Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Crit Care Med. Sep 9, 2021; 10(5): 260-277
Published online Sep 9, 2021. doi: 10.5492/wjccm.v10.i5.260
Neutrophil kinetics and function after major trauma: A systematic review
Liam DB Finlay, Andrew Conway Morris, Adam M Deane, Alexander JT Wood
Liam DB Finlay, Melbourne Medical School, University of Melbourne, Melbourne 3052, Victoria, Australia
Andrew Conway Morris, Department of Medicine, University of Cambridge, Cambridge 01223, United Kingdom
Adam M Deane, Alexander JT Wood, Centre for Integrated Critical Care, University of Melbourne, Parkville 3052, Victoria, Australia
Adam M Deane, Alexander JT Wood, Intensive Care Unit, Royal Melbourne Hospital, Parkville 3052, Victoria, Australia
Author contributions: Finlay LDB and Wood AJT screened and analysed included studies and wrote the manuscript; Conway Morris A and Deane AM assisted with critical review and editing of the manuscript; all authors have read and approved the final manuscript.
Supported by the Clinical Research Career Development Fellowship from the Wellcome Trust, No. WT 205214/Z/16/Z; the MRC Clinician Scientist Fellowship, No. MR/V006118/1; and the Career Development Fellowship from the National Health and Medical Research Council of Australia, No. APP1141870.
Conflict-of-interest statement: There are no conflicts of interest to declare.
PRISMA 2009 Checklist statement: The guidelines of the PRISMA 2009 Statement have been adopted.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Alexander JT Wood, MBBS, PhD, Doctor, Intensive Care Unit, Royal Melbourne Hospital, Intensive Care Unit Offices Level 5, B Block Royal Melbourne Hospital 300 Grattan Street, Parkville 3052, Victoria, Australia. alex.wood1@unimelb.edu.au
Received: February 21, 2021
Peer-review started: February 21, 2021
First decision: May 13, 2021
Revised: June 22, 2021
Accepted: July 27, 2021
Article in press: July 27, 2021
Published online: September 9, 2021
Processing time: 200 Days and 3.3 Hours
Abstract
BACKGROUND

Immune dysfunction following major traumatic injury is complex and strongly associated with significant morbidity and mortality through the development of multiple organ dysfunction syndrome (MODS), persistent inflammation, immunosuppression, and catabolism syndrome and sepsis. Neutrophils are thought to be a pivotal mediator in the development of immune dysfunction.

AIM

To provide a review with a systematic approach of the recent literature describing neutrophil kinetics and functional changes after major trauma in humans and discuss hypotheses as to the mechanisms of the observed neutrophil dysfunction in this setting.

METHODS

Medline, Embase and PubMed were searched on January 15, 2021. Papers were screened by two reviewers and those included had their reference list hand searched for additional papers of interest. Inclusion criteria were adults > 18 years old, with an injury severity score > 12 requiring admission to an intensive care unit. Papers that analysed major trauma patients as a subgroup were included.

RESULTS

Of 107 papers screened, 48 were included in the review. Data were heterogeneous and most studies had a moderate to significant risk of bias owing to their observational nature and small sample sizes. Key findings included a persistently elevated neutrophil count, stereotyped alterations in cell-surface markers of activation, and the elaboration of heterogeneous and immunosuppressive populations of cells in the circulation. Some of these changes correlate with clinical outcomes such as MODS and secondary infection. Neutrophil phenotype remains a promising avenue for the development of predictive markers for immune dysfunction.

CONCLUSION

Understanding of neutrophil phenotypes after traumatic injury is expanding. A greater emphasis on incorporating functional and clinically significant markers, greater uniformity in study design and assessment of extravasated neutrophils may facilitate risk stratification in patients affected by major trauma.

Keywords: Neutrophils; Multiple trauma; Immunophenotypes; Inflammation; Systemic inflammatory response syndrome; Intensive care units

Core Tip: Major trauma results in complex immune dysfunction, with dysregulated pro- and anti-inflammatory processes presenting as clinical syndromes such as acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). This review examines the role of neutrophils in immune dysfunction following major trauma requiring admission to the intensive care unit, with a focus on the kinetics of the neutrophil immunophenotype and how this correlates with clinical outcomes. This review also proposes new hypotheses as to the mechanisms of complications of immune dysfunction, including ARDS and MODS.