Very early posttraumatic serum alterations are significantly associated to initial massive RBC substitution, injury severity, multiple organ failure and adverse clinical outcome in multiple injured patients

Bogner V, Keil L, Kanz K-G, Kirchhoff C, Leidel Ba, Mutschler W, Biberthaler, Biberthaler P

Description

Multiple severe trauma frequently leads to massive dysbalances of the human immune system. This phenomenon is known as " Systemic Inflammatory Response Syndrome (SIRS) ". SIRS is connected to multiple organ failure and thereby entails higher morbidity and mortality in trauma patients. Pro-and anti-inflammatory cytokines such as Il-6, Il-8 and Il-10 seem to play a superior role in the development of SIRS. Several studies support the hypothesis that the very early cytokine release pattern determines the patients' subsequent clinical course. Most data about interleukins in trauma patients however refer to serum concentrations assessed sometime in the first 24 h, but there is only little information about release dynamics in a small-meshed time frame in the very initial post-trauma period. Patients and methods 58 multiple injured patients (Injury Severity Score > 16 points) were included. Blood samples were drawn on patient admission (not later then 90 minutes after trauma) and at 6 h, 12 h, 24 h, 48 h and 72 h. Il-6, Il-8 and Il-10 were measured using an automated chemiluminescence assay (IMMULITE, Siemens Healthcare Diagnostics GmbH). Interleukin levels were correlated to distinct epidemiological and clinical parameters. Results Interleukin serum concentrations are thoroughly elevated after trauma. Patients with haemorrhagic shock and consecutive massive RBC substitution (n = 27) exhibit higher Il-6, Il-8 and Il-10 levels as compared to patients with minor RBC transfusion extent (n = 31). Interleukin levels also differentiate patients with MOF (n = 43) from such without MOF (n = 15) already at the earliest post trauma time (90 minutes). Il-6, Il-8 and Il-10 concentrations also significantly distinguish patients with adverse outcome (n = 11) from such with favourable outcome (n = 47). Exclusively Il-10 has significant correlation to injury severity (ISS > 35). Conclusion The current study presents an image of the serum Il-6, 8 and 10 releases in multiple trauma patients in the very early post-trauma period. We could thereby demonstrate that interleukin levels can clearly differentiate the presence of hemorrhagic shock and subsequent massive blood product substitution, the development of multiple organ failure and clinical outcome. No significant connection to age, gender and brain injury could be detected. Most importantly, changes in interleukin levels can be observed in the very early posttraumatic phase, at the earliest 90 minutes after trauma.

Sujets

• Blood transfusion
• IL-6
• IL-8
• IL-10

Informations

• Publié par: biomed
• Publié le: 01 janvier 2009
• Nombre de lectures: 9
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

16 points) were included. Blood samples were drawn on patient admission (not later then 90 minutes after trauma) and at 6 h, 12 h, 24 h, 48 h and 72 h. Il-6, Il-8 and Il-10 were measured using an automated chemiluminescence assay (IMMULITE, Siemens Healthcare Diagnostics GmbH). Interleukin levels were correlated to distinct epidemiological and clinical parameters. Results Interleukin serum concentrations are thoroughly elevated after trauma. Patients with haemorrhagic shock and consecutive massive RBC substitution (n = 27) exhibit higher Il-6, Il-8 and Il-10 levels as compared to patients with minor RBC transfusion extent (n = 31). Interleukin levels also differentiate patients with MOF (n = 43) from such without MOF (n = 15) already at the earliest post trauma time (90 minutes). Il-6, Il-8 and Il-10 concentrations also significantly distinguish patients with adverse outcome (n = 11) from such with favourable outcome (n = 47). Exclusively Il-10 has significant correlation to injury severity (ISS > 35). Conclusion The current study presents an image of the serum Il-6, 8 and 10 releases in multiple trauma patients in the very early post-trauma period. We could thereby demonstrate that interleukin levels can clearly differentiate the presence of hemorrhagic shock and subsequent massive blood product substitution, the development of multiple organ failure and clinical outcome. No significant connection to age, gender and brain injury could be detected. Most importantly, changes in interleukin levels can be observed in the very early posttraumatic phase, at the earliest 90 minutes after trauma." />

2. Bogner:Umbruchvorlage 24.06.2009 16:02 Uhr Seite 284
284 EUROPEAN JOURNAL OF MEDICAL RESEARCH July 22, 2009
Eur J Med Res (2009) 14: 284-291 © I. Holzapfel Publishers 2009
VERY EARLY POSTTRAUMATIC SERUM ALTERATIONS ARE SIGNIFICANTLY
ASSOCIATED TO INITIAL MASSIVE RBC SUBSTITUTION, INJURY SEVERITY,
MULTIPLE ORGAN FAILURE AND ADVERSE CLINICAL OUTCOME IN
MULTIPLE INJURED PATIENTS
V. Bogner, L. Keil, K.-G. Kanz, C. Kirchhoff, B. A. Leidel, W. Mutschler, P. Biberthaler
Chirurgische Klinik und Poliklinik Innenstadt, Ludwig-Maximilians-University, Munich, Germany
Abstract subsequent massive blood product substitution, the
Background: Multiple severe trauma frequently leads development of multiple organ failure and clinical
to massive dysbalances of the human immune system. outcome. No significant connection to age, gender
This phenomenon is known as “Systemic Inflammatory and brain injury could be detected. Most importantly,
Response Syndrome (SIRS)”. SIRS is connected to changes in interleukin levels can be observed in the
multiple organ failure and thereby entails higher mor- very early posttraumatic phase, at the earliest 90 min-
bidity and mortality in trauma patients. Pro- and anti- utes after trauma.
inflammatory cytokines such as Il-6, Il-8 and Il-10
seem to play a superior role in the development of Key words: Multiple Trauma, Blood Transfusion, Il-6,
SIRS. Several studies support the hypothesis that the Il-8, Il-10, Clinical Outcome
very early cytokine release pattern determines the pa-
tients’ subsequent clinical course. Most data about in- INTRODUCTION
terleukins in trauma patients however refer to serum
concentrations assessed sometime in the first 24h, but Multiple, severe trauma causes pervasive haemody-
there is only little information about release dynamics namic and metabolic alterations.
in a small-meshed time frame in the very initial post- This frequently leads to massive alterations of the
trauma period. human immune system and damages organ systems
Patients and Methods: 58 multiple injured patients (In- that have originally not been touched by the traumatic
jury Severity Score > 16 points) were included. Blood event. This phenomenon has been subsumed as “Sys-
samples were drawn on patient admission (not later temic Inflammatory Response Syndrome” (SIRS), which
then 90 minutes after trauma) and at 6h, 12h, 24h, 48h affects both the specific and non-specific immune sys-
and 72h. Il-6, Il-8 and Il-10 were measured using an tem [4, 26]. The presence of SIRS not seldom leads to
automated chemiluminescence assay (IMMULITE, multiple organ dysfunction (MODS), multiple organ
Siemens Healthcare Diagnostics GmbH). Interleukin failure (MOF) and thereby determines morbidity and
levels were correlated to distinct epidemiological and mortality in multiple trauma patients [5, 22]. Regarding
clinical parameters. the development of SIRS, the last decade’s research
Results: Interleukin serum concentrations are thor- has postulated a major role of pro- and anti-inflamma-
oughly elevated after trauma. Patients with haemor- tory cytokines (for review, see [10 16]). This has been
rhagic shock and consecutive massive RBC substitu- especially well investigated during sepsis and septic
tion (n = 27) exhibit higher Il-6, Il-8 and Il-10 levels as multiple organ failure [30, 31]. In this respect, the pro-
compared to patients with minor RBC transfusion ex- inflammatory interleukin-6 and 8, and the anti-inflam-
tent (n = 31). Interleukin levels also differentiate pa- matory interleukin-10 have been quite well character-
tients with MOF (n = 43) from such without MOF (n ized (for review, see [15, 7]). In a precedent genome-
= 15) already at the earliest post trauma time (90 min- wide mRNA Microarray study, we could identify Il-8
utes). Il-6, Il-8 and Il-10 concentrations also signifi- as a strong predictor for clinical outcome in multiple
cantly distinguish patients with adverse outcome (n = trauma patients [6]. However it is not clear, how much
11) from such with favourable outcome (n = 47). Ex- of this mRNA is transcribed into protein and released
clusively Il-10 has significant correlation to injury into the systemic circulation.
severity (ISS > 35). There are some experimental investigations on sev-
Conclusion: The current study presents an image of eral cytokine levels in multiple, major trauma patients.
the serum Il-6, 8 and 10 releases in multiple trauma The details about the connection between cytokine re-
patients in the very early post-trauma period. We could lease and clinical entities are partly inconsistent. Some
thereby demonstrate that interleukin levels can clearly of these works gain information that interleukin levels
differentiate the presence of hemorrhagic shock and are significantly influenced by diverse clinical entities,2. Bogner:Umbruchvorlage 24.06.2009 16:02 Uhr Seite 285
July 22, 2009 EUROPEAN JOURNAL OF MEDICAL RESEARCH 285
STATISTICSlike for example gender [34] or MOF [29]. In other
studies, predictive values of MOF, outcome or connec-
tions to injury severity could not be certified [1, 33]. Statistical analyses of time dynamic interleukin con-
Most of these studies rather concentrate on assess- centration changes were performed calculating ANO-
ing interleukin levels anytime during the first trauma VA on ranks followed by Dunn’s Method, signifi-
day up to several days in a follow up investigation peri- cances according to dichotomous criteria were investi-
od [1, 21, 29]. Only little is known about interleukin gated by t-test or Mann-Whitney Rank Sum test (Sig-
®release dynamics in the very early, initial post trauma ma Stat 3.0 SpSS inc.). Statistical visualization of the
®phase. Furthermore, it remains unclear, if and how data was performed by Sigma Plot 8.0 , SpSS inc.)
fast it is possible to differentiate various clinical events
like the development of multiple organ dysfunction or RESULTS
definite clinical outcome using serum interleukin con-
PATIENTScentration levels. Therefore it was the aim of the cur-
rent study to investigate on the time dynamic release
of Il-6, Il-8 and Il-10 in the very early posttraumatic 58 Patients fulfilled the entry criteria and were includ-
period focussing a time frame from not later than 90 ed into the study. Patients’ ages ranged from 18 to 89
minutes up to 72h after trauma. Furthermore, we in- years, median 42 years. 40 patients were males, 18
tended to identify epidemiological and clinical vari- were females. 27 patients required resuscitation with
ables like age, gender, injury severity, massive red massive RBC substitution (more than 10 RBC
blood cell substitution, multiple organ failure and defi- units/24h after trauma), and thereby were supplied
nite clinical outcome that significantly influence inter- with 24,3 ± 2,0 RBC units (mean ± SEM) and 25,5 ±
leukin concentration alterations. 2,5 FFP units in the first 24h (mean ± SEM). In con-
trast to that, patients with moderate RBC require-
PATIENTS AND METHODS ments received 3,6 ± 0,5 RBC units and 5,7 ± 0,9
FFP (mean ± SEM). Depth of shock estimated by
The study was performed at our level 1 trauma centre Base Excess (BE) and Shock Index was calculated in
following the Good Clinical Practice Guidelines. Ethi- both groups. The two clinical transfusion groups do
cal Committee Permission was obtained from the local not show any significant difference in Shock Index.
institutional Review Board (reference number: However, on admission, serum base excess levels are
012/00). Patients at age having sustained blunt multi- found to be significantly lower (BE -9,2 ± 4,1, MW ±
ple injuries (Injury Severity Score (ISS) of >16 points SEM) in patients with hemorrhagic shock and subse-
[8]) who reached the emergency department within 90 quent massive RBC substitution as compared to those
minutes after trauma were enrolled into the study. who received not more than 10 RBC units/24h (BE -
Signed informed consent was retrieved from the pa- 4,8 ± 2,9; MW ± SEM; p< 0.001, t-test). At 24h post
tients or a legal representative. Patients with isolated trauma, BE levels are again significantly different but
brain injury or such who died within the first 24h after vice versa (massive transfusion group: BE -0,3 ± 4,6
trauma were excluded from the study. Resuscitation versus BE -2,2 ± 2,2; p<0.01, Mann-Whitney-Rank-
and operative treatment of the patients was performed Sum test).
according to standard of care. Retrospectively, the pa- During the observation period, 43 patients devel-
tient collective was divided into dichotomous groups oped clinical signs of multiple organ failure (MOF
along the following epidemiological and clinical crite- score ≥ 4 points) in contrast to such who did not (15
ria: age, gender, presence of massive red blood cell patients; MOF score < 4 points). Injury Severity of 35
substitution (more than 10 RBC units in the first 24h patients was below 35 points, whereas 23 Patients ex-
after trauma), injury severity estimated by the Injury ceeded an ISS of 35 points. 11 of the patients de-
Severity Score (ISS), the development of MOF (MOF ceased within 90 days after the traumatic event, where-
score ≥ 4), presence of concomitant head injury and as five died of fatal brain injury and 6 patients devel-
definite clinical outcome after 90 days. oped irreversib