Additives in intravenous anesthesia modulate pulmonary inflammation in a model of LPS-induced respiratory distress.
BACKGROUND
It has been suggested that propofol with ethylenediaminetetraacetic acid (EDTA) can modulate the systemic inflammatory response. Prolonged higher levels of pulmonary inflammation are associated with poor outcome of patients with acute lung injury. In the present study, we hypothesized that pulmonary inflammation could be modulated by propofol with EDTA compared with propofol with sulfite.


METHODS
Respiratory distress was induced in rats (n=25) by intratracheal nebulization of lipopolysaccharide (LPS). After 24 h, animals were randomized to either propofol with EDTA (Propofol(EDTA)), propofol with sulfite (Propofol(sulfite)) or ketamine/midazolam (Ket/Mid); control animals received saline (n=30). Animals were ventilated for 4 h and blood gases were measured hourly. Bronchoalveolar lavage (BAL) was performed for cytokine analysis of: tumor necrosis factor (TNF), interleukin (IL)-6 and macrophage inflammatory protein (MIP)-2.


RESULTS
LPS led to increased pulmonary inflammation in all groups compared with the control groups. Gas exchange deteriorated over time only in the LPS Propofol(sulfite) group and was significantly lower than the Ket/Mid group. Only IL-6 was significantly higher in the LPS Propofol(sulfite) group compared with both the Ket/Mid group and the Propofol(EDTA) group.


CONCLUSIONS
Pulmonary IL-6 can be modulated by additives in systemic anesthesia.


CONCLUSIONS
This study demonstrates that pulmonary inflammation caused by direct lung injury can be modulated by intravenous anesthesia used in critically ill patients.
Haitsma
J J
JJ
Departments of Anesthesiology, Surgery and Neurosurgery, University of Rochester, School of Medicine and Dentistry, Rochester, NY, USA.
Lachmann
B
B
Papadakos
P J
PJ
D055371:Acute Lung Injury / Q000139:chemically induced / Q000517:prevention & control*; D000759:Adjuvants, Anesthesia / Q000633:toxicity*; D000771:Anesthesia, Intravenous; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054426:Chemokine CXCL2 / Q000378:metabolism; D004492:Edetic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism*; D007649:Ketamine / Q000008:administration & dosage / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity; D008874:Midazolam / Q000008:administration & dosage / Q000633:toxicity; D015742:Propofol / Q000008:administration & dosage* / Q000633:toxicity; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000517:prevention & control*; D013447:Sulfites / Q000633:toxicity*; D018746:Systemic Inflammatory Response Syndrome / Q000139:chemically induced*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000759:Adjuvants, Anesthesia; D054426:Chemokine CXCL2; C513296:Cxcl2 protein, rat; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013447:Sulfites; D014409:Tumor Necrosis Factor-alpha; D007649:Ketamine; D004492:Edetic Acid; D008874:Midazolam; D015742:Propofol