British journal of anaesthesia
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Variability is high in predicted propofol concentrations during clinical anaesthesia titrated by target-controlled infusion (TCI) to maintain a processed EEG parameter (bispectral index [BIS]) within a specified range. We have shown that the potential for improving the pharmacokinetic model is minimal. The drug titration paradox revealed that titration challenges the classical relationship between drug dose and effect in both individuals and the population. We hypothesised that dynamic factors during surgery beyond the static genetic, epigenetic, and other factors such as age, height, and weight affect the necessary dose. We compared the variability of measured end-tidal sevoflurane concentrations with predicted effect-site propofol concentrations when titrated to a BIS range of 40-60, with the hypothesis that the variability in measured sevoflurane concentrations would not be less than the variability in estimated propofol concentrations. ⋯ Improvements in prediction accuracy of pharmacokinetic models beyond that of those already in clinical use are unlikely to reduce variability in target anaesthetic concentrations across patients in clinical practice.
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Editorial Comment
Achieving a preoperative haemoglobin above 130 g L-1 may be more important in female than in male patients before cardiac surgery.
Sex-specific preoperative haemoglobin levels and the need for perioperative red cell transfusion in men and women are still debated. Cavalli and colleagues examined the appropriateness of World Health Organization (WHO) anaemia thresholds (haemoglobin <130 g L-1 for males and <120 g L-1 for females) in a retrospective cohort analysis of >6000 adult patients undergoing cardiac surgery with cardiopulmonary bypass. The authors concluded that the WHO anaemia threshold disproportionately disadvantages female cardiac surgery patients, and a preoperative haemoglobin level of at least 130 g L-1 should be targeted in all cardiac surgical patients regardless of sex.
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Editorial Comment
The art of chasing numbers in titration of anaesthetic dose.
There is no difference in between-patient variability of concentrations when comparing propofol and sevoflurane titrated to a bispectral index of 40-60. There is about a 300% variation in hypnotic concentration between the bottom 5% and top 5% of the population. Anaesthesia titration cannot be based solely on measured or estimated drug concentrations.
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Editorial Comment
Similarities in consciousness occurring during sleep and sedation.
The subjective experiences of sedation or anaesthesia are underexplored. A recent study by Valli and colleagues (Br J Anaesth 2023; 131: 348-59) found similar frequency and content of recalled experiences after both non-rapid eye movement sleep and target-controlled infusions of propofol or dexmedetomidine titrated to verbal unresponsiveness. The authors find that the phenomenological similarities between consciousness during sleep and sedation mirror their physiological similarities. Intriguingly, in this small sample, conscious experience did not show a dose-dependent response suggesting other factors are important in determining the propensity for consciousness under sedation.