Dataset Information

Vasopressin versus norepinephrine in septic shock: a propensity score matched efficiency retrospective cohort study in the VASST coordinating center hospital.

ABSTRACT:

Purpose

It 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.

Methods

Vasopressin-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.

Results

Vasopressin- 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.

Conclusions

Before 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 registration

Registration: ISRCTN94845869.

SUBMITTER: Russell JA

PROVIDER: S-EPMC6240281 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Vasopressin versus norepinephrine in septic shock: a propensity score matched efficiency retrospective cohort study in the VASST coordinating center hospital.

Russell James A JA Wellman Hugh H Walley Keith R KR

Journal of intensive care 20181116

<h4>Purpose</h4>It 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.<h4>Methods</h4>Vasopress ...[more]

PMID: 30473792

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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.

Project description:BackgroundThe primary aim of this study was to compare survival from neoadjuvant chemoradiotherapy plus surgery (NCRS) versus neoadjuvant chemotherapy plus surgery (NCS) for the treatment of esophageal or junctional adenocarcinoma. The secondary aims were to compare pathological effects, short-term mortality and morbidity, and to evaluate the effect of lymph node harvest upon survival in both treatment groups.MethodsData were collected from 10 European centers from 2001 to 2012. Six hundred and eight patients with stage II or III oesophageal or oesophago-gastric junctional adenocarcinoma were included; 301 in the NCRS group and 307 in the NCS group. Propensity score matching and Cox regression analyses were used to compensate for differences in baseline characteristics.ResultsNCRS resulted in significant pathological benefits with more ypT0 (26.7% versus 5%; P < 0.001), more ypN0 (63.3% versus 32.1%; P < 0.001), and reduced R1/2 resection margins (7.7% versus 21.8%; P < 0.001). Analysis of short-term outcomes showed no statistically significant differences in 30-day or 90-day mortality, but increased incidence of anastomotic leak (23.1% versus 6.8%; P < 0.001) in NCRS patients. There were no statistically significant differences between the groups in 3-year overall survival (57.9% versus 53.4%; Hazard Ratio (HR)= 0.89, 95%C.I. 0.67-1.17, P = 0.391) nor disease-free survival (52.9% versus 48.9%; HR = 0.90, 95%C.I. 0.69-1.18, P = 0.443). The pattern of recurrence was also similar (P = 0.660). There was a higher lymph node harvest in the NCS group (27 versus 14; P < 0.001), which was significantly associated with a lower recurrence rate and improved disease free survival within the NCS group.ConclusionThe survival differences between NCRS and NCS maybe modest, if present at all, for the treatment of locally advanced esophageal or junctional adenocarcinoma. Future large-scale randomized trials must control and monitor indicators of the quality of surgery, as the extent of lymphadenectomy appears to influence prognosis in patients treated with NCS, from this large multi-center European study.

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:IntroductionPositive hemodynamic response to vasopressin after 6 hours of infusion was independently associated with lower mortality in a previous retrospective study of patients with septic shock. However, factors previously associated with higher plasma vasopressin concentration were not associated with response, and the relationship between plasma vasopressin concentration and hemodynamic response has not been evaluated.ObjectivesThis cross-sectional study compared plasma vasopressin concentrations in hemodynamic responders and nonresponders to vasopressin in patients with septic shock to evaluate plasma vasopressin concentration as a therapeutic target for hemodynamic response to vasopressin.MethodsAdult patients with septic shock were included if they were treated with fixed-dose vasopressin as an adjunct to catecholamines for at least 3 hours. Patients were assigned to groups based on vasopressin response.ResultsTen hemodynamic responders to vasopressin and eight nonresponders were included. Blood samples for plasma vasopressin concentration were collected 3-6 hours after vasopressin initiation. Baseline characteristics were similar between groups. No difference was detected in plasma vasopressin concentrations between hemodynamic responders and nonresponders (median 88.6 pg/ml [interquartile range (IQR) 84.4-107.5 pg/ml] vs 89.9 pg/ml [IQR 67.5-157.4 pg/ml], p=0.79, respectively). We also did not detect a difference between groups after correcting for vasopressin dose; median vasopressin plasma concentration per 0.01 units/minute of vasopressin infusion for responders was 25.9 pg/ml (IQR 21.8-31.8 pg/ml) versus 29.5 pg/ml (IQR 23.0-57.5 pg/ml, p=0.48) for nonresponders. No difference in clinical outcomes was detected between groups. The findings were robust to multiple sensitivity analyses.ConclusionsThis study does not support the use of plasma vasopressin concentrations as a therapeutic target to predict hemodynamic response to exogenous vasopressin in septic shock.

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:This review of vasopressin in septic shock differs from previous reviews by providing more information on the physiology and pathophysiology of vasopressin and vasopressin receptors, particularly because of recent interest in more specific AVPR1a agonists and new information from the Vasopressin and Septic Shock Trial (VASST), a randomized trial of vasopressin versus norepinephrine in septic shock. Relevant literature regarding vasopressin and other AVPR1a agonists was reviewed and synthesized. Vasopressin, a key stress hormone in response to hypotension, stimulates a family of receptors: AVPR1a, AVPR1b, AVPR2, oxytocin receptors and purinergic receptors. Rationales for use of vasopressin in septic shock are as follows: first, a deficiency of vasopressin in septic shock; second, low-dose vasopressin infusion improves blood pressure, decreases requirements for norepinephrine and improves renal function; and third, a recent randomized, controlled, concealed trial of vasopressin versus norepinephrine (VASST) suggests low-dose vasopressin may decrease mortality of less severe septic shock. Previous clinical studies of vasopressin in septic shock were small or not controlled. There was no difference in 28-day mortality between vasopressin-treated versus norepinephrine-treated patients (35% versus 39%, respectively) in VASST. There was potential benefit in the prospectively defined stratum of patients with less severe septic shock (5 to 14 ?g/minute norepinephrine at randomization): vasopressin may have lowered mortality compared with norepinephrine (26% versus 36%, respectively, P = 0.04 within stratum). The result was robust: vasopressin also decreased mortality (compared with norepinephrine) if less severe septic shock was defined by the lowest quartile of arterial lactate or by use of one (versus more than one) vasopressor at baseline. Other investigators found greater hemodynamic effects of higher dose of vasopressin (0.06 units/minute) but also unique adverse effects (elevated liver enzymes and serum bilirubin). Use of higher dose vasopressin requires further evaluation of efficacy and safety. There are very few studies of interactions of therapies in critical care--or septic shock--and effects on mortality. Therefore, the interaction of vasopressin infusion, corticosteroid treatment and mortality of septic shock was evaluated in VASST. Low-dose vasopressin infusion plus corticosteroids significantly decreased 28-day mortality compared with corticosteroids plus norepinephrine (44% versus 35%, respectively, P = 0.03; P = 0.008 interaction statistic). Prospective randomized controlled trials would be necessary to confirm this interesting interaction. In conclusion, low-dose vasopressin may be effective in patients who have less severe septic shock already receiving norepinephrine (such as patients with modest norepinephrine infusion (5 to 15 ?g/minute) or low serum lactate levels). The interaction of vasopressin infusion and corticosteroid treatment in septic shock requires further study.

Dataset Information

Vasopressin versus norepinephrine in septic shock: a propensity score matched efficiency retrospective cohort study in the VASST coordinating center hospital.

Purpose

Methods

Results

Conclusions

Trial registration

Publications

Vasopressin versus norepinephrine in septic shock: a propensity score matched efficiency retrospective cohort study in the VASST coordinating center hospital.

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