VITAL: TIVA and volatile maintenance produce the same 30-day recovery

VITAL asks a question that comes up in nearly every general anesthetic for major surgery: does maintaining anesthesia with a propofol infusion, rather than a volatile agent, change how older patients recover? For the outcome the trial was built around, the answer is no. Reading the result well means keeping three things apart: a precise null finding on days at home, smaller and less certain differences in early symptoms, and safety outcomes, including awareness, that were too rare to compare. Because the only two awareness cases were in the TIVA arm, this review also looks at what the evidence and guidance say about processed EEG (pEEG) monitoring during TIVA.

What the trial asked and why it matters

TIVA use has grown over the past 20 years, partly because of proposed links to cancer outcomes and partly because of concern about the environmental impact of volatile gases. The investigators point out that this growth has outpaced high-quality outcome data in noncardiac surgery. The largest earlier randomized comparison, MYRIAD, enrolled 5,400 patients having elective coronary bypass surgery. It was stopped for futility, with 1-year mortality of 2.8% in the volatile group and 3.0% in the TIVA group (relative risk 0.94; 95% CI, 0.69–1.29). Original report; MYRIAD.

VITAL tested whether TIVA was superior for days alive and at home at 30 days (DAH30). Patient partners chose this outcome as the measure that best reflects real-world recovery. The trial was not designed to prove the two techniques equivalent. Its result is still useful for that question, though, because the confidence interval around the primary estimate turned out to be very narrow.

How the study was designed

VITAL was a pragmatic, multicenter, open-label randomized trial at 49 UK National Health Service hospitals. It was embedded in the national Perioperative Quality Improvement Programme (PQIP), which supplied much of the outcome data. Patients were randomized between January 2022 and April 2024, and final follow-up was in October 2024. Eligible patients were at least 50 years old and scheduled for elective major noncardiac surgery under general anesthesia. Patients were excluded for a contraindication to either technique, an expectation of not surviving 30 days, inability to consent, or clinician refusal. Randomization (1:1) took place on the day of surgery, using minimization by surgical specialty, expected duration, cancer versus noncancer surgery, and Rockwood frailty category. Clinicians could not be blinded, and patients were not told their allocation. Original report, Methods; Published protocol.

The interventions were deliberately loose. Technique was defined by the intended main maintenance agent: intravenous propofol or a volatile agent. No minimum dose was set, and induction, airway, analgesia, and monitoring were left to the treating team. The protocol did not require depth-of-anesthesia monitoring in either arm and did not count interruptions shorter than 20 minutes as crossover. The sample of 2,500 gave 90% power to detect a 1-day difference in DAH30. A secondary noninferiority analysis of 90-day mortality assumed a 3.8% event rate. Protocol, interventions and sample size.

In practice, the two arms received different anesthetic bundles, not just different hypnotics. The table below comes from the original report's Table 2. Original report, Table 2.

Results

The participants' mean age was 67 years, and 55% were male. Three-quarters (75.4%) had cancer surgery, 72.1% had intra-abdominal surgery, and 98.1% had operations expected to last at least 2 hours. Most (80.5%) were rated as well on the frailty scale. One patient withdrew all consent after randomization. The primary analysis included 1,225 TIVA patients and 1,221 volatile patients. Original report, Results.

The absolute difference in mean DAH30 was 0.01 days (95% CI, −0.52 to 0.54). The investigators set the minimum clinically important difference at 3 days, so the interval rules out the 1-day effect the trial was powered to find as well as any clinically meaningful difference. A per-protocol analysis gave the same answer. No subgroup differences were apparent. Original report, Table 3 and Results.

On the Bauer questionnaire at day 1, TIVA patients reported less thirst (73.8% vs 78.2%), less hoarseness (47.6% vs 54.2%), and less nausea or vomiting (26.8% vs 36.1%). These were exploratory findings, and the analysis did not adjust for multiple comparisons. There were two certain or probable cases of unintentional awareness, both in the TIVA arm. Original report, Table 3. The published report does not detail those cases in the main text; any further description would need the journal supplement. A companion within-trial economic evaluation found similar 6-month costs and quality-adjusted life years in the two groups. Economic evaluation.

Strengths and limitations

VITAL's strengths are its size, concealed randomization with minimization, about 96% adherence in both arms, very little missing primary-outcome data, and an objective, patient-chosen primary outcome. The precision of the DAH30 estimate is its most useful feature. The limitations are just as important for applying it:

• Open-label delivery. The authors note that the unblinded design may have influenced patient-reported outcomes, which is where the TIVA advantages appeared. Mortality, length of stay, and readmission are less vulnerable to this bias.
• UK practice. Care followed NHS pathways, with regional techniques in 78% of patients and high-dependency unit admission in about 29% of each arm. US length-of-stay patterns, staffing, and monitoring habits may differ.
• Population. Only patients aged 50 or older having elective surgery were enrolled. Cardiac and nonmajor surgery were excluded, frail patients were only 4% of each arm, and emergency surgery was not studied.
• A blunt primary outcome. DAH30 counts any place other than an acute hospital as home. It reflects discharge and readmission, not functional recovery, and the authors note it can be shaped by local rehabilitation pathways.
• Questions not addressed. Three-quarters of patients had cancer surgery, but recurrence and disease-free survival were not measured. Environmental impact was not measured either.
• Rare events. Ninety-day mortality was far below the 3.8% assumed in planning, so mortality comparisons are imprecise. Two awareness cases cannot establish a difference between techniques. The authors point to a planned individual-patient meta-analysis with the US THRIVE trial.

THRIVE's two-center feasibility pilot randomized 300 US adults having elective noncardiac surgery. It reported 95% adherence in the TIVA arm, 99% in the inhaled arm, and complete modified Brice awareness screening, which supports a planned trial of about 13,000 patients. THRIVE pilot. Separately, the treatment bundles differed: TIVA patients got more opioid infusions and more depth monitoring. The early symptom differences should therefore be attributed to the TIVA approach as practiced in these hospitals, not to propofol alone.

Processed EEG when the maintenance drug cannot be measured

Why TIVA carries a distinct awareness risk. With a volatile agent, the end-tidal concentration confirms that the drug is reaching the patient. No such measurement exists during TIVA. Association of Anaesthetists/SIVA TIVA guideline. If propofol delivery is interrupted, for example by disconnection between the tubing and the cannula, the pump may still show normal delivery. NAP5 lists cannula disconnection or "tissuing" (subcutaneous infusion), disconnection at the pump or an intermediate connection, a paused pump or low battery, occlusion, and backtracking of propofol into a fluid line. NAP5, Chapter 18. The TIVA guideline also describes awareness when a propofol syringe was placed in a pump already programmed for remifentanil. It warns that subcutaneous delivery through an antecubital cannula may be hard to detect. TIVA guideline, practical aspects.

What NAP5 found. NAP5, the UK and Ireland national audit of accidental awareness from the Royal College of Anaesthetists and the Association of Anaesthetists of Great Britain and Ireland, estimated an incidence of about 1:19,600 anesthetics. The rate was about 1:8,200 with neuromuscular blockade and about 1:135,900 without it. NAP5 summary. Compared with national activity data, cases involving propofol infusion for maintenance were overrepresented roughly twofold. Of 27 TIVA or volatile-to-TIVA cases (excluding intermittent boluses), 25 (93%) involved a neuromuscular blocker. NAP5 recommended considering depth monitoring for TIVA with neuromuscular blockade, at conversion from volatile to TIVA, and during transfer. NAP5, Chapter 18.

What current UK guidance says. The 2018 Association of Anaesthetists and Society for Intravenous Anaesthesia guideline (published in Anaesthesia in 2019) recommends a pEEG monitor whenever a neuromuscular blocker is used with TIVA. Monitoring should start before the blocker is given and continue until nerve-stimulator monitoring confirms full recovery. The guideline also recommends lowering the threshold for pEEG when the cannula cannot be seen. TIVA guideline. The 2021 monitoring standards make this a minimum standard. They state that pEEG "should be used" for TIVA with a neuromuscular blocker, from before induction until full recovery from blockade, and that quantitative neuromuscular monitoring should continue until a train-of-four ratio above 0.9. Association of Anaesthetists monitoring standards 2021.

What the trials show, and what they don't. B-Aware randomized 2,463 high-risk adults having relaxant general anesthesia. Awareness occurred in 2 patients in the BIS-guided group and 11 in the routine-care group. B-Aware. B-Unaware (2 vs 2 definite cases) and BAG-RECALL (7/2,861 vs 2/2,852) did not show that a BIS protocol was superior. However, both compared BIS against end-tidal agent alerts, a comparator that does not exist during TIVA. B-Unaware; BAG-RECALL. Two trials looked at depth monitoring for other outcomes. In Balanced, targeting BIS 50 rather than 35 in 6,644 older high-risk patients did not change 1-year mortality (6.5% vs 7.2%; HR 0.88, 0.73–1.07). That trial was conducted with titrated volatile anesthesia. Balanced. In ENGAGES, EEG guidance reduced volatile exposure and EEG suppression but not delirium (26.0% vs 23.0%). ENGAGES. Taken together, these trials support pEEG as a safeguard against underdosing during TIVA. They do not show that targeting a particular index value improves longer-term outcomes.

Practical pEEG points for CRNAs:

• Know your device's range. B-Unaware and BAG-RECALL targeted BIS 40–60. Masimo recommends PSI 25–50 for general anesthesia maintenance. These are reference ranges, not targets that suit every patient. B-Unaware; Masimo PSI white paper.
• Don't rely on the number alone. The TIVA guideline advises reading the index together with the EEG waveform, signal quality, EMG activity, and burst suppression. TIVA guideline.
• Learn the propofol signature. During maintenance, propofol produces alpha (8–12 Hz) and slow (0.1–1 Hz) oscillations. Burst suppression, alternating activity and electrical silence, appears as vertical lines on the spectrogram. Older patients can go straight into burst suppression after an induction bolus. Purdon et al., Part I.
• Expect smaller signals in older patients. In patients aged 70–90 years, EEG amplitude was about two to three times lower, alpha power dropped more than slow power, and burst suppression was more likely. The authors conclude that commercial indices, which do not account for age, are likely to be inaccurate in elderly patients. Purdon et al., ageing brain.
• Anticipate ketamine and nitrous oxide. Both tend to produce faster oscillations that raise index values at clinical doses, and the TIVA guideline warns of paradoxical index increases with ketamine. Dexmedetomidine can do the opposite and lower the index. Purdon et al., Part I; TIVA guideline.
• Watch for EMG artifact. High EMG activity can be misread as EEG and falsely raise BIS, even when no artifact is flagged. Dahaba.
• Pay most attention at transitions. Keep the cannula visible when practical, load the syringe before programming the pump, and check the cannula as soon as the patient's response seems weaker than expected. Be especially careful during transfers and when switching from volatile to TIVA. TIVA guideline; NAP5, Chapter 18.

Bottom line for practice

For older patients having elective major noncardiac surgery, VITAL shows that TIVA and volatile maintenance lead to the same 30-day recovery. Choosing TIVA does not trade away days at home, and choosing a volatile agent does not cost them either. Patients at high risk of postoperative nausea and vomiting may still have reason to prefer TIVA, but that advantage comes from exploratory, unblinded data. When TIVA is used with a neuromuscular blocker, pEEG combined with careful attention to the infusion line is the UK minimum standard and a sensible safeguard everywhere. VITAL cannot settle cancer outcomes, environmental impact, or rare harms such as awareness.