Review Article

Heatstroke
Abhijit Goyal‑Honavar, Annsmol P. Markose, Kundavaram Paul Prabhakar Abhilash
Department of Emergency Medicine, Christian Medical College, Vellore, Tamil Nadu, India
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Abstract
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Heat‑related illnesses are a common cause of morbidity and mortality in tropical climates; they range from innocuous heat cramps to life‑threatening
heat strokes, and yet, the data regarding their evaluation and management are far from definitive. It is a condition with an evolving definition,
the most recent by the Japanese Association for Acute Medicine eschewing the use of specific temperature cutoffs. Cooling measures such as
evaporative cooling are of utmost importance in bringing about a rapid decrease in core body temperature, with evidence showing the effectiveness
of invasive measures and other techniques to reduce organ dysfunction unsatisfactory. High‑quality prospective studies comparing various
modalities of treatment is the need of the hour, and the implementation of preventive measures must be more widely undertaken.

Key words: Definition, evaluation prognosis, heat stroke, heat‑related illness, management

Address for correspondence: Dr. Abhijit Goyal‑Honavar, Department of Emergency Medicine, Christian Medical College, Vellore, Tamil Nadu, India.
E‑Mail: abhijitgoyalhonavar@gmail.com

Introduction
Heat‑related illnesses: A spectrum of severity
Heat‑related illnesses are a collection of disorders resulting from a mismatch between the metabolic production of heat and
physiological measures to ensure heat loss.[1] They present with a constellation of symptoms and signs consequent to failure of
thermoregulation and are characterized by hyperthermia, defined as the elevation of core body temperature above the normal
range of 36°C–37.5°C. It is important to differentiate this elevation of core body temperature from fever, which is induced by
cytokine activation during inflammation and is regulated at the level of the hypothalamus. They have a spectrum of severity,
ranging from heat cramps to heatstroke (HS).
Heat cramps are the most innocuous of the heat‑related illnesses, manifesting as brief cramps following periods of exertion. Despite
core body temperatures between 37°C and 39°C, mental function is unaltered in such patients. The painful, involuntary muscle
spasms that characterize heat cramps are caused by fluid and electrolyte loss following excessive exertion in hot environments.
Further along the spectrum of heat‑related illnesses lies heat exhaustion, wherein generalized weakness, fatigue, nausea, headache,
vertigo, and syncope predominate. Much like heat cramps, mental status is not disturbed despite a core body temperature of 37°C–40°C.
Heat cramps and heat exhaustion respond well to conservative measures, such as rest in a cool area and replenishing fluids and
nutritional needs of the body.
Heatstroke: A paradigm shift
Farthest along the spectrum of severity lies HS, which is characterized by much higher morbidity and mortality than the other
heat‑related illnesses, with some estimates of mortality ranging from 10% to 50%.[2] Despite its well‑recognized severity, even at

Date of Submission: 03‑Jan‑2020 Date of Review: 27‑Jan‑2020

Date of Acceptance: 06‑Feb‑2020 Date of Web Publication: 17-Apr-2020

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DOI:
10.4103/cmi.cmi_4_20 How to cite this article: Goyal-Honavar A, Markose AP, Abhilash KP.
Heatstroke. Curr Med Issues 2020;18:87-93.

© 2020 Current Medical Issues | Published by Wolters Kluwer - Medknow 87

 Goyal‑Honavar, et al.: A review of the assessment and management of heat‑related illnesses

states of Andhra Pradesh, Uttar Pradesh, and Punjab. They are

also much more common among males, although the number
of female deaths due to HS has risen steeply since 2014.
A study in our own center noted that 72 patients presented
with heat‑related illness between the predominant summer
months of April and May 2016. Almost two‑third of them
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were found to have HS, with near equal distribution between

exertional and classical varieties. More than half the patients
were male, although the disparity between genders was not
as wide as reported elsewhere. Notably, the highest mortality
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was attributed to classical HS (23.8%), followed closely by

exertional HS (20%) and heat exhaustion (15.4%).
Another study in Chennai, Tamil Nadu,[7] also found a slight
Figure 1: Principles of management of heat stroke. male predominance, with a mean age of 53 years. A fifth of
those patients had premorbid conditions, the most widely
the turn of this decade, it has not received the level of attention prevalent being diabetes and hypertension.
that it warrants. The definition of a HS is an evolving one, while
While heat‑related illnesses are classically a problem of
authors such as Bouchama and Knochel[3] once described it as a
Southeast and East Asian countries, changing global climate
condition characterized by core body temperature greater than
and increased occurrence of heat waves in temperate regions
40°C and altered mental status following exposure to severe
is resulting in the appearance of this illness in previously
environmental heat, more recent attention cast on the subject
unaffected countries, often leading to a diagnostic dilemma
by the Japanese Association for Acute Medicine (JAAM)[4] in
among physicians inexperienced with the condition.[8]
2014 led to a focus on organ dysfunction involving the central
nervous system (CNS), coagulation cascades, liver, and kidney Extensive research and evaluation is the need of the hour to
irrespective of temperature. The 2016 revision of the JAAM cope with the expected rise in HS deaths, which are expected
criteria by the HS Working Group[5] simplified the criteria to to rise to two and a half times their current mortality by the
patients exposed to high environmental temperature and met 2050s.[9]
at least one of the following:
1. Glasgow Coma Scale (GCS) score ≤14
2. Creatinine or total bilirubin levels of ≥1.2 mg/dL
Pathophysiology
3. JAAM disseminated intravascular coagulation (DIC) Regulation of normal body temperature is a function of the
score ≥4 [Table 1]. anterior hypothalamus. As body temperature increases, active
sympathetic cutaneous vasodilatation increases blood flow to
Despite its reliance on core body temperature, which has the skin and initiates sweating.[10] Further exposure to heat
been shown to be an inconsistent feature of HS, Bouchama’s leads to a reduction in intravascular volume, which may lead
definition remains the most commonly used worldwide to to heat syncope. Loss of water and salt depletion through this
diagnose HSs. process leads to heat exhaustion and cramps.[11] These can be
Two forms of HS are recognized.[3] Exertional HS primarily easily corrected by replenishing the lost fluids and electrolytes.
affects young, healthy, and athletic individuals exercising The pathophysiology of heatstroke, however, is a complicated
vigorously in hot and humid climates until the body’s normal cascade of acute physiological alterations. The cytotoxicity
thermoregulatory mechanisms are overwhelmed. Exertional
of heat, combined with systemic inflammatory response,
HS is characterized by a rapid onset and is frequently
oxidative damage, and attenuated heat shock responses lead
associated with a high core temperature.
to a state of multi‑organ dysfunction.[12]
Classic (passive or nonexertional) HS is caused by environmental
The physiological alterations implicated include arterial
exposure and occurs in young children, in elderly patients, or
hypotension, intracranial hypertension, cerebral hypoperfusion,
in patients with underlying chronic illnesses, who are exposed
and increased metabolic rate.
to extreme environmental conditions. Classic HS can develop
slowly over several days. Further, these inflammatory and procoagulant responses,
together with direct cytotoxic effects of heat, cause vascular
Epidemiology endothelial injury.[3] This leads to microthromboses and a
consequent consumption of platelets. Clinically, the HS‑induced
The National Crime Records Bureau reports that the annual
coagulation and fibrin formation leads to a state of DIC.
mortality due to HS has been on the rise over the past several
years, a trend which is expected to continue and attributable The circulatory shock and cerebral ischemia closely correlate to
to climate change.[6] These deaths are most numerous in the the release of certain endotoxins and cytokines, implying that

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 Goyal‑Honavar, et al.: A review of the assessment and management of heat‑related illnesses

Table 1: Definition of heat stroke

Bouchama’s definition[3] JAAM criteria[13] JAAM‑HS‑WG criteria[5]
Environment Exposure to environmental heat (classic HS) Exposure to high environmental temperature
Temperature Core body temperature >40°C ‑
Organ dysfunction
Central nervous Impaired consciousness JCS ≥2, cerebellar GCS score ≤14
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system symptoms, convulsive seizures

Coagulation Diagnosed as DIC by JAAM JAAM DIC score ≥4
Liver Follow‑up after admission to hospital, hepatic or Creatinine or total bilirubin
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Renal renal impairments requiring inpatient hospital care levels ≥1.2 mg/dL
Cardiovascular ‑ ‑
Respiratory ‑ ‑
JCS: Jouvet Coma Scale, DIC: Deviance information criterion, JAAM: Japanese Association for Acute Medicine, GCS: Glasgow Coma Scale,
JAAM‑HS‑WG: JAAM‑Heat Stroke‑Working Group, HS: Heat stroke

Table 2: Differential diagnoses of heat stroke

Infection Drug/toxin Neurologic Environmental Endocrine Oncologic
Sepsis Malignant hyperthermia Hypothalamic stroke High Thyroid storm Lymphoma
Meningitis Neuroleptic malignant syndrome Status epilepticus temperature Pheochromocytoma Leukemia
Encephalitis Withdrawal syndrome (e.g., alcohol) Cerebral hemorrhage and humidity Diabetic
Brain abscess Cocaine Catatonia ketoacidosis
Tetanus Sympathomimetic poisoning (e.g., amphetamine)
Typhoid fever Anticholinergic poisoning
Malaria Serotonin syndrome
Stimulant‑containing dietary drugs
Salicylate poisoning

Table 3: Prognostic factors among patients with heat stroke

Study Country Patients Outcome Factors
Varghese India Patients admitted to the medical Multi‑organ CPK >1000 U/l, metabolic acidosis, AST/ALT >twice
et al.[11] ICU with HS dysfunction normal, LDH >500 U/L, WBC >11,000/cu mm
Argaud France Nonexertional HS (core body 2‑year mortality Living at an institution, use of a long‑term
et al.[7] temperature >40°C) anti‑hypertensive, anuria, coma and cardiovascular
failure at admission
Hausfater France Nonexertional HS (core body 1‑year mortality Living at an institution, prior treatment with diuretics,
et al.[14] temperature >38.5°C) Age >80 years, presence of cardiac disease or
cancer, CBT >40 C, SBP <100 mmHg, GCS score
<12, and transportation to hospital in ambulance
Misset France HS by Bouchama’s definition Hospital death At a home/healthcare facility (vs. in public locations),
et al.[15] high SAPS II score, initial high body temperature,
prolonged prothrombin time, use of vasoactive drugs
within the 1st day of ICU admission and management
in an ICU without air conditioning
Tsuruta Japan Mechanically ventilated heat‑related Hospital death and SBP, SpO2 at scene, and arterial base excess
et al.[4] illness in the JAAM‑HS criteria incidence of sequelae
Hifumi et al.[5] Japan Heat‑related illness in the JAAM‑HS Hospital death SBP, GCS score, serum creatinine levels and DIC
criteria
HS: Heat stroke, ICU: Intensive care unit, JAAM‑HS: Japanese Association for Acute Medicine‑HS, CPK: Creatinine phosphokinase, AST: Aspartate
aminotransferase, ALT: Alanine aminotransferase, LDH: Lactate dehydrogenase, WBC: White blood cell, CBT: Cognitive behavioral therapy,
SBP: Systolic blood pressure, GCS: Glasgow Coma Scale, SAPS II: Simplified Acute Physiology Score II, DIC: Deviance information criterion

despite their core differences in the initiation, the propagation The presence of comorbid conditions adds to the temperature
of the HS response and sepsis bear certain similarities. dysregulation that causes HS. For example, diabetes mellitus

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 Goyal‑Honavar, et al.: A review of the assessment and management of heat‑related illnesses

causes decreased sweat gland innervation and cutaneous Other differentials to consider are listed in Table 2.
vasodilatation via its effect on the autonomic nervous system.
Some therapeutic measures may negatively impact the Prognostic Factors
temperature balance, such as the advent of SGLT2 inhibitors,
A study performed in the medical intensive care unit (ICU) of
which may themselves predispose to HS.
our center[17] reports that more than three‑quarter of patients
Another example of a drug that increases susceptibility to HS admitted with HS developed multi‑organ dysfunction. They
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is topiramate, which finds utility in the treatment of migraine noted respiratory failure to be the most common form of organ
and epilepsy. Up to 10% of pediatric patients may develop dysfunction.
oligohydrosis, and in combination with environmental factors
Predictors of multi‑organ dysfunction were recognized
or other medication it precipitates HS.
to be creatinine phosphokinase level >1000 U/L,
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Heat shock response; the role of heat shock proteins metabolic acidosis, elevated liver enzymes, aspartate
Heat shock proteins (HSPs) are a group of molecules that aminotransferase/alanine aminotransferase more than twice
play a critical role in achieving thermotolerance and protect normal, lactate dehydrogenase >500 U/L, and leukocytosis
from stress‑induced cellular damage induced by heat, cold, defined as white blood cell count >11,000/cu mm.
and ultraviolet radiation. [3,8] Advanced age, preexisting
A study from France by Argaud et al. among non‑exertional
illnesses, dehydration, insomnia, and poor physical fitness
HSs during the 2003 Paris heat wave considered all patients
are associated with low levels of expression of HSPs such
with core body temperature >40°C found much higher
as HSP70, and these factors thus predispose to developing
mortality among elderly patients with classical HS than
classical HSs.
younger patients with exertional HS (63% vs. 15%). They
Genetic factors in heatstroke noted that the risk of mortality rose substantially in patients
Recent evidence points to the role of genetic factors in the presenting with anuria, coma, or cardiovascular failure, as well
predisposition to HS, such as the calsequestrin 1 gene on as those who developed DIC during the course of treatment.[18]
chromosome 1.[16] This gene is known to modulate skeletal Another study during the same period in France used a different
muscle contraction by regulating the release of calcium cutoff for core body temperature (38.5°C) and identified
stored in the sarcoplasmic reticulum. Differential capacities of previous treatment with diuretics, living in an institution,
muscles among individuals to modulate and release heat may age >80 years, the presence of cardiac disease or cancer, core
play a part in causing thermal dysregulation. temperature >40°C, systolic arterial pressure <100 mmHg,
GSC scale <12, and transportation to hospital in ambulance as
Differential Diagnosis prognostic factors associated with death in nonexertional HS.
The most important differentials considered in a patient with A third French multicenter study examining patients affected
severe hyperthermia include neuroleptic malignant syndrome by the same heat wave using Bouchama’s original definition
and malignant hyperthermia. found high Simplified Acute Physiology Score II score, initial
As previously mentioned, HS is characterized by the high body temperature, prolonged prothrombin time, and the
preceding history of exercise and/or exposure to high ambient use of vasoactive drugs in the 1st day of ICU admission to be
temperature. This typical history can help differentiate it from predictors of hospital death.
other causes of hyperthermia. Interestingly, Misset et al. also found that the risk of hospital
Neuroleptic malignant syndrome death was almost twice as high among ICUs without
Neuroleptic malignant syndrome is an idiosyncratic reaction air conditioning as compared to those equipped with air
associated with the consumption of first‑generation, and less conditioning. There was no significant difference among ICUs
commonly, second‑generation antipsychotics. It is recognized with and without air conditioning in terms of beds, senior
by the presence of “lead pipe” muscle rigidity, altered mental physicians, or the number of heatstroke patients admitted per
status, choreoathetosis, tremors, and evidence of autonomic ICU.[19] Hence, it is our unbridled recommendation that all
dysfunction such as dysrhythmias, diaphoresis, and labile critical care units anticipating management of cases of HS
blood pressures. should be equipped with air‑conditioning facilities, as a simple
but effective means of lowering its mortality.
Malignant hyperthermia
Hifumi et al.[20] from Japan, using the JAAM‑HS criteria,
Malignant hyperthermia is an autosomal dominant disorder,
noted that patients who developed DIC were more than twice
caused by mutations in the Ryanodine calcium channel
as likely to suffer hospital mortality, with worsening mortality
receptor. It manifests following treatment with anesthetic
as the DIC score increased.
agents, most commonly succinylcholine and halothane.
Clinical findings include muscle rigidity, especially masseter These factors are summarised in Table 3. Thus, it appears that
stiffness, sinus tachycardia, hypercarbia, and skin cyanosis the development of coagulopathy significantly worsens the
with mottling. outcome of HS. In our center, we recommend the use of DIC,

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 Goyal‑Honavar, et al.: A review of the assessment and management of heat‑related illnesses

core body temperature >40°C, and significant renal or hepatic have been performed confirming the superiority of any initial
dysfunction in determining the prognosis of HS patients. cooling method and conclusive data on the comparative
efficacy of these are needed.
Treatment Also lacking is evidence to support a specific temperature
Patients with HS often present after a significant delay and with end‑point, though various studies have shown endpoints
compromised airway, breathing, circulation, or a combination between 38°C and 39.6°C to be safe.[28] The largest of these
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of these. Immediate recognition of this clinical syndrome will case series concluded that a rectal temperature of 39.4°C is a
enable concurrent initiation of urgent stabilizing measures as safe and achievable endpoint.[3]
well as definitive cooling methods. Since both the degree and the duration of hyperthermia
Following this, the management of a case of HS involves contribute to the damage inflicted by exertional HS, many
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preventing organ dysfunction and supporting organ systems authors conclude that lowering the core body temperature
[Figure 1]. within the “golden hour,” or the 1st h following HS is critical in
mitigating the mortality and sequelae caused by the episode.[29-31]
Cooling the patient: How, how much, and how fast?
The former, i.e., cooling the victim, is the cornerstone of In the experience of the authors of this review, evaporative
therapy and requires the creation of a gradient for heat loss and convectional cooling via application of sprayed water and
between the skin and environment. forced air currents over the body work well to lower the core
body temperature in HS and are easy to implement in most
This may employ the four physical phenomena for heat centers. We support rapid cooling of HS patients to a core
transfer, namely radiation, conduction, convection, and body temperature of 101.2°F (38.4°C) in the 1st h with an ideal
evaporation. Several cooling methods have been described, cooling rate between 0.1°C and 0.2°C/min.
ranging widely in cost, complexity, and mechanism, though
most seem to be equally effective. Management of organ dysfunction
HS is associated with an inexorable progression to organ
Noninvasive methods are simpler to implement and more dysfunction; hence, managing the complications of HS is an
widely used, including conductive whole‑body immersion, important component of treating the patient.
limb immersion, and ice packs in the neck, axillae, and groin
as well as evaporative wet sheets, water sprays, and fans.[21-23] A study in France[7] found that more than 40% of patients
with HS had severe limitation of activity by Knaus et al.
A prospective nonrandomized study showed that immersion classification 1‑year following HS. Nearly the same proportion
in ice water between 1°C and 3°C of the torso and upper of patients had a strong limitation of activity, while none
legs reduced the core body temperature at twice the had no limitation of activity at 1‑year following the HS. It
rate of exposure to 24.4°C ambient air without any fans is to be noted, however, that the subjects of this study had
(0.2°C/min vs. 0.11°C/min) and reduced rectal temperature several functional limitations to begin with, and only 1 of
by 1°C within 5.6 ± 0.6 s. However, like other studies on the the subjects had no functional limitation prior to having the
subject, it suffers many limitations that reduce the significance HS. Studies in younger subjects[32] found that prominent
of these findings.[24] neurological or behavioral sequelae in HS victims were rare
Invasive methods described include the use of cold water 6 months following hospitalization. Nakamura et al. observed
bladder, gastric, peritoneal, and rectal lavage,[25] as well that 1.5% of 1441 cases of HS exhibited CNS sequelae.
as hemodialysis and cardiopulmonary bypass. Novel Patients presenting with lower GCS scores and higher body
intravascular cooling methods have been described, such as the temperatures at admission were more likely to experience
use of intravascular balloon devices, and initial intravascular these sequelae.
cooling has been shown to have good results.[26] Intravascular While case reports indicate the usefulness of continuous
methods are particularly beneficial in effecting rapid cooling, electroencephalogram monitoring in predicting CNS sequelae,
with rates of up to 0.1°C/min. When compared to conventional there is no prospective, comparable study on adequate
cooling methods, intravascular methods achieved a significant neuromonitoring and the effect of temperature control on the
reduction in the Sequential Organ Failure Assessment score CNS.[33]
in the first 24 h.
Attempts to address the disordered coagulation in HS appear
Unlike external cooling methods, these do not result in promising, with measures including the use of antithrombin
peripheral vasoconstriction but do necessitate the placement type III and thrombomodulin hastening recovery and lowering
of an intravascular balloon catheter, which requires additional markers of inflammation in HS such as interleukin (IL)‑1B,
training and resources. tumor necrosis factor‑a, and IL‑6 levels.[34-37]
Extracorporeal circulation using hemodiafiltration circuits Multiple Japanese authors have reported the use of blood
has also been employed with some benefit;[27] however, it is purification therapy to clear pro‑inflammatory molecules from
important to consider that no prospective, comparative studies the circulation, namely continuous venovenous hemofiltration,

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 Goyal‑Honavar, et al.: A review of the assessment and management of heat‑related illnesses

plasma exchange, and continuous renal replacement 7. Argaud L, Ferry T, Le QH, Marfisi A, Ciorba D, Achache P, et al.
therapy (CRRT) in HS, observing lower 30‑day mortality in Short- and long-term outcomes of heatstroke following the 2003 heat
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patients treated with CRRT.[18,38] 8. JAMA. Final report of heatstroke study. Japanese Assoc Acute Med
2014;25:846-62.
Another recent case report described the use of a variant of 9. Kalaiselvan MS, Renuka MK, Arunkumar AS. A retrospective study of
plasma exchange called continuous plasma diafiltration, which clinical profile and outcomes of critically ill patients with heat-related
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risk factors, and indicators of aggravation. Japan Med Assoc J
comparable studies, with a predominance of case reports or
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26. Hamaya H, Hifumi T, Kawakita K, Okazaki T, Kiridume K,
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