Steffen Rex

Validation of a new arterial pulse contour-based cardiac output device.

Objective:To evaluate the accuracy and precision of an arterial pulse contour-based continuous cardiac output device (Vigileo). Vigileo cardiac output (VigileoCO) was compared with intermittent transpulmonary thermodilution cardiac output (TPCO) and an established arterial pulse contour-based cardiac output (PCCO). Design:Prospective clinical study. Setting:University hospital. Patients:Twenty-two patients undergoing coronary artery bypass graft surgery. Interventions:Defined volume load during surgery and in the postoperative period. Measurements and Main Results:We obtained 184 pairs of VigileoCO and TPCO, 140 pairs of VigileoCO and PCCO, and 140 pairs of PCCO and TPCO. Measurements were performed after induction of anesthesia (T1), after sternotomy (T2), immediately after (T3) and 20 mins after volume challenge with 10 mL·kg−1 hydroxyethyl starch 6% (T4), 15 mins after coronary pulmonary bypass (T5), after retransfusion of autologous blood (T6), after arrival at the intensive care unit (T7), and immediately after (T8) and 20 mins after (T9) a second volume load with 10 mL·kg−1 hydroxyethyl starch 6%. TPCO was used to calibrate PCCO. For pooled data, including uncalibrated PCCO data immediately after weaning from coronary pulmonary bypass (T5), the correlation coefficient of TPCO vs. VigileoCO, PCCO vs. VigileoCO, and TPCO vs. PCCO was 0.75, 0.60, and 0.75 respectively. Bland-Altman analysis showed a bias of 0.00, −0.01, and 0.02 L·min−1, the precision (=sd) was 0.87, 1.08, and 0.93 L·min−1, and the mean error was 33%, 40%, and 35%. When we compared calibrated PCCO values (T2–T4, T6, T7–9), the correlation coefficients of PCCO-VigileoCO and TPCO-PCCO were 0.72 and 0.85, bias was −0.16 and 0.19 L·min−1, and mean error was 33% and 27%, respectively. Best correlations and the least differences between TPCO and VigileoCO were observed in postbypass closed-chest conditions and in the intensive care unit. Conclusions:Our results showed that VigileoCO enables clinically acceptable assessment of cardiac output in postbypass closed-chest conditions and during stable conditions in the intensive care unit.

Dynamic preload indicators fail to predict fluid responsiveness in open-chest conditions*

Objective:Dynamic preload indicators like pulse pressure variation (PPV) and stroke volume variation (SVV) are increasingly being used for optimizing cardiac preload since they have been demonstrated to predict fluid responsiveness in a variety of perioperative settings. However, in open-chest conditions, the value of these indices has not been systematically examined yet. We, therefore, evaluated the ability of PPV and SVV to predict fluid responsiveness under open- and closed-chest conditions. Design:Prospective, controlled, clinical study. Setting:University hospital. Patients:Twenty-two patients scheduled for elective coronary artery bypass graft surgery. Interventions:Defined volume loads (VL) (10 mL kg−1 hydroxyethyl starch 6%) intra- and postoperatively. Measurements and Main Results:Stroke volume index was measured 1) before and after a VL intraoperatively in open-chest conditions, and 2) under closed-chest conditions within 1 hour after arrival in the intensive care unit. Central venous pressure and global end diastolic volume were assessed as static preload indicators. In addition, PPV and SVV (both obtained with PiCCO system) were recorded. Fluid-responders were defined by an increase in stroke volume index ≥12% subsequent to the VL. Receiver operating characteristic analysis showed that all preload indicators failed to predict fluid responsiveness in open-chest conditions. Under closed-chest conditions, the areas under the receiver operating characteristic curve for PPV and SVV were 0.884 (p = 0.004) and 0.911 (p = 0.003), respectively, whereas the static and volumetric preload parameters failed to predict fluid responsiveness. A PPV of ≥10% identified fluid-responders with a sensitivity of 64% and a specificity of 100%, while a SVV of >8% identified fluid-responders with a sensitivity of 100% and a specificity of 78%. Conclusions:Our results suggest that the dynamic preload indicators PPV and SVV are able to predict fluid responsiveness under closed-chest conditions, whereas all static and dynamic preload indicators fail to predict fluid responsiveness under open-chest conditions.

Levosimendan improves right ventriculovascular coupling in a porcine model of right ventricular dysfunction

Objective:Experimental data suggest that levosimendan has pulmonary vasodilatory properties which, in combination with its positive inotropic effects, would render it particularly attractive for the treatment of right ventricular dysfunction. To test this hypothesis, we developed an experimental model of right ventricular failure and analyzed the effects of levosimendan on ventriculovascular coupling between the right ventricle and pulmonary artery (PA). Design:Prospective, randomized, placebo-controlled animal study. Setting:University hospital laboratory. Subjects:Fourteen pigs (mean weight 36 ± 1 kg). Interventions:Pigs were instrumented with biventricular conductance catheters, a PA and right coronary artery flow probe, and a high-fidelity pulmonary pressure catheter. Right ventricular dysfunction was induced by repetitive episodes of ischemia/reperfusion in the presence of temporary PA constriction. Pigs were randomly assigned to receive levosimendan (120 &mgr;g·kg−1·min−1 for 10 mins followed by continuous infusion of 60 &mgr;g·kg−1·min−1 for 45 mins) or the placebo (control). Measurements and Main Results:Induction of right ventricular dysfunction resulted in a 42% decrease in contractility (reduction in slope of preload recruitable stroke work [Mw] from 2.5 ± 0.4 to 1.8 ± 0.5 mW·sec·mL−1; p = .02) and a 60% increase in right ventricular afterload (effective pulmonary arterial elastance [PA-Ea] from 0.6 ± 0.1 to 1.0 ± 0.3 mm Hg·mL−1; p < .01). Right ventriculovascular coupling, as assessed by the quotient of right ventricular end-systolic elastance (Emax) over PA-Ea, decreased from 1.23 ± 0.38 to 0.64 ± 0.21 (p = .03). Treatment with levosimendan improved right ventricular contractility (Mw from 1.9 ± 0.4 to 2.9 ± 0.5 mW·sec·mL−1; p < .01), lowered right ventricular afterload (PA-Ea from 1.1 ± 0.3 to 0.8 ± 0.3 mm Hg·mL−1; p = .02), and restored right ventriculovascular coupling to normal values (Emax/PA-Ea = 1.54 ± 0.51). Levosimendan also significantly increased coronary blood flow and left ventricular contractility (Mw from 7.2 ± 3.3 to 9.5 ± 2.9 mW·sec·mL−1; p = .01) but did not affect biventricular diastolic function. Conclusions:In an experimental model of acute right ventricular dysfunction, levosimendan improved global hemodynamics and optimized right ventriculovascular coupling via a moderate increase in right ventricular contractility and a mild reduction of right ventricular afterload.

Xenon reduces neurohistopathological damage and improves the early neurological deficit after cardiac arrest in pigs.

Objective:Treatment options to ameliorate brain damage following cardiopulmonary resuscitation from cardiac arrest are limited. Design:In a porcine model, we evaluated the effects of xenon treatment on neuropathologic and functional outcomes after cardiopulmonary resuscitation. Setting:Prospective, randomized laboratory animal study. Subjects:Male pigs. Interventions:Following successful resuscitation from 8 mins of cardiac arrest and 5 mins of cardiopulmonary resuscitation, 24 pigs were randomized to one of three groups receiving either 70% xenon for 1 or 5 hrs or untreated controls receiving 70% nitrogen. Measurements and Main Results:Gas exchange, hemodynamics, and lactate and glucose levels were measured at baseline and in the postresuscitation period. On four postoperative days, neurocognitive and overall neurologic deficits were assessed before day 5, when the brains were harvested for histologic analysis of predefined regions using a semiquantitative score (0–10% = 1, 10–20% = 2, 20–50% = 3, 50–80% = 4, 80–100% = 5). No differences in gas exchange, hemodynamics, or lactate and glucose levels were observed among the groups. Animals exposed to 1 and 5 hrs of xenon showed significantly reduced scores for necrotic neurons in the putamen (1.25 ± 0.5 and 1.25 ± 0.5 vs. 2.5 ± 1.2; p < 0.05), accompanied by significantly lesser scores for perivascular inflammation in putamen (0.8 ± 0.5 and 1.1 ± 0.8 vs. 2.1 ± 1.1; p < 0.05) and caudate nucleus (1.0 ± 0.8 and 0.6 ± 0.7 vs. 2.0 ± 1.1; p < 0.05). This resulted in improved neurocognitive and neurologic function on day 1 to 3 after cardiopulmonary resuscitation in xenon-treated animals. Conclusions:In this experimental study of cardiac arrest-induced neurologic damage, xenon conferred neurohistopathologic protection, translating in transiently improved functional outcome.

Dexmedetomidine is neuroprotective in an in vitro model for traumatic brain injury

BackgroundThe α2-adrenoreceptor agonist dexmedetomidine is known to provide neuroprotection under ischemic conditions. In this study we investigated whether dexmedetomidine has a protective effect in an in vitro model for traumatic brain injury.MethodsOrganotypic hippocampal slice cultures were subjected to a focal mechanical trauma and then exposed to varying concentrations of dexmedetomidine. After 72 h cell injury was assessed using propidium iodide. In addition, the effects of delayed dexmedetomidine application, of hypothermia and canonical signalling pathway inhibitors were examined.ResultsDexmedetomidine showed a protective effect on traumatically injured hippocampal cells with a maximum effect at a dosage of 1 μM. This effect was partially reversed by the simultaneous administration of the ERK inhibitor PD98059.ConclusionIn this TBI model dexmedetomidine had a significant neuroprotective effect. Our results indicate that activation of ERK might be involved in mediating this effect.

Performance of cardiac output measurement derived from arterial pressure waveform analysis in patients requiring high-dose vasopressor therapy

BACKGROUND Arterial pressure waveform analysis of cardiac output (APCO) without external calibration (FloTrac/Vigileo™) is critically dependent upon computation of vascular tone that has necessitated several refinements of the underlying software algorithms. We hypothesized that changes in vascular tone induced by high-dose vasopressor therapy affect the accuracy of APCO measurements independently of the FloTrac software version. METHODS In this prospective observational study, we assessed the validity of uncalibrated APCO measurements compared with transpulmonary thermodilution cardiac output (TPCO) measurements in 24 patients undergoing vasopressor therapy for the treatment of cerebral vasospasm after subarachnoid haemorrhage. RESULTS Patients received vasoactive support with [mean (sd)] 0.53 (0.46) µg kg(-1) min(-1) norepinephrine resulting in mean arterial pressure of 104 (14) mm Hg and mean systemic vascular resistance of 943 (248) dyn s(-1) cm(-5). Cardiac output (CO) data pairs (158) were obtained simultaneously by APCO and TPCO measurements. TPCO ranged from 5.2 to 14.3 litre min(-1), and APCO from 4.1 to 13.7 litre min(-1). Bias and limits of agreement were 0.9 and 2.5 litre min(-1), resulting in an overall percentage error of 29.6% for 68 data pairs analysed with the second-generation FloTrac(®) software and 27.9% for 90 data pairs analysed with the third-generation software. Precision of the reference technique was 2.6%, while APCO measurements yielded a precision of 29.5% and 27.9% for the second- and the third-generation software, respectively. For both software versions, bias (TPCO-APCO) correlated inversely with systemic vascular resistance. CONCLUSIONS In neurosurgical patients requiring high-dose vasopressor support, precision of uncalibrated CO measurements depended on systemic vascular resistance. Introduction of the third software algorithm did not improve the insufficient precision (>20%) for APCO measurements observed with the second software version.

The intraoperative decrease of selenium is associated with the postoperative development of multiorgan dysfunction in cardiac surgical patients

Objective:The trace elements selenium, copper, and zinc are essential for maintaining the oxidative balance. A depletion of antioxidative trace elements has been observed in critically ill patients and is associated with the development of multiorgan dysfunction and an increased mortality. Cardiac surgery using cardiopulmonary bypass provokes ischemia-reperfusion-mediated oxidative stress. We hypothesized that an intraoperative decrease of circulating trace elements may be involved in this response. Design:Prospective observational clinical study. Setting:University hospital cardiothoracic operation theater and intensive care unit. Patients:Sixty patients (age 65 ± 14 yrs) undergoing cardiac surgery with the use of cardiopulmonary bypass. Measurements and Main Results:Whole blood concentrations of selenium, copper, and zinc were measured after induction of anesthesia and 1 hr after admission to the intensive care unit. All patients were separated in a priori defined subgroups according to the development of no organ failure, single organ failure, and ≥2 organ failures in the postoperative period. Results:Fifty patients exhibited a significant selenium deficiency already before surgery, whereas copper and zinc concentrations were within the reference range.In all patients, blood levels of selenium, copper, and zinc were significantly reduced after end of surgery when compared to preoperative values (selenium: 89.05 ± 12.65 to 70.84 ± 10.46 &mgr;g/L; zinc: 5.15 ± 0.68 to 4.19 ± 0.73 mg/L; copper: 0.86 ± 0.15 to 0.65 ± 0.14 mg/L; p < .001).During their intensive care unit stay, 17 patients were free from any organ failure, while 31 patients developed single-organ failure and 12 patients multiple organ failure.Multilogistic regression analysis showed that selenium concentrations at end of surgery were independently associated with the postoperative occurrence of multiorgan failure (p = .0026, odds ratio 0.8479, 95% confidence interval 0.7617 to 0.9440). Conclusions:Cardiac surgery using cardiopulmonary bypass resulted in a profound intraoperative decrease of whole blood levels of antioxidant trace elements. Low selenium concentrations at end of surgery were an independent predictor for the postoperative development of multiorgan failure.

Levosimendan but not norepinephrine improves microvascular oxygenation during experimental septic shock

Objective:To determine the effects of norepinephrine and levosimendan on microvascular perfusion and oxygenation in a rat model of septic shock. Design:Controlled laboratory animal study. Setting:Research laboratory in a university hospital. Subjects:Forty Sprague-Dawley rats. Interventions:Sepsis was induced in 32 animals by cecal ligation and puncture. Eight animals served as sham controls. Animals were randomly assigned to five groups: 1) fluid resuscitation (25 ml·kg−1·h−1), 2) fluid resuscitation plus norepinephrine (0.5 &mgr;g·kg−1·min−1), 3) fluid resuscitation plus levosimendan (0.3 &mgr;g·kg−1·min−1), 4) no treatment and 5) sham control. Measurements and Main Results:Microvascular perfusion was quantitated using sidestream darkfield imaging and microvascular oxygenation (&mgr;PO2) was assessed by oxygen-dependent quenching of phosphorescence. Measurements were obtained on the buccal mucosa at baseline and at hourly intervals thereafter. In parallel, cardiac output (CO) was recorded. After induction of sepsis microvascular perfusion and &mgr;PO2 were impaired early followed by significant decreases in CO. Although levosimendan and norepinephrine were equally effective in restoring CO, only treatment with levosimendan significantly improved &mgr;PO2 after 1 and 2 hours of treatment (9.7 ± 2.0 vs. 15.1 ± 2.6 and 16.0 ± 3.7 mmHg; p < 0.05). Microvascular perfusion was not significantly influenced by any of the treatment strategies. Conclusions:In this model, treatment with levosimendan and norepinephrine showed comparable effects in restoring CO and had no significant influence on microvascular perfusion. However, only levosimendan significantly improved &mgr;PO2, suggesting that a mechanism relatively independent of macrocirculatory hemodynamics and overall microvascular perfusion might account for these observations.

Positron Emission Tomography Study of Regional Cerebral Metabolism during General Anesthesia with Xenon in Humans

Background:The precise mechanism by which the gaseous anesthetic xenon exerts its effects in the human brain remains unknown. Xenon has only negligible effects on inhibitory &ggr;-aminobutyric acid receptors, one of the putative molecular targets for most general anesthetics. Instead, xenon has been suggested to induce anesthesia by inhibiting excitatory glutamatergic signaling. Therefore, the authors hypothesized that xenon, similar to ketamine and nitrous oxide, increases global and regional cerebral metabolism in humans. Methods:The regional cerebral metabolic rate of glucose (rcMRGlu) was sequentially assessed in two groups of six volunteers each, using 18F-fluorodeoxyglucose as tracer. In the xenon group, rcMRGlu was determined at baseline and during general anesthesia induced with propofol and maintained with 1 minimum alveolar concentration xenon. In the control group, rcMRGlu was measured using the identical study protocol but without administration of xenon. rcMRGlu was assessed after the plasma concentration of propofol had decreased to subanesthetic levels (< 1.0 &mgr;g/ml). rcMRGlu was quantified in 10 cerebral volumes of interest. In addition, voxel-wise changes in rcMRGlu were analyzed using statistical parametric mapping. Results:Xenon reduced whole-brain metabolic rate of glucose by 26 ± 7% (from 43 ± 5 &mgr;mol · 100 g−1 · min−1 to 31 ± 3 &mgr;mol · 100 g−1 · min−1; P < 0.005) and significantly decreased rcMRGlu in all volumes of interest compared with the control group receiving propofol only. Voxel-based analysis revealed metabolic depression within the orbitofrontal, frontomesial, temporomesial, occipital, dorsolateral frontal, and lateral temporal cortices and thalami. No increases in rcMRGlu were detected during xenon anesthesia. Conclusions:Xenon induces metabolic depression in the human brain, suggesting that the inhibition of the glutamatergic system is likely to be of minor significance for the anesthetic action of xenon in vivo.

Clinical validation of a new thermodilution system for the assessment of cardiac output and volumetric parameters

IntroductionTranspulmonary thermodilution is used to measure cardiac output (CO), global end-diastolic volume (GEDV) and extravascular lung water (EVLW). A system has been introduced (VolumeView/EV1000™ system, Edwards Lifesciences, Irvine CA, USA) that employs a novel algorithm for the mathematical analysis of the thermodilution curve. Our aim was to evaluate the agreement of this method with the established PiCCO™ method (Pulsion Medical Systems SE, Munich, Germany, clinicaltrials.gov identifier: NCT01405040)MethodsSeventy-two critically ill patients with clinical indication for advanced hemodynamic monitoring were included in this prospective, multicenter, observational study. During a 72-hour observation period, 443 sets of thermodilution measurements were performed with the new system. These measurements were electronically recorded, converted into an analog resistance signal and then re-analyzed by a PiCCO2™ device (Pulsion Medical Systems SE).ResultsFor CO, GEDV, and EVLW, the systems showed a high correlation (r2 = 0.981, 0.926 and 0.971, respectively), minimal bias (0.2 L/minute, 29.4 ml and 36.8 ml), and a low percentage error (9.7%, 11.5% and 12.2%). Changes in CO, GEDV and EVLW were tracked with a high concordance between the two systems, with a traditional concordance for CO, GEDV, and EVLW of 98.5%, 95.1%, and 97.7% and a polar plot concordance of 100%, 99.8% and 99.8% for CO, GEDV, and EVLW, respectively. Radial limits of agreement for CO, GEDV and EVLW were 0.31 ml/minute, 81 ml and 40 ml, respectively. The precision of GEDV measurements was significantly better using the VolumeView™ algorithm compared to the PiCCO™ algorithm (0.033 (0.03) versus 0.040 (0.03; median (interquartile range), P = 0.000049).ConclusionsFor CO, GEDV, and EVLW, the agreement of both the individual measurements as well as measurements of change showed the interchangeability of the two methods. For the VolumeView method, the higher precision may indicate a more robust GEDV algorithm.Trial registrationclinicaltrials.gov NCT01405040.