Ventilator-induced central venous pressure variation can predict fluid responsiveness in post-operative cardiac surgery patients.

BACKGROUND: Ventilator-induced dynamic hemodynamic parameters such as stroke volume variation (SVV) and pulse pressure variation (PPV) have been shown to predict fluid responsiveness in contrast to static hemodynamic parameters such as central venous pressure (CVP). We hypothesized that the ventilator-induced central venous pressure variation (CVPV) could predict fluid responsiveness. METHODS: Twenty-two elective cardiac surgery patients were studied post-operatively on the intensive care unit during mechanical ventilation with tidal volumes of 6-8 ml/kg without spontaneous breathing efforts or cardiac arrhythmia. Before and after administration of 500mL hydroxyethyl starch, SVV and PPV were measured using pulse contour analysis by modified Modelflow® , while CVP was obtained from a central venous catheter positioned in the superior vena cava. CVPV was calculated as 100 × (CVPmax -CVPmin )/[(CVPmax + CVPmin) /2]. RESULTS: Nineteen patients (86%) were fluid responders defined as an increase in cardiac output of ≥ 15% after fluid administration. CVPV decreased upon fluid loading in responders, but not in non-responders. Baseline CVP values showed no correlation with a change in cardiac output in contrast to baseline SVV (r = 0.60, P = 0.003), PPV (r = 0.58, P = 0.005), and CVPV (r = 0.63, P = 0.002). Baseline values of SVV > 9% and PPV > 8% could predict fluid responsiveness with a sensitivity of 89% and 95%, respectively, both with a specificity of 100%. Baseline CVPV could identify all fluid responders and non-responders correctly at a cut-off value of 12%. There was no difference between the area under the receiver operating characteristic curves of SVV, PPV, and CVPV. CONCLUSION: The use of ventilator-induced CVPV could predict fluid responsiveness similar to SVV and PPV in post-operative cardiac surgery patients.

Non-invasive continuous arterial pressure and pulse pressure variation measured with Nexfin(®) in patients following major upper abdominal surgery: a comparative study.

We compared the accuracy and precision of the non-invasive Nexfin(®) device for determining systolic, diastolic, mean arterial pressure and pulse pressure variation, with arterial blood pressure values measured from a radial artery catheter in 19 patients following upper abdominal surgery. Measurements were taken at baseline and following fluid loading. Pooled data results of the arterial blood pressures showed no difference between the two measurement modalities. Bland-Altman analysis of pulse pressure variation showed significant differences between values obtained from the radial artery catheter and Nexfin finger cuff technology (mean (SD) 1.49 (2.09)%, p < 0.001, coefficient of variation 24%, limits of agreement -2.71% to 5.69%). The effect of volume expansion on pulse pressure variation was identical between methods (concordance correlation coefficient 0.848). We consider the Nexfin monitor system to be acceptable for use in patients after major upper abdominal surgery without major cardiovascular compromise or haemodynamic support.

Methodology of method comparison studies evaluating the validity of cardiac output monitors: a stepwise approach and checklist.

The validity of each new cardiac output (CO) monitor should be established before implementation in clinical practice. For this purpose, method comparison studies investigate the accuracy and precision against a reference technique. With the emergence of continuous CO monitors, the ability to detect changes in CO, in addition to its absolute value, has gained interest. Therefore, method comparison studies increasingly include assessment of trending ability in the data analysis. A number of methodological challenges arise in method comparison research with respect to the application of Bland-Altman and trending analysis. Failure to face these methodological challenges will lead to misinterpretation and erroneous conclusions. We therefore review the basic principles and pitfalls of Bland-Altman analysis in method comparison studies concerning new CO monitors. In addition, the concept of clinical concordance is introduced to evaluate trending ability from a clinical perspective. The primary scope of this review is to provide a complete overview of the pitfalls in CO method comparison research, whereas other publications focused on a single aspect of the study design or data analysis. This leads to a stepwise approach and checklist for a complete data analysis and data representation.

The effect of propofol on haemodynamics: cardiac output, venous return, mean systemic filling pressure, and vascular resistances.

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.

Predicting cardiac output responses to passive leg raising by a PEEP-induced increase in central venous pressure, in cardiac surgery patients.

BACKGROUND: Changes in central venous pressure (CVP) rather than absolute values may be used to guide fluid therapy in critically ill patients undergoing mechanical ventilation. We conducted a study comparing the changes in the CVP produced by an increase in PEEP and stroke volume variation (SVV) as indicators of fluid responsiveness. Fluid responsiveness was assessed by the changes in cardiac output (CO) produced by passive leg raising (PLR). METHODS: In 20 fully mechanically ventilated patients after cardiac surgery, PEEP was increased +10 cm H2O for 5 min followed by PLR. CVP, SVV, and thermodilution CO were measured before, during, and directly after the PEEP challenge and 30° PLR. The CO increase >7% upon PLR was used to define responders. RESULTS: Twenty patients were included; of whom, 10 responded to PLR. The increase in CO by PLR directly related (r=0.77, P<0.001) to the increase in CVP by PEEP. PLR responsiveness was predicted by the PEEP-induced increase in CVP [area under receiver-operating characteristic (AUROC) curve 0.99, P<0.001] and by baseline SVV (AUROC 0.90, P=0.003). The AUROC's for dCVP and SVV did not differ significantly (P=0.299). CONCLUSIONS: Our data in mechanically ventilated, cardiac surgery patients suggest that the newly defined parameter, PEEP-induced CVP changes, like SVV, appears to be a good parameter to predict fluid responsiveness.

A comparison of stroke volume variation measured by the LiDCOplus and FloTrac-Vigileo system.

The aim of this study was to compare the accuracy of stroke volume variation (SVV) as measured by the LiDCOplus system (SVVli) and by the FloTrac-Vigileo system (SVVed). We measured SVVli and SVVed in 15 postoperative cardiac surgical patients following five study interventions; a 50% increase in tidal volume, an increase of PEEP by 10 cm H2O, passive leg raising, a head-up tilt procedure and fluid loading. Between each intervention, baseline measurements were performed. 136 data pairs were obtained. SVVli ranged from 1.4% to 26.8% (mean (SD) 8.7 (4.6)%); SVVed from 2.0% to 26.0% (10.2 (4.7)%). The bias was found to be significantly different from zero at 1.5 (2.5)%, p < 0.001, (95% confidence interval 1.1-1.9). The upper and lower limits of agreement were found to be 6.4 and -3.5% respectively. The coefficient of variation for the differences between SVVli and SVVed was 26%. This results in a relative large range for the percentage limits of agreement of 52%. Analysis in repeated measures showed coefficients of variation of 21% for SVVli and 22% for SVVed. The LiDCOplus and FloTrac-Vigileo system are not interchangeable. Furthermore, the determination of SVVli and SVVed are too ambiguous, as can be concluded from the high values of the coefficient of variation for repeated measures. These findings underline Pinsky's warning of caution in the clinical use of SVV by pulse contour techniques.

Performance of three minimally invasive cardiac output monitoring systems.

We evaluated cardiac output (CO) using three new methods - the auto-calibrated FloTrac-Vigileo (CO(ed)), the non-calibrated Modelflow (CO(mf) ) pulse contour method and the ultra-sound HemoSonic system (CO(hs)) - with thermodilution (CO(td)) as the reference. In 13 postoperative cardiac surgical patients, 104 paired CO values were assessed before, during and after four interventions: (i) an increase of tidal volume by 50%; (ii) a 10 cm H(2)O increase in positive end-expiratory pressure; (iii) passive leg raising and (iv) head up position. With the pooled data the difference (bias (2SD)) between CO(ed) and CO(td), CO(mf) and CO(td) and CO(hs) and CO(td) was 0.33 (0.90), 0.30 (0.69) and -0.41 (1.11) l.min(-1), respectively. Thus, Modelflow had the lowest mean squared error, suggesting that it had the best performance. CO(ed) significantly overestimates changes in cardiac output while CO(mf) and CO(hs) values are not significantly different from those of CO(td). Directional changes in cardiac output by thermodilution were detected with a high score by all three methods.

An evaluation of cardiac output by five arterial pulse contour techniques during cardiac surgery.

The bias, precision and tracking ability of five different pulse contour methods were evaluated by simultaneous comparison of cardiac output values from the conventional thermodilution technique (COtd). The five different pulse contour methods included in this study were: Wesseling's method (cZ); the Modelflow method; the LiDCO system; the PiCCO system and a recently developed Hemac method. We studied 24 cardiac surgery patients undergoing uncomplicated coronary artery bypass grafting. In each patient, the first series of COtd was used to calibrate the five pulse contour methods. In all, 199 series of measurements were accepted by all methods and included in the study. COtd ranged from 2.14 to 7.55 l.min(-1), with a mean of 4.81 l.min(-1). Bland-Altman analysis showed the following bias and limits of agreement: cZ, 0.23 and - 0.80 to 1.26 l.min(-1); Modelflow, 0.00 and - 0.74 to 0.74 l.min(-1); LiDCO, - 0.17 and - 1.55 to 1.20 l.min(-1); PiCCO, 0.14 and - 1.60 to 1.89 l.min(-1); and Hemac, 0.06 and - 0.81 to 0.93 l.min(-1). Changes in cardiac output larger than 0.5 l.min(-1) (10%) were correctly followed by the Modelflow and the Hemac method in 96% of cases. In this group of subjects, without congestive heart failure, with normal heart rhythm and reasonable peripheral circulation, the best results in absolute values as well as in tracking changes in cardiac output were measured using the Modelflow and Hemac pulse contour methods, based on non-linear three-element Windkessel models.

Monitoring cardiac output using the femoral and radial arterial pressure waveform.

This study was performed to determine the interchangeability of femoral artery pressure and radial artery pressure measurements as the input for the PiCCO system (Pulsion Medical Systems, Munich, Germany). We studied 15 intensive care patients following cardiac surgery. Five-second averages of the cardiac output derived from the femoral artery pressure (COfem) were compared to 5-s averages derived from the radial artery pressure (COrad). One patient was excluded due to problems in the pattern recognition of the arterial pressure signal. In the remaining 14 patients, 14 734 comparative cardiac output values were analysed. The mean sample time was 88 min, range [30-119 min]. Mean (SD) COfem was 6.24 (1.1) l.min(-1) and mean COrad 6.23 (1.1) l.min(-1). Bland-Altman analysis showed an excellent agreement with a bias of - 0.01 l.min(-1), and limits of agreement from 0.60 to - 0.62 l.min(-1). If changes in CO were > 0.5 l.min(-1), the direction of changes in COfem and COrad were equal in 97% of instances. We conclude that femoral artery pressure and radial artery pressure are interchangeable as inputs for the PiCCO device.

Less invasive determination of cardiac output from the arterial pressure by aortic diameter-calibrated pulse contour.

BACKGROUND: Cardiac output by modelflow pulse contour method can be monitored quantitatively and continuously only after an initial calibration, to adapt the model to an individual patient. The modelflow method computes beat-to-beat cardiac output (COmf) from the radial artery pressure, by simulating a three-element model of aortic impedance with post-mortem data from human aortas. METHODS: In our improved version of modelflow (COmfc) we adapted this model to a real time measure of the aortic cross-sectional area (CSA) of the descending aorta just above the diaphragm, measured by a new transoesophageal echo device (HemoSonic 100). COmf and COmfc were compared with thermodilution cardiac output (COtd) in 24 patients in the intensive care unit. Each thermodilution value was the mean of four measurements equally spread over the ventilatory cycle. RESULTS: Least squares regression of COtd vs COmf gave y=1.09x[95% confidence interval (CI) 0.96-1.22], R2=0.15, and of COtd vs COmfc resulted in y=1.02x(95% CI 0.96-1.08), R2=0.69. The limits of agreement of the un-calibrated COmf were -3.53 to 2.79, bias=0.37 litre min(-1) and of the diameter-calibrated method COmfc, -1.48 to 1.32, bias=-0.08 litre min(-1). The coefficient of variation for the difference between methods decreased from 28 (un-calibrated) to 12% after diameter-calibration. CONCLUSIONS: After diameter-calibration, the improved modelflow pulse contour method reliably estimates cardiac output without the need of a calibration with thermodilution, leading to a less invasive cardiac output monitoring method.

Pulmonary artery thermodilution cardiac output vs. transpulmonary thermodilution cardiac output in two patients with intrathoracic pathology.

In two adult patients, one with a severe hemorrhage and one with a partial anomalous pulmonary vein, cardiac output (CO) measurements were performed simultaneously by means of the bolus transpulmonary thermodilution technique (COao) and continuous pulmonary artery thermodilution method (CCOpa). In both cases, the methods revealed clinically significant different cardiac output values based upon the site of measurement and the underlying pathology. The assessment of cardiac output (CO) is considered an important part of cardiovascular monitoring of the critically ill patient. Cardiac output is most commonly determined intermittently by the bolus thermodilution technique with a pulmonary artery catheter (COpa). As continuous monitoring of CO is preferable to this intermittent technique, two major techniques have been proposed. Firstly, a nearly continuous thermodilution method (CCOpa) using a heating filament mounted on a pulmonary artery catheter (Baxter Edwards Laboratories, Irvine, CA), with a clinically acceptable accuracy compared with the intermittent bolus technique. Based on these results we assumed CCOpa equivalent to real CO during hemodynamically stable conditions, and secondly, a continuous cardiac output system based on pulse contour analysis (PCCO), such as the PiCCO system (Pulsion Medical System, Munchen, Germany). To calibrate this device, which uses a derivation of the algorithm of Wesseling and colleagues, an independently obtained value of CO by the transpulmonary thermodilution method (COao) is used. Clinical validation studies in patients without underlying intrathoracic pathology, comparing transpulmonary COao with the pulmonary technique (COpa), mostly yielded good agreement.

Mean cardiac output by thermodilution with a single controlled injection.

OBJECTIVE: A new method to estimate mean cardiac output by thermodilution with a single duration-controlled injection was evaluated in patients. DESIGN: Prospective criterion standard study. SETTING: University hospital cardiac surgical intensive care unit and cardiac operation room. PATIENTS: Of 33 patients, 24 underwent coronary bypass graft surgery, four had a valve replacement, and five were treated in the intensive care unit. INTERVENTIONS: Interventions consisted of thermodilution cardiac output measurements. One single duration-controlled injection of cold fluid was used to calculate cardiac output. This controlled injection was performed with a duration equal to one whole ventilation cycle of the ventilator. An algorithm adapted to this duration-controlled injection calculated cardiac output. Moreover, this algorithm has properties to reduce errors caused by artificial ventilation and thermal noise. MEASUREMENTS AND MAIN RESULTS: In 33 patients, the averaged values of four measurements equally spread over the ventilatory cycle (phase-controlled) were compared with the values of two single duration-controlled measurements. The measurements were performed during periods of stable respiration and circulation. No significant difference was observed between the mean of four phase-controlled measurements and the mean of the two duration-controlled measurements. The cardiac output values in the intensive care patients were significantly higher compared with the two other patient groups (p <.05). The difference between the two methods could not be subdivided for the three patient groups (p >.05). The coefficient of variation of the single duration-controlled thermodilution measurements was significantly lower than the single phase-controlled measurements, 3% vs. 6% (p <.01). CONCLUSIONS: One single duration-controlled injection thermodilution measurement is as accurate and repeatable as the mean of four phase-controlled measurements and is clinically feasible.

The volume-dependency of parallel conductance throughout the cardiac cycle and its consequence for volume estimation of the left ventricle in patients.

OBJECTIVE: To study the hypothesis that the electrical conductance of tissues and fluids (parallel conductance (G(p))) around the ventricle depends on left ventricular volume throughout the cardiac cycle. METHODS: We extended a recently developed method to determine G(p) throughout the cardiac cycle. First, we compared the estimates of parallel conductances obtained with the new method (G(a)(p)) with those of the conventional one (G(1)(p)), both averaged over the cardiac cycles. Secondly, G(a)(p) was determined throughout the cardiac cycle and its volume dependency was assessed. Thirdly, the factor alpha was calculated as the ratio between stroke volume, obtained by the conductance method using G(1)(p), and that obtained by a thermodilution method. Because the non-homogeneous field was indicated to be the reason for the dependency of G(p) on left ventricular volume as well as for the need for alpha, we tested whether the hypothesis implies that a correction with alpha is not needed if G(p) is determined throughout the cardiac cycle. RESULTS: We found a negative linear relation between G(p) and left ventricular volume. This relation appeared to be reproducible within each patient. Furthermore, we found that alpha deviates from 1 primarily due to the dependency of G(p) on left ventricular volume. CONCLUSION: To obtain stroke volume or to determine absolute left ventricular volume continuously within a cardiac cycle, G(p) should be determined throughout each cardiac cycle and if a constant G(p) throughout the cardiac cycle is used a correction with the factor alpha should be made to correct for a possible influence of electrical field heterogeneity.

A comparison of cardiac output derived from the arterial pressure wave against thermodilution in cardiac surgery patients.

In three clinical centres, we compared a new method for measuring cardiac output with conventional thermodilution. The new method computes beat-to-beat cardiac output from radial artery pressure by simulating a three-element model of aortic input impedance, and includes non-linear aortic mechanical properties and a self-adapting systemic vascular resistance. We compared cardiac output by continuous model simulation (MF) with thermodilution cardiac output (TD) in 54 patients (18 female, 36 male) undergoing coronary artery bypass surgery. We made three or four conventional thermodilution estimates spread equally over the ventilatory cycle. In 490 series of measurements, thermodilution cardiac output ranged from 2.1 to 9.3, mean 5.0 litre min(-1). MF differed +0.32 (1.0) litre min(-1) on average with limits of agreement of -1.68 and +2.32 litre min(-1). Differences decreased when the first series of measurements in a patient was used to calibrate the model. In 436 remaining series, the mean difference became -0.13 (0.47) litre min(-1) with limits of agreement of -1.05 and +0.79 litre min(-1). When consecutive measurements were made, the change was greater than 0.5 litre min(-1), on 204 occasions. The direction of change was the same with both methods in 199. The difference between the methods remained near zero during surgery suggesting that a single calibration per patient was adequate. Aortic model simulation with radial artery pressure as input reliably monitors changes in cardiac output in cardiac surgery patients. Before calibration, the model cannot replace thermodilution, but after calibration the model method can quantitatively replace further thermodilution estimates.

Computer control versus manual control of systemic hypertension during cardiac surgery.

BACKGROUND: We recently demonstrated the feasibility of computer controlled infusion of vasoactive drugs for the control of systemic hypertension during cardiac surgery. The objective of the current study was to investigate the effects of computer controlled blood pressures on hemodynamic stability when compared to conventional manual control. METHOD: Systemic artery blood pressures were managed either by computer (80 patients) or by a well-trained anesthesiologist (80 patients). The vasodilator drugs sodium nitroprusside and nitroglycerin were used. Hemodynamic stability was determined from the standard deviation of the mean arterial pressure samples and from the percentages of time that arterial pressure was hypertensive or hypotensive. RESULTS: The average standard deviation of the mean arterial pressure samples was smaller for the computer controlled than for the manually controlled group: 7.5+/-2.2 (mean+/-SD) versus 8.9+/-2.3 mmHg (P<0.0001). The systemic artery pressure was less hypertensive and less hypotensive in the computer controlled than in the manually controlled group: 9.4+/-5.7 versus 13.1+/-6.0% (P<0.0001) and 8.0+/-5.9 versus 11.8+/-7.4% (P<0.0001), respectively. CONCLUSION: We conclude that, compared with manual control, computer control of systemic hypertension significantly improved hemodynamic stability during cardiac surgery.

A new approach to determine parallel conductance for left ventricular volume measurements.

OBJECTIVES: To determine absolute ventricular volume with the conductance catheter technique, the electrical conductance of tissues and fluids (parallel conductance) around the ventricle should be determined precisely. METHODS: A new objective method to estimate parallel conductance based on analysis of the dilution curve of hypertonic saline was investigated. The parallel conductances obtained with the new method (G(a)(p)) were compared to those obtained with the conventional method (G(l)(p)). The study was performed in the left ventricle of 12 patients. RESULTS: G(a)(p) was not significantly different from G(l)(p). For the G(l)(p) method the average percentage difference between duplicate values, both taken as absolute values, was 15.06% and for the G(a)(p) method it was 4. 01%. Thus the reproducibility of the method is a factor four better than that of the method. This difference appeared to be significant. CONCLUSION: We conclude that a smaller number of injections will be required to obtain the same precision using our method.

Automated cardiac output measurements by ultrasound are inaccurate at high cardiac outputs.

OBJECTIVE: The sonographic technique of automated cardiac output measurement (ACM) is a promising new method to measure cardiac output and could be of use in a high-risk obstetric unit in the treatment of pre-eclamptic patients. The aim was to determine the accuracy of the ACM method. DESIGN: Comparative study of the sonographic technique of ACM versus cardiac output measured by thermodilution (TD). METHODS: The study included 39 intensive care patients, 21 men, 13 non-pregnant women and five severely pre-eclamptic pregnant patients, with a wide range of cardiac outputs, in whom TD catheters had been inserted for clinical reasons. Two separate experienced observers, blinded to the results obtained with the other method, performed four successive measurements in each patient with either the ACM or TD technique. The averaged cardiac output value per patient and method was used for comparison. RESULTS: Cardiac output was successfully measured with ACM and TD in 85 and 100% of patients, respectively. Mean cardiac output measured by ACM (6.77 +/- 1.90 L/min) was significantly lower than that measured by TD (9.12 +/- 3.06 L/min). Although cardiac output values obtained with ACM were significantly correlated with those measured by TD, the ACM values were consistently lower than TD values in the higher cardiac output range; the relationship was represented by ACM = 0.35 TD + 3.55 L/min (r = 0.57, P < 0.001). The (ACM - TD) difference increased significantly with cardiac output, through a difference in stroke volume, not in heart rate. CONCLUSION: The ACM is not an accurate tool to measure cardiac output in patients with a high cardiac output, including treated pre-eclamptic women.

Conductance method for the measurement of cross-sectional areas of the aorta.

A modified conductance method to determine the cross-sectional areas (CSAs) of arteries in piglets was evaluated in vivo. The method utilized a conductance catheter having four electrodes. Between the outer electrodes an alternating current was applied and between the inner electrodes the induced voltage difference was measured and converted into a conductance. CSA was determined from measured conductance minus parallel conductance, which is the conductance of the tissues surrounding the vessel times the length between the measuring electrodes of the conductance catheter divided by the conductivity of blood. The parallel conductance was determined by injecting hypertonic saline to change blood conductivity. The conductivity of blood was calculated from temperature and hematocrit and corrected for maximal deformation and changes in orientation of the erythrocytes under shear stress conditions. The equations to calculate the conductivity of blood were obtained from in vitro experiments. In vivo average aortic CSAs. determined with the conductance method CSA(G) in five piglets, were compared to those determined with the intravascular ultrasound method CSA(IVUS). The regression equation between both values was CSA(G)=-0.09+1.00 x CSA(IVUS), r=0.97, n=53. The mean difference between the values was -0.29%+/-5.57% (2 standard deviations). We conclude that the modified conductance method is a reliable technique to estimate the average cross-sectional areas of the aorta in piglets.

Automated infusion of vasoactive and inotropic drugs to control arterial and pulmonary pressures during cardiac surgery.

OBJECTIVE: To evaluate the feasibility of a closed-loop system for simultaneous control of systemic arterial and pulmonary artery blood pressures during cardiac surgery. DESIGN: Feasibility study. SETTING: The cardiac surgery operating room. PATIENTS: The performance of the multiple-drug closed-loop system was evaluated during cardiac surgery in 30 patients who required treatment with more than one vasoactive or inotropic drug. INTERVENTIONS: A multiple-drug closed-loop system integrated five single-drug blood pressure controllers. Arterial hypertension was controlled using sodium nitroprusside or nitroglycerin, arterial hypotension was controlled using noradrenaline or dobutamine, and pulmonary hypertension was controlled using nitroglycerin. The anesthesiologist selected target pressures and single-drug blood pressure controllers. The multiple-drug closed-loop system had a set of priority rules that automatically activated from the selected single-drug controllers the optimum single-drug controller for each hemodynamic state. Drug infusion rates of the nonactive controllers were kept constant. The initial knowledge that was used to construct the priority rules was obtained from standard anesthetic protocols on perioperative management of cardiac surgical patients. A supervisory computer program defined the actions to be taken in cases of infusion pump problems, invalid pressure measurements, and during unexpected increases and decreases in systemic arterial pressure. MEASUREMENTS AND MAIN RESULTS: The activation of single-drug controllers by the priority rules was accurate and fast. On average, a different single-drug controller was activated once every 7.2 mins. As a measure of variability, the average deviation of mean arterial pressure and mean pulmonary artery pressure from their target values was evaluated and was 8.6+/-4.0 and 4.4+/-4.0 mm Hg, respectively, before cardiopulmonary bypass and 8.0+/-3.6 and 2.4+/-0.9 mm Hg, respectively, after cardiopulmonary bypass. None of the single-drug controllers showed any signs of unstable response. CONCLUSION: Closed-loop control of both arterial and pulmonary pressures using multiple drugs is feasible during cardiac surgery.

Tracing best PEEP by applying PEEP as a RAMP.

OBJECTIVE: The aim of this study was to show the feasibility of a slow, continuously increasing level of positive end-expiratory pressure (PEEP) (ramp manoeuvre) in selecting best PEEP and to evaluate whether best PEEP, as defined by maximal oxygen transport, coincides with best systemic arterial oxygenation or best compliance. DESIGN: In 11 anaesthetized piglets, PEEP was increased between 0 cmH2O (zero end-expiratory pressure; ZEEP) and 15 cmH2O (PEEP15) with a constant rate of 0.67 cmH2O x min(-1). This ramp manoeuvre was performed both under normal conditions and after induction of an experimental lung oedema. During the ramp manoeuvre, haemodynamic and pulmonary variables were monitored almost continuously. RESULTS: During the rise in PEEP, cardiac output declined in a non-linear way. In the series with normal conditions, best PEEP was always found at ZEEP. In the series with experimental lung oedema, best PEEP, as defined by maximum oxygen transport, was found at PEEP1-6, as defined by maximal compliance, at PEEP7.5 and by maximal arterial oxygen tension (PaO2) at PEEP10-14. CONCLUSIONS: Best PEEP according to oxygen transport is lower than best PEEP according to compliance and PaO2; the use of PEEP as a ramp might prevent unnecessarily high levels of PEEP.