Design and conduct of 'Xtreme Alps' : a double-blind, randomised controlled study of the effects of dietary nitrate supplementation on acclimatisation to high altitude

The study of healthy human volunteers ascending to high altitude provides a robust model of the complex physiological interplay that emulates human adaptation to hypoxaemia in clinical conditions. Nitric oxide (NO) metabolism may play an important role in both adaptation to high altitude and response to hypoxaemia during critical illness at sea level. Circulating nitrate and nitrite concentrations can be augmented by dietary supplementation and this is associated with improved exercise performance and mitochondrial efficiency. We hypothesised that the administration of a dietary substance (beetroot juice) rich in nitrate would improve oxygen efficiency during exercise at high altitude by enhancing tissue microcirculatory blood flow and oxygenation. Furthermore, nitrate supplementation would lead to measurable increases in NO bioactivity throughout the body. This methodological manuscript describes the design and conduct of the ‘Xtreme Alps’ expedition, a double-blind randomised controlled trial investigating the effects of dietary nitrate supplementation on acclimatisation to hypobaric hypoxia at high altitude in healthy human volunteers. The primary outcome measure was the change in oxygen efficiency during exercise at high altitude between participants allocated to receive nitrate supplementation and those receiving a placebo. A number of secondary measures were recorded, including exercise capacity, peripheral and microcirculatory blood flow and tissue oxygenation. Results from this study will further elucidate the role of NO in adaption to hypoxaemia and guide clinical trials in critically ill patients. Improved understanding of hypoxaemia in critical illness may provide new therapeutic avenues for interventions that will improve survival in critically ill patients

Survival after postoperative morbidity: a longitudinal observational cohort study

Prolonged morbidity after surgery is associated with a risk of premature death for a longer duration than perhaps is commonly thought; however, this risk falls with time. We suggest that prolonged postoperative morbidity measured in this way may be a valid indicator of the quality of surgical healthcare. Our findings reinforce the importance of research and quality improvement initiatives aimed at reducing the duration and severity of postoperative complication

The Postoperative Morbidity Survey was validated and used to describe morbidity after major surgery.

OBJECTIVES: To describe the reliability and validity of the Postoperative Morbidity Survey (POMS). To describe the level and pattern of short-term postoperative morbidity after major elective surgery using the POMS. STUDY DESIGN AND SETTING: This was a prospective cohort study of 439 adults undergoing major elective surgery in a UK teaching hospital. The POMS, an 18-item survey that address nine domains of postoperative morbidity, was recorded on postoperative days 3, 5, 8, and 15. RESULTS: Inter-rater reliability was perfect for 11/18 items (Kappa=1.0), with Kappa=0.94 for 6/18 items. A priori hypotheses that the POMS would discriminate between patients with known measures of morbidity risk, and predict length of stay were generally supported through observation of data trends, and there was statistically significant evidence of construct validity for all but the wound and neurological domains. POMS-defined morbidity was present in 325 of 433 patients (75.1%) remaining in hospital on postoperative day 3 after surgery, 231 of 407 patients (56.8%) on day 5, 138 of 299 patients (46.2%) on day 8, and 70 of 111 patients (63.1%) on day 15. Gastrointestinal (47.4%), infectious (46.5%), pain-related (40.3%), pulmonary (39.4%), and renal problems (33.3%) were the most common forms of morbidity. CONCLUSION: The POMS is a reliable and valid survey of short-term postoperative morbidity in major elective surgery. Many patients remain in hospital without any morbidity as recorded by the POMS

High altitude-related hypertensive crisis and acute kidney injury in an asymptomatic healthy individual

BACKGROUND: High-altitude exposure causes a mild to moderate rise in systolic and diastolic blood pressure. This case report describes the first documented case of a hypertensive crisis at altitude, as well as the first report of the occurrence of acute kidney injury in the context of altitude-related hypertension. CASE PRESENTATION: A healthy, previously normotensive 30-year old, embarked on a trek to Everest Base Camp (5300 m). During his 11-day ascent the subject developed increasingly worsening hypertension. In the absence of symptoms, the individual initially elected to remain at altitude as had previously been the plan. However, an increase in the severity of his hypertension to a peak of 223/119 mmHg resulted in a decision to descend. On descent he was found to have an acute kidney injury that subsequently resolved spontaneously. His blood pressure reverted to normal at sea level and subsequent investigations including a transthoracic echocardiogram, cardiac magnetic resonance imaging, renal ultrasound, and urinary catecholamines were normal. CONCLUSION: This report challenges the view that transient rises in blood pressure at altitude are without immediate risk. We review the evidence that altitude induces hypertension and discuss the implications for the management of hypertension at altitude

Critical care at the end of life: balancing technology with compassion and agreeing when to stop

Modern intensive care saves lives. However, the substantial related financial costs are, for many, married to substantial costs in terms of suffering. In the most sick, the experience of intensive care is commonly associated with the development of profound physical debility, which may last years after discharge. Likewise, the negative psychological impact commonly experienced by such patients during their care is now widely recognized, as is the persistence of psychological morbidity. Such issues become increasingly important as the population of the frail elderly increases, and the health and social care services face budgetary restriction. Efforts must be made to humanize intensive care as much as possible. Meanwhile, an open conversation must be held between those within the medical professions, and between such healthcare workers and the public in general, regarding the balancing of the positive and negative impacts of intensive care. Such conversations should extend to individual patients and their families when considering what care is genuinely in their best interests

Changes in labial capillary density on ascent to and descent from high altitude.

Present knowledge of how the microcirculation is altered by prolonged exposure to hypoxia at high altitude is incomplete and modification of existing analytical techniques may improve our knowledge considerably. We set out to use a novel simplified method of measuring in vivo capillary density during an expedition to high altitude using a CytoCam incident dark field imaging video-microscope. The simplified method of data capture involved recording one-second images of the mucosal surface of the inner lip to reveal data about microvasculature density in ten individuals. This was done on ascent to, and descent from, high altitude. Analysis was conducted offline by two independent investigators blinded to the participant identity, testing conditions and the imaging site.  Additionally we monitored haemoglobin concentration and haematocrit data to see if we could support or refute mechanisms of altered density relating to vessel recruitment. Repeated sets of paired values were compared using Kruskall Wallis Analysis of Variance tests, whilst comparisons of values between sites was by related samples Wilcoxon Signed Rank Test. Correlation between different variables was performed using Spearman's rank correlation coefficient, and concordance between analysing investigators using intra-class correlation coefficient. There was a significant increase in capillary density from London on ascent to high altitude; median capillaries per field of view area increased from 22.8 to 25.3 (p=0.021). There was a further increase in vessel density during the six weeks spent at altitude (25.3 to 32.5, p=0.017). Moreover, vessel density remained high on descent to Kathmandu (31.0 capillaries per field of view area), despite a significant decrease in haemoglobin concentration and haematocrit. Using a simplified technique, we have demonstrated an increase in capillary density on early and sustained exposure to hypobaric hypoxia at thigh altitude, and that this remains elevated on descent to normoxia. The technique is simple, reliable and reproducible

Application of the optimized carbon monoxide rebreathing method for the measurement of total haemoglobin mass in chronic liver disease

Background: Anemia is common in liver cirrhosis. This generally infers a fall in total hemoglobin mass (tHb‐mass). However, hemoglobin concentration ([Hb]) may fall due to an expansion in plasma volume (PV). The “optimized carbon monoxide rebreathing method” (oCOR) measures tHb‐mass directly and PV (indirectly using hematocrit). It relies upon carboxyhemoglobin (COHb) distribution throughout the entire circulation. In healthy subjects, such distribution is complete within 6–8 min. Given the altered circulatory dynamics in cirrhosis, we sought in this pilot study, to assess whether this was true in cirrhosis. The primary aim was to ascertain if the standard timings for the oCOR were applicable to patients with chronic liver disease and cirrhosis. The secondary aim was to explore the applicability of standard CO dosing methodologies to this patient population. Methods: Sixteen patients with chronic liver parenchymal disease were studied. However, tHb‐mass was determined using the standard oCOR technique before elective paracentesis. Three subjects had an inadequate COHb% rise. In the remaining 13 (11 male), mean ± standard deviation (SD ) age was 52 ± 13.8 years, body mass 79.1 ± 11.4 kg, height 175 ± 6.8 cm. To these, mean ± SD dose of carbon monoxide (CO) gas administered was 0.73 ± 0.13 ml/kg COHb values at baseline, 6 and 8 min (and “7‐min value”) were compared to those at 10, 12, 15 and 20 min after CO rebreathing. Results: The “7‐min value” for median COHb% (IQR) of 6.30% (6.21%–7.47%) did not differ significantly from those at subsequent time points (8 min: 6.30% (6.21%–7.47%), 10 min: 6.33% (6.00%–7.50%), 12 min: 6.33% (5.90%–7.40%), 15 min: 6.37% (5.80%–7.33%), 20 min: 6.27% (5.70%–7.20%)). Mean difference in calculated tHb‐mass between minute 7 and minute 20 was only 4.1 g, or 0.6%, p = .68. No subjects reported any adverse effects. Conclusions: The oCOR method can be safely used to measure tHb‐mass in patients with chronic liver disease and ascites, without adjustment of blood sample timings. Further work might refine and validate appropriate dosing regimens

Characteristics of medium-scale travelling ionospheric disturbances observed near the Antarctic Peninsula by HF radar

We present a survey of medium-scale traveling ionospheric disturbances (MSTIDs) observed by a Super Dual Auroral Radar Network HF radar located in the Falkland Islands between May 2010 and April 2011. The radar has a field of view that overlooks the Antarctic Peninsula, a known hot spot of gravity wave activity. We present observations of radar ground-backscatter data, in which the signatures of MSTIDs are manifested as structured enhancements in echo power. Observed periods were in the range 30–80 min, corresponding to frequencies of 0.2–0.6 mHz. Wavelengths were generally in the range 200–800 km and phase speeds in the range 100–300 m s−1. These values are within the ranges typically associated with medium-scale gravity waves. We find a primary population of northward (equatorward) propagating MSTIDs, which demonstrate an association with enhanced solar wind-magnetosphere coupling and a smaller, westward propagating population, that could be associated with atmospheric gravity waves excited by winds over the Andean and Antarctic Peninsula mountains or by the high winds of the Antarctic Polar Vortex

Testing nowcasts of the ionospheric convection from the expanding and contracting polar cap model

The expanding/contracting polar cap (ECPC) model, or the time-dependent Dungey cycle, provides a theoretical framework for understanding solar wind-magnetosphere-ionosphere coupling. The ECPC describes the relationship between magnetopause reconnection and substorm growth phase, magnetotail reconnection and substorm expansion phase, associated changes in auroral morphology, and ionospheric convective motions. Despite the many successes of the model, there has yet to be a rigorous test of the predictions or nowcasts made regarding ionospheric convection, which remains a final hurdle for the validation of the ECPC. In this study we undertake a comparison of ionospheric convection, as measured in situ by ion drift meters on board DMSP (Defense Meteorological Satellite Program) satellites and from the ground by SuperDARN (Super Dual Auroral Radar Network), with motions nowcasted by a theoretical model. The model is coupled to measurements of changes in the size of the polar cap made using global auroral imagery from the IMAGE FUV (Imager for Magnetopause to Aurora Global Exploration Far Ultraviolet) instrument, as well as the dayside reconnection rate, estimated using the OMNI data set. The results show that we can largely nowcast the magnitudes of ionospheric convection flows using the context of our understanding of magnetic reconnection at the magnetopause and in the magnetotail