Vasopressors in septic shock: which, when, and how much?
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SUBMITTER: Shi R
PROVIDER: S-EPMC7333107 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
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Vasopressors in septic shock: which, when, and how much?
Shi Rui R Hamzaoui Olfa O De Vita Nello N Monnet Xavier X Teboul Jean-Louis JL
Annals of translational medicine 20200601 12
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 pr ...[more]
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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:BackgroundWithout 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.MethodsWe 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.ResultsWe 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.InterpretationThis 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.
| S-EPMC3985969 | 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:BACKGROUND:Vasopressin (AVP) is commonly added to norepinephrine (NE) to reverse shock in patients with sepsis. However, there are no data to support the appropriate strategy of vasopressor tapering in patients on concomitant NE and AVP who are recovering from septic shock. Therefore, the objective of this study was to evaluate the incidence of hypotension while tapering vasopressors in patients on concomitant NE and AVP recovering from septic shock. METHODS:Patients with septic shock receiving concomitant NE and AVP were randomly assigned to taper NE first (NE group) or AVP first (AVP group). The primary end point was the incidence of hypotension within one hour of tapering of the first vasopressor. We also evaluated the association between serum copeptin levels and the occurrence of hypotension. RESULTS:The study was stopped early due to a significant difference in the incidence of hypotension after 38 and 40 patients were enrolled in the NE group and the AVP group, respectively. There were 26 patients (68.4%) in the NE group versus 9 patients (22.5%) in the AVP group who developed hypotension after tapering the first vasopressor (p?<?0.001). There was a similar finding during the subsequent tapering of the second vasopressor (64.5% in the NE vs 25.0% in the AVP group, p?=?0.020). Finally, NE tapering was significantly associated with hypotension during the study period (hazard ratio, 2.221; 95% confidence interval, 1.106-4.460; p?=?0.025). The serum copeptin level was lower in patients in whom hypotension developed during tapering of AVP than it was in those without hypotension. CONCLUSIONS:Tapering NE rather than AVP may be associated with a higher incidence of hypotension in patients recovering from septic shock who are on concomitant NE and AVP. However, further studies with larger sample sizes are required to better determine the appropriate strategy for vasopressor tapering. TRIAL REGISTRATION:ClinicalTrials.gov, NCT01493102 . Registered on 15 December 2011.
| S-EPMC5961479 | biostudies-literature
Project description:The priority in the management of patients with traumatic hemorrhagic shock is to control the bleeding with simultaneous volume resuscitation to maintain adequate tissue perfusion. Fluid replacement remains the mainstay of initial resuscitation in hemorrhagic shock. Traditionally, vasopressors are contraindicated in the early management of hemorrhagic shock due to their deleterious consequences, although vasopressors may have a role in resuscitation when vasoplegic shock ensues and blood pressure cannot be maintained by fluids alone. Use of vasopressors is not recommended according to the Advanced Trauma Life SupportR management principles. The role of vasopressors remains controversial with no clear guidelines on the timing, type, and dose of these drugs in hemorrhagic shock. Among vasopressors, norepinephrine and vasopressin have been used in the majority of the trials, although not many studies compare the effect of these two on long-term survival in trauma patients. This article reviews the pathophysiology of hemorrhagic shock, adverse effects of fluid resuscitation, and the various experimental and clinical studies on the use of vasopressors in the early phase of resuscitation in hemorrhagic shock.
| S-EPMC5374828 | biostudies-literature
Project description:In an ongoing translational research program involving microarray-based expression profiles in pediatric septic shock, we have now conducted longitudinal studies focused on the temporal expression profiles of canonical signaling pathways and gene networks. Genome-level expression profiles were generated from whole blood-derived RNA samples of children with septic shock (n = 30 individual patients) corresponding to days 1 and 3 of admission to the pediatric intensive care unit. Based on sequential statistical and expression filters, day 1 and day 3 of septic shock were characterized by differential regulation of 2,142 and 2,504 gene probes, respectively, relative to normal control patients. Venn analysis demonstrated 239 unique genes in the day 1 data set, 598 unique genes in the day 3 data set, and 1,906 genes common to both data sets. Analyses targeted toward derivation of biological function from these data sets demonstrated time-dependent, differential regulation of genes involved in multiple canonical signaling pathways and gene networks primarily related to immunity and inflammation. Notably, multiple and distinct gene networks involving T cell- and MHC antigen-related biological processes were persistently downregulated from day 1 to day 3. Further analyses demonstrated large scale and persistent downregulation of genes corresponding to functional annotations related to zinc homeostasis. These data represent the largest reported cohort of patients with septic shock, which has undergone longitudinal genome-level expression profiling. The data further advance our genome-level understanding of pediatric septic shock and support novel hypotheses that can be readily tested at both the experimental and translational levels. Keywords: Inflammation; sepsis; innate immunity; T cells; MHC antigen Keywords: to be updated
2007-06-14 | GSE8121 | GEO
Project description:BackgroundNorepinephrine (NE) has currently been the first-choice vasopressor in treating septic shock despite generally insufficient for patients with refractory septic shock. The aim of this update meta-analysis was to assess the safety and efficacy of a combination of non-catecholamine vasopressors (vasopressin/pituitrin/terlipressin/selepressin/angiotensin II) and NE versus NE in managing adult septic shock patients.MethodsWe conducted this study of literatures published from the inception to April 30, 2020, using PubMed, Embase, and the Cochrane Library databases without language restriction. Randomized controlled trials comparing NE with non-catecholamine vasopressors among adult septic shock patients were included in this meta-analysis. Pooled effects of relative risk (RR) or standard mean difference (SMD) and corresponding 95% confidence interval (CI) were calculated using a random-effects model.ResultsTwenty-three studies covering 4380 participants were finally enrolled. The combined analysis of non-catecholamine vasopressors resulted in a nonsignificant reduction in 90-day/ICU/hospital mortality except for a decreased in 28-day mortality (n = 4217; RR, 0.92; 95% CI 0.86-0.99; P = 0.02). This favorable result was subsequently verified by the subgroup analyses of low risk of bias studies (RR = 0.91, 95% CI = 0.84 to 0.98; P = 0.02) and catecholamine-resistant refractory shock patients group (RR, 0.84; 95% CI = 0.70-1.00; P = 0.048). The pooled analysis of non-catecholamine vasopressors showed a 14% higher success rate of shock reversal at 6 h, a 29% decreased risk of continuous renal replacement therapy, but a 51% increased risk of hyponatremia and a 2.43 times higher risk of digital ischemia. Besides, the pooled data showed that non-catecholamine vasopressors decreased heart rate (HR) (SMD, - 0.43; 95% CI - 0.66 - - 0.19; P < 0.001), serum creatinine (- 0.15; 95% CI - 0.29 - - 0.01; P = 0.04), and the length of mechanical ventilation (MV) (- 0.19; 95% CI - 0.31 - - 0.07; P < 0.01, but there was no significant difference in other parameters.ConclusionsCurrent pooled results suggest that the addition of NE to non-catecholamine vasopressors was associated with a marginally significant reduction in 28-day mortality. Moreover, they were able to shorten the length of MV, improved renal function, decreased HR, and increased the 6-h shock reversal success rate at the expense of increased the risk of hyponatremia and digital ischemia.
| S-EPMC7603734 | biostudies-literature
Project description:For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15-25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30-50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental.
| S-EPMC5538252 | biostudies-other