Arterial lactate in cardiogenic shock: Prognostic value of clearance versus single values
Selected in JACC: Cardiovascular Interventions by L. Biasco
This subanalysis of the IABP-SHOCK study shows how a negative trial, when properly conducted, can generate useful hypothesis-generating information with relevant clinical impact. Find out more!
References
Authors
Georg Fuernau, Steffen Desch, Suzanne de Waha-Thiele, Ingo Eitel, Franz-Josef Neumann, Marcus Hennersdorf, Stephan B. Felix, Andreas Fach, Michael Böhm, Janine Pöss, Christian Jung, Taoufik Ouarrak, Steffen Schneider, Karl Werdan, Uwe Zeymer, Holger Thiele
Reference
Vol 13, NO 19; 2020. October 12, 2020:2208-2016
Published
October 2020
Link
Read the abstractOur comment
Why this study? – the rationale/objective
Arterial lactates are considered as one of the major parameters able to assess prognosis and drive the decision-making process in the setting of cardiogenic shock.
The increase in their serum levels is a clear marker of the systemic transition from the aerobic to an anaerobic metabolism associated with tissue hypoxia in low cardiac output states. Lactates are widely available usually with a short turnaround time allowed by point-of-care testing, thus commonly used in clinical practice.
In the IABP-SHOCK II score (Intraaortic Balloon Pump in Cardiogenic Shock) a basal level > 5 mmol/L resulted in an independent predictor for short-term mortality in shock complicating an acute coronary syndrome.
The rationale of the sub-analysis of data derived from the IABP-SHOCK II trial (published in the NEJM in 2012) and its associated registry proposed by Thiele et al. is whether temporal trend of lactates in patients with cardiogenic shock complicating acute myocardial infarction might provide better prognostic stratification as compared to their baseline levels.
How was it executed? – the methodology
Study population:
The IABP-SHOCK II trial was a prospective, open-label, multicenter trial enrolling 600 patients with cardiogenic shock complicating acute myocardial infarction in whom early revascularization was planned. Patients were randomized in a 1:1 fashion to intraortic balloon counterpulsation vs standard medical care.
No differences in the 30-day mortality primary endpoint were evident between the two cohorts. All patients screened but not randomized in the trial were included in the associated prospective registry (183 patients). The present analysis included 666 patients enrolled either in the trial or in the prospective registry in whom lactates levels were known at baseline and 8 hours after initial randomization/enrollment, thus allowing calculation of lactate clearance defined as the percentage of lactate reduction over time as compared to baseline levels.
Methodology:
Primary outcome measure: all-cause mortality at 30-day.
Receiver operating characteristics and corresponding area under the curve (AUC) were calculated for baseline lactates, lactates at 8h and lactate clearance. Best cut off values were also calculated for prediction of the primary outcome. Univariable and multivariable analysis with a stepwise Cox regression approach were used to identify independent predictors of mortality at 30-day.
What is the main result?
- 30-day mortality in the studied population was 38,4% highlighting the dramatic prognostic relevance of cardiogenic shock complicating an acute myocardial infarction. Non-survivors were older and showed a greater burden of associated comorbidities such as renal diseases, diabetes, previous stroke or peripheral artery disease.
- Lactate levels were significantly different between survivors and non-survivors both at baseline and at 8 hours from randomization/enrollment. Lactate clearance was significantly slower in non-survivors. Cut-off levels that more accurately predicted death at 30-day were ≥5,1 mmol/L at baseline, ≥3,1 mmol/L at 8 hours and a clearance ≥-3,45%/h.
- Lactates at 8 hours showed a good discriminatory performance between survivors and non survivors at 30-day [AUC 0,760 (95% CI: 0,722-0,799)] while lower performances were observed for baseline lactates [AUC 0,686 (95% CI: 0,648-0,731)] and lactate clearance [AUC 0,593 (95%CI0,548-0,639)].
- At multivariable analysis, baseline lactate ≥5 mmol/L lost its association with outcome [Chi square test 3,5 (HR 1,35; 95% CI 0,99-1,83; p=0,06)] while lactate at 8 h ≥3,1 mmol/L [Chi square test 42,1 (HR 2,89; 95% CI 2,10-3,97; p<0,001)], lactate clearance ≥-3,45%/h [Chi square test 20,2 (HR 1,25; 95% CI 1,15-1,36; p<0,001)], age, creatinine > 100ɥmol/L , TIMI flow <3 after PCI and prior stroke confirmed their association with prognosis.
Critical reading and the relevance for clinical practice:
This subanalysis of the IABP shock study shows how a negative trial, when properly conducted, can generate useful hypothesis-generating information with relevant clinical impact.
The main message that can be drawn from the present data stays beyond the thresholds for lactate levels (e.g. above or below 5 mmol/L at baseline) or timing of samples (e.g. 8 hours after enrollment/randomization).
From a clinical standpoint, the main determinant of outcome appears to be the initial individual patient response to the medical and interventional therapies undertaken during the very first hours after the occurrence of cardiogenic shock in the setting of acute myocardial infarction.
Baseline lactate levels, a major parameter used among others clinical indicators to stratify prognosis as well as to decide on the opportunity to adopt more aggressive measures such as inotropic or mechanical air support, lost their relevance when their trend overtime is taken into account.
Values and timing proposed from the authors should not be adopted with a dogmatic approach into clinical practice as lactate levels showed wide confidence intervals with a certain degree of overlap (baseline lactates 5,8 mmol/L (95% CI 3,8-9,8) in non-survivors vs 3,2 (1,7-5,8) in survivors; lactates at 8 hours 5,1 (96% 2,3-11,0) vs 1,7 (95% 1,2-3,2) in survivors) and timing of lactate measurements were mandated as per trial protocol.
Nonetheless, according to the present results, high baseline lactate in cardiogenic shock should be considered as a justification to rapidly undertake all clinically appropriated supportive measures while leaving outcome prediction to evaluation of the initial hemodynamic response.
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