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

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

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

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

Re-designing the pathway to surgery: better care and added value

The case for radical pathway re-design before surgery is in part driven by healthcare system pressures which are in turn the result of continuously rising demand in the face of tightly constrained resources. Such circumstances tend to drive revolutionary, rather than incremental, change. The current approach to preoperative assessment, that typically occurs in the weeks leading up to surgery, but is all too often only a few days before surgery, results in a lost opportunity for perioperative physicians to improve patient care. Re-engineering this process based on a patient-focused, pathway-driven vision of perioperative medicine offers a means of exploiting this opportunity. This review explores drivers for change, the opportunity offered by pathway re-design, and suggests a variety of strategies to add value in the preoperative pathway, each of which is facilitated by early engagement between perioperative physician and patient: collaborative decision-making, collaborative behavioural change, targeted comorbidity management as well as expectation management and psychological preparation for surgery including surgery schools

Stroke at high altitude diagnosed in the field using portable ultrasound

A tool that can differentiate ischemic stroke from other neurological conditions (eg, hemorrhagic stroke, high-altitude cerebral edema) in the field could enable more rapid thrombolysis when appropriate. The resources (eg, an MRI or CT scanner) to investigate stroke at high altitude may be limited, and hence a portable tool would be of benefit. Such a tool may also be of benefit in emergency departments when CT scanning is not available. We report a case of a 49-year-old man who, while climbing at 5900 m, suffered a left middle cerebral infarct. The clinical diagnosis was supported using 2D Power Doppler. The patient received aspirin and continuous transcranial Doppler was used for its potential therapeutic effects for 12 hours. The patient was then evacuated to a hospital in Kathmandu over the next 48 hours. This case report suggests that portable ultrasound could be used in the prehospital arena to enable early diagnosis of thrombotic stroke

The role of nitrogen oxides in human adaptation to hypoxia

Lowland residents adapt to the reduced oxygen availability at high altitude through a process known as acclimatisation, but the molecular changes underpinning these functional alterations are not well understood. Using an integrated biochemical/whole-body physiology approach we here show that plasma biomarkers of NO production (nitrite, nitrate) and activity (cGMP) are elevated on acclimatisation to high altitude while S-nitrosothiols are initially consumed, suggesting multiple nitrogen oxides contribute to improve hypoxia tolerance by enhancing NO availability. Unexpectedly, oxygen cost of exercise and mechanical efficiency remain unchanged with ascent while microvascular blood flow correlates inversely with nitrite. Our results suggest that NO is an integral part of the human physiological response to hypoxia. These findings may be of relevance not only to healthy subjects exposed to high altitude but also to patients in whom oxygen availability is limited through disease affecting the heart, lung or vasculature, and to the field of developmental biology

Stroke at high altitude diagnosed in the field using portable ultrasound

A tool that can differentiate ischemic stroke from other neurological conditions (eg, hemorrhagic stroke, high-altitude cerebral edema) in the field could enable more rapid thrombolysis when appropriate. The resources (eg, an MRI or CT scanner) to investigate stroke at high altitude may be limited, and hence a portable tool would be of benefit. Such a tool may also be of benefit in emergency departments when CT scanning is not available. We report a case of a 49-year-old man who, while climbing at 5900 m, suffered a left middle cerebral infarct. The clinical diagnosis was supported using 2D Power Doppler. The patient received aspirin and continuous transcranial Doppler was used for its potential therapeutic effects for 12 hours. The patient was then evacuated to a hospital in Kathmandu over the next 48 hours. This case report suggests that portable ultrasound could be used in the prehospital arena to enable early diagnosis of thrombotic stroke

Current landscape of nutrition within prehabilitation oncology research: A scoping review.

Background: Prehabilitation aims to improve functional capacity prior to cancer treatment to achieve better psychosocial andclinical outcomes. Prehabilitation interventions vary considerably in design and delivery. In order to identify gaps in knowledgeand facilitate the design of future studies, we undertook a scoping review of prehabilitation studies: to map the range of work onprehabilitation being carried out in any cancer type and with a particular focus on diet or nutrition interventions.Objectives: Firstly, to describe the type of prehabilitation programs currently being conducted. Secondly, to describe the extent towhich prehabilitation studies involved aspects of nutrition, including assessment, interventions, implementation, and outcomes.Eligibility criteria: Any study of quantitative or qualitative design that employed a formal prehabilitation program before cancertreatment (“prehabilitation” listed in keywords, title, or abstract).Sources of evidence: Search was conducted in July 2020 using MEDLINE, PubMed, EMBASE, EMCARE, CINAHL, and AMED.Results: 550 unique articles were identified: 110 studies met inclusion criteria of a formal prehabilitation study in oncology.Prehabilitation studies were mostly cohort studies (41%) or randomized-controlled trials (38%) of multi-modal (49%) orexercise-only (44%) interventions that were applied before surgery (94%). Nutrition assessment was inconsistently applied acrossthese studies, and often conducted without validated tools (48%). Of the 110 studies, 37 (34%) included a nutrition interventioncomponent. Only half of these studies stated the goal for the nutrition component of their prehabilitation program; only 43%referenced accepted nutrition guidelines in surgery or oncology. Nutrition interventions largely consisted of counselling anddietary supplementation. The nutrition intervention was indiscernible in 24% of studies. Two-thirds of studies did not monitor thenutrition intervention nor evaluate nutrition outcomes.Conclusion: Prehabilitation literature lacks standardized and validated nutritional assessment, is frequently conducted withoutemploying evidence-based nutrition interventions and is typically implemented without monitoring the nutrition intervention orevaluating the intervention’s contribution to outcomes. We suggest the development of a core outcome set would improve thequality of the studies, enable pooling of evidence and address some of the research gaps identified