitude with placebo (n=22) or acetazolamide 250 mg/day (125 mg bid, n=22). AMS diagnosis required both an AMS-C score from the Environmental Symptom Questionnaire-IIIor=0.7 and a Lake Louise Symptom (LLS) questionnaire scoreor=3 plus headache. Acetazolamide reduced the incidence of AMS compared to placebo-treated subjects (14% vs. 45%, respectively, p=0.02), and the number needed to treat was 3. The AMS-C and LLS scores were lower in acetazolamide-treated subjects, indicating less severe AMS. Low-dose acetazolamide administered prior to ascent and on day 1 at 4300 m effectively reduced the incidence and severity of AMS in a high-risk setting.

This review presents the potential impact of high altitude exposure on preexisting neurological conditions in patients usually living at low altitude. The neurological conditions include permanent and transient ischemia of the brain, occlusive cerebral artery disease, cerebral venous thrombosis, intracranial hemorrhage and vascular malformations, multiple sclerosis, intracranial space-occupying lesions, dementia, extrapyramidal disorders, migraine and other headaches, and epileptic seizures. New developments in diagnostic work-up and treatment of preexisting neurological conditions are also mentioned where applicable. For each neurological disorder, the authors developed absolute and relative contraindications for a trip to high altitude. These recommendations are not based on the results of controlled randomized trials, but mainly on case reports, pathophysiological considerations, and extrapolations from the low altitude situation.

To evaluate whether women engage in outdoor activities and high altitude travel during pregnancy; the health care advice received regarding high altitude during pregnancy; and the association between high altitude exposure and self-reported pregnancy complications.An online survey of women with at least 1 pregnancy distributed on websites and e-mail lists targeting mothers and/or mountain activities. Outcome measures were outdoor activities during pregnancy, high altitude (2440 m) exposure during pregnancy, and pregnancy and perinatal complications.Hiking, running, and swimming were the most common activities performed during pregnancy. Women traveled to high altitude in over half of the pregnancies (244/459), and most did not receive counseling regarding altitude (355, 77%), although a small proportion (14, 3%) were told not to go above 2440 m. Rates of miscarriage and most other complications were similar between pregnancies with and without travel above 2440 m. Pregnancies with high altitude exposure were more likely to have preterm labor (odds ratio [OR] 2.3; 95% CI 0.97-5.4; P = .05). Babies born to women who went to high altitude during pregnancy were more likely to need oxygen at birth (OR 2.34; 95% CI 1.04-5.26; P.05) but had similar rates of neonatal intensive care unit admission (P = not significant).Our results suggest pregnant women who are active in outdoor sports and travel to high altitude have a low rate of complications. Given the limitations of our data, further research is necessary on the risks associated with high altitude travel and physical activity and how these apply to the general population.

Participation in wilderness and adventure sports is on the rise, and as such, practitioners will see more athletes seeking clearance to participate in these events. The purpose of this article is to describe specific medical conditions that may worsen or present challenges to the athlete in a wilderness environment.

how humans and other organisms sense and respond to hypoxia is a rapidly growing research field, with more than 19,000 MedLine citations on hypoxia in the last 2 years alone. Reflecting the growing and widespread interest in hypoxia, this is the fourth Highlighted Topic in the Journal of Applied

High-altitude athletes and adventurers face a number of environmental and medical risks. Clinicians often advise participants or guiding agencies before or during these experiences. Preparticipation evaluation (PPE) has the potential to reduce risk of high-altitude illnesses in athletes and adventurers. Specific conditions susceptible to high-altitude exacerbation also important to evaluate include cardiovascular and lung diseases. Recommendations by which to counsel individuals before participation in altitude sports and adventures are few and of limited focus. We reviewed the literature, collected expert opinion, and augmented principles of a traditional sport PPE to accommodate the high-altitude wilderness athlete/adventurer. We present our findings with specific recommendations on risk stratification during a PPE for the high-altitude athlete/adventurer.

The pathophysiology of acute mountain sickness and high-altitude cerebral edema, the cerebral forms of high-altitude illness, remain uncertain and controversial. Persistently elevated or pathological fluctuations in intracranial pressure are thought to cause symptoms similar to those reported by individuals suffering cerebral forms of high-altitude illness. This review first focuses on the basic physiology of the craniospinal system, including a detailed discussion of the long-term and dynamic regulation of intracranial pressure. Thereafter, we critically examine the available literature, based primarily on invasive pressure monitoring, that suggests intracranial pressure is acutely elevated at altitude due to brain swelling and/or elevated sagittal sinus pressure, but normalizes over time. We hypothesize that fluctuations in intracranial pressure occur around a slightly elevated or normal mean intracranial pressure, in conjunction with oscillations in arterial Po2 and arterial blood pressure. Then these modest fluctuations in intracranial pressure, in concert with direct vascular stretch due to dilatation and/or increased blood pressure transmission, activate the trigeminal vascular system and cause symptoms of acute mountain sickness. Elevated brain water (vasogenic edema) may be due to breakdown of the blood-brain barrier. However, new information suggests cerebral spinal fluid flux into the brain may be an important factor. Regardless of the source (or mechanisms responsible) for the excess brain water, brain swelling occurs, and a “tight fit” brain would be a major risk factor to produce symptoms; activities that produce large changes in brain volume and cause fluctuations in blood pressure are likely contributing factors.

Despite advances in outdoor clothing and medical management of frostbite, individuals still experience catastrophic amputations. This is a particular risk for those in austere environments, due to resource limitations and delayed definitive treatment. The emerging best therapies for severe frostbite are thrombolytics and iloprost. However, they must be started within 24 hours after rewarming for recombinant tissue plasminogen activator (rt-PA) and within 48 hours for iloprost. Evacuation of individuals experiencing frostbite from remote environments within 24 to 48 hours is often impossible. To date, use of these agents has been confined to hospitals, thus depriving most individuals in the austere environment of the best treatment. We propose that thrombolytics and iloprost be considered for field treatment to maximize chances for recovery and reduce amputations. Given the small but potentially serious risk of complications, rt-PA should only be used for grade 4 frostbite where amputation is inevitable, and within 24 hours of rewarming. Prostacyclin has less risk and can be used for grades 2 to 4 frostbite within 48 hours of rewarming. Until more field experience is reported with these agents, their use should probably be restricted to experienced physicians. Other modalities, such as local nerve blocks and improving oxygenation at high altitude may also be considered. We submit that it remains possible to improve frostbite outcomes despite delayed evacuation using resource-limited treatment strategies. We present 2 cases of frostbite treated with rt-PA at K2 basecamp to illustrate feasibility and important considerations.

This review focuses on the epidemiology, clinical description, pathophysiology, treatment, and prevention of high altitude cerebral edema (HACE). HACE is an uncommon and sometimes fatal complication of traveling too high, too fast to high altitudes. HACE is distinguished by disturbances of consciousness that may progress to deep coma, psychiatric changes of varying degree, confusion, and ataxia of gait. It is most often a complication of acute mountain sickness or high altitude pulmonary edema. The current leading theory of its pathophysiology is that HACE is a vasogenic edema; that is, a disruption of the blood-brain barrier, and we review possible mechanisms to explain this. Treatment and prevention of HACE are similar to those for the other altitude illnesses, but with greater emphasis on descent and steroids. We conclude the review with several case histories to illustrate key clinical features of the disorder.

To provide guidance to clinicians, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the out-of-hospital evaluation and treatment of victims of accidental hypothermia. The guidelines present the main diagnostic and therapeutic modalities and provide recommendations for the management of hypothermic patients. The panel graded the recommendations based on the quality of supporting evidence and the balance between benefits and risks/burdens according the criteria published by the American College of Chest Physicians. The guidelines also provide suggested general approaches to the evaluation and treatment of accidental hypothermia that incorporate specific recommendations.

To provide guidance to clinicians, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the out-of-hospital evaluation and treatment of victims of accidental hypothermia. The guidelines present the main diagnostic and therapeutic modalities and provide recommendations for the management of hypothermic patients. The panel graded the recommendations based on the quality of supporting evidence and the balance between benefits and risks/burdens according the criteria published by the American College of Chest Physicians. The guidelines also provide suggested general approaches to the evaluation and treatment of accidental hypothermia that incorporate specific recommendations. This is an updated version of the original Wilderness Medical Society Practice Guidelines for the Out-of-Hospital Evaluation and Treatment of Accidental Hypothermia published in Wilderness & Environmental Medicine 2014;25(4):425-445.

SUMMARYTraditionally, scientists and clinicians have explored peripheral physiological responses to acute hypoxia to explain the pathophysiological processes that lead to acute mountain sickness (AMS) and high-altitude cerebral edema (HACE). After more than 100 years of investigation, little is yet known about the fundamental causes of the headache and nausea that are the main symptoms of AMS. Thus, we review the evidence supporting a change in focus to the role of the central nervous system in AMS. Our justification is (i) that the symptoms of AMS and HACE are largely neurological, (ii) that HACE is considered to be the end-stage of severe AMS and was recently identified as a vasogenic edema, opening the door for a role for blood–brain barrier permeability in AMS, (iii) that new, non-invasive techniques make measurement of brain water levels and cerebral blood volume possible and (iv) that the available experimental evidence and theoretical arguments support a significant role for brain swelling in the pathophysiology of AMS. We believe that an examination of the responses of the central nervous system to acute hypoxia will reveal important new pathophysiological processes that may help explain AMS and HACE.

Despite normal cerebral oxygenation and normal global cerebral metabolism, vasogenic edema develops in humans (and sheep) who become moderately ill with AMS/ HACE during 24 hr or more of hypoxic exposure. Hypoxic cerebral vasodilatation appears to be a necessary ingredient but does not per se explain the development of brain edema. In addition to mechanical factors, a number of biochemical mediators might play a role in altering the blood-brain barrier. Brain cell swelling (cytotoxic edema) likely has a role only in the later stages of HACE and not in AMS. The hypothesis that AMS is due to cerebral edema appears to be true for moderate-to-severe illness, but whether early AMS, especially the headache, is caused by edema is not known. Other mechanisms for the headache, perhaps similar to those of migraine, need to be explored. New data suggest that the brain swells on ascent to high altitudes regardless of AMS. Whether this is due to edema or engorgement with blood is not yet clear. The "tight fit" hypothesis proposes that individual anatomy of the craniospinal axis determines tolerance to mild brain edema and might help explain individual susceptibility; preliminary studies support this notion. Therapy for AMS and HACE is directed to reducing brain volume and stopping the BBB leak (i.e., oxygenation, diuretics, and steroids) before secondary ischemia develops. New therapies directed specifically toward the defect in BBB permeability are likely to be successful.

Increasing numbers of people are traveling to high altitude for work or pleasure. Given the prevalence of medical conditions in the general population, it is likely that many of these travelers will have one or more underlying medical problems. Unsure of how they will tolerate high altitude, these patients often seek input from their primary care physicians or travel clinical providers to determine if it is safe for them to make such a sojourn and, if so, what precautions should be taken during their trip to avoid problems that might lead to unplanned interruption of their trip. Clinicians faced with these concerns must address whether the underlying medical condition could be adversely affected by the hypoxic environment or alters the traveler’s risk for developing high-altitude illness. This chapter provides information to guide clinicians in answering these questions as they pertain to patients with a wide variety of medical problems including pulmonary diseases such as chronic obstructive pulmonary disease, asthma, and obstructive sleep apnea; cardiac problems including coronary artery diseases, cardiomyopathy, and adult congenital heart diseases; as well as gastrointestinal, endocrine, hematologic, neurologic, and renal disorders. For each disorder we consider the primary challenges faced by those patients at altitude and provide recommendations for pretravel assessment as well as risk mitigation during the trip. The chapter concludes by considering medication use at high altitude and, in particular, whether medications used for treatment of underlying disorders have the potential for adverse interactions with medications used in the prophylaxis and treatment of acute altitude illness and whether the dose and choice of altitude illness medication needs to be altered depending on the patients underlying health issues.

Travelers to high altitude may have disturbed sleep due to periodic breathing with frequent central apneas. We tested whether a mask with added dead space could reduce the central apneas of altitude. 16 subjects were recruited, age 18-35, residing at 4600 ft (1400 m). They each slept one night with full polysomnographic monitoring, including end tidal CO2, in a normobaric hypoxia tent simulating 12,000 ft. (3658 m) altitude. Those who had a central apnea index (CAI)20/h returned for a night in the tent for dead space titration, during which they slept with increasing amounts of dead space, aiming for a CAI5/h or10% of baseline. Then each subject slept another night with the titrated amount of dead space. Of the 16 subjects, 5 had a central apnea index20/h mean 49.1, range 21.4-131.5/hr. In each of the 5, the dead space mask reduced the CAI by at least 88% to a mean of 3.1, range 0.9-7.1/h, (p=0.04). Hypopnea index was unchanged. Three subjects required 500 cc of dead space or less. One subject required 860 cc, and one required 2.1 L. Morning symptoms and arousal index were not significantly affected by the dead space mask. Dead space did not appear to increase the CO2 reserve. At 12,000 ft., central apneas can be effectively reduced with a dead space mask, but clinical utility will require further evaluation.