• Miklós Lipcsey, Anders Larsson, Mats B Eriksson, and Jan Sjölin.
• Section of Anesthesiology & Intensive Care, Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden. mlipcsey@eml.cc
• Shock. 2008 Feb 1;29(2):173-80.

AbstractThere 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.

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