Hrev_master [Emergency Care Journal 2014; 10:4279] [page 80] Two cases of paradoxical hypothermia in a Sahara desert multi-stage ultramarathon Elizabeth A. Kaufman,1 Grant S. Lipman,1 Louis J. Sharp,2,3 Brian J. Krabak4 1Department of Surgery, Division of Emergency Medicine, Stanford University School of Medicine, Stanford, CA; 2Emergency Medicine Residency, Presence Resurrection Medical Center, Chicago, IL; 3Department of Emergency Medicine, University of Illinois, Chicago, IL; 4Department of Rehabilitation, Orthopedics and Sports Medicine, University of Washington and Seattle Children’s Hospital, Seattle, WA, USA Abstract Exertional hypothermia in a hot environ- ment, a seemingly contradictory state, is a clinical presentation that has not been previ- ously described in the medical literature. We present two cases of symptomatic hypothermia of 34-35°C (95°F) which resolved with inges- tion of calories in otherwise healthy men com- peting in a multi-stage ultramarathon in the Sahara desert, Egypt 2012 with ambient tem- peratures of approximately 38-39°C (100- 102°F). Hypothermia is well documented in the medical literature as a presenting sign of hypoglycemia in both conscious and comatose patients. The mechanism by which hypo- glycemia contributes to hypothermia is poorly understood, but may represent a compensatory response that reflects a decrease in energy demand during glucose deprivation. Wilderness medicine practitioners at endurance events should be cognizant of hypothermia as a potential presenting sign of hypoglycemia, as it can be empirically treated and rapidly reversed. Introduction An ultramarathon is any race longer than the standard 42.2 km (26.2 mile) marathon.1 These races are gaining popularity in North America, with an almost 10% increase in annual participants, and more than 69,000 fin- ishers in 2013.2 Competitors often run through a variety of terrain in inclement conditions with temperatures ranging from below freez- ing to greater than 40°C (104°F).3 Although the majority of medical injuries encountered are often minor dermatologic and muscu- loskeletal issues,4,5 other serious and poten- tially debilitating conditions like exercise- associated hyponatremia (EAH)6 or acute kid- ney injury1 have been reported as well. Heat-related illnesses are a concern for any medical provider of ultramarathon runners with presentations that range from mild, usu- ally self-limited heat exhaustion to potentially fatal heat stroke.7 Heat-related illness can present similarly to EAH8 or altitude illness,9 but a concomitant concern for, or presentation of hypothermia has not been discussed in recent practice guidelines.10 Exertional hypothermia was first documented in the tem- perate 1901 Boston Marathon in one runner who had consumed large amounts of alcohol, and in another who was exhausted more than the average.11 However, as there are no report- ed cases of exertional hypothermia in hot con- ditions, a seemingly contradictory state, we introduce and define the term, paradoxical hypothermia. We present two cases of hypothermia in otherwise healthy men com- peting in a multi-stage ultramarathon in the Sahara desert, Egypt with ambient tempera- tures above 38°C (100.4°F). Case Report Case #1 A 42 year old male with no significant past medical history and taking no medications was a participant in RacingThePlanet© 250 km (155 mile) 7 day, 6 stage ultramarathon in the Sahara desert, Egypt October, 2012. On the third stage the individual was observed at checkpoint 2, 15.1 km (9.4 miles) from the start with ambi- ent temperatures of approximately 39°C (102.4°F), no wind or rain. He appeared fatigued with a pasty pale color, was walking slowly, and stated that he felt unwell and nau- seous. He had been unable to tolerate his regu- lar amount of water or electrolytes, and had resting heart rate of 84 beats per minute by pal- pitation. After 30 min of rest in the shade, the competitor continued on with the race. On arrival at checkpoint 3, 23.5 km (14.7 miles) from the start, he continued to complain of fatigue and nausea. He was pale, with cool and diaphoretic skin, and complained of feeling cold. He had a resting heart of 80 beats per minute by palpitation, blood pressure of 116/75 mm Hg by manual monitor, with an axillary temperature of 34.4°C (94°F) (digital ther- mometer; The Kroger Co., Atlanta, GA, USA). He was provided with a 12oz soda (150 cal; Pepsi Co., Sunnyvale, CA, USA) and placed in a sup- port vehicle to rest. After ingesting the soda his symptoms of coldness, nausea and fatigue resolved, and he continued on the course. The participant ultimately finished the stage. Case #2 A 50 year old male with no significant past medical history and not taking any medications was a participant in the same Racing ThePlanet© event. The patient was seen on stage 2 at checkpoint 1 at 9 am 11.2 km (7.0 miles) from the start with an ambient tempera- ture of approximately 38°C (100.4°F), with no wind or rain. He complained of feeling tired and had required frequent stops on the course, but felt better and continued to race after resting in the shade of the checkpoint. Further on the course he was seen several times hunched over, fatigued and apparently trying to catch his breath. He was stopped by a member of the medical team at 17 km (10.5 miles) from the start. He complained of feeling cold, with cool and moist skin. He appeared exhausted, with- out ataxia, and was leaning on the vehicle for support. He appeared agitated, repeatedly stat- ing, I’m OK, I can go on, and resisted efforts of medical assistance. His heart rate was 86 beats per min by palpitation, respiratory rate of 20 breaths per min, with an oral temperature of 35.1°C (95.3°F) (digital thermometer; The Kroger Co.). A repeat temperature several min- utes later was 35.0°C (95.0°F). The medical team member used the same thermometer to check his own oral temperature, which was 36.2°C (97.1°F). The competitor was withdrawn from the race, and symptoms of cold and fatigue resolved with ingestion of food and rest. Emergency Care Journal 2014; volume 10:4279 Correspondence: Elizabeth A. Kaufman, Department of Surgery, Division of Emergency Medicine, 300 Pasteur Drive, 94305-2200 Stanford, CA, USA. Tel. +1.619.459.5648. E-mail: ekaufman25@gmail.com Key words: hypothermia, ultramarathon, hypo- glycemia, multi-stage, desert. Contributions: EAK, researched the topic, per- formed literature search, drafted the paper; GSL, researched the topic, edited, and gave the final approval of the version to be published; LJS and BJK, gathered data (LJS) and helped with revis- ing the paper critically for important intellectual content. Conflict of interests: the authors declare no potential conflict of interests. Received for publication: 2 June 2014. Accepted for publication: 14 October 2014. This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0). ©Copyright E.A. Kaufman et al., 2014 Licensee PAGEPress, Italy Emergency Care Journal 2014; 10:4279 doi:10.4081/ecj.2014.4279 Non co mmerc ial us e o nly [page 81] [Emergency Care Journal 2014; 10:4279] Discussion There are little data that examine the inci- dence of hypothermia in geographical regions with a warm climate.12 Hypothermia is the con- dition when the body’s temperature falls to 35°C (95°F) or below,13 that can present as a primary environmental disease or a complicat- ing secondary state to a medical or traumatic condition. In hypothermic patients presenting to the emergency department, there is a 7% mortality with initial temperatures of mild hypothermia between 35 and 32.2°C, and a 23% mortality when less that 32.2°C.14 The pri- mary effect of cooling is a decrease in metabo- lism, but the body’s compensatory mechanisms are fully functional in cases of mild hypother- mia, with ataxia, dysarthria and apathy com- monly present.15 Factors that may contribute to the development of hypothermia range from environmental conditions such as wind, low temperatures, and moisture; to medical co- morbidities such as diabetes, hypothyroidism, or substance abuse.16 It is highly unlikely that these two participants in a multi-stage ultra- marathon in the hot and dry conditions of the Sahara desert presented with primary hypothermia. Rather, it is reasonable that it was a secondary manifestation to a disease such as hypoglycemia, a causative relationship that has been well described in hospital set- tings, but not previously in healthy ultrama- rathon runners. The presenting symptoms and signs of hypo- glycemia are well known to physicians. They may include anxiety, a sense of ill health, with feelings of detachment or apathy. There is often diaphoresis, ataxia, and if more severe, encephalopathy that may progress to coma and death if uncorrected. Hypothermia as a pre- senting sign of hypoglycemia was first described in 196417 and has been most fre- quently described in diabetics,18 but also in those with varying oncologic processes, liver disease, and alcohol abuse with and without starvation states.19 One of the early investiga- tions into the association between hypother- mia and hypoglycemia noted that 53% of con- secutive hypoglycemic patients had hypother- mia vs 5% of encephalopathy of other etiolo- gies.20 While the exact mechanism of hypothermia in hypoglycemia remains unclear, it is hypoth- esized that it may be due to increased heat dis- sipation from cutaneous vasodilation caused by disorder of the heat-regulating hypothala- mus.19 Experimental evidence for this centrally mediated mechanism was initially described by Freinkel et al. in studies that injected a syn- thetic intracellular glucose inhibitor that pro- duced hypoglycemia despite a serum eug- lycemic state. Healthy male volunteers’ tem- peratures decreased 1.1°C (3.4°F) below base- line for 6 h, indicating that hypothermia was triggered by intracellular glucopenia rather than by the availability of circulating glucose.21 Further animal studies found a 5-fold hypothermic response to injected centrally act- ing glucose inhibitor versus peripheral expo- sure,20 supporting the theory that thermoregu- latory centers in the hypothalamus are thought to be both glucose and insulin sensitive.22 These studies suggest that hypothermia is a direct consequence of neuroglucopenia, and the decreased body temperature may be pro- tective by preserving neuronal function while decreasing peripheral energy demands during times of glucose deprivation.18,19 Blood glucose levels in humans represent a balance between tissue uptake, hepatic glu- cose production – which in turn is dependent on glucose intake – glycogen reserves and glu- coneogenesis from amino acids and their pre- cursors.22 With exercise, skeletal muscles can increase their metabolic consumption by up to 20 times.23 The ultramarathon participants in these 2 cases had high energy consumption and may have developed hypoglycemia due to increased tissue uptake from exercise, insuffi- cient caloric intake, insufficient glycogen reserves, or a combination of all three. The ini- tial hypoglycemia is likely what caused decreased neuronal intracellular glucose lev- els, which led to a disruption of the thermoreg- ulatory centers in the hypothalamus. The rapid reversal of symptoms with intake of calories supports the supposition that the patients were hypoglycemic, as well as the proposed mechanism by which these athletes became hypothermic despite running through the heat of the Sahara desert. Some limitations in this case report exist, namely the lack of measurement of the two ultra-runners’ blood glucose concentration. Empirical evidence supports the assumption that a hypoglycemic state was present, and treatment of presumed hypoglycemia without definitive proof is supported by recent ultra- endurance consensus guidelines.7 At this time the theorized pathophysiology of the docu- mented hypothermia is unable to be definitive- ly proven. A rectal temperature, which is con- sidered the gold standard,7 would have provid- ed a more accurate measurement as axillary and oral thermometers may underestimate core temperatures. Rectal thermometer probes (like glucometers) were not available at the time of the patient’s care. Ultramarathon patients are often cared for in resource scarce wilderness settings, where a lack of adequate privacy and absence of multiple thermometers or glucometers per medical team members make empiric diagnoses and subsequent treat- ment a necessity. Conclusions Medical coverage of ultramarathons is usu- ally provided by a team composed of multiple volunteers with differing levels of medical knowledge, ranging from doctors to medical technicians and nurses, often working in a wilderness environment. Awareness of the potential association between hypoglycemia and hypothermia in the at-risk population of endurance athletes is clinically important, as hypothermia may be the only sign that a patient is hypoglycemic, and obtaining an accurate differential diagnosis with scant diagnostic resources is often based on nothing more technologically advanced than a history and physical. In the cases of the two runners who suffered from mild hypothermic symp- toms despite exercising in hot ambient tem- peratures, a state of paradoxical hypothermia, their rapidly reversal of symptoms after caloric ingestion supports hypoglycemia as the most reasonable mechanism. As treatment with simple carbohydrates is indicated in the field treatment of mild hypothermia7 and unlikely to harm a conscious hypothermic patient – it is an intervention available and easy to imple- ment by both medical and lay-people. Furthermore, this case report highlights the need for medical providers of endurance run- ners to consider carrying a point-of-care glycemic monitor, which is light, inexpensive, and a useful diagnostic tool. As much of the data that exist regarding the mechanism of hypothermia in hypoglycemia are several decades old, awareness of exertional hypo- glycemia in endurance athletes may confirm our observations and further research into this association would be potentially useful both for the endurance athlete and medical personnel. References 1. Lipman GS, Krabak BJ, Waite BL, et al. A prospective cohort study of acute kidney injury in multi-stage ultramarathon run- ners: the Biochemistry in Endurance Runner Study (BIERS). Res Sports Med 2014;22:185-92. 2. UltraRunning. 2013 UltraRunning partici- pation by the numbers. 2013. Available from: https://www.ultrarunning.com/fea- tured/2013-ultrarunning-participation-by- the-numbers/ 3. Krabak BJ, Waite B, Lipman GS. Injury and illnesses prevention for ultramarathoners. Curr Sports Med Rep 2013;12:183-9. 4. Jaworski CA. Medical concerns of marathons. Curr Sports Med Rep 2005;4:137-43. Case Report Non co mmerc ial us e o nly [Emergency Care Journal 2014; 10:4279] [page 82] 5. Krabak BJ, Waite B, Schiff MA. Study of injury and illness rates in multiday ultra- marathon runners. Med Sci Sports Exerc 2011;43:2314-20. 6. Hoffman MD, Fogard K, Winger J, et al. Characteristics of 161-km ultramarathon finishers developing exercise-associated hyponatremia. Res Sports Med 2013;21:164-75. 7. Hoffman MD, Pasternak A, Rogers IR, et al. Medical services at ultra-endurance foot races in remote environments: medical issues and consensus guidelines. Sports Med 2014;44:1055-69. 8. Backer HD, Shopes E, Collins SL, Barkan H. Exertional heat illness and hyponatrem- ia in hikers. Am J Emerg Med 1999;17:532- 9. 9. Ayus JC, Moritz ML. Exercise-associated hyponatremia masquerading as acute mountain sickness: are we missing the diagnosis? Clin J Sport Med 2008;18:383-6. 10. Lipman GS, Eifling KP, Ellis MA, et al. Wilderness Medical Society practice guidelines for the prevention and treat- ment of heat-related illness. Wild Environ Med 2013;24:351-61. 11. Blake JB, Larrabee RC. Observations upon long-distance runners. Boston Med Surg J 1903;148:195-206. 12. Elbaz G, Etzion O, Delgado J, et al. Hypothermia in a desert climate: severity score and mortality prediction. Am J Emerg Med 2008;26:683-8. 13. Giesbrecht GG. Emergency treatment of hypothermia. Emergen Med 2001;13:9-16. 14. Danzl DF, Pozos RS, Auerbach PS, et al. Multicenter hypothermia survey. Ann Emerg Med 1987;16:1042-55. 15. Finnoff JT. Environmental effects on brain function. Curr Sports Med Rep 2008;7:28- 32. 16. Castellani JW, Young AJ, Ducharme MB, et al. American College of Sports Medicine position stand: prevention of cold injuries during exercise. Med Sci Sport Exer 2006;38:2012-29. 17. Kedes LH, Field JB. Hypothermia: a clue to hypoglycemia. New Engl J Med 1964;271: 785-7. 18. Tran C, Gariani K, Herrmann FR, et al. Hypothermia is a frequent sign of severe hypoglycaemia in patients with diabetes. Diabetes Metab 2012;38:370-2. 19. Hanson PJ, Loughridge LW, Mulhall BP, Packham DK. Hypothermia in hypogly- caemia. Brit Med J 1984;288:1212-3. 20. Strauch BS, Philip F, Baxter JD, Schimpff SC. Hypothermia in hypoglycemia. J Am Med Assoc 1969;210:345-6. 21. Freinkel N, Metzger BE, Harris E, et al. The hypothermia of hypoglycemia. Studies with 2-deoxy-D-glucose in normal human subjects and mice. New Engl J Med 1972;287:841-5. 22. Carter WP Jr. Hypothermia: a sign of hypo- glycemia. JACEP 1976;5:594-5. 23. Maughan RJ, Shirreffs SM, Watson P. Exercise, heat, hydration and the brain. J Am Coll Nutr 2007;26:604-12. Case Report Non co mmerc ial us e o nly