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Pulse pressure variation (PPV) and stroke volume variation (SVV) do not predict fluid responsiveness when using a protective ventilation strategy: the use of functional haemodynamic tests can be useful to overcome this limitation.We tested the use of a tidal volume challenge (VTC), during 6 ml kg−1 [predicted body weight (PBW)] ventilation, and the end-expiratory occlusion test (EEOT) for prediction of fluid responsiveness.An interventional prospective study.Supine elective neurosurgical patients.The study protocol was, first, the initial EEOT test was performed during baseline 6 ml kg−1 PBW ventilation; second, VTC was performed by increasing the VT up to 8 ml kg−1 PBW and PPV and SVV changes were recorded after 1 min; third, a second EEOT was performed during 8 ml kg−1 PBW ventilation; and VT was reduced back to 6 ml kg−1 PBW and a third EEOT was performed. Finally, a 250 ml fluid challenge was administered over 10 min to identify fluid responders (increase in stroke volume index ≥10%).In the 40 patients analysed, PPV and SVV values at baseline and EEOT performed at 6 ml kg−1 PBW did not predict fluid responsiveness. A 13.3% increase in PPV after VTC predicted fluid responsiveness with a sensitivity of 94.7% and a specificity of 76.1%, while a 12.1% increase in SVV after VTC predicted fluid responsiveness with a sensitivity of 78.9% and a specificity of 95.2%. After EEOT performed at 8 ml kg−1 PBW, a 3.6% increase in cardiac index predicted fluid responsiveness with a sensitivity of 89.4% and a specificity of 85.7%, while a 4.7% increase in stroke volume index (SVI) with a sensitivity of 89.4% and a specificity of 85.7%.The changes in PPV and SVV obtained after VTC are reliable and comparable to the changes in CI and SVI obtained after EEOT performed at 8 ml kg−1 PBW in predicting fluid responsiveness in neurosurgical patients.ACTRN12618000351213.