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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: [email protected]
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: [email protected]
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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