Effects of angiotensin II in the management of perioperative hypotension in kidney transplant recipients

Abstract

Background Due to the mechanisms of action of conventional catecholamine vasopressors, there is increased risk of renal allograft injury and adverse events in transplant recipients with fluid‐refractory distributive shock during the perioperative period. As such, mechanistically alternative vasopressors like angiotensin II (ATII) may avoid these complications, but there is an absence of data supporting use in this population. Methods This was a single‐center, single‐arm, open‐label, phase 4 study conducted as a 1‐year pilot of 20 adult renal transplant recipients receiving ATII as their first continuous infusion vasopressor in the perioperative period. The study aim was to systematically assess the safety and hemodynamic effects of ATII. Safety was assessed based on the incidence of adverse events. Hemodynamic effect was assessed by the achievement of per protocol hemodynamic goals (i.e., SBP ≥120 mmHg) and the need for adjunct vasopressors. Results Most cases involved deceased donors (70%), with a corresponding mean (SD) cold ischemia time of 14.7 (8.6) h. Over a surgery duration of 5.3 (1.2) h, subjects received 3.2 (2.0) L of total volume resuscitation prior to ATII initiation. No adverse events were directly related to ATII administration. Throughout this period, ATII was utilized for a median of 1.0 (IQR, 1.5) h intraoperatively (N = 7), 26.5 (IQR, 84.8) h postoperatively (N = 4), and 63.8 (IQR, 57.8) h in subjects who required ATII both intra‐ and postoperatively (N = 9). Only one of the 20 patients needed adjunct continuous infusion vasopressors in addition to ATII. Conclusions Based on the observations of this pilot study, ATII is a safe and effective vasopressor option for renal transplant recipients requiring perioperative hypotension reversal.

Characterizing the Stability of Angiotensin II in 0.9% Sodium Chloride Using High Performance Liquid Chromatography and Liquid Chromatography Tandem Mass Spectrometry

“…[2][3][4][5] In addition, in patients receiving kidney transplantation, ANGII has been shown to reverse perioperative hypotension with less arrhythmias compared to catecholamine vasopressors with theoretical benefits on glomerular filtration and renal vasoconstriction potentially decreasing the risk of ischemia and acute kidney injury (AKI) post-transplant. 6,7 Despite these findings, ANGII has an average manufacturer price of $1800/mL (2.5 mg), making it about 17 times more expensive than norepinephrine and 10 times that of epinephrine which could result in underutilization by institutions who cannot justify its cost. [8][9][10][11][12][13] Extended stability data exists for existing first and second line catecholamine (ie, norepinephrine and epinephrine) allowing for increased flexibility of use, margin, and workflow optimization in the drug solution preparation process, serving as a benefit for institutions.…”

“…2 -5 In addition, in patients receiving kidney transplantation, ANGII has been shown to reverse perioperative hypotension with less arrhythmias compared to catecholamine vasopressors with theoretical benefits on glomerular filtration and renal vasoconstriction potentially decreasing the risk of ischemia and acute kidney injury (AKI) post-transplant. 6,7 Despite these findings, ANGII has an average manufacturer price of $1800/mL (2.5 mg), making it about 17 times more expensive than norepinephrine and 10 times that of epinephrine which could result in underutilization by institutions who cannot justify its cost. 8 -13…”