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IntroductionThe assessment of volume responsiveness and the decision to administer a fluid bolus is a common dilemma facing physicians caring for critically ill patients. Static markers of cardiac preload are poor predictors of volume responsiveness, and dynamic markers are often limited by the presence of spontaneous respirations or cardiac arrhythmias. Passive leg raising (PLR) represents an endogenous volume challenge that can be used to predict fluid responsiveness.MethodsMedical intensive care unit (ICU) patients requiring volume expansion were eligible for enrollment. Non-invasive measurements of stroke volume (SV) were obtained before and during PLR using a transthoracic Doppler ultrasound device prior to volume expansion. Measurements were then repeated following volume challenge to classify patients as either volume responders or non-responders based on their hemodynamic response to volume expansion. The change in SV from baseline during PLR was then compared with the change in SV with volume expansion to determine the ability of PLR in conjunction with SV measurement to predict volume responsiveness.ResultsA total of 102 fluid challenges in 89 patients were evaluated. In 47 of the 102 fluid challenges (46.1%), SV increased by ≥15% after volume infusion (responders). A SV increase induced by PLR of ≥15% predicted volume responsiveness with a sensitivity of 81%, specificity of 93%, positive predictive value of 91% and negative predictive value of 85%.ConclusionsNon-invasive SV measurement and PLR can predict fluid responsiveness in a broad population of medical ICU patients. Less than 50% of ICU patients given fluid boluses were volume responsive.

Isakow, Warren, and Daniel P. Schuster. Extravascular lung water measurements and hemodynamic monitoring in the critically ill: bedside alternatives to the pulmonary artery catheter.

Rationale: Few noninvasive biomarkers for pulmonary inflammation are currently available that can assess the lung-specific response to antiinflammatory treatments. Positron emission tomography with [ 18 F]fluorodeoxyglucose (FDG-PET) is a promising new method that can be used to quantify pulmonary neutrophilic inflammation. Objectives: To evaluate the ability of FDG-PET to measure the pulmonary antiinflammatory effects of hydroxymethylglutarylcoenzyme A reductase inhibitors (statins) and recombinant human activated protein C (rhAPC) in a human model of experimentallyinduced lung inflammation. Methods: Eighteen healthy volunteers were randomized to receive placebo, lovastatin, or rhAPC before intrabronchial segmental endotoxin challenge. FDG-PET imaging was performed before and after endotoxin instillation. The rate of [ 18 F]FDG uptake was calculated as the influx constant K i by Patlak graphical analysis. Bronchoalveolar lavage (BAL) was performed to determine leukocyte concentrations for correlation with the PET imaging results. Measurements and Main Results: There was a statistically significant decrease in K i in the lovastatin-treated group that was not seen in the placebo-treated group, suggesting attenuation of inflammation by lovastatin treatment despite a small decrease in BAL total leukocyte and neutrophil counts that was not statistically significant. No significant decrease in K i was observed in the rhAPCtreated group, correlating with a lack of change in BAL parameters and indicating no significant antiinflammatory effect with rhAPC. Conclusions: FDG-PET imaging is a sensitive method for quantifying the lung-specific response to antiinflammatory therapies and may serve as an attractive platform for assessing the efficacy of novel antiinflammatory therapies at early phases in the drug development process. Clinical trial registered with www.clinicaltrials.gov (NCT00741013).