Interleukin-6 as inflammatory marker referring to multiple organ dysfunction syndrome in severely injured children

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Abstract

Background

Despite the suggestion that the inflammatory response in traumatized children is functionally unique, prognostic markers predicting pediatric multiple organ failure are lacking. We intended to verify whether Interleukin-6 (IL-6) displays a pivotal role in pediatric trauma similar to adults.

Methods

Traumatized children less than 18 years of age with an Injury Severity Score >9 points and consecutive admission to the hospital’s pediatric intensive care unit were included. Organ function was evaluated according to the score by Marshall et al. while IL-6 levels were measured repetitively every morning.

Results

59 traumatized children were included (8.4 ± 4.4 years; 57.6% male gender). Incidence of MODS was 11.9%. No differences were found referring to age, gender, injury distribution or overall injury severity between children with and without MODS. Increased IL-6 levels during hospital admission were associated with injury severity (Spearman correlation: r = 0.522, p < 0.001), while an inconsistent association towards the development of MODS was proven at that time point (Spearman correlation: r = 0.180, p = 0.231; Pearson's correlation: r = 0.297, p = 0.045). However, increased IL-6 levels during the first two days were no longer associated with the injury severity but a significant correlation to MODS was measured.

Conclusions

The presented prospective study is the first providing evidence for a correlation of IL-6 levels with injury severity and the incidence of MODS in traumatized children.

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Most cited references 37

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Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome.

J C Marshall, D J Cook, N V Christou … (1995)

To develop an objective scale to measure the severity of the multiple organ dysfunction syndrome as an outcome in critical illness. Systematic literature review; prospective cohort study. Surgical intensive care unit (ICU) of a tertiary-level teaching hospital. All patients (n = 692) admitted for > 24 hrs between May 1988 and March 1990. None. Computerized database review of MEDLINE identified clinical studies of multiple organ failure that were published between 1969 and 1993. Variables from these studies were evaluated for construct and content validity to identify optimal descriptors of organ dysfunction. Clinical and laboratory data were collected daily to evaluate the performance of these variables individually and in aggregate as an organ dysfunction score. Seven systems defined the multiple organ dysfunction syndrome in more than half of the 30 published reports reviewed. Descriptors meeting criteria for construct and content validity could be identified for five of these seven systems: a) the respiratory system (Po2/FIO2 ratio); b) the renal system (serum creatinine concentration); c) the hepatic system (serum bilirubin concentration); d) the hematologic system (platelet count); and e) the central nervous system (Glasgow Coma Scale). In the absence of an adequate descriptor of cardiovascular dysfunction, we developed a new variable, the pressure-adjusted heart rate, which is calculated as the product of the heart rate and the ratio of central venous pressure to mean arterial pressure. These candidate descriptors of organ dysfunction were then evaluated for criterion validity (ICU mortality rate) using the clinical database. From the first half of the database (the development set), intervals for the most abnormal value of each variable were constructed on a scale from 0 to 4 so that a value of 0 represented essentially normal function and was associated with an ICU mortality rate of or = 50%. These intervals were then tested on the second half of the data set (the validation set). Maximal scores for each variable were summed to yield a Multiple Organ Dysfunction Score (maximum of 24). This score correlated in a graded fashion with the ICU mortality rate, both when applied on the first day of ICU admission as a prognostic indicator and when calculated over the ICU stay as an outcome measure. For the latter, ICU mortality was approximately 25% at 9 to 12 points, 50% at 13 to 16 points, 75% at 17 to 20 points, and 100% at levels of > 20 points. The score showed excellent discrimination, as reflected in areas under the receiver operating characteristic curve of 0.936 in the development set and 0.928 in the validation set. The incremental increase in scores over the course of the ICU stay (calculated as the difference between maximal scores and those scores obtained on the first day [i.e., the delta Multiple Organ Dysfunction Score]) also demonstrated a strong correlation with the ICU mortality rate. In a logistic regression model, this incremental increase in scores accounted for more of the explanatory power than admission severity indices. This multiple organ dysfunction score, constructed using simple physiologic measures of dysfunction in six organ systems, mirrors organ dysfunction as the intensivist sees it and correlates strongly with the ultimate risk of ICU mortality and hospital mortality. The variable, delta Multiple Organ Dysfunction Score, reflects organ dysfunction developing during the ICU stay, which therefore is potentially amenable to therapeutic manipulation. (ABSTRACT TRUNCATED)

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Pathophysiology of polytrauma.

Marius J.B. Keel, Otmar Trentz (2005)

Immediate and early trauma deaths are determined by primary brain injuries, or significant blood loss (haemorrhagic shock), while late mortality is caused by secondary brain injuries and host defence failure. First hits (hypoxia, hypotension, organ and soft tissue injuries, fractures), as well as second hits (e.g. ischaemia/reperfusion injuries, compartment syndromes, operative interventions, infections), induce a host defence response. This is characterized by local and systemic release of pro-inflammatory cytokines, arachidonic acid metabolites, proteins of the contact phase and coagulation systems, complement factors and acute phase proteins, as well as hormonal mediators: it is defined as systemic inflammatory response syndrome (SIRS), according to clinical parameters. However, in parallel, anti-inflammatory mediators are produced (compensatory anti-inflammatory response syndrome (CARS). An imbalance of these dual immune responses seems to be responsible for organ dysfunction and increased susceptibility to infections. Endothelial cell damage, accumulation of leukocytes, disseminated intravascular coagulation (DIC) and microcirculatory disturbances lead finally to apoptosis and necrosis of parenchymal cells, with the development of multiple organ dysfunction syndrome (MODS), or multiple organ failure (MOF). Whereas most clinical trials with anti-inflammatory, anti-coagulant, or antioxidant strategies failed, the implementation of pre- and in-hospital trauma protocols and the principle of damage control procedures have reduced post-traumatic complications. However, the development of immunomonitoring will help in the selection of patients at risk of post-traumatic complications and, thereby, the choice of the most appropriate treatment protocols for severely injured patients.

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Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion

Mitchell Cohen, Karim Brohi, Carolyn S Calfee … (2009)

Introduction High mobility group box nuclear protein 1 (HMGB1) is a DNA nuclear binding protein that has recently been shown to be an early trigger of sterile inflammation in animal models of trauma-hemorrhage via the activation of the Toll-like-receptor 4 (TLR4) and the receptor for the advanced glycation endproducts (RAGE). However, whether HMGB1 is released early after trauma hemorrhage in humans and is associated with the development of an inflammatory response and coagulopathy is not known and therefore constitutes the aim of the present study. Methods One hundred sixty eight patients were studied as part of a prospective cohort study of severe trauma patients admitted to a single Level 1 Trauma center. Blood was drawn within 10 minutes of arrival to the emergency room before the administration of any fluid resuscitation. HMGB1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, von Willebrand Factor (vWF), angiopoietin-2 (Ang-2), Prothrombin time (PT), prothrombin fragments 1+2 (PF1+2), soluble thrombomodulin (sTM), protein C (PC), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and D-Dimers were measured using standard techniques. Base deficit was used as a measure of tissue hypoperfusion. Measurements were compared to outcome measures obtained from the electronic medical record and trauma registry. Results Plasma levels of HMGB1 were increased within 30 minutes after severe trauma in humans and correlated with the severity of injury, tissue hypoperfusion, early posttraumatic coagulopathy and hyperfibrinolysis as well with a systemic inflammatory response and activation of complement. Non-survivors had significantly higher plasma levels of HMGB1 than survivors. Finally, patients who later developed organ injury, (acute lung injury and acute renal failure) had also significantly higher plasma levels of HMGB1 early after trauma. Conclusions The results of this study demonstrate for the first time that HMGB1 is released into the bloodstream early after severe trauma in humans. The release of HMGB1 requires severe injury and tissue hypoperfusion, and is associated with posttraumatic coagulation abnormalities, activation of complement and severe systemic inflammatory response.

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Author and article information

Contributors

Hagen Andruszkow

Janika Fischer

Michael Sasse

Ulf Brunnemer

Julia Helga Karla Andruszkow

Axel Gänsslen

Frank Hildebrand

Michael Frink

Journal

Journal ID (nlm-ta): Scand J Trauma Resusc Emerg Med

Journal ID (iso-abbrev): Scand J Trauma Resusc Emerg Med

Title: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine

Publisher: BioMed Central

ISSN (Electronic): 1757-7241

Publication date Collection: 2014

Publication date (Electronic): 3 March 2014

Volume: 22

Page: 16

Affiliations

[1 ]Department of Orthopaedic Trauma at Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany

[2 ]Center of Pediatric Surgery Hannover, Hannover Medical School and Bult Children’s Hospital, Carl Neuberg-Str. 1, 30625 Hannover, Germany

[3 ]Department for Trauma, Hand and Reconstructive Surgery, Medical Center Wolfsburg, Sauerbruchstr 7, 38440 Wolfsburg, Germany

[4 ]Department for Trauma, Hand and Reconstructive Surgery, University Medical Center Marburg, Baldingerstr, 35043 Marburg, Germany

[5 ]Trauma Department, Hannover Medical School, Carl Neuberg-Str. 1, 30625 Hannover, Germany

[6 ]Institute of Pathology, University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany

[7 ]Clinic for Paediatric Cardiology and Internal Medicine, Carl Neuberg-Str. 1, 30625 Hannover, Germany

Article

Publisher ID: 1757-7241-22-16

DOI: 10.1186/1757-7241-22-16

PMC ID: 3942614

PubMed ID: 24589345

SO-VID: 7446d6a7-0fdd-472f-8513-f8d46598b362

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Interleukin-6 as inflammatory marker referring to multiple organ dysfunction syndrome in severely injured children

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Abstract

Background

Methods

Results

Conclusions

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Irish Journal of Paramedicine

Most cited references 37

Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome.

Pathophysiology of polytrauma.

Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion

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