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Decreases in cerebral saturation in patients with septic shock are associated with increased risk of death: a prospective observational single center study.

ABSTRACT: BACKGROUND:The mortality rate from septic shock has been declining. Cerebral hypoxia, measured non-invasively with cerebral oximetry, has been correlated with neurologic and non-neurologic sequelae. Whether cerebral desaturations occur in septic shock patients and what consequences these may have is untested. METHODS:Adult patients with septic shock had cerebral saturation monitoring initiated. The primary objective was to determine if the incidence and magnitude of cerebral desaturations in septic shock patients correlated with delirium. We also compared the incidence and magnitude of cerebral desaturations in patients with septic shock with patients undergoing high-risk non-cardiac surgical procedures, a group known to be at high risk for cerebral desaturations. RESULTS:Fifteen patients were enrolled. Twelve (80 %) patients had a decrease in SctO2 below 65 %. Delirium was not associated with the area under the curve of an SctO2 of 65 % (p?=?0.84). Patients who died of septic shock had more significant decreases in SctO2 than those who survived (p?=?0.04). Decreased SctO2 was more common in patients with septic shock and was of greater magnitude than those undergoing high-risk non-cardiac surgery. CONCLUSIONS:Cerebral desaturations occur more commonly and are of a greater magnitude in septic shock patients compared with those undergoing high-risk non-cardiac surgery. There did not appear to be a relationship between the incidence or magnitude of decreases in SctO2 and ICU delirium. Patients who died of septic shock had more significant decreases in SctO2 than patients who survived.

SUBMITTER: Funk DJ

PROVIDER: S-EPMC4928281 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Decreases in cerebral saturation in patients with septic shock are associated with increased risk of death: a prospective observational single center study.

Funk Duane J DJ Kumar Anand A Klar Gregory G

Journal of intensive care 20160629

<h4>Background</h4>The mortality rate from septic shock has been declining. Cerebral hypoxia, measured non-invasively with cerebral oximetry, has been correlated with neurologic and non-neurologic sequelae. Whether cerebral desaturations occur in septic shock patients and what consequences these may have is untested.<h4>Methods</h4>Adult patients with septic shock had cerebral saturation monitoring initiated. The primary objective was to determine if the incidence and magnitude of cerebral desat ...[more]

PMID: 27366323

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Project description:BackgroundVasopressin is a second-line vasoactive agent for refractory septic shock. Vasopressin loading is not generally performed because of the lack of evidence for its effects and safety. However, based on our previous findings, we hypothesized it can predict the responsibility to vasopressin infusion with safety, and prospectively examined it in the present study.MethodsVasopressin loading was performed via the intravenous administration of a bolus of 1 U, followed by its continuous infusion at 1U/h in patients with septic shock treated with ≥ 0.2 μg/kg/min noradrenaline. An arterial pressure wave analysis was conducted, and endocrinological tests were performed immediately prior to vasopressin loading. We classified patients into responders/non-responders based on mean arterial pressure (MAP) changes after vasopressin loading. Based on our previous findings, the lower tertile of MAP changes was selected as the cut-off. The change in the catecholamine index (CAI) after 6 h was assigned as the primary outcome. Digital ischemia, mesenteric ischemia, and myocardial ischemia during the admission period were prospectively and systematically recorded as adverse events.ResultsNinety-two patients were registered during the study period and examined. Sixty-two patients with a MAP change > 22 mmHg were assigned as responders and the others as non-responders. Blood adrenocorticotropic hormone levels were significantly higher in non-responders. Stroke volume variations were higher in responders before loading, while stroke volume and dP/dtmax were higher in responders after loading. Median CAI changes were - 10 in responders and 0 in non-responders, which was significantly lower in the former (p < 0.0001). AUROC of MAP change with vasopressin loading to predict CAI change < 0 after continuous infusion was 0.843 with sensitivity of 0.92 and specificity of 0.77. Ischemia events were observed in 5 cases (5.4%).ConclusionsVasopressin loading may be safely introduced for septic shock. Vasopressin loading may be used to predict responses to its continuous infusion and select appropriate strategies to increase blood pressure.

Project description:BackgroundSeptic shock occurs when sepsis is related to severe hypotension and leads to a remarkable high number of deaths. The early diagnosis of septic shock is essential to reduce mortality. High-quality biomarkers can be objectively measured and evaluated as indicators to accurately predict disease diagnosis. However, single-gene prediction efficiency is inadequate; therefore, we identified a risk-score model based on gene signature to elevate predictive efficiency.MethodsThe gene expression profiles of GSE33118 and GSE26440 were downloaded from the Gene Expression Omnibus (GEO) database. These two datasets were merged, and the differentially expressed genes (DEGs) were identified using the limma package in R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of DEGs were performed. Subsequently, Lasso regression and Boruta feature selection algorithm were combined to identify the hub genes of septic shock. GSE9692 was then subjected to weighted gene co-expression network analysis (WGCNA) to identify the septic shock-related gene modules. Subsequently, the genes within such modules that matched with septic shock-related DEGs were identified as the hub genes of septic shock. To further understand the function and signaling pathways of hub genes, we performed gene set variation analysis (GSVA) and then used the CIBERSORT tool to analyze the immune cell infiltration pattern of diseases. The diagnostic value of hub genes in septic shock was determined using receiver operating characteristic (ROC) analysis and verified using quantitative PCR (qPCR) and Western blotting in our hospital patients with septic shock.ResultsA total of 975 DEGs in the GSE33118 and GSE26440 databases were obtained, of which 30 DEGs were remarkably upregulated. With the use of Lasso regression and Boruta feature selection algorithm, six hub genes (CD177, CLEC5A, CYSTM1, MCEMP1, MMP8, and RGL4) with expression differences in septic shock were screened as potential diagnostic markers for septic shock among the significant DEGs and were further validated in the GSE9692 dataset. WGCNA was used to identify the co-expression modules and module-trait correlation. Enrichment analysis showed significant enrichment in the reactive oxygen species pathway, hypoxia, phosphatidylinositol 3-kinases (PI3K)/Protein Kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling, nuclear factor-κβ/tumor necrosis factor alpha (NF-κβ/TNF-α), and interleukin-6 (IL-6)/Janus Kinase (JAK)/Signal Transducers and Activators of Transcription 3 (STAT3) signaling pathways. The receiver operating characteristic curve (ROC) of these signature genes was 0.938, 0.914, 0.939, 0.956, 0.932, and 0.914, respectively. In the immune cell infiltration analysis, the infiltration of M0 macrophages, activated mast cells, neutrophils, CD8 T cells, and naive B cells was more significant in the septic shock group. In addition, higher expression levels of CD177, CLEC5A, CYSTM1, MCEMP1, MMP8, and RGL4 messenger RNA (mRNA) were observed in peripheral blood mononuclear cells (PBMCs) isolated from septic shock patients than from healthy donors. Higher expression levels of CD177 and MMP8 proteins were also observed in the PBMCs isolated from septic shock patients than from control participants.ConclusionsCD177, CLEC5A, CYSTM1, MCEMP1, MMP8, and RGL4 were identified as hub genes, which were of considerable value in the early diagnosis of septic shock patients. These preliminary findings are of great significance for studying immune cell infiltration in the pathogenesis of septic shock, which should be further validated in clinical studies and basic studies.

Project description:BackgroundReduced cellular ATP synthesis due to impaired mitochondrial function of immune cells may be a factor influencing the immune response in septic shock. We investigate changes in mitochondrial function and bioenergetics of human monocytes and lymphocyte subsets.MethodsThirty patients with septic shock were studied at ICU admission, after 24 and 48 hours, and after resolution of shock. Enzymatic activities of citrate synthase and mitochondrial complexes I, IV, and ATP synthase and ATP content of monocytes, T-cells and B-cells and pro-inflammatory (IL-1β and IL-6) and anti-inflammatory (IL-10) cytokine plasma concentrations were compared to samples from 20 healthy volunteers.ResultsLarge variations in mitochondrial enzymatic activities of immune cells of septic patients were detected. In monocytes, maximum levels of citrate synthase activity in sepsis were significantly lower when compared to controls (p = 0.021). Maximum relative enzymatic activity (ratio relative to citrate synthase activity) of complex I (p<0.001), complex IV (p = 0.017) and ATP synthase (p<0.001) were significantly higher. In T-cells, maximum levels of citrate synthase (p = 0.583) and relative complex IV (p = 0.602) activity did not differ between patients and controls, whereas levels of relative complex I (p = 0.006) and ATP synthase (p = 0.032) were significantly higher in septic patients. In B-cells of patients, maximum levels of citrate synthase activity (p = 0.004) and relative complex I (p<0.001) were significantly higher, and mean levels of relative complex IV (p = 0.042) lower than the control values, whereas relative ATP synthase activity did not differ (p = 1.0). No significant difference in cellular ATP content was detected in any cell line (p = 0.142-0.519). No significant correlations between specific cytokines and parameters of mitochondrial enzymatic activities or ATP content were observed.ConclusionsSignificant changes of mitochondrial enzymatic activities occur in human peripheral blood immune cells in septic shock when compared to healthy controls. Assessed sub-types of immune cells showed differing patterns of regulation. Total ATP-content of human immune cells did not differ between patients in septic shock and healthy volunteers.

Project description:BackgroundThe relationship between cardiac output and septic acute kidney injury (AKI) remains unclear. The purpose of this study was to assess the association between the cardiac index (CI) and the renal outcomes in patients with septic shock.MethodsA one-year prospective cohort study was performed in the surgical and medical ICU of a teaching hospital in Nanjing, China. Twenty-nine septic shock patients who required early goal-directed fluid resuscitation were consecutively included. Pulse indicator continuous cardiac output (PiCCO) device was used to measure hemodynamic parameters before and after early goal-directed therapy (EGDT). Based on CI changes after EGDT, patients were assign to the CI increased group or the CI constant group, respectively. The incidence of poor renal outcome, which was defined as AKI on admission without recovery in following three days or new onset AKI within 28 days, was recorded. We investigated whether an increased CI was associated with a better renal outcome.ResultsAfter EGDT, there were 16 patients in the CI increased group and 13 patients in the CI constant group. The incidence of poor renal outcome was lower in CI increased group than in the CI constant group (6% vs. 62%; P = 0.003) with a relative risk of 0.10. The logistic regression showed that the CI percent change was associated with renal outcome, with an odd ratio of 0.003 (P = 0.056) after adjustment of possible confounding factors. The CI percent change would predict a good renal outcome (AU ROC 0.739, P = 0.012) with moderate accuracy (sensitivity 75% and specificity 89%) when using a 10% cut-off value from Youden index. The CI percent change was also positively correlated with creatinine clearance (CCr) after EGDT (ρ = 0.548; P = 0.002).ConclusionsThe increased CI after EGDT was a protective factor for kidney in patients with septic shock. A CI increased above 10% could be potentially used to predict development and reversibility of AKI in septic shock patients.Trial registrationClinicaltrials.gov:NCT01862588 (May 13, 2013).

Project description:BACKGROUND:The indication, composition and timing of administration of non-resuscitation fluid in septic shock have so far received little attention and accordingly the potential to reduce this source of fluid is unknown. The objective of the study was to quantify and characterize non-resuscitation fluid administered to patients with septic shock. METHODS:This prospective observational study was performed in eight intensive care units in Sweden and Canada during 4 months in 2018. Adult patients with septic shock within 24 h of admission to the intensive care unit were eligible for inclusion. Non-resuscitation fluids were defined as fluids other than colloids, blood products and crystalloids at a rate ≥ 5 ml/kg/h. Indication, volume and type of fluid were recorded during the first 5 days after admission. A maximum of 30 patients could be included per centre. To estimate the potential to reduce administration of non-resuscitation fluid, a pragmatic "restrictive" protocol for administration of non-resuscitation fluids was devised based on the most restrictive practice already in place for non-resuscitation fluids at any of the participating centres. Data are presented as median (interquartile range [IQR]). RESULTS:A total of 200 patients were included in the study and the 30-day mortality was 35%. Patients received a total of 7870 (4060-12,340) ml of non-resuscitation fluids and 2820 (1430-4580) of resuscitation fluids during the observation period. Median volumes of non-resuscitation and resuscitation fluids were similar at day 1 (1620 [710-2320] and 1590 [520-3000]) ml, respectively) and non-resuscitation fluids represented the largest source of fluid from day 2 and onwards after admission to the ICU. Vehicles for drugs such as vasoactive drugs and antibiotics constituted the largest fraction of non-resuscitation fluids (2400 [1270-4030] ml) during the 5-day observation period. Modelling suggested that volume of non-resuscitation fluids could be reduced by 2840 (1270-4900) ml during the first 5 days of admission to the ICU, mainly through reducing maintenance fluids. CONCLUSIONS:Non-resuscitation fluids constitute the major fraction of fluids administered in the ICU to patients suffering from septic shock and may represent the largest modifiable target to reduce fluid overload.

Dataset Information

Decreases in cerebral saturation in patients with septic shock are associated with increased risk of death: a prospective observational single center study.

Publications

Decreases in cerebral saturation in patients with septic shock are associated with increased risk of death: a prospective observational single center study.

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