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Clinical Trial
. 2020 Nov 1;202(9):1253-1261.
doi: 10.1164/rccm.201911-2172OC.

Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock. A Clinical Trial

Rinaldo Bellomo  1   2 , Lui G Forni  3   4 , Laurence W Busse  5 , Michael T McCurdy  6 , Kealy R Ham  7 , David W Boldt  8 , Johanna Hästbacka  9 , Ashish K Khanna  10   11 , Timothy E Albertson  12 , James Tumlin  13 , Kristine Storey  14 , Damian Handisides  14 , George F Tidmarsh  14   15 , Lakhmir S Chawla  14   16 , Marlies Ostermann  17
Affiliations
Clinical Trial

Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock. A Clinical Trial

Rinaldo Bellomo et al. Am J Respir Crit Care Med. .

Abstract

Rationale: Exogenous angiotensin II increases mean arterial pressure in patients with catecholamine-resistant vasodilatory shock (CRVS). We hypothesized that renin concentrations may identify patients most likely to benefit from such therapy.Objectives: To test the kinetic changes in renin concentrations and their prognostic value in patients with CRVS.Methods: We analyzed serum samples from patients enrolled in the ATHOS-3 (Angiotensin II for the Treatment of High-Output Shock) trial for renin, angiotensin I, and angiotensin II concentrations before the start of administration of angiotensin II or placebo and after 3 hours.Measurements and Main Results: Baseline serum renin concentration (normal range, 2.13-58.78 pg/ml) was above the upper limits of normal in 194 of 255 (76%) study patients with a median renin concentration of 172.7 pg/ml (interquartile range [IQR], 60.7 to 440.6 pg/ml), approximately threefold higher than the upper limit of normal. Renin concentrations correlated positively with angiotensin I/II ratios (r = 0.39; P < 0.001). At 3 hours after initiation of angiotensin II therapy, there was a 54.3% reduction (IQR, 37.9% to 66.5% reduction) in renin concentration compared with a 14.1% reduction (IQR, 37.6% reduction to 5.1% increase) with placebo (P < 0.0001). In patients with renin concentrations above the study population median, angiotensin II significantly reduced 28-day mortality to 28 of 55 (50.9%) patients compared with 51 of 73 patients (69.9%) treated with placebo (unstratified hazard ratio, 0.56; 95% confidence interval, 0.35 to 0.88; P = 0.012) (P = 0.048 for the interaction).Conclusions: The serum renin concentration is markedly elevated in CRVS and may identify patients for whom treatment with angiotensin II has a beneficial effect on clinical outcomes.Clinical trial registered with www.clinicaltrials.gov (NCT02338843).

Keywords: angiotensin I; angiotensin-converting enzyme defect; distributive shock; renin–angiotensin–aldosterone system.

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Figures

Figure 1.
Figure 1.
Renin–angiotensin–aldosterone system disturbance hypothesis. The green arrows indicate an increase, the red arrows a decrease, and the red cross marks loss of function. ACE = angiotensin-converting enzyme.
Figure 2.
Figure 2.
Serum angiotensin I and renin concentrations. (A) Serum angiotensin I concentrations. (B) Serum renin concentrations. All values are presented as the median (interquartile range).
Figure 3.
Figure 3.
Kaplan-Meier survival plot according to renin concentrations and treatment with angiotensin II or placebo. (A) Day 28 survival: renin concentration below population median. (B) Day 28 survival: renin concentration above population median. CI = confidence interval; HR = hazard ratio.
Figure 4.
Figure 4.
Cubic splines of mortality and baseline serum renin. Baseline renin is shown with log scale. LJPC501 = angiotensin II.
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References

    1. Lambden S, Creagh-Brown BC, Hunt J, Summers C, Forni LG. Definitions and pathophysiology of vasoplegic shock. Crit Care. 2018;22:174. - PMC - PubMed
    1. Sterling SA, Puskarich MA, Shapiro NI, Trzeciak S, Kline JA, Summers RL, et al. Emergency Medicine Shock Research Network (EMSHOCKNET) Characteristics and outcomes of patients with vasoplegic versus tissue dysoxic septic shock. Shock. 2013;40:11–14. - PMC - PubMed
    1. Brown SM, Lanspa MJ, Jones JP, Kuttler KG, Li Y, Carlson R, et al. Survival after shock requiring high-dose vasopressor therapy. Chest. 2013;143:664–671. - PMC - PubMed
    1. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock. 2016. Crit Care Med. 2017;45:486–552. - PubMed
    1. Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, et al. ATHOS-3 Investigators. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med. 2017;377:419–430. - PubMed

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