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Continuous neuromuscular blockade infusion for out-of-hospital cardiac arrest patients treated with targeted temperature management: A multicenter randomized controlled trial.

ABSTRACT: INTRODUCTION:The aim of this trial was to investigate the effect of a continuous infusion of a neuromuscular blockade (NMB) in comatose out-of-hospital cardiac arrest (OHCA) subjects who underwent targeted temperature management (TTM). METHODS:In this open-label, multicenter trial, subjects resuscitated from OHCA were randomly assigned to receive either NMB (38 subjects) or placebo (43 subjects) for 24 hours. Sedatives and analgesics were given according to the protocol of each hospital during TTM. The primary outcome was serum lactate levels at 24 hours after drug infusion. The secondary outcomes included in-hospital mortality, a poor neurological outcome at hospital discharge, changes in lactate levels, changes in the PaO2:FiO2 ratio over time and muscle weakness as assessed by the Medical Research Council (MRC) scale. RESULTS:Eighty-one subjects (NMB group: median age, 65.5 years, 30 male patients; placebo group: median age, 61.0 years, 29 male patients) were enrolled in this trial. No difference in the serum lactate level at 24 hours was observed between the NMB (2.8 [1.2-4.0]) and placebo (3.6 [1.8-5.2]) groups (p = 0.238). In-hospital mortality and a poor neurologic outcome at discharge did not differ between the two groups. No significant difference in the PaO2:FiO2 ratio over time (p = 0.321) nor the MRC score (p = 0.474) was demonstrated. CONCLUSIONS:In OHCA subjects who underwent TTM, a continuous infusion of NMB did not reduce lactate levels and did not improve survival or neurological outcome at hospital discharge. Our results indicated a limited potential for the routine use of NMB during early TTM. However, this trial may be underpowered to detect clinical differences, and future research should be conducted.

SUBMITTER: Lee BK

PROVIDER: S-EPMC6296517 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Continuous neuromuscular blockade infusion for out-of-hospital cardiac arrest patients treated with targeted temperature management: A multicenter randomized controlled trial.

Lee Byung Kook BK Cho In Soo IS Oh Joo Suk JS Choi Wook Jin WJ Wee Jung Hee JH Kim Chang Sun CS Kim Won Young WY Youn Chun Song CS

PloS one 20181217 12

<h4>Introduction</h4>The aim of this trial was to investigate the effect of a continuous infusion of a neuromuscular blockade (NMB) in comatose out-of-hospital cardiac arrest (OHCA) subjects who underwent targeted temperature management (TTM).<h4>Methods</h4>In this open-label, multicenter trial, subjects resuscitated from OHCA were randomly assigned to receive either NMB (38 subjects) or placebo (43 subjects) for 24 hours. Sedatives and analgesics were given according to the protocol of each ho ...[more]

PMID: 30557377

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Project description:BackgroundDefinition of temporal serum proteome profiles after out-of-hospital cardiac arrest may identify biological processes associated with severe hypoxia-ischaemia and reperfusion. It may further explore intervention effects for new mechanistic insights, identify candidate prognostic protein biomarkers and potential therapeutic targets. This pilot study aimed to investigate serum proteome profiles from unconscious patients admitted to hospital after out-of-hospital cardiac arrest according to temperature treatment and neurological outcome.MethodsSerum samples at 24, 48, and 72 h after cardiac arrest at three centres included in the Target Temperature Management after out-of-hospital cardiac arrest trial underwent data-independent acquisition mass spectrometry analysis (DIA-MS) to find changes in serum protein concentrations associated with neurological outcome at 6-month follow-up and targeted temperature management (TTM) at 33 °C as compared to 36 °C. Neurological outcome was defined according to Cerebral Performance Category (CPC) scale as "good" (CPC 1-2, good cerebral performance or moderate disability) or "poor" (CPC 3-5, severe disability, unresponsive wakefulness syndrome, or death).ResultsOf 78 included patients [mean age 66 ± 12 years, 62 (80.0%) male], 37 (47.4%) were randomised to TTM at 36 °C. Six-month outcome was poor in 47 (60.3%) patients. The DIA-MS analysis identified and quantified 403 unique human proteins. Differential protein abundance testing comparing poor to good outcome showed 19 elevated proteins in patients with poor outcome (log2-fold change (FC) range 0.28-1.17) and 16 reduced proteins (log2(FC) between - 0.22 and - 0.68), involved in inflammatory/immune responses and apoptotic signalling pathways for poor outcome and proteolysis for good outcome. Analysis according to level of TTM showed a significant protein abundance difference for six proteins [five elevated proteins in TTM 36 °C (log2(FC) between 0.33 and 0.88), one reduced protein (log2(FC) - 0.6)] mainly involved in inflammatory/immune responses only at 48 h after cardiac arrest.ConclusionsSerum proteome profiling revealed an increase in inflammatory/immune responses and apoptosis in patients with poor outcome. In patients with good outcome, an increase in proteolysis was observed, whereas TTM-level only had a modest effect on the proteome profiles. Further validation of the differentially abundant proteins in response to neurological outcome is necessary to validate novel biomarker candidates that may predict prognosis after cardiac arrest.

Dataset Information

Continuous neuromuscular blockade infusion for out-of-hospital cardiac arrest patients treated with targeted temperature management: A multicenter randomized controlled trial.

Publications

Continuous neuromuscular blockade infusion for out-of-hospital cardiac arrest patients treated with targeted temperature management: A multicenter randomized controlled trial.

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