scholarly journals Ulinastatin as an Adjuvant Therapy to Restricting Volumes of Resuscitation Fluid Strategy for Patients with Septic Shock after Initial Management

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Rensong Dong ◽  
Xi Zhang ◽  
Zhi Zhao
Keyword(s):  
Septic Shock ◽  
Adjuvant Therapy ◽  
Vascular Permeability ◽  
Fluid Resuscitation ◽  
Intravenous Infusion ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Thrombin Time ◽  
Pulmonary Vascular Permeability ◽  
Resuscitation Fluid

Septic shock is the most serious complication of sepsis, leading to unacceptably high morbidity and mortality worldwide. Fluid resuscitation using crystalloids has become the mainstay of early and aggressive treatment of severe sepsis and septic shock, while increased daily fluid balances from day 2 until day 7 have been related with increased mortality. Recently, pharmacological management has been recommended to combine with appropriate fluid resuscitation for the treatment of septic shock. In this study, we compared the clinical efficacy of restricting volumes of resuscitation fluid strategy with or without intravenous infusion of ulinastatin (UTI) in treating patients with septic shock and additionally examined the patient’s changes of the extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), systemic vascular resistance index (SVRI), cardiac function, lactic acid (LA) level, coagulation function, and renal function. The study included 182 patients with septic shock, among which 89 patients had undergone restricting volumes of resuscitation fluid strategy with intravenous infusion of UTI and 93 patients had undergone restricting volumes of resuscitation fluid strategy alone. It was found that patients with septic shock after restricting volumes of resuscitation fluid strategy with intravenous infusion of UTI showed an increased SVRI concomitant with declined PVPI and EVLWI, increased mean artery pressure (MAP), cardiac output (CO), left ventricular ejection fraction (LVEF), stroke volume (SV), and heart rate (HR), declined levels of cardiac troponin I (cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP), reduced LA level along with shortened prothrombin time (PT) and partially activated thrombin time (PATT), and decreased levels of blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA) when comparable to those after restricting volumes of resuscitation fluid strategy alone ( P < 0.05 ). We also observed fewer scores of the Acute Physiology and Chronic Health Evaluation (APACHE II) and the sequential organ failure assessment (SOFA) in patients undergoing restricting volumes of resuscitation fluid strategy with intravenous infusion of UTI than those undergoing restricting volumes of resuscitation fluid strategy alone ( P < 0.05 ). According to the above data, it is concluded that UTI as an adjuvant therapy for restricting volumes of resuscitation fluid strategy in treating septic shock may decrease the LA level, attenuate the inflammatory response, reduce vascular permeability, prevent pulmonary edema, and restore cardiac and renal functions.

Implication of anti-angiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Marcos Garces ◽  
C Rios-Navarro ◽  
L Hueso ◽  
A Diaz ◽  
C Bonanad ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Adjuvant Therapy ◽  
Ejection Fraction ◽  
Infarct Size ◽  
Systolic Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Coronary Reperfusion ◽  
Ventricular Ejection Fraction

Abstract Background Angiogenesis participates in re-establishing microcirculation after myocardial infarction (MI). Purpose In this study, we aim to further understand the role of the anti-angiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and explore its potential as a co-adjuvant therapy to coronary reperfusion. Methods Two mice MI models were formed: 1) permanent coronary ligation (non-reperfused MI), 2) transient 45-min coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. Serum and myocardial VEGF-A165b levels were determined. In both experimental MI models, functional and structural implication of VEGF-A165b blockade was assessed. In a cohort of 104 ST-segment elevation MI patients, circulating VEGF-A165b levels were correlated with cardiovascular magnetic resonance-derived left ventricular ejection fraction at 6-months and with the occurrence of adverse events (death, heart failure and/or re-infarction). Results In both models, circulating and myocardial VEGF-A165b presence was increased 21 days after MI induction. Serum VEGF-A165b levels inversely correlated with systolic function evaluated by echocardiography. VEGF-A165b blockage increased capillary density, reduced infarct size, and enhanced left ventricular function in reperfused, but not in non-reperfused MI experiments. In patients, higher VEGF-A165b levels correlated with depressed ejection fraction and worse outcomes. Conclusions In experimental and clinical studies, higher serum VEGF-A165b levels associates with a worse systolic function. Its blockage enhances neoangiogenesis, reduces infarct size, and increases ejection fraction in reperfused, but not in non-reperfused MI experiments. Therefore, VEGF-A165b neutralization represents a potential co-adjuvant therapy to coronary reperfusion. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (Exp. PIE15/00013, PI17/01836, PI18/00209 and CIBERCV16/11/00486).

Sequential Extracorporeal Therapy Collaborative Device and Timely Support for Endotoxic, Septic, and Cardiac Shock: A Case Report

2019 ◽  
Vol 49 (4) ◽  
pp. 502-508 ◽  
Author(s):  
Silvia De Rosa ◽  
Sara Samoni ◽  
Claudio Ronco
Keyword(s):  
Septic Shock ◽  
Myocardial Dysfunction ◽  
Endotoxic Shock ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Septic Cardiomyopathy ◽  
Ventricular Ejection Fraction ◽  
Circulatory Insufficiency ◽  
Extracorporeal Therapy ◽  
Va Ecmo

We report a 49-year-old man, without prior medical history, consulted in the emergency department with a 5 day history of cough, fever, and dysuria. He was admitted to the intensive care unit due to septic shock. Critical care management was initiated, including mechanical ventilation and vasopressors. Endotoxic shock was suspected (endotoxin activity assay [EAA] 0.75), and 2 treatments with Polymyxin B hemoperfusion (Toraymyxin®, Toray Medical Co., Ltd., Tokyo, Japan) were performed in 48 h, alternate with high-volume hemofiltration sessions. Initial blood cultures were positive for Neisseria meningitidis (serogroup B), and a lumbar puncture was deferred because of the coagulopathy and a bleeding risk. The circulatory efficiency significantly improved after the second procedure of hemoperfusion, and the treatment resulted in a marked decrease in the serum endotoxin level (EAA <0.4). However, after 48 h, tachycardia did not improve, left ventricular ejection fraction was 20%, and circulatory insufficiency progressed. Therefore, considering the involvement of septic cardiomyopathy and cardiogenic shock, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was initiated for circulation assistance on day 3 from admission. Continuous cytokine hemoadsorption (Cytosorb®, Cytosorbent Corporation, Monmouth Junction, NJ, USA) was incorporated into a VA-ECMO circuit for 48 h without a considerable improvement. For this reason, a 72-h continuous veno-venous hemodialysis session was started in which a high cutoff filter was used. Tachycardia and myocardial dysfunction improved by day 6, and VA-ECMO was withdrawn on the tenth day. Subsequently, nutrition management and rehabilitation were performed, and the patient was transferred to the department of respiratory medicine on day 80, he was discharged from our hospital on day 113. Sequential extracorporeal therapy may be beneficial when concomitant with circulatory assistance in uncontrollable cases of septic shock using catecholamines and blockers.

The Role of BCL2 Protein and Tumour Protein p53 in Septic Cardiomyopathy

2019 ◽  
Vol 70 (11) ◽  
pp. 3842-3846
Author(s):  
Peter Michael Reil ◽  
Teodor Traian Maghiar ◽  
Karlheinz Seidl ◽  
Ciprian Borza ◽  
Vharoon Nunkoo ◽  
...  
Keyword(s):  
Septic Shock ◽  
Systolic Function ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Septic Cardiomyopathy ◽  
Ventricular Ejection Fraction ◽  
P53 Expression ◽  
Protein P53 ◽  
Bcl2 Protein

A decreased left ventricular ejection fraction (LVEF) was observed in patients suffering from septic shock with normalization of systolic function after 10 days.�Similar courses of reversible myocardial dysfunction due to the systemic inflammatory response syndrome were also encountered in other critical illnesses. Since the pathological and histological mechanisms are not fully understood, the present study tries to understand the septic cardiomyopathy related to the apoptotic pathway. Thestudy included a number of 29�cases of adults that died of septic shock being analysed for BCL2 and p53 expression rates of myocardial tissue. This is the first time the expression of BCL2 protein, p53 tumour protein were evaluated in septic shock and septic cardiomyopathy of humans.�There was a strong link between the increased expression of BCL2 and of p53 protein in cardiac muscle cells in the studied group (p=0.0300).�The study showed a significant correlation between markedly increased values and poor outcome.

Efficacy and safety of first-line (1L) pertuzumab (P), trastuzumab (T), and docetaxel (D) in HER2-positive MBC (CLEOPATRA) in patients previously exposed to trastuzumab.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 600-600
Author(s):  
Eva Maria Ciruelos Gil ◽  
Adam Brufsky ◽  
Young-Hyuck Im ◽  
Sung-Bae Kim ◽  
Emma Clark ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Significant Risk ◽  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Efficacy And Safety ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Cox Regression Analysis ◽  
Study Population

600 Background: CLEOPATRA is a global phase III trial of P + T + D vs placebo + T + D in HER2-positive 1L MBC. Results showed a significant improvement in PFS (Baselga NEJM 2012) and OS (Swain SABCS 2012) favoring P + T + D. CLEOPATRA started recruitment in 2008 soon after the approval of T in the adjuvant setting in 2006 and mandated a disease-free interval (DFI) of ≥12 mos from the end of adjuvant therapy to MBC diagnosis. Due to this, a low proportion of pts with prior T exposure was included. Here we present the efficacy and safety of 1L P + T + D in the subset of pts in CLEOPATRA with prior T exposure. Methods: Pts received P + T + D or placebo + T + D, had a DFI ≥12 mos, baseline left ventricular ejection fraction (LVEF) ≥50% and no LVEF decline to <50% during/after prior T therapy. Exploratory analyses of PFS and OS in pts with (neo)adjuvant therapy with or without T were conducted. Results: Of the study population, 47% had received (neo)adjuvant therapy and 11% had received (neo)adjuvant T; 82% of the prior T group came from Europe or North America. A univariate Cox regression analysis did not identify prior T therapy as a statistically significant risk factor for developing left ventricular systolic dysfunction (LVSD). However, due to the low number of LVSD events overall, this analysis has limited sensitivity. Conclusions: Data from CLEOPATRA show that pts with HER2-positive 1L MBC who have received prior T (DFI ≥12 mos) derive the same magnitude of benefit from the combination of P + T + D when compared with the whole study population or those who are T-naïve. This is in agreement with prior evidence of the activity of P + T in pts pretreated with T (Baselga JCO 2010). Efficacy and safety of P-T-based therapy is being explored in the PERUSE and PHEREXA trials, in a pt population with wider exposure to prior T and a shorter DFI, which may better represent current clinical practice. Clinical trial information: NCT00567190. [Table: see text]

scholarly journals Prognostic Accuracy of the Afterload-related Cardiac Performance for 7-day Mortality Among Critical Ill Patients With Septic Shock

2020 ◽  
Author(s):  
Wei-yan Chen ◽  
Li-li Tao ◽  
Qi Xu ◽  
Xing Wei ◽  
Min-sheng Chen
Keyword(s):  
Septic Shock ◽  
Hospital Mortality ◽  
Characteristic Curve ◽  
Left Ventricular ◽  
Cox Proportional Hazards ◽  
Cardiac Performance ◽  
Left Ventricular Ejection ◽  
Septic Cardiomyopathy ◽  
Icu Mortality ◽  
Ventricular Ejection Fraction

Abstract BackgroundSeptic patients with cardiac impairment are with high mortality. Afterload-related cardiac performance (ACP), as a new tool for diagnostic septic cardiomyopathy (SCM), still needs to be evaluated its impact on the prognosis for patients with septic shock. MethodsIn this observational retrospective study, 119 patients with septic shock undertaken PiCCO monitoring were evaluated for the effects of ACP on 7-day mortality, ICU mortality and hospital mortality. The ability of ACP, cardiac index (CI) and left ventricular ejection fraction (LVEF) to discriminate between survivors and non-survivors was tested by comparing the area under the receiver operating characteristic curve (AUROC) analysis. Multivariable logistic regression and Cox proportional hazards regression analyses were performed to assess the associations of ACP with 7-day mortality. Curve estimation was used to describe the relationship between hazard ratio (HR) of death and ACP.ResultsACP assessed at 12 hours (ACP12h) after septic shock [AUROC 0.86 (95% CI 0.79 to 0.93), P < 0.001] demonstrated significantly greater discrimination for 7-day mortality than CI [AUROC 0.67 (95% CI 0.57 to 0.78), P = 0.001 ] and LVEF [AUROC 0.53 (95% CI 0.43 to 0.64), P = 0.58] (all P < 0.001). Similarly, when adjusted with gender, APACHEII score, VIS and MAP as possible confounders, ACP12h still outperformed both CI12h and LVEF for discrimination of 7-day mortality (both P < 0.001). The superior discriminatory performance of ACP12h over both CI12h and LVEF was further maintained when considering ICU mortality and hospital mortality when considered in isolation or adjusted with the baseline prediction. Compared with normal ACP, HR for slight, moderate and severe impairment were 4.84 (1.96 to 11.96), 12.13 (4.83 to 30.43) and 32.70 (7.76 to 137.86), respectively. After adjustment for risk factor, decrease ACP still associated with increasing 7-day mortality (P = 0.001). Exponential relationship was observed between ACP12h and HR of 7-day death.ConclusionsOur results suggested that ACP may serve as a new tool for diagnosing SCM. In addition, the assessment of ACP at 12 hours after septic shock in ICU significantly improves 7-day mortality, ICU mortality and hospital mortality predictions when compared to CI and LVEF.

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