Pharmacokinetics of Digoxin in Stomach Cancer Patients Undergoing a Gastrectomy under Enflurane Anesthesia

Lee, Soo il; Kim, Hyung Ho; Kim, Byung Jin; Lee, Do Kyung; Baik, Chang Youl; Lee, Jong Hwan

Abstract

BACKGROUND: Sometimes digoxin may be needed to be administered during anesthesia for the control of the ventricular rate and mitigation of lung congestion. For the lack of studies in surgical patients we wanted to determine digoxin pharmacokinetics (PK) in subjects undergoing a gastrectomy under enflurane anesthesia.
METHODS
Over 72 hours, 16 serum samples from each of 14 subjects (ASA status 1 or 2) diagnosed with gastric cancer were collected after a single intravenous dose of digoxin 10ng/kg actual body weight for serum concentration measurements by fluorescence polarization immunoassay. Digoxin was injected 30 minutes after beginning surgery. Two, three and non-compartmental (TwC, ThC and NC, respectively) PK parameters were determined using WinNonln. The important parameters (AUC, Cl, Vss, t beta 1/2 [elimination half-life], Vc, MRT) of 3 PK's were statistically evaluated about which compartment PK was appropriate to the data here. The parameters of TwC PK of the surgical subjects were compared to those of nonsurgical ones which had already been published by other investigators. The postoperative outcomes (ambulation date, diet date, discharge date, complications, APACHE II and MOF [multiple organ failure]) in 19 patients (nondigoxin group) not treated with digoxin were compared with 19 patients (digoxin group) treated with digoxin 5ng/kg two times at 2 hour intervals during surgery.
RESULTS
No significant differences were found in parameters between TwC and NC. Significant differences were observed in parameters of PK between ThC versus Twc and NC (P < 0.01). Cl and Vss of surgical subjects were larger than those of nonsurgical ones, and t beta 1/2 was similar. No significant effect of digoxin on postoperative outcomes was demonstrated.
CONCLUSIONS
The dosage of digoxin for surgical patients should be titrated to the bleeding amount and the severity of surgical trauma because of larger Cl and Vss. The effect of digoxin on postoperative outcomes remains to be studied.