Andrew M. Luks

Wilderness medical society consensus guidelines for the prevention and treatment of acute altitude illness

To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the prevention and treatment of acute mountain sickness (AMS), high altitude cerebral edema (HACE), and high altitude pulmonary edema (HAPE). These guidelines present the main prophylactic and therapeutic modalities for each disorder and provide recommendations for their roles in disease management. Recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to the prevention and management of each disorder that incorporate these recommendations.

Medication and dosage considerations in the prophylaxis and treatment of high-altitude illness.

With increasing numbers of people traveling to high altitude for work or pleasure, there is a reasonable chance that many of these travelers have preexisting medical conditions or are receiving various medications at the time of their sojourn. As with all travelers to high altitude, they are at risk for altitude illnesses such as acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema. While there are clear recommendations for pharmacologic measures to prevent or treat these illnesses, these recommendations are oriented toward healthy individuals and do not take into account the presence of preexisting medical conditions. In this review, we consider how the choice and dose of the medications used in the management of altitude illness-acetazolamide, dexamethasone, nifedipine, tadalafil, sildenafil, and salmeterol-are affected by a patients underlying medical conditions. We discuss the indications and current dosing recommendations for individuals without underlying disease, and then consider how drug selection or dosing regimens will be affected by the presence of renal insufficiency, hepatic insufficiency, other important medical conditions, and the potential for serious drug interactions. We include comments about interactions with antimalarial medications and antibiotics used in the treatment of travelers diarrhea, as well as the safety of use during pregnancy. By giving these issues adequate consideration, clinicians can increase the chances that properly evaluated patients with underlying medical conditions will enjoy a safe trip to high altitude.

Wilderness Medical Society Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2014 Update

To provide guidance to clinicians about best practices, the Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for prevention and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. These guidelines present the main prophylactic and therapeutic modalities for each disorder and provide recommendations about their role in disease management. Recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to prevention and management of each disorder that incorporate these recommendations. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in Wilderness & Environmental Medicine 2010;21(2):146-155.

High-altitude pulmonary hypertension is associated with a free radical-mediated reduction in pulmonary nitric oxide bioavailability

High altitude (HA)‐induced pulmonary hypertension may be due to a free radical‐mediated reduction in pulmonary nitric oxide (NO) bioavailability. We hypothesised that the increase in pulmonary artery systolic pressure (PASP) at HA would be associated with a net transpulmonary output of free radicals and corresponding loss of bioactive NO metabolites. Twenty‐six mountaineers provided central venous and radial arterial samples at low altitude (LA) and following active ascent to 4559 m (HA). PASP was determined by Doppler echocardiography, pulmonary blood flow by inert gas re‐breathing, and vasoactive exchange via the Fick principle. Acute mountain sickness (AMS) and high‐altitude pulmonary oedema (HAPE) were diagnosed using clinical questionnaires and chest radiography. Electron paramagnetic resonance spectroscopy, ozone‐based chemiluminescence and ELISA were employed for plasma detection of the ascorbate free radical (A·−), NO metabolites and 3‐nitrotyrosine (3‐NT). Fourteen subjects were diagnosed with AMS and three of four HAPE‐susceptible subjects developed HAPE. Ascent decreased the arterio‐central venous concentration difference (a‐cvD) resulting in a net transpulmonary loss of ascorbate, α‐tocopherol and bioactive NO metabolites (P < 0.05 vs. LA). This was accompanied by an increased a‐cvD and net output of A·− and lipid hydroperoxides (P < 0.05 vs. sea level, SL) that correlated against the rise in PASP (r= 0.56–0.62, P < 0.05) and arterial 3‐NT (r= 0.48–0.63, P < 0.05) that was more pronounced in HAPE. These findings suggest that increased PASP and vascular resistance observed at HA are associated with a free radical‐mediated reduction in pulmonary NO bioavailability.

Pulse oximetry at high altitude.

Pulse oximetry is a valuable, noninvasive, diagnostic tool for the evaluation of ill individuals at high altitude and is also being increasingly used to monitor the well-being of individuals traveling on high altitude expeditions. Although the devices are simple to use, data output may be inaccurate or hard to interpret in certain situations, which could lead to inappropriate clinical decisions. The purpose of this review is to consider such issues in greater detail. After examining the operating principles of pulse oximetry, we describe the available devices and the potential uses of oximetry at high altitude. We then consider the pitfalls of pulse oximetry in this environment and provide recommendations about how to deal with these issues. Device users should recognize that oxygen saturation changes rapidly in response to small changes in oxygen tensions at high altitude and that device accuracy declines with arterial oxygen saturations of less than 80%. The normal oxygen saturation at a given elevation may not be known with certainty and should be viewed as a range of values, rather than a specific number. For these reasons, clinical decisions should not be based on small differences in saturation over time or among individuals. Effort should also be made to minimize factors that cause measurement errors, including cold extremities, excess ambient light, and ill-fitting oximeter probes. Attention to these and other issues will help the users of these devices to apply them in appropriate situations and to minimize erroneous clinical decisions.

No evidence for interstitial lung oedema by extensive pulmonary function testing at 4,559 m

The aim of the present study was to better understand previously reported changes in lung function at high altitude. Comprehensive pulmonary function testing utilising body plethysmography and assessment of changes in closing volume were carried out at sea level and repeatedly over 2 days at high altitude (4,559 m) in 34 mountaineers. In subjects without high-altitude pulmonary oedema (HAPE), there was no significant difference in total lung capacity, forced vital capacity, closing volume and lung compliance between low and high altitude, whereas lung diffusing capacity for carbon monoxide increased at high altitude. Bronchoconstriction at high altitude could be excluded as the cause of changes in closing volume because there was no difference in airway resistance and bronchodilator responsiveness to salbutamol. There were no significant differences in these parameters between mountaineers with and without acute mountain sickness. Mild alveolar oedema on radiographs in HAPE was associated only with minor decreases in forced vital capacity, diffusing capacity and lung compliance and minor increases in closing volume. Comprehensive lung function testing provided no evidence of interstitial pulmonary oedema in mountaineers without HAPE during the first 2 days at 4,559 m. Data obtained in mountaineers with early mild HAPE suggest that these methods may not be sensitive enough for the detection of interstitial pulmonary fluid accumulation.

Should travelers with hypertension adjust their medications when traveling to high altitude

Luks, Andrew M. Should travelers with hypertension adjust their medications when traveling to high altitude? High Alt. Med. Biol. 10:11-15, 2009.-When advising travelers to high altitude, clinicians should consider how their patients underlying medical conditions may be affected by the high altitude and whether changes are necessary in their medical regimen. Given the high prevalence of hypertension in the general population, it is a common medical condition that is often considered in this regard. Little information exists, however, to guide the management of this condition at high altitude. This review considers the available data regarding systemic blood pressure responses and the risks of worsening blood pressure control at high altitude and which antihypertensive medications are more effective for blood pressure control in this environment. The available evidence suggests blood pressure rises to a modest extent in patients with mild to moderate hypertension upon acute ascent to high altitude, but there is no clear evidence of an increased risk of complications due to these increased pressures. There is, however, marked interindividual variability in blood pressure responses at altitude; as a result, patients with poorly controlled or very labile hypertension should monitor their blood pressure upon ascent to high altitude and travel with a plan for altering their medical regimen in the event marked or symptomatic blood pressure elevations occur.

Chronic Kidney Disease at High Altitude

With a prevalence of 10 to 11% in the general population, it is likely that many patients with chronic kidney disease will visit or reside in mountainous areas. Little is known, however, about whether short- or long-duration, high-altitude exposure poses a risk in this patient population. Given that many areas of the kidney are marginally oxygenated even at sea level and that kidney disease may result in further renal hypoxia and hypoxia-associated renal injury, there is concern that high altitude may accelerate the progression of chronic kidney disease. In this review, we address how chronic kidney disease and its management is affected at high altitude. We postulate that arterial hypoxemia at high altitude poses a risk of faster disease progression in those with preexisting kidney disease. In addition, we consider the risks of developing acute altitude illness in patients with chronic kidney disease and the appropriate use of medications for the prevention and treatment of these problems.

Transpulmonary Plasma ET-1 and Nitrite Differences in High Altitude Pulmonary Hypertension

The efficacy and safety of intermittent hypoxia training (IHT) were investigated in healthy, 60- to 74-yr-old men. Fourteen men (Gr 1) who routinely exercised daily for 20 to 30 min were compared with 21 (Gr 2) who avoided exercise. Their submaximal work-load power values before the IHT training were 94 +/- 3.7 and 66 +/- 3.1, respectively. Before and after 10 days of IHT, the ventilatory response to sustained hypoxia (SH; 12% O(2) for 10 min), work capacity (bicycle ergometer), and forearm cutaneous perfusion (laser Doppler) were determined. During SH, no negative electrocardiogram (ECG) changes were observed in either group, and the ventilatory response to SH was unaltered by IHT. In Gr 1, IHT (normobaric rebreathing for 5 min, final Sa(O(2)) = 85% to 86%, followed by 5 min normoxia, 4/day) produced no changes in hemodynamic indixes and work capacity. In Gr 2, IHT decreased blood pressure (BP) by 7.9 +/- 3.1 mmHg (p < 0.05) and increased submaximal work by 11.3% (p < 0.05) and anaerobic threshold by 12.7% (p < 0.05). The increase in HR and BP caused by a 55 W-work load was reduced by 5% and 6.5%, respectively (p < 0.05). Cutaneous perfusion increased by 0.06 +/- 0.04 mL/min/100 g in Gr 1 and by 0.11 +/- 0.04 mL/min/100 g in Gr 2 (p < 0.05). Hyperemia recovery time increased significantly by 15.3 +/- 4.6 sec in Gr 1 and by 25.2 +/- 11.2 sec in Gr 2. Thus, healthy senior men well tolerate IHT as performed in this investigation. In untrained, healthy senior men, IHT had greater positive effects on hemodynamics, microvascular endothelial function, and work capacity.

Physiology in Medicine: A physiologic approach to prevention and treatment of acute high-altitude illnesses

With the growing interest in adventure travel and the increasing ease and affordability of air, rail, and road-based transportation, increasing numbers of individuals are traveling to high altitude. The decline in barometric pressure and ambient oxygen tensions in this environment trigger a series of physiologic responses across organ systems and over a varying time frame that help the individual acclimatize to the low oxygen conditions but occasionally lead to maladaptive responses and one or several forms of acute altitude illness. The goal of this Physiology in Medicine article is to provide information that providers can use when counseling patients who present to primary care or travel medicine clinics seeking advice about how to prevent these problems. After discussing the primary physiologic responses to acute hypoxia from the organ to the molecular level in normal individuals, the review describes the main forms of acute altitude illness--acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema--and the basic approaches to their prevention and treatment of these problems, with an emphasis throughout on the physiologic basis for the development of these illnesses and their management.