High altitude respiratory physiology and patho- physiology

At high altitude, reduced atmospheric pressure causes the partial pressure of oxygen to decrease – creating an environment of hypobaric hypoxia which presents a unique set of challenges for the respiratory system. Pulmonary physiological responses such as the hypoxic ventilatory drive are essential for successful acclimatisation, whilst others such as hypoxic pulmonary vasoconstriction may be implicated in the development of altitude illnesses. Pulmonary conditions are some of the most common (e.g. high altitude cough) and also the most serious illnesses seen at altitude (e.g high altitude pulmonary oedema, HAPE). Minimising the chance of developing HAPE through planning an appropriate ascent profile should be strongly encouraged as HAPE can rapidly be fatal if left untreated. Whilst pharmacological agents such as nifedipine can help with the management of HAPE, rapid descent remains the single-most important treatment option once symptomatic. Given the increasing popularity of travelling to altitude, an awareness of how hypobaric hypoxia affects chronic respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD) is also becoming increasingly important for respiratory physician

Effects of dietary nitrate supplementation on microvascular physiology at 4559 m altitude – a randomised controlled trial (Xtreme Alps)

Native highlanders (e.g. Sherpa) demonstrate remarkable hypoxic tolerance, possibly secondary to higher levels of circulating nitric oxide (NO) and increased microcirculatory blood flow. As part of the Xtreme Alps study (a randomised placebo-controlled trial of dietary nitrate supplementation under field conditions of hypobaric hypoxia), we investigated whether dietary supplementation with nitrate could improve NO availability and microvascular blood flow in lowlanders. Plasma measurements of nitrate, nitrite and nitroso species were performed together with measurements of sublingual (sidestream dark-field camera) and forearm blood flow (venous occlusion plethysmography) in 28 healthy adult volunteers resident at 4559 m for 1 week; half receiving a beetroot-based high-nitrate supplement and half receiving an identically-tasting low nitrate 'placebo'. Dietary supplementation increased plasma nitrate concentrations 4-fold compared to the placebo group, both at sea level (SL; 19.2 vs 76.9 μM) and at day 5 (D5) of high altitude (22.9 vs 84.3 μM,

Clinical care in extreme environments: Physiology at high altitude and in space

□ High altitude or space environments present a number of extreme physiologic challenges that must be overcome in order to survive. □ Given sufficient time, humans can adapt to both hypobaric hypoxia and microgravity. □ Lack of adaptation can lead to environment-specific illnesses, such as acute mountain sickness,high-altitude pulmonary edema, decompression illness, or the acute worsening of comorbid conditions. □ These conditions can rapidly become fatal if not treated appropriately (e.g., with either descent to lower altitudes or returning to the Earth’s surface). □ Providing critical care or anesthesia in such environments is further complicated by their ex- treme levels of remoteness. □ Exploratory missions to such environments depend on the development and vetting of robust and simple health care protocols

Acute high-altitude pathologies and their treatment

Ascent to high altitude triggers a wide range of physiological changes. However, ascent is also associated with three acute pathologies: acute mountain sickness, high-altitude cerebral oedema (HACE) and high-altitude pulmonary oedema (HAPE). Awareness and understanding of these conditions allows measures to be taken to reduce the risk of them developing through careful planning and, where appropriate, pharmacological prophylaxis. Both HACE and HAPE are life threatening, necessitating prompt diagnosis and management. Acute mountain sickness, although usually benign, may progress, to HACE or HAPE, if not managed appropriately. This review examines each pathology providing options for risk reduction, diagnosis and management, as well as considering comorbidity at altitude, drawing upon recent advances and consensus guidelines in the field.</p

Oxygen targets during mechanical ventilation in the ICU: a systematic review and meta-analysis

Objectives: patients admitted to intensive care often require treatment with invasive mechanical ventilation and high concentrations of oxygen. Mechanical ventilation can cause acute lung injury that may be exacerbated by oxygen therapy. Uncertainty remains about which oxygen therapy targets result in the best clinical outcomes for these patients. This review aims to determine whether higher or lower oxygenation targets are beneficial for mechanically ventilated adult patients.Data sources: Excerpta Medica dataBASE, Medical Literature Analysis and Retrieval System Online, and Cochrane medical databases were searched from inception through to February 28, 2021.Study selection: randomized controlled trials comparing higher and lower oxygen targets in adult patients receiving invasive mechanical ventilation via an endotracheal tube or tracheostomy in an intensive care setting.Data extraction: study setting, participant type, participant numbers, and intervention targets were captured. Outcome measures included "mortality at longest follow-up" (primary), mechanical ventilator duration and free days, vasopressor-free days, patients on renal replacement therapy, renal replacement free days, cost benefit, and quality of life scores. Evidence certainty and risk of bias were evaluated using Grading of Recommendations Assessment, Development and Evaluation and the Cochrane Risk of Bias tool. A random-effects models was used. Post hoc subgroup analysis looked separately at studies comparing hypoxemia versus normoxemia and normoxemia versus hyperoxemia.Data synthesis: data from eight trials (4,415 participants) were analyzed. Comparing higher and lower oxygen targets, there was no difference in mortality (odds ratio, 0.95; 95% CI, 0.74-1.22), but heterogeneous and overlapping target ranges limit the validity and clinical relevance of this finding. Data from seven studies (n = 4,245) demonstrated targeting normoxemia compared with hyperoxemia may reduce mortality at longest follow-up (0.73 [0.57-0.95]) but this estimate had very low certainty. There was no difference in mortality between targeting relative hypoxemia or normoxemia (1.20 [0.83-1.73]).Conclusions: this systematic review and meta-analysis identified possible increased mortality with liberal oxygen targeting strategies and no difference in morbidity between high or low oxygen targets in mechanically ventilated adults. Findings were limited by substantial heterogeneity in study methodology and further research is urgently required to define optimal oxygen therapy targets.</p