Norepinephrine in Septic Shock: A Mixed Blessing.
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ABSTRACT:
SUBMITTER: Uhel F
PROVIDER: S-EPMC7491400 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionMost experts recommend norepinephrine as the first-line agent in septic shock. Our objective was to determine the effectiveness and safety of norepinephrine in patients with septic shock.MethodsWe searched the Cochrane Central Register of Controlled Trials and Epistemonikos, as well as MEDLINE from 1966 till August 2019. Screening of full texts, evaluation for eligibility, and data extraction were done by four independent reviewers. We estimated risk ratios (RR) and mean differences (MD) using a random-effects model with 95% confidence intervals (CI). The primary outcomes included the number of participants who achieved the target mean arterial pressure (MAP), time to achieve the target MAP, and number of participants with all-cause 28-day mortality. The secondary outcomes included the length of stay in the intensive care unit, length of hospital stay, incidence of arrhythmia and myocardial infarction, vasopressor-free days, and number of participants with all-cause 90-day mortality.ResultsWe identified 11 randomized controlled trials with a total of 4,803 participants. There was no difference in the number of participants who achieved the target MAP between those patients receiving norepinephrine and other vasopressors (RR 1.44; 95% CI, 0.32 to 6.54; P = 0.640; I2 = 94%; two trials, 116 participants). There was no significant difference in time to achieve the target MAP (MD -0.05; 95%, CI, -0.32 to 0.21; P = 0.690; I2 = 26%; two trials, 1763 participants) and all-cause 28-day mortality (RR 0.95; 95% CI, 0.89 to 1.02; P = 0.160; I2 = 0%; seven trials, 4,139 participants). Regarding the secondary outcome, norepinephrine may significantly reduce the incidence of arrhythmia as compared to other vasopressors (RR 0.64; 95% CI, 0.42 to 0.97; P = 0.030; I2 = 64%; six trials, 3974 participants). There was no difference in the incidence of myocardial infarction (RR 1.28; 95% CI, 0.79 to 2.09), vasopressor-free day (RR 0.46; 95% CI, -1.82 to 2.74) and all-cause 90-day mortality (RR 1.08; 95% CI, 0.96 to 1.21) between norepinephrine and vasopressors.ConclusionIn minimizing the occurrence of an arrhythmia, norepinephrine is superior to other vasopressors, making it safe to be used in septic shock. However, there was insufficient evidence concerning mortality and achievement of the target MAP outcomes.
| S-EPMC7972398 | biostudies-literature
Project description:Background:Use of high-dose norepinephrine is thought to have an immunosuppressive action that increases mortality. This study aimed to evaluate the correlation between norepinephrine dosage and prognosis of patients with septic shock. Methods:This study was a nested cohort of the DExmedetomidine for Sepsis in Intensive Care Unit Randomized Evaluation (DESIRE) trial. We evaluated 112 patients with septic shock and an initial Sequential Organ Failure Assessment Cardiovascular (SOFA-C) category score >?2 and initial lactate level >?2 mmol/L. We divided the patients into two groups according to the norepinephrine dosage administered over the initial 7 days: high dose (??416 ?g/kg/week) (H group, n?=?56) and low dose (<?416 ?g/kg/week) (L group, n?=?56). The primary outcome of interest was 28-day mortality. Secondary outcomes were ventilator-free days, initial 24-h infusion volume, initial 24- to 48-h infusion volume, and the need for renal replacement therapy. For comparisons between the H group and L group, we used the chi-square test or Fisher's exact test for categorical variables and the t test or Wilcoxon rank sum test for continuous variables. For time-to-event outcomes, Cox proportional hazards models were used. Kaplan-Meier survival curves were created for graphical representation. Results:Patient characteristics appeared to be similar between the two groups except for the SOFA-C score and fibrinogen degradation product level. The cumulative incidence of death at 28 days was 29.9% (16 patients) in the L group and 29.7% (15 patients) in the H group (p?=?0.99). The median number of 28-day ventilator-free days was 20 (0, 25) in the L group and 16 (0, 22) in the H group (p?<?0.05). Initial infusion volume at 0-24 h in the H group was significantly higher than that in the L group (p?=?0.004). Infusion volume at 24-48 h in the H group was also significantly higher than that in the L group (p?=?0.03). Conclusions:No statistically significant difference was observed in 28-day mortality between patients with septic shock treated with high-dose norepinephrine compared with those treated with low-dose norepinephrine. However, the number of ventilator-free days in the L group was higher than that in the H group. Trial registration:clinicaltrials.gov Identifier: NCT01760967 Date of trial registration: January 4, 2013.
| S-EPMC5828304 | biostudies-literature
Project description:Purpose: The meta-analysis aims to evaluate the efficacy and safety of terlipressin compared with norepinephrine for septic shock. Materials and Methods: The relevant studies from MEDLINE, Cochrane Library, Embase were searched by two independent investigators. A variety of keywords were used to search the studies. Stata software (version 11.0, Stata Corp LP, College Station, TX, USA) was used for statistical analysis. Results: A total of six studies were identified and incorporated into the meta-analysis. The results showed that there was no difference for 28-day mortality (RR = 0.99, 95% CI = [0.85,1.15], P = 0.849), AE (RR = 2.54, 95% CI = [0.58,11.08], P = 0.214), and MAP (SMD = -0.10, 95% CI = [-0.35,0.14], P = 0.405), OI, urinary output, Scr, total bilirubin, ALT, and AST between TP group and NE group. While TP could decrease HR at 24 and 48 h compared with NE. Conclusions: Current results suggest that terlipressin showed no added survival benefit for septic shock when compared with norepinephrine, while terlipressin could decrease heart rate in the late phase of septic shock compared with norepinephrine without further liver and kidney injury. Systematic Review Registration: PROSPERO (ID: CRD42019128743). Available online at: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42019128743.
| S-EPMC6936170 | biostudies-literature
Project description:IntroductionThe present study was designed to determine the effects of continuously infused norepinephrine (NE) plus (1) terlipressin (TP) or (2) arginine vasopressin (AVP) or (3) placebo on sublingual microcirculation in septic shock patients. The primary study end point was a difference of ≥ 20% in the microvascular flow index of small vessels among groups.MethodsThe design of the study was a prospective, randomized, double-blind clinical trial. NE was titrated to maintain mean arterial pressure (MAP) between 65 and 75 mmHg after establishment of normovolemia in 60 septic shock patients. Thereafter patients (n = 20 per group) were randomized to receive continuous infusions of either TP (1 μg/kg/hour), AVP (0.04 U/minute) or placebo (isotonic saline). In all groups, open-label NE was adjusted to maintain MAP within threshold values if needed. The sublingual microcirculatory blood flow of small vessels was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 6 hours after randomization.ResultsTP and AVP decreased NE requirements at the end of the 6-hour study period. The data are medians (25th and 75th interquartile ranges (IQRs)): 0.57 μg/kg/minute (0.29 to 1.04) vs. 0.16 μg/kg/minute (0.03 to 0.37) for TP and 0.40 μg/kg/minute (0.20 to 1.05) vs. 0.23 μg/kg/minute (0.03 to 0.77) for AVP, with statistical significance of P < 0.05 vs. baseline and vs. placebo. There were no differences in sublingual microcirculatory variables, systemic hemodynamics, oxygen transport and acid-base homeostasis among the three study groups during the entire observation period. The proportions of perfused vessels increased in relation to baseline within all study groups, and there were no significant differences between groups. The specific data were as follows (median (IQR)): 9.7% (2.6 to 19.8) for TP, 8.9% (0.0 to 17.8) for AVP, and 6.9% (3.5 to 10.1) for placebo (P < 0.05 vs. baseline for each comparison), as well as perfused vessel density 18.6% (8.6 to 36.9) for TP, 20.2% (-3.0 to 37.2) for AVP, and 11.4% (-3.0 to 19.4) for placebo (P < 0.05 vs. baseline for each comparison).ConclusionsThe present study suggests that to achieve a MAP of 65 to 75 mmHg in septic patients treated with NE, the addition of continuously infused low-dose TP or AVP does not affect sublingual microcirculatory blood flow. In addition, our results suggest that microcirculatory flow abnormalities are mainly related to other factors (for example, volume status, timing, hemodynamics and progression of the disease) rather than to the vasopressor per se.Trial registrationClinicalTrial.gov NCT00995839.
| S-EPMC3334762 | biostudies-literature
Project description:BackgroundThrough venous contraction, norepinephrine (NE) increases stressed blood volume and mean systemic pressure (Pms) and exerts a "fluid-like" effect. When both fluid and NE are administered, Pms may not only result from the sum of the effects of both drugs. Indeed, norepinephrine may enhance the effects of volume expansion: because fluid dilutes into a more constricted, smaller, venous network, fluid may increase Pms to a larger extent at a higher than at a lower dose of NE. We tested this hypothesis, by mimicking the effects of fluid by passive leg raising (PLR).MethodsIn 30 septic shock patients, norepinephrine was decreased to reach a predefined target of mean arterial pressure (65-70 mmHg by default, 80-85 mmHg in previously hypertensive patients). We measured the PLR-induced increase in Pms (heart-lung interactions method) under high and low doses of norepinephrine. Preload responsiveness was defined by a PLR-induced increase in cardiac index ≥ 10%.ResultsNorepinephrine was decreased from 0.32 [0.18-0.62] to 0.26 [0.13-0.50] µg/kg/min (p < 0.0001). This significantly decreased the mean arterial pressure by 10 [7-20]% and Pms by 9 [4-19]%. The increase in Pms (∆Pms) induced by PLR was 13 [9-19]% at the higher dose of norepinephrine and 11 [6-16]% at the lower dose (p < 0.0001). Pms reached during PLR at the high dose of NE was higher than expected by the sum of Pms at baseline at low dose, ∆Pms induced by changing the norepinephrine dose and ∆Pms induced by PLR at low dose of NE (35.6 [11.2] mmHg vs. 33.6 [10.9] mmHg, respectively, p < 0.01). The number of preload responders was 8 (27%) at the high dose of NE and 15 (50%) at the low dose.ConclusionsNorepinephrine enhances the Pms increase induced by PLR. These results suggest that a bolus of fluid of the same volume has a greater haemodynamic effect at a high dose than at a low dose of norepinephrine during septic shock.
| S-EPMC8379760 | biostudies-literature
Project description:BackgroundNorepinephrine (NE) is a cornerstone drug in the management of septic shock, with its dose being used clinically as a marker of disease severity and as mortality predictor. However, variations in NE dose reporting either as salt formulations or base molecule may lead to misinterpretation of mortality risks and hinder the process of care.MethodsWe conducted a retrospective analysis of the MIMIC-IV database to assess the impact of NE dose reporting heterogeneity on mortality prediction in a cohort of septic shock patients. NE doses were converted from the base molecule to equivalent salt doses, and their ability to predict 28-day mortality at common severity dose cut-offs was compared.Results4086 eligible patients with septic shock were identified, with a median age of 68 [57-78] years, an admission SOFA score of 7 [6-10], and lactate at diagnosis of 3.2 [2.4-5.1] mmol/L. Median peak NE dose at day 1 was 0.24 [0.12-0.42] μg/kg/min, with a 28-day mortality of 39.3%. The NE dose showed significant heterogeneity in mortality prediction depending on which formulation was reported, with doses reported as bitartrate and tartrate presenting 65 (95% CI 79-43)% and 67 (95% CI 80-47)% lower ORs than base molecule, respectively. This divergence in prediction widened at increasing NE doses. When using a 1 μg/kg/min threshold, predicted mortality was 54 (95% CI 52-56)% and 83 (95% CI 80-87)% for tartrate formulation and base molecule, respectively.ConclusionsHeterogeneous reporting of NE doses significantly affects mortality prediction in septic shock. Standardizing NE dose reporting as base molecule could enhance risk stratification and improve processes of care. These findings underscore the importance of consistent NE dose reporting practices in critical care settings.
| S-EPMC11220947 | 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:This study was designed to evaluate the hemodynamic effect of norepinephrine (NE) on the peak systolic velocity (PSV), diameter, and blood flow of the common carotid artery (CCA) using the point-of-care ultrasound (POCUS) in patients with septic shock. The study involved patients above 18 years old with septic shock. Arterial monitoring, carotid ultrasonography, and transthoracic echocardiography were performed before NE administration (T0). When the mean arterial pressure exceeded 65 mmHg after NE administration (T1), the measurement was repeated. Twenty-four patients (median age 67 [interquartile range: 54-77] years; 42% female) with septic shock were examined in this study. Before (T0) and after (T1) NE administration, the PSV (mean, standard deviation [SD]) changed from 85.3 (21.1) cm/s to 83.5 (23.5) cm/s (p = 0.417); this change was not significant. However, the diameter and blood flow of the CCA increased significantly from 0.6 (0.09) cm and 0.75 (0.27) L/min to 0.66 (0.09) cm and 0.85 (0.27) L/min, respectively (p < 0.001). The diameter of the left ventricular outflow tract (LVOT) remained unchanged, but the velocity time integral of the LVOT increased significantly from 21.7 (4.39) cm to 23.6 (5.14) cm. There was no significant correlation between changes in blood flow of the CCA and changes in cardiac output (coefficient -0.365, p = 0.079). In conclusion, NE increased the diameter and blood flow of the CCA significantly, without changing the PSV in patients with septic shock.
| S-EPMC8373863 | biostudies-literature
Project description:Background: Some septic shock patients have persistent hyperlactacidemia despite a normal systemic hemodynamics after resuscitation. Central venous oxygen saturation (ScvO2), mean arterial pressure (MAP), and central venous pressure (CVP) cannot be target in subsequent hemodynamic treatments. Vasoplegia is considered to be one of the main causes of oxygen metabolism abnormalities in septic shock patients, and norepinephrine (NE) is the first-line vasopressor in septic shock treatment; its dosage represents the severity of vasoplegia. This study was performed to determine whether vasoplegia, as assessed by NE dosage, can indicate patients' lactate clearance after the completion of resuscitation. Methods: A retrospective study was performed, and 106 patients with septic shock in an intensive care unit were analyzed. Laboratory values and hemodynamic variables were obtained upon completion of resuscitation (H 0) and 6 h after (H 6). Lactate clearance was defined as the percent decrease in lactate from H 0 to H 6. Student's t-test, Mann-Whitney U-test, Chi-square or Fisher's exact tests, logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were performed for statistical analysis. Results: Patients with a mean age of 63.7 ± 13.8 years, baseline APACHE II score of 21.0 ± 5.1, and SOFA score of 12.7 ± 2.7 were enrolled. The study found that after 6-h of resuscitation, lactate clearance (LC) was <10% in 33 patients (31.1%). Patients with 6-h LC <10% compared with 6-h LC ≥ 10% had a higher NE dose (μg·kg-1·min-1) (0.55 [0.36-0.84] vs. 0.25 [0.18-0.41], p < 0.001). Multivariate logistic regression analysis of statistically significant univariate variables showed that NE dose had a significant inverse relationship with 6-h LC < 10%. The cutoff for NE was ≥ 0.32 μg·kg-1·min-1 for predicting 6-h lactate clearance after resuscitation, with a sensitivity of 75.76% and a specificity of 70.00%. Septic shock patients with an NE dose ≥ 0.32 μg·kg-1·min-1, relative to patients with an NE dose < 0.32 μg·kg-1·min-1, had a greater 30-day mortality rate (69.8% vs. 26.4% p < 0.001). Conclusion: Some patients with septic shock had persistent oxygen metabolism disorders after hemodynamic resuscitation. NE dose may indicate vasoplegia and oxygen metabolism disorder. After resuscitation, septic shock patients with high-dose NE have lower lactate clearance and a greater 30-day mortality rate than those with low-dose NE.
| S-EPMC8688855 | biostudies-literature
Project description: Not available
| S-EPMC5415714 | biostudies-literature