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MILITARY MEDICINE, 174, 5:496, 2009

Exertional Heatstroke: Early Recognition and Outcome With Aggressive Combined Cooling—a 12-Year Experience CPT Pasiri Sithinamsuwan*; COL Kunchit Piyavechviratana†; LTC Thitisak Kitthaweesin‡; CPT Watcharapong Chusri*; LTC Patima Orrawanhanothai*; Senior COL Adisorn Wongsa†; COL Anan Wattanathum†; COL Yotin Chinvarun*; Senior COL Samart Nidhinandana*; LT Bancha Satirapoj‡; COL Ouppatham Supasyndh‡; COL Chantrapa Sriswasdi§; Senior COL Wichai Prayoonwiwat§; ¶Phramongkutklao Army Hospital Exertional Heatstroke Study Team ABSTRACT Objective: To determine the clinical outcomes of an aggressive combined cooling technique for exertional heatstroke in Thailand. Methods: We analyzed patients who were diagnosed with exertional heatstroke between 1995 and 2007. Outcomes were assessed both in hospital and at 3 months follow-up. Results: Twenty-eight cases of exertional heatstroke presented to Phramongkutklao Army Hospital over 12 years. All patients developed multiorgan dysfunction and encephalopathy. Twenty-four cases had acute renal failure, 7 of whom required dialysis. Disseminated intravascular coagulation (DIC) was detected in 9 patients (32.1%). In-hospital mortality was 7.1%. Most survivors recovered with nearly normal organ function. However, 9 exhibited prolonged neurologic dysfunction and 2 had chronic renal dysfunction requiring hemodialysis. At 3-month follow-up, neurologic and renal dysfunction in those patients persisted. Higher serum prothrombin time and DIC correlated to fatality. The patients whose core body temperature achieved 38°C within 3 hours revealed a significantly lower DIC and twice as low in the frequency of poor outcome than the patients cooled longer than 3 hours to reduce core body temperature to 38°C. Conclusions: Despite early recognition and aggressive combined cooling, exertional heatstroke remains associated with multiorgan dysfunction. However, our 7.1% in-hospital mortality rate was low compared to previous studies. Early diagnosis and prompt treatment are critical.

INTRODUCTION Heatstroke (HS) is a life-threatening illness that occurs when body temperature is very high and can lead to multiorgan dysfunction. It is defined as hyperthermia with core body temperature in excess of 40.0°C with central nervous system (CNS) dysfunction.1,2 This life-threatening illness results from failure of thermoregulatory mechanisms coupled with an exaggerated acute phase response, causing an elevation in core body temperature and producing multiorgan dysfunction.3 The high mortality rate and permanent neurologic deficit that can occur with heatstroke demand urgent attention. Early recognition, initiation of rapid cooling measures, and other supportive therapies can reduce the high fatality rate in such patients.4,5 Heatstroke has been classified as exertional or classic. Exertional heatstroke (EHS) is precipitated by heavy exertion in extremely hot and humid climates and is usually seen *Division of Neurology, Department of Medicine, Phramongkutklao Army Hospital and Medical College, Bangkok, 10400, Thailand. †Division of Critical Care, Department of Medicine, Phramongkutklao Army Hospital and Medical College, Bangkok, 10400, Thailand. ‡Division of Nephrology, Department of Medicine, Phramongkutklao Army Hospital and Medical College, Bangkok, 10400, Thailand. §Division of Hematology, Department of Medicine, Phramongkutklao Army Hospital and Medical College, Bangkok, 10400, Thailand. ¶Department of Medicine, Phramongkutklao Army Hospital and Medical College, Bangkok, 10400, Thailand. This manuscript was received for review in July 2008. The revised manuscript was accepted for publication in February 2009. Reprint & Copyright © by Association of Military Surgeons of U.S., 2009.

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in athletes, military recruits at training, construction workers, and otherwise healthy young people.5–7 Frequently encountered complications include acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), shock, rhabdomyolysis, acute renal failure (ARF), cerebral edema, seizures, and hepatic dysfunction. Laboratory studies may reveal coagulopathy, azotemia, elevated liver and muscle enzymes, and leucocytosis.5,6 In 1989, Srichaikul et al. first described this syndrome in Thailand, illustrating a 25% mortality.7 We now report our 12-year experience with Thai EHS and describe the frequency, clinical and laboratory profiles and outcomes of EHS associated with early recognition and aggressive combined cooling. MATERIALS AND METHODS Patient Selection Patients diagnosed with EHS and admitted to the medical intensive care unit (ICU) of Phramongkutklao Army Hospital, a military medical center, during January 1995 to December 2007 were enrolled in our study. In this retrospective study, we reviewed medical records from the emergency room (ER), ICU, and medical wards. Our diagnostic inclusion criteria for EHS were: (a) core body temperature of more than 40.0°C or documented evidence of cooling before the first recorded temperature and reliable history of compatible environmental exposure, (b) evidence of CNS dysfunction (seizures or altered of sensorium [disorientation, delirium, and coma]) that

MILITARY MEDICINE, Vol. 174, May 2009

Exertional Heatstroke: A 12-Year Experience

was documented by the attending physician, and (c) history of strenuous exercise. Exclusion criteria were those with proven CNS infection, systemic sepsis, malaria, malignancy, neuroleptic malignant syndrome, and malignant hyperthermia secondary to anesthetic agents at the time of admission. Relevant data were recorded and included demographic characteristics, core body temperature at admission, Glasgow coma scale, clinical features at presentation, vital parameters, laboratory data (serum creatine phosphokinase [CPK], lactate dehydrogenase [LDH], serum bicarbonate [HCO3], complete blood count [CBC], creatinine, liver function test [LFT], and chest X-ray [CXR]), length of ICU and hospital stay, condition at discharge, and 3-month outcome. Organ dysfunction was assessed by both clinical and laboratory parameters. The association between the final outcomes, organ dysfunction, and initial parameters was evaluated. The pertinent laboratory parameters we considered were elevation of serum CPK, LDH, LFT (aspartate aminotransferase and alanine aminotransferase of more than twice normal), presence of metabolic acidosis, leukocytosis, and computed-tomography (CT) brain scan. DIC was defined as more than 25% decrease in platelet count and at least one of the following conditions: prothrombin time of more than 25% of normal, increased fibrin degradation products, or increased D-dimer value.8 Infection was defined as a positive blood or urine culture (a catheterized urine specimen with pyuria and bacteriuria), or positive sputum culture with a concurrent positive chest radiograph, or substantial physical or radiographic evidence of closed-space infection.

TABLE I. Profile Age (year) Sex, male; n (%) Occupation; n (%) Soldier Nonsoldier Body weight (kg) Height (cm) Body mass index (kg/m2)

Demographic Characteristic Median

IQR

21 24

20–25.8 100%

25 3 69 169 24.4

89.3% 10.7% 64–75 166–170 22.8–26.7

IQR, interquartile range.

FIGURE 1. heatstroke.

The bar chart showing the monthly incidence of exertional

FIGURE 2. heatstroke.

The bar chart showing the yearly incidence of exertional

Follow-Up Attending neurologists assessed neurologic functions and recorded focal neurologic deficits, when present. The functional performance including activities of daily living (ADLs) and memory function were determined in the survivors before hospital discharge and 3 months after discharge. Dementia was diagnosed using clinical criteria based on the DSM IV.9 Data Analysis Data were presented as median, interquartile range (IQR), number and percent. Nominal data were compared by χ2 analysis or Fisher’s exact test. Continuous data were analyzed using the Mann-Whitney test. We assessed statistical analysis by SPSS for Window version 11.5. RESULTS Patient Characteristics Between 1995 and 2007, there were 28 patients who met the inclusion criteria of EHS in our hospital (Table I). All patients were male. Twenty-five cases were soldiers (89.3%), 2 cases were construction workers (7.1%) and 1 case was a college student (3.6%). The median (IQR) age was 21 (20–25.8) years and BMI was 24.4 kg/m2 (22.8–26.7). The highest incidence of EHS was found in May (35.7%). Most

MILITARY MEDICINE, Vol. 174, May 2009

of the cases (78.6%) occurred from March to June (Fig. 1). The highest frequency occurred in 2003 (25%) and 2004 (17.9%) (Fig. 2). Clinical Presentations, Cooling Techniques, and Temperature Reduction Twenty-seven patients (96.4%) reported to their colleagues about having low-grade fever for a few days before developing HS. Four patients (14.3%) had history of an upper respiratory tract (URI) infection for a few days before admission while 1 (3.6%) had history of diarrhea. Core body temperature (BT), vital signs, physical findings, and neurologic examination are shown in Table II. Median core BT in our series was 41.6°C.

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Exertional Heatstroke: A 12-Year Experience

Methods of Cooling at the ER We believed that the rapid cooling might improve HS outcome; therefore, we set the institute’s target temperature as the core body temperature (BT) £38.0°C within 30 minutes after presentation to our hospital. Multiple cooling approaches were employed in the emergency department, including either external or internal cooling strategies. External cooling techniques included application of cold packs or ice slush in the groin and axillary regions in 27 patients (96.4%), wetting and fanning in 23 patients (82.1%), cool water aerosol in 20 patients (71.4%), cooling blanket in 9 patients (32.1%), and ice bath in 1 patient (3.6%). Internal cooling with gastric lavage and cool saline was performed in 9 patients (32.1%). All patients received intravenous fluids loading for resuscitation. Additionally, antipyretic agents were prescribed in the ER in 19 patients (67.9%). Only 5 of 28 patients (17.9%) were cooled within our acceptable time frame. Median time to achieving BT of