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Timing of administration of epinephrine predicts the responsiveness to epinephrine in norepinephrine-refractory septic shock: a retrospective study.

ABSTRACT:

Background

Currently, the appropriate method of management of patients with refractory septic shock remains unclear. This study aimed to evaluate the factors associated with response to epinephrine in norepinephrine-refractory septic shock.

Methods

A retrospective single-center observational study was performed using data from adult patients (? 18?years old) admitted to our emergency and medical intensive care unit (ICU) from January 2014 to December 2017 who had received epinephrine to treat norepinephrine-refractory septic shock. The response was considered positive if there was increase in mean arterial pressure of 10?mmHg or decrease in arterial lactate level 3?h after epinephrine administration.

Results

Forty-one patients were included: 24 responders (59%) and 17 non-responders (41%). Responders showed higher rate of survival from shock (92% vs. 18%; P?P?P?=?0.011) and SOFA score (OR 0.19; 95% CI 0.04-0.88; P?=?0.034) were associated with epinephrine response. Time of epinephrine administration was also significantly associated with survival from shock (OR 0.42; P?=?0.005) and 28-day survival (OR 0.14; P?=?0.006), while SOFA score did not. Using inverse probability of treatment weighing (IPTW) adjustment of propensity score, epinephrine administration later than 24?h after ICU admission was associated with poor response (OR 0.07; 95% CI 0.02-0.21; P?ConclusionsEarly administration of epinephrine after ICU admission (i.e., within 24?h) is associated with better hemodynamic status in patients with refractory septic shock.

SUBMITTER: Kasugai D

PROVIDER: S-EPMC6451296 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe effect of the timing of norepinephrine initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to evaluate the impact of early and late start of norepinephrine support on clinical outcomes in patients with septic shock.MethodsWe searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of March 2020. We included studies involving adult patients (> 18 years) with septic shock. All authors reported our primary outcome of short-term mortality and clearly comparing early versus late norepinephrine initiation with clinically relevant secondary outcomes (ICU length of stay, time to achieved target mean arterial pressure (≥ 65 mmHg), and volume of intravenous fluids within 6 h). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI).ResultsFive studies including 929 patients were included. The primary outcome of this meta-analysis showed that the short-term mortality of the early group was lower than that of the late group (odds ratio [OR] = 0.45; 95% CI, 0.34 to 0.61; P < 0.00001; χ2 = 3.74; I2 = 0%). Secondary outcomes demonstrated that the time to achieved target MAP of the early group was shorter than that of the late group (mean difference = - 1.39; 95% CI, - 1.81 to - 0.96; P < 0.00001; χ2 = 1.03; I2 = 0%). The volume of intravenous fluids within 6 h of the early group was less than that of the late group (mean difference = - 0.50; 95% CI, - 0.68 to - 0.32; P < 0.00001; χ2 = 33.76; I2 = 94%). There was no statistically significant difference in the ICU length of stay between the two groups (mean difference = - 0.11; 95% CI, - 1.27 to 1.05; P = 0.86; χ2 = 0.85; I2 = 0%).ConclusionsEarly initiation of norepinephrine in patients with septic shock was associated with decreased short-term mortality, shorter time to achieved target MAP, and less volume of intravenous fluids within 6 h. There was no significant difference in ICU length of stay between early and late groups. Further large-scale RCTs are still required to confirm these results.

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.

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.

Project description:PurposeIt is not clear whether vasopressin versus norepinephrine changed mortality in clinical practice in the Vasopressin and Septic Shock Trial (VASST) coordinating center hospital after VASST was published. We tested the hypothesis that vasopressin changed mortality compared to norepinephrine using propensity matching of vasopressin to norepinephrine-treated patients in the VASST coordinating center hospital before (SPH1) and after (SPH2) VASST was published.MethodsVasopressin-treated patients were propensity score matched to norepinephrine-treated patients based on age, APACHE II, respiratory, renal, and hematologic dysfunction, mechanical ventilation status, medical/surgical status, infection site, and norepinephrine dose. The propensity score estimated the probability that a patient would have received vasopressin given baseline characteristics. For sensitivity analysis, we then excluded patients who had underlying severe congestive heart failure. The primary outcome was 28-day mortality.ResultsVasopressin- and norepinephrine-treated patients were similar after matching in SPH1 (pre-VASST); vasopressin-treated patients (n = 158) had a significantly higher mortality than norepinephrine-treated patients (n = 158) (60.8 vs. 46.2%, p = 0.009). In SPH2 after matching, the 28-day mortality rates were not significantly different; 31.2% and 26.9% in the vasopressin (n = 93) and norepinephrine (n = 93) groups, respectively (p = 0.518). The day 1 vasopressin dose in SPH1 vs. SPH2 was 0.036 units/min (SD 0.009) vs. 0.032 units/min (SD 0.005), p = 0.001, significantly lower in SPH2 after VASST.ConclusionsBefore VASST, vasopressin use was associated with increased mortality compared to norepinephrine in the VASST coordinating center hospital. After VASST, there was no difference in mortality between vasopressin- and norepinephrine-treated patients. This may be the first retrospective propensity-matched cohort study of a sepsis treatment in a center that had previously coordinated a large pivotal randomized controlled trial of that treatment and could be a useful approach for other sepsis therapies.Trial registrationRegistration: ISRCTN94845869.