Exercise-Induced Emergencies in the Heat: Rhabdomyolysis & Exertional Heat Stroke
- Jul 17th, 2017
- Michelle O’Connor
Authors: Michelle Y. O’Connor (@michelleyoc – Medical Student, Icahn School of Medicine at Mount Sinai) and Moira Carroll, MD (EM Resident Physician, Icahn School of Medicine at Mount Sinai – @SinaiEM) // Edited by: Alex Koyfman, MD (@ – EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) and Manpreet Singh, MD (@MPrizzleER – Assistant Professor of Emergency Medicine / Department of Emergency Medicine – Harbor-UCLA Medical Center)
With the increasing popularity of high-intensity exercise regimens, visits to the Emergency Department among otherwise young and healthy individuals may be more common.
The majority of metabolic abnormalities that occur after an extreme exercise event, whether a marathon or a new high-intensity exercise class, may resolve within a few days with rest and hydration . But for some, symptoms can be quite severe.
This article will examine the pathophysiology and management of two prevalent exercise-associated injuries: rhabdomyolysis and exertional heat stroke, which may be encountered in the ED.
- 28 year-old man with no past medical history presents to the emergency department with bilateral upper extremity soreness and weakness. This morning, his urine was dark red-brown.
- Yesterday, he completed a lifting workout which included bench pressing and pushups.
- He initially thought his soreness was a normal consequence of his workout, but became concerned when he noticed the dark urine.
- He is physically active with occasional running and biking, but does not typically strength train.
- Initial vital signs are HR 80 and a elevated temperature at 100.4 F
- On physical exam, his shoulders and upper arms are tender to palpation. Active range-of-motion in the upper extremities is full, but painful.
- Bloodwork and urinalysis reveal serum CK of 8000 IU; urine dipstick is positive for blood, but microscopic evaluation reveals no RBCs.
Rhabdomyolysis is characterized by rapid muscle breakdown leading to the leak of intracellular myocyte contents (myoglobin, creatinine kinase (CK)) and electrolytes (potassium, phosphorous) into the circulation. Severity can range from asymptomatic to life-threatening. The most lethal complications include acute kidney injury (AKI), symptomatic hyperkalemia, metabolic acidosis and hypovolemia [2, 3].
Rhabdomyolysis can stem from a variety of insults which share a final common pathway of muscle cell damage. Broadly, these causes are categorized as traumatic (trauma, crush injury), exertional (strenuous exercise, hyperthermia) or metabolic (infections, drug and other toxins) [2, 4].
The extreme metabolic demand on muscle cells which occurs during strenuous exercise makes athletes particularly vulnerable to rhabdomyolysis. As such, rhabdomyolysis has been reported in young, otherwise healthy individuals after particularly strenuous workouts provoked by personal training , Crossfit™ , spinning [7-10], marathons  and ultra-running or biking [12, 13]. Even low-intensity exercise has been reported as a trigger if that exercise is performed at high repetition . With the rise in popularity of strenuous exercise classes, we will focus on exercise-induced rhabdomyolysis.
All forms of rhabdomyolysis can present as a “classic triad” of muscle pain, weakness and dark urine, however less than 10% of patients tend to experience all three [2, 3]. When present, muscle pain is typically found in the proximal muscles such as the shoulders and thighs . Patients may have muscle weakness, cramping, stiffness and tenderness on palpation to muscles during physical exam. In more severe cases, the patient may experience symptoms such as fever, tachycardia abdominal pain, nausea, vomiting and malaise .
- Mechanical hemolytic anemia/intravascular hemolysis in runners 
- Inflammatory myopathy
- Infection-related myopathy or myositis
- Metabolic or genetic myopathy
- Specific to dark urine
- Hematuria and hemoglobinuria
- Various foods and medications
How is diagnosis made or confirmed?
Diagnostic testing should be performed in patients who present with:
- The combination of muscle soreness and pigmenturia (specifically, dark brown or red urine)
- Either muscle soreness OR pigmenturia who have a recent history positive for any of the potential causes for rhabdomyolysis listed above; categories defined as:
- Traumatic (trauma, crush injury)
- Exertional (strenuous exercise, hyperthermia)
- Metabolic (infections, drug and other toxins)
- A patient who has undergone prolonged immobilization, presents with absence of muscle soreness or pigmenturia OR is unable to describe symptoms and history, but has at least one of the following signs or symptoms which may be indicative of muscle breakdown:
- Muscle tenderness on exam
- Pressure-associated skin breakdown
- Signs of trauma or crush injury
- Serum chemistry suggestive of cell breakdown (hyperkalemia, hyperphosphatemia, hypocalcemia)
The two most important diagnostic laboratory tests when rhabdomyolysis is suspected are (1) serum CK and (2) urinalysis.
- Serum CK is the most sensitive marker of muscle damage .
The “classic” laboratory finding in rhabdomyolysis is a serum CK greater than 5 times the normal value, typically >5000 international units (IU)/L . This threshold of 5000 has been based off of the finding that patients with CK levels <5000 IU/L are considered low-risk for AKI .
Serum CK elevations are may be present without any clinical symptoms. A study of 37 finishers of the 2001 Boston Marathon found a 540% average rise in serum CK from baseline fours after finishing . Though this finding would be consistent with the levels of CK found in patients with rhabdomyolysis, none of the participants in this study experienced any adverse medical event and most marathon runners clear this excess CK over time with PO fluid intake .
- Urinalysis, both dipstick and microscopic analysis should be performed.
Myoglobin is a protein found inside myocytes. Because it contains a heme component, both myoglobin and hemoglobin appear as +blood on urine dipstick. Thus, microscopic analysis is important to differential RBC from myoglobin. Compared to serum CK, however, myoglobinuria is not as sensitive for rhabdomyolysis. Myoglobin is rapidly excreted and may have already been cleared by the time of testing. In fact, up to 25-50% of patients with rhabdomyolysis may have a normal urinalysis .
In addition to these two first laboratory tests, there are other additional tests which are recommended and can further evaluate for complications:
- CBC with differential and platelet count – evaluate for hemolytic anemia
- Blood urea nitrogen (BUN) and creatinine – evaluate renal function
- Routine electrolytes, including potassium – evaluate for electrolyte disturbances associated with tissue damage and dehydration; to evaluate renal function
- Electrocardiogram – While suspicion for myocardial infarction may be low in these patients, EKG may be helpful in revealing early evidence of arrhythmias secondary to electrolyte abnormalities
The goals of management of suspected rhabdomyolysis include :
- Initial stabilization and resuscitation with advanced life support (if needed). This is more likely to be necessary in cases of rhabdomyolysis caused by trauma or crush injuries .
- Recognition of any fluid and electrolyte abnormalities, including those indicative of AKI
- Preservation of kidney function by initiating early and aggressive crystalloid fluid replacement.
Once fluid administration has been initiated, management depends on presence of absence of concomitant AKI.
Management without AKI
In patients without acute kidney injury, the goal is to prevent further kidney injury by enhancing renal perfusion with aggressive fluid resuscitation. Specifically, recommendations call for infusion of 1-2 liters/hour of isotonic saline until CK is either stable or decreasing to <5000 IU/L.
Both urine alkalization with bicarbonate and diuretic use have been recommended, however, it been shown to be of little overall benefit . Nonetheless, bicarbonate may be useful in closely monitored patients who presented with severe rhabdomyolysis (serum CK >5000 IU/L) who do not have severe hypocalcemia, have an arterial pH of <7.5 and for whom serum bicarbonate is less than 30 mEq/L. To start, 130 mEq/L sodium bicarbonate at a rate of 200 mL/hr, with the rate titrated as needed to alkalinize the urine to a pH of >6.5.
After aggressive fluid replacement, patients with evidence of volume overload may benefit from administration of a loop diuretic. Loop diuretics have not been shown to be effective in preventing AKI in patients with myoglobinuria .
Management with AKI
AKI is the most serious, and potentially fatal, complication of rhabdomyolysis and can be found on presentation of severe disease or if rhabdomyolysis goes untreated . The incidence of AKI resulting from rhabdomyolysis has been estimated to be anywhere between 13-50% [22-24].
The prognosis in rhabdomyolysis is significantly worse if AKI is present . While the data on mortality varies with cause of rhabdomyolysis and AKI, studies have shown that in all causes, AKI increases the likelihood of mortality. For example, in a retrospective observational study of 26 patients with severe rhabdomyolysis admitted to the intensive care unit, patients with AKI had higher mortality (59%) than those without AKI (22%) . Of note, this study included exclusively patients who required ICU-level care and these mortality data do not reflect the overall population of patients with rhabdomyolysis presenting to the Emergency Department.
In patients found with AKI, either on presentation or after treatment is initiated, the goal of treatment is to support kidney recovery while maintaining physiologic electrolyte and fluid balance. Renal replacement therapy, or dialysis, may be indicated to treat severe volume overload and electrolyte abnormalities, particularly hyperkalemia and severe acidemia. Standard indications for dialysis in the setting of AKI are to be followed. If identified and appropriately treated, overall long-term survival of patients with AKI in the setting of rhabdomyolysis is estimated to be nearly 80%, the majority of whom ultimately recover full renal function .
Pearls, Pitfalls & Rare Complications
Patients may present with compartment syndrome associated with rhabdomyolysis , or alternatively, may develop after the initial presentation, likely precipitated by aggressive fluid administration . Although rare in this setting, compartment syndrome is a surgical and limb threatening emergency. Patients receiving IV fluid support should be periodically reassessed and reexamined to quickly identify this potential complication.
Confounding statin-induced myopathy
Myopathy is a known adverse effect of statin use. Baseline myopathy due to statin-use may lead to a lower threshold for the development of exercise-induced muscle breakdown and rhabdomyolysis in athletes taking statins. As such, there is a case report describing rhabdomyolysis-induced compartment syndrome three days after a vigorous workout in a 50-year old man taking atorvastatin , and another describing rhabdomyolysis in marathon runner taking statins .
- 17 year old male with no PMH is brought into the Emergency Department by EMS with altered mental status.
- Pt had been participating in day 4 of pre-season football training when he collapsed suddenly during a series of sprint drills.
- After collapse, EMS was called immediately, and arrived within 5 minutes of call
- Per EMS, in the field, patient was found sitting on the sidelines with his football uniform and padding removed
- He appeared lethargic, was hot to the touch and dry
Diagnosis: Exertional Heat Stroke
Definition/Terminology & Patient presentations
Exertional heat illness (EHI) represents a spectrum of disease caused by intense physical stress or exercise in the heat .
Along the spectrum of EHI, heat exhaustion is distinguished from exertional heat stroke (EHS). Both syndromes can present with an array of symptoms such as energy depletion, nausea, vomiting, dizziness, headache, muscle aches and tachycardia. However, the major distinguishing factor between the two is the degree of physiologic compensation. With heat exhaustion, body temperature may be normal or slightly elevated but physiologic thermoregulatory mechanisms remain intact, so profuse sweating may be present. By contrast, patients with EHS are in a state of physiologic decompensation. EHS involves (1) an elevated core body temperature (>40°C or >104°F) and (2) signs and symptoms of end-organ damage directly due to hyperthermia . This includes neurologic findings such as central nervous system dysfunction (encephalopathy) presenting as altered mental status, agitation, ataxia and even seizures or coma [1, 29]. EHS is “classically” characterized by lack of sweating, however it is possible that patients with EHS may continue to sweat. EHS can rapidly progress to florid thermoregulatory failure .
Athletes are at an elevated risk of EHS. In the United States, high school football players have the highest risk, estimated at 4.5 cases in 100,000 and 31 reported EHS-related deaths between 1995 and 2008 . A 2010 report published by the Center for Disease Control (CDC) estimated an annual incidence of EHI cases in high school athletes of 9,237 . Most EHI cases were associated with football and most commonly occurred during the month of August.
While exertion or exercise is a major precipitating factor for EHI, there are several confounders which should raise suspicion for more severe EHI, or the possibility of imminent EHS. While heat tolerance is both variable and multifactorial, the maximum limits of an individual’s heat tolerance can be attributed to individual factors such as acclimatization, age, physiologic reserve and fluid intake, and even varies with different background temperatures, encompassing concepts beyond the absolute temperature, such as relative humidity, dew-point, wet bulb globe temperature, which takes into consideration the humidity, wind conditions, sunlight intensity and cloud cover [32, 33]. Not surprisingly, a review temperature and participant data from multiple United States marathons found that hotter race days correlated with drop-out rate, hyponatremia incidence and heat stroke .
Differential diagnoses [34, 35]
Most patients with EHI present with collapse during exertion often followed by a period of altered mental status. The differential diagnosis should generally include potential causes of exercise-associated collapse such as:
- Cardiac arrest
- Hypertrophic obstructive cardiomyopathy (HOCM)-related arrhythmia
- Exertional hyponatremia
- Malignant hyperthermia
- Transient postural hypotension
Diagnosis & Management
When initially assessing patients presenting with likely EHI, consider two major guiding principles [36, 37]:
- The severity of illness may not be obvious at presentation
- Morbidity is directly related to the duration and severity of the elevated body temperature
The first principle dictates that suspicion for severity be maintained in any patient who presents with any symptoms along the EHI spectrum described above, as EHS may develop despite no obvious initial signs of thermoregulatory decompensation at presentation.
The second principle emphasized the importance of initiating immediate rapid cooling
to a temperature of 39°C, or 102°F (noting that most patients with EHS, per diagnostic criteria, will have an elevated core body temperature or >40°C, or >104°F at time of onset) . There are several external and internal cooling methods which can be employed in the setting of suspected EHS.
External cooling measures include water (cold or ice water immersion), ice packs to areas adjacent to large blood vessels (axilla and groin) and evaporative air cooling (fanning, air conditioners)  . If all potential cooling techniques are immediately available, ice water immersion has been shown to be the most effective . In fact, the National Athletic Trainers Association Position Statement recommends ice bags and a tub or kiddy pool be available either in the locker room or on the field during intense athletic training periods, such as preseason training .
Overall, the most valuable rapid cooling technique is whatever is most rapidly accessible to the patient and first responders at the time to prevent delay in cooling therapy. If ice water immersion is not available, alternative methods such putting the patient in a cold shower, spraying the patient with cold water from a hose and applying (preferably cold) wet towels to the patient’s body surface.
Internal cooling methods involve gastric, bladder and rectal cooling with cooled IV fluids . The use of IV cooling is a theoretical option which may be most useful in the setting of transport when a cooling tub is not available. However, this method has not been thoroughly studied in clinical trials and no specific recommendations or guidelines are available.
After rapid cooling, further treatment should include the following:
- Continue frequent vital sign monitoring, including pulse oximetry
- For temperature monitoring, a flexible rectal thermometer, which provides continues body temperature data, is preferred to a rigid rectal thermometer, which is used for interval updates. If only a rigid thermometer is available, interval updates ever 10 minutes is recommended.
- If volume loss is a concern, a Foley catheter can be placed for accurate monitoring of urine output and therefore renal perfusion/function
- Laboratory Assessments :
- Finger-stick glucose – patients are often hypoglycemic
- Serum electrolytes (including calcium)
- Renal function studies (BUN, Cr)
- Serum CK
- LFTs (ALT, AST)
- Coagulation studies (PT, INR, aPTT)
In addition to cooling, the following therapies and treatments may be warranted based on the patient’s clinical characteristics:
- IV fluid resuscitation
- Correction of electrolyte abnormalities
- Monitoring for further complications (see below)
- Liver failure
- Disseminated intravascular coagulation (DIC)
It is recommended that all patients with EHS be monitored for 24 at least hours, mindful of early identification of potential end-organ damage and complications .
A list of potential complications and their potential underlying etiologies, which may be either directly caused by hyperthermia or secondary to associated physiologic characteristics.
Note that depending on clinical picture, further workup regarding each of the following potential complications may be warranted. For example, neuroimaging is not generally performed in the setting of EHS. However, if AMS is prolonged and not improving despite response to rapid cooling and hydration, neuroimaging may be warranted.
- Central Nervous System
- Agitated delirium
- Confusion, AMS
- Electrolyte and other metabolic abnormalities
- Hypo- and hyperkalemia
- Hypo- and hypernatremia
- Electrolyte and other metabolic abnormalities
- Respiratory failure
- Acute respiratory distress syndrome
- Respiratory alkalosis
- Acute kidney injury
- Hepatic failure
- Coagulopathy or DIC
- Gastrointestinal bleeding secondary to ischemic bowel injury
- Myocardial injury
Case #1: Rhabdomyolysis
- Consider rhabdomyolysis in patients with a history of strenuous exercise presenting with muscle pain and/or dark urine.
- Order serum CK and urinalysis on all patients with rhabdomyolysis in the differential.
- Begin fluid resuscitation early in patients with suspected rhabdomyolysis.
Case #2: Exertional Heat Stroke
- Consider exertional heat stroke in patients presenting with any acute-onset neurologic deficit (altered mental status, agitation, ataxia) during physical exertion, particularly in the heat.
- The initial, primary goals of therapy is to initiate rapid cooling (ice water bath immersion being the most optimal choice, but many other techniques are available) until the patient’s core body temperature is below 39°
- Monitor patients with EHS for a minimum of 24 hours to look for signs of end organ damage.
This post is sponsored by www.ERdocFinder.com, a supporter of FOAM and medical education, who with their sponsorship are making FOAM material more accessible to emergency physicians around the world.
References / Further Reading
- Sanchez, L.D., B. Corwell, and D. Berkoff, Medical problems of marathon runners. Am J Emerg Med, 2006. 24(5): p. 608-15.
- Huerta-Alardin, A.L., J. Varon, and P.E. Marik, Bench-to-bedside review: Rhabdomyolysis — an overview for clinicians. Crit Care, 2005. 9(2): p. 158-69.
- Giannoglou, G.D., Y.S. Chatzizisis, and G. Misirli, The syndrome of rhabdomyolysis: Pathophysiology and diagnosis. Eur J Intern Med, 2007. 18(2): p. 90-100.
- Berry AC, et al., Exertional Rhabdomyolysis: A Case of Markedly Elevated Creatine Kinase Without Acute Kidney Injury. Journal of Medical Cases, 2014. 5(9): p. 483-485.
- Springer, B.L. and P.M. Clarkson, Two cases of exertional rhabdomyolysis precipitated by personal trainers. Med Sci Sports Exerc, 2003. 35(9): p. 1499-502.
- Rathi, M., Two Cases of CrossFit®-Induced Rhabdomyolysis: A Rising Concern. International Journal of Medical Students, 2014. 2(3): p. 132-134.
- DeFilippis, E.M., et al., Spinning-induced Rhabdomyolysis and the Risk of Compartment Syndrome and Acute Kidney Injury: Two Cases and a Review of the Literature. Sports Health, 2014. 6(4): p. 333-5.
- Parmar, S., et al., Rhabdomyolysis after spin class? J Fam Pract, 2012. 61(10): p. 584-6.
- Ramme, A.J., et al., Exertional rhabdomyolysis after spinning: case series and review of the literature. J Sports Med Phys Fitness, 2016. 56(6): p. 789-93.
- Brogan, M., et al., Freebie Rhabdomyolysis: A Public Health Concern. Spin Class-Induced Rhabdomyolysis. Am J Med, 2017. 130(4): p. 484-487.
- Clarkson, P.M., Exertional rhabdomyolysis and acute renal failure in marathon runners. Sports Med, 2007. 37(4-5): p. 361-3.
- Chlibkova, D., et al., Rhabdomyolysis and exercise-associated hyponatremia in ultra-bikers and ultra-runners. J Int Soc Sports Nutr, 2015. 12: p. 29.
- Magrini, D., et al., Serum creatine kinase elevations in ultramarathon runners at high altitude. Phys Sportsmed, 2017. 45(2): p. 129-133.
- Tran, M., et al., Low-Intensity Repetitive Exercise Induced Rhabdomyolysis. Case Rep Emerg Med, 2015. 2015: p. 281540.
- Deitrick, R.W., Intravascular haemolysis in the recreational runner. Br J Sports Med, 1991. 25(4): p. 183-7.
- de Meijer, A.R., et al., Serum creatine kinase as predictor of clinical course in rhabdomyolysis: a 5-year intensive care survey. Intensive Care Med, 2003. 29(7): p. 1121-5.
- Kratz, A., et al., Effect of marathon running on hematologic and biochemical laboratory parameters, including cardiac markers. Am J Clin Pathol, 2002. 118(6): p. 856-63.
- Wakabayashi, Y., et al., Rapid fall in blood myoglobin in massive rhabdomyolysis and acute renal failure. Intensive Care Med, 1994. 20(2): p. 109-12.
- Better, O.S. and I. Rubinstein, Management of shock and acute renal failure in casualties suffering from the crush syndrome. Ren Fail, 1997. 19(5): p. 647-53.
- Brown, C.V., et al., Preventing renal failure in patients with rhabdomyolysis: do bicarbonate and mannitol make a difference? J Trauma, 2004. 56(6): p. 1191-6.
- Bosch, X., E. Poch, and J.M. Grau, Rhabdomyolysis and acute kidney injury. N Engl J Med, 2009. 361(1): p. 62-72.
- Holt, S.G. and K.P. Moore, Pathogenesis and treatment of renal dysfunction in rhabdomyolysis. Intensive Care Med, 2001. 27(5): p. 803-11.
- Melli, G., V. Chaudhry, and D.R. Cornblath, Rhabdomyolysis: an evaluation of 475 hospitalized patients. Medicine (Baltimore), 2005. 84(6): p. 377-85.
- Ward, M.M., Factors predictive of acute renal failure in rhabdomyolysis. Arch Intern Med, 1988. 148(7): p. 1553-7.
- Woodrow, G., A.M. Brownjohn, and J.H. Turney, The clinical and biochemical features of acute renal failure due to rhabdomyolysis. Ren Fail, 1995. 17(4): p. 467-74.
- Dunphy, L., R. Morhij, and S. Tucker, Rhabdomyolysis-induced compartment syndrome secondary to atorvastatin and strenuous exercise. BMJ Case Rep, 2017. 2017.
- King, T.W., et al., Exertional compartment syndrome of the thigh: a rare diagnosis and literature review. J Emerg Med, 2010. 39(2): p. e93-9.
- Toussirot, E., F. Michel, and N. Meneveau, Rhabdomyolysis Occurring under Statins after Intense Physical Activity in a Marathon Runner. Case Rep Rheumatol, 2015. 2015: p. 721078.
- Binkley, H.M., et al., National Athletic Trainers’ Association Position Statement: Exertional Heat Illnesses. J Athl Train, 2002. 37(3): p. 329-343.
- Mueller, F. and R. Cantu, Catastrophic sports injury research: twenty-sixth annual report. University of North Carolina, Chapel Hill, 2008.
- Centers for Disease, C. and Prevention, Heat illness among high school athletes — United States, 2005-2009. MMWR Morb Mortal Wkly Rep, 2010. 59(32): p. 1009-13.
- Roberts, W.O., Heat and cold: what does the environment do to marathon injury? Sports Med, 2007. 37(4-5): p. 400-3.
- Sawka, M.N., et al., Human tolerance to heat strain during exercise: influence of hydration. J Appl Physiol (1985), 1992. 73(1): p. 368-75.
- Asplund, C.A., F.G. O’Connor, and T.D. Noakes, Exercise-associated collapse: an evidence-based review and primer for clinicians. Br J Sports Med, 2011. 45(14): p. 1157-62.
- O’Connor, F.G., et al., Practical management: a systematic approach to the evaluation of exercise-related syncope in athletes. Clin J Sport Med, 2009. 19(5): p. 429-34.
- Bouchama, A. and J.P. Knochel, Heat stroke. N Engl J Med, 2002. 346(25): p. 1978-88.
- Heled, Y., et al., The “golden hour” for heatstroke treatment. Mil Med, 2004. 169(3): p. 184-6.
- Costrini, A., Emergency treatment of exertional heatstroke and comparison of whole body cooling techniques. Med Sci Sports Exerc, 1990. 22(1): p. 15-8.
- Atha, W.F., Heat-related illness. Emerg Med Clin North Am, 2013. 31(4): p. 1097-108.