Time to vasopressor initiation and organ failure progression in early septic shock
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SUBMITTER: Black L
PROVIDER: S-EPMC7493499 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
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Project description:IntroductionDespite recent advances in the management of septic shock, mortality remains unacceptably high. Earlier initiation of key therapies including appropriate antimicrobials and fluid resuscitation appears to reduce the mortality in this condition. This study examined whether early initiation of vasopressor therapy is associated with improved survival in fluid therapy-refractory septic shock.MethodsUtilizing a well-established database, relevant information including duration of time to vasopressor administration following the initial documentation of recurrent/persistent hypotension associated with septic shock was assessed in 8,670 adult patients from 28 ICUs in Canada, the United States of America, and Saudi Arabia. The primary endpoint was survival to hospital discharge. Secondary endpoints were length of ICU and hospital stay as well as duration of ventilator support and vasopressor dependence. Analysis involved multivariate linear and logistic regression analysis.ResultsIn total, 8,640 patients met the definition of septic shock with time of vasopressor/inotropic initiation documented. Of these, 6,514 were suitable for analysis. The overall unadjusted hospital mortality rate was 53%. Independent mortality correlates included liver failure (odds ratio (OR) 3.46, 95% confidence interval (CI), 2.67 to 4.48), metastatic cancer (OR 1.63, CI, 1.32 to 2.01), AIDS (OR 1.91, CI, 1.29 to 2.49), hematologic malignancy (OR 1.88, CI, 1.46 to 2.41), neutropenia (OR 1.78, CI, 1.27 to 2.49) and chronic hypertension (OR 0.62 CI, 0.52 to 0.73). Delay of initiation of appropriate antimicrobial therapy (OR 1.07/hr, CI, 1.06 to 1.08), age (OR 1.03/yr, CI, 1.02 to 1.03), and Acute Physiology and Chronic Health Evaluation (APACHE) II Score (OR 1.11/point, CI, 1.10 to 1.12) were also found to be significant independent correlates of mortality. After adjustment, only a weak correlation between vasopressor delay and hospital mortality was found (adjusted OR 1.02/hr, 95% CI 1.01 to 1.03, P <0.001). This weak effect was entirely driven by the group of patients with the longest delays (>14.1 hours). There was no significant relationship of vasopressor initiation delay to duration of vasopressor therapy (P?=?0.313) and only a trend to longer duration of ventilator support (P?=?0.055) among survivors.ConclusionMarked delays in initiation of vasopressor/inotropic therapy are associated with a small increase in mortality risk in patients with septic shock.
| S-EPMC4075345 | biostudies-literature
Project description:Tachycardia is common in septic shock, but many patients with septic shock are relatively bradycardic. The prevalence, determinants, and implications of relative bradycardia (heart rate, < 80 beats/min) in septic shock are unknown. To determine mortality associated with patients who are relatively bradycardic while in septic shock.Retrospective study of patients admitted for septic shock to study ICUs during 2005-2013.One large academic referral hospital and two community hospitals.Adult patients with septic shock requiring vasopressors.None.Primary outcome was 28-day mortality. We used multivariate logistic regression to evaluate the association between relative bradycardia and mortality, controlling for confounding with inverse probability treatment weighting using a propensity score.We identified 1,554 patients with septic shock, of whom 686 (44%) met criteria for relative bradycardia at some time. Twenty-eight-day mortality in this group was 21% compared to 34% in the never-bradycardic group (p < 0.001). Relatively bradycardic patients were older (65 vs 60 yr; p < 0.001) and had slightly lower illness severity (Sequential Organ Failure Assessment, 10 vs 11; p = 0.004; and Acute Physiology and Chronic Health Evaluation II, 27 vs 28; p = 0.008). After inverse probability treatment weighting, covariates were balanced, and the association between relative bradycardia and survival persisted (p < 0.001).Relative bradycardia in patients with septic shock is associated with lower mortality, even after adjustment for confounding. Our data support expanded investigation into whether inducing relative bradycardia will benefit patients with septic shock.
| S-EPMC5512273 | biostudies-literature
Project description:Clinical guidelines recommend norepinephrine as initial vasopressor of choice for septic shock, with dopamine suggested as an alternative vasopressor in selected patients with low risk of tachyarrhythmias and absolute or relative bradycardia. We sought to determine practice patterns and outcomes associated with vasopressor selection in a large, population-based cohort of patients with septic shock that allows for assessment of outcomes in clinically important subgroups.We performed a retrospective cohort study to determine factors associated with choice of dopamine as compared with norepinephrine as initial vasopressor for patients with septic shock. We used propensity score matching to compare risk of hospital mortality based on initial vasopressor. We performed multiple sensitivity analyses using alternative methods to address confounding and hospital-level clustering. We investigated interaction between vasopressor selection and mortality in clinical subgroups based on arrhythmia and cardiovascular risk.Enhanced administrative data (Premier, Charlotte, NC) from 502 U.S. hospitals during the years 2010-2013.A total of 61,122 patients admitted with septic shock who received dopamine or norepinephrine as initial vasopressor during the first 2 days of hospitalization.None.Norepinephrine (77.6%) was the most frequently used initial vasopressor during septic shock. Dopamine was preferentially selected by cardiologists, in the Southern United States, at nonteaching hospitals, for older patients with more cardiovascular comorbidities and was used less frequently over time. Patients receiving dopamine experienced greater hospital mortality (propensity-matched cohort: n = 38,788; 25% vs 23.7%; odds ratio, 1.08; 95% CI, 1.02-1.14). Sensitivity analyses showed similar results. Subgroup analyses showed no evidence for effect modification based on arrhythmia risk or underlying cardiovascular disease.In a large population-based sample of patients with septic shock in the United States, use of dopamine as initial vasopressor was associated with increased mortality among multiple clinical subgroups. Areas where use of dopamine as initial vasopressor is more common represent potential targets for quality improvement intervention.
| S-EPMC5094367 | biostudies-literature
Project description:BackgroundSepsis shifts cardiac metabolic fuel preference and this disruption may have implications for cardiovascular function. A greater understanding of the role of metabolism in the development and persistence of cardiovascular failure in sepsis could serve to identify novel pharmacotherapeutic approaches.MethodsSecondary analysis of prospective quantitative proton nuclear magnetic resonance (1H-NMR) metabolomic data from patients enrolled in a phase II randomized control trial of L-carnitine in septic shock. Participants with a sequential organ failure assessment (SOFA) score of > = 5, lactate > = 2, and requiring vasopressor support for at least 4 h were eligible for enrollment. The independent prognostic value of metabolites to predict survival with shock resolution within 48 h and vasopressor free days were assessed. Concentrations of predictive metabolites were compared between participants with and without shock resolution at 48 h.ResultsSerum 1H-NMR metabolomics data from 228 patients were analyzed. Eighty-one (36%) patients met the primary outcome; 33 (14%) died prior to 48 h. The branched chain amino acids (BCAA), valine, leucine, and isoleucine were univariate predictors of the primary outcome after adjusting for multiple hypothesis testing, while valine remained significant after controlling for SOFA score. Similar results were observed when analyzed based on vasopressor free days, and persisted after controlling for confounding variables and excluding non-survivors. BCAA concentrations at 48 h significantly discriminated between those with shock resolution versus persistent shock.ConclusionsAmong patients with septic shock, BCAA concentrations independently predict time to shock resolution. This study provides hypothesis generating data into the potential contribution of BCAAs to the pathophysiology of cardiovascular failure in sepsis, opening areas for future investigations.
| S-EPMC8089113 | biostudies-literature
Project description:This study aimed to assess the effects of early fluid resuscitation (EFR) combined with high volume hemofiltration (HVHF) on the cardiopulmonary function and removal of inflammatory mediators in a septic shock swine model. Eighteen swine were randomized into three groups: control (n = 6) (extracorporeal circulating blood only), continuous renal replacement therapy (CRRT) (n = 6; ultrafiltration volume = 25 mL/Kg/h), and HVHF (n = 6; ultrafiltration volume = 85 mL/Kg/h). The septic shock model was established by intravenous infusion of lipopolysaccharides (50 µg/kg/h). Hemodynamic parameters (arterial pressure, heart rate, cardiac output, stroke volume variability, left ventricular contractility, systemic vascular resistance, and central venous pressure), vasoactive drug parameters (dose and time of norepinephrine and hourly fluid intake), pulmonary function (partial oxygen pressure and vascular permeability), and cytokines (interleukin-6 and interleukin-10) were observed. Treatment resulted in significant changes at 4-6 h. HVHF was beneficial, as shown by the dose of vasoactive drugs, fluid intake volume, left ventricular contractility index, and partial oxygen pressure. Both CRRT and HVHF groups showed improved removal of inflammatory mediators compared with controls. In conclusion, EFR combined with HVHF improved septic shock in this swine model. The combination decreased shock progression, reduced the need for vasoactive drugs, and alleviated the damage to cardiopulmonary functions.
| S-EPMC4620416 | biostudies-other
Project description:BACKGROUND:Thiamine, an essential vitamin for aerobic metabolism and glutathione cycling, may decrease the effects of critical illnesses. The objective of this study was to determine whether intravenous thiamine administration can reduce vasopressor requirements in patients with septic shock. METHODS:This study was a prospective randomized double-blind placebo-controlled trial. We included adult patients with septic shock who required a vasopressor within 1-24?h after admission between March 2018 and January 2019 at a tertiary hospital in Thailand. Patients were divided into two groups: those who received 200?mg thiamine or those receiving a placebo every 12?h for 7?days or until hospital discharge. The primary outcome was the number of vasopressor-free days over 7?days. The pre-defined sample size was 31 patients per group, and the study was terminated early due to difficult recruitment. RESULTS:Sixty-two patients were screened and 50 patients were finally enrolled in the study, 25 in each group. There was no difference in the primary outcome of vasopressor-free days within the 7-day period between the thiamine and placebo groups (mean: 4.9?days (1.9) vs. 4.0?days (2.7), p =?0.197, mean difference?-?0.9, 95% CI (-?2.9 to 0.5)). However, the reductions in lactate (p =?0.024) and in the vasopressor dependency index (p =?0.02) at 24?h were greater among subjects who received thiamine repletion vs. the placebo. No statistically significant difference was observed in SOFA scores within 7?days, vasopressor dependency index within 4?days and 7?days, or 28-day mortality. CONCLUSIONS:Thiamine was not associated to a significant reduction in vasopressor-free days over 7-days in comparison to placebo in patients with septic shock. Administration of thiamine could be associated with a reduction in vasopressor dependency index and lactate level within 24?h. The study is limited by early stopping and low sample size. TRIAL REGISTRATION:TCTR, TCTR20180310001. Registered 8 March 2018, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=3330 .
| S-EPMC7650202 | biostudies-literature
Project description:OBJECTIVE:High density lipoprotein (HDL) is important for defense against sepsis but becomes dysfunctional (Dys-HDL) during inflammation. We hypothesize that Dys-HDL correlates with organ dysfunction (sequential organ failure assessment (SOFA) score) early sepsis. METHODS:A prospective cohort study of adult ED sepsis patients enrolled within 24 hours. RESULTS:Eighty eight patients were analyzed. Dys-HDL (expressed as HDL inflammatory index (HII)) correlated with SOFA at enrollment (r = 0.23, p = 0.024) and at 48 hours (r = 0.24, p = 0.026) but HII change over the first 48 hours did not correlate with change in SOFA (r = 0.06, p = 0.56). Enrollment HII was significantly different in patients with most severe organ failure (2.31, IQR 1.33-5.2) compared to less severe organ failure (1.81, IQR 1.23-2.64, p = 0.043). Change in HII over 48 hours was significantly different for in-hospital non-survivors (-0.45, IQR-2.6, -0.14 p = 0.015) and for 28-day non-survivors (-1.12, IQR -1.52, 0.12, p = 0.044). In a multivariable linear regression equation (R2 = 0.13), for each unit HII increase, 48-hour SOFA increased by 0.72 (p = 0.009). CONCLUSION:HII correlated with SOFA and predicted 48-hour SOFA score in early sepsis. Future studies are needed to delineate potential mechanisms. TRIAL REGISTRATION:NCT02370186. Registered February 24, 2015.
| S-EPMC6138388 | biostudies-literature
Project description:BackgroundLeft ventricular ejection fraction (LVEF) is inconsistently associated with poor outcomes in patients with sepsis. Newer parameters such as LV longitudinal strain (LVLS), mitral annular plane systolic excursion (MAPSE) and LV longitudinal wall fractional shortening (LV-LWFS) may be more sensitive indicators of LV dysfunction, but are sparsely investigated. Our objective was to evaluate the association between five traditional and novel echocardiographic parameters of LV systolic function (LVEF, peak tissue Doppler velocity at the mitral valve (s´), LVLS, MAPSE and LV-LWFS) and outcomes in patients admitted to the Intensive Care Unit (ICU) with septic shock.MethodsA total of 152 patients admitted to the ICU with septic shock from two data repositories were included. Transthoracic echocardiograms were performed within 24 h of ICU admission. The primary outcome was myocardial injury, defined as high-sensitivity troponin T ≥ 45 ng/L on ICU admission. Secondary outcomes were organ support-free days (OSFD) and 30-day mortality. We also tested for the prognostic value of the systolic function parameters using multivariable analysis.ResultsLVLS, MAPSE and LV-LWFS, but not LVEF and s´, differed between patients with and without myocardial injury. After adjustment for age, pre-existing cardiac disease, Simplified Acute Physiology (SAPS3) score, Sequential Organ Failure Assessment (SOFA) score, plasma creatinine and presence of right ventricular dysfunction, only MAPSE and LV-LWFS were independently associated with myocardial injury. None of the systolic function parameters were associated with OSFD or 30-day mortality.ConclusionsMAPSE and LV-LWFS are independently associated with myocardial injury and outperform LVEF, s´ and LVLS. Whether these parameters are associated with clinical outcomes such as the need for organ support and short-term mortality is still unclear. Trial registration NCT01747187 and NCT04695119.
| S-EPMC10796855 | biostudies-literature
Project description:BACKGROUND:Septic shock is the most severe complication of sepsis and this syndrome is associated with high mortality. Treatment of septic shock remains largely supportive of hemodynamics and tissue perfusion. Early changes in organ function assessed by the Sequential Organ Function Assessment (SOFA) score are highly predictive of the outcome. However, the individual patient's response to supportive therapy is very heterogeneous, and the mechanisms underlying this variable response remain elusive. The aim of the study was to investigate the transcriptome of whole blood in septic shock patients with different responses to early supportive hemodynamic therapy assessed by changes in SOFA scores within the first 48 h from intensive care unit (ICU) admission. METHODS:We performed whole blood RNA sequencing in 31 patients: 17 classified as responders (R) and 14 as non-responders (NR). Gene expression was investigated at ICU admission (time point 1, or T1), comparing R with NR [padj <?0.01; Benjamini-Hochberg (BH)] and over time from T1 to T2 (48 h later) in R and NR independently (paired analysis, padj <?0.01; BH). Then the differences in gene expression trends over time were evaluated (Mann-Whitney, P <0.01). To identify enriched biological processes, we performed an over-representation analysis based on a right-sided hypergeometric test with Bonferroni step-down as multiple testing correction (padj <?0.05). RESULTS:At ICU admission, we did not identify differentially expressed genes (DEGs) between the two groups. In the transition from T1 to T2, the activation of genes involved in T cell-mediated immunity, granulocyte and natural killer (NK) cell functions, and pathogen lipid clearance was noted in the R group. Genes involved in acute inflammation were downregulated in both groups. CONCLUSIONS:Within the limits of a small sample size, our results could suggest that early activation of genes of the adaptive immune response is associated with an improvement in organ function.
| S-EPMC6249814 | biostudies-literature
Project description:ObjectivesTo determine if time to initial antimicrobial is associated with progression of severe sepsis to septic shock.DesignRetrospective cohort.SettingSix hundred fifty-six bed urban academic medical center.PatientsEmergency department patients greater than or equal to 18 years old with severe sepsis and/or septic shock and antimicrobial administration within 24 hours. Patients with shock on presentation were excluded.InterventionsNot available.Measurements and main resultsWe identified 3,929 severe sepsis patients, with overall mortality 12.8%. Nine hundred eighty-four patients (25.0%) progressed to septic shock. The median time to antimicrobial was 3.77 hours (interquartile range = 1.96-6.42) in those who progressed versus 2.76 hours (interquartile range = 1.60-4.82) in those who did not (p < 0.001). Multivariate logistic regression demonstrated that male sex (odds ratio = 1.18; 95% CI, 1.01-1.36), Charlson Comorbidity Index (odds ratio = 1.18; 95% CI, 1.11-1.27), number of infections (odds ratio = 1.05; 95% CI, 1.02-1.08), and time to first antimicrobial (odds ratio = 1.08; 95% CI, 1.06-1.10) were associated with progression. Each hour until initial antimicrobial administration was associated with a 8.0% increase in progression to septic shock. Additionally, time to broad-spectrum antimicrobial was associated with progression (odds ratio = 1.06; 95% CI, 1.05-1.08). Time to initial antimicrobial was also associated with in-hospital mortality (odds ratio = 1.05; 95% CI, 1.03-1.07).ConclusionsThis study emphasizes the importance of early, broad-spectrum antimicrobial administration in severe sepsis patients admitted through the emergency department, as longer time to initial antimicrobial administration is associated with increased progression of severe sepsis to septic shock and increased mortality.
| S-EPMC5374449 | biostudies-literature