Evaluation of Vasopressin for Septic Shock in Patients on Chronic Renin-Angiotensin-Aldosterone System Inhibitors

Erwin, Beth; Denaburg, Michael; Barker, Andrew B; McArdle, Philip; Windham, Samuel T.; Morgan, Charity

doi:10.1097/ccm.0000000000002729

Cited by 7 publications

(4 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Historically, in adult patients with sepsis and cardiogenic shock, vasoactive medication scoring systems have predominantly been used to classify the extent of hemodynamic support [ 21 – 23 ]. Vasoactive medications are used in an empiric fashion and often there are limited bedside data on cumulative vasopressor requirements [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Development and performance of a novel vasopressor-driven mortality prediction model in septic shock

Vallabhajosyula

Jentzer

Kotecha

et al. 2018

Ann. Intensive Care

View full text Add to dashboard Cite

BackgroundVasoactive medications are essential in septic shock, but are not fully incorporated into current mortality prediction risk scores. We sought to develop a novel mortality prediction model for septic shock incorporating quantitative vasoactive medication usage.MethodsQuantitative vasopressor use was calculated in a cohort of 5352 septic shock patients and compared using norepinephrine equivalents (NEE), cumulative vasopressor index and the vasoactive inotrope score models. Having best discrimination prediction, log10NEE was selected for further development of a novel prediction model for 28-day and 1-year mortality via backward stepwise logistic regression. This model termed ‘MAVIC’ (Mechanical ventilation, Acute Physiology And Chronic Health Evaluation-III, Vasopressors, Inotropes, Charlson comorbidity index) was then compared to Acute Physiology And Chronic Health Evaluation-III (APACHE-III) and Sequential Organ Failure Assessment (SOFA) scores in an independent validation cohort for its accuracy in predicting 28-day and 1-year mortality.Measurements and main resultsThe MAVIC model was superior to the APACHE-III and SOFA scores in its ability to predict 28-day mortality (area under receiver operating characteristic curve [AUROC] 0.73 vs. 0.66 and 0.60) and 1-year mortality (AUROC 0.74 vs. 0.66 and 0.60), respectively.ConclusionsThe incorporation of quantitative vasopressor usage into a novel ‘MAVIC’ model results in superior 28-day and 1-year mortality risk prediction in a large cohort of patients with septic shock.

show abstract

Section: Discussionmentioning

confidence: 99%

Development and performance of a novel vasopressor-driven mortality prediction model in septic shock

Vallabhajosyula

Jentzer

Kotecha

et al. 2018

Ann. Intensive Care

View full text Add to dashboard Cite

show abstract

“…It has previously been reported that multiple organ failure is the typical cause of mortality in patients with septic shock and symptoms of the disease include low perfusion of organs and an inability to maintain normal metabolic functions (12,13). Cardiac systolic and diastolic functions are directly associated with the prognosis of patients with septic shock (14,15).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑494‑3p protects rat cardiomyocytes against septic shock via PTEN

Kong

2018

Exp Ther Med

View full text Add to dashboard Cite

The aim of the present study was to investigate the role of microRNA (miR)-494-3p in myocardial injury in patients with septic shock and the underlying mechanism. A total of 22 patients with sepsis and 17 patients with septic shock were included in the present study. In addition, 20 healthy subjects were recruited as the control group. Peripheral blood was collected from all subjects and a rat cardiomyocyte model of myocardial injury was constructed. Reverse transcription-quantitative polymerase chain reaction was used to measure miR-494-3p expression, while cell counting kit-8 assays were performed to assess cell proliferation. Flow cytometry was performed to investigate cell cycle distribution and apoptosis. Lactate dehydrogenase (LDH) assays were performed to measure LDH levels. ELISA was also performed to measure LDH, tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels in cell culture supernatants. Western blotting was employed to detect phosphatase and tensin homolog (PTEN) protein expression and dual luciferase reporter assays were performed to identify the interaction between miR-494-3p and PTEN mRNA. Reduced miR-494-3p expression was correlated with myocardial damage in patients with septic shock. Sera from patients with septic shock downregulated miR-494-3p expression in rat cardiomyocytes. miR-494-3p overexpression inhibited rat cardiomyocyte injury induced by treatment with sera from patients with septic shock. Furthermore, miR-494-3p overexpression reduced the synthesis and release of TNF-α and IL-6 from rat cardiomyocytes. PTEN knockdown alleviated rat cardiomyocyte injury following treatment with serum from patients with septic shock. PTEN was demonstrated to induce the release of TNF-α and IL-6 from rat cardiomyocytes treated with septic shock serum, while miR-494-3p was demonstrated to bind to the 3′-untranslated seed region of PTEN mRNA to regulate its expression. The results of the present study suggest that miR-494-3p is downregulated in the peripheral blood of patients with septic shock and is negatively correlated with myocardial injury. The present study also indicates that miR-494-3p regulates PTEN expression, inhibits sepsis-induced myocardial injury and protects the function of cardiomyocytes. The protective effect and mechanism of action of miR-494-3p indicate that it has potential for use in the clinical diagnosis and therapy of myocardial damage.

show abstract

“…Indeed, exogenous APLN-13 or ELA incubated with septic plasma displayed a further shortened half-life ex vivo. Prehospital use of ACE1 inhibitors has been linked to less need for vasopressor administration and better outcomes in septic shock-may be through higher levels of APLN-13 before the onset of sepsis 38 , 39 . However, ACE1 blockade may be associated with sepsis-induced endothelial dysfunction and the resulting AngII deficiency related to refractory shock and impaired outcomes 40 .…”

Section: Discussionmentioning

confidence: 99%

Apelin-13 in septic shock: effective in supporting hemodynamics in sheep but compromised by enzymatic breakdown in patients

Coquerel

Lamoureux

Chagnon

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Sepsis is a prevalent life-threatening condition related to a systemic infection, and with unresolved issues including refractory septic shock and organ failures. Endogenously released catecholamines are often inefficient to maintain blood pressure, and low reactivity to exogenous catecholamines with risk of sympathetic overstimulation is well documented in septic shock. In this context, apelinergics are efficient and safe inotrope and vasoregulator in rodents. However, their utility in a larger animal model as well as the limitations with regards to the enzymatic breakdown during sepsis, need to be investigated. The therapeutic potential and degradation of apelinergics in sepsis were tested experimentally and in a cohort of patients. (1) 36 sheep with or without fecal peritonitis-induced septic shock (a large animal experimental design aimed to mimic the human septic shock paradigm) were evaluated for hemodynamic and renal responsiveness to incremental doses of two dominant apelinergics: apelin-13 (APLN-13) or Elabela (ELA), and (2) 52 subjects (33 patients with sepsis/septic shock and 19 healthy volunteers) were investigated for early levels of endogenous apelinergics in the blood, the related enzymatic degradation profile, and data regarding sepsis outcome. APLN-13 was the only one apelinergic which efficiently improved hemodynamics in both healthy and septic sheep. Endogenous apelinergic levels early rose, and specific enzymatic breakdown activities potentially threatened endogenous apelin system reactivity and negatively impacted the outcome in human sepsis. Short-term exogenous APLN-13 infusion is helpful in stabilizing cardiorenal functions in ovine septic shock; however, this ability might be impaired by specific enzymatic systems triggered during the early time course of human sepsis. Strategies to improve resistance of APLN-13 to degradation and/or to overcome sepsis-induced enzymatic breakdown environment should guide future works.

show abstract

Evaluation of Vasopressin for Septic Shock in Patients on Chronic Renin-Angiotensin-Aldosterone System Inhibitors

Cited by 7 publications

References 10 publications

Development and performance of a novel vasopressor-driven mortality prediction model in septic shock

Development and performance of a novel vasopressor-driven mortality prediction model in septic shock

MicroRNA‑494‑3p protects rat cardiomyocytes against septic shock via PTEN

Apelin-13 in septic shock: effective in supporting hemodynamics in sheep but compromised by enzymatic breakdown in patients

Contact Info

Product

Resources

About