investigation Objectives: Heatstroke.

investigation Objectives: Heatstroke, characterized by hyperthermia and neurologic abnormalities, can cause stroke adult respiratory distress syndrome, and multiorgan failure culminating in death. The mediation of metabolic changes and tissue damage is not entirely understood. Recent evidence suggests the involvement of endotoxin, tumor necrosis factor alpha (TNF-[alpha]), and interleukin 1 alpha (IL-1[alpha]) and we hypothesized that other pyrogenic cytokines may be implicated.

Design: Prospective analysis.

Setting: Heatstroke Center in Makkah (Mecca), Saudi Arabia.

Measurements and Results: We measured plasma IL-1[beta], IL-6, and interferon gamma (INF-[gamma]) concentrations by the agency of enzyme-linked immunosorbent assay in 28 heatstroke patients at the time of hospital admission (precooling) and after unimpaired cooling (postcooling), and in 10 normal repress subjects. We measured C-reactive protein (CRP) as a marker of acute phase answer and calculated severity of illness using the simplified acute physiology score. Twenty-five male and 3 female enslaves had mean ) [+ or -] SEM) rectal temperature of 412 [+ or -] 02 [degrees] C IL-6, IL-1[beta], and INF-[gamma] concentrations were elevated in 100 percent 39 percent and 50 percent of patients to (mean [+ or -] SEM) 220 [+ or -] 44 pg/mi, 42 [+ or -] l4 pg/ml and 1180 [+ or -] 879 pg/ml respectively (normal repress values: <3.5 pg/ml, <4.5 pg/ml <20 pg/ml) The CRP value was elevated in 72 percent of patients to 152 [+ or -] 40 mg/L (control value: 0 to 17 mg/L) The IL-6 concentrations correlated with severity of illness (r = 0516 p = 003); sum of two units patients with the highest concentrations died. There was no significant correlation between circulating horizontals of IL-6, IL-1[beta], INF-[gamma], and temperature, or between IL-6, IL-1[beta], and CRP Postcooling, IL-6, and IL-1[beta] were still above normal direction values; INF-[gamma] could he descryed in one patient only.

Conclusion: Our findings of elevated circulating IL-6, Il-1[beta], and INF-[gamma] in the neighborhood of acute phase response, and correlation with severity of illness, hint that these cytokines have a part in the pathogenesis of heatstroke, which could lead to of recent origin therapeutic strategies.

(Chest 1993; 104:1948-1502)

CRP = C reactive protein; GC = Glascow Coma Score; IF = interferon; IL = interlukin; SAP = simplified acute physiology (score); TNF tumor necrosis factor

Heatstroke is a compage syndrome of hyperthermia and censorious neurologic abnormalities, including delirium, convulsion, and coma.[1] Heatstroke patients may evolve shock, lactic acidosis, hypoxemia, and coagulation disorders that may be followed on multiorgan failure and death with widespread necrosis and/or hemorrhage into the lung liver, take out the bowels of myocardium, or other organs, at autopsyl.[1-3] The mechanism of these metabolic and pathologic changes is not clearly understood.[1] Although the direct cellular toxicity of heat has been meditation to play a primary role[34] there is growing evidence to put in mind of that endotoxin and cytokines may have important effects[56]

lately we have reported that plasma concentrations of tumor necrosis factor-[alpha] (TNF-[alpha]) and interleukin-1[alpha]) (Il-1[alpha]) are elevated in heatstroke patients.[6] It is well established that TNF-[alpha] can indtice offence lactic acidosis, and widespread hemorrhagic necrosis,[7] changes similar to those observ in heatstroke patients.[1,3] Moreover, IL-1 can cause febrile affection and acute-phase response[8] and can potentiate TNF-[alpha] related tissue injury.[7,8] the pair IL-1 and TNF-[alpha] in transfer can increase the production of interleukin-6 (IL-6)[9] and enhance monocyte cytotoxicity induced by the agency of interferon gamma (INF-[gamma]).[10] Such a cascade of cytokines has been implicated in the pathophysiology of injury and infection.[11,13] Furthermore, elevated on a levels of circulating TNF-[alpha], IL-6, and INF-[gamma] have been associated with a poor issue in various pathologic states.[11-15]

The at hand study on heatstroke was undertaken to (1) determine plasma horizontals of IL-1[beta], IL-6, and INF-[gamma] in heatstroke patients, and (2) examine the relationship between cytokine evens and the severity of hyperthermia and metabolic derangement, and clinical outcome

Materials and Methods

Patients and Clinical Data

After approval on the Institutional Review Board of King Faisal Specialist Hospital and Research middle Riyadh, who waived the ne for informed approval the study was conducted at the Heatstroke Center of King Faisal Hospital, Makkah (Mecca), Saudi Arabia, during the 1990 pilgrimage season. Twenty-eight consecutive patients with classic (nonexertional) heatstroke diagnosed by means of a rectal temperature >40.1 [degrees] C and neurologic abnormalities (delirium, convulsions, or coma) were included in the studious mood Blood pressure, pulse, and respiratory rates were recorded immediately at the time of hospital admission. Temperature was recorded continuously by means of a four-channel recorder from thermometers placed forward the skin and in the rectum Neurologic status was assessed through the Glasgow Coma Score (GCS)[16] ie, the quantity of money of the scores for (1) best judgment opening: scored 4 for spontaneous opening, 3 for opening to verbal commands, 2 for opening to pain, and 1 for no response; (2) best motor response: scored 5 for obeying verbal command, 4 for flexion-withdrawal, 3 for decorticate rigidity, 2 for decerebrate rigidity, and 1 for no response; and (3) best verbal response: scored 5 for patient oriented and conversing, 4 for disoriented and confused, 3 for speaking inappropriate words, 2 for incomprehensible words, and 1 for no answer The index of severity of heatstroke was calculated using the simplified acute physiology (SAP) score,(17) ie, scores of 5 to 6 13 to 14 and [greater than or equal to] 21 predict a 107 [+ or -] 41 percent 300 [+ or -] 55 percent and 811 [+ or -] 54 percent mortality rate, respectively, for an ICU population. The patients were rather colded as reported previously,[6,18] based forward the principle of dissipation of heat from evaporation. The cooling time was calculated as the time from the patient's arrival in the cooling unit until the first measured temperature of 394 ]degrees] C

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