Quiz Ref ID Invasive ventilation, one of the most frequently applied strategies in the intensive care unit (ICU), is increasingly recognized as a potentially harmful intervention.¹ There is evidence that lung-protective ventilation using low tidal volumes improves survival in patients with acute respiratory distress syndrome (ARDS),^2-4 but it is less certain whether tidal volume restriction benefits patients without ARDS. Two randomized clinical trials found tidal volume reduction to be associated with a lower number of pulmonary complications in patients without ARDS,^5,6 and 2 individual patient data meta-analyses suggested that tidal volume reduction may shorten the time spent on the ventilator and duration of stay in the ICU and hospital.^7,8

Background Although arterial hypotension occurs frequently with propofol use in humans, its effects on intravascular volume and vascular capacitance are uncertain. We hypothesized that propofol decreases vascular capacitance and therefore decreases stressed volume. Methods Cardiac output (CO) was measured using Modelflow^® in 17 adult subjects after upper abdominal surgery. Mean systemic filling pressure (MSFP) and vascular resistances were calculated using venous return curves constructed by measuring steady-state arterial and venous pressures and CO during inspiratory hold manoeuvres at increasing plateau pressures. Measurements were performed at three incremental levels of targeted blood propofol concentrations. Results Mean blood propofol concentrations for the three targeted levels were 3.0, 4.5, and 6.5 µg ml⁻¹. Mean arterial pressure, central venous pressure, MSFP, venous return pressure, Rv, systemic arterial resistance, and resistance of the systemic circulation decreased, stroke volume variation increased, and CO was not significantly different as propofol concentration increased. Conclusions An increase in propofol concentration within the therapeutic range causes a decrease in vascular stressed volume without a change in CO. The absence of an effect of propofol on CO can be explained by the balance between the decrease in effective, or stressed, volume (as determined by MSFP), the decrease in resistance for venous return, and slightly improved heart function. Clinical trial registration Netherlands Trial Register: NTR2486.

Objective: We studied the variable effects of norepinephrine infusion on cardiac output in postoperative cardiac surgical patients in whom norepinephrine increased mean arterial pressure. We hypothesized that the directional change in cardiac output would be determined by baseline cardiac function, as quantified by stroke volume variation, and the subsequent changes in mean systemic filling pressure and vasomotor tone. Design: Intervention study. Setting: ICU of a university hospital. Patients: Sixteen mechanically ventilated postoperative cardiac surgery patients. Interventions: Inspiratory holds were performed at baseline-1, during increased norepinephrine infusion, and baseline-2 conditions. Measurements and Main Results: We measured mean arterial pressure, heart rate, central venous pressure, cardiac output, stroke volume variation and, with use of inspiratory hold maneuvers, mean systemic filling pressure, then calculated resistance for venous return and systemic vascular resistance. Increasing norepinephrine by 0.04 ± 0.02 μg·kg^-1·min^-1 increased mean arterial pressure 20 mm Hg in all patients. Cardiac output decreased in ten and increased in six patients. In all patients mean systemic filling pressure, systemic vascular resistance and resistance for venous return increased and stroke volume variation decreased. Resistance for venous return and systemic vascular resistance increased more (p = 0.019 and p = 0.002) in the patients with a cardiac output decrease. Heart rate decreased in the patients with a cardiac output decrease (p = 0.002) and was unchanged in the patients with a cardiac output increase. Baseline stroke volume variation was higher in those in whom cardiac output increased (14.4 ± 4.2% vs. 9.1 ± 2.4%, p = 0.012). Stroke volume variation >8.7% predicted the increase in cardiac output to norepinephrine (area under the receiver operating characteristic curve 0.900). Conclusions: The change in cardiac output induced by norepinephrine is determined by the balance of volume recruitment (increase in mean systemic filling pressure), change in resistance for venous return, and baseline heart function. Furthermore, the response of cardiac output on norepinephrine can be predicted by baseline stroke volume variation.