The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study
Abstract Purpose The landiolol and organ failure in patients with septic shock (STRESS-L study) included a pre-planned sub-study to assess the effect of landiolol treatment on inflammatory and metabolomic markers. Methods Samples collected from 91 patients randomised to STRESS-L were profiled for im...
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2025-01-01
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| Series: | Intensive Care Medicine Experimental |
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| Online Access: | https://doi.org/10.1186/s40635-024-00708-6 |
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| author | Jarrod L. Thomas Kirsty C. McGee Anower Hossain Gavin D. Perkins Anthony C. Gordon Duncan Young Danny McAuley Mervyn Singer Ranjit Lall Tina Kramaric Janet M. Lord Tony Whitehouse Luis A. J. Mur for the STRESS-L. collaborators |
| author_facet | Jarrod L. Thomas Kirsty C. McGee Anower Hossain Gavin D. Perkins Anthony C. Gordon Duncan Young Danny McAuley Mervyn Singer Ranjit Lall Tina Kramaric Janet M. Lord Tony Whitehouse Luis A. J. Mur for the STRESS-L. collaborators |
| author_sort | Jarrod L. Thomas |
| collection | DOAJ |
| description | Abstract Purpose The landiolol and organ failure in patients with septic shock (STRESS-L study) included a pre-planned sub-study to assess the effect of landiolol treatment on inflammatory and metabolomic markers. Methods Samples collected from 91 patients randomised to STRESS-L were profiled for immune and metabolomic markers. A panel of pro- and anti-inflammatory cytokines were measured through commercially acquired multiplex Luminex assays and statistically analysed by individual and cluster-level analysis (patient). Metabolite fingerprinting was carried out by flow infusion electrospray ionisation high-resolution mass spectrometry and metabolomic data were analysed using the R-based platform MetaboAnalyst. The metabolites were identified using DIMEdb (dimedb.ibers.aber.ac.uk) from their mass/charge ratios. These metabolomic data were also re-analysed using individual and cluster-level analysis. The individual-level models were adjusted for confounders, such as age, sex, noradrenaline dosage and patient (random effect). Results Analysis was undertaken at cluster- and individual-level. There were no significant differences in cytokine concentration level between trial arms nor survivors and non-survivors over the duration of the observations from day 1 to day 4. Metabolomic analysis showed some separation in the levels of ceramides and cardiolipins between those who survived and those who died. Following adjusted analysis for confounders, plasma metabolite concentrations remained statistically different between landiolol and standard care arms for succinic acid, l-tryptophan, l-alanine, 2,2,2-trichloroethanol, lactic acid and d-glucose. Conclusions In a study of ICU patients with established septic shock and a tachycardia, landiolol treatment used to reduce the heart rate from above 95 to a range between 80 and 94 beats per minute did not induce significant cytokine changes. d-Glucose, lactic acid, succinic acid, l-alanine, l-tryptophan and trichloroethanol were pathways that may merit further investigation. Trial Registration: EU Clinical Trials Register Eudra CT: 2017-001785-14 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-001785-14/GB ); ISRCTN registry Identifier: ISRCTN12600919 ( https://www.isrctn.com/ISRCTN12600919 ). |
| format | Article |
| id | doaj-art-691497733e7e43dfb0ae5200d13d8e50 |
| institution | Kabale University |
| issn | 2197-425X |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-691497733e7e43dfb0ae5200d13d8e502025-01-26T12:10:17ZengSpringerOpenIntensive Care Medicine Experimental2197-425X2025-01-0113111010.1186/s40635-024-00708-6The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised StudyJarrod L. Thomas0Kirsty C. McGee1Anower Hossain2Gavin D. Perkins3Anthony C. Gordon4Duncan Young5Danny McAuley6Mervyn Singer7Ranjit Lall8Tina Kramaric9Janet M. Lord10Tony Whitehouse11Luis A. J. Mur12for the STRESS-L. collaboratorsInstitute of Inflammation and Ageing, College of Medical and Dental Sciences, University of BirminghamInstitute of Inflammation and Ageing, College of Medical and Dental Sciences, University of BirminghamWarwick Clinical Trials Unit, University of WarwickWarwick Clinical Trials Unit, University of WarwickDivision of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College LondonKadoorie Centre for Critical Care Research, Nuffield Division of Anaesthesia, University of OxfordRegional Intensive Care Unit, Royal Victoria Hospital, Belfast Health and Social Care TrustDepartment of Medicine and Wolfson Institute for Biomedical Research, Centre for Intensive Care Medicine, University College LondonWarwick Clinical Trials Unit, University of WarwickDepartment of Life Sciences, Aberystwyth UniversityInstitute of Inflammation and Ageing, College of Medical and Dental Sciences, University of BirminghamInstitute of Inflammation and Ageing, College of Medical and Dental Sciences, University of BirminghamDepartment of Life Sciences, Aberystwyth UniversityAbstract Purpose The landiolol and organ failure in patients with septic shock (STRESS-L study) included a pre-planned sub-study to assess the effect of landiolol treatment on inflammatory and metabolomic markers. Methods Samples collected from 91 patients randomised to STRESS-L were profiled for immune and metabolomic markers. A panel of pro- and anti-inflammatory cytokines were measured through commercially acquired multiplex Luminex assays and statistically analysed by individual and cluster-level analysis (patient). Metabolite fingerprinting was carried out by flow infusion electrospray ionisation high-resolution mass spectrometry and metabolomic data were analysed using the R-based platform MetaboAnalyst. The metabolites were identified using DIMEdb (dimedb.ibers.aber.ac.uk) from their mass/charge ratios. These metabolomic data were also re-analysed using individual and cluster-level analysis. The individual-level models were adjusted for confounders, such as age, sex, noradrenaline dosage and patient (random effect). Results Analysis was undertaken at cluster- and individual-level. There were no significant differences in cytokine concentration level between trial arms nor survivors and non-survivors over the duration of the observations from day 1 to day 4. Metabolomic analysis showed some separation in the levels of ceramides and cardiolipins between those who survived and those who died. Following adjusted analysis for confounders, plasma metabolite concentrations remained statistically different between landiolol and standard care arms for succinic acid, l-tryptophan, l-alanine, 2,2,2-trichloroethanol, lactic acid and d-glucose. Conclusions In a study of ICU patients with established septic shock and a tachycardia, landiolol treatment used to reduce the heart rate from above 95 to a range between 80 and 94 beats per minute did not induce significant cytokine changes. d-Glucose, lactic acid, succinic acid, l-alanine, l-tryptophan and trichloroethanol were pathways that may merit further investigation. Trial Registration: EU Clinical Trials Register Eudra CT: 2017-001785-14 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-001785-14/GB ); ISRCTN registry Identifier: ISRCTN12600919 ( https://www.isrctn.com/ISRCTN12600919 ).https://doi.org/10.1186/s40635-024-00708-6STRESS-Lβ-BlockerSepsisSeptic shockMetabolomicsCytokines |
| spellingShingle | Jarrod L. Thomas Kirsty C. McGee Anower Hossain Gavin D. Perkins Anthony C. Gordon Duncan Young Danny McAuley Mervyn Singer Ranjit Lall Tina Kramaric Janet M. Lord Tony Whitehouse Luis A. J. Mur for the STRESS-L. collaborators The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study Intensive Care Medicine Experimental STRESS-L β-Blocker Sepsis Septic shock Metabolomics Cytokines |
| title | The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study |
| title_full | The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study |
| title_fullStr | The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study |
| title_full_unstemmed | The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study |
| title_short | The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study |
| title_sort | effects of ultra selective beta1 antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline a sub investigation from the stress l randomised study |
| topic | STRESS-L β-Blocker Sepsis Septic shock Metabolomics Cytokines |
| url | https://doi.org/10.1186/s40635-024-00708-6 |
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