So, heat stroke can affect practically every organ system in the body, so the physiologic abnormalities that occur can be quite vast. The number and the severity of these signs and symptoms are largely related to what I call the temperature area under the curve, so the maximum temperature and then the duration of hyperthermia. So it's important that we recognize heat stroke symptoms early and we implement rapid cooling, rapid and aggressive cooling so we can lower that temperature AUC and improve outcomes. Now the critical care management of heat stroke is largely centered around supportive care, so it's important to understand the pathophysiology and the complications that may ensue. Under normal circumstances, the heat that's generated through normal metabolism or gained through the environment is dissipated through thermoregulatory mechanisms to maintain a quote-unquote normal body temperature. Now when these regulatory mechanisms become overwhelmed, and this can be either because of inability to disperse heat or because of excessive heat gains through high temperatures or exercise, what happens? Body temperature increases and as a result, we see damage to proteins, membrane lipids, DNA. There's an increase in pro-inflammatory cytokines, activation of the coagulation cascade, inhibition of fibrinolysis. At the organ system level, we have devastating neurologic injury, and I'm going to talk more about this in a minute, but from a cardiovascular standpoint, we see a picture of distributive shock as the body shunts blood to the skin and the muscles as an attempt to disperse heat. Splanchnic flow decreases, which leads to an increase in intestinal permeability and bacterial translocation, and endotoxinemia, and this is an important part of the overall pathophysiology. Coagulopathy occurs, and this can range anywhere from consumptive coagulopathy to microvascular thrombosis to extreme cases, DIC, and this is a very poor prognostic indicator. Rhabdomyolysis is common, and then again, don't forget about pavement injury. Asphalt can reach temperatures that exceeds 160 degrees, so these pavement burns can be quite severe, and this is common here in Arizona, particularly in the summertime when patients are found down or after trauma when they're lying in the road or off in the desert. So the neurologic damage that occurs with heat stroke is one of the more troublesome signs and symptoms to deal with. About 30% of patients will have some form of neurologic sequela, and this can last anywhere from days to weeks to months after their hospital discharge. Now brain injury appears to be concentrated in the cerebellum, and the mechanism of neurologic damage I like to think of in three different categories. There's direct cellular injury, there's local effects within the brain, and then systemic alterations that occur. So cell death begins to occur when temperature exceeds 40 degrees, and then cell death will increase exponentially as temperature increases from that point. Locally we see an increase in pro-inflammatory cytokines, disruption of the blood-brain barrier, and this is thought to be a major mechanism behind cerebral edema that occurs, so increase in intracranial pressure, decrease in cerebral blood flow. Seizures are common, and petechial hemorrhage is something that's noted in most autopsy findings. Systemically, we have breakdown of GI integrity, gut bacterial translocation, and endotoxinemia. Now if you think about the disruption in the blood-brain barrier that occurs, now these endotoxins have open access to the brain, and this further contributes to the neurologic damage. Now as far as treatment, I wish I had more I could offer in terms of clinical pearls, but by far the most important thing is rapid cooling. With rapid cooling, a lot of these adverse sequelae are mitigated. It's important to assess for cerebral edema and intracranial hypertension and treat that accordingly. Seizures should be treated with benzodiazepines, but there's no data supporting the routine administration of seizure prophylaxis, nor is there data supporting the routine administration of anti-inflammatory medications like steroids or other immune-modulating medications. It may seem intuitive to administer prophylactic antibiotics because of the bacterial translocation, but there's no data supporting the role of prophylactic antibiotics either. Now volume status is important, and I'm not going to rehash some of the latest studies with resuscitation strategies, but there's a couple important points when it comes to heat stroke. This is a study that evaluated CVP in heat stroke patients that was obtained during pilgrimage in Saudi Arabia. And if you see the top figure, about half of these patients had initial CVP values that were greater than 4. About a quarter were greater than 8. Recognizing the limitations of CVP, if we look at the bottom part of the figure, I think this is more important. This is the volume that was administered to these patients, and most patients received under 2 liters of fluid. So not everybody requires massive amounts of fluid. This is a study that performed right heart catheterization in 10 patients with heat stroke. And you can see the variability in right atrial pressures. Most patients presented with hyperdynamic shock. Only one patient had a low cardiac index. But one caveat to all of this is that another complicating factor of heat stroke is rhabdomyolysis. So in those patients that have signs and symptoms of rhabdo, yes, they do require aggressive resuscitation. But I think, collectively, this data emphasizes the importance of individualizing your resuscitation efforts using dynamic markers as endpoints for resuscitation. And obviously, patients who have rhabdo will need more aggressive fluid therapy. Now, antipyretic medications are widely used to treat hyperthermia in the ICU, but they are not recommended for treatment of heat stroke. And this is because the mechanism or the pathophysiology of heat stroke is very, very different than the pathophysiology encountered with hyperthermia related to fever or infection. And further, if we think about some of the adverse effects of these medications, namely the hepatotoxicity of acetaminophen, the risk for AKI with NSAIDs, clearly, they can cause harm. Now, one medication that's widely used for the treatment of malignant hyperthermia is dantrolene. And there is some credence to its use for heat stroke, looking at the mechanism. But when we look at the data, there's only two small randomized controlled trials. And you can see that dantrolene had minimal effect on cooling time. So its use is not recommended. So in this slide, you see a summary or an overview of ICU management. Obviously, I don't have time to go over all of these points, and this is in our paper. But just to highlight a couple of things, we talked about the neurologic injury, hemodynamic or adverse cardiovascular effects, respiratory failure due to aspiration, pneumonitis or ARDS can occur. Acute kidney injury happens in about 30% of patients. Liver failure can occur, especially when body temperature exceeds 41 degrees. Coagulation abnormalities are common, with DIC being an important prognostic indicator or an indicator for poor prognosis. There are some animal studies with agents like activated protein C, antithrombin 3. But these, again, are only in animal studies. And obviously, we need data in humans before these can be recommended. And then don't forget about skin breakdown. And this can be due either to pavement injury or frostbite that's obtained from our cooling efforts. So here's a list of some of the prognostic indicators. By far, the most important is cooling rate. In fact, when we reach our goal temperature of less than 40 within 30 minutes, mortality is significantly reduced. Maximum temperature, obviously, is important, going back to that temperature AUC. There's a scoring system called the Jay-Arado score. And this is listed here. And then pavement burns and organ failure, obviously, are indicators for poor prognosis. So when we were writing this paper, we realized that there were a lot of unanswered questions. So for example, what's the best cooling method to use in classic heat stroke? When you go back and look at the data, most of it is, or almost all of it, is with exertional heat stroke. And these studies are conducted in controlled environments with healthy volunteers, usually athletes. We really don't have any data for classic heat stroke. What's the best water temperature to use for immersion therapy? When should we stop? With regards to ICU management, what's the role of medications like immunomodulators or anticoagulants or prophylactic antibiotics? So these are questions that we hope are addressed in the upcoming years. So what are a few practical points that you can leave with, or what I like to call the four most important things I want you to remember when you leave the room? Number one, remember that heat stroke occurs on a continuum. So some patients may present for other reasons, but also have signs and symptoms of heat stroke. So rapid identification is important. Rapid cooling is essential. This is by far the most important point I want you to remember. Remember the pathophysiology, because our ICU management is largely going to surround supportive care. So our management is going to be centered around identification and treatment of cerebral edema, distributive shock, appropriate fluid administration, the things that we do every day as ICU clinicians. So with that, I thank you, and we'd like to thank the program committee for allowing us to present our paper. Thank you.

heat stroke

rapid cooling

organ failure

neurologic damage

treatment methods