Predicting immunosuppressant dosing in the early postoperative period with noninvasive indocyanine green elimination following orthotopic liver transplantation

Abstract

Twenty adult patients undergoing orthotopic liver transplantation (OLT) were enrolled in this study, with the noninvasive indocyanine green plasma disappearance rate (ICG-PDR) measured both during and after OLT to assess the relationship between ICG-PDR and the ability of patients to achieve therapeutic postoperative tacrolimus immunosuppressant blood levels. Liver function was determined at both 2 and 18 hours post reperfusion with the ICG-PDR k value (1/min). Postoperative standard serum measures of liver function as well as liver biopsies were also collected and analyzed. The median ICG-PDR k value for the study group at 2 hours post reperfusion was 0.20 (0.16, 0.27), whereas at 18 hours post reperfusion, it was 0.22 (0.18, 0.35). The median change in the k value between the two ICG-PDR measurements was 0.05 (Ϫ0.02, 0.07) with P ϭ 0.02. There was an interaction between the postoperative day 1 (18 hours post reperfusion) ICG-PDR k value and the linear increase in the tacrolimus blood level, such that the greater the k value was, the more gradual the observed rise was in tacrolimus over time [that is, the longer it took to achieve a therapeutic blood level (Ͼ12 ng/mL), P ϭ 0.003]. Of the 16 patients that received tacrolimus, comparable dosing on a per kilogram body weight basis was observed. Also, no significant association between ICG-PDR k values and postoperative liver biopsy results was seen. This study demonstrates that the ICG-PDR measurement is a modality with the potential to assist in achieving adequate blood levels of tacrolimus following OLT. Liver Transpl 14: [46][47][48][49][50][51][52] 2008. © 2007 AASLD.Received April 20, 2007; accepted July 31, 2007. Postoperative liver allograft function can significantly influence immunosuppressant levels, and as a result, frequent dosing changes of these agents are often required. Common immunosuppressive agents including cyclosporine, tacrolimus, and sirolimus are frequently dose-adjusted, as determined by measurements of whole blood concentration. In addition, these agents are principally metabolized by hepatic cytochrome enzymes, which are variably affected by age, blood flow, ischemia reperfusion (IR) injury, and other factors.1-3 Although this approach is commonly used in clinical practice, it provides a relatively late prediction of the patient's response to these drugs and can potentially lead to a prolonged period of suboptimal levels of a given immunosuppressant in the postoperative period, posing an increased risk for rejection. The ability to assess and predict graft metabolic function could be beneficial in determining appropriate individual immunosuppressant dosing in the posttransplant period. Because of the continuing shortage of suitable cadaveric donor livers for the ever-growing number of pa-

The Protective Role of CD59 and Pathogenic Role of Complement in Hepatic Ischemia and Reperfusion Injury

“…1 Nevertheless, hepatic ischemia-reperfusion (IR) remains a major deleterious factor influencing graft outcome in organ transplantation. The incidence of primary graft failure (5% to 15%) and initial poor function (10% to 25%) is strongly dependent on the extent of ischemia-reperfusion injury (IRI).…”

Plasma disappearance rate of indocyanine green: A tool to evaluate early graft outcome after liver transplantation

“…The decrease noted between the third and fifth days post-transplantation was an early marker of acute cellular rejection, which developed earlier than the increase in liver enzymes. Parker et al 27 reported that they did not find any association between PDR-ICG values and postoperative liver biopsy when the PDR-ICG values were evaluated only 2 and 18 hours postreperfusion. The mean PDR-ICG values were within the normal range; this was the same as our results on days 1 and 2.…”

Utility of daily image guidance with intensity‐modulated radiotherapy for tumors of the base of skull

“…The decrease noted between the third and fifth days post‐transplantation was an early marker of acute cellular rejection, which developed earlier than the increase in liver enzymes. Parker et al27 reported that they did not find any association between PDR‐ICG values and postoperative liver biopsy when the PDR‐ICG values were evaluated only 2 and 18 hours post‐reperfusion. The mean PDR‐ICG values were within the normal range; this was the same as our results on days 1 and 2.…”