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Predicting volume responsiveness in patients with spontaneous breathing activity is a difficult challenge in the emergency room as well as in the intensive care unit because heart–lung interactions indices cannot be reliably used as they can be in mechanically ventilated patients fully adapted to their ventilator. The aim of this review is to summarize the different tools that have been proposed to predict the hemodynamic response to fluid infusion in the presence of spontaneous breathing activity.Clinical studies recently demonstrated that neither indicators of cardiac preload (filling pressures and end-diastolic ventricular dimensions) nor arterial pulse pressure respiratory variation was an accurate predictor of volume responsiveness in patients with spontaneous breathing activity with or without mechanical support. In contrast, performing a passive leg-raising test has been proved as valuable for this purpose.The passive leg-raising test is the only method that has been repeatedly shown to be reliable for predicting volume responsiveness in patients who experience spontaneous breathing. The appropriate utilization of this test requires a real-time assessment of its effects on systemic blood flow.