Prescribed targets for titration of vasopressors in septic shock: a retrospective cohort study.
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ABSTRACT: Background
Without robust clinical evidence to guide titration of vasopressors in septic shock, it is unclear how dosing of these potent medications occurs. We sought to measure the proportion of vasopressor prescriptions for septic shock that were missing explicit targets and to describe the targets that we identified.Methods
We conducted a multicentre, retrospective cohort study involving 9 intensive care units (ICUs) located at 3 academic hospitals in Canada and Australia. We reviewed charts of consecutive patients aged 18 years or older who were admitted to the ICU for a presumptive diagnosis of sepsis. Other inclusion criteria were hypotension (systolic arterial pressure ≤ 90 mm Hg or mean arterial pressure [MAP] ≤ 65 mm Hg) and continuous infusion of vasopressors for at least 1 hour within the initial 48 hours of ICU stay, the period of observation for this study.Results
We included data from 369 patient charts. At least 1 target was specified in 99% of charts. The most common targets were MAP measurements (73%). The median initial MAP target was 65 (range 55-90) mm Hg. In multivariable regression models, hospital site and older age of the patient, but not comorbidities of the patient, were associated with MAP targets. In 40% of patients, the treating team modified the initial target at least once.Interpretation
This study suggests that an explicit blood pressure target accompanies nearly every vasopressor prescription and that patient characteristics have little influence on its value. Identification of a titration strategy that will maximize benefit and minimize harm constitutes a research priority.
SUBMITTER: St-Arnaud C
PROVIDER: S-EPMC3985969 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPatients with septic shock have the highest risk of death from sepsis, however, racial disparities in mortality outcomes in this cohort have not been rigorously investigated. Our objective was to describe the association between race/ethnicity and mortality in patients with septic shock.MethodsOur study is a retrospective cohort study of adult patients in the OneFlorida Data Trust (Florida, United States of America) admitted with septic shock between January 2012 and July 2018. We identified patients as having septic shock if they received vasopressors during their hospital encounter and had either an explicit International Classification of Disease (ICD) code for sepsis, or had an infection ICD code and received intravenous antibiotics. Our primary outcome was 90-day mortality. Our secondary outcome was in-hospital mortality. Multiple logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) for variable selection was used to assess associations.FindingsThere were 13,932 patients with septic shock in our cohort. The mean age was 61 years (SD 16), 68% of the cohort identified as White (n = 9419), 28% identified as Black (n = 3936), 2% (n = 294) identified as Hispanic ethnicity, and 2% as other races not specified in the previous groups (n = 283). In our logistic regression model for 90-day mortality, patients identified as Black had 1.57 times the odds of mortality (95% CI 1.07-2.29, p = 0.02) compared to White patients. Other significant predictors included mechanical ventilation (OR 3.66, 95% CI 3.35-4.00, p < 0.01), liver disease (OR 1.75, 95% CI 1.59-1.93, p < 0.01), laboratory components of the Sequential Organ Failure Assessment score (OR 1.18, 95% CI 1.16-1.21, p < 0.01), lactate (OR 1.10, 95% CI 1.08-1.12, p < 0.01), congestive heart failure (OR 1.19, 95% CI 1.10-1.30, p < 0.01), human immunodeficiency virus (OR 1.35, 95% CI 1.04-1.75, p = 0.03), age (OR 1.04, 95% CI 1.04-1.04, p < 0.01), and the interaction between age and race (OR 0.99, 95% CI 0.99-1.00, p < 0.01). Among younger patients (<45 years), patients identified as Black accounted for a higher proportion of the deaths. Results were similar in the in-hospital mortality model.InterpretationIn this retrospective study of septic shock patients, we found that patients identified as Black had higher odds of mortality compared to patients identified as non-Hispanic White. Our findings suggest that the greatest disparities in mortality are among younger Black patients with septic shock.FundingNational Institutes of Health National Center for Advancing Translational Sciences (1KL2TR001429); National Institute of Health National Institute of General Medical Sciences (1K23GM144802).
| S-EPMC10757245 | biostudies-literature
Project description:In addition to fluid resuscitation, the vasopressor therapy is a fundamental treatment of septic shock-induced hypotension as it aims at correcting the vascular tone depression and then at improving organ perfusion pressure. Experts' recommendations currently position norepinephrine (NE) as the first-line vasopressor in septic shock. Vasopressin and its analogues are only second-line vasopressors as strong recent evidence suggests no benefit of their early administration in spite of promising preliminary data. Early administration of NE may allow achieving the initial mean arterial pressure (MAP) target faster and reducing the risk of fluid overload. The diastolic arterial pressure (DAP) as a marker of vascular tone, helps identifying the patients who need NE urgently. Available data suggest a MAP of 65 mmHg as the initial target but a more individualized approach is often required depending on several factors such as history of chronic hypertension or value of central venous pressure (CVP). In cases of refractory hypotension, increasing NE up to doses ?1 µg/kg/min could be an option. However, current experts' guidelines suggest to combine NE with other vasopressors such as vasopressin, with the intent to rising the MAP to target or to decrease the NE dosage.
| S-EPMC7333107 | biostudies-literature
Project description:Intravenous fluid resuscitation is recommended first-line treatment for sepsis-associated hypotension and/or hypoperfusion. The rationale is to restore circulating volume and optimize cardiac output in the setting of shock. Nonetheless, there is limited high-level evidence to support this practice. Over the past decade emerging evidence of harm associated with large volume fluid resuscitation among patients with septic shock has led to calls for a more conservative approach. Specifically, clinical trials undertaken in Africa have found harm associated with initial fluid resuscitation in the setting of infection and hypoperfusion. While translating these findings to practice in other settings is problematic, there has been a re-appraisal of current practice with some recommending earlier use of vasopressors rather than repeated fluid boluses as an alternative to restore perfusion in septic shock. There is consequently uncertainty and variation in practice. The question of fluids or vasopressors for initial resuscitation in septic shock is the subject of international multicentre clinical trials.
| S-EPMC9729725 | biostudies-literature
Project description:ObjectiveInternational guidelines recommend dopamine or norepinephrine as first-line vasopressor agents in septic shock. Phenylephrine, epinephrine, vasopressin and terlipressin are considered second-line agents. Our objective was to assess the evidence for the efficiency and safety of all vasopressors in septic shock.MethodsSystematic review and meta-analysis. We searched electronic database of MEDLINE, CENTRAL, LILACS and conference proceedings up to June 2014. We included randomized controlled trials comparing different vasopressors for the treatment of adult patients with septic shock. Primary outcome was all-cause mortality. Other clinical and hemodynamic measurements were extracted as secondary outcomes. Risk ratios (RR) and mean differences with 95% confidence intervals (CI) were pooled.ResultsThirty-two trials (3,544 patients) were included. Compared to dopamine (866 patients, 450 events), norepinephrine (832 patients, 376 events) was associated with decreased all-cause mortality, RR 0.89 (95% CI 0.81-0.98), corresponding to an absolute risk reduction of 11% and number needed to treat of 9. Norepinephrine was associated with lower risk for major adverse events and cardiac arrhythmias compared to dopamine. No other mortality benefit was demonstrated for the comparisons of norepinephrine to epinephrine, phenylephrine and vasopressin / terlipressin. Hemodynamic data were similar between the different vasopressors, with some advantage for norepinephrine in central venous pressure, urinary output and blood lactate levels.ConclusionsEvidence suggests a survival benefit, better hemodynamic profile and reduced adverse events rate for norepinephrine over dopamine. Norepinephrine should be regarded as the first line vasopressor in the treatment of septic shock.
| S-EPMC4523170 | biostudies-literature
Project description: Not available
| S-EPMC8367735 | biostudies-literature
Project description:BackgroundThe role of thyroid hormones is crucial in the response to stress and critical illness, which has been reported to be closely associated with a poor prognosis in patients admitted to the intensive care unit (ICU). This study aimed to explore the relationship between thyroid hormone and prognosis in septic shock patients.MethodsA total of 186 patients with septic shock were enrolled in the analytical study between December 2014 and September 2022. The baseline variables and thyroid hormone were collected. The patients were divided into survivor group and non-survivor group according to whether they died during the ICU hospitalization. Among 186 patients with septic shock, 123 (66.13%) were in the survivor group and 63 (33.87%) were in the non-survivor group.ResultsThere were significant differences in the indictors of free triiodothyronine (FT3) (p = 0.000), triiodothyronine (T3) (p = 0.000), T3/FT3 (p = 0.000), acute physiology and chronic health evaluation II score (APACHE II) (p = 0.000), sequential organ failure assessment score (SOFA) (p = 0.000), pulse rate (p = 0.020), creatinine (p = 0.008), PaO2/FiO2 (p = 0.000), length of stay (p = 0.000) and hospitalization expenses (p = 0.000) in ICU between the two groups. FT3 [odds ratio (OR): 1.062, 95% confidence interval(CI): (0.021, 0.447), p = 0.003], T3 (OR: 0.291, 95% CI: 0.172-0.975, p = 0.037) and T3/FT3 (OR: 0.985, 95% CI:0.974-0.996, p = 0.006) were independent risk factors of the short-term prognosis of septic shock patients after adjustment. The areas under the receiver operating characteristic curves for T3 was associated with ICU mortality (AUC = 0.796, p < 0.05) and was higher than that for FT3 (AUC = 0.670, p < 0.05) and T3/FT3 (AUC = 0.712, p < 0.05). A Kaplan-Meier curve showed that patients with T3 greater than 0.48 nmol/L had a significantly higher survival rate than the patients with T3 less than 0.48 nmol/L.ConclusionsThe decrease in serum level of T3 in patients with septic shock is associated with ICU mortality. Early detection of serum T3 level could help clinicians to identify septic shock patients at high risk of clinical deterioration.
| S-EPMC10198161 | biostudies-literature
Project description:IntroductionSeptic shock is a life-threatening condition requiring vasopressor agents to support the circulatory system. Several agents exist with choice typically guided by the specific clinical scenario. We used a network meta-analysis approach to rate the comparative efficacy and safety of vasopressors for mortality and arrhythmia incidence in septic shock patients.MethodsWe performed a comprehensive electronic database search including Medline, Embase, Science Citation Index Expanded and the Cochrane database. Randomised trials investigating vasopressor agents in septic shock patients and specifically assessing 28-day mortality or arrhythmia incidence were included. A Bayesian network meta-analysis was performed using Markov chain Monte Carlo methods.ResultsThirteen trials of low to moderate risk of bias in which 3146 patients were randomised were included. There was no pairwise evidence to suggest one agent was superior over another for mortality. In the network meta-analysis, vasopressin was significantly superior to dopamine (OR 0.68 (95% CI 0.5 to 0.94)) for mortality. For arrhythmia incidence, standard pairwise meta-analyses confirmed that dopamine led to a higher incidence of arrhythmias than norepinephrine (OR 2.69 (95% CI 2.08 to 3.47)). In the network meta-analysis, there was no evidence of superiority of one agent over another.ConclusionsIn this network meta-analysis, vasopressin was superior to dopamine for 28-day mortality in septic shock. Existing pairwise information supports the use of norepinephrine over dopamine. Our findings suggest that dopamine should be avoided in patients with septic shock and that other vasopressor agents should continue to be based on existing guidelines and clinical judgement of the specific presentation of the patient.
| S-EPMC5606402 | biostudies-literature
Project description:BackgroundInitial goal-directed resuscitation for hypotensive shock usually includes administration of intravenous fluids, followed by initiation of vasopressors. Despite obvious immediate effects of vasopressors on haemodynamics, their effect on patient-relevant outcomes remains controversial. This review was published originally in 2004 and was updated in 2011 and again in 2016.ObjectivesOur objective was to compare the effect of one vasopressor regimen (vasopressor alone, or in combination) versus another vasopressor regimen on mortality in critically ill participants with shock. We further aimed to investigate effects on other patient-relevant outcomes and to assess the influence of bias on the robustness of our effect estimates.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015 Issue 6), MEDLINE, EMBASE, PASCAL BioMed, CINAHL, BIOSIS and PsycINFO (from inception to June 2015). We performed the original search in November 2003. We also asked experts in the field and searched meta-registries to identify ongoing trials.Selection criteriaRandomized controlled trials (RCTs) comparing various vasopressor regimens for hypotensive shock.Data collection and analysisTwo review authors abstracted data independently. They discussed disagreements between them and resolved differences by consulting with a third review author. We used a random-effects model to combine quantitative data.Main resultsWe identified 28 RCTs (3497 participants) with 1773 mortality outcomes. Six different vasopressors, given alone or in combination, were studied in 12 different comparisons.All 28 studies reported mortality outcomes; 12 studies reported length of stay. Investigators reported other morbidity outcomes in a variable and heterogeneous way. No data were available on quality of life nor on anxiety and depression outcomes. We classified 11 studies as having low risk of bias for the primary outcome of mortality; only four studies fulfilled all trial quality criteria.In summary, researchers reported no differences in total mortality in any comparisons of different vasopressors or combinations in any of the pre-defined analyses (evidence quality ranging from high to very low). More arrhythmias were observed in participants treated with dopamine than in those treated with norepinephrine (high-quality evidence). These findings were consistent among the few large studies and among studies with different levels of within-study bias risk.Authors' conclusionsWe found no evidence of substantial differences in total mortality between several vasopressors. Dopamine increases the risk of arrhythmia compared with norepinephrine and might increase mortality. Otherwise, evidence of any other differences between any of the six vasopressors examined is insufficient. We identified low risk of bias and high-quality evidence for the comparison of norepinephrine versus dopamine and moderate to very low-quality evidence for all other comparisons, mainly because single comparisons occasionally were based on only a few participants. Increasing evidence indicates that the treatment goals most often employed are of limited clinical value. Our findings suggest that major changes in clinical practice are not needed, but that selection of vasopressors could be better individualised and could be based on clinical variables reflecting hypoperfusion.
| S-EPMC6516856 | biostudies-literature
Project description:Recent publications suggest potential benefits from statins as a preventive or adjuvant therapy in sepsis. Whether ongoing statin therapy should be continued or discontinued in patients admitted in the intensive care unit (ICU) for sepsis is open to question.We retrospectively compared patients with severe sepsis and septic shock in whom statin therapy had been discontinued or continued. The primary endpoint was the number of organ failure-free days at day 14. Secondary end-points included hospital mortality and safety. The association of statin continuation with outcome was evaluated for crude analysis and after propensity score matching and adjustment. We also measured plasma atorvastatin concentrations in a separate set of ICU septic patients continuing the drug.Patients in whom statin therapy had been continued in the ICU (n = 44) had significantly more organ failure-free days (11 67891011121314 vs. 6 [0-12], mean difference of 2.34, 95%CI from 0.47 to 5.21, P = 0.03) as compared to others (n = 32). However, there were important imbalances between groups, with more hospital-acquired infections, more need for surgery before ICU admission, and a trend towards more septic shock at ICU admission in the discontinuation group. The significant association of statin continuation with organ failure free days found in the crude analysis did not persist after propensity-matching or multivariable adjustment: beta coefficients [95% CI] of 2.37 [-0.96 to 5.70] (P = 0.20) and 2.24 [-0.43 to 4.91] (P = 0.11) respectively. We found particularly high pre-dose and post-dose atorvastatin concentrations in ICU septic patients continuing the drug.Continuing statin therapy in ICU septic patients was not associated with reduction in the severity of organ failure after matching and adjustment. In addition, the very high plasma concentrations achieved during continuation of statin treatment advocates some caution.
| S-EPMC3387613 | biostudies-literature
Project description:BackgroundHaemoadsorption has been described as an effective way to control increased pro- and anti-inflammatory mediators ("cytokine storm") in septic shock patients. No prospective or randomised clinical study has yet confirmed these results. However, no study has yet prospectively specifically investigated patients in severe septic shock with sepsis-associated acute kidney injury (SA-AKI). Therefore, we aimed to examine whether haemoadsorption could influence intensive care unit (ICU) and hospital mortality in these patients. Furthermore, we examined the influence of haemoadsorption on length of stay in the ICU and therapeutic support.MethodsRetrospective control group and prospective intervention group design in a tertiary hospital in central Europe (Germany). Intervention was the implementation of haemoadsorption for patients in septic shock with SA-AKI. 76 patients were included in this analysis.ResultsSeverity of illness as depicted by APACHE II was higher in patients treated with haemoadsorption. Risk-adjusted ICU mortality rates (O/E ratios) did not differ significantly between the groups (0.80 vs. 0.83). We observed in patients treated with haemoadsorption a shorter LOS and shorter therapeutic support such as catecholamine dependency and duration of RRT. However, in multivariate analysis (logistic regression for mortality, competing risk for LOS), we found no significant differences between the two groups.ConclusionsThe implementation of haemoadsorption for patients in septic shock with acute renal failure did not lead to a reduction in ICU or hospital mortality rates. Despite univariate analysis delivering some evidence for a shorter duration of ICU-related treatments in the haemoadsorption group, these results did not remain significant in multivariate analysis. Trial registration CytoSorb® registry https://clinicaltrials.gov/ct2/show/NCT02312024 . December 9, 2014.Databasehttps://www.cytosorb-registry.org/ (registration for content acquisition is necessary).
| S-EPMC7672170 | biostudies-literature