Continuous right ventricular end diastolic volume and right ventricular ejection fraction during liver transplantation: A multicenter study

Cardiac preload is traditionally considered to be represented by its filling pressures, but more recently, estimations of end diastolic volume of the left or right ventricle have been shown to better reflect preload. One method of determining volumes is the evaluation of the continuous right ventricular end diastolic volume index (cRVEDVI) on the basis of the cardiac output thermodilution technique. Because preload and myocardial contractility are the main factors determining cardiac output during liver transplantation (LTx), accurate determination of preload is important. Thus, monitoring of cRVEDVI and cRVEF should help with fluid management and with the assessment of the need for inotropic and vasoactive agents. In this multicenter study, we looked for possible relationships between the stroke volume index (SVI) and cRVEDVI, cRVEF, and filling pressures at 4 predefined steps in 244 patients undergoing LTx. Univariate and multivariate autoregression models (across phases of the surgical procedure) were fitted to assess the possible association between SVI and cRVEDVI, pulmonary artery occlusion pressure (PAOP), and central venous pressure (CVP) after adjustment for cRVEF (categorized as 40%). SVI was strongly associated with both cRVEDVI and cRVEF. The model showing the best fit to the data was that including cRVEDVI. Even after adjustment for cRVEF, there was a statistically significant (P < 0.05) relationship between SVI and cRVEDVI with a regression coefficient (slope of the regression line) of 0.25; this meant that an increase in cRVEDVI of 1 mL m(-2) resulted in an increase in SVI of 0.25 mL m(-2). The correlations between SVI and CVP and PAOP were less strong. We conclude that cRVEDVI reflected preload better than CVP and PAOP

Severe reperfusion lung injury after double lung transplantation

AIM: To demonstrate the effects of combined inhaled nitric oxide and surfactant replacement as treatment for acute respiratory distress syndrome. This treatment has not previously been documented for reperfusion injury after double lung transplantation. METHOD: A 24-year-old female with cystic fibrosis underwent double lung transplantation. During implantation of the second lung a marked increase in pulmonary artery pressure associated with systemic hypotension, hypoxemia and low cardiac output were observed. Notwithstanding the patient received support from cardiovascular drugs and pulmonary vasodilators cardiopulmonary by-pass was necessary. In the intensive care unit the patient received the same drug support, inhaled nitric oxide and two bronchoscopic applications of bovine surfactant. RESULTS: A rapid improvement in PaO(2)/FiO(2) within 2–3 hours of administration of surfactant was seen. The patient is well at follow-up 1 year post-transplant. CONCLUSION: There is a potential role for a combined therapy with inhaled nitric oxide and surfactant replacement in reperfusion injury after lung transplantation

Continuous monitoring of cerebral oxygen saturation in elderly patients undergoing major abdominal surgery minimizes brain exposure to potential hypoxia

to develop cerebral desaturation because of the reduced physiologic reserve that accompanies aging. To evaluate whether monitoring cerebral oxygen saturation (rSO2) minimizes intraoperative cerebral desaturation, we prospectively monitored rSO2 in 122 elderly patients undergoing major abdominal surgery with general anesthesia. Patients were randomly allocated to an intervention group (the monitor was visible and rSO2 was maintained at 75% of preinduction values; n 56) or a control group (the monitor was blinded and anesthesia was managed routinely; n 66). Cerebral desaturation (rSO2 reduction 75% of baseline) was observed in 11 patients of the treatment group (20%) and 15 patients of the control group (23%) (P 0.82). Mean (95% confidence intervals) values of mean rSO2 were higher (66% [64%–68%]) and the area under the curve below 75% of baseline (AUCrSO2275% of baseline) was lower (0.4 min% [0.1– 0.8 min%]) in patients of the treatment group than in patients of the control group (61% [59%–63%] and 80 min% [2–144 min%], respectively; P 0.002 and P 0.017). When considering only patients developing intraoperative cerebral desaturation, a lower Mini Mental State Elimination (MMSE) score was observed at the seventh postoperative day in the control group (26 [25–30]) than in the treatment group (28 [26 –30]) (P 0.02), with a significant correlation between the AUCrSO2 75% of baseline and postoperative decrease in MMSE score from preoperative values (r20.25, P0.01). Patients of the control group with intraoperative cerebral desaturation also experienced a longer time to postanesthesia care unit (PACU) discharge (47 min [13–56 min]) and longer hospital stay (24 days [7–53] days) compared with patients of the treatment group (25 min [15–35 min] and 10 days [7–23 days], respectively; P 0.01 and P 0.007). Using rSO2 monitoring to manage anesthesia in elderly patients undergoing major abdominal surgery reduces the potential exposure of the brain to hypoxia; this might be associated with decreased effects on cognitive function and shorter PACU and hospital stay

Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study

Introduction Recent clinical data suggest that early administration of vasopressin analogues may be advantageous compared to a last resort therapy. However, it is still unknown whether vasopressin and terlipressin are equally effective for hemodynamic support in septic shock. The aim of the present prospective, randomized, controlled pilot trial study was, therefore, to compare the impact of continuous infusions of either vasopressin or terlipressin, when given as first-line therapy in septic shock patients, on open-label norepinephrine requirements. Methods We enrolled septic shock patients (n = 45) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomized to receive continuous infusions of either terlipressin (1.3 mu g.kg(-1).h(-1)), vasopressin (.03U.min(-1)) or norepinephrine (15 mu g.min(-1); n = 15 per group). In all groups, open-label norepinephrine was added to achieve a mean arterial pressure between 65 and 75 mmHg, if necessary. Data from right heart and thermo-dye dilution catheterization, gastric tonometry, as well as laboratory variables of organ function were obtained at baseline, 12, 24, 36 and 48 hours after randomization. Differences within and between groups were analyzed using a two-way ANOVA for repeated measurements with group and time as factors. Time-independent variables were compared with one-way ANOVA. Results There were no differences among groups in terms of systemic and regional hemodynamics. Compared with infusion of .03U of vasopressin or 15 mu g.min(-1) of norepinephrine, 1.3 mu g.kg(-1).h(-1) of terlipressin allowed a marked reduction in catecholamine requirements (0.8 +/- 1.3 and 1.2 +/- 1.4 vs. 0.2 +/- 0.4 mu g.kg(-1).min(-1) at 48 hours; each P < 0.05) and was associated with less rebound hypotension (P < 0.05). At the end of the 48-hour intervention period, bilirubin concentrations were higher in the vasopressin and norepinephrine groups as compared with the terlipressin group (2.3 +/- 2.8 and 2.8 +/- 2.5 vs. 0.9 +/- 0.3 mg.dL(-1); each P < 0.05). A time-dependent decrease in platelet count was only observed in the terlipressin group (P < 0.001 48 hours vs. BL). Conclusions The present study provides evidence that continuous infusion of low-dose terlipressin - when given as first-line vasopressor agent in septic shock - is effective in reversing sepsis-induced arterial hypotension and in reducing norepinephrine requirements

Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial

Previous findings suggest that a delayed administration of phenylephrine replacing norepinephrine in septic shock patients causes a more pronounced hepatosplanchnic vasoconstriction as compared with norepinephrine. Nevertheless, a direct comparison between the two study drugs has not yet been performed. The aim of the present study was, therefore, to investigate the effects of a first-line therapy with either phenylephrine or norepinephrine on systemic and regional hemodynamics in patients with septic shock. METHODS: We performed a prospective, randomized, controlled trial in a multidisciplinary intensive care unit in a university hospital. We enrolled septic shock patients (n = 32) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomly allocated to treatment with either norepinephrine or phenylephrine infusion (n = 16 each) titrated to achieve a mean arterial pressure between 65 and 75 mmHg. Data from right heart catheterization, a thermodye dilution catheter, gastric tonometry, acid-base homeostasis, as well as creatinine clearance and cardiac troponin were obtained at baseline and after 12 hours. Differences within and between groups were analyzed using a two-way analysis of variance for repeated measurements with group and time as factors. Time-independent variables were compared with one-way analysis of variance. RESULTS: No differences were found in any of the investigated parameters. CONCLUSIONS: The present study suggests there are no differences in terms of cardiopulmonary performance, global oxygen transport, and regional hemodynamics when phenylephrine was administered instead of norepinephrine in the initial hemodynamic support of septic shock

Acute hemodynamic effects of inhaled nitric oxide, dobutamine and a combination of the two in patients with mild to moderate secondary pulmonary hypertension

INTRODUCTION: The use of low-dose dobutamine to maintain hemodynamic stability in pulmonary hypertension may have a detrimental effect on gas exchange. The aim of this study was to investigate whether inhaled nitric oxide (INO), dobutamine and a combination of the two have beneficial effects in patients with end-stage airway lung disease and pulmonary hypertension. METHOD: Hemodynamic evaluation was assessed 10 min after the administration of each drug and of their combination, in 28 candidates for lung transplantation. RESULTS: Administration of INO caused a reduction in mean pulmonary arterial pressure (MPAP), an increase in PaO(2) with a significant reduction in venous admixture effect (Q(s)/Q(t)).Dobutamine administration caused an increase in cardiac index and MPAP, with a decrease in PaO(2) as a result of a higher Q(s)/Q(t). Administration of a combination of the two drugs caused an increase in the cardiac index without MPAP modification and an increase in PaO(2) and Q(s)/Q(t). CONCLUSION: Dobutamine and INO have complementary effects on pulmonary circulation. Their association may be beneficial in the treatment of patients with mild to moderate pulmonary hypertension

Microvascular Effects of Heart Rate Control With Esmolol in Patients With Septic Shock: A Pilot Study*

none14β-blocker therapy may control heart rate and attenuate the deleterious effects of β-stimulating catecholamines in septic shock. However, their negative chronotropy and inotropy may potentially lead to an inappropriately low cardiac output, with a subsequent compromise of microvascular blood flow. The purpose of the present pilot study was to investigate the effects of reducing heart rate to less than 95 beats per minute in patients with septic shock using the β-1 adrenoceptor blocker, esmolol, with specific focus on systemic hemodynamics and the microcirculation.Prospective, observational clinical study.Multidisciplinary ICU at a university hospital.After 24 hours of initial hemodynamic optimization, 25 septic shock patients with a heart rate greater than or equal to 95 beats per minute and requiring norepinephrine to maintain mean arterial pressure greater than or equal to 65 mm Hg received a titrated esmolol infusion to maintain heart rate less than 95 beats per minute. Sublingual microcirculatory blood flow was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 24 hours after esmolol administration. Heart rates targeted between 80 and 94 beats per minute were achieved in all patients. Whereas cardiac index decreased (4.0 [3.5; 5.3] vs 3.1 [2.6; 3.9] L/min/m; p < 0.001), stroke volume remained unchanged (34 [37; 47] vs 40 [31; 46] mL/beat/m; p = 0.32). Microcirculatory blood flow in small vessels increased (2.8 [2.6; 3.0] vs 3.0 [3.0; 3.0]; p = 0.002), while the heterogeneity index decreased (median 0.06 [interquartile range 0; 0.21] vs 0 [0; 0]; p = 0.002). PaO2 and pH increased while PaCO2 decreased (all p < 0.05). Of note, norepinephrine requirements were significantly reduced by selective β-1 blocker therapy (0.53 [0.29; 0.96] vs 0.41 [0.22; 0.79] µg/kg/min; p = 0.03).This pilot study demonstrated that heart rate control by a titrated esmolol infusion in septic shock patients was associated with maintenance of stroke volume, preserved microvascular blood flow, and a reduction in norepinephrine requirements.A. Morelli;A. Donati;C. Ertmer;S. Rehberg;T. Kampmeier;A. Orecchioni;A. D'Egidio;V. Cecchini;G. Landoni;P. Pietropaoli;M. Westphal;M. Venditti;A. Mebazaa;M. SingerA., Morelli; Donati, Abele; C., Ertmer; S., Rehberg; T., Kampmeier; A., Orecchioni; A., D'Egidio; V., Cecchini; G., Landoni; P., Pietropaoli; M., Westphal; M., Venditti; A., Mebazaa; M., Singe

Levosimendan for resuscitating the microcirculation in patients with septic shock: A randomized controlled study

__Introduction:__ The purpose of the present study was to investigate microcirculatory blood flow in patients with septic shock treated with levosimendan as compared to an active comparator drug (i.e. dobutamine). The primary end point was a difference of ≥ 20% in the microvascular flow index of small vessels (MFIs) among groups. __Methods:__ The study was designed as a prospective, randomized, double-blind clinical trial and performed in a multidisciplinary intensive care unit. After achieving normovolemia and a mean arterial pressure of at least 65 mmHg, 40 septic shock patients were randomized to receive either levosimendan 0.2 μg·kg-1·min-1(n = 20) or an active comparator (dobutamine 5 μg·kg-1·min-1; control; n = 20) for 24 hours. Sublingual microcirculatory blood flow of small and medium vessels was assessed by sidestream dark-field imaging. Microcirculatory variables and data from right heart catheterization were obtained at baseline and 24 hours after randomization. Baseline and demographic data were compared by means of Mann-Whitney rank sum test or chi-square test, as appropriate. Microvascular and hemodynamic variables were analyzed using the Mann-Whitney rank sum test. __Results:__ Microcirculatory flow indices of small and medium vessels increased over time and were significantly higher in the levosimendan group as compared to the control group; P = .02; MFIs 2.9. The relative increase of perfused vessel density vs. baseline was significantly higher in the levosimendan group than in the control group. In addition, the heterogeneity index decreased only in the levosimendan group. There was no statistically significant correlation between systemic and microcirculatory flow variables within each group. __Conclusions:__ Compared to a standard dose of 5 μg·kg-1·min-1of dobutamine, levosimendan at 0.2 μg·kg-1·min-1improved sublingual microcirculatory blood flow in patients with septic shock, as reflected by changes in microcirculatory flow indices of small and medium vessels.Trial registration: NCT00800306

Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock.

none15ABSTRACT: INTRODUCTION: The present study was designed to determine the effects of continuously infused norepinephrine (NE) plus (1) terlipressin (TP) or (2) arginine vasopressin (AVP) or (3) placebo on sublingual microcirculation in septic shock patients. The primary study end point was a difference of ≥ 20\% in the microvascular flow index of small vessels among groups. METHODS: The design of the study was a prospective, randomized, double-blind clinical trial. NE was titrated to maintain mean arterial pressure (MAP) between 65 and 75 mmHg after establishment of normovolemia in 60 septic shock patients. Thereafter patients (n = 20 per group) were randomized to receive continuous infusions of either TP (1 μg/kg/hour), AVP (0.04 U/minute) or placebo (isotonic saline). In all groups, open-label NE was adjusted to maintain MAP within threshold values if needed. The sublingual microcirculatory blood flow of small vessels was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 6 hours after randomization. RESULTS: TP and AVP decreased NE requirements at the end of the 6-hour study period. The data are medians (25th and 75th interquartile ranges (IQRs)): 0.57 μg/kg/minute (0.29 to 1.04) vs. 0.16 μg/kg/minute (0.03 to 0.37) for TP and 0.40 μg/kg/minute (0.20 to 1.05) vs. 0.23 μg/kg/minute (0.03 to 0.77) for AVP, with statistical significance of P < 0.05 vs. baseline and vs. placebo. There were no differences in sublingual microcirculatory variables, systemic hemodynamics, oxygen transport and acid-base homeostasis among the three study groups during the entire observation period. The proportions of perfused vessels increased in relation to baseline within all study groups, and there were no significant differences between groups. The specific data were as follows (median (IQR)): 9.7\% (2.6 to 19.8) for TP, 8.9\% (0.0 to 17.8) for AVP, and 6.9\% (3.5 to 10.1) for placebo (P < 0.05 vs. baseline for each comparison), as well as perfused vessel density 18.6\% (8.6 to 36.9) for TP, 20.2\% (-3.0 to 37.2) for AVP, and 11.4\% (-3.0 to 19.4) for placebo (P < 0.05 vs. baseline for each comparison). CONCLUSIONS: The present study suggests that to achieve a MAP of 65 to 75 mmHg in septic patients treated with NE, the addition of continuously infused low-dose TP or AVP does not affect sublingual microcirculatory blood flow. In addition, our results suggest that microcirculatory flow abnormalities are mainly related to other factors (for example, volume status, timing, hemodynamics and progression of the disease) rather than to the vasopressor per se. TRIAL REGISTRATION: ClinicalTrial.gov NCT00995839.A. Morelli;A. Donati;C. Ertmer;S. Rehberg;T. Kampmeier;A. Orecchioni;A. D. Russo;A. D'Egidio;G. Landoni;M. R. Lombrano;L. Botticelli;A. Valentini;A. Zangrillo;P. Pietropaoli;M. WestphalA., Morelli; Donati, Abele; C., Ertmer; S., Rehberg; T., Kampmeier; A., Orecchioni; A. D., Russo; A., D'Egidio; G., Landoni; M. R., Lombrano; L., Botticelli; A., Valentini; A., Zangrillo; P., Pietropaoli; M., Westpha

Activation of Regulatory T Cells during Inflammatory Response Is Not an Exclusive Property of Stem Cells

BACKGROUND: Sepsis and systemic-inflammatory-response-syndrome (SIRS) remain major causes for fatalities on intensive care units despite up-to-date therapy. It is well accepted that stem cells have immunomodulatory properties during inflammation and sepsis, including the activation of regulatory T cells and the attenuation of distant organ damage. Evidence from recent work suggests that these properties may not be exclusively attributed to stem cells. This study was designed to evaluate the immunomodulatory potency of cellular treatment during acute inflammation in a model of sublethal endotoxemia and to investigate the hypothesis that immunomodulations by cellular treatment during inflammatory response is not stem cell specific. METHODOLOGY/PRINCIPAL FINDINGS: Endotoxemia was induced via intra-peritoneal injection of lipopolysaccharide (LPS) in wild type mice (C3H/HeN). Mice were treated with either vital or homogenized amniotic fluid stem cells (AFS) and sacrificed for specimen collection 24 h after LPS injection. Endpoints were plasma cytokine levels (BD™ Cytometric Bead Arrays), T cell subpopulations (flow-cytometry) and pulmonary neutrophil influx (immunohistochemistry). To define stem cell specific effects, treatment with either vital or homogenized human-embryonic-kidney-cells (HEK) was investigated in a second subset of experiments. Mice treated with homogenized AFS cells showed significantly increased percentages of regulatory T cells and Interleukin-2 as well as decreased amounts of pulmonary neutrophils compared to saline-treated controls. These results could be reproduced in mice treated with vital HEK cells. No further differences were observed between plasma cytokine levels of endotoxemic mice. CONCLUSIONS/SIGNIFICANCE: The results revealed that both AFS and HEK cells modulate cellular immune response and distant organ damage during sublethal endotoxemia. The observed effects support the hypothesis, that immunomodulations are not exclusive attributes of stem cells