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

Link to article at PubMed

J Hepatol. 2023 Apr 21:S0168-8278(23)00229-5. doi: 10.1016/j.jhep.2023.04.006. Online ahead of print.


BACKGROUND AND AIM: High mean arterial pressure (MAP) improve renal outcomes in cirrhosis patients, however, it has not been studied in critically ill cirrhosis with septic shock (CIC). We compared the efficacy of high (80-85 mm Hg; H-MAP) versus low (60-65; L-MAP) strategy in improving 28-day mortality in CIC. Reversal of shock, acute kidney injury (AKI) at day 5, the incidence of intradialytic hypotension (IDH), and adverse events were also studied.

METHODS: We performed open-label trial randomization of 150 CIC (H-MAP-75, L-MAP-75).

RESULTS: The baseline characteristics were comparable. On intention-to-treat (ITT) 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 H-MAP and L-MAP groups, respectively. A lower incidence of IDH [12%vs48%; p<0.001] and higher adverse events necessitating protocol discontinuation [24% vs.11%; p=0.031] were noted in H-MAP. On PP analysis [L-MAP-67, H-MAP-57] a significantly higher reversal of AKI was observed in H-MAP [53% vs. 31%; p=0.02] with a lower incidence of IDH [4% vs. 53%; p<0.001]. 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 H-MAP group.

CONCLUSIONS: A higher MAP strategy does not confer survival benefit in CIC patients, but helps with better tolerance of dialysis, lactate clearnce and renal recovery. Higher adverse events indicate need for better tools for evaluating target microcirculation pressures in CIC patients [NCT03145168] IMPACT AND IMPLICATIONS OF RESEARCH: Maintaining an appropriate organ perfusion pressure during sepsis is the ultimate goal of hemodynamic management. A higher MAP improves renal outcomes in patients with hepatorenal syndrome. Cirrhosis patients with septic shock (CIC) have severe circulatory disturbances, low mean arterial pressure (MAP), and poor tissue perfusion. In these patients, targeting higher mean arterial pressure (MAP) versus lower MAP does not confer any survival benefit but is associated with more adverse events. A higher 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 improvement in markers of endothelial function. A higher strategy of MAP, with a close monitoring of adverse events, may be recommended for patients with cirrhosis and septic shock.


PMID:37088310 | DOI:10.1016/j.jhep.2023.04.006

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