I graduated from the University of Maryland in 1984. I remember vividly the shock, disbelief, and tailspin that the men's basketball program went through in 1986 when Len Bias died of a cocaine-induced cardiac arrest 2 d after being selected second in the National Basketball Association draft by the Boston Celtics. With the heat stroke-related death of freshman football player Jordan McNair in June 2018, and the subsequent firing of coach D.J. Durkin, Maryland athletics has been sent into another tailspin. Just as the Len Bias death was a wake-up call to the dangers of recreational cocaine usage, the Jordan McNair tragedy is a signal for the institution of serious changes in the prevention, recognition, and treatment of heat stroke in college athletics. As the late Yogi Berra would have said, “It's déjà vu all over again.”
The Jordan McNair heat stroke case is just the latest high profile death to occur in an athlete. One of the most famous cases is that of Korey Stringer, a former offensive tackle for the Minnesota Vikings, who died after a spring training workout in 2001. The tragic and avoidable death of Korey Stringer was a message to the National Football League (NFL) that changes and safeguards were necessary. In fact, there has not been a similar event in an NFL player in the last 18 yr. Stringer's widow, Kelci, is responsible for much of that effort. After her husband's death, she worked tirelessly to develop an exertional heat stroke prevention institute. She joined forces with Dr. Douglas Casa, an exertional heat stroke expert at the University of Connecticut, to form the Korey Stringer Institute (KSI) in April 2010. The mission of KSI is to provide research, education, advocacy, and consultation to maximize performance, optimize safety, and prevent sudden death for the athlete, warfighter, and laborer. KSI is partnered with the NFL, Gatorade, National Athletic Trainers’ Association, Camelback, Kestrel, Mission, HeartSmart.com, and Eagle Pharmaceuticals to further advance its efforts and goals.
Unfortunately, the NFL's success in preventing heat stroke-related deaths has not translated to the National Collegiate Athletic Association (NCAA). Since 2000, 30 college football players (nearly two every year) have collapsed and died from heat stroke during workouts. That figure climbs to more than 50 when other Division 1 athletes are included. The NCAA has not instituted or enforced interventions similar to the NFL. Cold-water immersion therapy is the mainstay of heat stroke treatment, but too often access is not made available. While we know how to prevent, recognize, and treat heat stroke, I wonder if there is something else that we might be missing with regard to who is at risk. When I hear about these heat-related deaths in seemingly well-conditioned, well-acclimated athletes who have exercised many times under similar conditions, the same questions go through my mind. Why did this happen to this individual and to none of his teammates on this particular day? What was different about that day compared with the hundreds of other days that this athlete trained under similar environmental conditions? Provided nothing sinister was ongoing in the training regimen, what were the unrecognized risk factors? Was Jordan simply pushed to his physical limits, or was something else going on? Could genetics have played a role?
Since my days at the University of Maryland, I joined the Navy, developed a career as an academic anesthesiologist, and became a professor at the University of Minnesota. So why would Jordan McNair's heat stroke death resonate with an anesthesiologist? Because I wonder if Jordan McNair, Korey Stringer, and others, were predisposed to heat injuries by an inherited condition called malignant hyperthermia (MH), a potentially lethal hyperthermic crisis previously thought to only have implications when triggered in those receiving general anesthesia. MH is an inherited, subclinical myopathy identified by an unexpected hypermetabolic reaction during and after exposure to the potent inhaled anesthetics and/or the intravenous depolarizing muscle relaxant succinylcholine (1). Mutations in the protein structure of the ryanodine receptor type 1 (RyR1) fast release calcium channel of skeletal muscle sarcoplasmic reticulum have been identified as the defect most strongly associated with MH susceptibility (MHS) (2). Thus, RyR1 gene (RYR1) analysis has become an invaluable diagnostic test for individuals and families with suspected MHS. While MH remains a pharmacogenomic disorder, we now also recognize that awake, non-anesthesia-related manifestations may be triggered in susceptible individuals by environmental heat and/or exercise (3–9). The treatment for MH includes whole-body cooling, just like exertional heat illness, and the intravenous administration of dantrolene, which corrects the abnormal calcium regulation of the skeletal muscle that leads to hyperthermia. Thus, dantrolene has potential as a therapeutic adjunct for heat stroke.
Before joining the faculty at the University of Minnesota, I served as the director of the MH Testing Center at the Uniformed Services University of the Health Sciences (USUHS) in Bethesda, Maryland. MHS is a medically disqualifying condition for serving in the military, and heat illness is a condition that often plagues our military members performing arduous duty in austere environments. As a result, MH and its relationship to other heat illnesses are of vital interest to the armed forces. Researchers at USUHS, as well as investigators at other institutions, have identified an association between MHS and unexplained exertional heat stroke and rhabdomyolysis. Multiple cases and examples have emerged (3–18). Additionally, other, non-MH-related genes also are being discovered that are likely instrumental in the development of the exercise and heat-induced muscle injury phenotypes (19).
In 2017, our research team published a report on a football player diagnosed with MHS and a RYR1 MH-causative gene mutation after experiencing a hypermetabolic crisis during general anesthesia for shoulder surgery (20). This athlete went on to play three injury-free seasons of college football before experiencing an incapacitating episode of exertional rhabdomyolysis. This example of precision medicine, or genome-guided health care, identified an athlete potentially at risk. While genetic testing may not be helpful in all circumstances, test fidelity is improving and may shed light on the etiology of unexpected or unexplained exercise-induced and heat-related injuries. Genetic testing may not have saved Jordan McNair, but postmortem genetic analysis of exercise-induced heat-related deaths may permit us to identify targets for future study. Postmortem genetic analysis has already been used to identify MH-causative RYR1 mutations in unexplained awake heat-related deaths (6,8,9).
Like Korey Stringer before him, Jordan McNair's heat stroke-related death is a wake-up call for the athletic community and health sciences to ask probing questions not just about prevention and treatment, but also about who may be predisposed. With college football’s next spring training right around the corner, we need to prevent another Jordan McNair tragedy. Can we do more? I offer that we should use precision medicine and genetic analyses in these situations. We already have data that support such an endeavor (6,8,9). And, multidisciplinary discussions, such as this one from an anesthesiologist publishing in a sports medicine journal, are necessary so that we can enhance discovery by looking at problems from several different angles. What more can we learn from Jordan McNair? I think that Jordan has much more that he can still teach us.
The author declares no conflict of interest and does not have any financial disclosures.
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