{"id":1098,"date":"2025-08-06T06:00:44","date_gmt":"2025-08-06T06:00:44","guid":{"rendered":"https:\/\/perfusfind.com\/ic\/?p=1098"},"modified":"2026-01-27T16:46:42","modified_gmt":"2026-01-27T16:46:42","slug":"continuous-versus-bolus-norepinephrine-administration-and-arterial-blood-pressure-stability-during-induction-of-general-anaesthesia-in-high-risk-noncardiac-surgery-patients-a-randomised-trial","status":"publish","type":"post","link":"https:\/\/perfusfind.com\/ic\/index.php\/2025\/08\/06\/continuous-versus-bolus-norepinephrine-administration-and-arterial-blood-pressure-stability-during-induction-of-general-anaesthesia-in-high-risk-noncardiac-surgery-patients-a-randomised-trial\/","title":{"rendered":"Continuous versus bolus norepinephrine administration and arterial blood pressure stability during induction of general anaesthesia in high-risk noncardiac surgery patients: a randomised trial"},"content":{"rendered":"<blockquote class=\"article-editor-blockquote article-editor-content__has-focus\">\n<p class=\"article-editor-paragraph article-editor-content__has-focus\"><strong>Summary <\/strong><\/p>\n<\/blockquote>\n<p class=\"article-editor-paragraph\">This randomized clinical trial compared the effects of continuous norepinephrine infusion versus intermittent manual bolus administration on arterial blood pressure stability during induction of general anesthesia in high-risk noncardiac surgical patients. Seventy-one patients were randomized, and blood pressure stability was measured as generalized average real variability of mean arterial pressure (ARV-MAP) during the first 15 minutes post-induction. The study found that continuous norepinephrine infusion significantly improved arterial blood pressure stability compared to bolus administration, suggesting it may be preferable in high-risk surgical patients.<\/p>\n<div class=\"article-editor-horizontal-rule__container\" contenteditable=\"false\">\n<hr class=\"article-editor-horizontal-rule\" \/>\n<div class=\"article-editor-horizontal-rule__delete-button-container\"><\/div>\n<\/div>\n<blockquote class=\"article-editor-blockquote\">\n<p class=\"article-editor-paragraph\"><strong>Key Points<\/strong><\/p>\n<\/blockquote>\n<ol class=\"article-editor-ordered-list\">\n<li class=\"article-editor-list-item\">\n<p class=\"article-editor-paragraph\"><strong>Clinical Significance of Post-Induction Hypotension<\/strong>: Post-induction hypotension is common in high-risk surgical patients and is linked to adverse outcomes such as acute kidney injury and increased morbidity, underscoring the clinical importance of maintaining stable hemodynamics during anesthetic induction.<\/p>\n<\/li>\n<li class=\"article-editor-list-item\">\n<p class=\"article-editor-paragraph\"><strong>Trial Design and Methods<\/strong>: This single-center randomized trial enrolled 72 adult patients scheduled for high-risk elective noncardiac surgery who were at least 45 years old, had ASA status II-IV, and required arterial blood pressure monitoring. Patients were randomized to continuous or bolus norepinephrine administration during anesthetic induction.<\/p>\n<\/li>\n<li class=\"article-editor-list-item\">\n<p class=\"article-editor-paragraph\"><strong>Measurement and Endpoint<\/strong>: The primary outcome, arterial blood pressure stability, was quantified as generalized ARV-MAP over a 15-minute period following anesthetic induction. This measure effectively captures the variability and stability of mean arterial pressure in real-time.<\/p>\n<\/li>\n<li class=\"article-editor-list-item\">\n<p class=\"article-editor-paragraph\"><strong>Improved Hemodynamic Stability<\/strong>: Continuous norepinephrine infusion resulted in significantly better blood pressure stability, with a mean ARV-MAP of 19 mmHg\/min, compared to 25 mmHg\/min in the bolus group, indicating more stable hemodynamics during a critical perioperative period.<\/p>\n<\/li>\n<li class=\"article-editor-list-item\">\n<p class=\"article-editor-paragraph\"><strong>Reduced Duration and Severity of Hypotension<\/strong>: Patients receiving continuous infusion experienced significantly shorter cumulative durations of MAP below 65 mmHg compared to those receiving manual boluses, suggesting better control and reduced exposure to hypotensive episodes.<\/p>\n<\/li>\n<li class=\"article-editor-list-item\">\n<p class=\"article-editor-paragraph\"><strong>Safety and Hypertension Risk<\/strong>: Although continuous norepinephrine infusion involved higher cumulative drug doses, it did not significantly increase the risk of hypertension, demonstrating its safety profile and manageable hemodynamic effects when carefully titrated.<\/p>\n<\/li>\n<li class=\"article-editor-list-item\">\n<p class=\"article-editor-paragraph\"><strong>Patient Selection and Risk Profile<\/strong>: The study specifically targeted older patients with chronic conditions such as hypertension, who are at greater risk for perioperative instability, highlighting the clinical relevance of these findings in real-world high-risk patient populations.<\/p>\n<\/li>\n<li class=\"article-editor-list-item\">\n<p class=\"article-editor-paragraph\"><strong>Practical Clinical Implications<\/strong>: The trial results advocate the routine use of continuous norepinephrine infusions to maintain stable blood pressure during induction of anesthesia in high-risk patients, potentially improving perioperative outcomes by minimizing hemodynamic instability.<\/p>\n<\/li>\n<li class=\"article-editor-list-item\">\n<p class=\"article-editor-paragraph\"><strong>Limitations and Future Research Needs<\/strong>: While promising, this study was limited by its small sample size, single-center design, short observational period, and lack of long-term clinical outcome assessments, indicating the necessity for larger multi-center trials.<\/p>\n<\/li>\n<li class=\"article-editor-list-item\">\n<p class=\"article-editor-paragraph\"><strong>Recommendations for Clinical Practice<\/strong>: The authors recommend considering continuous norepinephrine administration as a viable strategy for enhancing arterial blood pressure stability during anesthetic induction in patients undergoing high-risk noncardiac surgeries.<\/p>\n<\/li>\n<\/ol>\n<div class=\"article-editor-horizontal-rule__container\" contenteditable=\"false\">\n<hr class=\"article-editor-horizontal-rule\" \/>\n<div class=\"article-editor-horizontal-rule__delete-button-container\"><\/div>\n<\/div>\n<blockquote class=\"article-editor-blockquote\">\n<p class=\"article-editor-paragraph\"><strong>Conclusion<\/strong><\/p>\n<\/blockquote>\n<p class=\"article-editor-paragraph\">Continuous administration of norepinephrine during anesthetic induction significantly improves arterial blood pressure stability compared to intermittent bolus dosing in high-risk noncardiac surgery patients. This strategy offers a practical approach to enhance perioperative hemodynamic control, potentially reducing complications associated with post-induction hypotension.<\/p>\n<blockquote class=\"article-editor-blockquote\">\n<p class=\"article-editor-paragraph\"><a class=\"article-editor-link article-editor-link\" href=\"https:\/\/www.bjanaesthesia.org\/article\/S0007-0912(25)00408-8\/fulltext#fig1\" rel=\"noopener noreferrer\">ACCESS FULL ARTICLE HERE<\/a><\/p>\n<\/blockquote>\n<figure class=\"article-editor-figure-image\" data-id=\"83537dc8-5a35-4828-b6c2-729e39a5fcc9\">\n<div class=\"article-editor-inline-image__container article-editor-inline-image__container--full-width\" contenteditable=\"false\">\n<div class=\"article-editor-content__element-overlay\">\n<div class=\"article-editor-inline-image__buttons\">\n<div class=\"resize-image-control-button-tooltip resize-image-control-button-tooltip--hidden\">Minimize image<\/div>\n<div class=\"resize-image-control-button-tooltip 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\" alt=\"\" \/><\/p>\n<\/div>\n<\/figure>\n<div class=\"article-editor-horizontal-rule__container\" contenteditable=\"false\">\n<hr class=\"article-editor-horizontal-rule\" \/>\n<div class=\"article-editor-horizontal-rule__delete-button-container\"><\/div>\n<\/div>\n<p class=\"article-editor-paragraph\"><strong>Open Access<\/strong> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article&#8217;s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article&#8217;s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit <a class=\"article-editor-link article-editor-link\" href=\"http:\/\/creativecommons.org\/licenses\/by\/4.0\/\" rel=\"noopener noreferrer\"><strong>http:\/\/creativecommons.org\/licenses\/by\/4.0\/<\/strong><\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Summary This randomized clinical trial compared the effects of continuous norepinephrine infusion versus intermittent manual bolus administration on arterial blood pressure stability during induction of general anesthesia in high-risk noncardiac surgical patients. Seventy-one patients were randomized, and blood pressure stability was measured as generalized average real variability of mean arterial pressure (ARV-MAP) during the first [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":1099,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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