Vitamin E as a novel therapy in the treatment of acute aluminum phosphide poisoning

Abstract

Background/aim:
Aluminum phosphide (AlP) is commonly used as a fumigant in developing countries. Induction of oxidative stress is one of the most important mechanisms of its toxicity. In this regard, and considering that there is no specific antidote for its treatment, the aim of this study was to evaluate the effect of vitamin E in the treatment of acute AlP poisoning.

Materials and methods:
This was a clinical trial on acute AlP poisoned patients. All patients received supportive treatment. In addition, the treatment group received vitamin E (400 mg/BD/IM). Level of malondialdehyde (MDA) and total antioxidant capacity of plasma were measured.

Results:
There was no significant difference between the treatment and control groups with regard to demographic, clinical, or paraclinical data or Simplified Acute Physiology Score II (SAPSII) on admission. Systolic blood pressure significantly increased during the first 24 h in the treatment group (P < 0.05). The plasma MDA level significantly decreased in the treatment group (P < 0.05). Vitamin E administration decreased the necessity (30% vs. 62%, P < 0.05) and duration of intubation and mechanical ventilation (P < 0.05). It significantly reduced the mortality rate in the treatment group compared to the control group (15% vs. 50%, respectively, P < 0.05).

Conclusion:
Vitamin E along with supportive treatment could have a therapeutic effect in acute AlP poisoning.

Full text

795
http://journals.tubitak.gov.tr/medical/
Turkish Journal of Medical Sciences
Turk J Med Sci
(2017) 47: 795-800
© TÜBİTAK
doi:10.3906/sag-1512-6
Vitamin E as a novel therapy in the treatment of acute aluminum phosphide poisoning
Zahra HALVAEI1, Hiva TEHRANI1, Kambiz SOLTANINEJAD2, Mohammad ABDOLLAHI3,4, Shahin SHADNIA5,*
1Faculty of Pharmacy, Islamic Azad University of Medical Sciences, Tehran, Iran
2Department of Forensic Toxicology, Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran
3Department of Toxicology and Pharmaceutical, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center,
Tehran University of Medical Sciences, Tehran, Iran
4Toxicological and Diseases Group, Pharmaceutical Sciences Research Group, Tehran Unviversity of Medical Sciences, Tehran, Iran
5Toxicological Research Center, Excellent Center of Clinical Toxicology, Department of Clinical Toxicology, Loghman Hakim Hospital
Poison Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
* Correspondence: shahin1380@yahoo.com
1. Introduction
Aluminum phosphide (AlP) is used widely throughout
the world as a pesticide and fumigant because of
its ecacy and low cost (1). AlP is one of the most
frequently reported causes of acute chemical poisoning
in Asia (2–4). In Iran, it is available in 3-g tablets
containing 1 g of AlP and known as “rice tablet”; it
causes acute poisoning with a high mortality rate (5–7).
AlP toxicity is due to liberating phosphine (PH3) gas
aer its reaction with moisture, water, or hydrochloric
acid in the stomach (8,9). e major of mortality occurs
during the rst 12–24 h aer exposure and is mostly
due to cardiovascular and respiratory involvement
(8,9).
e exact mechanism of phosphine toxicity is not
clear and some mechanisms are reported (8,9). Previous
studies suggested that the induction of oxidative stress
has the main role in AlP toxicity (10,11), which is
emphasized by recent studies (12–15).
As there is no specic antidote for acute AlP poisoning,
its treatment is mainly supportive and symptomatic
(1,8,9). By considering the induction of oxidative stress as
the main mechanism of AlP toxicity and with regard to
the role of vitamin E in the enzymatic antioxidants defense
and function as a free radical scavenger (16–18), its use
may have a therapeutic eect in the treatment of AlP-
poisoned patients.
e aim of the present study was to investigate the
therapeutic eects of vitamin E in acute human AlP
poisoning.
2. Materials and methods
2.1. Patients
is was a prospective, randomized, control open label
trial on acute AlP intoxicated patients that were treated in
the intensive care unit (ICU) over a 1-year period.
Acute AlP-intoxicated patients above the age of 12
years who were admitted during the rst 6 h aer exposure
Background/aim: Aluminum phosphide (AlP) is commonly used as a fumigant in developing countries. Induction of oxidative stress is
one of the most important mechanisms of its toxicity. In this regard, and considering that there is no specic antidote for its treatment,
the aim of this study was to evaluate the eect of vitamin E in the treatment of acute AlP poisoning.
Materials and methods: is was a clinical trial on acute AlP poisoned patients. All patients received supportive treatment. In addition,
the treatment group received vitamin E (400 mg/BD/IM). Level of malondialdehyde (MDA) and total antioxidant capacity of plasma
were measured.
Results: ere was no signicant dierence between the treatment and control groups with regard to demographic, clinical, or
paraclinical data or Simplied Acute Physiology Score II (SAPSII) on admission. Systolic blood pressure signicantly increased during
the rst 24 h in the treatment group (P < 0.05). e plasma MDA level signicantly decreased in the treatment group (P < 0.05). Vitamin
E administration decreased the necessity (30% vs. 62%, P < 0.05) and duration of intubation and mechanical ventilation (P < 0.05). It
signicantly reduced the mortality rate in the treatment group compared to the control group (15% vs. 50%, respectively, P < 0.05).
Conclusion: Vitamin E along with supportive treatment could have a therapeutic eect in acute AlP poisoning.
Key words: Aluminum phosphide, oxidative stress, poisoning, vitamin E
Received: 03.12.2015 Accepted/Published Online: 22.01.2017 Final Version: 12.06.2017
Research Article

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HALVAEI et al. / Turk J Med Sci
with no advanced medical management for AlP poisoning
in any medical center before admission were included in
this study. e exclusion criteria were history of diabetes
mellitus, cardiovascular, respiratory, renal, and hepatic
failure, substance abuse, and co-ingestion.
e diagnosis was conrmed based on history of
exposure, clinical manifestations, laboratory ndings,
and other circumstantial evidence such as availability of a
poison bottle or a label. In fatal cases, toxicological analysis
and a histopathological examination were performed.
A positive silver nitrate test for PH3 gas on stomach
contents and tissues along with the liver postmortem
histopathological ndings conrmed the AlP poisoning.
According to the mentioned criteria, 36 patients were
included in the study consecutively. Each patient with an
even le number was included in the vitamin E treatment
group (n = 20) and the patients with odd le numbers were
included in the control group (n = 16).
2.2. Study design and treatments
All the patients received gastric decontamination with
sodium bicarbonate (44 mEq), permanganate potassium
(1:10,000), and activated charcoal (1 g/kg) in the rst
6 h aer exposure. All the patients were admitted to the
ICU, as they needed intubation, mechanical ventilation,
and intensive monitoring. ey were treated with the
same protocol (magnesium sulfate 4–6 g by IV infusion
daily, calcium gluconate 4 g by IV infusion daily,
adequate hydration, and norepinephrine 10 µg/min as
vasopressor) under the supervision of the same physicians
and nurses. e described treatments were based on the
clinical toxicology department protocols. In the vitamin
E treatment group, vitamin E (as DL-alpha tocopheryl
acetate, 100 IU/mL, OSVAH Pharmaceutical Co. Tehran,
Iran; 400 mg/IM, every 12 h) was administered up to 72 h.
We followed the patients up to discharge from the hospital
or death.
e protocol of the study was approved by the ethical
committee of Shahid Beheshti University of Medical
Sciences, Tehran, Iran.
2.3. Sampling and bioanalysis
Blood sampling was performed at the admission on
hospital and repeated each 24 h up to 72 h of hospitalization
in the ICU. Venous blood samples (5 mL) were collected in
dierent heparinized tubes and then plasma samples were
separated via centrifugation at 3500 rpm for 10 min and
frozen at –80 °C. On average, the time interval between
sampling and analysis was 1 week. Lipid peroxidation in the
plasma in two groups was evaluated by the thiobarbituric
acid reactive substances (TBARS) method (19). First
250 µL of 20% trichloroacetic acid (TCA) in 10 mL of
sodium sulfate (2 M) was added to 0.5 mL of plasma. Aer
precipitation of the protein with TCA, washing with 300
µL of sulfuric acid (0.05 M) was performed. en 300 µL of
thiobarbituric acid (TBA) (0.67% w/v) solution was added
to the mixture. e mixture was incubated in a boiling
water bath for 30 min. Aer cooling, the samples were
extracted with n-butanol and centrifuged at 3500 rpm.
e absorbance was read at 530 nm by ELISA microplate
reader (Synergy, BioTech Instruments Inc, Germany).
1,1,3,3-Tetramethoxy propane was used for drawing the
calibration curve. Malondialdehyde (MDA) was expressed
as micromoles of MDA per liter of plasma.
e total antioxidant capacity (TAC) of plasma was
evaluated using the ferric reducing ability of plasma
(FRAP) assay (20). Ferric tripyridyltirazine (Fe3+-TPTZ)
complex is reduced to the blue color marker ferrous (Fe2+)
form at acidic pH. To 50 µL of plasma was added 1500
µL of freshly prepared FRAP reagent [25 mL of acetate
buer (pH = 3.6, 300 mmol/L), 2.5 mL of FeCl3, 6H2O
(20 mmol/L), 2.5 mL of TPTZ (10 mmol/L TPTZ in 40
mmol/L HCl)]. Aer 15 min incubation at 37 °C in a water
bath, absorbance was determined by ELISA microplate
reader (Synergy, BioTech Instruments Inc, Germany) at
593 nm. en samples were placed at 37 °C in the water
bath and absorption was measured aer 4 min. FRAP
values were measured by calculation of the absorbance
change in plasma sample compared with that of trolox
standard (20).
2.4. Data collection and statistical analysis
We collected patients’ information regarding sex, age, cause
of poisoning, number of ingested AlP tablets, time interval
between exposure and beginning of treatment, route of
exposure, clinical and laboratory ndings at admission
and during the rst 24 h of hospitalization, duration of
hospitalization, and outcome and prepared qualifying case
records. All data were kept condential during the study.
e Glasgow Coma Scale (GCS) and Simplied Acute
Physiology Score II (SAPSII) were calculated at admission
(21,22). All data were analyzed with SPSS version 12. Data
were expressed as mean ± SD for quantitative variables
and as frequency and percentage for qualitative variables.
e chi-square test was used for statistical comparison
of qualitative variables. e normal distribution of
quantitative variables was tested by Kolmogorov–
Smirnov test. e Mann–Whitney U-test was used for
nonparametric variables and the independent Student’s
t-test was used for parametric variables. P values of 0.05 or
less were considered statistically signicant.
3. Results
In the present study, 36 patients (13 men, 23 women) with
acute AlP poisoning were included, of whom 20 (5 men,
15 women) were in the treatment group and 16 (8 men, 8
women) were controls. e route of exposure was deliberate
ingestion in all patients. e main clinical manifestation
was vomiting, observed in the most of the patients in the
treatment and control groups (90% vs. 87.5%, respectively).
Table 1 summarizes the demographic, clinical, and

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HALVAEI et al. / Turk J Med Sci
Table 1. Distribution of the AlP intoxicated patients according to demographic, clinical, and paraclinical characteristics at admission.
Parameter (normal range, unit) All patients (n = 36)
(%) Mean ± SD (range)
Treatment group (n = 20)
(%) Mean ± SD (range)
Control group (n = 16)
(%) Mean ± SD (range) P-value
Sex Male 13 (26) 5 (25) 8 (50) 0.17▲
Female 23 (64) 15 (75) 8 (50)
Age (years) 25.56 ± 8.37 (14–50) 24.95 ± 8.11 (15–44) 26.31 ± 8.90 (14–50) 0.46♦
Number of AlP tablets 1.40 ± 0.86 (0.25–4) 1.28 ± 0.75 (0.25–3) 1.57 ± 1 (0.5–4) 0.48♦
TBOPAH$ (min) 87.50 ± 64.36 (15–300) 98.25 ± 76.66 (15–300) 74.06 ± 43.29 (15–180) 0.52♦
Level of consciousness consciousness 20 (56) 11 (55) 9 (56) 1▲
unconsciousness 16 (44) 9 (45) 7 (44)
Systolic blood pressure (≤120 mmHg) 89.46 ± 15.76 (56–130) 89.16 ± 17.95 (56–130) 89.81 ± 13.29 (60–110) 0.90●
Diastolic blood pressure (≤80 mmHg) 57.79 ± 11.06 (37–80) 55.76 ± 11.03 (37–80) 60.67 ± 10.91 (40–70) 0.25●
Pulse rate (60–100 beats/min) 92.46 ± 15.94 (65–130) 90.50 ± 16.68 (65–130) 95.07 ± 15.04 (70–122) 0.41●
Respiratory rate (16–24 breaths/min) 19.25 ± 4.08 (12–30) 19.95 ± 4.16 (14–30) 18.38 ± 3.93 (12–26) 0.32♦
Electrocardiogram Normal 20 (56) 13 (65) 7 (44) 0.31▲
Abnormal 16 (44) 7 (35) 9 (56)
pH (7.35–7.45) 7.39 ± 0.08 (7.22–7.49) 7.40 ± 0.07 (7.24 ± 7.48) 7.38 ± 0.09 (7.22–7.49) 0.50●
PCO2 (35–45 mmHg) 30.03 ± 7.35 (16.90–43.10) 31.81 ± 7.06 (16.90–42.20) 27.81 ± 7.30 (18.10–43.10) 0.11●
Serum HCO3 (22–26 mEq/L) 18.64 ± 5.15 (9–29.1) 20.06 ± 5.47 (9.90–29.10) 16.88 ± 4.24 (9–24.5) 0.06●
Blood glucose (70–110 mg/dL) 148.75 ± 55.73 (74–282) 125.25 ± 48 (74–242) 178.13 ± 51.70 (101–282) 0.003**●
Blood urea nitrogen (7–18 mg/dL) 27.25 ± 11.61 (12–60) 29.45 ± 12.85 (12–60) 24.50 ± 9.51 (12–40) 0.20●
Creatinine (0.6–1.2 mg/dL) 0.94 ± 0.21 (0.60–1.40) 0.91 ± 0.21 (0.70–1.40) 1 ± 0.21 (0.60–1.30) 0.20♦
Sodium (135–145 mEq/L) 143.94 ± 5.07 (135–156) 143.40 ± 4.89 (137–155) 144.67 ± 5.38 (135–156) 0.48●
Potassium (3.5–5 mEq/L) 3.94 ± 0.46 (3–5.10) 3.86 ± 0.41 (3–4.60) 4.05 ± 0.53 (3.20–5.10) 0.52♦
Calcium (8.4–10.2 mg/dL) 8.82 ± 0.79 (7.50–10.50) 8.74 ± 0.86 (7.50–10.40) 8.91 ± 0.72 (8–10.50) 0.55●
Magnesium (1.9–2.5 mg/dL) 2.18 ± 0.58 (1.40–4) 2.08 ± 0.58 (1.40–4) 2.41 ± 0.56 (1.90–3.50) 0.07♦
White blood cell count (7–10 × 1000/µL) 15.55 ± 22.61 (3.20–141) 17.47 ± 29.42 (3.20–141) 12.81 ± 4.35 (5.80–20.60) 0.44♦
Hematocrit (35–45%) 38.53 ± 5.58 (27.50–48.10) 37.04 ± 6.05 (27.50–48.10) 40.65 ± 4.16 (32–46.60) 0.06●
Platelet (150–450 × 1000/µL) 268.76 ± 110.01 (95–609) 289.85 ± 122.86 (95–609) 238.64 ± 83.68 (101–374) 0.19●
Serum total protein (6.6–8.8 g/dL) 6.35 ± 0.78 (5.10–8.20) 6.54 ± 0.80 (5.10–8.20) 5.92 ± 0.58 (5.10–7.00) 0.08●
Albumin (3.5–5.3 g/dL) 4.00 ± 0.64 (3.10–5.10) 4.16 ± 0.63 (3.20–5.10) 3.71 ± 0.60 (3.10–4.60) 0.15●
Aspartate transaminase (up to 37 U/L) 26.48 ± 14.96 (10–64) 28 ± 15.53 (10–64) 24.38 ± 14.47 (11–62) 0.44●
Alanine transaminase (up to 41 U/L) 49.96 ± 75.35 (5–298) 46.11 ± 61.91 (12–242) 55.30 ± 93.34 (5–298) 0.31●
Alkaline phosphatase (80–306 U/L) 157.54 ± 37.53 (95–233) 143.38 ± 32.08 (95–187) 178 ± 36.83 (113–233) 0.03*●
Total bilirubin (0.1–1.2 mg/dL) 1.2 ± 0.52 (0.50–2.70) 1.17 ± 0.61 (0.50–2.70) 1.23 ± 0.37 (0.60–1.90) 0.29●
Lactate dehydrogenase (up to 513 U/L) 457.32 ± 135.85 (279–752) 445.45 ± 131.81 (298–740) 474.28 ± 144.66 (279–752) 0.55●
Creatine phosphokinase (24–195 U/L) 170.18 ± 64.69 (53–305) 190.15 ± 59.74 (56–305) 139.46 ± 61.84 (53–295) 0.03*●
$ Time between onset of poisoning and admission to hospital, SD = Standard deviation
* e dierence between the two groups is signicant at P < 0.05
** e dierence between the two groups is signicant at P < 0.005
▲ Chi-square test was used for statistical analysis
♦ Mann–Whitney U-test was used for statistical analysis
● t-test was used for statistical analysis

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laboratory results. SAPSII was determined in the treatment
(4.7 ± 2) and control groups (5.05 ± 3.13). e results
showed no signicant dierence (P = 0.68).
Systolic blood pressure (SBP) signicantly increased
during the rst 24 h in the treatment group (89.16 ± 17.95
mmHg at admission vs. 98.95 ± 15.45 mmHg 24 h aer
onset of poisoning, P < 0.05). e results also showed that
there was no signicant dierence between the two groups
due to SBP 24 h aer the onset of poisoning (98.95 ± 15.45
mmHg in the treatment group vs. 89.21 ± 20.25 mmHg in
the control group, P = 0.13).
We observed signicant increases in diastolic blood
pressure (DBP) in the treatment group (55.76 ± 11.03
mmHg at admission vs. 60.63 ± 13.58 mmHg 24 h aer the
onset of poisoning, P < 0.05) and signicant decreases in
DBP in the control group (60.67 ± 10.91 mmHg at admission
vs. 50.43 ± 12 mmHg 24 h aer the onset of poisoning,
P < 0.05). e data showed a signicant dierence between
the two groups with regard to DBP 24 h aer the onset of
poisoning (P < 0.05).
e results showed a signicant dierence in blood
pH between the treatment and control groups (7.43 ± 0.04
vs. 7.33 ± 0.1, P < 0.001) 24 h aer onset of poisoning.
In addition, there was no signicant dierence between
the two groups due to PCO2 (36.24 ± 7.57 mmHg in the
treatment group vs. 34.19 ± 6.91 mmHg in the control
group, P = 0.4). We observed a signicant dierence in
serum bicarbonate between the two groups 24 h aer the
onset of poisoning (24.22 ± 6.55 mEq/L in the treatment
group vs. 18.91 ± 5.62 mEq/L in the control group, P <
0.05).
ere was no signicant dierence in the TAC of
plasma in the treatment and control groups at admission
(Table 2). Twenty-four hours aer the onset of poisoning,
the TAC of plasma in the control group was signicantly
higher than that in the treatment group (Table 2).
At admission, the plasma MDA level was not signicantly
dierent between the treatment and control groups. e
plasma MDA level signicantly decreased in the treatment
group and it signicantly increased in the control group. e
plasma MDA level in the treatment group was signicantly
lower than that in the control group 24 h aer the onset of
poisoning (Table 2).
e percentage of patients who required intubation
and mechanical ventilation was signicantly lower in the
treatment group than in the control group (30% vs. 62%, P <
0.05). In addition, the duration of intubation and mechanical
ventilation in the treatment group was signicantly
lower compared to the control group. e total dose of
norepinephrine was not signicantly dierent between the
two groups (Table 3).
Although the duration of hospitalization was not
signicantly dierent between the two groups (Table 3), the
results showed that most of the fatality occurred during the
rst 12 h aer admission in the control group, and in the
treatment group most of the fatality was observed 20 h aer
admission (Figure). In addition, the data showed that the
mortality rate was signicantly lower in the treatment group
than in the control group (15% vs. 50%, P = 0.02).
4. Discussion
AlP poisoning is a major health problem with a high mortality
rate in Iran and other countries (2–4,6). Unfortunately, to
date, there is not a specic antidote for treatment of this type
of fatal poisoning and the only therapeutic measures are
supportive and symptomatic (9). In this regard, performing
studies that evaluate other therapeutic protocols is necessary.
ere are many suggested mechanisms for AlP poisoning.
One of the most important mechanisms is involvement
of oxidative stress (10–14). From this viewpoint, the
antioxidants may have a therapeutic role in the treatment of
AlP poisoning (10,12).
Table 2. Comparison of plasma TAC and MDA levels at admission and 24 h aer the onset of
poisoning in the treatment and control groups.
Parameters Group At admission
Mean ± SD
24 h aer onset of
poisoning Mean ± SD P-value
MDA (µmol/L) Treatment 130.91 ± 14.11■124.88 ± 8.23▲0.02*
Control 142.45 ± 29.28 151.51 ± 37.34 0.04*
TAC (mmol/L) Treatment 11.57 ± 6.05■10.45 ± 3.48▲0.23
Control 12.79 ± 3.63 13.26 ± 4.02 0.57
* e dierence between two groups is signicant at P < 0.05
■ ere is no signicant dierence between the treatment and control groups at admission
▲ ere is a signicant dierence between the treatment and control groups 24 h aer the onset of
poisoning at P < 0.05
Mann–Whitney U-test was used for all the statistical analysis

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HALVAEI et al. / Turk J Med Sci
Previous studies showed that vitamin E had a protective
role in the in vivo or in vitro toxicity of some poisons
through its antioxidant activity and lowering cell death
by decreased the levels of MDA, reactive oxygen species
production, and lipid peroxidation (18,23–25).
In the present study, we aimed to evaluate the ecacy
of intramuscular administration of vitamin E as an
antioxidant agent in patients with acute AlP poisoning.
e results showed signicant rises in SBP and DBP
in the treatment group 24 h aer the onset of poisoning,
which could be due to the role of vitamin E in reduction of
myocardial and vessels injury through the decrease in lipid
peroxidation (26,27).
e results in the control group showed progressive
metabolic acidosis during the rst 24 h aer the onset of
poisoning, which could be due to tissue hypoperfusion.
In the present study, the TAC and MDA levels at
admission showed no signicant dierence between the
two groups. In addition, the results showed that the serum
levels of MDA were signicantly decreased aer 24 h in
the treatment group, while in the control group they were
signicantly increased. ese results are in concordance of
our previous study, in which the administration of N-acetyl
cysteine as an antioxidant resulted in similar ndings (12).
Vitamin E administration decreased the necessity for
intubation and mechanical ventilation and was associated
with a decrease in duration of intubation and mechanical
ventilation. is result was similar to that of our previous
study (12). Although in the previous studies mortality
rates of 60%–80% were reported in the AlP poisoning
cases with conventional supportive and symptomatic
treatment (7,28,29), in the present study administration of
vitamin E signicantly reduced the mortality rate in the
treatment group compared to the control group (15% vs.
50%, respectively).
In conclusion, the present study showed that the
administration of vitamin E along with supportive
treatment decreased the mortality rate and so it could
be considered in the treatment of acute AlP poisoning in
combination with other therapeutic protocols.
e limitations of this study were small sample size and
lack of blinding in the study design.
Acknowledgment
is study was supported by a grant from the Toxicological
Research Center of Shahid Beheshti University of Medical
Sciences Tehran, Iran (Grant number: 90-M.T-12-306).
Table 3. Comparison of treatment and control groups according to duration of intubation, ventilation, hospitalization,
and dose of vasopressor
Parameters Treatment group (n = 20)
Mean ± SD (range)
Control group (n = 16)
Mean ± SD (range) P-value
Duration of intubation and ventilation (h) 4.15 ± 9 (0–32) 18.36 ± 28.37 (0–85.5) 0.04*
Total dose of norepinephrine (mg) 10.34 ± 14.35 (0–50.40) 10.15 ± 12.79 (0–43.20) 0.42
Duration of hospitalization (h) 69.09 ± 35.19 (21–159) 62.53 ± 68.87 (3.25–229) 0.16
*e dierence between the two groups is signicant at P < 0.05
t-test was used for all the statistical analysis
0
1
2
3
4
2-6 6-12 12-18 18-24 24-30 30-36
Duration of hospitalization in nonsurvivors
(h)
Number of fatal cases
Control group
Treatment group
Figure. Comparison of the duration of hospitalization between
nonsurvivors in the treatment and control groups.

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HALVAEI et al. / Turk J Med Sci
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