Title: Volatile vs Total intravenous Anaesthesia for major non-cardiac surgery – a pragmatic randomised controlled triaL (VITAL)
Funder: Department of Health and Social Care

Abstract: AIM: To perform a clinical trial to test whether total intravenous anaesthesia (TIVA) is better than inhalational anaesthesia for patients undergoing major non-cardiac surgery in the NHS. _x000D_ _x000D_ BACKGROUND: More than 1.5 million patients require general anaesthesia for major surgery each year in the NHS. General anaesthesia is most commonly maintained with inhalational anaesthesia where the patient breathes anaesthetic gas through a breathing tube whilst asleep. However, some patients receive an alternative called total intravenous anaesthesia, or ‘TIVA’. During a TIVA anaesthetic, the patient breathes oxygen through a breathing tube but is kept asleep by drugs given into a vein. Many anaesthetic doctors believe patients recover more quickly after TIVA, and small studies suggest patients prefer this technique. Some anaesthetists are enthusiastic about TIVA because very early research suggests better survival for patients undergoing cancer surgery. However, this has not been proven and others are worried about possible risks including excess deaths and waking up during surgery. The evidence for TIVA has been positive so far but the clinical trials were very small and the results are not reliable. There has been one large trial for patients undergoing specialist cardiac surgery but this involves a very different kind of anaesthesia which we cannot easily compare. Despite the limited evidence, some doctors are starting to use TIVA as routine. We need to find out which technique is better in terms of getting patients home earlier, patient survival and avoiding any accidental awareness under anaesthesia. Our findings will help doctors select the best method to improve care and reduce harm for many patients._x000D_ _x000D_ DESIGN AND METHODS: We will partner with a national audit hosted by the Royal College of Anaesthetists: the Perioperative Quality Improvement Project (PQIP). PQIP has been running successfully since 2017 and has collected data from more than 26,000 patients. We will use the PQIP database to collect data quickly and cheaply, limiting the burden to patients. If a patient consents to take part in VITAL, we will randomise them to either TIVA or inhalational anaesthesia. No other patient care will change. We will look for differences in the number of days surviving patients (the great majority) spend at home within 30 days after surgery, quality of recovery after anaesthesia (e.g. pain, nausea, vomiting), survival and accidental awareness under anaesthesia. We will follow up patients for six months to understand their experience of anaesthesia, and to work out the cost of their treatment. _x000D_ _x000D_ PATIENT AND PUBLIC INVOLVEMENT: Our two patient co-applicants have both received anaesthesia for major surgery and are experienced in supporting clinical research. They helped to design the trial and advised us which patient outcomes to measure. They will help write patient facing documents for the trial, and the results summary for participating patients and the public. Our proposal has strong support from Royal College of Anaesthetists Patient, Carer & Public Involvement & Engagement group._x000D_ _x000D_ DISSEMINATION: The VITAL trial will define the optimal choice of anaesthesia for 300 million patients having surgery worldwide every year. We will disseminate our findings widely, working with our patient co-applicants to produce patient accessible summaries. We will make recommendations for patient care to the Royal Colleges of Anaesthetists and Surgeons.

Lay abstract: RESEARCH QUESTION: In adult patients (aged 50 and over) undergoing major non-cardiac surgery, does total intravenous anaesthesia (TIVA) lead to improved patient outcomes compared to inhalational anaesthesia?_x000D_ _x000D_ BACKGROUND: More than 1.5 million major non-cardiac surgeries are performed in the NHS each year. The two main anaesthetic techniques are inhalational anaesthesia (patient inhales volatile anaesthetic gases) and TIVA (patient receives intravenous infusion of anaesthetic drug). Inhalational anaesthesia is historically more popular, but many anaesthetists are changing to TIVA on the basis of low-quality data on cancer recurrence and greenhouse gas effects. There has been one large trial for patients undergoing cardiac surgery but this involves specialist anaesthesia and peri-operative care which differs completely to non-cardiac surgery. There is little clinical data to describe the benefit and harms of either technique for patients undergoing non-cardiac surgery. The VITAL trial will provide robust generalisable data comparing each technique in terms of patient recovery, survival and safety._x000D_ _x000D_ AIM: To conduct a large data-efficient randomised trial comparing the clinical and cost effectiveness of TIVA and inhalational anaesthesia._x000D_ _x000D_ OBJECTIVES:_x000D_ 1. To test whether TIVA is superior to inhalational anaesthesia in terms of days alive and at home at 30 days (DAH30), survival and quality of recovery amongst patients undergoing major non-cardiac surgery._x000D_ 2. To evaluate the safety of TIVA._x000D_ 3. To assess the cost-effectiveness of TIVA._x000D_ _x000D_ METHODS:DESIGN: Multi-centre pragmatic randomised trial. We have partnered with the Perioperative Quality Improvement Programme (PQIP), a large national cohort study recruiting patients undergoing major non-cardiac surgery. VITAL will use the PQIP data collection procedures to maximise efficiency and reduce research burden. SETTING: 2500 patients undergoing major non-cardiac surgery in 40 NHS hospitals. INTERVENTION: Patients will be randomised to either TIVA or inhalational anaesthesia. OUTCOME MEASURES: The primary outcome is Days alive and at home at 30 days. Secondary outcomes: Days alive and at home at 90 days (DAH90); Mortality at 30 days, 90 days and six months; Quality of recovery after anaesthesia; Patient satisfaction with anaesthesia; postoperative complications; Accidental awareness under anaesthesia; Health resource use and health-related quality of life. SWAT: Rapid qualitative study of patient consent to examine ways of co-recruiting and consenting patients to complementary studies and explore patient, carer and staff views and experiences with different recruitment approaches._x000D_ _x000D_ TIMELINE FOR DELIVERY: The trial will start on 1st November 2020 and run for 54 months. Month 0-6: Ethics, regulatory approvals and data linkage agreements. Month 6-12: internal pilot and SWAT. Month 13-42: Patient recruitment. Month 43-48: Complete patient follow-up, data cleaning. Months 49-54: Data analysis, scientific reports, plan dissemination._x000D_ _x000D_ IMPACT AND DISSEMINATION: VITAL results will be a robust evaluation of clinical and cost effectiveness of intravenous and inhalational anaesthesia for patients undergoing major non-cardiac surgery. Dissemination will include an HTA monograph, publication in high-impact journal, and a patient-centered dissemination strategy to ensure our findings inform clinical guidelines and are accessible to patients and the public.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: GENERIC HEALTH RELEVANCE