Butorphanol and Ketamine Combined in Infusion Solutions for Patient-Controlled Analgesia Administration: A Long-Term Stability Study

Abstract

BackgroundKetamine in subanesthetic dose added to butorphanol has been reported to give superior pain control when used for intravenous patient-controlled analgesia (PCA) after surgery. However, this admixture is not available commercially and stability data applicable to hospital practice are limited.Material/MethodsThe butorphanol-ketamine admixtures were prepared in polyolefin bags and stored in the dark at 4°C, 25°C, or 37°C for 15 days. The initial concentrations were 50–150 microgram/ml for butorphanol and 1–4 mg/ml for ketamine, respectively. The stabilities were determined by visual inspection, pH measurement, and high-pressure liquid chromatography (HPLC) assay of drug concentrations.ResultsOver the 15 days, all solutions were clear in appearance, and no color change or precipitation was observed among the three temperatures. The percentages of initial concentration of each drug were over 95% during the study period, and the pH value did not change significantly.ConclusionsThe results indicate that the drug mixtures of butorphanol and ketamine in 0.9% sodium chloride injection were stable for 15 days when stored in polyolefin bags at 4°C, 25°C, or 37°C.

Physicochemical stability of ternary admixtures of butorphanol, ketamine, and droperidol in polyolefin bags for patient-controlled analgesia use

“…Combination of butorphanol tartrate with other drugs in solution has resulted in variable results. It is stable when combined with ketamine hydrochloride,8 droperidol,9 tramadol hydrochloride,18 fentanyl citrate,18 granisetron hydrochloride,19 tropisetron hydrochloride,20 perphenazine,21 and ropivacaine hydrochloride,22 but unstable with lornoxicam23 and lansoprazole24 in 0.9% sodium chloride injection. As for ketamine hydrochloride, the stability and compatibility test of ketamine hydrochloride combined with other drugs in infusion solutions has been widely demonstrated that ketamine hydrochloride is a highly stable drug.…”

“…Mixing two or more drugs together in infusion solutions via intravenous PCA can lead to physical and/or chemical changes, which may result in variations in therapeutic properties and unknown side effects 7. In the literature, the compatibility of butorphanol tartrate with ketamine hydrochloride or droperidol in binary admixtures was studied,8,9 but from daily practice there is a need for additional research on the compatibility of these drugs in ternary admixtures. Thus, the objective of the current study was to determine the compatibility and stability of the ternary admixture of butorphanol tartrate, ketamine hydrochloride, and droperidol in 0.9% sodium chloride injection when stored in polyolefin bags at 4°C and 25°C for 14 days.…”