Early Use of Norepinephrine for Sepsis: Promising Results That Require Confirmation.
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ABSTRACT:
SUBMITTER: El Beze N
PROVIDER: S-EPMC6888651 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC6888656 | biostudies-literature
Project description:IntroductionThe relationships between systemic hemodynamics and renal blood flow and renal microcirculation are poorly known in sepsis. Norepinephrine (NE) infusion may add another level of complexity.MethodsVentilated and anesthetized rats were submitted to various mean arterial pressure (MAP) steps by blood removal, in presence and absence of sepsis and/or NE. Renal blood flow (RBF) and blood velocity (Vm) in renal cortical capillaries (using Sidestream Dark Field Imaging) were measured. Data were analyzed using linear mixed models enabling us to display the effects of both the considered explanatory variables and their interactions.ResultsPositive correlations were found between MAP and RBF. Sepsis had no independent impact on RBF whereas norepinephrine decreased RBF, regardless of the presence of sepsis. The relationship between MAP and RBF was weaker above a MAP of 100 mmHg as opposed to below 100 mmHg, with RBF displaying a relative "plateau" above this threshold. Sepsis and NE impacted carotid blood flow (CBF) differently compared to RBF, demonstrating organ specificity. A positive relationship was observed between MAP and Vm. Sepsis increased Vm while nNE decreased Vm irrespective of MAP. Sepsis was associated with an increase in serum creatinine determined at the end of the experiments, which was prevented by NE infusion.ConclusionIn our model, sepsis at an early phase did not impact RBF over a large range of MAP. NE elicited a renal vasoconstrictive effect. Autoregulation of RBF appeared conserved in sepsis. Conversely, sepsis was associated with "hypervelocity" of blood flow in cortical peritubular capillaries reversed by NE infusion.
| S-EPMC4056525 | biostudies-literature
Project description:Background: Up to 7% of neonates born in high-income countries receive antibiotics for suspected early-onset sepsis (EOS). Culture-proven neonatal sepsis has a prevalence of 0.2%, suggesting considerable overtreatment. We studied the diagnostic accuracy of umbilical cord blood and infant blood procalcitonin (PCT) in diagnosing EOS to improve antibiotic stewardship. Methods: Umbilical cord blood PCT was tested in newborns ≥ 32 weeks of gestation. Groups were defined as following: A) culture-proven or probable EOS (n = 25); B) Possible EOS, based on risk factors for which antibiotics were administered for <72 h (n = 49); C) Risk factor(s) for EOS without need for antibiotic treatment (n = 181); D) Healthy controls (n = 74). Additionally, venous or capillary blood PCT and C-reactive protein (CRP) were tested if blood drawing was necessary for standard care. Results: Between June 2019 and March 2021, 329 newborns were included. Umbilical cord blood PCT was significantly higher in group A than in group C and D. No difference between venous or arterial samples was found. Sensitivity and specificity for cord blood procalcitonin were 83 and 62%, respectively (cut-off 0.1 ng/mL). Antepartum maternal antibiotic administration was associated with decreased PCT levels in both cord blood and infant blood directly postpartum in all groups combined. Conclusion: Umbilical cord blood PCT levels are increased in newborns ≥32 weeks with a proven or probable EOS and low in newborns with risk factors for infection, but PCT seems not a reliable marker after maternal antibiotic treatment. PCT could be useful to distinguish infected from healthy newborns with or without EOS risk factors.
| S-EPMC8704118 | biostudies-literature
Project description:Reduced monocyte human leukocyte antigen (mHLA)-DR surface expression in the late phase of sepsis is postulated as a general biomarker of sepsis-induced immunosuppression and an independent predictor of nosocomial infections.Fifty-nine patients with sepsis and blood culture growing pathogenic bacteria were studied. Blood samples were collected at day 1 or 2 after admission, for measurement of mHLA-DR by flow cytometry and mRNA expression of HLA-DRA and class II transactivator (CIITA) by qRT-PCR. Blood samples from blood donors were used as controls (n?=?30).A significant reduced expression of mHLA-DR, HLA-DRA, and CIITA was seen in septic patients compared with controls. HLA-DRA mRNA level in whole blood was highly correlated with surface expression of mHLA-DR.Patients with sepsis display a diminished expression of HLA-DR at the monocyte surface as well as in the gene expression at the mRNA level. The mRNA expression level of HLA-DRA monitored by qRT-PCR correlates highly with surface expression of HLA-DR and appears to be a possible future biomarker for evaluation of immunosuppression in sepsis.
| S-EPMC4057202 | biostudies-literature
Project description:Sepsis is a global healthcare problem, characterized by whole body inflammation in response to microbial infection, which leads to organ dysfunction. It is becoming a frequent complication in hospitalized patients. Early and differential diagnosis of sepsis is needed critically to avoid unnecessary usage of antimicrobial agents and for proper antibiotic treatments through the screening of biomarkers that sustains with diagnostic significance.Current targeting conventional markers (C-reactive protein, white blood cell, tumour necrosis factor-α, interleukins, etc.) are non-specific for diagnosing sepsis. Procalcitonin (PCT), a member of the calcitonin super family could be a critical tool for the diagnosis of sepsis. But to distinguish between bacterial versus viral infections, procalcitonin alone may not be effective. Rapid elevation in the concentration of procalcitonin and other newly emerging biomarkers during an infection and its correlation with severity of illness makes it an ideal biomarker for bacterial infection. Beside this, the procalcitonin levels can be used for monitoring response to antimicrobial therapy, diagnosis of secondary inflammations, diagnosis of renal involvement in paediatric urinary tract infection, etc. The present article summarizes the relevance of procalcitonin in the diagnosis of sepsis and how it can be useful in determining the therapeutic approaches.Further studies are needed to better understand the application of PCT in the diagnosis of sepsis, differentiating between microbial and non-microbial infection cases and determining the therapeutic approaches for sepsis.
| S-EPMC5543591 | biostudies-other
Project description:BACKGROUND:Early-onset sepsis (EOS) is an important cause of morbidity and mortality in neonates, and its diagnosis remains challenging. The complete blood cell count and differential have been previously evaluated as diagnostic tools for EOS in small, single-center reports. We evaluated the diagnostic accuracy of the complete blood cell count and differential in EOS in a large, multicenter population of neonates admitted to the neonatal intensive care unit. METHODS:Using a cohort of 166,092 neonates with suspected EOS with cultures admitted to 293 neonatal intensive care units, we calculated odds ratios and receiver operating characteristic curves for complete blood cell count indices and prediction of a positive culture. We determined sensitivity, specificity and likelihood ratios for various commonly used cutoff values from the complete blood cell count. RESULTS:Low white blood cell counts, low absolute neutrophil counts and high immature-to-total neutrophil ratios were associated with increasing odds of infection (highest odds ratios: 5.38, 6.84 and 7.97, respectively). Specificity and negative predictive values were high (73.7%-99.9% and >99.8%). However, sensitivities were low (0.3%-54.5%) for all complete blood cell count indices analyzed. CONCLUSION:Low white blood cell count, absolute neutrophil count and high immature-to-total neutrophil ratio were associated with increasing odds of infection, but no complete blood cell count-derived index possesses the sensitivity to rule out reliably EOS in neonates.
| S-EPMC3399972 | biostudies-literature
Project description:BackgroundThe events leading to sepsis start with an invasive infection of a primary organ of the body followed by an overwhelming systemic response. Intra-abdominal infections are the second most common cause of sepsis. Peritoneal fluid is the primary site of infection in these cases. A microarray-based approach was used to study the temporal changes in cells from the peritoneal cavity of septic mice and to identify potential biomarkers and therapeutic targets for this subset of sepsis patients.ResultsWe conducted microarray analysis of the peritoneal cells of mice infected with a non-pathogenic strain of Escherichia coli. Differentially expressed genes were identified at two early (1 h, 2 h) and one late time point (18 h). A multiplexed bead array analysis was used to confirm protein expression for several cytokines which showed differential expression at different time points based on the microarray data. Gene Ontology based hypothesis testing identified a positive bias of differentially expressed genes associated with cellular development and cell death at 2 h and 18 h respectively. Most differentially expressed genes common to all 3 time points had an immune response related function, consistent with the observation that a few bacteria are still present at 18 h.ConclusionsTranscriptional regulators like PLAGL2, EBF1, TCF7, KLF10 and SBNO2, previously not described in sepsis, are differentially expressed at early and late time points. Expression pattern for key biomarkers in this study is similar to that reported in human sepsis, indicating the suitability of this model for future studies of sepsis, and the observed differences in gene expression suggest species differences or differences in the response of blood leukocytes and peritoneal leukocytes.
| S-EPMC3621573 | biostudies-literature
Project description:Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host responses to infection (Third International Consensus definition for Sepsis and septic shock). Despite decades of research, sepsis remains the leading cause of death in intensive care units. More than 40 clinical trials, most of which have targeted the sepsis-associated pro-inflammatory response, have failed. Thus, antibiotics and fluid resuscitation remain the mainstays of supportive care and there is intense need to discover and develop novel, targeted therapies to treat sepsis. Both pre-clinical and clinical studies over the past decade demonstrate unequivocally that sepsis not only causes hyper-inflammation, but also leads to simultaneous adaptive immune system dysfunction and impaired antimicrobial immunity. Evidences for immunosuppression include immune cell depletion (T cells most affected), compromised T cell effector functions, T cell exhaustion, impaired antigen presentation, increased susceptibility to opportunistic nosocomial infections, dysregulated cytokine secretion, and reactivation of latent viruses. Therefore, targeting immunosuppression provides a logical approach to treat protracted sepsis. Numerous pre-clinical studies using immunomodulatory agents such as interleukin-7, anti-programmed cell death 1 antibody (anti-PD-1), anti-programmed cell death 1 ligand antibody (anti-PD-L1), and others have demonstrated reversal of T cell dysfunction and improved survival. Therefore, identifying immunosuppressed patients with the help of specific biomarkers and administering specific immunomodulators holds significant potential for sepsis therapy in the future. This review focusses on T cell dysfunction during sepsis and discusses the potential immunotherapeutic agents to boost T cell function during sepsis and improve host resistance to infection.
| S-EPMC5026606 | biostudies-literature
Project description:The lack of a reliable and innocuous mark-recapture method has limited studies that would provide essential information for the management of commercial sea cucumbers. Tagging sea cucumbers is notoriously difficult because of their plastic nature and autolysis capacities. The markers that have so far been tested, mainly on or through the body wall, were either lost rapidly or had major drawbacks (e.g. suitable only for batch identification, requiring complex analysis, causing infections, necrosis, behavioural changes and mortality). The present study explored the efficacy of passive integrated transponder (PIT) tags for individually marking sea cucumbers by assessing retention rates and long-term side effects of tags inserted in previously unstudied tissues/organs. Individuals of the species Cucumaria frondosa were tagged in the body wall, aquapharyngeal bulb and at the base of the oral tentacles. They were monitored closely for evidence of stress, infection, change in feeding and spawning behaviour and tag retention rate. Implanting the tag in an oral tentacle to reach the hydrovascular system of the aquapharyngeal bulb achieved the best retention rates in full-size individuals: from a maximum of 92% after 30 days to 68% at the end of the experimental period (300 days). Efficacy was lower in smaller individuals (84% after 30 d and 42% after 300 d). Following a slight increase in cloacal movements for 15 h post tagging, no side effect was noted in sea cucumbers tagged in the aquapharyngeal bulb via the tentacles. Feeding and spawning behaviours were not affected and no signs of infections or abnormal cell development in the vicinity of the tags were observed. This study indicates that marking sea cucumbers with 8.2 mm long PIT tags implanted via the oral tentacle is an effective technique, yielding relatively high retention rates over long periods without any detectable physiological or behavioural effects.
| S-EPMC4444348 | biostudies-literature
Project description:We sought to evaluate factors associated with choices about provided care for patients with septic shock, including the use of drotrecogin ? (activated) (DAA).We administered a mail-based survey to a random sample of intensivists. Study vignettes presented patients with septic shock with identical severity of illness scores but different ages, body mass indices, and comorbidities. Respondents estimated outcomes and selected care beyond standardized initial care (eg, antibiotics) for each hypothetical patient.For most vignettes (99.1%), respondents added care, most commonly low tidal volume ventilation (87.6%) and enteral nutrition (73.3%). Choosing to administer DAA was not associated with predictions about mortality or bleeding. Vignettes with early-stage lung cancer were less likely to receive DAA. Time since medical school graduation was also associated with lower odds of selecting DAA. Most respondents (52.6%) chose identical care for all 4 completed vignettes.There was wide variability in the therapeutic choices of respondents. The use of DAA was not associated with perceived risk of mortality or bleeding, as recommended by consensus guidelines. Physicians appear to base treatment decisions in septic shock on a consistent pattern of practice rather than estimates of patient outcome.
| S-EPMC2978258 | biostudies-literature