The inhibitory effects of thiopental, midazolam, and ketamine on human neutrophil functions.
We investigated the effect of thiopental, midazolam, and ketamine (at clinically relevant concentrations and at 0.1 and 10 times these concentrations) on several aspects of human neutrophil functions. The three intravenous (i.v.) anesthetics significantly decreased chemotaxis, phagocytosis, and reactive oxygen species (ROS) (O2-, H2O2, OH) production of neutrophils in a dose-dependent manner. At clinically relevant concentrations, thiopental and midazolam significantly depressed these neutrophil functions. However, ketamine at the clinical plasma concentration did not impair chemotaxis or ROS production, except phagocytosis. In contrast, the three anesthetics had no effect on the levels of ROS production by a cell-free ROS generating system. In addition, intracellular calcium concentrations in neutrophils stimulated by N-formyl-L-methionyl-L-leucil-L-phenylalanine were dose-dependently decreased in the presence of each of the three anesthetics. The suppression of an increase in intracellular calcium concentrations may be responsible for the inhibition of neutrophil functions by the i.v. anesthetics.


CONCLUSIONS
Neutrophils play an important role in the antibacterial host defense system and autotissue injury. We found that thiopental and midazolam (but not ketamine), at clinically relevant concentrations, impaired the neutrophil functions.
Nishina
K
K
Department of Anaesthesiology, Kobe University School of Medicine, Japan.
Akamatsu
H
H
Mikawa
K
K
Shiga
M
M
Maekawa
N
N
Obara
H
H
Niwa
Y
Y
D000777:Anesthetics / Q000009:adverse effects*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007649:Ketamine / Q000009:adverse effects*; D008874:Midazolam / Q000009:adverse effects*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013874:Thiopental / Q000009:adverse effects*
D000777:Anesthetics; D017382:Reactive Oxygen Species; D007649:Ketamine; D013874:Thiopental; D008874:Midazolam; D002118:Calcium