Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness.
9 Studies evaluating dose responsiveness have found a plateaued dose-response curve for PONV.
Pulse-pressure variation failed to predict volume responsiveness (ROC curve area = 0.555, P = 0.485).
Pulse-pressure variation failed to predict volume responsiveness (ROC curve area = 0.604, P = 0.461), even after hemorrhage (20% of estimated blood volume).
As a whole SVV failed to predict fluid responsiveness (area under curve (AUC) 0.53, P = 0.82).
Finally, nonmonotonic dose response curves, responsiveness to low doses well below "safe" no observable adverse effect levels (NOAELs) (Sheehan 2006; vom Saal et al. 2010), and synergistic interactions are well understood in endocrine physiology (Calabrese 2010; McEwen 2010), but these terms tend to be avoided or the concepts even dismissed in environmental toxicology.
In each animal, we compared visual responses close to and far from the injection by plotting a contrast threshold curve, in which responsiveness at a given contrast was normalized to the values measured at 90% contrast in penetrations distant from the delivery site.
In controls after hemorrhage, stroke volume increased in 67% of volume challenges and PPV was a predictor of fluid responsiveness (area under the ROC curve = 0.790, P = 0.001).
Sensitivity and specificity were assessed using Area under the Receiver Operating Curve (AUC) and responsiveness over time using effect sizes (ES).
In endotoxemia, 68% of volume challenges before hemorrhage increased the stroke volume by > 10%, but PPV did not predict fluid responsiveness (area under the ROC curve = 0.604, P = 0.461).
