Background: Respiratory variations in pulse oximetry plethysmographic waveform amplitude (Delta POP) are related to respiratory variations in pulse pressure (Delta PP) and are sensitive to changes in preload. The authors hypothesized that Delta POP can predict fluid responsiveness in mechanically ventilated patients during general anesthesia. Methods: Twenty-five patients referred for cardiac surgery were studied after induction of general anesthesia. Hemodynamic data (cardiac index, central venous pressure, pulmonary capillary wedge pressure, Delta PP, and Delta POP) were recorded before and after volume expansion (500 ml hetastarch, 6%). Fluid responsiveness was defined as an increase in cardiac index of 15% or greater. Results: Volume expansion induced changes in cardiac index (2.0 +/- 0.4 to 2.3 +/- 0.5 mmHg; P < 0.05), Delta PP (11 +/- 7 to 6 +/- 5%; P < 0.05), and Delta POP (12 +/- 9 to 7 +/- 5%; P < 0.05). Delta POP and Delta PP were higher in responders than in nonresponders (17 +/- 8 vs. 6 +/- 4 and 14 +/- 7 vs. 6 +/- 4%, respectively; P < 0.05 for both). A Delta POP greater than 13% before volume expansion allowed discrimination between responders and nonresponders with 80% sensitivity., and 90% specificity. There was a significant relation between Delta POP before volume expansion and percent change in cardiac index after volume expansion (r = 0.62; P < 0.05). Conclusions: Delta POP can predict fluid responsiveness noninvasively in mechanically ventilated patients during general anesthesia. This index has potential clinical applications.