Exertional Rhabdomyolysis in Athletes and Warfighters (2016): What the Military Medical Provider Needs to Know! Francis G. O’Connor, MD, MPH Professor and Chair, Department of Military and Emergency Medicine Medical Director, Consortium for Health and Military Performance Uniformed Services University of the Health Sciences

Why the Need to Understand Exertional Rhabdomyolysis?

 Update: Exertional Rhabdomyolysis – MSMR 2015. 22(3):22-25.

The Incidence Appears to be on the Rise!

High Intensity Exercise Lawsuit: Sailor Makimba Mimms





Former sailor experienced a severe case of exertional rhabdomyolysis from a high intensity exercise program Raised concerns across the military about dangers of popular workout regimens – Navy Times 2008

There are Questions About the Role of Extreme Exercise!

NCAA April 2010 

 

The National Collegiate Athletic Association (NCAA) adopted a policy requiring Division I institutions to perform sickle cell trait testing for all incoming student athletes. Policy was in part a result of legal settlement with Dale Lloyd Case. Exertional sickling associated with fatal exertional rhabdomyolyis may be the leading cause of sudden There are Questions death in collegiate football.

About the Role of Sickle Cell Trait!

DMAA Products Pulled from Base Shelves By Jon R. Anderson - Staff writer Posted : Thursday Dec 29, 2011 11:23:38 EST

The Defense Department has ordered an end to on-base sales of a number of workout supplements popular with military fitness buffs, concerned about potentially serious side effects of a key ingredient, DMAA. More than a dozen products containing DMAA have been yanked from on-base stores.

There are Concerns About the Role of Dietary Supplements!

Controversial Clinical Questions 



What is Exertional Rhabdomyolysis (ER) and is there a creatine kinase (CK) level that helps to defines (ER) in a warfighter/athlete (WA)? Is there guidance available to assist clinicians with deciding: – Which ER patients need a detailed evaluation; – When an ER patient can return to play/duty.

 



Does extreme exercise contribute to ER in a WA? Is sickle cell trait (SCT) a culprit or an innocent confounder in ER? Do dietary supplements contribute to ER in a WA?

Case 1

 Pt is 30 y/o former Marine personal

   

security instructor who presents to the sports medicine clinic for a second opinion. Was recently diagnosed with ER; incidental finding of 1,200 resting CK. Is AA and an avid weight lifter. Has been involved in combatives instruction for ten years. Denies supplement use and is asymptomatic.

What’s the Definition of Exertional Rhabdomyolysis?

Exertional Rhabdomyolysis: The Basics

Definition of ER

– Condition or syndrome of skeletal muscle breakdown with release of myocyte contents into the circulation – Myolysis may arise from a variety of stresses that cause injury to muscle tissue – Risk of developing metabolic abnormalities and acute renal failure are primary determinants of morbidity and mortality

Etiology of ER



Symptoms precipitated by strenuous exercise or exertion usually 24 to 48 hrs prior to presentation – Unaccustomed exercises – Eccentric exercise more damaging to muscle fibers than concentric exercise

Fowler WM et al. Changes in serum enzyme levels after exercise in trained and untrained subjects. J Appl Physiol. 1962;17:943-6.

Eccentric

Concentric

Pathophysiology of ER

 

Precise pathogenesis is not clearly understood Direct injury appears to be predominantly to Type II (white) muscle fibers

McEwen SA, Hulland TJ. Histochemical and morphometric evaluation of skeletal muscle from horses with exertional rhabdomyolysis (tying-up). Vet Pathol. 1986;23(4):400-10

Pathogenesis of Rhabdomyolysis Physical Injury Compression Ischemia Excessive contraction Electrical injury Hyperthermia

 Intracellular ATP

Reperfusion Injury

 Phospholipase A2  Ca++ Dependent

Sarcoplasmic Ca++ Influx

Non-Physical Injury Metabolic myopathies Drugs/toxins Infections Electrolytes Endocrine disorders

Compartment Syndrome

Phosphorylases  Nucleases  Proteases  Free Radicals  Local PMN Cells

Primary Cellular Injury   Intracellular Ca++  Secondary Injury  Activation

O’Connor FG, Deuster PA: Rhabdomyolysis. In Goldman L, Schafer A: Goldman’s Cecil Medicine 24th Edition. Philadelphia: Saunders Elsevier, 2012.

R H A B D O M Y O L Y S I S

Pathophysiology of ER

– Impairment of either ATP production or utilization – Muscle injury results in release of potassium, uric acid, calcium phosphate, myoglobin, and muscle enzymes (CK, LDH, AST, ALT) into plasma

Presentation of ER

 ER is a spectrum illness: 

asymptomatic to life threatening syndrome Clinical picture depends on: – Volume of muscle tissue injured – Ability to accommodate biochemical insult – Presence of other influences

Diagnosis of ER: What is the Clinical Definition? 

 

UpToDate: “classic presentation of rhabdomyolysis includes myalgias, red to brown urine due to myoglobinuria, and elevated serum muscle enzymes [including creatine kinase (CK)].” Harrison’s: “…defined as an acute increase in CK > 5 times upper limit of normal in the setting of skeletal muscle breakdown” American College of Cardiology: “…with marked CK elevation (typically substantially > 10 times upper limit of normal) ...”

What Defines Normal CK Levels in Athletes? Group

Lower reference limit

CI of lower reference limit

Upper reference limit

CI of upper reference limit

Male athletes

82

73–86

1083

881–1479

Female athletes

47

39–55

513

404–836

Male nonathletes

45

39–72

491

369–728

Female nonathletes

25

17–30

252

141–345

Mougios V. Reference intervals for serum creatine kinase in athletes. Br J Sports Med. 2007;41:674-678.

1200 1000

*

Caucasian African American Asian Hispanic

800 600 400 200 0

*p < 0.01

Creatine Kinase (IU/L)

Creatine Kinase (IU/L)

Role of Race and Gender in Baseline CK Levels 300 250

Men Women

200 150

*

100 50 0

Gender

Ethnic and Gender Differences in CK Distribution for Marine Corps Officer Candidates Francis G. O’Connor, MD; Patricia A. Deuster, PhD; Jennifer Davis, MS; Stacey Zeno, MS; Devin P. McFadden, MD; Peter J. Dillon MD; Richard L. Blumling, MSN; Francesca P. Cariello, PhD, CCRN

What CK Level Defines Physiologic ER? Baseline CK

Day 3 CK

Day 7 CK

Day 14 CK

Mean

223

734

1,226

667

Range

34 - 3,140

Median

157

478

567

486

% > 5x Normal

1.2

12.4

26.5

13.3

76 - 10,243 56 - 35,056

80 - 5,518

Kenney K et al. Serum CK after exercise – where to draw the line between physiologic response and exertional rhabdomyolysis. Muscle Nerve. 2012;45:356-62.

Controversial Clinical Questions 



What is Exertional Rhabdomyolysis (ER) and is there a creatine kinase (CK) level that defines (ER) in a warfighter/athlete (WA)? Is there guidance available to assist clinicians with deciding: – Which ER patients need a detailed evaluation; – When an ER patient can return to play/duty.

 



Does extreme exercise contribute to ER in a WA? Is sickle cell trait (SCT) a culprit or an innocent confounder in ER? Do dietary supplements contribute to ER in a WA?

Case 2: Return to Duty Decision Making 

 

28 y/o military female physician sustains a severe episode of ER after a brief, high intensity workout that she was previously able tolerate without consequence. She had a flu shot several days before the session. After recovering from the episode, she returned to activity and sustained a second and more severe ER from pushups.

Disability with a Low CK! 

25 y/o male participated in Army Physical Fitness Test: 2 mile run, push-ups and sit-ups – Within 6 hrs back pain and vomiting, nausea – CK to 2,268 U/L at 24 hrs; creatinine of 4.4 mg/dl – Vigorous fluid resuscitation – 9 day hospital stay with return to normal GFR by 3 months Tietjen DP and Guzzi LM. Exertional rhabdomyolysis and acute renal failure following the Army Physical Fitness Test. Mil Med. 1989;154(1):23-5

No Disability with a High CK! 

39 runners in Spartathalon Race: 246 km from Athens to Sparta – – – –



Mean age 41 yrs Mean finish time 33 hrs Mean CK before: 178 U/L Mean CK after: 43,762 ± 6,700 U/L

None were symptomatic or required medical attention Skenderi KP et al. Exertional rhabdomyolysis during a 246-km continuous running race. Med Sci Sports Exerc. 2006;38(6):1054-7.

What Determines Risk of Morbidity and Mortality?

 High CK levels can occur in



marathon runners without renal failure, and conversely, renal failure can occur with CK level <5,000 U/L Renal failure from ER likely results from a “perfect storm” of various factors. Clarkson PM. Exertional rhabdomyolysis and acute renal failure in marathon runners. Sports Med, 2007;37:361-3.

Factors Contributing to a “Perfect Storm”

 Exercise Factors – Experience and fitness level – Intensity – Duration – Type

 Non-exercise Factors – Illness – Sickle Cell Trait – High Ambient Temperature – Drugs – Nutraceuticals – Myopathies

Categories of Myopathies 

 

Muscular Dystrophy

– Duchenne, Becker’s, Limb Girdle Inflammatory

– Polymyositis, Dermatomyositis Toxic and Drug Induced

– Statins, alcohol

 Endocrine 

– Thyroid, growth hormone Congenital – Central core

 Channelopathies – Malignant hyperthermia, periodic paralysis

 Metabolic

Metabolic Myopathies

 

Represent defects in pathways of energy metabolism in skeletal muscle Hallmarks of clinical presentation are myalgias, cramping, and exercise intolerance – – – –

Myoadenylate Deaminase Deficiency Glycogen Storage Disease Fatty Oxidation Defects Mitochondrial Myopathies

Diagnostic Evaluation of High Risk Warfighter

Dr. Yuval Heled, Director, Heller Institute

http://www.usuhs.mil/mem/champ.html

Who is the High Risk Warrior Athlete? 

   

Delayed clinical recovery (more than a week) when activity has been restricted Persistent CK elevation despite 4 weeks at rest ER complicated by acute renal failure of any degree Muscle injury after low to moderate workload Personal or family history of: – Rhabdomyolysis − Sickle cell trait – Malignant hyperthermia − Significant heat injury – Recurrent muscle cramps/severe muscle pain that interfere with daily activities

 

Complicated by drug or supplement use (e.g. statin, ephedra, steroids, creatine) CPK peak > 100,000 U/L

High Risk WA Evaluation

Diagnostic Evaluation of High Risk Warrior Athlete

1. History and Physical Examination 2.Consultation with Regional Rhabdomyolysis Expert http://www.usuhs.mil/mem/champ.htm

Referral Warranted

1. Temporary Profile 2. Order Exercise Intolerance Panel, Guthrie Laboratory1 3. Coordinate Referral

Reassurance

Graduated Return to Duty

Initial Subspecialty Evaluation: History and Physical Examination EMG, Muscle Biopsy to include Myoglobinuria Panel at Athena Labs2 Secondary Subspecialty Evaluation: Consider: Heat Tolerance Testing Caffeine Contracture Test3 Two-Step Exercise Test

Exercise Intolerance Mutation Profile (EIMP)

 Screens for genetic variants known to be associated with ER – Carnitine Palmitoyltransferase II Deficiency  CPT2 Gene: S113L, 413delAG, P50H, R503C, G549D, R631C

– Myophosphorylase Deficiency  PYGM Gene: R49X, G204S – Myoadenylate Deaminase Deficiency  AMPD1 Gene: Q12X, P48L

Advanced Testing  Muscle Biopsy Tests – Myoglobinuria Test Panel – Caffeine Halothane Contracture Testing



Selected Additional Testing – – – –

Heat Tolerance Testing EMG/Nerve Conduction Testing Two-Step Exercise Test Sequencing

The Two Step Challenge Test 



 

Stepping up and down two stairs (30 cm) for 5 minutes at a pace of 54 steps/min followed by 15 knee bends completed within 1 minute (3 seconds count down and two seconds count up) Wears a backpack weighted at 30% of bodyweight Blood samples before, immediately after, and 48 and 72 hrs after completing exercise Participant defined as high responder when change in CK > 230 U/L

The Role of Genetic Polymorphisms  

Three SNPs were associated with ER: CKMM Ncol, ACTN3 R577X, and MYLK C37885A. ER cases were 3.1 times more likely to have the GG genotype of CKMM (odds ratio/OR = 3.1, CI 1.33-7.10), 3.0 times for the XX genotype of ACTN3 SNP (OR = 2.97, CI 1.303.37), and 5.7 times for an A allele of MYLK (OR = 21.35, CI 2.60-12.30).

Deuster PA, Contreras-Sesvold CL O'Connor FG, et al: Genetic polymorphisms associated with exertional rhabdomyolysis. Eur J Appl Physiol.2013 Aug;113(8):1997-2004.

Return to Duty



  

No consensus on return to activity following an episode of ER. It seems clear that the patient should be clinically improved and renal function should be normal. An appropriate CK level is not clear. Some literature cites normal to 1,000 to 5,000 before allowing return. Eichner ER. Exertional Rhabdomyolysis. Curr Sports Med Rep. 2008;7(1):3-4.

Return to Duty Guidelines

Szczepanik ME, Heled Y, Capacchione J, Campbell W, Deuster P, O'Connor FG: Exertional rhabdomyolysis: identification and evaluation of the athlete at risk http://www.usuhs.mil/mem/champ.html for recurrence. Curr Sports Med Rep. 2014 Mar-Apr;13(2):113-9.

Controversial Clinical Questions 



What is Exertional Rhabdomyolysis (ER) and is there a creatine kinase (CK) level that defines (ER) in a warfighter/athlete (WA)? Is there guidance available to assist clinicians with deciding: – Which ER patients need a detailed evaluation; – When an ER patient can return to play/duty.

 



Does extreme exercise contribute to ER in a WA? Is sickle cell trait (SCT) a culprit or an innocent confounder in ER? Do dietary supplements contribute to ER in a WA?

Case 3: Help Needed at Fort Hood!  33 yo male admitted to CRDAMC 2 days 



ago for ER. Developed intense bilateral upper extremity arm and forearm pain along with cola colored urine 24 h after participating in high intensity exercise. Peak CK during hospitalization was 145,000 (> 100,000 makes him "high risk" for recurrence) and but trending down with IV normal saline, maintaining urinary output at > 200 ml/h.

 Help!

Brockport ROTC Unit 

44 Cadets participated in ECP event

– 29 as individuals (IND) – 15 in teams (T) of 3 members



9/29 IND (31%) and 2/15 T (13%) were admitted to hospital for management of ER

 Longest hospitalization was 11 days.  No association of ER with “Murph” finish time or APFT score – (The

FIT were not protected)

University of South Carolina 2007 



Seven members men’s and women’s swimming team were hospitalized after a particularly demanding first practice of the season. Workouts consisting of alternating continuous push-ups for 1 minute followed by body weight squats for another minute, for a total of 10 minutes Galvez, Rupert; Stacy, Jason; Howley, Ashly: Exertional Rhabdomyolysis in Seven Division-1 Swimming Athletes. Clinical Journal of Sports Medicine 2008. 18(4):366-368.

McMinnville High School Sept 2010

 Superintendent Russell



said 24 players received treatment at Willamette Valley Medical Center at some point from Aug 1725, including 13 players who were admitted to the hospital. Chair dips http://public.health.oregon.gov/DiseasesConditions/InjuryFatalityData/Doc uments/OPHD_Football_Prelim_Report.pdf

University of Iowa January 2011

 Iowa players



described grueling, timed workouts consisting of 100 squats at ~20RM “A drill that never should be used.”

Common Themes

 Eccentric Exercise

  

Predominance Unaccustomed Exercise Sudden Increase in Volume or Intensity Timed!

CHAMP Workshop: High Intensity Exercise 

Problem: – Anecdotal reports of injury from warfighter participation in high intensity exercise (HIT) programs



Solution: – Held Joint Conference with DoD and ACSM on 13-14 September 2010 at USU to address issues involving HIT



Potential Outcome: – Funded clinical research – Improved implementation of functional training programs

Results

 Positive Aspects – Multifaceted – Functional Fitness Orientation – Core Emphasis – Group Orientation – Exciting, Fun and Motivating – Translation to Warrior Ethos

Results

 Negative Aspects – Inadequate Rest and Recovery – Demand for excellent technique – Lack of safe entry guidelines – Lack of all components of well balanced fitness program – Propensity for overreaching

Other Considerations – Dietary Supplements – Competing Exercise and Training Demands – Competing Operational Demands – Lack of Adequate Supervision – Inconsistency with Recognized Guidance on Well Balanced Fitness Principles

Research is Needed!!

Bergeron MF, Nindl BC, Deuster PA, Baumgartner N, Kane SF, Kraemer WJ, Sexauer LR, Thompson WR, O'Connor FG. Consortium for Health and Military Performance and American College of Sports Medicine Consensus Paper on Extreme Conditioning Programs in Military Personnel. Curr Sports Med Rep. 2011;10(6):383-389.

Recommendations   

 

Acclimatize Progressively for Utmost Safety Introduce New Conditioning Activities Gradually Do Not Use Exercise and Conditioning Activities as Punishment Ensure Proper Education, Experience, and Credentialing of S&CCs Provide Appropriate Medical Coverage

Controversial Clinical Questions 



What is Exertional Rhabdomyolysis (ER) and is there a creatine kinase (CK) level that defines (ER) in a warfighter/athlete (WA)? Is there guidance available to assist clinicians with deciding: – Which ER patients need a detailed evaluation;

– When an ER patient can return to play/duty.

 



Does extreme exercise contribute to ER in a WA? Is sickle cell trait (SCT) a culprit or an innocent confounder in ER? Do dietary supplements contribute to ER in a WA?

Case 4: The Role of Sickle Cell Trait 

 

A 20 y/o AA male midshipmen was unable to complete his fitness assessment due to severe leg pain and weakness 70 yards short of completing a 1.5 mile run. The patient had performed push-ups and sit-ups without difficulty immediately before the run. He was transported to the medical clinic; his only complaint was ongoing severe thigh and hamstring pain that made it difficult to walk.

What is Currently Known about SCT in Warfighters and Athletes? O'Connor FG, Bergeron MF, Cantrell J, et al: ACSM and CHAMP Summit on Sickle Cell Trait: Mitigating Risks for Warfighters and Athletes. Med Sci Sports Exerc. 2012 Nov;44(11):2045-2056.

Red Blood Cells, Hemoglobin and the Sickle Gene 



 

Red blood cells carry oxygen by utilizing the hemoglobin protein Hemoglobin consists of four protein subunits; two pairs of two types of globins, each attached to a heme subunit that carries oxygen. Mutations in the beta globin gene can cause hemoglobin S. SCD occurs when two sickle genes are inherited. SCT occurs when only one sickle gene is inherited.

What happens with Hemoglobin S in SCD? 

  



In SCD, the sickle-shaped red blood cells can die prematurely, which can lead to anemia. Sickle-shaped cells can cause serious medical complications. The average life expectancy is now in the mid 40 years of age. 1 in 600 African American and 1 in 1,400 Hispanic live births results in a child with SCD. SCD is a disqualifying medical condition for military service.

SCT is Common, and Generally Benign!   

Approximately 3 million people in the US and 300 million in the world have SCT. SCT appears to be protective against severe falciparum malaria. Prevalence in US:

– Blacks: 1/14, – Hispanic/Latino: 1/183, – Whites: 1/625



4/10 West Africans have SCT! Jordan LB et al. Screening U.S. college athletes for their sickle cell disease carrier status. American Journal of Preventive Medicine. 2011;41(6):S406-S12.

SCT Athletes have Excelled in Sports of All Levels 



SCT carriers on the Ivory Coast established 32/33 national records on running courses lower than 400 meters, suggesting greater ability of SCT carriers to perform in short and intense running events than in endurance courses. SCT athletes successfully competed in the Olympic games in Mexico City…. and the NFL. Terrell Owens Le Gallais D et al. Point: Sickle cell trait should be considered asymptomatic and as a benign condition during physical activity. J Appl Physiol. 2007;103(6):2137-8.

SCT is Associated with Sudden Death 

“Current cumulative evidence is convincing for associations with hematuria, renal papillary necrosis, hyposthenuria, splenic infarction, exertional rhabdomyolysis, and exercise-related sudden death.”

Tsaras G. Complications associated with sickle cell trait: a brief narrative review. Am J Med. 2009;122(6):507-12. Epub 2009 Apr 24.

Sickle Cell Trait and Sudden Death

 Military: – Study of >450,000 military recruits (1977-1981) – SST+ 30X risk sudden death: {RR 30 (11 – 84)} Kark J et al. Sickle-cell trait as a risk factor for sudden death in physical training. NEJM. 1987;317:781.

 Civilian – NCAA deaths 2004 to 2008; 5 SCT deaths. – SST +15X risk of sudden death. – DI football players alone, SCT African Americans (AA) have an AR of 1:805;37x risk AA Division I football players without SCT. Harmon K et al. Sickle Cell Trait Associated with a Relative Risk of Death of 37x in National Collegiate Athletic Association Football Athletes: A Database with 2 Million Athlete-Years as the Denominator. Br J Sports Med. 2012;46(5):325-30.

What is Currently Unknown about SCT in Athletes? O'Connor FG, Bergeron MF, Cantrell J, et al: ACSM and CHAMP Summit on Sickle Cell Trait: Mitigating Risks for Warfighters and Athletes. Med Sci Sports Exerc. 2012 Nov;44(11):2045-2056.

What is the Mechanism of Sudden Death?

This is a Theory!!

Loosemore M et al. Sudden exertional death in sickle cell trait. Br J Sports Med. 2012;46(5):312-4. Epub 2011 Sep 30.

Is it Heat, Hydration or Intensity?

 “Excess” sudden deaths in SCT due to Exertional Heat Illness (EHI) – & Sudden Cardiac Death – & Acute, Fulminant Renal Failure Kark et al: Exercise and hemoglobin S. Semin Hematol. 1994 Jul;31(3):181-225.

Dr. John Kark

“Heat isresults no more a trigger for Exercise in a greater decrease in RBC deformability in SCT carriers than controls, but adequate hydration can normalize hemorheological abnormalities of SCT carriers altitude, asthma, heedless valor,

exertional sickling than is

Connes P et al: Physiological or a reckless coach” responses of

sickle cell trait carriers during exercise. Sports CurrentMed. Sports2008;38(11):931-46. Med Reports, 2010, 9(6):349

Dr. Dr.Phillipe Randy Connes Eichner

Interpretation of the Post Mortem Examination 

“… since sickling is known to occur post mortem, it remains controversial as to whether the pathogenesis of these exercise-related deaths involves microvascular obstruction by sickled erythrocytes.” Wirthwein DP et al. Death due to microvascular occlusion in sickle-cell trait following physical exertion. J Forensic Sci. 2001;46(2):399-401.

Who is the Athlete or Warfighter at Risk? Can Genetic Studies Assist?

  



Risk of sudden death is 1:3,000 (SCT+ Trainee)…but who is the 1 in 3,000? “SCT has to be reconsidered as a singlehemoglobin gene mutation. This means that subjects with SCT are similar for this gene, but may be different for all other hemoglobin genes. …subjects with SCT may also be different with regard to all their remaining genes.”

BLUF: SCT Athletes may not all be the Same! Abkowitz JL, O'Connor FG, Deuster PA, Thompson AA: Sickle cell trait and safe athletic participation: the way forward. Curr Sports Med Rep.2014 May-Jun;13(3):192-3

Case 4 Follow Up  



 



Pt was hospitalized at Bethesda National Naval Medical Center. On hospital day 2, disseminated intravascular coagulation (DIC) emerged. As the patient became more obtunded, compartment syndromes developed; he underwent multicompartment fasciotomies of thighs and lower legs. Acidosis and hyperkalemia remained problematic despite renal dialysis. He was kept sedated on ventilator following surgery. With a CK peak of 3 million IU/L, hyperbaric oxygen therapy was begun to try to salvage nonnecrotic muscle. On hospital day 23, no brainstem reflexes could be elicited.

Controversial Clinical Questions 



What is Exertional Rhabdomyolysis (ER) and is there a creatine kinase (CK) level that defines (ER) in a warfighter/athlete (WA)? Is there guidance available to assist clinicians with deciding: – Which ER patients need a detailed evaluation; – When an ER patient can return to play/duty.

 



Does extreme exercise contribute to ER in a WA? Is sickle cell trait (SCT) a culprit or an innocent confounder in ER? Do dietary supplements contribute to ER in a WA?

Case 5: A Warrior Hurt Potentially with DMAA  





34yo AA male was admitted to hospital with bilateral lumbar paraspinal myonecrosis and ER. The day prior to admission he had used C4 in the morning prior to weight lifting focusing on back and shoulders. He used C4 in the evening prior to high intensity exercise training. He was hospitalized for 7 days and treated for ER. Four weeks for CK to normalize.

Dietary Supplement Ingredients and ER 

Thermogenics – Increase metabolic rate



Stimulants – Strain cardiovascular system – Increase blood pressure – Confers excessive sense of energy



Combinations of stimulants look-alikes – synephrine/caffeine – Potential for producing adverse reactions



Contaminants, adulterants – Steroids, stimulants, prescription drugs

Other Case Reports of ER and Dietary Supplements  Elsayed RK et al. Rhabdomyolysis associated with the use of a

   



mislabeled "acai berry" dietary supplement. Am J Med Sci. 2011;342:535. Dehoney S et al. Rhabdomyolysis associated with the nutritional supplement Hydroxycut. Am J Health Syst Pharm. 2009;66:142. Mazokopakis EE et al. Acute rhabdomyolysis caused by Spirulina (Arthrospira platensis). Phytomedicine. 2008;15:525. Anon. Rhabdomyolysis linked to Chinese red yeast rice. Prescrire Int. 2008;17:64. Burke J et al. A case of severe exercise-induced rhabdomyolysis associated with a weight-loss dietary supplement. Mil Med. 2007;172:656. Stahl CE et al. No pain, no gain--exercise-induced rhabdomyolysis associated with the performance enhancer herbal supplement ephedra. Med Sci Monit. 2006:CS81.

A Recent Fatal Event in a Warfighter

FDA Takes Action! 27 April 2012 FDA Challenges Marketing of DMAA Products for Lack of Safety Evidence Agency cites ten companies in warning letters

Percent of Respondents (%)

Adverse Event Reporting 70

Study 1: n = 401

60

Study 2: n = 251

50 40 30 20 10 0 Observ ed AE

Know How to Reported AE When Observed Report AE

Summary Lots of Work needs to be done as there are many more Questions than Answers! ER is a Health Issue, and also an issue that directly impacts Military Readiness and National Security!!

Resources

Consortium for Health and Military Performance (CHAMP) http://champ.usuhs.mil

Resources

Human Performance Resource Center

http://hprc-online.org/

 For further information please contact: [email protected]

 Dr. Francis G. O'Connor, COL, MC, USA

Medical Director, Uniformed Services University Consortium for Health and Military Performance [email protected]

 Dr. Patricia Deuster, PhD, MPH

Scientific Director, Uniformed Services University Consortium for Health and Military Performance [email protected]