Multimodal strategy to counteract vasodilation in septic shock

Léone, Marc; Einav, Sharon; Antonucci, Elio; Dépret, François; Lakbar, Inès; Martín‐Loeches, Ignacio; Wieruszewski, Patrick M.; Myatra, Sheila Nainan; Khanna, Ashish K.

doi:10.1016/j.accpm.2023.101193

Cited by 17 publications

(9 citation statements)

References 98 publications

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“…Early initiation of vasopressin was recently determined to be helpful (31). Similarly, a substantial part of early-multimodal vasopressor therapy comes from prior published large datasets demonstrating a dose-dependent relationship between exclusive monotherapy with catecholamines (mainly norepinephrine) and adverse outcomes (22, 32). These observational studies are clouded by confounding and are liable to become further unreliable, especially if they work across countries or areas with different norepinephrine formulations.…”

Section: Discussionmentioning

confidence: 99%

Position Paper on the Reporting of Norepinephrine Formulations in Critical Care from the Society of Critical Care Medicine and European Society of Intensive Care Medicine Joint Task Force

Wieruszewski,

Leone,

Kaas-Hansen

et al. 2024

Critical Care Medicine

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Objectives: To provide guidance on the reporting of norepinephrine formulation labeling, reporting in publications, and use in clinical practice. Design: Review and task force position statements with necessary guidance. Setting: A series of group conference calls were conducted from August 2023 to October 2023, along with a review of the available evidence and scope of the problem. Subjects: A task force of multinational and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Interventions: The implications of a variation in norepinephrine labeled as conjugated salt (i.e., bitartrate or tartrate) or base drug in terms of effective concentration of norepinephrine were examined, and guidance was provided. Measurements and Main Results: There were significant implications for clinical care, dose calculations for enrollment in clinical trials, and results of datasets reporting maximal norepinephrine equivalents. These differences were especially important in the setting of collaborative efforts across countries with reported differences. Conclusions: A joint task force position statement was created outlining the scope of norepinephrine-dose formulation variations, and implications for research, patient safety, and clinical care. The task force advocated for a uniform norepinephrine-base formulation for global use, and offered advice aimed at appropriate stakeholders.

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Section: Discussionmentioning

confidence: 99%

Position Paper on the Reporting of Norepinephrine Formulations in Critical Care from the Society of Critical Care Medicine and European Society of Intensive Care Medicine Joint Task Force

Wieruszewski,

Leone,

Kaas-Hansen

et al. 2024

Critical Care Medicine

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“…This bias can lead to unwanted high doses of norepinephrine and misinterpretation of clinical trial results. In addition, delayed vasopressin introduction may be less effective than an early multimodal strategy based on combination of several vasopressors [ 4 , 5 ].…”

Section: Correspondencementioning

confidence: 99%

Norepinephrine formulation for equivalent vasopressive score

2023

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“…Norepinephrine is the first-choice [2], but high doses increase the risk of adverse effects such as tachyarrhythmia, myocardial dysfunction, peripheral ischemia, and even immunosuppression [5,6]. Therefore, a combination of agents targeting different systems involved in blood pressure regulation and endothelial function has been recently proposed [7][8][9]. This "multimodal strategy" could help to restore tissue perfusion while decreasing the potential toxicity of single agents [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…Based on large datasets, it is increasingly recognized that a higher exposure to catecholamine vasopressors is associated with an increased risk of multiple organ failure and death in septic shock [8,16,17]; thus, the time of norepinephrine requirement is a justified intermediate patient-centered outcome [18] in order to pave the way for adding catecholamine-sparing agents to a multimodal strategy [7,19]. We designed this RCT to assess if early adjunctive MB administration could reduce the time to vasopressor discontinuation in patients with septic shock, as compared to placebo.…”

Section: Introductionmentioning

confidence: 99%

Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial

et al. 2023

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Purpose Methylene blue (MB) has been tested as a rescue therapy for patients with refractory septic shock. However, there is a lack of evidence on MB as an adjuvant therapy, its’ optimal timing, dosing and safety profile. We aimed to assess whether early adjunctive MB can reduce time to vasopressor discontinuation in patients with septic shock. Methods In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo. Primary outcome was time to vasopressor discontinuation at 28 days. Secondary outcomes included vasopressor-free days at 28 days, days on mechanical ventilator, length of stay in ICU and hospital, and mortality at 28 days. Results Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo. The MB group had a shorter time to vasopressor discontinuation (69 h [IQR 59–83] vs 94 h [IQR 74–141]; p < 0.001), one more day of vasopressor-free days at day 28 (p = 0.008), a shorter ICU length of stay by 1.5 days (p = 0.039) and shorter hospital length of stay by 2.7 days (p = 0.027) compared to patients in the control group. Days on mechanical ventilator and mortality were similar. There were no serious adverse effects related to MB administration. Conclusion In patients with septic shock, MB initiated within 24 h reduced time to vasopressor discontinuation and increased vasopressor-free days at 28 days. It also reduced length of stay in ICU and hospital without adverse effects. Our study supports further research regarding MB in larger randomized clinical trials. Trial registration ClinicalTrials.gov registration number NCT04446871, June 25, 2020, retrospectively registered.

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Multimodal strategy to counteract vasodilation in septic shock

Cited by 17 publications

References 98 publications

Position Paper on the Reporting of Norepinephrine Formulations in Critical Care from the Society of Critical Care Medicine and European Society of Intensive Care Medicine Joint Task Force

Position Paper on the Reporting of Norepinephrine Formulations in Critical Care from the Society of Critical Care Medicine and European Society of Intensive Care Medicine Joint Task Force

Norepinephrine formulation for equivalent vasopressive score

Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial

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