Systemic Artery Vasoconstrictor Therapy in Fontan Patients with High Cardiac Output-Heart Failure: A Single-Center Experience.

Failed Fontan Patients with high cardiac output (CO) heart failure (HF) might have vasodilatory syndrome and markedly high mortality rates. The aim of this study was to review the clinical effects of vasoconstrictor therapy (VCT) for failed Fontan hemodynamics. We retrospectively reviewed 10 consecutive patients with Fontan failure (median age, 33 years) and high CO-HF who had received VCT. The hemodynamics were characterized by high central venous pressure (CVP: median, 16 mm Hg), low systolic blood pressure (median, 83 mm Hg), low systemic vascular resistance (median, 8.8 U·m2), high cardiac index (median, 4.6 L/min/m2), and low arterial oxygen saturation (median, 89%). VCT included intravenous noradrenaline infusion for five unstable patients, oral midodrine administration for nine stable patients, and both for four patients. After VCT introduction with a median interval of 1.7 months, the median systolic blood pressure (102 mm Hg, p = 0.004), arterial oxygen saturation (90%, p = 0.03), and systemic vascular resistance (12.1 U·m2, p = 0.13) increased without significant changes in CVP or cardiac index. After a median follow-up of 21 months, the number of readmissions per year decreased from 4 (1-11) to 1 (0-9) (p = 0.25), and there were no VCT-related complications; however, five patients (50%) developed hepatic encephalopathy, and six patients (60%) eventually died. VCT was safely introduced and could prevent the rapidly deteriorating Fontan hemodynamics. VCT could be an effective therapeutic strategy for failed Fontan patients with high CO-HF.

Diuretic treatment in high-risk acute decompensation of advanced chronic heart failure-bolus intermittent vs. continuous infusion of furosemide: a randomized controlled trial.

BACKGROUND: Diuretic resistance is a common issue in patients with acute decompensation of advanced chronic heart failure (ACHF). The aim of this trial was to compare boluses and continuous infusion of furosemide in a selected population of patients with ACHF and high risk for diuretic resistance. METHODS: In this single-centre, double-blind, double-dummy, randomized trial, we enrolled 80 patients admitted for acute decompensation of ACHF (NYHA IV, EF ≤ 30%) with criteria of high risk for diuretic resistance (SBP ≤ 110 mmHg, wet score ≥ 12/18, and sodium ≤ 135 mMol/L). Patients were assigned in a 1:1 ratio to receive furosemide by bolus every 12 h or by continuous infusion. Diuretic treatment and dummy treatment were prepared by a nurse unassigned to patients' care. The study treatment was continued for up to 72 h. Coprimary endpoints were total urinary output and freedom from congestion at 72 h. RESULTS: 80 patients were enrolled with 40 patients in each treatment arm. Mean daily furosemide was 216 mg in continuous-infusion arm and 195 mg in the bolus intermittent arm. Freedom from congestion (defined as jugular venous pressure of < 8 cm, with no orthopnea and with trace peripheral edema or no edema) occurred more in the continuous infusion than in the bolus arm (48% vs. 25%, p = 0.04), while total urinary output after 72 h was 8612 ± 2984 ml in the bolus arm and 10,020 ± 3032 ml in the continuous arm (p = 0.04). Treatment failure occurred less in the continuous-infusion group (15% vs. 38%, p = 0.02), while there was no significant difference between groups in the incidence of worsening of renal function. CONCLUSION: Among patients with acute decompensation of ACHF and high risk of diuretic resistance, continuous infusion of intravenous furosemide was associated with better decongestion. DRAIN TRIAL: ClinicalTrials.gov number NCT03592836.

Crystalloids vs. colloids for fluid resuscitation in the Intensive Care Unit: A systematic review and meta-analysis.

PURPOSE: Guidelines recommend crystalloids for fluid resuscitation in sepsis/shock and switching to albumin in cases where crystalloids are insufficient. We evaluated hemodynamic response to crystalloids/colloids in critically ill adults. MATERIALS AND METHODS: The primary research question was: "Are crystalloids sufficient for volume replacement in severe indications (intensive care unit [ICU]/critical illness)?" Randomized, controlled trials (RCTs) were identified using PubMed and EMBASE, and screened against predefined inclusion/exclusion criteria. Meta-analyses were performed on extracted data. RESULTS: Fifty-five RCTs (N = 27,036 patients) were eligible. Central venous pressure was significantly lower with crystalloids than with albumin, hydroxyethyl starch (HES), or gelatin (all p < .001). Mean arterial pressure was significantly lower with crystalloids vs. albumin (mean difference [MD]: -3.5 mm Hg; p = .03) or gelatin (MD: -9.2 mm Hg; p = .02). Significantly higher volumes of crystalloids were administered vs. HES (MD: +1775 mL); volume administered was numerically higher vs. albumin (MD: +1985 mL). Compared with the albumin group, cardiac index was significantly lower in the crystalloid group (MD: -0.6 L/min/m2, p < .001). All mortality and 90-day mortality were significantly lower for crystalloids compared with HES (relative risk 0.91; p = .009 and 0.9; p = .005, respectively). CONCLUSIONS: Crystalloids were less efficient than colloids at stabilizing resuscitation endpoints; guidance on when to switch is urgently required.

Renoprotective effects of tolvaptan in hypertensive heart failure rats depend on renal decongestion.

The vasopressin type 2 receptor antagonist tolvaptan may have renoprotective effects in patients with heart failure (HF). This study aimed to reveal the renoprotective effect of tolvaptan from the viewpoint of hemodynamic combined with catheter and ultrasound examinations in a hypertensive HF model. Dahl salt-sensitive rats (n = 24) were fed an 8% high-salt diet after the age of 6 weeks and were treated with tolvaptan (n = 16) or vehicle (control group; n = 8). The tolvaptan-treated rats were divided into two groups: a low-dose group (0.01% tolvaptan diet; Low-Tol) and a high-dose group (0.05% tolvaptan diet; High-Tol). At 24 weeks, catheterizations to measure central venous pressure (CVP) and renal medullary pressure (RMP) were performed, followed by intrarenal Doppler (IRD) studies and contrast-enhanced ultrasonography (CEUS) to evaluate renal medullary perfusion. The tolvaptan diet reduced CVP (7.7 ± 1.5, 9.0 ± 1.1, and 12.2 ± 0.8 mmHg in the High-Tol, Low-Tol, and control groups, respectively; p < 0.001) and RMP (7.7 ± 0.8, 9.4 ± 1.3, and 13.7 ± 1.2 mmHg in the High-Tol, Low-Tol, and control groups, respectively; p < 0.001). Tolvaptan also reduced the venous impedance index (VII) in the IRD analysis (0.18 ± 0.03, 0.26 ± 0.04, and 0.40 ± 0.08 in the High-Tol, Low-Tol, and control groups, respectively; p < 0.001), and the time to peak intensity in CEUS (6.0 ± 0.5, 7.3 ± 1.3, 9.8 ± 1.8 s in the High-Tol, Low-Tol, and control groups, respectively; p < 0.001). Creatinine clearance (Ccr) was preserved in both the High-Tol and Low-Tol groups compared to the control group (4.80 ± 1.9, 4.24 ± 0.8, and 1.35 ± 0.3 mg/min, respectively; p = 0.001). Ccr was negatively correlated with RMP (R = -0.76, P < 0.001), the venous impedance index (R = -0.70, p < 0.001), time to peak intensity (R = -0.75, P < 0.001), and renal fibrosis (R = -0.70, p < 0.001). In contrast, Ccr had modest correlations with systolic blood pressure (R = -0.50, P = 0.02) and left ventricular ejection fraction (R = 0.48, P = 0.03). This study revealed that the renoprotective effects of tolvaptan in a hypertensive HF model depended on renal decongestion.

Should we measure the central venous pressure to guide fluid management? Ten answers to 10 questions.

The central venous pressure (CVP) is the most frequently used variable to guide fluid resuscitation in critically ill patients, although its use has been challenged. In this viewpoint, we use a question and answer format to highlight the potential advantages and limitations of using CVP measurements to guide fluid resuscitation.

Comparison of 3% Hypertonic Saline and 20% Mannitol for Reducing Intracranial Pressure in Patients Undergoing Supratentorial Brain Tumor Surgery: A Randomized, Double-blind Clinical Trial.

BACKGROUND: In the present study, we hypothesized that 3% hypertonic saline (HS) is more effective than 20% mannitol to reduce intracranial pressure (ICP) and to modify brain bulk in patients undergoing an elective supratentorial craniotomy. MATERIALS AND METHODS: After institutional review board approval, patients scheduled to undergo supratentorial craniotomy were enrolled into this prospective, randomized, double-blind study. The patients were monitored for routine hemodynamic parameters, depth of anesthesia, and ICP. They received 5 mL/kg 20% mannitol (n=20) or 3% HS (n=19) as infusion for 15 minutes. The patients' ICP values were monitored during hypertonic fluid infusion and throughout 30 minutes after infusion as a primary outcome. Secondary outcomes were hemodynamic variables, serum sodium value, blood gases, and surgeon brain relaxation assessment score (1=relaxed, 2=satisfactory, 3=firm, 4=bulging). In addition, the length of intensive care unit and hospital stay were recorded. RESULTS: Demographic and tumor characteristics were similar between groups. The basal (before hypertonic infusion, ICPT0) and last (30 min after hypertonic infusion finished, ICPT45) ICP values were 13.7±3.0 and 9.5±1.9 mm Hg, respectively, for the M group, which were comparable with the corresponding levels of 14.2±2.8 and 8.7±1.1 mm Hg in the HS group (P>0.05). The median amount of ICP reduction between T0 and T45 timepoints were 4 (1 to 7) and 5 (1 to 9) mm Hg for group M and group HS, respectively (P=0.035). Baseline central venous pressure, pulse pressure variation, and serum sodium and lactate values were similar between groups, but the last measured pulse pressure variation and lactate value were lower, and sodium value was higher in group HS than in group M (P<0.05). Duration of hospital and intensive care unit stay were similar between groups. CONCLUSIONS: Our results suggest that 3% HS provided more effective ICP reduction than 20% mannitol during supratentorial brain tumor surgery.

Observations on significant hemodynamic changes caused by a high concentration of epidurally administered ropivacaine: correlation and prediction study of stroke volume variation and central venous pressure in thoracic epidural anesthesia.

BACKGROUND: Thoracic epidural anesthesia (TEA) exacerbates hypotension due to peripheral vasodilator effects following the use of general anesthetics. This study aimed to compare the hemodynamic changes caused by three different concentrations of epidural ropivacaine and to evaluate the performance of the stroke-volume variation (SVV) and central venous pressure (CVP) during TEA with general anesthesia. METHODS: A total of 120 patients were administered 8 mL of ropivacaine solution via epidural injection, following randomization into one of three groups based on the concentration of ropivacaine in the study solution: 0.75%, 0.375%, or 0.2%. Hemodynamics were monitored for 30 min after loading. We analyzed the hemodynamic changes in the subgroups according to an age cutoff of 60 years. Receiver operating characteristic (ROC) analysis was performed to characterize the relationship of the SVV, CVP, and a 20% decrease in the mean arterial pressure (MAP) following TEA. RESULTS: Data from 109 patients were analyzed. MAP and systemic vascular resistance index were significantly decreased, and SVV was significantly increased after epidural loading only in the 0.75% ropivacaine group. There was a significant difference in hemodynamics between young and elderly subgroups in the 0.75% ropivacaine group. SVV showed a negative correlation with MAP, whereas CVP showed no correlation. The ROC analysis of SVV demonstrated a weak predictive ability of a 20% decrease in MAP at 10 min after the loading dose, with an area-under-the-curve of 0.687 and a 9.5% optimal cutoff value (sensitivity, 60.6%; specificity, 68.9%). CONCLUSIONS: A high concentration of ropivacaine through TEA caused a significant decrease in the systemic vascular resistance and blood pressure. More significant decreases were shown in the elderly patients. Though the change of SVV showed a negative correlation with hypotension and indicated functional hypovolemia after TEA, the predictability was limited. CLINICAL TRIALS REGISTRATION: Number: NCT01559285 , date: January 24, 2013.

Early anticoagulation therapy for severe burns complicated by inhalation injury in a rabbit model.

The aim of the present study was to determine the effects of early anticoagulation treatment on severe burns complicated by inhalation injury in a rabbit model. Under anesthetization, an electrical burns instrument (100˚C) was used to scald the backs of rabbits for 15 sec, which established a 30% III severe burns model. Treatment of the rabbits with early anticoagulation effectively improved the severe burns complicated by inhalation injury­induced lung injury, reduced PaO2, PaCO2 and SPO2 levels, suppressed the expression of tumor necrosis factor­α, interleukin (IL)­1ß and IL­6, and increased the activity of IL­10. In addition, it was found that early anticoagulation treatment effectively suppressed the activities of caspase­3 and caspase­9, upregulated the protein expression of vascular endothelial growth factor (VEGF) and decreased the protein expression of protease­activated receptor 1 (PAR1) in the severe burns model. It was concluded that early anticoagulation treatment affected the severe burns complicated by inhalation injury in a rabbit model through the upregulation of VEGF and downregulation of PAR1 signaling pathways. Thus, early anticoagulation is a potential therapeutic option for severe burns complicated by inhalation injury.

Stroke Volume Variation-Guided Versus Central Venous Pressure-Guided Low Central Venous Pressure With Milrinone During Living Donor Hepatectomy: A Randomized Double-Blinded Clinical Trial.

BACKGROUND: We previously demonstrated the usefulness of milrinone for living donor hepatectomy. However, a less-invasive alternative to central venous catheterization and perioperative contributors to good surgical outcomes remain undetermined. The current study evaluated whether the stroke volume variation (SVV)-guided method can substitute central venous catheterization during milrinone-induced profound vasodilation. METHODS: We randomly assigned 42 living liver donors to receive either SVV guidance or central venous pressure (CVP) guidance to obtain milrinone-induced low CVP. Target SVV of 9% was used as a substitute for CVP of 5 mm Hg. The surgical field grade evaluated by 2 attending surgeons on a 4-point scale was compared between the CVP- and SVV-guided groups (n = 19, total number of scores = 38 per group) as a primary outcome variable. Multivariable analysis was performed to identify independent factors associated with the best surgical field as a post hoc analysis. RESULTS: Surgical field grades, which were either 1 or 2, were not found to be different between the 2 groups via Mann-Whitney U test (P = .358). There was a very weak correlation between SVV and CVP during profound vasodilation such as CVP ≤ 5 mm Hg (R = -0.06; 95% confidence interval, -0.09 to -0.04; P < .001). Additional post hoc analysis suggested that younger age, lower baseline CVP, and longer duration of milrinone infusion might be helpful in providing the best surgical field. CONCLUSIONS: Milrinone-induced vasodilation resulted in favorable surgical environment regardless of guidance methods of low CVP during living donor hepatectomy. However, SVV was not a useful indicator of low CVP because of very weak correlation between SVV and CVP during profound vasodilation. In addition, factors contributing to the best surgical field such as donor age, proactive fasting, and proper dosing of milrinone need to be investigated further, ideally through prospective studies.

Comparison of Two Central Venous Pressure Control Strategies to Prevent Atrial Fibrillation After Coronary Artery Bypass Grafting.

BACKGROUND:: Atrial fibrillation (AF) takes place in 10-40% of patients undergoing coronary artery bypass grafting (CABG), and increases cardiovascular mortality. Enlargement of atrial chambers is associated with increased AF incidence, so patients with higher central venous pressure (CVP) are expected to have larger atrial distension, which increases AF incidence. OBJECTIVE:: To compare post-CABG AF incidence, following two CVP control strategies. METHODS:: Interventional, randomized, controlled clinical study. The sample comprised 140 patients undergoing CABG between 2011 and 2015. They were randomized into two groups, G15 and G20, with CVP maintained ≤ 15 cmH2O and ≤ 20 cmH2O, respectively. RESULTS:: 70 patients were included in each group. The AF incidence in G15 was 8.57%, and in G20, 22.86%, with absolute risk reduction of 14.28%, and number needed to treat (NNT) of 7 (p = 0.03). Mortality (G15 = 5.71%; G20 = 11.42%; p = 0.07), hospital length of stay (G15 = 7.14 days; G20 = 8.21 days; p = 0.36), number of grafts (median: G15 = 3, G2 = 2; p = 0.22) and cardiopulmonary bypass use (G15 = 67.10%; G20 = 55.70%; p = 0.22) were statistically similar. Age (p = 0.04) and hospital length of stay (p = 0.001) were significantly higher in patients who developed AF in both groups. CONCLUSION:: Keeping CVP low in the first 72 post-CABG hours reduces the relative risk of AF, and may be useful to prevent AF after CABG. FUNDAMENTO:: A fibrilação atrial (FA) ocorre em 10-40% dos pacientes submetidos a cirurgia de revascularização miocárdica (RM), e eleva a mortalidade cardiovascular. Como o aumento dos átrios está associado ao aumento da incidência de FA, espera-se que pacientes com pressão venosa central (PVC) mais alta tenham maior distensão atrial, o que eleva a incidência dessa arritmia. OBJETIVO:: Comparar a incidência de FA em pós-operatório de RM, seguindo duas estratégias de controle de PVC. MÉTODOS:: Estudo clínico randomizado controlado intervencionista. A amostra foi composta por 140 pacientes submetidos a RM entre 2011 e 2015. Os pacientes foram randomizados em dois grupos, G15 e G20, mantidos com PVC máxima de 15 cmH2O e 20 cmH2O, respectivamente. RESULTADOS:: Foram incluídos 70 pacientes em cada grupo. A incidência da arritmia em G15 foi de 8,57% e, no G20, de 22,86%, com redução de risco absoluto de 14,28% e número necessário para tratar (NNT) de 7 (p = 0,03). Mortalidade (G15 = 5,71%; G20 = 11,42%; p = 0,07), tempo de internamento (G15 = 7,14 dias; G20 = 8,21 dias; p = 0,36), número de enxertos (medianas: G15 = 3, G2 = 2; p = 0,22) e uso de circulação extracorpórea (G15 = 67,10%; G20 = 55,70%; p = 0,22) mostraram-se estatisticamente semelhantes. A idade (p = 0,04) e o tempo de internamento (p = 0,001) foram significativamente maiores nos pacientes que desenvolveram FA nos dois grupos. CONCLUSÃO:: Manter a PVC com valores mais baixos nas primeiras 72h após a cirurgia de RM reduz o risco relativo de FA e pode ser uma ferramenta útil na prevenção da FA após RM.

Comparison of Two Central Venous Pressure Control Strategies to Prevent Atrial Fibrillation After Coronary Artery Bypass Grafting / Comparação de Duas Estratégias de Controle de Pressão Venosa Central na Prevenção de Fibrilação Atrial em Pós-Operatório de Revascularização do Miocárdio

Abstract Background: Atrial fibrillation (AF) takes place in 10-40% of patients undergoing coronary artery bypass grafting (CABG), and increases cardiovascular mortality. Enlargement of atrial chambers is associated with increased AF incidence, so patients with higher central venous pressure (CVP) are expected to have larger atrial distension, which increases AF incidence. Objective: To compare post-CABG AF incidence, following two CVP control strategies. Methods: Interventional, randomized, controlled clinical study. The sample comprised 140 patients undergoing CABG between 2011 and 2015. They were randomized into two groups, G15 and G20, with CVP maintained ≤ 15 cmH2O and ≤ 20 cmH2O, respectively. Results: 70 patients were included in each group. The AF incidence in G15 was 8.57%, and in G20, 22.86%, with absolute risk reduction of 14.28%, and number needed to treat (NNT) of 7 (p = 0.03). Mortality (G15 = 5.71%; G20 = 11.42%; p = 0.07), hospital length of stay (G15 = 7.14 days; G20 = 8.21 days; p = 0.36), number of grafts (median: G15 = 3, G2 = 2; p = 0.22) and cardiopulmonary bypass use (G15 = 67.10%; G20 = 55.70%; p = 0.22) were statistically similar. Age (p = 0.04) and hospital length of stay (p = 0.001) were significantly higher in patients who developed AF in both groups. Conclusion: Keeping CVP low in the first 72 post-CABG hours reduces the relative risk of AF, and may be useful to prevent AF after CABG.

Resumo Fundamento: A fibrilação atrial (FA) ocorre em 10-40% dos pacientes submetidos a cirurgia de revascularização miocárdica (RM), e eleva a mortalidade cardiovascular. Como o aumento dos átrios está associado ao aumento da incidência de FA, espera-se que pacientes com pressão venosa central (PVC) mais alta tenham maior distensão atrial, o que eleva a incidência dessa arritmia. Objetivo: Comparar a incidência de FA em pós-operatório de RM, seguindo duas estratégias de controle de PVC. Métodos: Estudo clínico randomizado controlado intervencionista. A amostra foi composta por 140 pacientes submetidos a RM entre 2011 e 2015. Os pacientes foram randomizados em dois grupos, G15 e G20, mantidos com PVC máxima de 15 cmH2O e 20 cmH2O, respectivamente. Resultados: Foram incluídos 70 pacientes em cada grupo. A incidência da arritmia em G15 foi de 8,57% e, no G20, de 22,86%, com redução de risco absoluto de 14,28% e número necessário para tratar (NNT) de 7 (p = 0,03). Mortalidade (G15 = 5,71%; G20 = 11,42%; p = 0,07), tempo de internamento (G15 = 7,14 dias; G20 = 8,21 dias; p = 0,36), número de enxertos (medianas: G15 = 3, G2 = 2; p = 0,22) e uso de circulação extracorpórea (G15 = 67,10%; G20 = 55,70%; p = 0,22) mostraram-se estatisticamente semelhantes. A idade (p = 0,04) e o tempo de internamento (p = 0,001) foram significativamente maiores nos pacientes que desenvolveram FA nos dois grupos. Conclusão: Manter a PVC com valores mais baixos nas primeiras 72h após a cirurgia de RM reduz o risco relativo de FA e pode ser uma ferramenta útil na prevenção da FA após RM.

Methylene Blue to Treat Protamine-induced Anaphylaxis Reactions. An Experimental Study in Pigs.

Objective: To examine if methylene blue (MB) can counteract or prevent protamine (P) cardiovascular effects. Methods: The protocol included five heparinized pig groups: Group Sham -without any drug; Group MB - MB 3 mg/kg infusion; Group P - protamine; Group P/MB - MB after protamine; Group MB/P - MB before protamine. Nitric oxide levels were obtained by the nitric oxide/ozone chemiluminescence method, performed using the Nitric Oxide Analizer 280i (Sievers, Boulder, CO, USA). Malondialdehyde plasma levels were estimated using the thiobarbiturate technique. Results: 1) Groups Sham and MB presented unchanged parameters; 2) Group P - a) Intravenous protamine infusion caused mean arterial pressure decrease and recovery trend after 25-30 minutes, b) Cardiac output decreased and remained stable until the end of protamine injection, and c) Sustained systemic vascular resistance increased until the end of protamine injection; 3) Methylene blue infusion after protamine (Group P/MB) - a) Marked mean arterial pressure decreased after protamine, but recovery after methylene blue injection, b) Cardiac output decreased after protamine infusion, recovering after methylene blue infusion, and c) Sustained systemic vascular resistance increased after protamine infusion and methylene blue injections; 4) Methylene blue infusion before protamine (Group MB/P) - a) Mean arterial pressure decrease was less severe with rapid recovery, b) After methylene blue, there was a progressive cardiac output increase up to protamine injection, when cardiac output decreased, and c) Sustained systemic vascular resistance decreased after protamine, followed by immediate Sustained systemic vascular resistance increase; 5) Plasma nitrite/nitrate and malondialdehyde values did not differ among the experimental groups. Conclusion: Reviewing these experimental results and our clinical experience, we suggest methylene blue safely prevents and treats hemodynamic protamine complications, from the endothelium function point of view.

Methylene blue to treat protamine-induced anaphylaxis reactions. An experimental study in pigs

ABSTRACT Objective: To examine if methylene blue (MB) can counteract or prevent protamine (P) cardiovascular effects. Methods: The protocol included five heparinized pig groups: Group Sham -without any drug; Group MB - MB 3 mg/kg infusion; Group P - protamine; Group P/MB - MB after protamine; Group MB/P - MB before protamine. Nitric oxide levels were obtained by the nitric oxide/ozone chemiluminescence method, performed using the Nitric Oxide Analizer 280i (Sievers, Boulder, CO, USA). Malondialdehyde plasma levels were estimated using the thiobarbiturate technique. Results: 1) Groups Sham and MB presented unchanged parameters; 2) Group P - a) Intravenous protamine infusion caused mean arterial pressure decrease and recovery trend after 25-30 minutes, b) Cardiac output decreased and remained stable until the end of protamine injection, and c) Sustained systemic vascular resistance increased until the end of protamine injection; 3) Methylene blue infusion after protamine (Group P/MB) - a) Marked mean arterial pressure decreased after protamine, but recovery after methylene blue injection, b) Cardiac output decreased after protamine infusion, recovering after methylene blue infusion, and c) Sustained systemic vascular resistance increased after protamine infusion and methylene blue injections; 4) Methylene blue infusion before protamine (Group MB/P) - a) Mean arterial pressure decrease was less severe with rapid recovery, b) After methylene blue, there was a progressive cardiac output increase up to protamine injection, when cardiac output decreased, and c) Sustained systemic vascular resistance decreased after protamine, followed by immediate Sustained systemic vascular resistance increase; 5) Plasma nitrite/nitrate and malondialdehyde values did not differ among the experimental groups. Conclusion: Reviewing these experimental results and our clinical experience, we suggest methylene blue safely prevents and treats hemodynamic protamine complications, from the endothelium function point of view.

Impact of Initial Central Venous Pressure on Outcomes of Conservative Versus Liberal Fluid Management in Acute Respiratory Distress Syndrome.

OBJECTIVES: In acute respiratory distress syndrome, conservative fluid management increases ventilator-free days without affecting mortality. Response to fluid management may differ based on patients' initial central venous pressure. We hypothesized that initial central venous pressure would modify the effect of fluid management on outcomes. DESIGN: Retrospective analysis of the Fluid and Catheter Treatment Trial, a multicenter randomized trial comparing conservative with liberal fluid management in acute respiratory distress syndrome. We examined the relationship between initial central venous pressure, fluid strategy, and 60-day mortality in univariate and multivariable analysis. SETTING: Twenty acute care hospitals. PATIENTS: Nine hundred thirty-four ventilated acute respiratory distress syndrome patients with a central venous pressure available at enrollment, 609 without baseline shock (for whom fluid balance was managed by the study protocol). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among patients without baseline shock, those with initial central venous pressure greater than 8 mm Hg experienced similar mortality with conservative and liberal fluid management (18% vs 18%; p = 0.928), whereas those with central venous pressure of 8 mm Hg or less experienced lower mortality with a conservative strategy (17% vs 36%; p = 0.005). Multivariable analysis demonstrated an interaction between initial central venous pressure and the effect of fluid strategy on mortality (p = 0.031). At higher initial central venous pressures, the difference in treatment between arms was predominantly furosemide administration, which was not associated with mortality (p = 0.122). At lower initial central venous pressures, the difference between arms was predominantly fluid administration, with additional fluid associated with increased mortality (p = 0.013). CONCLUSIONS: Conservative fluid management decreases mortality for acute respiratory distress syndrome patients with a low initial central venous pressure. In this population, the administration of IV fluids seems to increase mortality.

Acute kidney injury after cardiac surgery: is minocycline protective?

BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) after cardiac bypass surgery (CABG) is common and carries a significant association with morbidity and mortality. Since minocycline therapy attenuates kidney injury in animal models of AKI, we tested its effects in patients undergoing CABG. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: This is a randomized, double-blinded, placebo-controlled, multi-center study. We screened high risk patients who were scheduled to undergo CABG in two medical centers between Jan 2008 and June 2011. 40 patients were randomized and 19 patients in each group completed the study. Minocycline prophylaxis was given twice daily, at least for four doses prior to CABG. Primary outcome was defined as AKI [0.3 mg/dl increase in creatinine (Cr)] within 5 days after surgery. Daily serum Cr for 5 days, various clinical and hemodynamic measures and length of stay were recorded. RESULTS: The two groups had similar baseline and intra-operative characteristics. The primary outcome occurred in 52.6% of patients in the minocycline group as compared to 36.8% of patients in the placebo group (p = 0.51). Peak Cr was 1.6 ± 0.7 vs. 1.5 ± 0.7 mg/dl (p = 0.45) in minocycline and placebo groups, respectively. Death at 30 days occurred in 0 vs. 10.5% in the minocycline and placebo groups, respectively (p = 0.48). There were no differences in post-operative length of stay, and cardiovascular events between the two groups. There was a trend towards lower diastolic pulmonary artery pressure [16.8 ± 4.7 vs. 20.7 ± 6.6 mmHg (p = 0.059)] and central venous pressure [11.8 ± 4.3 vs. 14.6 ± 5.6 mmHg (p = 0.13)] in the minocycline group compared to placebo on the first day after surgery. CONCLUSIONS: Minocycline did not protect against AKI post-CABG.

Baroreceptor unloading does not limit forearm sweat rate during severe passive heat stress.

This study tested the hypothesis that sweat rate during passive heat stress is limited by baroreceptor unloading associated with heat stress. Two protocols were performed in which healthy subjects underwent passive heat stress that elicited an increase in intestinal temperature of ∼1.8°C. Upon attaining this level of hyperthermia, in protocol 1 (n = 10, 3 females) a bolus (19 ml/kg) of warm (∼38°C) isotonic saline was rapidly (5-10 min) infused intravenously to elevate central venous pressure (CVP), while in protocol 2 (n = 11, 5 females) phenylephrine was infused intravenously (60-120 µg/min) to return mean arterial pressure (MAP) to normothermic levels. In protocol 1, heat stress reduced CVP from 3.9 ± 1.9 mmHg (normothermia) to -0.6 ± 1.4 mmHg (P < 0.001), while saline infusion returned CVP to normothermic levels (5.1 ± 1.7 mmHg; P > 0.999). Sweat rate was elevated by heat stress (1.21 ± 0.44 mg·cm(-2)·min(-1)) but remained unchanged during rapid saline infusion (1.26 ± 0.47 mg·cm(-2)·min(-1), P = 0.5), whereas cutaneous vascular conductance increased from 77 ± 10 to 101 ± 20% of local heating max (P = 0.029). In protocol 2, MAP was reduced with heat stress from 85 ± 7 mmHg to 76 ± 8 mmHg (P = 0.048). Although phenylephrine infusion returned MAP to normothermic levels (88 ± 7 mmHg; P > 0.999), sweat rate remained unchanged during phenylephrine infusion (1.39 ± 0.22 vs. 1.41 ± 0.24 mg·cm(-2)·min(-1); P > 0.999). These data indicate that both cardiopulmonary and arterial baroreceptor unloading do not limit increases in sweat rate during passive heat stress.

[Effects of the ß-blockers on cardiac protection and hemodynamics in patients with septic shock: a prospective study].

OBJECTIVE: To investigate the effects of ß-blockers on cardiac protection and hemodynamic in patients with septic shock. METHODS: A prospective randomized controlled trial was conducted. Forty-one patients with septic shock in accordance with early goal directed treatment and met the target within 6 hours, and admitted to intensive care unit (ICU) of Affiliated Huxi Hospital of Jining Medical College from January 2012 to January 2014 were enrolled. The patients were divided into treatment group (n=21) and control group (n=20) by random number table. The patients in both groups were given the standard treatment, esmolol was giving to patients in treatment group in order to control the heart rate(HR) below 100 bpm within 2 hours, and the patients in control group only received standard treatment. The changes in hemodynamic parameters [mean arterial pressure (MAP), central venous pressure (CVP), HR, cardiac index (CI), stroke volume index (SVI), systemic vascular resistance (SVRI), global end diastolic volume index (GEDVI)], biochemistry metabolic of tissue [central venous oxygen saturation (ScvO2), lactic acid (Lac)], and cardiac markers [troponin I (cTnI)] before and 12, 24, 48, 72 hours after the treatment were recorded. RESULTS: (1) Before treatment, the hemodynamic parameters, tissue metabolism index and cTnI had no significant differences in both groups (all P>0.05). (2) The hemodynamic parameters after treatment in the control group showed no significant difference compared with that before treatment. HR and CI in the treatment group were gradually declined after treatment, SVRI and GEDVI were gradually increased. There were significant differences in HR, CI, SVRI, and GEDVI between treatment group and control group from 12 hours on [HR (bpm): 93 ± 4 vs. 118 ± 13, CI (L × min⁻¹ × m⁻²): 3.3 ± 0.8 vs. 4.5 ± 0.6, SVRI (kPa×s × L⁻¹ × m⁻²): 159.2 ± 27.4 vs. 130.5 ± 24.2, GEDVI (mL/m²): 668 ± 148 vs. 588 ± 103, P<0.05 or P<0.01]. MAP, CVP and SVI in the treatment group showed no significant changes. (3) Lac after treatment in both groups was decreased slowly, Lac (mmol/L) at 12 hours after treatment was significantly decreased compared with that before treatment (control group: 8.8 ± 3.2 vs. 9.8 ± 3.4, treatment group: 9.5 ± 3.1 vs. 10.5 ± 4.1, both P<0.05). The Lac of control group and treatment group were 2.5 ± 1.2 and 2.7 ± 1.1 at 72 hours after treatment, and there was no significant difference between two groups (all P>0.05). The ScvO2was not decreased in both groups. (4) Compared with before treatment, cTnI in the control group was gradually increased, peaked at 72 hours, and that in the treatment group was gradually increased, peaked at 24 hours and then gradually declined. Compared with control group, the cTnI (µg/L) in the treatment group was decreased significantly at 24, 48, 72 hours (1.15 ± 0.57 vs. 1.74 ± 0.77, 0.93 ± 0.52 vs. 2.15 ± 1.23, 0.52 ± 0.36 vs. 2.39 ± 1.17, all P<0.01). CONCLUSIONS: ß-blockers (esmolol) can improve cardiac function and myocardial compliance, reduce the myocardial injury in patients with sepsis shock. Although ß-blockers can decrease cardiac output, it has no influence on the circulation function and tissue perfusion.

Assessment of the plethysmographic variability index as a predictor of fluid responsiveness in critically ill patients: a pilot study.

Optimising intravascular volume in patients with hypotension requiring vasopressor support is a key challenge of critical care medicine. The optimal haemodynamic parameter to assess fluid responsiveness in critically ill patients, particularly those requiring a noradrenaline infusion and mechanical ventilation, remains uncertain. This pilot study assessed the accuracy of the plethysmographic variability index (PVI), (Radical-7 pulse co-oximeter, Masimo®, Irvine, CA, USA) in predicting fluid responsiveness in 25 patients who required noradrenaline infusion to maintain mean arterial pressure over 65 mmHg and were mechanically ventilated with a 'lung-protective' strategy, and whether administering a fluid bolus was associated with a change in PVI (Δ PVI). In this study, fluid responsiveness was defined as an increase in stroke volume of greater than 15% after a 500 ml bolus of colloid infusion over 20 minutes. Of the 25 patients included in the study, only 12 (48%) were considered fluid responders. As static haemodynamic parameters, PVI, central venous pressure and inferior vena cava distensibility index were all inaccurate at predicting volume responsiveness with PVI being the least accurate (area under the receiver operating characteristic curve=0.41, 95% confidence interval 0.18 to 0.65). However, fluid responsiveness was associated with a change in PVI, but not a change in heart rate or central venous pressure. This association between Δ PVI and fluid responsiveness may be a surrogate marker of improved cardiac output following a fluid bolus and warrants further investigation.

[Changes of the intraabdominal pressure in patients with abdominal sepsis].

64 patients with abdominal sepsis were included in the study of the intraabdominal pressure changes before and after the operation. The study demonstrated that the use of the crystalloids alone leads to the development of the capillary leak syndrome in comparison with the therapy regimen using colloids. The aggressive fluid resuscitation, associated with high numbers of central venous pressure, increasing 1177Pa (120 mm H2O), was connected with the increase of the intraabdominal pressure.