Effect of the administration rate on the biological responses to a fixed dose of endotoxin in the anesthetized pig.
There have been difficulties to demonstrate a relationship between endotoxin concentration and clinical response. One hypothesis for this difficulty might be that a fast increase in endotoxin concentration elicits a stronger biological response than a more gradual one of the same dose. The aim of the present study was to investigate the existence of such a response. Eighteen randomized pigs were given the same amount of endotoxin either with an initial infusion rate of 4 microg kg(-1) h(-1), which after 1 h was tapered to 0.5 microg kg(-1) h(-1), and after 2 h to 0.063 microg kg(-1) h(-1) (group I), or with a reverse escalating order with the lowest infusion rate given first (group II). After 3 h, the endotoxin infusion was stopped, and the pigs were observed for another 3 h. The responses in TNF-alpha, core temperature, leukocytes, platelets, MAP, left ventricular stroke work index, mixed venous saturation, base excess, pH, and pulmonary compliance were greater in group I than in group II, whereas the IL-6 response did not differ between groups. The biological responses of inflammation, hypotension, hypoperfusion, and organ dysfunction are increased if the organism is exposed to a fixed amount of endotoxin more quickly.
Section of Anesthesiology & Intensive Care, Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden. mlipcsey@eml.cc
Miklós
M
Lipcsey
Anders
A
Larsson
Mats B
MB
Eriksson
Jan
J
Sjölin
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity*; D007022:Hypotension / Q000139:chemically induced; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D011897:Random Allocation; D012772:Shock, Septic / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D013552:Swine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha