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S H O R T C O M M U N I C A T I O N

Rhabdomyolysis/myoglobinemia and NSAID during 48 hultra-endurance exercise (adventure racing)

Emma Wichardt C. Mikael Mattsson

Bjorn Ekblom Karin Henriksson-Larsen

Accepted: 4 December 2010 / Published online: 23 December 2010

Springer-Verlag 2010

Abstract Our purpose is to determine whether rhabdo-

myolysis with myoglobinemia exists during a 48? hadventure race and if there is a correlation with NSAID

use, race time and perceived pain or exertion. Blood

samples for analyses of myoglobin (Mb) were collected,

and perception of exertion and pain was registered on the

Borg-RPE and CR scales, from 20 subjects (3 female,

17 male) Pre-, Mid- and Post-race. Subjects were asked

about NSAID use at each sampling and within 12 h pre-

race. The result observed was a significant rise in Mb

throughout the race, with the NSAID group (n =6) having

significantly lower Mb-Post than the no-NSAID group

(n =14). High Mb-Pre and Post correlated to shorter race

time and high Mb-Pre to lower Pain-post. Race time also

correlated to NSAID use, with the NSAID group having

significantly longer race time than the no-NSAID group.

Rhabdomyolysis with myoglobinemia, which might be

reduced with NSAID use, exists during a 48?h adventure

race. Indications that high Mb-levels correlate with shorter

race time and less pain, and the reasons for the NSAID

groups longer race time, warrants further investigation.

Keywords Myoglobin Myoglobinemia Analgesics

Exertional rhabdomyolysis Multisport

Introduction

Musculoskeletal injuries and complaints during adventure

races (AR) and other endurance races are commonly repor-

ted (Anglemet al. 2008; Newsham-West et al.2010; Townes

et al. 2004). Increased creatine kinase (CK) and/or myo-

globin (Mb) levels have been reported after several endur-

ance races (Boudou et al.1987; Fallon et al.1999; Skenderi

et al. 2006; Thomas and Motley 1984). It is therefore

reasonableto believe that a certaindegree of rhabdomyolysis

exists during an ultra-endurance event like AR.

The effects of NSAIDs (non-steroidal anti-inflammatory

drugs) on exercise-induced rhabdomyolysis are inconclusive.

Some previous studies have found higher levels of muscle

damage markers (CK) in the NSAID group compared to the

no-NSAID group (Donnelly et al.1990; Wharam et al. 2006).

Other studies have found no difference between the NSAID

and the no-NSAID groups (Bourgeois et al.1999; Donnelly

et al.1988; Hasson et al.1993; Lecomte et al.1998; Nieman

et al.2005; Page et al.2007). Yet other studies have shown

reduction in muscle damage markers after NSAID use

(OGrady et al.2000; Pizza et al.1999). To our knowledge,

the effects of NSAIDs on rhabdomyolysis during a multi-day

AR have not been studied previously.

The purpose of this study was to examine (1) if myo-

globinemia exists during a 48?h ultra-endurance AR and

(2) if there is a correlation between Mb-levels and NSAID

usage, level of perceived pain and exertion, and race time.

Communicated by Susan Ward.

E. Wichardt (&) K. Henriksson-Larsen

Sports Medicine Unit, Department of Surgery and Perioperative

Science, Umea University, Gosta Skoglunds vag 3,901 87 Umea, Sweden

e-mail: emma.wichardt@idrott.umu.se

E. Wichardt C. M. Mattsson B. Ekblom

K. Henriksson-Larsen

Astrand Laboratory of Work Physiology, The Swedish School

of Sport and Health Sciences, Stockholm, Sweden

e-mail: mikael.mattsson@gih.se

C. M. Mattsson B. Ekblom

Department of Physiology and Pharmacology,

Karolinska Institutet, Stockholm, Sweden

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Eur J Appl Physiol (2011) 111:15411544

DOI 10.1007/s00421-010-1774-2

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Method

The study took place during the Nordic Championships in

AR in Karlstad, Sweden, at the beginning of May 2008. It

was a non-stop AR, with an estimated winning time of

48 h, where teams of four (males and females) covered

approximately 500 km by foot, mountain bikes and kayaks.

A compulsory stop halfway through the race allowed theresearch team to administer the study.

Twenty racers (3 females, 17 males) from five teams

volunteered for the study. NSAID use within 12 h before

and/or during the race decided if subjects were placed in

the NSAID group (n =6) or the no-NSAID group

(n =14). Written informed consent was obtained from all

subjects. The design of the study conformed to the Dec-

laration of Helsinki and was approved by the Regional

Ethical Review Board in Stockholm, Sweden.

Blood samples for analyses of Mb-concentration in

plasma were obtained 12 h before race start (Mb-Pre),

halfway through (Mb-Mid) and within 30 min of racefinish (Mb-Post). Analyses were performed with ECLIA

(P-Myoglobin with Modular E170, Roche Diagnostics Ltd,

Sweden). Data are presented in the conventional clinically

used unit ng mL-1 to facilitate comparison with data in

referred articles. For conversion to the SI unit nmol L-1

multiply by 0.0571.

Subjects were asked about their NSAID use before each

blood sampling, and asked to rate their level of exertion on

the Borg-RPE scale (Borg1962, Borg1998) and their level

of pain on the Borg-CR scale (Borg1998) at the mid and

post samplings.

The five teams that participated in the study ranged from

elite to relative beginner, and this also showed on the result

list where they placed from top 5 to bottom 5.

Statistics

Statistical analyses were done in SPSS 17.0 (SPSS Inc.,

Illinois, USA). The Friedman test was used to analyze

changes in Mb over time, MannWhitneyUtest was used

for differences between groups and Wilcoxon test for dif-

ferences between Mb levels at different times. Spearman

correlation (two-tailed) was used to analyze relationships

between variables. Significance was accepted atp\ 0.05.

Data are reported as median (range).

Results

All 20 subjects completed the race and were available for

the final analysis. No differences for body mass, age, pre-

race heart rate or height existed between groups (Table1).

Race time was 54.4 (14) h and there was a difference

(p\ 0.05) between groups, with the no-NSAID group

having a shorter race time.

Incidence of NSAID use was 30% (n = 6). The six

subjects consumed a total of 20 NSAID tablets in aggre-

gate. 18 of those 20 were Diclofenac 25 mg, one was

Naproxen 500 mg and one was Ibuprofen 500 mg. Median

milligrams of Diclofenac intake spread over the full racewas 112.5 (75) per person. No subject took a higher than

recommended dose per day (Voltaren 75100 mg per day,

Novartis).

Mb-levels rose over time for both the NSAID and the

no-NSAID group (p\ 0.01). A significant change in

Mb-levels at Mb-Mid and Mb-Post compared with Mb-Pre,

both for the NSAID (p\ 0.05) and the no-NSAID group

(p\ 0.01) was observed. The NSAID group had lower

Mb-Post than the no-NSAID group (p\ 0.05). No differ-

ence between Mb-Mid and Mb-Post in either group

(Table2).

Perceived exertion and pain increased from mid- to post-

race, but the increase was only significant for pain

(p\ 0.05). Pain rose from 3.0 (5)4.5 (6) on the Borg

CR-scale, and exertion from 15.0 (8)16.5 (10) on the Borg

RPE-scale. There were no differences between groups for

perceived exertion or pain.

Spearmans rho test showed a negative correlation

between work time and Mb-Pre (p\ 0.05, r = -0.461)

and Mb-Post (p\ 0.05, r = -0.533). A high Mb-Post

correlated to both a high Mb-Mid (p\ 0.05, r =0.561)

and Mb-Pre (p\ 0.01, r =0.595). A high Mb-Pre corre-

lated to a lower Pain-Post (p\ 0.05, r = -0.512). Work

Table 1 Subject characteristics

NSAID

(n =6)

No-NSAID

(n = 14)

p value

Age (years) 28.0 (14) 31.7 (20) 0.322

Body mass (kg) 84.7 (26) 76.1 (23) 0.187

Height (cm) 180.5 (29) 180.0 (21) 0.868

Heart rate pre (beats min-1

) 131.5 (39) 131.5 (41) 0.836Race time (h) 57.5 (10) 51.9 (14) 0.044*

Values are median (range). Measurements of heart rate pre were made

during cycle exercise at steady-state conditions at fixed work

* Significant difference (p\ 0.05) between groups

Table 2 Change in myoglobin during race

NSAID (n =6) No-NSAID (n = 14) p value

Pre-race 26.6 (6) 32.0 (32) 0.086

Mid-race 389.0 (452) 518.0 (1296) 0.188

Post-race 293.0 (316) 533.5 (939) 0.039*

Values are median (range)

* Significant difference (p\ 0.05) between groups

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time was also correlated to NSAID intake (p\ 0.05,

r = 0.463).

Discussion

The incidence of NSAID use was 30% in this study, the

same as found after the New Zealnd Ironman Triathlon(Wharam et al. 2006) and the Brazil Ironman Triathlon

(Gorski et al. 2009). NSAID use is very common among

different types of sports and athletes (Alaranta et al.2006;

Corrigan and Kazlauskas2003; Taioli2007; Wharam et al.

2006) and more common for athletes than the general

population (Alaranta et al.2006).

Reasons for NSAID consumption during expedition-

length ARs are so far unknown, and probably vary, but one

aspect is certain: different kinds of musculoskeletal injuries

are commonly developed during these long races (Anglem

et al. 2008; Newsham-West et al. 2010; Townes et al.

2004). These injuries cause pain and discomfort for theracer. And accordingly, the main reason for NSAID con-

sumption during the Brazil Ironman Triathlon was pain

prevention (Gorski et al.2009). The pressure, self-imposed

or from teammates, to complete the race, in spite of pain,

may lead many to ingest NSAIDs (own unpublished data).

But the research on this subject is sparse and the effects of

NSAID consumption are unknown.

As stated in the introduction, the effects of NSAIDs on

exercise-induced myoglobinemia are inconclusive (Bour-

geois et al.1999; Donnelly et al.1988; Donnelly et al.1990;

Hasson et al.1993; Lecomte et al.1998; Nieman et al.2005;

OGrady et al.2000; Page et al. 2007; Pizza et al.1999;

Wharam et al. 2006). There are differences in the above-

mentioned studies that may partly explain the different

results, for example different exercise intensities and times.

If intensity is worse than duration it would explain why

some other studies have contradictory results to this study.

Long duration with low intensity is characteristic for AR

(Lucas et al.2008). After a triathlon race, characterized by

higher intensity than AR, the mean peak level of myoglobin

was 842 ng mL-1 over a 24 h period (Thomas and Motley

1984) compared to the mean peak level of myoglobin that

was 612 ng mL-1 in this study (median 571, range 1405).

Intensity increase resulting in increasing stride length has

been shown to increase shock attenuation (Cavanagh and

Kram 1989) and thereby the eccentric phase of running.

Eccentric loading has also been shown to increase SCK

levels more than concentric loading (Malm et al. 2004).

This could explain the lower Mb-levels in this study com-

pared to studies of triathlon races.

No difference between groups for perceived exertion

was noted in this study, contrary to results from Garcin

et al. (2005). They found that acetaminophen consumers

had significantly lower perceived exertion at velocity cor-

responding to the lactate concentration threshold than non-

consumers. A difference might be that the subjects in the

present study exercised below their lactate threshold during

the entire race.

This study indicates that higher Mb-Pre and Mb-Post

correlate to shorter race time and lower Pain-Post. Previ-

ously, High Mb-levels have also been shown to correlatewith shorter race time in triathlon (Thomas and Motley

1984). A reasonable explanation for better-performing

athletes having a higher Mb-Post could be that they work at

a higher relative intensity which causes more muscle cell

damage. The finding that also Mb-Pre correlates to a

shorter race time could be explained by the tendency of top

level athletes to train frequently at higher work rates, and

therefore have consistently higher Mb-levels in their blood

than less well-trained athletes. Mb is a marker of muscle

cell damage, and more muscle cell damage should logically

induce more pain. However, in this study high Mb-levels

correlate to less pain. To determine the accuracy of thesefindings, further research needs to be conducted.

The NSAID group had a significantly longer race time

compared to the no-NSAID group. This could have several

explanations. One reason could be that less well-trained

athletes, which tend to have longer race times and lower

pain tolerance compared to well-trained athletes, are more

likely to consume NSAID.

On the other, hand it may be that injured athletes are

more likely to consume NSAID and their injury decreases

speed and prolongs overall race time. It is impossible to

determine the cause and effect at this stage, but an inter-

esting question arises as to what effects NSAID use have

on performance.

The findings of the present study points towards that

NSAID use during races may decrease the level of myo-

globinemia, and therefore the risk of rhabdomyolysis, but

as discussed above such conclusions are preliminary. But if

the findings are true on a population basis, it must be

considered positive from a physiological view. Although,

from a strict racing performance point of view, it seems

that high Mb-levels would be beneficial, both for race

results and the athletes perception of pain during the race.

The major limitation of this study is that the NSAID use

was not randomised i.e., athletes themselves decided if, and

what dose, of NSAID to consume. And the number of

subjects in the NSAID group was small relative to the

no-NSAID group.

Conclusion

Our results indicate that rhabdomyolysis with myoglobin-

emia exists during a 48?h AR. The Mb-levels were

Eur J Appl Physiol (2011) 111:15411544 1543

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significantly lower for the NSAID-group. Contrary to

reigning clinical beliefs higher Mb-Pre and Post correlated

to less pain and shorter race time. However, it is premature

to develop guidelines for AR athletes on the effect of

NSAID use on their race results and well-being. We sug-

gest further studies under race-like conditions with larger

population samples and a controlled intake of NSAID.

Acknowledgments The study was financially supported by grants

from The Swedish National Centre for Research in Sports.

Conflict of interest The authors declare that they have no conflict

of interest.

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