comparison of ischemia modified albumin levels with total oxidant

comparison of ischemia modified albumin levels with total oxidant

Acta Medica Mediterranea, 2014, 30: 601
COMPARISON OF ISCHEMIA MODIFIED ALBUMIN LEVELS WITH TOTAL OXIDANT, TOTAL
ANTIOXIDANT STATUS, OXIDATIVE STRESS INDEX IN CARBON MONOXIDE POISONING
P OLAT D URUKAN *, M URAT K OYUNCU *, O MER S ALT **, C EMIL K AVALCI ***, S EDA O ZKAN ****, S EBAHATTIN
MUHTAROGLU*****, GULSUM KAVALCI******CAGLAR OZDEMIR*******, ALI DUZGUN*, IBRAHIM IKIZCELI********
*Erciyes University Faculty of Medicine, Department of Emergency Medicine - **Yozgat State Hospital Emergency Department,
Yozgat - ***Baskent University Faculty of Medicine Ankara Hospital, Department of Emergency Medicine, Ankara - ****Dişkapi
Yildirim Beyazit Training and Research Hospital, Ankara - *****Medical Biochemistry - ******Yenimahalle State Hospital, Anesthesia
Department, Ankara - *******Forensic Medicine, Kayseri - ********Istanbul University Cerrahpasa Faculty of Medicine, Department
of Emergency Medicine, Istanbul, Turkey
ABSTRACT
Aim: The most common cause of death in CO poisoning is ventricular arrhythmias due to tissue hypoxia. In this study we
aimed to investigate the relationship between severity of poisoning and Total Oxidant Status (TOS), total antioxidant status (TAS) and
oxidative stress index (OSI) and also change in the levels of ischemia modified albumin (IMA) and neutrophil gelatinase-associated
lipocalin (NGAL ) over time in the patients with CO poisoning.
Material and methods: This study was performed at Erciyes University Faculty of Medicine, Department of Emergency
Medicine. Fifty patients between the ages of 18-65 who were diagnosed CO poisoning in the emergency department were included in
the study. As a control group 30 adult individuals with no history of any disease were included in the study. Ischemia modified album,
NGAL, OSI, TOS and TAS levels were studied. Mann-Whitney U test was using to compare of control and patient group. The
Wilcoxon test was used to compare the change in TAS, TOS, OSI, IMA, NGAL, COHb and lactate. p<0.05 was considered as statistically significant.
Results: When the 0th hour levels of Lactate, TOS, OSI, and IMA and TAS of the patient group were compared to the control
group, there was a significant difference between these groups (p <0.05). There was no significant difference in terms of the NGAL
level (p> 0.05). When 0th, 3rd, 6th, 12 and 24th hrs TAS, TOS, OSI, IMA, NGAL and lactate levels compared with each other, there
was no difference between them (p>0.05).
Conclusion: The levels of IMA, TOS, TAS and OSI were detected high in CO poisoning, but it is not meaningful in evaluating
the effectiveness of treatment.
Key words: CO poisoning, emergency, oxidative stress.
Received February 18, 2014; Accepted March 24, 2014
Introduction
Carbon monoxide (CO) is a colorless, odorless, non-irritant gas that releases from incomplete
combustion of carbon-containing fuels. It is
believed that the cause of more than half of fatal
poisonings all over the world is CO (1). Carbon
monoxide and hemoglobin (Hb) form a recycled
compound that is called carboxyhemoglobin
(COHb). Carboxyhemoglobin carries less oxygen
than normal Hb, because the oxygen affinity of CO
is 200 times more than hemoglobin. Although the
exact mechanism of CO poisoning is not clear, it is
thought that; it breaks the chain of the mitochondrial cytochrome oxidase and prevents the formation
of adenosine triphosphate. It also has a direct toxic
effect on tissues. It causes free oxygen radicals formation and lipid peroxidation in brain and other tissues and leads to hypoxia especially in the heart
muscle. The most common cause of death in CO
poisoning is ventricular arrhythmias due to tissue
hypoxia(2-4).
In this study we aimed to investigate the relationship between severity of poisoning and Total
Oxidant Status (TOS), total antioxidant status
(TAS) and oxidative stress index (OSI) and also
602
change in the levels of ischemia modified albumin
(IMA) and neutrophil gelatinase-associated
lipocalin (NGAL ) over time in the patients with
CO poisoning.
Secondarily, we aimed to investigate, if TOS,
TAS, OSI, IMA and NGAL levels could be used in
the early diagnosis and follow-up in CO intoxication.
Materials and methods
This study was performed between December
2008 and December 2009 at Erciyes University
Faculty of Medicine, Department of Emergency
Medicine. Local ethics committee of Erciyes
University Faculty of Medicine approved the study
(Date: 07.04.2009 and No: 2009/221). Fifty patients
between the ages of 18-65 who were diagnosed CO
poisoning in the emergency department were
included in the study. Written Informed Consent
Form was taken from all of the patients or their relatives. Patients with history of coronary artery disease, kidney failure, liver failure, hematologic disease, chronic obstructive pulmonary disease, diabetes mellitus, cerebrovascular disease, malignancy
or pregnancy were excluded from study.
Follow-up and treatment of patients with CO
poisoning were performed in the emergency department or intensive care unit.
Moment of arrival of the patients to the emergency department was considered as 0th hour.
Lactate and COHb levels of the patients were studied at 0th, 3rd, 6th, 12th and 24th hours, from arterial
blood samples. At the same time 3 mL venous
blood samples were centrifuged for 5 min at 3000
rpm, and serum samples were separated for each
patient. Separated serum samples were stored at 70°C. One day before the study day, serum samples
were dissolved at room temperature. Ischemia modified album (absorbance units (ABSU), NGAL (µg /
L), TOS (H2O2 Equivalent mmol / L) and TAS
(Trolox Equivalent µmol / L) levels were studied in
the biochemistry laboratory. Determined TOS value
was divided by TAS and OSI value was determined.
As a control group 30 adult individuals with
no history of any disease were included in the
study. Venous blood samples were taken from these
people and IMA levels were studied once.
Analysis of data was performed using SPSS
(Statistical Package for Social Sciences) 20.0 and
Sigma Stat 3.5 statistical software package. The
variables were investigated using analytical meth-
Polat Durukan, Murat Koyuncu et Al
ods (Kolmogorov-Smirnov test) to determine
whether or not they are normally distributed.
Descriptive analyses were presented using medians
and interquartile range (IQR) for the non-normally
distributed and ordinal variables. Mann-Whitney U
test was using to compare of control and patient
group. The Wilcoxon test was used to compare the
change in TAS, TOS, OSI, IMA, NGAL, COHb
and lactate. p<0.05 was considered as statistically
significant.
Results
Totally 50, 27 female (54%) and 23 male
(46%), patients were included in the study. Mean
age in female patients were 37.89 ± 12.60 (18-60),
while in males 41.78 ± 12.62 (24-60) (Table 1).
n
%
Mean age
Male
23
%46
41.78±12.62
Female
27
%54
37.89±12.60
Total
50
%100
Table 1: The number of patients with respect to sex and
mean age of the patient groups.
When the 0th hour levels of Lactate, TOS,
OSI, and IMA and TAS of the patient group were
compared to the control group, there was a significant difference between these groups (p <0.05).
There was no significant difference in terms of the
NGAL level (p> 0.05) (Table 2).
Median
value
TOS
TAS
Lactate
(mmol H2O2 (μmol Trolox OSI
(mmol/L)
Equivalent/L) Equivalent/L)
NGAL
IMA
(µg/L) (ABSU)
Patient
0th hour
3.150
16.285
2.915
5.755
89.100
88.570
Control
group
1.641
8.985
3.055
3.055
74.550
29.815
Table 2: 0th-hour Lactate, TOS, TAS, OSI, NGAL and
IMA levels in patient and control groups.
When we analyzed the levels of COHb, we
have seen that; 0th hour COHb levels were highest
and it decreased with time. Additionally when 0th
3rd 6th 12th and 24th hour COHb levels compared
with each other, it has been found to be significantly different (p <0.05) (Figure 1).
When the levels of lactate were evaluated, the
highest levels of lactate were found on 0th hours and
it decreased with time. When the 0th, 3rd, 6th, 12 and
24th hrs lactate levels compared with each other
Comparison of ischemia modified albumin levels with total oxidant...
603
there has been a significant difference (p <0.05)
(Figure 2).
Figure 4. TAS levels of patients with respect to hours.
Figure 1. COHb levels of patients with respect to hours.
Oxidative Stress Indexes were calculated as
5.755 at 0th hour, 7.405 at 6th hour, 7.435 at 12th
hour and 7.155 at 24th hour. When the 0th, 3rd, 6th, 12
th and 24th hours OSI levels compared with each
other, there was no significant difference between
them (p = 0.748) (Figure 5).
Figure 2: Lactate levels of patients with respect to
hours.
When we evaluated the levels of TOS, we
have found out that; when the 0th hour TOS median
value was 16.285 mmol H2O2 Equivalent / L, it
raised out 21.080 mmol H2O2 Equivalent / L at 6th
hour. But this increase was not statistically significant. When 0th, 3rd, 6th, 12 and 24th hrs TOS levels
compared with each other, there was no difference
between them (p = 0.411) (Figure 3).
Figure 5: The levels of OSI of patients with respect to
hours.
When the levels of NGAL examined, it has
been found out that; 0th hour median level of
NGAL was 89.100 µg/L, 79.500 µg/L at 3rd hour,
76.200 µg/L at 6th hour, 81.150 µg/L at 12th hour,
and 69.300 µg/L at 24th hour. When the 0th, 3rd, 6th,
12th and 24th hours NGAL levels compared with
each other, there was no difference between them (p
= 0.318) (Figure 6).
Figure 3: TOS levels of patients with respect to hours.
When the levels of TAS examined, it has been
found out that; 0th hour median level of TAS was
2.915 μmol Trolox Equivalent/L, raised out 2.930
μmol Trolox Equivalent/L on 3 rd hour, and
decreased to 2.875 μmol Trolox Equivalent/L on
24th hour. However, this reduction was not statistically significant. When the 0th, 3rd, 6th, 12 and 24th
hours TAS levels compared with each other, there
was no difference between them (p = 0.338) (Figure
4).
Figure 6: T. NGAL levels of the patient with respect to
hours.
When the levels of IMA were examined, it has
been found out that; while the median value of the
IMA at 0th hour was 88.570 ABSU, it decreased to
67.315 ABSU at 24th hour. There was significant
difference between the 0th, 3rd, 6th, 12th hours and 24th
hour levels of IMA (p<0.05). When the 0th, 3rd, 6th,
604
12th hours levels of IMA compared with each other,
there was no difference between them (p = 0.318)
(Figure 7).
Figure 7: IMA levels of patients with respect to hours.
Discussion
Carbon monoxide poisoning is fairly common,
difficult to diagnose due to nonspecific clinical
signs and is potentially fatal. If it is learned from
the history of the patient that he/she inhaled CO, it
makes the diagnosis quite easy. However, in
patients who is unconscious or with nonspecific
symptoms it is difficult to diagnose. Especially in
the winter, CO poisonings are more common and
patients may admit with influenza-like signs or
abdominal pain. The most commonly used diagnostic and follow-up parameter in CO poisoning is
COHb level(5,6). In this study it has been found out
that the highest levels of COHb of the patients is at
the admission and it decreased with time in the follow up period. Even it decreased to the completely
normal level on 6th hour and this situation is consistent with the literature(1,5-7). In the diagnosis of CO
poisoning COHb that consist of binding CO with
Hb is used. Hemoglobin affinity of CO is 200 times
greater than oxygen. This situation decreases the
oxygen-carrying capacity of Hb to the tissues and
leads to tissue hypoxia. As a result of tissue hypoxia, free radicals like Nitric Oxide are released
(NO)(1,7).
Arterial pH is not compatible with the clinical
findings and does not show the severity of CO
intoxication all the time. However, the lactate level
in arterial blood gases is superior to COHb in
demonstrating the severity of poisoning. Lactate is
a biomarker that indicates the severity of poisoning(1,7,8). In this study, when the lactate levels were
highest at 0th hour it decreased progressively after
treatment. In terms of demonstrating the efficacy of
treatment in patients, lactate is a good biomarker.
This information is consistent with the literatures(1,7,8).
Polat Durukan, Murat Koyuncu et Al
Oxidative stress is seen as a result of oxidative
damage that results from the production of free
oxygen radicals in the body and activation of the
antioxidant system against this situation. In recent
years, in order to use in determining the severity of
oxidative damage a lot of researches are being conducted on several biomarkers (1,7). Oxidant and
antioxidant systems are in equilibrium with each
other in the body. Although the effectiveness of the
oxidant and antioxidant substances can be measured independently, these measurements comprise
time-consuming and high cost. In order to perform
measurements high-tech systems are needed. When
the levels of TAS and TOS are good indicators of
oxidative stress status, the level of OSI is a more
valuable indicator in terms of showing neuropathological complications that may develop later, compared to other parameters. It has been reported that
OSI levels may be used in planning the treatment of
CO poisoning(9).
In the study that was conducted by Kavakli et
al. it has been shown that TOS and OSI levels were
higher in patient group compared to control group
and in terms of TAS levels there was no significant
difference between these groups. After the treatment, TOS, OSI COHb levels decreased significantly whereas no significant difference was detected between the TAS levels. TAS TOS and OSI levels may be used to identify the pathophysiology of
CO poisoning(9). They have reported that; TOS, TAS
and OSI levels have a statistically significant
change with time. In this study it has been achieved
that TOS, TAS and OSI levels increase in CO poisoning but they can not be used as a parameter in
order to evaluate the efficacy of the treatment. This
result is compatible with the study of Kavakli et
al.(9).
Neutrophil Gelatinase-Associated Lipocalin is,
a 25-kDa size glycoprotein in the granules of neutrophils (10). It releases from renal tubular cells,
immune cells and hepatocytes in various pathological conditions(11). The amount of NGAL increases in
blood and urine after ischemic injury. Catabolism of
the NGAL is difficult because of the small molecular structure. But it is easy to identify in the blood
and urine (12) . In the literature it has not been
observed in any study that investigated the NGAL
levels in CO poisoning. In this study, there was no
difference between the NGAL levels of the 0th hour
patient group and the control group, and no significant changes were observed in terms of NGAL levels with treatment. This result is suggested that;
Comparison of ischemia modified albumin levels with total oxidant...
NGAL levels rise can not be used as an important
parameter to evaluate the efficacy of treatment in
CO poisoning.
Ischemia Modified Albumin is a new biomarker that can be used in the evaluation of myocardial
ischemia. High levels of IMA are not only detected
in myocardial hypoxia cases but also in other tissue
hypoxia situations. High IMA levels are used as a
diagnostic biomarker especially in pulmonary
thromboembolism, mesenteric ischemia, peripheral
arterial occlusion, deep vein thrombosis and acute
cardiac arrest that were manifested by tissue hypoxia. High level of IMA can be expected in CO poisoning with tissue hypoxia(13).
In the study of Turedi et al. IMA levels of the
patients at the admission were measured significantly higher compared to the control group. After a
three hour treatment, it was reported that there was
a significant decrease in the level of COHb, but
there was no significant change in the level of IMA.
It was found out that there was no relationship
between COHb levels and IMA levels(13).
In this study it was detected that there were
significant differences between the 0th hour patient
group and the control group in terms of IMA levels.
But there was no significant change in terms of
measured IMA levels during treatment. This is suggested that; IMA levels are high in CO poisoning
but it is not a meaningful parameter in order to
evaluate the effectiveness of treatment. The data
that obtained from the present study are consistent
with the study of Turedi et al.(13).
As conclusion; COHb and lactate are the parameters that can be used effectively in the diagnosis
and evaluation the efficacy of the treatment CO poisoning. The levels of NGAL, IMA, TOS, TAS and
OSI were detected high in CO poisoning, but it is
not meaningful in evaluating the effectiveness of
treatment. However, in order to clarify this situation
there are needed the studies with more number of
patients and longer follow-up period.
605
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_________
Request reprints from:
CEMIL KAVALCI, MD
Baskent University Faculty of Medicine
Emergency Department
Ankara
(Turkey)