Resuscitation

A previously healthy infant who survived sudden cardiac arrest at home was later found to have a de novo likely pathogenic genetic mutation in the SOS1 gene, which might be an unrecognized cause of sudden infant death, report clinicians from Missouri.

SOS1 gene variants are associated with Noonan syndrome, a genetic disorder that affects the RAS/MAPK signaling pathway. However, on presentation, the infant had none of the usual structural cardiac findings typical of Noonan syndrome, such as valvular disease or hypertrophic cardiomyopathy.

“To date, this is the first case reported of a ventricular fibrillation arrest in a patient with a RASopathy-related variant prior to development of the typically associated structural cardiac phenotype and may represent a previously unrecognized etiology of sudden death during infancy,” write Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO, from the Ward Family Heart Center, Children’s Mercy Kansas City, and the University of Missouri School of Medicine.

“Genetic testing in cases of unexplained aborted or sudden cardiac deaths, even in previously healthy children, can be valuable in establishing a diagnosis, determining the prognosis, and assessing risk to family members,” they add in a news release.

Dr. Follansbee and Dr. Malloy-Walton describe the case in a report published in the August issue of HeartRhythm Case Reports.
 

Case details

The case involved a 2-month-old girl who did not wake up as usual for her morning feeding. Her mother found her limp, pale, and having difficulty breathing.

When emergency medical services arrived, the infant had no pulse. Cardiopulmonary resuscitation was initiated and an external defibrillator revealed coarse ventricular fibrillation. An initial shock of 10 J was given with conversion to an atrial rhythm with aberrant ventricular conduction.

The infant developed increasing frequency of ectopy before degenerating to ventricular fibrillation. A second shock with 20 J was unsuccessful, but a third shock of 20 J successfully converted the rhythm to sinus with aberrant ventricular conduction and atrial ectopy with return of spontaneous circulation.

In the ICU, the infant displayed incessant, nonsustained ectopic atrial tachycardia, with rapid episodes of ectopic atrial tachycardia with ventricular rates up to 300 beats per minute in the setting of seizure activity, they report. 

With intravenous lorazepam, seizure activity resolved and treatment with amiodarone boluses led to transient establishment of sinus rhythm.

The QTc was noted to be above 500 ms and Brugada positioning of leads was unrevealing, the authors note.

Transthoracic echocardiogram showed a structurally normal heart with normal valve morphology and a patent foramen ovale with left-to-right flow. The initial ejection fraction was 49%. There was no evidence of ventricular hypertrophy, dilation, or noncompaction.

The infant was started on an esmolol infusion titrated to 225 μg/kg per min with frequent, nonsustained breakthrough of ectopic atrial tachycardia. Over the next 24 hours, the QTc interval normalized with normal T-wave morphology.

A procainamide challenge was negative. Cardiac MRI revealed normalization of ventricular function.

The genetics team was called in and a standard three-generation family history was obtained. An older sibling, 2 years of age, had no known medical conditions. The child’s paternal grandfather had died of a presumed myocardial infarction in his 50s, but no autopsy had been performed.

There was no family history of congenital heart disease, arrhythmia, sudden death, cardiomyopathy, recurrent syncope, congenital deafness, seizure, miscarriage, or developmental delay. Electrocardiograms obtained on the parents were normal.

Genetic testing using a comprehensive arrhythmia and cardiomyopathy next-generation sequencing panel revealed a de novo likely pathogenetic variant of the SOS1 gene associated with Noonan syndrome.

Given the aborted sudden cardiac death, the patient underwent dual-chamber epicardial implantable cardioverter-defibrillator implantation prior to discharge.

Dr. Follansbee and Dr. Malloy-Walton say a limitation to the case report is the lack of definitive association of the SOS1 variant with the presentation.

However, knowing the infant has the SOS1 variant and a history of aborted sudden death will allow for “monitoring and early intervention on typical manifestations of Noonan syndrome as the patient grows,” they say.

This research had no specific funding. Dr. Follansbee and Dr. Malloy-Walton have disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

A previously healthy infant who survived sudden cardiac arrest at home was later found to have a de novo likely pathogenic genetic mutation in the SOS1 gene, which might be an unrecognized cause of sudden infant death, report clinicians from Missouri.

SOS1 gene variants are associated with Noonan syndrome, a genetic disorder that affects the RAS/MAPK signaling pathway. However, on presentation, the infant had none of the usual structural cardiac findings typical of Noonan syndrome, such as valvular disease or hypertrophic cardiomyopathy.

“To date, this is the first case reported of a ventricular fibrillation arrest in a patient with a RASopathy-related variant prior to development of the typically associated structural cardiac phenotype and may represent a previously unrecognized etiology of sudden death during infancy,” write Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO, from the Ward Family Heart Center, Children’s Mercy Kansas City, and the University of Missouri School of Medicine.

“Genetic testing in cases of unexplained aborted or sudden cardiac deaths, even in previously healthy children, can be valuable in establishing a diagnosis, determining the prognosis, and assessing risk to family members,” they add in a news release.

Dr. Follansbee and Dr. Malloy-Walton describe the case in a report published in the August issue of HeartRhythm Case Reports.
 

Case details

The case involved a 2-month-old girl who did not wake up as usual for her morning feeding. Her mother found her limp, pale, and having difficulty breathing.

When emergency medical services arrived, the infant had no pulse. Cardiopulmonary resuscitation was initiated and an external defibrillator revealed coarse ventricular fibrillation. An initial shock of 10 J was given with conversion to an atrial rhythm with aberrant ventricular conduction.

The infant developed increasing frequency of ectopy before degenerating to ventricular fibrillation. A second shock with 20 J was unsuccessful, but a third shock of 20 J successfully converted the rhythm to sinus with aberrant ventricular conduction and atrial ectopy with return of spontaneous circulation.

In the ICU, the infant displayed incessant, nonsustained ectopic atrial tachycardia, with rapid episodes of ectopic atrial tachycardia with ventricular rates up to 300 beats per minute in the setting of seizure activity, they report. 

With intravenous lorazepam, seizure activity resolved and treatment with amiodarone boluses led to transient establishment of sinus rhythm.

The QTc was noted to be above 500 ms and Brugada positioning of leads was unrevealing, the authors note.

Transthoracic echocardiogram showed a structurally normal heart with normal valve morphology and a patent foramen ovale with left-to-right flow. The initial ejection fraction was 49%. There was no evidence of ventricular hypertrophy, dilation, or noncompaction.

The infant was started on an esmolol infusion titrated to 225 μg/kg per min with frequent, nonsustained breakthrough of ectopic atrial tachycardia. Over the next 24 hours, the QTc interval normalized with normal T-wave morphology.

A procainamide challenge was negative. Cardiac MRI revealed normalization of ventricular function.

The genetics team was called in and a standard three-generation family history was obtained. An older sibling, 2 years of age, had no known medical conditions. The child’s paternal grandfather had died of a presumed myocardial infarction in his 50s, but no autopsy had been performed.

There was no family history of congenital heart disease, arrhythmia, sudden death, cardiomyopathy, recurrent syncope, congenital deafness, seizure, miscarriage, or developmental delay. Electrocardiograms obtained on the parents were normal.

Genetic testing using a comprehensive arrhythmia and cardiomyopathy next-generation sequencing panel revealed a de novo likely pathogenetic variant of the SOS1 gene associated with Noonan syndrome.

Given the aborted sudden cardiac death, the patient underwent dual-chamber epicardial implantable cardioverter-defibrillator implantation prior to discharge.

Dr. Follansbee and Dr. Malloy-Walton say a limitation to the case report is the lack of definitive association of the SOS1 variant with the presentation.

However, knowing the infant has the SOS1 variant and a history of aborted sudden death will allow for “monitoring and early intervention on typical manifestations of Noonan syndrome as the patient grows,” they say.

This research had no specific funding. Dr. Follansbee and Dr. Malloy-Walton have disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

A previously healthy infant who survived sudden cardiac arrest at home was later found to have a de novo likely pathogenic genetic mutation in the SOS1 gene, which might be an unrecognized cause of sudden infant death, report clinicians from Missouri.

SOS1 gene variants are associated with Noonan syndrome, a genetic disorder that affects the RAS/MAPK signaling pathway. However, on presentation, the infant had none of the usual structural cardiac findings typical of Noonan syndrome, such as valvular disease or hypertrophic cardiomyopathy.

“To date, this is the first case reported of a ventricular fibrillation arrest in a patient with a RASopathy-related variant prior to development of the typically associated structural cardiac phenotype and may represent a previously unrecognized etiology of sudden death during infancy,” write Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO, from the Ward Family Heart Center, Children’s Mercy Kansas City, and the University of Missouri School of Medicine.

“Genetic testing in cases of unexplained aborted or sudden cardiac deaths, even in previously healthy children, can be valuable in establishing a diagnosis, determining the prognosis, and assessing risk to family members,” they add in a news release.

Dr. Follansbee and Dr. Malloy-Walton describe the case in a report published in the August issue of HeartRhythm Case Reports.
 

Case details

The case involved a 2-month-old girl who did not wake up as usual for her morning feeding. Her mother found her limp, pale, and having difficulty breathing.

When emergency medical services arrived, the infant had no pulse. Cardiopulmonary resuscitation was initiated and an external defibrillator revealed coarse ventricular fibrillation. An initial shock of 10 J was given with conversion to an atrial rhythm with aberrant ventricular conduction.

The infant developed increasing frequency of ectopy before degenerating to ventricular fibrillation. A second shock with 20 J was unsuccessful, but a third shock of 20 J successfully converted the rhythm to sinus with aberrant ventricular conduction and atrial ectopy with return of spontaneous circulation.

In the ICU, the infant displayed incessant, nonsustained ectopic atrial tachycardia, with rapid episodes of ectopic atrial tachycardia with ventricular rates up to 300 beats per minute in the setting of seizure activity, they report. 

With intravenous lorazepam, seizure activity resolved and treatment with amiodarone boluses led to transient establishment of sinus rhythm.

The QTc was noted to be above 500 ms and Brugada positioning of leads was unrevealing, the authors note.

Transthoracic echocardiogram showed a structurally normal heart with normal valve morphology and a patent foramen ovale with left-to-right flow. The initial ejection fraction was 49%. There was no evidence of ventricular hypertrophy, dilation, or noncompaction.

The infant was started on an esmolol infusion titrated to 225 μg/kg per min with frequent, nonsustained breakthrough of ectopic atrial tachycardia. Over the next 24 hours, the QTc interval normalized with normal T-wave morphology.

A procainamide challenge was negative. Cardiac MRI revealed normalization of ventricular function.

The genetics team was called in and a standard three-generation family history was obtained. An older sibling, 2 years of age, had no known medical conditions. The child’s paternal grandfather had died of a presumed myocardial infarction in his 50s, but no autopsy had been performed.

There was no family history of congenital heart disease, arrhythmia, sudden death, cardiomyopathy, recurrent syncope, congenital deafness, seizure, miscarriage, or developmental delay. Electrocardiograms obtained on the parents were normal.

Genetic testing using a comprehensive arrhythmia and cardiomyopathy next-generation sequencing panel revealed a de novo likely pathogenetic variant of the SOS1 gene associated with Noonan syndrome.

Given the aborted sudden cardiac death, the patient underwent dual-chamber epicardial implantable cardioverter-defibrillator implantation prior to discharge.

Dr. Follansbee and Dr. Malloy-Walton say a limitation to the case report is the lack of definitive association of the SOS1 variant with the presentation.

However, knowing the infant has the SOS1 variant and a history of aborted sudden death will allow for “monitoring and early intervention on typical manifestations of Noonan syndrome as the patient grows,” they say.

This research had no specific funding. Dr. Follansbee and Dr. Malloy-Walton have disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

Millions of Americans have been languishing for weeks in the oppressive heat and humidity of a merciless summer. Deadly heat has already taken the lives of hundreds in the Pacific Northwest alone, with numbers likely to grow as the full impact of heat-related deaths eventually comes to light.

In the final week of July, the National Weather Service issued excessive heat warnings for 17 states, stretching from the West Coast, across the Midwest, down south into Louisiana and Georgia. Temperatures 10° to 15° F above average threaten the lives and livelihoods of people all across the country.

After a scorching heat wave in late June, residents of the Pacific Northwest are once again likely to see triple-digit temperatures in the coming days. With the heat, hospitals may face another surge of people with heat-related illnesses.

Erika Moseson, MD, a lung and intensive care specialist, witnessed firsthand the life-threatening impacts of soaring temperatures. She happened to be running her 10-bed intensive care unit in a suburban hospital in Gresham, Ore., about 15 miles east of Portland, the weekend of June 26. Within 12 hours, almost half her ICU beds were filled with people found unconscious on the street, in the bushes, or in their own beds, all because their body’s defenses had become overwhelmed by heat.

“It was unidentified person after unidentified person, coming in, same story, temperatures through the roof, comatose,” Dr. Moseson recalled. Young people in their 20s with muscle breakdown markers through the roof, a sign of rhabdomyolysis; people with no other medical problems that would have put them in a high-risk category.

As a lifelong Oregonian, she’d never seen anything like this before. “We’re all trained for it. I know what happens to you if you have heatstroke, I know how to treat it,” she trailed off, still finding it hard to believe. Still reeling from the number of cases in just a few hours. Still shocked that this happened on what’s supposed to be the cooler, rainforest side of Oregon.

Among those she treated and resuscitated, the memory of a patient that she lost continues to gnaw at her.

“I’ve gone back to it day after day since it happened,” she reflected.

Adults, in their 50s, living at home with their children. Just 1 hour prior, they’d all said goodnight. Then 1 hour later, when a child came to check in, both parents were unconscious.

Dr. Moseson shared how her team tried everything in their power for 18 hours to save the parent that was brought to her ICU. But like hundreds of others who went through the heat wave that weekend, her patient didn’t survive.

It was too late. From Dr. Moseson’s experience, it’s what happens “if you’re cooking a human.”
 

How heat kills

Regardless of where we live on the planet, humans maintain a consistent internal temperature around 98° F for our systems to function properly. 

Our bodies have an entire temperature-regulating system to balance heat gain with heat loss so we don’t stray too far from our ideal range. The hypothalamus functions as the thermostat, communicating with heat sensors in our skin, muscles, and spinal cord. Based on signals about our core body temperature, our nervous system makes many decisions for us – opening up blood vessels in the peripheral parts of our body, pushing more blood toward the skin, and activating sweat glands to produce more sweat.  

Sweat is one of the most powerful tools we have to maintain a safe internal temperature. Of course, there are some things under our control, such as removing clothing, drinking more water, and finding shade (or preferably air conditioning). But beyond that, it’s our ability to sweat that keeps us cool. When sweat evaporates into the air, heat from our skin goes with it, cooling us off.

Over time, our sweat response can work better as we get used to warmer environments, a process that’s known as acclimatization. Over the period of a few days to weeks, the sweat glands of acclimated people can start making sweat at lower temperatures, produce more sweat, and absorb more salt back into our system, all to make us more efficient “sweaters.”

While someone who’s not used to the heat may only produce 1 liter of sweat per hour, people who have become acclimated can produce 2-3 liters every hour, allowing evaporation to eliminate more than two times the amount of heat.   

Because the process of acclimatization can take some time, typically it’s the first throes of summer, or heat waves in places where people don’t typically see high temperatures, that are the most deadly. And of course, the right infrastructure, like access to air conditioning, also plays a large role in limiting heat-related death and hospitalization.

A 2019 study showed that heat-related hospitalizations peak at different temperatures in different places. For example, hospitalizations typically peak in Texas when the temperature hits 105° F. But they might be highest in the Pacific Northwest at just 81° F.

Even with acclimatization, there are limits to how much our bodies can adapt to heat. When the humidity goes up past 75%, there’s already so much moisture in the air that heat loss through evaporation no longer occurs.

It’s this connection between heat and humidity that can be deadly. This is why the heat index (a measure that takes into account temperature and relative humidity) and wet bulb globe temperature (a measure commonly used by the military and competitive athletes that takes into account temperature, humidity, wind speed, sun angle, and cloud cover) are both better at showing how dangerous the heat may be for our health, compared to temperature alone.

Kristie L. Ebi, PhD, a professor in the Center for Health and the Global Environment at the University of Washington, Seattle, has been studying the effects of heat and other climate-sensitive conditions on health for over 20 years. She stresses that it’s not just the recorded temperatures, but the prolonged exposure that kills.

If you never get a chance to bring down that core body temperature, if your internal temperatures stay above the range where your cells and your organs can work well for a long time, that’s when you can have the most dangerous effects of heat.

“It depends then on your age, your fitness, your individual physiology, underlying medical conditions, to how quickly that could affect the functioning of those organs. There’s lots of variability in there,” Dr. Ebi said.

Our hearts take on the brunt of the early response, working harder to pump blood toward the skin. Water and salt loss through our skin can start to cause electrolyte changes that can cause heat cramps and heat exhaustion. We feel tired, nauseated, dizzy. With enough water loss, we may become dehydrated, limiting the blood flow to our brains, causing us to pass out.

These early signs are like a car’s check engine light – systems are already being damaged, but resting, refueling, and, most importantly, turning off the heat are critical steps to prevent fatal injury.

If hazardous heat exposure continues and our internal temperatures continue to rise, nerves stop talking to each other, the proteins in our body unfold and lose their shape, and the cells of our organs disintegrate. This in turn sets off a fire alarm in our blood vessels, where a variety of chemical messengers, including “heat-shock proteins,” are released. The release of these inflammatory proteins, coupled with the loss of blood flow, eventually leads to the death of cells throughout the body, from the brain, to the heart, the muscles, and the kidneys.

This process is referred to as heatstroke. In essence, we melt from the inside.

At a certain point, this cascade can’t be reversed. Just like when you cool a melting block of ice, the parts that have melted will not go back to their original shape. It’s a similar process in our bodies, so delays in cooling and treatment can lead to death rates as high as 80%.

On the outside, we see people who look confused and disoriented, with hot skin and rapid breathing, and they may eventually become unconscious. Core body temperatures over 105° F clinch the diagnosis, but at the first sign of feeling unwell, cooling should be started.

There is no fancier or more effective treatment than that: Cool right away. In emergency rooms in Washington State, doctors used body bags filled with ice and water to cool victims of the heat wave in late June.

“It was all from heat ... that’s the thing, you feel so idiotic ... you’re like, ‘I’ve given you ice’ ... you bring their temperature down. But it’s already set off this cascade that you can’t stop,” Dr. Moseson said.

By the time Dr. Moseson’s patient made it to her, cooling with ice was just the beginning of the attempts to resuscitate and revive. The patient was already showing evidence of a process causing widespread bleeding and clotting, known as disseminated intravascular coagulation, along with damage to the heart and failing kidneys. Over 18 hours, her team cooled the patient, flooded the blood vessels with fluids and blood products, attempted to start dialysis, and inserted a breathing tube – all of the technology that is used to save people from serious cardiovascular collapse from other conditions. But nothing could reverse the melting that had already occurred.

Deaths from heat are 100% preventable. Until they’re not.
 

No respite

As Dr. Ebi says, the key to preventing heat-related death is to cool down enough to stabilize our internal cells and proteins before the irreversible cascade begins.

But for close to 80% of Americans who live in urban areas, temperatures can be even higher and more intolerable compared to surrounding areas because of the way we’ve designed our cities. In effect, we have unintentionally created hot zones called “urban heat islands.”

Jeremy Hoffman, PhD, chief scientist for the Science Museum of Virginia, explains that things like bricks, asphalt, and parking lots absorb more of the sun’s energy throughout the day and then emit that back into the air as heat throughout the afternoon and into the evening. This raises the air and surface temperatures in cities, relative to rural areas. When temperatures don’t cool enough at night, there’s no way to recover from the day’s heat. You start the next day still depleted, with less reserve to face the heat of a new day.

When you dig even deeper, it turns out that even within the same city, there are huge “thermal inequities,” as Dr. Hoffman calls them. In a 2019 study, he found that wealthier parts of cities had more natural spaces such as parks and tree-lined streets, compared to areas that had been intentionally “redlined,” or systematically deprived of investment. This pattern repeats itself in over 100 urban areas across the country and translates to huge temperature differences on the order of 10-20 degrees Fahrenheit within the same city, at the exact same time during a heat wave.

“In some ways, the way that we’ve decided to plan and build our cities physically turns up the thermostat by several tens of degrees during heat waves in particular neighborhoods,” Dr. Hoffman said.

Dr. Hoffman’s work showed that the city of Portland (where the death toll from the heat wave in late June was the highest) had some of the most intense differences between formerly redlined vs. tree-lined areas out of the more than 100 cities that he studied.  

“Watching it play out, I was really concerned, not only as a climate scientist, but as a human. Understanding the urban heat island effect and the extreme nature of the inequity in our cities, thermally and otherwise, once you start to really recognize it, you can’t forget it.”
 

The most vulnerable

When it comes to identifying and protecting the people most vulnerable to heat stress and heat-related death, there is an ever-growing list of those most at risk. Unfortunately, very few recognize when they themselves are at risk, often until it’s too late.

According to Linda McCauley, PhD, dean of the Emory University School of Nursing in Atlanta, “the scope of who is vulnerable is quickly increasing.”

For example, we’re used to recognizing that pregnant women and young children are at risk. Public health campaigns have long advised us not to leave young children and pets in hot cars. We know that adolescents who play sports during hot summer months are at high risk for heat-related events and even death.

In Georgia, a 15-year-old boy collapsed and died after his first day back at football practice when the heat index was 105° F on July 26, even as it appears that all protocols for heat safety were being followed.

We recognize that outdoor workers face devastating consequences from prolonged exertion in the heat and must have safer working conditions.

The elderly and those with long-term medical and mental health conditions are also more vulnerable to heat. The elderly may not have the same warning signs and may not recognize that they are dehydrated until it is too late. In addition, their sweating mechanism weakens, and they may be taking medicines that interfere with their ability to regulate their temperature.

Poverty and inadequate housing are risk factors, especially for those in urban heat islands. For many people, their housing does not have enough cooling to protect them, and they can’t safely get themselves to cooling shelters.

These patterns for the most vulnerable fit for the majority of deaths in Oregon during the late June heat wave. Most victims were older, lived alone, and didn’t have air conditioning. But with climate change, the predictions are that temperatures will go higher and heat waves will last longer.

“There’s probably very few people today that are ‘immune’ to the effects of heat-related stress with climate change. All of us can be put in situations where we are susceptible,” Dr. McCauley said.

Dr. Moseson agreed. Many of her patients fit none of these risk categories – she treated people with no health problems in their 20s in her ICU, and the patient she lost would not traditionally have been thought of as high risk. That 50-something patient had no long-standing medical problems, and lived with family in a newly renovated suburban home that had air conditioning. The only problem was that the air conditioner had broken and there had been no rush to fix it based on past experience with Oregon summers.
 

Preventing heat deaths

Protecting ourselves and our families means monitoring the “simple things.” The first three rules are to make sure we’re drinking plenty of water – this means drinking whether we feel thirsty or not. If we’re not in an air-conditioned place, we’ve got to look for shade. And we need to take regular rest breaks.

Inside a home without air conditioning, placing ice in front of a fan to cool the air can work, but realistically, if you are in a place without air conditioning and the temperatures are approaching 90° F, it’s safest to find another place to stay, if possible.

For those playing sports, there are usually 1-week to 2-week protocols that allow for acclimatization when the season begins – this means starting slowly, without gear, and ramping up activity. Still, parents and coaches should watch advanced weather reports to make sure it’s safe to practice outside.

How we dress can also help us, so light clothing is key. And if we’re able to schedule activities for times when it is cooler, that can also protect us from overheating.

If anyone shows early signs of heat stress, removing clothing, cooling their bodies with cold water, and getting them out of the heat is critical. Any evidence of heatstroke is an emergency, and 911 should be called without delay. The faster the core temperature can be dropped, the better the chances for recovery.

On the level of communities, access to natural air conditioning in the form of healthy tree canopies, and trees at bus stops to provide shade can help a lot. According to Dr. Hoffman, these investments help almost right away. Reimagining our cities to remove the “hot zones” that we have created is another key to protecting ourselves as our climate changes.
 

Reaching our limits in a changing climate

Already, we are seeing more intense, more frequent, and longer-lasting heat waves throughout the country and across the globe.

Dr. Ebi, a coauthor of a recently released scientific analysis that found that the late June Pacific Northwest heat wave would have been virtually impossible without climate change, herself lived through the scorching temperatures in Seattle. Her work shows that the changing climate is killing us right now.

We are approaching a time where extreme temperatures and humidity will make it almost impossible for people to be outside in many parts of the world. Researchers have found that periods of extreme humid heat have more than doubled since 1979, and some places have already had wet-bulb temperatures at the limits of what scientists think humans can tolerate under ideal conditions, meaning for people in perfect health, completely unclothed, in gale-force winds, performing no activity. Obviously that’s less than ideal for most of us and helps explain why thousands of people die at temperatures much lower than our upper limit.

Dr. Ebi pointed out that the good news is that many local communities with a long history of managing high temperatures have a lot of knowledge to share with regions that are newly dealing with these conditions. This includes how local areas develop early warning and response systems with specific action plans.

But, she cautions, it’s going to take a lot of coordination and a lot of behavior change to stabilize the earth’s climate, understand our weak points, and protect our health.

For Dr. Moseson, this reality has hit home.

“I already spent the year being terrified that I as an ICU doctor was going to be the one who gave my mom COVID. Finally I’m vaccinated, she’s vaccinated. Now I’ve watched someone die because they don’t have AC. And my parents, they’re old-school Oregonians, they don’t have AC.”

A version of this article originally appeared on WebMD.com.

Millions of Americans have been languishing for weeks in the oppressive heat and humidity of a merciless summer. Deadly heat has already taken the lives of hundreds in the Pacific Northwest alone, with numbers likely to grow as the full impact of heat-related deaths eventually comes to light.

In the final week of July, the National Weather Service issued excessive heat warnings for 17 states, stretching from the West Coast, across the Midwest, down south into Louisiana and Georgia. Temperatures 10° to 15° F above average threaten the lives and livelihoods of people all across the country.

After a scorching heat wave in late June, residents of the Pacific Northwest are once again likely to see triple-digit temperatures in the coming days. With the heat, hospitals may face another surge of people with heat-related illnesses.

Erika Moseson, MD, a lung and intensive care specialist, witnessed firsthand the life-threatening impacts of soaring temperatures. She happened to be running her 10-bed intensive care unit in a suburban hospital in Gresham, Ore., about 15 miles east of Portland, the weekend of June 26. Within 12 hours, almost half her ICU beds were filled with people found unconscious on the street, in the bushes, or in their own beds, all because their body’s defenses had become overwhelmed by heat.

“It was unidentified person after unidentified person, coming in, same story, temperatures through the roof, comatose,” Dr. Moseson recalled. Young people in their 20s with muscle breakdown markers through the roof, a sign of rhabdomyolysis; people with no other medical problems that would have put them in a high-risk category.

As a lifelong Oregonian, she’d never seen anything like this before. “We’re all trained for it. I know what happens to you if you have heatstroke, I know how to treat it,” she trailed off, still finding it hard to believe. Still reeling from the number of cases in just a few hours. Still shocked that this happened on what’s supposed to be the cooler, rainforest side of Oregon.

Among those she treated and resuscitated, the memory of a patient that she lost continues to gnaw at her.

“I’ve gone back to it day after day since it happened,” she reflected.

Adults, in their 50s, living at home with their children. Just 1 hour prior, they’d all said goodnight. Then 1 hour later, when a child came to check in, both parents were unconscious.

Dr. Moseson shared how her team tried everything in their power for 18 hours to save the parent that was brought to her ICU. But like hundreds of others who went through the heat wave that weekend, her patient didn’t survive.

It was too late. From Dr. Moseson’s experience, it’s what happens “if you’re cooking a human.”
 

How heat kills

Regardless of where we live on the planet, humans maintain a consistent internal temperature around 98° F for our systems to function properly. 

Our bodies have an entire temperature-regulating system to balance heat gain with heat loss so we don’t stray too far from our ideal range. The hypothalamus functions as the thermostat, communicating with heat sensors in our skin, muscles, and spinal cord. Based on signals about our core body temperature, our nervous system makes many decisions for us – opening up blood vessels in the peripheral parts of our body, pushing more blood toward the skin, and activating sweat glands to produce more sweat.  

Sweat is one of the most powerful tools we have to maintain a safe internal temperature. Of course, there are some things under our control, such as removing clothing, drinking more water, and finding shade (or preferably air conditioning). But beyond that, it’s our ability to sweat that keeps us cool. When sweat evaporates into the air, heat from our skin goes with it, cooling us off.

Over time, our sweat response can work better as we get used to warmer environments, a process that’s known as acclimatization. Over the period of a few days to weeks, the sweat glands of acclimated people can start making sweat at lower temperatures, produce more sweat, and absorb more salt back into our system, all to make us more efficient “sweaters.”

While someone who’s not used to the heat may only produce 1 liter of sweat per hour, people who have become acclimated can produce 2-3 liters every hour, allowing evaporation to eliminate more than two times the amount of heat.   

Because the process of acclimatization can take some time, typically it’s the first throes of summer, or heat waves in places where people don’t typically see high temperatures, that are the most deadly. And of course, the right infrastructure, like access to air conditioning, also plays a large role in limiting heat-related death and hospitalization.

A 2019 study showed that heat-related hospitalizations peak at different temperatures in different places. For example, hospitalizations typically peak in Texas when the temperature hits 105° F. But they might be highest in the Pacific Northwest at just 81° F.

Even with acclimatization, there are limits to how much our bodies can adapt to heat. When the humidity goes up past 75%, there’s already so much moisture in the air that heat loss through evaporation no longer occurs.

It’s this connection between heat and humidity that can be deadly. This is why the heat index (a measure that takes into account temperature and relative humidity) and wet bulb globe temperature (a measure commonly used by the military and competitive athletes that takes into account temperature, humidity, wind speed, sun angle, and cloud cover) are both better at showing how dangerous the heat may be for our health, compared to temperature alone.

Kristie L. Ebi, PhD, a professor in the Center for Health and the Global Environment at the University of Washington, Seattle, has been studying the effects of heat and other climate-sensitive conditions on health for over 20 years. She stresses that it’s not just the recorded temperatures, but the prolonged exposure that kills.

If you never get a chance to bring down that core body temperature, if your internal temperatures stay above the range where your cells and your organs can work well for a long time, that’s when you can have the most dangerous effects of heat.

“It depends then on your age, your fitness, your individual physiology, underlying medical conditions, to how quickly that could affect the functioning of those organs. There’s lots of variability in there,” Dr. Ebi said.

Our hearts take on the brunt of the early response, working harder to pump blood toward the skin. Water and salt loss through our skin can start to cause electrolyte changes that can cause heat cramps and heat exhaustion. We feel tired, nauseated, dizzy. With enough water loss, we may become dehydrated, limiting the blood flow to our brains, causing us to pass out.

These early signs are like a car’s check engine light – systems are already being damaged, but resting, refueling, and, most importantly, turning off the heat are critical steps to prevent fatal injury.

If hazardous heat exposure continues and our internal temperatures continue to rise, nerves stop talking to each other, the proteins in our body unfold and lose their shape, and the cells of our organs disintegrate. This in turn sets off a fire alarm in our blood vessels, where a variety of chemical messengers, including “heat-shock proteins,” are released. The release of these inflammatory proteins, coupled with the loss of blood flow, eventually leads to the death of cells throughout the body, from the brain, to the heart, the muscles, and the kidneys.

This process is referred to as heatstroke. In essence, we melt from the inside.

At a certain point, this cascade can’t be reversed. Just like when you cool a melting block of ice, the parts that have melted will not go back to their original shape. It’s a similar process in our bodies, so delays in cooling and treatment can lead to death rates as high as 80%.

On the outside, we see people who look confused and disoriented, with hot skin and rapid breathing, and they may eventually become unconscious. Core body temperatures over 105° F clinch the diagnosis, but at the first sign of feeling unwell, cooling should be started.

There is no fancier or more effective treatment than that: Cool right away. In emergency rooms in Washington State, doctors used body bags filled with ice and water to cool victims of the heat wave in late June.

“It was all from heat ... that’s the thing, you feel so idiotic ... you’re like, ‘I’ve given you ice’ ... you bring their temperature down. But it’s already set off this cascade that you can’t stop,” Dr. Moseson said.

By the time Dr. Moseson’s patient made it to her, cooling with ice was just the beginning of the attempts to resuscitate and revive. The patient was already showing evidence of a process causing widespread bleeding and clotting, known as disseminated intravascular coagulation, along with damage to the heart and failing kidneys. Over 18 hours, her team cooled the patient, flooded the blood vessels with fluids and blood products, attempted to start dialysis, and inserted a breathing tube – all of the technology that is used to save people from serious cardiovascular collapse from other conditions. But nothing could reverse the melting that had already occurred.

Deaths from heat are 100% preventable. Until they’re not.
 

No respite

As Dr. Ebi says, the key to preventing heat-related death is to cool down enough to stabilize our internal cells and proteins before the irreversible cascade begins.

But for close to 80% of Americans who live in urban areas, temperatures can be even higher and more intolerable compared to surrounding areas because of the way we’ve designed our cities. In effect, we have unintentionally created hot zones called “urban heat islands.”

Jeremy Hoffman, PhD, chief scientist for the Science Museum of Virginia, explains that things like bricks, asphalt, and parking lots absorb more of the sun’s energy throughout the day and then emit that back into the air as heat throughout the afternoon and into the evening. This raises the air and surface temperatures in cities, relative to rural areas. When temperatures don’t cool enough at night, there’s no way to recover from the day’s heat. You start the next day still depleted, with less reserve to face the heat of a new day.

When you dig even deeper, it turns out that even within the same city, there are huge “thermal inequities,” as Dr. Hoffman calls them. In a 2019 study, he found that wealthier parts of cities had more natural spaces such as parks and tree-lined streets, compared to areas that had been intentionally “redlined,” or systematically deprived of investment. This pattern repeats itself in over 100 urban areas across the country and translates to huge temperature differences on the order of 10-20 degrees Fahrenheit within the same city, at the exact same time during a heat wave.

“In some ways, the way that we’ve decided to plan and build our cities physically turns up the thermostat by several tens of degrees during heat waves in particular neighborhoods,” Dr. Hoffman said.

Dr. Hoffman’s work showed that the city of Portland (where the death toll from the heat wave in late June was the highest) had some of the most intense differences between formerly redlined vs. tree-lined areas out of the more than 100 cities that he studied.  

“Watching it play out, I was really concerned, not only as a climate scientist, but as a human. Understanding the urban heat island effect and the extreme nature of the inequity in our cities, thermally and otherwise, once you start to really recognize it, you can’t forget it.”
 

The most vulnerable

When it comes to identifying and protecting the people most vulnerable to heat stress and heat-related death, there is an ever-growing list of those most at risk. Unfortunately, very few recognize when they themselves are at risk, often until it’s too late.

According to Linda McCauley, PhD, dean of the Emory University School of Nursing in Atlanta, “the scope of who is vulnerable is quickly increasing.”

For example, we’re used to recognizing that pregnant women and young children are at risk. Public health campaigns have long advised us not to leave young children and pets in hot cars. We know that adolescents who play sports during hot summer months are at high risk for heat-related events and even death.

In Georgia, a 15-year-old boy collapsed and died after his first day back at football practice when the heat index was 105° F on July 26, even as it appears that all protocols for heat safety were being followed.

We recognize that outdoor workers face devastating consequences from prolonged exertion in the heat and must have safer working conditions.

The elderly and those with long-term medical and mental health conditions are also more vulnerable to heat. The elderly may not have the same warning signs and may not recognize that they are dehydrated until it is too late. In addition, their sweating mechanism weakens, and they may be taking medicines that interfere with their ability to regulate their temperature.

Poverty and inadequate housing are risk factors, especially for those in urban heat islands. For many people, their housing does not have enough cooling to protect them, and they can’t safely get themselves to cooling shelters.

These patterns for the most vulnerable fit for the majority of deaths in Oregon during the late June heat wave. Most victims were older, lived alone, and didn’t have air conditioning. But with climate change, the predictions are that temperatures will go higher and heat waves will last longer.

“There’s probably very few people today that are ‘immune’ to the effects of heat-related stress with climate change. All of us can be put in situations where we are susceptible,” Dr. McCauley said.

Dr. Moseson agreed. Many of her patients fit none of these risk categories – she treated people with no health problems in their 20s in her ICU, and the patient she lost would not traditionally have been thought of as high risk. That 50-something patient had no long-standing medical problems, and lived with family in a newly renovated suburban home that had air conditioning. The only problem was that the air conditioner had broken and there had been no rush to fix it based on past experience with Oregon summers.
 

Preventing heat deaths

Protecting ourselves and our families means monitoring the “simple things.” The first three rules are to make sure we’re drinking plenty of water – this means drinking whether we feel thirsty or not. If we’re not in an air-conditioned place, we’ve got to look for shade. And we need to take regular rest breaks.

Inside a home without air conditioning, placing ice in front of a fan to cool the air can work, but realistically, if you are in a place without air conditioning and the temperatures are approaching 90° F, it’s safest to find another place to stay, if possible.

For those playing sports, there are usually 1-week to 2-week protocols that allow for acclimatization when the season begins – this means starting slowly, without gear, and ramping up activity. Still, parents and coaches should watch advanced weather reports to make sure it’s safe to practice outside.

How we dress can also help us, so light clothing is key. And if we’re able to schedule activities for times when it is cooler, that can also protect us from overheating.

If anyone shows early signs of heat stress, removing clothing, cooling their bodies with cold water, and getting them out of the heat is critical. Any evidence of heatstroke is an emergency, and 911 should be called without delay. The faster the core temperature can be dropped, the better the chances for recovery.

On the level of communities, access to natural air conditioning in the form of healthy tree canopies, and trees at bus stops to provide shade can help a lot. According to Dr. Hoffman, these investments help almost right away. Reimagining our cities to remove the “hot zones” that we have created is another key to protecting ourselves as our climate changes.
 

Reaching our limits in a changing climate

Already, we are seeing more intense, more frequent, and longer-lasting heat waves throughout the country and across the globe.

Dr. Ebi, a coauthor of a recently released scientific analysis that found that the late June Pacific Northwest heat wave would have been virtually impossible without climate change, herself lived through the scorching temperatures in Seattle. Her work shows that the changing climate is killing us right now.

We are approaching a time where extreme temperatures and humidity will make it almost impossible for people to be outside in many parts of the world. Researchers have found that periods of extreme humid heat have more than doubled since 1979, and some places have already had wet-bulb temperatures at the limits of what scientists think humans can tolerate under ideal conditions, meaning for people in perfect health, completely unclothed, in gale-force winds, performing no activity. Obviously that’s less than ideal for most of us and helps explain why thousands of people die at temperatures much lower than our upper limit.

Dr. Ebi pointed out that the good news is that many local communities with a long history of managing high temperatures have a lot of knowledge to share with regions that are newly dealing with these conditions. This includes how local areas develop early warning and response systems with specific action plans.

But, she cautions, it’s going to take a lot of coordination and a lot of behavior change to stabilize the earth’s climate, understand our weak points, and protect our health.

For Dr. Moseson, this reality has hit home.

“I already spent the year being terrified that I as an ICU doctor was going to be the one who gave my mom COVID. Finally I’m vaccinated, she’s vaccinated. Now I’ve watched someone die because they don’t have AC. And my parents, they’re old-school Oregonians, they don’t have AC.”

A version of this article originally appeared on WebMD.com.

Millions of Americans have been languishing for weeks in the oppressive heat and humidity of a merciless summer. Deadly heat has already taken the lives of hundreds in the Pacific Northwest alone, with numbers likely to grow as the full impact of heat-related deaths eventually comes to light.

In the final week of July, the National Weather Service issued excessive heat warnings for 17 states, stretching from the West Coast, across the Midwest, down south into Louisiana and Georgia. Temperatures 10° to 15° F above average threaten the lives and livelihoods of people all across the country.

After a scorching heat wave in late June, residents of the Pacific Northwest are once again likely to see triple-digit temperatures in the coming days. With the heat, hospitals may face another surge of people with heat-related illnesses.

Erika Moseson, MD, a lung and intensive care specialist, witnessed firsthand the life-threatening impacts of soaring temperatures. She happened to be running her 10-bed intensive care unit in a suburban hospital in Gresham, Ore., about 15 miles east of Portland, the weekend of June 26. Within 12 hours, almost half her ICU beds were filled with people found unconscious on the street, in the bushes, or in their own beds, all because their body’s defenses had become overwhelmed by heat.

“It was unidentified person after unidentified person, coming in, same story, temperatures through the roof, comatose,” Dr. Moseson recalled. Young people in their 20s with muscle breakdown markers through the roof, a sign of rhabdomyolysis; people with no other medical problems that would have put them in a high-risk category.

As a lifelong Oregonian, she’d never seen anything like this before. “We’re all trained for it. I know what happens to you if you have heatstroke, I know how to treat it,” she trailed off, still finding it hard to believe. Still reeling from the number of cases in just a few hours. Still shocked that this happened on what’s supposed to be the cooler, rainforest side of Oregon.

Among those she treated and resuscitated, the memory of a patient that she lost continues to gnaw at her.

“I’ve gone back to it day after day since it happened,” she reflected.

Adults, in their 50s, living at home with their children. Just 1 hour prior, they’d all said goodnight. Then 1 hour later, when a child came to check in, both parents were unconscious.

Dr. Moseson shared how her team tried everything in their power for 18 hours to save the parent that was brought to her ICU. But like hundreds of others who went through the heat wave that weekend, her patient didn’t survive.

It was too late. From Dr. Moseson’s experience, it’s what happens “if you’re cooking a human.”
 

How heat kills

Regardless of where we live on the planet, humans maintain a consistent internal temperature around 98° F for our systems to function properly. 

Our bodies have an entire temperature-regulating system to balance heat gain with heat loss so we don’t stray too far from our ideal range. The hypothalamus functions as the thermostat, communicating with heat sensors in our skin, muscles, and spinal cord. Based on signals about our core body temperature, our nervous system makes many decisions for us – opening up blood vessels in the peripheral parts of our body, pushing more blood toward the skin, and activating sweat glands to produce more sweat.  

Sweat is one of the most powerful tools we have to maintain a safe internal temperature. Of course, there are some things under our control, such as removing clothing, drinking more water, and finding shade (or preferably air conditioning). But beyond that, it’s our ability to sweat that keeps us cool. When sweat evaporates into the air, heat from our skin goes with it, cooling us off.

Over time, our sweat response can work better as we get used to warmer environments, a process that’s known as acclimatization. Over the period of a few days to weeks, the sweat glands of acclimated people can start making sweat at lower temperatures, produce more sweat, and absorb more salt back into our system, all to make us more efficient “sweaters.”

While someone who’s not used to the heat may only produce 1 liter of sweat per hour, people who have become acclimated can produce 2-3 liters every hour, allowing evaporation to eliminate more than two times the amount of heat.   

Because the process of acclimatization can take some time, typically it’s the first throes of summer, or heat waves in places where people don’t typically see high temperatures, that are the most deadly. And of course, the right infrastructure, like access to air conditioning, also plays a large role in limiting heat-related death and hospitalization.

A 2019 study showed that heat-related hospitalizations peak at different temperatures in different places. For example, hospitalizations typically peak in Texas when the temperature hits 105° F. But they might be highest in the Pacific Northwest at just 81° F.

Even with acclimatization, there are limits to how much our bodies can adapt to heat. When the humidity goes up past 75%, there’s already so much moisture in the air that heat loss through evaporation no longer occurs.

It’s this connection between heat and humidity that can be deadly. This is why the heat index (a measure that takes into account temperature and relative humidity) and wet bulb globe temperature (a measure commonly used by the military and competitive athletes that takes into account temperature, humidity, wind speed, sun angle, and cloud cover) are both better at showing how dangerous the heat may be for our health, compared to temperature alone.

Kristie L. Ebi, PhD, a professor in the Center for Health and the Global Environment at the University of Washington, Seattle, has been studying the effects of heat and other climate-sensitive conditions on health for over 20 years. She stresses that it’s not just the recorded temperatures, but the prolonged exposure that kills.

If you never get a chance to bring down that core body temperature, if your internal temperatures stay above the range where your cells and your organs can work well for a long time, that’s when you can have the most dangerous effects of heat.

“It depends then on your age, your fitness, your individual physiology, underlying medical conditions, to how quickly that could affect the functioning of those organs. There’s lots of variability in there,” Dr. Ebi said.

Our hearts take on the brunt of the early response, working harder to pump blood toward the skin. Water and salt loss through our skin can start to cause electrolyte changes that can cause heat cramps and heat exhaustion. We feel tired, nauseated, dizzy. With enough water loss, we may become dehydrated, limiting the blood flow to our brains, causing us to pass out.

These early signs are like a car’s check engine light – systems are already being damaged, but resting, refueling, and, most importantly, turning off the heat are critical steps to prevent fatal injury.

If hazardous heat exposure continues and our internal temperatures continue to rise, nerves stop talking to each other, the proteins in our body unfold and lose their shape, and the cells of our organs disintegrate. This in turn sets off a fire alarm in our blood vessels, where a variety of chemical messengers, including “heat-shock proteins,” are released. The release of these inflammatory proteins, coupled with the loss of blood flow, eventually leads to the death of cells throughout the body, from the brain, to the heart, the muscles, and the kidneys.

This process is referred to as heatstroke. In essence, we melt from the inside.

At a certain point, this cascade can’t be reversed. Just like when you cool a melting block of ice, the parts that have melted will not go back to their original shape. It’s a similar process in our bodies, so delays in cooling and treatment can lead to death rates as high as 80%.

On the outside, we see people who look confused and disoriented, with hot skin and rapid breathing, and they may eventually become unconscious. Core body temperatures over 105° F clinch the diagnosis, but at the first sign of feeling unwell, cooling should be started.

There is no fancier or more effective treatment than that: Cool right away. In emergency rooms in Washington State, doctors used body bags filled with ice and water to cool victims of the heat wave in late June.

“It was all from heat ... that’s the thing, you feel so idiotic ... you’re like, ‘I’ve given you ice’ ... you bring their temperature down. But it’s already set off this cascade that you can’t stop,” Dr. Moseson said.

By the time Dr. Moseson’s patient made it to her, cooling with ice was just the beginning of the attempts to resuscitate and revive. The patient was already showing evidence of a process causing widespread bleeding and clotting, known as disseminated intravascular coagulation, along with damage to the heart and failing kidneys. Over 18 hours, her team cooled the patient, flooded the blood vessels with fluids and blood products, attempted to start dialysis, and inserted a breathing tube – all of the technology that is used to save people from serious cardiovascular collapse from other conditions. But nothing could reverse the melting that had already occurred.

Deaths from heat are 100% preventable. Until they’re not.
 

No respite

As Dr. Ebi says, the key to preventing heat-related death is to cool down enough to stabilize our internal cells and proteins before the irreversible cascade begins.

But for close to 80% of Americans who live in urban areas, temperatures can be even higher and more intolerable compared to surrounding areas because of the way we’ve designed our cities. In effect, we have unintentionally created hot zones called “urban heat islands.”

Jeremy Hoffman, PhD, chief scientist for the Science Museum of Virginia, explains that things like bricks, asphalt, and parking lots absorb more of the sun’s energy throughout the day and then emit that back into the air as heat throughout the afternoon and into the evening. This raises the air and surface temperatures in cities, relative to rural areas. When temperatures don’t cool enough at night, there’s no way to recover from the day’s heat. You start the next day still depleted, with less reserve to face the heat of a new day.

When you dig even deeper, it turns out that even within the same city, there are huge “thermal inequities,” as Dr. Hoffman calls them. In a 2019 study, he found that wealthier parts of cities had more natural spaces such as parks and tree-lined streets, compared to areas that had been intentionally “redlined,” or systematically deprived of investment. This pattern repeats itself in over 100 urban areas across the country and translates to huge temperature differences on the order of 10-20 degrees Fahrenheit within the same city, at the exact same time during a heat wave.

“In some ways, the way that we’ve decided to plan and build our cities physically turns up the thermostat by several tens of degrees during heat waves in particular neighborhoods,” Dr. Hoffman said.

Dr. Hoffman’s work showed that the city of Portland (where the death toll from the heat wave in late June was the highest) had some of the most intense differences between formerly redlined vs. tree-lined areas out of the more than 100 cities that he studied.  

“Watching it play out, I was really concerned, not only as a climate scientist, but as a human. Understanding the urban heat island effect and the extreme nature of the inequity in our cities, thermally and otherwise, once you start to really recognize it, you can’t forget it.”
 

The most vulnerable

When it comes to identifying and protecting the people most vulnerable to heat stress and heat-related death, there is an ever-growing list of those most at risk. Unfortunately, very few recognize when they themselves are at risk, often until it’s too late.

According to Linda McCauley, PhD, dean of the Emory University School of Nursing in Atlanta, “the scope of who is vulnerable is quickly increasing.”

For example, we’re used to recognizing that pregnant women and young children are at risk. Public health campaigns have long advised us not to leave young children and pets in hot cars. We know that adolescents who play sports during hot summer months are at high risk for heat-related events and even death.

In Georgia, a 15-year-old boy collapsed and died after his first day back at football practice when the heat index was 105° F on July 26, even as it appears that all protocols for heat safety were being followed.

We recognize that outdoor workers face devastating consequences from prolonged exertion in the heat and must have safer working conditions.

The elderly and those with long-term medical and mental health conditions are also more vulnerable to heat. The elderly may not have the same warning signs and may not recognize that they are dehydrated until it is too late. In addition, their sweating mechanism weakens, and they may be taking medicines that interfere with their ability to regulate their temperature.

Poverty and inadequate housing are risk factors, especially for those in urban heat islands. For many people, their housing does not have enough cooling to protect them, and they can’t safely get themselves to cooling shelters.

These patterns for the most vulnerable fit for the majority of deaths in Oregon during the late June heat wave. Most victims were older, lived alone, and didn’t have air conditioning. But with climate change, the predictions are that temperatures will go higher and heat waves will last longer.

“There’s probably very few people today that are ‘immune’ to the effects of heat-related stress with climate change. All of us can be put in situations where we are susceptible,” Dr. McCauley said.

Dr. Moseson agreed. Many of her patients fit none of these risk categories – she treated people with no health problems in their 20s in her ICU, and the patient she lost would not traditionally have been thought of as high risk. That 50-something patient had no long-standing medical problems, and lived with family in a newly renovated suburban home that had air conditioning. The only problem was that the air conditioner had broken and there had been no rush to fix it based on past experience with Oregon summers.
 

Preventing heat deaths

Protecting ourselves and our families means monitoring the “simple things.” The first three rules are to make sure we’re drinking plenty of water – this means drinking whether we feel thirsty or not. If we’re not in an air-conditioned place, we’ve got to look for shade. And we need to take regular rest breaks.

Inside a home without air conditioning, placing ice in front of a fan to cool the air can work, but realistically, if you are in a place without air conditioning and the temperatures are approaching 90° F, it’s safest to find another place to stay, if possible.

For those playing sports, there are usually 1-week to 2-week protocols that allow for acclimatization when the season begins – this means starting slowly, without gear, and ramping up activity. Still, parents and coaches should watch advanced weather reports to make sure it’s safe to practice outside.

How we dress can also help us, so light clothing is key. And if we’re able to schedule activities for times when it is cooler, that can also protect us from overheating.

If anyone shows early signs of heat stress, removing clothing, cooling their bodies with cold water, and getting them out of the heat is critical. Any evidence of heatstroke is an emergency, and 911 should be called without delay. The faster the core temperature can be dropped, the better the chances for recovery.

On the level of communities, access to natural air conditioning in the form of healthy tree canopies, and trees at bus stops to provide shade can help a lot. According to Dr. Hoffman, these investments help almost right away. Reimagining our cities to remove the “hot zones” that we have created is another key to protecting ourselves as our climate changes.
 

Reaching our limits in a changing climate

Already, we are seeing more intense, more frequent, and longer-lasting heat waves throughout the country and across the globe.

Dr. Ebi, a coauthor of a recently released scientific analysis that found that the late June Pacific Northwest heat wave would have been virtually impossible without climate change, herself lived through the scorching temperatures in Seattle. Her work shows that the changing climate is killing us right now.

We are approaching a time where extreme temperatures and humidity will make it almost impossible for people to be outside in many parts of the world. Researchers have found that periods of extreme humid heat have more than doubled since 1979, and some places have already had wet-bulb temperatures at the limits of what scientists think humans can tolerate under ideal conditions, meaning for people in perfect health, completely unclothed, in gale-force winds, performing no activity. Obviously that’s less than ideal for most of us and helps explain why thousands of people die at temperatures much lower than our upper limit.

Dr. Ebi pointed out that the good news is that many local communities with a long history of managing high temperatures have a lot of knowledge to share with regions that are newly dealing with these conditions. This includes how local areas develop early warning and response systems with specific action plans.

But, she cautions, it’s going to take a lot of coordination and a lot of behavior change to stabilize the earth’s climate, understand our weak points, and protect our health.

For Dr. Moseson, this reality has hit home.

“I already spent the year being terrified that I as an ICU doctor was going to be the one who gave my mom COVID. Finally I’m vaccinated, she’s vaccinated. Now I’ve watched someone die because they don’t have AC. And my parents, they’re old-school Oregonians, they don’t have AC.”

A version of this article originally appeared on WebMD.com.

The rate of hospital admissions in the United Kingdom for food-induced anaphylaxis more than tripled over the 20 years from 1998 to 2018, but the case fatality rate fell by more than half, researchers report in BMJ.

“Cow’s milk is increasingly identified as the culprit allergen for fatal food reactions and is now the commonest cause of fatal anaphylaxis in children,” write Alessia Baseggio Conrado, PhD, a biochemist with the National Heart and Lung Institute at Imperial College London, and colleagues. “More education is needed to highlight the specific risks posed by cow’s milk to people who are allergic to increase awareness among food businesses.”

Whereas recognition of the risks posed by nut allergies has increased, people think milk allergy is mild, says senior author Paul. J. Turner, BMBCh, PhD, an allergist/immunologist at Imperial College. “This is often true in very young children, but school-aged children who still have milk allergy tend to have a more allergic profile, often with other allergies, including asthma,” Dr. Turner told this news organization. “Also, milk is very common in our diet, and you don’t need much milk to achieve a decent dose of allergen.”

During the study period, 101,891 people were hospitalized for anaphylaxis; 30,700 cases (30%) were coded as having been triggered by food.

These food-related admissions represent an increase from 1.23 to 4.04 per 100,000 population per year, for an annual increase of 5.7% (95% confidence interval, 5.5-5.9; P < .001), the authors write.

The largest jump occurred among children younger than 15 years, for whom admissions rose from 2.1 to 9.2 per 100,000 population per year, an annual increase of 6.6% (95% CI, 6.3-7.0). The annual increases were 5.9% (95% CI, 5.6-6.2) among persons aged 15 to 59 years and 2.1% (95% CI, 1.8-3.1) among those aged 60 years and older.

The investigators used data from England, Scotland, Wales, and Northern Ireland to track temporal trends and age and sex distributions for hospital admissions for which the primary diagnosis was anaphylaxis attributable to both food and nonfood triggers. These data were compared with nationally reported fatalities.

Over the 20-year period, 152 deaths were attributed to likely food-induced anaphylaxis. During that time, the case fatality rate for confirmed fatal food anaphylaxis fell from 0.7% to 0.19% (rate ratio, 0.931; 95% CI, 0.904-0.959; P < .001) and declined to 0.30% for suspected fatal food anaphylaxis (rate ratio, 0.970; 95% CI, 0.945-0.996; P = .024).

Between 1992 and 2018, at least 46% of all anaphylactic fatalities were deemed to be triggered by peanut or tree nut. Among school-aged children, 26% of anaphylactic fatalities were attributed to cow’s milk.

Not surprisingly, during the study period, there was an increase of 336% in prescriptions for adrenaline autoinjectors. Such prescriptions increased 11% per year.

Global trend

The data extend findings Dr. Turner and colleagues reported for England and Wales in 2014 regarding the entire United Kingdom population and align with epidemiologic trends in hospital admissions for anaphylaxis in the United States and Australia.

The researchers say better recognition and management of anaphylaxis could partly explain the decrease in fatalities, but the rise in hospitalizations remains puzzling. “Whether a true increase in the prevalence of anaphylaxis has occurred (rather than a reduction in the threshold to admit patients presenting with anaphylaxis) is unclear because evidence is lacking for an increase in prevalence of food allergy in the [United Kingdom] (and elsewhere) over the same time period,” they write.

Ronna L. Campbell, MD, PhD, an emergency physician at the Mayo Clinic in Rochester, Minn., has noted similar trends in the United States. “It may be that anaphylaxis recognition and diagnosis have improved, resulting in earlier administration of epinephrine,” Dr. Campbell said in an interview. “So while cases are increasing, earlier recognition and treatment result in decreased fatalities.” She is unaware of any new guidelines recommending increased hospitalization that would explain the puzzling rise in admissions.

According to the study authors, the clinical criteria used to diagnose anaphylaxis in the United Kingdom did not change during the study period. Although national guidance recommending the hospitalization of children younger than 16 who are suspected of having anaphylaxis was introduced in 2011 and may have boosted admissions, the year-on-year rate of increase has persisted since 2014. “Therefore the increase over the past 5 years cannot be attributed to the impact of the guidance,” they write.

The study was funded by grants from the U.K. Medical Research Council and U.K. Food Standards Agency. Two coauthors have disclosed financial relationships with industry outside of the submitted work. Dr. Conrado has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com

The rate of hospital admissions in the United Kingdom for food-induced anaphylaxis more than tripled over the 20 years from 1998 to 2018, but the case fatality rate fell by more than half, researchers report in BMJ.

“Cow’s milk is increasingly identified as the culprit allergen for fatal food reactions and is now the commonest cause of fatal anaphylaxis in children,” write Alessia Baseggio Conrado, PhD, a biochemist with the National Heart and Lung Institute at Imperial College London, and colleagues. “More education is needed to highlight the specific risks posed by cow’s milk to people who are allergic to increase awareness among food businesses.”

Whereas recognition of the risks posed by nut allergies has increased, people think milk allergy is mild, says senior author Paul. J. Turner, BMBCh, PhD, an allergist/immunologist at Imperial College. “This is often true in very young children, but school-aged children who still have milk allergy tend to have a more allergic profile, often with other allergies, including asthma,” Dr. Turner told this news organization. “Also, milk is very common in our diet, and you don’t need much milk to achieve a decent dose of allergen.”

During the study period, 101,891 people were hospitalized for anaphylaxis; 30,700 cases (30%) were coded as having been triggered by food.

These food-related admissions represent an increase from 1.23 to 4.04 per 100,000 population per year, for an annual increase of 5.7% (95% confidence interval, 5.5-5.9; P < .001), the authors write.

The largest jump occurred among children younger than 15 years, for whom admissions rose from 2.1 to 9.2 per 100,000 population per year, an annual increase of 6.6% (95% CI, 6.3-7.0). The annual increases were 5.9% (95% CI, 5.6-6.2) among persons aged 15 to 59 years and 2.1% (95% CI, 1.8-3.1) among those aged 60 years and older.

The investigators used data from England, Scotland, Wales, and Northern Ireland to track temporal trends and age and sex distributions for hospital admissions for which the primary diagnosis was anaphylaxis attributable to both food and nonfood triggers. These data were compared with nationally reported fatalities.

Over the 20-year period, 152 deaths were attributed to likely food-induced anaphylaxis. During that time, the case fatality rate for confirmed fatal food anaphylaxis fell from 0.7% to 0.19% (rate ratio, 0.931; 95% CI, 0.904-0.959; P < .001) and declined to 0.30% for suspected fatal food anaphylaxis (rate ratio, 0.970; 95% CI, 0.945-0.996; P = .024).

Between 1992 and 2018, at least 46% of all anaphylactic fatalities were deemed to be triggered by peanut or tree nut. Among school-aged children, 26% of anaphylactic fatalities were attributed to cow’s milk.

Not surprisingly, during the study period, there was an increase of 336% in prescriptions for adrenaline autoinjectors. Such prescriptions increased 11% per year.

Global trend

The data extend findings Dr. Turner and colleagues reported for England and Wales in 2014 regarding the entire United Kingdom population and align with epidemiologic trends in hospital admissions for anaphylaxis in the United States and Australia.

The researchers say better recognition and management of anaphylaxis could partly explain the decrease in fatalities, but the rise in hospitalizations remains puzzling. “Whether a true increase in the prevalence of anaphylaxis has occurred (rather than a reduction in the threshold to admit patients presenting with anaphylaxis) is unclear because evidence is lacking for an increase in prevalence of food allergy in the [United Kingdom] (and elsewhere) over the same time period,” they write.

Ronna L. Campbell, MD, PhD, an emergency physician at the Mayo Clinic in Rochester, Minn., has noted similar trends in the United States. “It may be that anaphylaxis recognition and diagnosis have improved, resulting in earlier administration of epinephrine,” Dr. Campbell said in an interview. “So while cases are increasing, earlier recognition and treatment result in decreased fatalities.” She is unaware of any new guidelines recommending increased hospitalization that would explain the puzzling rise in admissions.

According to the study authors, the clinical criteria used to diagnose anaphylaxis in the United Kingdom did not change during the study period. Although national guidance recommending the hospitalization of children younger than 16 who are suspected of having anaphylaxis was introduced in 2011 and may have boosted admissions, the year-on-year rate of increase has persisted since 2014. “Therefore the increase over the past 5 years cannot be attributed to the impact of the guidance,” they write.

The study was funded by grants from the U.K. Medical Research Council and U.K. Food Standards Agency. Two coauthors have disclosed financial relationships with industry outside of the submitted work. Dr. Conrado has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com

The rate of hospital admissions in the United Kingdom for food-induced anaphylaxis more than tripled over the 20 years from 1998 to 2018, but the case fatality rate fell by more than half, researchers report in BMJ.

“Cow’s milk is increasingly identified as the culprit allergen for fatal food reactions and is now the commonest cause of fatal anaphylaxis in children,” write Alessia Baseggio Conrado, PhD, a biochemist with the National Heart and Lung Institute at Imperial College London, and colleagues. “More education is needed to highlight the specific risks posed by cow’s milk to people who are allergic to increase awareness among food businesses.”

Whereas recognition of the risks posed by nut allergies has increased, people think milk allergy is mild, says senior author Paul. J. Turner, BMBCh, PhD, an allergist/immunologist at Imperial College. “This is often true in very young children, but school-aged children who still have milk allergy tend to have a more allergic profile, often with other allergies, including asthma,” Dr. Turner told this news organization. “Also, milk is very common in our diet, and you don’t need much milk to achieve a decent dose of allergen.”

During the study period, 101,891 people were hospitalized for anaphylaxis; 30,700 cases (30%) were coded as having been triggered by food.

These food-related admissions represent an increase from 1.23 to 4.04 per 100,000 population per year, for an annual increase of 5.7% (95% confidence interval, 5.5-5.9; P < .001), the authors write.

The largest jump occurred among children younger than 15 years, for whom admissions rose from 2.1 to 9.2 per 100,000 population per year, an annual increase of 6.6% (95% CI, 6.3-7.0). The annual increases were 5.9% (95% CI, 5.6-6.2) among persons aged 15 to 59 years and 2.1% (95% CI, 1.8-3.1) among those aged 60 years and older.

The investigators used data from England, Scotland, Wales, and Northern Ireland to track temporal trends and age and sex distributions for hospital admissions for which the primary diagnosis was anaphylaxis attributable to both food and nonfood triggers. These data were compared with nationally reported fatalities.

Over the 20-year period, 152 deaths were attributed to likely food-induced anaphylaxis. During that time, the case fatality rate for confirmed fatal food anaphylaxis fell from 0.7% to 0.19% (rate ratio, 0.931; 95% CI, 0.904-0.959; P < .001) and declined to 0.30% for suspected fatal food anaphylaxis (rate ratio, 0.970; 95% CI, 0.945-0.996; P = .024).

Between 1992 and 2018, at least 46% of all anaphylactic fatalities were deemed to be triggered by peanut or tree nut. Among school-aged children, 26% of anaphylactic fatalities were attributed to cow’s milk.

Not surprisingly, during the study period, there was an increase of 336% in prescriptions for adrenaline autoinjectors. Such prescriptions increased 11% per year.

Global trend

The data extend findings Dr. Turner and colleagues reported for England and Wales in 2014 regarding the entire United Kingdom population and align with epidemiologic trends in hospital admissions for anaphylaxis in the United States and Australia.

The researchers say better recognition and management of anaphylaxis could partly explain the decrease in fatalities, but the rise in hospitalizations remains puzzling. “Whether a true increase in the prevalence of anaphylaxis has occurred (rather than a reduction in the threshold to admit patients presenting with anaphylaxis) is unclear because evidence is lacking for an increase in prevalence of food allergy in the [United Kingdom] (and elsewhere) over the same time period,” they write.

Ronna L. Campbell, MD, PhD, an emergency physician at the Mayo Clinic in Rochester, Minn., has noted similar trends in the United States. “It may be that anaphylaxis recognition and diagnosis have improved, resulting in earlier administration of epinephrine,” Dr. Campbell said in an interview. “So while cases are increasing, earlier recognition and treatment result in decreased fatalities.” She is unaware of any new guidelines recommending increased hospitalization that would explain the puzzling rise in admissions.

According to the study authors, the clinical criteria used to diagnose anaphylaxis in the United Kingdom did not change during the study period. Although national guidance recommending the hospitalization of children younger than 16 who are suspected of having anaphylaxis was introduced in 2011 and may have boosted admissions, the year-on-year rate of increase has persisted since 2014. “Therefore the increase over the past 5 years cannot be attributed to the impact of the guidance,” they write.

The study was funded by grants from the U.K. Medical Research Council and U.K. Food Standards Agency. Two coauthors have disclosed financial relationships with industry outside of the submitted work. Dr. Conrado has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com

Resuscitation of critically ill patients in shock from cardiogenic, hypovolemic, obstructive, distributive, or neurogenic etiology is a cornerstone of the care delivered by emergency physicians (EPs).¹ Regardless of the etiology, it is essential that the treating EP initiate resuscitative measures in a timely manner and closely trend the patient’s response to these interventions.

The early goal-directed therapy (EGDT) initially proposed by Rivers et al² in 2001 demonstrated a bundled approach to fluid resuscitation by targeting end points for volume resuscitation, mean arterial blood pressure (MAP), oxygen (O₂) delivery/extraction (mixed venous O₂ saturation, [S_vO₂]), hemoglobin (Hgb) concentration, and cardiac contractility. Since then, advancements in laboratory testing and hemodynamic monitoring (HDM) devices further aid and guide resuscitative efforts, and are applicable to any etiology of shock.

In addition to these advancements, the growing evidence of the potential harm from improper fluid resuscitation, such as the administration of excessive intravascular fluid (IVF),³ underscores the importance of a precise, targeted, and individualized approach to care. This article reviews the background, benefits, and limitations of some of the common and readily available tools in the ED that the EP can employ to guide fluid resuscitation in critically ill patients.

Physical Examination

Background

The rapid recognition and treatment of septic shock in the ED is associated with lower rates of in-hospital morbidity and mortality.⁴ The physical examination by the EP begins immediately upon examining the patient. The acquisition of vital signs and recognition of physical examination findings suggestive of intravascular volume depletion allows the EP to initiate treatment immediately.

In this discussion, hypotension is defined as systolic blood pressure (SBP) of less than 95 mm Hg, MAP of less than 65 mm Hg, or a decrease in SBP of more than 40 mm Hg from baseline measurements. Subsequently, shock is defined as hypotension with evidence of tissue hypoperfusion-induced dysfunction.^5,6 Although the use of findings from the physical examination to guide resuscitation allows for rapid patient assessment and treatment, the predictive value of the physical examination to assess hemodynamic status is limited.

Benefits

The major benefit of the physical examination as a tool to evaluate hemodynamic status is its ease and rapid acquisition. The patient’s vital signs and physical examination can be obtained in the matter of moments upon presentation, without the need to wait on results of laboratory evaluation or additional equipment. Additionally, serial examinations by the same physician can be helpful to monitor a patient’s response to resuscitative efforts. The negative predictive value (NPV) of the physical examination in evaluating for hypovolemia may be helpful, but only when it is taken in the appropriate clinical context and is used in conjunction with other diagnostic tools. The physical examination can exclude hypovolemic volume status with an NPV of approximately 70%.⁷

A constellation of findings from the physical examination may include altered mentation, hypotension, tachycardia, and decreased urinary output by 30% to 40% intravascular volume loss.^8,9Findings from the physical examination to assess fluid status should be used with caution as interobserver reliability has proven to be poor and the prognostic value is limited.

Limitations

The literature shows the limited prognostic value of the physical examination in determining a patient’s volume status and whether fluid resuscitation is indicated. For example, in one meta-analysis,¹⁰ supine hypotension and tachycardia were frequently absent on examination—even in patients who underwent large volume phlebotomy.⁸ This study also showed postural dizziness to be of no prognostic value.

Another study by Saugel et al⁷ that compared the physical examination (skin assessment, lung auscultation, and percussion) to transpulmonary thermodilution measurements of the cardiac index, global end-diastolic volume index, and extravascular lung water index, found poor interobserver correlation and agreement among physicians.

The physical examination is also associated with weak predictive capabilities for the estimation of volume status compared to the device measurements. Another contemporary study by Saugel et al⁹ evaluated the predictive value of the physical examination to accurately identify volume responsiveness replicated these results, and reported poor interobserver correlation (κ coefficient 0.01; 95% caval index [CI] -0.39-0.42) among physical examination findings, with a sensitivity of only 71%, specificity of 23.5%, positive predictive value of 27.8%, and negative predictive value of 66.7%.⁹

Serum Lactate Levels

Background

In the 1843 book titled, Investigations of Pathological Substances Obtained During the Epidemic of Puerperal Fever, Johann Joseph Scherer described the cases of seven young peripartum female patients who died from a clinical picture of what is now understood to be septic shock.¹¹ In his study of these cases, Scherer demonstrated the presence of lactic acid in patients with pathological conditions. Prior to this discovery, lactic acid had never been isolated in a healthy individual. These results were recreated in 1851 by Scherer and Virchow,¹¹ who demonstrated the presence of lactic acid in the blood of a patient who died from leukemia. The inference based on Scherer and Virchow’s work correlated the presence of excessive lactic acid with bodily deterioration and severe disease. Since this finding, there has been a great deal of interest in measuring serum lactic acid as a means to identify and manage critical illness.

In a 2001 groundbreaking study of EGDT for severe sepsis and septic shock, Rivers et al² studied lactic acid levels as a marker for severe disease. Likewise, years later, the 2014 Protocol-Based Care for Early Septic Shock (PROCESS), Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE), and Australasian Resuscitation in Sepsis Evaluation (ARISE) trials used lactate levels in a similar manner to identify patients appropriate for randomization.^12-14 While the purpose of measuring lactic acid was only employed in these studies to identify patients at risk for critical illness, the 2012 Surviving Sepsis Campaign Guidelines recommended serial measurement of lactate, based on the assumption that improved lactate levels signified better tissue perfusion.¹⁵

Although much of the studies on lactate levels appear to be based on the treatment and management of septic patients, findings can be applied to any etiology of shock. For example, a serum lactate level greater than 2 mmol/L is considered abnormal, and a serum lactate greater than 4 mmol/L indicates a significantly increased risk for in-hospital mortality.¹⁶

Benefits

It is now a widely accepted belief that the rapid identification, triage, and treatment of critically ill patients has a dramatic effect on morbidity and mortality.⁴ As previously noted, lactate has been extensively studied and identified as a marker of severe illness.^17,18 A serum lactate level, which can be rapidly processed in the ED, can be easily obtained from a minimally invasive venous, arterial, or capillary blood draw.¹⁸ The only risk associated with serum lactate testing is that of any routine venipuncture; the test causes minimal, if any, patient discomfort.

Thanks to advances in point-of-care (POC) technology, the result of serum lactate assessment can be available within 10 minutes from blood draw. This technology is inexpensive and can be easily deployed in the prehospital setting or during the initial triage assessment of patients arriving at the ED.¹⁹ These POC instruments have been well correlated with whole blood measurements and permit for the rapid identification and treatment of at risk patients.

Limitations

The presence of elevated serum lactate levels is believed to represent the presence of cellular anaerobic metabolism due to impaired O₂ delivery in the shock state. Abnormal measurements therefore prompt aggressive interventions aimed at maximizing O₂ delivery to the tissues, such as intravenous fluid boluses, vasopressor therapy, or even blood product administration.

A return to a normalized serum lactate level is assumed to represent a transition back to aerobic metabolism. Lactate elevations, however, are not solely an indication of anaerobic metabolism and may only represent a small degree of lactate production.²⁰ While the specific cellular mechanics are out of the scope of this article, it has been postulated that the increase in plasma lactate concentration is primarily driven by β-2 receptor stimulation from increased circulating catecholamines leading to increased aerobic glycolysis. Increased lactate levels could therefore be an adaptive mechanism of energy production—aggressive treatment and rapid clearance may, in fact, be harmful. Type A lactic acidosis is categorized as elevated serum levels due to tissue hypoperfusion.²¹

However, lactate elevations do not exclusively occur in severe illness. The use of β-2 receptor agonists such as continuous albuterol treatments or epinephrine may cause abnormal lactate levels.²² Other medications have also been associated with elevated serum lactate levels, including, but not limited to linezolid, metformin, and propofol.^23-25 Additionally, lactate levels may be elevated after strenuous exercise, seizure activity, or in liver and kidney disease.²⁶ These “secondary” causes of lactic acidosis that are not due to tissue hypoperfusion are referred to as type B lactic acidosis. Given these multiple etiologies and lack of specificity for this serum measurement, a failure to understand these limitations may result in over aggressive or unnecessary medical treatments.

Central Venous Pressure

Background

Central venous pressure (CVP) measurements can be obtained through a catheter, the distal tip of which transduces pressure of the superior vena cava at the entrance of the right atrium (RA). Thus, CVP is often used as a representation of RA pressure (RAP) and therefore an estimate of right ventricular (RV) preload. While CVP is used to diagnose and determine the etiology of shock, evidence and controversy regarding the use of CVP as a marker for resuscitation comes largely from sepsis-focused literature.⁵ Central venous pressure is meant to represent preload, which is essential for stroke volume as described by the Frank-Starling mechanism; however, its use as a target in distributive shock, a state in which it is difficult to determine a patient’s volume status, has been popularized by EGDT since 2001.²

Since the publication of the 2004 Surviving Sepsis Guidelines, CVP monitoring has been in the spotlight of sepsis resuscitation, albeit with some controversy.²⁷ Included as the result of two studies, this recommendation has been removed in the most recent guidelines after 12 years of further study and scrutiny.^2,27,28

Hypovolemic and hemorrhagic shock are usually diagnosed clinically and while a low CVP can be helpful in the diagnosis, the guidelines do not support CVP as a resuscitation endpoint. Obstructive and cardiogenic shock will both result in elevated CVP; however, treatment of obstructive shock is generally targeted at the underlying cause. While cardiogenic shock can be preload responsive, the mainstay of therapy in the ED is identification of patients for revascularization and inotropic support.²⁹

Benefits

The CVP has been used as a surrogate for RV preload volume. If a patient’s preload volume is low, the treating physician can administer fluids to improve stroke volume and cardiac output (CO). Clinically, CVP measurements are easy to obtain provided a central venous line has been placed with the distal tip at the entrance to the RA. Central venous pressure is measured by transducing the pressure via manometry and connecting it to the patient’s bedside monitor. This provides an advantage of being able to provide serial or even continuous measurements. The “normal” RAP should be a low value (1-5 mm Hg, mean of 3 mm Hg), as this aids in the pressure gradient to drive blood from the higher pressures of the left ventricle (LV) and aorta through the circulation back to the low-pressure of the RA.³⁰ The value of the CVP is meant to correspond to the physical examination findings of jugular venous distension.^31,32 Thus, a low CVP may be “normal” and seen in patients with hypovolemic shock, whereas an elevated CVP can suggest volume overload or obstructive shock. However, this is of questionable value in distributive shock cases.

Aside from the two early studies on CVP monitoring during treatment of septic patients, there are few data to support the use of CVP measurement in the early resuscitation of patients with shock.^2,28 More recent trials (PROMISE, ARISE, PROCESS) that compared protocolized sepsis care to standard care showed no benefit to bundles including CVP measurements.^12-14 However, a subsequent, large observational trial spanning 7.5 years demonstrated improvements in sepsis-related mortality in patients who received a central venous catheter (CVC) and CVP-targeted therapy.³³ Thus, it is possible that protocols including CVP are still beneficial in combination with other therapies even though CVP in isolation is not.

Limitations

The traditional two assumptions in CVP monitoring are CVP value represents the overall volume status of the patient, and the LV is able to utilize additional preload volume. The latter assumption, however, may be hampered by the presence of sepsis-induced myocardial dysfunction, which may be present in up to 40% of critically ill patients.³⁴ The former assumption does not always hold true due to processes that change filling pressures independent of intravascular volume—eg, acute or chronic pulmonary hypertension, cardiac tamponade, intra-abdominal hypertension, or LV failure. Even before the landmark EGDT study, available data suggested that CVP was not a reliable marker for resuscitation management.³⁵ A recent systematic review by Gottlieb and Hunter³⁶ showed that the area under the receiver-operator curve for low, mid-range, or high CVPs was equivocal at best. In addition to its unreliability and lack of specificity, another significant drawback to using CVP to guide resuscitation therapy in the ED is that it necessitates placement of a CVC, which can be time-consuming and, if not otherwise indicated, lead to complications of infection, pneumothorax, and/or thrombosis.³⁷

Mixed Venous Oxygen

Background

Most EPs are familiar with the use of S_cvO₂ in EGDT protocols to guide volume resuscitation of septic patients.² A patient’s S_cvO₂ represents the O₂ saturation of venous blood obtained via a CVC at the confluence of the superior vena cava and the RA, and thus it reflects tissue O₂ consumption as a surrogate for tissue perfusion. The measurement parallels the S_vO₂ obtained from the pulmonary artery. In a healthy patient, S_vO₂ is around 65% to 70% and includes blood returning from both the superior and inferior vena cava (IVC). As such, S_cvO₂ values are typically 3% to 5% lower than S_vO₂ owing to the lower O₂ extracted by tissues draining into the IVC compared to the mixed venous blood sampled from the pulmonary artery.³⁸

Though a debate over the benefit of EGDT in treating sepsis continues, understanding the physiology of S_cvO₂ measurements is another potential tool the EP can use to guide the resuscitation of critically ill patients.³⁹ A patient’s S_vO₂ and, by extension, S_cvO₂ represents the residual O₂ saturation after the tissues have extracted the amount of O₂ necessary to meet metabolic demands (Figure 2).

Benefits

A critically ill patient’s S_cvO₂ can potentially provide EPs with insight into the patient’s global tissue perfusion and the source of any mismatch between O₂ delivery and consumption. Using additional tools and measurements (physical examination, serum Hgb levels, and pulse oximetry) in conjunction with an S_cvO₂ measurement, assists EPs in identifying targets for therapeutic intervention. The effectiveness of this intervention can then be assessed using serial S_cvO₂ measurements, as described in Rivers et al² EGDT protocol. Importantly, EPs should take care to measure serial S_cvO₂ values to maximize its utility.³⁸ Similar to a CVP measurement, S_cvO₂is easily obtained from blood samples for serial laboratory measurements, assuming the patient already has a CVC with the distal tip at the entrance to the RA (S_cvO₂) or a pulmonary artery catheter (PAC) (S_vO₂).

Limitations

Serial measurements provide the most reliable information, which may be more useful in patients who spend extended periods of their resuscitation in the ED. In comparison to other measures of global tissue hypoxia, work by Jones et al⁴¹ suggests non-inferiority of peripherally sampled, serial lactate measurements as an alternative to S_cvO₂. This, in conjunction with the requirement for an internal jugular CVC, subclavian CVC, or PAC with their associated risks, may make S_cvO₂ a less attractive guide for the resuscitation of critically ill patients in the ED.

Monitoring Devices

Background

As noted throughout this review, it is important not only to identify and rapidly treat shock, but to also correctly identify the type of shock, such that treatment can be appropriately directed at its underlying cause. However, prior work suggests that EPs are unable to grossly estimate CO or systemic vascular resistance when compared to objective measurements of these parameters.⁴² This is in agreement with the overall poor performance of physical examination and clinical evaluation as a means of predicting volume responsiveness or guiding resuscitation, as discussed previously. Fortunately, a wide variety of devices to objectively monitor hemodynamics are now available to the EP.

In 1970, Swan et al⁴³ published their initial experience with pulmonary artery catheterization at the bedside, using a balloon-tipped, flow-guided PAC in lieu of fluoroscopy, which had been mandated by earlier techniques. The ability to measure CO, right heart pressures, pulmonary arterial pressures, and estimate LV end diastolic pressure ushered in an era of widespread PAC use, despite an absence of evidence for causation of improved patient outcomes. The utilization of PACs has fallen, as the literature suggests that the empiric placement of PACs in critically ill patients does not improve mortality, length of stay, or cost, and significant complication rates have been reported in large trials.^44,45Subsequently, a number of non-invasive or less-invasive HDM devices have been developed. Amongst the more commonly encountered modern devices, the techniques utilized for providing hemodynamic assessments include thermodilution and pulse contour analysis (PiCCO^TM), pulse contour analysis (FloTrac/Vigileo^TM), and lithium chemodilution with pulse power analysis (LiDCOplus^TM).⁴⁶ The primary utility of these devices for the EP lies in the ability to quantify CO, stroke volume, and stroke volume or pulse pressure variation (PPV) to predict or assess response to resuscitative interventions (volume administration, vasopressors, inotropes, etc).

Benefits

Many of these devices require placement of an arterial catheter. Some require the addition of a CVC. Both of these procedures are well within the clinical scope of the EP, and are performed with fair frequency on critically ill patients. This is a distinct advantage when compared to pulmonary artery catheterization, a higher risk procedure that is rarely performed outside of the intensive care unit or cardiac catheterization laboratory. In addition, all of the devices below present hemodynamic data in a graphical, easy-to-read format, in real time. All of the devices discussed report stroke volume variation (SVV) or PPV continuously.

Limitations

Though these measures have validated threshold values that predict volume responsiveness, they require the patient to be intubated with a set tidal volume of greater than or equal to 8 mL/kg without spontaneous respirations and cardiac arrhythmias, in order to accurately do so. All of the HDM devices that rely on pulse contour analysis as the primary means of CO measurement cannot be used in the presence of significant cardiac arrhythmias (ie, atrial fibrillation), or mechanical circulatory assistance devices (ie, intra-aortic balloon counterpulsation). None of these devices are capable of monitoring microcirculatory changes, felt to be of increasing clinical importance in the critically ill.

The use of HDM devices to monitor CO with a reasonable degree of accuracy, trend CO, and assess for volume responsiveness using a number of previously validated parameters such as SVV is now in little doubt. However, these devices are still invasive, if less so than a pulmonary artery. The crux of the discussion of HDM devices for use in ED resuscitation revolves around whether or not the use of such devices to drive previously validated, protocolized care results in better outcomes for patients. The EP can now have continuous knowledge of a large number of hemodynamic parameters at their fingertips with relatively minimal additional efforts. At the time of this writing, though, this is both untested and unproven, with respect to the ED population.

Point-of-Care Ultrasound

Background

Over the past two decades, ultrasound (US) has become an integral part of the practice of emergency medicine (EM), and is now included in all United States Accreditation Council for Graduate Medical Education Emergency Medicine Residency Programs.^47,48 It has emerged as a very important bedside tool performed by the clinician to identify type of shock and guide resuscitation, and has been endorsed by both EM and critical care societies.^49-51 This section reviews the utility of US as a modality in identifying shock and guiding resuscitation, in addition to the pitfalls and limitations of this important tool.

In 2010, Perera et al⁴⁷ described in their landmark article the Rapid Ultrasound in SHock (RUSH) examination, which describes a stepwise (the pump, tank, pipes) approach to identify the type of shock (cardiogenic, hypovolemic, obstructive, or distributive) in the crashing, hypotensive ED patient. We do not describe the full RUSH examination in this review, but discuss key elements of it as examples of how POCUS can assist the EP to make a rapid diagnosis and aid in the management of patients in shock. The “pump” is the heart, which is assessed in four different views to identify a pericardial effusion and possible tamponade, assess contractility or ejection fraction of the LV (severely decreased, decreased, normal, or hyperdynamic), and right heart strain which is identified by an RV that is larger than the LV, indicative of a potential pulmonary embolus.

The “tank” is then assessed by visualizing the IVC in the subxiphoid plane, and is evaluated for respiratory collapsibility (CI) and maximum size. This has been quite the debated topic over the last two decades. In 1988, Simonson and Schiller⁵² were the first to describe a correlation in spontaneously breathing patients between IVC caliber (measured 2 cm from the cavoatrial junction) and variation and RAP, where a larger IVC diameter and less respiratory variation correlated with a high RAP. Kircher et al⁵³ later went on to describe that a CI greater than 50% correlated with an RAP of less than 10 mm Hg and vice versa in spontaneously breathing patients. Since then there have been more studies attempting to verify these findings in both spontaneously breathing and mechanically ventilated patients.^54-56 The purpose of performing these measurements is not to estimate CVP, but to assess fluid responsiveness (ie, a blood pressure response to a fluid challenge). It can be assumed in states of shock that a small IVC, or one with a high CI, in the presence of a hyperdynamic heart is indicative of an underfilled ventricle and fluid responsiveness, especially if the IVC size increases with fluid.^55,57 However, there are several caveats to this. First, in mechanically ventilated patients, the IVC is already plethoric due to positive pressure ventilation, and increases in diameter with inspiration and decreases with expiration as compared to spontaneously breathing patients. Second, the CI value to predict volume responsiveness in ventilated patients is set at 15% instead of 50%.⁵⁵ Third, it is important to always take the clinical scenario in context; a dilated IVC with small CI is not necessarily only due to volume overload and congestive heart failure, but can be due to elevated RAP from obstructive shock due to cardiac tamponade or massive pulmonary embolus, which is why it is important to assess the “pump” first.^47,58 It is also crucial to not forget to assess the abdominal and thoracic cavities, as intraperitoneal or pleural fluid with a collapsed IVC can potentially make a diagnosis of hemorrhagic or hypovolemic shock depending on the clinical scenario.⁴⁷ The final part of the RUSH protocol is to evaluate the “pipes,” inclusive of the lower extremity deep venous system for evaluation of potential thrombosis that could increase suspicion for a pulmonary embolism causing obstructive shock, and the aorta with the common iliac arteries if there is concern for aortic dissection or aneurysmal rupture.

Benefits

Some of the most significant advantages to the use of POCUS to guide resuscitation is that it is quick, non-invasive, does not use ionizing radiation, and can be easily repeated. As noted above, it is a requirement for EM residencies to teach its use, so that contemporary graduates are entering the specialty competent in applying it to the care of their patients. Furthermore, POCUS is done at the bedside, limiting the need to potentially transport unstable patients.

In the most basic applications, POCUS provides direct visualization of a patient’s cardiac function, presence or absence of lung sliding to suggest a pneumothorax, presence of pulmonary edema, assessment of CVP pressures or potential for fluid responsiveness, as well as identification of potential thoracic, peritoneal, or pelvic cavity fluid accumulation that may suggest hemorrhage. There is literature to support that these assessments performed by the EP have been shown to be comparable to those of cardiologists.^59,60 With continued practice and additional training, it is possible for EPs to even perform more “advanced” hemodynamic assessments to both diagnose and guide therapy to patients in shock (Figures 3 and 4).⁶¹

Limitations

Although POCUS has been shown as a remarkable tool to help assist the EP in making rapid decisions regarding resuscitation, it is always important to remember its limitations. Most of the studies regarding its use are of very small sample sizes, and further prospective studies have to be performed in order for this modality to be fully relied on.⁶²Compared to some of the previously mentioned HDM devices that may provide continuous data, POCUS needs to be performed by the treating physician, thereby occurring intermittently. Emergency physicians need to be aware of their own experience and limitations with this modality, as errors in misdiagnosis can lead to unnecessary procedures, with resulting significant morbidity and mortality. Blanco and Volpicelli⁶³ describe several common errors that include misdiagnosing the stomach as a peritoneal effusion, assuming adequate volume resuscitation when the IVC is seen to be plethoric in the setting of cardiac tamponade, or mistaking IVC movement as indicative of collapsibility, amongst other described misinterpretations. Several other studies have shown that, despite adequate performance of EPs in POCUS, diagnostic sensitivities remained higher when performed by radiologists.^64-67 Thus it remains important for the EPs to be vigilant and not anchor on a diagnosis when in doubt, and to consult early with radiology, particularly if there is any question, to avoid potential adverse patient outcomes.

Summary

There are several ways to diagnose and track resuscitation in the ED, which include physical examination, assessment of serum laboratory values, monitoring of hemodynamic status, and use of POCUS. Unfortunately, none of these methods provides a perfect assessment, and no method has been proven superior and effective over the others. Therefore, it is important for EPs treating patients in shock to be aware of the strengths and limitations of each assessment method (Table).

Resuscitation of critically ill patients in shock from cardiogenic, hypovolemic, obstructive, distributive, or neurogenic etiology is a cornerstone of the care delivered by emergency physicians (EPs).¹ Regardless of the etiology, it is essential that the treating EP initiate resuscitative measures in a timely manner and closely trend the patient’s response to these interventions.

The early goal-directed therapy (EGDT) initially proposed by Rivers et al² in 2001 demonstrated a bundled approach to fluid resuscitation by targeting end points for volume resuscitation, mean arterial blood pressure (MAP), oxygen (O₂) delivery/extraction (mixed venous O₂ saturation, [S_vO₂]), hemoglobin (Hgb) concentration, and cardiac contractility. Since then, advancements in laboratory testing and hemodynamic monitoring (HDM) devices further aid and guide resuscitative efforts, and are applicable to any etiology of shock.

In addition to these advancements, the growing evidence of the potential harm from improper fluid resuscitation, such as the administration of excessive intravascular fluid (IVF),³ underscores the importance of a precise, targeted, and individualized approach to care. This article reviews the background, benefits, and limitations of some of the common and readily available tools in the ED that the EP can employ to guide fluid resuscitation in critically ill patients.

Physical Examination

Background

The rapid recognition and treatment of septic shock in the ED is associated with lower rates of in-hospital morbidity and mortality.⁴ The physical examination by the EP begins immediately upon examining the patient. The acquisition of vital signs and recognition of physical examination findings suggestive of intravascular volume depletion allows the EP to initiate treatment immediately.

In this discussion, hypotension is defined as systolic blood pressure (SBP) of less than 95 mm Hg, MAP of less than 65 mm Hg, or a decrease in SBP of more than 40 mm Hg from baseline measurements. Subsequently, shock is defined as hypotension with evidence of tissue hypoperfusion-induced dysfunction.^5,6 Although the use of findings from the physical examination to guide resuscitation allows for rapid patient assessment and treatment, the predictive value of the physical examination to assess hemodynamic status is limited.

Benefits

The major benefit of the physical examination as a tool to evaluate hemodynamic status is its ease and rapid acquisition. The patient’s vital signs and physical examination can be obtained in the matter of moments upon presentation, without the need to wait on results of laboratory evaluation or additional equipment. Additionally, serial examinations by the same physician can be helpful to monitor a patient’s response to resuscitative efforts. The negative predictive value (NPV) of the physical examination in evaluating for hypovolemia may be helpful, but only when it is taken in the appropriate clinical context and is used in conjunction with other diagnostic tools. The physical examination can exclude hypovolemic volume status with an NPV of approximately 70%.⁷

A constellation of findings from the physical examination may include altered mentation, hypotension, tachycardia, and decreased urinary output by 30% to 40% intravascular volume loss.^8,9Findings from the physical examination to assess fluid status should be used with caution as interobserver reliability has proven to be poor and the prognostic value is limited.

Limitations

The literature shows the limited prognostic value of the physical examination in determining a patient’s volume status and whether fluid resuscitation is indicated. For example, in one meta-analysis,¹⁰ supine hypotension and tachycardia were frequently absent on examination—even in patients who underwent large volume phlebotomy.⁸ This study also showed postural dizziness to be of no prognostic value.

Another study by Saugel et al⁷ that compared the physical examination (skin assessment, lung auscultation, and percussion) to transpulmonary thermodilution measurements of the cardiac index, global end-diastolic volume index, and extravascular lung water index, found poor interobserver correlation and agreement among physicians.

The physical examination is also associated with weak predictive capabilities for the estimation of volume status compared to the device measurements. Another contemporary study by Saugel et al⁹ evaluated the predictive value of the physical examination to accurately identify volume responsiveness replicated these results, and reported poor interobserver correlation (κ coefficient 0.01; 95% caval index [CI] -0.39-0.42) among physical examination findings, with a sensitivity of only 71%, specificity of 23.5%, positive predictive value of 27.8%, and negative predictive value of 66.7%.⁹

Serum Lactate Levels

Background

In the 1843 book titled, Investigations of Pathological Substances Obtained During the Epidemic of Puerperal Fever, Johann Joseph Scherer described the cases of seven young peripartum female patients who died from a clinical picture of what is now understood to be septic shock.¹¹ In his study of these cases, Scherer demonstrated the presence of lactic acid in patients with pathological conditions. Prior to this discovery, lactic acid had never been isolated in a healthy individual. These results were recreated in 1851 by Scherer and Virchow,¹¹ who demonstrated the presence of lactic acid in the blood of a patient who died from leukemia. The inference based on Scherer and Virchow’s work correlated the presence of excessive lactic acid with bodily deterioration and severe disease. Since this finding, there has been a great deal of interest in measuring serum lactic acid as a means to identify and manage critical illness.

In a 2001 groundbreaking study of EGDT for severe sepsis and septic shock, Rivers et al² studied lactic acid levels as a marker for severe disease. Likewise, years later, the 2014 Protocol-Based Care for Early Septic Shock (PROCESS), Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE), and Australasian Resuscitation in Sepsis Evaluation (ARISE) trials used lactate levels in a similar manner to identify patients appropriate for randomization.^12-14 While the purpose of measuring lactic acid was only employed in these studies to identify patients at risk for critical illness, the 2012 Surviving Sepsis Campaign Guidelines recommended serial measurement of lactate, based on the assumption that improved lactate levels signified better tissue perfusion.¹⁵

Although much of the studies on lactate levels appear to be based on the treatment and management of septic patients, findings can be applied to any etiology of shock. For example, a serum lactate level greater than 2 mmol/L is considered abnormal, and a serum lactate greater than 4 mmol/L indicates a significantly increased risk for in-hospital mortality.¹⁶

Benefits

It is now a widely accepted belief that the rapid identification, triage, and treatment of critically ill patients has a dramatic effect on morbidity and mortality.⁴ As previously noted, lactate has been extensively studied and identified as a marker of severe illness.^17,18 A serum lactate level, which can be rapidly processed in the ED, can be easily obtained from a minimally invasive venous, arterial, or capillary blood draw.¹⁸ The only risk associated with serum lactate testing is that of any routine venipuncture; the test causes minimal, if any, patient discomfort.

Thanks to advances in point-of-care (POC) technology, the result of serum lactate assessment can be available within 10 minutes from blood draw. This technology is inexpensive and can be easily deployed in the prehospital setting or during the initial triage assessment of patients arriving at the ED.¹⁹ These POC instruments have been well correlated with whole blood measurements and permit for the rapid identification and treatment of at risk patients.

Limitations

The presence of elevated serum lactate levels is believed to represent the presence of cellular anaerobic metabolism due to impaired O₂ delivery in the shock state. Abnormal measurements therefore prompt aggressive interventions aimed at maximizing O₂ delivery to the tissues, such as intravenous fluid boluses, vasopressor therapy, or even blood product administration.

A return to a normalized serum lactate level is assumed to represent a transition back to aerobic metabolism. Lactate elevations, however, are not solely an indication of anaerobic metabolism and may only represent a small degree of lactate production.²⁰ While the specific cellular mechanics are out of the scope of this article, it has been postulated that the increase in plasma lactate concentration is primarily driven by β-2 receptor stimulation from increased circulating catecholamines leading to increased aerobic glycolysis. Increased lactate levels could therefore be an adaptive mechanism of energy production—aggressive treatment and rapid clearance may, in fact, be harmful. Type A lactic acidosis is categorized as elevated serum levels due to tissue hypoperfusion.²¹

However, lactate elevations do not exclusively occur in severe illness. The use of β-2 receptor agonists such as continuous albuterol treatments or epinephrine may cause abnormal lactate levels.²² Other medications have also been associated with elevated serum lactate levels, including, but not limited to linezolid, metformin, and propofol.^23-25 Additionally, lactate levels may be elevated after strenuous exercise, seizure activity, or in liver and kidney disease.²⁶ These “secondary” causes of lactic acidosis that are not due to tissue hypoperfusion are referred to as type B lactic acidosis. Given these multiple etiologies and lack of specificity for this serum measurement, a failure to understand these limitations may result in over aggressive or unnecessary medical treatments.

Central Venous Pressure

Background

Central venous pressure (CVP) measurements can be obtained through a catheter, the distal tip of which transduces pressure of the superior vena cava at the entrance of the right atrium (RA). Thus, CVP is often used as a representation of RA pressure (RAP) and therefore an estimate of right ventricular (RV) preload. While CVP is used to diagnose and determine the etiology of shock, evidence and controversy regarding the use of CVP as a marker for resuscitation comes largely from sepsis-focused literature.⁵ Central venous pressure is meant to represent preload, which is essential for stroke volume as described by the Frank-Starling mechanism; however, its use as a target in distributive shock, a state in which it is difficult to determine a patient’s volume status, has been popularized by EGDT since 2001.²

Since the publication of the 2004 Surviving Sepsis Guidelines, CVP monitoring has been in the spotlight of sepsis resuscitation, albeit with some controversy.²⁷ Included as the result of two studies, this recommendation has been removed in the most recent guidelines after 12 years of further study and scrutiny.^2,27,28

Hypovolemic and hemorrhagic shock are usually diagnosed clinically and while a low CVP can be helpful in the diagnosis, the guidelines do not support CVP as a resuscitation endpoint. Obstructive and cardiogenic shock will both result in elevated CVP; however, treatment of obstructive shock is generally targeted at the underlying cause. While cardiogenic shock can be preload responsive, the mainstay of therapy in the ED is identification of patients for revascularization and inotropic support.²⁹

Benefits

The CVP has been used as a surrogate for RV preload volume. If a patient’s preload volume is low, the treating physician can administer fluids to improve stroke volume and cardiac output (CO). Clinically, CVP measurements are easy to obtain provided a central venous line has been placed with the distal tip at the entrance to the RA. Central venous pressure is measured by transducing the pressure via manometry and connecting it to the patient’s bedside monitor. This provides an advantage of being able to provide serial or even continuous measurements. The “normal” RAP should be a low value (1-5 mm Hg, mean of 3 mm Hg), as this aids in the pressure gradient to drive blood from the higher pressures of the left ventricle (LV) and aorta through the circulation back to the low-pressure of the RA.³⁰ The value of the CVP is meant to correspond to the physical examination findings of jugular venous distension.^31,32 Thus, a low CVP may be “normal” and seen in patients with hypovolemic shock, whereas an elevated CVP can suggest volume overload or obstructive shock. However, this is of questionable value in distributive shock cases.

Aside from the two early studies on CVP monitoring during treatment of septic patients, there are few data to support the use of CVP measurement in the early resuscitation of patients with shock.^2,28 More recent trials (PROMISE, ARISE, PROCESS) that compared protocolized sepsis care to standard care showed no benefit to bundles including CVP measurements.^12-14 However, a subsequent, large observational trial spanning 7.5 years demonstrated improvements in sepsis-related mortality in patients who received a central venous catheter (CVC) and CVP-targeted therapy.³³ Thus, it is possible that protocols including CVP are still beneficial in combination with other therapies even though CVP in isolation is not.

Limitations

The traditional two assumptions in CVP monitoring are CVP value represents the overall volume status of the patient, and the LV is able to utilize additional preload volume. The latter assumption, however, may be hampered by the presence of sepsis-induced myocardial dysfunction, which may be present in up to 40% of critically ill patients.³⁴ The former assumption does not always hold true due to processes that change filling pressures independent of intravascular volume—eg, acute or chronic pulmonary hypertension, cardiac tamponade, intra-abdominal hypertension, or LV failure. Even before the landmark EGDT study, available data suggested that CVP was not a reliable marker for resuscitation management.³⁵ A recent systematic review by Gottlieb and Hunter³⁶ showed that the area under the receiver-operator curve for low, mid-range, or high CVPs was equivocal at best. In addition to its unreliability and lack of specificity, another significant drawback to using CVP to guide resuscitation therapy in the ED is that it necessitates placement of a CVC, which can be time-consuming and, if not otherwise indicated, lead to complications of infection, pneumothorax, and/or thrombosis.³⁷

Mixed Venous Oxygen

Background

Most EPs are familiar with the use of S_cvO₂ in EGDT protocols to guide volume resuscitation of septic patients.² A patient’s S_cvO₂ represents the O₂ saturation of venous blood obtained via a CVC at the confluence of the superior vena cava and the RA, and thus it reflects tissue O₂ consumption as a surrogate for tissue perfusion. The measurement parallels the S_vO₂ obtained from the pulmonary artery. In a healthy patient, S_vO₂ is around 65% to 70% and includes blood returning from both the superior and inferior vena cava (IVC). As such, S_cvO₂ values are typically 3% to 5% lower than S_vO₂ owing to the lower O₂ extracted by tissues draining into the IVC compared to the mixed venous blood sampled from the pulmonary artery.³⁸

Though a debate over the benefit of EGDT in treating sepsis continues, understanding the physiology of S_cvO₂ measurements is another potential tool the EP can use to guide the resuscitation of critically ill patients.³⁹ A patient’s S_vO₂ and, by extension, S_cvO₂ represents the residual O₂ saturation after the tissues have extracted the amount of O₂ necessary to meet metabolic demands (Figure 2).

Benefits

A critically ill patient’s S_cvO₂ can potentially provide EPs with insight into the patient’s global tissue perfusion and the source of any mismatch between O₂ delivery and consumption. Using additional tools and measurements (physical examination, serum Hgb levels, and pulse oximetry) in conjunction with an S_cvO₂ measurement, assists EPs in identifying targets for therapeutic intervention. The effectiveness of this intervention can then be assessed using serial S_cvO₂ measurements, as described in Rivers et al² EGDT protocol. Importantly, EPs should take care to measure serial S_cvO₂ values to maximize its utility.³⁸ Similar to a CVP measurement, S_cvO₂is easily obtained from blood samples for serial laboratory measurements, assuming the patient already has a CVC with the distal tip at the entrance to the RA (S_cvO₂) or a pulmonary artery catheter (PAC) (S_vO₂).

Limitations

Serial measurements provide the most reliable information, which may be more useful in patients who spend extended periods of their resuscitation in the ED. In comparison to other measures of global tissue hypoxia, work by Jones et al⁴¹ suggests non-inferiority of peripherally sampled, serial lactate measurements as an alternative to S_cvO₂. This, in conjunction with the requirement for an internal jugular CVC, subclavian CVC, or PAC with their associated risks, may make S_cvO₂ a less attractive guide for the resuscitation of critically ill patients in the ED.

Monitoring Devices

Background

As noted throughout this review, it is important not only to identify and rapidly treat shock, but to also correctly identify the type of shock, such that treatment can be appropriately directed at its underlying cause. However, prior work suggests that EPs are unable to grossly estimate CO or systemic vascular resistance when compared to objective measurements of these parameters.⁴² This is in agreement with the overall poor performance of physical examination and clinical evaluation as a means of predicting volume responsiveness or guiding resuscitation, as discussed previously. Fortunately, a wide variety of devices to objectively monitor hemodynamics are now available to the EP.

In 1970, Swan et al⁴³ published their initial experience with pulmonary artery catheterization at the bedside, using a balloon-tipped, flow-guided PAC in lieu of fluoroscopy, which had been mandated by earlier techniques. The ability to measure CO, right heart pressures, pulmonary arterial pressures, and estimate LV end diastolic pressure ushered in an era of widespread PAC use, despite an absence of evidence for causation of improved patient outcomes. The utilization of PACs has fallen, as the literature suggests that the empiric placement of PACs in critically ill patients does not improve mortality, length of stay, or cost, and significant complication rates have been reported in large trials.^44,45Subsequently, a number of non-invasive or less-invasive HDM devices have been developed. Amongst the more commonly encountered modern devices, the techniques utilized for providing hemodynamic assessments include thermodilution and pulse contour analysis (PiCCO^TM), pulse contour analysis (FloTrac/Vigileo^TM), and lithium chemodilution with pulse power analysis (LiDCOplus^TM).⁴⁶ The primary utility of these devices for the EP lies in the ability to quantify CO, stroke volume, and stroke volume or pulse pressure variation (PPV) to predict or assess response to resuscitative interventions (volume administration, vasopressors, inotropes, etc).

Benefits

Many of these devices require placement of an arterial catheter. Some require the addition of a CVC. Both of these procedures are well within the clinical scope of the EP, and are performed with fair frequency on critically ill patients. This is a distinct advantage when compared to pulmonary artery catheterization, a higher risk procedure that is rarely performed outside of the intensive care unit or cardiac catheterization laboratory. In addition, all of the devices below present hemodynamic data in a graphical, easy-to-read format, in real time. All of the devices discussed report stroke volume variation (SVV) or PPV continuously.

Limitations

Though these measures have validated threshold values that predict volume responsiveness, they require the patient to be intubated with a set tidal volume of greater than or equal to 8 mL/kg without spontaneous respirations and cardiac arrhythmias, in order to accurately do so. All of the HDM devices that rely on pulse contour analysis as the primary means of CO measurement cannot be used in the presence of significant cardiac arrhythmias (ie, atrial fibrillation), or mechanical circulatory assistance devices (ie, intra-aortic balloon counterpulsation). None of these devices are capable of monitoring microcirculatory changes, felt to be of increasing clinical importance in the critically ill.

The use of HDM devices to monitor CO with a reasonable degree of accuracy, trend CO, and assess for volume responsiveness using a number of previously validated parameters such as SVV is now in little doubt. However, these devices are still invasive, if less so than a pulmonary artery. The crux of the discussion of HDM devices for use in ED resuscitation revolves around whether or not the use of such devices to drive previously validated, protocolized care results in better outcomes for patients. The EP can now have continuous knowledge of a large number of hemodynamic parameters at their fingertips with relatively minimal additional efforts. At the time of this writing, though, this is both untested and unproven, with respect to the ED population.

Point-of-Care Ultrasound

Background

Over the past two decades, ultrasound (US) has become an integral part of the practice of emergency medicine (EM), and is now included in all United States Accreditation Council for Graduate Medical Education Emergency Medicine Residency Programs.^47,48 It has emerged as a very important bedside tool performed by the clinician to identify type of shock and guide resuscitation, and has been endorsed by both EM and critical care societies.^49-51 This section reviews the utility of US as a modality in identifying shock and guiding resuscitation, in addition to the pitfalls and limitations of this important tool.

In 2010, Perera et al⁴⁷ described in their landmark article the Rapid Ultrasound in SHock (RUSH) examination, which describes a stepwise (the pump, tank, pipes) approach to identify the type of shock (cardiogenic, hypovolemic, obstructive, or distributive) in the crashing, hypotensive ED patient. We do not describe the full RUSH examination in this review, but discuss key elements of it as examples of how POCUS can assist the EP to make a rapid diagnosis and aid in the management of patients in shock. The “pump” is the heart, which is assessed in four different views to identify a pericardial effusion and possible tamponade, assess contractility or ejection fraction of the LV (severely decreased, decreased, normal, or hyperdynamic), and right heart strain which is identified by an RV that is larger than the LV, indicative of a potential pulmonary embolus.

The “tank” is then assessed by visualizing the IVC in the subxiphoid plane, and is evaluated for respiratory collapsibility (CI) and maximum size. This has been quite the debated topic over the last two decades. In 1988, Simonson and Schiller⁵² were the first to describe a correlation in spontaneously breathing patients between IVC caliber (measured 2 cm from the cavoatrial junction) and variation and RAP, where a larger IVC diameter and less respiratory variation correlated with a high RAP. Kircher et al⁵³ later went on to describe that a CI greater than 50% correlated with an RAP of less than 10 mm Hg and vice versa in spontaneously breathing patients. Since then there have been more studies attempting to verify these findings in both spontaneously breathing and mechanically ventilated patients.^54-56 The purpose of performing these measurements is not to estimate CVP, but to assess fluid responsiveness (ie, a blood pressure response to a fluid challenge). It can be assumed in states of shock that a small IVC, or one with a high CI, in the presence of a hyperdynamic heart is indicative of an underfilled ventricle and fluid responsiveness, especially if the IVC size increases with fluid.^55,57 However, there are several caveats to this. First, in mechanically ventilated patients, the IVC is already plethoric due to positive pressure ventilation, and increases in diameter with inspiration and decreases with expiration as compared to spontaneously breathing patients. Second, the CI value to predict volume responsiveness in ventilated patients is set at 15% instead of 50%.⁵⁵ Third, it is important to always take the clinical scenario in context; a dilated IVC with small CI is not necessarily only due to volume overload and congestive heart failure, but can be due to elevated RAP from obstructive shock due to cardiac tamponade or massive pulmonary embolus, which is why it is important to assess the “pump” first.^47,58 It is also crucial to not forget to assess the abdominal and thoracic cavities, as intraperitoneal or pleural fluid with a collapsed IVC can potentially make a diagnosis of hemorrhagic or hypovolemic shock depending on the clinical scenario.⁴⁷ The final part of the RUSH protocol is to evaluate the “pipes,” inclusive of the lower extremity deep venous system for evaluation of potential thrombosis that could increase suspicion for a pulmonary embolism causing obstructive shock, and the aorta with the common iliac arteries if there is concern for aortic dissection or aneurysmal rupture.

Benefits

Some of the most significant advantages to the use of POCUS to guide resuscitation is that it is quick, non-invasive, does not use ionizing radiation, and can be easily repeated. As noted above, it is a requirement for EM residencies to teach its use, so that contemporary graduates are entering the specialty competent in applying it to the care of their patients. Furthermore, POCUS is done at the bedside, limiting the need to potentially transport unstable patients.

In the most basic applications, POCUS provides direct visualization of a patient’s cardiac function, presence or absence of lung sliding to suggest a pneumothorax, presence of pulmonary edema, assessment of CVP pressures or potential for fluid responsiveness, as well as identification of potential thoracic, peritoneal, or pelvic cavity fluid accumulation that may suggest hemorrhage. There is literature to support that these assessments performed by the EP have been shown to be comparable to those of cardiologists.^59,60 With continued practice and additional training, it is possible for EPs to even perform more “advanced” hemodynamic assessments to both diagnose and guide therapy to patients in shock (Figures 3 and 4).⁶¹

Limitations

Although POCUS has been shown as a remarkable tool to help assist the EP in making rapid decisions regarding resuscitation, it is always important to remember its limitations. Most of the studies regarding its use are of very small sample sizes, and further prospective studies have to be performed in order for this modality to be fully relied on.⁶²Compared to some of the previously mentioned HDM devices that may provide continuous data, POCUS needs to be performed by the treating physician, thereby occurring intermittently. Emergency physicians need to be aware of their own experience and limitations with this modality, as errors in misdiagnosis can lead to unnecessary procedures, with resulting significant morbidity and mortality. Blanco and Volpicelli⁶³ describe several common errors that include misdiagnosing the stomach as a peritoneal effusion, assuming adequate volume resuscitation when the IVC is seen to be plethoric in the setting of cardiac tamponade, or mistaking IVC movement as indicative of collapsibility, amongst other described misinterpretations. Several other studies have shown that, despite adequate performance of EPs in POCUS, diagnostic sensitivities remained higher when performed by radiologists.^64-67 Thus it remains important for the EPs to be vigilant and not anchor on a diagnosis when in doubt, and to consult early with radiology, particularly if there is any question, to avoid potential adverse patient outcomes.

Summary

There are several ways to diagnose and track resuscitation in the ED, which include physical examination, assessment of serum laboratory values, monitoring of hemodynamic status, and use of POCUS. Unfortunately, none of these methods provides a perfect assessment, and no method has been proven superior and effective over the others. Therefore, it is important for EPs treating patients in shock to be aware of the strengths and limitations of each assessment method (Table).

Resuscitation of critically ill patients in shock from cardiogenic, hypovolemic, obstructive, distributive, or neurogenic etiology is a cornerstone of the care delivered by emergency physicians (EPs).¹ Regardless of the etiology, it is essential that the treating EP initiate resuscitative measures in a timely manner and closely trend the patient’s response to these interventions.

The early goal-directed therapy (EGDT) initially proposed by Rivers et al² in 2001 demonstrated a bundled approach to fluid resuscitation by targeting end points for volume resuscitation, mean arterial blood pressure (MAP), oxygen (O₂) delivery/extraction (mixed venous O₂ saturation, [S_vO₂]), hemoglobin (Hgb) concentration, and cardiac contractility. Since then, advancements in laboratory testing and hemodynamic monitoring (HDM) devices further aid and guide resuscitative efforts, and are applicable to any etiology of shock.

In addition to these advancements, the growing evidence of the potential harm from improper fluid resuscitation, such as the administration of excessive intravascular fluid (IVF),³ underscores the importance of a precise, targeted, and individualized approach to care. This article reviews the background, benefits, and limitations of some of the common and readily available tools in the ED that the EP can employ to guide fluid resuscitation in critically ill patients.

Physical Examination

Background

The rapid recognition and treatment of septic shock in the ED is associated with lower rates of in-hospital morbidity and mortality.⁴ The physical examination by the EP begins immediately upon examining the patient. The acquisition of vital signs and recognition of physical examination findings suggestive of intravascular volume depletion allows the EP to initiate treatment immediately.

In this discussion, hypotension is defined as systolic blood pressure (SBP) of less than 95 mm Hg, MAP of less than 65 mm Hg, or a decrease in SBP of more than 40 mm Hg from baseline measurements. Subsequently, shock is defined as hypotension with evidence of tissue hypoperfusion-induced dysfunction.^5,6 Although the use of findings from the physical examination to guide resuscitation allows for rapid patient assessment and treatment, the predictive value of the physical examination to assess hemodynamic status is limited.

Benefits

The major benefit of the physical examination as a tool to evaluate hemodynamic status is its ease and rapid acquisition. The patient’s vital signs and physical examination can be obtained in the matter of moments upon presentation, without the need to wait on results of laboratory evaluation or additional equipment. Additionally, serial examinations by the same physician can be helpful to monitor a patient’s response to resuscitative efforts. The negative predictive value (NPV) of the physical examination in evaluating for hypovolemia may be helpful, but only when it is taken in the appropriate clinical context and is used in conjunction with other diagnostic tools. The physical examination can exclude hypovolemic volume status with an NPV of approximately 70%.⁷

A constellation of findings from the physical examination may include altered mentation, hypotension, tachycardia, and decreased urinary output by 30% to 40% intravascular volume loss.^8,9Findings from the physical examination to assess fluid status should be used with caution as interobserver reliability has proven to be poor and the prognostic value is limited.

Limitations

The literature shows the limited prognostic value of the physical examination in determining a patient’s volume status and whether fluid resuscitation is indicated. For example, in one meta-analysis,¹⁰ supine hypotension and tachycardia were frequently absent on examination—even in patients who underwent large volume phlebotomy.⁸ This study also showed postural dizziness to be of no prognostic value.

Another study by Saugel et al⁷ that compared the physical examination (skin assessment, lung auscultation, and percussion) to transpulmonary thermodilution measurements of the cardiac index, global end-diastolic volume index, and extravascular lung water index, found poor interobserver correlation and agreement among physicians.

The physical examination is also associated with weak predictive capabilities for the estimation of volume status compared to the device measurements. Another contemporary study by Saugel et al⁹ evaluated the predictive value of the physical examination to accurately identify volume responsiveness replicated these results, and reported poor interobserver correlation (κ coefficient 0.01; 95% caval index [CI] -0.39-0.42) among physical examination findings, with a sensitivity of only 71%, specificity of 23.5%, positive predictive value of 27.8%, and negative predictive value of 66.7%.⁹

Serum Lactate Levels

Background

In the 1843 book titled, Investigations of Pathological Substances Obtained During the Epidemic of Puerperal Fever, Johann Joseph Scherer described the cases of seven young peripartum female patients who died from a clinical picture of what is now understood to be septic shock.¹¹ In his study of these cases, Scherer demonstrated the presence of lactic acid in patients with pathological conditions. Prior to this discovery, lactic acid had never been isolated in a healthy individual. These results were recreated in 1851 by Scherer and Virchow,¹¹ who demonstrated the presence of lactic acid in the blood of a patient who died from leukemia. The inference based on Scherer and Virchow’s work correlated the presence of excessive lactic acid with bodily deterioration and severe disease. Since this finding, there has been a great deal of interest in measuring serum lactic acid as a means to identify and manage critical illness.

In a 2001 groundbreaking study of EGDT for severe sepsis and septic shock, Rivers et al² studied lactic acid levels as a marker for severe disease. Likewise, years later, the 2014 Protocol-Based Care for Early Septic Shock (PROCESS), Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE), and Australasian Resuscitation in Sepsis Evaluation (ARISE) trials used lactate levels in a similar manner to identify patients appropriate for randomization.^12-14 While the purpose of measuring lactic acid was only employed in these studies to identify patients at risk for critical illness, the 2012 Surviving Sepsis Campaign Guidelines recommended serial measurement of lactate, based on the assumption that improved lactate levels signified better tissue perfusion.¹⁵

Although much of the studies on lactate levels appear to be based on the treatment and management of septic patients, findings can be applied to any etiology of shock. For example, a serum lactate level greater than 2 mmol/L is considered abnormal, and a serum lactate greater than 4 mmol/L indicates a significantly increased risk for in-hospital mortality.¹⁶

Benefits

It is now a widely accepted belief that the rapid identification, triage, and treatment of critically ill patients has a dramatic effect on morbidity and mortality.⁴ As previously noted, lactate has been extensively studied and identified as a marker of severe illness.^17,18 A serum lactate level, which can be rapidly processed in the ED, can be easily obtained from a minimally invasive venous, arterial, or capillary blood draw.¹⁸ The only risk associated with serum lactate testing is that of any routine venipuncture; the test causes minimal, if any, patient discomfort.

Thanks to advances in point-of-care (POC) technology, the result of serum lactate assessment can be available within 10 minutes from blood draw. This technology is inexpensive and can be easily deployed in the prehospital setting or during the initial triage assessment of patients arriving at the ED.¹⁹ These POC instruments have been well correlated with whole blood measurements and permit for the rapid identification and treatment of at risk patients.

Limitations

The presence of elevated serum lactate levels is believed to represent the presence of cellular anaerobic metabolism due to impaired O₂ delivery in the shock state. Abnormal measurements therefore prompt aggressive interventions aimed at maximizing O₂ delivery to the tissues, such as intravenous fluid boluses, vasopressor therapy, or even blood product administration.

A return to a normalized serum lactate level is assumed to represent a transition back to aerobic metabolism. Lactate elevations, however, are not solely an indication of anaerobic metabolism and may only represent a small degree of lactate production.²⁰ While the specific cellular mechanics are out of the scope of this article, it has been postulated that the increase in plasma lactate concentration is primarily driven by β-2 receptor stimulation from increased circulating catecholamines leading to increased aerobic glycolysis. Increased lactate levels could therefore be an adaptive mechanism of energy production—aggressive treatment and rapid clearance may, in fact, be harmful. Type A lactic acidosis is categorized as elevated serum levels due to tissue hypoperfusion.²¹

However, lactate elevations do not exclusively occur in severe illness. The use of β-2 receptor agonists such as continuous albuterol treatments or epinephrine may cause abnormal lactate levels.²² Other medications have also been associated with elevated serum lactate levels, including, but not limited to linezolid, metformin, and propofol.^23-25 Additionally, lactate levels may be elevated after strenuous exercise, seizure activity, or in liver and kidney disease.²⁶ These “secondary” causes of lactic acidosis that are not due to tissue hypoperfusion are referred to as type B lactic acidosis. Given these multiple etiologies and lack of specificity for this serum measurement, a failure to understand these limitations may result in over aggressive or unnecessary medical treatments.

Central Venous Pressure

Background

Central venous pressure (CVP) measurements can be obtained through a catheter, the distal tip of which transduces pressure of the superior vena cava at the entrance of the right atrium (RA). Thus, CVP is often used as a representation of RA pressure (RAP) and therefore an estimate of right ventricular (RV) preload. While CVP is used to diagnose and determine the etiology of shock, evidence and controversy regarding the use of CVP as a marker for resuscitation comes largely from sepsis-focused literature.⁵ Central venous pressure is meant to represent preload, which is essential for stroke volume as described by the Frank-Starling mechanism; however, its use as a target in distributive shock, a state in which it is difficult to determine a patient’s volume status, has been popularized by EGDT since 2001.²

Since the publication of the 2004 Surviving Sepsis Guidelines, CVP monitoring has been in the spotlight of sepsis resuscitation, albeit with some controversy.²⁷ Included as the result of two studies, this recommendation has been removed in the most recent guidelines after 12 years of further study and scrutiny.^2,27,28

Hypovolemic and hemorrhagic shock are usually diagnosed clinically and while a low CVP can be helpful in the diagnosis, the guidelines do not support CVP as a resuscitation endpoint. Obstructive and cardiogenic shock will both result in elevated CVP; however, treatment of obstructive shock is generally targeted at the underlying cause. While cardiogenic shock can be preload responsive, the mainstay of therapy in the ED is identification of patients for revascularization and inotropic support.²⁹

Benefits

The CVP has been used as a surrogate for RV preload volume. If a patient’s preload volume is low, the treating physician can administer fluids to improve stroke volume and cardiac output (CO). Clinically, CVP measurements are easy to obtain provided a central venous line has been placed with the distal tip at the entrance to the RA. Central venous pressure is measured by transducing the pressure via manometry and connecting it to the patient’s bedside monitor. This provides an advantage of being able to provide serial or even continuous measurements. The “normal” RAP should be a low value (1-5 mm Hg, mean of 3 mm Hg), as this aids in the pressure gradient to drive blood from the higher pressures of the left ventricle (LV) and aorta through the circulation back to the low-pressure of the RA.³⁰ The value of the CVP is meant to correspond to the physical examination findings of jugular venous distension.^31,32 Thus, a low CVP may be “normal” and seen in patients with hypovolemic shock, whereas an elevated CVP can suggest volume overload or obstructive shock. However, this is of questionable value in distributive shock cases.

Aside from the two early studies on CVP monitoring during treatment of septic patients, there are few data to support the use of CVP measurement in the early resuscitation of patients with shock.^2,28 More recent trials (PROMISE, ARISE, PROCESS) that compared protocolized sepsis care to standard care showed no benefit to bundles including CVP measurements.^12-14 However, a subsequent, large observational trial spanning 7.5 years demonstrated improvements in sepsis-related mortality in patients who received a central venous catheter (CVC) and CVP-targeted therapy.³³ Thus, it is possible that protocols including CVP are still beneficial in combination with other therapies even though CVP in isolation is not.

Limitations

The traditional two assumptions in CVP monitoring are CVP value represents the overall volume status of the patient, and the LV is able to utilize additional preload volume. The latter assumption, however, may be hampered by the presence of sepsis-induced myocardial dysfunction, which may be present in up to 40% of critically ill patients.³⁴ The former assumption does not always hold true due to processes that change filling pressures independent of intravascular volume—eg, acute or chronic pulmonary hypertension, cardiac tamponade, intra-abdominal hypertension, or LV failure. Even before the landmark EGDT study, available data suggested that CVP was not a reliable marker for resuscitation management.³⁵ A recent systematic review by Gottlieb and Hunter³⁶ showed that the area under the receiver-operator curve for low, mid-range, or high CVPs was equivocal at best. In addition to its unreliability and lack of specificity, another significant drawback to using CVP to guide resuscitation therapy in the ED is that it necessitates placement of a CVC, which can be time-consuming and, if not otherwise indicated, lead to complications of infection, pneumothorax, and/or thrombosis.³⁷

Mixed Venous Oxygen

Background

Most EPs are familiar with the use of S_cvO₂ in EGDT protocols to guide volume resuscitation of septic patients.² A patient’s S_cvO₂ represents the O₂ saturation of venous blood obtained via a CVC at the confluence of the superior vena cava and the RA, and thus it reflects tissue O₂ consumption as a surrogate for tissue perfusion. The measurement parallels the S_vO₂ obtained from the pulmonary artery. In a healthy patient, S_vO₂ is around 65% to 70% and includes blood returning from both the superior and inferior vena cava (IVC). As such, S_cvO₂ values are typically 3% to 5% lower than S_vO₂ owing to the lower O₂ extracted by tissues draining into the IVC compared to the mixed venous blood sampled from the pulmonary artery.³⁸

Though a debate over the benefit of EGDT in treating sepsis continues, understanding the physiology of S_cvO₂ measurements is another potential tool the EP can use to guide the resuscitation of critically ill patients.³⁹ A patient’s S_vO₂ and, by extension, S_cvO₂ represents the residual O₂ saturation after the tissues have extracted the amount of O₂ necessary to meet metabolic demands (Figure 2).

Benefits

A critically ill patient’s S_cvO₂ can potentially provide EPs with insight into the patient’s global tissue perfusion and the source of any mismatch between O₂ delivery and consumption. Using additional tools and measurements (physical examination, serum Hgb levels, and pulse oximetry) in conjunction with an S_cvO₂ measurement, assists EPs in identifying targets for therapeutic intervention. The effectiveness of this intervention can then be assessed using serial S_cvO₂ measurements, as described in Rivers et al² EGDT protocol. Importantly, EPs should take care to measure serial S_cvO₂ values to maximize its utility.³⁸ Similar to a CVP measurement, S_cvO₂is easily obtained from blood samples for serial laboratory measurements, assuming the patient already has a CVC with the distal tip at the entrance to the RA (S_cvO₂) or a pulmonary artery catheter (PAC) (S_vO₂).

Limitations

Serial measurements provide the most reliable information, which may be more useful in patients who spend extended periods of their resuscitation in the ED. In comparison to other measures of global tissue hypoxia, work by Jones et al⁴¹ suggests non-inferiority of peripherally sampled, serial lactate measurements as an alternative to S_cvO₂. This, in conjunction with the requirement for an internal jugular CVC, subclavian CVC, or PAC with their associated risks, may make S_cvO₂ a less attractive guide for the resuscitation of critically ill patients in the ED.

Monitoring Devices

Background

As noted throughout this review, it is important not only to identify and rapidly treat shock, but to also correctly identify the type of shock, such that treatment can be appropriately directed at its underlying cause. However, prior work suggests that EPs are unable to grossly estimate CO or systemic vascular resistance when compared to objective measurements of these parameters.⁴² This is in agreement with the overall poor performance of physical examination and clinical evaluation as a means of predicting volume responsiveness or guiding resuscitation, as discussed previously. Fortunately, a wide variety of devices to objectively monitor hemodynamics are now available to the EP.

In 1970, Swan et al⁴³ published their initial experience with pulmonary artery catheterization at the bedside, using a balloon-tipped, flow-guided PAC in lieu of fluoroscopy, which had been mandated by earlier techniques. The ability to measure CO, right heart pressures, pulmonary arterial pressures, and estimate LV end diastolic pressure ushered in an era of widespread PAC use, despite an absence of evidence for causation of improved patient outcomes. The utilization of PACs has fallen, as the literature suggests that the empiric placement of PACs in critically ill patients does not improve mortality, length of stay, or cost, and significant complication rates have been reported in large trials.^44,45Subsequently, a number of non-invasive or less-invasive HDM devices have been developed. Amongst the more commonly encountered modern devices, the techniques utilized for providing hemodynamic assessments include thermodilution and pulse contour analysis (PiCCO^TM), pulse contour analysis (FloTrac/Vigileo^TM), and lithium chemodilution with pulse power analysis (LiDCOplus^TM).⁴⁶ The primary utility of these devices for the EP lies in the ability to quantify CO, stroke volume, and stroke volume or pulse pressure variation (PPV) to predict or assess response to resuscitative interventions (volume administration, vasopressors, inotropes, etc).

Benefits

Many of these devices require placement of an arterial catheter. Some require the addition of a CVC. Both of these procedures are well within the clinical scope of the EP, and are performed with fair frequency on critically ill patients. This is a distinct advantage when compared to pulmonary artery catheterization, a higher risk procedure that is rarely performed outside of the intensive care unit or cardiac catheterization laboratory. In addition, all of the devices below present hemodynamic data in a graphical, easy-to-read format, in real time. All of the devices discussed report stroke volume variation (SVV) or PPV continuously.

Limitations

Though these measures have validated threshold values that predict volume responsiveness, they require the patient to be intubated with a set tidal volume of greater than or equal to 8 mL/kg without spontaneous respirations and cardiac arrhythmias, in order to accurately do so. All of the HDM devices that rely on pulse contour analysis as the primary means of CO measurement cannot be used in the presence of significant cardiac arrhythmias (ie, atrial fibrillation), or mechanical circulatory assistance devices (ie, intra-aortic balloon counterpulsation). None of these devices are capable of monitoring microcirculatory changes, felt to be of increasing clinical importance in the critically ill.

The use of HDM devices to monitor CO with a reasonable degree of accuracy, trend CO, and assess for volume responsiveness using a number of previously validated parameters such as SVV is now in little doubt. However, these devices are still invasive, if less so than a pulmonary artery. The crux of the discussion of HDM devices for use in ED resuscitation revolves around whether or not the use of such devices to drive previously validated, protocolized care results in better outcomes for patients. The EP can now have continuous knowledge of a large number of hemodynamic parameters at their fingertips with relatively minimal additional efforts. At the time of this writing, though, this is both untested and unproven, with respect to the ED population.

Point-of-Care Ultrasound

Background

Over the past two decades, ultrasound (US) has become an integral part of the practice of emergency medicine (EM), and is now included in all United States Accreditation Council for Graduate Medical Education Emergency Medicine Residency Programs.^47,48 It has emerged as a very important bedside tool performed by the clinician to identify type of shock and guide resuscitation, and has been endorsed by both EM and critical care societies.^49-51 This section reviews the utility of US as a modality in identifying shock and guiding resuscitation, in addition to the pitfalls and limitations of this important tool.

In 2010, Perera et al⁴⁷ described in their landmark article the Rapid Ultrasound in SHock (RUSH) examination, which describes a stepwise (the pump, tank, pipes) approach to identify the type of shock (cardiogenic, hypovolemic, obstructive, or distributive) in the crashing, hypotensive ED patient. We do not describe the full RUSH examination in this review, but discuss key elements of it as examples of how POCUS can assist the EP to make a rapid diagnosis and aid in the management of patients in shock. The “pump” is the heart, which is assessed in four different views to identify a pericardial effusion and possible tamponade, assess contractility or ejection fraction of the LV (severely decreased, decreased, normal, or hyperdynamic), and right heart strain which is identified by an RV that is larger than the LV, indicative of a potential pulmonary embolus.

The “tank” is then assessed by visualizing the IVC in the subxiphoid plane, and is evaluated for respiratory collapsibility (CI) and maximum size. This has been quite the debated topic over the last two decades. In 1988, Simonson and Schiller⁵² were the first to describe a correlation in spontaneously breathing patients between IVC caliber (measured 2 cm from the cavoatrial junction) and variation and RAP, where a larger IVC diameter and less respiratory variation correlated with a high RAP. Kircher et al⁵³ later went on to describe that a CI greater than 50% correlated with an RAP of less than 10 mm Hg and vice versa in spontaneously breathing patients. Since then there have been more studies attempting to verify these findings in both spontaneously breathing and mechanically ventilated patients.^54-56 The purpose of performing these measurements is not to estimate CVP, but to assess fluid responsiveness (ie, a blood pressure response to a fluid challenge). It can be assumed in states of shock that a small IVC, or one with a high CI, in the presence of a hyperdynamic heart is indicative of an underfilled ventricle and fluid responsiveness, especially if the IVC size increases with fluid.^55,57 However, there are several caveats to this. First, in mechanically ventilated patients, the IVC is already plethoric due to positive pressure ventilation, and increases in diameter with inspiration and decreases with expiration as compared to spontaneously breathing patients. Second, the CI value to predict volume responsiveness in ventilated patients is set at 15% instead of 50%.⁵⁵ Third, it is important to always take the clinical scenario in context; a dilated IVC with small CI is not necessarily only due to volume overload and congestive heart failure, but can be due to elevated RAP from obstructive shock due to cardiac tamponade or massive pulmonary embolus, which is why it is important to assess the “pump” first.^47,58 It is also crucial to not forget to assess the abdominal and thoracic cavities, as intraperitoneal or pleural fluid with a collapsed IVC can potentially make a diagnosis of hemorrhagic or hypovolemic shock depending on the clinical scenario.⁴⁷ The final part of the RUSH protocol is to evaluate the “pipes,” inclusive of the lower extremity deep venous system for evaluation of potential thrombosis that could increase suspicion for a pulmonary embolism causing obstructive shock, and the aorta with the common iliac arteries if there is concern for aortic dissection or aneurysmal rupture.

Benefits

Some of the most significant advantages to the use of POCUS to guide resuscitation is that it is quick, non-invasive, does not use ionizing radiation, and can be easily repeated. As noted above, it is a requirement for EM residencies to teach its use, so that contemporary graduates are entering the specialty competent in applying it to the care of their patients. Furthermore, POCUS is done at the bedside, limiting the need to potentially transport unstable patients.

In the most basic applications, POCUS provides direct visualization of a patient’s cardiac function, presence or absence of lung sliding to suggest a pneumothorax, presence of pulmonary edema, assessment of CVP pressures or potential for fluid responsiveness, as well as identification of potential thoracic, peritoneal, or pelvic cavity fluid accumulation that may suggest hemorrhage. There is literature to support that these assessments performed by the EP have been shown to be comparable to those of cardiologists.^59,60 With continued practice and additional training, it is possible for EPs to even perform more “advanced” hemodynamic assessments to both diagnose and guide therapy to patients in shock (Figures 3 and 4).⁶¹

Limitations

Although POCUS has been shown as a remarkable tool to help assist the EP in making rapid decisions regarding resuscitation, it is always important to remember its limitations. Most of the studies regarding its use are of very small sample sizes, and further prospective studies have to be performed in order for this modality to be fully relied on.⁶²Compared to some of the previously mentioned HDM devices that may provide continuous data, POCUS needs to be performed by the treating physician, thereby occurring intermittently. Emergency physicians need to be aware of their own experience and limitations with this modality, as errors in misdiagnosis can lead to unnecessary procedures, with resulting significant morbidity and mortality. Blanco and Volpicelli⁶³ describe several common errors that include misdiagnosing the stomach as a peritoneal effusion, assuming adequate volume resuscitation when the IVC is seen to be plethoric in the setting of cardiac tamponade, or mistaking IVC movement as indicative of collapsibility, amongst other described misinterpretations. Several other studies have shown that, despite adequate performance of EPs in POCUS, diagnostic sensitivities remained higher when performed by radiologists.^64-67 Thus it remains important for the EPs to be vigilant and not anchor on a diagnosis when in doubt, and to consult early with radiology, particularly if there is any question, to avoid potential adverse patient outcomes.

Summary

There are several ways to diagnose and track resuscitation in the ED, which include physical examination, assessment of serum laboratory values, monitoring of hemodynamic status, and use of POCUS. Unfortunately, none of these methods provides a perfect assessment, and no method has been proven superior and effective over the others. Therefore, it is important for EPs treating patients in shock to be aware of the strengths and limitations of each assessment method (Table).

A national shortage of norepinephrine in the United States was associated with higher rates of mortality among patients hospitalized with septic shock, investigators reported.

Rates of in-hospital mortality in 2011 were 40% during quarters when hospitals were facing shortages and 36% when they were not, Emily Vail, MD, and her associates said at the International Symposium on Intensive Care and Emergency Medicine. The report was published simultaneously in JAMA.

The link between norepinephrine shortage and death from septic shock persisted even after the researchers accounted for numerous clinical and demographic factors (adjusted odds ratio, 1.2; 95% confidence interval, 1.01 to 1.30; P = .03), wrote Dr. Vail of Columbia University, New York (JAMA. 2017 Mar 21. doi: 10.1001/jama.2017.2841).

Drug shortages are common in the United States, but few studies have explored their effects on patient outcomes. Investigators compared mortality rates among affected patients during 3-month intervals when hospitals were and were not using at least 20% less norepinephrine than baseline. The researchers used Premier Healthcare Database, which includes both standard claims and detailed, dated logs of all services billed to patients or insurance, with minimal missing data.

A total of 77% patients admitted with septic shock received norepinephrine before the shortage. During the lowest point of the shortage, 56% of patients received it, the researchers reported. Clinicians most often used phenylephrine instead, prescribing it to up to 54% of patients during the worst time of the shortage. The absolute increase in mortality during the quarters of shortage was 3.7% (95% CI, 1.5%-6.0%).

Several factors might explain the link between norepinephrine shortage and mortality, said the investigators. The vasopressors chosen to replace norepinephrine might result directly in worse outcomes, but a decrease in norepinephrine use also might be a proxy for relevant variables such as delayed use of vasopressors, lack of knowledge of how to optimally dose vasopressors besides norepinephrine, or the absence of a pharmacist dedicated to helping optimize the use of limited supplies.

The study did not uncover a dose-response association between greater decreases in norepinephrine use and increased mortality, the researchers noted. “This may be due to a threshold effect of vasopressor shortage on mortality, or lack of power due to relatively few hospital quarters at the extreme levels of vasopressor shortage,” they wrote.

Because the deaths captured included only those that occurred in-hospital, “the results may have underestimated mortality, particularly for hospitals that tend transfer patients early to other skilled care facilities,” the researchers noted.

The cohort of patients was limited to those who received vasopressors for 2 or more days and excluded patients who died on the first day of vasopressor treatment, the researchers said.

The Herbert and Florence Irving Scholars Program at Columbia University provided funding. One coinvestigator disclosed grant funding from the National Institutes of Health and personal fees from UpToDate. The other investigators reported having no conflicts of interest.

A national shortage of norepinephrine in the United States was associated with higher rates of mortality among patients hospitalized with septic shock, investigators reported.

Rates of in-hospital mortality in 2011 were 40% during quarters when hospitals were facing shortages and 36% when they were not, Emily Vail, MD, and her associates said at the International Symposium on Intensive Care and Emergency Medicine. The report was published simultaneously in JAMA.

The link between norepinephrine shortage and death from septic shock persisted even after the researchers accounted for numerous clinical and demographic factors (adjusted odds ratio, 1.2; 95% confidence interval, 1.01 to 1.30; P = .03), wrote Dr. Vail of Columbia University, New York (JAMA. 2017 Mar 21. doi: 10.1001/jama.2017.2841).

Drug shortages are common in the United States, but few studies have explored their effects on patient outcomes. Investigators compared mortality rates among affected patients during 3-month intervals when hospitals were and were not using at least 20% less norepinephrine than baseline. The researchers used Premier Healthcare Database, which includes both standard claims and detailed, dated logs of all services billed to patients or insurance, with minimal missing data.

A total of 77% patients admitted with septic shock received norepinephrine before the shortage. During the lowest point of the shortage, 56% of patients received it, the researchers reported. Clinicians most often used phenylephrine instead, prescribing it to up to 54% of patients during the worst time of the shortage. The absolute increase in mortality during the quarters of shortage was 3.7% (95% CI, 1.5%-6.0%).

Several factors might explain the link between norepinephrine shortage and mortality, said the investigators. The vasopressors chosen to replace norepinephrine might result directly in worse outcomes, but a decrease in norepinephrine use also might be a proxy for relevant variables such as delayed use of vasopressors, lack of knowledge of how to optimally dose vasopressors besides norepinephrine, or the absence of a pharmacist dedicated to helping optimize the use of limited supplies.

The study did not uncover a dose-response association between greater decreases in norepinephrine use and increased mortality, the researchers noted. “This may be due to a threshold effect of vasopressor shortage on mortality, or lack of power due to relatively few hospital quarters at the extreme levels of vasopressor shortage,” they wrote.

Because the deaths captured included only those that occurred in-hospital, “the results may have underestimated mortality, particularly for hospitals that tend transfer patients early to other skilled care facilities,” the researchers noted.

The cohort of patients was limited to those who received vasopressors for 2 or more days and excluded patients who died on the first day of vasopressor treatment, the researchers said.

The Herbert and Florence Irving Scholars Program at Columbia University provided funding. One coinvestigator disclosed grant funding from the National Institutes of Health and personal fees from UpToDate. The other investigators reported having no conflicts of interest.

A national shortage of norepinephrine in the United States was associated with higher rates of mortality among patients hospitalized with septic shock, investigators reported.

Rates of in-hospital mortality in 2011 were 40% during quarters when hospitals were facing shortages and 36% when they were not, Emily Vail, MD, and her associates said at the International Symposium on Intensive Care and Emergency Medicine. The report was published simultaneously in JAMA.

The link between norepinephrine shortage and death from septic shock persisted even after the researchers accounted for numerous clinical and demographic factors (adjusted odds ratio, 1.2; 95% confidence interval, 1.01 to 1.30; P = .03), wrote Dr. Vail of Columbia University, New York (JAMA. 2017 Mar 21. doi: 10.1001/jama.2017.2841).

Drug shortages are common in the United States, but few studies have explored their effects on patient outcomes. Investigators compared mortality rates among affected patients during 3-month intervals when hospitals were and were not using at least 20% less norepinephrine than baseline. The researchers used Premier Healthcare Database, which includes both standard claims and detailed, dated logs of all services billed to patients or insurance, with minimal missing data.

A total of 77% patients admitted with septic shock received norepinephrine before the shortage. During the lowest point of the shortage, 56% of patients received it, the researchers reported. Clinicians most often used phenylephrine instead, prescribing it to up to 54% of patients during the worst time of the shortage. The absolute increase in mortality during the quarters of shortage was 3.7% (95% CI, 1.5%-6.0%).

Several factors might explain the link between norepinephrine shortage and mortality, said the investigators. The vasopressors chosen to replace norepinephrine might result directly in worse outcomes, but a decrease in norepinephrine use also might be a proxy for relevant variables such as delayed use of vasopressors, lack of knowledge of how to optimally dose vasopressors besides norepinephrine, or the absence of a pharmacist dedicated to helping optimize the use of limited supplies.

The study did not uncover a dose-response association between greater decreases in norepinephrine use and increased mortality, the researchers noted. “This may be due to a threshold effect of vasopressor shortage on mortality, or lack of power due to relatively few hospital quarters at the extreme levels of vasopressor shortage,” they wrote.

Because the deaths captured included only those that occurred in-hospital, “the results may have underestimated mortality, particularly for hospitals that tend transfer patients early to other skilled care facilities,” the researchers noted.

The cohort of patients was limited to those who received vasopressors for 2 or more days and excluded patients who died on the first day of vasopressor treatment, the researchers said.

The Herbert and Florence Irving Scholars Program at Columbia University provided funding. One coinvestigator disclosed grant funding from the National Institutes of Health and personal fees from UpToDate. The other investigators reported having no conflicts of interest.