Quantification of exhaled propofol is not feasible during single-lung ventilation using double-lumen tubes: A multicenter prospective observational trial

Background

Volatile propofol can be measured in exhaled air and correlates to plasma concentrations with a time delay. However, the effect of single-lung ventilation on exhaled propofol is unclear. Therefore, our goal was to evaluate exhaled propofol concentrations during single-lung compared to double-lung ventilation using double-lumen tubes.

Methods

In a first step, we quantified adhesion of volatile propofol to the inner surface of double-lumen tubes during double- and single-lumen ventilation in vitro. In a second step, we enrolled 30 patients scheduled for lung surgery in two study centers. Anesthesia was provided with propofol and remifentanil. We utilized left-sided double-lumen tubes to separately ventilate each lung. Exhaled propofol concentrations were measured at 1-min intervals and plasma for propofol analyses was sampled every 20 min. To eliminate the influence of dosing on volatile propofol concentration, exhalation rate was normalized to plasma concentration.

Results

In-vitro ventilation of double-lumen tubes resulted in increasing propofol concentrations at the distal end of the tube over time. In vitro clamping the bronchial lumen led to an even more pronounced increase (Δ AUC +62%) in propofol gas concentration over time. Normalized propofol exhalation during lung surgery was 31% higher during single-lung compared to double-lung ventilation.

Conclusion

During single-lung ventilation, propofol concentration in exhaled air, in contrast to our expectations, increased by approximately one third. However, this observation might not be affected by change in perfusion-ventilation during single-lung ventilation but rather arises from reduced propofol absorption on the inner surface area of the double-lumen tube. Thus, it is only possible to utilize exhaled propofol concentration to a limited extent during single-lung ventilation.

Registration of Clinical Trial

DRKS-ID DRKS00014788 ( www.drks.de ).     

Praxis der perioperativen Prävention von Phantomschmerz: eine deutschlandweite Umfrage

Die Anaesthesiologie - Phantomschmerzen haben eine hohe Prävalenz nach Majoramputationen und sind mit einer zusätzlichen Einschränkung der Lebensqualität verbunden....     

High central venous saturation after cardiac surgery is associated with increased organ failure and long-term mortality: an observational cross-sectional study

IntroductionCentral venous saturation (S_cvO₂) monitoring has been suggested to address the issue of adequate cardiocirculatory function in the context of cardiac surgery. The aim of this study was to determine the impact of low (L) (<60%), normal (N) (60%-80%), and high (H) (>80%) S_cvO₂ measured on intensive care unit (ICU) admission after cardiac surgery.MethodsWe conducted a retrospective, cross-sectional, observational study at three ICUs of a university hospital department for anaesthesiology and intensive care. Electronic patient records of all adults who underwent cardiac surgery between 2006 and 2013 and available admission measurements of S_cvO₂ were examined. Patients were allocated to one of three groups according to first S_cvO₂ measurement after ICU admission: group L (<60%), group N (60%-80%), and group H (>80%). Primary end-points were in-hospital and 3-year follow-up survival.ResultsData from 4,447 patients were included in analysis. Low and high initial measurements of S_cvO₂ were associated with increased in-hospital mortality (L: 5.6%; N: 3.3%; H: 6.8%), 3-year follow-up mortality (L: 21.6%; N: 19.3%; H: 25.8%), incidence of post-operative haemodialysis (L: 11.5%; N: 7.8%; H: 15.3%), and prolonged hospital length of stay (L: 13 days, 9–22; N: 12 days, 9–19; H: 14 days, 9–21). After adjustment for possible confounding variables, an initial S_cvO₂ above 80% was associated with adjusted hazard ratios of 2.79 (95% confidence interval (CI) 1.565-4.964, P <0.001) for in-hospital survival and 1.31 (95% CI 1.033-1.672, P = 0.026) for 3-year follow-up survival.ConclusionsPatients with high S_cvO₂ were particularly affected by unfavourable outcomes. Advanced haemodynamic monitoring may help to identify patients with high S_cvO₂ who developed extraction dysfunction and to establish treatment algorithms to improve patient outcome in these patients.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-0889-6) contains supplementary material, which is available to authorized users.     

Kariesexkavation: Ansätze und Strategien

Der Freie Zahnarzt -     

Different in vitro and in vivo tools for elucidating the human metabolism of alpha‐cathinone‐derived drugs of abuse

In vitro and in vivo experiments are widely used for studying the metabolism of new psychoactive substances (NPS). The availability of such data is required for toxicological risk assessments and development of urine screening approaches. This study investigated the in vitro metabolism of the 5 pyrrolidinophenone‐derived NPS alpha‐pyrrolidinobutyrophenone (alpha‐PBP), alpha‐pyrrolidinopentiothiophenone (alpha‐PVT), alpha‐pyrrolidinohexanophenone (alpha‐PHP), alpha‐pyrrolidinoenanthophenone (alpha‐PEP, PV8), and alpha‐pyrrolidinooctanophenone (alpha‐POP, PV9). First, they were incubated with pooled human liver microsomes (pHLM) or pooled human liver S9 fraction (pS9) for identification of the main phase I and II metabolites. All substances formed hydroxy metabolites and lactams. Longer alkyl chains resulted in keto group and carboxylic acid formation. Comparing these results with published data obtained using pHLM, primary human hepatocytes (PHH), and authentic human urine samples, PHH provided the most extensive metabolism. Second, enzyme kinetic studies showed that the initial metabolic steps were formed by cytochrome P450 isoforms (CYP) CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 resulting in pyrrolidine, thiophene or alkyl hydroxy metabolites depending on the length of the alkyl chain. The kinetic parameters indicated an increasing affinity of the CYP enzymes with increase of the length of the alkyl chain. These parameters were then used to calculate the contribution of a single CYP enzyme to the in vivo hepatic clearance. CYP2C19 and CYP2D6 were mainly involved in the case of alpha‐PBP and CYP1A2, CYP2C9 and CYP2C19 in the case of alpha‐PVT, alpha‐PHP, alpha‐PEP, and alpha‐POP.     

Allogeneic Blood Transfusion Does Not Affect Outcome After Curative Resection for Advanced Cholangiocarcinoma

Purpose

To assess the impact of perioperative blood transfusion on overall and disease-free survival in patients undergoing curative resection for cholangiocarcinoma.

Methods

In a single-center study, 128 patients undergoing curative resection for cholangiocarcinoma between 2001 and 2010 were assessed. The median follow-up period was 19 months. Transfused and nontransfused patients were compared by Cox regression and propensity score analyses.

Results

Overall, 38 patients (29.7 %) received blood transfusions. The patient characteristics were highly biased with respect to receiving transfusions (propensity score 0.69 ± 0.22 vs. 0.11 ± 0.16, p < 0.001). In the unadjusted analysis, blood transfusion was associated with a 105 % increased risk of mortality [hazard ratio (HR) 2.05, 95 % CI 1.19–3.51, p = 0.010]. In the multivariate (HR 1.14, 95 % CI 0.52–2.48, p = 0.745) and the propensity score-adjusted Cox regression (HR 1.02, 95 % CI 0.39–2.62, p = 0.974), blood transfusion had no influence on overall survival. Similarly, in the propensity score-adjusted Cox regression (HR 0.62, 95 % CI 0.24–1.58, p = 0.295), no relevant effect of blood transfusion on disease-free survival was observed.

Conclusions

To our knowledge, this is the first propensity score-based analysis providing compelling evidence that the worse oncological outcome after curative resection for advanced cholangiocarcinoma in patients receiving perioperative blood transfusions is caused by the clinical circumstances requiring the transfusions, not by the blood transfusions themselves.