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Hepatic Perfusion Alterations in Septic Shock Patients: Impact of Early Goal-directed Therapy.

ABSTRACT: Early goal-directed therapy (EGDT) has become an important therapeutic management in early salvage stage of septic shock. However, splenic organs possibly remained hypoperfused and hypoxic despite fluid resuscitation. This study aimed to evaluate the effect of EGDT on hepatic perfusion in septic shock patients.A prospective observational study was carried out in early septic shock patients who were admitted to Intensive Care Unit within 24 h after onset and who met all four elements of the EGDT criteria after treatment with the standard EGDT procedure within 6 h between December 1, 2012 and November 30, 2013. The hemodynamic data were recorded, and oxygen metabolism and hepatic functions were monitored. An indocyanine green clearance test was applied to detect the hepatic perfusion. The patients' characteristics were compared before treatment (T0), immediately after EGDT (T1), and 24 h after EGDT (T2). This study is registered at ClinicalTrials.org, NCT02060773.Twenty-one patients were included in the study; however, the hepatic perfusion data were not included in the analysis for two patients; therefore, 19 patients were eligible for the study. Hemodynamics data, as monitored by pulse-indicator continuous cardiac output, were obtained from 16 patients. There were no significant differences in indocyanine green plasma disappearance rate (ICG-PDR) and 15-min retention rate (R15) at T0 (11.9 ± 5.0%/min and 20.0 ± 13.2%), T1 (11.4 ± 5.1%/min and 23.6 ± 14.9%), and T2 (11.0 ± 4.5%/min and 23.7 ± 15.3%) (all P > 0.05). Both of the alterations of ICG-PDR and R15 showed no differences at T0, T1, and T2 in the patients of different subgroups that achieved different resuscitation goal numbers when elected (P > 0.05).There were no hepatic perfusion improvements after EGDT in the early phase of patients with septic shock.Clinicaltrials.gov NCT02060773 (https://clinicaltrials.gov/ct2/show/NCT02060773).

SUBMITTER: Zhang XW

PROVIDER: S-EPMC4960955 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Hepatic Perfusion Alterations in Septic Shock Patients: Impact of Early Goal-directed Therapy.

Zhang Xi-Wen XW Xie Jian-Feng JF Liu Ai-Ran AR Huang Ying-Zi YZ Guo Feng-Mei FM Yang Cong-Shan CS Yang Yi Y Qiu Hai-Bo HB

Chinese medical journal 20160701 14

<h4>Background</h4>Early goal-directed therapy (EGDT) has become an important therapeutic management in early salvage stage of septic shock. However, splenic organs possibly remained hypoperfused and hypoxic despite fluid resuscitation. This study aimed to evaluate the effect of EGDT on hepatic perfusion in septic shock patients.<h4>Methods</h4>A prospective observational study was carried out in early septic shock patients who were admitted to Intensive Care Unit within 24 h after onset and who ...[more]

PMID: 27411453

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Project description:ObjectiveEchocardiography 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).MethodsWe 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.ResultsThirty 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).ConclusionsNo 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 registrationThis 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:Central venous catheterization (CVC) can be an important component of the management of patients with severe sepsis and septic shock. CVC, however, is a time- and resource-intensive procedure associated with serious complications. The effects of the absence of shock or the presence of relative contraindications on undertaking central line placement in septic emergency department (ED) patients eligible for early goal-directed therapy (EGDT) have not been well described. We sought to determine the association of relative normotension (sustained systolic blood pressure >90 mmHg independent of or in response to an initial crystalloid resuscitation of 20 mL/kg), obesity (body mass index [BMI] ≥30), moderate thrombocytopenia (platelet count <50,000 per μL), and coagulopathy (international normalized ratio ≥2.0) with unattempted CVC in EGDT-eligible patients.This was a retrospective cohort study of 421 adults who met EGDT criteria in 5 community EDs over a period of 13 months. We compared patients with attempted thoracic (internal jugular or subclavian) CVC with those who did not undergo an attempted thoracic line. We also compared patients with any attempted CVC (either thoracic or femoral) with those who did not undergo any attempted central line. We used multivariate logistic regression analysis to calculate adjusted odd ratios (AORs).In our study, 364 (86.5%) patients underwent attempted thoracic CVC and 57 (13.5%) did not. Relative normotension was significantly associated with unattempted thoracic CVC (AOR 2.6 95% confidence interval [CI], 1.6-4.3), as were moderate thrombocytopenia (AOR 3.9; 95% CI, 1.5-10.1) and coagulopathy (AOR 2.7; 95% CI, 1.3-5.6). When assessing for attempted catheterization of any central venous site (thoracic or femoral), 382 (90.7%) patients underwent attempted catheterization and 39 (9.3%) patients did not. Relative normotension (AOR 2.3; 95% CI, 1.2-4.5) and moderate thrombocytopenia (AOR 3.9; 95% CI, 1.5-10.3) were significantly associated with unattempted CVC, whereas coagulopathy was not (AOR 0.6; 95% CI, 0.2-1.8). Obesity was not significantly associated with unattempted CVC, either thoracic in location or at any site.Septic patients eligible for EGDT with relative normotension and those with moderate thrombocytopenia were less likely to undergo attempted CVC at any site. Those with coagulopathy were also less likely to undergo attempted thoracic central line placement. Knowledge of the decision-making calculus at play for physicians considering central venous catheterization in this population can help inform physician education and performance improvement programs.

Project description: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).

Project description:ObjectivesAs the catabolic state induced by septic shock together with the physical inactivity of patients lead to the rapid loss of muscle mass and impaired function, the purpose of this study was to test whether an early physical therapy during the onset of septic shock regulates catabolic signals and preserves skeletal muscle mass.DesignRandomized controlled trial.SettingTertiary mixed ICU.PatientsAdult patients admitted for septic shock within the first 72 hours.InterventionsPatients were assigned randomly into two groups. The control group benefited from manual mobilization once a day. The intervention group had twice daily sessions of both manual mobilization and 30-minute passive/active cycling therapy.Measurements and main resultsSkeletal muscle biopsies and electrophysiology testing were performed at day 1 and day 7. Muscle biopsies were analyzed for histology and molecular components of signaling pathways regulating protein synthesis and degradation as well as inflammation markers. Hemodynamic values and patient perception were collected during each session. Twenty-one patients were included. Three died before the second muscle biopsy. Ten patients in the control and eight in the intervention group were analyzed. Markers of the catabolic ubiquitin-proteasome pathway, muscle atrophy F-box and muscle ring finger-1 messenger RNA, were reduced at day 7 only in the intervention group, but without difference between groups (muscle atrophy F-box: -7.3% ± 138.4% in control vs -56.4% ± 37.4% in intervention group; p = 0.23 and muscle ring finger-1: -30.8% ± 66.9% in control vs -62.7% ± 45.5% in intervention group; p = 0.15). Muscle fiber cross-sectional area (µm) was preserved by exercise (-25.8% ± 21.6% in control vs 12.4% ± 22.5% in intervention group; p = 0.005). Molecular regulations suggest that the excessive activation of autophagy due to septic shock was lower in the intervention group, without being suppressed. Markers of anabolism and inflammation were not modified by the intervention, which was well tolerated by the patients.ConclusionsEarly physical therapy during the first week of septic shock is safe and preserves muscle fiber cross-sectional area.

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Hepatic Perfusion Alterations in Septic Shock Patients: Impact of Early Goal-directed Therapy.

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Hepatic Perfusion Alterations in Septic Shock Patients: Impact of Early Goal-directed Therapy.

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