Dr Gavin Clark: It was a crisp October day, ∼45°F (7°C), and the local children's hospital half marathon was in full swing. A 28-y-old male runner without significant past medical history presented to the Emergency Department (ED) via ambulance after collapsing at the end of the race. According to his partner, he was an avid runner and had been running 10+ mi during his training periods without difficulty prior to the race. On arrival, the patient was awake but profoundly diaphoretic and confused.
Dr Sam Kocen: It sounds so far like a classic case of exercise-associated collapse with several differential diagnoses. Was there any additional history you gained from talking to Emergency Medical Services, witnesses, or family?
Dr Clark: According to the patient's partner, who ran with him during the race, they had just finished an uphill section when the patient appeared to become unsteady and stopped responding to her questions. The running partner was unable to comment on the patient’s running pace at this time, limiting our ability to comment on the impact of excess motivation on his ensuing collapse. After the patient collapsed, race-side Emergency Medical Services personnel were able to attend to him immediately. According to the report, the patient was initially in supraventricular tachycardia with a heart rate of 160 beats/min on a 12-lead monitor, but responsive. He soon became unresponsive, and 6 mg adenosine was administered. The patient's heart rate improved to around 120 beats/min, and a nasopharyngeal airway was placed. His oxygen saturation remained in the high 90s (percent).
Dr Kocen: What about any recent medical issues, illnesses, medications, or a history of prior collapse?
Dr Clark: The patient’s running partner reported that he had no history of arrhythmia and did not take medications but had had COVID-19 6 d prior to the race. He had been afebrile for 2 d prior to the race and had run 3 mi the day before. He felt fine on race day. He had no history of prior syncope and had eaten and hydrated prior to the race. It is unclear how his race running pace compared with his training pace and whether this was a contributing factor.
Dr Kocen: How did he look when he arrived? What were his initial vital signs and your clinical concerns?
Dr Clark: On arrival, the patient appeared profoundly diaphoretic, felt cool to touch, and had a Glasgow Coma Scale score of 14 given his continued confusion. He was fully amnestic to the events bringing him to the ED. He was wearing long synthetic moisture-wicking running underwear beneath a cotton T-shirt, a bib, and synthetic running shorts. His vital signs were a heart rate of 115 beats/min, blood pressure of 88/39 mmHg, SpO2 of 93%, and an oral temperature of 37.6°C. There were no signs of outward trauma and no head injury. A rectal temperature was then taken that read 40.9°C.
Dr Kocen: So you are saying that it was 45°F outside during the race, and he felt cool to touch. What made you check a rectal temperature with this story and a normal oral temperature? What causes this disparity in thermometer readings, and is it common?
Dr Clark: Honestly, there is no magic involved here and no subtle clinical finding that prompted the second temperature check. Because heat stroke was on the differential for an ill-appearing athlete who collapsed, we recognized the need for accurate core temperature determination, and a rectal temperature is the standard of care for heat stroke evaluation.
Dr Nicholas Daniel, board-certified emergency medicine physician with fellowship training in wilderness medicine and current director of the Wilderness Medicine Fellowship at Dartmouth-Hitchcock Medical Center weighs in:
Dr Nicholas Daniel: It is well researched that oral temperature readings average ∼1°F (roughly 0.5°C) lower than rectal temperatures.
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However, many of the comparison trials gauging this difference were in undifferentiated population samples. In varying environmental and physiologic conditions there are variables that can affect this significantly. In the setting of physical exertion, or in this case an endurance race, drinking cold beverages, hyperventilating, and mouth breathing all may alter the oral temperature.
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Physiologic factors such as hypotension or shock from a variety of etiologies could decrease perfusion to the facial and mouth structures, and extremes of core temperature can alter the standard physiologic responses to hypo- and hyperthermia. As an emergency medicine physician, I can tell you that the difference between oral and rectal temperatures is quite often >0.5°C in sick individuals. In this patient, I suspect that the temperature disparity was due to a combination of cold skin from the ambient temperature combined with sweating, hypotension, and core temperature dysregulation. We also don’t know if he was given cold beverages to drink.
Dr Kocen: It sounds like you’ve got a relatively unstable patient on your hands. What were your next steps for the resuscitation?
Dr Clark: At this point, we were able to make a diagnosis of exertional heat stroke (EHS), as defined by a core temperature >40.5°C with altered mental status; active cooling needed to be done in tandem with anything else we were going to do. The patient's clothes were removed, and ice packs were placed in the axilla, neck, and groin. Fans were placed blowing toward him, and he was continually misted with water while constant temperature monitoring was performed via rectal probe. We also drew lab samples with concern for end-organ damage, including a complete blood count, a basic metabolic profile, liver function tests, lipase, venous blood gas with lactate, creatine kinase, urinalysis, high-sensitivity troponins, and disseminated intravascular coagulation labs (eg, D-dimer, prothrombin time/International Normalized Ratio, and fibrinogen). We obtained a chest x-ray and non-contrast-enhanced computed tomography of the head, both of which resulted in no significant or contributory findings. Two liters of normal saline were administered. An electrocardiogram showed sinus tachycardia without ischemia or other syncope-related findings.
Dr Kocen: Heat stroke can be a disaster if not treated quickly and adequately. Active cooling using immersion or evaporative cooling is exactly the right next step. Did you have a goal temperature?
Dr Clark: We were aiming for a 39°C core temperature and return to normal mental status with the goal to get the patient there as quickly as possible.
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We avoided antipyretics because there is no indication for them in EHS. We definitely considered immersion cooling because this is the best method to rapidly decrease the core temperature. However, it was not feasible in our ED environment. We were able to get his temperature to goal in roughly 30 min of initiating cooling. We stopped our cooling at that point, and he managed to maintain a temperature around 37.4°C.
Dr Daniel: Dr Clark is absolutely correct that immersion cooling is the best method to rapidly decrease core temperature.
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The thermal conductivity of water is 24 times greater than that of air, which results in more rapid heat loss when immersed in water. Full-body immersion can be a challenge in the ED due to the need for an appropriately sized vessel for the water and an inability to perform cardiac monitoring on unstable patients. For EHS, it has been recommended that the cooling rate reach ≥0.155°C·min–1 with the target temperature met within 30 min.
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If cold water immersion isn’t feasible, several other options exist, including innovations to mimic immersive cooling without a water vessel. Tarp-assisted cooling with oscillation has been shown to produce effective cooling rates.
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In this method, a patient is placed on a plastic sheet or tarp, ice water is poured onto and around the patient, and the corners are then lifted to oscillate the ice-water slurry. Alternatively, the Quantico method can be used. This method does require more personnel because the patient is placed on a litter overtop a tub while the torso is doused continuously with ice water, and ice packs are applied to junctional areas (eg, axilla, groin, and neck) while ice massage is done continuously from ankle to groin.
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Ice-sheet cooling is a more simplified method, although with slower cooling rates. In this approach, ice-water-soaked sheets are placed in the groin and across the chest/axilla and neck.
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In an ED setting, a cadaver bag can be effectively used for this method.
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Finally, evaporative cooling has long been a mainstay in EHS management. The method involves misting water onto the unclothed patient and using fans to maximize evaporative and convective heat loss. Cooling rates in evaporative cooling have been shown to be slower than cold water immersion (0.11 vs 0.20°C·/min–1, respectively).
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In our case, cold packs and evaporative cooling achieved the target temperature within 30 min.
Dr Kocen: Were any of the patient’s laboratory values abnormal?
Dr Clark: His initial labs were significant for a lactate concentration of 9.2 mmol·L–1, creatinine at 1.82 mg·dL–1 showing acute kidney injury, an elevated but nonischemic troponin series, a D-dimer elevation to 2549 ng·mL–1 fibrinogen-equivalent units, and a slightly elevated lipase concentration of 63 units·L–1. His liver enzymes, complete blood count, and creatine kinase concentration were normal. His lactate improved to 2.3 mmol·L–1 after fluid resuscitation.
Dr Kocen: After you were out of the acute resuscitation phase, what did you learn from reevaluating the patient?
Dr Clark: He remained mildly encephalopathic but had improved with normalization of temperature. After further discussion, it was revealed that he had a recent tick exposure, so a tick-borne infection panel and Lyme testing were done; a day later he was found to be Lyme IgM positive, suggesting active infection.
Dr Kocen: What makes heat stroke so dangerous?
Dr Daniel: Although fever is due to an elevated temperature setpoint and is adaptive, heat stroke is a pathologic condition in which the thermoregulatory functions that prevent dangerous hyperpyrexia are overwhelmed. Cellular structures start to take direct damage due to heat at temperatures >41.6°C (107°F). In addition to direct heat cytotoxicity, the inflammatory cascade is activated. Extreme and prolonged peripheral vasodilation and the compensatory decrease in splanchnic blood flow can lead to ischemic stress in the intestinal lining (along with other organs), which leads to increased gut permeability and a leaky gut. Endotoxins that are usually confined to the gut lumen are released into the bloodstream, causing an inflammatory cascade. This leads to a heat-induced systemic inflammatory response syndrome, and subsequent morbidity and mortality are due to multiorgan dysfunction or failure.
Dr Kocen: This is an interesting case because this patient didn’t have many of the normally associated risk factors for developing EHS, such as age, medications, chronic disease, and physical deconditioning, and the ambient race temperature was quite cool. How much of a role did you feel that the patient's recent COVID-19 illness and active Lyme disease played in his presentation?
Dr Clark: You’re right in that he was fit and without comorbidities or contributing medications, but in many instances, finish-line collapse and EHS occur while performing previously tolerated activities. However, the patient often ran up to 10 mi at a time, which is fairly similar to half-marathon distance, and no traditional risk for EHS was identified. This suggested that there was something else at play leading to an increased risk of EHS, and temperature dysregulation in the setting of recent viral illness and Lyme infection could fit the bill.
Dr Kocen: What does the literature say about temperature dysregulation in the setting of recent viral illness?
Dr Daniel: All of us have had a fever during an acute viral illness. The body increases or resets the goal temperature setpoint, which helps acutely with immune function. It is important to note that the patient in this case appeared to be past the acute phase of his COVID-19 infection, was asymptomatic on race day, and had not been febrile in 2 d. The wake of the COVID-19 pandemic revealed several long-term complications of the virus, including autonomic dysfunction.10–14 When the autonomic nervous system does not function properly, the regulation of normal involuntary processes such as blood pressure, heart rate, digestion, and temperature control can be altered. One study assessing subjects after a mild COVID-19 infection found that 68% perceived symptoms of impaired thermoregulation.
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Case reports demonstrate extreme hyperpyrexia associated with acute COVID-19.
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On the contrary, a recent study demonstrated that COVID-19 was not associated with impaired thermoregulation during exercise-induced heat stress. Of note, this study had a 38-wk mean timeframe between active infection, which could have led to waning thermal dysregulation in comparison with this case, in which COVID-19 infection was within a week.
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Post-COVID postural orthostatic tachycardia syndrome has been well described as a sequela related to autonomic dysfunction.
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In addition to the COVID-19 coronavirus, retrovirus, herpesvirus, flavivirus, enterovirus 71, and lyssavirus have been reported to cause autonomic dysfunction. Human immunodeficiency virus (retrovirus) and varicella-zoster virus (herpes) are reported to cause autonomic dysfunction.19,20 We suspect that the patient in this case was much more susceptible to EHS due to some degree of dysautonomia related to his recent COVID-19 infection. While admittedly this is speculative, as you mentioned, Dr Kocen, it otherwise seems pretty unlikely that a young, healthy male who frequently ran 10 miles at a time would develop EHS during a 13-mi race in 45°F weather.
Dr Kocen: That's a very interesting discussion. What about the Lyme disease element?
Dr Daniel: Well, the discovery of a concomitant Lyme disease is also very interesting. In our region, where Lyme disease is endemic, the presence of a fever plus another lab abnormality such as transaminitis, hyponatremia, or thrombocytopenia often prompts the addition of labs for tickborne illness. This patient certainly had symptomatic COVID-19 in the days prior, but it is also possible that acute Lyme disease infection had caused the recent fever or had made him more apt to develop hyperpyrexia. Late-stage Lyme disease and post-treatment Lyme disease syndrome have been associated with autonomic dysfunction, as has tickborne viral encephalitis.21,22 The clinical picture here did not fit tickborne viral encephalitis given his rapid improvement in mental status with temperature correction alone; however, the concomitant Lyme disease also may have contributed to his EHS. Finally, Lyme disease can cause atrioventricular conduction abnormalities. The patient's PR interval on his electrocardiogram was not indicative of an atrioventricular block, but a link between the episode of supraventricular tachycardia and his Lyme disease could be considered.
Dr Kocen: Which of these issues was contributing most to the collapse and overall clinical picture?
Dr Daniel: That is an excellent question, with these additional diagnoses. This patient clearly had EHS leading to his altered mentation and multiorgan dysfunction. However, this case report could be even more pertinent to learn from as a presentation of finish-line collapse and the associated differentials. In young, healthy athletes, when we think past dehydration and exhaustion, some of the most dangerous conditions to consider are EHS, exercise-associated hyponatremia, and arrhythmia. This patient had one and possibly two of these conditions.
Dr Kocen: What was the outcome for this patient?
Dr Clark: Fortunately, he did very well! He developed mild rhabdomyolysis, his troponins suggested mild demand ischemia, and his aspartate aminotransferase and alanine aminotransferase levels peaked at 874 and 1281 units·L–1, respectively. His renal function improved with intravenous fluids, suggesting a prerenal acute kidnet injury, and his organ dysfunction improved with intravenous fluids and rest alone.
Dr Kocen: A really cool and unique case you have here. What are some takeaways that I can use when I see my next patient with EHS?
Dr Clark: Focus on resuscitation, and be sure to keep your differential broad. Consider all the most deadly differentials for the downed athlete. Once the diagnosis of EHS is made, focus on rapid cooling for the best outcome.
