{"id":1545,"date":"2026-03-22T12:12:15","date_gmt":"2026-03-22T12:12:15","guid":{"rendered":"https:\/\/perfusfind.com\/ic\/?p=1545"},"modified":"2026-03-22T15:31:23","modified_gmt":"2026-03-22T15:31:23","slug":"the-metabolic-response-to-stress-in-critical-illness-updated-review-on-the-pathophysiological-mechanisms-consequences-and-therapeutic-implications","status":"publish","type":"post","link":"https:\/\/perfusfind.com\/ic\/index.php\/2026\/03\/22\/the-metabolic-response-to-stress-in-critical-illness-updated-review-on-the-pathophysiological-mechanisms-consequences-and-therapeutic-implications\/","title":{"rendered":"The metabolic response to stress in critical illness: updated review on the pathophysiological mechanisms, consequences, and therapeutic implications"},"content":{"rendered":"<h3 id=\"ember63\" class=\"ember-view reader-text-block__heading-3\">Why this article matters<\/h3>\n<p id=\"ember64\" class=\"ember-view reader-text-block__paragraph\">Critical illness triggers a profound, highly coordinated metabolic stress response that extends far beyond \u201chypercatabolism.\u201d This comprehensive review reframes how we understand energy metabolism, nutrition, endocrine signaling, immune function, and recovery across the <strong>acute, subacute, and chronic phases<\/strong> of critical illness. Importantly, it challenges long-standing assumptions around \u201cearly full feeding\u201d and high-protein strategies, advocating instead for <strong>phase-appropriate, physiology-aligned metabolic care<\/strong>.<\/p>\n<p><img fetchpriority=\"high\" decoding=\"async\" class=\"aligncenter wp-image-1547 size-large\" src=\"https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938728816-1024x662.png\" alt=\"\" width=\"1024\" height=\"662\" srcset=\"https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938728816-1024x662.png 1024w, https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938728816-300x194.png 300w, https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938728816-768x497.png 768w, https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938728816.png 1488w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><\/p>\n<p>&nbsp;<\/p>\n<h3 id=\"ember66\" class=\"ember-view reader-text-block__heading-3\">Key concepts you need to know<\/h3>\n<h3 id=\"ember67\" class=\"ember-view reader-text-block__heading-3\">1. The metabolic response to stress is phasic, not static<\/h3>\n<p id=\"ember68\" class=\"ember-view reader-text-block__paragraph\">The authors describe <strong>three overlapping phases<\/strong>:<\/p>\n<ul>\n<li><strong>Acute phase:<\/strong> Sympathetic activation, cortisol dominance, insulin resistance, and rapid catabolism<\/li>\n<li><strong>Subacute phase:<\/strong> Persistent inflammation, mitochondrial dysfunction, anabolic resistance<\/li>\n<li><strong>Chronic phase \/ recovery:<\/strong> Either transition toward anabolic repair <em>or<\/em> progression to chronic critical illness (CCI) and PICS<\/li>\n<\/ul>\n<p id=\"ember70\" class=\"ember-view reader-text-block__paragraph\">Failure to recognize these phases leads to mistimed nutrition and iatrogenic harm.<\/p>\n<p><img decoding=\"async\" class=\"aligncenter wp-image-1548 size-large\" src=\"https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938760334-1024x719.png\" alt=\"\" width=\"1024\" height=\"719\" srcset=\"https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938760334-1024x719.png 1024w, https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938760334-300x211.png 300w, https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938760334-768x539.png 768w, https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938760334.png 1425w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><\/p>\n<p>&nbsp;<\/p>\n<h3 id=\"ember72\" class=\"ember-view reader-text-block__heading-3\">2. Early catabolism is adaptive \u2014 forcing anabolism may be harmful<\/h3>\n<p id=\"ember73\" class=\"ember-view reader-text-block__paragraph\">During early critical illness, endogenous energy production remains high and <strong>cannot be fully suppressed by feeding<\/strong>. Excess early calories or protein:<\/p>\n<ul>\n<li>Inhibit autophagy<\/li>\n<li>Worsen mitochondrial dysfunction<\/li>\n<li>Increase lipotoxicity and oxidative stress<\/li>\n<\/ul>\n<p id=\"ember75\" class=\"ember-view reader-text-block__paragraph\">This explains why trials supporting <strong>early full feeding or high protein<\/strong> have largely failed to improve outcomes.<\/p>\n<hr class=\"reader-divider-block__horizontal-rule\" \/>\n<h3 id=\"ember76\" class=\"ember-view reader-text-block__heading-3\">3. Mitochondrial dysfunction is central to metabolic failure<\/h3>\n<p id=\"ember77\" class=\"ember-view reader-text-block__paragraph\">Critical illness shifts energy production away from efficient \u03b2-oxidation toward:<\/p>\n<ul>\n<li>Glycolysis<\/li>\n<li>Lactate utilization<\/li>\n<li>Ketone metabolism<\/li>\n<\/ul>\n<p id=\"ember79\" class=\"ember-view reader-text-block__paragraph\">Markers such as <strong>N-formylmethionine, acylcarnitines, and lactate<\/strong> reflect impaired oxidative phosphorylation. Inadequate autophagy allows damaged mitochondria to accumulate, directly linking metabolic failure to mortality.<\/p>\n<p><img decoding=\"async\" class=\"aligncenter wp-image-1549 size-large\" src=\"https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938796164-1024x728.png\" alt=\"\" width=\"1024\" height=\"728\" srcset=\"https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938796164-1024x728.png 1024w, https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938796164-300x213.png 300w, https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938796164-768x546.png 768w, https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938796164.png 1407w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><\/p>\n<p>&nbsp;<\/p>\n<h3 id=\"ember81\" class=\"ember-view reader-text-block__heading-3\">4. Lactate and ketones are not \u201cwaste products\u201d<\/h3>\n<p id=\"ember82\" class=\"ember-view reader-text-block__paragraph\">The review reframes lactate as a <strong>key alternative fuel and signaling molecule (\u201clactormone\u201d)<\/strong>, supporting:<\/p>\n<ul>\n<li>Brain, immune, and renal metabolism<\/li>\n<li>Immune modulation and inflammation resolution<\/li>\n<\/ul>\n<p id=\"ember84\" class=\"ember-view reader-text-block__paragraph\">Similarly, <strong>\u03b2-hydroxybutyrate<\/strong> activates protective pathways, including autophagy, mitochondrial biogenesis, and inflammasome suppression \u2014 highlighting why aggressive glucose-centric thinking is outdated.<\/p>\n<hr class=\"reader-divider-block__horizontal-rule\" \/>\n<h3 id=\"ember85\" class=\"ember-view reader-text-block__heading-3\">5. Stress hyperglycaemia is context-dependent<\/h3>\n<p id=\"ember86\" class=\"ember-view reader-text-block__paragraph\">Early insulin resistance is <strong>adaptive<\/strong>, redirecting glucose to vital organs. However:<\/p>\n<ul>\n<li>Persistent insulin resistance becomes maladaptive<\/li>\n<li>Tight glycaemic control offers <strong>no mortality benefit<\/strong> and increases hypoglycaemia<\/li>\n<\/ul>\n<p id=\"ember88\" class=\"ember-view reader-text-block__paragraph\">Current evidence supports <strong>moderate glucose targets (140\u2013200 mg\/dL)<\/strong> rather than aggressive normalization.<\/p>\n<hr class=\"reader-divider-block__horizontal-rule\" \/>\n<h3 id=\"ember89\" class=\"ember-view reader-text-block__heading-3\">6. High-protein strategies fail to improve outcomes \u2014 and may cause harm<\/h3>\n<p id=\"ember90\" class=\"ember-view reader-text-block__paragraph\">Across multiple RCTs and meta-analyses:<\/p>\n<ul>\n<li>Higher protein intake <strong>does not improve survival, ventilator days, or functional recovery<\/strong><\/li>\n<li>Potential harm is seen in patients with <strong>acute kidney injury<\/strong><\/li>\n<li>Anabolic resistance limits effective protein utilization<\/li>\n<\/ul>\n<p id=\"ember92\" class=\"ember-view reader-text-block__paragraph\">The message is clear: <strong>more protein is not better<\/strong>, especially early.<\/p>\n<hr class=\"reader-divider-block__horizontal-rule\" \/>\n<h3 id=\"ember93\" class=\"ember-view reader-text-block__heading-3\">7. Chronic critical illness reflects failed metabolic resolution<\/h3>\n<p id=\"ember94\" class=\"ember-view reader-text-block__paragraph\">Some patients transition to <strong>persistent inflammation, immunosuppression, and catabolism (PICS)<\/strong>, characterized by:<\/p>\n<ul>\n<li>Ongoing muscle wasting<\/li>\n<li>Immune dysfunction<\/li>\n<li>Endocrine suppression<\/li>\n<li>Long-term disability<\/li>\n<\/ul>\n<p id=\"ember96\" class=\"ember-view reader-text-block__paragraph\">This reinforces the need for <strong>biomarkers and metabolomics<\/strong> to identify when patients are ready for anabolic strategies.<\/p>\n<div class=\"reader-image-block reader-image-block--full-width\">\n<figure class=\"reader-image-block__figure\">\n<div class=\"ivm-image-view-model reader-image-block__img-container\">\n<div class=\"ivm-view-attr__img-wrapper \"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-1550 size-large\" src=\"https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938826155-1024x710.png\" alt=\"\" width=\"1024\" height=\"710\" srcset=\"https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938826155-1024x710.png 1024w, https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938826155-300x208.png 300w, https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938826155-768x533.png 768w, https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938826155.png 1442w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><\/div>\n<\/div>\n<div>\n<h3 id=\"ember98\" class=\"ember-view reader-text-block__heading-3\">Clinical takeaways for ICU practice<\/h3>\n<ul>\n<li>\ud83d\udd39 Early phase: <strong>Permissive underfeeding (\u224850\u201370% EE)<\/strong>, trophic enteral nutrition<\/li>\n<li>\ud83d\udd39 Avoid early high-protein dosing<\/li>\n<li>\ud83d\udd39 Use <strong>indirect calorimetry<\/strong> when available<\/li>\n<li>\ud83d\udd39 Moderate glycaemic control over tight targets<\/li>\n<li>\ud83d\udd39 Recognize metabolic phase before escalating nutrition<\/li>\n<li>\ud83d\udd39 Future direction: metabolic endotyping to personalize care<\/li>\n<\/ul>\n<hr class=\"reader-divider-block__horizontal-rule\" \/>\n<h3 id=\"ember100\" class=\"ember-view reader-text-block__heading-3\">Bottom line<\/h3>\n<p id=\"ember101\" class=\"ember-view reader-text-block__paragraph\">This review marks a <strong>paradigm shift<\/strong> in critical care metabolism. The goal is no longer to \u201creplace what is lost\u201d immediately, but to <strong>support adaptive stress responses early<\/strong>, protect mitochondria, preserve autophagy, and <strong>time anabolic support correctly<\/strong>. Precision metabolic care \u2014 not blanket nutrition targets \u2014 represents the future of ICU practice.<\/p>\n<hr class=\"reader-divider-block__horizontal-rule\" \/>\n<p id=\"ember102\" class=\"ember-view reader-text-block__paragraph\">As always, thank you for being part of the <strong>One Article a Day Challenge<\/strong>. Your continued engagement is what drives evidence-based critical care forward.<\/p>\n<p><strong><a class=\"article-editor-link article-editor-link\" style=\"font-size: 16px; background-color: #ffffff;\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2110582026000476?via%3Dihub\" rel=\"noopener noreferrer\">ACCESS FULL ARTICLE HERE<\/a><\/strong><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-1551\" src=\"https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938927969-300x300.png\" alt=\"\" width=\"300\" height=\"300\" srcset=\"https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938927969-300x300.png 300w, https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938927969-150x150.png 150w, https:\/\/perfusfind.com\/ic\/wp-content\/uploads\/2026\/03\/1765938927969.png 450w\" sizes=\"(max-width: 300px) 100vw, 300px\" \/><\/p>\n<\/div>\n<p id=\"ember105\" class=\"ember-view reader-text-block__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\u2019s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article\u2019s 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=\"QPSBGRTTCToxrpUoVsOUnfwcbljCvWXALY \" tabindex=\"0\" href=\"http:\/\/creativecommons.org\/licenses\/by\/4.0\/\" target=\"_self\" data-test-app-aware-link=\"\">http:\/\/creativecommons.org\/licenses\/by\/4.0\/<\/a>.<\/p>\n<\/figure>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Why this article matters Critical illness triggers a profound, highly coordinated metabolic stress response that extends far beyond \u201chypercatabolism.\u201d This comprehensive review reframes how we understand energy metabolism, nutrition, endocrine signaling, immune function, and recovery across the acute, subacute, and chronic phases of critical illness. Importantly, it challenges long-standing assumptions around \u201cearly full feeding\u201d and [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":1546,"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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center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[9],"tags":[550,548,549,24],"class_list":["post-1545","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-miscellaneous","tag-critical-illness","tag-metabolic-response","tag-metabolism","tag-nutrition"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.1.1 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>The metabolic response to stress in critical illness: updated review on the pathophysiological mechanisms, consequences, and therapeutic implications - Perfusfind Intensive Care<\/title>\n<meta name=\"description\" content=\"This comprehensive review reframes how we understand energy metabolism, nutrition, endocrine signaling, immune function, and recovery across the acute, subacute, and 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