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.
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
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.
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.
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§ionid=252529206
Samantha Fredrickson is currently a student in Drexel University’s Physician Assistant program.
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?
Individuals with symptoms after 2 weeks of a positive COVID-19 test without hospitalization,
Individuals with symptoms after 2 weeks after hospital discharge,
Anyone who required care in the intensive care unit (ICU), and
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:
Individuals who have symptoms after 2 weeks of a positive COVID-19 test without hospitalization
Individuals who have symptoms after 2 weeks after hospital discharge
Any patient who required care in the intensive care unit (ICU)
Any patient who developed myocarditis or thromboembolic events
General recommendations for anyone before high-altitude travel:
Monitor pulse oximetry after arrival of high altitude, and access care or descend if symptoms worsen.
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.
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)
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:
Severely elevated pulmonary artery pressures may be a reason to forego high-altitude travel altogether.
High-altitude travel should likely be avoided while active inflammation is present in myocarditis.
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.
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.
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.
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.
As someone with family history of cardiac illness and a personal history of both supraventricular tachycardia (SVT) and high blood pressure, I have always tried to manage my modifiable risk factors through a healthy diet and exercise. Over the past year or two, most of my exercise has been in the form of running, since it is more conducive to the schedule of a physician assistant student during COVID restrictions. However, in the past I have been a regular rock climber and soccer player. Through my own personal experience I have noticed that when I stick to a healthy diet, not giving in to my sweet tooth, and keeping up with regular exercise that my episodes of SVT are less frequent. However, recently I traveled up from Denver, Colorado for a rotation at the Ebert Family Clinic in the mountain town of Frisco, and in the first two days at high elevation experienced an episode of SVT for the first time in nearly 6 months.
In my first day at over 9000 feet, I experienced a slight headache after a full day seeing patients, but did not think much of it or even consider it to be a side effect of the altitude. I spent my first day at altitude without exercising but I decided that on day two I had acclimated enough to go for a short run. Midway into my run, and shorter of breath than I expected, I experienced an episode of SVT that lasted for about 2-3 minutes and forced me to sit for several more minutes to catch my breath. Catching my breath afterward took slightly longer compared to my normal episodes, which made sense to me given the reduced availability of oxygen, but it did lead me to wonder if the altitude was a contributing factor to precipitating an episode of SVT after several months without one.
About one year ago, High Altitude Health interviewed Dr. Peter Lemis, a cardiologist in Summit County, Colorado about his thoughts and findings practicing cardiology at elevation. The discussion included questions about arrhythmias at altitude and Dr. Lemis stated that “studies have shown that cardiac arrhythmias are increased initially, but people become acclimated after about 3-5 days and the risk returns to baseline”. However, Dr. Lemis also states that the studies may not have been conducted for a sufficient length of time due to his personal experience of seeing a great deal of both atrial fibrillation and atrial flutter in his own practice. He states that the hypoxia leads to an increase in arrhythmias, but that for atrial arrhythmias, patients may experience relief from them when placed on nocturnal oxygen. Dr. Lemis also notes that “many people have central apnea during sleep at altitude due to the brain’s blunted response to high CO2 and low O2”, which can be a risk factor for the development of heart problems. The use of Diamox can be helpful in acclimating to altitude due to making “your blood a little acidotic which increases your respiratory drive” and the use of nocturnal oxygen can also help with acclimatization to altitude.
In March of 2021, the journal of Frontiers in Medicine published an article titled Nocturnal Heart Rate and Cardiac Repolarization in Lowlanders with Chronic Obstructive Pulmonary Disease at High Altitude: Data from a Randomized, Placebo-Controlled Trial of Nocturnal Oxygen Therapy by Maya Bisang, Tsogyal Latshang, Sayaka Aeschbacher, et al. This study compared COPD patients at altitude with and without oxygen therapy at night and COPD patients not at altitude without oxygen looking at QT interval, heart rate, and SpO2. The results of the study found that without oxygen use at altitude patients experienced an increase in heart rate, a lengthened QT interval, and naturally, a lower SpO2 at night compared to those at altitude who utilized oxygen and those that were not at elevation. This study was observing patients that had COPD. The results could potentially be relevant to younger patients without COPD, like myself, but would need further research.
I also looked into information regarding high blood pressure at altitude and found some helpful information from the Institute for Altitude Medicine. They state that for patients visiting altitude with a history of hypertension (HTN), even if it is well controlled on pharmacotherapy, may still experience a temporary increase in blood pressure at altitude. “One explanation for this is due to the higher levels of adrenaline or stress hormones in your body due to lower oxygen levels,” as they describe. Their research has also found that increases in blood pressure at altitude generally return to base line after 1-2 weeks. In order to help manage HTN at altitude they recommend ensuring that blood pressure is well controlled at sea level, reducing salt from the diet, remaining on any medications for HTN, checking blood pressure at altitude, and observing for symptoms of HTN that would need medical care such as headache, dizziness, chest pain, or shortness of breath.
Through my research regarding effects of altitude and the possible role of them in my recent episode of SVT, I have found that altitude can have several different impacts on cardiac function that definitely could have played a role in triggering an episode. Coming to altitude, I likely had an increase in blood pressure to compensate for the reduced availability of oxygen that increased strain on my cardiac muscle. I may have had EKG changes overnight related to decreased responsiveness of my central nervous system to CO2 levels. I also had an increased risk of arrhythmia based on coming to elevation. It is possible that any or all of these effects could have contributed or triggered my episode of SVT. Thankfully, after almost a month of staying at altitude I have adjusted more and have not experienced another episode. I have continued to exercise after a short break to allow more time to acclimate, but I have not pushed myself as hard.
I have learned that no matter how healthy you are or what your risk factors are, there are important steps to stay healthy when coming to altitude. If possible, at least one day at an intermediate altitude can help your body begin to adjust to the change. Drinking plenty of water to stay hydrated and avoiding alcohol can lead to a more comfortable stay and more rapid acclimatization. Meeting with a healthcare provider could also allow you to start a prophylactic course of Diamox or supplemental oxygen use. Utilizing a personal pulse oximeter allows you to monitor your SpO2 level and determine if nocturnal supplemental oxygen could be useful as well. If you have risks for cardiac conditions or already have a diagnosis of heart disease, these recommendations are even more important to prevent poor outcomes including myocardial infarctions due to reduced oxygen availability. Finally, it is important to remember that traveling to altitude is not a benign choice and a discussion with your healthcare provider is important to be sure that your personal risks are appropriately managed so that you can enjoy your trip to high elevation.
Justin Frazier is currently in his second year of PA school at Red Rocks Community College in Arvada, CO, a member of the class of 2021 graduating in November. He attended Appalachian State University in Boone, NC for his undergraduate degree majoring in Cell and Molecular Biology with a double minor in Chemistry and Medical Humanities. During his undergraduate he worked for two and a half years as a CNA at a local nursing and rehabilitation facility. After completing his undergraduate degree he started working as an EMT for almost a year before transitioning to work in a family medicine office where he worked as a Medical Assistant until starting PA school. He enjoys working in a primary care setting where he can help to keep people healthy throughout their lives and wants to pursue a career in pediatrics after graduating this year. He enjoys hiking, camping, rock climbing, and spending time with his wife and young son.
According to recent research, nearly thirty million individuals in the United states have been diagnosed with diabetes. Due to this higher rate of prevalence, more people are aware of the basic information surrounding a diabetic diagnosis. However, there are common misconceptions surrounding the average diabetic patient, with most information focused on the more common form of diabetes, type 2. Although the majority of diabetic patients in the United states do have type 2 diabetes, an estimated 5 to 10% of people with diabetes actually have type 1. Type 1 diabetes is an autoimmune disease in which the body’s own immune system destroys the cells in the pancreas that make insulin. Insulin is a very important hormone that enables sugar to enter the bloodstream in order for it to be used by the cells for energy, as well as stored for later use. Unlike type 2 diabetes, there is no cure for type 1 diabetes and the treatment options are limited; the only management for this form of diabetes is insulin therapy. The most common therapeutic regimens for type 1 diabetes includes constant monitoring of blood sugars using a glucometer or continuous glucose device. These devices combined with either syringes, preloaded insulin pens, and/or an insulin pump are the means to survival for type 1 diabetics. However, there have been many advancements in the ways physicians are able to help their type 1 diabetics control and manage their disease. Because of this, type 1 diabetics are able to live their lives with far less complications. When desired, type 1 diabetics are able to compete at high levels of activity and complete amazing feats, such as wilderness activities.
It is inspiring to know how type 1 diabetics are still able to perform in high intensity activities such as ultramarathons, ironmen/ironwomen, as well as professional sports, to name a few. However, with such strenuous activity, it is important to note that diabetes control is more challenging. Of note, it cannot be stressed enough, that baseline diabetic control is already challenging in itself. By adding the addition of a strenuous environment and activity, diabetes control becomes more difficult as it is multifactorial.
To help address this issue, the Wilderness Medical Society (WMS) worked to form clinical practice guidelines for wilderness athletes with diabetes. The WMS gathered a group of experts in wilderness medicine endocrinology, primary care, and emergency medicine to compose these guidelines. These guidelines are outlined for both type 1 and 2 diabetics who participate in mild-vigorous intensity events in wilderness environment with reduced medical access and altitudes greater than or equal to 8250ft; the objective to help individuals with diabetes better plan and execute their wilderness goals. The foundation summarizes their recommendations into pre-trip preparation, including a list of essential items to bring when on your wilderness trip, potential effects of high altitude on blood glucose control and diabetes management, and an organized algorithm to treat hyperglycemia and ketosis in the backcountry.
Effects of High Altitude on Diabetes Management:
At baseline, the various types of exercise activities are broken into aerobic, anaerobic, and high intensity exercise. Each type of exercise utilizes the energy stored in our bodies, in the form of sugar. In a healthy person without any comorbidities, during aerobic activities, glucose uptake into the large muscle groups is increased due to the increase in energy expenditure. To keep glucose higher during this form of exercise, insulin secretion is reduced. Simultaneously, other hormones such as adrenaline, cortisol, and glucagon are released into the system to promote further glucose release from processes such as gluconeogenesis and glycogenolysis.
Again, the body is utilizing its resource of glucose to move to the larger muscle groups to keep them moving and active. During anerobic and high intensity exercise, the same process occurs, but since these forms of exercise tend to be in short bursts, insulin levels tend to rise particularly in the post workout period. This helps to diminish the effects of the counterregulatory hormones and keep blood sugar levels stable. If the athlete is unable to properly regulate insulin secretions during these various forms of exercise, then it is likely that he/she will experience frequent episodes of hyperglycemia. Also, due to the increase in insulin sensitivity in muscles post workouts lasting >60 min, hypoglycemia can also ensue.
In general, the WMS and other research demonstrates brief episodes of high intensity exercise are linked to hyperglycemia for diabetics. On the other hand, longer duration aerobic exercise will cause hypoglycemia. Unfortunately, due to the complex intricacies of glycemic control during exercise, in addition to the individuality of each patient and the multiple variables involved in each wilderness expedition (temperature, altitude, duration, etc.), the definitive guidance for adjustment of daily insulin continues to need refinement. This is why the WMS recommends extensive pre-trip planning with the various tools, research, and supplies that will be needed when planning any form of wilderness adventure.
Like all endeavors, preparation is key in order to be better equipped to deal with the majority of future scenarios. Planning is especially important when going on a wilderness expedition. Preparation becomes even more important with the diagnosis of diabetes. The WMS outlines the specific recommendations that should be included as a diabetic wilderness athlete. For example, pre-trip prep should generally include: (1) a medical screening, (2) research of the endeavor and how it may affect glucose management, and lastly (3) essential diabetes-specific medical supplies and backups.
Additionally, according to the American diabetes association, persons with diabetes should discuss with their primary care provider and or endocrinologist before a strenuous wilderness activity. This follow up ensures that athletes are up to date on their screenings, health maintenance labs, and prescriptions needed for therapy. Due to the various ways that diabetes can affect the body, the WMS also recommends that if a patient has cardiovascular involvement, retinopathy, neuropathy, or nephropathy, there should be a more extensive risk assessment by the provider. Although these complications are less commonly seen in high intensity wilderness athletes, adequate histories should be taken to avoid adverse circumstances.
As discussed earlier, altitude accompanied with increased strenuous exercise demands also has various effects on blood glucose management. As it pertains to altitude and blood sugar management in type 1 diabetes, multiple studies have shown an increase in insulin requirements at altitudes above 4000m (13,123′). At this time, researchers are unsure if this finding is due to the effects of acute mountain sickness or hypobaric hypoxia. Therefore, wilderness athletes with diabetes should be aware of the insulin resistance increase at these extreme altitudes. In conjunction with altitude changes, as previously noted, the type of exercise will also play a role in insulin control. Aerobic exercise for longer than 60 minutes can cause a hypoglycemic episode in type 1 diabetics due to the increased muscle sensitization to insulin. Therefore, at altitudes 4000m or above, wilderness athletes will be in a mixed long duration anaerobic/aerobic exercise. With the combination of these factors, there is a counter regulation effect, and the athlete becomes both more sensitive to insulin due to increase duration of exercise and less sensitive due to altitude demands. In order to better predict the effects of altitude combined with exercise, the WMS recommends close monitoring on shorter trips to recognize their specific glycemic trends prior to an extreme high-altitude expedition, as well as increased close monitoring of glucose management during their high-altitude endeavors.
Lastly, in preparation of a high-altitude excursion, there are recommended items that should be packed for daily management of glucose, in addition to back up items to ensure athletes with diabetes aren’t left in a dangerous situation. Fortunately, the WMS was able to create a well-organized table on the recommended supplies.
Treatment of ketoacidosis or HHS:
To be properly prepared, an athlete should complete his/her own research on how changes of altitude and exercise can affect blood glucose management. This includes complete pre-trip preparation and packing. Once cleared, a diabetic athlete can finally head out on the high-altitude adventure. In case of emergency, a diabetic should be aware of the proper steps if he/she were to experience diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), or even acute mountain sickness (AMS). Hyperglycemia is described as a blood glucose greater than 250 mg/dL and without adequate treatment can lead to either DKA or HHS. Type 1 diabetics are more likely to go into DKA, while type 2 diabetics are more inclined to present in HHS. One of the most important indicators if a person were to be in DKA are ketones in blood or urine. This is why it is very important to make sure a wilderness athlete carries ketone strips in his/her emergency medical pack. Typically, if a patient finds ketones in their urine after using a ketone strip, then he/she is educated to seek emergent medical attention. When on a wilderness adventure, this can be a difficult task to accomplish. This is why the WMS also developed a flowchart in order to manage hyperglycemia and DKA without medical support. Refer to table 3 for their flowchart.
One issue that diabetics have when dealing with high-altitude is differentiating hypoglycemia and hyperglycemia side effects from AMS. The most reliable differentiating factor is increased blood sugar readings correlating with symptoms. WMS states that either a continuous glucose monitor or increased finger sticks for a higher frequency of blood sugar readings is important to determine if a person with diabetes is experiencing blood sugar complications of AMS. When discussing treatment of AMS in diabetics, the same methods are used as are recommended for a non-diabetic individual: Acetazolamide and dexamethasone in initial medical management. In regard to diabetes, it is important to discuss the potential additional side effects. Acetazolamide can worsen dehydration and acidosis if used at the wrong time. Dexamethasone is known to worsen blood glucose control. Both are still useful in acute mountain sickness but must be weighed against causing worsened complications.
When participating in a wilderness adventure, individuals with diabetes will be prone to more medical side effects. Changes in altitude, along with the level of activity are known to affect diabetic control, so proper preparation prior to departure is required in order to ensure the health and safety of a diabetic wilderness athlete. After being cleared by a medical professional and obtaining proper information, diabetics can plan to complete a wilderness adventure similar to that of a healthy individual with no comorbidities. However, it is common for diabetics to experience hyperglycemia with high intensity activities and an increase in altitude. Therefore, diabetics (particularly type 1 diabetics), should be prepared with extra insulin to counteract elevated glucose levels. Alternatively, if a diabetic were to be at higher altitude with a longer duration of aerobic or anaerobic exercise, then he/she may be prone to hypoglycemia — lower blood sugar levels. In either case, individuals with diabetes will need to monitor blood sugar levels more closely. The WMS provides diabetics with an outline of recommended supplies that may be needed in the wilderness. The outline also suggests for diabetics to bring ketone strips, as this is the most accurate measurement to determine if a diabetic is in DKA or HHS. The ultimate goal of the WMS is to ensure the health and safety of diabetic athletes. Diabetes is a difficult disease to manage but becomes even more challenging when partaking in a wilderness adventure.
(All tables and figures imported from WMS)
de Mol P, de Vries ST, de Koning EJ, Gans RO, Tack CJ, Bilo HJ. Increased insulin requirements during exercise at very high altitude in type 1 diabetes. Diabetes Care. 2011;34(3):591-595. doi:10.2337/dc10-2015
VanBaak KD, Nally LM, Finigan RT, et al. Wilderness Medical Society Clinical Practice Guidelines for Diabetes Management. Wilderness Environ Med. 2019;30(4S):S121-S140. doi:10.1016/j.wem.2019.10.003
Jonathan Edmunds is a second-year physician assistant student at RRCC PA Program in Arvada Colorado. Jonathan is a Colorado native, born and raised in Littleton, CO. He attended Colorado State University in Fort Collins, CO where he competed in Track and Field as a long jump/triple jumper, as well as earned his bachelor’s Biological Sciences. During his junior year in college, he was diagnosed with Type 1 diabetes and quickly became an advocate the support of diabetes education. After graduating in 2015, he focused his medical career aspirations on becoming a PA. He volunteered at Banner Fort Collins Medical Center and work at Bonfils Blood Center as a phlebotomist for 2 years before applying to PA school. In his free time, he enjoys coaching track and field at Littleton high school his alma mater, doing all things outdoors, and cozying up to his three “Irish” chihuahuas at home.
As a California native, I was unfamiliar with the impact high altitude had on the human body. I had only briefly learned about it in my exercise physiology course during my undergraduate studies. At best, I understood the difference between acclimation and acclimatization, and the advantages of living at high altitude for exercise performance. What I never really understood was how much all that information would mean to me when the next chapter in my life took me to Colorado.
In hindsight, I did everything against the book after moving to Colorado because I wanted to stay active and enjoy as much as I could before school started. I continued my daily workout routines, went whitewater rafting, and had a few drinks. More importantly, I was not hydrating adequately because I didn’t know you could drink straight from the tap. So… what happened? The end of my workout routines was met with dizziness and lightheadedness. On some occasions, I would notice my fingertips turn purple. My sleep would be interrupted by episodes of apnea. Though these symptoms did resolve eventually, they could have been prevented if I had followed a few simple rules.
As a student at Ebert Family Clinic in Frisco, CO at 9000′ alongside high altitude expert Dr. Christine Ebert-Santos, I had the opportunity to learn more about high altitude illness, interviewing Dr. Gustavo Zubieta-Calleja and his daughter Dr. Natalia Zubieta-Urioste from the High Altitude Pulmonary and Pathology Institute (IPPA) in La Paz, Bolivia. Dr. Zubieta has been practicing internal medicine and pulmonology at his father’s high altitude clinic since 1981. During our interview, we discussed their most recent publication Acute Mountain Sickness, High Altitude Pulmonary Edema, and High-Altitude Cerebral Edema: A view from the High Andes. When asked about what inspired him to follow his father’s footsteps, he replied, “My father created the first high altitude clinic in the world and that was a great inspiration to me. He did it with a visionary idea because at the time in 1970, nobody thought about putting a clinic like that out. I was born at home because my father was a physician and he preferred to deliver us. We [me and my siblings] were all delivered at home and then that home became the clinic in 1970. The clinic turned 50 this past year and our father also became our mentor at this clinic.”
The article addresses the two types of adaptation: genetic and physiologic. In his publication, he primarily addresses the physiologic mechanisms that must occur for one to adapt to the hypobaric environment that is high altitude. During my research, however, I found that Tibetans experienced the fastest phenotypically observable evolution in human history partially because their community has spent centuries living at that altitude. When I discussed my findings with Dr. Zubieta, he stated that much still needs to be done to determine if the Andean population has made similar genetic adaptations. He was optimistic about the studies to come as he strongly believes that all organisms must adapt if they want to survive and reproduce at high altitude. According to Dr. Zubieta, change is inevitable. He believes that the energy expenditure from the body’s initial response to the hypobaric environment is too costly forcing the human body to adapt in a manner that will render it more effective in managing this energy expenditure via metabolism at the mitochondrial level.
We also discussed the different attitudes towards the use of acetazolamide, or Diamox. In the United States, acetazolamide is a diuretic commonly used to prevent the onset of acute mountain sickness. Dr. Ebert Santos highly recommends the use of acetazolamide to prevent acute mountain sickness while Dr. Zubieta and other providers reluctantly use it due to the risk of dehydration. A 125-milligram dose is adequate and unlikely to cause side effects, which Dr. Zubieta said can include fatigue, nausea, vomiting, abdominal pain, and diarrhea. (Most visitors to Colorado taking acetazolamide only experience tingling of the hands and feet and a flat taste to carbonated beverages.) Dr. Zubieta justifies his avoidance of acetazolamide as an “opportunity” to treat the patient’s underlying issues, stating that ascension to high altitude is a testament of one’s cardiovascular fitness and the use of acetazolamide compromises adaptation to high altitude. At the IPPA they have uncovered underlying conditions that explain their patients’ symptoms at altitude and resulted in better health upon returning to sea level.
The Wilderness Medical Society has established a risk stratification for acute mountain sickness which further supports Dr. Zubieta’s infrequent use of acetazolamide. The society’s 2019 guidelines suggest that individuals with no history of altitude illness and ascending to an elevation no greater than 2,800 meters, and individuals who take more than two days to arrive at an altitude between 2,500 and 3,000 meters are considered low risk and the use of acetazolamide is not recommended. Instead, Dr. Zubieta recommends Ibuprofen and Acetaminophen for headache relief and oxygen in those with persistent symptoms of acute mountain sickness. He also emphasizes that oral hydration can be important in preventing high altitude illnesses.
Overall, Dr. Zubieta’s perspective on high altitude is fascinating. During my master’s program, I learned a systematic way to treat patients using guidelines or criteria backed by years of evidence that helps you, the provider, make an informed decision on a patient’s particular case. Dr. Zubieta reinforced the importance of treating each patient’s case individually to determine the underlying cause, rather than suggesting acetazolamide to everyone who doesn’t want to deal with acute mountain sickness. As for myself, seeing how physicians in other countries approach certain illnesses has definitely made me think twice about how to approach high altitude illness.
To learn more about Dr. Gustavo Zubieta and his clinic, you can visit his website at: https://altitudeclinic.com/
Born and raised in Northern Orange County of California, Michael Le is a second-year physician assistant student at the Red Rocks Community College Physician Assistant Program in Arvada, CO. Michael attended California State Polytechnic University Pomona otherwise known locally as Cal Poly Pomona where he earned his bachelor’s degree in Kinesiology. Shortly after, he worked as an EMT for Lifeline Ambulance, and physical therapy aide and post-anesthesia care unit technician at Fountain Valley Regional Hospital in Fountain Valley, CA. In his free time, Michael likes to cook and breed show rabbits.
Dr. Margot Daly DVM, CCRP, CVA, of the Frisco Animal Hospital in Frisco, CO, graduated from the University of California – Davis in 2013, and has worked in general practice, emergency practice, and most recently in specialty practice as a full-time rehabilitation and sports medicine veterinarian. Prior to veterinary school, she studied Sociology at UC Berkeley, and had a career as a professional equestrian, which led to an interest in orthopedics, biomechanics, and physical rehabilitation. Following graduation, she received the Certified Canine Rehabilitation Practitioner designation from the University of Tennessee – Knoxville, and the Certified Veterinary Acupuncturist designation from the Chi Institute in Reddick, Florida. She has been with the Frisco Animal Hospital for a year and a half, and when she is not working, she can be found riding a horse or one of her many bicycles, fostering dogs and kittens, reading books, skiing, or traveling somewhere new!
We interviewed Dr. Daly on her advice for canine high country health, winter dog gear, common winter injuries, and winter activities to participate in with your dog.
One of the most common things to be aware of is canine “weekend warrior syndrome.” Dog owners must be sure their dogs are fit enough to participate in physically intense weekend activities. Many dogs only go out in their yard or take a few short walks during the week and then go on big hikes, back country ski trips, or long mountain bike rides on the weekends. Unfortunately, during the high intensity activity the dog’s adrenaline is high and the dog won’t show signs of fatigue, yet the next day with dog will feel awful and be extremely sore. It is comparable to a human doing cross fit only once per week … [imagine] how he or she would feel the next day. To avoid this phenomenon, ensure your dog is fit enough by practicing 30-60 minutes of moderate exercise at least three times per week, which can include 30 minutes of jogging or 60 minutes of active walking. If your dog is doing less than that during the week, it is important to be thoughtful of what you are asking of your dog or what you are giving them the opportunity to do over the weekend. Unfortunately, a fun weekend can become overly taxing on your dog very quickly.
Signs your dog may have done too much over the weekend include not wanting to go up or down stairs, refusing to jump in and out of the car, or not wanting to get up or down from the couch. Your dog may not necessarily be limping since they are more likely to have general full-body fatigue, aches, and soreness. Your dog should still eat and drink normally, and if they aren’t that is reason to call your vet.
Winter Clothing & Gear
Booties: Dog clothing can be helpful as dogs can get cold just like humans do during outdoor winter activities. Booties can be advantageous during both summer and winter activities. The best policy is to pay attention to your dog’s behavior to determine how necessary booties are. Some dogs make it clear that they are uncomfortable in the snow and slush by holding their paws high in an alternating fashion, sitting down, or refusing to walk. Some dogs are more sensitive than others and some have a higher tolerance for the cold than others.
The key to booties is acclimating your dog over a week or so before taking the booties out on an adventure. The best way to do this is to put your new booties on your dog in your house and then give them a treat or play with their favorite toy. This will help reinforce the booties and make them a fun experience for your dog! This may take several days before the dog will tolerate the booties and walk around comfortably in them. Essentially, don’t wait until the morning of the big hike to put the booties on your dog for the first time. Another strategy is to start with lightweight booties made of felt with one Velcro strap. These are a lightweight cheap option and are the same booties sled dogs on the Iditarod use. It is best to buy a few sets of these to start as some will inevitably get lost. If you find that your dog requires something more substantial, Dr. Daly recommends RuffWear boots which have a heavy rubber sole. Beware these booties may cause difficulty for a dog with mobility issues where heavy booties may impair the dog’s ability to walk safely. Custom booties are also an option and are recommended for dogs with atypically shaped feet such as greyhounds. A company called TheraPaw will coordinate with your vet to get measurements of your dog’s feet and make custom booties.
If your dog is totally intolerant of booties but could benefit from them, you can try musher wax. It provides a slightly waterproof barrier between your dog’s paws and the roads. It also helps prevent ice balls in dogs with a lot of feathering on their paws or between their toes. Put the wax on right before your take your dog outside and wipe the dog’s paws as soon as you get home. This can help protect dogs who have a lot of road time to protect them from road salt, sand, and ice chemicals.
Jackets: Dr. Daly confirms that there are dogs that may benefit from a jacket especially when participating in winter hiking or backcountry skiing. If you see your dog shivering, hunching their back, or crouching their neck and shoulders, your dog is likely cold and would benefit from a jacket. When choosing a jacket, it is imperative that you choose a jacket that has a full chest and short sleeves vs one that just has a strap across the chest. This ensures that the snow will slide off the chest and not become trapped against the dog’s skin. It is hard for a dog to overheat in the winter, but it is a good idea to provide layering for your dog. Most importantly, do not choose a cotton fabric, but a fabric that will wick and dry quickly such as fleece, soft shell, or a technical fabric. If your dog’s jacket becomes wet or soaked, it is important to take it off, because a wet jacket is no longer providing warmth and will end up making your dog colder.
Goggles: There are a large number of canine patients with eye problems related to the UV light exposure at high altitude. In particular, pannus, an eye condition exacerbated by UV light, is common in dogs living at high altitude due to more UV exposure and increased UV reflection off snow. This immune-mediated condition affects the cornea and causes pink or grey granular tissue to grow from the lateral cornea toward the medial cornea. It is a type of chronic superficial keratitis that certain breeds, specifically German shepherds, are more prone to. For this reason, goggles are recommended for dogs living at high altitude especially if the dog is a high risk breed or if they are already diagnosed with pannus. Weekend warriors are at a much lower risk of developing pannus and goggles are not as strongly recommended. As with dog booties, dogs must be acclimated to goggles and the goggles reinforced with treats or play time. It is not recommended to try out goggles for the first time out on the mountain. Aim for about a week of acclimation around the house and neighborhood so your dog tolerates the equipment well. Dr. Daly has had good luck with RexSpecs which do not require a vet to measure the dog, but she is always happy to help owners measure their dogs.
Sunscreen: Surprisingly, canine sunburn is rare, even at high altitude. If it does occur, the burn is normally anywhere the dog has thin to no hair or pink to white skin. Most commonly it occurs on the nose and belly, especially if the dog prefers to lounge on its back in the sun. Mineral-based sunscreens with an active ingredient of titanium dioxide, such as California Baby Brand Sunscreen, are recommended. After putting sunscreen or any ointment on a dog’s nose it is a good idea to immediately give him or her a treat or chew toy to avoid the dog licking the ointment right off.
Prevention at High Altitude
The one best thing you can do to make sure your pet stays healthy and happy at altitude is to ensure adequate hydration. Dr. Daly does not recommend supplemental electrolytes but encourages owners not to depend on mountain streams, rivers, lakes, snow, or puddles to provide adequate hydration for active high country dogs. The high country has giardia and leptospirosis in natural water sources. Giardia can cause gastrointestinal symptoms, and leptospirosis can cause liver and kidney failure as well as having the potential to be transmitted to humans. Bring as much water for your dog as you do for yourself. If you bring one liter then also bring one liter for your dog. Signs your dog may be dehydrated include lethargy, decreased appetite, odd behavior, head-shaking, crying out, or barking. Dogs normally tend to drink more water while at altitude, and this behavior is only concerning if the dog has blood in the urine, appears to be in pain while urinating, or is having accidents in the house when the dog was previously housetrained.
Lastly, if you go camping with your dog it is imperative that you bring your dog’s daily medications with you and not skip a day simply because you are camping. Chronic medications can’t be skipped for even one dose.
Common High Altitude Diagnoses
Dr. Daly sees many recreational injuries and ACL tears between February and April. During this time of year, the snow has a crusty top layer with soft snow underneath. This leads to dogs punching through the top layer and injuring themselves when the soft snow underneath gives way. This post-holing causes many ligament strains and tears this time of year. In the beginning of winter when the conditions are predominantly slippery and icy, she sees wrist and toe strains and sprains from dogs trying to grip with their feet.
Another common injury are lacerations from back country skis. Many people enjoy taking their canine companion back country skiing but fail to train the dog to stay behind them while cruising down the slope. As a result, many dogs end up with lacerations from running in front of or beside their owner and making contact with their owner’s skis. This can lead to lacerations on the dog’s lower legs including around their tendons. It is also important to teach your dog to stay behind you if they come mountain biking. Many dogs end up with injuries from running in front of or beside their owner’s mountain bikes.
Acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), re-entry HAPE, or high altitude cerebral edema (HACE) are exceedingly rare in dogs. The only situation which may predispose a dog to breathing problems is one coming from sea level with underlying cardiac or pulmonic pathology, such as heart failure or a pulmonary contusion. When coming from sea level with an older dog or one with an underlying comorbidity, it is recommended to stop in Denver for 2-3 nights to let the dog acclimate to the altitude and resultant lower oxygen concentration. Dogs can be prescribed home oxygen concentrators, but these should only be used under the supervision of a veterinarian as they require a specific home kennel or tubing being sewn into the dog’s nare. If your dog falls into a high risk category, Dr. Daly describes “head pressing” as an alarm sign requiring an emergency call to a local vet. This is described as a dog leaning headfirst into a wall, furniture, or other upright object as though it is using the object to hold its head up. Other concerning signs include severe lethargy, vomiting or diarrhea that does not resolve within 24 hours, or respiratory distress of any kind.
Strengthening & Exercise
Most dogs will benefit from some degree of core and hind limb strengthening, as well as exercises to improve proprioception, or body awareness. The stronger and more coordinated the dog is, the lower risk of injury, even with high impact activities. Additionally, dogs can benefit from a personalized exercise program based on their confirmation, for example a long back or short legs, and pre-existing injuries. Dr. Daly’s background in sports medicine gives her a unique viewpoint allowing her to assess any dog and provide a program to prevent future and, more importantly, repeat injuries. If an owner is hoping that his or her companion can return to hiking 14ers after a ligament tear, then a home exercise program is imperative. Plans generally require about 20 minutes of treatment averaging three times a week and incorporating everyday activities such as stairs and working the dog on alternative surfaces. This ensures dog owners don’t necessarily have to invest in additional equipment.
Are there any winter dog sports clubs you recommend?
Dr. Daly has found that many types of active dogs enjoy the variety of mushing sports that can be done in the winter. These include everything from single or double dog skijoring, bikejoring, and canicross (which is a version of cross country running with your dog), all the way to dogsledding with two or more dogs. She is a part of the Colorado Mountain Mushers which is a great place to start for anyone interested in exploring these activities. The club consists of retired professional veterans to amateur mushers and is a friendly, welcoming, all-inclusive group with abundant resources and advice. The club usually runs about four events per year (COVID pending) and can help you learn some new ways to connect with your canine companion, Huskies not required!
Courtney Zak is currently in her second year of PA school at Red Rocks Community College in Arvada, CO. She is a member of the class of 2021 graduating in November. She attended the University of North Carolina at Chapel Hill in Chapel Hill, NC for her undergraduate degree in American Studies. She then completed an Occupational Therapy Assistant (OTA) program at Cape Fear Community College in Wilmington, NC. She practiced five years as an OTA working primarily with the geriatric population helping rehab people with various orthopedic injuries, strokes, heart attacks, and general deconditioning. After working up to management, Courtney decided she wanted to gain more medical insight and expand her scope of practice, so she decided to pursue a career as a physician assistant. Courtney now lives in Golden with her husband Jack, three dogs Brooks, Arlo, and Chloe, and her horse, Cannon. She enjoys horseback riding, hiking, paddle boarding, camping, and mountain biking in her free time.
Acetazolamide is already known for its success with treating Acute Mountain Sickness (AMS) and helping patients with their transition to higher altitudes, but what other options are available? What about those who don’t want a prescription, that are looking for other alternatives to help them with AMS and being at high altitude?
During my time in Frisco, Colorado (9000’/2743 m) I was fortunate enough to interview two resident Naturopathic Doctors. Mountain River Naturopathic Clinic on Main Street of this little mountain town is a wonderful oasis for anyone in Colorado’s Summit County looking for alternative care and treatment for their mind and body.
Dr. Kimberly Nearpass, ND and Dr. Justin Pollack, ND took the time to educate Dr. Chris Ebert-Santos, my classmate Rachel Mader, and myself about all the naturopathic remedies available for AMS and residents at altitude.
Tell us about Naturopathic medicine and why you picked this path of medicine?
Dr. Kimberly Nearpass: I thought I was going to be an OBGYN and then I did more research. I talked to doctors, midwives and herbalists and found that the Western medicine model didn’t feel right to me. So I thought, “Do I go to medical school and try to operate functionally from the inside or do I find another track?” I did not know about naturopathic medicine until a few years later. I took some time off; I traveled and went to the Peace Corps and then I discovered naturopathic medicine and loved it. I had lived in Ecuador in the rainforest as a naturalist guide so I learned a lot about traditional medicine that way. I learned a lot about traditional medicine when I lived in rural Africa as well. Living in these rural areas and watching the indigenous people — and they certainly use modern medicine — but they did not have a lot of access. Especially in the rainforest, they were using a lot of plants and I was fascinated by that. But I still wanted the medical training. Then I discovered naturopathic school. So, it’s four years of medical school, we get the medical training, but we also have that more holistic, natural, herbal based approach.
What naturopathic remedies are available for acute mountain sickness (AMS)?
Dr. Nearpass: So I will tell you Acli-Mate is our go-to. I’m not tied to this product, a friend of mine, it is her company, she is a naturopathic doctor in Gunnison. She formulated this, she started it out as a high-altitude electrolyte drink. Everybody that comes in our door, we start with this. This stuff works AMAZING. We rarely have to go anywhere else. I think the combination of the electrolytes and that it is hydrating has a great benefit. It helps with the headache and the nausea. For mild to moderate symptoms of AMS it is incredible. What we do is if we have family coming to visit from sea level is we have them start drinking it before they come.
Acli-Mate is found to be highly effective at helping people who are suffering from AMS. The blend includes herbs Ginkgo biloba and Rhodiola, both of which have proven effective in preventing and treating altitude related sickness. Both herbs seem to improve circulation, especially through cerebral vessels, and cellular energy function through improved uptake and utilization of oxygen, reducing toxic brain edema. Ginkgo has also been shown to inhibit platelet clumping, keeping red blood cells evenly dispersed, which improves delivery of oxygen to tissues, while Rhodiola appears to help the body deal with stress.
Nutrients in Acli-Mate: Vitamin C, and many of the B vitamins: thiamin (B1), riboflavin (B2), niacin (B3), pantothene (B5) and cobolamin (B12).
Have you noticed that when you have patients drink it before they arrive at high altitude, they have a better outcome?
Dr. Nearpass: Yes. And I have a patient who is 70 now and 5-10 years ago she went with some girlfriend to hike Mount Kilimanjaro. She had all her girlfriends take it and emailed me after saying, “We all did great!” And I don’t want to put all my eggs in one basket but this is almost always all we need.
Dr. Justin Pollack: There is something about that blend of Rhodiola, Ginkgo and the B vitamins that seems to work. We’ve had tons of people use it clinically.
Dr. Nearpass: For other options, I think Rhodiola is a good one. It’s interesting to me because Rhodiola grows in Mongolia, it grows in high altitude. One of the things we talk about in herbal medicine is often the plants we need are there. For example, dandelion root grows everywhere and it is good for liver detox and helps with hepatic function. So, it is interesting to me that dandelion is popping up on the side of the highways and in areas that we could probably use a little cleansing and detoxing.
Dr. Chris Ebert-Santos: What about Coca?
Dr. Nearpass: Oh yes! Coca works amazing. It is a plant that grows in the high altitudes of South America and when I was living in Ecuador the folks that live in the Andes drink coca tea all the time. They also take coca leaves and shove a wad in their mouth like chew. While they are doing work, cardiovascular work, they just put it in their mouth and that is their medicine. It gives them more stamina and reduces fatigue. There is not much research on it because you cannot even get it in the states.
Is there a reason you can’t get it here?
Dr. Nearpass: Because it’s the same plant as cocaine. We used to have a homeopathic version of it. Do you know what homeopathic medicine is? You take a remedy and you dilute it until you don’t have any molecules of the original substance but you basically are getting an energetic imprint. For example, Rhus tox, poison ivy, the homeopathic rhus tox is used to treat red itchy inflamed poison ivy type symptoms. But with coca, even homeopathically, the herb is used in concentrated doses to treat high altitude sickness and increase energy and stamina. But because there is such a control over coca, we can’t even get the homeopathic version, which is ridiculous because there is not a single molecule of the plant in the remedy.
Dr. Pollack: When Kim and I were on our honeymoon, we passed through Bolivia and Peru. In Bolivia in la Paz there was a coca museum. It was really fascinating because something around 1,000lbs of coca leaves must be distilled down into 1 gram to make cocaine. When you make tea out of the raw leaves it seems to have the subtle effect of suppressing appetite and allowing people to do better at altitude. Marijuana has a whole stigma around it, even though it has been legalized, and so the research and researchers are stigmatized, yet there are a lot of useful compound coming out of the plant. So, I’m sure that coca is the same, and hopefully somewhere down the line we will be able to use coca leaf for altitude.
Dr. Nearpass: And certainly, coca is the number one herb in the Andes that people use. You can get it everywhere, it’s like black tea down there.
So because coca is not available for your patients, and if you found Acli-Mate was not successful, what would you recommend?
Dr. Nearpass: This is the thing about naturopathic doctors, we look at each individual. If it’s a resident, per se, we are going to draw blood work. We are going to try to figure out what’s going on, what is the underlying issue. Do you have relative anemia? We will run iron but also ferritin. They may have normal blood cells, normal H&H but their ferritin is a 2. One of the things that is tricky about being a naturopathic doctor is, we will be at a party and someone will ask, “Well what do you do for hypertension?” or “What do you do for digestive issues?” We always say we don’t treat symptoms; we don’t treat disease, we treat people. If someone is having recurrent altitude sickness, we are going to look at the individual and look at what is going on. What’s their diet? Are they hydrated enough? Are they drinking too much alcohol? Do they have subclinical hypothyroidism that might affect their metabolism and their ability to adapt when they get here? Might their ferritin levels be really low? And then we would sit down with the patient and say, “Well what are your symptoms? Is nausea the main symptom? Is headache the main symptom?” And then, what other factors could be contributing to these symptoms? If it’s headache then CoQ10 would be what I would go to.
Dr. Chris Ebert-Santos: And what do you look for on physical exams on residents that are having trouble with altitude?
Dr. Nearpass: On physical exams we are doing the standard physical that you would do but we are also looking at the tongue. I am not a Chinese Medicine doctor but the tongue does give you some insight on what is going on in the digestive tract. If we are seeing inflammation or glossitis or geographic tongue, we are thinking, “Oh, this person may have some underlying digestive issue.” We might look at Arroyo’s sign, it’s a traditional sign when you shine a light on someone’s pupil and most of the time their pupil will constrict, but Arroyo’s sign is both pupils will stay dilated. This is a red light for adrenal issues, for hyper cortisol output or adrenaline output. If someone is in a chronically stressed state, their pupils are going to be dilated all the time. If it looks like someone has chronic stress, it takes you out of the parasympathetic, and so their digestion is going to be weaker. The way we look at it is the body has to prioritize, and there is only so much that one body can do. And I suspect that living at high altitude puts chronic stress on the body. I see this huge lack of libido in the women. I see women in their 20s, 30s, 40s, 50s. But it kind of makes sense right? If the body is chronically stressed, having a baby is a huge energy output for a woman. So, I think we may see the chronic stress impacts of living at high altitude.
Dr. Chris Ebert-Santos: So what do you do for the libido?
Dr. Nearpass: That is one that if I could invent one pill, it would be that one. Libido is really hard, especially in women. Unfortunately, what I see is its one of the first things to go in women and it’s one of the last things to respond. So, my suspicion is that this altitude is another physical stress on our bodies. I think we can see multiple systems being affected by it, maybe not severely but still.
Rachel Mader PA-S: Is there anything for sleep at altitude? I know a lot of people struggle with that.
Dr. Nearpass: Yes, again for us there is no magic bullet. Melatonin is very well known and that can be very helpful for some people, but it sure doesn’t work for everybody. When patients come in and say, “What do you use for sleep?” I want to take every person back and have a conversation with them. Ask, “Are you having a hard time falling asleep? Are you having a hard time staying asleep? Are you waking up to go to the bathroom?” Right? So, there isn’t a magic bullet that will work for everyone. Breaking it down, I think you could have 50 people with altitude sickness and we’re going to do 50 different things. I mean, I would start with Acli-Mate, but every patient will be different.
Do you think there’s benefit to adding Acli-Mate in combination with an Acetazolamide prescription?
Dr. Nearpass: As far as I know, there’s no issue combining the two. Most people that come to us are usually trying to avoid medication, but what I always say to them in that situation is, “Try this other stuff to see if it helps.” But if it’s someone who had trouble in the past with AMS, I’ll say go to your medical doctor and get the prescription so that you have it if you need it. I think another issue is that people fly here right from Texas. They fly to Denver, they get right on the shuttle, and they drive right up here. If they’ve had trouble in the past, they should drive here and take their time. Spend a couple days in Denver if they have to. That does seem to help people.
Thank you so much Dr. Nearpass. Is there anything else about naturopathic medicine and high altitude you would like to share with us?
Dr. Nearpass: I guess I would say again that from a naturopathic perspective it is really about looking at the individual.
Is there anything that could specifically help with nausea symptoms of AMS?
Dr. Nearpass: Ipecacuanha! Ipecac syrup — which in full doses will make you throw up, so the homeopathic Ipecacuanha we use for nausea — that is one I have actually used quite a bit for people who have that aspect of AMS. It is really good for nausea and pregnancy too.
The way I see Healthcare is a full spectrum, and on one end you have the brain surgeons and on the other end you have the Reiki energy healers. Then you have everything in between. I see us sitting in the middle. For patients, the best thing is to be aware of where they belong on that spectrum. I’m not going to replace a brain surgeon, but sometimes a little bit of massage and energy can do the trick. It is so great for us as practitioners to be able to talk and converse with the medical doctors. We’ve been really lucky in this community.
Available research articles on Naturopathic Remedies and AMS:
Zhang DX, Zhang YK, Nie HJ, Zhang RJ, Cui JH, Cheng Y, Wang YH, Xiao ZH, Liu JY, Wang H. [Protective effects of new compound codonopsis tablets against acute mountain sickness]. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2010 May;26(2):148-52. Chinese. PMID: 20684264.
Tsai TY, Wang SH, Lee YK, Su YC. Ginkgo biloba extract for prevention of acute mountain sickness: a systematic review and meta-analysis of randomized controlled trials. BMJ Open. 2018;8(8):e022005. Published 2018 Aug 17. doi:10.1136/bmjopen-2018-022005
Gertsch JH, Basnyat B, Johnson EW, Onopa J, Holck PS. Randomised, double blind, placebo-controlled comparison of ginkgo biloba and acetazolamide for prevention of acute mountain sickness among Himalayan trekkers: the prevention of high-altitude illness trial (PHAIT). BMJ. 2004;328(7443):797. doi:10.1136/bmj.38043.501690.7C
Ke T, Wang J, Swenson ER, et al. Effect of acetazolamide and gingko biloba on the human pulmonary vascular response to an acute altitude ascent. High Alt Med Biol. 2013;14(2):162-167. doi:10.1089/ham.2012.1099
Wang J, Xiong X, Xing Y, et al. Chinese herbal medicine for acute mountain sickness: a systematic review of randomized controlled trials. Evid Based Complement Alternat Med. 2013;2013:732562. doi:10.1155/2013/732562
Lee SY, Li MH, Shi LS, Chu H, Ho CW, Chang TC. Rhodiola crenulata Extract Alleviates Hypoxic Pulmonary Edema in Rats. Evid Based Complement Alternat Med. 2013;2013:718739. doi:10.1155/2013/718739
Hannah Addison (she, her, hers) is a second-year physician assistant student at Red Rocks Community College Physician Assistant Program in Arvada Colorado. Hannah was born and raised in the South Denver area of Colorado. She spent four years getting her bachelor’s in biomedical science at Colorado State University in Fort Collins, CO where she decided her life career goal was to become a PA. After graduating and while applying for PA programs, Hannah worked at Littleton Adventist Hospital of Centura as a CNA, Telemetry Technician and Unit Clerk. In her free time, Hannah enjoys hiking and discovering all the delicious food and drink Colorado has to offer.
After a horrendous Autumn of forest fires in Colorado, we’ve received well over a foot of snow in a series of storms, and it’s safe to say Winter has arrived. Hiking season is never truly over in the Rockies, but Colorado’s famed Fourteeners are now blanketed in snow, increasing the risk of any attempted ascent exponentially. But through the fire and ice, the Summer yielded ample opportunity for at least one enthusiast to check off more of her bucket list adventures.
Since leaving her home in Paraguay, mountaineer and hiking expert Clarissa Acevedo Santos has spent over a decade ascending Colorado and Hawai’i’s highest peaks. In addition to her excursions in the Ko’olau and Kahalawai ranges including Maui’s Haleakalā crater, she has summited well over half the 58 peaks in Colorado over 14,000 feet, making her the first from her country of record to do so.
She was invited on her first Fourteener years ago when friends took her up Quandary outside of Breckenridge, CO, at 14,271′ (4350 m).
“When I hiked that first mountain, it was hard, because I wasn’t used to gaining that much elevation. I didn’t really enjoy it so much because of how cold it was on the summit. Even though I made it to the top, I wasn’t really having fun with not feeling my lips and not feeling my fingers because it was really, really cold. I could barely smile, and we couldn’t even enjoy the summit because of how windy it was!
“After that hike, I didn’t hike for a while, and I got invited again to climb Mt. Elbert in 2012. It was actually much more enjoyable because it was with a big group of college kids from Summit and the weather was just perfect. We were able to summit it and enjoy the day and have lunch up there. So that’s what started to change my mind about hiking Fourteeners because I enjoyed my time up top. That’s when I realized it’s not always difficult to be up there. I think I got what all the hikers call ‘Peak Fever’. So after that is when I feel like I started going non-stop, and I met more friends that were into hiking, and researched more about the mountain before I go.
“I always go with people who knew more about it, so I started learning more with other friends and other hikers. And I started feeling actually great when I got higher. It was always harder to get started close to the beginning [of the trail], just to gain all that elevation. But then when I was getting close to the summit, I just got more energy. I just got more excited to be at the top. That’s the goal. It’s a great feeling.”
Clarissa has an app that she uses to record all her summits called Colorado 14ers that allows her to keep record of and upload photos from every Fourteener she’s hiked. She pulls it up as she recounts year after year of more and more summits, some she’s even done more than once.
There is a class system rating every trail by level of difficulty, Class 1 being the easiest and Class 4 being the most difficult. The most difficult peak Clarissa recounts climbing is Long’s Peak, as well as the most dangerous weather she’s climbed in.
“It was a little bit late to summit it. It was not a good idea. If the rocks got wet, it could be very dangerous. There were people turning around. We decided to wait on a ridge. There were three [of us], and one turned around. He wasn’t feeling good, he was getting tired, he wasn’t used to hiking that many hours.
“We decided to wait for the clouds to go away. After that we just kept going. It did not rain on us, thankfully.”
Clarissa has seen her share of altitude sickness as well. One of her frequent hiking companions repeatedly gets stomachaches and headaches everytime they hike, in spite of being an experienced hiker as well.
“I always ask [one of my friends in particular] if she wants to stop or if she wants something. She normally doesn’t eat before she starts a hike. No breakfast. But I also carry ginger candy … I learned that from other hikers telling me it can help settle your stomach a little bit. It’s everywhere, in all the stores. Now they’ve created gums. I’ve started chewing them on my hikes just in case. You never know. I’ve seen people who hike all the time, and they ate something that didn’t digest well, and they feel sick and get a little dizzy.
“I’ve never experienced any headaches on the way up. The only time I remember having a headache is when I ran out of water. I hiked Oxford and Belford in the Saguache range in the same day. My head hurt and it lasted for that night. Now I take a filter with me so I can fill my [Camelbak] bladder. And I also take electrolytes. And I’ve started hiking with poles more as well, just because you put alot of weight on your knees when you’re hiking down. It’s very smart to start using poles.”
When it comes to preparing such demanding ascents, Clarissa recommends spending some time at an intermediate altitude before hitting the trail, and staying well-hydrated. Caffeine and alcohol the night before doesn’t typically help.
“It doesn’t matter how fit you are … you can still get really sick. I’ve heard of people who get headaches for several days because [they’re] not used to [the elevation here].”
She also says it’s important that you start any hiking at all to build the strength in your lungs.
“It does hurt,” she says about the stress on your respiratory system. “I remember when I was hiking Quandary, my chest was so pressed, my heart was [beating] so fast, my stomach was feeling weird, like I had to pee or I had to do number two or something. It was such a difficult part of … gaining all that elevation.”
“You’ve gotta find a good pace for yourself. I see many of my friends going really fast ahead of me, then they’re very tired and they have a hard time getting to the top. I’ve waited for many people because they are struggling so much at the end. Take as many breaks as you think [you need]. Carry enough water!“
Clarissa keeps seeing a lot of hikers running out of water. “They just bring a tiny plastic bottle. That’s a huge mistake. And bring food, too. You will get hungry after a mountain. It’s so funny how many people are unprepared. If I’m hiking with newbies, I make sure they have everything, and they’re always thankful.”
When it comes to clothes and shoes, Clarissa recommends really good traction. She’s tried some more affordable brands, but says the durability is worth paying more for.
Don’t ever hike in new hiking shoes before you’ve broken them in. Good hiking socks also have more padding at the heels and toes and help prevent blisters. She also will double-up on socks, or even bring an extra pair to help mitigate possible cold.
“I reapply sunscreen on my hikes two to three times. Many times my nose will burn. I always carry sunglasses. You’re so close to the sun, you don’t realize. You don’t want to burn your eyes or your face. Even with the sunglasses, having a hat on top of it doesn’t hurt. Even in the Summer in the mountains, carry additional gloves or layers, because you don’t know what the weather could be. Temperature changes quick.
“I just recently purchased a nice puffy Northface that helped me. I will always have a thin layer underneath because you get hot and cold. You’re gaining elevation, you get hot, then you get cold in the middle …”
When it comes to navigation, Clarissa’s main resource is 14ers.com, which allows you to download offline maps, so you aren’t relying completely on having cell service.
“Even though I have hiked many of them, I want to be sure I’m going the right direction … I just love reading everything I can beforehand. I read about the class, how much exposure, how long it’s going to take, then I download the maps, look at the maps, what kind of road it’s going to be, if my car can make it up higher or if I have to hike longer.”
Clarissa has heard of other Paraguayans hiking around the world, but has never met another one on a Fourteener personally. But she does meet a lot of people from around the world on these ascents who ask if there are mountains in Paraguay. The highest is Cerro Peró at 2762′ (842 m) in this landlocked country known more for its rivers and the hydroelectricity they provide for Paraguay and its neighboring countries, including Brazil and Argentina.
Clarissa says she’s learning more and more each year about mountaineering and advocates learning as much as possible about each ascent before you go. The weather may be different every single time.
Bring the layers, whether you think you’ll need them or not. And leave no trace.
Thank you, Clarissa, for sharing your continuing legacy, and be safe up there!
Roberto Santos is from the remote island of Saipan, in the Commonwealth of the Northern Mariana Islands. He has since lived in Japan and the Hawaiian Islands, and has made Colorado his current home, where he is a web developer, musician, avid outdoorsman and prolific reader. When he is not developing applications and graphics, you can find him performing with the Denver Philharmonic Orchestra, snowboarding Vail or Keystone, soaking in hot springs, or reading non-fiction at a brewery. Clarissa is his wife who is increasingly a much faster, more experienced mountaineer than he is, but he will occasionally feel ambitious enough to join her on a Fourteener, at the top of which they both enjoy a delicious cider, weather permitting.
Typical symptoms of acute mountain sickness (AMS) are headache, loss of appetite, disturbed sleep, nausea, vomiting, fatigue, and dizziness. However, more serious conditions such as high altitude pulmonary edema (HAPE) or cerebral edema (HACE) can present with this illness. Avoiding these unpleasant symptoms while at elevatione is possible through gradual pre-acclimatization when possible (what science recommends!), or there are specific medications that can potentially prevent the development of AMS, such as acetazolamide. This article will address how acetazolamide (also known as Diamox) can help prevent AMS, discuss the physiological effects of the medication, some side effects, and whether or not this drug can enhance physical performance.
How does it work?
Acetazolamide is a carbonic anhydrase inhibitor. Carbonic anhydrase regulates kidney absorption of sodium bicarb and chloride. Acetazolamide works by inhibiting carbonic anhydrase, preventing the reabsorption of sodium bicarb and chloride, causing acidosis in the blood. When experiencing AMS, the body is in a state of respiratory alkalosis. By taking acetazolamide, which causes metabolic acidosis it drives receptors in the body to increase the patient’s minute ventilation by as much as 50%, improving arterial PO2 and increasing oxygen saturation.
How can I obtain acetazolamide and when should I start taking it?
Acetazolamide requires a doctor’s prescription, and the typical dose for the prevention of AMS is 125 mg twice daily. The typical recommendation is to start taking acetazolamide one day before your exposure to high altitude and continue usage throughout your trip. When taken one day before exposure, studies show that acetazolamide reduced AMS incidence and enhanced tolerance to submaximal exercise on the first day at high altitude versus starting administration the day of arrival.2 However, if, for some reason, the medication isn’t started a day before arrival to high altitude, then the medication should be started upon arrival, which still shows a decreased incidence in the development of AMS.
Allergies & Side Effects
Acetazolamide belongs to a classification of drugs known as sulfonamides, which is broken down further into two categories: antibiotics and nonantibiotics. Acetazolamide is considered a nonantibiotic sulfonamide, which varies significantly from sulfonamide antibiotics because these antibiotics contain what is known as an arylamine group in their chemical structure. This arylamine group is a key component of the allergic response to sulfonamide antibiotics (sulfamethoxazole, sulfasalazine, sulfadiazine, and the anti-retrovirals amprenavir and fosamprenavir); however, this structure is not present in other sulfonamide drugs like acetazolamide.1 There is available evidence that suggests patients who are allergic to arylamine sulfonamides do not cross-react to sulfonamides that lack the arylamine group and so may safely take non-arylamine sulfonamides.1 Patients with known allergies to sulfonamide drugs should consult with their healthcare provider before taking acetazolamide.
Like all other medications, there are risks that side effects will occur with acetazolamide’s administration. The common side effects are fatigue, malaise, changes in taste, paresthesia, diarrhea, electrolyte disorders, polyuria, and tinnitus. While conducting research, I found 3 – 4 people from my hometown, located at 69 feet above sea level, who have taken acetazolamide while rapidly ascending to 8,000+ feet to ski or hunt. When asked how their experience was taking acetazolamide, the common response was that they stopped using it within the first two days due to the change in the taste of their beer! The pleasurable “fizz” in our carbonated drinks is attributed to chemical excitation of nociceptors in the oral cavity via the conversion of CO2 to the carbonic acid in a reaction catalyzed by carbonic anhydrase. So administering a carbonic anhydrase inhibitor like acetazolamide results in flat-tasting carbonated drinks, or, as described by the aforementioned subjects, a “nasty beer”!4 While a bad tasting beer is no fun, AMS is a lot less fun, and one would be best advised to continue taking acetazolamide while at high altitude.
Can taking acetazolamide increase physical performance and endurance at high altitudes?
Though enticing, it doesn’t seem to work out that way. There are multiple studies on exercise endurance in hypoxic conditions with the administration of acetazolamide, but the produced results are confounding. The majority of the studies show that for a non-acclimated person taking acetazolamide in hypoxic conditions, endurance and exhaustion time were increased with submaximal and maximal exercise. A few reasons this may be true are the induction of metabolic acidosis and its effects on muscle cells, the diuretic effect of the drug inducing dehydration, and additional increases in work of breathing cause vasoconstriction in locomotor muscles, which can impair exercise performance.3 Regardless, this medication’s proven science in the prevention of AMS should not be mistaken with the multiple confounding studies on exercise endurance.
From Opelousas, Louisiana, Scott Rogers is currently a Family Nurse Practitioner student at Walden University after having practiced five years as an RN following his BSN from the University of Louisiana at Lafayette. He has lived in Colorado for the past four years where he enjoys hiking with his wife and dog, snowboarding all the resorts in Summit County, and basketball, and hopes to pursue more work with acute physical rehabilitation, orthopedics, and sports medicine.
1. American Academy of Allergy Asthma & Immunology. (2019, June 23). Acetazolamide and sulfonamide allergy: AAAAI. Retrieved November 13, 2020, from https://www.aaaai.org/ask-the-expert/acetazolamide
2. Burtscher, M., Gatterer, H., Faulhaber, M., & Burtscher, J. (2014). Acetazolamide pre-treatment before ascending to high altitudes: when to start?. International journal of clinical and experimental medicine, 7(11), 4378–4383.
3. Garske, L., Medicine, 1., Brown, M., Morrison, S., Y, B., G., B., . . . Zoll, J. (2003, March 01). Acetazolamide reduces exercise capacity and increases leg fatigue under hypoxic conditions. Retrieved November 13, 2020, from https://journals.physiology.org/doi/full/10.1152/japplphysiol.00746.2001
4. Jean-Marc Dessirier, Christopher T. Simons, Mirela Iodi Carstens, Michael O’Mahony, E. Carstens, Psychophysical and Neurobiological Evidence that the Oral Sensation Elicited by Carbonated Water is of Chemogenic Origin, Chemical Senses, Volume 25, Issue 3, June 2000, Pages 277–284, https://doi.org/10.1093/chemse/25.3.277