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DOI: 10.1177/147323001204000117
2012 40: 167 Journal of International Medical Research
MT Gokdemir, O Sogut, H Kaya, MB Sayhan, M Cevik, MA Dokuzoglu and ME Boleken
Trauma
Role of Oxidative Stress in the Clinical Outcome of Patients with Multiple Blunt

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The Journal of International Medical Research
2012; 40: 167 173
167
Role of Oxidative Stress in the Clinical
Outcome of Patients with Multiple Blunt
Trauma
MT GOKDEMIR
1
, O SOGUT
1
, H KAYA
1
, MB SAYHAN
3
, M CEVIK
2
, MA DOKUZOGLU
1
AND ME BOLEKEN
2
1
Department of Emergency Medicine, and
2
Department of Paediatric Surgery, Faculty of
Medicine, Harran University, Sanliurfa, Turkey;
3
Department of Emergency Medicine,
Faculty of Medicine, Trakya University, Edirne, Turkey
OBJECTIVE: This prospective study
evaluated serum total oxidant status
(TOS), total antioxidant status (TAS) and
oxidative stress index (OSI), along with
the Revised Trauma Score (RTS) and
Injury Severity Score (ISS), as predictors of
clinical outcome in the early post-
traumatic period in patients with multiple
blunt trauma (MBT). METHODS: The
study included 52 patients admitted to the
emergency department with MBT and 40
age- and sex-matched healthy control
subjects. RESULTS: The overall MBT
patient mortality was 32.7% (17/52). There
was no significant association between
age and mortality in MBT patients, but
there was a negative correlation between
mortality and RTS, and a positive
correlation between mortality and ISS.
TOS levels were significantly higher in
nonsurvivors compared with survivors.
There was no correlation between TAS or
OSI and survival. ISS and RTS showed
positive and negative correlations with
TOS level, respectively, but neither was
significantly related to TAS or OSI.
CONCLUSIONS: These findings suggest
that TOS, as an early oxidative stress
biomarker, may be an objective
alternative criterion to the ISS and RTS for
managing patients with MBT during the
early period following traumatic injury.
KEY WORDS: MULTIPLE BLUNT TRAUMA; TOTAL OXIDANT STATUS; TOTAL ANTIOXIDANT STATUS;
OXIDATIVE STRESS INDEX; INJURY SEVERITY SCORE; MORTALITY
Introduction
Multitrauma is defined as physical insults or
injuries occurring simultaneously in several
parts of the body. Multitrauma patients have
usually sustained multiple traumatic injuries
to the body, affecting different organs and
body systems. For example, patients may
have head injuries, multiple fractures and
injuries to the internal organs of the chest
and/or abdomen. The severity of illness is
usually correlated with the number of body
systems involved.
1
Oxidative stress, an
imbalance between oxidants and
antioxidants, plays a critical role in the
development of organ damage during the
early post-traumatic period following blunt
These data were first presented as an oral presentation at
the 12th European Congress of Trauma & Emergency
Surgery, Milan, Italy, 27 30 April 2011 (abstract
published in: Eur J Trauma Emerg Surg Suppl 2011; 37: S67).
168
MT Gokdemir, O Sogut, H Kaya et al.
Role of oxidative stress in multiple blunt trauma
trauma. In critical illnesses such as sepsis,
trauma and burn injury, the occurrence of
increased oxidative stress or reduced
antioxidative status is related to a poor
prognosis.
2
Experimental and human studies
have indicated that destructive oxidative
events reach their peak within the first 24 h
after trauma and that this peak can be the
cause of death in affected patients.
3 7
Oxidative stress plays a critical role in the
development of secondary injuries following
traumatic brain injury.
5,8
Although multitrauma is associated with
high rates of patient mortality and
morbidity, no biomarkers have been reported
to have demonstrable clinical utility capable
of indicating injury severity and outcome
during the early post-traumatic period in
patients with multiple blunt trauma (MBT).
The present study evaluated early oxidative
changes in order to assess whether the
outcome of patients with MBT could be
predicted by evaluating serum total oxidant
status (TOS), total antioxidant status (TAS)
or oxidative stress index (OSI).
Patients and methods
STUDY POPULATION
This prospective clinical study collected
venous blood samples from consecutive
patients with MBT, within 24 h of trauma
onset, between 12 November 2010 and 20
February 2011. Patients who presented to the
Department of Emergency Medicine (Faculty
of Medicine, Harran University, Sanliurfa,
Turkey) with MBT due to various causes
(vehicle accidents, vehiclepedestrian
accidents, falling from a height, or assault)
as the primary injury were included in the
study. Patients were divided into survivor
and nonsurvivor groups. Healthy age- and
sex-matched volunteers, with no acute
traumatic injuries, were recruited as a
control group from the local population of
Sanliurfa, southeast Turkey.
Exclusion criteria were as follows: (i) pre-
existing conditions that may affect oxidative
markers, including congestive heart failure,
chronic obstructive lung disease, diabetes
mellitus, chronic renal failure, malignant
hypertension, coronary artery disease,
peripheral vascular disease and renal
dysfunction; (ii) use of sedative hypnotic
drugs or anxiolytic medications; (iii) use of
anabolic drugs, diuretics, vitamins or other
antioxidants such as vasoactive and -
blocking agents; (iv) tobacco smoking; (v)
measurable blood alcohol concentration or
consumption of alcohol prior to the study;
(vi) subjects following a special diet, e.g.
vegetarians; (vii) pregnancy or elevated
human chorionic gonadotropin (hCG) levels
detected by a quantitative blood test (-
hCG); (viii) patients with penetrating wound
trauma such as gunshot or sharp
penetrating object wounds; and (ix) subjects
known to be using drugs that affect lipid or
lipoprotein metabolism.
The study protocol was carried out in
accordance with the Declaration of Helsinki
(as revised in 1989) and was approved by the
Ethical Committee of the Faculty of
Medicine, Harran University, Sanliurfa,
Turkey. Written informed consent was
provided by all participants, or from their
legal guardians in the case of unconscious
patients. Vital function monitoring of
patients was performed prior to consent
being requested.
ASSESSMENT OF TOS, TAS, TRAUMA
AND INJURY SCORES
Patients were provided with basic life support
at presentation, and advanced life support if
required. Blood samples were drawn from
the antecubital vein of each subject
immediately after presentation to the
emergency room; samples were immediately
169
MT Gokdemir, O Sogut, H Kaya et al.
Role of oxidative stress in multiple blunt trauma
placed on ice at 4C. Plasma was separated
from the cells by centrifugation at 2509 g for
5 min and stored at 80C until analysis.
Plasma TOS and TAS were assessed using
an automated measurement method, as
described previously.
9
TAS levels were
expressed as mmol Trolox

(6-hydroxy-
2,5,7,8-tetramethylchroman-2-carboxylic
acid) equivalents/l. TOS levels were
expressed as mol H
2
O
2
equivalents/l.
9
OSI
was calculated according to the following
formula: OSI (arbitrary units) = TOS (mol
H
2
O
2
equivalents/l)/TAS (mmolTrolox

equivalents/l) 10
1
. The Revised Trauma
Score (RTS)
10
and Injury Severity Score (ISS)
11
were calculated for each patient. The causes
of MBT and MBT-related death (if the patient
died) were recorded for each patient.
STATISTICAL ANALYSES
Statistical analyses were performed using
SPSS

software package, version 15.0 (SPSS
Inc., Chicago, IL, USA) for Windows

.
Intergroup comparisons (controls versus
patients) were performed using the
2
-test
and Students t-test, and intragroup
comparisons (survivor versus nonsurvivor)
were performed using the MannWhitney U-
test. Spearmans rank correlation coefficient
was used to evaluate any correlation between
TOS level and data that were not normally
distributed (ISS and RTS). A P-value < 0.05
was considered statistically significant.
Results
The study recruited a total of 52 patients with
MBT and 40 healthy control subjects. There
were no statistically significant differences in
age or gender distribution between the two
groups (Table 1). The overall mortality rate of
MBT patients was 32.7% (17/52 patients)
Data regarding the causes of MBT and MBT-
related death are given in Table 2. The
male/female ratio in MBT patients was 1.89
(34/18 patients). The demographic
characteristics and oxidative stress
parameters of patients and control subjects
are shown in Table 1. Plasma TOS and OSI
levels were significantly higher (P < 0.001 for
both comparisons), and plasma TAS levels
were significantly lower (P < 0.001), in patients
with MBT versus control subjects (Table 1).
The oxidative stress parameters of
patients with MBT, divided according to
survival, are shown in Table 3. TOS levels
were significantly higher in nonsurvivors
than in survivors (P = 0.043), but there were
no significant between-group differences in
TAS and OSI levels. RTS was significantly
lower and ISS was significantly higher in
TABLE 1:
Demographic characteristics and oxidative stress parameters in patients with multiple
blunt trauma and healthy control subjects
Multiple blunt trauma Control Statistical
Characteristic n = 52 n = 40 significance
a,b
Age, years 24.15 18.80 23.53 14.29 NS
Gender, male/female 34/18 31/9 NS
TOS, mol H
2
O
2
equivalents/l 14.88 4.69 8.84 1.79 P < 0.001
TAS, mmol Trolox

equivalents/l 1.01 0.15 1.15 0.19 P < 0.001

OSI, arbitrary units 1.47 0.45 0.78 0.21 P < 0.001
Data are presented as mean SD, or n patients.
a

2
-test (age, gender);
b
Students t-test (TOS, TAS, OSI).
TOS, total oxidant status; TAS, total antioxidant status; Trolox

, 6-hydroxy-2,5,7,8-tetramethylchroman-2-
carboxylic acid; OSI, oxidative stress index; NS, not statistically significant (P > 0.05).
170
MT Gokdemir, O Sogut, H Kaya et al.
Role of oxidative stress in multiple blunt trauma
nonsurvivors compared with survivors (P <
0.001 for both comparisons). There was no
significant difference in age between the two
groups. ISS and RTS showed positive and
negative correlations with TOS level,
respectively (Spearmans rank correlation
coefficient: 0.425, P = 0.002, and 0.357, P =
0.009; respectively), but neither was
significantly related to TAS or OSI.
Discussion
Trauma is one of the most substantial health
problems worldwide. Although MBT injuries
are seen in people of all ages and of both
genders, the incidence is higher in young
men than in other groups.
12 14
Trauma is
responsible for 10% of all deaths worldwide
and blunt trauma is more frequently
experienced by younger rather than older
people.
12,13
Basoglu et al.
15
reported that 55%
of 521 patients with blunt trauma were
between 20 and 49 years old. The mean age
of blunt trauma patients has been variously
reported as 30.6 years,
16
32.4 years
17
and
25.2 years.
18
The mean SD age of patients
in the present study was 24.15 18.80 years,
which is lower than that reported
elsewhere,
16 18
but there was no significant
association between age and mortality in
this population.
Anatomical and physiological scoring
scales such as the ISS and RTS provide some
predictive features of survival, but they fail
to explain 10% of the variability in survival
probability.
10,19,20
The ISS is the most
frequently used scoring system for multi -
TABLE 2:
Causes of multiple blunt trauma and multiple blunt trauma-related deaths in patients
admitted to the emergency department
Total cases Deaths
Cause of multiple blunt trauma n = 52 n = 17
Fall from a height 7 (13) 4 (24)
Motor vehiclepedestrian crash 14 (27) 3 (18)
Motor vehicle crash 27 (52) 9 (53)
Assault 4 (8) 1 (6)
Data are presented patient numbers (%).
TABLE 3:
Age and oxidative stress parameters in patients with multiple blunt trauma according to
whether they were survivors or nonsurvivors
Survivors Nonsurvivors Statistical
Characteristic n = 35 n = 17 significance
a
Age, years 26.17 20.55 20.50 14.54 NS
Revised Trauma Score 11.17 1.39 6.24 3.41 P < 0.001
Injury Severity Score 25.03 18.58 54.82 16.03 P < 0.001
TOS, mol H
2
O
2
equivalents/l 13.97 3.84 16.75 5.78 P = 0.043
TAS, mmol Trolox

equivalents/l 0.99 0.17 1.07 0.07 NS

OSI, arbitrary units 1.45 0.46 1.51 0.43 NS
Data are presented as mean SD.
a
MannWhitney U-test.
TOS, total oxidant status; TAS, total antioxidant status; Trolox

, 6-hydroxy-2,5,7,8-tetramethylchroman-2-
carboxylic acid; OSI, oxidative stress index; NS, not statistically significant (P > 0.05).
171
MT Gokdemir, O Sogut, H Kaya et al.
Role of oxidative stress in multiple blunt trauma
trauma patients, with mortality rate
increasing significantly with increasing ISS.
20
Other studies have demonstrated that the
RTS is a significant predictor of mortality in
trauma patients.
10,21
RTS and ISS have been
shown to be useful for the evaluation of
injury severity and survival in cases of
trauma.
17
The ISS and RTS were significantly
related to mortality in the present study. The
ISS was significantly higher in nonsurvivors,
and the RTS was significantly higher in
survivors. A trauma study involving 207
patients found that a fatal outcome
prevailed in cases with an ISS > 15,
22
and an
ISS 12 was found to be indicative of severe
blunt trauma.
23
Patients with high ISS
should be hospitalized rapidly.
13
The mean
SD ISS in the nonsurvivor group of the
present study was more than double that
observed in patients who survived. All of the
patients had severe injuries and were
hospitalized after being stabilized in the
emergency room. The mean ISS for surviving
patients with MBT in the present study was
unexpectedly high (mean of 25.03)
compared with that reported elsewhere
(mean of 15).
22
Although the reason for the
high ISS in surviving patients in the present
study was not specifically analysed, it might
be attributed to the lower sample size and
the fact that the more severe injuries
sustained in the present study may have
affected the outcome; this limits comparison
with external data.
22,23
Patients with severe trauma show
oxidative stress, reflecting an imbalance
between the intra- and extracellular
environments in favour of oxidants.
24
This
imbalance induces certain chemical reactions
that can be both beneficial and detrimental,
depending upon the systems involved and the
disease processes.
25
Other attempts to assess
redox status in patients with severe trauma
have been limited to measurements of single
parameters, such as concentrations of
individual antioxidants or levels of lipid
peroxidation.
25,26
Although these parameters
may be helpful, they may not provide the
clinician with a complete assessment of the
degree of oxidative stress occurring in a
patient with severe trauma. In addition,
measuring these parameters is both laborious
and time consuming and is, therefore,
impractical in a clinical setting.
24
Clinical
data have confirmed an important role of
increased oxidative stress in acute dysfunction
of the respiratory, renal and cerebral
systems.
27
In one study, injury severity and
serum amyloid A levels were correlated with
plasma oxidationreduction potential (ORP)
in patients with MBT, and there was a
significant association between plasma ORP
and severity of injury.
28
The present study
found that plasma TOS and OSI levels were
significantly higher, and plasma TAS levels
were significantly lower, in MBT patients
compared with control subjects; this suggests
a positive correlation between degree of
oxidative stress and severity of injury. TOS
level, as a marker of early oxidative stress,
may reflect the severity of injury and provide
an early indication of clinical outcome.
Maintenance of fluid volume is an
important component of survival in patients
with severe trauma. Intravenous fluid
administration can cause haemodilution,
thereby decreasing levels of oxidants and
reductants, and affecting the true plasma
ORP in a patient with severe trauma.
24
In the
present study, blood was extracted when the
patient presented to the emergency room,
before intravenous fluids were administered.
The assessment of oxidative stress
defined as increased reactive oxygen species
production and exhaustion of antioxidant
stores requires a multimodal approach.
Oxidative damage can be much better
estimated by quantifying the oxidative by-
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Authors address for correspondence
Assistant Professor Ozgur Sogut
Harran Universitesi Tip Fakultesi, Acil Tip Anabilim Dali, Morfoloji Binasi, Yenisehir
Kampusu, TR-63300, Sanliurfa, Turkey.
E-mail: drosogut@harran.edu.tr
173
MT Gokdemir, O Sogut, H Kaya et al.
Role of oxidative stress in multiple blunt trauma