TY - JOUR
T1 - Renin-angiotensin-aldosterone system dynamics after targeted blood pressure control using angiotensin II or norepinephrine in cardiac surgery
T2 - mechanistic randomised controlled trial
AU - Coulson, Tim G.
AU - Miles, Lachlan F.
AU - Zarbock, Alex
AU - Burrell, Louise M.
AU - Patel, Sheila K.
AU - von Groote, Thilo
AU - Pilcher, David
AU - Weinberg, Laurence
AU - Landoni, Giovanni
AU - Bellomo, Rinaldo
N1 - Funding Information:
The Australian and New Zealand College of Anaesthetists Clinical Trials Network (P2004) and a grant from the Austin Medical Research Foundation. Angiotensin II was provided by La Jolla Pharmaceuticals (La Jolla, CA, USA) without cost for compassionate use during the first COVID wave, surplus vials were then provided to the Austin Health Department of Intensive Care.
Publisher Copyright:
© 2023 British Journal of Anaesthesia
PY - 2023/10
Y1 - 2023/10
N2 - Background: The role of the renin-angiotensin-aldosterone axis in vasoplegia after cardiac surgery remains unclear. We tested the hypothesis that, compared with norepinephrine, infusion of angiotensin II titrated to achieve similar mean arterial pressure (MAP) would suppress plasma renin concentration (PRC) while maintaining aldosterone levels. Methods: In a double-blind, randomised controlled trial, subjects received either an infusion of angiotensin II or norepinephrine to maintain MAP 70–80 mm Hg from induction of anaesthesia. We compared PRC, aldosterone, dipeptidyl peptidase-3, and angiotensin-converting enzyme 2 activity between treatment groups, before surgery, on ICU admission, and 24 h after surgery. Results: In 60 patients (11.7% female; mean age 68 yr [11 yr]), norepinephrine increased median PRC at ICU admission (median difference [MD] 46 [inter-quartile range, IQR, 3–88] μU ml−1; P<0.001) but angiotensin II did not (MD −3 [IQR −62 to 35] μU ml−1; P=0.36). Aldosterone levels increased with both. The aldosterone:PRC ratio did not change with norepinephrine (MD −0.01 [IQR −0.14 to 0.03] μU ml−1 per ng dl−1, P=0.76) but increased with angiotensin II (MD 0.05 [IQR 0.004–0.26] μU ml−1 per ng dl−1, P<0.001). The upper quartile of PRC before surgery was associated with higher vasopressor requirements when norepinephrine was used to maintain MAP, but not angiotensin II. Dipeptidyl peptidase-3 levels and angiotensin-converting enzyme 2 activities were similar at all time points. Conclusions: Angiotensin II suppressed renin release while maintaining aldosterone levels compared with norepinephrine. Higher plasma renin concentration before surgery was associated with greater vasopressor requirement for norepinephrine, but not angiotensin II. Clinical trial registration: Australian and New Zealand Clinical Trials Registry—ACTRN12621000195853 23/02/2021.
AB - Background: The role of the renin-angiotensin-aldosterone axis in vasoplegia after cardiac surgery remains unclear. We tested the hypothesis that, compared with norepinephrine, infusion of angiotensin II titrated to achieve similar mean arterial pressure (MAP) would suppress plasma renin concentration (PRC) while maintaining aldosterone levels. Methods: In a double-blind, randomised controlled trial, subjects received either an infusion of angiotensin II or norepinephrine to maintain MAP 70–80 mm Hg from induction of anaesthesia. We compared PRC, aldosterone, dipeptidyl peptidase-3, and angiotensin-converting enzyme 2 activity between treatment groups, before surgery, on ICU admission, and 24 h after surgery. Results: In 60 patients (11.7% female; mean age 68 yr [11 yr]), norepinephrine increased median PRC at ICU admission (median difference [MD] 46 [inter-quartile range, IQR, 3–88] μU ml−1; P<0.001) but angiotensin II did not (MD −3 [IQR −62 to 35] μU ml−1; P=0.36). Aldosterone levels increased with both. The aldosterone:PRC ratio did not change with norepinephrine (MD −0.01 [IQR −0.14 to 0.03] μU ml−1 per ng dl−1, P=0.76) but increased with angiotensin II (MD 0.05 [IQR 0.004–0.26] μU ml−1 per ng dl−1, P<0.001). The upper quartile of PRC before surgery was associated with higher vasopressor requirements when norepinephrine was used to maintain MAP, but not angiotensin II. Dipeptidyl peptidase-3 levels and angiotensin-converting enzyme 2 activities were similar at all time points. Conclusions: Angiotensin II suppressed renin release while maintaining aldosterone levels compared with norepinephrine. Higher plasma renin concentration before surgery was associated with greater vasopressor requirement for norepinephrine, but not angiotensin II. Clinical trial registration: Australian and New Zealand Clinical Trials Registry—ACTRN12621000195853 23/02/2021.
KW - aldosterone
KW - angiotensin II
KW - cardiac surgery
KW - noradrenaline
KW - renin
KW - vasoplegia
KW - vasopressor
UR - https://www.scopus.com/pages/publications/85165659311
U2 - 10.1016/j.bja.2023.06.056
DO - 10.1016/j.bja.2023.06.056
M3 - Article
C2 - 37481435
AN - SCOPUS:85165659311
SN - 0007-0912
VL - 131
SP - 664
EP - 672
JO - British Journal of Anaesthesia
JF - British Journal of Anaesthesia
IS - 4
ER -