Dataset Information

Timing of vasopressor initiation and mortality in septic shock: a cohort study.

ABSTRACT:

Introduction

Despite recent advances in the management of septic shock, mortality remains unacceptably high. Earlier initiation of key therapies including appropriate antimicrobials and fluid resuscitation appears to reduce the mortality in this condition. This study examined whether early initiation of vasopressor therapy is associated with improved survival in fluid therapy-refractory septic shock.

Methods

Utilizing a well-established database, relevant information including duration of time to vasopressor administration following the initial documentation of recurrent/persistent hypotension associated with septic shock was assessed in 8,670 adult patients from 28 ICUs in Canada, the United States of America, and Saudi Arabia. The primary endpoint was survival to hospital discharge. Secondary endpoints were length of ICU and hospital stay as well as duration of ventilator support and vasopressor dependence. Analysis involved multivariate linear and logistic regression analysis.

Results

In total, 8,640 patients met the definition of septic shock with time of vasopressor/inotropic initiation documented. Of these, 6,514 were suitable for analysis. The overall unadjusted hospital mortality rate was 53%. Independent mortality correlates included liver failure (odds ratio (OR) 3.46, 95% confidence interval (CI), 2.67 to 4.48), metastatic cancer (OR 1.63, CI, 1.32 to 2.01), AIDS (OR 1.91, CI, 1.29 to 2.49), hematologic malignancy (OR 1.88, CI, 1.46 to 2.41), neutropenia (OR 1.78, CI, 1.27 to 2.49) and chronic hypertension (OR 0.62 CI, 0.52 to 0.73). Delay of initiation of appropriate antimicrobial therapy (OR 1.07/hr, CI, 1.06 to 1.08), age (OR 1.03/yr, CI, 1.02 to 1.03), and Acute Physiology and Chronic Health Evaluation (APACHE) II Score (OR 1.11/point, CI, 1.10 to 1.12) were also found to be significant independent correlates of mortality. After adjustment, only a weak correlation between vasopressor delay and hospital mortality was found (adjusted OR 1.02/hr, 95% CI 1.01 to 1.03, P <0.001). This weak effect was entirely driven by the group of patients with the longest delays (>14.1 hours). There was no significant relationship of vasopressor initiation delay to duration of vasopressor therapy (P?=?0.313) and only a trend to longer duration of ventilator support (P?=?0.055) among survivors.

Conclusion

Marked delays in initiation of vasopressor/inotropic therapy are associated with a small increase in mortality risk in patients with septic shock.

SUBMITTER: Beck V

PROVIDER: S-EPMC4075345 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Timing of vasopressor initiation and mortality in septic shock: a cohort study.

Beck Vance V Chateau Dan D Bryson Gregory L GL Pisipati Amarnath A Zanotti Sergio S Parrillo Joseph E JE Kumar Anand A

Critical care (London, England) 20140512 3

<h4>Introduction</h4>Despite recent advances in the management of septic shock, mortality remains unacceptably high. Earlier initiation of key therapies including appropriate antimicrobials and fluid resuscitation appears to reduce the mortality in this condition. This study examined whether early initiation of vasopressor therapy is associated with improved survival in fluid therapy-refractory septic shock.<h4>Methods</h4>Utilizing a well-established database, relevant information including dur ...[more]

PMID: 24887489

Similar Datasets

Project description:BACKGROUND:The 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. METHODS:We 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). RESULTS:Five 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; ?2 = 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; ?2?=?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; ?2?=?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; ?2?=?0.85; I2 =?0%). CONCLUSIONS:Early 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:IntroductionIt is unclear to which level mean arterial blood pressure (MAP) should be increased during septic shock in order to improve outcome. In this study we investigated the association between MAP values of 70 mmHg or higher, vasopressor load, 28-day mortality and disease-related events in septic shock.MethodsThis is a post hoc analysis of data of the control group of a multicenter trial and includes 290 septic shock patients in whom a mean MAP > or = 70 mmHg could be maintained during shock. Demographic and clinical data, MAP, vasopressor requirements during the shock period, disease-related events and 28-day mortality were documented. Logistic regression models adjusted for the geographic region of the study center, age, presence of chronic arterial hypertension, simplified acute physiology score (SAPS) II and the mean vasopressor load during the shock period was calculated to investigate the association between MAP or MAP quartiles > or = 70 mmHg and mortality or the frequency and occurrence of disease-related events.ResultsThere was no association between MAP or MAP quartiles and mortality or the occurrence of disease-related events. These associations were not influenced by age or pre-existent arterial hypertension (all P > 0.05). The mean vasopressor load was associated with mortality (relative risk (RR), 1.83; confidence interval (CI) 95%, 1.4-2.38; P < 0.001), the number of disease-related events (P < 0.001) and the occurrence of acute circulatory failure (RR, 1.64; CI 95%, 1.28-2.11; P < 0.001), metabolic acidosis (RR, 1.79; CI 95%, 1.38-2.32; P < 0.001), renal failure (RR, 1.49; CI 95%, 1.17-1.89; P = 0.001) and thrombocytopenia (RR, 1.33; CI 95%, 1.06-1.68; P = 0.01).ConclusionsMAP levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock. Elevating MAP >70 mmHg by augmenting vasopressor dosages may increase mortality. Future trials are needed to identify the lowest acceptable MAP level to ensure tissue perfusion and avoid unnecessary high catecholamine infusions.

Project description:Clinical guidelines recommend norepinephrine as initial vasopressor of choice for septic shock, with dopamine suggested as an alternative vasopressor in selected patients with low risk of tachyarrhythmias and absolute or relative bradycardia. We sought to determine practice patterns and outcomes associated with vasopressor selection in a large, population-based cohort of patients with septic shock that allows for assessment of outcomes in clinically important subgroups.We performed a retrospective cohort study to determine factors associated with choice of dopamine as compared with norepinephrine as initial vasopressor for patients with septic shock. We used propensity score matching to compare risk of hospital mortality based on initial vasopressor. We performed multiple sensitivity analyses using alternative methods to address confounding and hospital-level clustering. We investigated interaction between vasopressor selection and mortality in clinical subgroups based on arrhythmia and cardiovascular risk.Enhanced administrative data (Premier, Charlotte, NC) from 502 U.S. hospitals during the years 2010-2013.A total of 61,122 patients admitted with septic shock who received dopamine or norepinephrine as initial vasopressor during the first 2 days of hospitalization.None.Norepinephrine (77.6%) was the most frequently used initial vasopressor during septic shock. Dopamine was preferentially selected by cardiologists, in the Southern United States, at nonteaching hospitals, for older patients with more cardiovascular comorbidities and was used less frequently over time. Patients receiving dopamine experienced greater hospital mortality (propensity-matched cohort: n = 38,788; 25% vs 23.7%; odds ratio, 1.08; 95% CI, 1.02-1.14). Sensitivity analyses showed similar results. Subgroup analyses showed no evidence for effect modification based on arrhythmia risk or underlying cardiovascular disease.In a large population-based sample of patients with septic shock in the United States, use of dopamine as initial vasopressor was associated with increased mortality among multiple clinical subgroups. Areas where use of dopamine as initial vasopressor is more common represent potential targets for quality improvement intervention.

Project description:BACKGROUND:Thiamine, an essential vitamin for aerobic metabolism and glutathione cycling, may decrease the effects of critical illnesses. The objective of this study was to determine whether intravenous thiamine administration can reduce vasopressor requirements in patients with septic shock. METHODS:This study was a prospective randomized double-blind placebo-controlled trial. We included adult patients with septic shock who required a vasopressor within 1-24?h after admission between March 2018 and January 2019 at a tertiary hospital in Thailand. Patients were divided into two groups: those who received 200?mg thiamine or those receiving a placebo every 12?h for 7?days or until hospital discharge. The primary outcome was the number of vasopressor-free days over 7?days. The pre-defined sample size was 31 patients per group, and the study was terminated early due to difficult recruitment. RESULTS:Sixty-two patients were screened and 50 patients were finally enrolled in the study, 25 in each group. There was no difference in the primary outcome of vasopressor-free days within the 7-day period between the thiamine and placebo groups (mean: 4.9?days (1.9) vs. 4.0?days (2.7), p =?0.197, mean difference?-?0.9, 95% CI (-?2.9 to 0.5)). However, the reductions in lactate (p =?0.024) and in the vasopressor dependency index (p =?0.02) at 24?h were greater among subjects who received thiamine repletion vs. the placebo. No statistically significant difference was observed in SOFA scores within 7?days, vasopressor dependency index within 4?days and 7?days, or 28-day mortality. CONCLUSIONS:Thiamine was not associated to a significant reduction in vasopressor-free days over 7-days in comparison to placebo in patients with septic shock. Administration of thiamine could be associated with a reduction in vasopressor dependency index and lactate level within 24?h. The study is limited by early stopping and low sample size. TRIAL REGISTRATION:TCTR, TCTR20180310001. Registered 8 March 2018, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=3330 .

Project description:BackgroundSeptic shock is a life-threatening condition that challenges immune cells to reprogram their mitochondrial metabolism towards to increase ATP synthesis for building an appropriate immunity. This could print metabolic signatures in mitochondria whose association with disease progression and clinical outcomes remain elusive.MethodThis is a single-center prospective cohort study performed in the ICU of one tertiary referral hospital in Brazil. Between November 2017 and July 2018, 90 consecutive patients, aged 18 years or older, admitted to the ICU with septic shock were enrolled. Seventy-five patients had Simplified Acute Physiology Score (SAPS 3) assessed at admission, and Sequential Organ Failure Assessment (SOFA) assessed on the first (D1) and third (D3) days after admission. Mitochondrial respiration linked to complexes I, II, V, and biochemical coupling efficiency (BCE) were assessed at D1 and D3 and Δ (D3-D1) in isolated lymphocytes. Clinical and mitochondrial endpoints were used to dichotomize the survival and death outcomes. Our primary outcome was 6-month mortality, and secondary outcomes were ICU and hospital ward mortality.ResultsThe mean SAPS 3 and SOFA scores at septic shock diagnosis were 75.8 (± 12.9) and 8 (± 3) points, respectively. The cumulative ICU, hospital ward, and 6-month mortality were 32 (45%), 43 (57%), and 50 (66%), respectively. At the ICU, non-surviving patients presented elevated arterial lactate (2.8 mmol/L, IQR, 2-4), C-reactive protein (220 mg/L, IQR, 119-284), and capillary refill time (5.5 s, IQR, 3-8). Respiratory rates linked to CII at D1 and D3, and ΔCII were decreased in non-surviving patients. Also, the BCE at D1 and D3 and the ΔBCE discriminated patients who would evolve to death in the ICU, hospital ward, and 6 months after admission. After adjusting for possible confounders, the ΔBCE value but not SOFA scores was independently associated with 6-month mortality (RR 0.38, CI 95% 0.18-0.78; P = 0.009). At a cut-off of - 0.002, ΔBCE displayed 100% sensitivity and 73% specificity for predicting 6-month mortality CONCLUSIONS: The ΔBCE signature in lymphocytes provided an earlier recognition of septic shock patients in the ICU at risk of long-term deterioration of health status.

Project description:ObjectiveTo identify the optimal estimated glomerular filtration rate (eGFR) at which to initiate dialysis in people with advanced chronic kidney disease.DesignNationwide observational cohort study.SettingNational Swedish Renal Registry of patients referred to nephrologists.ParticipantsPatients had a baseline eGFR between 10 and 20 mL/min/1.73 m2 and were included between 1 January 2007 and 31 December 2016, with follow-up until 1 June 2017.Main outcome measuresThe strict design criteria of a clinical trial were mimicked by using the cloning, censoring, and weighting method to eliminate immortal time bias, lead time bias, and survivor bias. A dynamic marginal structural model was used to estimate adjusted hazard ratios and absolute risks for five year all cause mortality and major adverse cardiovascular events (composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) for 15 dialysis initiation strategies with eGFR values between 4 and 19 mL/min/1.73 m2 in increments of 1 mL/min/1.73 m2. An eGFR between 6 and 7 mL/min/1.73 m2 (eGFR6-7) was taken as the reference.ResultsAmong 10 290 incident patients with advanced chronic kidney disease (median age 73 years; 3739 (36%) women; median eGFR 16.8 mL/min/1.73 m2), 3822 started dialysis, 4160 died, and 2446 had a major adverse cardiovascular event. A parabolic relation was observed for mortality, with the lowest risk for eGFR15-16. Compared with dialysis initiation at eGFR6-7, initiation at eGFR15-16 was associated with a 5.1% (95% confidence interval 2.5% to 6.9%) lower absolute five year mortality risk and 2.9% (0.2% to 5.5%) lower risk of a major adverse cardiovascular event, corresponding to hazard ratios of 0.89 (95% confidence interval 0.87 to 0.92) and 0.94 (0.91 to 0.98), respectively. This 5.1% absolute risk difference corresponded to a mean postponement of death of 1.6 months over five years of follow-up. However, dialysis would need to be started four years earlier. When emulating the intended strategies of the Initiating Dialysis Early and Late (IDEAL) trial (eGFR10-14 v eGFR5-7) and the achieved eGFRs in IDEAL (eGFR7-10 v eGFR5-7), hazard ratios for all cause mortality were 0.96 (0.94 to 0.99) and 0.97 (0.94 to 1.00), respectively, which are congruent with the findings of the randomised IDEAL trial.ConclusionsVery early initiation of dialysis was associated with a modest reduction in mortality and cardiovascular events. For most patients, such a reduction may not outweigh the burden of a substantially longer period spent on dialysis.

Dataset Information

Timing of vasopressor initiation and mortality in septic shock: a cohort study.

Introduction

Methods

Results

Conclusion

Publications

Timing of vasopressor initiation and mortality in septic shock: a cohort study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure