@article{b8aeccfc9a5540a0a7eb9ea181e6dc2a,
title = "A double-blind randomised feasibility trial of angiotensin-2 in cardiac surgery",
abstract = "Acute kidney injury is common after cardiac surgery. Vasoplegic hypotension may contribute to kidney injury, and different vasopressors may have variable effects on kidney function. We conducted a double-blind, randomised feasibility trial comparing peri-operative angiotensin-2 with noradrenaline. We randomly allocated 60 patients at two centres to a blinded equipotent angiotensin-2 or noradrenaline infusion intra-operatively and for up to 48 h postoperatively, titrated to mean arterial pressure of 70–80 mmHg. Primary feasibility outcomes included consent rate, protocol adherence, infusion duration, mean arterial pressure maintenance in the target range and major adverse outcomes. Secondary outcomes included kidney injury rate. The consent rate was 47%. Protocol adherence was 100% in the angiotensin-2 group and 94% in the noradrenaline group. Study drug duration was median (IQR [range]) 217 (160–270 [30–315]) vs. 185 (135–301 [0–480]) min (p = 0.78) min intra-operatively, and 5 (0–16 [0–48]) vs. 14.5 (4.8–29 [0–48]) hours (p = 0.075) postoperatively for angiotensin-2 and noradrenaline, respectively. The mean arterial pressure target was achieved postoperatively in 25 of 28 (89%) of the angiotensin-2 group and 27 of 32 (84%) of the noradrenaline group. One participant had a stroke, one required extracorporeal support and three required renal replacement therapy, all in the noradrenaline group (p = 0.99, p = 0.99 and p = 0.1). Acute kidney injury occurred in 7 of 28 in the angiotensin-2 group vs. 12 of 32 patients in the noradrenaline group (p = 0.31). This pilot study suggests that a trial comparing angiotensin-2 with noradrenaline is feasible. Its findings justify further investigations of angiotensin-2 in cardiac surgery.",
keywords = "angiotensin-2, cardiac surgery, kidney injury, noradrenaline, norepinephrine, randomised controlled trial, renal dysfunction, renal failure",
author = "Coulson, {T. G.} and Miles, {L. F.} and {Serpa Neto}, A. and D. Pilcher and L. Weinberg and G. Landoni and A. Zarbock and R. Bellomo",
note = "Funding Information: The trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12621000195853 23/02/2021). This work was supported by a pilot grant from the Australian and New Zealand College of Anaesthetists Clinical Trials Network and a grant from the Austin Medical Research Foundation. The authors would like to thank the following for their hard work in randomisation, collection of data and samples and ensuring protocols were followed: the Alfred Department of Anaesthesia and Intensive Care Research Team and the Austin Hospital Department of Anaesthesia and Department of Intensive Care Research Team. The authors would also like to thank Drs R. Glick, A. Peirce, J. Chan, A. Hungenahally and J. Patel (Cardiac Anaesthesia Fellows) who assisted with data collection; Professor P. S. Myles for critical review of the manuscript, and Dr E. See for assistance in generating and uploading the random sequence. Angiotensin‐2 was provided by La Jolla Pharmaceuticals (La Jolla, CA, USA) without cost for compassionate use during the first COVID‐19 wave, surplus vials were then provided to the Austin Health Department of Intensive Care. AZ has received lecture and consultant fees from Paion Pharmaceuticals; GL has received a speaker fee from Paion Pharmaceuticals. No other competing interests declared. Open access publishing facilitated by Monash University, as part of the Wiley ‐ Monash University agreement via the Council of Australian University Librarians. No other competing interests. Funding Information: The trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12621000195853 23/02/2021). This work was supported by a pilot grant from the Australian and New Zealand College of Anaesthetists Clinical Trials Network and a grant from the Austin Medical Research Foundation. The authors would like to thank the following for their hard work in randomisation, collection of data and samples and ensuring protocols were followed: the Alfred Department of Anaesthesia and Intensive Care Research Team and the Austin Hospital Department of Anaesthesia and Department of Intensive Care Research Team. The authors would also like to thank Drs R. Glick, A. Peirce, J. Chan, A. Hungenahally and J. Patel (Cardiac Anaesthesia Fellows) who assisted with data collection; Professor P. S. Myles for critical review of the manuscript, and Dr E. See for assistance in generating and uploading the random sequence. Angiotensin-2 was provided by La Jolla Pharmaceuticals (La Jolla, CA, USA) without cost for compassionate use during the first COVID-19 wave, surplus vials were then provided to the Austin Health Department of Intensive Care. AZ has received lecture and consultant fees from Paion Pharmaceuticals; GL has received a speaker fee from Paion Pharmaceuticals. No other competing interests declared. Open access publishing facilitated by Monash University, as part of the Wiley - Monash University agreement via the Council of Australian University Librarians. No other competing interests. Publisher Copyright: {\textcopyright} 2022 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.",
year = "2022",
month = sep,
doi = "10.1111/anae.15802",
language = "English",
volume = "77",
pages = "999--1009",
journal = "Anaesthesia",
issn = "0003-2409",
publisher = "Wiley-Blackwell",
number = "9",
}