Functional hemodynamic tests: a systematic review and a metanalysis on the reliability of the end-expiratory occlusion test and of the mini-fluid challenge in predicting fluid responsiveness

Abstract

Background: Bedside functional hemodynamic assessment has gained in popularity in the last years to overcome the limitations of static or dynamic indexes in predicting fluid responsiveness. The aim of this systematic review and metanalysis of studies is to investigate the reliability of the functional hemodynamic tests (FHTs) used to assess fluid responsiveness in adult patients in the intensive care unit (ICU) and operating room (OR).

Methods: MEDLINE, EMBASE, and Cochrane databases were screened for relevant articles using a FHT, with the exception of the passive leg raising. The QUADAS-2 scale was used to assess the risk of bias of the included studies. In-between study heterogeneity was assessed through the I2 indicator. Bias assessment graphs were plotted, and Egger's regression analysis was used to evaluate the publication bias. The metanalysis determined the pooled area under the receiving operating characteristic (ROC) curve, sensitivity, specificity, and threshold for two FHTs: the end-expiratory occlusion test (EEOT) and the mini-fluid challenge (FC).

Results: After text selection, 21 studies met the inclusion criteria, 7 performed in the OR, and 14 in the ICU between 2005 and 2018. The search included 805 patients and 870 FCs with a median (IQR) of 39 (25-50) patients and 41 (30-52) FCs per study. The median fluid responsiveness was 54% (45-59). Ten studies (47.6%) adopted a gray zone analysis of the ROC curve, and a median (IQR) of 20% (15-51) of the enrolled patients was included in the gray zone. The pooled area under the ROC curve for the end-expiratory occlusion test (EEOT) was 0.96 (95%CI 0.92-1.00). The pooled sensitivity and specificity were 0.86 (95%CI 0.74-0.94) and 0.91 (95%CI 0.85-0.95), respectively, with a best threshold of 5% (4.0-8.0%). The pooled area under the ROC curve for the mini-FC was 0.91 (95%CI 0.85-0.97). The pooled sensitivity and specificity were 0.82 (95%CI 0.76-0.88) and 0.83 (95%CI 0.77-0.89), respectively, with a best threshold of 5% (3.0-7.0%).

Conclusions: The EEOT and the mini-FC reliably predict fluid responsiveness in the ICU and OR. Other FHTs have been tested insofar in heterogeneous clinical settings and, despite promising results, warrant further investigations.

Keywords: End-expiratory occlusion test; Fluid responsiveness; Functional hemodynamic test; Mini-fluid challenge.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1

Flow of the studies. FC, fluid challenge; ICU, intensive care unit; FA, atrial fibrillation; OR, operating room; FHT functional hemodynamic test

Fig. 2

Pooled ROC curves of EEOT and mini-FC. Pooled receiver operating characteristic (ROC) curves of end-expiratory occlusion test (EEOT) [left panel, eight studies, area under the ROC curve = 0.96 (solid blue line) (95%CI 0.92–1.00; dashed blue lines)] and mini-fluid challenge (mini-FC) [right panel, seven studies, area under the ROC curve = 0.91 (solid blue line) (95%CI 0.85–0.97; dashed blue lines)] constructed by considering the hemodynamic effects of the EEOT or mini-FC on stroke volume or its surrogates and those induced by fluid challenge administration. Red circles represent each study included in the metanalysis and the size of each solid circle indicates the size of each study (software MetaDiSC®, version 1.4, see text and Table 3 for details)

Fig. 3

EEOT forest plot of included studies. Forest plot reporting the pooled sensitivity and specificity (green diamonds) of the end-expiratory occlusion test (EEOT) in predicting of fluid responsiveness by considering the changes in stroke volume or its surrogates after the test and those induced by fluid challenge administration. Black squares represent the values of sensitivity and specificity (with 95% confidence intervals; black lines) of each study included in the metanalysis, and the size of each square indicates the size of each study. The definitions Monnet et al. “a” and “b” refer to the two populations investigated in the study [50] (see also Table 3 and see text for details). 95%CI, 95% confidence intervals

Fig. 4

Mini-FC forest plot of included studies. Forest plot reporting the pooled sensitivity and specificity (green diamonds) of the mini-fluid challenge (mini-FC) in predicting fluid responsiveness by considering the changes in stroke volume or its surrogates after the test and those induced by fluid challenge administration. Black squares represent the values of sensitivity and specificity (with 95% confidence intervals; black lines) of each study included in the metanalysis, and the size of each square indicates the size of each study. 95%CI, 95% confidence intervals

Fig. 5

Clinical algorithm for EEOT and mini-FC application in the ICU and the OR. In the OR, FHTs can be added to the dynamic indexes evaluation, considering the gray zone reported in the literature [21]. When PPV or SVV values range within the gray zone, we suggest the use of the EEOT, as the first step. A clear positive response (SV increase > 5%) suggests fluid responsiveness, whereas a negative/uncertain response could be further investigated by the consequent use of the mini-FC, as indicated. In critically ill patients, the need of FC administration is often evaluated combining different signs and measurements [58]. In this context, the EEOT (in patient undergoing controlled mechanical ventilation) and the mini-FC (in patients retaining to some extent a spontaneous breathing effort) can be useful when the PLR is unsuitable.*We suggest a FC of 4 ml/kg [55] over 10 min. **Intra-abdominal hypertension; uncontrolled pain, cough, discomfort, and awakening; hip/leg fractures; uncontrolled intracranial hypertension. ICU, intensive care unit; OR, operating room; FC, fluid challenge; PLR, passive leg raising; CMV, controlled mechanical ventilation; SB, spontaneously breathing patients; AMV, assisted mechanical ventilation; PPV, pulse pressure variation; SVV, stroke volume variation; EEOT, end-expiratory occlusion test; SV, stroke volume