Volatile vs Total intravenous Anaesthesia for major non-cardiac surgery: a pragmatic randomised triaL (VITAL).

BACKGROUND: Improving outcomes after surgery is a major public health research priority for patients, clinicians and the NHS. The greatest burden of perioperative complications, mortality and healthcare costs lies amongst the population of patients aged over 50 years who undergo major non-cardiac surgery. The Volatile vs Total Intravenous Anaesthesia for major non-cardiac surgery (VITAL) trial specifically examines the effect of anaesthetic technique on key patient outcomes: quality of recovery after surgery (quality of recovery after anaesthesia, patient satisfaction and major post-operative complications), survival and patient safety. METHODS: A multi-centre pragmatic efficient randomised trial with health economic evaluation comparing total intravenous anaesthesia with volatile-based anaesthesia in adults (aged 50 and over) undergoing elective major non-cardiac surgery under general anaesthesia. DISCUSSION: Given the very large number of patients exposed to general anaesthesia every year, even small differences in outcome between the two techniques could result in substantial excess harm. Results from the VITAL trial will ensure patients can benefit from the very safest anaesthesia care, promoting an early return home, reducing healthcare costs and maximising the health benefits of surgical treatments. TRIAL REGISTRATION: ISRCTN62903453. September 09, 2021.

Medical student wellbeing during COVID-19: a qualitative study of challenges, coping strategies, and sources of support.

BACKGROUND: Medical students face challenges to their mental wellbeing and have a high prevalence of mental health problems. During training, they are expected to develop strategies for dealing with stress. This study investigated factors medical students perceived as draining and replenishing during COVID-19, using the 'coping reservoir' model of wellbeing. METHODS: In synchronous interactive pre-recorded webinars, 78 fourth-year medical students in the UK responded to reflective prompts. Participants wrote open-text comments on a Padlet site. Responses were analysed using reflexive thematic analysis. RESULTS: Analysis identified five themes. COVID-19 exacerbated academic pressures, while reducing the strategies available to cope with stress. Relational connections with family and friends were affected by the pandemic, leading to isolation and reliance on housemates for informal support. Relationships with patients were adversely affected by masks and telephone consultations, however attending placement was protective for some students' wellbeing. Experiences of formal support were generally positive, but some students experienced attitudinal and practical barriers. CONCLUSIONS: This study used a novel methodology to elicit medical students' reflections on their mental wellbeing during COVID-19. Our findings reinforce and extend the 'coping reservoir' model, increasing our understanding of factors that contribute to resilience or burnout. Many stressors that medical students typically face were exacerbated during COVID-19, and their access to coping strategies and support were restricted. The changes to relationships with family, friends, patients, and staff resulted in reduced support and isolation. Recognising the importance of relational connections upon medical students' mental wellbeing can inform future support.

Characterizing Cardiac Function in ICU Survivors of Sepsis: A Pilot Study Protocol.

Background: Sepsis is one of the most common reasons for ICU admission and a leading cause of mortality worldwide. More than one-half of survivors experience significant physical, psychological, or cognitive impairments, often termed post-intensive care syndrome (PICS). Sepsis is recognized increasingly as being associated with a risk of adverse cardiovascular events that is comparable with other major cardiovascular risk factors. It is plausible that sepsis survivors may be at risk of unidentified cardiovascular disease, and this may play a role in functional impairments seen after ICU discharge. Research Question: What is the prevalence of myocardial dysfunction after an ICU admission with sepsis and to what extent might it be associated with physical impairments in PICS? Study Design and Methods: Characterisation of Cardiovascular Function in ICU Survivors of Sepsis (CONDUCT-ICU) is a prospective, multicenter, pilot study characterizing cardiovascular function and functional impairments in survivors of sepsis taking place in the west of Scotland. Survivors of sepsis will be recruited at ICU discharge and followed up 6 to 10 weeks after hospital discharge. Biomarkers of myocardial injury or dysfunction (high sensitivity troponin and N-terminal pro B-type natriuretic peptide) and systemic inflammation (C-reactive protein, IL-1ß, IL-6, IL-10, and tumor necrosis factor alpha) will be measured in 69 patients at recruitment and at follow-up. In addition, a cardiovascular magnetic resonance substudy will be performed at follow-up in 35 patients. We will explore associations between cardiovascular magenetic resonance indexes of cardiac function, biomarkers of cardiac dysfunction and inflammation, and patient-reported outcome measures. Interpretation: CONDUCT-ICU will provide data regarding the cause and prevalence of cardiac dysfunction in survivors of sepsis and will explore associations with functional impairment. It will provide feasibility data and operational learning for larger studies investigating mechanisms of functional impairment after ICU admission and the association between sepsis and adverse cardiovascular events. Trial Registry: ClinicalTrials.gov; No.: NCT05633290; URL: www.clinicaltrials.gov.

Study protocol for IMPRoVE: a multicentre prospective observational cohort study of the incidence, impact and mechanisms of perioperative right ventricular dysfunction in non-cardiac surgery.

INTRODUCTION: Perioperative myocardial injury evidenced by elevated cardiac biomarkers (both natriuretic peptides and troponin) is common after major non-cardiac surgery. However, it is unclear if the rise in cardiac biomarkers represents global or more localised cardiac injury. We have previously shown isolated right ventricular (RV) dysfunction in patients following lung resection surgery, with no change in left ventricular (LV) function. Given that perioperative RV dysfunction (RVD) can manifest insidiously, we hypothesise there may be a substantial burden of covert yet clinically important perioperative RVD in other major non-cardiac surgical groups. The Incidence, impact and Mechanisms of Perioperative Right VEntricular dysfunction (IMPRoVE) study has been designed to address this knowledge gap. METHODS AND ANALYSIS: A multicentre prospective observational cohort study across four centres in the West of Scotland and London. One hundred and seventy-five patients will be recruited from five surgical specialties: thoracic, upper gastrointestinal, vascular, colorectal and orthopaedic surgery (35 patients from each group). All patients will undergo preoperative and postoperative (day 2-4) echocardiography, with contemporaneous cardiac biomarker testing. Ten patients from each surgical specialty (50 patients in total) will undergo T1-cardiovascular magnetic resonance (CMR) imaging preoperatively and postoperatively. The coprimary outcomes are the incidence of perioperative RVD (diagnosed by RV speckle tracking echocardiography) and the effect that RVD has on days alive and at home at 30 days postoperatively. Secondary outcomes include LV dysfunction and clinical outcomes informed by Standardised Endpoints in Perioperative Medicine consensus definitions. T1 CMR will be used to investigate for imaging correlates of myocardial inflammation as a possible mechanism driving perioperative RVD. ETHICS AND DISSEMINATION: Approval was gained from Oxford C Research Ethics Committee (REC reference 22/SC/0442). Findings will be disseminated by various methods including social media, international presentations and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05827315.

Mechanisms of Acute Right Ventricular Injury in Cardiothoracic Surgical and Critical Care Settings: Part 2.

The right ventricle (RV) is intricately linked in the clinical presentation of critical illness; however, the basis of this is not well-understood and has not been studied as extensively as the left ventricle. There has been an increased awareness of the need to understand how the RV is affected in different critical illness states. In addition, the increased use of point-of-care echocardiography in the critical care setting has allowed for earlier identification and monitoring of the RV in a patient who is critically ill. The first part of this review describes and characterizes the RV in different perioperative states. This second part of the review discusses and analyzes the complex pathophysiologic relationships between the RV and different critical care states. There is a lack of a universal RV injury definition because it represents a range of abnormal RV biomechanics and phenotypes. The term "RV injury" (RVI) has been used to describe a spectrum of presentations, which includes diastolic dysfunction (early injury), when the RV retains the ability to compensate, to RV failure (late or advanced injury). Understanding the mechanisms leading to functional 'uncoupling' between the RV and the pulmonary circulation may enable perioperative physicians, intensivists, and researchers to identify clinical phenotypes of RVI. This, consequently, may provide the opportunity to test RV-centric hypotheses and potentially individualize therapies.

Study protocol for COVID-RV: a multicentre prospective observational cohort study of right ventricular dysfunction in ventilated patients with COVID-19.

INTRODUCTION: COVID-19 can cause severe acute respiratory failure requiring management in intensive care unit with invasive ventilation and a 40% mortality rate. Cardiovascular manifestations are common and studies have shown an increase in right ventricular (RV) dysfunction associated with mortality. These studies, however, comprise heterogeneous patient groups with few requiring invasive ventilation. This study will investigate the prevalence and prognostic significance of RV dysfunction in ventilated patients with COVID-19 which may lead to targeted interventions to improve patient outcomes. METHODS AND ANALYSIS: This prospective multicentre observational cohort study will perform transthoracic echocardiography (TTE) in 150 patients with COVID-19 requiring invasive ventilation for more than 48 hours. RV dysfunction will be defined as TTE evidence of RV dilatation along with the presence of septal flattening. Baseline demographics, disease severity data and clinical information relating to proposed aetiological mechanisms of RV dysfunction (acute respiratory distress syndrome (ARDS), disordered coagulation, direct myocardial injury and ventilation) will be collected and analysed.Primary outcome measures include the prevalence of RV dysfunction and its association with 30-day mortality. Exploratory outcome measures will investigate the association of the proposed aetiological mechanisms of RV dysfunction to the primary outcomes.Prevalence of RV dysfunction will be determined along with 95% Clopper-Pearson CIs and 30-day survival will be analysed using logistic regression adjusting for patient demographics, phase of disease and baseline severity of illness. The role of potential aetiological factors (ARDS, disordered coagulation, direct myocardial injury and ventilation) in relation to the primary outcomes will be analysed using logistic regression. ETHICS AND DISSEMINATION: Approval was gained from Scotland A Research Ethics Committee (REC reference 20/SS/0059). Findings will be disseminated by various methods including webinars, international presentations and publication in peer-reviewed journals.

Can soluble urokinase plasminogen receptor predict outcomes after cardiac surgery?

OBJECTIVES: Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker that has been implicated in several cardiac pathologies and has been shown to be elevated in critically ill populations. We measured plasma suPAR in a cohort of cardiac surgical patients to evaluate its ability to predict prolonged intensive care unit (ICU) and hospital length of stay and development of complications following surgery. We compared suPAR against EuroSCORE II and C-reactive protein (CRP). METHODS: Ninety patients undergoing cardiac surgery were recruited with samples taken preoperatively and on postoperative days 1, 2 and 3. suPAR was measured using enzyme-linked immunosorbent assay. Area under the receiver operator curve (AUROC) was used to test predictive capability of suPAR. Comparison was made with EuroSCORE II and CRP. RESULTS: suPAR increased over time (P < 0.001) with higher levels in patients requiring prolonged ICU and hospital stay, and prolonged ventilation (P < 0.05). suPAR was predictive for prolonged ICU and hospital stay, and prolonged ventilation at all time points (AUROC 0.66-0.74). Interestingly, this association was also observed preoperatively, with preoperative suPAR predicting prolonged ICU (AUROC 0.66), and hospital stay (AUROC 0.67) and prolonged ventilation (AUROC 0.74). The predictive value of preoperative suPAR compared favourably to EuroSCORE II and CRP. CONCLUSIONS: suPAR increases following cardiac surgery and levels are higher in those who require prolonged ICU stay, prolonged hospital stay and prolonged ventilation. Preoperative suPAR compares favourably to EuroSCORE II and CRP in the prediction of these outcomes. suPAR could be a useful biomarker in predicting outcome following cardiac surgery, helping inform clinical decision-making. CLINICAL REGISTRATION: West of Scotland Research Ethics Committee Reference: 12/WS/0179 (AM01).

Intraoperative mechanical ventilation practice in thoracic surgery patients and its association with postoperative pulmonary complications: results of a multicenter prospective observational study.

BACKGROUND: Intraoperative mechanical ventilation may influence postoperative pulmonary complications (PPCs). Current practice during thoracic surgery is not well described. METHODS: This is a post-hoc analysis of the prospective multicenter cross-sectional LAS VEGAS study focusing on patients who underwent thoracic surgery. Consecutive adult patients receiving invasive ventilation during general anesthesia were included in a one-week period in 2013. Baseline characteristics, intraoperative and postoperative data were registered. PPCs were collected as composite endpoint until the 5th postoperative day. Patients were stratified into groups based on the use of one lung ventilation (OLV) or two lung ventilation (TLV), endoscopic vs. non-endoscopic approach and ARISCAT score risk for PPCs. Differences between subgroups were compared using χ2 or Fisher exact tests or Student's t-test. Kaplan-Meier estimates of the cumulative probability of development of PPC and hospital discharge were performed. Cox-proportional hazard models without adjustment for covariates were used to assess the effect of the subgroups on outcome. RESULTS: From 10,520 patients enrolled in the LAS VEGAS study, 302 patients underwent thoracic procedures and were analyzed. There were no differences in patient characteristics between OLV vs. TLV, or endoscopic vs. open surgery. Patients received VT of 7.4 ± 1.6 mL/kg, a PEEP of 3.5 ± 2.4 cmH2O, and driving pressure of 14.4 ± 4.6 cmH2O. Compared with TLV, patients receiving OLV had lower VT and higher peak, plateau and driving pressures, higher PEEP and respiratory rate, and received more recruitment maneuvers. There was no difference in the incidence of PPCs in OLV vs. TLV or in endoscopic vs. open procedures. Patients at high risk had a higher incidence of PPCs compared with patients at low risk (48.1% vs. 28.9%; hazard ratio, 1.95; 95% CI 1.05-3.61; p = 0.033). There was no difference in the incidence of severe PPCs. The in-hospital length of stay (LOS) was longer in patients who developed PPCs. Patients undergoing OLV, endoscopic procedures and at low risk for PPC had shorter LOS. CONCLUSION: PPCs occurred frequently and prolonged hospital LOS following thoracic surgery. Proportionally large tidal volumes and high driving pressure were commonly used in this sub-population. However, large RCTs are needed to confirm these findings. TRIAL REGISTRATION: This trial was prospectively registered at the Clinical Trial Register (www.clinicaltrials.gov; NCT01601223 ; registered May 17, 2012.).

The Utility of Eccentricity Index as a Measure of the Right Ventricular Function in a Lung Resection Cohort.

CONTEXT: Right ventricular (RV) dysfunction occurs after lung resection and is associated with postoperative morbidity. Noninvasive evaluation of the RV is challenging, particularly in the postoperative period. A reliable measure of RV function would have value in this population. AIMS: This study compares eccentricity index (EI) obtained by transthoracic echocardiography (TTE) with cardiovascular magnetic resonance (CMR) determined measures of RV function in a lung resection cohort. CMR is the reference method for noninvasive assessment of RV function. DESIGN AND SETTING: Prospective observational cohort study at a single tertiary hospital. MATERIALS AND METHODS: Twenty-eight patients scheduled for elective lung resection underwent contemporaneous TTE and CMR imaging preoperatively, on postoperative day (POD) 2 and at 2-month. Systolic and diastolic EI was measured offline from anonymized and randomized TTE and CMR images. STATISTICAL ANALYSIS: Bland-Altman analysis was performed to determine agreement between EITTE and EICMR. Changes over time and comparison with CMR determined RV ejection fraction (RVEFCMR) was assessed. RESULTS: Bland-Altman analysis showed a negligible mean difference between EITTE and EICMR, but limits of agreement were wide (SD 0.24 and 0.28). There were no significant changes in EITTE and EICMR over time (P > 0.35). We found no association between EITTE with RVEFCMR at all-time points (P > 0.22). Systolic and diastolic EICMR on POD 2 demonstrated moderate association with RVEFCMR (r = -0.54 and r = -0.59, P ≤ 0.01). At 2-month, only diastolic EICMR correlated with RVEFCMR (r = -0.43, P = 0.03). There were no meaningful associations between EITTE and EICMR with TTE-derived RV systolic pressure (P > 0.31). CONCLUSIONS: TTE determined EI is not useful as a noninvasive method of assessing RV function following lung resection.

The right ventricular response to lung resection.

OBJECTIVES: Lung cancer is a leading cause of cancer death and in suitable cases the best chance of cure is offered by surgery. Lung resection is associated with significant postoperative cardiorespiratory morbidity, with dyspnea and reduced functional capacity as dominant features. These changes are poorly associated with deterioration in pulmonary function and a potential role of right ventricular (RV) dysfunction has been hypothesized. Cardiovascular magnetic resonance imaging is a reference method for noninvasive assessment of RV function and has not previously been applied to this population. METHODS: We used cardiovascular magnetic resonance imaging to assess the RV response to lung resection. Cardiovascular magnetic resonance imaging with volume and flow analysis was performed on 27 patients preoperatively, on postoperative day 2 and at 2 months. Left ventricular ejection fraction and RV ejection fraction, the ratio of stroke volume to end systolic volume, pulmonary artery acceleration time, and distensibility of main and branch pulmonary arteries were studied. RESULTS: Mean ± standard deviation RV ejection fraction deteriorated from 50.5% ± 6.9% preoperatively to 45.6% ± 4.5% on postoperative day 2 and remained depressed at 44.9% ± 7.7% by 2 months (P = .003). The ratio of stroke volume to end systolic volume deteriorated from median 1.0 (quartile 1, quartile 3: 0.9, 1.2) preoperatively to median 0.8 (quartile 1, quartile 3: 0.7, 1.0) on postoperative day 2 (P = .011). On postoperative day 2 there was a decrease in pulmonary artery acceleration time and operative pulmonary artery distensibility (P < .030 for both). There were no changes in left ventricular ejection fraction during the study period (P = .621). CONCLUSIONS: These findings suggest RV dysfunction occurs following lung resection and persists 2 months after surgery. The deterioration in the ratio of stroke volume to end systolic volume suggests a mismatch between afterload and contractility. There is an increase in indices of pulsatile afterload resulting from the operative pulmonary artery.

B-type natriuretic peptide predicts deterioration in functional capacity following lung resection.

OBJECTIVES: Following lung resection, there is a decrease in the functional capacity and quality of life, which is not fully explained by changes in pulmonary function. Previous work demonstrates that B-type natriuretic peptide (BNP) is associated with short- and long-term complications following lung resection, leading to the suggestion that cardiac dysfunction may contribute to functional deterioration. Our aim was to investigate any relationship between BNP and subjective and objective indices of functional deterioration following lung resection surgery. METHODS: Twenty-seven patients undergoing lung resection had serum BNP measured preoperatively, on postoperative day (POD)1 and POD2, and at 2 months postoperatively. The functional deterioration was assessed using 6-min walk tests and the Medical Research Council dyspnoea scale. 'Deterioration in functional capacity' was defined as either an increase in the Medical Research Council dyspnoea score or a significant decrease in the 6-min walk test distance. RESULTS: BNP increased over time (P < 0.01) and was significantly elevated on POD1 and POD2 (P < 0.02 for both). Seventeen patients demonstrated functional deterioration 2 months postoperatively. At all perioperative time points, BNP was significantly higher in patients showing deterioration (P < 0.05 for all). Preoperative BNP was predictive of functional deterioration at 2 months with an area under the receiver-operating characteristic curve of 0.82 (P = 0.01, 95% confidence interval 0.65-0.99). CONCLUSIONS: This study has demonstrated, using subjective and objective measures, that preoperative BNP is a predictor of functional deterioration following lung resection. BNP may have a role in preoperative risk stratification in this population, allowing therapy in future to be targeted towards high-risk patients with the aim of preventing postoperative cardiac dysfunction. CLINICAL TRIAL REGISTRATION NUMBER: NCT01892800.

Assessment of Pulmonary Edema: Principles and Practice.

Pulmonary edema increasingly is recognized as a perioperative complication affecting outcome. Several risk factors have been identified, including those of cardiogenic origin, such as heart failure or excessive fluid administration, and those related to increased pulmonary capillary permeability secondary to inflammatory mediators. Effective treatment requires prompt diagnosis and early intervention. Consequently, over the past 2 centuries a concentrated effort to develop clinical tools to rapidly diagnose pulmonary edema and track response to treatment has occurred. The ideal properties of such a tool would include high sensitivity and specificity, easy availability, and the ability to diagnose early accumulation of lung water before the development of the full clinical presentation. In addition, clinicians highly value the ability to precisely quantify extravascular lung water accumulation and differentiate hydrostatic from high permeability etiologies of pulmonary edema. In this review, advances in understanding the physiology of extravascular lung water accumulation in health and in disease and the various mechanisms that protect against the development of pulmonary edema under physiologic conditions are discussed. In addition, the various bedside modalities available to diagnose early accumulation of extravascular lung water and pulmonary edema, including chest auscultation, chest roentgenography, lung ultrasonography, and transpulmonary thermodilution, are examined. Furthermore, advantages and limitations of these methods for the operating room and intensive care unit that are critical for proper modality selection in each individual case are explored.

Transpulmonary Thermodilution: Its Role in Assessment of Lung Water and Pulmonary Edema.

Tissue edema, in particular pulmonary edema, increasingly is recognized as a perioperative complication affecting outcome. Management strategies directed at avoiding excessive fluid administration, reducing inflammatory response, and decreasing capillary permeability commonly are advocated in perioperative care protocols. In this review, transpulmonary thermodilution (TPTD) as a bedside tool to quantitatively monitor lung water accumulation and optimize fluid therapy is examined. Furthermore, the roles of TPTD as an early detector of fluid accumulation before the development of overt pulmonary edema and in risk stratification are explored. In addition, the ability of TPTD to provide insight into the etiology of pulmonary edema, specifically differentiating hydrostatic versus increased pulmonary capillary permeability, is emerging as an aid in therapeutic decision-making. The combination of hemodynamic and lung water data afforded by TPTD offers unique benefits for the care of high-risk perioperative patients.