Angiotensin II in septic shock.
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ABSTRACT:
SUBMITTER: Correa TD
PROVIDER: S-EPMC4360936 | biostudies-literature | 2015 Mar
REPOSITORIES: biostudies-literature
Publications
Angiotensin II in septic shock.
Corrêa Thiago D TD Takala Jukka J Jakob Stephan M SM
Critical care (London, England) 20150316
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2015 and co-published as a series in Critical Care. Other articles in the series can be found online at http://ccforum.com/series/annualupdate2015. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901. ...[more]
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Project description:Angiotensin II (Ang II), part of the renin-angiotensin-aldosterone system (RAS), is a potent vasoconstrictor and has been recently approved for use by the US Food and Drug Administration in high-output shock. Though not a new drug, the recently published Angiotensin II for the Treatment of High Output Shock (ATHOS-3) trial, as well as a number of retrospective analyses have sparked renewed interest in the use of Ang II, which may have a role in treating refractory shock. We describe refractory shock, the unique mechanism of action of Ang II, RAS dysregulation in shock, and the evidence supporting the use of Ang II to restore blood pressure. Evidence suggests that Ang II may preferentially be of benefit in acute kidney injury and acute respiratory distress syndrome, where the RAS is known to be disrupted. Additionally, there may be a role for Ang II in cardiogenic shock, angiotensin converting enzyme inhibitor overdose, cardiac arrest, liver failure, and in settings of extracorporeal circulation.
| S-EPMC6067786 | biostudies-literature
Project description:In an ongoing translational research program involving microarray-based expression profiles in pediatric septic shock, we have now conducted longitudinal studies focused on the temporal expression profiles of canonical signaling pathways and gene networks. Genome-level expression profiles were generated from whole blood-derived RNA samples of children with septic shock (n = 30 individual patients) corresponding to days 1 and 3 of admission to the pediatric intensive care unit. Based on sequential statistical and expression filters, day 1 and day 3 of septic shock were characterized by differential regulation of 2,142 and 2,504 gene probes, respectively, relative to normal control patients. Venn analysis demonstrated 239 unique genes in the day 1 data set, 598 unique genes in the day 3 data set, and 1,906 genes common to both data sets. Analyses targeted toward derivation of biological function from these data sets demonstrated time-dependent, differential regulation of genes involved in multiple canonical signaling pathways and gene networks primarily related to immunity and inflammation. Notably, multiple and distinct gene networks involving T cell- and MHC antigen-related biological processes were persistently downregulated from day 1 to day 3. Further analyses demonstrated large scale and persistent downregulation of genes corresponding to functional annotations related to zinc homeostasis. These data represent the largest reported cohort of patients with septic shock, which has undergone longitudinal genome-level expression profiling. The data further advance our genome-level understanding of pediatric septic shock and support novel hypotheses that can be readily tested at both the experimental and translational levels. Keywords: Inflammation; sepsis; innate immunity; T cells; MHC antigen Keywords: to be updated
2007-06-14 | GSE8121 | GEO
Project description:BackgroundIn patients with vasodilatory shock, plasma concentrations of angiotensin I (ANG I) and II (ANG II) and their ratio may reflect differences in the response to severe vasodilation, provide novel insights into its biology, and predict clinical outcomes. The objective of these protocol prespecified and subsequent post hoc analyses was to assess the epidemiology and outcome associations of plasma ANG I and ANG II levels and their ratio in patients with catecholamine-resistant vasodilatory shock (CRVS) enrolled in the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study.MethodsWe measured ANG I and ANG II levels at baseline, calculated their ratio, and compared these results to values from healthy volunteers (controls). We dichotomized patients according to the median ANG I/II ratio (1.63) and compared demographics, clinical characteristics, and clinical outcomes. We constructed a Cox proportional hazards model to test the independent association of ANG I, ANG II, and their ratio with clinical outcomes.ResultsMedian baseline ANG I level (253 pg/mL [interquartile range (IQR) 72.30-676.00 pg/mL] vs 42 pg/mL [IQR 30.46-87.34 pg/mL] in controls; P < 0.0001) and median ANG I/II ratio (1.63 [IQR 0.98-5.25] vs 0.4 [IQR 0.28-0.64] in controls; P < 0.0001) were elevated, whereas median ANG II levels were similar (84 pg/mL [IQR 23.85-299.50 pg/mL] vs 97 pg/mL [IQR 35.27-181.01 pg/mL] in controls; P = 0.9895). At baseline, patients with a ratio above the median (≥1.63) had higher ANG I levels (P < 0.0001), lower ANG II levels (P < 0.0001), higher albumin concentrations (P = 0.007), and greater incidence of recent (within 1 week) exposure to angiotensin-converting enzyme inhibitors (P < 0.00001), and they received a higher norepinephrine-equivalent dose (P = 0.003). In the placebo group, a baseline ANG I/II ratio <1.63 was associated with improved survival (hazard ratio 0.56; 95% confidence interval 0.36-0.88; P = 0.01) on unadjusted analyses.ConclusionsPatients with CRVS have elevated ANG I levels and ANG I/II ratios compared with healthy controls. In such patients, a high ANG I/II ratio is associated with greater norepinephrine requirements and is an independent predictor of mortality, thus providing a biological rationale for interventions aimed at its correction.Trial registrationClinicalTrials.gov identifier NCT02338843. Registered 14 January 2015.
| S-EPMC7006163 | biostudies-literature
Project description:BackgroundVasodilatory shock refractory to catecholamine vasopressors and arginine vasopressin is highly morbid and responsible for significant mortality. Synthetic angiotensin II is a potent vasoconstrictor that may be suitable for use in these patients.Research questionWhat is the safety and effectiveness of angiotensin II and what variables are associated with a favorable hemodynamic response?Study design and methodsWe performed a multicenter, retrospective study at five tertiary medical centers in the United States. The primary end point of hemodynamic responsiveness to angiotensin II was defined as attainment of mean arterial pressure (MAP) of ≥ 65 mm Hg with a stable or reduced total vasopressor dosage 3 h after drug initiation.ResultsOf 270 included patients, 181 (67%) demonstrated hemodynamic responsiveness to angiotensin II. Responders showed a greater increase in MAP (+10.3 mm Hg vs +1.6 mm Hg, P < .001) and reduction in vasopressor dosage (-0.20 μg/kg/min vs +0.04 μg/kg/min; P < .001) compared with nonresponders at 3 h. Variables associated with favorable hemodynamic response included lower lactate concentration (OR 1.11; 95% CI, 1.05-1.17, P < .001) and receipt of vasopressin (OR, 6.05; 95% CI, 1.98-18.6; P = .002). In severity-adjusted multivariate analysis, hemodynamic responsiveness to angiotensin II was associated with reduced likelihood of 30-day mortality (hazard ratio, 0.50; 95% CI, 0.35-0.71; P < .001). Arrhythmias occurred in 28 patients (10%) and VTE was identified in 4 patients.InterpretationIn postmarketing use for vasopressor-refractory shock, 67% of angiotensin II recipients demonstrated a favorable hemodynamic response. Patients with lower lactate concentrations and those receiving vasopressin were more likely to respond to angiotensin II. Patients who responded to angiotensin II experienced reduced mortality.
| S-EPMC7856533 | biostudies-literature
Project description:BackgroundShock in drug poisoning is a life-threatening condition and current management involves fluid resuscitation and vasopressor therapy. Management is limited by the toxicity of high-dose vasopressors such as catecholamines. Clinical trials have shown the efficacy of angiotensin II as an adjunct vasopressor in septic shock. The aim of this review is to assess the use of angiotensin II in patients with shock secondary to drug overdose.MethodsMedline (from 1946), Embase (from 1947) and PubMed (from 1946) databases were searched until July 2021 via OVID. Included studies were those with shock due to drug poisoning and received angiotensin II as part of their treatment regimen. Of the 481 articles identified, 13 studies (case reports and scientific abstracts) were included in the final analysis with a total of 14 patients. Extracted data included demographics, overdose drug and dosage, angiotensin II dosage, time of angiotensin II administration, haemodynamic changes, length of hospital stay, mortality, complications, cardiac function and other treatment agents used.ResultsThirteen studies were included consisting of 6 case reports, 6 scientific abstracts and 1 case series. Overdose drugs included antihypertensives (n = 8), psychotropics (n = 4), isopropanol (n = 1) and tamsulosin (n = 1). Out of a total of 14 patients, 3 patients died. Ten patients had their haemodynamic changes reported. In terms of MAP or SBP changes, three patients (30%) had an immediate response to angiotensin II, four patients (40%) had responses within 30 min, one patient (10%) within two hours and two patients (20%) did not have their time reported. Two patients were shown to have direct chronotropic effects within 30 min of angiotensin II administration. The median hospital stay for patients was 5 days (IQR = 4). The time from overdose until angiotensin II administration ranged from 5 to 56 h. Other vasopressors used included phenylephrine, noradrenaline, adrenaline, vasopressin, dobutamine, dopamine, methylene blue and ephedrine. A median of 3 vasopressors were used before initiation of angiotensin II. Twelve patients received angiotensin II as their final treatment.ConclusionsAngiotensin II may be useful as an adjunct vasopressor in treating shock secondary to drug poisoning. However, the current literature consisted of only very low-quality studies. To truly assess the utility of angiotensin II use in drug-induced poisoned patients, further well-designed prospective studies are required.
| S-EPMC8938563 | biostudies-literature
Project description:Angiotensin II (ATII) was approved for septic or other distributive shock due to its property of increasing blood pressure within 3 hours. Limited data exist regarding its effectiveness when used in real-world clinical practice.ObjectivesThis study examined ATII as a third-line vasopressor based on institutional approval.DesignRetrospective observational cohort study.Setting and participantsMedical ICU at an academic tertiary care medical center. Adult patients requiring 3 or more vasopressor agents for septic shock or other forms of distributed shock from September 1, 2018, to January 31, 2020.Main outcomes and measuresEffect of ATII after norepinephrine and vasopressin on mortality and mean arterial blood pressure response after 3 hours of administration.ResultsOne-hundred forty-seven patients, 56 receiving ATII and 91 receiving another vasopressor (non-ATII), were enrolled. Patients in the ATII group had higher mortality compared to the non-ATII group, and more required 5 or greater vasopressor agents (p < 0.01). After propensity score weighting, there remains a trend in higher mortality in the ATII compared to non-ATII group, but not statistically significant (86.0% vs 71.0%, p = 0.16). More patients in the ATII group continued to require 5 or greater vasopressor agents compared to the non-ATII group after propensity score weighting (45.9% vs 12.5%, p < 0.01). SOFA score was the only variable associated with mortality (OR = 1.25, 95% CI, 1.05-1.49; p = 0.01). Patients were considered a "responder" if mean arterial pressure greater than 65 mm Hg at 3 hours after the third vasopressor was initiated. Among the ATII group, 37.5% patients were responders compared to 45.1% responders in the non-ATII group (relative risk = 1.07, 95% CI, 0.6-1.93; p = 0.81).Conclusions and relevanceAlthough previous data support the use of ATII due to its favorable hemodynamic response in patients with distributive shock, there was no observed benefit in mortality or hemodynamic response with ATII as a third-line vasopressor in our study of real-world patients.
| S-EPMC8769135 | biostudies-literature
Project description:For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15-25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30-50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental.
| S-EPMC5538252 | biostudies-other
Project description:BackgroundData to support the use of specific vasopressors in septic shock are limited. Since angiotensin II (AT2) was approved by the Food and Drug Administration in 2017, multiple mechanistically distinct vasopressors are available to treat septic shock, but minimal data exist regarding which patients are most likely to benefit from each agent. Renin and dipeptidyl peptidase 3 (DPP3) are components of the renin-angiotensin-aldosterone system which have been shown to outperform lactate in predicting sepsis prognosis, and preliminary data suggest they could prove useful as biomarkers to guide AT2 use in septic shock.MethodsThe DARK-Sepsis trial is an investigator-initiated industry-funded, open-label, single-center randomized controlled trial of the use of AT2 versus standard of care (SOC) vasopressor therapy in patients admitted to the intensive care unit (ICU) with vasodilatory shock requiring norepinephrine ≥ 0.1 mcg/kg/min. In both groups, a series of renin and DPP3 levels will be obtained over the first 24 h of treatment with AT2 or SOC. The primary study outcome will be the ability of these biomarkers to predict response to vasopressor therapy, as measured by change in total norepinephrine equivalent dose of vasopressors at 3 h post-drug initiation or the equivalent timepoint in the SOC arm. To determine if the ability to predict vasopressor response is specific to AT2 therapy, the primary analysis will be the ability of baseline renin and DPP3 levels to predict vasopressor response adjusted for treatment arm (AT2 versus control) and Sequential Organ Failure Assessment (SOFA) scores. Secondary outcomes will include rates of acute kidney injury, need for mechanical ventilation and kidney replacement therapy, lengths of stay in the ICU and hospital, ICU and hospital mortality, and rates of prespecified adverse events.DiscussionWith an armamentarium of mechanistically distinct vasopressor agents now available, sub-phenotyping patients using biomarkers has the potential to improve septic shock outcomes by enabling treatment of the correct patient with the correct vasopressor at the correct time. However, this approach requires validation in a large definitive multicenter trial. The data generated through the DARK-Sepsis study will prove crucial to the optimal design and patient enrichment of such a pivotal trial.Trial registrationClinicalTrials.gov NCT05824767. Registered on April 24, 2023.
| S-EPMC10935947 | biostudies-literature
Project description:Septic shock by pneumopathy was studied in prospective way in 20 patients and compared to normal blood. Blood samples were taken within 12 hours of diagnosis and the resulting transcritomes were compared to 42 normal control samples (selected samples from series GSE10715, GSE12711, GSE16728 and GSE7400). keywords: patient cohort study, septic shock, transcription-profile, blood
2017-09-08 | GSE33118 | GEO
Project description:PurposeAdrecizumab, a non-neutralizing antibody of adrenomedullin (ADM) was recently investigated regarding its potential to restore endothelial barrier function in septic shock patients with high plasma ADM levels. Circulating dipeptidyl peptidase 3 (cDPP3), a protease involved in the degradation of several cardiovascular mediators, represents another biological pathway strongly associated with outcome in septic shock, although unrelated to ADM. Therefore, the prognosis of patients with elevated cDPP3 may not be influenced by Adrecizumab. Also, time until initiation of treatment may influence efficacy.ObjectiveTo evaluate effects of cDPP3-based enrichment on treatment efficacy of Adrecizumab.Materials and methodsPost-hoc analysis of AdrenOSS-2, a phase-II, double-blind, randomized, placebo-controlled biomarker-guided trial of Adrecizumab.ResultsCompared to the total study cohort [HR for 28-day mortality of 0.84 (95% CI 0.53;1.31), p = 0.439], therapeutic benefit of Adrecizumab tended to be more pronounced in the subgroup of 249 patients with low cDPP3 (<50 ng/mL); [HR of 0.61 (95% CI 0.34;1.08), p = 0.085]. Median duration to study drug infusion was 8.5 h. In the subgroup of 129 patients with cDPP3 <50 ng/mL and an early start of treatment (<8.5 h after septic shock diagnosis) HR for 28-day mortality vs. placebo was 0.49 (95% CI 0.21-1.18), p = 0.105. In multivariate interaction analyses corrected for baseline disease severity, both cDPP3, as well as the cDPP3 * treatment interaction term were associated with a reduced HR for 28-day mortality in the Adrecizumab treated group; p = 0.015 for cDPP3 in univariate analysis, p = 0.025 for the interaction term between cDPP3 and treatment group. In contrast, treatment timing was not significantly associated with 28-day mortality in multivariate interaction analyses.DiscussionIn septic shock patients with high ADM levels, a further post-hoc enrichment strategy based on cDPP3 may indicate (with all the caveats to be considered for post-hoc subgroup analyses) that therapeutic efficacy is most pronounced in patients with lower cDPP3 levels.
| S-EPMC9751049 | biostudies-literature