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Early goal-directed therapy using a physiological holistic view: the ANDROMEDA-SHOCK-a randomized controlled trial.

ABSTRACT: BACKGROUND:Septic shock is a highly lethal condition. Early recognition of tissue hypoperfusion and its reversion are key factors for limiting progression to multiple organ dysfunction and death. Lactate-targeted resuscitation is the gold-standard under current guidelines, although it has several pitfalls including that non-hypoxic sources of lactate might predominate in an unknown proportion of patients. Peripheral perfusion-targeted resuscitation might provide a real-time response to increases in flow that could lead to a more timely decision to stop resuscitation, thus avoiding fluid overload and the risks of over-resuscitation. This article reports the rationale, study design and analysis plan of the ANDROMEDA-SHOCK Study. METHODS:ANDROMEDA-SHOCK is a randomized controlled trial which aims to determine if a peripheral perfusion-targeted resuscitation is associated with lower 28-day mortality compared to a lactate-targeted resuscitation in patients with septic shock with less than 4 h of diagnosis. Both groups will be treated with the same sequential approach during the 8-hour study period pursuing normalization of capillary refill time versus normalization or a decrease of more than 20% of lactate every 2 h. The common protocol starts with fluid responsiveness assessment and fluid loading in responders, followed by a vasopressor and an inodilator test if necessary. The primary outcome is 28-day mortality, and the secondary outcomes are: free days of mechanical ventilation, renal replacement therapy and vasopressor support during the first 28 days after randomization; multiple organ dysfunction during the first 72 h after randomization; intensive care unit and hospital lengths of stay; and all-cause mortality at 90-day. A sample size of 422 patients was calculated to detect a 15% absolute reduction in mortality in the peripheral perfusion group with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. CONCLUSIONS:If peripheral perfusion-targeted resuscitation improves 28-day mortality, this could lead to simplified algorithms, assessing almost in real-time the reperfusion process, and pursuing more physiologically sound objectives. At the end, it might prevent the risk of over-resuscitation and lead to a better utilization of intensive care unit resources. Trial registration ClinicalTrials.gov Identifier: NCT03078712 (registered retrospectively March 13th, 2017).

SUBMITTER: Hernandez G

PROVIDER: S-EPMC5913056 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Early goal-directed therapy using a physiological holistic view: the ANDROMEDA-SHOCK-a randomized controlled trial.

Hernández Glenn G Cavalcanti Alexandre Biasi AB Ospina-Tascón Gustavo G Zampieri Fernando Godinho FG Dubin Arnaldo A Hurtado F Javier FJ Friedman Gilberto G Castro Ricardo R Alegría Leyla L Cecconi Maurizio M Teboul Jean-Louis JL Bakker Jan J

Annals of intensive care 20180423 1

<h4>Background</h4>Septic shock is a highly lethal condition. Early recognition of tissue hypoperfusion and its reversion are key factors for limiting progression to multiple organ dysfunction and death. Lactate-targeted resuscitation is the gold-standard under current guidelines, although it has several pitfalls including that non-hypoxic sources of lactate might predominate in an unknown proportion of patients. Peripheral perfusion-targeted resuscitation might provide a real-time response to i ...[more]

PMID: 29687277

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Project description:Objective:Echocardiography is often used to guide septic shock resuscitation, but without evidence for efficacy. We conducted an intensive care unit (ICU)-based randomized controlled feasibility trial comparing echocardiography-guided septic shock resuscitation (ECHO) with early goal-directed therapy (EGDT). Methods:We conducted a single center, randomized controlled feasibility trial at a 468-bed academic tertiary care center in Utah, USA. Adult patients with early septic shock were assessed and treated at defined intervals over 6 h using an echocardiogram-guided resuscitation protocol or a slightly modified EGDT protocol. Feasibility outcomes were fluid balance, dobutamine administration, and time to lactate clearance. The primary clinical outcome was changed in sequential organ failure assessment score at 48 h (delta SOFA). Secondary outcomes included inpatient mortality, ICU-free days, and ventilator-free days at 28 days. Results:Thirty participants, 15 per group, were randomized and completed the study. Baseline characteristics were similar between groups. Patients were randomized within a median of 3.5 h of meeting inclusion criteria but had received a median of 3 L crystalloid by then. Fluid administration during the study protocol was similar in both groups (median ECHO 0 vs EGDT 1 L, p?=?0.61). Eleven (73%) subjects in each arm received ??1 L fluid. Dobutamine administration was also similar (20% vs 13%, p?>?0.99). Twenty-one patients (70%) had lactate clearance prior to the first study assessment. No difference was observed in delta SOFA (median -?4 for ECHO vs -?6 for EGDT, p?=?0.10) nor mortality (33% ECHO vs 20% EGDT, p?=?0.68). Conclusions:No experimental separation was observed in this randomized, controlled feasibility trial. Early lactate clearance, coupled with substantial fluid administration before randomization, suggests that patients were already resuscitated before arrival in the ICU. Future trials of echocardiogram-guided sepsis resuscitation will likely need to enroll in the emergency department. Trial registration:This study was retrospectively registered at clinicaltrials.gov (identifier NCT02354742, title Echo vs EGDT in severe sepsis and septic shock) on February 3, 2015. Registration was completed before review or analysis of any data.

Project description:OBJECTIVE:To assess the efficacy of a simple, goal-directed sepsis treatment protocol for reducing mortality in patients with severe sepsis in Zambia. DESIGN:Single-center nonblinded randomized controlled trial. SETTING:Emergency department, ICU, and medical wards of the national referral hospital in Lusaka, Zambia. PATIENTS:One hundred twelve patients enrolled within 24 hours of admission with severe sepsis, defined as systemic inflammatory response syndrome with suspected infection and organ dysfunction INTERVENTIONS:: Simplified Severe Sepsis Protocol consisting of up to 4 L of IV fluids within 6 hours, guided by jugular venous pressure assessment, and dopamine and/or blood transfusion in selected patients. Control group was managed as usual care. Blood cultures were collected and early antibiotics administered for both arms. MEASUREMENTS AND MAIN RESULTS:Primary outcome was in-hospital all-cause mortality. One hundred nine patients were included in the final analysis and 88 patients (80.7%) were HIV positive. Pulmonary infections were the most common source of sepsis. In-hospital mortality rate was 64.2% in the intervention group and 60.7% in the control group (relative risk, 1.05; 95% CI, 0.79-1.41). Mycobacterium tuberculosis complex was isolated from 31 of 82 HIV-positive patients (37.8%) with available mycobacterial blood culture results. Patients in Simplified Severe Sepsis Protocol received significantly more IV fluids in the first 6 hours (2.7 L vs 1.7 L, p = 0.002). The study was stopped early because of high mortality rate among patients with hypoxemic respiratory failure in the intervention arm (8/8, 100%) compared with the control arm (7/10, 70%; relative risk, 1.43; 95% CI, 0.95-2.14). CONCLUSION:Factors other than tissue hypoperfusion probably account for much of the end-organ dysfunction in African patients with severe sepsis. Studies of fluid-based interventions should utilize inclusion criteria to accurately capture patients with hypovolemia and tissue hypoperfusion who are most likely to benefit from fluids. Exclusion of patients with severe respiratory distress should be considered when ventilatory support is not readily available.

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Early goal-directed therapy using a physiological holistic view: the ANDROMEDA-SHOCK-a randomized controlled trial.

Publications

Early goal-directed therapy using a physiological holistic view: the ANDROMEDA-SHOCK-a randomized controlled trial.

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