Liver and Bile
J Hepatol. 2023;79(2):349–61
A randomized controlled trial (TARGET-C) of high vs. low target mean arterial pressure in patients with cirrhosis and septic shock
Background and 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). The authors compared the efficacy of a high (80–85 mmHg; H-MAP) versus low (60–65 mmHg; L-MAP) target MAP strategy in improving 28-day mortality in CICs.
Methods: They performed open-label 1:1 randomization of 150 CICs (H-MAP 75; L-MAP 75). The primary end point was 28-day mortality and secondary end points included reversal of shock, acute kidney injury (AKI) at day 5, the incidence of intradialytic hypotension (IDH), and adverse events. Endothelial markers were analyzed 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 (a disintegrin and metalloproteinase with thrombospondin motifs; 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 mean arterial pressure strategy does not confer a survival benefit in critically ill patients with cirrhosis and septic shock (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.