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Maternal Exercise and Its Effect on the Development of High-Altitude Pulmonary Hypertension in Children

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by Julia Wu, PA-S

Every newborn I have managed while rotating at Ebert Family Clinic in Frisco, Colorado at 9000′ has needed oxygen supplementation. It is known that at high altitudes, there is a lower oxygen concentration in the air, which poses challenges to our bodies. What exactly happens, and what are the consequences of chronic high-altitude exposure? There are approximately 140 million people that live at high altitudes, defined as at least 2500 meters above sea level, who are affected by chronic hypoxic conditions.1 In this article, I will focus on how hypoxia — low levels of oxygen in the blood — affects pregnant women, alters fetal to newborn transition and development, and whether cardiorespiratory exercise by mothers during pregnancy can prevent diseases such as high-altitude pulmonary hypertension (HAPH) development in offspring.  

Pulmonary hypertension (PH) is abnormally high blood pressure in the pulmonary arteries. PH is classified into 5 groups based on the cause. High-altitude pulmonary hypertension (HAPH) is Group III PH and defined as mean pulmonary arterial pressure (PAP) ≥25 mm Hg. Chronic high-altitude hypoxia can lead to the development of HAPH, which has adverse effects on the heart from right ventricular wall thickening to reduced cardiac output, and eventual right heart failure and death. HAPH can occur in utero, so it’s imperative to understand how hypoxia affects mothers and their fetuses during and after birth.2

During pregnancy, the fetus doesn’t breathe air and the lungs are not used. The fetus receives all its oxygen and nutrition needs from the mother’s blood, which flows through the blood vessels in the umbilical cord to the placenta and then to the baby.3 Circulating blood bypasses the lungs by flowing in different pathways through openings called shunts that close at birth to allow for adult circulation. In utero, the baby’s lungs fill with a special fluid that helps the lungs grow.4 The fluid in the lungs, in combination with naturally thicker pulmonary vascular and pulmonary vessel vasoconstriction from low PO2, causes higher vascular resistance in pulmonary circulation that allows for the diversion of blood away from the lungs through the shunts.2 At low altitudes, in the first few days after birth, the high PAP in the lungs drops. The sharp drop in PAP is due to “expansion of the lungs, pulmonary vasodilation from higher PO2, a gradual receding of fluid, a thinning of pulmonary vascular smooth muscle, and… closing of the [shunts]”. This process is known as cardiopulmonary transition. However, at altitude, perinatal hypoxia negatively affects cardiopulmonary transition. The elevated pressures in the pulmonary arteries and vascular resistance persist into early childhood delaying cardiopulmonary transition, which can have developmental consequences such as HAPH and right heart failure, as discussed.

It was discovered that cardiopulmonary transition delay is linked to a high-altitude hypoxia-induced proinflammatory state within the pulmonary vasculature that leads to pulmonary artery remodeling and HAPH. Hypoxia activates or upregulates transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NK-kB), that signals for inflammatory mediators such as hypoxia-inducible factors (HIF). HIF-1a inhibits mammalian target of rapamycin (mTOR). mTOR signaling has an important role in cell metabolism, cell proliferation, and survival, thus inhibiting mTOR prevents “non-proliferative branching and elongation of conducting airways and fluid removal from the lungs,” which contributes to increases in pulmonary vascular resistance and lung development during the cardiopulmonary transition and the onset of newborn gas exchange. 2,5 HIF also contributes to the uncontrolled proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMC) which is also a crucial contributing factor to pulmonary vessel wall thickening, pulmonary vascular remodeling, and vascular resistance. 5 Metabolic studies showed that chronic hypoxia not only increased the expression of these proinflammatory molecules and mediators but also reduced anti-inflammatory products like omega-3 fatty acids.2

Studies have shown that cardiorespiratory exercise reduces proinflammatory markers and increases anti-inflammatory stimulus in healthy and HAPH populations.2 However, exercise training is not sufficient to reverse PAH, so we need to prevent HAPH from developing in utero with maternal exercise.  The American College of Obstetrics and Gynecologists (ACOG) recommends resistance training twice a week and moderate-intensity cardiorespiratory training daily for a total of 150 minutes a week. Studies showed that pregnant women who followed this recommendation had a 25% reduced risk of developing conditions like gestational diabetes and hypertension that contribute to compromised uterine blood flow and fetal hypoxic conditions. At low altitudes, exercise by pregnant mothers leads to benefits such as decreased fat mass, leptin, oxidative stress, pulmonary valve defects, aortic valve defects and inflammation, and increased neurogenesis in the fetus. Some animal studies at high altitudes showed that offspring of physically active pregnant rodents also received similar benefits from maternal exercise. The offspring were protected against proinflammatory stressors evidenced by low levels of inflammatory mediators, which protected them against the inflammatory processes that drive pulmonary artery remodeling and pressures that lead to HAPH. Further animal studies should be conducted to further explore the possibilities that maternal exercise can counteract the inflammatory changes and prevent HAPH development in fetus and newborns.

Resources

  1. Mirrakhimov AE, Strohl KP. High-altitude Pulmonary Hypertension: an Update on Disease Pathogenesis and Management. The Open Cardiovascular Medicine Journal. 2016; 10: 19-27. doi: 10.2174/1874192401610010019
  2. Leslie E, Gibson AL, Gonzalez Bosc LV, Mermier C, Wilson SM, Deyhle MR. Can Maternal Exercise Prevent High-Altitude Pulmonary Hypertension in Children?. High Altitude Medicine & Biology. 2023; 24: 1-6. https://doi.org/10.1089/ham.2022.0098
  3. 2023. Blood Circulation in the Fetus and Newborn. Stanford Medicine Children’s Health. https://www.stanfordchildrens.org/en/topic/default?id=blood-circulation-in-the-fetus-and-newborn-90-P02362
  4. 2023. Transient tachypnea- newborn. Icahn School of Medicine at Mount Sinai. https://www.mountsinai.org/health-library/diseases-conditions/transient-tachypnea-newborn#:~:text=As%20the%20baby%20grows%20in,start%20removing%20or%20reabsorbing%20it.
  5. He S, Zhu T, Fang Z. The Role and Regulation of Pulmonary Artery Smooth Muscle Cell in Pulmonary Hypertension. International Journal of Hypertension. 2020; 2020: 1478291. doi: 10.1155/2020/1478291
Acclimation, Altitude Science, Athletic Training, Health, High Altitude, High Altitude Training & Fitness

Training Student Athletes at Altitude: An Interview with Hurdles Coach, Jay Peltier

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article by Caitlin De Castro, PA-S

Several students from Summit High School’s Track & Field team attended the Colorado State Track and Field Championships in Lakewood in May, where they competed with top runners across the state. The boys team placed 20th out of 39 teams, and the girls team tied for 9th place out of 40 teams in Class 4A rankings. Throughout the season, many students set new personal records and broke previous school records. 

I had the pleasure of speaking with Summit High School hurdles coach, Jay Peltier, about training young athletes in high altitude. Jay has coached Track & Field for 15 years and has even helped lead some high schools to win state titles. He has trained student athletes in cities close to sea level as well as ones in higher elevation, like Colorado Springs. This is his second season coaching in Summit County. 

Exercising at high altitude can be a challenge due to the decreased oxygen concentration at higher elevations. Because of this, there is reduced oxygen availability to muscles, causing fatigue to occur sooner at lower working rates. Given his experiences coaching at different altitudes, I asked Jay how he has adjusted his training to being at 9,000 ft. He notes that with elevation as high as this, it’s difficult to train hard for long periods. His workouts at high altitude include longer rest times between reps and less volume per workout. For example, one of Jay’s staple workouts for sprinters when he was training at lower elevation included running twelve 200 meter sprints, totaling up to a volume of 2,400 meters. At high altitude, he would decrease the volume to about 1,800 meters. 

I also asked Jay about how competing at track meets at a lower elevation affects athletes that have been living and training at high altitude. Generally, athletes that run events greater than 400 meters should be faster running at lower elevations because there is increased oxygen availability. This is because distance running is a form of aerobic exercise in which the body uses oxygen as the primary source for energy. Sprinters, on the other hand, may not see the same benefit competing at lower elevation because sprinting is a form of anaerobic exercise, where the body relies on burning carbohydrates for energy. Despite this, Jay recognizes that there are many other variables that can affect these high altitude athletes competing at lower elevations, including weather. Jay notes that competing in lower areas, like Denver or Grand Junction, can also be 20 degrees warmer compared to Summit County. Increased temperatures can lead to exhaustion faster, especially for distance runners.  

Jay and his fellow coaches try to tell their athletes after every practice to “Eat right. Sleep right. Drink right.” in order to maximize their workout. This includes getting a good balance of carbs, protein, fruits, and vegetables in their diet to properly fuel their body. He recommends his athletes get at least 9 hours of sleep at night. He notes that sleep deprivation can significantly impact how one trains, especially at altitude. Lastly, he emphasizes to his athletes the importance of staying hydrated. While this is essential for all athletes, the risk of dehydration is higher at altitude. He recommends they drink half their bodyweight in ounces, plus an extra 10 ounces for being at elevation.

Resources

Jones, Cody. “State Champion Again: Summit’s Ella Hagen Wins 1,600-Meter State Title at Final Day of the Colorado State Track and Field Meet.” SummitDaily.Com, 24 May 2023, www.summitdaily.com/news/state-champion-again-summits-ella-hagen-wins-1600-meter-state-title-at-final-day-of-the-colorado-state-track-and-field-meet/. 

Mancera-Soto, Erica M., et al. “Effect of Hypobaric Hypoxia on Hematological Parameters Related to Oxygen Transport, Blood Volume and Oxygen Consumption in Adolescent Endurance-Training Athletes.” Journal of Exercise Science & Fitness, vol. 20, no. 4, 18 Oct. 2022, pp. 391–399, https://doi.org/10.1016/j.jesf.2022.10.003. 

Acclimation, Altitude Science, Athletic Training, Backpacking, Exposure, Health, High Altitude, High Altitude Training & Fitness, Mountaineering

Mountain People Can Still Get Mountain Sickness: HL-HAPE, a Fourth Type of High Altitude Pulmonary Edema

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There are three types of High Altitude Pulmonary Edema (HAPE) recognized in visitors and people living at high altitudes. These include classic HAPE (C-HAPE), which involves an individual that lives at low altitude traveling to high altitude. Re-entry HAPE (RE-HAPE)  is seen in an individual that lives at high altitude who travels to low altitude and then returns to high altitude, and high-altitude resident pulmonary edema (HARPE) which occurs in an individual that lives at high altitude and does not change altitude (Ebert-Santos, Wiley). While these have been extensively studied and are subtypes that people are warned of, a fourth unexpected type of HAPE has been recently described by pediatric pulmonologist Santiago Ucros in Bogota, Columbia at the Universidad de los Andes. (Ucros)

Highlanders HAPE (HL-HAPE) occurs in people that live at high altitude who then travel to higher altitudes. Though most people who live at high altitudes for long periods of time assume they are immune to HAPE, the recognition of HL-HAPE shows this is not the case. One man had a run-in with HL-HAPE during his long-awaited trip to Mt. Kilimanjaro. 

A man wearing a neck gator under a grey baseball cap and dressed in cold-weather jacket and pants sits on a rock next to a tall giant groundsel plant with cushions of dead leaves puffing up heads of light-green leaves before the sloping of the mountain down into a valley with a white cloud floating above it.

A resident of Summit County, Colorado, Jonathan Huffman set out to climb Mt. Kilimanjaro with his wife Katie when he was 37 years old. He is originally from Texas, but has been living in Breckenridge, Colorado, elevation 9,600 ft, for 15 years. In preparation for the climb, he spent the summer hiking multiple fourteen thousand foot peaks in Colorado, trail running at 9,000-12,000 ft, and mountain biking. 

Two people stand smiling toward the camera with an arm around each other, dressed warmly in long pants, thick jackets and hats, one holding a water bottle, standing on an open field of high alpine shrubs with Mt. Kilimanjaro illuminated in the pink light of the sun, streaked with long, narrow clouds in the background

The elevation of Mt. Kilimanjaro is 19,341 feet and the summit generally takes each group anywhere from 5 to 9 days, depending on the route taken. In September, Jonathan and Katie traveled to Tanzania where they spent two days adjusting to jet lag and preparing for their climb. They had chosen to follow the Lemosho Route which is 42 miles long with an elevation gain of 16,000 to 17,000 feet. 

On the first day, Jonathan and his party started at the Lemosho trailhead (7,742 feet) and hiked up 9,498 feet to the first camp. He noticed that his throat felt dry and he found himself having to clear it often. He attributed this symptom to the dusty environment. 

On the second day, he felt as though his body was fighting the dust, which had found its way into his eyes, sinuses, and throat. He also felt extremely fatigued and stated that every action felt more difficult. Though he could tell his body was struggling to adapt, Jonathan continued to push forward with full force. He made it to the second camp at 11,500 feet. 

A group of orange and white panelled tents sit in the shade of a rocky mountain peak streaked with snow, illuminated in sun above the camp against a cloudless blue sky.

“Day three, we went from 11,500 feet to 13,800 feet,” Jonathan recounts. “After we arrived to this camp, our guides offered to allow us to take a break then hike even higher. This was [an] optional acclimatization test … but I actually skipped it. I was so tired when I got to camp on this day, I decided to just nap in the tent until dinner time.”

On the fourth day, Jonathan’s group hiked up an overpass to Lava Tower located at 15,190 feet. This was also an altitude test, and he passed. He stated that this was the highest he had ever climbed, but that he was beginning to feel more like his normal self. The group stopped for lunch at the tower, but he did not have much of an appetite. He ate the food anyways at the insistence of the guides. 

A sea of clouds illuminated in blues and soft pinks stretches out behind several tents pitched over a shaded, rocky mountain slope in the foreground.

“Then after lunch, we descended down to Barranco Camp [from 15,190 feet to 13,044 feet] and this is where I realized I had HAPE.”

As they were nearing the camp, he felt fluid building in his lungs that was easy to cough up. By the evening, however, he felt as though he was drowning and was unable to lay down. While the guides encouraged him to immediately hike down, he did not want to hike in the dark. He spent the night propped up on duffle bags or sitting in a kitchen chair, with his oxygen reaching as low as 67% at one point. 

Two people sit in the dark of a tent, one with an oxygen mask on and a red head lamp illuminating tin food containers and medical supplies in the foreground as he is administered oxygen.

In the morning, he received 30 minutes of oxygen treatment before beginning his 8-hour descent. His symptoms improved when he reached 6,500 feet. He was picked up in a rescue vehicle and received further treatment at a hospital in Moshi. While he made a full recovery, he stated that he still felt the effects of HAPE while exercising in Colorado at times, up to months after the experience. While Jonathan was only about 2 days away from the summit, he knew that turning back was the best choice. He plans to re-attempt the climb in a few years. 

Jonathan’s story serves as an important reminder to those living at altitude that HAPE can affect anyone. Jonathan’s wife Katie along with everyone else in the group also experienced mild symptoms of altitude sickness including headaches. Research still needs to be conducted on the cause and prevention of this condition in all types. While this shouldn’t stop hikers and climbers from climbing mountains, they should be aware of the signs and symptoms of HAPE, when to seek treatment, and the best ways to prevent it from occurring. 

A map of the Lemosho route as listed on the Ultimate Kilimanjaro guide site can be found here.

A group of people in bright colored pants, jackets and backpacks make their way down a red dirt trail surrounded by tall green grasses and trees extending over a white SUV with a red cross symbol on it in the background down the road.
A man in a beige baseball cap takes a selfie with three men in hats and jackets behind him smiling toward the camera with a white jeep labelled with a red cross in the background behind them.
Acclimation, Alcohol at Altitude, Altitude Science, Athletic Training, Backcountry, Backpacking, Child Growth & Development, Exposure, Health, High Altitude, High Altitude Training & Fitness, Huts, Hyperbaric Therapy, Medicine, Mountaineering, Naturopathic Medicine, Sleep at Altitude, Summit Huts

HAFE: High-Altitude Flatus Expulsion

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Often, at high altitude we hear complaints of gas pain and increased flatus in our infant population. Parents often wonder, are we doing something wrong? Is my child reacting to breastmilk, or showing an intolerance to certain foods?  Actually there is another explanation for increased flatus and gas pain in the high-altitude region of Colorado. 

The term HAFE was coined by Dr. Paul Auerbach and Dr. York Miller and published in the Western Journal of Medicine in 1981. Their discovery began In the summer of 1980, when the two doctors were hiking in the San Juan Mountains of Colorado on a quest to summit three 14ers. During their ascent they noticed that something didn’t smell right! As the pair continued to emit noxious fumes, they began to put their scientific brains to work and discovered HAFE. The symptoms include an increase in frequency and volume of flatus, or in other terms an increase in toots! We all have familiarity in watching our bag of potato chips blow up when reaching altitude or our water bottle expanding as we head into the mountains. This reaction is due to a decrease in barometric pressure. Based on Boyle’s law, decreased barometric pressure causes the intestinal gas volume to expand, thus causing HAFE (Skinner & Rawal, 2019).

A graphic illustrating how Boyle's law works: the pressure of a gas increases as its volume decreases.

To my surprise, a gas bubble the size of a walnut in Denver, Colorado (5280 ft) would be the size of a grapefruit in the mountain region of Summit County, CO (8000+ ft)! Trapped gas is known to lead to discomfort and pain. The use of simethicone may have merit in mitigating the effects of HAFE. Simethicone works by changing the surface tension of gas bubbles, allowing easier elimination of gas. This medication, while benign, can be found over the counter and does not appear to be absorbed by the GI tract (Ingold, C. J., & Akhondi, H., 2022). 

While this phenomenon may not be as debilitating as high-altitude pulmonary edema (HAPE), it deserves recognition, as it can cause a significant inconvenience and discomfort to those it inflicts. As the Radiolab podcast explained in their episode The Flight Before Christmas , expelled gas in a plane or car when driving up to the mountains can be embarrassing. While HAFE can be inconvenient, it is a benign condition and a matter of pressure changes rather than a disease or pathological process. We would love to talk more about HAFE at Ebert Family Clinic if you have any questions or concerns!

A bald eagle flies over a misty settled into the valley against the blue-green pine forest of a mountain.
A bald eagle flies toward its nest atop a bare lodgepole pine.

As always, stay happy, safe, and healthy 😊

Taylor Hollingsworth is finishing her final semester as a family nurse practitioner (FNP) student at Georgetown University. Originally from the east coast, Taylor plans to start her FNP career in North Carolina close to family. She has a passion for pediatric and family wellness and has worked as a pediatric intensive care unit nurse for 6 years! In her free time, Taylor loves to hike, fly fish, run, and spend time with her fiancé Logan. 

References

Auerbach, P. & Miller, Y. (1981). High altitude flatus expulsion. The Western Journal of Medicine, 134(2), 173-174.

Chemistry Learner. (2023). Boyle’s Law. https://www.chemistrylearner.com/boyles-law.html

Ingold, C. J., & Akhondi, H. (2022). Simethicone. StatPearls Publishing. 

McKnight, T. (2023). The Flight Before Christmas [Audio podcast]. Radiolab. https://radiolab.org/episodes/flight-christmas

Skinner, R. B., & Rawal, A. R. (2019). EMS flight barotrauma. StatPearls Publishing. 

Acclimation, Altitude Science, Athletic Training, Backpacking, Exposure, Health, High Altitude, High Altitude Training & Fitness, Mountaineering

When Altitude gets High, does Stroke get higher?

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Does altitude increase or decrease risk of strokes? As one review put it, “Due to limited literature, lack of large series, and controlled studies, the understanding of stroke at high altitude is still sketchy and incomplete”. What is clear is that stroke at high altitude can often be misdiagnosed (or underdiagnosed), due to the similarity of initial presentation with high altitude cerebral edema (HACE). Both conditions present with imbalance or ataxia, and both can present with focal neurological deficits.  There are few large urban populations at high altitude (Addis Ababa in Ethiopia is 7,726 ft), so medical providers have fewer resources.  Without the ability to perform neuroimaging with a CT scan or MRI in a timely manner a diagnosis of HACE vs. stroke could be uncertain. HACE often causes global cerebral dysfunction, differentiating it from an early stroke before the onset of focal symptoms can and often does prove challenging. 

While the prevalence of strictly hemorrhagic and ischemic strokes at high altitude remains murky, it is known that exposure to high altitude can result in conditions such as TIA, cerebral venous thrombosis (CVT), seizures, and cranial nerve palsies. Most of the research that has been done on strokes is focused on “moderate” and “high” altitudes, as opposed to “very high” or “extremely high” altitudes. As such, there is very little research on populations living at 3500m or higher. There was at least one tangible piece of evidence indicating that the higher the elevation, the earlier the mean onset of stroke – Dhiman et al. (2018) found that at an elevation of 2,000m, the mean age of onset of stroke was 62 years. The age decreased to a mean of 57.9 years at 2,200m in another study (Mahajan et al. (2004)). Yet another study (Razdan et al. (1989)) found 10.9% of the patients in their sample suffered strokes aged < 40, though this was at an altitude of only 1,530m. Some reports suggest higher stroke prevalence at higher altitudes, and at a strikingly young age – between age 20 and age 45.

Student presentation on stroke at altitude at Colorado Medical Society meeting 2022

There have been mixed results on the effect that altitude has on strokes. One systematic review study found 10 studies displaying an increase in stroke prevalence with higher altitude, 5 other studies showing that altitude was actually protective against stroke, and 2 studies in which the results were ambiguous. This study and other sources alluded to the fact that poorer stroke outcomes at higher altitude may be due to polycythemia and increased viscosity of blood. Specifically, Ortiz-Prado et. al noted that “living in high-altitude regions (>2500m) increases the risk of developing thrombosis through hypoxia-driven polycythaemia which leads to a hypercoagulation unbalance”, which was associated with increased risk for stroke. Ortiz-Prado et. al noted that most of their info came from “very few cross-sectional analyses”. These analyses did find “a significant association between living in high-altitude regions and having a greater risk of developing stroke, especially among younger populations”. When the effects of altitude on stroke were broken down by race (Gerken, Huber, Barron, & Zapata, 2022) it was found to be protective in some populations (Whites, African Americans), but detrimental in other populations (Hispanics, Asian-Pacific, and American-Indian). Going back to the work of Ortiz-Prado et. al, altitude increased the risk of stroke at elevations above 3500m, when the time spent at this elevation was at least 28 days, and more so in younger persons (below the age of 45). At lower elevations, between 1500m and 3500m, increased / easier acclimatization and adaptation to hypoxia seemed to offer protective effects against the risk of stroke. Chronic exposure to hypoxia at high altitude triggers adaptive / compensatory mechanisms, such as higher pulmonary arterial flow and improved oxygen diffusing capacity. Ortiz-Prado et. al concluded that a window of ideal elevation seems to exist – below an altitude of 2000m the adaptive mechanisms do not seem to be sufficient to yield a protective effect – however, above 3500m, adaptive mechanisms may actually become maladaptive (excessive polycythemia & blood stasis), yielding a higher risk for stroke. A lack of any adaptation (i.e. in altitude naïve persons) was even more detrimental at such high altitudes, with the authors concluding that “above 3500–4000m, the risk of developing stroke increases, especially if the exposure is acute among non-adapted populations” (Ortiz-Prado et. al, 2022).

Strokes are more common in males compared to females, and this held true at altitudes of 3380m, 4000m, and 4572m. In addition to the standard vascular risk factors such as hypertension, smoking, and diabetes, the higher incidence of polycythemia in persons living at high altitude is thought to play a role. One study (Jha et al. (2002)) found that 75% of the patients in their sample who had suffered strokes had some form of polycythemia – this was at an altitude of 4270m. (Dr. Christine Ebert-Santos of Ebert Family Clinic in Frisco, Colorado at 2743m suspects everyone who lives at altitude has polyerythrocythemia as more accurately described by Dr. Gustavo Zubieta-Calleja of La Paz, Bolivia at 3625m.)

Only about 2% of the world’s population resides at what is considered “high altitude”. Given the current world population (over 8 billion, 5 million), that is still over 160,100,000 people. The sheer number of people that may be at increased risk of stroke is all the more reason for us to act, and act soon, to get more research done. This is further exemplified by the fact that “cerebrovascular events or stroke is the second leading cause of death worldwide, affecting more than 16 million people each year” (Ortiz-Prado et. al). Guidelines need to be implemented to assist in the diagnosis and treatment of stroke at high altitude, to help differentiate it from related conditions such as HACE, giving patients the standard of care that they need and deserve. While a fascinating topic, stroke seems to be delegated to the sidelines in the mountains, cast aside by culprits such as HAPE, HACE, altitude sickness, and hypoxia. More research, more resources, and more funding need to be funneled into understanding stroke at higher altitudes. Overall, it is clear living at or even exposure to higher altitudes can result in a multitude of neurological symptoms, and that a higher incidence of stroke may yet be one of them.

References

Maryam J. Syed, Ismail A. Khatri, Wasim Alamgir, and Mohammad Wasay. Stroke at Moderate and High Altitude. High Altitude Medicine & Biology.Mar 2022.1-7. http://doi.org.mwu.idm.oclc.org/10.1089/ham.2021.0043

Current World Population – https://www.worldometers.info/world-population/ 

Ortiz-Prado E, Cordovez SP, Vasconez E, Viscor G, Roderick P. Chronic high-altitude exposure and the epidemiology of ischaemic stroke: a systematic review. BMJ Open. 2022;12(4):e051777. Published 2022 Apr 29. doi:10.1136/bmjopen-2021-051777

Gerken, Jacob (MS), Huber, Nathan (MS), Barron, Ileana (MD, MPH-S), Zapata, Isain (PhD). “Influence of Elevation of Stroke and Cardiovascular Outcomes”. Poster presented at a conference in Colorado, in 2022.

Links

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058702/ https://www-liebertpub-com.mwu.idm.oclc.org/doi/full/10.1089/ham.2021.0043

Born in Salt Lake City, Utah, Piotr Poczwardowski has also lived in Upstate New York, Florida, and Colorado (where he spent the 13 years prior to moving to Glendale for PA school). While attending the University of Denver, he volunteered at a nearby hospital Emergency Department, and also participated in a study abroad program in Italy. After earning a degree in Psychology, he worked as both a Primary Care Medical Scribe and Neurology MA. His main hobbies include skiing, watching movies, hiking, swimming, playing video games, reading, and playing ping pong. Piotr has also volunteered at the Sky Ridge Medical Center Emergency Department and secured a job as a Primary Care Medical Scribe after graduating from the University of Denver in 2018. Piotr is now attending Midwestern University’s PA program in Glendale, AZ.

Acclimation, Altitude Science, Athletic Training, Child Growth & Development, Doc Talk, Exposure, Health, High Altitude, High Altitude Training & Fitness, Medicine, Mountaineering

Going Home to the Mountains Can Be Dangerous: Re-Entry HAPE (High Altitude Pulmonary Edema)

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Louie was excited to get out on the slopes after spending Thanksgiving with family in Vermont. He got tired early and felt his breathing was harder than usual, leaving early to go home and rest. As a competitive skier he thought that was strange. But he was getting over a cold. He could not have imagined that in 24 hours he would be in the emergency room, fighting for his life.

Louie experienced a dangerous condition, set off by altitude, and inflammation from his “cold”, that caused his lungs to fill with fluid.  His oxygen saturation was 54 % instead of the normal 92, he had been vomiting and feeling very weak and short of breath. His blood tests showed dehydration, hypoxemia and acute kidney injury. His chest x-ray looked like a snowstorm. He was transferred to Children’s Hospital in Denver and admitted to the intensive care unit.

The diagnosis of Re-entry HAPE was confirmed by echocardiogram showing increased pressures in his lungs. He improved rapidly with oxygen and low altitude.

Re-entry HAPE is not rare, affecting several Summit County children every year.  Many do not come to medical attention because after their first episode parents carefully monitor their oxygen and have a concentrator available in their home when they return from travel. 

Medical providers may not be aware of this risk, expecting that children living at altitude are acclimatized. (See blog entry on Acclimatization vs. Adaptation, April 17, 2019) Re-entry HAPE seems to occur mostly in children between the ages of 4 and 15. Inflammation, such as a viral respiratory infection, seems to play a role.  Trauma may also predispose a returning resident to Re-entry HAPE, as described in our blog post from February 5, 2018, Trauma related High Altitude Pulmonary Edema

Louie agreed to share his story on our blog to help educate medical personnel and families living in the mountains about this dangerous condition. Further research will help define who is at risk. 

Acclimation, Altitude Science, Athletic Training, High Altitude, High Altitude Training & Fitness, Hyperbaric Therapy, Technology

Interview with Retired Fighter Pilot Andrew Breithaupt: Altitude Earth and Sky

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I had the honor of interviewing Andrew Breithaupt who recently retired from US Customs and Border Protection in the Department of Homeland Security where he served as an Air Interdiction Agent piloting multiple types of aircraft.  He currently serves as a Lieutenant Colonel on active duty for the US Army, stationed in Minneapolis, MN.  He began Army flight school in 1992 to become a helicopter pilot, ultimately qualifying in 4 different types of Army helicopters including the UH-1H, OH-58, AH-1, and the AH-64 Apache for which he became an Instructor Pilot training new Army aviators at Fort Rucker, Alabama.  Later he began his transition to fixed-wing aircraft in the civilian community. After nearly 10 years of Army active duty and multiple overseas tours, he was selected to enter service for US Customs and Border Protection where he served as a federal law enforcement agent for over 20 years, retired in December of 2021.  He holds his commercial pilot license for single engine & multi-engine fixed wing as well as rotorcraft with instrument privileges and aircraft type ratings. He has over 30 years of aviation experience and more than 2,500 hours of flight time over his career. I sat down to chat with him about his accomplished career and learn more about his aviation and altitude expertise.

In army flight school, specifically aeromedical training, he was taught the effects of aviation on the body. One of the first lessons they learned in their training was how to recognize the early warning signs of hypoxia. These include shortness of breath, dysphoria, nausea, vomiting and lightheadedness. This type of training is often done in altitude chambers, so trainees can experience these effects before they are in the air, including how aviation can affect your vestibular senses. A position change as simple as looking down to change a radio or instrument can completely disorient a pilot due to the change in direction of the fluid within the inner ear against the cilia. This can lead to the sensation that the plane has rotated and flying sideways. They are taught to trust their instruments because an overcorrection can lead to what they teach in flight school as a “death spiral.” The training is often done in a Barany Chair and simulates vestibular senses experienced during flight.

Elevation in Summit County, Colorado ranges from 7,947 feet to 14,270 feet, the highest peak being Gray’s Peak. With people living as high as 11,200 feet, as Andrew does at his home in Blue River located south of of Breckenridge, CO.  Andrew shared some very interesting aviation altitude requirements which might surprise some. He spent much of his career operating non-pressurized helicopters and Federal Aviation Regulations prohibited him from going between 10,000 feet to 12,000 feet for more than 30 minutes without oxygen. When flying above 12,000 feet, pilots are required to have supplemental oxygen regardless of the amount of time spent at that elevation depending on the category of aviation being conducted such as commercial operations. This is according to the CFR (Code of Federal Regulations) Part 135 which governs commercial aircraft operations. How interesting is it that pilots have these regulations, yet many people who live in Summit County or those summiting 14ers (peaks at 14,000 ft. or above) are at or above these elevations with no supplemental oxygen on a daily basis. When flying private aircraft, CFR part 91.211 specifies flight crew can fly without pressurization or supplemental O2 below 14,000 feet and passengers below 15,000 feet.

While in the Army, Andrew would rarely operate aircraft above 8,000 feet and would typically not have supplemental oxygen on board. They were trained to begin descent immediately if they were to notice the early signs of hypoxia. Keeping a pilot’s license requires strict annual or even semi-annual FAA physicals and continued training to ensure their bodies can withstand the effects of aviation.  As you can imagine those holding these licenses are some of the most fit men and women in the country.  Andrew rarely felt the effects of altitude even with altitude changes as great as 8,000 feet coming from sea level. He would typically remain at these elevations for two hours or less piloting non-pressurized aircraft.

To give some perspective, when you hop on a commercial flight for your next adventure these planes typically fly around 28,000 to 36,000 feet of elevation. When beginning the ascent, the aircraft pressure stabilizes at 6,000 to 8,000 feet, approximately when the dreaded “popping of the ears” is felt. Supplemental oxygen and quick donning masks are required on all these aircraft in case depressurization were to occur due to the rapid hypoxia which would occur at such high altitudes.

Andrew moved to Summit County in November of 2021 from Stafford, VA with his wife and five sons ages 24, 22, 19, 14, and 11.  Andrew and his family spent a significant amount of time in Summit County for snowboarding and skiing competitions and quickly fell in love with the area prior to spending the last 5 years living in Stuttgart, Germany. This is when they decided one day, they would become full-time residents of the county. They moved here for the “people, climate and lifestyle,” a combination I am learning is hard to beat outside of Summit County. With ski and snowboard season right around the corner, he and his family are excited to get back out on the slopes.   Andrew currently travels between his home in Blue River and Minneapolis for his position in the Army. With each trip back he feels his body more quickly adjust to the altitude changes. Thank you for your service Andrew, and welcome to the community!

Ellie Martini grew up in Richmond, VA and is currently a second-year Physician Assistant student at Drexel University in Philadelphia, PA. She completed her undergraduate degree at The College of William and Mary in Williamsburg, VA where she received her BS in Biology. Before PA school she worked as a rehab tech and medical scribe at an addiction clinic. In her free time she enjoys hiking, biking, group fitness, traveling and spending time with friends and family. 

Acclimation, Altitude Science, Athletic Training, Backcountry, Health, High Altitude, High Altitude Training & Fitness, Huts, Hyperbaric Therapy, Mountaineering, Sleep at Altitude

Sleep at High Altitude

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Have you thought of what it would be like living in the mountains year-round? Medical professionals find it is important to look at what living at high elevations can do to the human body. One activity heavily affected is sleep. As mentioned in previous blog posts, visitors often have trouble falling asleep, staying asleep, and feeling rested in the morning. A recent study published in Physiological Reports measured the effects of sleeping patterns at high elevation. The participants experienced a simulated elevation inside a hyperbaric chamber. This mimicked sleeping at elevations of 3000 meters (9,842 feet) and 4050 meters (13,287 ft) for one night and then sleeping at sea level for several nights to establish a baseline for the research participants. Participants exercised for 3 hours in the hyperbaric chamber allowing researchers to observe how the lower oxygen concentrations affected their ability to perform strenuous tasks. The group that slept in a simulated 4050 meter environment had an increased heart rate that was 28% higher and an oxygen saturation 15% lower than the 3000 meter participants. When comparing sleep itself, the group at 4050 meters had 50% more awakening events throughout each night. This goes along with previous research on this blog that states that people who sleep at high altitude complain of insomnia and frequent awakening when first arriving at high elevation.

These numbers increase even more dramatically when compared to participants at sea level. Related symptoms reported during this study showed the incidence of acute mountain sickness occurred in 10% of the participants at a simulated 3000 meters, increasing to 90% at 4050 meters. As mentioned, the average heart rate increases and oxygen saturation decreases as the elevation increases. The baseline heart rate at sea level was 62 beats per minute, increasing to 80 at 3000 meters and 93 at 4050 meters. Ideally health care providers aim to oxygenate vital organs by keeping the oxygen saturation level between 92-100%. The lower the oxygen level the harder it is to keep organs properly profused. Age, health status, and place of residence are taken into consideration when examining study reports. Oxygen saturation at sea level was 98% decreasing to 92% at 3000 meters and 84% at 4050 meters.

As mentioned in a previous post by Dr. Neale Lange, sleeping at high altitudes can be hard due to the frequent awakenings and nocturnal hypoxia caused by the low oxygen levels at higher elevation. This study reiterates these findings with the results of the average oxygen saturation at 3000 meters being around 92%. Dr. Lange also found that sleep apnea was often more prominent and had more negative effects on the human body in environments that were lower in oxygen. This study agrees with that statement finding that people with sleep apnea had twice the hourly awakenings compared to those at higher elevation that did not have sleep apnea. Dr. Lange also pointed out that the contribution of hypobaric atmosphere to symptoms at altitude as opposed to pure hypoxemia is unknown. Frisco, Colorado is at an elevation of 2800 meters. Ongoing research at Ebert Family Clinic including residents and visitors along with laboratory studies such as this one can guide decisions about interventions and treatment to improve sleep and help us enjoy our time in the mountains.

References

  1. Figueiredo PS, Sils IV, Staab JE, Fulco CS, Muza SR, Beidleman BA. Acute mountain sickness and sleep disturbances differentially influence cognition and mood during rapid ascent to 3000 and 4050 m. Physiological Reports. 2022;10(3). doi:10.14814/phy2.15175
  2. Blog post: HOW DO YOU DEFINE A GOOD NIGHT’S SLEEP?:AN INTRODUCTION TO THE SLEEPIMAGE RING, AN INTERVIEW WITH DR. NEALE LANGE

Casey Weibel is a 2nd year student at Drexel University, born and raised in Pittsburgh, Pennsylvania. He went to Gannon University for his undergrad and got a degree in biology.  Before PA school, Casey was an EMT.  He enjoys hiking and kayaking and is a big sports fan. 

Acclimation, Alcohol at Altitude, Altitude Science, Athletic Training, Genetics, Health, High Altitude, High Altitude Training & Fitness, Sickle Cell

Dad, put your clothes on! Unique presentations of altitude illness, a Discussion with EMS director Thomas Resignolo

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After his father-in-law arrived in the mountains, Thomas noticed later that night he seemed intoxicated despite not seeing him drink alcohol. Thomas woke up the next morning to see him reading the paper in nothing but black socks and a black tie. Thomas knew right away he wasn’t drunk, he had high altitude cerebral edema (HACE). HACE is a complication of acute mountain sickness (AMS). HACE can occur from increased pressure in the blood vessels in the brain, leading to fluid leakage and swelling (edema). This increased vessel pressure can result from the lower atmospheric pressure at high altitude1. Breathing in lower atmospheric pressure gives you less oxygen molecules per breath. Thomas estimates that EMS in Summit County see one case of HACE a year. EMS look for two hallmark signs of HACE, altered mentation and ataxia. When EMS arrive to a patient with altered mentation, they have the patient walk heel-to-toe to evaluate for ataxia. If ataxia is present, immediate descent is necessary. Rapid descent is necessary because HACE can progress rapidly. Years ago, Thomas had a patient walk into the emergency department and die within 10 minutes after arrival. Unlike high altitude pulmonary edema (HAPE), descent is the only cure for HACE.

HAPE is a more common complication of AMS. Similar to HACE, edema occurs from the high pressure inside pulmonary blood vessels pushing fluid into the lungs. The high pressure is caused by a rapid vasoconstriction response to hypoxia or low oxygen partial pressures. Luckily, HAPE has a simple treatment, oxygen. Therefore, visitors with HAPE do not need to descend to lower altitude as with HACE. HAPE is much harder to recognize than HACE and EMS is well trained in how to recognize it. Often, headache is the only symptom2. Thomas explains the HAPE protocol for EMS: In the first 20 seconds of arriving, an oxygen saturation is obtained; they obtain vitals in the next two minutes and then start high flow oxygen if the saturation is below 89%; they then listen to the lungs for signs of fluid. EMS does not treat HACE or HAPE with any medications since descent and oxygen are the effective treatments.

So, who is prone to AMS?

Unfortunately, better physical fitness does not protect you from AMS. Thomas reports that athletes with resting heart rates of 40 or below have a difficult time acclimating. Younger age also doesn’t mean easier acclimation. According to Thomas, the best age for acclimation is late 30s/early 40s. Surprisingly, previous hypoxia can help acclimation to high altitude. For example, Thomas reports that smokers have an easier time acclimating because their body is used to having the vasoconstriction response to hypoxia and breathing faster and deeper to get adequate oxygen intake.

But don’t worry, your conditioning wasn’t for nothing. A healthy diet and regular exercise prevents heart disease. Thomas estimates there are about 12 acute MI’s on the ski hill each year. These patients usually have to be transported to Denver for a stent to be placed. Exacerbation of coronary artery disease (CAD) is so common that EMS refers to altitude travel as the “altitude stress test.” This mimics a cardiac stress test in those with CAD, producing chest pain that wasn’t present at lower altitude.

Those with sickle cell disease are at risk of developing sickle cell crisis when traveling to high altitude. The lower atmospheric pressure allows the normal red blood cells to lose their integrity and become sickle. Thomas reports that EMS encounters this every couple months in patients (usually of Mediterranean descent) that present with diffuse abdominal pain with no obvious cause. This pain results from the sickle cells aggregating together and causing an occlusion. The occlusion leads to tissue hypoxia and ischemia3. These patients are transported to the hospital for treatment.

How can mountain tourists avoid AMS?

Thomas’s first recommendation is to take a staggered stop for one night at an elevation of 5,000-6,000ft, like Denver. When arriving to altitude, take it easy the first 3 days: don’t drink alcohol and do light activity. Save the long hike for the end of the trip. Also avoid substances that blunt the respiratory system like alcohol, opioids, benzodiazepines, etc. Prepare by hydrating the week before and keep drinking plenty of water while on the trip. If you have had a previous episode of AMS, you can speak to your medical provider about prophylactic medication to take before arriving at high altitude.

References

1. Hackett PH, Dietz TE. Travel Medicine. Fourth ed. Edinburgh: Elsevier; 2019. https://www-clinicalkey-com.ezproxy2.library.drexel.edu/#!/content/book/3-s2.0-B9780323546966000422?scrollTo=%23hl0000521. Accessed November 22, 2021.

2. Schafermeyer, R. W. DynaMed. Acute Altitude Illnesses. EBSCO Information Services. https://www.dynamed.com/condition/acute-altitude-illnesses. Accessed November 19, 2021.

3. Sheehan VA, Gordeuk VR, Kutlar A. Disorders of Hemoglobin Structure: Sickle Cell Anemia and Related Abnormalities. In: Kaushansky K, Prchal JT, Burns LJ, Lichtman MA, Levi M, Linch DC. eds. Williams Hematology, 10e. McGraw Hill; 2021. Accessed November 23, 2021. https://accessmedicine-mhmedical-com.ezproxy2.library.drexel.edu/content.aspx?bookid=2962&sectionid=252529206

Samantha Fredrickson is currently a student in Drexel University’s Physician Assistant program.

Acclimation, Altitude Science, Athletic Training, Backcountry, Backpacking, COVID-19, Health, High Altitude, High Altitude Training & Fitness, Mountaineering, Pandemic

Return to High Altitude after Recovery from Coronavirus Disease 2019

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Andrew M. Luks and Colin K. Grissom

https://www.colorado.com/activities/colorado-hiking

Prior to COVID-19, I would hike the beautiful mountains of Colorado known as 14ers, a name given to these mountains for being over 14,000 ft. I, like most high-altitude travelers faced the more common concerns associated with hiking such as acute mountain sickness (AMS), high altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). With the increase in high-altitude travel, I wondered if there are any new precautions that we should consider before resuming the activities that we love.

The purpose of this article is to highlight the recommendations for patients who wish to return to high-altitude travel after a COVID infection. Not everyone needs an evaluation after a COVID infection. The recommendations noted in this article are based on the duration and severity of the illness of each individual person.

So, who should receive an evaluation before high-altitude travel?

  1. Individuals with symptoms after 2 weeks of a positive COVID-19 test without hospitalization,
  2. Individuals with symptoms after 2 weeks after hospital discharge,
  3. Anyone who required care in the intensive care unit (ICU), and
  4. Anyone who developed myocarditis or thromboembolic events. The recommendations are to undergo pulse oximetry at rest and with activity, spirometry, lung volumes, and diffusion capacity for carbon monoxide(DLCO), chest imaging, electrocardiography (EKG), B-type natriuretic peptide, high sensitivity cardiac troponin (hsTn), and echocardiography.

It is expected that people with lower oxygen levels (hypoxemia) at rest or with exertion in lower elevations will experience greater hypoxemia with ascent to high altitude. It has been shown that ascent to high altitude causes a decrease in barometric pressure leading to a decrease in ambient and inspired partial pressure of oxygen. The decrease in partial pressure of oxygen in alveoli (PaO2) will trigger vasoconstriction of pulmonary arterioles that slows the rate of oxygen diffusion and activates chemoreceptors that increase minute ventilation from hypoxia. However, it is still unclear whether people with low oxygen levels at low elevations are at greater risk for acute altitude illness after ascent. The recommendation is to monitor pulse oximetry after arrival of high altitude.

Individuals with abnormal lung function tests don’t have to avoid high altitude travel as previous studies have shown that patients with COPD with abnormal lung functions tolerate exposure. Furthermore, in people with mild to severe COVID-19 symptoms, the lung mechanic markers such as forced expiratory volume (FEV1), forced vital capacity (FVC) and total lung capacity (TLC) normalize in up to 150 days of infection.  However, if individuals have severe limitations with exercise capacity, they should monitor their oxygen levels with pulse oximetry after ascent. Reduction in exercise capacity is possible after COVID infection and depends on the severity of the illness. Blokland et al., 2020 has shown that previously intubated individuals had a median VO2 max of 15ml/kg per min (average male 35 to 40 and average female 27 and 30), roughly 57% predicted immediately after hospitalization. 

In acute hypoxia, the heart rate increases, which leads to an increase in cardiac output. Individuals with reduced ventricular function from COVID infection do not have to avoid travel. Previous research has shown that individuals with heart failure can tolerate exercise with hypoxia. Moreover, data has shown that individuals with COVID infection maintain preserved left ventricular function and only 3% show a reduced ejection fraction. Individuals with abnormal EKG rhythms and ischemia should be referred to cardiology.  If high sensitivity troponin was abnormally elevated, this would require evaluation for myocarditis with a cardiac MRI. Knight et al., (2020), found that 45% of patients with unexplained elevations of high-sensitivity troponin were found to have myocarditis during hospitalization. It is still unclear how long these abnormalities will last and how it will affect people.

 A concerning finding on ECHO is pulmonary hypertension, as previous research has shown an increased risk in developing HAPE. A study reported that 10% of patients hospitalized for COVID without mechanical ventilation had right ventricular dysfunction for over 2 months. Several studies reported that 7-10% of individuals may have pulmonary hypertension after COVID infection. A vasodilating drug such as nifedipine can be given prophylactically if pulmonary hypertension is unrelated to left heart dysfunction but nifedipine can worsen hypoxemia.

The recommendation for patients who developed myocarditis from a COVID infection is to have an ECHO, Holter monitor, and exercise EKG 3-6 months after illness. Travel can resume after a normal ECHO, no arrhythmias on exercise EKG, and after inflammatory markers (ESR and/or CRP) have normalized. Previous studies suspected that areas with low atmospheric pressures (e.g., high-altitude) that induce hypoxia have increased risk for clot formation. However, this suspicion has never been firmly established; therefore there is no reason to believe that high-altitude will increase the risk for clot formation in individuals who developed an arterial or venous clot from COVID infection.

A few things to consider before planning a high-altitude excursion includes planning to visit areas with access to medical resources or the ability to descend rapidly. If you are new to high altitude, it is recommended to slow the ascent rate. Traveling to high elevations (>4000m) should be avoided until tolerance has developed with moderate elevations (2000-3000m). A more gradual return to physical activity at high altitude is recommended rather than immediate resumption of heavy exertion. As the pandemic subsides and with increase in mountain travel, more research will develop that can better address these risks.

Good news! The Ebert Family Clinic in Frisco, CO provides pulse oximeters for free. So, make sure to visit and grab your pulse oximeter before your next ascent.

Quick Summary of Recommendations

Individuals who require evaluation prior to high-altitude travel:

  1. Individuals who have symptoms after 2 weeks of a positive COVID-19 test without hospitalization
  2. Individuals who have symptoms after 2 weeks after hospital discharge
  3. Any patient who required care in the intensive care unit (ICU)
  4. Any patient who developed myocarditis or thromboembolic events

General recommendations for anyone before high-altitude travel:

  1. Monitor pulse oximetry after arrival of high altitude, and access care or descend if symptoms worsen.
  2. Rest and avoid high-altitude travel for at least 2 weeks after a positive test, and consider a gradually return to physical activity at higher altitudes.
  3. All individuals planning high-altitude travel should be counseled on how to recognize, prevent, and treat the primary forms of acute altitude illness (AMS, HACE, and HAPE)
  4. Limit the extent of planned exertion after ascent and, instead, engage in graded increases in activity that allow the individual to assess performance and avoid overextending themselves.

Reasons to forgo high-altitude travel:

  1. Severely elevated pulmonary artery pressures may be a reason to forego high-altitude travel altogether.
  2. High-altitude travel should likely be avoided while active inflammation is present in myocarditis.
  3. Patients who experienced arterial thromboembolic events due to COVID-19, (e.g. myocardial infarction or stroke) should defer return to high altitude for several months after that event or any associated revascularization procedures.

References:

  1. Andrew M. Luks and Colin K. Grissom. Return to High Altitude After Recovery from Coronavirus Disease 2019. High Altitude Medicine & Biology. http://doi.org/10.1089/ham.2021.0049
  2. Christensen CC, Ryg M, Refvem OK, Skjønsberg OH. Development of severe hypoxaemia in chronic obstructive pulmonary disease patients at 2,438 m (8,000 ft) altitude. Eur Respir J. 2000 Apr;15(4):635-9. doi: 10.1183/09031936.00.15463500. PMID: 10780752.
  3. Blokland IJ, Ilbrink S, Houdijk H, Dijkstra JW, van Bennekom CAM, Fickert R, de Lijster R, Groot FP. Inspanningscapaciteit na beademing vanwege covid-19 [Exercise capacity after mechanical ventilation because of COVID-19: Cardiopulmonary exercise tests in clinical rehabilitation]. Ned Tijdschr Geneeskd. 2020 Oct 29;164:D5253. Dutch. PMID: 33331718.
Image of Jesse Santana, dark brown hair, brown skin, beard and moustache with a stethoscope draped over his white coat, striped, collared shirt and maroon tie.

Jesse Santana is a second-year PA student at Red Rocks Community College in Denver, Colorado. He grew up in Colorado Springs, CO and attended the University of Colorado-Colorado Springs where he earned a bachelor’s in Biology and Psychology. Jesse worked as a Certified Nursing Assistant for two years before pursuing a Master’s in Biomedical Sciences at Regis University in Denver. Shortly after, he coordinated clinical trials in endocrinology and weight loss as a Clinical Research Coordinator at University of Colorado Anschutz Medical Campus. He enjoys hiking Colorado’s 14ers, spending time with family and friends, and camping.