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Pearls and Pitfalls

The Vagaries of Exertional Rhabdomyolysis

Eichner, E. Randy MD, FACSM

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Current Sports Medicine Reports: May 2021 - Volume 20 - Issue 5 - p 229-230
doi: 10.1249/JSR.0000000000000833
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Introduction

Exertional rhabdomyolysis (ER) continues to present diagnostic and management problems, especially among athletes and warfighters. Exactly how to diagnose ER remains controversial, as does the decision whether — and/or how long — to hospitalize a patient. Just saying “individualize it” is not enough. Recent reports on ER shed light yet need comment or clarity. I cover them here, first a “civilian” report, then military reports.

ER in a Civilian

A healthy, fit White male, aged 22 years, with no medical history and on no medications, went to an emergency department because of generalized body aches and dark urine for 1 d. The pain was most severe in his chest, upper back, shoulders, and arms. Two days before, after a break of a few weeks from his exercise routine, he did 3 h of different and intense exercise in a CrossFit gym, including abdominal crunches, sit-ups, and weight lifting. His creatine kinase (CK) was elevated at 132,540 U·L−1, but serum creatinine was normal at 1.05 mg·dL−1. He was hospitalized and “treated aggressively” with intravenous and oral fluid. He did not develop acute kidney injury (AKI) or any other complication of his ER. His CK fell steadily day by day, but he was kept until day 6, when CK was 7980 U·L−1 (1).

The main question here is: Why 6 days in hospital? The authors cite a study they say shows “CK level of 20,000 U·L−1 is the threshold to begin treatment to prevent renal failure with rhabdomyolysis.” However, this and similar algorithms come from trauma centers, where most cases of rhabdomyolysis are from life-threatening events, like gunshot wounds, car crashes, and crush injuries. This threshold should not apply to ER, especially ER from novel overexertion in healthy athletes. Nor does a firm CK threshold exist for hospitalization of such athletes with ER. Serum CK levels up to 250,000 U·L−1 are not unusual in novel overexertion; in severe cases, the CK can exceed 500,000 or even 1,000,000 U·L−1. Usually, an athlete with a CK level of 20,000 to 50,000 (or even higher), who is stable in the emergency department and has normal serum creatinine and good urine output (even if dark urine at first), will recover smoothly with oral hydration and close outpatient follow-up.

ER in the Military

ER continues to be a concern and focus of research in our military, which reported 512 cases of ER in 2019, apparently none fatal (2). ER occurs most often from late spring through early fall at bases that support basic combat/recruit training or major Army or Marine Corps combat units, where troops undergo physical training and field training exercises, regardless of weather conditions (2). Recent military reports show that defining, preventing, and managing ER remain controversial or problematic. A new military perspective article on clinical practice guidelines for ER (3) is useful but incomplete on why ER is more common and more severe in the face of sickle cell trait (SCT). Another new military report is misleading on ER and SCT (4); I will cover this below. First, other recent reports on ER in the military.

The Israeli military reports three cases of ER in army recruits after strenuous crawling over hard surfaces during an intense military selection process. Their CK levels were markedly raised (highest was 176,599 U·L−1), but they did fine and two were cleared for warfare support or service (5). Pearl: As in the civilian described above, high CK values in novel overexertion ER are not necessarily an alarm signal.

Even defining ER can be problematic. In a study of 499 army recruits in basic combat training, none developed “clinically significant” ER, but muscle pain/soreness was common, and nearly 90% of the recruits had elevations in CK. Just over 10% had a CK greater than 10 times the upper limit of normal (ULN). It was concluded that although ER is commonly diagnosed when CK is more than five times the ULN, maybe CK greater than 50 times the ULN is more specific for meaningful ER in basic combat training (6). Also, in a pilot study of Air Force Special Warfare training, CK levels went as high as 28,000 U·L−1, but no AKI was seen. It was concluded that “nonpathologic” elevation of CK is prevalent in high-intensity military training (7). This is similar to three studies of serial CK values during college football camps, where elevated CK levels were common and judged to be “physiologic” for the intensity of the football training (8).

Criteria for hospitalization also are murky, as in a case series of 30 with ER admitted to Tripler Army Medical Center in Hawaii from 2010 to 2012. Diagnosis of ER was via the ICD-9 code for rhabdomyolysis, excluding those with trauma or heat illness. Most were young men; some ER was from CrossFit or other intense gym or home fitness workouts, but 40% of cases were from routine Army physical training or ruck marches. Mean CK on admission was 61,391 U·L−1 (range, 697–233,180 U·L−1); mean CK on discharge was 23,865 U·L−1 (range, 1410–94,665 U·L−1). No compartment syndrome was seen. Only six patients got AKI, mild in five. Peak CK did not portend AKI, but clinicians were influenced by CK levels, as length of stay correlated with peak CK levels. No CK threshold was seen for admission or discharge; however, 29 of 30 patients were discharged after CK down trended (9). Pearl: Treat patients, not numbers.

Military Misdirection

Finally, I must say that our military is still confused on exertional sickling (ES) in the face of SCT, and how it relates to mortality risk and to ER. Earlier I commented on the misleading study (published in The New England Journal of Medicine in 2016) by Army and Stanford epidemiologists. They found that SCT in Black active-duty soldiers is tied to a roughly 50% higher risk of ER, but not to a higher risk of death. The main problem is they missed several Army ES deaths during the timeframe of their study (10).

I end on a new and even more misleading study from the U.S. Air Force (USAF). They studied ER and SCT status in the USAF from 2009 through 2018, finding ER via ICD-9 and ICD-10 codes and chart review. They found 377 cases of ER in that decade but were able to review medical charts on only 200. More than one third of these 200 failed to meet diagnostic criteria for ER; 53 had low peak CK values and 16 had symptoms beginning at rest! It seems many ER cases were mild; no deaths were mentioned. They found 11 with SCT, and saw no key clinical differences in their ER course compared with airmen without SCT. So they conclude: “Although SCT is a risk factor for developing ER, it does not appear to influence its progression or severity” (4).

Nothing could be further from the truth. They missed all eight USAF deaths from ES during the decade of their study (and three more USAF ES deaths in the 8 months after their study timeframe ended, but >1 year before their study appeared). I have USAF investigation reports and/or autopsy reports on all eight of the ES deaths they missed during their study. All 11 who died from ES during or soon after their study collapsed during or soon after the timed 1.5-mile USAF fitness run. All had the classical “conscious collapse” and “fulminant” ER of ES; these features of ES are mentioned in the new military perspective article on ER (3). We know the “metabolic storm” from the “explosive ER” in ES can soon stop even the normal heart.

There must be a fatal flaw in coding or logic in this new USAF study (4). They imply the risk of death from ER with SCT is zero (0 of 11), but including the eight ES deaths they missed, the USAF death rate from the ER of ES was 42%. And if you include the three who died from ES soon after their study ended, the death rate is 11 of 22, or 50%! Some of these 11 USAF ES deaths were widely reported; one even hit the front page of The New York Times. How these researchers missed all these USAF ES deaths is a mystery to me.

Final Pearl: The USAF conclusion that, in ER, the “presence of SCT (does not) portend a higher risk of complications or worse clinical outcomes” should be disregarded. It seems to be military misdirection, if inadvertent. Sad but true.

The author declares no conflict of interest and does not have any financial disclosures.

References

1. Adhikari P, Hari A, Morel L, Bueno Y. Exertional rhabdomyolysis after CrossFit exercise. Cureus. 13:e12630. doi:10.7759/cureus.12630.
2. Update: Exertional rhabdomyolysis, active component, U.S. Armed Forces, 2015–2019. MSMR. 2020; 27:10–4.
3. Nye NS, Kasper K, Madsen CM, et al. Clinical practice guidelines for exertional rhabdomyolysis: a military medicine perspective. Curr. Sports Med. Rep. 2021; 20:169–78.
4. Webber BJ, Nye NS, Covey CJ, et al. Exertional rhabdomyolysis and sickle cell trait status in the U.S. Air Force, January 2009–December 2018. MSMR. 2021; 28:15–9.
5. Atias-Varon D, Sherman H, Yanovich R, Heled Y. Rhabdomyolysis after crawling military training. Mil. Med. 2017; 182:e1948–52.
6. Kenney K, Landau ME, Gonzalez RS. Serum creatine kinase after exercise: drawing the line between physiological response and exertional rhabdomyolysis. Muscle Nerve. 2012; 45:356–62.
7. Shumway J, Irvin A, Shia R, Goodyear CD. Biomarkers, creatine kinase, and kidney function of special operation candidates during intense physiological training. Mil. Med. 2020; 185:e982–7.
8. Eichner ER. News and views on caffeine, creatine kinase levels, and sickle cell trait. Curr. Sports Med. Rep. 2017; 16:373–4.
9. Oh RC, Arter JL, Tiglao SM, Larson SL. Exertional rhabdomyolysis: a case series of 30 hospitalized patients. Mil. Med. 2015; 180:201–7.
10. Eichner ER. Exertional rhabdomyolysis stays in the news. Curr. Sports Med. Rep. 2016; 15:378–9.
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