Nghiên cứu biến đổi nồng độ IL-6, IL-10 huyết tương và mối liên quan với thời điểm phẫu thuật kết hợp xương ở bệnh nhân đa chấn thương có gãy xương lớn

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INTRODUCTION
Polytrauma a major public health concern which receives much
attention from global health systems health care systems of the
world, including Vietnam. Management of polytrauma patients with
major fracture remains controversial, particularly surgical timing, as
well as the optimal techniques of external fixation related to the
physiopathological progress of multiple injured patients.
Systemic inflammation response and immune response occurs
due to excessive release of pro-inflammatory cytokines, which, in
turn, results in an imbalance among them. Interleukin-6 (IL-6) and
antiflammation cytokines such as interleukin-10 (IL-10) occur after
severe trauma and surgical intervention.
Globally, there have been numerous reports on assessment of role
of plasma IL-6, IL-10 levels in monitoring, prognosis as well as
investigation of its relation to injury severity, surgical timing and
prognostic value of fixation-attributable complications in patients
with multiple trauma. In Vietnam, this issue needs further study.
Thus, the thesis named “Research on changes of plasma IL-6,
IL-10 level and their association with timing of external fixation
of major fracture in patients with multiple trauma” was
conducted aiming:
1. Investigate changes of plasma IL-6, IL-10 level and IL-6/IL-10
ratio; their association with characteristics, severity of injury in
multiple trauma patients with major fracture;
2. Identify the correlation of IL-6 and IL-10 level as well as IL6/IL-10 ratio with surgical timing of fracture fixation in polytrauma
patients.
New contributions and practical significance of the thesis
Based on two aforementioned objectives, the research has
provided further scientific evidence on the changes in plasma levels

of IL-10 and IL-6 as well as IL-6/IL-10 ratios post-trauma, also
determined their correlation with severity as well as features of
injury, surgical timing, prognostic value of these cytokines,
complications following fracture fixation. With findings reported in


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the current study, we found that the measurement of IL-6, IL-10
levels in polytrauma patients with major fractures contributes to
predict promptly and accurately as well as make treatment decisions
among physicians. Osteosynthesis should not be performed until at
least 5 days after injury.
Organization of the thesis
The thesis is comprised of 127 pages (excluding references and
appendices), of which 02 pages for Introduction, 35 pages for
Overview, 20 pages for Subjects and Methods, 32 pages for Results,
34 pages for Discussion and 02 pages for Conclusion, 01 page for
Recommendation, 01 page for Limitations of thesis. Additionally, the
thesis also includes 62 tables, 8 figures and 19 charts and 147
references with 20 in Vietnamese and 127 in English.
Chapter 1 OVERVIEW
1.1. Overview on polytrauma
1.1.1. Definition
At a medical conference held by French (1971), Patel A. and
Trillat A. were the first to introduce the definition of polytrauma,
where a polytrauma patient was defined as having two or more
significant injuries, affecting respiratory and circulatory system.
1.1.2. Trauma Severity Classification Scores and prognostic
index used as an assessment of multiple trauma patients.

Benefits of Trauma Severity Classification Scores: The scoring
system for the trauma enables the usage of a common language for
the trauma classification, convenience in the transport and triage of
the patients, irrespective of specific features of each patient: injury
mechanism, age, geographical regions, trauma systems. They
include: Revised Trauma Score established by Champion et al
(1989),
Abbreviated Injury
Scale (AIS)
created
by
the Association for the Advancement of Automotive Medicine
and Injury Severity Score (ISS) by Baker S.P et al (1974). RTS, ISS


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are the scoring systems widely used for the classification of multipletrauma patients globally as well as in Vietnam.
1.2. The management of major fracture in patients with multiple
trauma
1.2.1. Early total care
Early total care is defined by Enninghorst et al (2011) that
early radical surgery for extremity injuries is performed with other
injuries in the first 24 h post trauma. Indications for early
osteosynthesis don’t depend on injury severity, minor or major
fracture or the need for patient’s resuscitation. The technique of
fracture fixation provides several advantages. It allows a lower
complcation rate and a shorter hospital stay (Nicola R., 2013).

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1.2.2. Damage control orthopedic surgery
Damage control surgery is minimally invasive surgical
techniques, shorter operating time, simple-to-perform. Damage
control
emphasizes
the
stabilization
and
control
of
hemorrhagic shock and hemostatic resuscitation as soon as possible;
often with use of spanning external fixation, rather than immediate
fracture repair. In a study by Pape HC et al (2002) on
polytraumatized patients (ISS ≥ 18) with femoral shaft fracture, the
authors reported a significantly lower complication rate of multiple
organ failure (MOF) following damage control orthopedic surgery
compared to early total care.
1.2.3. Secondary surgery
Secondary surgery for major fracture is to stabilize fractured
bones. The optimal timing of surgical stabilization of fractures is a
determinant to the outcomes of treatment and rehabilitation. There is
an accumulating body of evidence to suggest that one of the
key determinants of surgical
indication
and
timing of surgical stabilization of fractures is injury severity.
1.3. Inflammatory response in polytrauma
1.3.1. Plasma level of interleukin-6 (IL-6) and interleukin-10 IL10 in polytrauma

Interleukin-6 (IL-6): is an important pro-inflammatory cytokine
Interleukin-6 release from peripheral blood serves as an early marker
of injury severity following major trauma.
Conventionally, there is an elevated IL-6 level immediately after
trauma, surgery and can be detected after as early as 70 minutes after
injury. IL-6 showed a sharp rise to peak within the first 24 hours,
then fell rapidly to the baseline levels. The presence and persistence
of IL-6 in peripheral blood up to 10 days post trauma allows an
assessment on the extent of inflammatory response. Elevated IL-6
levels can predict MOF-related mortality.


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Human interleukin-10 (IL-10)
is
a potent
antiinflammatory cytokine that canprevent immunopathology during
inflammatory responses. IL-10 has protective effects under
inflammatory conditions. Excessive production of IL-10 increases
the susceptibility of infection and is prone to developing severe
sepsis. IL-10 plasma levels reflects severity of injury and are
elevated in patients with sepsis, MOF or acute respiratory distress
syndrome and mortality. IL-10 occurs early within 60 minutes
following injury. Dekker et al’s study demonstrated that elevated IL10 was correlated with incidence of sepsis and MOF.
Association of IL-6, IL-10 with the injury severity
Numerous
studies
reveal
an early

increase of IL6 immediately after trauma. This response initially corresponds to the
first-hit phenomenon. Subsequently, the second hit impact following
surgical procedure results in a higher response of plasma IL-6 level.
According to a report by Svoboda (1994), plasma IL-6 level upon
admission was significantly correlated with injury severity as
assessed by ISS value. An early increase in IL-6 was associated with
MOF. IL-10 plasma concentrations on day 1 post-trauma and postoperation were equally and significantly elevated (Tschoeke et al,
2007).
Role of IL-6, IL-10 and their prognostic value
A higher plasma level of IL-6 has been shown to have a high
predictive value for the mortality among polytraumatized patients,
especially within the first 24 hours post-trauma. By contrast,
prognostic value of IL-10 concentrations was lower. This
corresponds to the findings reported by Gebhard F et al (2000), in
which 19% of 94 patients died and elevated IL-6 was found among
the deaths at 4, 6, 12 hours following injury. Lausevic Z. et al
revealed high level of IL-6 were raised in patients with MOF and
were elevated early post-trauma. Pape H-C noted that in patients
with the most severe injuries, IL-6 plasma levels remained elevated
at post-operative day 5 and was strongly associated with MOF.
Role of IL-6, IL-10 and surgical timing


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Inflammatory response has been reported to be higher in patients
undertaking secondary surgery at days 2-4 than those operated at
days 6 - 8 (study by Pape H-C et al). Additionally, the finding
revealed the high likelihood of MOF in patients with elevated IL-6 at
admission undergoing secondary surgery. Stahel P.F et al. (2005)

suggested that progress of systemic inflammatory response and
immune response was the crucial factor for the time of second
surgery. Starting from 24 hours after trauma, based on systemic
inflammatory and immune response, polytrauma can be divided into
four stages: phase of increased systemic inflammatory response
(days 2 - 4), window period (days 5 - 10), immunodeficiency period
(3rd week) and recovery period (after 3 weeks). The author stated that
the second surgery should be performed at the window period and
the recovery period after trauma. In contrast, if surgery performs
during the period of increased systemic inflammation and
immunodeficiency stage, postoperative complication rate will be so
high.
1.4. International and domestic researches on IL-6, IL-10 among
traumatized patients.
1.4.1. International researches
Patients with minor injury had elevated concentrations as well but
to a far lesser extent.
Bogener V (2009) found that patients with severe injuries had
higher IL-6, IL-8 and IL-10 plasma levels. By contrast, those with
minor injury had less elevated concentrations. Furthermore,
excessively elevated IL-10 was strongly associated with major
trauma (ISS>35). Svoboda P et al noted that increased IL-6 level
following trauma was correlated with MOD and there was a close
correlation between higher IL-6 and ISS value (r = 0.73). In a study
by Gouel-Cheron A et al in 100 patients of whom 37% developed
sepsis, IL-10 was found to be increased in the death group and did
not correlate with prognosis. Casey LC et al (1993) reported that
concentrations of plasma IL-6 and IL-10 were used as marker to

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predict systemic inflammation response syndrome (SIRS), sepsis and
multi-organ dysfunction syndrome (MODS)
1.4.2. Domestic researches
In Vietnam, there have been a limited number of investigations on
posttraumatic cytokine alterations and their role of in the setting of
polytrauma. Nguyen Viet Quang’s study revealed a higher IL-6
concentration in the deaths than in the survivors and IL-6 was
positively correlated with age but negatively with Glassgow scale.
Nguyen Truong Giang’s study (2018) found an early increase in IL-6
and IL-10 immediately after trauma; IL-6 and IL-6/IL-10 ratio were
positively correlated with the injury severity as assessed by ISS, RTS
values and can predict the mortality, MODFand sepsis in traumatized
patients. In a study by Nguyen Luong Bang et al, the highest IL-6
plasma levels were found in the first day after surgery and fell
gradually over time. IL-6 levels on the first postoperative day closely
correlate positively with the Injury Severity Score (ISS).
CHAPTER 2: SUBJECTS AND METHODS OF
RESEARCH
2.1. Subjects of the study
In the present study, 59 polytrauma patients with major fracture
were enrolled. These patients were performed emergency surgery
and treated at Military Hospital 103 in the period study from July,
2015 to January, 2018.
2.1.1. Selection criteria
- Patients were diagnosed with multiple trauma according to
definition of polytrauma by Patel A (1971) and Trentz O (2000).
- Patient underwent emergency surgery at Military Hospital 103
within the first 6 hours since injury and received no treatment at

tertiary center prior to hospital admission.
- Multiple trauma patients were accompanied with major fracture.
The major bones include pelvis, femur, tibia and humerus. Patients
underwent fracture fixation at Military Hospital 103 during their
hospital stay.


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2.1.2. Exclusion criteria
- Patients died prior to surgery
- Patients were definitively treated at other hospital before
transfer.
- Patients were was intubated, had tracheotomy
- Patients were sent to other hospital prior to undertaking external
fixation or were eligible for discharge.
- Patients had insufficient sample-based data
2.2. Research methods
2.2.1. Study design:
This is a prospective, descriptive clinial study with longitudinal
follow-up.
2.2.2. Sampling size
Convenient sample included 59 patients who fulfiled inclusion
criteria.
2.2.3. Procedures
Buil up medical record for patient registries and collect variables
based on sampling health record.
2.2.3.1. Patient-related variables
- Age, gender, causes of trauma, injury mechanism: (Baker SP et
al, 1974).

- Incidence of the number of injured regions
- Incidence of deaths and survivors caculated from
the number of injured regions.
- Mechanism of combined injuries, rate of major fracture.
- Mortality rate, traumatic shock and acute respiratroy distress
- Mortality rate, traumatic shock and acute respiratroy distress
according to injury mechanism.
- Time from trauma to hospital admission.
- Survival and death rate.


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2.2.3.2. Organ function assessment in multiple trauma
patients
- Timing of assement: During treatment
- Organ for assessement: Ciculation, Perception...
2.2.3.3. Assessment of trauma severity by scoring
system RTS, AIS and ISS
- Timing of assessment: Hospital admission
- Trauma severity scoring system
+ Revised Trauma Score (RTS) by Champion HR et al (1989)
+ Abbreviated Injury Scale (AIS): in 1990 and 1998 version AIS 90 and AIS - 98) created by American Association for Automotive
Medicine
+ Injury Severity Score (ISS) by Baker SP et al (1974).
- Changes in plasma of IL-6, IL-10 levels and their association
with injury severity
+ Investigation of changes in plasma of IL-6, IL-10 levels,
IL6/IL-10 ratios at time points
+ IL-6, IL-10 levels and IL6/IL-10 ratios in the group of death

and survivors
+ Predictive value of IL-6, IL-10 levels and IL6/IL-10 ratios
for death
+ Alterations of plasma of IL-6, IL-10 levels and IL6/IL-10 ratios
at time points of study related to scoring systems assessed by RTS,
AIS, ISS
2.2.3.4. Association of changes in IL-6 and IL-10 levels
with surgical timing of fracture fixation
- Timing of external fixation: From day 2 to day 4 after trauma
and day 5 onward after trauma.
- Indications for osteosynthesis: Based on the patient’s health
condition (Trentz O., 2000).
- Fracture fixation devices: External fixation frames,
intramedullary nails, screw-plate fixation.


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- Complications following fracture fixation: Pneumonia, sepsis,
MOF, surgical site infection.
- Surgical results:
- The number of survivors and deaths.
- Association as well as prognostic value of IL-6, IL-10 levels
pre-and-post operation with surgical complication.
- Association between surgical timing and complications.
- Comparison between IL-6, IL-10 post surgery and timing of
fracture fixation.
2.2.3.5 Process of treatment
Compliance with the process of diagnosis and treatment of Military
Hospital 103

- Intensive care
- Polytrauma management by Stahel P.F (2005):
- External fixation as a second-procedure.
2.2.3.6. Quantification of serum IL-6, IL-10 levels
Timing of blood collection of determination for serum
IL-6, IL-10 levels: T0: Blood samples were collected in
the first 6 hours after trauma; T1: 12 hours after trauma;
T2: 24 hours after trauma, T3: 48 hours after trauma, T4:
72 hours after trauma, T5: immediately prior to external
fixation osteosynthesis; T6: 24 hours after fracture
fixation.
- Location for biochemical test: The Center of Medical
Pharmaceutical Research, Vietnam Military Medical University –
Quantification methods: IL-6, IL-10 concentration were determined
by kit of AviBion - Orgenium company, Finland and
ELISA
2.3. Time and location for study:
+ Study period: From July, 2015 to January, 2018
+ Location: Military Hospital 103, The Center of Medical
Pharmaceutical Research, Vietnam Military Medical University


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2.4. Data processing
Data were stored and processed by SPSS 22.0 software
2.5. Ethics in research
The study was compliance with the diagnostic and treatment
process of Military Hospital 103, did not affect the treatment process
for the patient, the data was only performed for the study for no other

purpose, the list of patient names was coded according to regulations.
Chapter 3 RESULTS OF RESEARCH
3.1. Patient characteristics
3.1.1. Age, gender
- Age: The majority of injured patients were within the age range
of 20 – 59, mostly from 20-39 years of age (49.1%).
- Gender: Males outnumbered females, of whom, 76.3% were
men and 23.7% were women.
3.1.2. Causes of trauma:
The most common causes of traumatic injuries identified were
traffic accident (74.6%), high fall (22.0%), others (3.4%).
3.1.3. Characteristics of injury
- Number of injured regions:
Three injured body regions (55.9%) were frequently encountered,
23.7% in two body regions, 20.4% in four body regions and no cases
had injuries in more than four body regions.
- Association between mortality rate and number of injured
regions
The mortality rate in patients with four injured body regions was
58.3%, 21.2% in three body regions whereas there was one death for
two injured body regions.
- Combined injuries
Traumatic brain injury (69.5%) chest injury (45,8%), abdominal
injuries (33.9%), maxillofacial injuries (30.5%), burn (18.6%).


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- Characteristics of major fracture
In the current study, one bone fracture occurred in 69.5%; twobone fracture in 20.3%; three-bone fracture in 10.2%; femoral shaft

fracture in 71.2%, pelvic fracture in 27.1%.
3.1.4. Time of admission
Average time of admission was 2.85 ± 1.08 hours, earliest
admission was within the first one hour and late admission was after
six hours of trauma
3.2. Changes in IL-6 and IL-10 concentrations in multiple
trauma patients

3.2.1. Changes in IL-6 concentrations in multiple trauma
patients
Table 3.1: IL-6 concentrations at time-points of study
IL-6

Lowest

Highest

Median

Total

Time points

(ng/L)

(ng/L)

(ng/L)

(n)

T0

2,99

215,25

68,79 ± 59,52

59

T1

8,95

245,11

95,90 ± 69,72

T2

6,36

258,05

79,90 ± 62,89

T3

4,17

226,70

75,27 ± 62,56

T4

4,37

301,20

75,09 ± 60,99

T5

2,79

317,03

74,23 ± 63,61

T6

11,75

348,20

120,10 ± 76,85

59

p

0,02
6

59

0,00
7

56

0,04
6

53

0,04
7

59

0,04

55

0,02
8

13

(* p < 0.05 vs. T0)
IL-6 levels peaked at T1 and reached a second peak at T6.
3.2.2. Changes in IL-6 concentrations in multiple trauma
patients
Table 3.2: IL-10 concentrations at time-points of study
IL-10

Lowest

Highest

Median

Total

Time-points

(ng/L)

(ng/L)

(ng/L)

(n)

T0

15,76

347,82

128,02 ± 73,87

59

T1

13,60

363,47

149,20 ± 80,89

59

0,036

T2

11,81

498,84

180,09 ± 119,88

59

0,047

T3

9,30

408,49

169,94 ± 96,34

56

0,039

T4

9,09

516,13

215,79 ± 132,22

53

0,045

T5

11,81

413,01

204,17 ± 96,97

59

0,043

T6

52,55

564,23

264,12 ± 118,96

55

0,034

p

(* p < 0.05 vs. T0)
IL-10 level was higher at all time-points and reached its peak at
72 hours after trauma and the first post-operative day.
3.2.3. IL-6/IL-10 ratios


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Table 3.3: IL-6/ IL-10 ratios at all time-points of study
IL-6/IL-10
Time-points

Lowest

Highest

Median

Total
(n)

p

T0
T1
T2
T3
T4
T5
T6

0,03
0,09
0,07
0,07
0,04
0,04
0,13

2,26
6,48
1,99
1,82
2,11
1,88
1,82

0,58 ± 0,49
0,77 ± 0,92
0,52 ± 0,46
0,52 ± 0,44
0,44 ± 0,47
0,41 ± 0,41
0,48 ± 0,35

59
59
59
56
53
59
55

0,002
0,000
0,000
0,000
0,000

0,000

The ratio of IL-6 to IL-10 was highest at T1, equivalent to early
peak of IL-6.
3.3. The severity of injury
3.3.1. Clinical assessment of injury severity
- Mortality rate, traumatic shock and acute respiratory distress
Acute respiratory distress occurred in 61%; traumatic shock in
50.8% and mortality in 25.4%.
- Mortality rate, traumatic shock and acute respiratory distress
according to injury mechanism:
There was a high rate of traumatic shock, occurring in patients
with pelvic and femoral fractures. Mortality and traumatic shock
among abdominal trauma patients were found to have the highest
rate (40% and 85.0%, respectively). The incidence of acute
respiratory distress was the highest in chest trauma patients (88.9%).
3.3.2. Assessment of injury severity by AIS scoring systems
The mean AIS was 3.69 ± 0.701; AIS3: 44.1%, AIS4: 42.4%,
AIS5:13.5%.
Table 3.4: Association between AIS and fracture sites (n=59)
Fracture
Non-fracture
Features
p
Fracture sites
n
± SD
n
± SD
Pelvic

16
3.81 ± 0.750
43
3.65 ± 0.686 0.47


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Femoral

42

3.57 ± 0.668

17

4.0 ± 0.707

Tibial

13

3.62 ± 0.650

46

3.72 ± 0.720

Distal radius

9

3.78 ± 0.667

50

3.68 ± 0.713

3
0.03
2
0.67
4
0.70
4

3.3.3. Assessment of injury severity by RTS scoring system
The mean RTS was 8.24 ± 1.92, the lowest score was 5 and the
highest was 12. RTS score from 8-10 was seen in 49.1%
Table 3.5: Injury severity by RTS score (n=59)
Survival

RTS score

Mortality

n = 44

Rate (%)

n = 15

Rate (%)

Moderate or minor (>10) (1)

6

85.71

1

14.29

Serious (8-10) (2)

27

93.1

2

6.9

Severe (≤ 7) (3)

11

47.83

12

52.17

p

p2-3 = 0.01

p3-2 = 0.01

Table 3.6: RTS score in the survival and death group
Group
RTS score
Mean

Mortality
(n=15)

Survival
n=44

p

6.80 ± 1.521

8.73 ± 1.796

0.000

Mean RTS score was lower in the death than in the survival group

(p<0.05).
3.3.4. Assessment of injury severity by ISS scoring system
Average ISS score at admission ranged from 17 - 68 with mean
score of 32.02 ± 11.91.
Table 3.7: Assessment of injury severity by ISS scoring system
Group
ISS score

Survival
n = 44

Rate

Mortality
n = 15

Rate

Total
n

Rate


16
(%)

(%)

(%)

Serious (16 - 25) (1)
Severe (26 - 40) (2)

19
18

90.5
78.3

2
5

9.5
21.7

21
23

100
100

Critical (> 40) (3)

7

46.7

8

53.3

15

100

(p2-3= 0.009)
Table 3.8: Mean ISS score in the survival and death group
Groups
ISS score
ISS score (points)

Mortality
n=15

Survival
n=44

p

38.80 ± 11.85

29.70 ±11.14

0.009

3.4. Association between changes in IL-6, IL-10 concentration
and the injury severity
3.4.1. Concentration of IL-6 and IL-10 and ratio of IL-6/IL-10 in
the mortality group

Table 3.9: Concentration of IL-6 in the survival and death group
Death

Group
Time points

n

T0
T1
T2
T3
T4
T5
T6

15
15
15
12
9
15
11

± SD
136,81 ±53,00
155,38 ±48,22
136,20 ±49,15
138,21 ±48,41
120,66 ± 71,25

128,44 ± 79,33
191,43 ± 83,94

Survival
n
44
44
44
44
44
44
44

± SD

Total
(n)

p

45,60 ± 41,24
75,63 ± 64,38
60,71 ± 55,38
53,81 ± 51,61
59,56 ± 48,93
55,75 ± 45,10
95,79 ± 57,37

59
59

59
56
53
59
55

0,000
0,000
0,000
0,000
0,000
0,000
0,000

Table 3.10: Concentration of IL-10 in the survival and death group
Group
Time points
T0
T1
T2
T3

n
15
15
15
12

Death
± SD

149,20 ± 83,44
175,33 ± 81,20
192,81 ± 99,02
199,46 ± 93,81

n
44
44
44
44

Survival
± SD
120,79 ± 69,88
140,28 ± 79,75
175,75 ± 126,95
159,87 ± 96,16

Total
(n)
59
59
59
56

p
0,201
0,149
0,638
0,171

17
T4
T5
T6

9
15
11

240,20 ± 132,51 44
243,69 ± 87,62 44
315,39 ± 99,56 44

207,47 ± 132,61
190,70 ± 97,23
246,64 ± 120,96

53
59
55

0,412
0,067
0,052

Table 3.11: Ratio of IL-6/IL10 in the survival and death group
Groups
Time points

T0
T1
T2
T3
T4
T5
T6

n
15
15
15
12
9
15
11

Death
± SD
1.07 ± 0.46
1.04 ± 0.44
0.88 ± 0.50
0.85 ± 0.47
0.66 ± 0.57
0.66 ± 0.57
0.71 ± 0.50

Survival
± SD
0.41 ± 0.38

0.68 ± 1.02
0.40 ± 0.38
0.40 ± 0.37
0.36 ± 0.41
0.32 ± 0.30
0.40 ± 0.24

n
44
44
44
44
44
44
44

Total
(n)
59
59
59
56
53
59
55

p
0.000
0.200
0.000

0.000
0.03
0.05
0.003

There was a disparity between ratios of IL-6/IL-10 and two groups
of death and survivors at all timepoints but T1 (p < 0.05).
Table 3.12: Prognostic value of IL-6, IL-10 and ratios of IL-6/IL10
at all time-points
AUC
Time points
T0
T1
T2
T3
T4
T5
T6

IL-6
AUC
p

IL-10
AUC
p

IL-6/IL-10
AUC
p

0,920
0,836
0,848
0,894
0,772
0.818
0.848

0,607
0,628
0,588
0,609
0,579
0,648
0,694

0,903
0,798
0,839
0,826
0,752
0,736
0,729

0,000
0,000
0,000
0,000
0,002

0,000
0,000

0,220
0,141
0,313
0,210
0,365
0,088
0,026

Total
(n)

0,000
0,001
0,000
0,000
0,004
0,007
0,009

59
59
59
56
53
59
55

3.4.2. Association of IL-6, IL-10, IL-6/IL-10 ratios with RTS and
ISS
Table 3.132: Correlation coefficiency between IL-6 and RTS, ISS
Time points
T0
T1
T2
T3

RTS score
-0,378
-0,412
-0,338
-0,386

p
0,003
0,001
0,009
0,003

ISS score
0,171
0,087
0,161
0,245

p
0,195
0,511

0,223
0,062

Total(n)
59
59
59
56


18
T4
T5
T6

-0,272
-0,268
-0,331

0,037
0,040
0,011

0,203
0,338
0,277

0,123
0,009
0,033

53
59
55

IL-6 was negatively correlated with RTS score (p<0.05) but
positively correlated with ISS score at T5, T6
Table 3.33: Correlation coefficiency between IL-6 and RTS, ISS
Time points
T0
T1
T2
T3
T4
T5
T6

RTS score
-0,305
-0,172
-0,110
-0,187
-0,070
-0,059
-0,169

p
0,019
0,192
0,405

0,156
0,600
0,655
0,201

ISS score
-0,098
-0,185
-0,226
-0,110
-0,192
-0,100
-0,076

p
0,460
0,161
0,085
0,406
0,145
0,449
0,570

Total (n)
59
59
59
56
53
59

55

There was a negative correlation between IL-10 and RTS at T0.
Table 3.34: Correlation coefficiency between ratio of IL-6/IL-10 and
RTS, ISS
Time points
T0
T1
T2
T3
T4
T5
T6

RTS score
-0,257
-0,163
-0,279
-0,366
-0,110
-0,256
-0,230

p

ISS score

p

0,050

0,217
0,032
0,004
0,405
0,051
0,080

0,267
0,149
0,409
0,415
0,386
0,474
0,417

0,041
0,259
0,001
0,001
0,003
0,000
0,001

Total (n)
59
59
59
56
53
59

55


19

3.5. External fixation as a second procedure
3.5.1. Timing and technique of external fixation
- Timing of external fixation as a second procedure: 24
patients underwent external fixation at days 2-4 and 35 patients on
the fifth day following injury.
- Technique of external fixation: Fractures were
stabilized using different implants like intramedullary
nailing (66,1%), external fixators (20.3%) and plate-screw
fixation (13.6%)
3.5.2. Association of IL-6, IL-10 concentration, IL-6/IL-10 ratios
with surgical timing and complications of external fixation.
Table 3.37: IL-6, IL-10 concentration, IL-6/IL-10 ratios immediately
pre- and post-surgery (n=59)
Concentration

Preoperation
(n = 59)

Postoperation day 1
(n = 55)

p

IL-6 (ng/L)

74.23 ± 63.61

120.10 ± 76.85

0.000

IL-10 (ng/L)

204.17 ± 96.97

264.12 ± 118.96

0.000

0.41 ± 0.40

0.48 ± 0.35

0.05

IL-6/IL-10

There was an elevated concentration of IL-6 and IL-10 postoperation vs. pre-operation (p<0.05).
Table 3.14: Assosication between concentration of IL-6, IL-10, ratios
of plasma IL-6/IL-10 and complications of fracture fixation
Concentration
Preoperation
(T5)
Postoperation
(T6)

IL-6 (ng/L)
IL-10 (ng/L)
IL-6/IL10
IL-6 (ng/L)
IL10 (ng/L)
IL-6/IL10

Complications
(n=22)
123.45 71.24
223.72 99.93
0.71 0.52
186.31 79.85
311.44 125.20
0.70 0.46

Non-complications
(n=37)
44.97 34.61
192.55 94.62
0.23 0.13
80.74 39.04
235.99 107.11
0.35 0.15

p
0.000
0.236
0.000

0.000
0.017
0.000


20

- Prognostic value of plasma level of IL-6, IL-10, IL-6/IL-10
ratio with some complications.
Table 3.15: Prognostic value of plasma IL-6 and IL-10 levels and IL6/IL-10 ratios in determining postoperative complications (n=59)
Complications
Cytokines
Preoperation
(T5)

Postoperation
(T6)

MOF
(n=14)
AUC
p

IL-6

0.843

0.000

IL-10

0.865

0.000

IL-6/IL10

0.719

0.01

IL-6

0.763

0.003

IL10

0.730

0.047

IL-6/IL10

0.700

0.05

Sepsis

(n=13)
AUC
p
0.85
0.000
1
0.95
0.000
0
0.58
0.268
0
0.67
0.053
8
0.79
0.000
1
0.79
0.000
9

Pneumonia
(n=12)
AUC
p
0.803

0.001

0.849

0.001

0.635

0.138

0.672

0.081

0.723

0.013

0.693

0.019

(* p<0.05). AUC:
- Association of surgical timing with IL-6 and IL-10 level, ratios
of IL-6/IL-10 post-surgery
Table 3.16: Association of surgical timing with postoperative plasma IL6, IL-10 levels and IL-6/IL-10 ratios
Surgical timing
Concentration
IL-6 at T6 (ng/L)
IL-10 at T6 (ng/L)
IL-6/IL-10 at T6

Days 2-4
160.29 ± 75.45
332.26 ± 131.46
0.55 ± 0.41

After day 5
onward
92.55 ± 65.59
217.40 ± 83.22
0.44 ± 0.30

p
0.001
0.000
0.241

Plasma IL-6, IL-10 levels were higher in patients undergoing
external fixation at days 2-4 than those opertated after day 5 onward
(p<0.05).
- Association between surgical timing and early outome


21

Table 3.17: Association between surgical timing of osteosynthesis
and postoperative complications
Surgical timing

After day 5
onward

(n = 35)

Days 2-4
(n = 24)

Complications

Total
(n)

p

n

Rate (%)

n

Rate (%)

Pneumonia

9

75%

3

25%

12

0.007

MOF
Sepsis

11
10

78.6%
76.9%

3
3

21.4%
23.1%

14
13

0.001
0.003

Death

9

60%

6

40%

15

0.078

Patients undergoing external fixation at days 2-4 had higher rate
of complication than those operated after day 5 of trauma (p<0.05).
CHAPTER 4: DISCUSSION
4.1. Patient characteristics
4.1.1. Characteristics of age and gender
Age and gender distribution in the current study were consistent
with those in study by Nguyen Truong Giang: 78.2% were males
with the majority being under 50 years of age (82.7%). Pape et al
(2014) reported a mean age of 42.9 ± 20.2 years, male in 72%,
female in 28%.
4.1.2. Causes of trauma
Trauma was caused by traffic accidents in (74.6%), followed by
high fall (22%) and others. This coincides with the results of other
authors: Trinh Van Dong et al (2007): traffic accidents were observed
in 71.7% and labor accident in 21.7%; Hildebrand F et al (2015):
traffic accident in Germany and England was 69.1% and 77.3%,
respectively.


22

4.1.3. Features of trauma
Traumatic brain injury had the highest rate (69.5%).
The mortality rates of the patients with four injured body regions
constituted 58.3%, 21.2% had three injured body regions and 7.1%
had two body regions. In a study by Nguyen Truong Giang (2007),
Increasing number of injured body regions increased the
likelihood of the mortality rate. The death rate in patients with 4
injured body regions was 45.3% compared to 18,2% in those with 2
body regions
4.1.4. Admission time to hospital
Mean time of hospital admission in the present study was 2.85 ±
1.08 hours, 2.7 ± 0.9 hours (1-5 hours) in Le Tien Dung’s research,
and 1.4 hours after trauma (1.4 ± 3.4) in a study by Sauaia A et al.
4.2. Changes in plasma concentration of IL-6 and IL-10 in
polytrauma patients.
4.2.1. Changes in IL-6 levels
Early increase in plasma IL-6 levels ocurred immediately after
trauma and at all timepoints. IL-6 levels peaked early at 12 hours
after injury (95.90 ± 69.72 ng/L). Plasma IL-6 levels peaked and
reached a second peak (120.10 ± 76.85 ng/L) on post-op day 1, in
which IL-6 levels at a second peak were higher than at a first one.
Billeter A et al (2009) noted that IL-6 levels peaked on day 1
following injury and fell gradually, returned to low threshold of
nearly zero on day 14 after trauma.
4.2.2. Changes in IL-6 levels
Early increase in plasma IL-10 levels ocurred immediately after
trauma and at all timepoints. However, IL-10 levels were increased
gradually, and showed a later maximum level than IL-6 at 72 hours

23

after trauma (Il -10 levels were 215.79 ± 132.22 ng/L). IL-10 levels
then rose again and reached a second peak on post-operative day 1.
Study by Nguyen Truong Giang et al (2018) reported a more delayed
increase in IL-10 levels than elevated IL-6 and that the IL10 level was the highest on day 3 after injur
4.2.3. Ratio of IL-6/IL-10
IL-6/IL-10 ratio was found to be highest at 12 hours following
injury, There was no significant change in this ratio on day 1
compared to pre-operation .
4.3. The severity of injury
4.3.1. Injury severity in clinical study
In the current study, patients with respiratory failure was present
in 61.0% and traumatic shock in 50.8%. This respective rate in a
study by Nguyen Truong Giang et al was 70% and 66.7% whereas
Schroeder et al (Germany, 2008) reported an acute respiratory
distress rate of 49%.
4.3.2. The severity of injury assessed by AIS scoring system
All patients had AIS ≥ 3, of whom AIS3 was seen in 44.1%, AIS4
in 42.4% and AIS5 in 13.5%.
4.3.3. The severity of injury assessed by RTS scoring system
The RTS score range is 5-12 points with mean score of 8.24 ±
1.92. Most patients had a RTS score of 8-10 (49.1%). One patient
died with RTS score > 10 points; two patients died with a RTS score
of 8 - 10 points; the death group with RTS score ≤ 7 points explained
for a high rate of 52.7%. Mean RTS score in the death group (6.80 ±
1.521 points) was substantially higher than the survival group (8.73 ±
1.796 points).

24

4.3.4. The severity of injury assessed by ISS scoring system
More than 70% of patients had ISS score > 25. Patients with a
critical ISS score and at high risk of death accounted for the majority
(39.0%), followed by those with severe trauma (35.6%) and serious
injury (25.4), no patients with moderate ISS score were observed.
Study by Nguyen Luong Bang showed that mean ISS score was
25.95, lowest 17 points and highest 42 points. ISS score in the death
group (30.27 ± 6.75) was higher compared to the survival group
(25.46 ± 6.19) (p < 0.05). Hildebrand et al’s research noted a mean
ISS score of 26.5 ± 6.8 in Germany and 28.7 ± 10.7 in England
among multiple trauma patients
4.4. Association of injury severity with IL-6 and IL-10
4.4.1. Plasma levels of IL-6 and IL-10 as well as ratio of IL-6/IL10 in death group
Our research revealed an early increase in IL-6 after trauma and
was higher in patients who died than those who survived at all time
points (p<0.05). IL-6 levels at 6 hours after injury have predictive
value of death with AUC=0.92 (p<0.05), which predicts mortality
with a specificity of 100% in case IL-6 level was ≥ 201.59 whereas
value of IL-10 in predicting death reached AUC = 0.69(p < 0.05).
Ratio of IL-6/IL-10 was substantially higher in patients who died at
all timepoints.
4.4.2. Association of IL-6 and IL-10 as well as IL-6/IL-10 ratio
with RTS and ISS scoring system
In the current study, IL-6 levels correlated negatively with RTS
score at all timepoints and positively with ISS at surgery and postoperative day 1 but its correlation was not significant. Plasma IL-10
levels were negatively associated with RTS score at 6 hours
following injury whereas there was no correlation between IL-10

25

level and RTS as well as ISS score at other timepoints. Ratio of IL6/IL-10 reveales a better correlation with ISS score than with IL-6
and IL-10. In line with our findings, Mimasaka et al. showed in 2006
that IL-6 was associated with AIS and ISS score among polytrauma
patients with correlation coefficient r = 0.45 and 0.33, respectively.
4.5. Second procedure as fracture fixation
4.5.1. Surgical timing and technique of fracture fixtation
In the present study, there were 24 patients (40.6%) undergoing
external fixation at days 2-4 and 35 patients (59.4%) operated at day
5 onward.
4.5.2. Association of IL-6 and IL-10 level with surgical timing
and their prognostic value of fixation-related systemic
complication
Plasma IL-6 and IL-10 concentration were increased on initial
day following fracture fixation. Reduction in IL-6/IL-10 ratios partly
reflects post-operative greater changes of IL-10 than those of IL-6.
Plasma IL-6 level was found to be higher after second fracture
fixation (reported by . Pape et al, 2002) whereas an early increase in
plasma level of IL-10 was observed at 24 hours after surgery
(Bogner et al’s research, 2009)
This study showed that pre-operative IL-6 level and IL-6/IL-10
ratio were higher in complicated patients than those without
complication (p<0.05). On postoperative first day, significantly
higher IL-6 and IL-10 concentrations as well as IL-6/IL-10 ratio
were noted in the complicated patients compared to noncomplication group. Pre-operative IL-6 levels had prognostic value
of early complication following fracture fixation (AUC > 0.8 and p <
0.05) whereas pre-operative IL-10 levels had prognostic value of
MOD (AUC= 0.72 and p < 0.05). IL-6 levels and IL-6/IL-10 ratios

can predict post-operative early complications such as surgical site