Category Archives: Medicine

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The Nobel Prize: Hypoxia studies Won in 2019!

The Nobel prizes are announced this month. Alfred Nobel invented dynamite in 1866. Within 30 years, Nobel made a large fortune from his invention. He demonstrated his passion for literature and science by creating a yearly prize to discoveries most beneficial to humankind. The five prize categories include physics, chemistry, medicine (physiology), literature and peace. The Nobel prize nominations are made by university professors, national assemblies, state governments, and international courts. The prize is awarded yearly to individuals who have discovered a new paradigm or a paradigm shift within their field. The prize recipients are declared on the first Monday of October of every year and the award is presented by the Nobel assembly on November 10th, the anniversary of Alfred Nobel’s death. The Nobel prize consists of a gold medal, a diploma of recognition of achievement, and a cash prize in the amount of $1 million U.S. dollars. 

There is no limit to the number of nominations that can be made or the number of times that an individual can be nominated. There were 400 candidates nominated in the field of medicine in 2019, all of which inspired, challenged, and demonstrated greatness in their field. In 2019 the Nobel Prize in Medicine honored three scientists for their discovery of the human body’s ability to adapt to low oxygen environments. 

Hypoxia is a state of which oxygen supply is insufficient for normal life functions, experienced by the human body at high altitude. Tissues and cells require a range of oxygen in order to survive. Oxygen is required by mitochondria, in all cells, to convert food into useable energy. “Otto Warburg, the recipient of the 1931 Nobel Prize in Physiology or Medicine, revealed that this conversion is an enzymatic process.” At low oxygen environments, as experienced at high altitude, the body must adapt in order to maintain basic cellular function. There are several mechanisms in the human body that increase oxygen concentration including breathing rate, regulated by the carotid body, increased heart rate, stimulated by the vagus nerve, and increased production of red blood cells (RBCs)  through the bone marrow, regulated by the kidney. 

The carotid body is a chemoreceptor near the carotid artery that detects oxygen, carbon dioxide and pH levels in the blood. At low oxygen, the carotid body relays an afferent (ingoing) signal to the the brain via the glossopharyngeal nerve. The medullary center in the brain then sends an efferent (outgoing) signal that increases the respiratory rate to maximize oxygen delivery to the brain. The carotid sinus is a baroreceptor near the aorta of the heart which senses changes in pressure. As pressure increases in the atmosphere, experienced at high altitude, the carotid sinus sends a signal along the vagus nerve to the brain which then increases the heart rate. “The 1938 Nobel Prize in Physiology or Medicine was awarded to Corneille Heymans for discoveries showing how blood oxygen sensing via the carotid body controls our respiratory rate by communicating directly with the brain.”

At low oxygen environments, the kidney increases production of erythropoietin, which stimulates RBC generation in the bone marrow,  called erythropoiesis, resulting in higher oxygen delivery to the brain and skeletal muscles needed at high altitude. Erythropoiesis was discovered in the early 20th century, however oxygen’s role in the process was not completely understood. The cell’s ability to sense and adapt to oxygen availability was discovered and explained by three scientists, William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza. 

2019 Nobel Prize, Physiology: 

Thanks to the work of Dr. Gregg L. Semenza and Sir Peter J. Ratcliffe, we now understand that the oxygen sensing mechanism that stimulates erythropoieten is present in all tissues, not just the kidney. Semenza conducted research on liver cells using gene-modified mice and found that a specific protein binds to an individual gene (the EPO gene), dependent upon oxygen availability. Semenza named the binding protein the Hypoxia-Inducible-Factor (HIF). The HIF protein was found to compose two transcription factors, HIF-1alpha and ARNT. In 1995, Semenza published his findings of the HIF protein. His work explained that when the body is at high oxygen environments, there is very little HIF-1alpha present within cells. At high oxygen availability, HIF-1alpha is rapidly degraded by a proteasome within cells. The degradation is signaled by a protein called ubiquitin which binds to HIF-1alpha at high oxygen, flagging HIF-1alpha for degradation by the proteasome. This process was recognized by the 2004 Nobel Prize in Chemistry, Aaron Ciechanover, Avram Hershko and Irwin Rose. 

The mechanism by which ubiquitin binds, causing the degradation of HIF-1alpha at high oxygen environments was explained by the work of William Kaelin, Jr. who conducted research on von Hippel-Lidau’s (VHL) disease. The VHL gene mutation causes an increased risk of cancer. Kaelin showed that the VHL gene encodes a protein that prevents the onset of cancer and was involved in controlling responses to hypoxia. VHL is part of a complex that labels proteins with ubiquitin. Ratcliffe discovered the physical interaction of the VHL gene with HIF-1alpha, causing degradation of the HIF-1alpha at normal oxygen levels. 

At hypoxic environments, HIF-1α is protected from degradation and accumulates in the nucleus, where it associates with ARNT and binds to specific DNA sequences (HRE) in hypoxia-regulated genes (1). At normal oxygen levels, HIF-1α is rapidly degraded by the proteasome (2). Oxygen regulates the degradation process by the addition of hydroxyl groups (OH) to HIF-1α (3). The VHL protein can then recognize and form a complex with HIF-1α leading to its degradation in an oxygen-dependent manner (4). 


At hypoxic environments, HIF-1α is protected from degradation and accumulates in the nucleus, where it associates with ARNT and binds to specific DNA sequences (HRE) in hypoxia-regulated genes (1). At normal oxygen levels, HIF-1α is rapidly degraded by the proteasome (2). Oxygen regulates the degradation process by the addition of hydroxyl groups (OH) to HIF-1α (3). The VHL protein can then recognize and form a complex with HIF-1α leading to its degradation in an oxygen-dependent manner (4).

Kaelin and Ratcliffe’s research identified how oxygen levels regulate the interaction between VHL and HIF-1alpha. Their work demonstrated that at normal oxygen levels, hydroxyl groups are added to specific positions within HIF-1alpha, causing modification of the protein and allowing VHL to recognize and bind to HIF-1alpha, leading to degradation of the protein complex.  At high altitude, cells produce a greater amount of the HIF-1alpha protein which binds to the EPO gene, up-regulating the production of erythropoietin hormone, stimulating RBC production. Together, Semenza, Kaelin, and Ratcliffe explained the oxygen sensing mechanism.

Doc Talk: Pregnancy at Altitude & What You Need to Know, an Interview with Dr. Javier Gutierrez, MD (OB/GYN)

A man with gray hair in blue hospital scrubs and a white surgical mask hanging tied from his neck smiles widely with bright teeth showing
Dr. Javier Gutierrez

Dr. Gutierrez is originally from Mexico City and attended medical school at Universidad La Salle Medical School. He completed his residency at the University of Miami School of Medicine, Jackson Memorial Hospital and has been Board Certified by the American Board of Obstetrics and Gynecology since 1986. He worked in Mexico City with his father who is also an OBGYN before moving to Summit County in 1998. He says that he dealt with pregnancy at altitude even in Mexico City as a young doctor but now has become even more experienced while practicing at St. Anthony Summit Hospital in Summit County, Colorado. In his career he has delivered more than 7,000 babies.

Gutierrez estimates that about 3% of his patients are visitors to Summit County. Most of these patients are not at full term in their pregnancy and present in the ER with signs of premature labor due to dehydration. Usually, these patients are stabilized and sent to Denver for definitive treatment given St. Anthony Summit Hospital only has a Level 1 nursery (basic newborn care).

The most common conditions that he sees occurring in pregnant women at altitude are pregnancy-induced hypertension (PIH), intrauterine growth restriction (IUGR), and small for gestational age (SGA). Because of this, he says that the main difference of observing pregnancy at altitude is more frequent ultrasounds to monitor the growth of the baby. Luckily, most pregnant women at altitude are very fit and healthy because of the active lifestyle that Summit County encourages. However, some women also have a difficult time restricting their activity level enough to maintain proper growth of the baby. The recommended maximum heart rate during pregnancy is 80% of your maximum heart rate, which can be hard to not exceed in an active pregnant female living at altitude.

Nevertheless, the risk of high altitude pulmonary edema (HAPE), high altitude cerebral edema (HACE), and sleep problems are about the same as in pregnant women not living at altitude. In general, pregnant women past 24 weeks have difficulty sleeping no matter where they live. In addition, if you know you are at high risk for developing HAPE or have a history of HAPE you are just as likely to develop HAPE during your pregnancy as you are not pregnant.

Sleeping with oxygen is recommended and has many benefits for all individuals living at altitude, pregnant women included. However, it likely wouldn’t decrease the number of SGA babies because of the activity level of most individuals as mentioned earlier. A woman’s body increases blood volume, red blood cell count, respiratory rate, and vasodilates blood vessels to accommodate for the growing fetus. This in turn allows the body to compensate well and usually maintain normal oxygen saturation levels at altitude.  But Dr. Gutierrez feels eventually it will be recommended for everyone to sleep with oxygen, most people just don’t want to.

Especially with dehydration, he has seen very high red blood cell concentrations. However, these individuals usually only need rehydration and do not suffer any complications. He has not seen a drastic increase in the number of blood clots in pregnant females at altitude even though they are likely at higher risk. But if a pregnant female who is dehydrated and recently traveled to altitude presents with shortness of breath, he definitely puts HAPE and pulmonary embolism (PE) higher on his list of possible diagnoses than he would not at sea level.

An important and simple recommendation is increasing their fluid intake. At altitude you have more insensible water loss and are likely more physically active, which in turn can lead to faster dehydration causing premature labor. Luckily this complication is easily managed with adequate fluid intake. In addition, if you know you are at high risk for developing HAPE it is recommended that you do not travel to altitude, especially later in your pregnancy.

The baby lives in a hypoxic environment in the womb anyway so there are no known advantages to living at altitude while being pregnant, other than the active and healthy lifestyle Summit County promotes.

One of the most challenging cases Dr. Gutierrez has treated was severe maternal respiratory distress during early third trimester due to HAPE. The most definitive treatment was to transport her to a lower altitude, however, they had to stabilize the mother enough to be able to transfer her and her baby. In addition, Summit County does not have a high level nursery to take care of a very premature baby even if they were able to deliver the baby safely to take stress off the mother’s body. He said it was a delicate balance trying to determine what was best and safest for both the mother and the baby.

Bailie Holst is a second-year Physician Assistant student at Red Rocks Community College in Arvada, CO. Bailie was born in Longmont, Colorado and spent her life in Northern Colorado until moving to Minneapolis, Minnesota for her undergraduate studies at the University of Minnesota. She also spent her life traveling throughout the country competing in gymnastics competitions and eventually earning a full-ride athletic scholarship for gymnastics to the University of Minnesota. She finished her gymnastics career and graduated with a Bachelor’s degree in Physiology in 2017. Prior to PA school she worked as a medical assistant in a sports medicine and rehabilitation office in Colorado for two years. In her free time, Bailie now enjoys golfing, traveling, spending time with family, and playing with her brand-new puppy.

Nocturnal Hypoxia at High Altitude

The long-awaited results for the Ebert Family Clinic study on sleep at altitude were analyzed in collaboration with Colorado Sleep Institute (CSI). Christine Ebert-Santos, MD, MPS and Tara Taylor, FNP organized and conducted the Overnight Pulse Oximeter Study In Healthy Adults at three elevations, with the support of the local mountain community and the American Embassy in La Paz, Bolivia. The purpose of the study was to evaluate nocturnal oxygen saturation levels in populations living at 3800 m (12,467′), 2800 m (9,186′) and 2500 m (8,202′) and determine treatment recommendations for central apnea and hypoxia. Volunteers were recruited by the clinic from residents in the community and current patients, and by the American Embassy nurse practitioner Annette Blakelee. Informed consent was obtained by the clinic staff and providers. Each participant completed a health questionnaire on length of residence at altitude, medical history and possible symptoms related to higher elevations. Blood pressure, height, weight, and BMI were measured and documented at enrollment. Patients enrolled in study sites for routine care had past Hb/Hct added to the questionnaire. The device (pulse oximeter) was dispensed to the participants with instructions for use. The participants wore the device at night during sleep before returning it to the research staff at the clinic. The results were downloaded from a USB device, recorded onto a spreadsheet, and analyzed by a statistician. If the results were concerning for hypoxia, (<89% for over 20% of the study), participants were asked to repeat the test, completely off any substance (e.g., drugs, alcohol). The study also accounted for factors such as years at altitude and percent of life at altitude to assess potential adaptations to the environment and subsequently, changes in oxygen saturation levels. The goal of the study is to inform providers and residents which symptoms are related to altitude or sleep disorders and recommend treatment that will allow them to feel better and be more active, as well as reduce complications from hypoxia, such as pulmonary and systemic hypertension, fatigue, and daytime drowsiness.

Results of the study concluded that years at altitude, percent of life at altitude, gender, and age do not explain the variance of adaptation to altitude, as measured by time <88% oxygen saturation (SpO2) in these data. The only factor statistically significant in adaptation to altitude was body mass index (BMI). This data provides direction for future studies.

P>0.05 is non-significant. This suggests that there is something else besides percent of the life spent at altitude that explains the level of adaptation participants are experiencing.

Overlapping fit lines (colored) and range estimates (gray) means that the groups are not different. Thus gender cannot explain the difference in adaptation responses.

 Tara Taylor FNP had the primary role of reviewing and discussing sleep study results with individuals participating in this study. Tara has worked at the Ebert Family Clinic for over 3 years as a family practitioner, before which she was an intensive care nurse for adults and children for 14 years. She is passionate about sleep issues that occur at high altitude. Tara states that “the most interesting finding was that normal, healthy adults without any comorbidities who are of normal weight and do not have any other medical conditions, had basal oxygen levels <90%, and most had 88-89% basal oxygen. We did see some drops to 85-87% oxygen saturation (SpO2) overnight without any apnea. We checked the length of time spent in different ranges. I found that healthy adults were spending more time below 90% SpO2 than anticipated. We used the index per hour, which gave us a preliminary idea of how many times oxygen increases and decreases.” Based on the results, patients would be notified on any follow up that was needed.

The new Colorado Sleep Institute (CSI) in Frisco will allow patients to receive comprehensive care with more accurate results than can be found at a lower elevation clinic. Dr. Mark Hickey, MD, Board Certified Specialist in Sleep Medicine, and Dr. Ellen Stothard reviewed and interpreted the data collected by Ebert Family Clinic. Dr. Stothard is currently the Research and Development Director at the Colorado Sleep Institute. Her passion lies in conducting sleep research, collecting relevant data, and readily communicating findings, as she believes that good sleep is fundamental for a healthy lifestyle. Dr. Stothard discussed the difference between central versus obstructive sleep apnea and a highly prevalent process called treatment emergent central sleep apnea (TECSA), which is the persistence of central sleep apnea during treatment for obstructive sleep apnea. According to Dr. Stothard, “TECSA is seen when one is treated for obstructive sleep apnea with the continuous positive airway pressure (CPAP), causing a disruption to the central sensing mechanism, resulting in central sleep apnea. Following this phenomenon, patients with obstructive sleep apnea believe that they are resistant to treatment when the CPAP doesn’t improve their symptoms.” These patterns are actually central events which can be helped with decreasing pressure of the CPAP and readjusting air flow. Essentially, CPAP settings should be adjusted based on altitude and elevation, as this is a huge factor influencing nocturnal oxygen saturation levels.

Dr. Stothard has worked with numerous patients receiving CPAP treatment including those at lower altitudes. Since opening her clinic at high altitude, the providers at CSI have noticed that patients tend to feel more fatigue, reporting less relief from treatment with CPAP. Symptoms the patients are experiencing require an individualized approach. “Sleep medicine is so unique,” states Dr. Stothard  “and you have to take the time to tailor the treatment and titrate it to perfection to match the patient’s physiology, tolerance for the air, and whether they wear a nasal mask or full-face mask. We spend a lot of time on those specific things in our clinic.”

Dr. Stothard discussed the influence altitude has on conditions such as obesity, explaining that “BMI is a known risk factor for sleep apnea. Someone with a higher BMI will have a different physiology due to its effect on airway collapsibility. Recommendations to reduce sleep apnea are to maintain a healthy weight, which can improve the success of treatment.” Dr. Stothard also spoke about the role of physical therapy in sleep hygiene and how it can help improve sleep, especially in people who have traumatic brain injuries. “Understanding the way sleep facilitates recovery and repair of the body is crucial” and physical therapists can help bridge that gap. Sleep not only allows for the body to restore and re-energize, but also allows for the toxins to be cleansed out from the brain. Moreover, “while we sleep, there is an increase in the interstitial space in the brain allowing the cerebrospinal fluid to flush out chemicals, such as adenosine.” Excess retention of adenosine can cause sleepiness and grogginess acutely, while chronically, it can cause inflammation, fibrosis, and organ damage.

The Overnight Pulse Oximeter Study In Healthy Adults gives us some interesting preliminary information. The CSI and Ebert Family Clinic will be collaborating on future studies to help us understand sleep at altitude in greater depth. For more information on the high prevalence of central apnea at altitude at all ages and the importance of using oxygen at night for residents 50 and older, see previous blog posts on sleep and interviews with local providers Dr. Craig Perrinjaquet and Dr. Peter Lemis.

Arti Kandalam is a second-year physician assistant student at the Red Rocks Community College Physician Assistant Program in Arvada, CO. Arti was born and raised in Sugar Land, TX and lived there until graduating high school. She then moved to Austin, TX to attend the University of Texas in pursuit of her Bachelors in English degree. Shortly after, she obtained her Masters in Biomedical Sciences at the University of Houston in Victoria. She moved back to Sugar Land, TX, where she worked as a Medical Assistant and Scribe at Texas Pain Centers for 4 years. In her free time, Arti enjoys dancing/teaching Bollywood choreography, biking, and hiking.

Maternal Intermittent Hypoxia and the Effect on Adult Respiratory Control and the Gut Microbiome in Male Offspring

On Friday, June 4th, I had the pleasure of attending the, online, Fifth Annual Center for Physiological Genomics of Low Oxygen (CPLGO) Summit. There were many great presentations that I had the opportunity to watch, including the presentation of Dr. Christine Ebert-Santos’ study looking at nighttime pulse oximetry in participants living at high altitude for longer than one year. The presentation this post will discuss is about research conducted at the University of Florida by Dr. Tracy Baker, PhD. This presentation was particularly of interest because it looks at hypoxia in relationship to Obstructive Sleep Apnea (OSA). OSA occurs when patency of the upper airway is compromised and air is inhibited from passing, leading to hypopnea and obstructive apneas1. Hypopnea are episodes of greater than 30% decrease in air flow that lasts ≥ 10 seconds with continued respiratory effort1. Obstructive apnea is a total stop in airflow that lasts ≥ 10 seconds with chest and abdominal efforts to continue breathing1. Patients with OSA have a higher apnea-hypopnea index (AHI) at altitude than at sea level, meaning that their time with decreased oxygenation while sleeping is increased at higher altitude2. Additionally, patients living at altitude with mild or moderate sleep apnea may have a false negative sleep apnea result when having a sleep study performed at sea level, which means that patients who have OSA at altitude will not show signs of sleep apnea at sea level, therefore missing the diagnosis on sleep study2.

Currently, it is understood that the effects of hypoxia secondary to sleep apnea takes a toll on the body over time. Patients often experience snoring and daytime sleepiness in addition to other symptoms or changes to the body that may not be as easily recognizable, such as living in an increased inflammatory state1,3. Further, it is well known that an adverse maternal environment during pregnancy can lead to long term fetal complications3. Combining these two concepts, Dr. Baker wanted to further investigate the adverse effects of hypoxia due to maternal sleep apnea to get a better understanding of the subsequent consequences this deprived oxygen state has on mothers and their offspring. The hypothesis of this study was: Intermittent hypoxia during pregnancy has detrimental and long-lasting consequences on offspring neural function.

To test this hypothesis, Dr. Baker and her team exposed pregnant rats to intermittent hypoxia during days 10-21 of gestation. OSA was modeled from hypoxia episodes, but not the sleep fragmentation that accompanies the disease. It is understood that both components of sleep apnea, hypoxia and sleep fragmentation, would have their own influence on the offspring. The rats were put into a chamber and delivered 15 episodes of hypoxia per hour, as people can experience up to 10-20 episodes of apnea per hour during pregnancy, in increments of 90 seconds with 90 seconds of normoxia in between. During hypoxic episodes, oxygen levels were brought down to 10% and oxygen saturation was reliably reduced to 85% with adequate re-saturation during episodes of normoxia. Control rats were exposed to normoxia, 21% oxygen “on and off”, to control for and take into consideration confounding factors such as air flow within the chamber. While in labor, the rats were then removed from the chamber to give birth in a normal environment. The baby rats, or pups, were never exposed to hypoxia after they were born. Lastly, the pups were followed into adulthood to monitor for long term effects.3

Next, data from the gestational induced hypoxia (GIH) offspring and the control rat offspring (GNX) was compared. The GIH offspring showed no evidence for obesity and no difference in the volume of fat pads from shortly after birth to 12 weeks, as they had the same trajectory as the GNX offspring. There was also no difference between gestational length, number of pups, pup retrieval time, or pup survival between the two groups. To evaluate effects of gestational hypoxia on breathing, the adult offspring were placed in a plethysmography chamber. A plethysmography chamber measures changes in volume in the body to assess how much air is in the lungs when breathing. The rats were given one-hour to acclimate in the chamber and ventilation was then measured over the following three hours. Of the two groups, male GIH offspring had a significantly increased number of spontaneous apneas per hour compared to male and female GNX offspring and female GIH offspring, who had no change in the number of apneic episodes. Apneic episodes are defined as a pause in breathing that lasts longer than the duration of two breaths. Spontaneous apneic episodes are episodes of apnea with no apparent trigger on plethysmography signal. Approximately 60% of GIH male offspring had spontaneous apnea out of the 95% confidence interval, suggesting gestational intermittent hypoxia altered the phenotype in the male offspring. Again, this was not a congruent finding in GIH females.3

An additional factor to be considered in this scenario is respiratory plasticity, which is the body’s ability to help animals adapt to life changing circumstances, such as hypoxia and sleep apnea. A body’s ability to have respiratory plasticity is suggestive of a healthy neural system because breathing is an automatic and rhythmic function of the brain stem. Ultimately, the respiratory system you are born with is not the one you will die with. Recurrent central apnea can promote respiratory plasticity. Dr. Baker’s team further investigated whether the GIH rats had an altered adaptive response to conditions that alter the body’s natural response to breathing, which in this case is recurrent central apnea. Her team mechanically ventilated adult offspring that were vagalized, paralyzed, and urethane anesthetized to study neural control of breathing independent from the process of ventilation, and data was recorded via phrenic neurograms. A neural apnea was caused by lowering PaCO2 levels lower than the level for breathing and was then stopped by raising PaCO2 back to baseline levels. Recurrent neural apneas triggered plasticity mechanisms to make it harder to elicit the next apnea. Data showed adult male GIH offspring have impaired responses to recurrent reductions in respiratory neural activity and did not express plasticity following a triggered central apnea episode. Like prior results, female GIH offspring did not have this same neural plasticity impairment as the males, showing no elevations in spontaneous apnea and intact compensatory plasticity triggered by central apneas.3

Further, adult offspring were assessed for increased inflammation. To no surprise, GIH males had increased basal neuroinflammation. Although both male and female GIH offspring had increased inflammatory markers, the females were able to suppress the inflammation by an unknown mechanism that the male GIH offspring could not. Adult offspring of GIH and GNX groups were exposed to bacterial lipopolysaccharide (LPS), which confirmed that the GIH males mounted a greater inflammatory response compared to the other offspring, suggesting these males have an altered inflammation response. In the central nervous system (CNS), microglia are innate immune cells that can produce inflammatory cytokines and comprise 5-10% of CNS cells. Dr. Baker’s team pharmacologically depleted these cells in the adult offspring by administering the drug PLX3397 for seven days. This resulted in a stark reduction of microglia by 86%. The GIH male offspring with depleted microglia were able to regain compensatory plasticity triggered by recurrent central apneas. Three days after stopping PX3397, the microglia came back and expanded. When the microglia repopulated, there was restoration of the impaired plasticity phenotype in GIH males.3

To get a better understanding of what could be driving the persistent microglial inflammation in the GIH males, the gut-brain-axis was assessed. In human literature, it is suggested that sleep apnea is associated with gut dysbiosis. Investigating this link, feces was collected from the rats which showed diversity in the bacterial species present in GIH males compared to GIH females and both sexes of the GNX group. Dr. Mangalam looked at the GI bacteria shift and determined the gut microbiomes were comprised of two main phyla of bacteria, Bacteroidetes and Firmicutes. GIH males had increased Bacteroidetes and decreased Firmicutes compared to the other offspring. Initially unsure of this significance, Dr. Mangalam deduced that the decreased bacteria in the GIH male microbiome produce a short string fatty acid called butyrate. Once produced, this fatty acid stimulates the release of neuropeptides and serotonin, which are up taken by the portal vein. From there, butyrate enters the blood circulation and crosses the blood brain barrier (BBB), stimulating active receptors on the vagus nerve. Butyrate supports plasticity in the brain and reduces inflammation.3

This leads to the final question: can the neural plasticity deficit be rescued by decreasing neuroinflammation by supplementing male GIH offspring with butyrate? GIH male rats were supplemented with eight doses of 2mg/kg of Tributyrin over 22 days, which is converted into butyrate3. Upon creating central apnea in the GIH males treated with Tributyrin, it was found that their respiratory plasticity was fully rescued3. So, what does this mean?

Simply, this means gestational intermittent hypoxia has sex-specific, long-lasting effects on adult offspring physiology. This is shown by: 1) gut dysbiosis in male offspring, 2) increased central apneas during sleep with impaired respiratory plasticity, 3) enhanced basal inflammation of microglia in male offspring with increased inflammatory response upon provocation, and 4) microglial depletion or butyrate supplementation repaired deficits in respiratory plasticity.3

The research conducted by Dr. Baker’s team opens additional research opportunities regarding effects of hypoxia on vulnerable populations, such as pregnant mothers and their offspring. The findings from this study can be retested and built upon as research continues to be done. Although this research was not conducted at altitude, it is still interesting and pertinent to the altitude community, as hypoxia and OSA are common problems at altitude. This study contributes important knowledge to the science and medical community; however, more research will need to be done to confirm and fully understand the adverse effects of hypoxia during pregnancy. Further, more information is needed to understand how effects of gestational hypoxia can be applied to populations experiencing hypoxia secondary to living at altitude in a low oxygen environment.

References:

  1. Guilleminault C, Zupancic M. Sleep Disorders Medicine. Third Edition. Philadelphia, PA. Saunders. 2017. pp: 319-339.
  2. Patz D, Spoon M, Corbin R, et al. The effect of altitude descent on obstructive sleep apnea. CHEST. 2006; 130(6): 1744-1750. Doi: https://doi.org/10.1378/chest.130.6.1744
  3. Baker T. CoBAD: Maternal Intermittent Hypoxia and the Effect on Adult Respiratory Control and the Gut Microbiome in Male Offspring. Oral presentation at: the Fifth Annual Center for Physiological Genomics of Low Oxygen (CPLGO) Summit; June 4th, 2021; online.

Amanda Smith is a second year PA student at Drexel University in Philadelphia, Pennsylvania. Amanda was raised in the “sweetest place on Earth”, Hershey, Pennsylvania. She obtained her B.S. in Health Science with a double minor in Creative Writing and Community Health at Hofstra University on Long Island. Between obtaining her undergraduate and graduate degrees, Amanda worked as an Emergency Department scribe, pediatric nurse aide, and as a lead research coordinator in Neurosurgery/Neuro-Oncology at the Penn State Hershey Neuroscience Institute. Amanda loves to travel and was able to incorporate her love for traveling and medicine by traveling across the country for clinical rotations, rotating at sites in New York, California, Pennsylvania, and Colorado, with her next destination in Alaska!

A Summation of Wilderness Medical Society Clinical Practice Guidelines for Diabetes Management

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.

Pre-trip Prep:

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.

Table 1: Environmental Effects on Diabetes, Imported from WMS

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.

Table 2: Medical Kit Preparation, Imported from WMS

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.

Table 3: Algorithm for management of hyperglycemia and ketosis in the backcountry. EDD, estimated daily dose, PO, oral intake, Imported from WMS

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.

Conclusion:

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)

References:

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. 

High Country Winter Dogs

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.

Dog booties!

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.

Head pressing

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.

Doc Talk: ALTITUDE AND THE EYES, AN INTERVIEW WITH DR. PAUL COOK, OD

Have you ever wondered why a bag of chips will swell almost to the point of bursting when you travel from a lower elevation?  As the altitude increases  the barometric pressure decreases. The difference between the high pressure inside the bag and the low pressure outside causes the bag to swell (and sometimes burst) to reach equilibrium with the surrounding environment.

The same concept applies to our biological tissue, including our eyes. Luckily there is not normally gas in our eyes, but there are procedures where air bubbles are injected into the eye, such as a vitrectomy: part of the vitreous humor of the eye is replaced with air so that a nearby site has the chance to heal. Common indications include a retinal detachment, macular hole or removal of scar tissue. It’s important to remain at the elevation your ophthalmologist or optometrist indicates because you don’t want your eye to suffer the same fate as a bag of chips!

This was one of many interesting things I learned while speaking with D. Paul Cook, OD and his wife and practice manager Karen Cook at Summit Eye Center on Main Street in beautiful Frisco, CO. The following is my interview with Dr. Cook, Karen Cook, and my preceptor Christine Ebert-Santos, MD, MPS.

How many years have you been practicing optometry in Frisco, CO?

I don’t recall the exact year, but I remember it was the year the Broncos lost the Superbowl.

Dr. Paul Cook at the entrance of Summit Eye Center.

I did a little research and this must have been either the 1986 or 1987 season, as the Broncos lost both of those Superbowls. Fortunately, those Superbowl losses were not a bad omen as Dr. Cook has successfully served the Frisco area every year since.

What conditions do you see commonly here at altitude?

One thing I see commonly here is recurrent corneal abrasions. The classic patient lives at a lower altitude and previously had a corneal abrasion. They received treatment but the abrasion site never completely heals. After arrival in the high country where it’s extremely dry that abrasion site dries up and becomes inflamed.

Usually what I do is give a bandage contact lens to cover up that recurrent corneal abrasion, which usually works, but if it’s extremely painful, we can use amniotic membrane, which is expensive. But it is effective.

The cornea is the outermost layer of the eye (if you don’t count the tear film). A corneal abrasion occurs when any foreign object scrapes the corneal surface. Symptoms include a foreign body sensation, pain, clear discharge, blurry vision and sensitivity to light. A corneal abrasion needs a healthy, moist environment in order to heal. You can see how the dryness that comes along with altitude could lead to a recurrent corneal abrasion.

I also see a fair amount of snow blindness, usually in the spring though.

I suppose it has to do with the sun being higher in the sky and people being out and about hiking. When people are out skiing in the cold winter they wear their goggles, but if it’s spring time and somebody’s hiking they might forget their glasses.

Snow blindness is only one potential cause of a disease called photokeratitis. Other causes are staring at the sun, looking at an arc welder, or catching too many refracted UV rays from surfaces such as sun, water, ice and snow. The pathophysiology for each disease is the same: too many UV rays are focused onto the cornea at one time which causes damage. Symptoms include pain, redness, blurriness, sensitivity to bright light, headache, and occasionally temporary vision loss. Treatment for photokeratitis caused by snow blindness is supportive, but the most important thing is resting your eyes. Try to get into a dark room and avoid anything that makes your eyes uncomfortable. In a few days your cornea should heal.

Prevention  is straightforward: wear sunglasses or ski goggles with adequate sun protection.

Are cataracts a more common condition at altitude?

Oh yes, because of sun exposure and our aging population here. The people of Summit County are so active, which increases their exposure to the damaging rays of the sun. We’re also treating cataracts so much sooner than we used to, so that’s part of what makes it more common.

Do you have any recommendations for healthy aging at altitude as it relates to the eyes?

Karen: Getting your annual eye exam. We always tell patients there are a lot of things we can do to preserve your vision, there’s almost nothing we can do to give it back to you.

So if you live in Frisco, CO and don’t have an optometrist, make sure to see Dr. Paul Cook!

Is blurry vision a common malady in patients that have recently received a LASIK procedure and then ascended to higher elevations?

I have not seen that with LASIK. About 30 years ago though there was a procedure called Radial Keratotomy (RK) that involved a surgeon making radial cuts on the cornea in order to correct nearsightedness. Those patients used to require one pair of glasses for where they lived at lower elevation and one pair of glasses at higher elevation. It’s not a procedure commonly done nowadays but patients that had RK roughly 30 years ago may have that problem.

LASIK stands for Laser Assisted In Situ Keratomileusis. It essentially means that the surgeon will use a laser to reshape the cornea so that the light refracting through it will be appropriately concentrated on the retina. LASIK is faster, cheaper, safer and more effective than RK. It has largely usurped RK for surgical treatment of nearsightedness or farsightedness.

What are some interesting cases you have seen over your years of practice?

I treated a patient that traveled from the Midwest and had a genetic condition called retinitis pigmentosa. Clinically that means the patient had limited peripheral vision at baseline.  He and his wife decided to hike the Colorado Trail. Unfortunately during the hike he developed blurred vision and ended up coming into my office. Turns out he had macular edema and I referred him to an ophthalmologist down in Denver because the altitude was probably the cause of his macular swelling. I called him a few weeks later and his vision had returned to normal.

Another  patient came into the office because his wife had noticed growths on his iris that turned out to be nevi (colloquially known as moles when they’re on the skin). So I dilated his eyes and noticed growths on his retina. I referred him down to oncology in Denver for a biopsy and it turned out to be melanoma. I think they’re closely monitoring that melanoma at this point. It’s uncommon to see cancers of the eye but I see them once every few years.

Dr. Cook performing an eye exam on me.

For my last question, do you have any general recommendations for residents or visitors?

Wear sunglasses, eat your vegetables, eat your fish at least two times per week, keep your cholesterol in check, keep your sugars in check, take breaks from looking at the computer, don’t sleep in your contacts, and see your optometrist once per year.

Seth Selby is a second-year physician assistant student at Des Moines University. He was raised in Eaton, CO and attended Colorado State University with a bachelor’s degree in Health and Exercise Science. Prior to PA school, Seth worked for 3 years as a Cardiovascular Technician at Boulder Community Hospital. In his spare time Seth loves backpacking, hunting, fishing, skiing and astronomy.

Doc Talk: an Interview with Emergency Medicine Physician Dr. Jack Gervais

While doing a clinical rotation with Dr. Chris at the Ebert Family Clinic in Frisco, CO I had the pleasure of interviewing local emergency medicine physician, Dr. Jack Gervais.

To start off, if you don’t mind just telling us about yourself, where you work, and how you got into the ED

Dr. Jack Gervais: I grew up in Summit County and then did my undergrad at the University of Denver, and then medical school at University of Colorado in Denver as well, and then did a three-year residency for emergency medicine in Portland, Maine. Then I came back to Frisco in 2011, so this was my first job out of residency, and I’ve been here ever since. As far as what got me into emergency medicine, it just kind of seemed like a good mix of everything, really, and I like doing procedures but didn’t necessarily want to be a surgeon, and so I kind of gravitated towards that.

What percent of your practice involves tourists?

Dr. Jack Gervais: It depends on the season. Obviously during the higher tourist seasons it goes up, but I would say probably on average maybe 50-60% and then during the heavy winter tourism times it’s probably more like 80%, and fall and spring much less.

Let’s say that there is a visitor in Frisco who brought a pulse oximeter with them. At what point, with either their O2 saturation or their symptoms, would you recommend that they go to the ER or seek oxygen administration?

Dr. Jack Gervais: It really depends primarily on the symptoms. People can be symptomatic with a fairly typical kind of mountain sickness symptoms and have a normal oxygenation. We consider anything above 88-90% acceptable.  We get a lot of patients that come in with an ankle injury and their O2 saturation is 85% and they’re really asymptomatic. 

Certainly, anybody who’s symptomatic we will offer O2 to them even if they have a normal saturation. Anybody around 85-86% if they’re not having symptoms and they’re going home in a day or two, I offer oxygen to them, but I don’t necessarily say “oh you have to be on oxygen ’cause you’re 85%”. Anybody who’s under 80%, I would say absolutely should be on O2 regardless ’cause they’re going to end up getting worse.

Let’s say they’re skiing, they check their oxygen saturation, and it’s 85% but they feel fine. Would you say “keep going and be aware if you develop symptoms”? 

Dr. Jack Gervais: Yeah, I think that’s reasonable. People tend to do worse at night, so someone is 85% when they’re standing in the day, they’re probably in the 80s at night. So, what I’ll often do with people with those kind of borderline sats is offer them oxygen. It’s really easy to get the delivery from the various companies so it’s pretty straightforward, more of a cost issue for some people, but I tell them “use it when you sleep the whole time you’re here”. Probably most tourists would benefit from sleeping on oxygen regardless because you don’t know how low they’re getting at night. I would guess most people are sleeping in the mid 80s and don’t realize it. That leads to the headaches and waking up at night and those sorts of things that we see a lot.

What conditions do you see here at altitude and how commonly, i.e. cases of Acute Mountain Sickness (AMS), HAPE (High Altitude Pulmonary Edema), HACE (High Altitude Cerebral Edema), sleep problems, blood pressure issues, etc.?

Dr. Jack Gervais: Typical AMS would be shortness of breath, headache, and nausea being the most common. Any combination of those in people who recently traveled from lower elevation or when locals come back from as few as 4 days of vacation can be AMS. People reset really quickly after they descend, we see a lot of people who get reentry HAPE. Kids will go down for spring break in Florida and come back and get HAPE.

It’s tough to say exactly what incidences, I would estimate probably 20-25% at least people visiting from lower elevation — and that’s when it’s just semantics, but it’s elevation, not altitude, and everybody says “altitude sickness”. Altitude is your height above the ground used by pilots. Elevation is how high you are above sea level, but anyway we see that all the time. That’s pretty simple, you know, basically treat the symptoms: something for nausea and actually ibuprofen has been studied in comparison to acetazolamide and is essentially as effective at preventing acute mountain sickness. I tell everyone just put yourself on an NSAID as long as there’s no clear contraindications to it.

I see at least 12 patients a month with HAPE, so it’s something we see really commonly.  This year is kind of weird though ’cause we’re not having as much tourism. We see a lot more when a storm comes in ’cause the pressure drops-so that 10% drop in barometric pressure is like going up another 500 feet, and so that will often kind of push people over the edge. Again, we tend to see a lot of people who get worse at night because they sleep with low O2 saturation or they struggle through the night and come in first thing in the morning saying “I didn’t sleep at all last night, I’ve got this terrible headache, I’ve got this cough”.

HACE is fairly rare here, but not impossible at this elevation. It’s certainly seen more in high trekkers on Everest and in South America. I would say at the hospital we probably have maybe 3-4 cases a year.

Sleep problems are super common, a lot of people wake up feeling short of breath, they’re dehydrated, they get headaches and of course everything else people are doing on vacation exacerbates all that. We actually have this joke of the Summit County Syncope Syndrome: visiting from low elevation, hot tub, alcohol, overexertion, and cannabis. If you have 3/5, there is no way that your syncope is a dangerous cause!

I don’t know why people bring their blood pressure monitors on vacation, but we definitely see a rise in baseline blood pressure at higher elevation. They say, “I have a little headache” (it’s probably from their acute mountain sickness), they check their blood pressure and its 160 and they end up in the ER, which they don’t need to be.

There are actually some folks at the altitude research center in Denver [who] have a little publication about it, but I certainly see a lot of first-time seizures or breakthrough seizures in people who have never had a seizure before. I think it’s just that little bit of change in oxygenation to the brain if you have a seizure predisposition. We see a lot of people that either have their first-time seizure, and there’s nothing else going on, or they’re really well controlled at home, come up and have a breakthrough seizure a couple of days in.

 One other thing about HAPE that’s interesting is people will come in and they’re like, “oh I haven’t slept for the last two nights, I feel terrible, I’ve had a splitting headache,” and I assume they’ve had that for 24-72 hours before they actually come in. Which means they’ve been sitting around with [low oxygen] — most of the HAPE we see is certainly below 80%. I presume these people have been walking around with sats in the 70s for 24-48 hours and it’s amazing that they’re fine. If you were walking around with your O2 saturation in the 70s at sea level, you’d be dead! So, it’s not just a hypoxia that kills people when they have respiratory illness, it’s got to be the hypercarbia and acidosis and all the other stuff that goes along with it.

HAPE tends to also settle in around day 2-3, some people get it quickly but most of the people say I felt fine on day one, I skied yesterday, felt a little crummy night 2, and then day 3 they feel terrible, night 3 can’t sleep and they’ve got HAPE.

 It’s interesting to see the nurses check in a patient with an O2 sat of 50% and it is really no big deal, just put him in any room — it’s not like a big STEMI activation or something. We stick them on oxygen and no one freaks out. People freak out on their first shift if they’re new and it took me a good year to kind of get used to that.  

 Often, we don’t really need to do anything if we can fix them with oxygen and determine from history and physical that there’s nothing else going on. But that gets tricky ’cause you always worry all these people traveling and they’ve got a little bloody cough, they’re tachycardic and hypoxic, so trying to figure out who we want to work up for a PE (pulmonary embolism) is probably our biggest conundrum. A lot of people will get a little bit of a troponin bump just from probably that hypoxic constraint on the heart so that can be a little tricky to figure out who needs to go get a cardiac work up.  

What does a classic HAPE patient look like?

Dr. Jack Gervais: A healthy 26-year-old male who’s got the classic story of progressive increase in shortness of breath, feel like there’s fluid in their lungs, a raspy cough, a little pink sputum, and their sat’s 65% and they get better pretty quickly on oxygen.

What is the typical treatment for HAPE?

Dr. Jack Gervais: The treatment for HAPE patients is to put them on high flow oxygen, around 15 liters.  So, with HAPE, patients get inflammation and acute pulmonary hypertension which causes fluid buildup in the lungs. So, oxygen is really good at reversing that. We oxygenate the lungs which opens up those blood vessels, reduces the pulmonary hypertension, and that fluid can start to resorb in the lungs.

The typical HAPE patient is in the emergency department for 1-3 hours depending on how bad they were and how they’re doing on the high flow oxygen. We wean them down, with a goal of getting them on a nasal cannula with 3-4 liters of O2, which is what the O2 concentrators and portable O2 tanks can manage. And if we can keep someone above 90% on 3-4L they go home with an oxygen prescription. I tell those people to be on oxygen for 24 hours and to just rest and see how it goes, see how you feel. If you start feeling bad again you should be on oxygen. Rarely we see patients come back in because they aren’t doing well, and those people who do, we tell them, “OK you’re out, time to go down to Denver until your plane leaves”.

Are there any medications you use to treat high altitude illnesses?

Dr. Jack Gervais: I don’t tend to use a lot of other medicines. If the oxygen works, why bother adding a bunch of side effects from medications. Some providers tend to be a lot more into giving nifedipine, a calcium channel blocker, which does reduce pulmonary hypertension. A lot of them will use dexamethasone, but it doesn’t so much help with the respiratory component it tends to help more with the headache aspect, but the oxygen will often fix that too. Dexamethasone is also the temporizing treatment for HACE, but they need to descend immediately. People will use Acetazolamide (Diamox), but it’s really only effective if you start it 2-3 days before you come up to the higher elevation. Starting it after you’ve already got acute mountain sickness is probably worthless and it’s got some funky side effects that makes anything carbonated taste weird and it’s a diuretic so you’re adding dehydration to someone who’s already a little dehydrated.

I tend to be more of a minimalist, so I treat the symptoms and give oxygen if they need it and pretty much leave it at that. I was just listening to a podcast talking about inhaled vasodilators. Inhaled/nebulized nitroglycerin — it goes directly to the pulmonary vessels as a vasodilator, but you don’t get the systemic vasodilation that you would with nifedipine or oral nitroglycerin. This was talking more for acute exacerbations of chronic pulmonary hypertension among other things, but I have to wonder if that would work for our patients.

I know you mentioned ibuprofen, but are there any other over-the-counter options you might suggest someone try for AMS?

Dr. Jack Gervais: There are a whole bunch of supplements and stuff that claim to help with altitude sickness, they’re just not studied in any real scientific way to know for sure. For me it’s really just treating the symptoms, so I usually use Zofran for the nausea or Phenergan if there’s a contraindication, and then alternating Tylenol and ibuprofen and oxygen if needed. So, nothing else as far as a preventative that I’m aware of. If you kind of get into the naturopathic realm there’s probably a whole bunch of suggestions out there.

Everyone fixates on staying hydrated which is important. You’re losing extra fluid and if you’re used to living in Florida, you’re going to lose A LOT of fluid when you come up to higher elevation because of the dry air. I tell most people to try and double what you would drink at home. Hydration is really most effective with the headache part of it. It doesn’t change whether you’re going to get HAPE or not. 

Oh, and the little oxygen cans you see in the convenience stores … those are garbage! For oxygen to be effective it needs to be on continuously. Even if you puffed on that thing for a minute and could get your O2 saturation up from 85% to 90% it’s going to drop right back down. In the hospital, if you turn the oxygen off, their saturation will be back where it was within minutes, so yeah, those things are just a total waste of money.

What has been your experience with COVID-19? 

Dr. Jack Gervais: Luckily, we have had it much better off than places like New York, LA, and even down in Denver. I think that part of it is that overall, we have a pretty healthy population compared to a lot of the bigger city areas and suburbs. There have been some studies out there suggesting that people living in higher elevations do better with COVID than lower elevations and I don’t know if it’s just ’cause your body and your pulmonary system has adapted in some way that helps you deal with COVID, but we’ve certainly had some perfectly healthy local folks get pretty sick from it. 

When the tourists were gone back in March/April/May it was great because everyone is local and if you had respiratory symptoms it was probably COVID. Now that the tourists are coming back, it’s a lot harder to tell clinically, and the other thing is the x-ray in HAPE and the x-ray in COVID look very much the same.

We had one patient in particular who came in and said, “I got here yesterday, had a positive COVID test 14 days ago,” and of course they thought they were fine to come up to the mountains, and sure enough they were short of breath. The people who are foolishly traveling either with active COVID or on the tail end of it do not adapt very well when they get up to this elevation, but most of them just need some oxygen.

We finally have rapid tests at the hospital, so it makes it much easier to kind of tell people “this is just altitude” or “this is altitude plus COVID” or “this is straight-up COVID”. In the summer when we didn’t have a rapid test, we’d get these people who have the overlapping symptoms that could be either. It’s tough to tell them what they should do as far as self-quarantine and isolation.  Can you travel? Can you go try to ski tomorrow because it was just altitude sickness?  

The treatment for COVID ends up being the same: oxygen if you need it and then actually dexamethasone has shown to be effective for patients with COVID who are requiring oxygen.

Even before COVID we would send patients home on oxygen with pneumonia or URI symptoms fairly routinely, which is really not a thing in other places. If you need oxygen with pneumonia in Portland, ME you’re getting admitted. If I called Dr. Chris and said I’ve got a kid of yours who looks like they’ve got bronchiolitis or a URI or even COVID, their sat’s 85% — the answer is almost always going to be “oh, put them on oxygen and if they are OK on a reasonable amount of oxygen they’re probably OK to go home”.

Do you admit COVID patients to the hospital up here if needed?

Dr. Jack Gervais: It’s been really tricky for us to figure out who we can reasonably admit here versus transfer to Denver. Both need to have a higher level of care and be at lower elevation. We have kept COIVID patients here successfully. The thing is, even if you live up here and are used to the altitude you’ve got a respiratory process and you’re hypoxic as a result, it makes sense that you would probably do better down in Denver and probably have less of an oxygen requirement and hopefully not progress to high flow oxygen. You can get someone on high flow here but then they’re stuck here until they get better or they get intubated to be transferred.

What is the most memorable case that you have seen in the ER related to high altitude?

Dr. Jack Gervais: So, I had a professional snowboarder who had gone back to sea level for the summer and then flew back out here and had a shoulder surgery in Vail and was staying in Summit County. He was a day or two post-op and had probably been back in the mountains for three or four days so kind of fit the time frame to develop altitude sickness, and he’s probably on a muscle relaxant, some opiates, some respiratory depressants. So, this is the very end of the night shift, I had a STEMI going on in the other room and this guy comes in at 84-85%. He didn’t look super sick but needed some oxygen. I’m like, “oh, he probably took too much oxycodone,” and so I throw him on some oxygen while I go back and deal with this STEMI.

 I go back, and he wasn’t any better! He was still at like 86% on high flow oxygen. So, we got a chest x-ray and he had a little bit of fluid here and there, so it looks like probably early HAPE, or potentially pneumonia, but fit with more of an altitude issue exacerbated by his post-op care.  So, we put him on Bipap and he’s not getting any better and now he’s low 80s on Bipap, so we intubate him.

Now he’s getting worse and now he’s dropping his blood pressure. This is over probably an hour, so this guy is sick, and we could not get him oxygenated even on max vent support. We were begging him, and I thought he was going to just die right in front of me. Finally, he dropped his blood pressure more and we’re like “well, maybe he’s septic, maybe he aspirated, and this is pneumonia.” So, we give him norepinephrine, which is a vasopressor, it constricts all the blood vessels to help increase the blood pressure and adds ionotropic support to make the heartbeat stronger. Then his blood pressure finally got better, and his oxygen got better, and he went down to the ICU in Denver and I’m like, “thank God I didn’t kill this guy at the end of a 13 hour night shift”.

So, it turns out — and this is what makes it the most interesting — he had a PFO, patent foramen ovale — so, a hole in his heart. It’s very common, but people tend to not notice because in general, the pressure in the left side of your heart outweighs the pressure in your right significantly so that patent foramen ovale stays closed against the septum.

Like I was saying earlier, HAPE is caused by acute pulmonary hypertension which then raises the pressures on the right side of your heart. So, he blew open his PFO and now had a right to left shunt — so blood from the right side of the heart doesn’t go up through the lungs and oxygenate, it goes straight to the left and goes back out into the body unoxygenated. That’s why everything we did made him worse. When you put someone on Bipap, and especially when you intubate them, you’ve got that positive pressure that increases the intrathoracic pressure, which increases the preload on the heart.

Dr. Chris Ebert-Santos: 30% of the population may have PFO!

Dr. Jack Gervais: Coincidentally, the norepinephrine that I put him on trying to treat as sepsis increased the after load — the arterial resistance, which then increased the pressure on the left side of the heart enough that it was able to squeeze his PFO back down.

Dr. Chris Ebert-Santos: The ironic thing is that it’s so random! All of this altitude stuff is SO random, even people who have had AMS or HAPE or whatever they may never get again. I mean 90% probably never have a recurrence.

Dr. Jack Gervais: Yeah people get really frustrated and say “I’ve been here 10 times before, it can’t be altitude sickness” — that can happen, and it does. People have this myth of like, “I used to live here, I’m fine,” and it’s absolutely false.

Another interesting thing you see at altitude is people with sickle cell trait (so not full-blown sickle cell disease, generally thought to be a harmless and completely asymptomatic condition) will get splenic infarcts when they come up. You almost can’t even find reports of it in the literature, but I probably see 8 or 10 a year. It’s kind of easy to pin down, the person is like, “I just got here, I’ve got this left upper quadrant pain, no trauma” — not much in your left upper quadrant, so most of the time the minute they hit triage you know what’s going on. We treat just like you would any sickle cell crisis: fluids, pain medicine, oxygen.

I know you mentioned the myth about people who have lived here before believing they aren’t able to get mountain sickness, but do you have any other myths that you frequently have to clarify?

Dr. Jack Gervais: The big one we run into is people who are taking acetazolamide wrong and are surprised that they’re having altitude sickness. People start getting symptoms and they call their doctor and they may prescribe it too late and I just tell them, “don’t bother”. 

People who think they’ve got an infection or bronchitis so their doctor back home calls in antibiotics, which they don’t need even if it is bronchitis. Or the people who ignore it for 2-4 days to assume it’s the bronchitis and say “the antibiotics aren’t working, doctor what’s wrong?” Well, your lungs are filling up with fluid! The good news is HAPE tends to be gradually progressive over hours to days, not minutes. Very rarely we see patients who are really actively dying from HAPE. In 10 years I have probably seen hundreds if not 1,000 HAPE patients and I’ve only probably had 2-3 who were really, really hard to fix. Probably 10-20 that I’ve had to put on Bipap and transfer down. I think I’ve maybe only intubated 1-2. People get in trouble if they’re up high — 20,000 feet on Mount Everest, don’t have oxygen, that’s where you’d end up dying with HAPE. 

Dr. Chris Ebert-Santos: And how many die at home?

Dr. Jack Gervais: I would say a handful. I’ve had at least one lady who was camping. Had HAPE-like symptoms and came in dying, she was the one I intubated, and she actually lived. I had a guy camping last summer who sounded like (from what his mom described) altitude-related symptoms, although he was just up from the Front Range. I don’t know what they ever found on him, but he was dead when the paramedics got to him. I would say it’s a handful, but not dozens a year.

Thank you for your time Dr. Gervais. Is there anything more you would like to share about high altitude medicine?

Dr. Jack Gervais: I would say probably anybody with any serious cardiac or pulmonary comorbidities who is going to vacation here should really be on oxygen at least at night. That would prevent a huge number of these problems. I actually see a lot of people (locals) who sleep on oxygen at night even if they’re 40 and healthy and don’t really have any issues and they just sleep much better.

And the other thing is you know, especially the people who have lived up in Leadville for 60 years tend to develop a gradually progressive chronic pulmonary hypertension which adds to blood pressure management issues and so that’s an issue we definitely see. So I tell anybody who has any sort of symptoms and is going to be here for a while, “just buy yourself a (oxygen) concentrator, keep it at your house,” that way when they come up for a week vacation every winter they’ve got it and just sleep with O2 every night and avoid all the hassle. And don’t bring your blood pressure cuff on vacation!!

There’s a cardiologist who works over in Vail, he was really convinced that living at altitude is really bad for your chronic blood pressure issues.

Dr. Chris Ebert-Santos: Our interview with three other high-altitude physicians in primary care and cardiology say their standard is “if you’re 50 and you’ve lived here 10 years and you want to live here for another 10 years you should be sleeping on oxygen.”

Rachel Mader is a second-year physician assistant student at Red Rocks Community College. She was born and raised in Colorado Springs and attended Colorado State University where she graduated with a bachelor’s in biology. Before starting PA school, Rachel worked as a Physical Therapy Aide at CSU Health and Medical Center, a CNA at a nursing home, and a Clinical Assistant at Children’s Hospital in Colorado Springs. In her spare time she enjoys spending time with her family, friends, and pets, and eating at new restaurants.

The Plants We Need Are There: A Naturopathic Approach to Acute Mountain Sickness

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).

Acli-Mate in a variety of applications.

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, a woman in a white hoodie, long brunette hair, and a maroon mask, stands in front of a wall of shelves of naturopathic medicine in brown glass jars with black lids at the Backcountry Apothecary in Frisco, CO.
Dr. Kimberly Nearpass

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.

PA student Hannah Addison with Dr. Pollock, Dr. Nearpass and Dr. Chris in front of the Naturopathic clinic and apothecary in Frisco, CO.

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.

Visit Mountain River Naturopathic Clinic’s website or stop by their shop and clinic: http://www.mountainriverclinic.com

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

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Hannah Addison, PA-S

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.

COVID in the Mountains: What Works?

As the nation experiences its second, and by far more significant, increase in COVID-19 cases, visitors continue to flock to the Colorado Rocky Mountain region, while advisories from the CDC and government officials across the world continue urging people to stay isolated and home for the holidays. Unlike the Northern Mariana Islands or New Zealand, where physical distancing, the use of masks, travel bans and mandatory quarantines have allowed these island nations to maintain zero community spread, Colorado remains open to the potentially millions of travelers it sees every Winter season, and with far fewer mandates to control infection.

Although the beginning of the pandemic saw facilities managing to protect their staff with protective equipment and protocols, during this dramatic second wave of reported cases, we are seeing an increase in cases among essential health care workers. And with the regular flu season well underway, it seems more critical than ever that we do everything we can to limit exposure.

Ebert Family Clinic, in the heart of Summit County, Colorado, surrounded by world-class ski resorts drawing visitors from all over the world, has successfully managed to avoid infection among all its staff, in spite of continuing to serve its patient population since the initial lockdown this past March.

How?

“First of all, we kept our door locked. You can only come in one at a time, we meet you at the door, screen your temperature, ask if you have any symptoms; we screen when you make an appointment and make sure if anyone in your household is sick, you reschedule your appointment. If so, we made you a telehealth appointment,” says pediatrician and president Christine Ebert-Santos, MD, MPS.

And the telehealth appointments have been a success all year, saving a lot of travel and risk of exposure, making primary health care even more accessible.

Even now, Ebert Family Clinic’s pandemic protocol hasn’t changed. “But just as importantly, all of our employees are maintaining a bubble with close contacts,” adds Dr. Chris.

Operations weren’t always smooth: “Two times, when someone close to a staff member, like in our family, was sick, we stayed home,” says The Doc about having to close the clinic. I stayed home until [my husband’s] test was negative, [our nurse practitioner,] Tara stayed home until her husband’s test was negative; until we knew we didn’t have COVID. We based the risk of COVID on the standard that is described of having been within six feet of an infected person in a closed space.”

Is the vaccine going to change protocols?

“The vaccine isn’t going to change anything. The announcement from Public Health today tells exactly how many doses. That’s a drop in the bucket. What’s that when we have 30,000 residents and 90,000 visitors? It’s going to be six to nine months before we see any protection from this vaccine,” Dr. Chris confirms.

“Essential workers all have their protocols, and they’re just as important as ever. [If you can’t work] — all the parents who have to stay home with their kids, or the restaurant servers who are laid off — I’m hoping that the people who are doing well in our community can continue to help those who are suffering. There is a big sector of our community, like real estate or repairs or construction workers who have been able to continue working through this pandemic. I think [these people who are out of work] are getting help from the FIRC or applying for rent assistance. I haven’t had anyone say that they’re really struggling. And we conduct social welfare interviews, “Do you feel safe? Do you have food?” We’re doing anxiety and depression screenings on everybody. And there is a high level of anxiety among all ages. 

“We had a meeting with Heart-Centered Counseling, and now we’re plugged in with them. We have their brochures, and we’ve just signed care coordination to connect people with providers [who can help in this situation].”

Dr. Chris encourages everyone in the community to reach out with their needs. Ebert Family Clinic and other health care institutions have done very well maintaining a cohesive network of resources for everyone in search of financial, physical, mental, and emotional assistance.

Feel free to inquire about appointments or referrals to local resources at info@ebertfamilyclinic.com, or call the clinic at (970) 668-1616.

Dr. Chris with her granddaughter, comfy-cozy.

“Everybody enjoy their Christmas Zoom with their relatives. As for us, we are having a small family Christmas with six of us who work and live together, and we’re all wearing hoodie-footie flannel jammies.”

Happy Holidays from Dr. Chris, Ebert Family Clinic, and highaltitudehealth.com!

robert-ebert-santos

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.