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Impact of Very Early Physical Therapy During Septic Shock on Skeletal Muscle: A Randomized Controlled Trial.

ABSTRACT: OBJECTIVES:As 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. DESIGN:Randomized controlled trial. SETTING:Tertiary mixed ICU. PATIENTS:Adult patients admitted for septic shock within the first 72 hours. INTERVENTIONS:Patients 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 RESULTS:Skeletal 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. CONCLUSIONS:Early physical therapy during the first week of septic shock is safe and preserves muscle fiber cross-sectional area.

SUBMITTER: Hickmann CE

PROVIDER: S-EPMC6110624 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Impact of Very Early Physical Therapy During Septic Shock on Skeletal Muscle: A Randomized Controlled Trial.

Hickmann Cheryl E CE Castanares-Zapatero Diego D Deldicque Louise L Van den Bergh Peter P Caty Gilles G Robert Annie A Roeseler Jean J Francaux Marc M Laterre Pierre-François PF

Critical care medicine 20180901 9

<h4>Objectives</h4>As 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.<h4>Design</h4>Randomized controlled trial.<h4>Setting</h4>Tertiary mixed ICU.<h4>Patients</h4>Adult patients admitted for septic shock within the first 72 ...[more]

PMID: 29957714

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Project description:Sepsis is defined as a dysregulated host response to infection leading to organs failure. Among them, sepsis induces skeletal muscle (SM) alterations that contribute to acquired-weakness in critically ill patients. Proteomics and metabolomics could unravel biological mechanisms in sepsis-related organ dysfunction. Our objective was to characterize a distinctive signature of septic shock in human SM by using an integrative multi-omics approach. Muscle biopsies were obtained as part of a multicenter non-interventional prospective study. Study population included patients in septic shock (S group, with intra-abdominal source of sepsis) and two critically ill control populations: cardiogenic shock (C group) and brain dead (BD group). The proteins and metabolites were extracted and analyzed by High-Performance Liquid Chromatography-coupled to tandem Mass Spectrometry, respectively. Fifty patients were included, 19 for the S group (53% male, 64 ± 17 years, SAPS II 45 ± 14), 12 for the C group (75% male, 63 ± 4 years, SAPS II 43 ± 15), 19 for the BD group (63% male, 58 ± 10 years, SAPS II 58 ± 9). Biopsies were performed in median 3 days [interquartile range 1-4]) after intensive care unit admission. Respectively 31 patients and 40 patients were included in the proteomics and metabolomics analyses of 2264 proteins and 259 annotated metabolites. Enrichment analysis revealed that mitochondrial pathways were significantly decreased in the S group at protein level: oxidative phosphorylation (adjusted p = 0.008); branched chained amino acids degradation (adjusted p = 0.005); citrate cycle (adjusted p = 0.005); ketone body metabolism (adjusted p = 0.003) or fatty acid degradation (adjusted p = 0.008). Metabolic reprogramming was also suggested (i) by the differential abundance of the peroxisome proliferator-activated receptors signaling pathway (adjusted p = 0.007), and (ii) by the accumulation of fatty acids like octanedioic acid dimethyl or hydroxydecanoic. Increased polyamines and depletion of mitochondrial thioredoxin or mitochondrial peroxiredoxin indicated a high level of oxidative stress in the S group. Coordinated alterations in the proteomic and metabolomic profiles reveal a septic shock signature in SM, highlighting a global impairment of mitochondria-related metabolic pathways, the depletion of antioxidant capacities, and a metabolic shift towards lipid accumulation.ClinicalTrial registration: NCT02789995. Date of first registration 03/06/2016.

Project description:OBJECTIVE:Evaluation of the ratio of oxyhaemoglobin to total haemoglobin in skeletal muscle (StO2) using near-infrared spectroscopy may aid in the monitoring of patients with sepsis. This study assessed the benefits and risks of targeting StO2 in adults with severe sepsis or septic shock. DESIGN:A European randomised controlled trial was performed on two parallel groups. SETTING:Five intensive care units (ICU) in France, Greece, Spain and Germany were used for the study. PARTICIPANTS:A total of 103 adults with severe sepsis or septic shock on ICU admission were randomised (54 subjects in the experimental arm and 49 subjects in the control arm). INTERVENTIONS:Haemodynamic management using an algorithm that was adapted from the 2004 Surviving Sepsis Campaign guidelines with (experimental arm) or without (control arm) targeting an StO2 value greater than 80% at a minimum of two different sites. OUTCOMES:The primary outcome was a composite: 7-day all-cause mortality or worsening of organ function, defined as a positive difference in Sepsis-related Organ Failure Assessment (SOFA) score between day 7 and randomisation (ie, delta SOFA >0). Secondary endpoints: 30-day mortality, duration of mechanical ventilation and vasopressor therapy up to 30 days from randomisation. RESULTS:The study ended prematurely due to lack of funding after enrolment of 103/190 patients. Eighteen patients (33.3%) in the experimental arm and 14 (28.6%, P=0.67) in the control arm died or exhibited delta SOFA >0 on day 7. The mean number of days on mechanical ventilation was 12.2±10.6 in the experimental group and 7.6±7.9 in the control group (P=0.03). Thirty-one (57%) patients in the experimental arm and 14 (29%) patients in the control arm received red cells by day 7 (P=0.01). CONCLUSION:Despite the limitation related to premature termination, this study provides no data to support the routine implementation of resuscitation protocols incorporating StO2 >80% at two or more muscle sites as a target. StO2-guided therapy may be associated with prolonged use of mechanical ventilation and an increased number of red blood cell transfusions. TRIAL REGISTRATION NUMBER:NCT00167596; Results.

Project description:BACKGROUND:Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock. METHODS:A total of 337 patients with sepsis requiring VP support for at least 6 h were initially selected from a prospectively collected database in a 90-bed mixed-ICU during a 24-month period. They were classified into very-early (VE-VPs) or delayed vasopressor start (D-VPs) categories according to whether norepinephrine was initiated or not within/before the next hour of the first resuscitative fluid load. Then, VE-VPs (n = 93) patients were 1:1 propensity matched to D-VPs (n = 93) based on age; source of admission (emergency room, general wards, intensive care unit); chronic and acute comorbidities; and lactate, heart rate, systolic, and diastolic pressure at vasopressor start. A risk-adjusted Cox proportional hazard model was fitted to assess the association between VE-VPs and day 28 mortality. Finally, a sensitivity analysis was performed also including those patients requiring VP support for less than 6 h. RESULTS:Patients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (0[0-510] vs. 1500[650-2300] mL, p < 0.001) and during the first 8 h of resuscitation (1100[500-1900] vs. 2600[1600-3800] mL, p < 0.001), with no significant increase in acute renal failure and/or renal replacement therapy requirements. VE-VPs was related with significant lower net fluid balances 8 and 24 h after VPs. VE-VPs was also associated with a significant reduction in the risk of death compared to D-VPs (HR 0.31, CI95% 0.17-0.57, p < 0.001) at day 28. Such association was maintained after including patients receiving vasopressors for < 6 h. CONCLUSION:A very early start of vasopressor support seems to be safe, might limit the amount of fluids to resuscitate septic shock, and could lead to better clinical outcomes.

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.

Dataset Information

Impact of Very Early Physical Therapy During Septic Shock on Skeletal Muscle: A Randomized Controlled Trial.

Publications

Impact of Very Early Physical Therapy During Septic Shock on Skeletal Muscle: A Randomized Controlled Trial.

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