International consensus is needed on a core outcome set to advance the evidence of best practice in cancer prehabilitation services and research.

Prehabilitation aims to optimise patients' physical and psychological status before treatment. The types of outcomes measured to assess the impact of prehabilitation interventions vary across clinical research and service evaluation, limiting the ability to compare between studies and services and to pool data. An international workshop involving academic and clinical experts in cancer prehabilitation was convened in May 2022 at Sheffield Hallam University's Advanced Wellbeing Research Centre, England. The workshop substantiated calls for a core outcome set to advance knowledge and understanding of best practice in cancer prehabilitation and to develop national and international databases to assess outcomes at a population level.

Perioperative hyperoxia and myocardial injury after surgery: a randomized controlled trial.

BACKGROUND: The World Health Organization recommends hyperoxia (80% fraction of inspired oxygen, FiO2) during and for 2-6 hours following surgery to reduce surgical site infection (SSI). However, some studies suggest increased cardiovascular complications with such a high perioperative FiO2. The goal of our study was to compare the appearance of cardiovascular complications in elective adult colorectal surgery comparing the use of FiO2>0.8 versus conventional therapy (FiO2<0.4). METHODS: We performed a randomized controlled trial in intubated patients undergoing elective major colorectal surgery. Patients were randomly assigned to receive perioperative FiO2>0.8 or FiO2<0.4. The primary outcome, expressed as Odds Ratio (OR) ±95% Confidence Interval (95%CI), was the incidence of MINS (myocardial injury after noncardiac surgery evaluated for the first 4 postoperative days). Secondary outcomes included MACCE (major adverse cardiovascular and cerebral events) up to 30 postoperative days, SSI, other postoperative complications (according to Clavien-Dindo classification) and length of stay. RESULTS: We included in the final analyses 403 patients. Comparing the FiO2>0.8 and FiO2<0.4 groups, there was no difference in the appearance of MINS (6.0% vs. 10.4%; OR 0.55; 95% CI: 0.26-1.14; P=0.945). There were no differences between the groups for important secondary outcomes including MACCE to 30 days, SSI, postoperative complications or length of stay. CONCLUSIONS: Perioperative hyperoxia therapy (FiO2>0.8) with the aim of decreasing SSI did not increase cardiovascular complications after elective colorectal surgery in a general population.

The Perioperative Quality Improvement Programme (PQIP patient study): protocol for a UK multicentre, prospective cohort study to measure quality of care and outcomes after major surgery.

INTRODUCTION: Major surgery accounts for a substantial proportion of health service activity, due not only to the primary procedure, but the longer-term health implications of poor short-term outcome. Data from small studies or from outside the UK indicate that rates of complications and failure to rescue vary between hospitals, as does compliance with best practice processes. Within the UK, there is currently no system for monitoring postoperative complications (other than short-term mortality) in major non-cardiac surgery. Further, there is variation between national audit programmes, in the emphasis placed on quality assurance versus quality improvement, and therefore the principles of measurement and reporting which are used to design such programmes. METHODS AND ANALYSIS: The PQIP patient study is a multi-centre prospective cohort study which recruits patients undergoing major surgery. Patient provide informed consent and contribute baseline and outcome data from their perspective using a suite of patient-reported outcome tools. Research and clinical staff complete data on patient risk factors and outcomes in-hospital, including two measures of complications. Longer-term outcome data are collected through patient feedback and linkage to national administrative datasets (mortality and readmissions). As well as providing a uniquely granular dataset for research, PQIP provides feedback to participating sites on their compliance with evidence-based processes and their patients' outcomes, with the aim of supporting local quality improvement. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Health Research Authority in the UK. Dissemination of interim findings (non-inferential) will form a part of the improvement methodology and will be provided to participating centres at regular intervals, including near-real time feedback of key process measures. Inferential analyses will be published in the peer-reviewed literature, supported by a comprehensive multi-modal communications strategy including to patients, policy makers and academic audiences as well as clinicians.

Association of Upper Gastrointestinal Surgery of Great Britain and Ireland (AUGIS)/Perioperative Quality Initiative (POQI) consensus statement on intraoperative and postoperative interventions to reduce pulmonary complications after oesophagectomy.

BACKGROUND: Pulmonary complications are the most common morbidity after oesophagectomy, contributing to mortality and prolonged postoperative recovery, and have a negative impact on health-related quality of life. A variety of single or bundled interventions in the perioperative setting have been developed to reduce the incidence of pulmonary complications. Significant variation in practice exists across the UK. The aim of this modified Delphi consensus was to deliver clear evidence-based consensus recommendations regarding intraoperative and postoperative care that may reduce pulmonary complications after oesophagectomy. METHODS: With input from a multidisciplinary group of 23 experts in the perioperative management of patients undergoing surgery for oesophageal cancer, a modified Delphi method was employed. Following an initial systematic review of relevant literature, a range of anaesthetic, surgical, and postoperative care interventions were identified. These were then discussed during a two-part virtual conference. Recommendation statements were drafted, refined, and agreed by all attendees. The level of evidence supporting each statement was considered. RESULTS: Consensus was reached on 12 statements on topics including operative approach, pyloric drainage strategies, intraoperative fluid and ventilation strategies, perioperative analgesia, postoperative feeding plans, and physiotherapy interventions. Seven additional questions concerning the perioperative management of patients undergoing oesophagectomy were highlighted to guide future research. CONCLUSION: Clear consensus recommendations regarding intraoperative and postoperative interventions that may reduce pulmonary complications after oesophagectomy are presented.

Comparison of time taken to obtain an arterial blood gas result at the bedside using the ProximaTM point of care machine vs. a standard remote arterial blood gas analyser: A randomized controlled trial.

Introduction: The ProximaTM point of care (POC) device enables arterial blood gas (ABG) samples to be analysed without the nurse leaving the patient. The benefits of this for work efficiency have not been evaluated. Methods: We compared the time taken to obtain an ABG result using ProximaTM versus a standard ABG sampling system. Twenty patients were randomized to ABG sampling using ProximaTM, or a standard ABG system. Nurses were observed performing all ABG sampling episodes for a minimum of 24 hours and no more than 72 hours. Results: The mean time taken to obtain a result using ProximaTM was 4:56 (SD = 1:40) minutes compared to 6:31 (SD = 1:53) minutes for the standard ABG technique (p < 0.001). Mean time away from the patient's bedside was 3.07 (SD = 1:17) minutes using the standard system and 0 minutes using ProximaTM (p < 0.001). Conclusions: Reduced time for blood gas sampling and avoidance of time away from patients may have significant patient safety and resource management implications, but the clinical and financial significance were not evaluated.

Compassionate use of Pulmonary Vasodilators in Acute Severe Hypoxic Respiratory Failure due to COVID-19.

BACKGROUND: There have been over 200 million cases and 4.4 million deaths from COVID-19 worldwide. Despite the lack of robust evidence one potential treatment for COVID-19 associated severe hypoxaemia is inhaled pulmonary vasodilator (IPVD) therapy, using either nitric oxide (iNO) or prostaglandins. We describe the implementation of, and outcomes from, a protocol using IPVDs in a cohort of patients with severe COVID-19 associated respiratory failure receiving maximal conventional support. METHODS: Prospectively collected data from adult patients with SARS-CoV-2 admitted to the intensive care unit (ICU) at a large teaching hospital were analysed for the period 14th March 2020 - 11th February 2021. An IPVD was considered if the PaO2/FiO2 (PF) ratio was less than 13.3kPa despite maximal conventional therapy. Nitric oxide was commenced at 20ppm and titrated to response. If oxygenation improved Iloprost nebulisers were commenced and iNO weaned. The primary outcome was percentage changes in PF ratio and Alveolar-arterial (A-a) gradient. RESULTS: Fifty-nine patients received IPVD therapy during the study period. The median PF ratio before IPVD therapy was commenced was 11.33kPa (9.93-12.91). Patients receiving an IPVD had a lower PF ratio (14.37 vs. 16.37kPa, p = 0.002) and higher APACHE-II score (17 vs. 13, p = 0.028) at ICU admission. At 72 hours after initiating an IPVD the median improvement in PF ratio was 33.9% (-4.3-84.1). At 72 hours changes in PF ratio (70.8 vs. -4.1%, p < 0.001) and reduction in A-a gradient (44.7 vs. 14.8%, p < 0.001) differed significantly between survivors (n = 33) and non-survivors (n = 26). CONCLUSIONS: The response to IPVDs in patients with COVID-19 associated acute hypoxic respiratory failure differed significantly between survivors and non-survivors. Both iNO and prostaglandins may offer therapeutic options for patients with severe refractory hypoxaemia due to COVID-19. The use of inhaled prostaglandins, and iNO where feasible, should be studied in adequately powered prospective randomised trials.

COVID-19: UK frontline intensivists' emerging learning.

The Intensive Care Society held a webinar on 3 April 2020 at which representatives from 11 of the most COVID-19 experienced hospital trusts in England and Wales shared learning around five specific topic areas in an open forum. This paper summarises the emerging learning and practice shared by those frontline clinicians.

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.

Replicating measurements of total hemoglobin mass (tHb-mass) within a single day: precision of measurement; feasibility and safety of using oxygen to expedite carbon monoxide clearance.

Hemoglobin concentration ([Hb]) is a function of total hemoglobin mass (tHb-mass) and plasma volume. [Hb] may fall by dilution due to plasma volume expansion and changes in the perioperative period may therefore correlate poorly with blood loss. A simple, reliable, repeatable way to measure plasma volume and tHb-mass would have substantial clinical utility. The "optimized carbon monoxide re-breathing method" (oCOR) meets these criteria. However, it is recommended that a minimum of 12 h (when breathing room air) is left between repeat measurements. Twenty-four subjects underwent 3 days of testing. Two oCOR tests were performed (T1 and T2), 3 h apart, with a different CO clearance method employed between tests aiming to keep the carboxyhemoglobin level below 10%. The primary aim was to ascertain whether tHb-mass testing could be safely repeated within 3 h if carboxyhemoglobin levels were actively reduced by breathing supplemental oxygen (PROCA ). Secondary aims were to compare two other clearance methods; moderate exercise (PROCB ), or a combination of the two (PROCC ). Finally, the reliability of the oCOR method was assessed. Mean (SD) tHb-mass was 807.9 ± (189.7 g) (for T1 on day 1). PROCA lowered the carboxyhemoglobin level from the end of T1 (mean 6.64%) to the start of T2 (mean 2.95%) by a mean absolute value of 3.69%. For PROCB and PROCC the mean absolute decreases in carboxyhemoglobin were 4.00% and 4.31%, respectively. The fall in carboxyhemoglobin between T1 and T2 was greatest in PROCC ; this was statistically significantly lower than that of PROCA (P = 0.0039) and PROCB (P = 0.0289). The test-retest reliability for the measurement of total hemoglobin mass was good with a mean typical error (TE) of 2.0%. The oCOR method is safe and can be repeated within 3 h when carbon monoxide is suitably cleared between tests. Using oxygen therapy alone adequately achieves this.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Nutrition Screening and Therapy Within a Surgical Enhanced Recovery Pathway.

Perioperative malnutrition has proven to be challenging to define, diagnose, and treat. Despite these challenges, it is well known that suboptimal nutritional status is a strong independent predictor of poor postoperative outcomes. Although perioperative caregivers consistently express recognition of the importance of nutrition screening and optimization in the perioperative period, implementation of evidence-based perioperative nutrition guidelines and pathways in the United States has been quite limited and needs to be addressed in surgery-focused recommendations. The second Perioperative Quality Initiative brought together a group of international experts with the objective of providing consensus recommendations on this important topic with the goal of (1) developing guidelines for screening of nutritional status to identify patients at risk for adverse outcomes due to malnutrition; (2) address optimal methods of providing nutritional support and optimizing nutrition status preoperatively; and (3) identifying when and how to optimize nutrition delivery in the postoperative period. Discussion led to strong recommendations for implementation of routine preoperative nutrition screening to identify patients in need of preoperative nutrition optimization. Postoperatively, nutrition delivery should be restarted immediately after surgery. The key role of oral nutrition supplements, enteral nutrition, and parenteral nutrition (implemented in that order) in most perioperative patients was advocated for with protein delivery being more important than total calorie delivery. Finally, the role of often-inadequate nutrition intake in the posthospital setting was discussed, and the role of postdischarge oral nutrition supplements was emphasized.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Patient-Reported Outcomes in an Enhanced Recovery Pathway.

Patient-reported outcomes (PROs) are measures of health status that come directly from the patient. PROs are an underutilized tool in the perioperative setting. Enhanced recovery pathways (ERPs) have primarily focused on traditional measures of health care quality such as complications and hospital length of stay. These measures do not capture postdischarge outcomes that are meaningful to patients such as function or freedom from disability. PROs can be used to facilitate shared decisions between patients and providers before surgery and establish benchmark recovery goals after surgery. PROs can also be utilized in quality improvement initiatives and clinical research studies. An expert panel, the Perioperative Quality Initiative (POQI) workgroup, conducted an extensive literature review to determine best practices for the incorporation of PROs in an ERP. This international group of experienced clinicians from North America and Europe met at Stony Brook, NY, on December 2-3, 2016, to review the evidence supporting the use of PROs in the context of surgical recovery. A modified Delphi method was used to capture the collective expertise of a diverse group to answer clinical questions. During 3 plenary sessions, the POQI PRO subgroup presented clinical questions based on a literature review, presented evidenced-based answers to those questions, and developed recommendations which represented a consensus opinion regarding the use of PROs in the context of an ERP. The POQI workgroup identified key criteria to evaluate patient-reported outcome measures (PROMs) for their incorporation in an ERP. The POQI workgroup agreed on the following recommendations: (1) PROMs in the perioperative setting should be collected in the framework of physical, mental, and social domains. (2) These data should be collected preoperatively at baseline, during the immediate postoperative time period, and after hospital discharge. (3) In the immediate postoperative setting, we recommend using the Quality of Recovery-15 score. After discharge at 30 and 90 days, we recommend the use of the World Health Organization Disability Assessment Scale 2.0, or a tailored use of the Patient-Reported Outcomes Measurement Information System. (4) Future study that consistently applies PROMs in an ERP will define the role these measures will have evaluating quality and guiding clinical care. Consensus guidelines regarding the incorporation of PRO measures in an ERP were created by the POQI workgroup. The inclusion of PROMs with traditional measures of health care quality after surgery provides an opportunity to improve clinical care.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Postoperative Gastrointestinal Dysfunction Within an Enhanced Recovery Pathway for Elective Colorectal Surgery.

The primary driver of length of stay after bowel surgery, particularly colorectal surgery, is the time to return of gastrointestinal (GI) function. Traditionally, delayed GI recovery was thought to be a routine and unavoidable consequence of surgery, but this has been shown to be false in the modern era owing to the proliferation of enhanced recovery protocols. However, impaired GI function is still common after colorectal surgery, and the current literature is ambiguous with regard to the definition of postoperative GI dysfunction (POGD), or what is typically referred to as ileus. This persistent ambiguity has impeded the ability to ascertain the true incidence of the condition and study it properly within a research setting. Furthermore, a rational and standardized approach to prevention and treatment of POGD is needed. The second Perioperative Quality Initiative brought together a group of international experts to review the published literature and provide consensus recommendations on this important topic with the goal to (1) develop a rational definition for POGD that can serve as a framework for clinical and research efforts; (2) critically review the evidence behind current prevention strategies and provide consensus recommendations; and (3) develop rational treatment strategies that take into account the wide spectrum of impaired GI function in the postoperative period.

Caudwell Xtreme Everest: A prospective study of the effects of environmental hypoxia on cognitive functioning.

BACKGROUND: The neuropsychological consequences of exposure to environmental hypobaric hypoxia (EHH) remain unclear. We thus investigated them in a large group of healthy volunteers who trekked to Mount Everest base camp (5,300 m). METHODS: A neuropsychological (NP) test battery assessing memory, language, attention, and executive function was administered to 198 participants (age 44.5±13.7 years; 60% male). These were studied at baseline (sea level), 3,500 m (Namche Bazaar), 5,300 m (Everest Base Camp) and on return to 1,300 m (Kathmandu) (attrition rate 23.7%). A comparable control group (n = 25; age 44.5±14.1 years; 60% male) for comparison with trekkers was tested at/or near sea level over an equivalent timeframe so as to account for learning effects associated with repeat testing. The Reliable Change Index (RCI) was used to calculate changes in cognition and neuropsychological function during and after exposure to EHH relative to controls. RESULTS: Overall, attention, verbal ability and executive function declined in those exposed to EHH when the performance of the control group was taken into account (RCI .05 to -.95) with decline persisting at descent. Memory and psychomotor function showed decline at highest ascent only (RCI -.08 to -.56). However, there was inter-individual variability in response: whilst NP performance declined in most, this improved in some trekkers. Cognitive decline was greater amongst older people (r = .42; p < .0001), but was otherwise not consistently associated with socio-demographic, mood, or physiological variables. CONCLUSIONS: After correcting for learning effects, attention, verbal abilities and executive functioning declined with exposure to EHH. There was considerable individual variability in the response of brain function to sustained hypoxia with some participants not showing any effects of hypoxia. This might have implications for those facing sustained hypoxia as a result of any disease.

Preparing the patient for surgery to improve outcomes.

The time between contemplation of surgery and the procedure offers a window of opportunity to optimize patients' nutritional, functional and psychological state prior to surgery. Traditionally, preoperative pathways have focused on the underlying disease process and 'fitness for surgery' with physical pre-assessment and risk counselling late in the pathway when little time is available to intervene. With an increasingly elderly and co-morbid surgical population, early physiological assessment and multidisciplinary collaborative decision-making is increasingly important. Multimodal prehabilitation programmes may improve surgical outcome, facilitating rapid recovery from surgery and limiting post-operative functional dependence. Patient education and engagement is important if compliance with behavioural change is to be achieved and maintained. To date, there has been evidence supporting preoperative exercise training, smoking cessation, reduction in alcohol intake, anaemia management and psychosocial support. Further research is needed to identify the most effective elements of these complex preoperative interventions, as well as their optimum timing and duration.

Cerebral hemodynamics at altitude: effects of hyperventilation and acclimatization on cerebral blood flow and oxygenation.

OBJECTIVE: Alterations in cerebral blood flow (CBF) and cerebral oxygenation are implicated in altitude-associated diseases. We assessed the dynamic changes in CBF and peripheral and cerebral oxygenation engendered by ascent to altitude with partial acclimatization and hyperventilation using a combination of near-infrared spectroscopy, transcranial Doppler ultrasound, and diffuse correlation spectroscopy. METHODS: Peripheral (Spo2) and cerebral (Scto2) oxygenation, end-tidal carbon dioxide (ETCO2), and cerebral hemodynamics were studied in 12 subjects using transcranial Doppler and diffuse correlation spectroscopy (DCS) at 75 m and then 2 days and 7 days after ascending to 4559 m above sea level. After obtaining baseline measurements, subjects hyperventilated to reduce baseline ETCO2 by 50%, and a further set of measurements were obtained. RESULTS: Cerebral oxygenation and peripheral oxygenation showed a divergent response, with cerebral oxygenation decreasing at day 2 and decreasing further at day 7 at altitude, whereas peripheral oxygenation decreased on day 2 before partially rebounding on day 7. Cerebral oxygenation decreased after hyperventilation at sea level (Scto2 from 68.8% to 63.5%; P<.001), increased after hyperventilation after 2 days at altitude (Scto2 from 65.6% to 69.9%; P=.001), and did not change after hyperventilation after 7 days at altitude (Scto2 from 62.2% to 63.3%; P=.35). CONCLUSIONS: An intensification of the normal cerebral hypocapnic vasoconstrictive response occurred after partial acclimatization in the setting of divergent peripheral and cerebral oxygenation. This may help explain why hyperventilation fails to improve cerebral oxygenation after partial acclimatization as it does after initial ascent. The use of DCS is feasible at altitude and provides a direct measure of CBF indices with high temporal resolution.

Changes in muscle proteomics in the course of the Caudwell Research Expedition to Mt. Everest.

This study employed differential proteomic and immunoassay techniques to elucidate the biochemical mechanisms utilized by human muscle (vastus lateralis) in response to high altitude hypoxia exposure. Two groups of subjects, participating in a medical research expedition (A, n = 5, 19 d at 5300 m altitude; B, n = 6, 66 d up to 8848 m) underwent a ≈ 30% drop of muscular creatine kinase and of glycolytic enzymes abundance. Protein abundance of most enzymes of the tricarboxylic acid cycle and oxidative phosphorylation was reduced both in A and, particularly, in B. Restriction of α-ketoglutarate toward succinyl-CoA resulted in increased prolyl hydroxylase 2 and glutamine synthetase. Both A and B were characterized by a reduction of elongation factor 2 alpha, controlling protein translation, and by an increase of heat shock cognate 71 kDa protein involved in chaperone-mediated autophagy. Increased protein levels of catalase and biliverdin reductase occurred in A alongside a decrement of voltage-dependent anion channels 1 and 2 and of myosin-binding protein C, suggesting damage to the sarcomeric structures. This study suggests that during acclimatization to hypobaric hypoxia the muscle behaves as a producer of substrates activating a metabolic reprogramming able to support anaplerotically the tricarboxylic acid cycle, to control protein translation, to prevent energy expenditure and to activate chaperone-mediated autophagy.

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

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).