Goal-directed colloid versus crystalloid therapy and microcirculatory blood flow following ischemia/reperfusion.

OBJECTIVE: Ischemia/reperfusion can impair microcirculatory blood flow. It remains unknown whether colloids are superior to crystalloids for restoration of microcirculatory blood flow during ischemia/reperfusion injury. We tested the hypothesis that goal-directed colloid - compared to crystalloid - therapy improves small intestinal, renal, and hepatic microcirculatory blood flow in pigs with ischemia/reperfusion injury. METHODS: This was a randomized trial in 32 pigs. We induced ischemia/reperfusion by supra-celiac aortic-cross-clamping. Pigs were randomized to receive either goal-directed isooncotic hydroxyethyl-starch colloid or balanced isotonic crystalloid therapy. Microcirculatory blood flow was measured using Laser-Speckle-Contrast-Imaging. The primary outcome was small intestinal, renal, and hepatic microcirculatory blood flow 4.5 h after ischemia/reperfusion. Secondary outcomes included small intestinal, renal, and hepatic histopathological damage, macrohemodynamic and metabolic variables, as well as specific biomarkers of tissue injury, renal, and hepatic function and injury, and endothelial barrier function. RESULTS: Small intestinal microcirculatory blood flow was higher in pigs assigned to isooncotic hydroxyethyl-starch colloid therapy than in pigs assigned to balanced isotonic crystalloid therapy (768.7 (677.2-860.1) vs. 595.6 (496.3-694.8) arbitrary units, p = .007). There were no important differences in renal (509.7 (427.2-592.1) vs. 442.1 (361.2-523.0) arbitrary units, p = .286) and hepatic (604.7 (507.7-701.8) vs. 548.7 (444.0-653.3) arbitrary units, p = .376) microcirculatory blood flow between groups. Pigs assigned to colloid - compared to crystalloid - therapy also had less small intestinal, but not renal and hepatic, histopathological damage. CONCLUSIONS: Goal-directed isooncotic hydroxyethyl-starch colloid - compared to balanced isotonic crystalloid - therapy improved small intestinal, but not renal and hepatic, microcirculatory blood flow in pigs with ischemia/reperfusion injury. Whether colloid therapy improves small intestinal microcirculatory blood flow in patients with ischemia/reperfusion needs to be investigated in clinical trials.

Effect of thoracic epidural anesthesia on postoperative outcome in major liver surgery: a retrospective cohort study.

PURPOSE: Postoperative complications after major liver surgery are common. Thoracic epidural anesthesia may provide beneficial effects on postoperative outcome. We strove to compare postoperative outcomes in major liver surgery patients with and without thoracic epidural anesthesia. METHODS: This was a retrospective cohort study in a single university medical center. Patients undergoing elective major liver surgery between April 2012 and December 2016 were eligible for inclusion. We divided patients into two groups according to whether or not they had thoracic epidural anesthesia for major liver surgery. The primary outcome was postoperative hospital length of stay, i.e., from day of surgery until hospital discharge. Secondary outcomes included 30-day postoperative mortality and major postoperative complications. Additionally, we investigated the effect of thoracic epidural anesthesia on perioperative analgesia doses and the safety of thoracic epidural anesthesia. RESULTS: Of 328 patients included in this study, 177 (54.3%) received thoracic epidural anesthesia. There were no clinically important differences in postoperative hospital length of stay (11.0 [7.00-17.0] vs. 9.00 [7.00-14.0] days, p = 0.316, primary outcome), death (0.0 vs. 2.7%, p = 0.995), or the incidence of postoperative renal failure (0.6 vs. 0.0%, p = 0.99), sepsis (0.0 vs. 1.3%, p = 0.21), or pulmonary embolism (0.6 vs. 1.4%, p = 0.59) between patients with or without thoracic epidural anesthesia. Perioperative analgesia doses - including the intraoperative sufentanil dose (0.228 [0.170-0.332] vs. 0.405 [0.315-0.565] µg·kg-1·h-1, p < 0.0001) - were lower in patients with thoracic epidural anesthesia. No major thoracic epidural anesthesia-associated infections or bleedings occurred. CONCLUSION: This retrospective analysis suggests that thoracic epidural anesthesia does not reduce postoperative hospital length of stay in patients undergoing major liver surgery - but it may reduce perioperative analgesia doses. Thoracic epidural anesthesia was safe in this cohort of patients undergoing major liver surgery. These findings need to be confirmed in robust clinical trials.

Continuous intra-arterial versus intermittent oscillometric arterial pressure monitoring and hypotension during induction of anaesthesia: the AWAKE randomised trial.

BACKGROUND: Hypotension during induction of anaesthesia is associated with organ injury. Continuous arterial pressure monitoring might help reduce hypotension. We tested the hypothesis that continuous intra-arterial compared with intermittent oscillometric arterial pressure monitoring reduces hypotension during induction of anaesthesia in noncardiac surgery patients. METHODS: In this single-centre randomised trial, 242 noncardiac surgery patients in whom intra-arterial arterial pressure monitoring was planned were randomised to unblinded continuous intra-arterial or to intermittent oscillometric arterial pressure monitoring (with blinded intra-arterial arterial pressure monitoring) during induction of anaesthesia. The primary endpoint was the area under a mean arterial pressure (MAP) of 65 mm Hg within the first 15 min of induction of anaesthesia. Secondary endpoints included areas under MAP values of 60, 50, and 40 mm Hg and durations of MAP values <65, <60, <50, and <40 mm Hg. RESULTS: There were 224 subjects available for analysis. The median (25th-75th percentile) area under a MAP of 65 mm Hg was 15 (2-36) mm Hg • min in subjects assigned to continuous intra-arterial monitoring and 46 (7-111) mm Hg • min in subjects assigned to intermittent oscillometric monitoring (P<0.001). Subjects assigned to continuous intra-arterial monitoring had smaller areas under MAP values of 60, 50, and 40 mm Hg and shorter durations of MAP values <65, <60, <50, and <40 mm Hg than subjects assigned to intermittent oscillometric monitoring. CONCLUSION: Continuous intra-arterial arterial pressure monitoring reduces hypotension during induction of anaesthesia compared with intermittent oscillometric arterial pressure monitoring in noncardiac surgery patients. In patients for whom an arterial catheter is planned, clinicians might therefore consider inserting the arterial catheter before rather than after induction of anaesthesia. CLINICAL TRIALS REGISTRATION: NCT04894019.

Effects of fluids vs. vasopressors on spinal cord microperfusion in hemorrhagic shock induced ischemia/reperfusion.

OBJECTIVE: Spinal cord injury induced by ischemia/reperfusion is a devastating complication of aortic repair. Despite developments for prevention and treatment of spinal cord injury, incidence is still considerably high majorly impacting patient outcome. Microcirculation is paramount for tissue perfusion and oxygen supply and often dissociated from macrohemodynamic parameters used to guide resuscitation. Effects of fluids vs. vasopressors in the setting of hemodynamic resuscitation on spinal cord microperfusion are unknown. Aim of this study was to compare the effects of vasopressor and fluid resuscitation on spinal cord microperfusion in a translational acute pig model of hemorrhagic shock induced ischemia/reperfusion injury. METHODS: We designed this study as prospective randomized explorative large animal study. We induced hemorrhagic shock in 20 pigs as a model of global ischemia/reperfusion injury. We randomized animals to receive either fluid or vasopressor resuscitation. We measured spinal cord microperfusion using fluorescent microspheres as well as laser-Doppler probes. We monitored and analyzed macrohemodynamic parameters and cerebrospinal fluid pressure. RESULTS: Spinal cord microperfusion decreased following hemorrhagic shock induced ischemia/reperfusion injury. Both fluids and vasopressors sufficiently restored spinal cord microperfusion. There were no important changes between groups (percentage changes compared to baseline: fluids 14.0 (0.31-27.6) vs. vasopressors 24.3 (8.12-40.4), p = .340). However, cerebrospinal fluid pressure was higher in animals receiving fluid resuscitation (percentage changes compared to baseline: fluids 27.7 (12.6-42.8) vs. vasopressors -5.56 ((-19.8)-8.72), p = .003). Microcirculatory resuscitation was in line with improvements of macrohemodynamic parameters. CONCLUSIONS: Both, fluids and vasopressors, equally restored spinal cord microperfusion in a porcine acute model of hemorrhagic shock induced ischemia/reperfusion injury. However, significant differences in cerebrospinal fluid pressure following resuscitation were present. Future studies should evaluate these effects in perfusion disruption induced ischemia/reperfusion conditions of microcirculatory deterioration.

Assessing volume responsiveness using right ventricular dynamic indicators of preload.

PURPOSE: Dynamic indicators of preload currently only do reflect preload requirements of the left ventricle. To date, no dynamic indicators of right ventricular preload have been established. The aim of this study was to calculate dynamic indicators of right ventricular preload and assess their ability to predict ventricular volume responsiveness. MATERIALS AND METHODS: The study was designed as experimental trial in 20 anaesthetized pigs. Micro-tip catheters and ultrasonic flow probes were used as experimental reference to enable measurement of right ventricular stroke volume and pulse pressure. Hypovolemia was induced (withdrawal of blood 20 ml/kg) and thereafter three volume-loading steps were performed. ROC analysis was performed to assess the ability of dynamic right ventricular parameters to predict volume response. RESULTS: ROC analysis revealed an area under the curve (AUC) of 0.82 (CI 95% 0.73-0.89; p < 0.001) for right ventricular stroke volume variation (SVVRV), an AUC of 0.72 (CI 95% 0.53-0.85; p = 0.02) for pulmonary artery pulse pressure variation (PPVPA) and an AUC of 0.66 (CI 95% 0.51-0.79; p = 0.04) for pulmonary artery systolic pressure variation (SPVPA). CONCLUSIONS: In our experimental animal setting, calculating dynamic indicators of right ventricular preload is possible and appears promising in predicting volume responsiveness.

The use of pulse pressure variation for predicting impairment of microcirculatory blood flow.

Dynamic parameters of preload have been widely recommended to guide fluid therapy based on the principle of fluid responsiveness and with regard to cardiac output. An equally important aspect is however to also avoid volume-overload. This accounts particularly when capillary leakage is present and volume-overload will promote impairment of microcirculatory blood flow. The aim of this study was to evaluate, whether an impairment of intestinal microcirculation caused by volume-load potentially can be predicted using pulse pressure variation in an experimental model of ischemia/reperfusion injury. The study was designed as a prospective explorative large animal pilot study. The study was performed in 8 anesthetized domestic pigs (German landrace). Ischemia/reperfusion was induced during aortic surgery. 6 h after ischemia/reperfusion-injury measurements were performed during 4 consecutive volume-loading-steps, each consisting of 6 ml kg-1 bodyweight-1. Mean microcirculatory blood flow (mean Flux) of the ileum was measured using direct laser-speckle-contrast-imaging. Receiver operating characteristic analysis was performed to determine the ability of pulse pressure variation to predict a decrease in microcirculation. A reduction of ≥ 10% mean Flux was considered a relevant decrease. After ischemia-reperfusion, volume-loading-steps led to a significant increase of cardiac output as well as mean arterial pressure, while pulse pressure variation and mean Flux were significantly reduced (Pairwise comparison ischemia/reperfusion-injury vs. volume loading step no. 4): cardiac output (l min-1) 1.68 (1.02-2.35) versus 2.84 (2.15-3.53), p = 0.002, mean arterial pressure (mmHg) 29.89 (21.65-38.12) versus 52.34 (43.55-61.14), p < 0.001, pulse pressure variation (%) 24.84 (17.45-32.22) versus 9.59 (1.68-17.49), p = 0.004, mean Flux (p.u.) 414.95 (295.18-534.72) versus 327.21 (206.95-447.48), p = 0.006. Receiver operating characteristic analysis revealed an area under the curve of 0.88 (CI 95% 0.73-1.00; p value < 0.001) for pulse pressure variation for predicting a decrease of microcirculatory blood flow. The results of our study show that pulse pressure variation does have the potential to predict decreases of intestinal microcirculatory blood flow due to volume-load after ischemia/reperfusion-injury. This should encourage further translational research and might help to prevent microcirculatory impairment due to excessive fluid resuscitation and to guide fluid therapy in the future.

Real-Time Assessment of Spinal Cord Microperfusion in a Porcine Model of Ischemia/Reperfusion.

Spinal cord injury is a devastating complication of aortic repair. Despite developments for the prevention and treatment of spinal cord injury, its incidence is still considerably high and therefore, influences patient outcome. Microcirculation plays a key role in tissue perfusion and oxygen supply and is often dissociated from macrohemodynamics. Thus, direct evaluation of spinal cord microcirculation is essential for the development of microcirculation-targeted therapies and the evaluation of existing approaches in regard to spinal cord microcirculation. However, most of the methods do not provide real-time assessment of spinal cord microcirculation. The aim of this study is to describe a standardized protocol for real-time spinal cord microcirculatory evaluation using laser-Doppler needle probes directly inserted in the spinal cord. We used a porcine model of ischemia/reperfusion to induce deterioration of the spinal cord microcirculation. In addition, a fluorescent microsphere injection technique was used. Initially, animals were anesthetized and mechanically ventilated. Thereafter, laser-Doppler needle probe insertion was performed, followed by the placement of cerebrospinal fluid drainage. A median sternotomy was performed for exposure of the descending aorta to perform aortic cross-clamping. Ischemia/reperfusion was induced by supra-celiac aortic cross-clamping for a total of 48 min, followed by reperfusion and hemodynamic stabilization. Laser-Doppler Flux was performed in parallel with macrohemodynamic evaluation. In addition, automated cerebrospinal fluid drainage was used to maintain a stable cerebrospinal pressure. After completion of the protocol, animals were sacrificed, and the spinal cord was harvested for histopathological and microsphere analysis. The protocol reveals the feasibility of spinal cord microperfusion measurements using laser-Doppler probes and shows a marked decrease during ischemia as well as recovery after reperfusion. Results showed comparable behavior to fluorescent microsphere evaluation. In conclusion, this new protocol might provide a useful large animal model for future studies using real-time spinal cord microperfusion assessment in ischemia/reperfusion conditions.

Detrimental effects of cerebrospinal fluid pressure elevation on spinal cord perfusion: first-time direct detection in a large animal model.

OBJECTIVES: Cerebrospinal fluid (CSF) drainage is routinely utilized to mitigate perioperative and postoperative spinal cord ischaemia in open and endovascular thoraco-abdominal aortic aneurysm repair to prevent permanent paraplegia. Clinical decision-making in the vulnerable perioperative period, however, is still based on limited clinical and experimental data. Our aim was to investigate the isolated effect of CSF pressure elevation on spinal cord perfusion in an established large animal model. METHODS: Ten juvenile pigs with normal (native) arterial inflow (patent segmental arteries and collaterals) underwent iatrogenic CSF pressure elevation (×2, ×3, ×4 from their individual baseline pressure). Each pressure level was maintained for 30 min to mimic clinical response time. After the quadrupling of CSF pressure, the dural sac was slowly depressurized against gravity allowing CSF pressure to passively return to baseline values. Measurements were taken 30 and 60 min after normalization, and microspheres for regional blood flow analysis were injected at each time point. RESULTS: Spinal cord perfusion decreased significantly at all mid-thoracic to lumbar cord segments at the doubling of CSF pressure and declined to values <53% compared to baseline when pressure was quadrupled. Normalizing CSF pressure led to an intense hyperperfusion of up to 186% at the cervical level and 151% within the lumbar region. CONCLUSIONS: CSF pressure elevation results in a relevant impairment of spinal cord blood supply. Close perioperative and postoperative monitoring of CSF pressure is crucial for maintaining sufficient spinal cord perfusion. Radical and rapid withdrawal of CSF is followed by significant hyperperfusion in all spinal cord segments and may lead to 'drainage-related' iatrogenic reperfusion injury-aggravating the risk of delayed spinal cord injury-and should therefore be avoided.

Sonographic real-time imaging of tissue perfusion in a porcine haemorrhagic shock model.

Injection of fluorescence-labelled microspheres (FMs) in pigs allows only the postmortem determination of organ perfusion. Colour duplex ultrasound (CDU) and contrast-enhanced ultrasound were established as techniques for real-time imaging of tissue perfusion in a porcine haemorrhagic shock model. Haemorrhagic shock was provoked in nine domestic pigs by taking at least 15% of the calculated blood volume. Ultrasound examinations were performed with a Hitachi HI VISION Ascendus. SonoVue was injected for contrast-enhanced ultrasound. Monitoring of the resistive index and time-to-peak ratio enabled quantification of tissue perfusion in vivo during the entire study, allowing real-time differentiation of animals with systemic shock versus failing shock effect. Postmortem analyses of injected FMs confirmed the sonographic in vivo results. Determination of the resistive index and time-to-peak ratio by CDU and contrast-enhanced ultrasound allowed real-time monitoring of tissue perfusion. Effects of haemorrhagic shock and therapeutic approaches related to organ perfusion can be observed live and in vivo.

Volume Based Resuscitation and Intestinal Microcirculation after Ischaemia/Reperfusion Injury: Results of an Exploratory Aortic Clamping Study in Pigs.

OBJECTIVES: In the presence of ischaemia/reperfusion (I/R) induced endothelial injury, volume administration may not correlate with increased microcirculation. The aim of this study was to evaluate intestinal microcirculation after standardised sequential volume loading in an animal model of I/R injury following supracoeliac aortic clamping. METHODS: This was a prospective exploratory pilot animal study. Intestinal I/R injury was induced in eight pigs during experimental thoraco-abdominal aortic repair. After 6 h of I/R, microcirculatory blood flow (mFlux, measured in the ileum using direct laser speckle contrast imaging) and macrohaemodynamic parameters (using trans-cardiopulmonary thermodilution) were measured and measurements were repeated after each of four sequential volume loading steps (VLS1 - 4). Each load was administered over 5 min followed by another 5 min for equilibration. RESULTS: All animals survived until after VLS4. After 6 h of I/R cardiac output (CO) (p < .001) and mFlux (p < .001) had both decreased. CO increased again after VLS1 (p < .001) and VLS2 (p = .036), whereas mFlux did not change. In contrast, mFlux further decreased after VLS3 (p < .01) and VLS4 (p < .001), whereas CO did not change anymore. Extravascular lung water continued to increase after VLS2 (p = .046) and VLS4 (p = .049). CONCLUSIONS: I/R leads to impaired intestinal microcirculation, which was not restored by volume administration in spite of improved CO. In contrast, further volume administration exceeding preload reserves was associated with additional decreases in the intestinal microcirculation. The potentially negative effect of excessive volume resuscitation after I/R injury should encourage further translational research.

Assessment of central hemodynamic effects of phenylephrine: an animal experiment.

Phenylephrine is an α1-adrenergic receptor agonist widely used to treat perioperative hypotension. Its other hemodynamic effects, in particular on preload and contractility, remain controversial. We, therefore, investigated the effect of continuously applied phenylephrine on central hemodynamics in eight mechanically ventilated domestic pigs. Mean arterial pressure (MAP) was increased in steps by 50%, and 100% using phenylephrine. Besides stroke volume (SV), cardiac output (CO), and MAP, mean systemic vascular resistance (SVR) and dynamic arterial elastance (Eadyn) were assessed for characterization of afterload. Changes in preload were assessed by central venous pressure (CVP), global end-diastolic volume (GEDV), mean systemic filling pressure analog (Pmsfa), pulse pressure variation (PPV), and stroke volume variation (SVV). Further, cardiac function index (CFI), global ejection fraction and dPmax were measured as markers of preload dependent contractility. MAP, SV, and CO significantly increased following both interventions, as did SVR. In contrast, Eadyn did not show significant changes. Although the volumetric preload variable GEDV increased after the first step of phenylephrine, this was not reflected by significant changes in CVP or Pmsfa. CFI and dPmax significantly increased after both steps. Phenylephrine does not only affect cardiac afterload, but also increases effective preload. In contrast to CVP and Pmsfa, this effect can be monitored by GEDV. Further, phenylephrine affects contractility.

Feasibility Study of a Novel High-Flow Cold Air Cooling Protocol of the Porcine Brain Using MRI Temperature Mapping.

Early, prehospital cooling seeks to reduce and control the body temperature as early as possible to protect the brain and improve patient outcome in cardiac arrest, stroke, and traumatic brain injury. In this study, we investigate the feasibility of localized cooling of the porcine brain by using a novel high-flow cold air protocol, which utilizes the close proximity between the nasal cavity and the brain. Five adult pigs were anesthetized and temperature change was mapped before, during, and after cooling by using the proton resonance frequency method on a 3 T Siemens Magnetom Skyra system. Cooling was performed by inserting a tube blowing high-flow (250 L/min) cold air (-10°C) through the nasal cavity for 5-20 minutes. The brain temperature change was measured by using an MRI phase mapping technique utilizing the temperature-dependent proton resonance frequency change. MRI maps showed significant temperature reduction of the porcine brain. On average, a mean whole-brain cooling effect of -0.33°C ± 0.30°C was found after 5 minutes of cooling. The anterior part of the brain was directly exposed to the cold and showed a significantly larger temperature drop (-0.83°C ± 0.51°C) than the posterior part (-0.03°C ± 0.21°C). However, a large variability of the temperature drop was observed between the animals. This variability may be caused by not well-controlled factors confounding the MRI temperature mapping, for example, subject movement, or cooling effectiveness, for example, core temperature or nasal patency. The results indicate that the proposed high-flow cold air protocol allows for localized cooling of the frontal porcine brain, which may be clinically relevant for traumatic injuries of the frontal brain where systemic cooling is unfavorable.

Reliability of transcardiopulmonary thermodilution cardiac output measurement in experimental aortic valve insufficiency.

BACKGROUND: Monitoring cardiac output (CO) is important to optimize hemodynamic function in critically ill patients. The prevalence of aortic valve insufficiency (AI) is rising in the aging population. However, reliability of CO monitoring techniques in AI is unknown. The aim of this study was to investigate the impact of AI on accuracy, precision, and trending ability of transcardiopulmonary thermodilution-derived COTCPTD in comparison with pulmonary artery catheter thermodilution COPAC. METHODS: Sixteen anesthetized domestic pigs were subjected to serial simultaneous measurements of COPAC and COTCPTD. In a novel experimental model, AI was induced by retraction of an expanded Dormia basket in the aortic valve annulus. The Dormia basket was delivered via a Judkins catheter guided by substernal epicardial echocardiography. High (HPC), moderate (MPC) and low cardiac preload conditions (LPC) were induced by fluid unloading (20 ml kg-1 blood withdrawal) and loading (subsequent retransfusion of the shed blood and additional infusion of 20 ml kg-1 hydroxyethyl starch). Within each preload condition CO was measured before and after the onset of AI. For statistical analysis, we used a mixed model analysis of variance, Bland-Altman analysis, the percentage error and concordance analysis. RESULTS: Experimental AI had a mean regurgitant volume of 33.6 ± 12.0 ml and regurgitant fraction of 42.9 ± 12.6%. The percentage error between COTCPTD and COPAC during competent valve function and after induction of substantial AI was: HPC 17.7% vs. 20.0%, MPC 20.5% vs. 26.1%, LPC 26.5% vs. 28.1% (pooled data: 22.5% vs. 24.1%). The ability to trend CO-changes induced by fluid loading and unloading did not differ between baseline and AI (concordance rate 95.8% during both conditions). CONCLUSION: Despite substantial AI, transcardiopulmonary thermodilution reliably measured CO under various cardiac preload conditions with a good ability to trend CO changes in a porcine model. COTCPTD and COPAC were interchangeable in substantial AI.

The influence of PEEP and positioning on central venous pressure and venous hepatic hemodynamics in patients undergoing liver resection.

PURPOSE: In order to assess the occurrence of blood congestion in the liver during liver resection, we aimed to evaluate the influence of a positive-end-expiratory-pressure (PEEP) and positioning of patients on central venous pressure (CVP) and venous hepatic blood flow parameters. We further analyzed correlations between CVP and venous hepatic blood flow parameters. METHODS: In 20 patients scheduled for elective liver resection we measured CVP and quantified venous hepatic hemodynamics by ultrasound assessment of flow-velocity and diameter of the right hepatic vein and the portal vein after equilibration following these maneuvers: M1: 0° supine position, PEEP 0 cmH2O; M2: 0° supine position, PEEP 10 cmH2O; M3: 20° reverse-trendelenburg position; PEEP 10 cmH2O; M4: 20° reverse-trendelenburg position, PEEP 0cmH2O. RESULTS: Changing from supine to reverse-trendelenburg position led to a significant decrease in CVP (M3 5.95 ± 2.06 vs. M1 7.35 ± 2.18 mmHg and M2 8.55 ± 1.79 mmHg). A PEEP of 10 cmH2O and reverse-trendelenburg position led to significant reduction of systolic (VsHV) and diastolic (VdHV) flow-velocities of the right hepatic vein (VsHV M3 19.96 ± 6.47 vs. M1 27.81 ± 11.03 cm s-1;VdHV M3 14.94 ± 6.22 vs. M1 20.15 ± 10.34 cm s-1 and M2 20.19 ± 13.19 cm s-1) whereas no significant changes of flow-velocity occurred in the portal vein. No correlations between CVP and diameters or flow-velocities of the right hepatic and the portal vein were found. CONCLUSIONS: Changes of central venous pressure due to changes of PEEP and positioning were not correlated with changes of venous hepatic blood flow parameters as measured after equilibration. Strategies aiming for low central venous pressure cannot be supported by these results. However, before ruling out low-CVP-strategies during liver resections these results should be confirmed by further studies.

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

BACKGROUND: Assessment 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. METHODS: Thirty 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. RESULTS: A 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. CONCLUSIONS: Extravascular 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.

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

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.

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.

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 µg ml(-1) [95% confidence interval (CI) 40.0 to 44.6] in group Sevo1.8% and 21.0 µg 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 µg kg(-1) (95% CI 10.52 to 17.19) in group Sevo1.8% and 4.06 µg kg(-1) (95% CI 2.67 to 5.97) in group SevoBIS (P < 0.001). Pearson's 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.

Effects of thoracic epidural anesthesia on survival and microcirculation in severe acute pancreatitis: a randomized experimental trial.

INTRODUCTION: Severe acute pancreatitis is still a potentially life threatening disease with high mortality. The aim of this study was to evaluate the therapeutic effect of thoracic epidural anaesthesia (TEA) on survival, microcirculation, tissue oxygenation and histopathologic damage in an experimental animal model of severe acute pancreatitis in a prospective animal study. METHODS: In this study, 34 pigs were randomly assigned into 2 treatment groups. After severe acute pancreatitis was induced by intraductal injection of glycodesoxycholic acid in Group 1 (n = 17) bupivacaine (0.5%; bolus injection 2 ml, continuous infusion 4 ml/h) was applied via TEA. In Group 2 (n = 17) no TEA was applied. During a period of 6 hours after induction, tissue oxygen tension (tpO2) in the pancreas and pancreatic microcirculation was assessed. Thereafter animals were observed for 7 days followed by sacrification and histopathologic examination. RESULTS: Survival rate after 7 days was 82% in Group 1 (TEA) versus 29% in Group 2: (Control) (P <0.05). Group 1 (TEA) also showed a significantly superior microcirculation (1,608 ± 374 AU versus 1,121 ± 510 AU; P <0.05) and tissue oxygenation (215 ± 64 mmHg versus 138 ± 90 mmHG; P <0.05) as compared to Group 2 (Control). Consecutively, tissue damage in Group 1 was reduced in the histopathologic scoring (5.5 (3 to 8) versus 8 (5.5 to 10); P <0.05). CONCLUSIONS: TEA led to improved survival, enhanced microcirculatory perfusion and tissue oxygenation and resulted in less histopathologic tissue-damage in an experimental animal model of severe acute pancreatitis.

Prediction of volume-responsiveness during one-lung ventilation: a comparison of static, volumetric, and dynamic parameters of cardiac preload.

OBJECTIVES: The aim of this study was to evaluate the ability of static, volumetric, and dynamic parameters of cardiac preload to predict volume responsiveness during one-lung ventilation (OLV). DESIGN: Prospective experimental study. SETTING: Laboratory of the animal facility of the University Medical Center Hamburg-Eppendorf. PARTICIPANTS: Twenty-three German domestic pigs. INTERVENTIONS: Hypovolemia was induced by withdrawing 20 mL/kg body weight (BW) of blood. OLV was established, and the volume withdrawn was re-transfused in 3 volume-loading steps, each consisting of 7 mL/kg BW. An ultrasonic flow probe around the pulmonary artery was used to measure the stroke-volume index (SVI) and to evaluate the volume response. An increase in the SVI of ≥ 15% was considered a positive response. For each measurement time point, central venous pressure (CVP), left atrial pressure (LAP), the global end-diastolic volume index (GEDI), stroke-volume variation (SVV), and pulse-pressure variation (PPV) were recorded. The ability to predict volume responsiveness was assessed using ROC analysis. MEASUREMENTS AND MAIN RESULTS: A total of 69 volume loading steps were performed, 48 of which showed a positive volume response. ROC analysis revealed the following area under the curve (AUC) values: CVP, 0.88; LAP, 0.65; GEDI, 0.75; SVV, 0.78; and PPV, 0.83. A comparison of the areas under the ROC curves did not reveal any statistically significant differences (p>0.05), with the exception of LAP compared with CVP (p = 0.005). CONCLUSIONS: Under these OLV experimental conditions, the volumetric and dynamic parameters of preload, as well as CVP, seemed to be of similar value in predicting volume responsiveness.