Cardiopulmonary bypass changes the physiology of anesthesia in ways that make routine volatile anesthetic dosing less predictable. Hemodilution, nonpulsatile flow, altered gas exchange, cooling, and changing cerebral perfusion can all affect how anesthetic agents behave during cardiac surgery. In this systematic review and meta-analysis, the authors set out to answer a practical clinical question: what end-tidal sevoflurane concentration is most likely to maintain adequate anesthetic depth during cardiopulmonary bypass when bispectral index, or BIS, is kept in the commonly accepted range of 40 to 60?
The paper followed PRISMA methods and was registered in PROSPERO, which strengthens transparency in study design. The authors searched PubMed, Embase, and the Cochrane Library for eligible prospective studies involving adult cardiac surgery patients receiving sevoflurane during bypass. Their primary outcome was the mean end-tidal sevoflurane concentration, abbreviated ETsevo, associated with a BIS range of 40 to 60. To handle repeated measurements within studies, they used a three-level random-effects meta-analysis with robust variance estimation, an approach chosen because several studies reported multiple effect sizes at different temperatures or time points during bypass.
The search identified 60 records, which were reduced to 45 after duplicates were removed. After screening and full-text review, five prospective studies met inclusion criteria. These studies included a total of 129 patients, with sample sizes ranging from 9 to 50. Most participants underwent coronary artery bypass grafting, though some studies also included mitral valve replacement, aortic valve replacement, or mixed elective cardiac procedures. The mean patient age across studies was 62 years, and the median body temperature during cardiopulmonary bypass was 32.9 degrees Celsius, reflecting the mild-to-moderate hypothermic conditions often used in clinical practice.
A challenge in the dataset was that not every study reported anesthetic delivery the same way. Three studies reported end-tidal sevoflurane concentrations directly, one reported inspired concentrations only, and another reported both inspired and end-tidal values. Where needed, the authors converted inspired concentrations into estimated end-tidal concentrations using a reference conversion ratio. This matters because the meta-analysis aimed to generate a clinically useful pooled end-tidal target rather than a mix of delivery measures that are harder to compare at the bedside.
The main result was straightforward and clinically relevant. The pooled estimated ETsevo concentration required to maintain BIS values between 40 and 60 during cardiopulmonary bypass was 0.88 vol%. The confidence interval was wide, from 0.29 to 1.46 vol%, and heterogeneity was substantial, with an I2 of 87.6%. Even so, the finding gives anesthesiologists a practical reference value in an area where dosing has not been well standardized. The authors further note that for patients in their 60s, this level corresponds to roughly 0.53 to 0.58 minimum alveolar concentration, or MAC, suggesting that bypass may require lower volatile anesthetic concentrations than many clinicians might expect outside the bypass period.
One of the most interesting findings was the effect of age. Older patients appeared to need less sevoflurane to achieve the same BIS-defined anesthetic depth. In the binary moderator analysis, studies with a mean patient age above 62 years required 0.45 vol% less ETsevo than younger groups. In sensitivity analysis, the authors found that required sevoflurane concentration fell by 0.05 vol% for each additional year of age. This result supports the broader anesthetic principle that aging reduces inhalational anesthetic requirements, and it suggests that clinicians may need to titrate more conservatively in older cardiac surgery patients on bypass.
By contrast, body temperature did not significantly alter sevoflurane requirements in this analysis. The moderator effect was 0.26 vol%, but the confidence interval crossed zero and the p value was not significant. The authors suggest that this may reflect the relatively narrow temperature range in the included studies, where deep hypothermia was uncommon. They also note that blood pressure and cerebral autoregulation may influence BIS readings during bypass, which could blur a true temperature effect when anesthetic dosing is guided by processed EEG rather than by pharmacokinetic measures alone.
Study quality was mixed but not poor. Using ROBINS-I, the authors judged three studies to have moderate risk of bias and two to have low risk, with no study categorized as high risk. Still, the certainty of evidence for the pooled mean sevoflurane requirement was rated very low because of serious heterogeneity, imprecision, and limitations inherent to the included studies. That means the result is useful as a directional clinical estimate, but not yet strong enough to serve as a definitive dosing standard for all cardiopulmonary bypass cases.
Overall, this article contributes a helpful evidence-based benchmark for anesthetic management during bypass. Its central message is that an ETsevo concentration of about 0.88 vol% may maintain appropriate BIS-guided anesthetic depth during cardiopulmonary bypass, with lower requirements in older patients and no clearly demonstrated independent effect of body temperature in the available dataset. For clinicians, that makes the paper most valuable as a dosing reference and as a reminder that age-adjusted titration may matter more than temperature alone in this setting. For researchers, it highlights the need for larger, standardized, outcome-linked trials to refine volatile anesthetic dosing during cardiac surgery.
