The increase in cardiac output induced by a decrease in positive end-expiratory pressure reliably detects volume responsiveness: the PEEP-test study

Abstract

Background: In patients on mechanical ventilation, positive end-expiratory pressure (PEEP) can decrease cardiac output through a decrease in cardiac preload and/or an increase in right ventricular afterload. Increase in central blood volume by fluid administration or passive leg raising (PLR) may reverse these phenomena through an increase in cardiac preload and/or a reopening of closed lung microvessels. We hypothesized that a transient decrease in PEEP (PEEP-test) may be used as a test to detect volume responsiveness.

Methods: Mechanically ventilated patients with PEEP ≥ 10 cmH₂O ("high level") and without spontaneous breathing were prospectively included. Volume responsiveness was assessed by a positive PLR-test, defined as an increase in pulse-contour-derived cardiac index (CI) during PLR ≥ 10%. The PEEP-test consisted in reducing PEEP from the high level to 5 cmH₂O for one minute. Pulse-contour-derived CI (PiCCO2) was monitored during PLR and the PEEP-test.

Results: We enrolled 64 patients among whom 31 were volume responsive. The median increase in CI during PLR was 14% (11-16%). The median PEEP at baseline was 12 (10-15) cmH₂O and the PEEP-test resulted in a median decrease in PEEP of 7 (5-10) cmH₂O, without difference between volume responsive and unresponsive patients. Among volume responsive patients, the PEEP-test induced a significant increase in CI of 16% (12-20%) (from 2.4 ± 0.7 to 2.9 ± 0.9 L/min/m², p < 0.0001) in comparison with volume unresponsive patients. In volume unresponsive patients, PLR and the PEEP-test increased CI by 2% (1-5%) and 6% (3-8%), respectively. Volume responsiveness was predicted by an increase in CI > 8.6% during the PEEP-test with a sensitivity of 96.8% (95% confidence interval (95%CI): 83.3-99.9%) and a specificity of 84.9% (95%CI 68.1-94.9%). The area under the receiver operating characteristic curve of the PEEP-test for detecting volume responsiveness was 0.94 (95%CI 0.85-0.98) (p < 0.0001 vs. 0.5). Spearman's correlation coefficient between the changes in CI induced by PLR and the PEEP-test was 0.76 (95%CI 0.63-0.85, p < 0.0001).

Conclusions: A CI increase > 8.6% during a PEEP-test, which consists in reducing PEEP to 5 cmH₂O, reliably detects volume responsiveness in mechanically ventilated patients with a PEEP ≥ 10 cmH₂O. Trial registration ClinicalTrial.gov (NCT 04,023,786). Registered July 18, 2019. Ethics Committee approval CPP Est III (N° 2018-A01599-46).

Keywords: ARDS; Fluid responsiveness; Hemodynamic monitoring; Passive leg raising; Shock.

Fig. 1

Changes in cardiac index with passive leg raising, PEEP-test and volume expansion in volume responsive and volume unresponsive patients. CI Cardiac index, PEEP Positive end-expiratory pressure, PLR Passive leg raising, VE Volume expansion. Volume responsive patients are represented in blue and volume unresponsive patients in red. Volume expansion was performed in 30 volume responsive patients. *p < 0.05

Fig. 2

Area under the receiver-operating characteristic curves expressing the ability to detect volume responsiveness of changes in cardiac index, absolute changes in pulse pressure variation and changes in pulse pressure during a PEEP-test. AUC Area under the receiver-operating characteristic curve, CI Cardiac index, PP Pulse pressure, PPV Pulse pressure variation

Fig. 3

Sensitivity and specificity of the changes in cardiac index induced by the PEEP-test depending on the test result. The gray zone represents the uncertain zone with cut-off values with a sensitivity of < 90% or a specificity of < 90%. ∆CI_PEEP-test: changes in cardiac index induced by the decrease in positive end-expiratory pressure from baseline to 5 cmH₂O