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We present a 16-year-old male athlete with hyperthermia, altered mental status, and respiratory distress during summer football practice. Multisystem organ failure ensued, which he survived. Malignant hyperthermia was suspected in this patient who had a history of rhabdomyolysis. Specific muscle contracture testing later eliminated this diagnosis. This case discusses the importance of rapid hydration with isonatremic fluid, aggressive cooling, and full support measures, including plasmapheresis, further diagnostic efforts to evaluate potential causes of rhabdomyolysis, and planning for physical and emotional rehabilitation.
Heatstroke in the Super-sized Athlete
Ericka Fink, MD,* Barbara W. Brandom, MD,yand Klaus D. Torp, MDz
Abstract: We present a 16-year-old male athlete with hyperthermia,
altered mental status, and respiratory distress during summer football
practice. Multisystem organ failure ensued, which he survived.
Malignant hyperthermia was suspected in this patient who had a
history of rhabdomyolysis. Specific muscle contracture testing later
eliminated this diagnosis. This case discusses the importance of rapid
hydration with isonatremic fluid, aggressive cooling, and full support
measures, including plasmapheresis, further diagnostic efforts to
evaluate potential causes of rhabdomyolysis, and planning for physi-
cal and emotional rehabilitation.
Key Words: heatstroke, exertional heat injury, multiorgan system
injury, rhabdomyolysis, dantrolene
A 16-year old, 135-kg male athlete presented to a local
hospital unresponsive, hyperthermic, tachypneic, diaphoretic, and
cyanotic immediately after summer football team practice in humid,
26.78C (808F) weather. The patient was admitted overnight 7 days
before this presentation for treatment of exertional rhabdomyolysis.
At that time, he complained of generalized muscle cramps after
vigorous practice with peak creatinine 1.6 mg/dL, creatine kinase
(CK) 1384 IU, and normal electrolytes. After a few days of rest, he
resumed practice. He did not take any medications and had no
surgical history. He strongly denied exposure to any performance-
enhancing substances such as ephedra.
In the emergency department, his rectal temperature was
42.28C.An endotracheal tube was placed secondary to altered
mental status, and cooling measures, including nasogastric and
bladder ice washes, fans, and a cooling blanket, were applied by
emergency personnel while the patient was transported to the local
emergency department. Initial vital signs included heart rate
168/min, respiratory rate 57/min, and blood pressure 146/103 mm
Hg. His initial arterial blood pH was 7.33 with base deficit of 8.5
meq/L. Serum potassium was 5.9 meq/L, and CK was 785 IU. Two
liters of normal saline were infused, and 500 mL of urine was
collected in the first hour of treatment. Then the patient became
oliguric. The intensive care unit physician supervising transport of
this critically ill patient to the tertiary care facility requested
treatment with sodium bicarbonate, calcium gluconate, kayexalate
enema, administration of 4 more liters of normal saline, and
dantrolene. After 1 hour of cooling measures, his rectal temperature
was 38.08C, and blood pH and potassium were normal. Twenty-five
milligrams of dantrolene, all that was available, (which contains
300 mg of mannitol/20 mg dantrolene per vial) and an additional 25
g of mannitol were given before transport to maintain temperature
control and urine output.
The patient was admitted to the pediatric intensive care unit
with the diagnoses of heatstroke and exertional rhabdomyolysis.
Computerized tomography of his head was normal, and 18 hours
later, his mental status and pulmonary status had improved. The
endotracheal tube was removed. He received oxygen via facemask
without respiratory complication. To treat rhabdomyolysis and renal
failure (creatinine 2.3 mg/dL), bicarbonate was added to his
intravenous fluids to maintain urine pH above 7, and urine output
was maintained at greater than 2 mL/kg per hour using furosemide
and mannitol (3 g/h) infusions. On the second hospital day, fever
returned to 398C, prompting resumption of dantrolene (1 mg/kg)
every 6 hours intravenously. At this time, troponin I was found to be
9.2 ng/mL (normal < 0.08) with occasional inverted T waves on
electrocardiogram. An echocardiogram showed normal findings. On
the first hospital day, CK was 5947 IU. On the second day, it was
19,140 IU. On the third hospital day, CK peaked at 90,720 IU. Urine
myoglobin reached a peak of 66,700 mg/L on the fourth hospital day.
The patient met criteria for liver failure with a combination of
impaired coagulation (peak prothrombin time, international normal-
ized ratio, and partial thromboplastin time: 26.1, 2.3, and 33.7,
respectively) and elevated liver function tests (peak aspartate
transaminase 8682 U/L and alanine transaminase 7430 U/L). On
the third hospital day, peak total and direct bilirubin of 7.5 mg/dL and
5.7 mg/dL, respectively, peak ammonia of 53 mg/dL, and
thrombocytopenia (low 49,000/mL) on the fourth hospital day.
These data prompted institution of plasma exchange and vitamin K
treatment of disseminated intravascular coagulation (DIC) and
multiple organ failure for 2 consecutive days. After consultation
with the liver transplantation service, the patient received continuous
fresh frozen plasma, alprostadil to dilate the hepatic vasculature, and
lactulose until liver function approached normal. Results of plasma
exchange were remarkable for resolution of coagulopathy, decrease
in CK by 67%, aspartate transaminase and alanine transaminase by
88%, and gradual increase in platelet count by more than 100,000/
mL. Methylprednisolone was added on the fourth hospital day for a
7-day course based on preliminary animal studies showing increased
survival benefits in heatstroke. Toxicology reports were positive for
caffeine and negative for amphetamine, including ephedrine.
Ampicillin-sulbactam, later changed to ceftazidime, was started
on the third hospital day to treat a nosocomial urinary tract infection
with Escherichia coli and Klebsiella pneumoniae.No fevers occurred
after the third hospital day. Myoglobinuria was present until the tenth
hospital day.
Dantrolene was discontinued on the eighth hospital day and
mannitol on the tenth hospital day without rebound of symptoms or
worsening of laboratory studies. No adverse events were observed
during the course of these medications.
510 Pediatric Emergency Care Volume 22, Number 7, July 2006
Illustrative Case
From the *Children’s Hospital of Pittsburgh, Pittsburgh, PA; yDepartment of
Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh,
PA; and zMayo College of Medicine, Mayo Clinic, Jacksonville, FL.
Supported by internal funding of the Department of Anesthesiology, UPMC.
Address correspondence and reprint requests to Barbara W. Brandom, MD,
North American Malignant Hyperthermia Registry, Department of
Anesthesiology, Children’s Hospital of Pittsburgh, 3705 Fifth Avenue,
DeSoto St, Room 7446, Pittsburgh, PA 15213. E-mail:
Copyright n2006 by Lippincott Williams & Wilkins
ISSN: 0749-5161/06/2207-0510
Copyr ight © Lippincott Williams & Wilkins. Unauthor ized reproduction of this article is prohibited.
The patient was discharged on the fourteenth hospital day. His
electrocardiogram was normal, and a liver ultrasound with Doppler
was normal. His only medication was nystatin for oral thrush. Upon
follow-up 1 month after discharge, he complained of weakness and
muscle pain when he walked further than 1 block. His CK was more
than 1000 IU for several weeks after hospital discharge. Because he
still wanted to play team sports, he underwent muscle biopsy and
contracture testing to evaluate his risk for malignant hyperthermia
(MH), which has been previously associated with exertional
rhabdomyolysis and heatstroke. The result of his contracture test
was normal. His muscle was not subject to other histological or
histochemical tests. He did not have any history of adverse events
with anesthesia nor did he have family history suggestive of MH, and
therefore, his exertional heatstroke occurred independently of the
MH Syndrome.
Heatstroke is a life-threatening acute illness. By defi-
nition, heatstroke is the presence of a core temperature more
than 408C accompanied by altered mental status manifested as
delirium, coma, or seizure. Heatstroke may occur because of
environmental exposure or exertion. Classic heatstroke is the
term applied to an individual who develops heatstroke while
exposed to a hot ambient temperature. Typically, classic heat-
stroke occurs in the elderly with chronic medical conditions or
in the very young confined with inadequate ventilation and
cooling during summer heat waves. Anhydrosis, as well as
pyrexia, and altered level of consciousness are typical of
classic heatstroke. The cytokine profile of patients with clas-
sic heatstroke resembles that of sepsis: increased levels of
endotoxin, tumor necrosis factor alpha (TNF-a), interleukin
(IL) 1B, IL-6, and IL-2. These inflammatory cytokines may be
released during cerebral ischemia and help explain the clinical
effects of heatstroke.
In contrast, exertional heatstroke (EHS) describes the
individual who collapses with signs of heatstroke during or
shortly after strenuous exercise. Exertional heatstroke may
occur in any ambient temperature, although it is more common
during hot and humid weather. Exertional dehydration, muscle
cramps, heat exhaustion, and rhabdomyolysis may precede
EHS. Exertional heatstroke results from both an elevation
of body core temperature and the circulatory responses to
exercise and thermoregulation. During exercise, there is pro-
fuse sweating, peripheral vasodilation and increases in heart
rate and cardiac index to promote heat loss through evapo-
ration and radiation. Sweat rates in excess of 2 L/h can be
observed. Thus, dehydration leads to abnormal heat dissipa-
tion. Increased heat production may continue during exertion,
leading to abnormal central regulation of temperature and the
development of EHS. In severe EHS, splanchnic ischemia
produced either primarily by shock or heat can elicit the
systemic inflammatory response. Elevated concentrations of
cytokines have been measured 2 hours after onset of exertional
heat illness, but these may not always correlate well with rectal
temperatures. When core temperature is elevated long enough,
multiorgan dysfunction syndrome (MODS) will occur.
This patient met the diagnostic criteria for heatstroke:
core temperature more than 408C and central nervous system
This patient also developed MODS with renal
failure, respiratory failure, liver failure, coagulopathy, and
myocardial injury. Lastly, rhabdomyolysis was demonstrated
by myoglobinuria and elevated CK.
The primary treatment of heatstroke is cooling, and
more rapid cooling has been shown to improve survival.
Modalities of cooling include water immersion, evaporative
cooling using sprayed water and fans, ice pack or blanket
application, invasive cooling such as through a nasogastric
tube or peritoneal lavage, and intravenous dantrolene.
literature review demonstrated that the choice of cooling
modality is dependent on the patient’s age, clinical back-
ground, and location. For example, a player on the field can
be splashed with cool water and fanned until reaching a
hospital where nasogastric cold-water flush can be instituted.
Time is of the essence. A study by Chou et al
showed that
neuronal damage increased with increasing lag time to in-
stitution of hypothermia in their model using a cooling
blanket applied to rats with heatstroke.
There is no literature stating how much fluid
resuscitation should be undertaken in heatstroke. However,
our patient had good outcome and increasing urine output
using aggressive intravenous hydration with approximately
45 mL/kg of normal saline.
Hypertonic saline has been advocated by Kuo et al
who found that intravenous treatment with 3% saline before
or immediately after onset of heatstroke significantly reduced
hypotension, and improved cerebral perfusion, cerebral is-
chemic damage, and survival times in a rat model. Possible
explanations for the beneficial effect of 3% saline include
reduction in intracranial pressure postischemia, attenuation of
cytokine production, and maintenance of mean arterial
pressure. One can argue about the fluid of choice, but aggres-
sive hydration to restore intravascular volume and urine out-
put should be a goal of initial therapy, which in this case was
accomplished with normal saline.
Mannitol may also be useful in the treatment of EHS.
Mannitol attenuated cerebral ischemia and neuronal damage
in a rat model of heatstroke. Niu et al
proposed the
mechanism to be mannitol’s ability to reduce intracranial
pressure after ischemia-induced cerebral edema and its
antioxidant properties. Mannitol also produces alkaline
urine, which will decrease the toxic effect of myoglobin on
renal tubules. Mannitol was used concomitantly with 1
2 times maintenance fluid in our patient primarily to promote
excellent urine output and was decreased as the patient’s
renal function improved.
The use of dantrolene for the treatment of heatstroke is
controversial. Although one study supports
its use, a ran-
domized, placebo-controlled study showed that 2 mg/kg
dantrolene ‘‘did not prove beneficial’’ to patients with
environmental heatstroke. In particular, dantrolene did not
alter cooling times, complications, and length of hospital
But these patients reported by Bouchama et al
were not
typical EHS. Their characteristics were predominantly those
of environmental heat illness. Dantrolene decreased intracel-
lular calcium elevation in muscle fibers from patients with
exertional rhabdomyolysis by 83%, associated with an
n2006 Lippincott Williams & Wilkins 511
Pediatric Emergency Care Volume 22, Number 7, July 2006 Heat Illness in an Athlete
Copyr ight © Lippincott Williams & Wilkins. Unauthor iz ed reproduction of this article is prohibited.
improvement in clinical symptoms and laboratory values.
addition, dantrolene has been reported to decrease Ca
elevation in macrophages in response to lipopolysaccharide.
Dantrolene could affect the inflammatory response that is a
result of heatstroke. Dantrolene was given to this patient at a
dose of 1 mg/kg IV every 6 hours while myoglobinuria per-
sisted. This is similar to the maintenance dose of dantrolene
recommended for the treatment of MH.
Steroids have been shown to improve survival and
neurological morbidity when given before onset of heat-
stroke in an animal model.
This is thought to be secondary
to an inhibitory effect on proinflammatory cytokines, par-
ticularly TNF-aand IL-1. Lu et al
demonstrated that in
exertional heatstroke, IL-1B, TNF-a, IL-6, interferon gamma,
IL-2R, IL-4, and IL-10, and plasma chemokines IL-8, mono-
cyte chemoattractant protein 1, and RANTES were signifi-
cantly higher than in exertional control subjects. An IL-1
receptor antagonist, given before onset of heatstroke in
rats, decreased cerebral ischemia and improved neuronal
Lui et al
found that pretreatment and posttreat-
ment with dexamethasone attenuated arterial hypotension,
cerebral ischemia, neuronal damage, and IL-1B levels and
increased time to death in induced heatstroke in rats. Human
studies of the effects of steroids in heatstroke are limited
to case reports. Controlled studies are needed. In this case, a
7-day course of methylprednisolone was given.
Disseminated intravascular coagulation is often a
feature of heatstroke, possibly as a secondary effect after
cerebral ischemia and its release of inflammatory cytokines.
Bleeding complications are the most common manifestations
in heatstroke with the occurrence of microthrombi affecting
the perfusion of multiple organs. Bouchama et al
that levels of thrombin-antithrombin III, fibrin monomers,
plasmin-alpha 2-antiplasmin, and dimerized plasmin frag-
ment D were elevated in heatstroke patients versus normal
controls and correlated with the degree of hyperthermia. In a
study of 52 consecutive patients with heatstroke, thirteen
developed DIC.
Liver damage and, rarely, liver failure
accompany heatstroke and may be due to direct thermal injury
and hypoxia secondary to splanchnic ischemia. Thus, both
consumption of clotting factors and inadequate production
may produce bleeding in EHS. Plasma exchange is one treat-
ment option that has been shown to be successful in a small
case series in patients with DIC and multiorgan failure.
It may also be useful in removing inflammatory cytokines.
In our patient, administration of fresh frozen plasma did not
lead to amelioration of coagulopathy. Coagulopathy resolved
after plasma exchange for 2 days.
This patient had an episode of exertional rhabdomyol-
ysis 1 week before his life-threatening episode of EHS. What
risk factors did he have that could have contributed to this
repeated injury? If the individual is not accustomed to the
environment in which exercise occurs and if the intensity of
exercise is much greater than accustomed, the risk of EHS is
greater. This episode of EHS occurred early in the training
season when there was much motivation to exercise as hard as
possible. Performance-enhancing drugs, such as ephedra and
diuretics, may be used in such circumstances and will increase
the risk of dehydration and muscle injury. The National
Football League, National Collegiate Athletic Association,
International Olympic Committee, and minor league baseball
banned the use of ephedra, whether synthetic or derived from
the herb Ma-huang. Our patient denied the use of these drugs
and herbs, but caffeine was identified in his urine. Thus,
toxicological urine screening did not change the course of this
patient’s management, but we suggest that such measure-
ments should be performed.
His massive bulk certainly made it more difficult for
him to loose heat. Could there have been anything else about
his muscle that would increase his risk of EHS? Controlled
studies of high-force eccentric exercise found that approxi-
mately 3% of patients experience rhabdomyolysis of the
exercised muscle.
It is not known if these 3% have an in-
herent difference in muscle that makes them more susceptible
to injury induced by exercise. Exercise-induced rhabdomyol-
ysis came to the attention of the medical community from
reports of military training units. For example, a 25-year-old
man with exertional rhabdomyolysis had muscle pain and
acute renal failure, with no other findings.
He collapsed after
30 minutes of jogging, and mixed upper and lower body
exercises were performed in a tropical climate. There was no
history of muscle disease in the patient or the family. The
findings from the histological examination of his muscle
tissue were normal. He had a positive result on the diagnostic
test of MH susceptibility, the caffeine halothane contracture
Malignant hyperthermia is a generally asymptomatic
condition, due in most cases to excess calcium release from
the sarcoplasmic reticulum through the ryanodine receptor.
Mostly in the presence of inhaled anesthetics and succinyl-
choline does the MH-susceptible person experience extreme
rhabdomyolysis. But there have been documented cases of
EHS in MH-susceptible individuals.
For example, there was a male adolescent who experi-
enced heatstroke with muscle rigidity after vigorous participa-
tion in a game. This athlete had experienced anesthesia-induced
hypermetabolism and rhabdomyolysis, the syndrome known
as MH, 8 months before his collapse after the game. Post-
mortem, he was found to have a mutation in the skeletal
muscle ryanodine receptor 1 (RYR1) that is known to be
causative of MH.
Exercise-induced rhabdomyolysis has
been found in other patients known to be MH susceptible and
to have mutations in the RYR1 gene.
25– 27
In more than 350
exertional heatstroke cases, there were metabolic abnormal-
ities in muscle found in 78% and MH susceptibility diagnosed
by contracture testing in 18% to 26%.
Because there may be a subset of patients who present
with heatstroke that are also susceptible to MH, it was
recommended that our patient undergo testing for MH sus-
ceptibility by muscle biopsy and contracture testing at one of
the specialized MH diagnostic centers.
The addresses of
these centers can be found at The outcome of
a contracture test will influence the future anesthetic manage-
ment of the patient. It could also influence professional athletic
or military training. The result of the contracture test of this
EHS patient was negative. After months of rehabilitation, he
returned to the active practice of his sport. In the following
512 n2006 Lippincott Williams & Wilkins
Fink et al Pediatric Emergency Care Volume 22, Number 7, July 2006
Copyr ight © Lippincott Williams & Wilkins. Unauthor iz ed reproduction of this article is prohibited.
competitive season, his performance was excellent. A sports
scholarship a year later allowed him to continue his education.
However, he could not complete his first semester because of
posttraumatic stress disorder. He was unable to dress for the
sport without debilitating recall of the EHS episode.
Increased metabolism and muscle breakdown can
have many causes unrelated to genetic abnormalities in the
excitation-contraction coupling mechanism such as the RYR1
mutations associated with MH. Rhabdomyolysis may be
caused by an enzyme deficiency in muscle,
although this
seems an unlikely diagnosis in this athlete. Ingestion of
performance-enhancing drugs, even caffeine, can place ge-
netically healthy muscle at increased risk of exertional injury.
It may be that a previous episode of heat-related illness, such
as was experienced by this patient a week before the episode
of heatstroke, produced greater risk of a second episode. The
duration of such increased risk is not known.
Other than the factors related to the individual as dis-
cussed above, environmental conditions are important risk
factors for EHS. The wet-bulb globe temperature combines
temperature, radiant heat, and humidity to provide a stratified
risk category for that particular area and time.
The hot and
humid climate increased our patient’s risk of EHS. In the
presence of adverse environmental conditions, behavior modi-
fication is necessary. Prevention of exertional heat injury and
EHS is possible through the education of athletes and their
families, trainers, and coaches. The American College of
Sports Medicine has published recommendations for reducing
the risk of heatstroke in athletes, including discussions
regarding which conditions present the highest risk for heat-
stroke, and fluid management during sports.
We report the successful management of a case of EHS
in an athlete, discuss several treatment modalities, and suggest
a diagnostic pathway that may be pursued to support optimal
care of the athlete after recovery from the acute episode.
Heatstroke and exertional rhabdomyolysis are not common
diseases in North America. Few of the patients with EHS may
have abnormalities in ryanodine receptor function. This
patient had a good physical outcome because of rapid
institution of conventional and additional life-saving meas-
ures. Greater awareness in communities of the early warning
signs of exertional heat illness, and in some cases, medications
and supplements that athletes are consuming could help to
decrease both its occurrence and its progression to MODS.
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... Exposure to these triggering agents stimulates a massive calcium (Ca 2+ ) release within skeletal muscles resulting in sustained contractions leading to severe hyperthermia [1,5,6]. Awake cases of MH have also been reported in response to vigorous exercise and heat stress (i.e. in the absence of anesthesia exposure) and, therefore, awake MH cases can be difficult to distinguish from EHS [7][8][9][10][11][12][13][14]. ...
... Attempts to cool awake MH patients with ice packs, cool IV fluids or non-steroidal anti-inflammatory drugs (e.g., acetaminophen, aspirin) have proven ineffective, whereas DS is often prescribed prophylactically to these patients, thus highlighting the positive Ca 2+ feedback loop in skeletal muscles as the mechanism for awake MH [8,11,13,14,68,73]. Patients with a large muscular build (whether inherited or recently acquired) appear to have a predisposition towards recurrent muscle cramps, "fever" of unknown origin, and exertional rhabdomyolysis that can culminate in a fullblown awake MH episode [10][11][12]73] (Table 1). In many case reports, there was a precipitating event (prior anesthesia exposure, illness, trauma, drug use) that may be linked to the MH episode. ...
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Exertional heat stroke (EHS) and malignant hyperthermia (MH) are life-threatening conditions, triggered by different environmental stimuli that share several clinical symptoms and pathophysiological features. EHS manifests during physical activity normally, but not always, in hot and humid environments. MH manifests during exposure to haloalkane anesthetics or succinylcholine, which leads to a rapid, unregulated release of calcium (Ca2+) within the skeletal muscles inducing a positive-feedback loop within the excitation–contraction coupling mechanism that culminates in heat stroke-like symptoms, if not rapidly recognized and treated. Rare cases of awake MH, independent of anesthesia exposure, occur during exercise and heat stress. It has been suggested that EHS and MH are mediated by similar mechanisms, including mutations in Ca2+ regulatory channels within the skeletal muscle. Rapid cooling, which is the most effective treatment for EHS, is ineffective as an MH treatment; rather, a ryanodine receptor antagonist drug, dantrolene sodium (DS), is administered to the victim to prevent further muscle contractions and hyperthermia. Whether DS can be an effective treatment for EHS victims remains uncertain. In the last decade, multiple reports have suggested a number of mechanistic links between EHS and MH. Here, we discuss aspects related to the pathophysiology, incidence, diagnosis and treatment. Furthermore, we present evidence regarding potential overlapping mechanisms between EHS and MH and explore current knowledge to establish what is supported by evidence or a lack thereof (i.e. conjecture).
... As a result, we found 110 articles about heat stroke with rhabdomyolysis. Among these cases, we found 17 cases involving individuals with heat stroke complicated with rhabdomyolysis in which the time course of the CPK level was described [1,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. We summarized these cases, including the present case, in Table 2. ...
... Thereafter, his condition rapidly deteriorated and he eventually died, despite the provision of aggressive treatment. In addition, Fink et al. reported the case of a 16-year-old male athlete with heat stroke and rhabdomyolysis [19]. The patient survived and was discharged on day 14, but his CPK level was more than 1000 IU/L for several weeks after his discharge. ...
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Background Severe heat stroke tends to be complicated with rhabdomyolysis, especially in patients with exertional heat stroke. Rhabdomyolysis usually occurs in the acute phase of heat stroke. We herein report a case of heat stroke in a patient who experienced bimodal rhabdomyolysis in the acute and recovery phases. Case presentationA 34-year-old male patient was found lying unconscious on the road after participating in a half marathon in the spring. It was a sunny day with a maximum temperature of 24.2 °C. His medical and family history was unremarkable. Upon arrival, his Glasgow Coma Scale score was 10. However, the patient’s marked restlessness and confusion returned. A sedative was administered and tracheal intubation was performed. On the second day of hospitalization, a blood analysis was compatible with a diagnosis of acute hepatic failure; thus, he received fresh frozen plasma and a platelet transfusion was performed, following plasma exchange and continuous hemodiafiltration. The patient’s creatinine phosphokinesis (CPK) level increased to 8832 IU/L on the fifth day of hospitalization and then showed a tendency to transiently decrease. The patient was extubated on the eighth day of hospitalization after the improvement of his laboratory data. From the ninth day of hospitalization, gradual rehabilitation was initiated. However, he felt pain in both legs and his CPK level increased again. Despite the cessation of all drugs and rehabilitation, his CPK level increased to 105,945 IU/L on the 15th day of hospitalization. Fortunately, his CPK level decreased with a fluid infusion. The patient’s rehabilitation was restarted after his CPK level fell to <10,000 IU/L. On the 31st day of hospitalization, his CK level decreased to 623 IU/L and he was discharged on foot. Later, a genetic analysis revealed that he had a thermolabile genetic phenotype of carnitine palmitoyltransferase II (CPT II). Conclusions Physicians should pay special attention to the stress of rehabilitation exercises, which may cause collapsed muscles that are injured by severe heat stroke to repeatedly flare up.
... Young children are also at risk because of high body surface-tomass ratio, small blood volume relative to the surface area, low sweat rate, and the reliance on others to provide fluids. 2 There are numerous articles in the literature describing deaths in infants confined to a closed car in hot weather. 6,7 In adolescents and young adults, physical exertion in hot weather and/or high humidity is the most frequent mechanism. 8,11 Heatstroke results in organ injury through damage at the cellular level. ...
The spectrum of historical features and clinical presentations of heat illness and heatstroke in the pediatric population has received limited focus in the emergency medicine literature. The majority of published cases involve children trapped in closed spaces and adolescent athletes undergoing high-intensity training regimens in geographical regions with moderately high ambient temperatures and high humidity. There has been less research on the potential impact of extreme temperatures and radiant heat that are the hallmarks of the US southwest region. We performed a retrospective review of pediatric heat illness at our facility located in a North American desert climate.
... 1,2 Markers of of inflamma1on and cytokine release has been observed in pilgrimages, 3 marathons, 4 and even football. 5 • Circula1ng cytokines have been examined when the rise of body temperature was aFenuated while cycling in a water bath, 6 however no research to date has examined the influence of any other cooling modality during exercise on the cytokine response with football equipment. ...
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Background: With climate change, heat waves are expected to become more frequent in the near future. Already, on average more than 25 000 "heat deaths" are estimated to occur in Europe every year. However, heat stress and heat illnesses arise not just when ambient temperatures are high. Physical exertion increases heat production within the organism many times over; if not enough heat is lost, there is a risk of exertional heat stress. This review article discusses contributing factors, at-risk groups, and the diagnosis and treatment of heat illnesses. Methods: A selective literature search was carried out on PubMed. Current guidelines and expert recommendations were also included. Results: Apart from muscular heat production (>70% of converted energy), there are other factors that singly or in combination can give rise to heat stress: clothing, climate/acclimatization, and individual factors. Through its insulating properties, clothing reduces the evaporation of sweat (the most effective physiological cooling mechanism). A sudden heat wave, or changing the climate zone (as with air travel), increases the risk of a heat-related health event. Overweight, low fitness level, acute infections, illness, dehydration, and other factors also reduce heat tolerance. In addition to children, older people are particularly at risk because of their reduced physiological adaptability, (multi-)morbidity, and intake of prescription drugs. A heat illness can progress suddenly to life-threatening heat stroke. Successful treatment depends on rapid diagnosis and cooling the body down as quickly as possible. The aim is to reduce core body temperature to <40 °C within 30 minutes. Conclusion: Immediately effective cooling interventions are the only causal treatment for heat stroke. Time once lost cannot be made up. Prevention (acclimatization, reduced exposure, etc.) and terminating the heat stress in good time (e.g., stopping work) are better than any cure.
Objective: To investigate the efficacy of Lando® dermal scaffold for promoting repair of acute full-thickness skin defects in pigs and explore the possible mechanism. Methods: Three 5 cm×5 cm full-thickness skin defects were created on the left dorsal skin (control group) and another 3 on the right dorsal skin (treatment group) of each of 6 Tibetan pigs. The wounds in the treatment group were covered with a bilayer artificial skin (Lando) and the control wounds with vaseline gauze. In both groups, autogenous split-thickness skin were grafted to the wounds 2 weeks later (with the silicone rubber membrane removed before grafting in the treatment group). At 3 days and 2 and 10 weeks after the injury, the wounds were assessed for general condition and contraction, and tissue samples were collected from the wounds to examine the expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) using immunohistochemistry and the expressions of MMP-1 and TIMP-1 mRNA using RT-PCR. Results: At 3 days after the injury, the wounds in the 2 groups showed no significant differences in the results of any examinations. At 2 weeks after the injury, the wounds in the treatment group showed rich and more smooth granulation tissues with more regular wound edges compared with the control wounds. At 2 and 10 weeks after the injury, the wound contraction rates in the treatment group were (30.5∓3.4)% and (39.2∓2.8)%, respectively, significantly lower than the rates of (51.8∓2.6)% (t=-29.840, P=0.000) and (60.7∓2.2)% (t=-50.213, P=0.000) in the control group. At 2 weeks, the wound tissues in the treatment group expressed significantly higher levels of α-SMA (t=15.921, P=0.000) and TGF-β1 (t=29.995, P=0.000) than the control wounds, but at 10 weeks, the expressions of α-SMA (t=-41.823, P=0.000) and TGF-β1 (t=-99.777, P=0.000) in the treatment group were significantly lower than those in the control group. Compared with those in the control group, the expression of MMP-1 mRNA in the treatment group was significantly lower at 2 weeks (t=-45.412, P=0.000) but significantly higher at 10 weeks (t=78.769, P=0.000), and the expression of TIMP-1 mRNA in the treatment group was significantly lower both at 2 weeks (t=-27.064, P=0.000) and at 10 weeks (t=-40.535, P=0.000). Conclusions: Lando® dermal scaffold can promote granulation tissue growth possibly in relation with increased TGF-β1 and decreased MMP-1 expression in the wounds. This scaffold material also reduces wound contraction and lessens scar hyperplasia and contracture after wound healing, probably as a result of decreased α-SMA, TGF-β1, and TIMP-1 and increased MMP-1 expressions.
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Limited research exists regarding peripheral hand cooling (HC) modalities with negative pressure during American football and it is unclear if reductions in internal body temperature will positively influence, perceptual measures, athletic performance, and circulating inflammatory cytokines. Two separate research studies, an environmental controlled laboratory and an observational field study, examined HC while wearing a full American football uniform. Study#1: Rectal temperature was significantly decreased from minute 66 through post-exercise in the HC with fluid condition (p
Objective: To overview the concept, pathogenesy, clinical features as well as treatment and prevention of exertional rhabdomyolysis, so as to instruct the clinical application and scientific training. Data Sources: An online search of Medline was undertaken to identify articles about the rhabdomyolysis published in English between January 1989 and April 2006 by using the key words of "rhabdomyolysis". Meanwhile, Chinese literatures about the rhabdomyolysis published between January 2000 and April 2006 were collected from the CNKI database with the key words of "rhabdomyolysis" in Chinese. Study Selection: The literatures were checked firstly, and those related to rhabdomyolysis were selected and then looked for the full-texts. Inclusive criteria: Experimental researches on rhabdomyolysis. Exclusive criteria: Repeated studies and Meta analytical papers. Data Extraction: A total of 199 literatures about rhabdomyolysis were collected, including 48 reviews, 17 experimental researches and 134 clinical case reports. DATA SYNTHESIS: 17 experimental researches included about 74 patients and 340 experimental animals, and it was proved that unscientific movement training might cause the waste of organism energy, increase of free radicals, reinforced permeability of tissues, and thus causing the releasing of inflammatory factors and induce the injury in muscles. Acute renal failure and multi-organ functional disorder were even found in some patients. It is the most important now to perform the treatment according to the cause of disease, decrease muscular injuries, recover the blood flow, and prevent and cure acute renal failure. Conclusion: Rhabdomyolysis is a skeletal muscle injury caused by over-exercise, which represent in clinic as myosalgia, engorgement, powerless, and brown urine. Its main symptoms are increased serum creatin kinase and myoglobulin with myoglobulinuria accompanied by acute renal failure. Early recognition and treatment in the acute phase of rhabdomyolysis is key to the prognosis and clinical treatment of acute renal failure.
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In 1980, 1700 people died during a prolonged heat wave in a region under-prepared for heat illness prevention. Dramatically underreported, heat-related pathology contributes to significant morbidity as well as occasional mortality in athletic, elderly, paediatric and disabled populations. Among US high school athletes, heat illness is the third leading cause of death. Significant risk factors for heat illness include dehydration, hot and humid climate, obesity, low physical fitness, lack of acclimatisation, previous history of heat stroke, sleep deprivation, medications (especially diuretics or antidepressants), sweat gland dysfunction, and upper respiratory or gastrointestinal illness. Many of these risk factors can be addressed with education and awareness of patients at risk. Dehydration, with fluid loss occasionally as high as 6–10% of bodyweight, appears to be one of the most common risk factors for heat illness in patients exercising in the heat. Core body temperature has been shown to rise an additional 0.15–0.2°C for every 1% of bodyweight lost to dehydration during exercise. Identifying athletes at risk, limiting environmental exposure, and monitoring closely for signs and symptoms are all important components of preventing heat illness. However, monitoring hydration status and early intervention may be the most important factors in preventing severe heat illness.
To the Editor: Malignant hyperthermia (MH) is an autosomal dominant condition in which certain anesthetics trigger calcium dysregulation in skeletal muscle, resulting in a catastrophic, life-threatening hypermetabolic syndrome.1 More than 50% of families with MH have mutations in the gene encoding the ryanodine receptor (RYR1).2 In a porcine model of MH, nonanesthetic, stress-induced deaths have been reported in pigs homozygous for the Arg614Cys mutation in the RYR1 gene,3 but this phenomenon has not been reported in humans with MH mutations. To our knowledge, we report the first case of nonanesthetic, stress-induced hyperpyrexic death in an individual with a history of MH.
The prognosis of heat stroke in patients is directly related to the degree of hyperthermia and its duration. Therefore, the most important feature in the treatment of heat stroke is rapid cooling. Several cooling methods have been presented in the literature including immersion in water at different temperatures, evaporative cooling, ice pack application, pharmacological treatment and invasive techniques. This article describes the various cooling techniques in terms of efficacy, availability, adverse effects and mortality rate. Data suggest that cooling should be initiated immediately at time of collapse and should be based on feasible field measures including ice or tepid water (1–16°C), which are readily available. In the emergency department, management should be matched to the patient’s age and medical background and include immersion in ice water (1–5°C) or evaporative cooling.
BACKGROUND: In July 1995, Chicago sustained a heat wave that resulted in more than 600 excess deaths, 3300 excess emergency department visits, and a substantial number of intensive care unit admissions for near-fatal heat stroke. OBJECTIVE: To describe the clinical features of patients admitted to an intensive care unit with near-fatal classic heat stroke. Patients were followed for 1 year to assess delayed functional outcome and mortality. DESIGN: Observational study. SETTING: Intensive care units in the Chicago area. PATIENTS: 58 patients admitted to the hospital from 12 July to 20 July 1995 who met the case definition of classic heat stroke. MEASUREMENTS: The data collection tool was designed to compile demographic and survival data and to permit analysis of organ system function by abstracting data on physical examination findings, electrocardiography and echocardiography results, fluid resuscitation, radiography results, and laboratory findings. Data on functional status at discharge and at 1 year were collected by using a modified Stanford Health Assessment Questionnaire. RESULTS: Patients experienced multiorgan dysfunction with neurologic impairment (100%), moderate to severe renal insufficiency (53%), disseminated intravascular coagulation (45%), and the acute respiratory distress syndrome (10%). Fifty-seven percent of patients had evidence of infection on admission. In-hospital mortality was 21%. Most survivors recovered near-normal renal, hematologic, and respiratory status, but disability persisted, resulting in moderate to severe functional impairment in 33% of patients at hospital discharge. At 1 year, no patient had improved functional status, and an additional 28% of patients had died. CONCLUSIONS: Near-fatal classic heat stroke is associated with multiorgan dysfunction. A high percentage of patients had infection at presentation. A high mortality rate was observed during acute hospitalization and at 1 year. In addition, substantial functional impairment at discharge persisted 1 year. The degree of functional disability correlated highly with survival at 1 year. Language: en
• In urethane-anaesthetized rats, we assessed the protective effects of glucocorticoids against heatstroke-induced arterial hypotension and ischaemic neuronal damage. • Heatstroke was induced by exposing the animals to an ambient temperature of 42°C. The time at which both the mean arterial pressure (MAP) and local cerebral blood flow (CBF) in the striatum decreased from their peak levels was taken as the onset of heatstroke. Control rats were exposed to a temperature of 24°C. • The values of MAP and CBF after heatstroke onset were all significantly lower than those in control rats. However, the neuronal damage score in the striatum and serum levels of interleukin-1 (IL-1) were greater. • Systemic pretreatment or treatment with an exogenous glucocorticoid, dexamethasone (4 mg or 6 mg kg−1, i.v.), reduced the heatstroke-induced arterial hypotension, serum IL-1 levels, cerebral ischaemia and neuronal damage, and resulted in prolongation of the time to death (TTD; the interval between the onset of heat stress and cardiac arrest). • Following bilateral adrenalectomy, MAP, CBF and TTD values were found to be significantly lower in the adrenalectomized (ADX) rats than in the sham-ADX rats after heat exposure. These changes were attenuated by dexamethasone. • The data support the argument that glucocorticoids reduce the plasma IL-1 concentration and may provide the neuroprotective effects observed in rat heatstroke.
Rhabdomyolysis, a syndrome of skeletal muscle breakdown with leakage of muscle contents, is frequently accompanied by myoglobinuria, and if sufficiently severe, acute renal failure with potentially life-threatening metabolic derangements may ensue. A diverse spectrum of inherited and acquired disorders affecting muscle membranes, membrane ion channels, and muscle energy supply causes rhabdomyolysis. Common final pathophysiological mechanisms among these causes of rhabdomyolysis include an uncontrolled rise in free intracellular calcium and activation of calcium-dependent proteases, which lead to destruction of myofibrils and lysosomal digestion of muscle fiber contents. Recent advances in molecular genetics and muscle enzyme histochemistry may enable a specific metabolic diagnosis in many patients with idiopathic recurrent rhabdomyolysis. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002
Rhabdomyolysis is a condition characterized by muscle damage and degeneration of muscle cells after strenuous, overexertion exercise. Although the incidence of severe rhabdomyolysis is rare, this condition can be dangerous and even fatal. Eccentric exercise protocols are currently being used to induce and study mild forms of muscle damage. However, serious adverse events can occur in these laboratory investigations. The purpose of this report was to expose some of the adverse events resulting from performance of eccentric exercise protocols to study muscle damage in humans. The following case studies involved an eccentric exercise protocol where two sets of 25 maximal eccentric actions of the elbow flexors were performed, separated by a 5-min rest period. Case reports are presented that reveal prolonged losses in the ability of the muscle to generate force lasting 43-47 d, extreme swelling of the exercised arm lasting several weeks, and greatly elevated serum creatine kinase levels. Although adverse events resulting from eccentric exercise are rare, our laboratory has observed a 3% incidence rate during the past year. Investigators should be knowledgeable of the sequelae of events that are associated with muscle damage after high-force eccentric exercise and take appropriate precautions.
To determine the efficacy of dantrolene sodium in the treatment of heatstroke. Randomized, double-blind, placebo-controlled trial. Heatstroke center in Makkah, Saudi Arabia. Fifty-two adult patients with heatstroke. Patients were assigned to receive either dantrolene sodium (2 mg/kg body weight iv) or placebo. Conventional cooling therapy was initiated in all. There was no significant difference in the mean cooling times for the treatment and control groups (67.9 vs. 69 min). There was only one death in the control group. Complications were seen in six (23%) patients receiving dantrolene sodium and seven (27%) patients receiving placebo; the difference was not statistically significant. There was no significant difference in the mean number of hospital days (4.7 +/- 2.0 vs. 2.9 +/- 0.9 days). Treatment with dantrolene sodium at the dose used, did not prove beneficial to patients with heatstroke.