Pharmacokinetics and pharmacodynamics of propofol in cancer patients undergoing major lung surgery.

Despite the growing number of cancer cases and cancer surgeries around the world, the pharmacokinetics (PK) and pharmacodynamics (PD) of anesthetics used in this population are poorly understood. Patients operated due to cancer are usually in severe state and often require chemotherapy. It might affect the PK/PD of drugs used in this population. Therefore, in this study we explored the PK/PD of propofol in cancer patients having a major lung surgery. 23 patients that underwent a propofol-fentanyl total intravenous anesthesia were included in the analysis. A large set of demographic, biochemical and hemodynamic parameters was collected for the purpose of covariate analysis. Nonlinear mixed effect modeling in NONMEM was used to analyze the collected data. A three-compartment model was sufficient to describe PK of propofol. The anesthetic effect (AAI index) was linked to the propofol effect site concentrations through a sigmoidal E max model. A slightly higher value of clearance, a lower value of distribution clearance, and a decreased volume of peripheral compartment were observed in our patients, as compared with the literature values reported for healthy volunteers by Schnider et al. and by Eleveld et al. Despite these differences, both models led to a clinically insignificant bias of -8 and -1 % in concentration predictions, as reflected by the median performance error. The C e50 and propofol biophase concentration at the time of postoperative orientation were low and equaled 1.40 and 1.13 mg/L. The population PK/PD model was proposed for cancer patients undergoing a major lung surgery. The large body of studied covariates did not affect PK/PD of propofol significantly. The modification of propofol dosage in the group of patients under study is not necessary when TCI-guided administration of propofol by means of the Schnider model is used.

Lower preoperative fluctuation of heart rate variability is an independent risk factor for postoperative atrial fibrillation in patients undergoing major pulmonary resection.

OBJECTIVES: The following study presents a special independent atrial fibrillation (AF) risk factor-preoperative fluctuation of heart rate variability (HRV), as well as other perioperative AF risk factors in patients qualified for pneumonectomy and undergoing pneumonectomy or lobectomy for lung cancer. METHODS: The prospective study was performed in patients who had undergone anatomical resection for non-small-cell lung cancer. A total of 117 patients (92 men and 25 women) qualified for statistical research. In order to determine the risk factors, all patients were divided into two groups: Group A-98 patients without AF and Group B-19 patients with AF during the perioperative time. A number of different risk factors of AF have been analysed and further divided into preoperative, operative and postoperative. RESULTS: Postoperative AF occurred in 19 patients (16%), all of them were male. The patients with higher short-term HRV parameters (SD1, RMSSD), slower mean heart rate and those with a lower fluctuation of HRV-related parameters (HRV Afternoon, Night, Day (A/N/D)) before the operation, were more prone to AF. Postoperative risk of AF was higher in patients with a higher number of ventricular ectopic beats before the operation, a higher number of supraventricular and ventricular ectopic beats and a higher maximal heart rate after the operation. Statistical analysis revealed that male gender and the extent of pulmonary resection, particularly left pneumonectomy, constituted significant risk factors. AF was more often observed in patients who had ASA physical status score of III, in comparison with ASAI and ASAII patients. CONCLUSIONS: Along with other concomitant AF risk factors presented in this work, the evaluation of the fluctuation tendencies of HRV parameters should be taken into consideration before any major lung resection. The balance disturbance between the sympathetic and parasympathetic nervous systems is responsible for AF.

Comparative efficacy and usefulness of acebutolol and diltiazem for the prevention of atrial fibrillation during perioperative time in patients undergoing pulmonary resection.

BACKGROUND: Postthoracic surgery atrial fibrillation (AF) is the most frequently occurring arrhythmia. Strategies for preventing AF have been amply evaluated, but currently there are no clearly defined guidelines for treatment of AF after thoracic surgery. METHODS: The study was prospective and randomized controlled trial. Acebutolol and diltiazem versus placebo were compared, among 117 patients postpneumonectomy or lobectomy at the Thoracosurgery Clinic, Poznan University of Medical Sciences in Poland. Patients who were enrolled in the study were randomly assigned to one of the three groups: those who received acebutolol (Group 1) or diltiazem (Group 2) and compared with patients without antiarrhythmic drugs (Group 0). Each group consisted of 39 patients. The patients were continuously monitored postoperatively with 24 ECG (Holter monitor) in the intensive care unit. RESULTS: In patients receiving acebutolol AF occurred in 5% compared with 23% of patients receiving diltiazem and 20% of patients receiving placebo (difference not statistically significant). CONCLUSIONS: Acebutolol and diltiazem appear to have been non-effective for the treatment or prevention of AF. Side effects were mild. In comparison to diltiazem, however, acebutolol had a beneficial effect on the circulatory system. Patients who had received acebutolol proved to have had fewer tachycardia episodes and supraventricular ectopy during the postoperative period. It seems that acebutolol can be useful, especially in patients with sympathetic activity dominance.