Solubility of Haloether Anesthetics in Human and Animal Blood

Abstract

Background Anesthetic blood solubility predicts pharmacokinetics for inhaled agents and is essential for determination of blood anesthetic concentrations from end-tidal gas concentrations using Henry’s Law. Though used to model anesthetic effects in humans, there are limited interspecies solubility comparisons that include modern haloethers. This study aimed to measure hematocrit-adjusted blood:gas anesthetic partition coefficients (λB:G) for desflurane, sevoflurane, isoflurane, and methoxyflurane in humans and animals. Methods Whole blood was collected from 20 rats, 8 horses, and 4 each of cats, cattle, humans, dogs, goats, pigs, rabbits, and sheep. Plasma or cell volume was removed to adjust all samples to a packed cell volume of 40%. A single agent calibration gas headspace was added to blood in a glass syringe and was mixed and equilibrated at 37°C for 2 hours. Agent concentrations in the calibration gas and syringe headspace were measured using gas chromatography. Anesthetic solubility in saline, citrate-phosphate-dextrose-adenine, and olive oil were similarly measured. Results Except for goats, all animal species had at least one λB:G measurement that differed significantly from humans. For each agent, λB:G positively correlated with serum triglyceride concentrations, but this only explained 25% of interspecies variability. Desflurane was significantly less soluble in blood than sevoflurane in some species (e.g., humans) but not in others (e.g., rabbits). Conclusions Anesthetic partition coefficients differ significantly between humans and most animals for haloether anesthetics. Because of their similar λB:G values, goats may be a better animal model for inhaled anesthetic pharmacokinetics in people.

Effects of oxymorphone hydrochloride or hydromorphone hydrochloride on minimal alveolar concentration of desflurane in sheep

“…The 10-minute period was derived from the number of time constants needed for equilibration of desflurane concentration within the brain. 34,35 Differences between inspired and alveolar concentrations of desflurane were maintained at < 0.25% in the present study, suggesting that equilibration occurred within 10 minutes. Each time constant allows for 63% equilibration; therefore, 1 time constant allows 63% of equilibration, 2 time constants allow 86% equilibration, and 3 time constants allow 95% equilibration.…”

Blood/Gas Partition Coefficients for Isoflurane, Sevoflurane, and Desflurane in a Clinically Relevant Patient Population

“…Those of isoflurane and sevoflurane are similar to the results 1,20-23 based on other techniques. 7 According to our results, age, body mass index, gender, hemoglobin concentration, or hematocrit do not have significant effects on the blood solubility of the 3 volatile anesthetics. Nevertheless, the fluid/gas partition coefficients of isoflurane, sevoflurane, and desflurane in crystalloid solutions have been shown to decrease when the osmolarity of the solution increases.…”

Anesthetic synergy between two n-alkanes

“…To determine alkane concentrations in oocyte perfusate solutions, the Ostwald saline-gas partition coefficients for butane and pentane were measured in frog Ringer’s solution at 23°C using a glass syringe headspace equilibration method previously described for measurement of ether anesthetic distribution constants (Soares et al 2012). These partition coefficients were then used to calculate aqueous hydrocarbon concentrations of chamber perfusates aspirated into a glass syringe and equilibrated with an air headspace that was analyzed by gas chromatography.…”