pKa of Fentanyl Varies With Temperature: Implications for Acid-Base Management During Extremes of Body Temperature

Objective: The pKa of fentanyl has not been measured previously at varying extremes of body temperature. The goal of this laboratory investigation was to test the hypothesis that the pKa of fentanyl changes with temperature. Design: The investigation involved measuring the pKa values of aqueous fentanyl at varying temperatures. Setting: The investigation was conducted in a controlled laboratory environment. Participants: No human or animal subjects were involved. Interventions: Because no live subjects were involved in the investigation, no interventions were necessary. Measurements and Main Results: This paper reports the effect of temperature on the pKa of fentanyl. The pKa of aqueous fentanyl was measured at 15°C, 25°C, 37°C, 42°C, and 47.5°C by potentiometric titration in 0.01 mmol/L of potassium chloride after extensive degassing. Data were analyzed using the least squares method with an appropriately fitting equation. The pKa of fentanyl was found to change in a similar manner to the neutral point of water at varying temperatures. Conclusions: This finding has implications for the bioavailability of fentanyl at extremes of body temperature in association with the clinical acid-base management of the patient. Clinical implications for differing methods of intraoperative acid-base management at varying temperatures are discussed.