Original Contribution

Acid-base interpretation can be the predictor of outcome among patients with acute organophosphate poisoning before hospitalization

Jiung-Hsiun Liu MD, Che-Yi Chou MD, Yao-Lung Liu MD, Pen-Yuan Liao MD, Po-Wen Lin MD, Hsin-Hung Lin MD, Ya-Fei Yang MD*

Division of Nephrology, Department of Internal Medicine, China Medical university hospital, Taichung, Taiwan

Received 28 January 2007; revised 15 March 2007; accepted 18 March 2007

Abstract

Objectives: Acute organophosphate (OP) poisoning causing alteration in acid-base equilibrium was reported before. Hence, different acid-base statuses may present in patients with acute poisoning due to OP exposure. This study aims to determine the impact of acid-base interpretation in patients with Acute OP poisoning before hospitalization in medical care units and to describe the pattern of mortality with different acid-base statuses.

Design and Patients: Over a 9-year retrospective study, from July 1996 to August 2005, a total of 82 consecutive patients with acute OP poisoning were admitted to the China Medical University Hospital (Taichung, Taiwan) within 24 hours after exposure to OP and were enrolled into this study. Results: Patients with acute OP poisoning were divided into 4 groups: without acidosis, metabolic acidosis, respiratory acidosis, and mixed acidosis. Overall survival (Kaplan-Meier curves) among groups was statistically significant ( P b.0001). The mortality rate of acute OP Poisoned patients with metabolic acidosis was 25%, and 75% of those patients died of cardiovascular failure. The mortality rate of acute OP poisoning with respiratory acidosis was 50%, and 50% of those patients died of respiratory failure. Conclusions: Acid-base interpretation can be effective in quick diagnosis and prediction of the outcome of patients with acute OP poisoning (without acidosis b metabolic acidosis b respiratory acidosis b mixed acidosis) before hospitalization. Major causes of death are different between the respiratory acidosis and metabolic acidosis groups of patients with acute OP poisoning.

D 2008

Introduction

Organophosphate (OP) compounds are important insec- ticides used in agriculture and are possibly the most common acute poisonings in Developing countries. Al-

* Corresponding author. Tel.: +886 4 22052121×7963; fax: +886 4

22038883.

E-mail address: [email protected] (Y.-F. Yang).

though Taiwan has recently become an industrial nation, many people still use OP compounds in agriculture or in their gardens. Therefore, the arrival of patients at the emergency department (ED) for treatment of acute OP poisoning is not an infrequent occurrence. Organophosphate pesticides are inhibitors of both muscarinic and nicotinic acetylcholinesterase and affect the central nervous system. Hemodynamic instability and Respiratory insufficiency frequently develop after acute OP poisoning. Hypotension,

0735-6757/$ - see front matter D 2008 doi:10.1016/j.ajem.2007.03.017

hypertension, bradycardia, tachycardia, increased salivation, and bronchospasm are common symptoms in those patients. Hence, after initial treatment at the ED, they need to be admitted to Intensive care units for regular monitoring of the vital organs until the Clinical patterns become stabilized. The lethality of OP is unpredictable [1-7] but the rate may be as high as 37% [1]. The mortality rate of acute OP poisoning depends on the type of compound used, amount ingested, general health of the patient, and delayed diagnosis or treatment [8]. From clinical experience, information on the type and amount of compound are sometimes unavailable when patients arrive at hospital. There is no rapidly available and objective information for clinical physicians to decide the outcome of patients with acute OP poisoning when they are not delayed in discovery or transport. Acute OP poisoning causes alteration in acid-base equilibrium, as has been reported before [9]. Different acid-base statuses may present in patients with acute poisoning due to OP exposure. The present study aims to determine the impact of acid-base interpretation in patients with acute OP poisoning before hospitalization in medical care units and to describe the pattern of mortality with different acid-base statuses.

Methods

Study design and patient selection

Over a 9-year retrospective study, from July 1996 to August 2005, a total of 86 consecutive patients with acute OP intoxication were admitted to the China Medical University Hospital (Taichung, Taiwan) within 24 hours after exposure to OP. The hospital was a 1800-bed tertiary teaching facility with a 52-bed ICU for patients with critical medical conditions. Only 82 patients were included in this study. Four patients were excluded because of co-intoxica- tion with other known poisons or because they were dead on arrival. The mean age was 50.1 F 14.8 years, with a male to female ratio of 3.6:1. The diagnosis of acute OP was based on the following criteria: (1) a history of intake or exposure to OP; (2) clinically muscarinic or nicotinic manifestations of OP intoxication, including miosis, excessive salivation, or fasciculation; and (3) low plasma cholinesterase level measured at the ED, ward, or ICU. To be included in this study, each patient had to present with all 3 criteria. Thereafter, during the course of the disease, the plasma cholinesterase level plus clinical manifestations were deter- mined, aiming for successful mechanical ventilator cessation and extubation once the patient develops respiratory failure. Normal value for plasma cholinesterase activity in our hospital was 4900 to 11 900 U/L. The plasma cholinesterase activity was measured by using cholinesterase reagent in conjunction with SYNCHRON LX System (Unicel DxC System, Beckman\Coulter, Fullerton, CA).

Data on age, sex, vital signs, need for assisted ventilation, hospital stay, and the in-hospital outcome were

obtained from case notes. Pulse rate, respiratory rate, blood pressure, and Electrocardiograms were taken on arrival in the ED. During the hospital stay, electrocardio- graph recordings were carried out in the ICU or ED. Electrocardiographic analysis included the rate, rhythm, ST segment/T abnormalities, conduction defects, and measure- ment of PR and QT intervals. QT intervals were also corrected to QTc. Patients with carbamate compound intoxication were excluded from this study. ED staff determined the patient’s Glasgow Coma Scale score and Acute physiology and chronic health evaluation II score as soon as the patient arrived after the information was available. Depending on the respira- tory pattern and general condition of the patients, they would also decide whether to perform endotracheal intubation and/or provide mechanical ventilator support. After diagnosis, the patient would receive initial treatment with skin and hair decontamination, gastric lavage, activated charcoal, and intravenous antidote therapies based on physician’s judgment. Plasma cholinesterase concen- trations, biochemistry, white blood cell count, and arterial blood gas were measured in the clinical pathology laboratory of the hospital.

Drug treatment

Not all patients received the same therapies. Among

82 patients, 72 received intravenous pralidoxime and

74 received intravenous atropine sulfate. pralidoxime chloride was administered at 4 to 6 g daily with continuous intravenous infusion as long as possible for each patient who received the treatment. As soon as acute OP poisoning was diagnosed, atropine sulfate was administered at 2 mg every hour until signs or symptoms of atropine intoxication appeared. Thereafter, continuous infusion was changed to 20 mg per day with dosage adjusted according to the pupil size, heart rate, status of hypersecretion, and general conditions of the patient judged by the physician’s experience in our ED, ICU, or ward.

Definition of mortality pattern

In case of death, cause of death was determined as either cardiovascular or respiratory failure. Cardiovascular failure was defined as a cause of death if treatment-irresponsive shock followed Cardiac manifestations of acute OP poison- ing. Cardiac manifestations of acute OP poising included the following: (1) cardiogenic pulmonary edema; (2) ECG abnormalities including prolonged QTc interval, ST-T change, or conduction defects; (3) cardiac arrhythmias. Comparisons with prior ECGs were recorded if earlier records in the hospital were available. Cardiac manifestation would not be considered if the same ECG abnormalities had been presented before. Respiratory failure was defined when mechanical ventilation was used for correction of hypoxia, hypercapnia, or airway protection as per physicians’ decision. If both cardiovascular and respiratory failure

coexisted at the time of death, the preceding event would be determined as the cause of death.

Arterial blood gas interpretation and analysis

If arterial blood gas interpretation was done more than once during the patient’s hospital stay, the first analysis of arterial blood gas sample was used as the outcome predictor. Determination of whether the arterial blood gas samples were acidotic, alkalotic, or normal (pH 7.35-7.45) and the interpretation of arterial blood gas were based on the criteria in the ICU book [10]. Patients who had normal pH values or alkalosis of arterial blood gas samples were considered as bwithout acidosisQ group in this study.

Statistical analysis

All values are expressed as mean F SD or frequency (%) as appropriate and were analyzed with Student t test or

1-way analysis of variance. The v² test (with Yates correction) was applied to compare differences in results of qualitative variables. Multivariate logistic regression was used to analyze the potential risk factors between the groups of survivors and fatalities. Patients with or without acidosis were estimated for survival curves by using the Kaplan- Meier technique and tested by using the log-rank test. A P value of .05 or less was considered to be statistically significant. All calculations were performed with SPSS version 10.0 for Windows (SPSS, Chicago, IL).

Results

During the study period, 86 patients were admitted into the ICU and 82 patients were enrolled in this study (Fig. 1). After initial evaluation, in 56 cases, OP was ingested by the patients themselves for the intention of committing suicide,

Fig. 1 Flow chart of patients enrolled in the study. RF indicates respiratory failure; CF, cardiovascular failure; Resp, respiratory; Meta, metabolic.

Table 1 Characteristics and laboratory data of patients with acute OP poisoning
	Deaths	Survivors	P
No. of patients	22	60
Age (y)	59.9 F 16.7	47.7 F 13.7	.004
Female/male	6/16	12/48	.686
Suicide	16	40	.799
Respiratory failurea	16	20	.003
GCS score	7.1 F 5.2	11.3 F 4.5	.002
Systolic blood pressure (mm Hg)	136.1 F 33.0	141.3 F 32.3	.528
Diastolic blood pressure (mm Hg)	72.8 F 24.	81.6 F 19.4	.146
Heart rate (beats/min)	93.0 F 22.5	96.1 F 26.7	.599
Blood glucose (mg/dL)	204.3 F 106.9	198.9 F 166.6	.864
WBC count (/lL)	12,342 F 3887	13,998 F 6524	.166
Serum urea nitrogen (mg/dL)	16.9 F 5.7	13.8 F 5.3	.136
Creatinine (mg/dL)	1.2 F 0.3	1.0 F 0.3	.120
AST (IU/L)	39.5 F 17.2	86.3 F 110.3	.107
ALT (IU/L)	24.1 F 10.6	40.6 F 47.6	.014
Na (mmol/L)	140.7 F 5.4	138.7 F 2.9	.303
K (mmol/L)	3.5 F 0.7	3.5 F 0.4	.844
Arterial blood gas
pH value	7.18 F 0.17	7.36 F 0.14	b.001
Pco2, mm Hg	40.9 F 13.0	32.7 F 8.4	.010
HCO3 (mmol/L)	16.8 F 7.5	20.4 F 4.6	.039
Plasma cholinesterase (U/L)	686.9 F 1387.1	1459.2 F 2375.4	.075
Values are expressed as mean F SD unless otherwise indicated. Because patients received laboratory examination more than once during hospital stay, the first data were used for statistical analysis. All the laboratory data were results of serum component or hematologic investigation. a Defined as patients who underwent intubation with ventilator support regardless of the cause of intubation.

of which 16 patients died and 40 survived. Table 1 shows characteristics of patients in the survival and death groups. All patients who died within 30 days were classified as the death group. The mortality rate was 26.8% in patients of the study. Thirty-six (43.9%) of 82 patients developed respiratory failure with intubation, and 16 (44.4%) of them died. After detailed analysis of cardiac manifestations of the death group, only 11 of

22 patients died of btrueQ respiratory failure as cause of death (as defined in the Methods section). The cause of death of the other 11 death cases was cardiovascular failure (1 patient had pulmonary edema, 6 patients had Abnormal ECGs, and 4 patients had arrhythmias). In addition, the mortality rate of patients was independent of medicinal therapies (atropine and pralidoxime; yes vs no), drug dosage (intravenous atropine or pralidoxime), and days of admin- istration (data not shown). No statistical differences were found in terms of suicide intent, sex, blood pressure, heart rate, WBC count, and levels of blood glucose, serum urea nitrogen, serum creatinine, aspartate aminotransferase , serum sodium, serum potassium, or serum cholin- esterase after initial evaluation between the survival and death groups. Analysis of the potential risk factors that influence the mortality of patients with acute OP poisoning are presented in Table 2. The multivariate logistic regression model using mortality as the dependent variable showed that decreasing pH values (pH b 7.2 vs z 7.2; odds ratio [OR] 10.1; 95% confidence interval [CI], 2.37-42.5; P = .002) and increasing age (z 50 vs b50 years; OR, 5.59; 95% CI,

1.53-21.11; P = .009) had a significant positive independent association with mortality.

Next is the evaluation of the influence in the different patterns of acidosis among patients with acute OP poisoning; 50 patients were with acidosis, 8 patients had initial respiratory acidosis, 32 patients had metabolic acidosis, and 10 patients had mixed respiratory and metabolic acidosis. Table 3 summarizes the data based on age, GCS score, pH, AST, alanine aminotransferase (ALT), serum urea nitrogen, serum creatinine level, blood glucose, WBC count, and plasma cholinesterase level among patients with various acidosis. There were no statistically significant differences between those parameters, but a higher average age in patients of the respiratory acidosis group ( P = .001). Fig. 2 shows a comparison of the survival curve among patients with respiratory acidosis, metabolic acidosis, mixed respiratory and metabolic acido- sis, and without acidosis. The curve shows a statistically significant difference among those 4 groups ( P b .0001). Of the 32 patients without acidosis, the mortality rate was

Table 2 Logistic regression analysis of potential risk factors for mortality of acute OP poisoning
	P	OR	95% CI
			Lower	Upper
pH (b7.20 vs z7.20)	.002	10.1	2.37	42.59
Age (z50 vs b50 y) .009 5.69 1.53 21.11

Table 3 Demographic and laboratory characteristics of patients with acidosis
	Respiratory acidosis (n = 8)	Metabolic acidosis (n = 32)	Mixed acidosis (n = 10)	P
Age (y)	68.0 F 15.9	45.5 F 13.0	54.2 F 15.4	.001
GCS score	8.3 F 4.4	8.0 F 5.2	7.8 F 6.1	.984
pH	7.3 F 0.1	7.2 F 0.2	7.2 F 0.1	.190
AST (IU/L)	42.0 F 13.6	46.1 F 35.1	44.8 F 20.1	.942
ALT (IU/L)	28.3 F 6.6	33.9 F 6.1	23.2 F 12.0	.563
Serum urea nitrogen (mg/dL)	16.5 F 9.2	13.5 F 6.1	15.3 F 1.8	.416
Creatinine, mg/dL	1.03 F 0.24	1.08 F 0.34	1.20 F 0.29	.477
Blood glucose (mg/dL)	203.7 F 73.6	215.7 F 11.5	207.8 F 99.4	.951
WBC count (/ll)	15375 F 2135	16175 F 6873	13136 F 1662	.345
serum cholinesterase (U/L)	452.5 F 424.5	1334.1 F 2892.5	929.8 F 1213.7	.633

only 6.25% (2/32), and the cause of death was respiratory failure for the 2 death cases (Fig. 1). One thing deserves to be mentioned: the mortality rate was statistically higher in patients of the respiratory acidosis group (50%, 4/8) than in the metabolic acidosis group (25%, 8/32). Analysis and comparison of the cause of death between the respiratory acidosis and metabolic acidosis groups showed that the major cause of death was cardiovascular failure (18.75%, 6/32) for patients in the metabolic acidosis group, and only 6.25% (2/32) of patients died of respiratory failure in this group (Table 4). On the other hand, for patients in the respiratory acidosis group, causes of death were cardiovas- cular failure and respiratory failure (25%, 2/8 for both groups) (Fig. 1 and Table 4). Patients with mixed respiratory and metabolic acidosis had the highest mortality rate (80%, 8/10). Of the 10 patients with mixed respiratory and metabolic acidosis, 5 died of respiratory failure and 3 died of cardiovascular failure (Fig. 1).

Discussion

Patients with acute OP poisoning had a higher mortality rate because the OP had already exerted its effects before the patients’ arrival at the hospital. However, by that time,

physicians may have some clues to judge the outcome of patients with acute OP poisoning. Some studies have reported some potential risk factors of acute OP poisoning, including serum cholinesterase level [1,4], male sex [11,12], QT interval prolongation of ECG [13-15], hypox- emia, acidosis, and electrolyte derangement [16]. In this study, the average age was higher than that in other studies [1,2,9,10]; because Taiwan is an industrial nation, fewer Young people work in farms and the average age of farmers has become higher. Senior age was indeed a risk factor for acute OP poisoning in this study, which was probably related to the poorer health condition in those patients. It may be the major reason that leads to a relatively higher mortality rate in this study (26.8%) than in other studies [11,12]. On the other hand, there was no direct evidence on the relationships between mortality and plasma cholines- terase level, male sex, and electrolyte derangement when compared with other studies [1,4,11,12,16].

Probable risk factors included for analysis were mainly based on measurements of APACHE II score. Because some authors also reported that acute OP poisoning could induce hyperglycemia and abnormal serum AST and ALT levels [17-19], we also set those parameters for analysis in patients in our study.

Fig. 2 Overall survival (Kaplan-Meier curve) for patients with acute OP intoxication ( P b .0001).

Table 4 Cause of death in patients with OP poisoning
	Metabolic acidosis (n = 32)	Respiratory acidosis (n = 8)
Respiratory failure	2 (6.25)	2 (25)
Cardiovascular failure	6 (18.75)	2 (25)
Total mortality	8 (25)	4 (50)
Data are expressed as number (%).

Lee and Tai [20] have recently reported that APACHE II score may be used as an alternative index of severity in patients with OP poisoning. They found that the APACHE II score was correlated with the severity of OP poisoning and mortality. However, detailed description of APACHE II was not provided in that study. In our study, we found that several parameters such as age, GCS score, and arterial blood gas interpretation of APACHE II score were well correlated with the outcome in patients with acute OP poisoning.

There was considerable evidence for the decline in cholinergic indices (choline acetyltransferase, acetylcholin- esterase, and muscarinic acetylcholine receptors) with aging. A previous study showed that aged animals/humans were more sensitive to cholinergic agonists, although with reduced receptors [21]. The inhibition of cholinesterase activity leads to the accumulation of acetylcholine at synapses, which not only influences muscarinic and nicotic receptors but also overstimulates both central and Peripheral nervous systems. The neuropathy from OP poisoning induces a depressed level of consciousness and influences the GCS score in those patients. In addition, several causes of hemodynamic instability including arrhythmia and hypotension result in hypoperfusion of the central nervous system after acute OP poisoning. The impact of those factors is associated with poorer consciousness status and leads to the decrease in GCS score of these patients. Grmec et al [22] reported that a GCS score of 6 or less was found to be a useful guideline of in-hospital mortality (sensitivity, 70.2%; specificity, 87.3%) in OP poisoning. Our results were similar to theirs (data not shown).

Acidosis is a major predisposing factor that influences the outcome of patients with OP poisoning [16]. Few studies have compared the mortality rate among different patterns of acidosis in patients with acute OP poisoning. We found the acid-base interpretation to be well correlated with the severity of acute OP poisoning and mortality ( P b .0001; Fig. 2). Therefore, in addition to other known markers, the arterial blood gas interpretation (on arrival) may then be used as an alternative index to predict mortality in patients with acute OP poisoning managed in hospital.

Respiratory failure was the leading cause of mortality of patients with acute OP poisoning without the delay in discovery and transport [3]. As reported by an earlier study, respiratory failure with intubation and mechanical ventilation support was also a potential risk factor of mortality [6]. This study revealed that the mortality rate

was higher in the group with respiratory failure (44.4%, 16/36) than in the group without respiratory failure (13.0%, 6/46). Textbooks ascribe most deaths to respira- tory failure occurring in either of the 2 distinct clinical syndromes: acute cholinergic respiratory failure (type I syndrome) or the intermediate syndrome. Neurologic syndromes of OP poisoning contribute to those syndromes and lead to the main cause of respiratory failure in those patients. Interestingly, we found that in 36 of our patients developing respiratory failure, 23 developed type I respiratory failure and 13 had type II respiratory failure. Such results were beyond expectation because main Neurologic manifestations were contributed to type II respiratory pattern. This implied that some factors were still playing important roles in respiratory failure in addition to neuropathy in patients with acute OP poison- ing. Other complications of acute OP poisoning might play important roles other than solitarily Neurologic dysfunction of OP poisoning. Tsao et al [6] found that severity of poisoning, Cardiovascular collapse, and pneumonia were the Predisposing factors to respiratory failure. Those factors may contribute to type I respiratory failure rather than type II.

The mortality rate of patients with acute OP poisoning was lowest in the group of patients without acidosis and highest in the group with mixed acidosis. Of the patients studied, those with metabolic acidosis (39%, 32/82) were distributed more commonly than those with respiratory acidosis (9.7%, 8/82) (not including patients with mixed acidosis). Many authors [23,24] have reported that OP poisoning contributes to a variety of cardiac and ECG manifestations and may result in hypotension or hypoperfu- sion. Such results might be the main contribution that led to the metabolic acidosis in acute OP poisoning. The metabolic acidosis secondary to OP poisoning was easily corrected with sodium bicarbonate infusion, and in turn improved the protective effects of atropine and oxime therapy [9,25,26]. On the other hand, alkalinization of the blood with a higher pH with sodium bicarbonate treatment might increase the hydrolysis of the ester portion of the OP molecule, thus decreasing its toxicity, was also reported recently [26,27]. The main cause of mortality in the metabolic acidosis group was cardiovascular failure, and the mortality rate was relatively lower than that in the group with respiratory acidosis in the study, which implied that in patients with acute OP poisoning with initial metabolic acidosis presen- tation, the outcome was relatively better than that of the patients in the respiratory acidosis group. Ventilatory insufficiency clearly represented the most life-threatening element of the toxicity of acute OP poisoning before, but it was not the case in the patients with metabolic acidosis in our study. The relatively low mortality rate might be associated with the easy correction of the acid-base status after sodium bicarbonate infusion [25,27]. In addition, fewer life-threatening cardiac manifestations developed after the therapeutic alkalinization procedure.

There were several limitations in this study. First, severe underlying or coexisting diseases could not be well defined if patients’ chart records were insufficient or they were visiting the hospital for the first time. Second, previous ECG records might not be available if patients had visited other hospitals and the mortality pattern might be misplaced into the wrong group. Third, the study was retrospective in design.

In conclusion, acute OP poisoning is a highly fatal condition that requires quick and precise diagnosis and adequate support and treatment. Acid-base interpretation can be effective in quick diagnoses and in prediction of the outcome of patients with acute OP poisoning before hospital- ization. In addition, the real cause of mortality can be found in those patients if one can make painstaking investigations.

References

1. Goswamy R, Chaudhuri A, Mahashur AA. Study of respiratory failure in organophosphate and Carbamate poisoning. Heart Lung 1994;23:466 - 72.
2. Bardin PG, van-Eeden SF, Joubert JR. Intensive care management of acute organophosphate poisoning. A 7-year experience in the western Cape. S Afr Med J 1987;72:593 - 7.
3. Yamashita M, Yamashita M, Tanaka J, et al. Human mortality in organophosphate poisonings. Vet Hum Toxicol 1997;39:84 - 5.
4. Ram JS, Kumar SS, Jayarajan A, et al. Continuous infusion of high doses of atropine in the management of organophosphorus compound poisoning. J Assoc Physicians India 1991;39:190 - 3.
5. Satoh T, Hosokawa M. Organophosphates and their impact on the global environment. Neurotoxicity 2000;21:223-7.
6. Tsao TC, Juang YC, Lan RS, et al. Respiratory failure of acute organophosphate and carbamate poisoning. Chest 1990;98:631 - 6.
7. Rivera JA, Rivera M. Organophosphate poisoning. Bol Asoc Med P R

1990;82:419 - 22.

1. Buckley NA, Karalliedde L, Dawson A, et al. Where is the evidence for the management of pesticide poisoning-is clinical toxicology fiddling while the developing world burns. J Toxicol Clin Toxicol 2004;42:113 - 6.
2. Cordoba D, Cadavid S, Angulo D, et al. Organophosphate poisoning: modifications in acid-base equilibrium and use of sodium bicarbonate as an aid in the treatment of toxicity in dogs. Vet Hum Toxicol 1983;25:1 - 3.
3. Marino PL. Acid-base interpretations. In: Marino PL Editor. The ICU book, 2nd ed. New York7 William & Wilkins, 1998. p. 581 - 91.
4. Emerson GM, Gray NM, Jelinek GA, et al. Organophosphate poisoning in Perth, Western Australia, 1987-1996. J Emerg Med 1999;17:273 - 7.
5. Khan MM, Reza H. The pattern of suicide in Pakistan. Crisis 2000;21:31 - 5.
6. Ludomirsky A, Klein HO, Sarelli P, et al. Q-T prolongation and polymorphous (bTorsade de pointesQ) ventricular arrhythmias associ- ated with organophosphorus Insecticide poisoning. Am J Cardiol 1982;49:1654 - 88.
7. Jang SW, Lin JL, Chuang FR. electrocardiographic findings of organophosphate intoxication in emergency department as predictors of prognosis: a retrospective analysis. Changgeng-YiXue-Za-Zhi 1995;18:120 - 5.
8. Chuang FR, Jang SW, Lin JL, et al. QTc prolongation indicates a poor prognosis in patients with organophosphate poisoning. Am J Emerg Med 1996;14:451 - 3.
9. Saadeh AM, Farsakh NA, al-Aki MK. Cardiac manifestations of acute carbamate and organophosphate poisoning. Heart 1997; 77:461 - 4.
10. Mack R. Toxic encounters of the dangerous kind. N C Med J 1983;44:

103 - 5.

1. Kamal AA, Elgarhy MT, Maklady F, et al. Serum choline esterase and liver function among a group of organophosphorus pesticides sprayers in Egypt. J Toxicol Clin Exp 1990;10:427 - 35.
2. Sungur M, Guven M. Intensive care management of organophosphate insecticide poisoning. Crit Care 2001;5:211 - 5.
3. Lee P, Tai DY. Clinical features of patients with acute organophos- phate poisoning requiring intensive care. Intensive Care Med 2001;27:694 - 9.
4. Overstreet DH. Organophosphate pesticides, cholinergic function and cognitive performance in advanced age. Neurotoxicology 2000; 21:75 - 81.
5. Grmec S, Mally S, Klemen P. Glasgow Coma Scale score and QTc interval in the prognosis of organophosphate poisoning. Acad Emerg Med 2004;11:925 - 30.
6. Karki P, Ansari JA, Bhandary S, et al. Cardiac and electrocardio- graphical manifestations of acute organophosphate poisoning. Singa- pore Med J 2004;45:385 - 9.
7. Wang MH, Tseng CD, Bair SY. Q-T interval prolongation and pleomorphic ventricular tachyarrhythmia (dtorsade de pointesT) in organophosphate poisoning: report of a case. Hum Exp Toxicol 1998;17:587 - 90.
8. Setlur R, Sharma RM. Severe metabolic acidosis secondary to organophosphate poisoning. [letter]Anesth Analg 2005;101:1894.
9. Stefanovic D, Antonijevic B, Bokonjic D, et al. Effect of sodium bicarbonate in rats acutely poisoned with dichlorvos. Basic Clin Pharmacol Toxicol 2006;98:173 - 80.
10. Balali-Mood M, Ayati MH, Ali-Akbarian H. Effects of high doses of sodium bicarbonate in acute organophosphate pesticide poisoning. Clin Toxicol 2005;43:571 - 4.