Abnormal blood flow in the sublingual microcirculation at high altitude

We report the first direct observations of deranged microcirculatory blood flow at high altitude, using sidestream dark-field imaging. Images of the sublingual microcirculation were obtained from a group of 12 volunteers during a climbing expedition to Cho Oyu (8,201 m) in the Himalayas. Microcirculatory flow index (MFI) was calculated from the moving images of microcirculatory red blood cell flow, and comparison was made between the baseline and high altitude measurements. Peripheral oxygen saturation (SpO2) and Lake Louise scores (LLS) were recorded along with MFI. Our data demonstrate that there was a significant reduction in MFI from baseline to 4,900 m in small (less than 25 μm) and medium (26–50 μm) sized blood vessels (P = 0.025 and P = 0.046, respectively). There was no significant correlation between MFI and SpO2 or MFI and LLS. Disruption of blood flow within microcirculatory may explain persistent abnormal oxygen flux to tissues following the normalisation of systemic oxygen delivery that accompanies acclimatisation to high altitude

The use of skeletal muscle near infrared spectroscopy and a vascular occlusion test at high altitude

Abstract Martin, Daniel, Denny Levett, Rick Bezemer, Hugh Montgomery, and Mike Grocott. The use of skeletal muscle near infrared spectroscopy and a vascular occlusion test at high altitude. High Alt Med Biol 14:256-262, 2013.-Microcirculatory function, central to tissue regulation of oxygen flux, may be altered by the chronic hypoxemia experienced at high altitude. We hypothesized that at high altitude, adaptations within skeletal muscle would result in reduced oxygen consumption and reduced microcirculatory responsiveness, detectable by near infrared spectroscopy (NIRS) during a vascular occlusion test (VOT). The VOT comprised 3 min of noninvasive arterial occlusion; thenar eminence tissue oxygenation (Sto2) was measured by NIRS during the VOT at sea level, 4900 m and 5600 m (after 7 and 17 days at altitude, respectively) in 12 healthy volunteers. Data were derived from Sto2 time-curves using specifically designed computer software. Mean (±SD) resting Sto2 was reduced at 4900 m and 5600 m (69.3 (±8.2)% (p=0.001) and 64.2 (±6.1)% (p <0.001) respectively) when compared to sea level (84.4 (±6.0)%. The rate of Sto2 recovery after vascular occlusion (Sto2 upslope) was significantly reduced at 4900 m (2.4 (±0.4)%/sec) and 5600 m (2.4 (±0.8)%/sec) compared to sea level (3.7 (±1.3)%/sec) (p=0.021 and p=0.032, respectively). There was no change from sea level in the rate of desaturation during occlusion (Sto2 downslope) at either altitude. The findings suggest that in resting skeletal muscle of acclimatizing healthy volunteers at high altitude, microvascular reactivity is reduced (Sto2 upslope after a short period of ischemia) but that oxygen consumption remains unchanged (Sto2 downslope

Hospital-level evaluation of the effect of a national quality improvement programme: time-series analysis of registry data

Background and objectives A clinical trial in 93 National Health Service hospitals evaluated a quality improvement programme for emergency abdominal surgery, designed to improve mortality by improving the patient care pathway. Large variation was observed in implementation approaches, and the main trial result showed no mortality reduction. Our objective therefore was to evaluate whether trial participation led to care pathway implementation and to study the relationship between care pathway implementation and use of six recommended implementation strategies. Methods We performed a hospital-level time-series analysis using data from the Enhanced Peri-Operative Care for High-risk patients trial. Care pathway implementation was defined as achievement of >80% median reliability in 10 measured care processes. Mean monthly process performance was plotted on run charts. Process improvement was defined as an observed run chart signal, using probability-based ‘shift’ and ‘runs’ rules. A new median performance level was calculated after an observed signal. Results Of 93 participating hospitals, 80 provided sufficient data for analysis, generating 800 process measure charts from 20 305 patient admissions over 27 months. No hospital reliably implemented all 10 processes. Overall, only 279 of the 800 processes were improved (3 (2–5) per hospital) and 14/80 hospitals improved more than six processes. Mortality risk documented (57/80 (71%)), lactate measurement (42/80 (53%)) and cardiac output guided fluid therapy (32/80 (40%)) were most frequently improved. Consultant-led decision making (14/80 (18%)), consultant review before surgery (17/80 (21%)) and time to surgery (14/80 (18%)) were least frequently improved. In hospitals using ≥5 implementation strategies, 9/30 (30%) hospitals improved ≥6 care processes compared with 0/11 hospitals using ≤2 implementation strategies. Conclusion Only a small number of hospitals improved more than half of the measured care processes, more often when at least five of six implementation strategies were used. In a longer term project, this understanding may have allowed us to adapt the intervention to be effective in more hospitals

Variation in human performance in the hypoxic mountain environment

Ascent to altitude is associated with a fall in barometric pressure, and with it a decline in the partial pressure of atmospheric (and thus alveolar) oxygen. As a result, a variety of adaptive physiological processes are engaged to mitigate the fall in tissue convective oxygen delivery which might otherwise occur. The magnitude and nature of such changes is also modified with time, a process known as acclimatization. However, other phenomena are at work; the ability to perform physical work at altitude falls in a manner which is not wholly related to changes in arterial oxygen content. Indeed, alterations in local skeletal muscle blood flow and metabolism may play an axial role. Thus, for those who are not native to high altitude, the ability to compete at altitude is likely to be impaired. The magnitude of such impairment in performance, however, differs greatly between individuals, and it seems that genetic variation underpins much of this difference. The identification of the relevant genetic elements is in its infancy in humans, but ongoing work is likely to help us gain an increasing understanding of how humans adapt to altitude and to develop mitigating interventions

Identifying research priorities in anaesthesia and perioperative care:final report of the joint National Institute of Academic Anaesthesia/James Lind Alliance Research Priority Setting Partnership

OBJECTIVE: To identify research priorities for Anaesthesia and Perioperative Medicine. DESIGN: Prospective surveys and consensus meetings guided by an independent adviser. SETTING: UK. PARTICIPANTS: 45 stakeholder organisations (25 professional, 20 patient/carer) affiliated as James Lind Alliance partners. OUTCOMES: First ‘ideas-gathering’ survey: Free text research ideas and suggestions. Second ‘prioritisation’ survey: Shortlist of ‘summary’ research questions (derived from the first survey) ranked by respondents in order of priority. Final ‘top ten’: Agreed by consensus at a final prioritisation workshop. RESULTS: First survey: 1420 suggestions received from 623 respondents (49% patients/public) were refined into a shortlist of 92 ‘summary’ questions. Second survey: 1718 respondents each nominated up to 10 questions as research priorities. Top ten: The 25 highest-ranked questions advanced to the final workshop, where 23 stakeholders (13 professional, 10 patient/carer) agreed the 10 most important questions: ▸ What can we do to stop patients developing chronic pain after surgery? ▸ How can patient care around the time of emergency surgery be improved? ▸ What long-term harm may result from anaesthesia, particularly following repeated anaesthetics? ▸ What outcomes should we use to measure the ‘success’ of anaesthesia and perioperative care? ▸ How can we improve recovery from surgery for elderly patients? ▸ For which patients does regional anaesthesia give better outcomes than general anaesthesia? ▸ What are the effects of anaesthesia on the developing brain? ▸ Do enhanced recovery programmes improve short and long-term outcomes? ▸ How can preoperative exercise or fitness training, including physiotherapy, improve outcomes after surgery? ▸ How can we improve communication between the teams looking after patients throughout their surgical journey? CONCLUSIONS: Almost 2000 stakeholders contributed their views regarding anaesthetic and perioperative research priorities. This is the largest example of patient and public involvement in shaping anaesthetic and perioperative research to date

Changes in sublingual microcirculatory flow index and vessel density on ascent to altitude

We hypothesized that ascent to altitude would result in reduced sublingual microcirculatory flow index (MFI) and increased vessel density. Twenty-four subjects were studied using sidestream dark-field imaging, as they ascended to 5300 m; one cohort remained at this altitude (n = 10), while another ascended higher (maximum 8848 m; n = 14). The MFI, vessel density and grid crossings (GX; an alternative density measure) were calculated. Total study length was 71 days; images were recorded at sea level (SL), Namche Bazaar (3500 m), Everest base camp (5300 m), the Western Cwm (6400 m), South Col (7950 m) and departure from Everest base camp (5300 m; 5300 m-b). Peripheral oxygen saturation (SpO2), heart rate and blood pressure were also recorded. Compared with SL, altitude resulted in reduced sublingual MFI in small (&lt;25 µm; P &lt; 0.0001) and medium vessels (26-50 µm; P = 0.006). The greatest reduction in MFI from SL was seen at 5300 m-b; from 2.8 to 2.5 in small vessels and from 2.9 to 2.4 in medium-sized vessels. The density of vessels &lt;25 µm did not change during ascent, but those &gt;25 µm rose from 1.68 (± 0.43) mm mm-2 at SL to 2.27 (± 0.57) mm mm-2 at 5300 m-b (P = 0.005); GX increased at all altitudes (P &lt; 0.001). The reduction in MFI was greater in climbers than in those who remained at 5300 m in small and medium-sized vessels (P = 0.017 and P = 0.002, respectively). At 7950 m, administration of supplemental oxygen resulted in a further reduction of MFI and increase in vessel density. Thus, MFI was reduced whilst GX increased in the sublingual mucosa with prolonged exposure to hypoxia and was exaggerated in those exposed to extreme altitude

The cerebral venous system and anatomical predisposition to high altitude headache

Abstract Objective: As inspired oxygen availability falls with ascent to altitude, some individuals develop ‘high altitude headache’ (HAH). We postulated that HAH results when hypoxia-associated increases in cerebral blood flow occur in the context of restricted venous drainage, and is worsened when cerebral compliance is reduced. We explored this hypothesis in three studies. Methods: High Altitude Studies: Retinal venous distension (RVD) was opthalmoscopically-assessed in 24 (6 female) and sea-levelcranial Magnetic Resonance Imaging performed in12 subjects ascending to 5300m. Correlation of headache burden (summed severity scores [0-4] ≤24 hours from arrival at each altitude) with RVD, and with cerebral/CSF/venous compartment volumes was sought. Sea-Level Hypoxic Study: Eleven subjects underwent Gadolinium-enhanced Magnetic Resonance Venography before and during hypoxic challenge (FiO2 0.11, 1 hour). Results: High Altitude Study: Headache burden correlated with both RVD (Spearman's rho 0.55, p=0.005), and with the degree of narrowing of one or both transverse venous sinuses (r -0.56 p=0.03). It also related inversely to both the lateral+third ventricle summed volumes (Spearman's Rho -0.5, p=0.05) and peri-cerebellar CSF volume (r-0.56, p=0.03). Hypoxic Study: Cerebral and retinal vein engorgement were correlated, and rose as Combined Conduit Score fell (a measure of venous outflow restriction: r=-0.66, p<0.05 and r=-0.75, p<0.05 respectively)

Impact of nocturnal hypoxia on glycaemic control, appetite, gut microbiota and inflammation in adults with T2DM: a single-blind crossover trial

High altitude residents have a lower incidence of type 2 diabetes mellitus (T2DM). Therefore, we examined the effect of repeated overnight normobaric hypoxic exposure on glycaemic control, appetite, gut microbiota and inflammation in adults with T2DM. Thirteen adults with T2DM [glycated haemoglobin (HbA1c): 61.1 ± 14.1 mmol mol−1; aged 64.2 ± 9.4 years; four female] completed a single-blind, randomised, sham-controlled, cross-over study for 10 nights, sleeping when exposed to hypoxia (fractional inspired O2