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British Journal of Anaesthesia, 1995, Vol. 74, No. 5 553-557
© 1995 The Board of Management and Trustees of the British Journal of Anaesthesia

research-article

Potency of lipid and protein formulation of 5{alpha}-pregnanolone at induction of anaesthesia and the corresponding regional brain distribution

M. D. WANG, MD, G. WAHLSTRÖM, PHD, MD, K. W. GEE, PHD and T. BÄCKSTRÖM, PHD, MD

Department of Obstetrics and Gynaecology and Physiology, University of Umeå S-901 85, Umeå, Sweden
Department of Pharmacology, University of Umeå S-901 85, Umeå, Sweden
Department of Pharmacology, University of California Irvine, CA 92717, USA

We have studied the anaesthetic potencies of 5{alpha}-pregnanolone albumin solution (PAS) and 5{alpha}-pregnanolone Intralipid emulsion (PLE) at equivalent concentrations in male rats using an EEG threshold method. The criterion of anaesthesia was burst suppression of the EEG of 1 s or more (the "silent second" (SS)) as a sign of deep anaesthesia. The potency of the two formulations was assessed by comparing the threshold doses of 5{alpha}-pregnanolone at three dose rates (1 0, 2.0 and 3.0 mg kg–1 min–1 We found that SS was initiated in all rats after infusions of PAS, while no SS could be induced in rats after infusion of PLE at a larger dose. A higher concentration of 5{alpha}-pregnanolone was found in all brain and peripheral tissues of PAS-treated rats than in those treated with PLE. In rats with PAS-induced anaesthesia (3.0 mg kg–1 min–1 the highest concentrations were detected in striatum (mean 19.40 (SD 1.21) ng mg–1 Although there was a small insignificant reduction in threshold doses with dose rates at 2.0–3.0 mg kg–1 min–1 the tissue concentrations in striatum, frontal cortex and occipital cortex were found to be significantly increased. We conclude that PAS was more potent than PLE in inducing anaesthesia. Brain distribution of 5{alpha}-pregnanolone varied regionally in a manner similar to the variation in GABAA receptor sensitivity to this neuroactive steroid. (Br. J. Anaesth. 1995; 74: 553–557)


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