Non-anemic iron deficiency predicts prolonged hospitalisation following surgical aortic valve replacement: a single-centre retrospective study.

BACKGROUND: Iron deficiency has deleterious effects in patients with cardiopulmonary disease, independent of anemia. Low ferritin has been associated with increased mortality in patients undergoing cardiac surgery, but modern indices of iron deficiency need to be explored in this population. METHODS: We conducted a retrospective single-centre observational study of 250 adults in a UK academic tertiary hospital undergoing median sternotomy for non-emergent isolated aortic valve replacement. We characterised preoperative iron status using measurement of both plasma ferritin and soluble transferrin receptor (sTfR), and examined associations with clinical outcomes. RESULTS: Measurement of plasma sTfR gave a prevalence of iron deficiency of 22%. Patients with non-anemic iron deficiency had clinically significant prolongation of total hospital stay (mean increase 2.2 days; 95% CI: 0.5-3.9; P = 0.011) and stay within the cardiac intensive care unit (mean increase 1.3 days; 95% CI: 0.1-2.5; P = 0.039). There were no deaths. Defining iron deficiency as a plasma ferritin < 100 µg/L identified 60% of patients as iron deficient and did not predict length of stay. No significant associations with transfusion requirements were evident using either definition of iron deficiency. CONCLUSIONS: These findings indicate that when defined using sTfR rather than ferritin, non-anemic iron deficiency predicts prolonged hospitalisation following surgical aortic valve replacement. Further studies are required to clarify the role of contemporary laboratory indices in the identification of preoperative iron deficiency in patients undergoing cardiac surgery. An interventional study of intravenous iron targeted at preoperative non-anemic iron deficiency is warranted.

The Effect of High-Altitude Acclimatisation on Ultra-Short Heart Rate Variability.

Introduction: High-altitude (HA) exposure affects heart rate variability (HRV) and has been inconsistently linked to acute mountain sickness (AMS). The influence of increasing HA exposure on ultra-short HRV and its relationship to gold standard HRV measures at HA has not been examined. Methods: This was a prospective observational study of adults aged ≥ 18 years undertaking a HA trek in the Dhaulagiri region of the Himalayas. Cardiac inter-beat-intervals were obtained from a 10-s recording of supra-systolic blood pressure (Uscom BP+ device) immediately followed by 300 s single lead ECG recording (CheckMyHeart device). HRV was measured using the RMSSD (root mean square of successive differences of NN intervals) at sea level (SL) in the United Kingdom and at 3,619, 4,600, and 5,140 m at HA. Oxygen saturations (SpO2) were measured using finger-based pulse oximetry. The level of agreement between the 10 and 300 s RMSSD values were examined using a modified Bland-Altman relative-difference analysis. Results: Overall, 89 participants aged 32.2 ± 8.8 years (range 18-56) were included of which 70.8% were men. HA exposure (SL vs. 3,619 m) was associated with an initial increase in both 10 s (45.0 [31.0-82.0]) vs. 58.0 [33.0-119.0] ms) and 300 s (45.67 [33.24-70.32] vs. 56.48 [36.98-102.0] ms) in RMSSD. Thereafter at 4,600 and 5,140 m both 10 and 300 s RMSSD values were significantly lower than SL. From a total of 317 paired HRV measures the 10 and 300 s RMSSD measures were moderately correlated (Spearman r = 0.66; 95% CI: 0.59-0.72; p < 0.0001). The median difference (bias) in RMSSD values (300 s - 10 s) was -2.3 ms with a lower and upper limit of agreement of -107.5 and 88.61 ms, respectively with no differences with altitude. Overall, 293/317 (92.4%) of all paired HRV values fell within the 95% CI limits of agreement. Neither HRV method was predictive of AMS. Conclusion: Increasing HA affects ultra-short HRV in a similar manner to gold-standard 300 s. Ultra-short HRV has a moderate agreement with 300 s measurements. HRV did not predict AMS.

Perioperative Management of Pulmonary Hypertension. a Review.

Pulmonary hypertension is a rare and progressive pathology defined by abnormally high pulmonary artery pressure mediated by a diverse range of aetiologies. It affects up to twenty-six individuals per one million patients currently living in the United Kingdom (UK), with a median life expectancy of 2.8 years in idiopathic pulmonary hypertension. The diagnosis of pulmonary hypertension is often delayed due to the presentation of non-specific symptoms, leading to a delay in referral to specialists services. The complexity of treatment necessitates a multidisciplinary approach, underpinned by a diverse disease aetiology from managing the underlying disease process to novel specialist treatments. This has led to the formation of dedicated specialist treatment centres within centralised UK cities. The article aimed to provide a concise overview of pulmonary hypertension's clinical perioperative management, including key definitions, epidemiology, pathophysiology, and risk stratification.

Fuel Use during Exercise at Altitude in Women with Glucose-Fructose Ingestion.

PURPOSE: This study compared the coingestion of glucose and fructose on exogenous and endogenous substrate oxidation during prolonged exercise at terrestrial high altitude (HA) versus sea level, in women. METHOD: Five women completed two bouts of cycling at the same relative workload (55% Wmax) for 120 min on acute exposure to HA (3375 m) and at sea level (~113 m). In each trial, participants ingested 1.2 g·min of glucose (enriched with C glucose) and 0.6 g·min of fructose (enriched with C fructose) before and every 15 min during exercise. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate fat oxidation, total and exogenous carbohydrate oxidation, plasma glucose oxidation, and endogenous glucose oxidation derived from liver and muscle glycogen. RESULTS: The rates and absolute contribution of exogenous carbohydrate oxidation was significantly lower at HA compared with sea level (effect size [ES] > 0.99, P < 0.024), with the relative exogenous carbohydrate contribution approaching significance (32.6% ± 6.1% vs 36.0% ± 6.1%, ES = 0.56, P = 0.059) during the second hour of exercise. In comparison, no significant differences were observed between HA and sea level for the relative and absolute contributions of liver glucose (3.2% ± 1.2% vs 3.1% ± 0.8%, ES = 0.09, P = 0.635 and 5.1 ± 1.8 vs 5.4 ± 1.7 g, ES = 0.19, P = 0.217), and muscle glycogen (14.4% ± 12.2% vs 15.8% ± 9.3%, ES = 0.11, P = 0.934 and 23.1 ± 19.0 vs 28.7 ± 17.8 g, ES = 0.30, P = 0.367). Furthermore, there was no significant difference in total fat oxidation between HA and sea level (66.3 ± 21.4 vs 59.6 ± 7.7 g, ES = 0.32, P = 0.557). CONCLUSIONS: In women, acute exposure to HA reduces the reliance on exogenous carbohydrate oxidation during cycling at the same relative exercise intensity.

Non-flushing of IV administration sets: an under-recognised under-dosing risk.

BACKGROUND: intravenous (IV) drugs are administered widely and under-dosing can result in therapy failure. The aim of this study was to quantify frequency, volume and dose of drug discarded within administration sets in the clinical setting. METHODS: residual volume for 24 different administration sets was measured under controlled conditions in a laboratory. Clinical assessment of current practice regarding post-infusion flushing occurred in 6 departments of one teaching hospital in the UK over 7 days. Details of drug last infused, (concentration, diluent and volume) and type and brand of administration set were collected. RESULTS: 74% of administration sets were not flushed. Non-flushing exceeded 90% and 61% for gravity and pump infusions respectively (p<0.001) in all areas excluding oncology. Oncology was the only area where flushing was standard practice for all infusions (p<0.001). Mean residual volume of the administration sets was 13.1 ml and 16.7 ml for gravity and pump sets respectively. Antibiotics were commonly infused and up to 21% of antibiotic dose was frequently discarded. CONCLUSIONS: the findings suggest disposal of substantial volumes of drugs occurs frequently in general hospital areas. Without clear national and local policies this unrecognised under-dosing will continue.

A pilot investigation into the effects of acute normobaric hypoxia, high altitude exposure and exercise on serum angiotensin-converting enzyme, aldosterone and cortisol.

INTRODUCTION: Aldosterone decreases at high altitude (HA) but the effect of hypoxia on angiotensin-converting enzyme (ACE), a key step in the renin-angiotensin-aldosterone system, is unclear. METHODS: We investigated the effects of exercise and acute normobaric hypoxia (NH, ~11.0% FiO2) on nine participants and six controls undertaking the same exercise at sea level (SL). NH exposure lasted 5 hours with 90 minutes of submaximal treadmill walking. Blood samples for aldosterone, ACE and cortisol were taken throughout exposure and at rest during a trek to HA (5140 m) in eight separate participants. RESULTS: There was no difference in cortisol or aldosterone between groups pre-exercise. Aldosterone rose with exercise to a greater extent at SL than in NH (post-exercise: 700 ± 325 versus 335 ± 238 pmol/L, mean ± SD, p = 0.044). Conversely, cortisol rose to a greater extent in NH (post-exercise: 734 ± 165 versus 344 ± 159 nmol/L, mean ± SD, p = 0.001). There were no differences in ACE activity. During the trek to HA, resting aldosterone and cortisol reduced with no change in ACE. CONCLUSIONS: Acute NH subdues the exercise-associated rise in aldosteroe but stimulates cortisol, whereas prolonged exposure at HA reduces both resting aldosterone and cortisol. As ACE activity was unchanged in both environments, this is not the mechanism underlying the fall in aldosterone.

The relationship between anxiety and acute mountain sickness.

INTRODUCTION: Whilst the link between physical factors and risk of high altitude (HA)-related illness and acute mountain sickness (AMS) have been extensively explored, the influence of psychological factors has been less well examined. In this study we aimed to investigate the relationship between 'anxiety and AMS risk during a progressive ascent to very HA. METHODS: Eighty health adults were assessed at baseline (848m) and over 9 consecutive altitudes during a progressive trek to 5140m. HA-related symptoms (Lake Louise [LLS] and AMS-C Scores) and state anxiety (State-Trait-Anxiety-Score [STAI Y-1]) were examined at each altitude with trait anxiety (STAI Y-2) at baseline. RESULTS: The average age was 32.1 ± 8.3 years (67.5% men). STAI Y-1 scores fell from 848m to 3619m, before increasing to above baseline scores (848m) at ≥4072m (p = 0.01). STAI Y-1 scores correlated with LLS (r = 0.31; 0.24-0.3; P<0.0001) and AMS-C Scores (r = 0.29; 0.22-0.35; P<0.0001). There was significant main effect for sex (higher STAI Y-1 scores in women) and altitude with no sex-x-altitude interaction on STAI Y-1 Scores. Independent predictors of significant state anxiety included female sex, lower age, higher heart rate and increasing LLS and AMS-C scores (p<0.0001). A total of 38/80 subjects (47.5%) developed AMS which was mild in 20 (25%) and severe in 18 (22.5%). Baseline STAI Y-2 scores were an independent predictor of future severe AMS (B = 1.13; 1.009-1.28; p = 0.04; r2 = 0.23) and STAI Y-1 scores at HA independently predicted AMS and its severity. CONCLUSION: Trait anxiety at low altitude was an independent predictor of future severe AMS development at HA. State anxiety at HA was independently associated with AMS and its severity.

High Altitude Affects Nocturnal Non-linear Heart Rate Variability: PATCH-HA Study.

Background: High altitude (HA) exposure can lead to changes in resting heart rate variability (HRV), which may be linked to acute mountain sickness (AMS) development. Compared with traditional HRV measures, non-linear HRV appears to offer incremental and prognostic data, yet its utility and relationship to AMS have been barely examined at HA. This study sought to examine this relationship at terrestrial HA. Methods: Sixteen healthy British military servicemen were studied at baseline (800 m, first night) and over eight consecutive nights, at a sleeping altitude of up to 3600 m. A disposable cardiac patch monitor was used, to record the nocturnal cardiac inter-beat interval data, over 1 h (0200-0300 h), for offline HRV assessment. Non-linear HRV measures included Sample entropy (SampEn), the short (α1, 4-12 beats) and long-term (α2, 13-64 beats) detrend fluctuation analysis slope and the correlation dimension (D2). The maximal rating of perceived exertion (RPE), during daily exercise, was assessed using the Borg 6-20 RPE scale. Results: All subjects completed the HA exposure. The average age of included subjects was 31.4 ± 8.1 years. HA led to a significant fall in SpO2 and increase in heart rate, LLS and RPE. There were no significant changes in the ECG-derived respiratory rate or in any of the time domain measures of HRV during sleep. The only notable changes in frequency domain measures of HRV were an increase in LF and fall in HFnu power at the highest altitude. Conversely, SampEn, SD1/SD2 and D2 all fell, whereas α1 and α2 increased (p < 0.05). RPE inversely correlated with SD1/SD2 (r = -0.31; p = 0.002), SampEn (r = -0.22; p = 0.03), HFnu (r = -0.27; p = 0.007) and positively correlated with LF (r = 0.24; p = 0.02), LF/HF (r = 0.24; p = 0.02), α1 (r = 0.32; p = 0.002) and α2 (r = 0.21; p = 0.04). AMS occurred in 7/16 subjects (43.8%) and was very mild in 85.7% of cases. HRV failed to predict AMS. Conclusion: Non-linear HRV is more sensitive to the effects of HA than time and frequency domain indices. HA leads to a compensatory decrease in nocturnal HRV and complexity, which is influenced by the RPE measured at the end of the previous day. HRV failed to predict AMS development.

Continuous Glucose Monitoring at High Altitude-Effects on Glucose Homeostasis.

PURPOSE: Exposure to high altitude has been shown to enhance both glucose and lipid utilization depending on experimental protocol. In addition, high and low blood glucose levels have been reported at high altitude. We hypothesized that gradual ascent to high altitude results in changes in glucose levels in healthy young adults. METHODS: Twenty-five adult volunteers, split into two teams, took part in the British Services Dhaulagiri Medical Research Expedition completing 14 d of trekking around the Dhaulagiri circuit in Nepal reaching a peak altitude of 5300 m on day 11 of the trek. Participants wore blinded continuous glucose monitors (CGM) throughout. Blood samples for C-peptide, proinsulin, and triacylglycerides were taken at sea level (United Kingdom) and in acclimatization camps at 3600, 4650, and 5120 m. Energy intake was determined from food diaries. RESULTS: There was no difference in time spent in hypoglycemia stratified by altitude. Nocturnal CGM readings (2200-0600 h) were chosen to reduce the short-term effect of physical activity and food intake and showed a significant (P < 0.0001) increase at 3600 m (5.53 ± 0.22 mmol·L), 4650 m (4.77 ± 0.30 mmol·L), and 5120 m (4.78 ± 0.24 mmol·L) compared with baseline altitude 1100 m (vs 4.61 ± 0.25 mmol·L). Energy intake did not differ by altitude. Insulin resistance and beta-cell function, calculated by homeostatic model assessment, were reduced at 3600 m compared with sea level. CONCLUSIONS: We observed a significant increase in nocturnal CGM glucose at 3600 m and greater despite gradual ascent from 1100 m. Taken with the changes in insulin resistance and beta-cell function, it is possible that the stress response to high altitude dominates exercise-enhanced insulin sensitivity, resulting in relative hyperglycemia.

Changes in balance and joint position sense during a 12-day high altitude trek: The British Services Dhaulagiri medical research expedition.

Postural control and joint position sense are essential for safely undertaking leisure and professional activities, particularly at high altitude. We tested whether exposure to a 12-day trek with a gradual ascent to high altitude impairs postural control and joint position sense. This was a repeated measures observational study of 12 military service personnel (28±4 years). Postural control (sway velocity measured by a portable force platform) during standing balance, a Sharpened Romberg Test and knee joint position sense were measured, in England (113m elevation) and at 3 research camps (3619m, 4600m and 5140m) on a 12-day high altitude trek in the Dhaulagiri region of Nepal. Pulse oximetry, and Lake Louise scores were also recorded on the morning and evening of each trek day. Data were compared between altitudes and relationships between pulse oximetry, Lake Louise score, and sway velocity were explored. Total sway velocity during standing balance with eyes open (p = 0.003, d = 1.9) and during Sharpened Romberg test with eyes open (p = 0.007, d = 1.6) was significantly greater at altitudes of 3619m and 5140m when compared with sea level. Anterior-posterior sway velocity during standing balance with eyes open was also significantly greater at altitudes of 3619m and 5140m when compared with sea level (p = 0.001, d = 1.9). Knee joint position sense was not altered at higher altitudes. There were no significant correlations between Lake Louise scores, pulse oximetry and postural sway. Despite a gradual ascent profile, exposure to 3619 m was associated with impairments in postural control without impairment in knee joint position sense. Importantly, these impairments did not worsen at higher altitudes of 4600 m or 5140 m. The present findings should be considered during future trekking expeditions when developing training strategies targeted to manage impairments in postural control that occur with increasing altitude.

The role of neutrophil gelatinase-associated lipocalin (NGAL) in the detection of blast lung injury in a military population.

PURPOSE: To study the relationship between serum neutrophil gelatinase-associated lipocalin (NGAL) and military blast and gunshot wound (GSW) to establish whether potential exists for NGAL as a biomarker for blast lung injury (BLI). METHOD: Patients from the intensive care unit (ICU) of the Role 3 Medical Treatment Facility at Camp Bastion, Helmand Province, Afghanistan were studied over a five month period commencing in 2012. Age, mechanism, trauma injury severity score (TRISS) and serum NGAL were recorded on ICU admission (NGAL1). Serum NGAL (NGAL2) and PaO2/FiO2 ratio (P/F ratio2) were recorded at 24h. RESULTS: 33 patients were injured by blast and 23 by GSW. NGAL1 inversely correlated with TRISS (p=0.020), pH (p=0.002) and P/F ratio 2 (p=0.009) overall. When data was stratified into blast and GSW, NGAL1 also inversely correlated with P/F ratio 2 in the blast injured group (p=0.008) but not GSW group (p=0.27). CONCLUSION: Raised NGAL correlated with increased severity of injury (worse survival probability i.e. TRISS and low pH) in both patient groups. There was an inverse correlation between admission NGAL and a marker of blast lung injury (low P/F ratio) at 24h in blast injured group but not GSW group that warrants further investigation.

Smartphone-Enabled Heart Rate Variability and Acute Mountain Sickness.

INTRODUCTION: The autonomic system and sympathetic activation appears integral in the pathogenesis of acute mountain sickness (AMS) at high altitude (HA), yet a link between heart rate variability (HRV) and AMS has not been convincingly shown. In this study we investigated the utility of the smartphone-derived HRV score to predict and diagnose AMS at HA. METHODS: Twenty-one healthy adults were investigated at baseline at 1400 m and over 10 days during a trek to 5140 m. HRV was recorded using the ithlete HRV device. RESULTS: Acute mountain sickness occurred in 11 subjects (52.4%) at >2650 m. HRV inversely correlated with AMS Scores (r = -0.26; 95% CI, -0.38 to -0.13: P < 0.001). HRV significantly fell at 3700, 4100, and 5140 m versus low altitude. HRV scores were lower in those with both mild (69.7 ± 14.0) and severe AMS (67.1 ± 13.1) versus those without AMS (77.5 ± 13.1; effect size n = 0.043: P = 0.007). The HRV score was weakly predictive of severe AMS (AUC 0.74; 95% CI, 0.58-0.89: P = 0.006). The change (delta) in the HRV Score (compared with baseline at 1400 m) was a moderate diagnostic marker of severe AMS (AUC 0.80; 95% CI, 0.70-0.90; P = 0.0004). A fall in the HRV score of >5 had a sensitivity of 83% and specificity of 60% to identify severe AMS (likelihood ratio 1.9). Baseline HRV at 1400 m was not predictive of either AMS at higher altitudes. CONCLUSIONS: The ithlete HRV score can be used to help in the identification of severe AMS; however, a baseline score is not predictive of future AMS development at HA.

The British Services Dhaulagiri Medical Research Expedition 2016: a unique military and civilian research collaboration.

INTRODUCTION: High-altitude environments lead to a significant physiological challenge and disease processes which can be life threatening; operational effectiveness at high altitude can be severely compromised. The UK military research is investigating ways of mitigating the physiological effects of high altitude. METHODS: The British Service Dhaulagiri Research Expedition took place from March to May 2016, and the military personnel were invited to consent to a variety of study protocols investigating adaptation to high altitudes and diagnosis of high-altitude illness. The studies took place in remote and austere environments at altitudes of up to 7500 m. RESULTS: This paper gives an overview of the individual research protocols investigated, the execution of the expedition and the challenges involved. 129 servicemen and women were involved at altitudes of up to 7500 m; 8 research protocols were investigated. CONCLUSIONS: The outputs from these studies will help to individualise the acclimatisation process and inform strategies for pre-acclimatisation should troops ever need to deploy at high altitude at short notice.

Working Memory Capacity and Surgical Performance While Exposed to Mild Hypoxic Hypoxemia.

INTRODUCTION: Medical Emergency Response Team (MERT) helicopters fly at altitudes of 3000 m in Afghanistan (9843 ft). Civilian hospitals and disaster-relief surgical teams may have to operate at such altitudes or even higher. Mild hypoxia has been seen to affect the performance of novel tasks at flight levels as low as 5000 ft. Aeromedical teams frequently work in unpressurized environments; it is important to understand the implications of this mild hypoxia and investigate whether supplementary oxygen systems are required for some or all of the team members. METHODS: Ten UK orthopedic surgeons were recruited and in a double blind randomized experimental protocol, were acutely exposed for 45 min to normobaric hypoxia [fraction of inspired oxygen (FIo2) ∼14.1%, equivalent to 3000 m (10,000 ft)] or normobaric normoxia (sea-level). Basic physiological parameters were recorded. Subjects completed validated tests of verbal working memory capacity (VWMC) and also applied an orthopedic external fixator (Hoffmann® 3, Stryker, UK) to a plastic tibia under test conditions. RESULTS: Significant hypoxia was induced with the reduction of FIo2 to ∼14.1% (Spo2 87% vs. 98%). No effect of hypoxia on VWMC was observed. The pin-divergence score (a measure of frame asymmetry) was significantly greater in hypoxic conditions (4.6 mm) compared to sea level (3.0 mm); there was no significant difference in the penetrance depth (16.9 vs. 17.2 mm). One hypoxic frame would have failed early. DISCUSSION: We believe that surgery at an altitude of 3000 m, when unacclimated individuals are acutely exposed to atmospheric hypoxia for 45 min, can likely take place without supplemental oxygen use but further work is required.Parker PJ, Manley AJ, Shand R, O'Hara JP, Mellor A. Working memory capacity and surgical performance while exposed to mild hypoxic hypoxemia. Aerosp Med Hum Perform. 2017; 88(10):918-923.

Changes in appetite, energy intake, body composition, and circulating ghrelin constituents during an incremental trekking ascent to high altitude.

PURPOSE: Circulating acylated ghrelin concentrations are associated with altitude-induced anorexia in laboratory environments, but have never been measured at terrestrial altitude. This study examined time course changes in appetite, energy intake, body composition, and ghrelin constituents during a high-altitude trek. METHODS: Twelve participants [age: 28(4) years, BMI 23.0(2.1) kg m-2] completed a 14-day trek in the Himalayas. Energy intake, appetite perceptions, body composition, and circulating acylated, des-acylated, and total ghrelin concentrations were assessed at baseline (113 m, 12 days prior to departure) and at three fixed research camps during the trek (3619 m, day 7; 4600 m, day 10; 5140 m, day 12). RESULTS: Relative to baseline, energy intake was lower at 3619 m (P = 0.038) and 5140 m (P = 0.016) and tended to be lower at 4600 m (P = 0.056). Appetite perceptions were lower at 5140 m (P = 0.027) compared with baseline. Acylated ghrelin concentrations were lower at 3619 m (P = 0.046) and 4600 m (P = 0.038), and tended to be lower at 5140 m (P = 0.070), compared with baseline. Des-acylated ghrelin concentrations did not significantly change during the trek (P = 0.177). Total ghrelin concentrations decreased from baseline to 4600 m (P = 0.045). Skinfold thickness was lower at all points during the trek compared with baseline (P ≤ 0.001) and calf girth decreased incrementally during the trek (P = 0.010). CONCLUSIONS: Changes in plasma acylated and total ghrelin concentrations may contribute to the suppression of appetite and energy intake at altitude, but differences in the time course of these responses suggest that additional factors are also involved. Interventions are required to maintain appetite and energy balance during trekking at terrestrial altitudes.

The Effect of Sex on Heart Rate Variability at High Altitude.

There is evidence suggesting that high altitude (HA) exposure leads to a fall in heart rate variability (HRV) that is linked to the development of acute mountain sickness (AMS). The effects of sex on changes in HRV at HA and its relationship to AMS are unknown. METHODS: HRV (5-min single-lead ECG) was measured in 63 healthy adults (41 men and 22 women) 18-56 yr of age at sea level (SL) and during a HA trek at 3619, 4600, and 5140 m, respectively. The main effects of altitude (SL, 3619 m, 4600 m, and 5140 m) and sex (men vs women) and their potential interaction were assessed using a factorial repeated-measures ANOVA. Logistic regression analyses were performed to assess the ability of HRV to predict AMS. RESULTS: Men and women were of similar age (31.2 ± 9.3 vs 31.7 ± 7.5 yr), ethnicity, and body and mass index. There was main effect for altitude on heart rate, SD of normal-to-normal (NN) intervals (SDNN), root mean square of successive differences (RMSSD), number of pairs of successive NN differing by >50 ms (NN50), NN50/total number of NN, very low-frequency power, low-frequency (LF) power, high-frequency (HF) power, and total power (TP). The most consistent effect on post hoc analysis was reduction in these HRV measures between 3619 and 5140 m at HA. Heart rate was significantly lower and SDNN, RMSSD, LF power, HF power, and TP were higher in men compared with women at HA. There was no interaction between sex and altitude for any of the HRV indices measured. HRV was not predictive of AMS development. CONCLUSIONS: Increasing HA leads to a reduction in HRV. Significant differences between men and women emerge at HA. HRV was not predictive of AMS.

Markers of physiological stress during exercise under conditions of normoxia, normobaric hypoxia, hypobaric hypoxia, and genuine high altitude.

PURPOSE: To investigate whether there is a differential response at rest and following exercise to conditions of genuine high altitude (GHA), normobaric hypoxia (NH), hypobaric hypoxia (HH), and normobaric normoxia (NN). METHOD: Markers of sympathoadrenal and adrenocortical function [plasma normetanephrine (PNORMET), metanephrine (PMET), cortisol], myocardial injury [highly sensitive cardiac troponin T (hscTnT)], and function [N-terminal brain natriuretic peptide (NT-proBNP)] were evaluated at rest and with exercise under NN, at 3375 m in the Alps (GHA) and at equivalent simulated altitude under NH and HH. Participants cycled for 2 h [15-min warm-up, 105 min at 55% Wmax (maximal workload)] with venous blood samples taken prior (T0), immediately following (T120) and 2-h post-exercise (T240). RESULTS: Exercise in the three hypoxic environments produced a similar pattern of response with the only difference between environments being in relation to PNORMET. Exercise in NN only induced a rise in PNORMET and PMET. CONCLUSION: Biochemical markers that reflect sympathoadrenal, adrenocortical, and myocardial responses to physiological stress demonstrate significant differences in the response to exercise under conditions of normoxia versus hypoxia, while NH and HH appear to induce broadly similar responses to GHA and may, therefore, be reasonable surrogates.

Manubrium-limited ministernotomy versus conventional sternotomy for aortic valve replacement (MAVRIC): study protocol for a randomised controlled trial.

BACKGROUND: Aortic valve replacement is one of the most common cardiac surgical procedures performed worldwide. Conventional aortic valve replacement surgery is performed via a median sternotomy; the sternum is divided completely from the sternal notch to the xiphisternum. Minimally invasive aortic valve replacement, using a new technique called manubrium-limited ministernotomy, divides only the manubrium from the sternal notch to 1 cm below the manubrio-sternal junction. More than one third of patients undergoing conventional sternotomy develop clinically significant bleeding requiring post-operative red blood cell transfusion. Case series data suggest a potentially clinically significant difference in red blood cell transfusion requirements between the two techniques. Given the implications for National Health Service resources and patient outcomes, a definitive trial is needed. METHODS/DESIGN: This is a single-centre, single-blind, randomised controlled trial comparing aortic valve replacement surgery using manubrium-limited ministernotomy (intervention) and conventional median sternotomy (usual care). Two hundred and seventy patients will be randomised in a 1:1 ratio between the intervention and control arms, stratified by baseline logistic EuroSCORE and haemoglobin value. Patients will be followed for 12 weeks from discharge following their index operation. The primary outcome is the proportion of patients who receive a red blood cell transfusion post-operatively within 7 days of surgery. Secondary outcomes include red blood cell and blood product transfusions, blood loss, re-operation rates, sternal wound pain, quality of life, markers of inflammatory response, hospital discharge, health care utilisation, cost and cost effectiveness and adverse events. DISCUSSION: This is the first trial to examine aortic valve replacement via manubrium-limited ministernotomy versus conventional sternotomy when comparing red blood cell transfusion rates following surgery. Surgical trials present significant challenges; strengths of this trial include a rigorous research design, standardised surgery performed by experienced consultant cardiothoracic surgeons, an agreed anaesthetic regimen, patient blinding and consultant-led patient recruitment. The MAVRIC trial will demonstrate that complex surgical trials can be delivered to exemplary standards and provide the community with the knowledge required to inform future care for patients requiring aortic valve replacement surgery. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) ISRCTN29567910 . Registered on 3 February 2014.