Lactate outperforms shock index in early mortality prediction across intermediate and high-risk pulmonary embolism: results from a multicentre registry

Background Risk stratification in acute pulmonary embolism (PE) is crucial to guide therapeutic decisions. The shock index (SI), calculated as heart rate divided by systolic blood pressure, is a readily available haemodynamic marker, but its discriminatory ability as an isolated predictor is limited. Lactate, a marker of tissue hypoperfusion, has shown prognostic value in PE, but the optimal cut-off remains unclear, with previous studies using thresholds ranging from 2.0 to 3.3 mmol/L1,2,3. Objective To identify the optimal lactate threshold for predicting 30-day mortality in intermediate-high and high-risk PE, and to compare its prognostic value with the Pulmonary Embolism Severity Index (PESI) and SI. Methods Multicentre cohort study from the Spanish Registry of Catheter Intervention in Pulmonary Embolism, involving 18 hospitals. Consecutive patients with intermediate-high or high-risk PE confirmed by CTPA were included. Venous lactate was measured at emergency department arrival. The primary endpoint was 30-day all-cause mortality. The optimal lactate cut-off was determined using the Youden index. Patients were stratified into four groups according to SI (cut-off 1.0) and the lactate threshold. Internal validation was performed using bootstrap resampling (1,000 iterations). Results Among 606 patients (median age 65 [IQR 52–74] years, 55.3% male), 462 (76.2%) were intermediate-high risk and 144 (23.8%) high risk; 108 (17.8%) received systemic fibrinolysis and 399 (65.8%) underwent catheter-directed intervention. Overall, 43 (7.1%) died within 30 days. The optimal lactate cut-off was 3.6 mmol/L (sensitivity 60.5%, specificity 82.8%). Patients with lactate ≥3.6 mmol/L (n=123; 20.3%) had significantly higher mortality (21.1% vs 3.5%; P<0.001). In multivariable analysis adjusted for PESI, lactate ≥3.6 mmol/L remained an independent predictor (OR 4.68; 95% CI: 2.20–9.96; P<0.001), with each 1 mmol/L increase associated with 18% higher odds of death (OR 1.18; 95% CI: 1.08–1.28). The AUC for lactate (0.720) was numerically higher than for SI (0.646) and PESI (0.695). Half of deaths in the high-lactate group occurred within 48 hours vs 20% in the low-lactate group (Figure 1). Combined SI–lactate stratification revealed a mortality gradient from 3.3% (low SI/low lactate) to 20.0% (high SI/high lactate) (Figure 2). Patients with normal SI but elevated lactate had nearly five-fold higher mortality than those with elevated SI alone (16.7% vs 3.5%). Among low-PESI patients (<105 points), lactate ≥3.6 mmol/L identified a mortality rate of 17.6% vs 2.4%. Conclusions Lactate ≥3.6 mmol/L independently predicts 30-day mortality in intermediate-high and high-risk PE, even in patients with normal SI and low PESI, likely reflecting occult tissue hypoperfusion. This readily available biomarker may help identify candidates warranting closer monitoring and early consideration of reperfusion therapies.