Dataset Information

Systematic assessment of fluid responsiveness during early septic shock resuscitation: secondary analysis of the ANDROMEDA-SHOCK trial.

ABSTRACT: BACKGROUND:Fluid boluses are administered to septic shock patients with the purpose of increasing cardiac output as a means to restore tissue perfusion. Unfortunately, fluid therapy has a narrow therapeutic index, and therefore, several approaches to increase safety have been proposed. Fluid responsiveness (FR) assessment might predict which patients will effectively increase cardiac output after a fluid bolus (FR+), thus preventing potentially harmful fluid administration in non-fluid responsive (FR-) patients. However, there are scarce data on the impact of assessing FR on major outcomes. The recent ANDROMEDA-SHOCK trial included systematic per-protocol assessment of FR. We performed a post hoc analysis of the study dataset with the aim of exploring the relationship between FR status at baseline, attainment of specific targets, and clinically relevant outcomes. METHODS:ANDROMEDA-SHOCK compared the effect of peripheral perfusion- vs. lactate-targeted resuscitation on 28-day mortality. FR was assessed before each fluid bolus and periodically thereafter. FR+ and FR- subgroups, independent of the original randomization, were compared for fluid administration, achievement of resuscitation targets, vasoactive agents use, and major outcomes such as organ dysfunction and support, length of stay, and 28-day mortality. RESULTS:FR could be determined in 348 patients at baseline. Two hundred and forty-two patients (70%) were categorized as fluid responders. Both groups achieved comparable successful resuscitation targets, although non-fluid responders received less resuscitation fluids (0 [0-500] vs. 1500 [1000-2500] mL; p 0.0001), exhibited less positive fluid balances, but received more vasopressor testing. No difference in clinically relevant outcomes between FR+ and FR- patients was found, including 24-h SOFA score (9 [5-12] vs. 8 [5-11], p?=?0.4), need for MV (78% vs. 72%, p?=?0.16), need for RRT (18% vs. 21%, p?=?0.7), ICU-LOS (6 [3-11] vs. 6 [3-16] days, p?=?0.2), and 28-day mortality (40% vs. 36%, p?=?0.5). Only thirteen patients remained fluid responsive along the intervention period. CONCLUSIONS:Systematic assessment allowed determination of fluid responsiveness status in more than 80% of patients with early septic shock. Fluid boluses could be stopped in non-fluid responsive patients without any negative impact on clinical relevant outcomes. Our results suggest that fluid resuscitation might be safely guided by FR assessment in septic shock patients. TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT03078712. Registered retrospectively on March 13, 2017.

SUBMITTER: Kattan E

PROVIDER: S-EPMC6979284 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Systematic assessment of fluid responsiveness during early septic shock resuscitation: secondary analysis of the ANDROMEDA-SHOCK trial.

Kattan Eduardo E Ospina-Tascón Gustavo A GA Teboul Jean-Louis JL Castro Ricardo R Cecconi Maurizio M Ferri Giorgio G Bakker Jan J Hernández Glenn G

Critical care (London, England) 20200123 1

<h4>Background</h4>Fluid boluses are administered to septic shock patients with the purpose of increasing cardiac output as a means to restore tissue perfusion. Unfortunately, fluid therapy has a narrow therapeutic index, and therefore, several approaches to increase safety have been proposed. Fluid responsiveness (FR) assessment might predict which patients will effectively increase cardiac output after a fluid bolus (FR+), thus preventing potentially harmful fluid administration in non-fluid r ...[more]

PMID: 31973735

Similar Datasets

Project description:Septic shock is the leading cause of cardiovascular failure in the intensive care unit (ICU). Cardiac output is a primary component of global oxygen delivery to organs and a sensitive parameter of cardiovascular failure. Any mismatch between oxygen delivery and rapidly varying metabolic demand may result in tissue dysoxia, hence organ dysfunction. Since the intricate alterations of both vascular and cardiac function may rapidly and widely change over time, cardiac output should be measured repeatedly to characterize the type of shock, select the appropriate therapeutic intervention, and evaluate patient's response to therapy. Among the numerous techniques commercially available for measuring cardiac output, transpulmonary thermodilution (TPT) provides a continuous monitoring with external calibration capability, whereas critical care echocardiography (CCE) offers serial hemodynamic assessments. CCE allows early identification of potential sources of inaccuracy of TPT, including right ventricular failure, severe tricuspid or left-sided regurgitations, intracardiac shunt, very low flow states, or dynamic left ventricular outflow tract obstruction. In addition, CCE has the unique advantage of depicting the distinct components generating left ventricular stroke volume (large cavity size vs. preserved contractility), providing information on left ventricular diastolic properties and filling pressures, and assessing pulmonary artery pressure. Since inotropes may have deleterious effects if misused, their initiation should be based on the documentation of a cardiac dysfunction at the origin of the low flow state by CCE. Experts widely advocate using CCE as a first-line modality to initially evaluate the hemodynamic profile associated with shock, as opposed to more invasive techniques. Repeated assessments of both the efficacy (amplitude of the positive response) and tolerance (absence of side-effect) of therapeutic interventions are required to best guide patient management. Overall, TPT allowing continuous tracking of cardiac output variations and CCE appear complementary rather than mutually exclusive in patients with septic shock who require advanced hemodynamic monitoring.

Project description:IntroductionRecent evidence suggests that early, aggressive resuscitation in patients with septic shock reduces mortality. The objective of this survey was to characterize reported resuscitation practices of Canadian physicians caring for adult critically ill patients with early septic shock.MethodsA scenario-based self-administered national survey was sent out to Canadian critical care physicians. One hypothetical scenario was developed to obtain information on several aspects of resuscitation in early septic shock, including monitoring and resuscitation end-points, fluid administration, red blood cell transfusion triggers, and use of inotropes. The sampling frame was physician members of Canadian national and provincial critical care societies.ResultsThe survey response rate was 232 out of 355 (65.3%). Medicine was the most common primary specialty (60.0%), most respondents had practiced for 6 to 10 years (30.0%), and 82.0% were male. The following monitoring devices/parameters were reported as used/measured 'often' or 'always' by at least 89% of respondents: oxygen saturation (100%), Foley catheters (100%), arterial blood pressure lines (96.6%), telemetry (94.3%), and central venous pressure (89.2%). Continuous monitoring of central venous oxygen saturation was employed 'often' or 'always' by 9.8% of respondents. The two most commonly cited resuscitation end-points were urine output (96.5%) and blood pressure (91.8%). Over half of respondents used normal saline (84.5%), Ringers lactate (52.2%), and pentastarch (51.3%) 'often' or 'always' for early fluid resuscitation. In contrast, 5% and 25% albumin solutions were cited as used 'often' or 'always' by 3.9% and 1.3% of respondents, respectively. Compared with internists, surgeons and anesthesiologists (odds ratio (95% confidence interval): 9.8 (2.9 to 32.7) and 3.8 (1.7 to 8.7), respectively) reported greater use of Ringers lactate. In the setting of a low central venous oxygen saturation, 52.5% of respondents reported use of inotropic support 'often' or 'always'. Only 7.6% of physicians stated they would use a red blood cell transfusion trigger of 100 g/l to optimize oxygen delivery further.ConclusionOur survey results suggest that there is substantial practice variation in the resuscitation of adult patients with early septic shock. More randomized trials are needed to determine the optimal approach.

Project description:ObjectivesEvidence to guide fluid resuscitation evidence in sepsis continues to evolve. We conducted a multicountry survey of emergency and critical care physicians to describe current stated practice and practice variation related to the quantity, rapidity and type of resuscitation fluid administered in early septic shock to inform the design of future septic shock fluid resuscitation trials.MethodsUsing a web-based survey tool, we invited critical care and emergency physicians in Canada, the UK, Scandinavia and Saudi Arabia to complete a self-administered electronic survey.ResultsA total of 1097 physicians' responses were included. 1 L was the most frequent quantity of resuscitation fluid physicians indicated they would administer at a time (46.9%, n=499). Most (63.0%, n=671) stated that they would administer the fluid challenges as quickly as possible. Overall, normal saline and Ringer's solutions were the preferred crystalloid fluids used 'often' or 'always' in 53.1% (n=556) and 60.5% (n=632) of instances, respectively. However, emergency physicians indicated that they would use normal saline 'often' or 'always' in 83.9% (n=376) of instances, while critical care physicians said that they would use saline 'often' or 'always' in 27.9% (n=150) of instances. Only 1.0% (n=10) of respondents indicated that they would use hydroxyethyl starch 'often' or 'always'; use of 5% (5.6% (n=59)) or 20-25% albumin (1.3% (n=14)) was also infrequent. The majority (88.4%, n=896) of respondents indicated that a large randomised controlled trial comparing 5% albumin to a crystalloid fluid in early septic shock was important to conduct.ConclusionsCritical care and emergency physicians stated that they rapidly infuse volumes of 500-1000 mL of resuscitation fluid in early septic shock. Colloid use, specifically the use of albumin, was infrequently reported. Our survey identifies the need to conduct a trial on the efficacy of albumin and crystalloids on 90-day mortality in patients with early septic shock.

Project description:ObjectivesRapid fluid resuscitation has become standard in sepsis care, despite "low-quality" evidence and absence of guidelines for populations "at risk" for volume overload. Our objectives include as follows: 1) identify predictors of reaching a 30 mL/kg crystalloid bolus within 3 hours of sepsis onset (30by3); 2) assess the impact of 30by3 and fluid dosing on clinical outcomes; 3) examine differences in perceived "at-risk" volume-sensitive populations, including end-stage renal disease, heart failure, obesity, advanced age, or with documentation of volume "overload" by bedside examination.DesignRetrospective cohort study. All outcome analyses controlled for sex, end-stage renal disease, heart failure, sepsis severity (severe sepsis vs septic shock), obesity, Mortality in Emergency Department Sepsis score, and time to antibiotics.SettingUrban, tertiary care center between January 1, 2014, and May 31, 2017.PatientsEmergency Department treated adults (age ≥18 yr; n = 1,032) with severe sepsis or septic shock.InterventionsAdministration of IV fluids by bolus.Measurements and main resultsIn total, 509 patients received 30by3 (49.3%). Overall mortality was 17.1% (n = 176), with 20.4% mortality in the shock group. Patients who were elderly (odds ratio, 0.62; 95% CI, 0.46-0.83), male (odds ratio, 0.66; CI, 0.49-0.87), obese (odds ratio, 0.18; CI, 0.13-0.25), or with end-stage renal disease (odds ratio, 0.23; CI, 0.13-0.40), heart failure (odds ratio, 0.42; CI, 0.29-0.60), or documented volume "overload" (odds ratio, 0.30; CI, 0.20-0.45) were less likely to achieve 30by3. Failure to meet 30by3 had increased odds of mortality (odds ratio, 1.52; CI, 1.03-2.24), delayed hypotension (odds ratio, 1.42; CI, 1.02-1.99), and increased ICU stay (~2 d) (β = 2.0; CI, 0.5-3.6), without differential effects for "at-risk" groups. Higher fluid volumes administered by 3 hours correlated with decreased mortality, with a plateau effect between 35 and 45 mL/kg (p < 0.05).ConclusionsFailure to reach 30by3 was associated with increased odds of in-hospital mortality, irrespective of comorbidities. Predictors of inadequate resuscitation can be identified, potentially leading to interventions to improve survival. These findings are retrospective and require future validation.

Project description:ImportanceAbnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established.ObjectiveTo determine if a peripheral perfusion-targeted resuscitation during early septic shock in adults is more effective than a lactate level-targeted resuscitation for reducing mortality.Design, setting, and participantsMulticenter, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018.InterventionsPatients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period.Main outcomes and measuresThe primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation-, renal replacement therapy-, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay.ResultsAmong 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, -8.5% [95% CI, -18.2% to 1.2%]). Peripheral perfusion-targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, -1.00 [95% CI, -1.97 to -0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed.Conclusions and relevanceAmong patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality.Trial registrationClinicalTrials.gov Identifier: NCT03078712.

Project description:BACKGROUND:Capillary refill time (CRT) may improve more rapidly than lactate in response to increments in systemic flow. Therefore, it can be assessed more frequently during septic shock (SS) resuscitation. Hyperlactatemia, in contrast, exhibits a slower recovery in SS survivors, probably explained by the delayed resolution of non-hypoperfusion-related sources. Thus, targeting lactate normalization may be associated with impaired outcomes. The ANDROMEDA-SHOCK trial compared CRT- versus lactate-targeted resuscitation in early SS. CRT-targeted resuscitation associated with lower mortality and organ dysfunction; mechanisms were not investigated. CRT was assessed every 30 min and lactate every 2 h during the 8-h intervention period, allowing a first comparison between groups at 2 h (T2). Our primary aim was to determine if SS patients evolving with normal CRT at T2 after randomization (T0) exhibited a higher mortality and organ dysfunction when allocated to the LT arm than when randomized to the CRT arm. Our secondary aim was to determine if those patients with normal CRT at T2 had received more therapeutic interventions when randomized to the LT arm. To address these issues, we performed a post hoc analysis of the ANDROMEDA-SHOCK dataset. RESULTS:Patients randomized to the lactate arm at T0, evolving with normal CRT at T2 exhibited significantly higher mortality than patients with normal CRT at T2 initially allocated to CRT (40 vs 23%, p?=?0.009). These results replicated at T8 and T24. LT arm received significantly more resuscitative interventions (fluid boluses: 1000[500-2000] vs. 500[0-1500], p?=?0.004; norepinephrine test in previously hypertensive patients: 43 (35) vs. 19 (19), p?=?0.001; and inodilators: 16 (13) vs. 3 (3), p?=?0.003). A multivariate logistic regression of patients with normal CRT at T2, including APACHE-II, baseline lactate, cumulative fluids administered since emergency admission, source of infection, and randomization group) confirmed that allocation to LT group was a statistically significant determinant of 28-day mortality (OR 3.3; 95%CI[1.5-7.1]); p?=?0.003). CONCLUSIONS:Septic shock patients with normal CRT at baseline received more therapeutic interventions and presented more organ dysfunction when allocated to the lactate group. This could associate with worse outcomes.

Dataset Information

Systematic assessment of fluid responsiveness during early septic shock resuscitation: secondary analysis of the ANDROMEDA-SHOCK trial.

Publications

Systematic assessment of fluid responsiveness during early septic shock resuscitation: secondary analysis of the ANDROMEDA-SHOCK trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets