Location via proxy:   [ UP ]  
[Report a bug]   [Manage cookies]                

Factors For Determining Survival in Acute Organophosphate Poisoning

Download as pdf or txt
Download as pdf or txt
You are on page 1of 6

ORIGINAL ARTICLE

DOI: 10.3904/kjim.2009.24.4.362

Factors for Determining Survival in Acute Organophosphate


Poisoning
Eun-Jung Kang, Su-Jin Seok, Kwon-Hyun Lee, Hyo-Wook Gil, Jong-Oh Yang, Eun-Young Lee, and Sae-Yong Hong

Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea

Background/Aims: Organophosphate poisoning has a high mortality rate. Recently, differences among
organophosphorus insecticides in human self-poisoning were reported. This study investigated the prognostic
risk factors and the mortality of different organophosphates following acute organophosphate poisoning.
Methods: This retrospective study included 68 patients with acute organophosphate poisoning. We investigated
patient survival according to initial parameters, including the initial Acute Physiology and Chronic Health Evaluation
(APACHE) II score, serum cholinesterase level, and hemoperfusion and evaluated the mortality according to
organophosphate types.
Results: Thirteen of the 68 patients died. The agents responsible for mortality were different. The APACHE II
score was a significant predictor of mortality (odds ratio [OR], 1.194; p<0.01; 95% confidence interval [CI], 1.089
to 1.309) and respiratory failure (OR, 1.273; p<0.01; 95% CI, 1.122 to 1.444). The mortality was 0% for dichlorvos,
malathion, chlorpyrifos and profenofos. However, other organophosphates showed different mortality (16.7% for
O-ethyl-O-4-nitrophenyl phenylphosphonothioate, 25% for phenthoate, 37.5% for phosphamidon, 50% for
methidathion). The usefulness of hemoperfusion appears to be limited.
Conclusions: The initial APACHE II score is a useful prognostic indicator, and different organophosphates have
different mortality. (Korean J Intern Med 2009;24:362-367)

Keywords: Organophosphate; Survival; APACHE

INTRODUCTION Combined atropine and pralidoxime therapy is the


cornerstone of OP poisoning treatment. Extracorporeal
Organophosphates (OP) inhibit acetylcholinesterase elimination may be a useful adjunctive strategy. However,
and cause excessive acetylcholine accumulation, which the use of hemoperfusion in the management of severe OP
affects muscarinic and nicotinic receptors at synapses poisoning remains controversial [7-10].
within the peripheral and central nervous systems [1]. OP Recently, a difference among OP insecticides in human
poisoning causes neurotoxic sequela and has a high self-poisoning was reported. Moreover, the toxicity differed
mortality rate [2-4]. in humans and animals. These finding suggest that each
The World Health Organization (WHO) estimates OP has a different toxicity, although textbooks and articles
that the incidence of pesticide poisoning in developing have traditionally considered acute OP poisoning as a
countries has doubled during the past 10 years [5]. In homogenous entity.
Korea, the mortality due to poisoning has increased rapidly This study determined the predictors of a poor outcome
since 1998 [6]. Herbicides and pesticides constituted in patients with acute OP poisoning and differences of
the largest proportion of deaths due to poisoning of all toxicity according to OP type.
causes, although OP were not evaluated specifically [6].

Received: September 10, 2008


Accepted: December 8, 2008

Correspondence to Hyo-Wook Gil, M.D.


Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, 23-20 Bongmyung-dong, Cheonan 330-721, Korea
Tel: 82-41-570-3671, Fax: 82-41-574-5762, E-mail: hwgil@schca.ac.kr
Kang EJ, et al. Acute organophosphate poisoning 363

Table 1. Characteristics of patients with acute METHODS


organophosphate poisoning

Characteristic Value Study population


(n=68) This retrospective study examined the comprehensive
Age, yr 54.5 (16-91)*
medical, nursing, and intensive care records of 68 patients
Men 38 (56) admitted to the Institute of Pesticide Poisoning at
Agent Soonchunhyang University Cheonan Hospital, Cheonan,
Dichlorvos 21 (30.9) Korea, for acute OP poisoning between January 2000 and
EPN 12 (17.6) December 2006. The Investigational Review Board at
Phosphamidon 8 (11.8) Soonchunhyang Cheonan Hospital approved this study.
Phenthoate 4 (5.9) Initial diagnoses were established in all cases based on
Malathion 3 (4.4) cholinergic clinical features, the odor of OP in the gastric
Methidathion 2 (2.9) contents, history, and other circumstantial evidence, such
Profenofos 2 (2.9)
as the poison or a label of an OP-containing product found
Unknown 15 (22.1)
by relatives. All patients were given the classic treatment
Estimated amount ingested, mL 60 (5-500)*
for OP poisoning: gastric lavage, whole body surface
Time interval between exposure 3 (0.25-148)*
washing, activated charcoal administration (1 g/kg by
and hospital arrival, hr
Serum cholinesterase, IU/L 209 (7-2707)*
nasogastric tube), intravenous atropine and pralidoxime,
APACHE II score 10.7210.97 and supportive measures such as mechanical ventilation
Hemoperfusion 40 (58.8) (if necessary). Hemoperfusion (Absorba 300; Gambro,
Death 13 (19.1) Hechingen, Germany) was performed for 3.5 hours when
Ventilation required 35 (51.5) patients developed respiratory failure or mental changes.
Complete blood cell counts, measures of liver and renal
Value are number (%) except where indicated otherwise.
EPN,O-ethyl-O-4-nitrophenyl phenylphosphonothioate; function, and arterial blood gases were obtained. The Acute
APACHE, Acute Physiology and Chronic Health Evaluation. Physiology and Chronic Health Evaluation (APACHE) II
*Median (range). scores of all patients were determined. The 68 subjects

MeanSD.
were allocated to two groups: a respiratory failure group
(the RF group) requiring mechanical ventilation, and a
non-respiratory failure group (the non-RF group).

Table 2. Comparison of the initial parameters in patients with or without respiratory failure (RF)

RF Non-RF p value

APACHE II score 16.610.4 4.54.3 0.00


Serum cholinesterase, IU/L 222.0333.6 3056.42584.1 0.00
White blood cell, mm3 15153.16144.7 12293.05231.6 0.04
Lactate dehydrogenase, IU/L 648.1391.3 470.397.1 0.01
Glutamic-oxaloacetic transaminase, IU/L 86.4130.6 38.430.7 0.04
Glutamic-pyruvic transaminase, IU/L 54.8102.0 26.614.4 0.11
Amylase, IU/L 367.4458.7 299.3355.6 0.50
Lipase, IU/L 120.2197.2 139.7287.9 0.75
pH 7.30.2 7.40.1 0.04
PCO2, mmHg 37.118.1 35.36.9 0.58
PaO2, mmHg 85.830.6 87.729.0 0.79
HCO3, mmol/L 17.15.6 20.44.8 0.01

Values are meanSD.


APACHE, Acute Physiology and Chronic Health Evaluation.
364 The Korean Journal of Internal Medicine Vol. 24, No. 4, December 2009

Table 3. Multiple logistic regression analysis of the initial parameters associated with respiratory failure

Variable Odds ratio 95% Confidence interval p value

Age 0.932 0.855-1.015 0.106


Estimated amount ingested 0.985 0.963-1.007 0.186
Hemoperfusion 1.405 0.108-18.313 0.795
Serum cholinesterase, IU/L 0.995 0.990-0.999 0.019
APACHE II score 1.663 1.019-2.715 0.042

APACHE, Acute Physiology and Chronic Health Evaluation.

Figure 1. The comparison of clinical outcome in patients with


or without hemoperfusion treatment. The Acute Physiology and
Chronic Health Evaluation (APACHE) II scores were higher in
patients with hemoperfusion treatment, but hemoperfusion
treatment did not affect mortality.
Figure 2. The association between serum cholinesterase and
the Acute Physiology and Chronic Health Evaluation (APACHE) II.
A negative correlation between the APACHE II score and serum
Statistical analysis cholinesterase level was significant.
Data are presented as the meanSD. Probability values
of p<0.05 were considered significant, and all statistical
analyses were performed using SPSS version 12.0 (SPSS (n=8), phenthoate (n=4), malathion (n=3), methidathion
Inc., Chicago, IL, USA). Continuous variables were analyzed (n=2), profenofos (n=2), chlorpyrifos (n=1), and an
using the Students t-test, and categorical variables were unidentified OP (n=15).
analyzed using the chi-square test. Binary logistic regression The RF group included 35 of the 68 patients. The mean
or multiple logistic regression analysis was used to identify duration of mechanical ventilation was 9.58.3 days. A
factors associated with a poor outcome. tracheostomy was performed in 17 of these 35 patients.
Table 2 shows the comparison of initial parameters in the
RF and non-RF groups. The APACHE II score, white
RESULTS blood cell count, and lactate dehydrogenase and aspartate
aminotransferase levels were higher in the RF group, and
The general characteristics of the 68 study subjects, the serum cholinesterase and bicarbonate levels were
who all had acute OP poisoning at presentation, are sum- lower than the non-RF group. No significant difference in
marized in Table 1. The mean amount of ingested OP was the arterial oxygen partial pressures at presentation was
60 mL (range, 5 to 500) and the agents responsible for observed between the two groups. The APACHE II score
poisoning were dichlorvos (n=21), O-ethyl-O-4-nitrophenyl was a significant predictor of respiratory failure (odds ratio
phenylphosphonothioate (EPN, n=12), phosphamidon [OR], 1.273; p<0.01; 95% confidence interval [CI], 1.122 to
Kang EJ, et al. Acute organophosphate poisoning 365

Table 4. Comparison of the initial parameters between survivors and non-survivors

Survivors Non-survivors p value

Age, yr 50.617.1 65.912.6 0.03


Estimated amount ingested, mL 90.0105.5 215.4159.3 0.02
APACHE II score 7.87.1 23.511.1 <0.01
Serum cholinesterase, IU/L 1848.22389.8 110.7167.9 <0.01
White blood cells, L 13031.55158.7 16869.27673.7 0.11
Lactate dehydrogenase, IU/L 509.5135.1 782.9596.7 0.13
Aspartate aminotransferase, IU/L 43.935.6 144.3198.8 0.10
Alanine aminotransferase , IU/L 30.418.5 86.3163.9 0.24
Amylase, IU/L 358.9451.8 234.5116.6 0.08
Lipase, IU/L 147.1267.4 53.438.6 0.03
pH 7.4 0.1 7.20.3 0.15
PaCO2, mmHg 34.912.4 42.017.8 0.19
PaO2, mmHg 86.625.8 87.243.6 0.96
HCO3, mmol/L 19.05.1 17.36.8 0.40

Values are meanSD.


APACHE, Acute Physiology and Chronic Health Evaluation II score.

1.444). In addition, the APACHE II score was an important 28.003). Hemoperfusion treatment was not related to a
predictor of RF in the multiple logistic regression analysis better outcome, although the patients who underwent
(Table 3). hemoperfusion were in poorer condition (e.g., their
Information on the patients according to hemoperfusion APACHE II scores were higher).
treatment is presented in Fig. 1. The APACHE II scores Regarding the agents responsible, the death rate was
were higher in patients with hemoperfusion treatment, 0% (0 of 21 of cases) for dichlorvos, 16.7% (2/12) for EPN,
but hemoperfusion treatment did not affect mortality. 37.5% (3/8) for phosphamidon, 25% (1/4) for phenthoate,
Regardless of hemoperfusion treatment, the APACHE II 0% (0/3) for malathion, 50% (1/2) for methidathion, 0%
scores were higher and cholinesterase levels were lower in (0/2) for profenofos, 0% (0/1) for chlorpyrifos, and 40%
those who died. (6/15) for unidentified OP.
Thirteen of the 68 patients died. The clinical parameters
are summarized in Table 4. The serum cholinesterase
levels were lower in those who died. Twelve of the 35 RF DISCUSSION
group patients and only one of the non-RF patients died.
Therefore, the need for mechanical ventilation was a OP poisoning is a serious clinical entity and causes
significant predictor of a poor outcome (OR, 16.70; p<0.01; considerable mortality and polyneuropathy in survivors
95% CI, 2.03 to 137.60). that is not always completely reversible. The estimated
In addition, the APACHE II score was a significant mortality following OP ingestion ranges from 20 to 50%
predictor of mortality (OR, 1.194; p<0.01; 95% CI, 1.089 [3,10-12].
to 1.309). An APACHE II score <10 was a significant In this study, the total mortality was 19% (13 deaths in
predictor of mortality (OR, 16.11; p<0.01; 95% CI, 3.17 to 68 patients), and 12 of these deaths occurred in the 35
81.73); a serum cholinesterase <1,000 IU/L was patients with respiratory failure. In our study, age,
significantly associated with a poor outcome (OR, 0.676; amount ingested, APACHE II score, initial cholinesterase
p<0.05; 95% CI, 0.54 to 0.845). level, and respiratory failure requiring mechanical
Pearsons correlation analysis revealed a significant ventilation were significantly associated with a poor
negative correlation between the APACHE II score and outcome. The usefulness of the serum cholinesterase
serum cholinesterase level (r=0.415, p<0.01, Fig. 2). level in this context remains controversial [13,14]. In our
An age over 60 years was also a significantly predictor patients, the cholinesterase level was correlated with
of a poor outcome (OR, 6.852; p<0.01; 95% CI, 1.677 to the APACHE II score (Fig. 2), but this findings casts
366 The Korean Journal of Internal Medicine Vol. 24, No. 4, December 2009

doubt on the usefulness of the cholinesterase level in results suggest that hemoperfusion is of limited benefit
patients with a low APACHE II score. The APACHE II in cases of severe OP poisoning. Further randomized
score is a reliable general index that is useful for evalu- controlled studies of the beneficial effects of hemoperfusion
ating a wide spectrum of patients in intensive care units on patient survival are required.
[15], and essentially shows that the degree of physiological
derangement is closely correlated with outcome in critically
ill patients. In a previous study, an APACHE II score >26 REFERENCES
was a poor prognostic indicator in cases of OP poisoning
[16], and the both APACHE II score and Glasgow coma 1. Goldfrank LR. Goldfranks Toxicologic Emergencies. 7th ed. New
York: McGraw Hill, 2002;1346-1360.
scale predicted outcome [17,18]. In our study, the APACHE
2. Bardin PG, van Eeden SF, Joubert JR. Intensive care management
II score was correlated with respiratory failure and
of acute organophosphate poisoning: a 7-year experience in the
outcome. In particular, an APACHE II score >10 predicted
western Cape. S Afr Med J 1987;72:593-597.
a poor outcome.
3. Munidasa UA, Gawarammana IB, Kularatne SA, Kumarasiri
Extracorporeal methods of blood purification have PV, Goonasekera CD. Survival pattern in patients with acute
recently been recommended as a therapeutic approach organophosphate poisoning receiving intensive care. J Toxicol
to OP poisoning because of their ability to remove Clin Toxicol 2004;42:343-347.
xenobiotics from blood, particularly hemoperfusion 4. Rajapakse VP, Wijesekera S. Outcome of mechanical ventilation
systems involving activated charcoal or resins [9,19,20]. in Sri Lanka. Ann R Coll Surg Engl 1989;71:344-346.
However, the therapeutic benefits of this approach have 5. World Health Organization. WHO Recommended Classification

not been substantiated by other investigators, and this of Pesticides by Hazard and Guidelines to Classification 2000-
2001. WHO/PCS/01.4. Geneva: World Health Organization, 2001.
has been explained by the large volume of distribution.
6. Shin SD, Suh GJ, Rhee JE, Sung JH, Kim JY. Epidemiologic
The use of hemoperfusion for managing severe OP
characteristics of death by poisoning in 1991-2001 in Korea. J
poisoning is also controversial [7,9]. In a study of 52 OP-
Korean Med Sci 2004;19:186-194.
poisoned patients, Altinop et al. [7] reported that hemo- 7. Altintop L, Aygun D, Sahin H, et al. In acute organophosphate
perfusion was useful in severe cases. By contrast, in our poisoning the efficacy of hemoperfusion on clinical status and
study, hemoperfusion was ineffective for improving mortality. J Intensive Care Med 2005;20:346-350.
survival, although it should be emphasized that the 8. Martinez-Chuecos J, del Carmen Jurado M, Paz Gimenez M,
patients who were hemoperfused had high APACHE II Martinez D, Menendez M. Experience with hemoperfusion for
scores, which makes it difficult to evaluate the effect of organophosphate poisoning. Crit Care Med 1992;20:1538-1543.
hemoperfusion. Randomized controlled studies are 9. Okonek S. Probable progress in the therapy of organophosphate

required to investigate the effect of hemoperfusion on poisoning: extracoporeal hemodialysis and hemoperfusion. Arch
Toxicol 1976;35:221-227.
survival in patients with severe OP poisoning.
10. Yamanaka S, Yoshida M, Yamamura Y, Nishimura M, Takaesu Y.
Various types of OP were included in this study. No
Study on acute organophosphorus poisoning-changes in the
death occurred in 21 patients with dichlorvos poisoning,
activity and isoenzyme patterns of serum cholinesterase in
although the mean patient APACHE II score was 5.52 human poisoning. Nippon Eiseigaku Zasshi 1993;48:955-965.
5.01. By contrast, 2 of 12 EPN cases, 3 of 8 phosphamidon 11. Yamashita M, Tanaka J, Ando Y. Human mortality in organophos-
cases, and 1 of 4 phenthoate cases died. This suggests phate poisoning. Vet Hum Toxicol 1997;39:84-85.
that different OP have different toxicities. Eddlestone 12. Wyckoff DW, Davies JE, Barquet A, Davis JH. Diagnostic and
reported differences in the toxicity of OP [21]. In addition, therapeutic problems of parathion poisonings. Ann Intern Med
the human toxicity differed from the animal toxicity 1968;68:875-882.
suggested by WHO methods based on the toxicity in rats 13. Aygun D, Doganay Z, Altintop L, et al. Serum acetylcholinesterase
and prognosis of acute organophosphate poisoning. J Toxicol Clin
after oral dosing. That report suggested that each OP be
Toxicol 2002;40:903-910.
considered as an individual poison. Our findings were
14. Nouira S, Abroug F, Elatrous S, Boujdaria R, Bouchoucha S.
consistent with that opinion.
Prognostic value of serum cholinesterase in organophosphate
We conclude that the initial APACHE II score is a useful
poisoning. Chest 1994;106:1811-1814.
prognostic indicator in cases of OP poisoning. Each OP 15. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II:
might have a different toxicity. The management protocol a severity of disease classification system. Crit Care Med 1985;13:
for each OP in humans needs further study. Moreover, our 818-829.
Kang EJ, et al. Acute organophosphate poisoning 367

16. Lee P, Tai DY. Clinical features of patients with acute organophos- Evseev NG, Barsukov UF. Plasma perfusion through charcoal in
phate poisoning requiring intensive care. Intensive Care Med 2001; methylparathion poisoning. Lancet 1977;1:38-39.
27:694-699. 20.Okonek S, Tonnis J, Baldamus CA, Hofmann A. Hemoperfusion
17. Eizadi-Mood N, Saghaei M, Jabalameli M. Predicting outcomes in versus hemodialysis in the management of patients severely
organophosphate poisoning based on APACHE II and modified poisoned by organophosphorus insecticides and bipyridyl
APACHE II scores. Hum Exp Toxicol 2007;26:573-578. herbicides. Artif Organs 1979;3:341-345.
18. Davies JO, Eddleston M, Buckley NA. Predicting outcome in 21. Eddleston M, Eyer P, Worek F, et al. Differences between
acute organophosphorus poisoning with a poison severity score organophosphorus insecticides in human self-poisoning. Lancet
or the Glasgow coma scale. QJM 2008;101:371-379. 2005;366:1452-1459.
19. Luzhnikov EA, Yaroslavsky AA, Molodenkov MN, Shurkalin BK,

You might also like