|Year : 2014 | Volume
| Issue : 3 | Page : 87-90
Open-label randomized controlled study comparing continuous infusion versus intermittent bolus dose of atropine with or without pralidoxime in the treatment of organophosphorus poisoning in a teaching hospital
RC Kumaraswamy1, KM Sudha Madhavi2, SP Basavanthappa3, MR Nagendra Gowda4
1 Department of Internal Medicine, Basaveshwara Medical College and Research Center, Chitradurga, Karnataka, India
2 Department of Ophthalmology, Basaveshwara Medical College and Research Center, Chitradurga, Karnataka, India
3 Department of Pediatrics, Basaveshwara Medical College and Research Center, Chitradurga, Karnataka, India
4 Department of Community Medicine, Basaveshwara Medical College and Research Center, Chitradurga, Karnataka, India
|Date of Web Publication||6-Sep-2014|
R C Kumaraswamy
Department of Internal Medicine, Basaveshwara Medical College Hospital and Research Center, NH 4 By Pass, Near Housing Board Colony, Chitradurga 577 501, Karnataka
Background: Severe organophosphorus (OPC) poisoning is one of the serious problems in developing world, taking great toll on life. Though Atropine is used as an antidote, there are no clear guidelines. We conducted an open label randomized controlled clinical study to compare the efficacy of continuous infusion of atropine to that of intermittent bolus dose in the treatment of OPC poisoning. Methods and Material: Patients aged above 12 years with clinical evidence of OPC poisoning were studied. Both the groups received initial bolus of 1to3 mg of atropine. Then, Group-A received intermittent bolus and group-B, continuous infusion, until adequately atropinized. Results: Out of 743 patients (group-A: 356 and group-B: 387), females were 54%. 83% had suicidal intent. Mean atropine dose was 126.6mg in group-A and 78mg in group-B (P < 0.0001) . 21.07% (group-A) and 12.92% (group-B) developed intermediate syndrome (P = 0.003) , mortality was 27.25%(97) in group-A v/s 13%(50) in group-B (P < 0.0001) . Ventilator support needed in 36%(group-A) against 17% in group-B (P < 0.0001) and duration of ventilation was 1.5 days lesser in group B (P < 0.0001) . 23.03% had atropine toxicity in group-A as compared to 8% in group-B (P < 0.0001) . Hospital stay was 1.67 (P < 0.0001) days shorter for group-B. Conclusion: Continuous atropine infusion should be standard of care in treating OPC poisoning.
Keywords: Atropine, continuous versus intermittent, organophosphorus, poisoning
|How to cite this article:|
Kumaraswamy R C, Sudha Madhavi K M, Basavanthappa S P, Nagendra Gowda M R. Open-label randomized controlled study comparing continuous infusion versus intermittent bolus dose of atropine with or without pralidoxime in the treatment of organophosphorus poisoning in a teaching hospital. Sahel Med J 2014;17:87-90
|How to cite this URL:|
Kumaraswamy R C, Sudha Madhavi K M, Basavanthappa S P, Nagendra Gowda M R. Open-label randomized controlled study comparing continuous infusion versus intermittent bolus dose of atropine with or without pralidoxime in the treatment of organophosphorus poisoning in a teaching hospital. Sahel Med J [serial online] 2014 [cited 2021 Jul 31];17:87-90. Available from: https://www.smjonline.org/text.asp?2014/17/3/87/140287
| Introduction|| |
Severe organophosphorus (OPC) poisoning is a serious and life-threatening medical problem,  accounting for the major proportion of cases of self-poisoning,  with a mortality rate of nearly 30%.  Though OPC poisoning is common,  there is no sufficient scientific data on its management guideline, especially in the developing world, where there are scares resources and high burden of OPC poisoning. 
Although there are several antimuscarinic agents used in the management of OPC poisoning, atropine is the most universally used specific antidote.  There are more than 30 different protocols on atropinization with varying rates of success,  but none has been tested in a large scale randomized controlled trial. A recent study from Bangladesh  quoted that incremental bolus followed by continuous infusion is superior to intermittent atropine bolus in the management of OPC poison.
We determined the efficacy and outcome of intermittent bolus atropine therapy and continuous infusion in the management of OPC poisoning.
| Materials and methods|| |
This was an open-label nonblinded randomized controlled study conducted during the period from March 2009 to August 2012 at a tertiary care, teaching hospital. Clearance was obtained from the Institutional Ethical Committee.
Patients aged above 12 years, who were brought with a clear history of OPC poisoning and clinical evidence of cholinergic effects, were included in the study. In all cases, attempts are made to retrieve the poison container. Patients with comorbidities including pregnancy, chronic obstructive and restrictive lung disease, and ischemic heart disease and chest deformities were excluded from the study.
At the time of admission, all patients who were eligible for inclusion were consecutively and systematically allocated to either Group A, or B by our study statistician who had no role in treatment decision makings. Demographic data such as age domicile, marital status, level of education, and clinical findings at admission were recorded on a data sheet specially designed for this study.
Gastric lavage was given to all who consumed the OPC and body wash was given to all the patients irrespective of the mode of exposure and duration since exposure.
Initial bolus dose of 1-3 mg of atropine was given to patients in both groups. Subsequently, conventional intermittent atropine bolus dosage, which consisted of 2-3 mg of atropine bolus every 10 min, was instituted to Group A patients. Group B patients were started on continuous infusion of atropine at 1 mg/min in patients below 50 kg weight and 1.5 mg/min for those who were above 50 kg, until target end point [Table 1]  is achieved. Subsequently, they were put on maintenance infusion of 1-2 mg/h and titrated up or down depending on the level of atropinization. Both groups were regularly assessed for vital signs, fasciculations, respiratory efforts, need for mechanical ventilation, and atropine toxicity.
Prolidoxime was used only in those patients who had fasciculations, in the dose of 0.5-1 g intravenous infusion over 30 min every sixth hourly until the disappearance of fasciculations.
Data were analyzed using PASW statistics 18 by SPSS Inc, software. Continuous data were recorded as mean ± standard deviation. Independent sample t-test and Chi-square test were used to compare the quantitative and qualitative variables, respectively. P <<i> 0.05 was considered to be statistically significant.
| Results|| |
During the study period of 30 months, 743 patients with OPC poisoning who attended to the emergency department were qualified for the inclusion. 356 (47.9%) patients were in Group A and 387 (52.9%) in Group B.
[Table 2] shows that there were no significant differences in the demographic and baseline clinical data between the groups at admission. Females dominated the study group. Majority of the patients were in their thirties and were married. Oral consumption with suicidal intent was the most common mode of exposure. Major proportion of patients in this study hailed from a rural background.
There were statistically significant differences between the groups in the amount of atropine needed to treat; time taken for atropinization, atropine toxicity and the physical or pharmacological restraining needed to keep the patient calm. The details are summarized in [Table 3] compared to Group B, A patients took an average 5 more hours to be atropinized, they required 48.7 more mg of atropine, and developed 15% more atropine toxicity requiring some form of restraint in 14% more patients.
It was observed that Group A patients had wider heart rate excursions; as low as 48 beats before atropine bolus to as high as 156 beats immediately after atropine bolus as compared with relatively narrow heart rate range from 66 to 117 beats in Group B.
[Table 4] summarizes the observations and outcomes in the study. Continuous atropine infusion significantly lowered the need for ventilation. In those patients who were ventilated, they were ventilated by an average 1.5 days lesser in Group B as compared to Group A. Patients in Group B stayed an average 1.6 days shorter in the hospital than Group A. It is also evident from the study that 8% fewer patients developed intermediate syndrome in Group B than Group A. There was statistically significant reductions in mortality in Group B compared to Group A. However, there was no difference in the rate of convulsions between the groups.
| Discussion|| |
Organophosphorus compounds have become cheap, easily accessible weapon for suicide or suicidal attempt. In most developing countries, these compounds are unrestricted and widely available. ,
Mortality in patients with OPC poisoning in the early stage of the disease is due to cholinergic overstimulation resulting in centrally mediated respiratory depression, cardiovascular collapse and profuse oropharyngeal and respiratory secretions and bronchospasm.  In later stages, it is due to respiratory failure, cardiac arrest, hypotension, and complications of ventilation such as pneumonia, septicemia, and renal failure. Mortality rate varied greatly in different studies  ranging from 1.85% to 40%, respectively. In this study, it was 27.24% in bolus atropine treated group and 13% in continuous atropine infusion treated group demonstrating a statistically significant reduction in mortality in continuous infusion group. Similar observations have been made in previous two related studies. ,
Consumption of OPC compound with suicidal intent was the most common reason for OPC exposure and related admissions across the globe. ,,,, In the present study, 83% of the patients attempted suicide with OPC. This can be partly prevented by bringing in the stringent laws to govern OPC marketing.
In this study, 54% of the victims were females, they dominated the study group and 84% of them were from a rural background. Similar rates were reported in two studies, , which was in contrast to male dominance in most of the previous studies. ,
Atropine is the only proven drug available to treat the OPC poisoning. Several treatment protocols have been proposed by different authors.  It is clear from our study that continuous atropine infusion is superior to atropine bolus injection. We observed that continuous infusion required lesser time to atropinize with relatively smaller dose of atropine. Hence, there were fewer atropine toxicity and reduced duration of hospital stay, and morbidity in this group. This is similar to observed outcomes reported in two previous studies. ,
Excessive stimulation of peripheral nicotinic receptor is associated with fasciculations and if the stimulation persists it may result in depolarizing type of muscle paralysis, which can end up with respiratory failure, requiring assisted ventilation. Patients can often develop sudden respiratory failure with intact consciousness. This is part of intermediate syndrome and may result in death if not appropriately managed. , A recent study by Abedin et al.  showed that continuous atropine infusion significantly reduced the need for mechanical ventilation, duration of ventilation, incidence of intermediate syndrome, and duration of hospital stay when compared with conventional atropine treated patients. This finding is in concordance with the observations made in the present study.
| Conclusions|| |
It is concluded that continuous atropine infusion is safer and associated with a better outcome compared to intermittent regimen in the management of OPC poisoning. One limitation of this study was that we did not control for exposure to different OPC, which may affect their toxicity and outcome.
| References|| |
|1.||Jeyaratnam J. Acute pesticide poisoning: A major global health problem. World Health Stat Q 1990;43:139-44. |
|2.||World Health Organization. World Health Report 2002. Reducing Risks, Promoting Healthy Life. Geneva: World Health Organization; 2002. |
|3.||Eddleston M. Patterns and problems of deliberate self-poisoning in the developing world. QJM 2000;93:715-31. |
|4.||Eddleston M, Phillips MR. Self poisoning with pesticides. BMJ 2004;328:42-4. |
|5.||Johnson MK, Jacobsen D, Meredith TJ. Evaluation of antidotes for poisoning by organophosphorus pesticides. Emerg Med 2000;12:22-37. |
|6.||Eddleston M, Buckley NA, Checketts H, Senarathna L, Mohamed F, Sheriff MH, et al. Speed of initial atropinisation in significant organophosphorus pesticide poisoning - A systematic comparison of recommended regimens. J Toxicol Clin Toxicol 2004;42:865-75. |
|7.||Abedin MJ, Sayeed AA, Basher A, Maude RJ, Hoque G, Faiz MA. Open-label randomized clinical trial of atropine bolus injection versus incremental boluses plus infusion for organophosphate poisoning in Bangladesh. J Med Toxicol 2012;8:108-17. |
|8.||Bardin PG, van Eeden SF, Moolman JA, Foden AP, Joubert JR. Organophosphate and carbamate poisoning. Arch Intern Med 1994;154:1433-41. |
|9.||Hayes MM, van der Westhuizen NG, Gelfand M. Organophosphate poisoning in Rhodesia. A study of the clinical features and management of 105 patients. S Afr Med J 1978;54:230-4. |
|10.||Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet 2008;371:597-607. |
|11.||Ram JS, Kumar SS, Jayarajan A, Kuppuswamy G. Continuous infusion of high doses of atropine in the management of organophosphorus compound poisoning. J Assoc Physicians India 1991;39:190-3. |
|12.||Dash SK, Mohanty MK, Patnaik KK, Mohanty S. The sociodemographic profile of the poisoning cases. J Indian Acad Forensic Med 2005;3:133-8. |
|13.||Siwach SB, Gupta A. The profile of acute poisonings in Harayana-Rohtak Study. J Assoc Physicians India 1995;43:756-9. |
|14.||Gnyp L, Lewandowska-Stanek H. The analysis of organophosphates poisoning cases treated at the centre for acute poisonings in Lublin provincial hospital in 1994-1996. Przegl Lek 1997;54:734-6. |
|15.||Emerson GM, Gray NM, Jelinek GA, Mountain D, Mead HJ. Organophosphate poisoning in Perth, Western Australia, 1987-1996. J Emerg Med 1999;17:273-7. |
|16.||Sahin HA, Sahin I, Arabaci F. Sociodemographic factors in organophosphate poisonings: A prospective study. Hum Exp Toxicol 2003;22:349-53. |
|17.||Kora SA, Doddamani GB, Halagali GR, Vijayamahantesh SN, Umakanth B. Sociodemographic profile of the organophosphorus poisoning cases in Southern India. J Clin Diagn Res 2011;5:953-6. |
|18.||Wadia RS, Sadagopan C, Amin RB, Sardesai HV. Neurological manifestations of organophosphorous insecticide poisoning. J Neurol Neurosurg Psychiatry 1974;37:841-7. |
|19.||Senanayake N, Karalliedde L. Neurotoxic effects of organophosphorus insecticides. An intermediate syndrome. N Engl J Med 1987;316:761-3. |
[Table 1], [Table 2], [Table 3], [Table 4]