2High altitude Moderate altitude High altitude Extreme altitude 5,000 – 10,000 feet above sea levelHighest U.S. ski resortsHigh altitude10,000 – 18,000 feet above sea levelHigh peaks in the lower 48, EuropeExtreme altitudeGreater that 18,000 feet above sea levelDenali, Himalaya, Karakoram, Andes
3EpidemiologyMost cases of high-altitude illness take place in people rapidly ascending to altitudes between 8,000 and 12,000 feetCan affect people who live at low altitude as well as people who live at high altitude and return from travel to lower altitude (re-entry)Millions at risk each year – roughly 20-40% affected by some type of altitude illness30 million Western states visitors12,000 Mt. Everest trekkers1,200 Denali climbers1 million visitors to extreme high ranges worldwide
4High-altitude environments Decreased barometric pressure = logarithmically lower partial pressure of oxygen (PO2) in inspired airHigher latitudes have lower barometric pressure at equivalent altitudesWeather systems can significantly lower barometric pressure transientlyCold, dry conditions may be contribute to high-altitude illness
6AcclimatizationSeries of physiologic adaptations to maintain tissue oxygenationAbility to acclimatize varies geneticallyHours: Hypoxic ventilatory response (HVR), fluid shift to increase hematocrit, increase in cardiac outputDays: Increased erythropoiesis, return of cardiac function to baseline, increase in 2,3-DPGWeeks: Increased plasma volume and red blood cell mass
7Hypoxic ventilatory response Most important component of acclimatizationAffected by genetics, ethanol, sleep medications, caffeine, cocoa, progesteronePaO2 = PiO2 (PaCO2/R)Hyperventilation decreases the partial pressure of CO2 in the alveoli, thereby increasing the partial pressure of oxygen in the alveoli to facilitate oxygenationResulting metabolic alkalosis slows HVR, and ventilation slowly increases over several days as kidneys excrete bicarbCan be facilitated by acetazolamidePeople with low HVR at higher risk for illnessPaO2 = partial pressure of alveolar oxygenPiO2 = partial pressure of inspired oxygenPaCO2 = partial pressure of carbon dioxide in alveolusR = respiratory quotientAcetazolamide has several mechanisms of action that allow it to aid in acclimatization, including facilitating excretion of bicarb for faster rise in ventilation. See later slide.
8CardiovascularInitial increase in resting HR, which normalizes with acclimatizationDecrease in maximal heart rateDecrease in plasma volume -> lower stroke volume, increase in hematocritShift to extracellular spaceDiuresis from bicarbonate excretionDecrease in max HR and SV are cardioprotective – myocardial ischemia is rare
9Hematopoietic response Initial increase in hematocrit due to fluid shift and diuresisErythropoietin stimulated early, resulting in new RBCs within 4-5 daysOver weeks to months, red cell and total circulating volume expand to meet demand
10Oxygen-hemoglobin curve Above 10,000 feet (PO2 ~ 60), small changes in PO2 cause large changes in SaO2Initial increase in 2,3-diphosphoglycerate (DPG) promotes O2 release to tissuesOpposed by respiratory alkalosis, which shifts curve left, favoring oxygen uptake in the lung and higher SaO2Studies have shown that people with genetically left-shifted curves have less dyspnea at altitude and no change in exercise performance. Over time at altitude, a left-shifted curve is likely adaptive.
11Sleep and periodic breathing Disturbed sleep with less deep sleep and significant arousals commonPeriodic breathing commonHyperpnea and respiratory alkalosis cause apneaCO2 builds during apnea, causing hyperpneaNot usually associated with significant hypoxemia or high-altitude illnessDecreases with acclimatizationPeople with low HVR may have overall regular breathing pattern with periods of more significant apnea and hypoxemia, which are associated with high-altitude illness
12Acute high-altitude illness Spectrum of disease with intertwining pathophysiologyAcute mountain sickness (AMS)High altitude cerebral edema (HACE)High altitude pulmonary edema (HAPE)All correct rapidly with descent
13Prevention of high-altitude illness Avoid ascent to greater than 8,000 feet in one daySpend 2-3 nights at 8,000-9,000 feet before further ascentDon’t ascend sleeping altitude more than 1500 feet per dayLimit exertion, alcohol, and sedative-hypnotics during first days at altitudeDay trips to higher altitude while maintaining sleeping altitude can speed acclimatizationAcetazolamide mg BID
14Acute mountain sickness Most common with rapid ascent from below 3,000 feet to above 8,000 feetDevelops within hours of ascentHeadache plus at least one of:Gastrointestinal discomfortSleep disturbanceGeneralized weakness or fatigueDizziness or lightheadednessHeadache is usually throbbing, bitemporal, worse at night and with Valsalva
15AMS: Pathophysiology Pathophysiology incompletely understood Vasodilatory response to hypoxemia, fluid shift, inflammatory mediators, and alterations in cerebrospinal fluid buffering capacity are all implicatedNo evidence of cerebral edema in AMS, but some studies suggest transient ICP elevations with exertion and ValsalvaAt risk may be people with low HVR and people with smaller CSF capacity (“tight fit”)Hyperbaria contributes, but role unclear (AMS does not develop with hypoxia alone)
16AMS: ManagementUsually resolves within 1-3 days if no additional ascentMild: Stop ascent, symptomatic treatment, may consider acetazolamideModerate to severe: Low-flow oxygen, acetazolamide +/- dexamethasone 4 mg q 6 hours, hyperbarics, or descendImmediate descent if s/sx HAPE or HACE
17Acetazolamide Carbonic anhydrase inhibitor Promotes bicarbonate diuresis and metabolic acidosis, speeding acclimatizationDecreases CSF productionMaintains oxygenation during sleepSide effects: polyuria and paresthesiasmg BID for treatment and prevention of AMS
18High-altitude cerebral edema Least common but most severe form of high-altitude illnessIncidence 1-2% of ascentsUsually develops above 12,000 feetUsually preceded by AMS and associated with HAPEMost commonly develops days 1-3 after ascent, but can develop later
19HACE: PresentationAtaxia and altered mentation are hallmarks – ataxia usually first symptomFocal neuro deficits may be presentSeizures uncommon but reportedUsually preceded by AMS symptomsAny ataxia or change in consciousness in a person at altitude should elicit immediate action!
20HACE: Pathophysiology Vasogenic cerebral edema caused by same group of mechanisms as AMS (vasodilation, leakage of fluid from vessels) – reversibleIncreased ICP causes decreased cerebral blood flow, resulting in cell deathAt advanced stages, cytotoxic edema and necrosis are present - not reversible
21HACE: Management Immediate descent is key High-flow oxygen and dexamethasone 8 mg (IV, IM, PO) followed by 4 mg q 6 hours if availableHyperbarics may result in temporary improvement but may delay descentIntubation, hyperventilation if severely alteredCan try mannitol or furosemide but caution due to dehydration common at altitude
22HACE: PrognosisIf descent initiated early, may be completely reversible over days to weeks without sequelaeReports of ataxia and other neuro deficits persisting months to yearsMortality rate greater than 60% if progresses to coma
23High-altitude pulmonary edema Most common cause of altitude-related deathIncidence up to 15% of ascentsUsually greater than 10,000 feet, or greater than 8,000 feet with heavy exertionDevelops within 2-4 days of ascent, classically on the second night
24HAPE: PresentationEarly signs are severe dyspnea on exertion, fatigue with minimal activity, and dry coughDyspnea at rest and clear, watery sputum develop as illness progressesDyspnea at rest is red flag for HAPE and should prompt immediate action!Patchy infiltrates on CXR, worst right middle lobe
25HAPE: Pathophysiology Hypoxic vasoconstriction causes pulmonary hypertensionUneven vasoconstriction (areas of extreme hypoxia or anatomic difference) causes hyperperfusion of some areas, leading to vascular leak and patchy edemaBoth hypoxia and pulmonary hypertension are exacerbated by exertionThe hypoxic vasoconstrictor response is physiologic when there is a small area of the lung that is poorly ventilated – this allows blood to flow to well-perfused areas. However, when hypoxia is global, the result is pulmonary hypertension.
26HAPE: ManagementSymptoms resolve quickly upon descent of feetMild cases may be treated with bedrest and O2 to maintain SaO2 > 90Descent for severe symptoms, minimizing exertionHigh-flow oxygenContinuous positive airway pressure if availableAir drops of O2 may be lifesaving if descent not possibleHyperbarics may help conserve O2 supply
27HyperbaricsPortable, lightweight, manually-pressurized hyperbaric bagsRaise atmospheric pressure 2 psi (103 mmHg)Simulates descent of 4,000-5,000 feet at moderate altitudes, more at higher altitudesCan be lifesaving in HAPE and HACE, relieving symptoms so that patients can descend without evacuationPhoto: Rosen’s Emergency Medicine, Courtesy of Thomas Dietz, MD
28Take-homeSlow ascent and acetazolamide are effective in preventing illnessAtaxia, altered mentation, and dyspnea at rest are red flags for serious illnessEarly recognition of HAPE and HACE with descent prevents morbidity and mortalityHave fun up there!