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.

Study protocol for a randomised controlled trial to investigate the effectiveness of thoracic epidural and paravertebral blockade in reducing chronic post-thoracotomy pain: 2 (TOPIC 2).

BACKGROUND: Thoracotomy is considered one of the most painful surgical procedures and can cause debilitating chronic post-surgical pain lasting months or years postoperatively. Aggressive management of acute pain resulting from thoracotomy may reduce the likelihood of developing chronic pain. This trial compares the two most commonly used modes of acute analgesia provision at the time of thoracotomy (thoracic epidural blockade (TEB) and paravertebral blockade (PVB)) in terms of their clinical and cost-effectiveness in preventing chronic post-thoracotomy pain. METHODS: TOPIC 2 is a multi-centre, open-label, parallel group, superiority, randomised controlled trial, with an internal pilot investigating the use of TEB and PVB in 1026 adult (≥ 18 years old) patients undergoing thoracotomy in up to 20 thoracic centres throughout the UK. Patients (N = 1026) will be randomised in a 1:1 ratio to receive either TEB or PVB. During the first year, the trial will include an integrated QuinteT (Qualitative Research Integrated into Trials) Recruitment Intervention (QRI) with the aim of optimising recruitment and informed consent. The primary outcome is the incidence of chronic post-surgical pain at 6 months post-randomisation defined as 'worst chest pain over the last week' equating to a visual analogue score greater than or equal to 40 mm indicating at least a moderate level of pain. Secondary outcomes include acute pain, complications of regional analgesia and surgery, health-related quality of life, mortality and a health economic analysis. DISCUSSION: Both TEB and PVB have been demonstrated to be effective in the prevention of acute pain following thoracotomy and nationally practice is divided. Identification of which mode of analgesia is both clinically and cost-effective in preventing chronic post-thoracotomy pain could ameliorate the debilitating effects of chronic pain, improving health-related quality of life, facilitating return to work and caring responsibilities and resulting in a cost saving to the NHS. TRIAL REGISTRATION: NCT03677856 [ClinicalTrials.gov] registered September 19, 2018. https://clinicaltrials.gov/ct2/show/NCT03677856 . First patient recruited 8 January 2019.

A qualitative study exploring the lived experiences of patients living with mild, moderate and severe frailty, following hip fracture surgery and hospitalisation.

It is well recognised that hip fracture surgery is associated with a negative impact on short and long-term post-operative physical health and emotional well-being for patients. Furthermore, these patients are known to be frail with multiple co-morbidities. This study explores how frailty shapes the lived experiences of rehabilitation and recovery for patients who have undergone hip fracture surgery. Semi-structured interviews were conducted with sixteen participants, recently discharged from hospital following hip fracture surgery. Interpretative phenomenological analysis was applied to explore the lived experiences of frail patients and ascertain important themes. Patient experiences were captured in seven overarching themes: 1) the hospital as a place of "safety", 2) placing trust in others, 3) the slow recovery journey impeded by attitude and support, 4) maintaining autonomy and dignity whilst feeling vulnerable, 5) seeking a new normal, 6) loneliness and social isolation and 7) the ageing body. Based on our study findings, we have been able to suggest a number of opportunities to improve support for frailer patients in finding a new routine to their everyday lives, these include on-going physical and psychological support, information and education and a robust pathway for transition of care into the community. A conceptual thematic diagram is presented which helps to understand the experience and the complex needs of frail older people undergoing hip fracture surgery.

Platform trials for anaesthesia and perioperative medicine: a narrative review.

Large randomised trials provide the most reliable evidence of effectiveness of new treatments in clinical practice. However, the time and resources required to complete such trials can be daunting. An overarching clinical trial platform focused on a single condition or type of surgery, aiming to compare several treatments, with an option to stop any or add in new treatment options, can provide greater efficiency. This has the potential to accelerate knowledge acquisition and identify effective, ineffective, or harmful treatments faster. The master protocol of the platform defines the study population(s) and standardised procedures. Ineffective or harmful treatments can be discarded or study drug dose modified during the life cycle of the trial. Other adaptive elements that can be modified include eligibility criteria, required sample size for any comparison(s), randomisation assignment ratio, and the addition of other promising treatment options. There are excellent opportunities for anaesthetists to establish platform trials in perioperative medicine. Platform trials are highly efficient, with the potential to provide quicker answers to important clinical questions that lead to improved patient care.

Clinical effectiveness and safety of spinal anaesthesia compared with general anaesthesia in patients undergoing hip fracture surgery using a consensus-based core outcome set and patient-and public-informed outcomes: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: We conducted a systematic review and meta-analysis of contemporary RCTs to determine the clinical effectiveness of spinal vs general anaesthesia (SA vs GA) in patients undergoing hip fracture surgery using a consensus-based core outcome set, and outcomes defined as important by patient and public involvement (PPI) initiatives. METHODS: RCTs comparing any of the core outcomes (mortality, time from injury to surgery, acute coronary syndrome, hypotension, acute kidney injury, delirium, pneumonia, orthogeriatric input, being out of bed at day 1 postoperatively, and pain) or PPI-defined outcomes (return to preoperative residence, quality of life, and mobility status) between SA and GA were identified from MEDLINE, Embase, Cochrane Library, and Web of Science (2000 to February 2022). Pooled relative risks (RRs) and mean differences (95% confidence intervals [CIs]) were estimated. RESULTS: There was no significant difference in the risk of delirium comparing SA vs GA (RR=1.07; 95% CI, 0.90-1.29). Comparing SA vs GA, the RR for mortality was 0.56 (95% CI, 0.22-1.44) in-hospital, 1.07 (95% CI, 0.52-2.23) at 30 days, and 1.08 (95% CI, 0.55-2.12) at 90 days. Spinal anaesthesia reduced the risk of acute kidney injury compared with GA: RR=0.59 (95% CI, 0.39-0.89). There were no significant differences in the risk of other outcomes. Few studies reported PPI-defined outcomes, with most studies reporting on one to three core outcomes. CONCLUSIONS: Except for acute kidney injury, there were no differences between SA and GA in hip fracture surgery when using a consensus-based core outcome set and patient and public involvement-defined outcomes. Most studies reported limited outcomes from the core outcome set, and few reported outcomes important to patients, which should be considered when designing future RCTs. PROSPERO REGISTRATION: CRD42021275206.

Perioperative oxygen therapy: a protocol for an overview of systematic reviews and meta-analyses.

BACKGROUND: Oxygen is routinely given to patients during and after surgery. Perioperative oxygen administration has been proposed as a potential strategy to prevent and treat hypoxaemia and reduce complications, such as surgical site infections, pulmonary complications and mortality. However, uncertainty exists as to which strategies in terms of amount, delivery devices and timing are clinically effective. The aim of this overview of systematic reviews and meta-analyses is to answer the research question, 'For which types of surgery, at which stages of care, in which sub-groups of patients and delivered under what conditions are different types of perioperative oxygen therapy clinically effective?'. METHODS: We will search key electronic databases (MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, CENTRAL, Epistemonikos, PROSPERO, the INAHTA International HTA Database and DARE archives) for systematic reviews and randomised controlled trials comparing perioperative oxygen strategies. Each review will be mapped according to type of surgery, surgical pathway timepoints and clinical comparison. The highest quality reviews with the most comprehensive and up-to-date coverage of relevant literature will be chosen as anchoring reviews. Standardised data will be extracted from each chosen review, including definition of oxygen therapy, summaries of interventions and comparators, patient population, surgical characteristics and assessment of overall certainty of evidence. For clinical outcomes and adverse events, the overall pooled findings and results of subgroup and sensitivity analyses (where available) will be extracted. Trial-level data will be extracted for surgical site infections, mortality, and potential trial-level effect modifiers such as risk of bias, outcome definition and type of surgery to facilitate quantitative data analysis. This analysis will adopt a multiple indication review approach with panoramic meta-analysis using review-level data and meta-regression using trial-level data. An evidence map will be produced to summarise our findings and highlight any research gaps. DISCUSSION: There is a need to provide a panoramic overview of systematic reviews and meta-analyses describing peri-operative oxygen practice to both inform clinical practice and identify areas of ongoing uncertainty, where further research may be required. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021272361.

On the horns of a dilemma: choosing total intravenous anaesthesia or volatile anaesthesia.

There are two established techniques of delivering general anaesthesia: propofol-based total intravenous anaesthesia (TIVA) and volatile agent-based inhaled anaesthesia. Both techniques are offered as standard of care and have an established safety track record lasting more than 30 years. However, it is not currently known whether the choice of anaesthetic technique results in a fundamentally different patient experience or affects early, intermediate-term, and longer-term postoperative outcomes. This editorial comments on a recently published study that suggests that inhaled volatile anaesthesia might be associated with fewer postoperative surgical complications than propofol-based TIVA for patients undergoing colorectal cancer surgery. We consider the strengths and limitations of the study, place these findings in the context of the broader evidence, and discuss how the current controversies regarding anaesthetic technique can be resolved, thereby helping to bring precision medicine into the modern practice of perioperative care.

Effect of Regional vs General Anesthesia on Incidence of Postoperative Delirium in Older Patients Undergoing Hip Fracture Surgery: The RAGA Randomized Trial.

Importance: In adults undergoing hip fracture surgery, regional anesthesia may reduce postoperative delirium, but there is uncertainty about its effectiveness. Objective: To investigate, in older adults undergoing surgical repair for hip fracture, the effects of regional anesthesia on the incidence of postoperative delirium compared with general anesthesia. Design, Setting, and Participants: A randomized, allocation-concealed, open-label, multicenter clinical trial of 950 patients, aged 65 years and older, with or without preexisting dementia, and a fragility hip fracture requiring surgical repair from 9 university teaching hospitals in Southeastern China. Participants were enrolled between October 2014 and September 2018; 30-day follow-up ended November 2018. Interventions: Patients were randomized to receive either regional anesthesia (spinal, epidural, or both techniques combined with no sedation; n = 476) or general anesthesia (intravenous, inhalational, or combined anesthetic agents; n = 474). Main Outcomes and Measures: Primary outcome was incidence of delirium during the first 7 postoperative days. Secondary outcomes analyzed in this article include delirium severity, duration, and subtype; postoperative pain score; length of hospitalization; 30-day all-cause mortality; and complications. Results: Among 950 randomized patients (mean age, 76.5 years; 247 [26.8%] male), 941 were evaluable for the primary outcome (6 canceled surgery and 3 withdrew consent). Postoperative delirium occurred in 29 (6.2%) in the regional anesthesia group vs 24 (5.1%) in the general anesthesia group (unadjusted risk difference [RD], 1.1%; 95% CI, -1.7% to 3.8%; P = .48; unadjusted relative risk [RR], 1.2 [95% CI, 0.7 to 2.0]; P = .57]). Mean severity score of delirium was 23.0 vs 24.1, respectively (unadjusted difference, -1.1; 95% CI, -4.6 to 3.1). A single delirium episode occurred in 16 (3.4%) vs 10 (2.1%) (unadjusted RD, 1.1%; 95% CI, -1.7% to 3.9%; RR, 1.6 [95% CI, 0.7 to 3.5]). Hypoactive subtype in 11 (37.9%) vs 5 (20.8%) (RD, 11.5; 95% CI, -11.0% to 35.7%; RR, 2.2 [95% CI, 0.8 to 6.3]). Median worst pain score was 0 (IQR, 0 to 20) vs 0 (IQR, 0 to 10) (difference 0; 95% CI, 0 to 0). Median length of hospitalization was 7 days (IQR, 5 to 10) vs 7 days (IQR, 6 to 10) (difference 0; 95% CI, 0 to 0). Death occurred in 8 (1.7%) vs 4 (0.9%) (unadjusted RD, -0.8%; 95% CI, -2.2% to 0.7%; RR, 2.0 [95% CI, 0.6 to 6.5]). Adverse events were reported in 106 episodes in the regional anesthesia group and 102 in the general anesthesia group; the most frequently reported adverse events were nausea and vomiting (47 [44.3%] vs 34 [33.3%]) and postoperative hypotension (13 [12.3%] vs 10 [9.8%]). Conclusions and Relevance: In patients aged 65 years and older undergoing hip fracture surgery, regional anesthesia without sedation did not significantly reduce the incidence of postoperative delirium compared with general anesthesia. Trial Registration: ClinicalTrials.gov Identifier: NCT02213380.

[Cardiac arrest under special circumstances]. / Kreislaufstillstand unter besonderen Umständen: Leitlinien des European Resuscitation Council 2021.

These guidelines of the European Resuscitation Council (ERC) Cardiac Arrest under Special Circumstances are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. This section provides guidelines on the modifications required for basic and advanced life support for the prevention and treatment of cardiac arrest under special circumstances; in particular, specific causes (hypoxia, trauma, anaphylaxis, sepsis, hypo-/hyperkalaemia and other electrolyte disorders, hypothermia, avalanche, hyperthermia and malignant hyperthermia, pulmonary embolism, coronary thrombosis, cardiac tamponade, tension pneumothorax, toxic agents), specific settings (operating room, cardiac surgery, cardiac catheterization laboratory, dialysis unit, dental clinics, transportation [in-flight, cruise ships], sport, drowning, mass casualty incidents), and specific patient groups (asthma and chronic obstructive pulmonary disease, neurological disease, morbid obesity, pregnancy).

The risks associated with tourniquet use in lower limb trauma surgery: a systematic review and meta-analysis.

PURPOSE: Tourniquet use in lower limb fracture surgery may reduce intra-operative bleeding, improve surgical field of view and reduce length of procedure. However, tourniquets may result in pain and the production of harmful metabolites cause complications or affect functional outcomes. This systematic review aimed to compare outcomes following lower limb fracture surgery performed with or without tourniquet. METHODS: We searched databases for RCTs comparing lower limb fracture surgery performed with versus without tourniquet reporting on outcomes pain, physical function, health-related quality of life, complications, cognitive function, blood loss, length of stay, length of procedure, swelling, time to union, surgical field of view, volume of anaesthetic agent, biochemical markers of inflammation and injury, and electrolyte and acid-base balance. Random-effects meta-analysis was performed. PROSPERO ID CRD42020209310. RESULTS: Six RCTs enabled inclusion of 552 procedures. Pooled analysis demonstrated that tourniquet use reduced length of procedure by 6 minutes (95% CI -10.12 to -1.87; p < 0.010). We were unable to exclude increased harms from tourniquet use. Pooled analysis showed post-operative pain score was higher in tourniquet group by 12.88 on 100-point scale (95% CI -1.25-27.02; p = 0.070). Risk differences for wound infection, deep venous thrombosis and re-operation were 0.06 (95% CI -0.00-0.12; p = 0.070), 0.05 (95% CI -0.02-0.11; p = 0.150) and 0.03 (95% CI -0.03-0.09; p = 0.340). CONCLUSION: Tourniquet use was associated with a reduced length of procedure. It is possible that tourniquets also increase incidence of important complications, but the data are too sparse to draw firm conclusions. Methodological weaknesses of the included RCTs prevent any solid conclusions being drawn for outcomes investigated. Further studies are required to address these limitations.

European Resuscitation Council Guidelines 2021: Cardiac arrest in special circumstances.

These European Resuscitation Council (ERC) Cardiac Arrest in Special Circumstances guidelines are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. This section provides guidelines on the modifications required to basic and advanced life support for the prevention and treatment of cardiac arrest in special circumstances; specifically special causes (hypoxia, trauma, anaphylaxis, sepsis, hypo/hyperkalaemia and other electrolyte disorders, hypothermia, avalanche, hyperthermia and malignant hyperthermia, pulmonary embolism, coronary thrombosis, cardiac tamponade, tension pneumothorax, toxic agents), special settings (operating room, cardiac surgery, catheter laboratory, dialysis unit, dental clinics, transportation (in-flight, cruise ships), sport, drowning, mass casualty incidents), and special patient groups (asthma and COPD, neurological disease, obesity, pregnancy).

A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study.

BACKGROUND: Tumour necrosis factor receptor 1 (TNFR1) signalling mediates the cell death and inflammatory effects of TNF-α. OBJECTIVE: The current clinical trial investigated the effects of a nebulised TNFR1 antagonist (GSK2862277) on signs of lung injury in patients undergoing oesophagectomy. DESIGN: Randomised double-blind (sponsor unblind), placebo-controlled, parallel group study. SETTING: Eight secondary care centres, the United Kingdom between April 2015 and June 2017. PATIENTS: Thirty-three patients undergoing elective transthoracic oesophagectomy. INTERVENTIONS: Patients randomly received a single nebulised dose (26 mg) of GSK2862277 (n = 17) or placebo (n = 16), given 1 to 5 h before surgery; 14 and 16, respectively competed the study. MAIN OUTCOME MEASUREMENTS: Physiological and biochemical markers of lung injury, pharmacokinetic and safety endpoints were measured. The primary endpoint was the change from baseline in pulmonary vascular permeability index (PVPI) at completion of surgery, measured using single-indicator transpulmonary thermodilution. Adjusted point estimates and 95% credible intervals (analogous to conventional confidence intervals) were constructed for each treatment using Bayesian statistical models. RESULTS: The mean change (with 95% credible intervals) from baseline in PVPI on completion of surgery was 0.00 (-0.23, 0.39) in the placebo and 0.00 (-0.24, 0.37) in the GSK2862277 treatment groups. There were no significant treatment-related differences in PaO2/FiO2 or Sequential Organ Failure Assessment score. Levels of free soluble TNFR1, Macrophage Inflammatory Protein-1 alpha and total protein were significantly reduced in the bronchoalveolar lavage fluid of patients treated with GSK2862277 (posterior probability of decrease with GSK2862277 vs. placebo:≥0.977; equivalent to P < 0.05). The frequency of adverse events and serious adverse events were distributed evenly across the two treatment arms. CONCLUSION: Pre-operative treatment with a single 26 mg inhaled dose of GSK2862277 did not result in significantly lower postoperative alveolar capillary leak or extra vascular lung water. Unexpectedly small increases in transpulmonary thermodilution-measured PVPI and extra vascular lung water index at completion of surgery suggest less postoperative lung injury than historically reported, which may have also compromised a clear assessment of efficacy in this trial. GSK2862277 was well tolerated, resulted in expected lung exposure and reduced biomarkers of lung permeability and inflammation. TRIAL REGISTRATION: clinicaltrials.gov: NCT02221037.

Randomised controlled trial to investigate the effectiveness of thoracic epidural and paravertebral blockade in reducing chronic post-thoracotomy pain (TOPIC): a pilot study to assess feasibility of a large multicentre trial.

OBJECTIVES: Thoracotomy is considered one of the most painful surgical procedures. The incidence of chronic post-thoracotomy pain (CPTP) is up to 50%. Paravertebral blockade (PVB) may be superior to thoracic epidural blockade (TEB) in preventing CPTP. The specific objective of this pilot study was to assess the feasibility of conducting a larger trial to determine whether PVB at thoracotomy is more effective in reducing CPTP compared with TEB. DESIGN: A randomised, parallel, external pilot study was conducted to assess whether a large randomised trial of TEB and PVB with CPTP as the primary outcome is feasible. SETTING: Two adult thoracic centres in the UK. PARTICIPANTS: All adult patients admitted for elective open thoracotomy. Participants were excluded if they were American Society of Anesthesiologists physical status IV or V; or if there is contraindication to local anaesthetics; infection near the proposed puncture site; coagulation/thoracic spine disorders; required chest wall resection or emergency thoracic surgery or had a previous thoracotomy. RESULTS: All patients presenting for thoracotomy were screened over a 12-month period with 194 found to be eligible. Of these, 69 (36%) were randomised (95% CI 29% to 42%). Discounting five participants who died, 54 of 64 participants (84%) returned questionnaire booklets at 6 months. The number of participants indicating at least a moderate level of chest pain at 6 months was lower with PVB but with high levels of uncertainty (RR: 0.7; 95% CI 0.3 to 1.7 for worst pain; RR: 0.3; 95% CI 0.0 to 2.8 for average pain). There were no safety concerns. CONCLUSIONS: A large, multicentre randomised controlled trial of PVB versus TEB is feasible as it is possible to randomise and follow up participants with high fidelity. Pain scores were lower on average with PVB compared with TEB but a much larger trial is required to confirm this reliably. TRIAL REGISTRATION NUMBER: ISRCTN45041624.

Effect of regional versus general anaesthesia on postoperative delirium in elderly patients undergoing surgery for hip fracture: a systematic review.

OBJECTIVE: Older patients with hip fractures who are undergoing surgery are at high risk of significant mortality and morbidity including postoperative delirium. It is unclear whether different types of anaesthesia may reduce the incidence of postoperative delirium. This systematic review will investigate the impact of anaesthetic technique on postoperative delirium. Other outcomes included mortality, length of stay, complications and functional outcomes. DESIGN: Systematic review of randomised controlled trials and non-randomised controlled studies. DATA SOURCES: Bibliographic databases were searched from inception to June 2018. Web of Science and ZETOC databases were searched for conference proceedings. Reference lists of relevant articles were checked, and clinical trial registers were searched to identify ongoing trials. ELIGIBILITY CRITERIA: Studies were eligible if general and regional anaesthesia were compared in patients (aged 60 and over) undergoing hip fracture surgery, reporting primary outcome of postoperative delirium and secondary outcomes of mortality, length of hospital stay, adverse events, functional outcomes, discharge location and quality of life. Exclusion criteria were anaesthetic technique or drug not considered current standard practice; patients undergoing hip fracture surgery alongside other surgery and uncontrolled studies. RESULTS: One hundred and four studies were included. There was no evidence to suggest that anaesthesia type influences postoperative delirium or mortality. Some studies suggested a small reduction in length of hospital stay with regional anaesthesia. There was some evidence to suggest that respiratory complications and intraoperative hypotension were more common with general anaesthesia. Heterogeneity precluded meta-analysis. All findings were described narratively and data were presented where possible in forest plots for illustrative purposes. CONCLUSIONS: While there was no evidence to suggest that anaesthesia types influence postoperative delirium, the evidence base is lacking. There is a need to ascertain the impact of type of anaesthesia on outcomes with an adequately powered, methodologically rigorous study. PROSPERO REGISTRATION NUMBER: CRD42015020166.

Comparison of regional with general anaesthesia on postoperative delirium (RAGA-delirium) in the older patients undergoing hip fracture surgery: study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Postoperative delirium (POD) is a common serious postoperative complication especially in older people and is associated with increased mortality, morbidity and healthcare costs. There is no clear consensus which anaesthesia is associated with less incidence of POD for older patients. We aim to assess whether regional anaesthesia results in lower incidence of POD comparing with general anaesthesia (GA) among older patients undergoing hip fracture surgery. METHODS AND ANALYSIS: RAGA-delirium is a pragmatic, multicentre, prospective, parallel grouped, randomised controlled clinical trial comparing RA or GA for hip fracture surgery. A total of 1000 patients who are 65 years or over and who are having planned hip fracture surgery in nine clinical trial centres of China will be randomised in a 1:1 ratio to receive either anaesthesia for the surgery. The primary endpoint will be the incidence of POD at day 7. The secondary endpoints will be the subtype, severity and duration of delirium, postoperative acute pain score, incidence of other postoperative non-delirium complications, quality of life and cost-effective outcomes. Randomisation will be performed at the patient level using computer-generated assignment. Outcome assessors will be blinded from intervention assignment. Assessments will be conducted before surgery, intraoperatively, postoperatively, during the hospital stay, at 30-day, 6-month and 1-year postoperative intervals. POTENTIAL IMPACT OF STUDY: This study will provide clinical evidence with a more robust methodology to help anaesthetists in selecting appropriate anaesthesia for older patients with high risk for POD. At the era of increasing emphasis on delirium prevention, this trial has the potential to inform the future national guideline to reduce POD. ETHICS AND DISSEMINATION: Ethical approved by the local institutional review board. Trial results will be presented at national and international academic conferences, and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT02213380); pre-results.

Randomised controlled pilot study to investigate the effectiveness of thoracic epidural and paravertebral blockade in reducing chronic post-thoracotomy pain: TOPIC feasibility study protocol.

INTRODUCTION: Open chest surgery (thoracotomy) is considered the most painful of surgical procedures. Forceful wound retraction, costochondral dislocation, posterior costovertebral ligament disruption, intercostal nerve trauma and wound movement during respiration combine to produce an acute, severe postoperative pain insult and persistent chronic pain many months after surgery is common. Three recent systematic reviews conclude that unilateral continuous paravertebral blockade (PVB) provides analgesia at least equivalent to thoracic epidural blockade (TEB) in the postoperative period, has a lower failure rate, and symptom relief that lasted months. Crucially, PVB may reduce the development of subsequent chronic pain by intercostal nerve protection or decreased nociceptive input. The overall aim is to determine in patients who undergo thoracotomy whether perioperative PVB results in reducing chronic post-thoracotomy pain (CPTP) compared with TEB. This pilot study will evaluate feasibility of a substantive trial. METHODS AND ANALYSIS: TOPIC is a randomised controlled trial comparing the effectiveness of TEB and PVB in reducing CPTP. This is a pilot study to evaluate feasibility of a substantive trial and study processes in 2 adult thoracic centres, Heart of England NHS Foundation Trust (HEFT) and University Hospital of South Manchester NHS Foundation Trust (UHSM). The primary objective is to establish the number of patients randomised as a proportion of those eligible. Secondary objectives include evaluation of study processes. Analyses of feasibility and patient-reported outcomes will primarily take the form of simple descriptive statistics and where appropriate, point estimates of effects sizes and associated 95% CIs. ETHICS AND DISSEMINATION: The study has obtained ethical approval from NHS Research Ethics Committee (REC number 14/EM/1280). Dissemination plan includes: informing patients and health professionals; engaging multidisciplinary professionals to support a proposal of a definitive trial and submission for a full HTA application dependent on the success of the study. TRIAL REGISTRATION NUMBER: ISRCTN45041624; Pre-results.

Intra-operative adherence to lung-protective ventilation: a prospective observational study.

BACKGROUND: Lung-protective ventilation in patients with acute respiratory distress syndrome improves mortality. Adopting this strategy in the perioperative period has been shown to reduce lung inflammation and postoperative pulmonary and non-pulmonary sepsis complications in patients undergoing major abdominal surgery. We conducted a prospective observational study into the intra-operative ventilation practice across the West Midlands to assess the use of lung-protective ventilation. METHODS: Data was collected from all adult ventilated patients undergoing surgery across 14 hospital trusts in the West Midlands over a 2-day period in November 2013. Data collected included surgical specialty, patient's biometric data, duration of procedure, grade of anesthetist, and ventilatory parameters. Lung-protective ventilation was defined as the delivery of a tidal volume between 6 and 8 ml/kg/predicted body weight, a peak pressure of less than 30 cmH2O, and the use of positive end expiratory pressure of 6-8 cmH2O. Categorical data are presented descriptively, while non-parametric data are displayed as medians with statistical tests from Mann-Whitney U tests or Kruskal-Wallis tests for independent samples while paired samples are represented by Wilcoxon signed rank tests. RESULTS: Four hundred six patients with a median age of 56 years (16-91) were included. The majority of operations (78 %) were elective procedures with the principal anesthetist being a consultant. The commonest surgical specialties were general (29 %), trauma and orthopedic (19 %), and ENT (17 %). Volume-controlled ventilation was the preferred ventilation strategy in 70 % of cases. No patients were ventilated using lung-protective ventilation. Overall peak airway pressure (pPeak) was low (median 20 cmH2O (inter-quartile range [IQR] 10-43 cmH2O)) with median delivered tidal volumes of 8.4 ml/kg/predicted body weight (PBW) (IQR 3.5-14.5 ml/kg/PBW). The median positive end expiratory pressure (PEEP) was only 4 cmH2O (0-5 cmH2O) with PEEP not used in 152 cases. CONCLUSIONS: Perioperative lung protection ventilation can improve patient outcomes from major surgery. This large prospective study demonstrates that within the West Midlands lung-protective ventilation during the perioperative period is uncommon, especially in relation to the use of PEEP, and that perhaps further trials are required to promote wider adoption of practice.

Regional versus general anaesthesia in elderly patients undergoing surgery for hip fracture: protocol for a systematic review.

BACKGROUND: With an ageing population, the incidence of hip fractures requiring surgery is increasing. Post-operative delirium is common following hip fracture surgery. Delirium is associated with high mortality and morbidity, poor long-term functional outcomes and institutionalisation. There is some evidence to suggest that perioperative intervention, specifically the anaesthetic technique employed, may reduce the incidence of delirium in this population. The aim of this systematic review is to investigate the impact of anaesthesia type on post-operative delirium. METHOD: We will conduct a systematic literature review using Embase, MEDLINE, CINAHL and the Cochrane Library (CENTRAL) bibliographic databases and the ZETOC and Web of Science websites. Authors of these trials will be invited to contribute unpublished data. PROSPERO register and clinical trial registers will also be searched to identify any ongoing reviews and trials. Eligible studies will assess the incidence of post-operative delirium in patients having regional or general anaesthesia for hip fracture surgery. The primary outcome of interest will be post-operative delirium; secondary outcomes will include mortality, measures of functional outcome, quality of life, length of hospital stay, discharge location and adverse events. Two reviewers will independently screen references identified by electronic literature searches. Two independent reviewers will extract data from studies fulfilling our inclusion criteria using a piloted data extraction form. Methodological quality and bias of included randomised controlled trials will be assessed using the 'Cochrane Collaborations tool for assessing risk of bias'; for non-randomised studies, this will be assessed using the Newcastle-Ottawa scale. Data on similar outcomes will be pooled when possible. Where possible, meta-analysis will be undertaken using Review Manager (RevMan version 5.3) software. DISCUSSION: This systematic review will provide an updated evidence base with which to guide clinical practice and research for this group of challenging patients. If the anaesthetic technique employed is shown to reduce the incidence of post-operative cognition dysfunction, then this may lead to a change in evidence-based practice, influence future guidelines and support further randomised controlled trial research. There is no known effective treatment for delirium, creating the urgent need for research into delirium prevention. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015020166.

Paravertebral block versus thoracic epidural for patients undergoing thoracotomy.

BACKGROUND: Operations on structures in the chest (usually the lungs) involve cutting between the ribs (thoracotomy). Severe post-thoracotomy pain can result from pleural (lung lining) and muscular damage, costovertebral joint (ribcage) disruption and intercostal nerve (nerves that run along the ribs) damage during surgery. Poor pain relief after surgery can impede recovery and increase the risks of developing complications such as lung collapse, chest infections and blood clots due to ineffective breathing and clearing of secretions. Effective management of acute pain following thoracotomy may prevent these complications and reduce the likelihood of developing chronic pain. A multi-modal approach to analgesia is widely employed by thoracic anaesthetists using a combination of regional anaesthetic blockade and systemic analgesia, with both non-opioid and opioid medications and local anaesthesia blockade.There is some evidence that blocking the nerves as they emerge from the spinal column (paravertebral block, PVB) may be associated with a lower risk of major complications in thoracic surgery but the majority of thoracic anaesthetists still prefer to use a thoracic epidural blockade (TEB) as analgesia for their patients undergoing thoracotomy. In order to bring about a change in practice, anaesthetists need a review that evaluates the risk of all major complications associated with thoracic epidural and paravertebral block in thoracotomy. OBJECTIVES: To compare the two regional techniques of TEB and PVB in adults undergoing elective thoracotomy with respect to:1. analgesic efficacy;2. the incidence of major complications (including mortality);3. the incidence of minor complications;4. length of hospital stay;5. cost effectiveness. SEARCH METHODS: We searched for studies in the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 9); MEDLINE via Ovid (1966 to 16 October 2013); EMBASE via Ovid (1980 to 16 October 2013); CINAHL via EBSCO host (1982 to 16 October 2013); and reference lists of retrieved studies. We handsearched the Journal of Cardiothoracic Surgery and Journal of Cardiothoracic and Vascular Anesthesia (16 October 2013). We reran the search on 31st January 2015. We found one additional study which is awaiting classification and will be addressed when we update the review. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) comparing PVB with TEB in thoracotomy, including upper gastrointestinal surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors (JY and SG) independently assessed the studies for inclusion and then extracted data as eligible for inclusion in qualitative and quantitative synthesis (meta-analysis). MAIN RESULTS: We included 14 studies with a total of 698 participants undergoing thoracotomy. There are two studies awaiting classification. The studies demonstrated high heterogeneity in insertion and use of both regional techniques, reflecting real-world differences in the anaesthesia techniques. Overall, the included studies have a moderate to high potential for bias, lacking details of randomization, group allocation concealment or arrangements to blind participants or outcome assessors. There was low to very low-quality evidence that showed no significant difference in 30-day mortality (2 studies, 125 participants. risk ratio (RR) 1.28, 95% confidence interval (CI) 0.39 to 4.23, P value = 0.68) and major complications (cardiovascular: 2 studies, 114 participants. Hypotension RR 0.30, 95% CI 0.01 to 6.62, P value = 0.45; arrhythmias RR 0.36, 95% CI 0.04 to 3.29, P value = 0.36, myocardial infarction RR 3.19, 95% CI 0.13, 76.42, P value = 0.47); respiratory: 5 studies, 280 participants. RR 0.62, 95% CI 0.26 to 1.52, P value = 0.30). There was moderate-quality evidence that showed comparable analgesic efficacy across all time points both at rest and after coughing or physiotherapy (14 studies, 698 participants). There was moderate-quality evidence that showed PVB had a better minor complication profile than TEB including hypotension (8 studies, 445 participants. RR 0.16, 95% CI 0.07 to 0.38, P value < 0.0001), nausea and vomiting (6 studies, 345 participants. RR 0.48, 95% CI 0.30 to 0.75, P value = 0.001), pruritis (5 studies, 249 participants. RR 0.29, 95% CI 0.14 to 0.59, P value = 0.0005) and urinary retention (5 studies, 258 participants. RR 0.22, 95% CI 0.11 to 0.46, P value < 0.0001). There was insufficient data in chronic pain (six or 12 months). There was no difference found in and length of hospital stay (3 studies, 124 participants). We found no studies that reported costs. AUTHORS' CONCLUSIONS: Paravertebral blockade reduced the risks of developing minor complications compared to thoracic epidural blockade. Paravertebral blockade was as effective as thoracic epidural blockade in controlling acute pain. There was a lack of evidence in other outcomes. There was no difference in 30-day mortality, major complications, or length of hospital stay. There was insufficient data on chronic pain and costs. Results from this review should be interpreted with caution due to the heterogeneity of the included studies and the lack of reliable evidence. Future studies in this area need well-conducted, adequately-powered RCTs that focus not only on acute pain but also on major complications, chronic pain, length of stay and costs.