Norepinephrine for Early Shock Control in Sepsis.
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ABSTRACT:
SUBMITTER: Tung M
PROVIDER: S-EPMC6888656 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDespite advances in diagnostic and therapeutic approaches, candidemia remains associated with high mortality rates. This study aimed at identifying predictors of mortality among patients with candidemia, with a focus on early interventions that can improve prognosis.MethodsThis was a single-center retrospective study including all adult patients with at least 1 positive blood culture for Candida species from 2014 to 2021.ResultsA total of 222 episodes of candidemia were included. Most candidemias were of unknown origin (36%) or vascular catheter related (29%). Septic shock developed in 29% episodes. Overall, 14-day mortality rate was 23%. In univariate analyses, septic shock was associated with higher 14-day mortality, whereas catheter-related candidemia and early (<72 hours) interventions, such as appropriate antifungal therapy, source control, and infectious diseases consultation, were associated with improved survival. In a Cox multivariate regression model, septic shock (odds ratio [OR], 3.62 [95% confidence interval {CI}, 2.05-6.38]) was associated with higher mortality. While the impact of early antifungal therapy did not reach statistical significance, early (<72 hours) infectious diseases consultation (OR, 0.46 [95% CI, .23-.91]) and early source control (OR, 0.15 [95% CI, .08-.31]) were associated with better survival. Subanalyses showed that the benefits of early source control, specifically catheter removal, were significant among patients with sepsis or septic shock, but not among those without sepsis. These associations remained significant after exclusion of patients who died prematurely or were in palliative care.ConclusionsEarly source control, in particular catheter removal, was a key determinant of outcome among candidemic patients with sepsis or septic shock.
| S-EPMC9361172 | biostudies-literature
Project description: Not available
| S-EPMC6888651 | biostudies-literature
Project description:IntroductionThe rate of weaning of vasopressors drugs is usually an empirical choice made by the treating in critically ill patients. We applied fuzzy logic principles to modify intravenous norepinephrine (noradrenaline) infusion rates during norepinephrine infusion in septic patients in order to reduce the duration of shock.MethodsSeptic patients were randomly assigned to norepinephrine infused either at the clinician's discretion (control group) or under closed-loop control based on fuzzy logic (fuzzy group). The infusion rate changed automatically after analysis of mean arterial pressure in the fuzzy group. The primary end-point was time to cessation of norepinephrine. The secondary end-points were 28-day survival, total amount of norepinephine infused and duration of mechanical ventilation.ResultsNineteen patients were randomly assigned to fuzzy group and 20 to control group. Weaning of norepinephrine was achieved in 18 of the 20 control patients and in all 19 fuzzy group patients. Median (interquartile range) duration of shock was significantly shorter in the fuzzy group than in the control group (28.5 [20.5 to 42] hours versus 57.5 [43.7 to 117.5] hours; P < 0.0001). There was no significant difference in duration of mechanical ventilation or survival at 28 days between the two groups. The median (interquartile range) total amount of norepinephrine infused during shock was significantly lower in the fuzzy group than in the control group (0.6 [0.2 to 1.0] microg/kg versus 1.4 [0.6 to 2.7] microg/kg; P < 0.01).ConclusionsOur study has shown a reduction in norepinephrine weaning duration in septic patients enrolled in the fuzzy group. We attribute this reduction to fuzzy control of norepinephrine infusion.Trial registrationTrial registration: Clinicaltrials.gov NCT00763906.
| S-EPMC2646320 | 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:IntroductionWe sought to compare the outcomes of patients with cryptic versus overt shock treated with an emergency department (ED) based early sepsis resuscitation protocol.MethodsPre-planned secondary analysis of a large, multicenter ED-based randomized controlled trial of early sepsis resuscitation. All subjects were treated with a quantitative resuscitation protocol in the ED targeting 3 physiological variables: central venous pressure, mean arterial pressure and either central venous oxygen saturation or lactate clearance. The study protocol was continued until all endpoints were achieved or a maximum of 6h. Outcomes data of patients who were enrolled with a lactate ? 4mmol/L and normotension (cryptic shock) were compared to those enrolled with sustained hypotension after fluid challenge (overt shock). The primary outcome was in-hospital mortality.ResultsA total of 300 subjects were enrolled, 53 in the cryptic shock group and 247 in the overt shock group. The demographics and baseline characteristics were similar between the groups. The primary endpoint of in-hospital mortality was observed in 11/53 (20%, 95% CI 11-34) in the cryptic shock group and 48/247 (19%, 95% CI 15-25) in the overt shock group, difference of 1% (95% CI -10 to 14; log rank test p=0.81).ConclusionSevere sepsis with cryptic shock carries a mortality rate not significantly different from that of overt septic shock. These data suggest the need for early aggressive screening for and treatment of patients with an elevated serum lactate in the absence of hypotension.
| S-EPMC3179778 | biostudies-literature
Project description: Not available
| S-EPMC7491400 | biostudies-literature
Project description:ImportanceHemorrhagic shock is a common cause of preventable death after injury. Vasopressor administration for patients with blunt trauma and hemorrhagic shock is often discouraged.ObjectiveTo evaluate the association of early norepinephrine administration with 24-hour mortality among patients with blunt trauma and hemorrhagic shock.Design, setting, and participantsThis retrospective, multicenter, observational cohort study used data from 3 registries in the US and France on all consecutive patients with blunt trauma from January 1, 2013, to December 31, 2018. Patients were alive on admission with hemorrhagic shock, defined by prehospital or admission systolic blood pressure less than 100 mm Hg and evidence of hemorrhage (ie, prehospital or resuscitation room transfusion of packed red blood cells, receipt of emergency treatment for hemorrhage control, transfusion of >10 units of packed red blood cells in the first 24 hours, or death from hemorrhage). Blunt trauma was defined as any exposure to nonpenetrating kinetic energy, collision, or deceleration. Statistical analysis was performed from January 15, 2021, to February 22, 2022.ExposureContinuous administration of norepinephrine in the prehospital environment or resuscitation room prior to hemorrhage control, according to European guidelines.Main outcomes and measuresThe primary outcome was 24-hour mortality, and the secondary outcome was in-hospital mortality. The average treatment effect (ATE) of early norepinephrine administration on 24-hour mortality was estimated according to the Rubin causal model. Inverse propensity score weighting and the doubly robust approach with 5 distinct analytical strategies were used to determine the ATE.ResultsA total of 52 568 patients were screened for inclusion, and 2164 patients (1508 men [70%]; mean [SD] age, 46 [19] years; median Injury Severity Score, 29 [IQR, 17-36]) presented with acute hemorrhage and were included. A total of 1497 patients (69.1%) required emergency hemorrhage control, 128 (5.9%) received a prehospital transfusion of packed red blood cells, and 543 (25.0%) received a massive transfusion. Norepinephrine was administered to 1498 patients (69.2%). The 24-hour mortality rate was 17.8% (385 of 2164), and the in-hospital mortality rate was 35.6% (770 of 2164). None of the 5 analytical strategies suggested any statistically significant association between norepinephrine administration and 24-hour mortality, with ATEs ranging from -4.6 (95% CI, -11.9 to 2.7) to 2.1 (95% CI, -2.1 to 6.3), or between norepinephrine administration and in-hospital mortality, with ATEs ranging from -1.3 (95% CI, -9.5 to 6.9) to 5.3 (95% CI, -2.1 to 12.8).Conclusions and relevanceThe findings of this study suggest that early norepinephrine infusion was not associated with 24-hour or in-hospital mortality among patients with blunt trauma and hemorrhagic shock. Randomized clinical trials that study the effect of early norepinephrine administration among patients with trauma and hypotension are warranted to further assess whether norepinephrine is safe for patients with hemorrhagic shock.
| S-EPMC9547317 | biostudies-literature
Project description:BACKGROUND:Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock. METHODS:A total of 337 patients with sepsis requiring VP support for at least 6 h were initially selected from a prospectively collected database in a 90-bed mixed-ICU during a 24-month period. They were classified into very-early (VE-VPs) or delayed vasopressor start (D-VPs) categories according to whether norepinephrine was initiated or not within/before the next hour of the first resuscitative fluid load. Then, VE-VPs (n = 93) patients were 1:1 propensity matched to D-VPs (n = 93) based on age; source of admission (emergency room, general wards, intensive care unit); chronic and acute comorbidities; and lactate, heart rate, systolic, and diastolic pressure at vasopressor start. A risk-adjusted Cox proportional hazard model was fitted to assess the association between VE-VPs and day 28 mortality. Finally, a sensitivity analysis was performed also including those patients requiring VP support for less than 6 h. RESULTS:Patients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (0[0-510] vs. 1500[650-2300] mL, p < 0.001) and during the first 8 h of resuscitation (1100[500-1900] vs. 2600[1600-3800] mL, p < 0.001), with no significant increase in acute renal failure and/or renal replacement therapy requirements. VE-VPs was related with significant lower net fluid balances 8 and 24 h after VPs. VE-VPs was also associated with a significant reduction in the risk of death compared to D-VPs (HR 0.31, CI95% 0.17-0.57, p < 0.001) at day 28. Such association was maintained after including patients receiving vasopressors for < 6 h. CONCLUSION:A very early start of vasopressor support seems to be safe, might limit the amount of fluids to resuscitate septic shock, and could lead to better clinical outcomes.
| S-EPMC7023737 | biostudies-literature
Project description:For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15-25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30-50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental.
| S-EPMC5538252 | biostudies-other
Project description:Early prognostic prediction of sepsis is essential in adjusting therapeutic protocols to prevent deterioration and reduce mortality. We compared the predictive value of the serum concentration of the soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) for 28-day mortality and for the development of severe sepsis or septic shock on the third day with the levels of interleukin (IL)-6, C-reactive protein (CRP) and procalcitonin (PCT). The study was conducted on 85 patients with sepsis. sTREM-1, CRP, PCT and IL-6 concentrations were measured upon study inclusion (day 0) and on days 1, 2, 3 and 5. APACHE II, SAPS II and SOFA scores were analyzed. The sTREM-1 levels (pg/ml) were higher in non-survivors than in survivors at admission (773 vs. 391, p < 0.001) and on days 1, 2, 3 and 5. In predicting the development of severe sepsis, the highest AUCs were found for PCT (0.744, 95% CI 0.638-0.85) and sTREM-1 (0.664, 95% CI 0.55-0.778); and in septic shock prediction, for PCT (0.766, 95% CI 0.665-0.867) and IL-6 (0.707, 95% CI 0.595-0.819). sTREM-1 positively correlated with APACHE II, SAPS II and SOFA scores. At inclusion, significant AUC for predicting 28-day mortality was 0.772 for the sTREM-1 (95% CI 0.672-0.871), 0.858 for APACHE II (95% CI 0.768-0.948), 0.847 for SAPS II (95% CI 0.733-0.96), 0.806 for SOFA score (95% CI 0.698-0.915). sTREM-1 can early predict the 28-day sepsis mortality, although its effectiveness is lower in comparison with clinical severity scores.
| S-EPMC6061141 | biostudies-literature