Mar 24, 2001 - mary health care centers. In emergency service, pralidoxime (PAM) was administered to only 29.2% of cases. According to ECG examination, ...
Environmental Research Section A 88, 82}88 (2002) doi:10.1006/enrs.2001.4320, available online at http://www.idealibrary.com on
Sociodemographic, Clinical, and Laboratory Features of Cases of Organic Phosphorus Intoxication who Attended the Emergency Department in the Southeast Anatolian Region of Turkey I smail Hamdi Kara,* Cahfer GuK logy lu,- Aziz Karabulut,? and Murat Orak*Department of Family Medicine, -Department of First Aid and Emergency Medicine, and ?Department of Cardiology, Dicle University Faculty of Medicine, Aile Hekimligy i ABD, 21280, Diyarbaknr, Turkey Received March 24, 2001
Key Words: organic phosphorus compound; intoxication; suicide; emergency service; arrhythmia.
In this study, sociodemographic, laboratory, and clinical features of cases of organic phosphorus (OP) intoxication in the Southeast Anatolian region of Turkey were investigated. Patients with OP intoxication admitted to the Emergency Service of Dicle University Hospital in Diyarbaky1r City between May and August 1998 were evaluated. This prospective cohort study included Ave male (M) and 19 female (F) consecutive patients. Five cases were accidental intoxication; however, 19 cases were suicide attempts. Mean age of cases was 24 ⴞ 11 years; 54.2% of them were under the age of 20 years and 83.3% of them were under the age of 30 years. The M/F ratio was 1.0/3.8. The cases of suicidal purposeful intoxications were mostly determined in singles (58.3%, P < 0.05). Most of the cases had a primary education level (16, 66.7%) and a lower socioeconomic status (14, 58.3%); 79.2% of cases admitted to our emergency service received atropine in primary health care centers. In emergency service, pralidoxime (PAM) was administered to only 29.2% of cases. According to ECG examination, tachycardia (14, 58.3%), ST changes (13, 54.2%), and T changes (3, 12.5%) were mostly seen; bradycardia and serious ventricular arrhythmias were not seen in any case. Patients who received atropine plus PAM had higher rates of arrhythmias, but this was not statistically signiAcant (P > 0.05). The most observed biochemical features of cases were leukocytosis (21 cases), hypokalemia (18 cases), and hyponatremia (4 cases). Other biochemical features were not evidently altered. In present cases, the most frequently seen symptoms and Andings were vomiting (18, 75%), feeling faint (17, 70.8%), and tachycardia and dozing off (14, 58.3%). Serious ventricular arrhythmias were not observed, and in our region, OP intoxication especially affected young unmarried females, and most of them resulted from a suicidal purpose. 2002 Elsevier Science (USA)
Organic phosphorus (OP) components are commonly used in the agriculture sector in Turkey. Because they cause intoxications, they are used for suicide purposes, and mistakes in their use are common (1). The rate of suicide in Turkey was 2.2/100,000 persons and a total of 28,408 suicide deaths were reported between 1974 and 1998. The rate of suicide among males is higher than that among females (2.7/100,000 persons vs 1.7/100,000 persons) (P(0.001). The male/female (M/F) ratio was 1.5/1 (2). OP intoxication cases make up a great percentage of patients who come to emergency service because of intoxication. There is no standard classi7cation for the acute OP intoxications. If the effect of these intoxications on the metabolism is known well, effective and correct 7rst aid techniques can be applied (3, 4). Organic phosphorus compounds inhibit acetylcholine esterase irreversibly and thus cause acetylcholine to accumulate at the synapse. Because OP compounds dissolve well in fat, they are absorbed well by the conjunctiva, skin, lung, stomach, and intestines (3, 5). Anticholinesterase medicines inhibit acetylcholine esterase, which causes acetylcholine (Ach) to accumulate at the cholinergic junctions and synapses. This causes nicotinic effects in addition to the parasympathicomimetic (muscarinic) effects (4, 5). OP compounds stimulate sympathic and parasympathic ganglions and striped muscles. They cannot 82
0013-9351/02 $35.00 2002 Elsevier Science (USA) All rights reserved.
ORGANIC PHOSPHORUS INTOXICATION IN SOUTHEAST TURKEY
directly affect regions that contain muscarinic receptor but no cholinergic nerves because Ach does not accumulate in these regions. They can only affect these regions in an indirect way if taken a very high dose (3}7). The aim of this study was to describe the biological effects of OP intoxication and to evaluate the demographic and clinical characteristics of those poisoned with OP. MATERIALS AND METHODS
The scope of the study was chosen to include cases of OP intoxication in the Emergency Department of Dicle University Medical Faculty in Diyarbakir between May and August 1998. Diyarbakir is located in the southeast Anatolian region of Turkey. The population is around 500,000. The southeast Anatolia region is in upper Mesopotamia, covering Diyarbakir, Batman, Mardin, SanliUrfa, etc. The University Hospital, in which this study was conducted, has about 1200 beds with all specialties. In this cross-sectional study, 5 of the cases were male (20.8%) and 19 were female (79.2%). Their mean age was 24$11 years. Low, middle, and high economic status was determined as (1000 U.S. Dollars/year, 1000}5000 U.S. Dollars/year, and'5000 U.S. Dollars/ year, respectively. At 7rst, patients were thoroughly decontaminated by clothing removal and a soap and water (or hypochlorite) bath or shower before entering the emergency department (ED). The patients were examined physically (neurological and cardiological), and they were given atropine 2 mg iv every 15 to 20 min using the drying of secretions or evidence of toxicity as an end point. Atropine will treat the muscarinic effects only. As a cholinesterase reactivator, pralidoxime (2-PAM) were applied 1}2 g iv for 15}20 min in every 4}6 h. End point for therapy includes improved muscle strength (oximes). The study participants were followed at least 2 weeks to 1 month. In the present study, the type of OP compound, the time that had passed after the intoxication, the age of the patient, where the compound came, and the symptoms observed in the patients (absentmindedness, vomiting, diarrhea, mydriasis, miosis, agitation, disorientation, cyanoses, tachycardia, hypersecretion, inhalation pneumonia, Babinski sign positiveness, balance loss, dizziness, slumbering, fever, unconsciousness) were investigated. Complete blood count [hematocrit (HCT, males: 42}52%, females: 37}48%), leukocytes (count: 4.3}10.8; 103/mm3 ), thrombocytes (count: 130,000}400,000/
mm3 )], biochemical [serum glutamate oxaloacetate transaminase (SGOT; normal, 0}38 IU/L), serum glutamate pyruvate transaminase (SGPT; normal, 0}41 IU/L), creatine phosphokinase (CK; females: (10}70 U/L), males: (25}90 U/L)), lactate dehydrogenase (LDH; 100}190 U/L), glucose (normal, 75}115 mg/dL), urea (normal, 20 to 48 mg/dL), creatinine (normal, 0.7 to 1.4 mg/dL), electrolytes Na>: (normal, 136}145 mmol/L), K> (normal, 3.5}5.0 mmol/L), chloride (Cl\, normal, 98}106 mmol/L)], and electrocardiography (ECG) results are shown in the tables and graphs. Statistical analyses were carried out with the SPSS 7.5 software using 2 (Fisher’s exact) test. A difference of P(0.05 was considered statistically meaningful. Data are given as means$SD. RESULTS
Sociodemographic characteristics of the cases are given in Table 1. According to their educational level, 19 are primary school or junior high school graduates, 2 are high school graduates, and 1 is a university graduate; 2 have no literacy. According to their economical level, 20 belong to the low or
TABLE 1 Sociodemographic Characteristics of Patients and OP Compound Exposure
Gender Male Female Education level Illiterateness Primary school graduates Junior high school graduates High school graduates University graduates Economical status Low Middle High City (in southeast of Turkey) Diyarbakir SanliUrfa Batman Mardin Organic phosphorus compound Diazinon (Basudin) Diklorodifeniltrikloretan (DDT) Diklorvos (DDVP) ASYEM Total
2 16 3 2 1
8.3 66.7 12.5 8.3 4.2
14 6 4
58.3 25.0 16.7
12 5 4 3
50 20.8 16.7 12.5
8 5 2 1 24
33.3 20.8 8.3 4.2 100
KARA ET AL.
TABLE 2 Cause of Intoxication in Terms of the Patient’s Marital Status Married
Accident Suicide Total
3 5 8
12.5 20.8 33.3
2 14 16
8.3 58.3 66.7 FIG. 2. Distribution of the patients according to their ages.
intermediate economic level group, and 4 belong to upper intermediate or high economic level group. The type of OP compound that caused the intoxication could be determined in 16 of the cases, while in 8 of them it was unknown. Twelve of the cases came from Diyarbakmr (50%). The most common OP compounds that cause intoxication seem to be Diazinon (Basudin) (8 cases) and Diklorodifeniltrikloretan (DDT) (5 cases). Table 2 shows the list of marital status of the cases. Most of the patients who tried to suicide were unmarried (58.3%, P0.05), and most who attempted suicide are female (70.8%, P(0.05) (Fig. 1). The distributions of the cases according to their ages are shown in Fig. 2. Most of them were 11}20 (13 cases, 54.2%) and 21}30 (7 cases, 29.1%) years old. The ECG results are shown in Table 3, the biochemical results are shown in Table 4, and blood count values are shown in Table 5. PAM was administered to 29.2% of the cases at the emergency department. The average time from poisoning to arrival at the emergency department was 190$180 (range: 30}720) min. The most common symptoms were vomiting (18 cases), unconsciousness (17 cases), tachycardia (14 cases), and slumber (14 cases) (Table 6).
Because OP intoxication is a serious cause of morbidity and mortality, effective emergency therapy techniques can result in better outcomes in these cases. Because OP compounds are commonly used in agriculture, different types of intoxication due to OP compounds are encountered. Poisoning often is related to agricultural workers; thus, males aged 15}45 years are more frequent victims. Because OP compounds affect cholinergic nerves directly and the strong cholinesterase inhibition of them, are very effective toxics (7, 8). The nicotinic (sympathomimetic) effects of accumulation of acetylcholine at motor end plates cause persistent depolarization of skeletal muscles, resulting in fasciculations, muscle weakness, hypertension, and tachycardia. Muscarinic effects from potentiation of postganglionic parasympathetic activity of smooth muscles may cause smooth muscle contractions in all organs (e.g., lung, GI, eye, bladder, secretory glands) and reduction of sinus node and AV conduction, causing bradyarrhythmias or resultant ventricular dysrhythmias. CNS effects
FIG. 1. Distribution of the patients according to their gender.
ORGANIC PHOSPHORUS INTOXICATION IN SOUTHEAST TURKEY
Frequency and Percentage of Different ECG Changes in Cases Poisoned with OPs
Changes in Complete Blood Count Values of Patients Poisoned with OPs
ST change Tachycardia T change Bradycardia Other (PSVT, VT)
13 14 3 0 0
54.2 58.3 12.5 0 0
Leukocytes (;1000/mm3 ) Erythrocytes (;1000/mm3 ) Platelets (;1000/mm3 ) Hematocrit (%) MCV (8)
may cause excessive stimulation (possible seizure), leading to depression and coma. Actual signs and symptoms depend on the balance between muscarinic and nicotinic receptors. One study showed that 92% of victims had muscarinic symptoms, 44% had nicotinic symptoms, 40% had CNS symptoms, and 17% had combined symptoms (9}11). However, our results indicated that 70.8% of victims had muscarinic symptoms, 58.3% had nicotinic symptoms, 33.3% had CNS symptoms, and 20.8% had combined symptoms. In some studies, it was reported that the vast majority of the victims were male. One study showed that 86% of victims were males, and of these patients 91% were under 30 years of age. According to this study, poisoning was due to ingestion with suicidal intent in the majority. In addition to the acute cholinergic features, important manifestations were delayed onset respiratory paralysis and delayed polyneuropathy. The overall mortality was 18% (12). In another study, there were 17 (46%) males and 20 (54%) females, with M/F ratio being 1/1.2, and 62% of patients were unmarried. The most common reason for poisoning was suicide (32 patients,
TABLE 4 Biochemical Parameters and Values of Cases Poisoned with OPs
Parameter Glucose (mg/dL) Urea (mg/dL) Creatinine (mg/dL) SGOT (U/L) SGPT (U/L) CK (U/L) LDH (U/L) Na> (mMol/L) K> (mMol/L) Cl\ (mMol/L)
182$68 25$7 0.8$0.3 37$14 54$46 304$229 252$122 138$6 3.5$0.8 106$6
81}338 11}45 0.2}1.5 17}69 12}218 83}945 102}511 117}145 2.6}5.8 95}118
Normal High Low (n) (n) (n) 3 24 24 15 16 10 17 20 15 17
21 ; ; 9 8 14 7 ; 1 5
; ; ; ; ; ; ; 4 8 2
4.700$800 2.300}6.400 285$89 40$6 86$9
80}472 23}52 57}102
Normal High (n) (n)
23 22 22
; 1 1
1 1 1
86.5%). The overall mortality among hospitalized patients was 8% (13). There are two larger studies in the literature. One of them, a larger epidemiological study, was conducted on 270 patients who died at the General Hospital, Port-of-Spain, after presenting with deliberate self-poisoning between January 1986 and June 1990. This study showed that the M to F ratio was 2.7/1 and the majority of cases (52.6%) were in the age group 11}34 years. ‘‘Lovers’ quarrels’’ (35.4% of cases), psychiatric illness (27.8% of cases), and family disputes (27% of cases) were reported as the most frequent precipitating events in suicide (14).
TABLE 6 Symptoms and Findings Observed in Our Cases
Vomiting Unconsciousness Tachycardia Slumbering Dizziness Disorientation Absentmindedness Decrease in re8exes Hypersecretion Loss of balance Cough Miosis Agitation Cyanosis Coma Convulsion Pneumonia Fever Diarrhea Increase in re8exes Mydriasis
18 17 14 14 13 13 12 11 11 10 8 8 7 5 5 5 4 2 1 0 0
75 70.8 58.3 58.3 54.2 54.2 50 45.8 45.8 41.6 33.3 33.3 29.2 20.8 20.8 20.8 16.7 8.3 4.2 0 0
KARA ET AL.
In the other large study, of a total of 606 organophosphate poisoning cases, 75% (450) were suicides and or parasuicides, 21% (126) were accidental, 2% (12) were homicides, and 5% (30) were of an undetermined nature. The mortality rate was established at 8% (48). The study revealed that the 21 to 30-year-old age group is signi7cantly more prone to poisoning (42% of the total) than other age groups (15). In his study, Agarwal (8) investigated OP intoxication cases at India Ahmedabad Faculty of Medicine Hospital. In this study, 128 of the 190 cases were suicide trials, 30 were accidental, and 32 were the cause of the cases’ occupations. Their ages were between 11 and 60 (most of them in the 21}30 range), and the M/F ratio was 1.0/2.1. In Agarwal’s study (8), 98 of the patients were married, 92 of them were unmarried, and 71.6% of the cases had low, 24.2% had intermediate, and 4.2% had high educational levels. The economic level of 24.2% of the cases was low, 69.4% were intermediate, and 9.5% were high. Also, 74.7% of the patients lived in the cities while 25.3% lived in the villages. In the Finkelstein et al. study (16), 53 patients who came to Israel National Toxic Control Center because of OP toxication were investigated. Thirtyone patients were younger than 18 years. Patients who were 15}18 of age were all the ones who tried to suicide. Their age ranged between 1 and 73, but most of them were in the age range 21}30 years. Sociodemographic data of our cases (Table 1) reveals that their mean age is 24$11 years most are primary school graduates (16 cases, 66.7%), most have low economic status (14 cases, 58.3%), and most are from Diyarbakmr (12 cases, 50%). The OP intoxication resulted accidentally in 5 cases, while in 19 cases the reason was suicide. Most of the patients who attempted suicide were unmarried (58.3%) (P0.05). It was considered that the higher rate among unmarried individuals is due to the higher rate of suicides among women. As seen in Fig. 1, most of the patients were female (19 cases, 79.2%), and 5 were male (20.8%), which leads us to a M/F ratio of 1.0/3.8. This ratio was different from that in other studies and it is interesting that there was predominance of females in our study. Their ages ranged between 15 and 51, most of them were between 15 and 20 (13 cases, 54.2%), 54.2% were younger than 20, and 83.3% were younger than 30 (Fig. 2). The 7rst 24}48 h is very critical in cases of OP intoxication, but because OP dissolves well in fats, it may take several weeks (17, 18). The time between the intoxication and arrival at the emergency de-
partment was 190$180 min in our study: 58% of the patients came in 120 min, 79% came in 240 min, and 5 came in longer than 300 min. A female patient who came after 720 min has been exitus in the Nephrology Clinic of our hospital. If the patients were given 7rst aid, and started to be treated at the periphery, and then taken to the hospitals, then chances of survival would be increased. C , evik and colleagues (19) studied ECG changes in acute OP intoxications, early ECG changes caused by the OP intoxication, and the relationships between these changes and 7rst plasma cholinesterase activities (pChEA) and mortality rates. They observed that in 44 of 58 cases (75.86%), mean Q-T interval was extended (0.4 s) and also observed sinus arrhythmia in one case and ventricular extrasystols in three cases. They postulated that in the acute stages of OP toxication the Q-T interval is extended, when pChEA decreases the rate of Q-T interval extension increases, and the amount of change in the ECG gives us an idea about the level of intoxication. Agarwal (8) observed sinus tachycardia in 25.3% of the cases. ST segment changes in 6.3% of the cases, and T changes in 1.1% of the cases. In Finkelstein’s study (16), the cases were investigated according to CVS results. The patients were given higher doses of obidoxime and relatively lower doses of atropine. Seven of these patients were exitus while they were at the hospital and 22 have shown CVS 7ndings. Higher rates of cardiac arrhythmias were observed in patients to whom higher doses of atropine and obidoxime were given cumulatively. Supraventricular arrhythmias (PSVT) were observed in four cases (18%), asymptomatic long Q-T intervals in six cases (27%) asymptomatic ventricular premature heartbeats in four cases (18%), and ventricular tachycardia (VT) and/or ‘‘torsades de pointes’’ in eight cases (37%). In our study, 79.2% of the patients were given atropine before coming to the emergency department and 29.2% of the patients were given PAM at the Emergency Department. When the ECG results were investigated according to type of OP compound, the most common compounds that caused ST-T changes were Basudin (7 cases) and ASYEM (1 case) (P(0.05). Fourteen cases (58.3%) of tachycardia, 13 cases (54.2%) of ST changes, three cases (12.5%) of T changes, and in no case bradycardia was observed (Table 3). Higher rates of arrhythmias were observed in patients given atropine and PAM together, but that was not statistically signi7cant. Tachycardia was observed in the six of seven patients to whom atropine and PAM were given
ORGANIC PHOSPHORUS INTOXICATION IN SOUTHEAST TURKEY
together, and T changes in only one case. PSVT, VT, and bradycardia were not observed in any of our patients, because of atropine application before coming to the Emergency Department. Although some studies report ECG changes in the cases, other studies report no ECG changes (such as Rivera’s study (20)). Hyperglycemia has been reported in OP intoxication studies (21}24). Increases in SGOT and SGPT levels were observed in 5 of the 53 cases in Finkelstein’s study (16). Rivera study (20) observed leukocytosis in 10 of the 14 cases hyperglycemia in 5 cases, and hypokalemia in 4 cases. According to the biochemical results in our study (Table 4), hypokalemia, hyponatremia, and hypochloridemia were observed. In 21 cases glucose, in 14 cases CK, in 9 cases SGOT, in 8 cases SGPT, in 7 cases LDH, and in 5 cases chlorine were observed at high levels. The mean values of glucose, SGPT, CK, and LDH were higher than normal. The value of leukocytes was high in most of the cases (21 cases). The value of erythrocyte was high in 6 cases, low in 1 case, and normal in 17 cases. The values of the other parameters did not show any meaningful changes (Table 5). The most common symptoms in Agarwal’s study (8) were vomiting (96.8%), nausea (82.1%), miosis (64.2%), and excessive secretion (61.1%). The most common symptoms in Rivera’s study (20) were nausea (6 cases) and excessive bronchial secretion (8 cases). The most common symptoms and 7ndings in our study were vomiting (18 cases, 75%), unconsciousness (17 cases, 70.8%), tachycardia (14 cases, 58.3%), and slumbering (14 cases, 58.3%) (Table 6). In the Moral et al. study (25), which is a retrospective analysis of 211 OP intoxication cases during 1986}1992, the authors postulate that being older than 40, having an initial measured value of plasma cholinesterase activity (pChEA) under 400 U/L, insuf7cient respiration, excessive hypersecretion and unconsciousness, and taking the OP compound orally are the essential indicators of mortality. They also postulate that agents of the oxime group do not have any effect on decreasing the mortality rate. OP intoxication cases in our region are mostly unmarried, young female, patients they are most commonly caused by suicide. Serious arrhythmias (PSVT and/or VT) were not observed in our cases. Although tachycardia and ST changes were observed in most of our cases, bradycardia was not observed. Higher rates of tachycardia and ST changes were observed in patients given atropine and PAM together, but that did not have any statistical signi7cance.
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