Steroids And Heat Stroke: A Dangerous Combination?

Heat stroke is a severe form of heat illness with significant morbidity and mortality, including long-term multiorgan dysfunction and susceptibility to further heat illness. Certain drugs, both prescription and over the counter, can interfere with thermoregulation, which is the body’s natural ability to control its internal temperature. This can increase the risk of heat stroke. Corticosteroids, a class of medication that includes steroids, are known to reduce lipopolysaccharide (LPS) and cytokine levels, which are elevated during heat stroke. This suggests that steroids may improve outcomes for those experiencing heat stroke. However, further research is needed to determine the optimal dose and duration of treatment for steroids in this context.

Corticosteroids reduce cytokine levels

Corticosteroids are a class of medication that can reduce cytokine levels in the body. Cytokines are small proteins that are crucial for cell signalling and regulating immune and inflammatory responses. During a heatwave, the body experiences a systemic pro-inflammatory response, which is characterised by elevated levels of cytokines and endotoxemia from elevated lipopolysaccharide (LPS) levels.

Glucocorticoids, a type of corticosteroid, inhibit the expression and action of most cytokines. This is part of the in vivo feedback system between inflammation-derived cytokines and corticosteroids produced by the CNS-adrenal axis. By binding to and inactivating key pro-inflammatory transcription factors, glucocorticoids can reduce cytokine levels and prevent several aspects of inflammation, including the activation and recruitment of inflammatory cells.

In the context of heat stress and heatstroke, corticosteroids have been found to reduce LPS and cytokine levels, suggesting a potential benefit in improving outcomes. Animal studies have shown that the administration of corticosteroids before or at the onset of heat stress improved mortality and reduced organ dysfunction. Corticosteroids were found to prevent a detectable increase in serum LPS and improve the heatstroke-activated inflammatory response by reducing complement proteins and increasing anti-inflammatory cytokines.

However, it is important to note that the relevance of these findings to humans in clinical practice is uncertain. While animal models used in studies, such as rats and primates, exhibit similar inflammatory, metabolic, and cardiovascular features to humans during heat stress, there may still be interspecies variations in the stress response and pharmacodynamics of corticosteroids.

Furthermore, the optimal dose and duration of corticosteroid treatment for heat-related conditions are yet to be determined. While some studies suggest a dose-dependent improvement in outcomes, the specific glucocorticoid, dosage, and timing of administration may vary depending on the individual and the nature of heat stress or heatstroke.

In summary, corticosteroids, particularly glucocorticoids, have been shown to reduce cytokine levels and play a crucial role in modulating the inflammatory response. While animal studies indicate potential benefits in reducing morbidity and mortality from heatstroke, further clinical research is needed to establish the effectiveness and optimal use of corticosteroids in humans.

Steroids improve mortality and organ dysfunction

Heat-related illnesses such as heat exhaustion and heat stroke are dangerous conditions that can be life-threatening. While our bodies have a natural ability to control internal temperature through thermoregulation, certain drugs can interfere with this process, increasing the risk of heat-related illnesses.

The Role of Steroids

Steroids, including prescription and over-the-counter medications, can alter the body's natural responses to heat and sun exposure. Psychiatric medications can interfere with communication between the brain and body, disrupting the body's ability to regulate temperature and thirst. Additionally, antibiotics and topical acne medications can increase sun sensitivity, making individuals more susceptible to sunburn.

Impact on Mortality and Organ Dysfunction

Systemic steroids, when administered before or at the onset of heat stress, have been found to improve mortality and reduce organ dysfunction in animal studies. This is particularly evident in cases of severe hyperthermia, where a systemic pro-inflammatory response occurs, characterized by elevated cytokines and endotoxemia from elevated lipopolysaccharide (LPS) levels. Corticosteroids play a crucial role in reducing LPS and cytokine levels, thereby improving outcomes.

In a review of five studies, steroids improved survival time and reduced organ dysfunction due to heat stress in 80% of the studies. Notably, higher doses of steroids extended survival time, and administration before the onset of heat stress yielded greater survival rates. However, one study on primates showed a worsening in survival and organ dysfunction markers, contrary to the other studies.

While steroids show promise in improving mortality and organ dysfunction associated with heat stress, further studies are needed to determine their effectiveness in humans. The optimal dose and duration of treatment remain to be determined, and the relevance of animal studies to human clinical practice requires further investigation.

Practical Considerations

It is important to be cautious when taking medications that may increase the risk of heat-related illnesses. Regularly reviewing prescriptions, staying hydrated, and taking frequent breaks in the shade or in air-conditioned spaces are essential during hot weather. Additionally, consulting a doctor before engaging in outdoor activities and adjusting medication doses or exploring alternative treatments may be necessary to enjoy the summer safely.

Steroids improve survival time

Steroids have been found to improve survival time in patients with severe cases of COVID-19. In a study led by Professor Anthony Gordon from Imperial College London, patients receiving intensive care who were treated with a regular fixed dose of the steroid hydrocortisone for seven days had a better chance of recovery compared to those who did not receive the steroid. This research is one of three studies that suggest steroids improve survival of the sickest COVID-19 patients. As a result, the World Health Organization will be issuing new guidelines to include the use of steroids to treat critically ill COVID-19 patients.

Steroids are anti-inflammatory drugs that reduce lung inflammation in patients with COVID-19 who are seriously ill and require oxygen support for their breathing difficulties. In the hydrocortisone study, the trial showed that using a fixed dose of hydrocortisone led to a 93% chance of a better outcome (greater chance of survival and less need for organ support) than not using hydrocortisone.

In addition to COVID-19, steroids have also been found to improve survival time in cases of extreme hyperthermia and heatstroke. A systematic review of published research evidence found that steroids administered before or at the onset of heat stress improved mortality or reduced organ dysfunction. Survival time was greatest when steroid administration preceded heat stress. A dose response was also observed, with higher doses extending survival time. Animal studies also suggest that steroids improve mortality and/or organ dysfunction after an episode of heat stress or extreme hyperthermia.

Steroids reduce endotoxin levels

Steroids can reduce endotoxin levels, which is significant in the context of heat stroke as endotoxemia is associated with heat stress.

Endotoxemia is the presence of endotoxins in the blood, which are toxic components of bacterial cell walls. Endotoxemia is associated with a pro-inflammatory response, which can be triggered by trauma and toxic insults, such as heat stress. Endotoxemia initiates the release of pro-inflammatory cytokines, which are reduced by corticosteroids.

In a study of 20 patients undergoing cardiopulmonary bypass, it was found that steroid pretreatment may reduce endotoxin release. The study found that endotoxin levels in the inferior vena cava blood were significantly lower in steroid-pretreated patients than in those not receiving steroids.

In another study, it was found that estrogen reduced endotoxin levels by the estrogen beta receptor. Rats were randomly assigned into 10 groups, with one group receiving estrogen and another receiving a combination of estrogen and progesterone. The study found that DPN, an estrogen receptor beta agonist, caused a significant reduction in serum levels of endotoxin compared to the group that did not receive estrogen.

In a systematic review, it was found that corticosteroids reduce lipopolysaccharide (LPS) and cytokine levels, suggesting that they may improve outcomes in cases of extreme hyperthermia and heat stroke. LPS is a large molecule that forms part of the outer membrane of gram-negative bacteria and contains a hydrophobic domain known as endotoxin. Animal studies included in the review suggest that steroids improve mortality and/or organ dysfunction after an episode of heat stress or extreme hyperthermia.

Steroids are more effective before heat stress

Heat stress is associated with a profound pro-inflammatory response. Corticosteroids reduce lipopolysaccharide (LPS) and cytokine levels, which are elevated during heatstroke. This suggests that steroids may improve outcomes.

A systematic review of five studies found that systemic steroids administered before or at the onset of heat stress improved mortality and reduced organ dysfunction. Survival time was greatest when steroid administration preceded heat stress. Animal studies suggest that steroids improve mortality and/or organ dysfunction after heat stress or extreme hyperthermia.

The administration of steroids before the onset of heat stress improved survival time compared to administration after the onset. Higher doses of steroids also extended survival time.

However, the relevance of these findings to humans in clinical practice is uncertain. Further studies are needed to examine dose responses to corticosteroid administration in humans, particularly when delivery occurs after the onset of heat stress.

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