Plasma viscosity and cremophor-containing anaesthetics

Area of Science:

• Biochemistry
• Pharmacology
• Anesthesiology

Background:

• Cremophor is a commonly used excipient in intravenous formulations.
• Anesthetic agents containing cremophor have been associated with adverse reactions.
• The physicochemical properties of cremophor and its interaction with biological fluids require further investigation.

Purpose of the Study:

• To investigate the effect of cremophor-containing anesthetic agents on plasma viscosity.
• To elucidate the mechanism by which cremophor influences plasma viscosity.

Main Methods:

• In vitro addition of anesthetic agents and cremophor to human plasma.
• Administration of cremophor-containing anesthetics to patients undergoing anesthesia induction.
• Measurement of plasma viscosity at a shear rate of 11.5 s-1 before and after anesthetic administration.
• In vitro experiments with Triton X-100 and concentrated urea.

Main Results:

• Cremophor, anesthetic agents, and cremophor alone significantly decreased plasma viscosity by approximately 45% in vitro.
• In patients, a mean decrease in plasma viscosity of 42% was observed 5 minutes after injection.
• The viscosity-reducing effect was transient, disappearing within 50 minutes.
• Triton X-100 demonstrated a similar viscosity-reducing effect, and its interaction with urea mirrored that of cremophor.

Conclusions:

• Cremophor-containing anesthetics transiently reduce plasma viscosity.
• The mechanism likely involves cremophor increasing structured water around proteins, preventing aggregation.
• These findings may have implications for understanding the physiological effects of cremophor-based formulations.