Unpressurized aircraft routinely operate at altitudes where hypoxia may be of concern. A systematic literature review was conducted regarding hypoxic impairment, including mental functions, sensory deficits, and other pertinent research findings that may affect aviation-related duties at moderate altitude (8000 to 15,000 ft/2438 to 4572 m). The results of this review suggest that cognitive and psychomotor deficits may include learning, reaction time, decision-making, and certain types of memory. However, results are difficult to quantify and reliably reproduce. Inconsistency of results may be related to the subtlety of deficits compared to high altitude, differences among individual compensatory mechanisms, variation in methodology or sensitivity of metrics, presence or absence of exercise, heterogeneous neuronal central nervous system (CNS) response, and interindividual variation. Literature regarding hypoxic visual decrements is more consistent. Rod photoreceptors are more susceptible to hypoxia; visual degradation has been demonstrated at 4000 to 5000 ft (1219 to 1524 m) under scotopic and 10,000 ft (3048 m) under photopic conditions. Augmented night vision goggle resolution demonstrates more resilience to mild hypoxic effects than the unaided eye under starlight conditions. Hypocapnia enhances visual sensitivity and contrast discrimination. Hyperventilation with resulting respiratory alkalosis and cerebral vasoconstriction may confound both cognitive/ psychomotor and visual experimental results. Future research should include augmentation of validated neuropsychological metrics (surrogate investigational end points) with actual flight metrics, investigation of mixed gas formulations, contribution of hypocapnic vasoconstrictive effects on hypoxic performance, and further investigation into cellular- and systems-level approaches for heterogeneous CNS response. Research is also required into the contribution of mild-moderate hypoxia in human factors- and spatial disorientation-related mishaps.

Background: Sea level natives ascending rapidly to altitudes above 1,500 m often develop acute mountain sickness (AMS), including nausea, headaches, fatigue, and lightheadedness. Acetazolamide (AZ), a carbonic anhydrase inhibitor, is a commonly used medication for the prevention and treatment of AMS. However, there is continued debate about appropriate dosing, particularly when considering rapid and physically demanding ascents to elevations above 3,500 m by emergency medical and military personnel. Aims: Our goal in the present analysis was to evaluate and synthesize the current literature regarding the use of AZ to determine the most effective dosing for prophylaxis and treatment of AMS for rapid ascents to elevations >3,500 m. These circumstances are specifically relevant to military and emergency medical personnel who often need to ascend rapidly and perform physically demanding tasks upon arrival at altitude. Methods: We conducted a literature search from April 2018 to February 2020 using PubMed, Google Scholar, and Web of Science to identify randomized controlled trials that compared AZ with placebo or other treatment with the primary endpoint of AMS incidence and severity. We included only research articles/studies that focused on evaluation of AZ use during rapid ascent. Results: Four doses of AZ (125, 250, 500, and 750 mg daily) were identified as efficacious in decreasing the incidence and/or severity of AMS during rapid ascents, with evidence of enhanced effectiveness with higher doses. Conclusions: For military, emergency medical, or other activities involving rapid ascent to altitudes >3,500 m, doses 500-750 mg/day within 24 hours of altitude exposure appear to be the most effective for minimizing symptoms of AMS.

Blood flow through intrapulmonary arteriovenous anastomoses (Q) occurs in healthy humans at rest and during exercise when breathing hypoxic gas mixtures at sea level and may be a source of right-to-left shunt. However, at high altitudes, Q is reduced compared with sea level, as detected using transthoracic saline contrast echocardiography (TTSCE). It remains unknown whether the reduction in Q (i.e., lower bubble scores) at high altitude is due to a reduction in bubble stability resulting from the lower barometric pressure (P) or represents an actual reduction in Q. To this end, Q, pulmonary artery systolic pressure (PASP), cardiac output (Q), and the alveolar-to-arterial oxygen difference (AaDO) were assessed at rest and during exercise (70-190 W) in the field (5,260 m) and in the laboratory (1,668 m) during four conditions: normobaric normoxia (NN; [Formula: see text] = 121 mmHg, P = 625 mmHg; n = 8), normobaric hypoxia (NH; [Formula: see text] = 76 mmHg, P = 625 mmHg; n = 7), hypobaric normoxia (HN; [Formula: see text] = 121 mmHg, P = 410 mmHg; n = 8), and hypobaric hypoxia (HH; [Formula: see text] = 75 mmHg, P = 410 mmHg; n = 7). We hypothesized Q would be reduced during exercise in isooxic hypobaria compared with normobaria and that the AaDO would be reduced in isooxic hypobaria compared with normobaria. Bubble scores were greater in normobaric conditions, but the AaDO was similar in both isooxic hypobaria and normobaria. Total pulmonary resistance (PASP/Q) was elevated in HN and HH. Using mathematical modeling, we found no effect of hypobaria on bubble dissolution time within the pulmonary transit times under consideration (<5 s). Consequently, our data suggest an effect of hypobaria alone on pulmonary blood flow. NEW & NOTEWORTHY Blood flow through intrapulmonary arteriovenous anastomoses, detected by transthoracic saline contrast echocardiography, was reduced during exercise in acute hypobaria compared with normobaria, independent of oxygen tension, whereas pulmonary gas exchange efficiency was unaffected. Modeling the effect(s) of reduced air density on contrast bubble lifetime did not result in a significantly reduced contrast stability. Interestingly, total pulmonary resistance was increased by hypobaria, independent of oxygen tension, suggesting that pulmonary blood flow may be changed by hypobaria.

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