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Evaluation of the potential cardiotoxic effects in acute

organophosphate toxicity as a prognostic factor

Conference Paper · September 2018

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Heba Lashin
Tanta University
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 By
Heba Lashin, MSc, MD
Lecturer of Forensic Medicine and Clinical Toxicology
Faculty of Medicine, Tanta University
 Introduction

• Organophosphorus compounds are

the most commonly used pesticides.
• They are highly toxic compounds for
human beings.
 Introduction

• In Egypt, organophosphorus poisoning

is a common cause of morbidity and
mortality.

• It represents more than 50% of

insecticide poisoned patients.
Introduction
Introduction
 Introduction

Life-threatening cardiac complications

may occur after OPP :

• Various arrhythmias

• Blood pressure changes

• Myocardial ischemia

• Non-cardiogenic pulmonary edema

 Introduction

• Studies on cardiac effects of

organophosphorus poisoning were:

Reported
Inconclusive conflicting
results
 Introduction

• These studies were based mainly on ECG

abnormalities which are not definite
diagnostic sign of myocardial injuries.
• Limited studies have evaluated cardiac
biochemical markers such as troponin I.
 Design and setting:
• This prospective observational cohort
study was carried out on 48
organophosphate acutely intoxicated
patients.

• Admitted to the poison control center

(Tanta University Emergency
hospitals).
 All adult patients who were diagnosed
with acute organophosphate toxicity.

The severity of acute OPP was clinically

evaluated into mild, moderate and severe
poisoning.
-Patients with history of cardiac
diseases.

-Co-ingestion with other agents.

-Patients who received undocumented
medical treatment for acute
organophosphorus poisoning before
admission.
-Patients with any pre-existing chronic
diseases in which serum cardiac Tn-I
level may be elevated.
All participants were subjected to:

 Socio-demographic data: age, gender,

occupation, residence and education.
 Full patient’s history: including
toxicological and medical history.

 Clinical examination: regarding

consciousness level, vital signs and
general examination
 Laboratory investigations:

Routine Serum cardiac

investigations troponin I
level

Butyrylcholinesterase
level
 Electrocardiography (ECG): was recorded
on admission and repeated every 6 hours
and whenever an arrhythmia or any
other abnormality was observed on
cardiac monitor.
• The ECG was analyzed for:
Rate, rhythm and voltage
ST and T wave abnormalities
Conduction defects, PR interval, QT interval
Corrected QT interval (QTc)
The QT interval: is the time from the
beginning of the QRS complex
(ventricular depolarization) to the end of
the T wave (ventricular repolarization).
 Corrected QT interval (QTc) is
frequently used due to the heart rates
effects.

 Normally the QTc is ≤ 0.44 second. It

is calculated using the Bazett’s
formula:
• ECG changes induced by acute OPP were
graded according to the poisoning
severity score into minor, moderate and
severe.
 Echocardiography: was done as soon as
possible after admission.
 Outcome assessment:
• The primary outcome was either the
patient improved, died or unknown.

• Secondary (major) outcome included:

 Need for endotracheal intubation
 Need for mechanical ventilation
 Death
(either alone or with each other)
The data was recorded in a specially
designed sheet.
Distribution of acute OP poisoned
patients according to OPP severity
into mild, moderate and severe
(n=48)
Distribution of acute OP poisoned patients with
and without ECG changes (n=48)
Electrocardiographic abnormalities of acute OP
poisoned studied patients (n=39)

ECG changes n = 39 %
 Arrhythmic findings: 17 43.6%
Atrial extrasystole 1 5.9%
Ventricular extrasystole 2 11.8%
Bundle branch block 3 17.6%
Supraventricular tachycardia 1 5.9%
Atrial fibrillation 5 29.4%
Transiant interventricular conduction defect 1 5.9%

Ventricular tachycardia 1 5.9%

Changes in PR Prolonged PR 1 5.9%
interval Short PR 2 11.8%
Electrocardiographic abnormalities of acute OP
poisoned studied patients (n=39)

ECG changes n = 39 %
 Ischemic finding: 26 66.7%

Changes in T wave Flat T wave 3 11.5%

Inverted T wave 11 42.3%
Biphasic T wave 1 3.9%
Hyperacute T wave 2 7.7%
Changes in ST ST elevation 5 19.2%
segment ST depression 1 3.9%
Abnormal Q wave 3 11.5%
 Other findings: 5 12.8%
Changes in P wave High voltage P wave 1 20%

Hyperacute P wave 1 20%

Poor R wave progression 2 40%

Persistent S wave 1 20%
An ECG from a female patient (aged 48 years) with
attempted suicidal ingestion of unidentified
organophosphorus compound showed sinus
tachycardia (rate= 150 beat/ minute, regular). Serum
Tn-I (6.5 ng/ml) and the case died after she was
diagnosed as myocardial infarction.

𝐐𝐓𝐜 = 𝐐𝐓/ 𝑹𝑹
An ECG from a female patient (aged 48 years) with
attempted suicidal ingestion of unidentified
organophosphorus compound showed sinus
tachycardia (rate= 150 beat/ minute, regular). Serum
Tn-I (6.5 ng/ml) and the case died after she was
diagnosed as myocardial infarction.

𝐐𝐓𝐜 = 𝟎. 𝟑𝟐/ 𝟎. 𝟒𝟒=0.48 seconds

Distribution of acute OP poisoned patients according to
their ECG grading into patients with normal, moderate
and severe ECG grading (n=48)
Comparison between ECG grading of studied patients
and acute organophosphorus poisoning severity:

Pearson Chi-
Acute OPP Severity
Total Square
ECG grading (n=48) Mild Moderate Severe X2 PMC
(n=9) (n=17) (n=22)
Normal 9 (18.75%) 5 4 0
(n=9 ) (23.5%) (0%)
(55.6%)
18.897 0.000*
Moderate 33 4 13 16
(68.75%) (76.5%) (72.7%)
(n=33 ) (44.4%)

Severe 6 0 0 6 (27.3%)
(n=6 )
(12.5%) (0%) (0%)
Analysis of mode and route of poisoning among acute
OP poisoned patients according to their ECG grading:

ECG grading Pearson Chi-Square

Toxicological data Normal Moderate Severe X2 PMC
(n=9) (n=33) (n=6)
Mode of poisoning
Occupational 8 (88.9%) 17 (51.5%) 0 (0%)
11.411 0.002*
Suicidal 1 (11.1%) 16 (48.5%) 6
(100%)
Route of poisoning
Ingestion 1 (11.1%) 15 (45.5%) 6
(100%) 12.132 0.017*
Combined 8 (88.9%) 17 (51.5%) 0 (0%)
(Inhalational/Dermal)

Unknown 0 (0%) 1 (3%) 0 (0%)

Analysis of oxygen saturation among acute OP poisoned
patients according to their ECG grading:
Kruskal-Wallis
ECG grading
Test
Vital signs
Normal Moderate Severe X2 P
(n=9) (n=33) (n=6)
Oxygen saturation (%) (Normal: 95-97%)
89-99 54-99 38-99
Minimum-Maximum

Mean±SD 96.2±4 89.6±11.8 74.5±22

Median 98 95 78 8.101 0.017*
Inter-quartile range 92.5-99 88.5-97 56-93
KS test of normality D=0.337 D=0.243 D=0.212
p=0.004* p=0.000* p=0.200 NS
Pair-wise comparison (between group comparison)
Dunn-Bonferroni test
Normal to moderate Normal to severe Moderate to severe
2.082 2.774 1.530
P = 0.112 P = 0.017* P = 0.378
Comparison of butyrylcholinesterase activity level
among acute OP poisoned patients according to their
ECG grading:
ECG grading Kruskal-Wallis
Butyrylcholinesterase Test
activity level at
Normal Moderate Severe
admission (U/L) X2 P
(n=9) (n=33) (n=6)
Minimum- 1888-10827 89-11485 476-1180

Maximum
4421.8± 2813.4± 722.3±
Mean± SD 2739.3 2617 259.9
Median 3512 2150 665
15.173 0.001*
Inter-quartile range 2788-5546 1039.5-3490 501.5-923.5
KS test of normality D=0.271 D=0.204 D=0.201
p=0.056 NS p=0.001* p=0.200 NS
Pair-wise comparison (between group comparison)
Dunn-Bonferroni test
Normal to moderate Normal to severe Moderate to severe
2.063 3.893 2.875
P = 0.117 P =0.000* P = 0.012*
Distribution of acute OP poisoned patients as
regarding echocardiographic findings (n=48)
Comparison of serum cardiac troponin I (Tn-I) level
among mildly, moderately and severely OP
intoxicated patients

Serum cardiac Kruskal-

Tn-I level Acute OPP Severity Wallis Test
(ng/ml)
Total
(peak value)
(n=48) Mild Moderate Severe X2 P
(Reference value:
(n=9) (n=17) (n=22)
up to 1.5 ng/mL)

Minimum- 0.1-6.5 0.13-0.65 0.1-1.19 0.1-6.5

maximum
Mean ± SD 0.37± 0.95 0.23±0.16 0.2± 0.26 0.56±1.37

Median 0.13 0.19 0.1 0.13

0.109
Inter-quartile 40.1-0.2 0.15-0.21 0.1-0.17 0.1-0.31 4.430
NS
range
KS test of D=0.386 D=0.414 D=0.346 D=0.383
normality p=0.000* p=0.000* p=0.000* p=0.000*
Comparison of serum cardiac troponin I (Tn-
I) level among acute OP poisoned patients
according to their ECG grading

Serum cardiac Tn-I

ECG grading Kruskal-Wallis Test
level (ng/ml)
(peak value)
Normal Moderate Severe X2 P
(Reference value:
(n=9) (n=33) (n=6)
up to 1.5 ng/mL)

Minimum- 0.1-1.19 0.1-1.3 0.1-6.5

Maximum
0.32± 0.37 0.19± 1.49±2.5
Mean± SD
0.21
5.242 0.073 NS
Median 0.16 0.13 0.39
Inter-quartile 0.115- 0.1-0.195 0.123-
range 0.425 2.68
KS test of normality D=0.403 D=0.337 D=0.347
p=0.000* p=0.000* p=0.023*
Distribution of acute OP poisoned patients as
regarding QTc interval (n=48)
Comparison of QTc interval among mildly,
moderately and severely OP intoxicated
patients
Kruskal-Wallis
QTc Acute OPP Severity
Total Test
interval
(n=48) Mild Moderate Severe X2 P
(n=9) (n=17) (n=22)
Minimum-maximum 0.35-0.61 0.38-0.48 0.35-0.51 0.39-0.61
Mean ± SD 0.46± 0.42±0.0 0.42± 0.5±
0.062 33 0.045 0.061
Median 0.44 0.42 0.42 0.48
16.288 0.000*
Inter-quartile range 0.41-0.49 0.4-0.45 0.39-0.46 0.45-0.55
KS test of normality D=0.128 D=0.221 D=0.125 D=0.172
p=0.047* p=0.200 p=0.200 p=0.090
NS NS NS
Pair-wise comparison (between group comparison)
Dunn-Bonferroni test
Mild to moderate Mild to severe Moderate to severe

0.049 2.988 3.598

p=1.000 NS p=0.008* p=0.001*
Comparison of socio-demographic,
toxicological data and clinical manifestations
in acute OP poisoned patients with normal
and prolonged QTc interval
QTc interval Pearson Chi-Square
Normal Prolonged X2 PMC
(n=25) (n=23)
Gender
Male 24 (96%) 16 (69.6%)
1 (4%) 7 (30.4%) 6.027 FE
Female
0.020*
Mode of poisoning
Suicidal 6 (24%) 17 (73.9%)
Accidental 19 (76%) 6 (26.1%) 11.958 0.001*
Route of poisoning
Ingestion 6 (24%) 16 (69.6%)
Combined 19 (76%) 6 (26.1%) 0.000*
12.243
(Inhalational/Dermal)
Unknown 0 (0%) 1 (4.3%)
Disturbed conscious level 22 (88%) 13 (56.5%) 6.011 0.014*
Hypotonia 12 (48%) 19 (82.6%) 6.273 0.012*

Muscle Fasciculation 7 (28%) 13 (56.5%) 4.009 0.045*

Comparison of socio-demographic,
toxicological data and clinical manifestations
in acute OP poisoned patients with normal
and prolonged QTc interval
QTc interval Mann-Whitney U test

Normal Prolonged
Z P
(n=25) (n=23)
Age 35.96 ± 11.03 36.17 ± 14.97 0.217 0.828 NS

Pre-hospitalization
6.9 ± 4.88 6.36 ± 6.08 0..725 0.468 NS
period (hours)
Mean arterial blood
89.73 ±19.69 89.42 ± 17.34 0.217 0.828 NS
pressure (mmHg)
Pulse(beat/minute) 82±29.46 96±33.96 1.807 0.071 NS

Oxygen saturation
94.52 ± 5.01 82.95 ± 17.21 2.559 0.011*
(%)
PH 7.45± 0.07 7.37 ± 0.11 2.357 0.018*

Na(mEq/L) 142.58±4.13 141.13±5.14 1.301 0.193

k(mEq/L) 3.5±0.67 3.67±0.57 1.042 0.297

Comparison of primary outcome in acute OP
poisoned patients

Pearson Chi-
Primary Outcome
Outcome Square
Improved Died Unknown X2 PMC
assessment
40 (83.3%) 6 (12.5%) 2 (4.2%)
Acute OPP Severity
Mild 9 (100%) 0 (0%) 0 (0%)
(n=9)
Moderate 16 (94.1%) 0 (0%) 1 (5.9%) 0.061
8.737
(n=17) NS
Severe 15 (68.2%) 6 (27.3%) 1 (4.5%)
(n=22)
ECG grading
Normal 9 (100%) 0 (0%) 0 (0%)
(n=9)
Moderate 31 (93.9%) 0 (0%) 2 (6.1%)
48.655 0.000*
(n=33)
Severe 0 (0%) 6 (100%) 0 (0%)
(n=6)
Comparison of primary outcome in acute OP
poisoned patients

Primary Outcome Pearson Chi-Square

Outcome
Improved Died Unknown X2 PMC
assessment
40 (83.3%) 6 (12.5%) 2 (4.2%)
QTc interval
Normal 23 (92%) 1 (4%) 1 (4%)
(n=25)
3.489
Prolonged 17 (73.9%) 5 (21.7%) 1 (4.3%) 0.183 NS
(n=23)
Echocardiography changes
Normal 24(92.3%) 0(0%) 2(7.7%)
(n=26)
Abnormal 16(94.1%) 1(5.9%) 0(0%)
40.818 0.000*
(n=17)
Not done 0(0%) 5(100%) 0(0%)
(n=5)
Serum cardiac Troponin I level (ng/ml) (peak value) ANOVA Test
F P
Mean ± SD 0.22±0.26 1.49±2.5 0.15±0.06 1.536 0.302 NS
Comparison of major outcome in acute OP
poisoned patients

Major outcome Pearson Chi-

Outcome Square
assessment No Yes X2 PMC
37 (77.1%) 11 (22.9%)
Acute OPP Severity
Mild 9 (100%) 0 (0%)
(n=9)
Moderate 17 (100%) 0 (0%)
16.865 0.000*
(n=17)
Severe 11 (50%) 11 (50%)
(n=22)
ECG grading
Normal 9 (100%) 0 (0%)
(n=9)
Moderate 28 (84.8%) 5 (15.2%)
23.984 0.000*
(n=33)
Severe 0 (0%) 6 (100%)
(n=6)
Comparison of major outcome in acute OP
poisoned patients
Major outcome Pearson Chi-
Outcome Square
assessment No Yes X2 PMC
37 (77.1%) 11 (22.9%)
QTc interval
Normal 24 (96%) 1 (4%)
(n=25)
10.569 0.002*
Prolonged 13 (56.5%) 10 (43.5%)
(n=23)
Echocardiography changes
Normal 25(96.2%) 1(3.8%)
(n=26)
Abnormal 12(70.6%) 5(29.4%)
22.577 0.000*
(n=17)
Not done 0(0%) 5(100%)
(n=5)
Serum cardiac Troponin I level (ng/ml) (peak value) ANOVA test
T(Welch) P
Mean ± SD 0.23±0.27 0.89±1.9 1.132 0.284
NS
The best cut-off value, sensitivity,
specificity, and AUC of QTc interval and
serum cardiac Tn-I level for predicting major
outcome of acute OP poisoned patients
(95% CI)
Cut- Sensitivity Specificity Accuracy ROC- P
off % % % AUC value
value
QTc ≥0.46 90.9 67.6 87.8 0.878 0.000*
interval
(seconds)

Serum ≥0.25 45.5 83.8 0.615 61.5 0.249

cardiac
Tn-I
(peak
value)
(ng/mL)
Conclusions

The ability of severe OPP to cause

direct myocardial injury apart from
rhythm disturbances was assured
within few hours of exposure
including myocardial infarction.
Conclusions

ECG grading is a predictor for both

primary and major outcome of acute
OP poisoned patients.
Conclusions

Corrected QT interval could be

considered as an excellent parameter
to predict morbidity and mortality in
acute OP poisoned patients.
Conclusions

Serum cardiac Tn-I level could be

considered an effective predictor of
direct myocardial toxic effect induced
by OPCs.
Recommendations

A baseline and daily ECG should

be performed in all acute OP
intoxicated patients.
Recommendations

Special attention should be given to

patients who had markedly prolonged
QTc interval. They should not be
discharged before QTc interval
normalization.
Recommendations

Serum cardiac Tn-I level and

elective echocardiography should be
done as a routine for all severe OP
poisoned patients.
Recommendations

Collaboration
between different
poison control centers
for data-gathering
about cases of acute
OP poisoning.
 Thank you
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