Peri-operative care pathways: re-engineering care to achieve the 'triple aim'.

Elective surgical pathways offer a particular opportunity to plan radical change in the way care is delivered, based on patient need rather than provider convenience. Peri-operative pathway redesign enables improved patient experience of care (including quality and satisfaction), population/public health, and healthcare value (outcome per unit of currency). Among physicians with the skills to work within peri-operative medicine, anaesthetists are well positioned to lead the re-engineering of such pathways. Re-engineered pre-operative pathways open up opportunities for intervention before surgery including shared decision-making, comorbidity management and collaborative behavioural change. Individualised, risk-adapted, intra-operative interventions will drive more reliable and consistent care. Risk-adapted postoperative care, particularly around transitions of care, has a significant role in improving value through peri-operative medicine. Improved integration with primary care providers offers the potential for minimising errors around transitions of care before and after surgery, as well as maximising opportunities for population health interventions, including lifestyle modification (e.g. activity/exercise, smoking and/or alcohol cessation), pain management and sleep medicine. Systematic data collection focused on quality improvement is essential to drive continuous clinical improvement and will be enabled by technological development in predictive analytics, systems modelling and artificial intelligence.

Advance-care-planning and end-of-life discussions in the perioperative period: a review of healthcare professionals' knowledge, attitudes, and training.

Whilst the risk of dying after an operation in the UK is very small, the volume of surgery means that there are 20 000-25 000 deaths each year. For these patients and others who suffer major complications, critical illness often leads to a loss of capacity. If wishes are not discussed in advance, the patients may be excluded from meaningful involvement in decisions affecting their care. The preoperative period has been postulated as one where advance care planning could begin by engaging in voluntary conversations about an individual's wishes, priorities, and values should he/she loses capacity. There remain unanswered questions as to whether healthcare professionals are supportive of a move towards better engagement in such discussions with patients. Even if the reception to the idea is positive, it is clear that appropriate training and understanding will be required. The aims of this review were to describe the current knowledge and attitudes of healthcare professionals towards advance care planning in the perioperative setting, and to outline any educational programmes or training limitations that have been identified. Seven articles that met the inclusion criteria were identified. They indicate that healthcare professionals mostly have a positive view of advance care planning in the perioperative period, and there is little training or educational content available. Despite this, most healthcare professionals report feeling well equipped to have such discussions. Evidence was not found of advance care planning becoming a routine part of training or practice in the care of patients in the lead up to high-risk surgery.

The anion study: effect of different crystalloid solutions on acid base balance, physiology, and survival in a rodent model of acute isovolaemic haemodilution.

BACKGROUND: Commercially available crystalloid solutions used for volume replacement do not exactly match the balance of electrolytes found in plasma. Large volume administration may lead to electrolyte imbalance and potential harm. We hypothesised that haemodilution using solutions containing different anions would result in diverse biochemical effects, particularly on acid-base status, and different outcomes. METHODS: Anaesthetised, fluid-resuscitated, male Wistar rats underwent isovolaemic haemodilution by removal of 10% blood volume every 15 min, followed by replacement with one of three crystalloid solutions based on acetate, lactate, or chloride. Fluids were administered in a protocolised manner to achieve euvolaemia based on echocardiography-derived left ventrical volumetric measures. Removed blood was sampled for plasma ions, acid-base status, haemoglobin, and glucose. This cycle was repeated at 15-min intervals until death. The primary endpoint was change in plasma bicarbonate within each fluid group. Secondary endpoints included time to death and cardiac function. RESULTS: During haemodilution, chloride-treated rats showed significantly greater decreases in plasma bicarbonate and strong ion difference levels compared with acetate- and lactate-treated rats. Time to death, total volume of fluid administered: chloride group 56 (3) ml, lactate group 62 (3) ml, and acetate group 65 (3) ml; haemodynamic and tissue oxygenation changes were, however, similar between groups. CONCLUSIONS: With progressive haemodilution, resuscitation with a chloride-based solution induced more acidosis compared with lactate- and acetate-based solutions, but outcomes were similar. No short-term impact was seen from hyperchloraemia in this model.

A systematic review and consensus definitions for standardised end-points in perioperative medicine: pulmonary complications.

BACKGROUND: There is a need for robust, clearly defined, patient-relevant outcome measures for use in randomised trials in perioperative medicine. Our objective was to establish standard outcome measures for postoperative pulmonary complications research. METHODS: A systematic literature search was conducted using MEDLINE, Web of Science, SciELO, and the Korean Journal Database. Definitions were extracted from included manuscripts. We then conducted a three-stage Delphi consensus process to select the optimal outcome measures in terms of methodological quality and overall suitability for perioperative trials. RESULTS: From 2358 records, the full texts of 81 manuscripts were retrieved, of which 45 met the inclusion criteria. We identified three main categories of outcome measure specific to perioperative pulmonary outcomes: (i) composite outcome measures of multiple pulmonary outcomes (27 definitions); (ii) pneumonia (12 definitions); and (iii) respiratory failure (six definitions). These were rated by the group according to suitability for routine use. The majority of definitions were given a low score, and many were imprecise, difficult to apply consistently, or both, in large patient populations. A small number of highly rated definitions were identified as appropriate for widespread use. The group then recommended four outcome measures for future use, including one new definition. CONCLUSIONS: A large number of postoperative pulmonary outcome measures have been used, but most are poorly defined. Our four recommended outcome measures include a new definition of postoperative pulmonary complications, incorporating an assessment of severity. These definitions will meet the needs of most clinical effectiveness trials of treatments to improve postoperative pulmonary outcomes.

Effect of goal-directed haemodynamic therapy on postoperative complications in low-moderate risk surgical patients: a multicentre randomised controlled trial (FEDORA trial).

BACKGROUND: The aim of this study was to evaluate postoperative complications in patients having major elective surgery using oesophageal Doppler monitor-guided goal-directed haemodynamic therapy (GDHT), in which administration of fluids, inotropes, and vasopressors was guided by stroke volume, mean arterial pressure, and cardiac index. METHODS: The FEDORA trial was a prospective, multicentre, randomised, parallel-group, controlled patient- and observer-blind trial conducted in adults scheduled for major elective surgery. Randomization and allocation were carried out by a central computer system. In the control group, intraoperative fluids were given based on traditional principles. In the GDHT group, the intraoperative goals were to maintain a maximal stroke volume, with mean arterial pressure >70 mm Hg, and cardiac index ≥2.5 litres min-1 m-2. The primary outcome was percentage of patients with moderate or severe postoperative complications during the first 180 days after surgery. RESULTS: In total, 450 patients were randomized to the GDHT group (n=224) or control group (n=226). Data from 420 subjects were analysed. There were significantly fewer with complications in the GDHT group (8.6% vs 16.6%, P=0.018). There were also fewer complications (acute kidney disease, pulmonary oedema, respiratory distress syndrome, wound infections, etc.), and length of hospital stay was shorter in the GDHT group. There was no significant difference in mortality between groups. CONCLUSIONS: Oesophageal Doppler monitor-guided GDHT reduced postoperative complications and hospital length of stay in low-moderate risk patients undergoing intermediate risk surgery, with no difference in mortality at 180 days. CLINICAL TRIAL REGISTRATION: ISRCTN93543537.

Could patient-controlled thirst-driven fluid administration lead to more rapid rehydration than clinician-directed fluid management? An early feasibility study.

BACKGROUND: Fluid management is a major factor determining perioperative outcome, yet in reality, fluid administration practice is variable. Thirst however, is a highly sensitive and reliable indicator of fluid deficits. We explored the use of thirst sensation to trigger i.v. fluid boluses to guide individualized fluid management. METHODS: We performed a randomised double crossover trial on 16 healthy male volunteers, of mean age 31 yr and BMI 24.4 kg m-2. Twice, after administrations of oral furosemide (40 mg) and 12 h of oral fluid restriction, participants received a 4-h i.v. fluid infusion. In the experimental arm, participants pressed a trigger to relieve their thirst, administering a 200 ml bolus. In the control arm, i.v. fluid was infused following National Institute for Health and Clinical Excellence (NICE) guidelines at 1.25 ml kg-1 h-1 with a clinician delivered 500 ml i.v. bolus in response to clinical signs of dehydration. Plasma osmolality and urine specific gravity were measured before and after each infusion. RESULTS: More fluid was infused in response to thirst than by adherence to NICE guidelines, with a mean difference of 743 ml (P=0.0005). Thirst-driven fluid administration was fitted to an exponential function of time, plateauing after a mean half-life of 98.8 min. In the experimental arm there was a greater reduction in urine specific gravity and thirst score with mean differences 0.0053 g cm-3 (P=0.002) and 3.3 (P=0.003), respectively. Plasma osmolality demonstrated no fluid overload. CONCLUSIONS: A system delivering i.v. fluid in response to subjective thirst corrects fluid deficits in healthy participants. A clinical feasibility study will assess the potential use of this system in the perioperative setting. CLINICAL TRIAL REGISTRATION: NCT 03176043.

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.

Cohort study of preoperative blood pressure and risk of 30-day mortality after elective non-cardiac surgery.

BACKGROUND: Preoperative blood pressure (BP) thresholds associated with increased postoperative mortality remain unclear. We investigated the relationship between preoperative BP and 30-day mortality after elective non-cardiac surgery. METHODS: We performed a cohort study of primary care data from the UK Clinical Practice Research Datalink (2004-13). Parsimonious and fully adjusted multivariable logistic regression models, including restricted cubic splines for numerical systolic and diastolic BP, for 30-day mortality were constructed. The full model included 29 perioperative risk factors, including age, sex, comorbidities, medications, and surgical risk scale. Sensitivity analyses were conducted for age (>65 vs <65 years old) and the timing of BP measurement. RESULTS: A total of 251 567 adults were included, with 589 (0.23%) deaths within 30 days of surgery. After adjustment for all risk factors, preoperative low BP was consistently associated with statistically significant increases in the odds ratio (OR) of postoperative mortality. Statistically significant risk thresholds started at a preoperative systolic pressure of 119 mm Hg (adjusted OR 1.02 [95% confidence interval (CI) 1.01-1.02]) compared with the reference (120 mm Hg) and diastolic pressure of 63 mm Hg [OR 1.24 (95% CI 1.03-1.49)] compared with the reference (80 mm Hg). As BP decreased, the OR of mortality risk increased. Subgroup analysis demonstrated that the risk associated with low BP was confined to the elderly. Adjusted analyses identified that diastolic hypertension was associated with increased postoperative mortality in the whole cohort. CONCLUSIONS: In this large observational study we identified a significant dose-dependent association between low preoperative BP values and increased postoperative mortality in the elderly. In the whole population, elevated diastolic, not systolic, BP was associated with increased mortality.

The future of UK healthcare: problems and potential solutions to a system in crisis.

The UK's Health System is in crisis, central funding no longer keeping pace with demand. Traditional responses-spending more, seeking efficiency savings or invoking market forces-are not solutions. The health of our nation demands urgent delivery of a radical new model, negotiated openly between public, policymakers and healthcare professionals. Such a model could focus on disease prevention, modifying health behaviour and implementing change in public policy in fields traditionally considered unrelated to health such as transport, food and advertising. The true cost-effectiveness of healthcare interventions must be balanced against the opportunity cost of their implementation, bolstering the central role of NICE in such decisions. Without such action, the prognosis for our healthcare system-and for the health of the individuals it serves-may be poor. Here, we explore such a new prescription for our national health.

The effect of neoadjuvant chemotherapy and chemoradiotherapy on exercise capacity and outcome following upper gastrointestinal cancer surgery: an observational cohort study.

BACKGROUND: In 2014 approximately 21,200 patients were diagnosed with oesophageal and gastric cancer in England and Wales, of whom 37 % underwent planned curative treatments. Potentially curative surgical resection is associated with significant morbidity and mortality. For operable locally advanced disease, neoadjuvant chemotherapy (NAC) improves survival over surgery alone. However, NAC carries the risk of toxicity and is associated with a decrease in physical fitness, which may in turn influence subsequent clinical outcome. Lower levels of physical fitness are associated with worse outcome following major surgery in general and Upper Gastrointestinal Surgery (UGI) surgery in particular. Cardiopulmonary exercise testing (CPET) provides an objective assessment of physical fitness. The aim of this study is to test the hypothesis that NAC prior to upper gastrointestinal cancer surgery is associated with a decrease in physical fitness and that the magnitude of the change in physical fitness will predict mortality 1 year following surgery. METHODS: This study is a multi-centre, prospective, blinded, observational cohort study of participants with oesophageal and gastric cancer scheduled for neoadjuvant cancer treatment (chemo- and chemoradiotherapy) and surgery. The primary endpoints are physical fitness (oxygen uptake at lactate threshold measured using CPET) and 1-year mortality following surgery; secondary endpoints include post-operative morbidity (Post-Operative Morbidity Survey (POMS)) 5 days after surgery and patient related quality of life (EQ-5D-5 L). DISCUSSION: The principal benefits of this study, if the underlying hypothesis is correct, will be to facilitate better selection of treatments (e.g. NAC, Surgery) in patients with oesophageal or gastric cancer. It may also be possible to develop new treatments to reduce the effects of neoadjuvant cancer treatment on physical fitness. These results will contribute to the design of a large, multi-centre trial to determine whether an in-hospital exercise-training programme that increases physical fitness leads to improved overall survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT01325883 - 29(th) March 2011.

Hypoxia causes increased monocyte nitric oxide synthesis which is mediated by changes in dimethylarginine dimethylaminohydrolase 2 expression in animal and human models of normobaric hypoxia.

BACKGROUND: Tissue hypoxia is a cardinal feature of inflammatory diseases and modulates monocyte function. Nitric oxide is a crucial component of the immune cell response. This study explored the metabolism of the endogenous inhibitor of nitric oxide production asymmetric dimethylarginine(ADMA) by monocyte dimethylarginine dimethylaminohydrolase 2(DDAH2), and the role of this pathway in the regulation of the cellular response and the local environment during hypoxia. METHODS: Peritoneal macrophages were isolated from a macrophage-specific DDAH2 knockout mouse that we developed and compared with appropriate controls. Cells were exposed to 3% oxygen followed by reoxygenation at 21%. Healthy volunteers underwent an 8 h exposure to normobaric hypoxia with an inspired oxygen percentage of 12%. Peripheral blood mononuclear cells were isolated from blood samples taken before and at the end of this exposure. RESULTS: Intracellular nitrate plus nitrite(NOx) concentration was higher in wild-type murine monocytes after hypoxia and reoxygenation than in normoxia-treated cells (mean(SD) 13·2(2·4) vs 8·1(1·7) pmols/mg protein, p = 0·009). DDAH2 protein was 4·5-fold (SD 1·3) higher than in control cells (p = 0·03). This increase led to a 24% reduction in ADMA concentration, 0·33(0.04) pmols/mg to 0·24(0·03), p = 0·002). DDAH2-deficient murine monocytes demonstrated no increase in nitric oxide production after hypoxic challenge. These findings were recapitulated in a human observational study. Mean plasma NOx concentration was elevated after hypoxic exposure (3·6(1.8)µM vs 6·4(3·2), p = 0·01), which was associated with a reduction in intracellular ADMA in paired samples from 3·6(0.27) pmols/mg protein to 3·15(0·3) (p < 0·01). This finding was associated with a 1·9-fold(0·6) increase in DDAH2 expression over baseline(p = 0·03). DISCUSSION: This study shows that in both human and murine models of acute hypoxia, increased DDAH2 expression mediates a reduction in intracellular ADMA concentration which in turn leads to elevated nitric oxide concentrations both within the cell and in the local environment. Cells deficient in DDAH2 were unable to mount this response.

Caudwell Xtreme Everest: An Overview.

The Caudwell Xtreme Everest (CXE) expedition in the spring of 2007 systematically studied 222 healthy volunteers as they ascended from sea level to Everest Base Camp (5300 m). A subgroup of climbing investigators ascended higher on Everest and obtained physiological measurements up to an altitude of 8400 m. The aim of the study was to explore inter-individual variation in response to environmental hypobaric hypoxia in order to understand better the pathophysiology of critically ill patients and other patients in whom hypoxaemia and cellular hypoxia are prevalent. This paper describes the aims, study characteristics, organization and management of the CXE expedition.