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 | 2019 Nov
REPOSITORIES: biostudies-literature
Publications
Early Use of Norepinephrine for Sepsis: Promising Results That Require Confirmation.
El Bèze Nathan N Kimmoun Antoine A Asfar Pierre P
American journal of respiratory and critical care medicine 20191101 9
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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:One of the most important components of sepsis management is hemodynamic restoration. If the target mean arterial pressure (MAP) is not obtained, the first recommendation is for volume expansion, and the second is for norepinephrine (NE). We describe the methodology of a randomized multicenter trial aiming to assess the hypothesis that low-dose NE given early in adult patients with sepsis will provide better control of shock within 6 hours from therapy starting compared to standard care. This trial includes ICU septic patients in whom MAP decrease below 65 mmHg to be randomized into 2 groups: early NE-group versus standard care-group. The patient's attending clinician will determine how much volume expansion is necessary to meet the target of a MAP > 65 mm Hg. If this target not achieved, after at least 30 ml/kg and guided by the available indices of fluid responsiveness, NE will be used in a usual way. The latter must follow a consensual schedule elaborated by the investigating centers. Parameters to be taken at inclusion and at H6 are: lactates, cardiac ultrasound parameters (stroke volume (SV), cardiac output (CO), E/E' ratio), and P/F ratio. MAP and diuresis are recorded hourly. Our primary outcome is the shock control defined as a composite criterion (MAP > 65 mm Hg for 2 consecutive measurements and urinary output > 0.5 ml/kg/h for 2 consecutive hours) within 6 hours. Secondary outcomes: Decrease in serum lactate> 10% from baseline within 6 hours, the received fluid volume within 6 hours, variation of CO and E/E', and 28 days-Mortality. The study is ongoing and aims to include at least 100 patients per arm. This study is likely to contribute to support the indication of early initiation of NE with the aim to restrict fluid intake in septic patients. (ClinicalTrials.gov ID: NCT05836272).
| S-EPMC11257256 | biostudies-literature
Project description:BackgroundAntibiotic use for early-onset sepsis represents a high percentage of antibiotic consumption in the neonatal setting. Measures to assess infants at risk of early-onset sepsis are needed to optimize antibiotic use. Our primary objective was to assess the impact of a departmental guideline on antibiotic use among term infants with suspected EOS not confirmed, in our neonatal unit.MethodsRetrospective cohort study, to compare antibiotic use in term infants during a baseline period of January to December 2018, and a postintervention period from October 2019, to September 2020, respectively. The primary outcome was antibiotic use measured by days of therapy, the antibiotic spectrum index, the antibiotic use rate, and the length of therapy.ResultsWe included 71 infants in the baseline period and 66 infants in the postintervention period. Compared to those in the baseline period, there was a significant reduction in overall antibiotic measures in the postintervention period, (P < 0.001). The total days of therapy/1000 patient-days decreased from 63/1000 patient-days during the baseline period to 25.8/1000 patient-days in the postintervention period, representing a relative reduction of 59%. The antibiotic use rate decreased by more than half of the infants, from 3.2% during the baseline period to 1.3% in the postintervention period.ConclusionsThe use of a departmental guideline to assess infants at risk of early-onset sepsis based on their clinical condition and prompt discontinuation of antibiotics, is a simple and low-cost measure that contributed to an important decrease in antibiotic use.
| S-EPMC10996240 | 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:Sepsis is a dysregulated systemic response to infection and can lead to organ damage and death. Obesity is a significant problem worldwide and affects outcomes from sepsis. Our laboratory demonstrated that white adipose tissue (WAT) undergoes browning during sepsis, a process whereby WAT adopts a brown adipose tissue phenotype. However, this browning process was not observed in obese mice during sepsis. White adipose tissue browning is detrimental in patients with burn injury and cancer. We hypothesize that norepinephrine (NE) induces WAT browning in nonobese mice but not in obese mice similarly to sepsis-induced WAT browning. Six-week-old C57BL/6 male mice were randomized to a high-fat diet or normal diet. After 6-7 wk of feeding, polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Norepinephrine was administered intraperitoneally via osmotic minipumps for 18 h or 72 h (no CLP) at which time tissue and plasma were harvested. Controls were mice that underwent CLP (no NE) with 18-h harvest. A separate group of mice underwent pretreatment with NE or vehicle infusion for 72 h, CLP was performed, and at 18 h had tissue and plasma harvested. Sepsis resulted in significant weight loss in both nonobese and obese mice. NE treatment alone caused weight loss in obese mice. Septic nonobese mice had higher uncoupling protein-1 (UCP1) expression compared with control and obese septic mice. NE treatment increased UCP1 expression in nonobese, but not obese mice. NE-treated obese septic mice had lower lung myeloperoxidase (MPO) activity, alanine aminotransferase (ALT), aspartate aminotransferase (AST), TNFα, and IL-6 levels compared with NE-treated nonobese septic mice. Obesity protects mice from septic-induced and NE-induced WAT browning.NEW & NOTEWORTHY White adipose tissue browning is detrimental in patients with burn injury and cancer. WAT browning occurs in nonobese mice and can be induced by β receptor norepinephrine infusion, but obese mice are resistant to sepsis-induced and norepinephrine-induced WAT browning. We propose that the lack of WAT browning and unchanged inflammatory cytokine response may contribute to the protection of obese mice from sepsis.
| S-EPMC8461795 | 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: Broad-spectrum antimicrobial therapy is a key driver of antimicrobial resistance. Here, we aimed to review indications for antimicrobial therapy, determine the proportion of suspected bacterial infections that are confirmed by culture, and assess the time taken for microbiology test results to become available in the paediatric intensive care unit (PICU). Methods: A single-centre prospective observational cohort study of 100 consecutive general PICU admissions from 30 October 2019 to 19 February 2020. Data were collected from the hospital medical record and entered into a study database prior to statistical analysis using standard methods. Results: Of all episodes of suspected infection, 22% of lower respiratory tract infection, 43% of bloodstream and 0% of central nervous system infection were associated with growth on microbiology culture. 90% of children received antimicrobial therapy. Hospital-acquired infection occurred less commonly than primary infection, but an organism was grown in a greater proportion (64%) of cultures. Final laboratory reports for negative cultures were issued at a median of 120.3 hours for blood cultures and 55.5 hours for endotracheal tube aspirate cultures. Conclusions: Despite most critically children receiving antimicrobial therapy, infection was often not microbiologically confirmed. Novel molecular diagnostics may improve rationalisation of treatment in this population.
| S-EPMC8902261 | 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: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