Dataset Information

Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis.

ABSTRACT: Sepsis mortality is closely linked to multi-organ failure, and impaired microcirculatory blood flow is thought to be pivotal in the pathogenesis of sepsis-induced organ failure. We hypothesized that changes in microcirculatory flow during resuscitation are associated with changes in organ failure over the first 24 h of sepsis therapy.Prospective observational study.Emergency Department and Intensive Care Unit.Septic patients with systolic blood pressure <90 mmHg despite intravenous fluids or lactate >or=4.0 mM/L treated with early goal-directed therapy (EGDT).We performed Sidestream Dark Field (SDF) videomicroscopy of the sublingual microcirculation <3 h from EGDT initiation and again within a 3-6 h time window after initial. We imaged five sites and determined the mean microcirculatory flow index (MFI) (0 no flow to 3 normal) blinded to all clinical data. We calculated the Sequential Organ Failure Assessment (SOFA) score at 0 and 24 h, and defined improved SOFA a priori as a decrease >or=2 points. Of 33 subjects; 48% improved SOFA over 0-24 h. Age, APACHE II, and global hemodynamics did not differ significantly between organ failure groups. Among SOFA improvers, 88% increased MFI during EGDT, compared to 47% for non-improvers (P = 0.03). Median change in MFI was 0.23 for SOFA improvers versus -0.05 for non-improvers (P = 0.04).Increased microcirculatory flow during resuscitation was associated with reduced organ failure at 24 h without substantial differences in global hemodynamics. These data support the hypothesis that targeting the microcirculation distinct from the macrocirculation could potentially improve organ failure in sepsis.

SUBMITTER: Trzeciak S

PROVIDER: S-EPMC2821162 | biostudies-other | 2008 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis.

Trzeciak Stephen S McCoy Jonathan V JV Phillip Dellinger R R Arnold Ryan C RC Rizzuto Michael M Abate Nicole L NL Shapiro Nathan I NI Parrillo Joseph E JE Hollenberg Steven M SM

Intensive care medicine 20080702 12

<h4>Objective</h4>Sepsis mortality is closely linked to multi-organ failure, and impaired microcirculatory blood flow is thought to be pivotal in the pathogenesis of sepsis-induced organ failure. We hypothesized that changes in microcirculatory flow during resuscitation are associated with changes in organ failure over the first 24 h of sepsis therapy.<h4>Design</h4>Prospective observational study.<h4>Setting</h4>Emergency Department and Intensive Care Unit.<h4>Participants</h4>Septic patients w ...[more]

PMID: 18594793

Similar Datasets

Project description:IntroductionThe aim of the study was to evaluate and compare the microcirculatory perfusion during experimental sepsis in different potentially available parts of the body, such as sublingual mucosa, conjunctiva of the eye, and mucosa of jejunum and rectum.MethodsPigs were randomly assigned to sepsis (n = 9) and sham (n = 4) groups. The sepsis group received a fixed dose of live Escherichia coli infusion over a 1-hour period (1.8 × 10(9)/kg colony-forming units). Animals were observed 5 hours after the start of E. coli infusion. In addition to systemic hemodynamic assessment, we performed conjunctival, sublingual, jejunal, and rectal evaluation of microcirculation by using Sidestream Dark Field (SDF) videomicroscopy at the same time points: at baseline, and at 3 and 5 hours after the start of live E. coli infusion. Assessment of microcirculatory parameters of convective oxygen transport (microvascular flow index (MFI) and proportion of perfused vessels (PPV)), and diffusion distance (perfused vessel density (PVD) and total vessel density (TVD)) was done by using a semiquantitative method.ResultsInfusion of E. coli resulted in a hypodynamic state of sepsis associated with low cardiac output and increased systemic vascular resistance despite fluid administration. Significant decreases in MFI and PPV of small vessels were observed in sublingual, conjunctival, jejunal, and rectal locations 3 and 5 hours after the start of E. coli infusion in comparison with baseline variables. Correlation between sublingual and conjunctival (r = 0.80; P = 0.036), sublingual and jejunal (r = 0.80; P = 0.044), and sublingual and rectal (r = 0.79; P = 0.03) MFI was observed 3 hours after onset of sepsis. However, this strong correlation between the sublingual and other regions disappeared 5 hours after the start of E. coli infusion. Overall, the sublingual mucosa exhibited the most-pronounced alterations of microcirculatory flow in comparison with conjunctival, jejunal, and rectal microvasculature (P < 0.05).ConclusionsIn this pig model, a time-dependent correlation exists between sublingual and microvascular beds during the course of a hypodynamic state of sepsis.

Project description:IntroductionSeveral recent studies have shown that a positive fluid balance in critical illness is associated with worse outcome. We tested the effects of moderate vs. high-volume resuscitation strategies on mortality, systemic and regional blood flows, mitochondrial respiration, and organ function in two experimental sepsis models.Methods48 pigs were randomized to continuous endotoxin infusion, fecal peritonitis, and a control group (n = 16 each), and each group further to two different basal rates of volume supply for 24 hours [moderate-volume (10 ml/kg/h, Ringer's lactate, n = 8); high-volume (15 + 5 ml/kg/h, Ringer's lactate and hydroxyethyl starch (HES), n = 8)], both supplemented by additional volume boli, as guided by urinary output, filling pressures, and responses in stroke volume. Systemic and regional hemodynamics were measured and tissue specimens taken for mitochondrial function assessment and histological analysis.ResultsMortality in high-volume groups was 87% (peritonitis), 75% (endotoxemia), and 13% (controls). In moderate-volume groups mortality was 50% (peritonitis), 13% (endotoxemia) and 0% (controls). Both septic groups became hyperdynamic. While neither sepsis nor volume resuscitation strategy was associated with altered hepatic or muscle mitochondrial complex I- and II-dependent respiration, non-survivors had lower hepatic complex II-dependent respiratory control ratios (2.6 +/- 0.7, vs. 3.3 +/- 0.9 in survivors; P = 0.01). Histology revealed moderate damage in all organs, colloid plaques in lung tissue of high-volume groups, and severe kidney damage in endotoxin high-volume animals.ConclusionsHigh-volume resuscitation including HES in experimental peritonitis and endotoxemia increased mortality despite better initial hemodynamic stability. This suggests that the strategy of early fluid management influences outcome in sepsis. The high mortality was not associated with reduced mitochondrial complex I- or II-dependent muscle and hepatic respiration.

Project description:ObjectiveApproximately one-third of sepsis patients experience poor outcomes including chronic critical illness (CCI, intensive care unit (ICU) stay > 14 days) or early death (in-hospital death within 14 days). We sought to characterize lipoprotein predictive ability for poor outcomes and contribution to sepsis heterogeneity.DesignProspective cohort study with independent replication cohort.SettingEmergency department and surgical ICU at two hospitals.PatientsSepsis patients presenting within 24 h.MethodsMeasures included cholesterol levels (total cholesterol, high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C]), triglycerides, paraoxonase-1 (PON-1), and apolipoprotein A-I (Apo A-I) in the first 24 h. Inflammatory and endothelial markers, and sequential organ failure assessment (SOFA) scores were also measured. LASSO selection assessed predictive ability for outcomes. Unsupervised clustering was used to investigate the contribution of lipid variation to sepsis heterogeneity.Measurements and main results172 patients were enrolled. Most (~ 67%, 114/172) rapidly recovered, while ~ 23% (41/172) developed CCI, and ~ 10% (17/172) had early death. ApoA-I, LDL-C, mechanical ventilation, vasopressor use, and Charlson Comorbidity Score were significant predictors of CCI/early death in LASSO models. Unsupervised clustering yielded two discernible phenotypes. The Hypolipoprotein phenotype was characterized by lower lipoprotein levels, increased endothelial dysfunction (ICAM-1), higher SOFA scores, and worse clinical outcomes (45% rapid recovery, 40% CCI, 16% early death; 28-day mortality, 21%). The Normolipoprotein cluster patients had higher cholesterol levels, less endothelial dysfunction, lower SOFA scores and better outcomes (79% rapid recovery, 15% CCI, 6% early death; 28-day mortality, 15%). Phenotypes were validated in an independent replication cohort (N = 86) with greater sepsis severity, which similarly demonstrated lower HDL-C, ApoA-I, and higher ICAM-1 in the Hypolipoprotein cluster and worse outcomes (46% rapid recovery, 23% CCI, 31% early death; 28-day mortality, 42%). Normolipoprotein patients in the replication cohort had better outcomes (55% rapid recovery, 32% CCI, 13% early death; 28-day mortality, 28%) Top features for cluster discrimination were HDL-C, ApoA-I, total SOFA score, total cholesterol level, and ICAM-1.ConclusionsLipoproteins predicted poor sepsis outcomes. A Hypolipoprotein sepsis phenotype was identified and characterized by lower lipoprotein levels, increased endothelial dysfunction (ICAM-1) and organ failure, and worse clinical outcomes.

Project description:ObjectivesSepsis-3 defines organ dysfunction as an increase in the Sequential Organ Failure Assessment score by greater than or equal to 2 points. However, some Sequential Organ Failure Assessment score components are not routinely recorded in all hospitals' electronic health record systems, limiting its utility for wide-scale sepsis surveillance. The Centers for Disease Control and Prevention recently released the Adult Sepsis Event surveillance definition that includes simplified organ dysfunction criteria optimized for electronic health records (eSOFA). We compared eSOFA versus Sequential Organ Failure Assessment with regard to sepsis prevalence, overlap, and outcomes.DesignRetrospective cohort study.SettingOne hundred eleven U.S. hospitals in the Cerner HealthFacts dataset.PatientsAdults hospitalized in 2013-2015.InterventionsNone.Measurements and main resultsWe identified clinical indicators of presumed infection (blood cultures and antibiotics) concurrent with either: 1) an increase in Sequential Organ Failure Assessment score by 2 or more points (Sepsis-3) or 2) 1 or more eSOFA criteria: vasopressor initiation, mechanical ventilation initiation, lactate greater than or equal to 2.0 mmol/L, doubling in creatinine, doubling in bilirubin to greater than or equal to 2.0 mg/dL, or greater than or equal to 50% decrease in platelet count to less than 100 cells/μL (Centers for Disease Control and Prevention Adult Sepsis Event). We compared area under the receiver operating characteristic curves for discriminating in-hospital mortality, adjusting for baseline characteristics. Of 942,360 patients in the cohort, 57,242 (6.1%) had sepsis by Sequential Organ Failure Assessment versus 41,618 (4.4%) by eSOFA. Agreement between sepsis by Sequential Organ Failure Assessment and eSOFA was good (Cronbach's alpha 0.81). Baseline characteristics and infectious diagnoses were similar, but mortality was higher with eSOFA (17.1%) versus Sequential Organ Failure Assessment (14.4%; p < 0.001) as was discrimination for mortality (area under the receiver operating characteristic curve, 0.774 vs 0.759; p < 0.001). Comparisons were consistent across subgroups of age, infectious diagnoses, and comorbidities.ConclusionsThe Adult Sepsis Event's eSOFA organ dysfunction criteria identify a smaller, more severely ill sepsis cohort compared with the Sequential Organ Failure Assessment score, but with good overlap and similar clinical characteristics. Adult Sepsis Events may facilitate wide-scale automated sepsis surveillance that tracks closely with the more complex Sepsis-3 criteria.

Project description:BackgroundMicrocirculatory perfusion disturbances are associated with increased morbidity and mortality in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Technological advancements made it possible to monitor sublingual microcirculatory perfusion over time. The goal of this review is to provide an overview of the course of alterations in sublingual microcirculatory perfusion following CPB. The secondary goal is to identify which parameter of sublingual microcirculatory perfusion is most profoundly affected by CPB.MethodsPubMed and Embase databases were systematically searched according to PRISMA guidelines and as registered in PROSPERO. Studies that reported sublingual microcirculatory perfusion measurements before and after onset of CPB in adult patients undergoing cardiac surgery were included. The primary outcome was sublingual microcirculatory perfusion, represented by functional capillary density (FCD), perfused vessel density (PVD), total vessel density (TVD), proportion of perfused vessels (PPV), and microvascular flow index (MFI).ResultsThe search identified 277 studies, of which 19 fulfilled all eligibility criteria. Initiation of CPB had a profound effect on FCD, PVD, or PPV. Seventeen studies (89%) reported one or more of these parameters, and in 11 of those studies (65%), there was a significant decrease in these parameters during cardiac surgery; the other 6 studies (35%) reported no effect. In 29% of the studies, FCD, PVD, or PPV normalized by the end of cardiac surgery, and in 24% percent of the studies, this effect lasted at least 24?h. There was no clear effect of CPB on TVD and a mixed effect on MFI.ConclusionCPB during cardiac surgery impaired sublingual microcirculatory perfusion as reflected by reduced FCD, PVD, and PPV. Four studies reported this effect at least 24?h after surgery. Further research is warranted to conclude on the duration of CPB-induced microcirculatory perfusion disturbances and the relationship with clinical outcome.Trial registrationPROSPERO, CRD42019127798.

Project description:ContextSevere sepsis is typically characterized by initial cytokine-mediated hyperinflammation. Whether this hyperinflammatory phase is followed by immunosuppression is controversial. Animal studies suggest that multiple immune defects occur in sepsis, but data from humans remain conflicting.ObjectivesTo determine the association of sepsis with changes in host innate and adaptive immunity and to examine potential mechanisms for putative immunosuppression.Design, setting, and participantsRapid postmortem spleen and lung tissue harvest was performed at the bedsides of 40 patients who died in intensive care units (ICUs) of academic medical centers with active severe sepsis to characterize their immune status at the time of death (2009-2011). Control spleens (n = 29) were obtained from patients who were declared brain-dead or had emergent splenectomy due to trauma; control lungs (n = 20) were obtained from transplant donors or from lung cancer resections.Main outcome measuresCytokine secretion assays and immunophenotyping of cell surface receptor-ligand expression profiles were performed to identify potential mechanisms of immune dysfunction. Immunohistochemical staining was performed to evaluate the loss of immune effector cells.ResultsThe mean ages of patients with sepsis and controls were 71.7 (SD, 15.9) and 52.7 (SD, 15.0) years, respectively. The median number of ICU days for patients with sepsis was 8 (range, 1-195 days), while control patients were in ICUs for 4 or fewer days. The median duration of sepsis was 4 days (range, 1-40 days). Compared with controls, anti-CD3/anti-CD28-stimulated splenocytes from sepsis patients had significant reductions in cytokine secretion at 5 hours: tumor necrosis factor, 5361 (95% CI, 3327-7485) pg/mL vs 418 (95% CI, 98-738) pg/mL; interferon γ, 1374 (95% CI, 550-2197) pg/mL vs 37.5 (95% CI, -5 to 80) pg/mL; interleukin 6, 3691 (95% CI, 2313-5070) vs 365 (95% CI, 87-642) pg/mL; and interleukin 10, 633 (95% CI, -269 to 1534) vs 58 (95% CI, -39 to 156) pg/mL; (P < .001 for all). There were similar reductions in 5-hour lipopolysaccharide-stimulated cytokine secretion. Cytokine secretion in sepsis patients was generally less than 10% that in controls, independent of age, duration of sepsis, corticosteroid use, and nutritional status. Although differences existed between spleen and lung, flow cytometric analysis showed increased expression of selected inhibitory receptors and ligands and expansion of suppressor cell populations in both organs. Unique differences in cellular inhibitory molecule expression existed in immune cells isolated from lungs of sepsis patients vs cancer patients and vs transplant donors. Immunohistochemical staining showed extensive depletion of splenic CD4, CD8, and HLA-DR cells and expression of ligands for inhibitory receptors on lung epithelial cells.ConclusionsPatients who die in the ICU following sepsis compared with patients who die of nonsepsis etiologies have biochemical, flow cytometric, and immunohistochemical findings consistent with immunosuppression. Targeted immune-enhancing therapy may be a valid approach in selected patients with sepsis.

Dataset Information

Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis.

Publications

Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets