A randomised-controlled trial (TARGET-C) of high vs. low target mean arterial pressure in patients with cirrhosis and septic shock.

Autor: Maiwall R; Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India., Rao Pasupuleti SS; Department of Statistics, Mizoram University (A Central University), Pachhunga University College Campus, Aizawl, India; Department of Applied Mathematics and Statistics, Mizoram University (A Central University), Pachhunga University College Campus, Aizawl, India., Hidam AK; Department of Clinical and Molecular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India., Kumar A; Department of Clinical and Molecular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India., Tevethia HV; Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India., Vijayaraghavan R; Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India., Majumdar A; Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India., Prasher A; Department of Clinical and Molecular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India., Thomas S; Department of Biochemistry, Institute of Liver and Biliary Sciences, New Delhi, India., Mathur RP; Department of Nephrology, Institute of Liver and Biliary Sciences, New Delhi, India., Kumar G; Department of Statistics, Institute of Liver and Biliary Sciences, New Delhi, India., Sarin SK; Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India. Electronic address: sksarin@ilbs.in.
Jazyk: angličtina
Zdroj: Journal of hepatology [J Hepatol] 2023 Aug; Vol. 79 (2), pp. 349-361. Date of Electronic Publication: 2023 Apr 23.
DOI: 10.1016/j.jhep.2023.04.006
Abstrakt: Background & Aims: A high mean arterial pressure (MAP) target has been associated with improved renal outcomes in patients with cirrhosis, though it has not been studied in critically ill patients with cirrhosis and septic shock (CICs). We compared the efficacy of a high (80-85 mmHg; H-MAP) vs. low (60-65; L-MAP) target MAP strategy in improving 28-day mortality in CICs.
Methods: We performed open-label 1:1 randomisation of 150 CICs (H-MAP 75; L-MAP 75). The primary endpoint was 28-day mortality and secondary endpoints included reversal of shock, acute kidney injury (AKI) at day 5, the incidence of intradialytic hypotension (IDH), and adverse events. Endothelial markers were analysed in a subset of patients.
Results: The baseline characteristics were comparable. On intention-to-treat analysis, 28-day mortality (65% vs. 56%; p = 0.54), reversal of shock (47% vs. 53%; p = 0.41) and AKI development (45% vs. 31%;p = 0.06) were not different between the H-MAP and L-MAP groups, respectively. A lower incidence of IDH (12% vs. 48%; p <0.001) and higher adverse events necessitating protocol discontinuation (24% vs. 11%; p = 0.031) were noted in the H-MAP group. On per-protocol analysis (L-MAP 67; H-MAP 57), a significantly higher reversal of AKI (53% vs. 31%; p = 0.02) and a lower incidence of IDH (4% vs. 53%; p <0.001) were observed in the H-MAP group. Endothelial repair markers such as ADAMTS (2.11 ± 1.13 vs. 1.15 ± 0.48; p = 0.002) and angiopoietin-2 (74.08 ± 53.00 vs. 41.80 ± 15.95; p = 0.016) were higher in the H-MAP group.
Conclusions: A higher MAP strategy does not confer a survival benefit in CICs, but improves tolerance to dialysis, lactate clearance and renal recovery. Higher adverse events indicate the need for better tools to evaluate target microcirculation pressures in CICs.
Impact and Implications: Maintaining an appropriate organ perfusion pressure during sepsis is the ultimate goal of haemodynamic management. A higher mean arterial pressure (MAP) improves renal outcomes in patients with hepatorenal syndrome. Patients with cirrhosis and septic shock have severe circulatory disturbances, low MAP, and poor tissue perfusion. In these patients, targeting higher MAP vs. lower MAP does not confer any survival benefit but is associated with more adverse events. A higher target strategy was associated with better tolerance and lesser episodes of hypotension on dialysis. Patients who could achieve the higher target MAP, without the development of adverse events, had improved renal outcomes and better lactate clearance. Higher MAP was also associated with improvements in markers of endothelial function. A higher target MAP strategy, with close monitoring of adverse events, may be recommended for patients with cirrhosis and septic shock.
Clinical Trial Number: NCT03145168.
(Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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