Meta-Analysis

. 2025 Jul 10;7(7):e1280.

doi: 10.1097/CCE.0000000000001280. eCollection 2025 Jul 1.

Effect of Inhaled Volatile and IV Anesthetics on Biological Markers of Inflammation in Adult ICU and Thoracic Surgical Patients: A Systematic Review and Meta-Analysis

Soroush Rouhani^{1

2}, Sanchit Gupta³, Hira Raheel^{1

2}, Aggie Duan Gao^{1

2}, Ciara Hanley⁴, Xingshan Cao⁵, Alla Iansavitchene⁶, Brian H Cuthbertson^{3

5

7

8}, Marat Slessarev^{1

2}, Ewan C Goligher^{9

10

11

12}, Aleksandra Leligdowicz^{1

2

13}, Douglas D Fraser^{2

14}, Beverley A Orser³, Angela Jerath^{3

5

8

15}; SAVE-ICU Investigators

Collaborators, Affiliations

Collaborators

SAVE-ICU Investigators:
Martin Chapman¹⁶, Damon Scales¹⁶, Julie Nardi¹⁶, Beth Linseman¹⁶, Phil Lau¹⁶, Eily Shaw¹⁶, Lilia Kaustov¹⁶, Emmanuel Charbonney¹⁷, Michaël Chassé¹⁷, Martin Girard¹⁷, Antoine Halwagi¹⁷, Guillaume Plourde¹⁷, Han Ting Wang¹⁷, Francois Carrier¹⁷, Frédérick D'Aragon¹⁸, Maxime Tissot-Therrien¹⁸, François Lamontagne¹⁸, Dominique Bérard¹⁸, Yiorgos Alexandros Cavayas¹⁹, Martin Albert¹⁹, Francis Bernard¹⁹, Karim Serri¹⁹, David Williamson¹⁹, Virginie Williams¹⁹, Patricia Martinez Barrios¹⁹, Sabrina Araujo De Franca¹⁹, Etienne J Couture²⁰, Adreanne Côté²⁰, Mathieu Simon²⁰, Pierre-Alexis Lépine²⁰, Dave Gleeton²⁰, John Basmaji²¹, Marat Slessarev²¹, Ahmed Hegazy²¹, Tracey Bentall²¹, Eileen Campbell²¹, Michelle Stephens²¹, Tim Winterburn²¹, Roupen Hatzakorzian²², Kosar Khwaja²², Peter Goldberg²², Jason Shahin²², Jeremy Richard Grushka²², Jonathan Hooper²³, Sherissa Microys²³, Hilary Meggison²³, David Leilipovitz²³, Jessica Haines²³, Irene Watpool²³, Rebecca Porteous²³, Stephanie Dunster²³, Sylvie Bourbonnais²³, Ewan Goligher²⁴, Lorenzo Del Sorbo²⁴, Niall Ferguson²⁴, Philip Graham²⁴, Michael Long²⁴, Tina Yan²⁴, Denise Morris²⁴, Maria Kobylecky²⁴, Hesham Abdelhady²⁴, Tina Romagnuolo²⁴, Ian Randall²⁵, Elizabeth Wilcox²⁵, Bourke Tillman²⁵, Michael Jacka²⁶, Oleksa Rewa²⁶, Vincent Lau²⁶, Sean Bagshaw²⁶, Nadia Baig²⁶, Janek Senaratne, Lazar Milovanovic, Tammi Breymann, Larissa Johnson, Anushka Jayasekara, Bernadette Fernando, Paula Sharman, Vanessa Dolimount, Jennifer Hamilton, Mehvash Qureshi

Affiliations

¹ Department of Medicine, London Health Sciences Centre, London, ON, Canada.
² Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
³ Department of Anesthesiology and Pain Management, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁴ Department of Anaesthesia and Critical Care, University Hospital Galway, Galway, Ireland.
⁵ Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
⁶ London Health Sciences Centre, Corporate Academics, London, ON, Canada.
⁷ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
⁸ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁹ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Medicine and Physiology, University of Toronto, Toronto, ON, Canada.
¹¹ Critical Care Section, University Health Network, Toronto, ON, Canada.
¹² Toronto General Hospital Research Institute, Toronto, ON, Canada.
¹³ Robarts Research Institute, Western University, London, ON, Canada.
¹⁴ Department of Pediatrics, London Health Sciences Centre, London, ON, Canada.
¹⁵ Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.
¹⁶ Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada.
¹⁷ Centre hospitalier universitaire de Sherbrooke (CHUS).
¹⁸ Centre intégré universitaire de santé et de services sociaux du Nord-de-Ille-de-Montréal (Sacre Coeur).
¹⁹ Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec City, Canada.
²⁰ London Health Sciences Centre.
²¹ McGill University Health Centre.
²² The Ottawa Hospital.
²³ Toronto General Hospital.
²⁴ Toronto Western Hospital.
²⁵ University of Alberta Hospital.
²⁶ Grey Nuns Community Hospital.

PMID: 40637441
PMCID: PMC12440536
DOI: 10.1097/CCE.0000000000001280

Meta-Analysis

Effect of Inhaled Volatile and IV Anesthetics on Biological Markers of Inflammation in Adult ICU and Thoracic Surgical Patients: A Systematic Review and Meta-Analysis

Soroush Rouhani et al. Crit Care Explor. 2025.

. 2025 Jul 10;7(7):e1280.

doi: 10.1097/CCE.0000000000001280. eCollection 2025 Jul 1.

Authors

Collaborators

SAVE-ICU Investigators:
Martin Chapman¹⁶, Damon Scales¹⁶, Julie Nardi¹⁶, Beth Linseman¹⁶, Phil Lau¹⁶, Eily Shaw¹⁶, Lilia Kaustov¹⁶, Emmanuel Charbonney¹⁷, Michaël Chassé¹⁷, Martin Girard¹⁷, Antoine Halwagi¹⁷, Guillaume Plourde¹⁷, Han Ting Wang¹⁷, Francois Carrier¹⁷, Frédérick D'Aragon¹⁸, Maxime Tissot-Therrien¹⁸, François Lamontagne¹⁸, Dominique Bérard¹⁸, Yiorgos Alexandros Cavayas¹⁹, Martin Albert¹⁹, Francis Bernard¹⁹, Karim Serri¹⁹, David Williamson¹⁹, Virginie Williams¹⁹, Patricia Martinez Barrios¹⁹, Sabrina Araujo De Franca¹⁹, Etienne J Couture²⁰, Adreanne Côté²⁰, Mathieu Simon²⁰, Pierre-Alexis Lépine²⁰, Dave Gleeton²⁰, John Basmaji²¹, Marat Slessarev²¹, Ahmed Hegazy²¹, Tracey Bentall²¹, Eileen Campbell²¹, Michelle Stephens²¹, Tim Winterburn²¹, Roupen Hatzakorzian²², Kosar Khwaja²², Peter Goldberg²², Jason Shahin²², Jeremy Richard Grushka²², Jonathan Hooper²³, Sherissa Microys²³, Hilary Meggison²³, David Leilipovitz²³, Jessica Haines²³, Irene Watpool²³, Rebecca Porteous²³, Stephanie Dunster²³, Sylvie Bourbonnais²³, Ewan Goligher²⁴, Lorenzo Del Sorbo²⁴, Niall Ferguson²⁴, Philip Graham²⁴, Michael Long²⁴, Tina Yan²⁴, Denise Morris²⁴, Maria Kobylecky²⁴, Hesham Abdelhady²⁴, Tina Romagnuolo²⁴, Ian Randall²⁵, Elizabeth Wilcox²⁵, Bourke Tillman²⁵, Michael Jacka²⁶, Oleksa Rewa²⁶, Vincent Lau²⁶, Sean Bagshaw²⁶, Nadia Baig²⁶, Janek Senaratne, Lazar Milovanovic, Tammi Breymann, Larissa Johnson, Anushka Jayasekara, Bernadette Fernando, Paula Sharman, Vanessa Dolimount, Jennifer Hamilton, Mehvash Qureshi

Affiliations

¹ Department of Medicine, London Health Sciences Centre, London, ON, Canada.
² Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
³ Department of Anesthesiology and Pain Management, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁴ Department of Anaesthesia and Critical Care, University Hospital Galway, Galway, Ireland.
⁵ Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
⁶ London Health Sciences Centre, Corporate Academics, London, ON, Canada.
⁷ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
⁸ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁹ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Medicine and Physiology, University of Toronto, Toronto, ON, Canada.
¹¹ Critical Care Section, University Health Network, Toronto, ON, Canada.
¹² Toronto General Hospital Research Institute, Toronto, ON, Canada.
¹³ Robarts Research Institute, Western University, London, ON, Canada.
¹⁴ Department of Pediatrics, London Health Sciences Centre, London, ON, Canada.
¹⁵ Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.
¹⁶ Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada.
¹⁷ Centre hospitalier universitaire de Sherbrooke (CHUS).
¹⁸ Centre intégré universitaire de santé et de services sociaux du Nord-de-Ille-de-Montréal (Sacre Coeur).
¹⁹ Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec City, Canada.
²⁰ London Health Sciences Centre.
²¹ McGill University Health Centre.
²² The Ottawa Hospital.
²³ Toronto General Hospital.
²⁴ Toronto Western Hospital.
²⁵ University of Alberta Hospital.
²⁶ Grey Nuns Community Hospital.

PMID: 40637441
PMCID: PMC12440536
DOI: 10.1097/CCE.0000000000001280

Abstract

Objectives: Inhaled anesthetics may reduce alveolar and systemic inflammation in surgical and critically ill patients. This study aimed to perform a systematic review and meta-analysis comparing the effect of inhaled volatile and IV anesthetics on alveolar and plasma cytokines in patients with surgical or medical acute lung injury.

Data sources: Medline, Embase, and Cochrane CENTRAL databases from 2000 to July 2021.

Study selection: Randomized control trials, prospective, and retrospective observational studies comparing inhaled volatile to IV anesthetics in ventilated adult patients with acute lung injury from lung resection or critical illness.

Data extraction: A systematic review and meta-analysis was performed. Primary outcome was alveolar inflammatory cytokines levels that were meta-analyzed using a random effects model. Secondary outcomes were plasma inflammatory cytokine levels, mortality, pulmonary complications, and duration of hospital and ICU stay. The quality of studies was assessed using the Cochrane Risk of Bias tool for randomized control trials and the Cochrane Risk Of Bias In Non-randomized Studies of Interventions tool for retrospective cohort studies.

Data synthesis: From 2522 screened studies, 28 (27 thoracic surgery and 1 ICU, n = 4175) were included. Meta-analysis of patients undergoing lung resection demonstrated lower levels of alveolar tumor necrosis factor-alpha (TNF-α) (standard mean difference 1.04; 95% CI, 0.32-1.77; p < 0.01; I2 82%) and interleukin (IL)-6 (0.64; 95% CI, 0.52-0.75; I2 0%; p < 0.01) at 1-2 hours in the inhaled anesthesia group, with no difference in other cytokines at various time points. The single ICU study demonstrated lower plasma TNF-α and IL-6 and alveolar TNF-α, IL-6, and IL-8 at 48 hours in patients sedated with sevoflurane compared with midazolam. Clinical outcomes were infrequently reported.

Conclusions: Limited evidence suggests that inhaled anesthesia may reduce proinflammatory cytokines TNF-α and IL-6 during lung resection and critical illness. Further studies are needed to clarify its effects on biological markers and clinical outcomes.

Keywords: critical care; cytokine; inflammation; lung injury; lung resection; one-lung ventilation; thoracic surgery; volatile anesthetics.

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Conflict of interest statement

Drs. Jerath and Cuthbertson are supported by the Merit Award, Department of Anesthesiology and Pain Medicine, University of Toronto. Drs. Jerath, Slessarev, and Cuthbertson have received grant funding from the Canadian Institute of Health Research and the Ontario Government. Drs. Jerath and Cuthbertson received funding from Alternate Funding Plan, Ministry of Ontario. Drs. Jerath, Slessarev, and Cuthbertson received funding Government of Ontario. Drs. Slessarev and Jerath have an ongoing clinical trial examining the effects of inhaled anesthetics on cognitive outcomes in critically ill adult patients. Dr. Leligdowicz is a recipient of the Wolfe-Western Fellowship award.

Figures

**Figure 1.**
Preferred Reporting Items for Systematic Review and Meta-Analysis study flowchart.

**Figure 2.**
Temporal changes in mean bronchoalveolar lavage (BAL) and plasma cytokine levels across studies. Units are in pg/mL. IL = interleukin, TNF-α = tumor necrosis factor-alpha.

See this image and copyright information in PMC

References

1. Jerath A, Ferguson ND, Cuthbertson B: Inhalational volatile-based sedation for COVID-19 pneumonia and ARDS. Intensive Care Med 2020; 46:1563–1566 - PMC - PubMed
1. Jerath A, Ferguson ND, Steel A, et al. : The use of volatile anesthetic agents for long-term critical care sedation (VALTS): Study protocol for a pilot randomized controlled trial. Trials. 2015; 16:560. - PMC - PubMed
1. Gorsky K, Cuninghame S, Jayaraj K, et al. : Inhaled volatiles for status asthmaticus, epilepsy, and difficult sedation in adult ICU and PICU: A systematic review. Crit Care Explor. 2024; 6:e1050. - PMC - PubMed
1. Stollings LM, Jia LJ, Tang P, et al. : Immune modulation by volatile anesthetics. Anesthesiology 2016; 125:399–411 - PMC - PubMed
1. Yuki K, Eckenhoff RG: Mechanisms of the immunological effects of volatile anesthetics: A review. Anesth Analg 2016; 123:326–335 - PMC - PubMed

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Effect of Inhaled Volatile and IV Anesthetics on Biological Markers of Inflammation in Adult ICU and Thoracic Surgical Patients: A Systematic Review and Meta-Analysis

Collaborators

Affiliations

Effect of Inhaled Volatile and IV Anesthetics on Biological Markers of Inflammation in Adult ICU and Thoracic Surgical Patients: A Systematic Review and Meta-Analysis

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources