CLINICAL CRITERIA FOR THE OUTCOME FORECAST OF ACUTE EXOGENOUS INTOXICATIONS WITH ORGANOPHOSPHORUS PESTICIDES

Abstract

Purpose: The wide-spread use of organophosphorus pesticides (OPP) and their substantial toxicity determine the high frequency of poisoning with them. Despite the modern treatment methods, the acute exogenous intoxications (AEI) continue to exhibit high lethality and are the source of one of the most serious problems in the clinical toxicology. A number of not commonly accepted criteria have been suggested to estimate the gravity of the organophosphorous intoxication. Until now no system of clinical criteria exists that would forecast the outcome of this type of acute poisoning. The aim of this study is to develop an outcome forecast of AEI with OPP with the help of basic clinical criteria.
Materials/Methods: The subjects of the study are 160 patients. We explore the significance of five of the most typical clinical indicators of the acute poisoning with OPP for the outcome of the intoxication and the need of artificial pulmonary ventilation, with the aid of discriminatory statistical analysis. The selected indicators form a discriminatory model with automatically built discrimination function.
Results: The obtained classification coefficients allow us to construct a forecast matrix containing score estimates designed for practical applications.

Full text

J of IMAB. 2017 Apr-Jun;23(2) https://www.journal-imab-bg.org 1541
ABSTRACT
Purpose: The wide-spread use of organophosphorus
pesticides (OPP) and their substantial toxicity determine
the high frequency of poisoning with them. Despite the
modern treatment methods, the acute exogenous
intoxications (AEI) continue to exhibit high lethality and
are the source of one of the most serious problems in the
clinical toxicology. A number of not commonly accepted
criteria have been suggested to estimate the gravity of the
organophosphorous intoxication. Until now no system of
clinical criteria exists that would forecast the outcome of
this type of acute poisoning. The aim of this study is to
develop an outcome forecast of AEI with OPP with the help
of basic clinical criteria.
Materials and Methods: The subjects of the study
are 160 patients. We explore the significance of five of the
most typical clinical indicators of the acute poisoning with
OPP for the outcome of the intoxication and the need of
artificial pulmonary ventilation, with the aid of discrimi-
natory statistical analysis. The selected indicators form a
discriminatory model with automatically built discrimina-
tion function.
Results: The obtained classification coefficients al-
low us to construct a forecast matrix containing score esti-
mates designed for practical applications.
Key words: organophosphorus pesticides, acute poi-
soning, prognosis
INTRODUCTION
The organophosphorus pesticides (OPP) are the most
often used substances for plant protection in Bulgaria as
well as in many other countries. Their popularity and sub-
stantial toxicity determine the high frequency of the acute
poisoning with them. Despite substituting the highly toxic
OPP with less toxic compounds and the integration of mod-
ern treatment methods, the acute exogenous intoxications
(AEI) continue to exhibit high lethality and are the source
of one of the most serious problems in the clinical toxicol-
ogy [1-8].
A number of not commonly accepted criteria have
been suggested to estimate the gravity of organo-
phosphorous intoxication [9]. The large practical impor-
tance notwithstanding, so far no system of clinical criteria
has been developed to forecast the outcome of this type of
acute poisoning [10]. It is known that patients with low
values of acetylcholinesterase face a bad forecast. It has
been proven that patients with a prolonged corrected QT-
interval and low GCS (Glasgow Coma State) more often
develop acute respiratory insufficiency and require intu-
bation. For them the forecast is worse, and respectively the
lethality is higher [11-15]. Acute Physiology and Chronic
Health Evaluation (APACHE) II score and Simplifed Acute
Physiology Score (SARS) II may be used to predict the
mortality rate in OPP [16-18]. Serum bicarbonate concen-
tration, APACHE II score and pneumonia during
haspitalization were the important prognostic factors in pa-
tients with OPP [19]. OPP often cause respiratory failure
[20, 21]. Systolic blood pressure of <100 mm Hg and FiO2
of >40% to maintain a SpO2 of >92% within the first 24 h
were recognized as poor prognostic indicators among me-
chanically ventilated patients [22]. Hypotension, respira-
tory failure, coma and QTc prolongation were significant
risk factors for mortality [23]. The difference in C-teactive
protein value between initial and 24 hours follow-up (D-
CRP) was associated with mortality of patients with OPP
[24]. Multiple organ insufficiency syndrome (MOIS) and re-
nal failure are relatively rare but correlated with death [25].
Original article
CLINICAL CRITERIA FOR THE OUTCOME
FORECAST OF ACUTE EXOGENOUS
INTOXICATIONS WITH ORGANOPHOSPHORUS
PESTICIDES
Petko Marinov1,3, Snezha Zlateva1,3, Dobri Ivanov2, Georgi Bonchev1, Yulichka
Sabeva3, Kaloyan Georgiev4, Ivaylo Vazharov5
1) Clinic for Intensive Treatment of Acute Intoxications and Toxicoallergies,
Naval Hospital – Varna, Military Medical Academy, Bulgaria
2) Department of Biology, Faculty of Pharmacy, Medical University – Varna,
Bulgaria
3) Department of Pharmacology, Toxicology and Pharmacotherapy, Faculty of
Pharmacy, Medical University – Varna, Bulgaria
4) Department of Pharmaceutical Technologies, Faculty of Pharmacy, Medical
University – Varna, Bulgaria
5) Clinic of Internal Diseases, Naval Hospital – Varna, Military Medical
Academy, Bulgaria
Journal of IMAB - Annual Proceeding (Scientific Papers). 2017 Apr-Jun;23(2):
Journal of IMAB
ISSN: 1312-773X
https://www.journal-imab-bg.org
https://doi.org/10.5272/jimab.2017232.1541

1542 https://www.journal-imab-bg.org J of IMAB. 2017 Apr-Jun;23(2)
Our aim is to develop an outcome forecast of AEI
with organophosphorus pesticides with the help of basic
clinical criteria.
MATERIAL AND METHODS
The subjects of the study are 160 patients aged be-
tween 14 and 86 years (96 male and 64 female) treated dur-
ing a 10-year period at the Clinic for Intensive Treatment
of Acute Intoxications and Toxicoallergies, Naval Hospi-
tal – Varna.
We explore the significance of 5 of the most typical
clinical indicators of acute OPP poisoning to the intoxica-
tion outcome and the need of artificial pulmonary ventila-
tion with the help of discriminatory statistical analysis.
RESULTS AND DISCUSSION
To forecast the outcome of the OPP intoxication we
get simplified mathematical expressions in the form of
score estimates. The aim is to as quickly and easily as pos-
sible, even while checking in the patient, to find an an-
swer to the following questions:
1. Is it sufficiently likely for the patient to be suc-
cessfully treated, respectively what is the probability of a
lethal outcome of the intoxication?
2. What is the probability of requiring an artificial
pulmonary ventilation?
Taking into consideration the respective assump-
tions and requirements of the mathematical statistics and
the data volume, 160 cases, leads to the logical conclu-
sion that the target model should contain no more than five
indicators (at least 30 patients per indicator). On the other
hand, many of the indicators are mutually dependent in a
direct fashion and must not be simultaneously present when
looking for mathematical functional dependencies. In con-
nection to this, with the help of preliminary analysis we
have pre-selected the following most important indicators:
presence of spasms; type of conscience; presence of pul-
monary edema; presence of a shock; presence of a
multiorgan insufficiency syndrome (MOIS).
The indicators we have determined are non-paramet-
ric (qualitative) which necessitates the use only of non-
parametric statistical models. For the indicators that have
more than two possible manifestations (symptoms), in our
case “type of conscience” and “spasms”, it is necessary to
develop scales of well-chosen weight coefficients (Tabl. 1).
In view of the type and features of the indicated vari-
ables we propose to use a discriminatory analysis as the
solely appropriate statistical method to forecast the outcome
of the disease and the need of artificial pulmonary ventila-
tion. The idea of the method we have chosen is to find those
indicators that have the largest statistical significance to sepa-
rate the observed cases into two or more classes (sub-groups).
The objective is to achieve this in the most effective man-
ner, i.e. with the lowest number of indicators containing the
largest group significance. The latter means that individu-
ally they may happen not to display the largest significance,
but when viewed together they interact in such a way that
mutually compensates their statistical scattering.
The selected indicators form a discriminatory model
with an automatically constructed discriminatory function,
while their classification is carried out through a “classifi-
cation function”. It constitutes a mathematical expression
of the linear polynomial type and is directly related to the
auxiliary discriminatory function. Although the selection
(in the sense of the best group of indicators) is automatic
in this case, it is possible to choose one of the three popu-
lar strategies: Forward stepwise, Backward stepwise, and
Standard (manual input or output). There is a trade-off for
each strategy yet with sufficiently robust relations they
should lead to identical final results. With the data of our
study the end results coincides following all three strate-
gies, i.e. we get a subgroup of the two most significant in-
dicators: “pulmonary edema” and “MOIS” (Tabl. 2).
Tabl. 2. Classification function coefficients to determine the lethality of OPP (n = 140)
Indicator Healed Exitus letalis Confidence level
Pulmonary edema 17.1 30.8 p< 0.001
MOIS 6.41 10.47 p< 0.001
Constant -12.7 -39.9 p< 0.001
Tabl. 1. Weight coefficients for the manifestations of the “type of conscience” and “spasms” for AEI with OPP
Indicator “Type of conscience” Weight coefficient Indicator “Spasms” Weight coefficient
Without change 1 None 1
Obnibulation 1 Miofibrilation 2.5
Somnolence 2.7 Clonic-tonic 4
Stupor 3.0
Coma 4.25

J of IMAB. 2017 Apr-Jun;23(2) https://www.journal-imab-bg.org 1543
Fischer criterion for the overall model: F (2, 137 d.f.)
= 157.1. Confidence level for the overall model: p < 0.001.
Mahalanobis distance between the two classes: 14.3. The
respective classification functions are as follows:
- “healed” class – 17.1 (pulmonary edema) + 6.41
(MOIS) – 12.7
- “exitus letalis” class – 30.8 (pulmonary edema) +
10.47 (MOIS) – 39.9
According to the discriminatory analysis method the
patient is added to that class for which the calculated func-
tion is bigger. For this the indicators for “pulmonary edema”
and “MOIS” are replaced with their weight coefficients.
When the value for the “exitus letalis” is almost equal that
of the “healed” class (a difference of less than six), the pa-
tient is added to the “exitus letalis” class only when the con-
science type has a weight coefficient equal to at least 2.7,
i.e. the conscience must be at least of the “somnolence” type.
We use the obtained coefficients to check the qual-
ity of identification with respect to the basic and the con-
trol data set (Tabl. 3, Tabl. 4).
With the obtained coefficients we can build a fore-
cast matrix that will contain the score estimates destined
for practical work (Tabl. 5).
From the table we see that the presence of a pulmo-
nary edema almost unambiguously determines the lethal
outcome, which we confirm with the direct data check.
In a similar manner, using the method of discrimina-
tory analysis we get a classification matrix also for the cases
when artificial pulmonary ventilation is needed (Tabl. 6).
Tabl. 3. Classification matrix for the identification quality of the basic data set (n = 140)
Classes Correct answers (%) Healed Exitus Total
HEALED 97.3 110 2 112
EXITUS 89.3 3 25 28
TOTAL 95.7 113 27 140
Tabl. 4. Classification matrix for the identification quality of the control data set (n = 20)
Classes Correct answers (%) Healed Exitus Total
HEALED 87.5 12 2 14
EXITUS 100.0 0 6 6
TOTAL 90.0 12 8 20
Tabl. 5. Classification matrix “healed” - “deceased” with AEI from OPP
Indicator “Healed” class, score estimate “Exitus” class, score estimate
1. Pulmonary edema
- Absent 17 31
- Present 34 62
2. MOIS
- No 6.5 10.5
- Yes 13 21
3. Constant 27 0

1544 https://www.journal-imab-bg.org J of IMAB. 2017 Apr-Jun;23(2)
We can observe that the column “no need of artifi-
cial pulmonary ventilation” contains a constant equal to
14, in opposition to a constant of zero in the right column.
The straight-forward analysis demonstrates that the artifi-
cial pulmonary ventilation will be necessary when this con-
stant will “melt” from the difference in the respective score
estimates. This may take place in the following two cases:
1. Conscience impairment from the “stupor” or
“coma” type, independent of the presence or absence of
spasms, since the difference in the score estimates for “stu-
por” [4] may not “disappear”.
2. Conscience impairment from the “somnolence”
type, accompanied by the presence of myofibrillations or
spasms.
In all remaining cases, independent of the “type of
conscience” and “spasm” indicators, there is no need of ar-
tificial pulmonary ventilation.
CONCLUSIONS
The conducted study allows us to determine the ba-
sic clinical indicators that are related to the outcome fore-
cast for acute exogenous intoxications with organophos-
phorus pesticides: type of conscience, pulmonary edema,
shock, spasm and multiorgan insufficiency syndrom
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Score for the”No need” class Score for the”It is needed” class
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- obnibulation 2 7
- somnolence 5.5 18
- stupor 6 19
- coma 9 28
2. Spasm
- none 2 3
- myofibrillar 5 8.5
- clonic-tonic 8 13.5
3. Constant 14 0

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Georgi Bonchev, PhD
Head, Laboratory of Analytical Toxicology, Military Medical Academy, Naval
Hospital - Varna,
3, Hristo Smirnenski Blvd., 9010 Varna, Bulgaria
Tel: + 359 (52) 386 204
E-mail: toxilab.varna@abv.bg
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Please cite this article as: Marinov P, Zlateva S, Ivanov D, Bonchev G, Sabeva Y, Georgiev K, Vazharov I. Clinical criteria
for the outcome forecast of acute exogenous intoxication with organophosphorus pesticides. J of IMAB. 2017 Apr-
Jun;23(2):1541-1545. DOI: https://doi.org/10.5272/jimab.2017232.1541
Received: 10/03/2017; Published online: 10/05/2017