Cerebral blood flow and oxygen delivery at high altitude

During acclimatization to moderate altitudes, a simple calculation from data of others shows that the rise in cerebral blood flow (CBF) is sufficient that oxygen delivery to brain (DaO2) is constant as arterial oxygen content (CaO2) falls. This balance occurs on average even though the hypocapnia caused by hypoxic hyperventilation causes cerebral vasoconstriction, conflicting with hypoxic cerebral vasodilation. The relative strengths of the ventilatory and cerebral vascular sensitivities may affect this balance in individual subjects. There is no evidence for a mechanism to detect or respond directly to DaO2. Hypoxic cerebral vasodilation is believed to depend upon tissue and capillary PO2 and content, not arterial. Despite these reservations it is of interest that the average resultant DO2 remains constant. I speculate here that this match may relate to the well-known local hyperemic response to neuronal activity which now has been shown to initially overcompensate, in that tissue PO2 and pH rise in the first few seconds after neural activity. Analysis of results from the paper by Severinghaus et al. (Circ. Res. 1966;19:274-282) shows that in their subjects, despite approximately 20% reductions in arterial oxygen content at 3,810 m altitude, the data does not show any significant fall in DaO2 as a result of increased cerebral blood flows.     

Energy at high altitude

For the military doctor, an understanding of the metabolic effects of high altitude (HA) exposure is highly relevant. This review examines the acute metabolic challenge and subsequent changes in nutritional homeostasis that occur when troops deploy rapidly to HA. Key factors that impact on metabolism include the hypoxic-hypobaric environment, physical exercise and diet. Expected metabolic changes include augmentation of basal metabolic rate (BMR), decreased availability of oxygen in peripheral metabolic tissues, reduction in VO2 max, increased glucose dependency and lactate accumulation during exercise. The metabolic demands of exercise at HA are crucial. Equivalent activity requires greater effort and more energy than it does at sea level. Soldiers working at HA show high energy expenditure and this may exceed energy intake significantly. Energy intake at HA is affected adversely by reduced availability, reduced appetite and changes in endocrine parameters. Energy imbalance and loss of body water result in weight loss, which is extremely common at HA. Loss of fat predominates over loss of fat-free mass. This state resembles starvation and the preferential primary fuel source shifts from carbohydrate towards fat, reducing performance efficiency. However, these adverse effects can be mitigated by increasing energy intake in association with a high carbohydrate ration. Commanders must ensure that individuals are motivated, educated, strongly encouraged and empowered to meet their energy needs in order to maximise mission-effectiveness.     

Delirium at high altitude

A 35-year-old man on a trek to the Mount Everest region of Nepal presented with a sudden, acute confusional state at an altitude of about 5000 m. Although described at higher altitudes, delirium presenting alone has not been documented at 5000 m or at lower high altitudes. The differential diagnosis which includes acute mountain sickness and high altitude cerebral edema is discussed. Finally, the importance of travelling with a reliable partner and using proper insurance is emphasized in treks to the Himalayas.     

Sleep at high altitude

New arrivals to altitude commonly experience poor-quality sleep. These complaints are associated with increased fragmentation of sleep by frequent brief arousals, which are in turn linked to periodic breathing. Changes in sleep architecture include a shift toward lighter sleep stages, with marked decrements in slow-wave sleep and with variable decreases in rapid eye movement (REM) sleep. Respiratory periodicity at altitude reflects alternating respiratory stimulation by hypoxia and subsequent inhibition by hyperventilation-induced hypocapnia. Increased hypoxic ventilatory responsiveness and loss of regularization of breathing during sleep contribute to the occurrence of periodicity. Interventions that improve sleep quality at high altitude include acetazolamide and benzodiazepines.     

Safe upper limits for oxygen enrichment of room air at high altitude

Oxygen enrichment of room air at high altitude has been shown to improve mental performance, sleep quality, and work capacity. Until now, the usual strategy has been to use an oxygen concentration that reduces the equivalent altitude to about 3,000 m, where the equivalent altitude is that which gives the same inspired PO2 during air breathing. However, standards adopted by the National Fire Protection Association allow considerably higher oxygen concentrations without introducing a fire hazard. For example, by raising the oxygen concentration to 31.5% at an altitude of 5,000 m, the equivalent altitude can be safely reduced to less than 2,000 m. At the extreme altitude of 8,000 m, the equivalent altitude can be reduced to less than 4,000 m without increasing the fire hazard. These increased levels of oxygen enrichment are feasible in practice using oxygen concentrators. They may be useful if lowlanders need to ascend rapidly and stay at high altitude, or for treating people with high altitude illnesses.     

Supplemental oxygen and sleep at altitude

Windsor, Jeremy S., and George W. Rodway. Supplemental oxygen and sleep at altitude. High Alt. Med. Biol. 7:307-311, 2006.--The purpose of this study was to examine the effect supplemental oxygen has on the respiratory and cardiovascular system of a mountaineer during sleep at high altitude by using a novel ambulatory, multisensor, continuous monitoring device. Supplemental oxygen was administered to a healthy subject via a nasal demand system (0, 16.7, 33.3, or 50 mL/sec per pulse dose delivered over 1 sec) during the first three nights of sleep at 4900 and 5700 m. Increases in pulse dose resulted in a consistent rise in Sa(O(2)) and a fall in minute ventilation (p < 0.05). The 50-mL pulse dose resulted in the greatest changes, with an increase in Sa(O(2)) from 68.5% to 81% (p < 0.05) and a fall in minute ventilation from 13.1 to 10.9 L/min (p < 0.05) being noted. Changes in Sa(O(2)) and minute ventilation also coincided with a fall in apnea/hypopnea index (AHI). At 4900 m the AHI fell from 12.5-52.3 (breathing air) to 0-7.5 (50-mL oxygen pulse), whereas at 5700 m a decrease from 49.1-80.4 to 3.5-10.0 was observed. No changes in respiratory rate or heart rate were identified when different pulse doses were compared (p < 0.05). The multisensor monitoring device proved to be a highly effective system, demonstrating marked improvements in Sa(O(2)), tidal volume, and AHI in our participant when supplemental oxygen was administered via a nasal demand system.     

Supplemental oxygen and hyperbaric treatment at high altitude: cardiac and respiratory response

INTRODUCTION: The most effective treatment for high altitude sickness is prompt descent. However, rapid descent is sometimes impossible and alternative solutions are desirable. Supplemental oxygen at ambient pressure and hyperbaric oxygen in a hyperbaric tent have both been demonstrated to improve symptoms and increase arterial oxygenation (SaO2) in those with high altitude sickness; however, their use in combination has not previously been described in a controlled study. METHODS AND RESULTS: In this feasibility study, the SaO2 of six healthy, well-acclimatized participants rose from 76.5 to 97.5% at 4900 m and 72.5 to 96.0% at 5700 m following the administration of oxygen via a nasal demand circuit (33 ml of oxygen per pulse) inside a hyperbaric tent (107 mmHg above ambient barometric pressure) (p < 0.05). This contrasted with an increase in SaO2 to 89.5% at 4900 m and 86.3% at 5700 m with only supplemental oxygen and an increase in SaO2 to 92.8% (4900 m) and 90.5% (5700 m) with only hyperbaric exposure. In addition, combining treatments also resulted in an increase in tidal volume (29.0 and 31.0%) and minute ventilation (12.0 and 23.0%) together with a fall in heart rate (15.0 and 17.0%) at 4900 and 5700 m, respectively. No significant differences in heart rate, tidal volume, minute ventilation, SaO2, or respiratory rate were seen when hyperbaric treatment and supplemental oxygen were directly compared. CONCLUSIONS: In healthy, well-acclimatized subjects the combination of hyperbaric exposure and supplemental oxygen has a noteworthy effect on physiological parameters at high altitude. Awareness of this knowledge may enhance the treatment of patients with life-threatening high altitude sickness.     

Angiotensin-converting enzyme genotype and arterial oxygen saturation at high altitude in Peruvian Quechua

The I-allele of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been associated with performance benefits at high altitude (HA). In n = 142 young males and females of largely Quechua origins in Peru, we evaluated 3 specific hypotheses with regard to the HA benefits of the I-allele: (1) the I-allele is associated with higher arterial oxygen saturation (Sa(O(2))) at HA, (2) the I-allele effect depends on the acclimatization state of the subjects, and (3) the putative I-allele effect on Sa(O(2)) is mediated by the isocapnic hypoxic ventilatory response (HVR, l/min(1)/% Sa(O(2))(1)). The subject participants comprised two different study groups including BLA subjects (born at low altitude) who were lifelong sea-level residents transiently exposed to hypobaric hypoxia (<24 h) and BHA subjects (born at HA) who were lifelong residents of HA. To control for the possibility of population stratification, Native American ancestry proportion (NAAP) was estimated as a covariate for each individual using a panel of 70 ancestry-informative molecular markers (AIMS). At HA, resting and exercise Sa(O(2)) was strongly associated with the ACE genotype, p = 0.008 with approximately 4% of the total variance in Sa(O(2)) attributed to ACE genotype. Moreover, I/I individuals maintained approximately 2.3 percentage point higher Sa(O(2)) compared to I/D and D/D. This I-allele effect was evident in both BLA and BHA groups, suggesting that acclimatization state has little influence on the phenotypic expression of the ACE gene. Finally, ACE genotype was not associated with the isocapnic HVR, although HVR had a strong independent effect on Sa(O(2)) (p = 0.001). This suggests that the I-allele effect on Sa(O(2)) is not mediated by the peripheral control of breathing, but rather by some other central cardiopulmonary effect of the ACE gene on the renin-angiotensin-aldosterone system (RAAS).     

Ketamine anesthesia at high altitude

There is a clinical need for a safe and effective anesthetic technique in high altitude and remote areas. This report presents a series of 11 consecutive cases documenting the use of ketamine anesthesia in a remote hospital at an altitude of 3,900 m, by primary-care physicians without specialist training in anesthesia. The method of administration is fully described. At a low dose of 2.0 mg/kg, ketamine produces a dissociative anesthesia that does not depress the hypoxic drive, or interfere with the pharyngeal or laryngeal reflexes. Although supplemental oxygen is useful in the recovery phase for less acclimatized individuals, it is usually not required as reductions in oxygen saturation can be raised by physical stimulation that encourages the patient to breathe faster and deeper. The common side effect of emergent nightmares was avoided using midazolam as premedication and a quiet recovery area. This study offers the first available evidence that ketamine with midazolam offers a safe and effective means of anaesthesia at very high altitude, without the need for specialist equipment or training, by careful clinicians experienced in basic airway management.     

Cardiac arrhythmias at high altitude

Palpitations at high altitude have been experienced, but seldom recorded, for centuries. The hypoxia, sympathetic activation and alkalosis of altitude predispose to cardiac ischaemia and arrhythmia. Indeed, sudden cardiac death is responsible for 30% of all deaths during mountain sports at altitude. This article reviews the literature to date on the evidence for cardiac arrhythmias at altitude.     

Cardiovascular physiology at high altitude

The role of the cardiovascular system is to deliver oxygenated blood to the tissues and remove metabolic effluent. It is clear that this complex system will have to adapt to maintain oxygen deliver in the profound hypoxia of high altitude. The literature on the adaptation of both the systemic and pulmonary circulations to high altitude is reviewed.     

The placenta at high altitude

The influence of oxygen pressure on placental and villous vascular development is reviewed and considered relative to the natural experiment afforded by residence at high altitude. Data obtained from normal high altitude pregnancies are compared with those from IUGR and preeclampsia, conditions believed to be caused by placental hypoxia. High altitude placentas are characterized by increased villous vascularization, thinning of the villous membranes, proliferation of the villous cytotrophoblast, and reduced perisyncytial fibrin deposition relative to low altitude placentas. The significance of reduced fibrin deposition is unknown; it could be explained by less apoptosis along the barrier membrane, less syncytiotrophoblast turnover, or altered ratios of local proversus anticoagulant production. Increased villous capillary density and thinning of the villous membranes increases oxygen diffusion capacity and is generally considered a beneficial adaptation. Nonetheless, there is evidence that hypoxia and/or reduced blood flow reduce placental nutrient transporter densities, and this may act in additive or synergistic fashion to reduce birth weight at high altitude. The available literature on high altitude placentas derives from less than 100 pregnancies from three different continents and six different ethnic groups, and were acquired in pregnancies ranging from 2500 to 4300 m in altitude. Thus differences between studies are likely to be due to variation in altitude and/or to ethnic variation, which in turn may be due to differences in population history of residence at high altitude (e.g., Andeans vs. Europeans). Nonetheless, systematic examination of human placental development under conditions of lowered maternal arterial oxygen pressure (high altitude > 2700 m) may provide useful insights into the etiology of pathological conditions believed to be associated with placental hypoxia.     

Diabetic retinopathy at high altitude

The objective of this study was to determine whether altitude hypoxia favors the development of diabetic retinopathy (DR) in healthy type 1 diabetic climbers with tight glycemia control. The retinas of 7 type 1 diabetic climbers with a history of stays at high altitude were studied through nonmydriatic chamber retinography (Ffo-CNM). The retinographies were performed before and after a 7,143 m peak expedition. One of the subjects presented evidence of DR prior to the ascent, in addition to a microhemorrhage afterward; the rest of the retinographies were normal. Fine glycemia management and adequate acclimatization are not the only cautions for diabetics going to altitude; an ophthalmologic exam beforehand is also recommended.     

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.     

高原环境下高原病再发的流行病学研究

目的了解在高原环境下住院高原病患者的预后。方法以医院(海拔3658m)40年间收治、并符合筛选标准的19118例住院病历为样本,随访1～15年,样本中以高原病首次住院为病例组,以非高原病首次住院者为对照组。随访两组高原病的发病情况,并进行临床流行病学的分析。结果(1)对照组的急性高原病发病率、总体发病率随观察年限延长而增加且呈正相关(r急=08259,P<001,r总=06815,P<005);急性高原病组和慢性高原病组的慢性高原病发病率随观察年限延长而减低,且呈负相关(r急1～7=08993,P<001;r慢1～9=09068,P<0001)。(2)病例组总体高原病逐年发病率在急性高原病组和慢性高原病组均显著高于对照组(P<001),RR=1129。(3)各型高原病发病率在急性高原病组和慢性高原病组均显著高于对照组(P<001)。急性高原病组以急性轻型高原病和高原肺水肿发病率最高,达1712%和2766%,RR=759;慢性高原病组以急性轻型高原病和Monges病发病率最高,达1284%和1119%,RR=531。结论高原病患者再发生高原病的风险显著增加,不适宜长期滞留高原地区。