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|Year : 2003 | Volume
| Issue : 2 | Page : 85-87
Treatment of Organophosphate Poisoning
Ruby Hall Clinic, Pune
Ruby Hall Clinic, Pune
|How to cite this article:|
Wadia R S. Treatment of Organophosphate Poisoning. Indian J Crit Care Med 2003;7:85-7
Organophosphate poisoning continues to be one of the most important problems of self-poisoning presenting in the ICU. Since first described as a problem in India over 40 years ago, the problem has continued and clearly increased with India and Sri Lanka being the countries with the highest number of cases. Epidemiological studies in Sri Lanka estimate that in 1995 there were 15730 cases with 1571 deaths from pesticide poisoning and it was the 6th commonest cause of hospital death in Sri Lanka. The WHO estimates that the yearly death number is around 50,000. In India or even Maharashtra, clear figures are not available but the yearly incidence of cases is in the order of 500 at the Sassoon General Hospital, Pune.
What is the present day management of these cases? The initial steps are clear. As the poison can be absorbed from the intact skin, it is necessary to remove any soiled clothing and wash the skin if there is evidence of contamination. A stomach wash is required and this may profitably be repeated after 2-3 hours as the drug is secreted back in the stomach, and to remove any residue not fully removed. As organophosphate phosphorylates the esteratic site of the enzyme Cholinesterase (ACHE), it is unable to hydrolyze Acetylcholine. This accumulates at receptors & produces muscarinic and nicotinic signs. Muscarinic signs such as meiosis, diarrhea, vomiting, sweating, bronchial secretions are usually first to appear, and are treated with atropine. Nicotinic signs usually appear later, and do not respond to atropine. Though large dose of atropine are given in some units, 3-10 mg may be the loading dose, depending on severity. Once atropinized, a maintenance type dose at 1-3 mg 1/2 hourly is usually sufficient. Atropinization is assessed by a combination of signs including pupils, pulse rate, pulmonary secretions and mental state. It is not desirable to use any one criterion alone, because cases are seen where the pupils do not dilate or pulse does not become fast inspite of adequate doses. The use of atropine also tends to cause depressed reflexes to reappear as the internuncial neurons in the cord are also muscarinic. Instead of atropine, glycopyrrolate may be used in similar doses. Glycopyrrolate does not enter the brain and so will not cause toxic delirium, and does not dry up secretions as much as atropine. However as it does not enter the brain, initial central muscarinic signs like coma or drowsiness will not respond, and I would think initial treatment should be with atropine and glycopyrrolate should be used later.
The next unclear issue is about Oximes such as P2AM. P2AM is generally given in most intensive care units in India, at a dose of 1 gm 4 to 6 hourly. Oximes displace the organophosphates from the acetylchoine esterases and bind to the enzyme itself. Later it disassociates and ACHE is reactivated. After animal studies, Johnson et al believe that the effective dose is one which causes a blood level of 4 ng/ml. This could be achieved in an adult human by a dose of approximately 12 gms per day.
P2AM is not effective after the combination of pesticides and ACHE has aged, and therefore is best given in the first 36 - 48 hrs. Later it is usually ineffective though some effect may be noted in later doses. Some units have used P2AM by infusion, 1 gm over 8 hrs. This would be an error as the first gram would only be completed after 8 hrs, and the second dose 16 hours after admission. Bolus doses would complete 2 gm in 4 hours.
The problem with oximes is that its use has not been validated in humans in a controlled clinical trial. Cherian et al reported one such trial and found that the drug showed no benefit. Recently a careful survey in fact found only 6 controlled clinical trials of P2AM6 with best medical care, 5 of these used either historic controls or were not double blind, and only one trial was apparently methodically correct. However in that trial the 2 groups ( control and with P2AM) were not comparable. The mean CHE in the control group was 743.7 + 1254, and that in the P2AM group was 283 + 243. The number of cases with CHE less than 50% was 50% in the control group, and 66% in the oximes group. The large standard deviation of CHE levels in the control group also suggests that several cases had CHE levels of 2000 and above. The mortality in the control group was 5.4%, which was much less than in any of the other 5 trials in the meta - analysis. The second lowest mortality in the control group was 9% and others were much higher. In the study by Cherian et al, the oximes group had many more cases requiring mechanical ventilation, and had a mortality of 29%. Cherian et al interpreted the greater need for use of mechanical ventilation as evidence of failed effect of P2AM, but that would depend on when the ventilator was required, and may also show that the oximes group had more seriously ill cases requiring ventilation in the first place.
Strangely, the oximes group mortality in that series was in fact 29.1%. We have been treating organophosphate cases for years before P2AM was available, and our mortality has hovered between 8-13%.
It cannot be argued that the authors group got only critically ill cases because the control group mortality was in fact only 5.4%. In view of all this, I interpret that the 2 groups were unequal by chance. Thus the conclusion that oximes increases mortality is not valid. I accept however that apparently no one has proved the value of oximes in humans, though the idea is sound and animal experiments suggest it is useful.
Perhaps the most useful advance in the management of organophosphate poisoning, is the advances in ventilator therapy. I remember well the time when the need for a ventilator in organophosphate poisoning (or Guillain Barre Syndrome) meant an extremely high chance of death (well over 50%) This of course was due to the technological inferiority of the older machines and the absence of trained manpower. One cannot neglect the aspect of manpower. The Copenhagen polio epidemic when scores of patients were treated by manual mechanical ventilation done by medical students and nurses is history. I have seen a relation of a medico treated in Sassoon Hospital by mechanical ventilation by an Ambu bag for over 3 weeks in Guillain Barre Syndrome and survive. We have come a long way from that era & the advances in ventilation have undoubtedly played a major role in the treatment. When would one use a ventilator? Perhaps the indication is subjective but it is well accepted that as in Guillain Barre syndrome, the ventilator would be required if the vital capacity is reduced to less than 15 m l/ kg (tidal volume less than 5ml/kg), or if there was paradoxical breathing. One clearly cannot use the criteria of unexplained tachycardia, or sweating as an indication for ventilation in organophosphate poisoning because the poison and atropine would nullify that. A fall in respiratory rate to less than 12, or a tachypnoea of more than 36/ mm, would also be an indication. Blood gas changes are late to appear in respiratory paralysis but paO2 < 60 or a paCO2 > 45, would be an indication. These indications would also be influenced by the time when they were noted and the time when the drug was ingested and the type of compound. Thus tachypnoea or low paO2 noted on admission in a case of a Carbamate poisoning may not be an indication, because administration of atropine would rapidly reduce the pulmonary oedema and obviate the need for mechanical ventilation, especially because Carbamates are very short acting in any case.
What is the mortality of organophosphate in the ventilator era? The Ruby Hall / Sassoon hospital data is surprising. In our first 25 cases in 1962, our mortality was 8%. When we reported 350 cases in 1975-80 the mortality was 9% and when we reviewed our data in 1994-99 in Ruby Hall ITU, mortality was in fact 11-12% (2 different series of 100-120 cases each.) These last 3 series are all P2AM treated and thus my surprise at the 29.1% mortality reported by Cherian et al. The Sri Lanka figures quoted at start of this article, give a mortality of 10% in a community. It is not that the ITU series only includes serious cases, because all organophosphate admissions at Ruby Hall Clinic now go to the ITU. One of the factors influencing mortality in organophosphates poisoning is the organophosphate used. In 1960-80 the organophosphates available in India were limited and we were able to show convincingly that Fenthion is clearly more lethal than Sumithion and Malathion. Now a whole host of organophosphates are available and some are clearly more toxic. Another interesting factor is that when we first described organophosphate suicidal poisoning, the pesticide was available as a 20% solution. Later the government decided that the pesticide would be sold only as a 2% solution and serious poisoning cases disappeared. Now formulations of 50 % - 70 % solution are marketed for agriculture, presumably to save storage space. Ingestion of these is more serious. There is a further reason why the mortality has not fallen. Nowadays ITU physicians are quick to start ventilators. Death due to Carbamates like Baygon were not seen in the past. Baygon is a carbamate, which depresses CHE and causes severe muscarinic signs and pulmonary oedema. However if atropine is given in large doses, the oedema clears and the patient is well in 6-8 hours. If a patient is put on a ventilator and infection supervenes, (which is not unusual), things could become worse. We have seen more than a couple of deaths after 7-14 days on mechanical ventilation in such cases. The ventilator is of course life saving, but inappropriate use could cause complications which are potentially lethal.
How do we reduce mortality of Pesticide poisoning? The vast majority of the 50,000 mortality reported by WHO (220,000 if all pesticides are included) is in the developing world where proper safeguards and resources for their safe use are not available. Thus WHO and Eddleston et al urge the restriction of use of pesticides. WHO classes these as class I (extremely toxic) to class III (slightly hazardous).They urge ban or major restriction of use of class 1 pesticides and reduction of pesticide use to a minimal number of less hazardous compounds. In 1981 Jordan banned Parathion use and the poisoning autopsies in Amman fell from 50 a year in 1981, to below 10 in 1983 to 85. In Samoa, the same finding occurred after banning Paraquat. In India no such ban seems in the pipeline and surely Aluminium phosphide would be the most deserving candidate to be considered for being banned. It's mortality rate in those reaching hospital is 50-70% the deaths each year exceeding those due the Bhopal gas tragedy by a good margin. In a recent report, Aluminium phosphide poisoning was responsible for 80% of all autopsies in poisoning in Chandigarh between 1992-97.
So how can we lower the mortality of pesticide poisoning? What we do in the hospital I.T.U's, seems minor. We as a collective body, should strive for a ban on the hazardous forms and restriction on use of a number of pesticides. In our country banning Aluminium phosphide and high concentration formulations should be the first goal, and then we could proceed further.
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