Welcome. My name is Dr. Beth Haas and I'm here with Dr. Jacob Lee. I am the medical director of psychiatry at Carson Tahoe Hospital in Reno, in Carson City, Nevada. Jacob is a child fellow at the University of Hawaii. We are both members of the EPA Committee on Climate Change and Mental Health. We are going to talk to you about heat waves for the practicing psychiatrists, what you need to know to protect your patients in psychiatry and community. We were hoping to talk a little bit about wildfires also, but we really feel that we have too much material on heat. Neither one of us has any disclosures. So our learning objectives for this are going to be to review the thermoregulatory system and our capacity for and limits in acclimatization to higher temperatures, to review the signs and symptoms of heat illness, and understand how psychiatric meds and psychiatric illnesses themselves impact the body's temperature response, and to know how to protect our patients with mental illnesses from the dangers of extreme heat. So we're going to start off talking a little bit about what heat has been like recently, and Jacob is going to take over for this section. Excellent. I want to start us off with a slide showing data from the National Oceanic and Atmospheric Administration. This shows us how surface temperatures have changed in the last 140 years. So we're looking at the time period from 1880 to 2020. For each of the last four decades, starting in 1980, we've seen successively warmer temperatures than any preceding decade since 1850. In 2020, global average surface temperature was 1.76 degrees Fahrenheit above the 20th century average or baseline temperature, making it the second hottest year in history. 2022 isn't over, but it's a close rival so far. Here more from NOAA showing average surface temperatures across the USA in June of this year, 2.2 degrees warmer than the seasonal average. If we turn our attention to the South, we see 9 degrees hotter and 25% drier. Looking at Europe three weeks ago, temperatures in mid-July were above 86% for most of Europe, and turning our attention to southern Spain, we see temperatures over 104 degrees. This slide shows temperatures in June in the United States. Everything in dark gray is over 90, light gray over 100, maroon over 110. In Arizona, Southern California, and Southern Nevada, temperatures in June were often over 100 and at times reached over 115 degrees. Temperatures like that are non-physiologic, meaning without water to evaporate off heat or air conditioning, almost all people would die as the organs of unacclimatized people generally begin to fail over 104 degrees Fahrenheit. In 2021, four areas of the world saw temperatures of 122 degrees, Iran, Oman, Kuwait, and United Arab Emirates. These harsh conditions were particularly dangerous as they were often faced with air conditioning. This year, Iran and Pakistan have been over 126 degrees Fahrenheit and others have matched their own record highs. All of this leads those people who do not have AC, 95% of those in India, 92% of those in Pakistan, to try and cope with life-threatening high day and high night temperatures through water-based cooling and shade alone. There's only so much cooling can do, which leads to the kind of ongoing risk of mass heat deaths that we saw in Pakistan, which saw 2,000 people die in 2015 and again suffered significant heat deaths in 2018. As many likely remember, we also saw death during Texas' heat wave earlier this year. This might be a good time to point out that even air conditioners can fail over 100 degrees for several reasons. The system requires the air temperature outside to be lower than the hot air released by the unit in order to keep functioning because the refrigerator's exchange between gas and liquid and the tubing inside and outside the house is how they provide cooling. The compressor in the AC also has to work harder at high temperatures and can also fail. What's most noticeable in all this is the tremendous injustice of adverse heat effects, with poor nations and disadvantaged populations at vastly greater risk of heat-related illness and death. Even here in the United States, where air conditioning is easily available and some 90% of people have ACs, the impact of heat is far greater for minority groups, people who are more economically vulnerable, more likely to live in red-lined and urban areas where heat islands raise local temperatures. We see homeless populations and outdoor workers especially exposed to unbuffered high temperatures. Economically vulnerable families often have limited access to the air conditioning that can save lives. And we see the urban heat islands much more likely to impact Black, Indigenous, and people of color. The likelihood of residing in areas with elevated heat-related risks has been shown to be over 20% higher for Hispanics, over 30% higher for Asians, and over 50% higher for African Americans. In a study of over 100 cities by Hoffman et al., those living in a red-lined versus non-red-lined area faced average land surface temperatures over 4.5 degrees higher on average, and temperatures were nearly 13 degrees higher in select cities. Heat-related emergency room visits have been shown to be up almost 90% higher for those red-lined districts. From 1991 to 2006, agricultural workers died of heat-related illness at a rate 20 times higher than other professions. And we also know this is happening in a context where 25% of low-income households are unable to pay their energy bill each year in the state. Millions of Americans are affected. Fortunately, we now have an administration which gives us a great deal of support for heat impacts through national information systems that include the National Oceanic and Atmospheric Administration, we talked about earlier, as well as the National Weather Service and the NIH HIS. You might be asking, what is the NIH HIS? It's the National Integrative Heat Health Information System, a collaboration between CDC, NOAA, the EPA, FEMA, OSHA, Health and Human Services, the Forest and Park Service, the VA, SAMHSA, and other governmental agencies. Their website, heat.gov, provides a great deal of data about the current heat conditions, as well as webinars, programs, and other materials for heat safety. The NIH HIS also links you to the CDC Climate and Health Program, where you can track heat-related data, as shown here, the number of ER visits for heat-related complaints per capita, sorted by day, week, or month. You can also see associated temperatures and other information, allowing us to intelligently prepare our systems for heat risks. The picture on your screen shows July 26th, when ER visits reached the high 500s for heat-related problems in Texas. Among the resources the NIH HIS provides is a page for healthcare professionals that prominently includes the Coping with Heat resource sheets, prepared by a frequent collaborator of Dr. Haas and I, Dr. Robin Cooper of the Climate Psychiatry Alliance. So, congrats to Dr. Cooper for reaching national acclaim. This is what Dr. Cooper's tip sheet for Caring for the Mentally Ill and Other Vulnerable Populations in Extreme Heat looks like. It can be printed for office use, and we'll talk more about these and other heat interventions later. Thanks, Jacob. We're going to turn our attention now to talking about heat physiology for psychiatrists, the basics of the thermoregulatory system. This is going to be a little bit of a dry review, so you might want to pick up an espresso and a glass of wine, but I think we owe it to ourselves to understand something about this system as it is governed by neurotransmitters, and it dictates our ability to survive extreme heat so that we can be a clear voice in this climate crisis. The thermoregulatory system is really complex and very tightly regulated. It's also one of our most important. We use about 75 percent of our energy to maintain temperature, so it's an important physiological task. It's made up of two compartments. There's an external shell, which is highly sensitive to the environment, and an internal core, which is relatively stable. Human core temperature is more narrowly regulated than most functions, ranging only about half a degree centigrade in terms of menstrual cycles and so forth, and a degree or plus or minus centigrade overnight. When temperature in the core shifts by 0.2 degrees Celsius, the body makes a shift as far as from basal dilatation even to shivering in order to adjust the entire body to stabilize that core. Core temperature is called TC, essentially used synonymously with TB, the temperature of the body, although officially TB includes also the temperature of the skin. Our core temperature is set at the most optimal temperature to be able to raise or lower a degree of water thermodynamically with the least use of energy, and this may be why it's evolved in that way. Thermoregulation is also notable for the properties of being asymmetric and extremely flexible. By asymmetry, we mean that the core is tightly regulated, whereas the external shell is not. Thermoregulatory asymmetry also gives us the flexibility in our temperature that we need for large swings in response to large swings in external temperature. How flexible exactly is this thermoregulatory response? For core temperature, the lowest temperature from which a human being has recovered is 56.7 degrees Fahrenheit, and survival has been documented extending up to 114 degrees in the body core. On the surface, skin temperatures can vary 77 degrees Fahrenheit. Frostbite occurs if you have skin contact with temperatures at freezing, and burns occur at temperatures of over 109.5, but the first two or three centimeters of your body tissue, up to 54 percent of your body mass, varies by 36 degrees frequently all over the course of the day, and exercising skeletal muscle can vary by 18 degrees Fahrenheit from the rest of the body for hours. Bazit, writing in 1949, said that the idea of body temperature is stable is one of the major fallacies that held up thermoregulatory work for decades. Also notable in our thermoregulatory apparatus is our vulnerability to heat. Next slide. Particularly for this talk, it's important to remember that humans run hot. They run hotter than their environment, at least until recently. Evolutionarily, we might want to ask why this is so. It turns out that the emergence of a body temperature hotter than our environment emerged with the proliferation of birds and mammals around the globe. Evolutionary biology suggests that higher temperatures gave us mammals and us birds a survival advantage by allowing enough energy for us to take flight and to survive in cold and nighttime temperatures, temperatures to which we're also poorly adapted. But this evolutionary advantage also leaves us more vulnerable to heat stress than to cold. Our usual temperature of 98.6 is set only 9 degrees Fahrenheit from our heat tolerance limit, but 18 degrees Fahrenheit from our cold tolerance limit. Most cell types and cell enzymes don't do well with high temperatures, including pathogens. That's the reason we raise our body temperatures in order to get rid of bacteria. DVR helps us eliminate them. It's also a reason that the higher temperatures we're facing now cause damage to our cells by impairing enzymatic reactions and denaturing proteins. And here's an interesting aside. Bad body temperature in contrast is regularly around 105 degrees. That means that viruses that survive at the high temperatures we're seeing now have a greater odds of surviving the jump. It also means that we're more vulnerable to those viruses because we can't eliminate them with our fever response. Arturo Casadevall, a professor of microbiology and immunology at Johns Hopkins, has said, every time we have an extreme heat day, we have a selection event, and we can expect heat waves from climate change to generate more zoonotic illnesses that our bodies have a lesser chance of defending against. Next slide. So what does this heat system look like? It's comprised of central systems, a central coordinator of temperature in the preoptic area and the periventricular nucleus of the hypothalamus, where efferent fibers transmit messages that regulate unconsciously much more of your behavior than you may actually be aware of, and continually adjust the vascular system and the metabolic pathways in response to the external environment. And it's comprised of sensory receptors in the deep viscera and in the skin, which send their heat messages to integrative neurons in the spinal cord, which relay these messages up to the central systems via the lateral paraspinobrachial tract. Each element of this system is responsible for about 20 percent of thermoregulatory adjustment. As the external shell signals the brain about surface temperature, the body initiates compensatory mechanisms. These are feedback mechanisms, but they're also feedforward mechanisms. Skin receptors help the body make anticipatory change, such as shivering and vasodilatation, to keep the core temperature from being destabilized much at all. The major ways we respond to cold temperatures are shivering, brown fat thermogenesis, and exercise. Shivering is the most common autonomic response to cold and can double metabolic rate. It pales in comparison to the effectiveness of exercise, however, which can raise heat production by tenfold. The serotonin 3 receptor seems to be very important for shivering. Agonists released from the perioptic area of the hypothalamus can raise body temperature by causing shivering in combination with vasodilatation to get this warmer blood from the muscles out to the periphery. In a meta-analysis of 14 randomized controlled trials, Zofran or Andancetron, a serotonin 3 antagonist can reverse post-operative shivering, which can be quite dangerous in that setting. We also raise temperature from fat thermogenesis. Brown fat is packed with mitochondria and creates heat directly without shivering. It's activated when your ATP drops and noradrenaline is released from sympathetic nerve fibers. Beta-3 adrenergic agonists, catechins, capsinoids, and some nutritional products in brown fat tissue can activate this process. The sympathetic stimulation acts on a protein called UCP1, an uncoupling protein, which releases fatty acids and glucose from the brown fat. These are passed down through these mitochondrial-rich cells and broken into ATP on mitochondrial membranes. Body heat is also preserved by a vasoconstriction, which can drop local heat an amazing 10-fold. This is often looked at by looking at the gradient from the forearm to the fingertip, and 7-degree drops signal vasoconstriction. Vasoconstriction is mediated by central alpha-1 and peripheral alpha-2 receptors. Finally, heat is preserved by interpersonal behaviors, cuddling with other people and animals, and nest building in animals, which kicks in automatically once you hit a particular set point. How do we lower our body temperature? How do we deal with heat rather than cold? The major mechanisms we have for releasing heat, as we do during heat waves, are vasodilatation and sweating, which lead to convective, conductive, and radiant heat loss. Human and animals also automatically reduce activity as body temperature rises. It's an automatic behavior and will, on reflex, seek shade, expose themselves, fan themselves, expose their bellies or genitals, or other vascularly rich areas. In the periphery, heat is released through AV shunts, which are physiologically distinct from capillaries. These shunts are dramatically important for releasing heat. They can dilate by 100-fold, whereas vasoconstriction can only reduce flow by 10-fold. These AV shunts are receptive only to local catechols and, interestingly, not to circulating catechols. This next point is very important. Overall, blood vessels involved in heat release are tonically shut down by the sympathetic system, except during heat stress, and require GABAergic signals to dilate. While I would love to be able to tell you exactly how this works, it is, at this point, somewhat speculative. Overall, obviously, there must be compensations in cardiac output and central versus peripheral regional blood flow to dilate an AV shunt around the body by a factor of 100. Stroke volume increases. To preserve blood flow to this dilated periphery, splanchnic and brain vessels both contract. It's an energy-intensive process which increases respiratory and heart rate, and can lead to the exhaustion of heat exhaustion. When the blood returning fails to keep up with the significant increase in cardiac output of those 100-fold dilated AV shunts, you are at risk of cardiovascular collapse. Our other major mechanism of getting rid of heat is sweating via M1 postganglionic cholinergic neurons, which act on epinephrine sweat glands. These are dependent also on adrenergic input and an intriguing example of the parasympathetic and sympathetic systems working together. A liter of sweat represents the absorption of 584 calories of heat energy. This is one of the major ways that we acclimatize. As we acclimatize and as we get more athletic, we're able to release many more liters of sweat. What we have is a complex system of both involuntary and voluntary behaviors with multiple organ and vascular responses that are sensitive to an incredible range of external temperatures, so far mediated by GABAergic, cholinergic, and sympathetic inputs. Sounds like neurotransmitters and what we do with them could be important for heat illness. Next slide. This is my dog, Berkeley. He is demonstrating masking response. Give us a little two-second break. How did you achieve this elegance of response? It turns out to be through a family of transient receptor potential channels known as thermal TRPVs. The mammalian TRPV superfamily consists of 30 channels divided into six subfamilies. The V and the M families in one of the TRPA family receptors are important for thermoregulation. Generally speaking, cold receptors are close to the surface and thermal receptors are a bit deeper. And TRPV1 through 4 are considered the most important for the heat response. As shown here, though, really I think showing the extreme elegance of evolution, each of these receptors is active within a very narrow temperature range. But cumulatively, the range they cover is very broad from 0 to 50 degrees Celsius, giving an iterative system of overlapping nuanced responses so that these microcircuits can change how your body adjusts to the temperature in a sophisticated, precision oriented, fine-tuning kind of way. Next slide. So here's a summary of the system, a very complex slide. TRPVs sense the outside temperature and send the signal up. Heat-sensitive pathways are on the left. Sensory information about temperature is supplied via sensory neurons type A and C, relayed upward via primarily glutaminergic spheropinogravial pathways, which respond tonically with vasoconstriction, with vasodilatation, when GABAergic neurons take the brakes off, this more tonic sympathetic tone. Next slide. In the central area, we have two important areas, the preoptic area of the hypothalamus, which is really the central command of the brain in terms of heat regulation, and the periventricular nucleus, which may be responsible for heat conservation. Serotonergic neurons from the nearby dorsal raphe nucleus may communicate to these two nuclei. The ascending parabrachial information that is coming from those tracks. The POA is endowed with special sensory neurons that compare actual with target temperature values. Mismatch leads to behavioral change. The POA also has a population of specifically warm temperature sensitive neurons, which are critical in responding to hyperthermia. These are very complex and interesting neurons, which are under active study, but are sensitive to GABA, estrogen, glutamate, and BDNF, among other neurotransmitters that are active in their function. Outgoing tracks from the POA can be in changing aspects of the heat response. For example, coordinating with cardiac sympathetic neurons in the midbrain to increase heart rate, affecting midbrain structures that control thirst to increase fluid intake, affecting blood pressure through the renin system and sleep through orexin. There is literally no hormone known that does not have some thermoregulatory function. We're most familiar with hormones like FSH and LH with menstrual changes and hot flashes, and with thyroid hormone, but all hormones are involved. And it may be that 5-HT2A receptors mediate hypothermia. Next slide. There you have it. Human thermoregulation is the very complex system that involves voluntary and involuntary behaviors, sympathetic and parasympathetic systems, localized and centrally mediated responses. All right, so that's our basic science review. We're now going to start thinking about how psychiatric patients are different when it comes to their heat response. In this section, we'll cover temperature variations in patients with mental illness, the ways that external temperature changes, the seasonal epidemiology of psychiatric illnesses and symptoms, and the risks of violence, suicide, and negative affect associated with uncomfortable and extreme heat. And Jacob will pick it up from here. So once again, just to start with a summary of what we are and what we've already talked about and what we know, we've established that there's numerous thermoregulatory systems and that largely they're mediated by neurotransmitters, the kinds that we think of as being impacted by psychiatric medications. We can think of noradrenaline and adrenaline playing major roles in all aspects of preserving body heat. Of serotonin 3 receptors involved in increasing body heat, the possible role for serotonin 2A in decreasing body heat. We also have acetylcholine, critical for the release of heat through sweat, and gabonergic mechanisms, critical for vasodilation, for coordinating the heat and thirst responses. An understanding of these relationships between heat waves, psychiatric medications, and mental illness will need to reflect the diversity of neurotransmitters involved in this list. Some early research is demonstrating that our patients have abnormal thermoregulatory indicators. People with depression, bipolar disorder, panic disorder, and prior suicide attempts have all been found to have abnormalities in electrodermal activity, including sympathetic tones, sweating, and emotional effects associated with abnormal skin conductance. Depressed patients also have increased body temperature, while body temperature in patients with schizophrenia is slightly decreased, and they also have less ability to raise skin temperature in the heat. The study also suggests the population could have greater heat preservation in the cold, which might be protective in some cases. We're also very familiar with a number of hyperthermic syndromes that are linked to neurotransmitter function. These are the ones you might remember from boards and other topics. These include neuroleptic malignant syndrome, malignant hyperthermia, serotonin syndrome, anticholinergic poisoning, and sympathetic toxicity, the kind you see with methamphetamine or cocaine. All of these cause life-threatening elevations in temperature. Understanding these illnesses should potentially be able to tell us something about why the heat response in psychiatric patients and those with neurotransmitter functions manipulated by our medicines could be impaired. If we try and think about this mechanistically, we'll quickly run into the limits of our knowledge, but let's start with what we know, and then we can theorize a bit together. Malignant hyperthermia is a disease associated with the RYR1 ranodine receptor. It's an abnormality in 50% of families. We also see a CACNA1S and STACs gene mutations. Symptomatically, skeletal mycoplasma experience an influx of calcium that leads to muscle rigidity, producing heat, lowering oxygen, increasing carbon dioxide, depleting cellular energy and ATP, and sometimes leading to cell membrane failure, seizures, and death. The treatment is weight-based dosing of dantrolene. You might need to keep this in mind because malignant hyperthermia is not only triggered by sesenylcholine, isoflurane, and the other anesthetics, but may also, in some cases, be triggered by high temperatures and emotional stress. Sesenylcholine, the classic causative agent, it's a nicotinic agonist, but one so potent, it triggers desensitization. So functionally, this allows the drug to act as an anticholinergic for muscles while also producing excessive sweating. It's not clear where all the temperature increase comes from, but some portion of it seems to come from muscular work. Malignant hyperthermia may also involve excess sympathetic activity generated by the overactivated muscle in both the heat-induced and the genetic case. Neuroleptic malignant syndrome is a disorder where, in theory, central D2 blockade by antipsychotics leads to lower central dopamine, but it can also be associated, rarely, with a sudden withdrawal of D2 blockade. It has similar symptoms of fever production, rigidity, and sweating, as do serotonin syndrome, a disorder of serotonin excess, cocaine and methamphetamine intoxication, which is a disorder of dopamine excess, and malignant catatonia, a disorder we treat by improving GABA stores with benzodiazepines. So if the same symptom of overheating is produced by low dopamine, high dopamine, low GABA, high serotonin, and cholinergic blockade, clearly there is more to know. We could, however, hypothesize that all of these relationships reflect aberrant signaling regarding the balance of heat dissipation through GABA in that same preoptic area and heat retention through that periventricular nucleus. If GABA drives our dissipation of heat, it would make sense that malignant catatonia, cured by benzodiazepines, could resolve this through increased GABA tone. If dopamine and epinephrine drive the periventricular nucleus to conserve heat, it would make sense that dopamine depletion from neuroleptics and dopamine excess from cocaine and methamphetamine would respectively lower and increase core temperatures. If serotonin modulates the periventricular nucleus, which raises heat, it might make sense for high serotonin states to lead to the high temperatures that we observe. All this is speculative, but potentially interesting research that could open up new avenues for hyperthermia treatment. It's also been long observed that there are seasonal fluctuations in psychiatric illnesses. In the warmer months, both mania and post-traumatic stress disorder presentations increase, while depression, controlled for seasonal affective disorder, and bulimia both decrease. In a 2007 study by Kessler, rates of mental disorders in a country decreased as temperatures increased, although we only saw this between like 50 and 78 degrees. We also saw colder temperatures found to correlate with higher SSRI prescriptions. So as we can see, some psychiatric conditions become better in warm seasons, while some get worse. As temperatures warm, however, negative emotions have been documented to rise, as have the number of days rated as experiencing poor mental health and in ER visits for mental health reasons. Some have speculated this might be mediated in part by the temperature-dependent changes in sleep. Rates of suicide and violence in particular have been found and associated with increased temperatures outside of the range of human comfort, and you can see this by looking at the crossover points where suicide increases compared to the baseline. What we see is for about every degree Celsius, increase in temperatures over a comfortable 37 Celsius is associated with a 0.7 to 2.3% increase in population-wide suicides. As temperature goes up, so do the suicides. This heat-related increase in suicide is independent of and sometimes greater than the impact of economic stress. This association is found both in association with monthly average temperatures and falling heat waves, and it's the kind of thing that's projected to add nine to 50,000 suicides by 2050 under our business-as-usual climate emissions pathway. This graph, it's the work of James Alan Fox, a Lipman Family Professor of Criminology, Law, and Public Policy at Northwestern University. He correlated the number of violent crimes and temperature over the course of the year 2007, focusing on Columbus, Ohio. It's a helpful visual because it shows the correlation in such a practical way. We know this intuitively, right? We've got sayings like my blood boiled and they're hot-headed. Some part of us knows heat can bring about these changes. Going back to that every one Celsius increase in temperature, we see a 4% increase in interpersonal and intergroup violence. This can be seen in behavior in a wide range of circumstances. We see this everywhere from aggression on the baseball field to homicide and violence rates in domestic settings. In this 2016 meta-analysis led by Solomon Sung, every type of violence they looked at, interpersonal, sexual, civic, national, they all increased with higher or abnormally high temperatures. Projections indicate nine excess violent crimes per 100,000 people for each two degrees Fahrenheit temperature rise. One study suggested that by 2099, the United States of America will have seen 22,000 murders, 180,000 rapes, 1.2 million aggravated assaults, 2.3 million simple assaults and over 4 million other non-violent crimes in excess of what would be expected at current temperatures. We're looking at a total of 7.5 million extra violent events by 2099. We also find violence may be especially violent when excess rainfall or drought leads to greater economic stress and factors like unemployment. But the main risk from heat for patients, it's heat. So we're now gonna delve into the impact of heat on psychiatric morbidity and mortality and how psychiatric medications can increase heat-related risk. It's difficult to get a good feel for what the level of heat-related illnesses around the country and to make predictions about how it could increase with our climate crisis. Across the nations and even across areas of the United States, heat waves are defined differently. It's quite heterogeneous. When patients die of a heart attack or stroke, the most common heat-related deaths, heat doesn't always make it on the death certificate. In fact, it often won't. How impacted a person is by heat will also be highly variable depending on other factors like the area's humidity, their personal level of acclimatization, their substance use, and many other factors. Nevertheless, we know that patients with mental illness have very high rates of heat-related death. Starting in the 1970s, patients began to die during heat waves in the New York State Psychiatric Institute. Researcher Nigel Bark studied this, publishing a RR of 1.5 to 1.74 of death for psychiatric patients after the introduction of antipsychotics. So antipsychotics, increasing risk for death. Heat waves are defined as over 89 degrees. How we wish that was still our heat wave set point. Unfortunately, times have changed and the intensity and the highs record-breaking, sometimes record-smashing highs are higher than ever. Semeneza et al., writing in the New England Journal of Medicine in 1996, found that those with mental illness had three and a half times the odds of dying in the July heat wave in Chicago that year. And Hansen et al. found an elevated risk of hospitalization over 80 degrees Fahrenheit. It's elevated risk they found was 7%, but they also found an increased incident ratio of mortality of almost two and a half times overall for those with mental illness. When they zoomed in on men with early onset dementia, they found a 12.7% overall increase in mortality. In Bukama's classic meta-analysis, The Causes of Heat-Related Death, published in the archives in Internal Medicine in 2007, those with preexisting mental illness had a higher rate of death during heat waves. It surpassed even cardiopulmonary illness, similar to Semenza's findings of an odds ratio, something like 3.6. Page et al., looking at over 22,000 deaths in England, found a 5% increase in mortality for every one degree Celsius for those with mental illness compared with others. This is when temperatures were in the top 7% of normal, particularly in young people with alcohol use disorder, taking antipsychotics or anxiolytics. The general risk factors for death during heat waves include being bedridden, homebound, dependent on care, or those with cardiopulmonary disease. We also know financial hardship, as we mentioned, can limit access to air conditioning, which is a protective factor. And in general, we find more heat-related hardships in the mentally ill. These higher heat illness impacts demands our behavioral health system make changes to accommodate them. Shcherbakov et al. found that mental health admissions increased 4% with higher temperatures in California. ER visits in New York increased 16% in extreme temperatures. And according to you et al., Smets and Gamble, according to you et al., Smets and Gamble showed how heat affects fall disproportionately on male and minority populations with mental illness. Wang et al. found that even over 83 degrees Celsius, a lower threshold, if you lived in Toronto, you could expect to see 29% more patients in your ER, 30% more patients in your ER, and 15% of your patients required to go to the ER. These are huge numbers. It's likely that psychiatric drugs are among the most likely contributors to this heat-related morbidity and mortality. In a classic European study of inpatient psychiatric heat admissions by Martin, Larry et al. in 2007, those in psychiatric meds were much more likely than controls who were not admitted during the heat wave and took at least one other medicine as a control. These people were much more likely to be treated with anticholinergic drugs, antipsychotic, or anxiolytics. We can also orient ourselves to the heat impacts on psychiatric patients by thinking about the number of side effects of psychiatric medications that are related to the vascular system and sweating. I'm thinking like SSRIs, SNRIs, right? They're causing or impairing sweating and sometimes causing fever outright, especially things like tricyclics, which are gonna impact your cardiac output, your blood pressure, or stimulants, which are involved both suppressing the vasodilatability and suppressing the vasodilatory response during heat and vasoconstriction during the cold. You also think of things like our D2-blocking antipsychotics, which have long been associated with both hypothermia in older studies and hyperthermia in NMS, which is also treated with dopamine agonists like Dantrolene. There's numerous other ways that medications we prescribe may interact with thermoregulation and worsening heat outcomes. I don't want you to think of this as a comprehensive list, but I just wanna show kind of the wide catalog of medication-related effects. Lithium can both contribute to dehydration. It's also more likely to reach toxic levels if our patients are dehydrated in the heat. And dehydration is its own right, a risk for heat stroke. With dopamine agonists, like the kind we prescribe for restless leg syndrome or Parkinson's disease, we're gonna see vasoconstrictive effects, which might impede our heat release. Data blockers, which you might use for tremor or anxiety, could contribute to cardiovascular collapse. And other medications that more directly regulate the vasomotor tone, such as ACE inhibitors, might also impact the way blood flow is directed as we overheat. General anesthetics significantly impair thermoregulation, raising the tight control of core temperatures we discussed earlier, that interthreshold range, 20-fold, from 0.2 all the way to four degrees Celsius. This leads to intraoperative and postoperative hypothermia, as the body is blocked from its own adjustments to the OR temperature. We also know opioids, especially opioids like meparidine and propofol, these lower the temperature at which shivering begins. Some anesthetics like isoflurane and desflurane do this in unpredictable, nonlinear ways. And medicines that depend on renal clearance, many of our medicines are talking lithium, new anticoagulants, common diabetic medicines, gabapentin, pregabalin. There's many medicines in this category, and renal clearance being decreased during dehydration could be a real issue. Let's not also forget illegal drugs, particularly those that raise central nervous dopamine, drugs like cocaine, MDMA, and methamphetamine. But they're also associated with heat-related death. There's a great little study by Auger et al, it shows the relationship between temperature and the odds of death from a cocaine overdose. We're looking at the temperatures five days before the overdose event here. As you can see on the left, both colder temperatures and temperatures warmer than 68 degrees Fahrenheit increase your odds of dying, even if those temperature events were six days prior, especially if it's hotter the day of, or in like the two or three days before you take the cocaine. This speaks to the short-term thermoregulatory acclimatization influencing the danger of these drugs. And I'll pass back to Dr. Poss to talk about the assessment and treatment of heat illness. All right, so thank you, Jacob. So far, we have looked at how we heat and cool our bodies successfully, and how psychiatric patients in particular deal with heat. We're now gonna turn to defining heat illness and think about how we can promote our body's adaptation to high temperature through acclimatization. We're gonna talk about heat shock and heat exhaustion and how we can prevent them and treat them. Next slide. So let's start with some definitions of a heat exposure. A heat advisory is issued within 12 hours of onset if the maximum heat index temperature is gonna be over 100 for at least two days. A heat wave is defined when the daily maximum is in excess of 95, or if it's 90 degrees and it's been nine degrees or more above the maximum of the preceding day, so it shot up quickly. Excessive heat is defined as 105 degrees higher for at least two days, and nighttime temperatures that will not drop below 75 degrees. We also have words like heat watch and heat outlook, which we use for one to three and three to seven days if we're not exactly sure what's gonna happen. And we also give measures of the wet bulb temperature, which keeps under account humidity, wind speed, sun angle, and cloud cover in coming up with the total measure of the heat stress that people will face. Next slide. There are a number of heat illnesses recognized by the World Health Organization. So sunburn and heat cramps, prickly heat, and heat edema, which can actually be quite extreme, tropical anhydrosis, which is a failure of your heat system in high humidity environments, such that your sweat glands shut down, rhabdomyolysis, these are other heat illnesses, but the most common are heat exhaustion and heat stroke. How we respond to the heat vastly varies depending on how tolerant we are to it. Heat acclimatization can be achieved through either passive or active exposure to heat. For most people, we can tolerate a drop in core temperature of 10 degrees Celsius and a rise in core temperature of five degrees Celsius without acclimatization. An unacclimatized subject at rest in a hot human environment of 108 with 92% humidity will tend to have a rectal temperature of 101.3 Fahrenheit and will be near their heat limit for survival. But this graph here shows how much we can change our temperature tolerance with temperature on the X-axis and humidity on the Y-axis. If you look at the orange dot, which is my house in Nevada, even at 100 degrees and 9% humidity, we can be quite comfortable. But most people will live closer to the red dot, which is 65 degrees Fahrenheit and 50% humidity, and that will be their temperate zone. Next slide. With acclimatization though, you can achieve a number of changes. Over 130 genes will upregulate and 89 genes downregulate during the acclimatization process. In one study, 24 subjects could not walk at all in 120 degrees Fahrenheit heat, could walk for 100 minutes after only eight days of acclimatization training. Cyclists who are acclimatized to heat can go 43 kilometers at 98.6 degrees Fahrenheit outside, sustaining a core body temperature of 104 the entire way. So we're able to make huge jumps. What happens when we acclimatize? Seasonal and general adaptation to the heat includes reducing your core temperature by 0.3 degrees Fahrenheit, increasing your sweat rate, reducing your heart rate by three to eight beats, and reducing your sweat sodium. This can be quite dramatic, up to 60%. There are dramatic changes in sweat gland function with more sodium resorption, more dilated sweat glands, earlier onset of sweating at a lower temperature, and the decrease in sodium per liter of sweat may drop from 60 to 10 milliequivalents per liter. The body also acclimatizes by holding on to two to three more liters of fluid, and this plasma volume occurs by day four. Your thirst sensitivity increases so much that the rate of voluntary dehydration in people in a group decreases by 30%. Your blood and muscle lactate levels with exercise will also decrease with heat acclimatization, the reason that hot yoga works, and the heart slows but becomes more efficient. Additionally, heat shock proteins are protectively expressed to protect your proteins. Next slide. About 70 to 80% of heat acclimatization occurs in the first four to seven days. These show the things that are changing rapidly during that time, heart rate, plasma volume, exercise capacity, comfort, skin temperature, and sweating rate. Good heat acclimatization persists about two to four weeks, but after two weeks, you start to lose your acclimatization rapidly, something that might be important for your patients to know. Next slide. There are literally dozens of ways that you can acclimatize to the heat. The CDC recommends two hours a day of heat exposure dividing into one-hour increments. For really good heat acclimatization, you must exercise aerobically and vigorously for at least 30 minutes, and you should continue this for seven to 14 days. OSHA has a protocol for workers that they start a new job with 20% of their work done in a high heat environment and increase by 20% per day. If you've been off work for at least three days, you need to start back in a high heat environment with only 50% of your usual work duration, and increase by 10% to 20% over several days. Next slide. There are many ways that you can get acclimatized to the heat and make significant gains, but for many of us, we will not be able to acclimatize to the very high temperatures that we're seeing now. And this slide explores the impact on medical illnesses from these high temperatures. This is a meta-analysis by Bunker et al. in 2016. The impact of high temperatures on medical illness is shown in red and cold temperatures shown in blue. The numbers at the bottom represent the percent increase in morbidity and mortality for one degree temperature change measured a wide degree of waves and in different kinds of studies looking at millions of people. And basically what they showed was that a 1% degree increase in temperature from average increased cardiovascular mortality by 3.4%, respiratory mortality 0.6%, and cerebrovascular mortality by 1.4%. They didn't look at psychiatric illnesses that we didn't really find anything. There are a number of other things that go up with heat morbidity and mortality. It's harder to get an ambulance because more people are sick, more people will drown because more people are swimming. And then there's some environmental factors like GI illnesses and red toxic algae, which was killing people in the Sierras last year that are associated with higher temperatures. But most of the deaths from heat are from strokes, heart attacks, and respiratory illness. For regular people, next slide, and for sick people, as we get exposed to heat, we will start to develop heat exhaustion. Heat exhaustion is defined as a core temperature over 101. Our heart rate picks up, our peripheral vessels dilate, our blood pressure drops, and vessels to the gut and to the brain contracts so that the blood can go to the surface. This leads to nausea and a pounding headache. And if your patient has nausea or a pounding headache, they are already at significant cerebral hypoperfusion and significant dehydration. If they are thirsty, they are already down three liters of fluid. And once they are dehydrated, it's easier for their body temperature to increase quickly. Next slide. As heat exhaustion progresses to heat stroke, sweating begins to be impaired. Heat stroke is defined as a body temperature over 105 and a failure of body temperature regulation. The old, the young, the poor, and the sickly are most vulnerable, and the mortality can be up to 80%. Heart rate continues to increase, blood pressure falls more. Interleukin-6 rises along with anti-inflammatory acute phase reactants, particularly heat shock proteins, especially one called HSP-72, which accumulates in the brain and would be a good subject for psychiatric research. These heat protective molecules are likely trying to prevent the denaturing of proteins. In the brain and in the gut, as heat stroke progresses, all the cell barriers break down and toxins accumulate, and the brain causes damages with seizures, confusion, and eventually coma. Hyponatremia, acidosis, and renal failure are common as well as DIC. In as little as one hour at this temperature, enzymatic lysis begins. I love that expression. Cell enzymes can't function normally. In the brain, cerebellar damage and central pontine myelinolysis are most common. I think it's important to emphasize that this core temperature of 105 is extremely easily reached when the outside temperatures of 115 and 120 were seen now, unless you're an extremely acclimatized athlete. Next slide. Just to give some feel for the pathophysiology of this, we thought we'd show you what the brain and the gut might look like. These are the MRIs of two men, ages 82 and 79, who lived for nine days and two days respectively. Both came in after being found in hot bathtubs, one in a hot tub, and both were in DIC for experiments of organ function and consciousness. It had been thought that hyperthermia involved particularly the cerebellum, basal ganglia, interior horn, and peripheral nerves. I saw a woman last year who developed a movement disorder from a basal ganglia lesion after a heat event and also became manic. MRI and CT studies have also demonstrated, however, loss of the gray-white matter junction, white matter involvement in cerebellar atrophy. And it wasn't clear how much of the damage was from micro-thrombosis from DIC or cytotoxic or vagogenic edema, similar to the PRESS syndrome. So these authors wanted to look at that. They looked at the pattern of brain involvement and what they saw was that edema seems to predominate in a PRESS-like dominant occipital parietal pattern. Next slide. What does the gut look like when heat edema strikes? This slide is from a rat study, but shows pretty clearly how the villi deteriorate when the gut becomes edematous and leaky and how the intracellular contents can leak out causing peritonitis and sepsis. Next slide. So heat stroke and heat exhaustion are pretty bad. What do you do if you see a patient that has these problems? Well, you want to move the person to a cool shady area, lie them down, and elevate their legs. You're trying to return fluid to the gut, the heart, and the brain. You then will begin to spray them or shower them with cold water, cover them with cold, wet clothing, and fan them or use a fan or air conditioning to cool them down. Don't give them caffeine or alcohol, but try to get them to drink. And if they won't drink, that is a reason to call 911. You should also call 911 for fainting, confusion, agitation, or seizures, something I had to do with my partner once when he began to tell me that he wouldn't drink enough and that the car was rolling downhill on a flat surface. Next slide. If you send your patient to the hospital, this is what they're going to do. They may be given cold air through a ventilator, cold fluid through an IV. They may be hooked up to an equiment-low machine through a central catheter. But most likely, they're going to be covered with cold water or cooling blankets, which is as acceptable as the rest of the studies in comparative studies. Next slide. What can you advise your patients about surviving in the heat? Well, the first thing is to get ready. I just recently bought the silver foil on the left, which you can stick up on your windows. It's called Rabbit Goo, and it costs nine bucks. You can also buy the kind of silver foil and put it in your windows that you get for your car. And you should prepare a to-go kit that includes obviously a lot of water as well as other essentials that you might need for an emergency for power failures. Your patients can download an app from FEMA, which will give them heat alerts, or they can always go to the NOAA weather radio for heat alerts. And if they text shelter and their zip code to 4FEMA, it will immediately tell them the nearest cooling center. Finally, you got to check on your dogs and your neighbors, and it can be helpful to set up a phone tree to do this. Next slide. Patients should limit their time outdoors during the heat of the day and take frequent rests. If they're going outside to work in the heat, they should use a buddy system so they don't collapse alone. They must keep hydrated, obviously, and they should wear light, loose clothing, sunscreen, and a hat. And it's recommended that they eat relatively lightly. Next slide. In terms of cooling advices, oops, sorry, let's go back. This April, actually, OSHA put in a new program for workers called the National Emphasis Program. It's a wonderful new supportive program for worker heat protection, which provides for compliance in high-risk industries, inspection of heat-related complaints, regardless of whether the industry is high-risk or not, and proactive help and technical assistance to help keep workers safe from a central federal administration. It also requires a lot of managers. It calls on employees and managers to train themselves in the hazards of heat-related risk, to know how to attend to the symptoms and signs and do first aid, and to have an EAP for care of heat illness. Companies are required to provide hats outdoors, to provide loose reflective clothing, cooling vests, water-cooled clothes, and so on, and to provide monitors for their employees, like heart rate monitors or things that will monitor core temperature, like this bracelet or a dermal pad. Companies are encouraged to use air conditioning and venting, to provide shade structures to decrease the temperature of environments, and to seal off reflective surfaces with reflective coatings or steam with leak covers and other things that can reduce leaking steam or other heat. They're also encouraged to provide flexible work hours so people can work in the early mornings or overnight, and relief workers for very hot days with work-rest schedules as needed. Next slide. And these are some of the cooling devices that you can now buy. It's actually pretty funny if you look. You can buy things that you could put in your hat. You can buy vests that have ice packs that you can easily insert and then refreeze quickly, or the same thing for your neck. The bottom left is a spot-cleaning or a spot-cooling device that can rapidly lower the temperature in a particularly hot area. Companies with just an ice chest can have a cooling blanket if there's an emergency. And again, you're encouraged to get heat monitors for your employees to monitor the core temperature and heart rate, with the goal of keeping the heart rate less than 120 and stopping work over 180. So those are the recommendations for helping with heat illness in our psychiatric patients. And we will now be available, I think, for a few questions. Thank you very much for coming tonight and for your attention, and I hope the information will be useful. Thank you. A quick comment as we await our questions here. There's 1.5 credits of CME available for attending this webinar. Attendees will receive a follow-up email within one hour of our webinar concluding, and the follow-up email will include instructions to claim credit via the ABA's Learning Center. If you have any questions, there will also be an email to reach out to. Thank you all for attending. All right, so I think there may not be any questions. It's late. I think particularly on the East Coast, we encourage you to reach out for us. We are eager to have people join the Climate Committee, and we hope that you do a great job protecting your patients from high temperature and pursuing this topic. Thanks so much. Thank you. ♪♪

heat waves

mental health

heat-related illnesses

global average surface temperatures

extreme heat events

disadvantaged populations

heat exhaustion

heat stroke

psychiatric medications

heat acclimatization