Cardiovascular effects of fentanyl in conscious rats

The polymicrobial sepsis induced by cecal ligation and puncture (CLP) in th e rat is widely used in shock research. For ethical reasons, narcotic analg esics are often administered in this model, with the potential risk of conf ounding effects. In conscious non-septic rats, we investigated the cardiova scular effects of a continuous i.v. infusion of fentanyl (20 mug/kg per h) administered with fluid loading (10 ml/kg per h) for 24 h, a regimen common ly applied in rat CLP. Animals were randomly allocated to receive analgesia with fluid loading (Fentanyl c1roup), or fluid loading alone (Control). Al l endpoints were assessed after 24 h of infusion. At that time, Control ani mals had mild respiratory alkalosis, which was essentially abolished by fen tanyl. Analgesia mildly elevated the plasma norepinephrine levels [median ( interquartile range): Control 232 pg/ml (0-292), Fentanyl 302 pg/ml (234-67 6), P=0.045] but was devoid of any effect on blood pressure, heart rate, ca rdiac output (mean +/- SD: Control 388 +/- 61 ml/kg per min, Fentanyl 382 /- 62 mne, per min, P=0.87) and indices of left ventricular function derive d from high-fidelity recordings of left ventricular pressure (dP/dt(max): C ontrol 11782 +/- 2324 mmHg/s, Fentanyl 12107 +/- 2816 mmHg/s, P=0.77). In e x vivo experiments carried out immediately after animal sacrifice, no diffe rences were noted between the Control and Fentanyl groups in the sensitivit y of endothelium-intact aortic rings to norepinephrine-induced vasoconstric tion (-logEC(50): Control 8.78 +/-0.28, Fentanyl 8.83 +/-0.26, P=0.52) or a cetylcholine-induced vasodilatation (-logEC(50): Control 7.00 +/-0.37, Fent anyl 7.06 +/-0.26 +/- 0.53, P=0.75). In conclusion, the present data provid e no contraindication, and even some support for the ethical use of a high dose i.v. infusion of fentanyl in cardiovascular studies of conscious cathe terized rats undergoing CLP or other painful procedures.