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.

Schilling T, Kozian A, Senturk M, Huth C, Reinhold A, Hedenstierna G, Hachenberg T: Effects of volatile and intravenous anesthesia on the alveolar and systemic inflammatory response in thoracic surgical patients. ANESTHESIOLOGY 2011; 115:65–74
De Conno E, Steurer MP, Wittlinger M, Zalunardo MP, Weder W, Schneiter D, Schimmer RC, Klaghofer R, Neff TA, Schmid ER, Spahn DR, Z'graggen BR, Urner M, Beck-Schimmer B: Anesthetic-induced improvement of the inflammatory response to one-lung ventilation. ANESTHESIOLOGY 2009; 110:1316–26
Schilling T, Kozian A, Kretzschmar M, Huth C, Welte T, Bhling F, Hedenstierna G, Hachenberg T: Effects of propofol and desflurane anaesthesia on the alveolar inflammatory response to one-lung ventilation. Br J Anaesth 2007; 99:368–75
O'Donnell NG, McSharry CP, Wilkinson PC, Asbury AJ: Comparison of the inhibitory effect of propofol, thiopentone and midazolam on neutrophil polarization in vitro  in the presence or absence of human serum albumin. Br J Anaesth 1992; 69:70–4
Allaouchiche B, Debon R, Goudable J, Chassard D, Duflo F: Oxidative stress status during exposure to propofol, sevoflurane and desflurane. Anesth Analg 2001; 93:981–5
Marik PE: Propofol: An immunomodulating agent. Pharmacotherapy 2005; 25: 28S–33S
Baker MT, Dehring DJ, Gregerson MS: Sulfite supported lipid peroxidation in propofol emulsions. ANESTHESIOLOGY 2002; 97:1162–7
Haitsma JJ, Lachmann B, Papadakos PJ: Additives in intravenous anesthesia modulate pulmonary inflammation in a model of LPS-induced respiratory distress. Acta Anaesthesiol Scand 2009; 53:176–82
Herr DL, Kelly K, Hall JB, Ulatowski J, Fulda GJ, Cason B, Hickey R, Nejman AM, Zaloga GP, Teres D: Safety and efficacy of propofol with EDTA when used for sedation of surgical intensive care unit patients. Intensive Care Med 2000; 26 Suppl 4:S452–62
Wahr J, Vender J, Gilbert HC, Spiess B, Horrow JC, Maddi R: Effect of propofol with and without EDTA on haemodynamics and calcium and magnesium homeostasis during and after cardiac surgery. Intensive Care Med 2000; 26 Suppl 4:S443–51