SummaryThe aim of this study was to investigate the pharmacokinetics of sevoflurane uptake into the brain and body by comparing sevoflurane concentrations in internal jugular-bulb blood (Jsev), arterial blood (Asev) and pulmonary arterial blood (PAsev) over a fixed inspired sevoflurane concentration. Ten patients (aged 51-73 years), undergoing coronary artery bypass grafting surgery were enrolled in this study. They were anaesthetised using a constant 3.5% inspired sevoflurane concentration (C I sev) during the first hour of anaesthesia. During constant volume-controlled ventilation, we measured C I sev and end-tidal sevoflurane (C E sev) using infrared analysis. The sevoflurane concentration in the blood was analysed using gas chromatography, and cardiac output was measured using an Opti-Q pulmonary artery catheter. We found that it took 40 min for the brain concentration to equilibrate with arterial blood (Asev). Both C I sev-C E sev and Asev-PAsev gradients persisted during the study period. There was no further uptake of sevoflurane into the brain after 40 min; however, there was near-constant uptake into the body. Sevoflurane is widely used in clinical anaesthesia because of its relative lack of airway irritation or myocardial suppression effects. It has rapid induction and emergence characteristics compared with other available inhalation anaesthetic agents [1][2][3]. Sevoflurane, has a low blood ⁄ gas solubility coefficient and has been thought to have rapid uptake pharmacokinetics in human volunteers [4,5]. The brain ⁄ blood partition coefficient of volatile anaesthetics is important in determining the rate of brain tissue wash-in and wash-out, and wash-in and wash-out characteristics are the main determinants of the rate of induction of and recovery from anaesthesia.The uptake pattern of sevoflurane remains poorly quantified and its uptake into the brain and body has not yet been fully elucidated. However, it has been shown that there is a well-defined relationship between volatile anaesthetic partial pressure in the brain and anaesthetic effects [6,7]. The aim of inhalation anaesthesia is to produce, safely and conveniently, a partial pressure adequate for anaesthesia. The aim of this study was to establish the time required for sevoflurane changes in arterial blood (Asev), right internal jugular-bulb blood (Jsev) and pulmonary arterial blood (PAsev) under constant inspired concentrations of sevoflurane during the first hour of anaesthesia. The primary purpose of this study was to explore the relationship among end-tidal sevoflurane concentrations (C E sev), Asev, PAsev and Jsev at a fixed inspired sevoflurane concentration during the first hour of sevoflurane anaesthesia. Second, we compared the different uptake patterns of sevoflurane in the Anaesthesia, 2003, 58, pages 951-956

SummaryThe aim of this study was to investigate the pharmacokinetics of desflurane uptake into the brain and body by comparing desflurane concentrations in internal jugular-bulb blood (Jdes), arterial blood (Ades) and pulmonary arterial blood (PAdes) at a fixed inspired desflurane concentration. Thirteen patients (aged 42-72 years) undergoing coronary artery bypass grafting surgery were enrolled in this study. They were anaesthetised using a constant 5% inspired desflurane concentration (C I des) during the first hour of anaesthesia. Under constant volume-controlled ventilation, C I des and end-tidal desflurane (C E des) were measured with an infrared analyser. The desflurane concentration in the blood was analysed using gas chromatography, and cardiac output was measured using an Opti-Q pulmonary artery catheter. It took 24 min for the Jdes to equilibrate with Ades. Both C I des-C E des and Ades-PAdes gradients persisted during the study period. There was no further uptake of desflurane into the brain after 24 min but there was near-constant uptake into the body.

We investigated the effect of the inspired isoflurane concentration (C_Iiso) on body uptake by comparing the isoflurane concentration in the pulmonary artery blood (PAiso) and that in the arterial blood (Aiso) in 16 patients undergoing coronary artery bypass grafting surgery during the 1st, hour of isoflurane anesthesia. The patients received standardized anesthetics consisting of fentanyl and thiopental and were then allocated to receive either 1% or 2% C_Iiso (n = 8 in each group). C_Iiso and end-tidal isoflurane concentration (C_Eiso) were measured by infrared analysis, and Aiso and PAiso were analyzed by gas chromatography. The cardiac output was measured by thermodilution by use of a pulmonary artery catheter. The body tissue could be represented by the gradient C_Iiso–C_Eiso or Aiso–PAiso over time, respectively. The 2% inspired isoflurane group had twice the gradients (either C_Iiso–C_Eiso or Aiso-PAiso) than the 1% inspired isoflurance group. Additionally, both C_Iiso–C_Eiso and Aiso–PAiso were nearly constant over the hour of the study. The inspired concentration-dependent and near- constant uptake of isoflurane over time has important implications which enable us to apply the uptake pattern of isoflurane to clinical practice.

Investigation of isoflurane washout from the human body and brain provides more precise information about elimination in anesthesia. The elimination pattern of isoflurane remains poorly quantified, and therefore this study tried to clarify the pharmacokinetic pattern of isoflurane elimination. Sixteen patients (aged 48–78 years), undergoing coronary arterial bypass grafting surgery were enrolled in this study. Sixty minutes prior to the end of surgery, we kept a fixed 2% inspired isoflurane in 6,000 ml min^–1 oxygen flow. Isoflurane supplement was then discontinued to study the 20-min isoflurane elimination. An infrared analyzer was used to determine both inspired isoflurane and end-tidal isoflurane. The isoflurane concentration in the internal jugular bulb blood, arterial blood and pulmonary arterial blood were analyzed by gas chromatography. Biexponential decay function was the best fitted for the end-tidal isoflurane- and arterial blood isoflurane-time curves. There were two distinct components, including initial 5-min fast component and the next 15-min slow component. Monoexponential decay function was the best fitted for the pulmonary arterial blood- and jugular bulb blood-time curves. During elimination, the initial washout of isoflurane from functional residual capacity of lungs is reflected in the fast component of the isoflurane concentration time curves. The later slow component is dominated by the tangible manifestation of physiological membrane barriers, including the existence of alveoli-pulmonary capillary, blood-brain barriers.

Objective:Estrogen has the potential to influence brain physiology implicated in dementia pathogenesis. Hormone replacement therapy (HRT) might be expected to influence the risk of dementia. Observational data indicated that HRT was associated with reductions in dementia risk, but experimental evidence demonstrates that HRT increases the incidence of dementia. To determine the effect of HRT on risk of dementia, a retrospective cohort study was performed using a nationwide claims dataset in Taiwan.Methods:A population-base longitudinal study was performed using data from the Longitudinal Health Insurance Database in Taiwan. A total of 35,024 women with HRT were enrolled as the exposed cohort and 70,048 women without HRT were selected on the basis of propensity matching as the comparison cohort. All of the subjects were followed up until the diagnosis of dementia, death, or at the end of December 31, 2013, whichever occurred first. Overall, the average duration of follow-up (±SD) in the HT and comparison cohort was 12.3(±2.3) and 12.2 (±2.4), respectively. The Cox proportional hazards regression models were conducted to produce hazard ratios (HRs) with 95% confidence intervals (CIs) to evaluate the association of HRT with the risk of dementia.Results:In the follow-up period, the cumulative incidence of dementia for the HRT cohort (20.04 per 1,000) was significantly higher than the corresponding cumulative incidence for the comparison cohort (15.79 per 1,000), resulting in an adjusted hazard ratio of 1.35 (95% CI, 1.13-2.62). There was an increased risk of dementia with a higher cumulative dose of HRT prescription (p for trend <0.0001).Conclusion:This cohort study documented that HRT was associated with an increased risk of dementia. The clinical implications of this study merit further investigations.