(1)Associate.Professor., Department of Pharmacology & Toxicology.
(2)Asst. Professor, Department of Pharmacology & Toxicology
(3)Associate Professor., Department of Forensic Medicine.
(4)Associate Professor, Deptt. Of Pharmacology & Toxicology
S.G.R.D.Inst. Of Med. Sc. & Research, Mehta Road, Amritsar.
Suicidal or homicidal poisoning with drugs overdosage is one of the common causes of morbidity and mortality in India. Patients generally presents with varying degree of signs and symptoms in emergency. On arrival of the patient assessment of the danger should be done followed by common procedures like gut decontamination using activated charcoal, maintenance of fluid balance and airway control. Gastric levage is an important procedure especially if done with in 60 minutes of poisoning but due consideration must be given to contraindication. In India generally two types of poisoning is seen as agriculture based and with pharmacological agents i.e. drugs. India is an agriculture-based country with over usage of pesticides. In emergency two types of pesticide poisoning is common as with organophosphates and with aluminium phosphide. The mortality rates are much lower if early treatment is started in both the case. Over dose with opioids is another important cause of mortality especially in addicts. The other poisons encountered are with paracetamol, aspirin, chloroquine, alcohol, theophylline and iron. The specific management with antidotes generally reverses the symptoms of poisoning saving the patients life.
Acute poisoning is a common problem worldwide. In the United Kingdom (UK) it accounts for an estimated 10- 20% of acute medical admissions and 5-10% of the workload of Accident and Emergency (A&E) departments. Episodes of self-poisoning continue to rise, with the rates being the highest in Europe1. The severity of poisoning has decreased over the past decade with the introduction of safer drugs, such as the selective serotonin reuptake inhibitors. However, in India the exact incidence cannot be defined as there is under reporting of cases of poisoning. Infact, there is no check on sale of poison and any body can purchase it over the counter. This paper will address common pitfalls in the management of poisoned patients where clinical management could be improved and medico legal problems can be avoided.
It is generally divided in two parts as
1) General Management
It is the most important aspect of the management of poisoned patients2. The majority of patients who present with self-poisoning develop minimal or no clinical effects, and therefore the aim is to identify as early as possible the patients who will proceed to develop significant clinical features and complications. As a general rule, complete elimination of a drug takes approximately the duration of five half-lives of the drug and so the patient needs to be supported during this phase with monitoring for and treatment of any secondary organ dysfunction or other features that develop
2. The initial management of the patient should be on the basis of (ABCD’s) of the poisoning treatment.
This means removing toxins from skin or GIT.
1. Skin: Remove contaminated clothes and wash the skin with soap and water.
2.GIT: There is controversy regarding efficacy of gut emptying by emesis or gastric levage after one hour of poisoning. The various methods employed are
3.Emesis: Emetic agents like ipecac syrup are sometimes used to treat childhood ingestion at home. The contraindications are corrosive poison, petroleum products and rapidly acting convulsants.
4.Gastric levage: this is done in awake or intubated patients with large sized nasogastric tube with N saline preferably.
It is also called universal antidote as its large surface adsorbs many drugs. The mainstay of gut decontamination is the administration of activated charcoal within one hour of a significant ingestion of a toxin that binds to charcoal3. It is given in the ratio of 10:1 to charcoal: dose of toxin by weigh. However, it don’t bind iron, lithium, K+ and poorly to cyanide and alcohol. Multiple-dose activated charcoal (MDAC) increases the elimination of some drugs by interrupting their enteroenteric and entero-hepatic circulation. The dose given is 50 G (1 G/kg in children) of activated charcoal every four hours4. Indications for MDAC are carbamazepine, dapsone, phenobarbitone, quinine and theophylline poisoning. In addition to these indications, MDAC should be considered seriously in salicylate poisoning (to prevent delayed absorption) until the salicylate level peaks. Gastric levage is much less widely used now. Although there have been descriptive case reports of removal of tablet debris using gastric levage, no clinical studies have demonstrated that this has any impact on outcome. There is also the possibility that levage may increase absorption by pushing the tablets into the small intestine5. It can also result in hypoxia and tacycardia. Gastric levage should therefore only be considered if it can be carried out within one hour of a life-threatening ingestion and the patient should be monitored closely during the procedure.
WBI with Polyethylene glycol is a newer method of gut decontamination. There are published reports describing the use of WBI in poisoning with a number of substances including iron, lithium, latex packets of cocaine in bodypackers, lead and sustained-release preparations including verapamil. Whole bowel irrigation is generally well tolerated, and polyethylene glycol is not absorbed and does not result in significant changes in fluid or electrolyte balance. The dosage of polyethylene glycol used for WBI is 1,500-2,000 ml/hr for adults, 1,000 ml/hr for children of six to twelve years and 500 ml/hr for children six months to six years of age; it should be continued until the rectal effluent is clear. It can be given orally or via a nasogastric tube. Indications for WBI are:
Large ingestions of agents not adsorbed to activated charcoal. e.g. lithium. Iron, large ingestions of sustained release or enteric-coated drugs e.g. calcium channel blockers. Contraindications to WBI are Bowel obstruction or ileus, significant gastrointestinal hemorrhage, hemodynamic instability.
This is a commonly used drug in management of acidosis due to poisoning with methanol, ethylene glycol, cyanide and salicylates and for urinary alkalinisation to enhance elimination of salicylate (and less commonly for phenobarbitone, chlorpropamide and some pesticides) or prevent renal deposition of myoglobin after severe rhabdomyolysis, cardiotoxicity caused by tricyclic antidepressants, flecanide, quinidine, chloroquine, dextropropoxyphene, procainamide, disopyramide, phenothiazines.
In clinical practice basically two types of poisoning is commonly encountered as
India is an agriculture-based country with over usage of pesticides. In emergency two types of pesticide poisoning is common as
1. Organophosphorus Compounds (OPC). These include DDT, parathion, malathion, diazenon and highly toxic nerve7 gas poison like tabun, serine and soman.
Clinical Features: These can be as
2. CNS: In low concentration there can be diffuse activation of EEG and subjective altering response. In high concentration there is tremors, generalized convulsion followed by coma and respiratory arrest.
3. Eye, GIT, Respiratory and Urinary system: There can be miosis, hypotension, bradycardia, bronchospasm, voiding of urine, marked salivation and diarrhea.
Diagnosis: RBC and serum cholinesterase decrease by3 50% due to binding by phosphate group of pesticides. RBC cholinesterase reflect a better index than serum cholinesterase as latter is decreased in other diseases like liver diseases (hepatitis, cirrhosis, ascites, obstructive jaundice and metastatic carcinoma), congestive heart failure and congenital disorders. An experimental method11 using frog rectus preparation has been suggested by the author and colleague. This is relatively cheap, easy to perform and convenient technique but requires technical skill.
Treatment:8,9: Apart from general support the treatment is atropine and pralidoxime. Atropine in dosage of 2 mg IV slowly repeated at every 5 to 15 minutes until signs of reversal (dry mouth, mydriasis) are seen. There is no theoretical limit to its dosage as more than 1 gm/ day can be given for 1 month for full control of muscarinic excess. Pralidoxime a cholinesterase reactivator is also used. It is given as infusion as 1-2 gm over 15-30 minutes. Contraindications to use are Carbamates poisoning (propoxur/baygon/carbaryl and sevin). Treatment with pralidoxime should be started early (within 24 hours) to avoid phophorylation of cholinesterase enzyme.
Aluminium Phosphide is widely used fumigant and preservative of wheat and grains due to high potency, cheap and easy storage. Due to these factors it has become a common suicidal poison.
Mechanism of action: When taken orally it reacts with acidic media (HCL) of stomach and releases Phosphine (PH3) gas, which is rapidly absorbed from gastro-intestinal tract by simple diffusion in body system and also lungs by inhalation. After absorption it is metabolized in liver where more of PH3 is released accenting for prolonged action of PH3. The absorbed PH3 is oxidized to oxyacids and is excreted in the form of hypophosphite in the urine and a significant amount is also excreted through lungs. PH3 is a protoplasmic poison interfering with enzymes and protein synthesis esp. that of cardiovascular and respiratory systems. The ultimate result is peripheral vascular collapse, cardiac arrest and failure, and pulmonary edema. In animal studies PH3 has been shown to cause non-competitive inhibition of cytochrome oxidase of myocardial mitochondria.
Signs and symptoms: Symptoms are generally related to the cardiovascular and pulmonary systems. These include restlessness, irritability, drowsiness, tremors, paresthesia, vertigo, diplopia, ataxia, cough, dyspnoea, retrosternal discomfort, abdominal pain and vomiting. Signs are many like various stage of cardiovascular collapse as hypotension, reduction in cardiac output, tachycardia, oliguria, anuria, cyanosis, pulmonary edema, tacypnoea, jaundice, hepatosplenomegaly, ileus, seizures and diminished reflexes. Electrocardiographic finding includes ST elevation or depression, T wave inversion, sinus tachycardia, atrial fibrillation and infarction and atrioventricular conduction problems esp. right bundle branch block, and complete atrioventricular dissociation. The myocardial damage is reversible as ECG returns to normal in 10 to 25 days if patient survives. X ray chest reveals pulmonary edema. Lab finding reveals abnormalities in myocardial and liver enzymes. Blood urea nitrogen and creatinine levels are usually raised. Significant hypomagnesaemia and hypermagnesemia have been reported in patients with massive myocardial necrosis. Blood gas abnormalities demonstrate combined respiratory and metabolic acidosis.
Treatment: initially remove clothing and wash the skin. The next management includes oxygen, intravenous fluids, vasopressors, plasma expanders, fresh blood transfusion, bronchodilators and digoxin or calcium channel blockers depending upon clinical situation of the patients. Diuretics should be considered for pulmonary edema provided hypotension is excluded. Calcium gluconate and 25% magnesium sulfate due to their membrane stabilizing effects have been advocated. Gastric levage with potassium permagnate solution (1:10,000 dilution) is recommended for oral ingestion as permanganate oxidizes PH3 to form phosphate esp. if given with I hour of ingestion.
Acute poisoning of drugs is very common in India and world wise.
Naloxone has been used as a specific antidote for opioids poisoning since the 1960s. A frequent error in the management of opioids poisoned patients is to administer either excessive or insufficient doses of naloxone. The goal of naloxone treatment is reversal of respiratory depression to a minimum respiratory rate of ten (with adequate respiratory depth and oxygen saturation) and reversal of central nervous system (CNS) depression aiming for a Glasgow Coma Score of 4,5. Naloxone can precipitate acute withdrawal syndrome (AWS) in chronic opioids users.12,13. The agitation, hypertension and tachycardia produced, although rarely life-threatening, may produce significant distress to both the patient and doctor. . The agitation that results from AWS makes it difficult to monitor the patient condition and patients in this state may opt to leave the A&E department against medical advice. In addition, vomiting commonly occurs in acute withdrawal and, in-patient not regaining consciousness immediately after naloxone, can result in aspiration. The bolus dose required to reverse the depressant effects of an opioids is generally between 0.4 mg and 2.0 mg IV, although this should not be given as a single large bolus dose8. 2 mg of naloxone is made up in a 10 ml syringe with saline and given in 100-200 mcg boluses to a maximum of 10 mg, titrated according to the effect produced. The half-life of naloxone is between 30 and 100 minutes. Because the duration of action of most opioids exceeds that of naloxone either repeated doses or an intravenous infusion of naloxone are often required14.
Paracetamol remains the most common substance taken in overdose in Europe, accounting for 50% of all selfpoisoning episodes and 100-200 deaths per year. The vast majority of cases of early, lone paracetamol poisoning are asymptomatic at presentation; therefore management is best guided by blood tests15.
A number of factors may increase the risk of hepatotoxicity in patients with paracetamol poisoning and identify them as high risk. Risk factors in paracetamol overdose are: Regular ethanol consumption in excess of currently recommended limits (21 units/week in males; 14 units/week in females), Regular use of enzyme-inducing drugs (e.g. phenytoin, carbamazepine, rifampicin, phenobarbitone), Conditions causing glutathione depletion ( e.g. HIV, eating disorders, cystic fibrosis, malnutrition).
The decision to use N acetylcysteine (NAC) in patients with early paracetamol poisoning is based on the plasma paracetamol concentration plotted on the Prescott normogram30. Blood should be taken for a plasma paracetamol concentration on presentation (or four hours post-ingestion, whichever is later). NAC is an effective, safe antidote and if given within eight to ten hours of paracetamol ingestion provides almost 100% protection against the development of hepatic and renal toxicity30. Therefore, in patients who present early, if the result of the plasma paracetamol concentration is available by eight hours post-ingestion, the decision to start NAC can be based directly on the plasma paracetamol concentration. However, in patients who present at more than eight hours after ingestion of a potentially hepatotoxic dose of paracetamol (> I 50 mg/ kg or 75 mg/kg in high-risk patients), NAC should be started on presentation after blood is taken for a plasma paracetamol concentration; the NAC can be stopped if the plasma paracetamol concentration is found on analysis to be well below the relevant treatment line on the Prescott nomogram.18
This group is difficult to manage. In any patient presenting within eight to twenty-four hours of ingestion of a potentially hepatotoxic dose of paracetamol, NAC should be started immediately and blood taken for International Normalized Ratio (INR), liver function tests, serum creatinine and plasma (venous) bicarbonate. The decision to continue the infusion will be determined by these blood results, the history and the clinical condition of the patient. However, in late-presenting patients, the detection limit of the plasma paracetamol assay may not be sufficient to distinguish between toxic and non-toxic amounts19. Therefore, the plasma paracetamol concentration in late-presenting patients needs to be considered with caution and patients may need to be given NAC on the basis of ingestion of a potentially hepatotoxic dose of paracetamol (150 mg/kg or 75 mg/ kg for ‘at risk’ groups)18.The maxim to be followed in practice is, ‘If in doubt, treat.
The plasma paracetamol concentration cannot be used to assess patients presenting at more than 24 hours post ingestion. In these patients, blood should be taken for INR, liver function tests, and serum creatinine and plasma venous bicarbonate. If the patient is asymptomatic and the blood results are normal he/she may be medically discharged20 if not, the National Poisons Information Service (NPIS) at AIIMS, New Delhi should be contacted for management advice.
Meticulous supportive care is important in these patients and if possible liver transplant unit should be contacted for evidence of hepatotoxicity at any stage or doubt about its management, particularly if markers of severe toxicity are present21.
Markers of severe paracetamol poisoning and indications for referral to a liver unit are: Progressive coagulopathy or INR >2 at 24 hours, INR >4 at 48 hours, INR >6 at 72 hours, Renal impairment (creatinine >200 mmol/L), Hypoglycemia, Metabolic acidosis (pH <7.3, bicarbonate <18) despite adequate rehydration, Hypotension despite fluid resuscitation, Encephalopathy.
The plasma paracetamol concentration cannot be used to guide management in those patients who have taken a number of doses of paracetamol over a prolonged period of time. A baseline INR, liver function tests, serum creatinine and plasma venous bicarbonate should be taken, but the ingested dose is the most important factor and patients who have ingested more than 150 mg/kg over a 24-hour period (75 mg/kg for high-risk patients) should be treated with NAC.
The mortality rate in published studies of chloroquine overdose is between 12-35%, among the highest in clinical toxicology24. Ingestion of more than 5 g of chloroquine is probably the most accurate predictor of a fatal outcome; death is usually due to cardiotoxicity25. The interval between ingestion and onset of symptoms is usually between one to three hours, with death within 12 hours. Chloroquine blood concentrations are not required for the institution of treatment. As clinical features, involving the cardiovascular and CNS are more important. Activated charcoal should be given to patients presenting within one hour of ingestion of more than 15 mg/kg chloroquine. It is essential to intubated and ventilate early in the course of chloroquine poisoning if arrhythmias, hypotension, seizures or significant CNS depression are present. Anti-arrhythmic agents should be avoided if possible as they may precipitate further arrhythmias. Intravenous sodium bicarbonate is the treatment of choice for arrhythmias26 and should be used in patients with widened QRS and QTc intervals (1-2 ml/ kg 8,4% sodium bicarbonate repeated as necessary aiming for a pH of 7.45-7.5). Overdrive pacing is the treatment of choice for ventricular tachycardia or torsade de pointes. Inotropes may also be necessary for hypotension unresponsive to a fluid challenge. Plasma potassium should be monitored, although hypokalemia may have a protective effect and should not be aggressively corrected. In the early stages of poisoning as there is no total body deficit of potassium and attempted early correction can worsen cardiotoxicity. If hypokalemia persists beyond eight hours, potassium should be replaced cautiously. High dose diazepam has been reported to have a specific cardio protective action in severe chloroquine poisoning. It is recommended that after intubation 2 mg/kg of intravenous diazepam should be given over 30 minutes and then 1 to 2 mg/kg for two to four days. Continuous and aggressive cardiorespiratory support appears to be the most critical factor in survival.
Salicylate poisoning is much less common now a day. Delay in diagnosis is associated with a mortality of 15% compared to a much lower rate in those patients in whom early diagnosis and initiation of therapy is made27. Children and the elderly may suffer toxicity with lower ingested doses and at relatively lower plasma salicylate concentrations. There is no antidote to salicylate poisoning, and management is directed towards preventing further absorption and enhancing elimination of the drug. The use of MDAC is controversial in salicylate overdose28. The plasma salicylate concentration should be determined on admission provided that the patient is more than four hours post-ingestion29. As salicylates can delay gastric emptying and may form concretions in the stomach resulting in delayed absorption, the plasma salicylate concentration should be repeated every three to four hours to ensure the concentration does not continue to rise. The plasma salicylate concentration correlates very roughly with toxicity although the presence of symptoms and signs and the degree of acidosis should be considered when interpreting the plasma salicylate concentration and deciding on further management. Metabolic acidosis is a particularly important negative predictor as it increases the CNS transit of salicylate and decreases salicylate renal elimination. After ingestion of enteric-coated preparations, plasma salicylate concentrations on admission are unreliable guides to the severity of poisoning, as levels may not peak till 12-18 hours after ingestion.
Clinical features: These depend on type of poisoning as
Patients with salicylate poisoning are often dehydrated because of vomiting, hyperventilation and sweating; rehydration is therefore an important aspect of management. Patients with severe salicylate poisoning are also at risk of pulmonary edema, however, and it is important not to cause fluid overload; in the elderly or those with cardiac disease a central line may be necessary to guide rehydration8.
Urinary alkalinisation is an effective method of increasing salicylate elimination and is indicated in patients with moderate salicylate poisoning30. In adults this is achieved by administering I L of 1.26% sodium bicarbonate over three to four hours and regularly checking the urinary pH with indicator paper aiming for a urinary pH 7.5-8.5; an increase in the infusion rate or bolus of 8-4% sodium bicarbonate may be required if an alkaline urine is not achieved as patients can have a significant base deficit. The plasma potassium should be monitored as the serum potassium can fall precipitously once adequate urinary alkalinisation is achieved and also it is very difficult to produce alkaline urine if the patient is hypokalemic. We would therefore recommend adding 20-40 mmol potassium to each liter of intravenous fluid administered. Haemodialysis reduces both the mortality and morbidity of poisoning, and, as well as being effective at increasing salicylate clearance it also corrects acid-base and fluid balance abnormalities. It should be considered if the patient has a metabolic acidosis resistant to correction with 8,4% sodium bicarbonate, especially if the pH is <7.2, the salicylate concentration is >800 mg/L in adults or 700 mg/L in children or elderly, or the patient has features of severe poisoning. It is important that alkalinisation is still achieved in those salicylate-poisoned patients undergoing haemodialysis in order to reduce plasma levels quickly, prevent acidaemia and promote elimination of as much salicylate as possible via the kidneys.
The most common area of mismanagement in overdoses is failure to recognize the potential severity of poisoning and instigate early treatment.
Severe theophylline poisoning (ingestion of more than 3 g in adults or 40 mg/kg in children) is associated with a high mortality8. Theophylline is most commonly used in sustained release formulations leading to delayed absorption in overdose and delayed onset of toxicity, as late as 12-24 hours post-ingestion.
Clinical features: This depends upon the severity (grades) 30 as
Management is most appropriately guided by the severity on the Sessler grading scheme31. All patients with theophylline poisoning should receive MDAC. Vomiting, which may be profuse, occurs in overdose in more than 70% of patients31. It may respond to metoclopramide but is more likely to be controlled by a 5HT3-receptor antagonist such as ondansetron. All patients should have cardiac monitoring. Sinus or supraventricular arrhythmias not causing hemodynamic compromise are best left untreated. In non-asthmatic patients, symptomatic supraventricular tachycardia should be treated with propranolol (0.01-0.03 mg/kg IV) or esmolol (25-50 mg/ kg), repeated according to response. Asthmatic patients should be treated with verapamil or cautiously with esmolol (short half-life and relative beta 1 selectivity). Ventricular arrhythmias are treated with DC cardioversion or magnesium sulphate, convulsions with intravenous diazepam. The patient should be intubated and ventilated. Plasma potassium concentration should be monitored frequently (everyone to two hours in severely poisoned patients) as hypokalemia is a potentially life-threatening consequence of theophylline poisoning. The blood glucose should be checked, as hyperglycemia is also common.
The clinical course of iron poisoning may be divided into four stages32. During the initial 30 minutes to several hours after ingestion, the corrosive effects of iron result in gastrointestinal upset leading to nausea and vomiting, abdominal pain and diarrhea. In severe cases gastrointestinal hemorrhage and shock can occur. The second phase, usually lasts from six to twenty-four hours after ingestion. This phase can be deceptively asymptomatic as patient during this phase can go on to develop severe toxicity. Phase three occurs from 12-48 hours after ingestion and may include severe lethargy, coma, convulsions, gastrointestinal hemorrhage, shock, metabolic acidosis, and hepatic failure with hypoglycemia, coagulopathy, pulmonary edema and renal failure. Phase four occurs between two and five weeks if the patient survives. Scarring from the initial corrosive damage can result in small bowel strictures and pyloric stenosis. It is important when assessing the ingested dose of iron that the elemental content of different iron preparations is considered. Undissolved iron tablets are radiopaque and an abdominal X-ray (AXR) should be taken in all patients to determine the need for gut decontamination. However the absence of radiopaque material on AXR does not exclude iron ingestion. If any tablets are visible on the AXR, whole bowel irrigation should be undertaken. Blood should be taken four hours after ingestion for determination of the serum iron concentration. If desferrioxamine is to be given before four hours for severe poisoning, blood should be taken for determination of the serum iron level just prior to its administration as once desferrioxamine has been given colorimetric assay methods may underestimate the amount of free serum iron33. A blood level taken more than six to eight hours after ingestion may underestimate the amount of free iron because of distribution into the tissues. For sustained-release preparations an initial serum concentration should be checked at four hours and again two to four hours later. The serum iron concentration should not be interpreted in isolation but patient’s clinical condition and an accurate history of the ingested dose should be considered as well. Measurement of the total iron binding capacity is of no value in the management of these patients. There have been no controlled studies looking at the use of desferrioxamine in iron poisoning. However it is recommend that it should be used in patients with hypotension, shock, severe lethargy, coma or convulsions or a serum iron level >90 mmol/L.8 Patients with a serum iron concentration of 55-90 mmol/L should be observed for 24-48 hours postingestion. They do not require chelation therapy unless they develop symptoms or have hematemesis / melaena. The recommended initial dose of desferrioxamine is 15 mg/kg/hour. reduced after two to four hours up to a maximum of 80 mg/kg in 24 hours. More rapid infusion rates can cause hypotension, and there is a risk of pulmonary complications such as ARDS with doses of more than 80 mg/kg/24hrs. Chelation with desferrioxamine should be continued until the urine has returned to a normal color, symptoms have abated and all radiopacities have disappeared. Haemodialysis or haemofiltration may be required to remove the iron-desferrioxamine complex in patients with renal failure.
Although rare, acute cyanide poisoning requires immediate action as it produces its effects, which include metabolic acidosis and CNS, cardiac and respiratory depression19. The immediate diagnosis of cyanide poisoning is difficult. This poses a therapeutic dilemma for the clinician who must rapidly decide whether to administer specific antidotes, some of which are themselves toxic. The blood cyanide concentration is considered the gold standard in confirmation of acute cyanide poisoning; they are, however, rarely of use in emergency management because they cannot be carried out rapidly enough to guide treatment34. A sample should be taken before antidote administration for cyanide quantification at a later stage. Many patients suffering from smoke inhalation or burns may also have cyanide toxicity and may present with a lactic acidosis not responding to oxygen administration. A recent study has shown that immediate and serial measurements of plasma lactate concentrations are useful in assessing the severity of cyanide poisoning in patients in whom the diagnosis is strongly suspected on a clinical basis. In burn victims without severe burns, a plasma lactate concentration of >90 mg/dL (10 mmol/L) is a sensitive and specific indicator of cyanide intoxication. Decontamination is an important aspect of management. If hydrogen cyanide gas or liquid cyanide is involved, protective clothing and breathing apparatus is necessary and if the patient is intubated a closed circuit should be used. In cyanide salt exposure, contaminated clothing should be removed and placed in sealed bags, and the skin washed with soapy water. Meticulous supportive care is important in the management of cyanide poisoning. All patients should receive high-flow oxygen, and comatose patients will require intubation. Patients who present with an established metabolic acidosis should be treated with 12 ml of 8.4% sodium bicarbonate to correct the acidosis. The other aspect of the management of cyanide poisoning is the use of antidotes. Dicobalt edetate can be associated with severe adverse effects including cardiotoxicity, facial and laryngeal edema, bronchospasm and rashes. These effects are more likely to occur if it is administered in the absence of cyanide ions or if the drug is injected too rapidly. It should therefore be used only if the diagnosis of cyanide poisoning is certain and the patient has severe clinical features8. If the diagnosis is uncertain or dicobalt edetate is unavailable, the patient should be treated with a combination of intravenous sodium thiosulphate and sodium nitrite35. Hydroxocobalamin (at a dose of 5 g for an adult) is a newer cyanide antidote and is both effective and well tolerated.
This involves supportive care together with the use of competitive inhibitors of alcohol dehydrogenase (e.g. ethanol, 4-methylpyrazole) to reduce the formation of their toxic metabolites36. In addition, aggressive bicarbonate therapy in patients with a metabolic acidosis decreases CNS transit of both ethylene glycol and methanol, and reduces optic nerve toxicity with methanol. Ethanol remains the antidote of choice in most cases for ingestion of these substances. All patients who have ingested a significant amount of ethylene glycol or methanol should receive a loading dose of ethanol while awaiting confirmatory laboratory results. An infusion should then be commenced in patients with confirmed poisoning (usually on the basis of a history of methanol or ethylene glycol ingestion in association with a raised osmolal gap) aiming for a blood ethanol concentration of 100-150 mg/ dL. Ethanol has unpredictable kinetics therefore patients who require an ethanol infusion should have hourly to two-hourly monitoring of blood ethanol concentrations until the serum ethanol concentration is 100-150 mg/dL. and then two to four-hourly monitoring once this concentration is achieved. Patients with severe methanol/ethylene glycol poisoning (e.g. severe, resistant metabolic acidosis, acute renal failure, ocular toxicity with methanol poisoning) may require haemodialysis37; the dose of ethanol should be increased in these patients, or ethanol put in the dialysate to maintain a serum ethanol concentration of 100-150 mg/dL. Sodium bicarbonate is frequently used in the management of poisoned patients. Dose should be titrated to clinical effect and very large doses may be required, for instance in severe tricyclic antidepressant poisoning the initial boluses of 1-2 mL 8.4% sodium bicarbonate followed by further dose titrated to a pH of 7.45-7.5. It is important that drowsy patients are ventilated to prevent the potential carbon dioxide retention that can occur and result in a paradoxical intracellular acidosis in these patients treated with sodium bicarbonate.
Carbon monoxide is the common cause of death by poisoning in the rural area. Two areas of particular concern are the clinical assessment of the patient and adequate oxygen therapy. Patients should have a thorough neurological examination, which includes heel-toe walking and other tests of cerebellar function. A carboxyhaemoglobin saturation level is of value in confirming the diagnosis but its level is not indicative of the severity of poisoning22. An electrocardiogram (ECG) is essential in any patient with severe poisoning or in those with pre-existing heart disease because arrhythmias and myocardial ischemia are a common cause of morbidity and mortality in severe carbon monoxide poisoning.64-70 Arterial blood gas analysis is also required in significant poisoning; oxygen saturation monitors are misleading as they measure both oxyhaemoglobin and carboxyhaemoglobin. All patients should receive high flow oxygen through a tightly fitting facemask and this should be continued for at least 12 hours. The use of hyperbaric oxygen is controversial and some published randomized trials disagree on its efficacy23. Until further, well-controlled evidence is available it is recommend that hyperbaric oxygen therapy in the groups of patients with carbon monoxide poisoning should be given. Current recommendations for hyperbaric oxygen therapy are any history of unconsciousness, carboxyhaemoglobin concentration of >40% at any time, presence of any neurological features (especially cerebellar signs), pregnancy and ECG changes.
S.G.R.D.Inst. Of Med. Sc. and Research,
Mehta Road, Amritsar