Lactate Clearance as a Surrogate for Mortality in Cardiogenic Shock: Insights From the DOREMI Trial

Jeffrey A Marbach, Pietro Di Santo, Navin K Kapur, Katherine L Thayer, Trevor Simard, Richard G Jung, Simon Parlow, Omar Abdel-Razek, Shannon M Fernando, Marino Labinaz, Michael Froeschl, Rebecca Mathew, Benjamin Hibbert, Jeffrey A Marbach, Pietro Di Santo, Navin K Kapur, Katherine L Thayer, Trevor Simard, Richard G Jung, Simon Parlow, Omar Abdel-Razek, Shannon M Fernando, Marino Labinaz, Michael Froeschl, Rebecca Mathew, Benjamin Hibbert

Abstract

Background Recent studies have shown improved outcomes in cardiogenic shock through protocols directed toward early identification and initiation of mechanical circulatory support. However, objective therapeutic targets-based on clinical and/or laboratory data-to guide real-time clinical decision making are lacking. Lactate clearance has been suggested as a potential treatment target because of its independent association with mortality. Methods and Results In a post hoc analysis of the DOREMI (Dobutamine Compared to Milrinone in the Treatment of Cardiogenic Shock) trial-a randomized, double-blind, controlled trial comparing milrinone to dobutamine in the treatment of cardiogenic shock-we used prospectively collected lactate data to evaluate lactate clearance as a surrogate marker for in-hospital mortality. In total, 82 (57.7%) patients survived to hospital discharge (survivors). In multivariate logistic regression analysis, complete lactate clearance, percentage lactate clearance, and percentage lactate clearance per hour were independently associated with survival beginning as early as 8 hours after enrollment. Complete lactate clearance was the strongest predictor of survival at all time points, with odds ratios ranging between 2.46 (95% CI, 1.09-5.55; P=0.03) at 8 hours to 5.44 (95% CI, 2.14-13.8; P<0.01) at 24 hours. Conclusions Complete lactate clearance is a strong and independent predictor of in-hospital survival in patients with cardiogenic shock. Together with previously published data, these results further support the validity of lactate clearance as an appropriate surrogate for mortality and as a potential therapeutic target in future cardiogenic shock trials. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03207165.

Keywords: cardiogenic shock; lactate clearance; mortality; surrogate end point.

Figures

Figure 1. Representation of blood lactate as…
Figure 1. Representation of blood lactate as a surrogate end point in cardiogenic shock, demonstrating the relationship between myocardial dysfunction, lactate levels, and mortality.
Figure 2. Patient flow.
Figure 2. Patient flow.
CICU indicates cardiac intensive care unit.
Figure 3. Box‐and‐whisker plots of absolute lactate…
Figure 3. Box‐and‐whisker plots of absolute lactate levels over time, grouped by survivors and nonsurvivors.
Figure 4. Association between survival and complete…
Figure 4. Association between survival and complete lactate clearance.
A, Proportion of survivors and nonsurvivors who achieved complete lactate clearance from 4 to 36 hours. B, Probability of survival for patients with and without complete lactate clearance at 24 hours.B, Probability of survival for patients with and without complete lactate clearance at 24 hours.
Figure 5. Receiver operator curves of multivariate…
Figure 5. Receiver operator curves of multivariate logistic regression for association between complete lactate clearance and death at 8 hours, 12 hours, and 24 hours.
Receiver operator curves of multivariate logistic regression for association between complete lactate clearance and death at 8 hours (Blue), 12 hours (Purple), and 24 hours (Red). AUC – area under the curve.

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