We appreciate the great interest of Dr. Yalcin and Dr. Aydogan in reading our article,1and we would like to thank them for their important comment regarding the different physiologic responses of propofol and its additives. Propofol has become one of the most widely administered drugs for induction and maintenance of anesthesia and for sedation in the intensive care unit. Therefore, we have chosen this substance as well to provide standardized total intravenous anesthesia in the control group of our clinical study. In patients who received total intravenous anesthesia with propofol, release of proinflammatory cytokines into the alveoli of the ventilated lung was more increased after one-lung ventilation and open thoracic surgery, in comparison with the administration of desflurane or sevoflurane in other patient groups. The time course of pulmonary cytokine release confirms previous clinical studies, which demonstrate an enhanced mediator expression during propofol anesthesia for thoracic surgery.2,3
However, highly lipid-soluble drugs such as propofol may also affect the inflammatory response. Propofol decreases granulocyte recruitment and neutrophil activation by reduction of polarization, chemotaxis, and inhibition of the respiratory burst in clinically used concentrations.4In addition, it exerts antioxidative properties, which may prevent the organism from oxidative stress.5The pronounced proinflammatory response should therefore not be interpreted as being increased by propofol administration in our study. This immune reaction was unquestionably diminished as well but to a lesser extent.6
Moreover, the additives EDTA and sodium metabisulfite are biologically active and are used to retard bacterial contamination in propofol formulations. Whereas sulfite supports lipid peroxidation in propofol emulsions7and increases proinflammatory interleukin-6 release in lipopolysaccharide-injured rat lungs,8antiinflammatory properties of EDTA may have beneficial effects in patients with sepsis and systemic inflammatory response syndrome. Accordingly, surgical intensive care unit patients who received propofol with EDTA had significantly reduced mortality rates in comparison with those who received propofol without EDTA.9In contrast, clinical variables and incidence of adverse events were not affected by propofol/EDTA in patients after cardiac surgery.10
The administration of propofol formulations with EDTA or sodium metabisulfite may thus increase the variability of the inflammatory response. For that reason, we used a single propofol formulation without EDTA or sulfite (Propofol-Lipuro 20 mg/ml, B. Braun Melsungen, Melsungen, Germany) in our study.1This preparation contains refined soybean oil, medium-chain triglycerides, glycerol, egg lecithin, and sodium oleate.
In conclusion, it is essential to take the immunomodulatory properties of different anesthetic drugs and their potential additives into account to avoid misinterpretation of clinical reports. However, the amount of reliable data on inflammatory effects of additive drugs is limited and often conflicting; therefore, more experimental and clinical studies are needed.