TY - JOUR

T1 - Influence of endotoxin-induced sepsis on the requirements of propofol-fentanyl infusion rate in pigs

AU - Bollen, Peter J A

AU - Nielsen, Bjørn J

AU - Toft, Palle

PY - 2007

Y1 - 2007

N2 - Endotoxin-induced sepsis in pigs is a recognized experimental model for the study of human septic shock. Generally, pigs are brought into general anaesthesia before sepsis is induced. It is our experience that drug dosages of propofol and fentanyl need to be reduced during endotoxin-induced sepsis, in order to prevent respiratory and cardiovascular depression, but the scientific evidence for this observation is lacking. Therefore, we measured the consumption of propofol and fentanyl at equal level of anaesthesia in pigs with (n = 5) and without (n = 5) endotoxin-induced sepsis, using the cerebral state index (CSI) as measure of anaesthetic depth. Infusion rates of propofol (P < 0.01) and fentanyl (P < 0.05) were significantly lower in septic pigs. Pigs with endotoxin-induced sepsis had an infusion rate of 2.2 mg/kg/hr (S.D. 0.5) for propofol and 12 microg/kg/hr (S.D. 2) for fentanyl, whereas healthy pigs had infusion rates of 3.5 mg/kg/hr (S.D. 0.6) and 17 microg/kg/hr (S.D. 4), respectively. CSI was equal in both groups throughout the experiment, and had a lowest average value of 47 (S.D. 10) at t = 30 in healthy pigs and reached a highest average value of 67 (S.D. 19) at t = 240 in pigs with endotoxin-induced sepsis. Anaesthetic depth was sufficient, assessed clinically, throughout the experiment in both groups. We concluded that the consumption of propofol and fentanyl was significantly reduced in pigs with endotoxin-induced sepsis. In the present study, we adjusted the level of anaesthesia according to clinical signs, and found good agreement with CSI.

AB - Endotoxin-induced sepsis in pigs is a recognized experimental model for the study of human septic shock. Generally, pigs are brought into general anaesthesia before sepsis is induced. It is our experience that drug dosages of propofol and fentanyl need to be reduced during endotoxin-induced sepsis, in order to prevent respiratory and cardiovascular depression, but the scientific evidence for this observation is lacking. Therefore, we measured the consumption of propofol and fentanyl at equal level of anaesthesia in pigs with (n = 5) and without (n = 5) endotoxin-induced sepsis, using the cerebral state index (CSI) as measure of anaesthetic depth. Infusion rates of propofol (P < 0.01) and fentanyl (P < 0.05) were significantly lower in septic pigs. Pigs with endotoxin-induced sepsis had an infusion rate of 2.2 mg/kg/hr (S.D. 0.5) for propofol and 12 microg/kg/hr (S.D. 2) for fentanyl, whereas healthy pigs had infusion rates of 3.5 mg/kg/hr (S.D. 0.6) and 17 microg/kg/hr (S.D. 4), respectively. CSI was equal in both groups throughout the experiment, and had a lowest average value of 47 (S.D. 10) at t = 30 in healthy pigs and reached a highest average value of 67 (S.D. 19) at t = 240 in pigs with endotoxin-induced sepsis. Anaesthetic depth was sufficient, assessed clinically, throughout the experiment in both groups. We concluded that the consumption of propofol and fentanyl was significantly reduced in pigs with endotoxin-induced sepsis. In the present study, we adjusted the level of anaesthesia according to clinical signs, and found good agreement with CSI.

KW - Anesthesia, Intravenous

KW - Anesthetics, Intravenous/administration & dosage

KW - Animals

KW - Endotoxins

KW - Fentanyl/administration & dosage

KW - Infusions, Intravenous

KW - Propofol/administration & dosage

KW - Sepsis/chemically induced

KW - Sodium Bicarbonate/pharmacology

KW - Swine

U2 - 10.1111/j.1742-7843.2007.00099.x

DO - 10.1111/j.1742-7843.2007.00099.x

M3 - Journal article

C2 - 17697040

VL - 101

SP - 192

EP - 196

JO - Basic and Clinical Pharmacology and Toxicology

JF - Basic and Clinical Pharmacology and Toxicology

SN - 1742-7835

IS - 3

ER -