Constantin J. C. Trepte

Goal-Directed Fluid Therapy Using Stroke Volume Variation Does Not Result in Pulmonary Fluid Overload in Thoracic Surgery Requiring One-Lung Ventilation

Background. Goal-directed fluid therapy (GDT) guided by functional parameters of preload, such as stroke volume variation (SVV), seems to optimize hemodynamics and possibly improves clinical outcome. However, this strategy is believed to be rather fluid aggressive, and, furthermore, during surgery requiring thoracotomy, the ability of SVV to predict volume responsiveness has raised some controversy. So far it is not known whether GDT is associated with pulmonary fluid overload and a deleterious reduction in pulmonary function in thoracic surgery requiring one-lung-ventilation (OLV). Therefore, we assessed the perioperative course of extravascular lung water index (EVLWI) and paO2/FiO2-ratio during and after thoracic surgery requiring lateral thoracotomy and OLV to evaluate the hypothesis that fluid therapy guided by SVV results in pulmonary fluid overload. Methods. A total of 27 patients (group T) were enrolled in this prospective study with 11 patients undergoing lung surgery (group L) and 16 patients undergoing esophagectomy (group E). Goal-directed fluid management was guided by SVV (SVV < 10%). Measurements were performed directly after induction of anesthesia (baseline—BL), 15 minutes after implementation OLV (OLVimpl15), and 15 minutes after termination of OLV (OLVterm15). In addition, postoperative measurements were performed at 6 (6postop), 12 (12postop), and 24 (24postop) hours after surgery. EVLWI was measured at all predefined steps. The paO2/FiO2-ratio was determined at each point during mechanical ventilation (group L: BL-OLVterm15; group E: BL-24postop). Results. In all patients (group T), there was no significant change (P > 0.05) in EVLWI during the observation period (BL: 7.8 ± 2.5, 24postop: 8.1 ± 2.4 mL/kg). A subgroup analysis for group L and group E also did not reveal significant changes of EVLWI. The paO2/FiO2-ratio decreased significantly during the observation period (group L: BL: 462 ± 140, OLVterm15: 338 ± 112 mmHg; group E: BL: 389 ± 101, 24postop: 303 ± 74 mmHg) but remained >300 mmHg except during OLV. Conclusions. SVV-guided fluid management in thoracic surgery requiring lateral thoracotomy and one-lung ventilation does not result in pulmonary fluid overload. Although oxygenation was reduced, pulmonary function remained within a clinically acceptable range.

Hemodynamic management of septic shock: is it time for "individualized goal-directed hemodynamic therapy" and for specifically targeting the microcirculation?

ABSTRACT Septic shock is a life-threatening condition in both critically ill medical patients and surgical patients during the perioperative phase. In septic shock, specific alterations in global cardiovascular dynamics (i.e., the macrocirculation) and in the microcirculatory blood flow (i.e., the microcirculation) have been described. However, the presence and degree of microcirculatory failure are in part independent from systemic macrohemodynamic variables. Macrocirculatory and microcirculatory failure can independently induce organ dysfunction. We review current diagnostic and therapeutic approaches for the assessment and optimization of both the macrocirculation and the microcirculation in septic shock. There are various technologies for the determination of macrocirculatory hemodynamic variables. We discuss the data on early goal-directed therapy for the resuscitation of the macrocirculation. In addition, we describe the concept of “individualized goal-directed hemodynamic therapy.” Technologies to assess the local microcirculation are also available. However, adequate resuscitation goals for the optimization of the microcirculation still need to be defined. At present, we are not ready to specifically monitor and target the microcirculation in clinical routine outside studies. In the future, concepts for an integrative approach for individualized hemodynamic management of the macrocirculation and in parallel the microcirculation might constitute a huge opportunity to define additional resuscitation end points in septic shock.

Changes in sevoflurane plasma concentration with delivery through the oxygenator during on-pump cardiac surgery

BACKGROUND It is unclear what factors affect the uptake of sevoflurane administered through the membrane oxygenator during cardiopulmonary bypass (CPB) and whether this can be monitored via the oxygenator exhaust gas. METHODS Stable delivery of sevoflurane was administered to 30 elective cardiac surgery patients at 1.8 vol% (inspiratory) via the anaesthetic circuit and ventilator. During CPB, sevoflurane was administered in the oxygenator fresh gas supply (Compactflo Evolution™; Sorin Group, Milano, Italy). Sevoflurane plasma concentration (SPC) was measured using gas chromatography. Changes were correlated with bispectral index (BIS), patient temperature, haematocrit, plasma albumin concentration, oxygenator fresh gas flow, and the sevoflurane concentration in the oxygenator exhaust at predefined time points. RESULTS The mean SPC pre-bypass was 54.9 µg ml(-1) [95% confidence interval (CI): 50.6-59.1]. SPC decreased to 43.2 µg ml(-1) (95% CI: 40.3-46.1; P<0.001) after initiation of CPB, and was lower still during rewarming and weaning from bypass, 39.4 µg ml(-1) (95% CI: 36.6-42.3; P<0.001). BIS did not exceed a value of 55. SPCs were higher during hypothermia (P<0.001) and with an increase in oxygenator fresh gas flow (P=0.015), and lower with haemodilution (P=0.027). No correlation was found between SPC and the concentration of sevoflurane in the oxygenator exhaust gas (r=-0.04; 95% CI: -0.18 to 0.09; P=0.53). CONCLUSIONS The uptake of sevoflurane delivered via the membrane oxygenator during CPB seems to be affected by hypothermia, haemodilution, and changes in the oxygenator fresh gas supply flow. Measuring the concentration of sevoflurane in the exhaust from the oxygenator is not useful for monitoring sevoflurane administration during bypass.

Electrical impedance tomography (EIT) for quantification of pulmonary edema in acute lung injury.

BackgroundAssessment of pulmonary edema is a key factor in monitoring and guidance of therapy in critically ill patients. To date, methods available at the bedside for estimating the physiologic correlate of pulmonary edema, extravascular lung water, often are unreliable or require invasive measurements. The aim of the present study was to develop a novel approach to reliably assess extravascular lung water by making use of the functional imaging capabilities of electrical impedance tomography.MethodsThirty domestic pigs were anesthetized and randomized to three different groups. Group 1 was a sham group with no lung injury. Group 2 had acute lung injury induced by saline lavage. Group 3 had vascular lung injury induced by intravenous injection of oleic acid. A novel, noninvasive technique using changes in thoracic electrical impedance with lateral body rotation was used to measure a new metric, the lung water ratioEIT, which reflects total extravascular lung water. The lung water ratioEIT was compared with postmortem gravimetric lung water analysis and transcardiopulmonary thermodilution measurements.ResultsA significant correlation was found between extravascular lung water as measured by postmortem gravimetric analysis and electrical impedance tomography (r = 0.80; p < 0.05). Significant changes after lung injury were found in groups 2 and 3 in extravascular lung water derived from transcardiopulmonary thermodilution as well as in measurements derived by lung water ratioEIT.ConclusionsExtravascular lung water could be determined noninvasively by assessing characteristic changes observed on electrical impedance tomograms during lateral body rotation. The novel lung water ratioEIT holds promise to become a noninvasive bedside measure of pulmonary edema.

Thermodilution-derived indices for assessment of left and right ventricular cardiac function in normal and impaired cardiac function.

Objective:The aim of this study was to assess whether thermodilution-derived parameters of right and left ventricular cardiac function (right ventricular ejection fraction, global ejection fraction, cardiac function index) are able to track changes of cardiac contractile function and whether they are influenced by substantial preload reduction. Design:Prospective animal study. Setting:University-affiliated animal research laboratory. Subjects:Domestic pigs. Interventions:Sixteen domestic pigs were studied. Right ventricular ejection fraction, global ejection fraction, and cardiac function index were compared to direct measurement of left ventricular rate of maximum systolic pressure rise and the left ventricular rate of maximum systolic pressure rise corrected to preload. Measurements were done with normal cardiac function during normo- and hypovolemia. Thereafter, cardiac function was impaired by continuous infusion of verapamil and measurements were repeated during normo- and hypovolemia (withdrawal of blood 20 mL kg−1 body weight). Measurements and Main Results:With normal cardiac function, hypovolemia led to a significant decrease of right ventricular ejection fraction from 36.7% ± 6.6% to 29.8% ± 5.8% (p < .001), global ejection fraction from 40.5% ± 6.2% to 33.6% ± 7.6% (p < .001), and the left ventricular rate of maximum systolic pressure rise from 2104 ± 390 mm Hg sec−1 to 1297 ± 438 mm Hg sec−1 (p < .001). Cardiac function index (8.92 ± 2.20 min−1 to 7.93 ± 1.54 min−1) and the left ventricular rate of maximum systolic pressure rise corrected to preload (18.2 ± 4.7 mm Hg sec−1 mL to 15.2 ± 4.3 mm Hg sec−1 mL) did not change significantly. Infusion of verapamil led to a significant reduction of right ventricular ejection fraction, global ejection fraction, cardiac function index, the left ventricular rate of maximum systolic pressure rise, and the left ventricular rate of maximum systolic pressure rise corrected to preload (p < .001). Now, hypovolemia led to a significant decrease of right ventricular ejection fraction (29.1% ± 4.6% to 24.9% ± 5.9%; p < .001), global ejection fraction (37.1% ± 4.7% to 31.9% ± 3.9%; p < .05), cardiac function index (7.58 ± 1.02 to 6.27 ± 1.19 min−1; p < .05), and the left ventricular rate of maximum systolic pressure rise (733 ± 141 mm Hg sec−1 to 426 ± 108 mm Hg sec−1; p < .05). Only the left ventricular rate of maximum systolic pressure rise corrected to preload did not change significantly (6.7 ± 1.3 mm Hg sec−1 mL to 4.6 ± 1 mm Hg sec−1 mL; p > .05). Conclusions:Right ventricular ejection fraction, global ejection fraction, and cardiac function index enable detection of changes in load-independent, intrinsic cardiac contractility. Importantly, they also reflect changes of contractile function caused by substantial decrease of preload, emphasizing the importance of assessing both cardiac contractile function in coherence with cardiac preload to differentiate between reduced intrinsic contractility and hypovolemia.

Effects of one-lung ventilation on thermodilution-derived assessment of cardiac output

BACKGROUND Cardiac output (CO) monitoring can be useful in high-risk patients during one-lung ventilation (OLV), but it is unclear whether thermodilution-derived CO monitoring is valid during OLV. Therefore, we compared pulmonary artery (CO(PATD)) and transcardiopulmonary thermodilution (CO(TPTD)) with an experimental reference in a porcine model. METHODS CO(PATD) and CO(TPTD) were measured in 23 pigs during double-lung ventilation (DLV) and 15 min after the onset of OLV, during conditions of normovolaemia and after haemorrhage. An ultrasonic flow probe placed around the pulmonary artery (CO(PAFP)) was used for reference. RESULTS The range of CO in these experiments was 1.5-3 litre min(-1). Normovolaemia: during DLV and conditions of normovolaemia, the mean (95% limits of agreement) bias for CO(PATD) compared with CO(PAFP) was -0.05 (-0.92 and 0.83) litre min(-1), and 0.58 (-0.40 and 1.55) litre min(-1) for CO(TPTD). During OLV, the bias for CO(PATD) remained unchanged at 0.08 (-0.51 and 0.66) litre min(-1), P=0.15, and the bias for CO(TPTD) increased significantly to 0.85 (0.05 and 1.64) litre min(-1), P=0.047. Hypovolaemia: during DLV, the bias for CO(PATD) compared with CO(PAFP) was 0.22 (-0.20 and 0.66) litre min(-1) and for CO(TPTD) was 0.60 (0.12 and 1.10) litre min(-1). There was no significant change of bias during OLV for CO(PATD) [0.30 (-0.10 and 0.70) (litre min(-1)), P=0.25] or bias CO(TPTD) [0.72 (0.21 and 1.22) (litre min(-1)), P=0.14]. Trending ability during OLV, quantified by the mean of angles θ, showed good values for both CO(PATD) (θ=11.2°) and CO(TPTD) (θ=1.3°). CONCLUSIONS CO(TPTD) is, to some extent, affected by OLV, whereas CO(PATD) is unchanged. Nonetheless, both methods provide an acceptable estimation of CO and particularly of relative changes of CO during OLV.

Comparison of an automated respiratory systolic variation test with dynamic preload indicators to predict fluid responsiveness after major surgery

BACKGROUND Predicting the response of cardiac output to volume administration remains an ongoing clinical challenge. The objective of our study was to compare the ability to predict volume responsiveness of various functional measures of cardiac preload. These included pulse pressure variation (PPV), stroke volume variation (SVV), and the recently launched automated respiratory systolic variation test (RSVT) in patients after major surgery. METHODS In this prospective study, 24 mechanically ventilated patients after major surgery were enrolled. Three consecutive volume loading steps consisting of 300 ml 6% hydroxyethylstarch 130/0.4 were performed and cardiac index (CI) was assessed by transpulmonary thermodilution. Volume responsiveness was considered as positive if CI increased by >10%. RESULTS In total 72 volume loading steps were analysed, of which 41 showed a positive volume response. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve (AUC) of 0.70 for PPV, 0.72 for SVV and 0.77 for RSVT. Areas under the curves of all variables did not differ significantly from each other (P>0.05). Suggested cut-off values were 9.9% for SVV, 10.1% for PPV, and 19.7° for RSVT as calculated by the Youden Index. CONCLUSION In predicting fluid responsiveness the new automated RSVT appears to be as accurate as established dynamic indicators of preload PPV and SVV in patients after major surgery. The automated RSVT is clinically easy to use and may be useful in guiding fluid therapy in ventilated patients.

Respiratory systolic variation test in acutely impaired cardiac function for predicting volume responsiveness in pigs

BACKGROUND Predicting the response of cardiac output (CO) to volume administration remains difficult, in particular in patients with acutely compromised cardiac function, where, even small amounts of i.v. fluids can lead to volume overload. We compared the ability to predict volume responsiveness of different functional haemodynamic parameters, such as pulse pressure variation (PPV), stroke volume variation (SVV), the static preload parameter right atrial pressure (RAP), and global end-diastolic volume (GEDV) with the recently proposed respiratory systolic variation test (RSVT) in acutely impaired cardiac function. METHODS In 13 mechanically ventilated pigs, cardiac function was acutely reduced by continuous application of verapamil to reach a decrease in peak change of left ventricular pressure over time (dP/dt) of 50%. After withdrawal of 20 ml kg(-1) BW blood to establish hypovolaemia, four volume loading steps of 7 ml kg(-1) BW using the shed blood and 6% hydroxyethylstarch 130/0.4 were performed. Volume responsiveness was considered as positive, if CO increased more than 10%. RESULTS Receiver operating characteristic curve analysis revealed an area under the curve (AUC) of 0.88 for the RSVT, 0.84 for PPV, 0.82 for SVV, 0.78 for RAP, and 0.77 for GEDV. CONCLUSIONS Functional parameters of cardiac preload, including the RSVT, allow prediction of fluid responsiveness in an experimental model of acutely impaired cardiac function.

Bispectral index guided titration of sevoflurane in on-pump cardiac surgery reduces plasma sevoflurane concentration and vasopressor requirements: a prospective, controlled, sequential two-arm clinical study.

BACKGROUND Electroencephalographic-based monitoring systems such as the bispectral index (BIS) may reduce anaesthetic overdose rates. OBJECTIVE We hypothesised that goal-directed sevoflurane administration (guided by BIS monitoring) could reduce the sevoflurane plasma concentration (SPC) and intraoperative vasopressor doses during on-pump cardiac surgery. DESIGN A prospective, controlled, sequential two-arm clinical study. SETTING German university medical centre with more than 2500 cardiac surgery interventions per year. PATIENTS Sixty elective on-pump cardiac surgery patients. INTERVENTION In group Sevo1.8% (n = 29), the sedation depth was maintained with a sustained inspired concentration of sevoflurane 1.8% before and during cardiopulmonary bypass (CPB). In group SevoBIS (n = 31), the inspired sevoflurane concentration was titrated to maintain a BIS target between 40 and 60. OUTCOME MEASURES SPC during CPB and the intraoperative administration of noradrenaline. Additional analyses were performed on intraoperative awareness, postoperative blood lactate concentration, duration of mechanical ventilation, intensive care unit length of stay and kidney injury. RESULTS Mean inspired sevoflurane concentration was 0.8% in group SevoBIS, representing a 57.1% reduction (P < 0.001) compared with group Sevo1.8%. The mean SPC was 42.3 &mgr;g ml−1 [95% confidence interval (CI) 40.0 to 44.6] in group Sevo1.8% and 21.0 &mgr;g ml−1 (95% CI 18.8 to 23.3) in group SevoBIS, representing a 50.2% reduction (P < 0.001). During CPB, the mean cumulative dose of noradrenaline administered was 13.48 &mgr;g kg−1 (95% CI 10.52 to 17.19) in group Sevo1.8% and 4.06 &mgr;g kg−1 (95% CI 2.67 to 5.97) in group SevoBIS (P < 0.001). Pearsons correlation coefficient (between the cumulative applied dosage of sevoflurane calculated from the area under the curve of the SPC over time and the administered cumulative noradrenaline dose) was 0.607 (P < 0.001). No intraoperative awareness signs were detected. CONCLUSION BIS-guided titration of sevoflurane reduces the SPC and decreases noradrenaline administration compared with routine care during on-pump cardiac surgery.

Individualized early goal-directed therapy in systemic inflammation: is full utilization of preload reserve the optimal strategy?

Objectives:In severe acute pancreatitis, the administration of fluids in the presence of positive fluid responsiveness is associated with better outcome when compared to guiding therapy on central venous pressure. We compared the effects of such consequent maximization of stroke volume index with a regime using individual values of stroke volume index assessed prior to severe acute pancreatitis induction as therapeutic hemodynamic goals. Design:Prospective, randomized animal study. Setting:University animal research laboratory. Subjects:Thirty domestic pigs. Interventions:After randomization, fluid resuscitation was started 2 hours after severe acute pancreatitis induction and continued for 6 hours according to the respective treatment algorithms. In the control group, fluid therapy was directed by maximizing stroke volume index, and in the study group, stroke volume index assessed prior to severe acute pancreatitis served as primary hemodynamic goal. Measurements and Main Results:Within the first 6 hours of severe acute pancreatitis, the study group received a total of 1,935.8 ± 540.7 mL of fluids compared with 3,462.8 ± 828.2 mL in the control group (p < 0.001). Pancreatic tissue oxygenation did not differ significantly between both groups. Vascular endothelial function, measured by flow-mediated vasodilation before and 6 hours after severe acute pancreatitis induction, revealed less impairment in the study group after treatment interval (–90.76% [study group] vs –130.89% [control group]; p = 0.046). Further, lower levels of heparan sulfate (3.41 ± 5.6 pg/mL [study group] vs 43.67 ± 46.61 pg/mL [control group]; p = 0.032) and interleukin 6 (32.18 ± 8.81 pg/mL [study group] vs 77.76 ± 56.86 pg/mL [control group]; p = 0.021) were found in the study group compared with control group. Histopathological examination of the pancreatic head and corpus at day 7 revealed less edema for the study group compared with the control group (1.82 ± 0.87 [study group] vs 2.89 ± 0.33 [control group, pancreatic head]; p = 0.03; 2.2 ± 0.92 [study group] vs 2.91 ± 0.3 [control group, pancreatic corpus]; p = 0.025). Conclusions:Individualized optimization of intravascular fluid status during the early course of severe acute pancreatitis, compared with a treatment strategy of maximizing stroke volume by fluid loading, leads to less vascular endothelial damage, pancreatic edema, and inflammatory response.