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DRUG THERAPY OF ACUTE POISONING Two of the most dreaded and insidous mushrooms found in Swedish forests: the hepatoxic Amanita virosa and the nephrotoxic Cortinarius speciocissimus Acute Poisoning in the Emergency Department Common - 3-5% of ED attendances 2000 Deaths per year Some of the highest rates of deliberate poisoning in Europe Often multiple drugs DON’T FORGET ALCOHOL !! Poisoning Poisoning can be defined as a chemical injury to body organs or a chemically induced disturbance of the functions in biological systems. Such toxic effects may follow the exposure to exogenous (environmental) substances. By tradition an agent has been considered as a poison if it may damage the organism in a very small dose. The toxic properties of a certain poison are often specific, and hence the clinical symptoms after exposure to a poison may be quite characteristic. Substances that normally are considered as harmless may also, if the dose is big enough, cause deleterious effects and thereby act as poisons. Examples of this are sodium chloride, oxygen and water. The science devoted to the study of the structures, effects and fate of poisonous substances is called toxicology. This is nowadays a wide, heterogeneous and rapidly expanding discipline. Clinical toxicology is a subentity that deals with problems related to poisonings in humans and their treatment. Biological poisoning Acute poisoning is exposure to a poison on one occasion or during a short period of time. Symptoms develop in close relation to the exposure. Absorption of a poison is necessary for systemic poisoning. In contrast, substances that destroy tissue but do not absorb, such as lye, are classified as corrosives rather than poisons. Chronic poisoning is long-term repeated or continuous exposure to a poison where symptoms do not occur immediately or after each exposure. The patient gradually becomes ill, or becomes ill after a long latent period. Chronic poisoning most commonly occurs following exposure to poisons that bioaccumulate such as mercury and lead. Types of poisoning Deliberate: Overdose as self-harm or suicide attempt Child abuse ± Munchausen's syndrome by proxy Third party (attempted homicide, terrorist, warfare) Accidental: Most episodes of paediatric poisoning. Dosage error: Recreational use Environmental: Iatrogenic Patient error Plants Food Venomous stings/bites Industrial exposures General Management A (Airway) B (Breathing) C (Circulation) D (Disability-AVPU/ Glasgow Coma Scale) DEFG ( Don’t ever forget the Glucose) GET A SET OF BASIC OBSERVATIONS For effective management of an acutely poisoned victim, five complementary steps are required: 1. Resuscitation and initial stabilization 2. Diagnosis of type of poision 3. Nonspecific therapy 4. Specific therapy 5. Supportive care Resuscitation Airway: Open, suction, maintain and intubate as necessary. Breathing: Assess work and effectiveness of ventilation. Give oxygen ±assisted ventilation (avoid mouth-to-mouth). Respiratory depression - consider opiates, benzodiazepines, early salicylate poisoning. Tachypnoea - consider metabolic acidosis e.g. salicylates, methanol. Resuscitation (cont’d) Circulation: Attach a cardiac monitor, assess pulse, blood pressure and perfusion. Establish intravenous access. Tachycardia/irregular pulse - consider overdose of salbutamol, antimuscarinics, tricyclics, quinine, phenothiazine, chloral hydrate, cardiac glycosides, amfetamines, and theophylline poisoning. If hypotensive consider giving fluid bolus (colloid) or, if necessary, inotropes. Resuscitation (cont’d) Disability: Assess consciousness level (Glasgow Coma Scale). Coma may suggest benzodiazepines, alcohol, opiates, tricyclics, or barbiturates. Check pupils and eye movements: Large - consider anticholinergics, sympathomimetics, tricyclics. Small - consider opiates or cholinergics. If opiates suspected give 0.8-2 mg naloxone iv/im every 2-3mins up to 10 mg until response (children: 10 mcg/kg iv/im repeated up to 0.2 mg/kg), repeated doses may be required thereafter as it has a shorter half-life than most opiates. Unreactive - causes include barbiturates, carbon monoxide, hydrogen sulphide, cyanide/cyanogens, head injury/hypoxia. Unequal - slight variation can be normal - but consider head injury. Strabismus - can be seen with carbamazepine overdose. Papilloedema - associated with methanol, carbon monoxide and glutethimide. Nystagmus - seen with CNS acting agents e.g. phenytoin. Resuscitation (cont’d) Disability: Check blood glucose - if hypoglycaemic give 50 ml 50% dextrose iv (children: 5 ml/kg of 10% dextrose iv). Hyperglycaemia - organophosphates, theophyllines, MAOIs or salicylate. Hypoglycaemia - insulin, oral hypoglycaemics, alcohol or salicylate. Seizures - if prolonged/recurrent initially give diazepam 5-10 mg iv (Child: 0.25-0.4 mg/kg iv or pr) or midazolam (0.15 mg/kg) IM/IV. Many drugs can induce seizures including tricyclics, theophylline, opiates, cocaine and amfetamines. History What was taken, how much, when, and by what route? Was alcohol consumed too? Any vomiting since ingestion? Past medical history, current medications and allergies. Was a suicide note left? Is the patient pregnant? Histories from others including: family, friends, paramedics, police and observers. General examination Directed cardiovascular, respiratory, abdominal and neurological examination. Vital signs, pupils etc. mentioned in Resuscitation section above. Temperature - hypothermia (phenothiazines, barbiturates, or tricyclics) or hyperthermia (amfetamines, ecstasy, MAOIs, cocaine, antimuscarinics, theophylline, serotonin syndrome). Muscle rigidity (ecstasy, amfetamines). Skin - cyanosis (methaemoglobinaemia), very pink (carboxyhaemoglobinaemia, cyanide, hydrogen sulphide), blisters (barbiturates, TCAs, benzodiazepines), needle tracks, hot/flushed (anticholinergics). Breath - ketones (diabetic/alcoholic ketoacidosis), "bitter almonds" (cyanide), "garlic-like" (organophosphates, arsenic), "rotten eggs" (hydrogen sulphide), organic solvents. Mouth - perioral acneiform lesions (solvent abuse), dry mouth (anticholinergics), hypersalivation (parasympathomimetics). Investigations 12 lead electrocardiogram. U+E, lab glucose, anion gap ± lactate & osmolal gap. LFT & clotting Arterial blood gases. Drug levels (at appropriate interval: paracetamol, salicylates; others: theophylline, digoxin, lithium, antiepileptics if it was likely that they had been taken). Comprehensive toxicology screens not normally indicated in the emergency treatment. Carboxyhaemoglobin levels if carbon monoxide poisoning suspected. Urinalysis - rhabdomyolysis, save sample for possible toxicological analysis. CXR if pulmonary oedema/aspiration suspected. CT brain may be needed to exclude other causes of alterations in conscious level. Laboratory Investigations : A few simple bedside tests are helpful in diagnosing the chemical ingested. A pinkish colour of urine occurs in phenothiazine intoxication, as well as in myoglobinuria and haemoglobinuria. Chocolatecoloured blood is indicative of methaemoglobinaemia. Presence of oxalate crystals in urine is typical of ethylene glycol ingestion. Ketonuria without any metabolic change occurs in isopropyl alcohol and acetone intoxication while ketonuria with metabolic acidosis is suggestive of salicylate poisoning. Abdominal X-ray may be useful in diagnosing certain radiopaque toxins which include chloral hydrate, heavy metals, iron, iodides, phenothiazines, sustained-release preparations and solvents (chloroform, carbon tetrachloride). However, one must not exclude a poisoning on the basis of absence of radiopaque density on X-ray. Treatment Initial management Initial management for all poisonings includes ensuring adequate cardiopulmonary function and providing treatment for any symptoms such as seizures, shock, and pain. Poisons that have been injected (e.g. from the sting of poisonous animals) can be treated by binding the affected body part with a pressure bandage and by placing the affected body part in hot water (with a temperature of 50°C). The pressure bandage makes sure the poison is not pumped troughout the body and the hot water breaks down the poison. This treatment however only works with poisons that are composed of protein-molecules.[5] Treatment Decontamination if appropriate: Avoid contaminating yourself and wear protective clothing. Ensure area is well-ventilated. The patient should remove soiled clothing and wash him/herself if possible. Put soiled clothing in a sealed container. Wash all contaminated skin/hair with liberal amounts of warm water ±soap. Decontamination may be achieved using activated charcoal, gastric lavage, whole bowel irrigation, or nasogastric aspiration. Routine use of emetics (syrup of Ipecac), cathartics or laxatives are no longer recommended. Treatment (cont’d) Decrease absorption: Gastric emptying - this is contraindicated if the airway is unprotected or overdose of corrosives or hydrocarbons taken. Complications include pulmonary aspiration and oesophageal perforation. Only 30% of gastric contents are returned and it is proven to be effective if within 1 hour of ingestion (so this is only generally done if patients present early having taken a potentially fatal dose of drug). Controversially this is sometimes extended if delayed gastric emptying (e.g. presence of coma or overdose of tricyclics or salicylates) is thought likely. Emesis - no longer recommended. Gastric lavage - Place patient in left lateral head down (20°) position, insert large (36-40F) bore tube (children: 16 to 28F) into stomach. Remove contents with sequential administration and aspiration of small (200-300 ml) quantities of warm water or saline (children: 10-20 ml/kg preferably saline). Alternatively the stomach contents can just be aspirated. Treatment (cont’d) Activated charcoal is the treatment of choice to prevent absorption of the poison. It is usually administered when the patient is in the emergency room or by a trained emergency healthcare provider such as a Paramedic or EMT. However, charcoal is ineffective against metals such as sodium, potassium, and lithium, and alcohols and glycols; it is also not recommended for ingestion of corrosive chemicals such as acids and alkalis. Treatment (cont’d) Whole bowel irrigation cleanses the bowel, this is achieved by giving the patient large amounts of a polyethylene glycol solution. The osmotically balanced polyethylene glycol solution is not absorbed into the body, having the effect of flushing out the entire gastrointestinal tract. Its major uses are following ingestion of sustained release drugs, toxins that are not absorbed by activated charcoal (i.e. lithium, iron), and for the removal of ingested packets of drugs (body packing/smuggling) Treatment (cont’d) o Nasogastric aspiration involves the placement of a tube via the nose down into the stomach, the stomach contents are then removed via suction. This procedure is mainly used for liquid ingestions where activated charcoal is ineffective, e.g. ethylene glycol poisoning. o Cathartics were postulated to decrease absorption by increasing the expulsion of the poison from the gastrointestinal tract. There are two types of cathartics used in poisoned patients; saline cathartics (sodium sulfate, magnesium citrate, magnesium sulfate) and saccharide cathartics (sorbitol). They do not appear to improve patient outcome and are no longer recommended Enhanced excretion In some situations elimination of the poison can be enhanced using diuresis, hemodialysis, hemoperfusion, hyperbaric medicine, peritoneal dialysis, exchange transfusion or chelation. However, this may actually worsen the poisoning in some cases, so it should always be verified based on what substances are involved. Increase elimination: Forced diuresis - no longer recommended. Haemoperfusion and acid/alkaline diuresis - rarely used now. Haemodialysis - severe salicylate, ethylene glycol, methanol, lithium, phenobarbital and chlorate poisonings. Multiple doses of activated charcoal - interrupts enterohepatic or enteroenteric recirculation. Use 50g 4-hourly (children 1g/kg) or 12.5g hourly (children 0.25g/kg) to reduce vomiting, but beware severe constipation, fluid depletion and avoid repeating cathartic agent doses within 24hrs. Used with carbamazepine, dapsone, phenobarbital, quinine, salicylate, colchicine, dextropropoxyphene, digoxin, verapamil and theophylline overdoses. Specific Therapy If the toxin can be identified, specific therapy using antidotes should be administered: Paracetamol (acetaminophen) N-acetylcysteine vitamin K anticoagulants, e.g. warfarin vitamin K opioids naloxone iron (and other heavy metals) benzodiazepines desferrioxamine, Deferasirox or Deferiprone Organophosphates Atropine and flumazenil SUPPORTIVE THERAPY Since the antidotes are available only for a few toxins, treatment of most cases of poisoning is largely supportive The aim is to preserve the vital organ functions till poison is eliminated from the body and the patient resumes normal physiological functions. Therefore, functions of central nervous system, cardiopulmonary system and renal system should be supported with proper care for coma, seizures, hypotension, arrhythmias, hypoxia, and acute renal failure. The fluid, electrolyte and acidbase status should be closely monitored in all patients. Prevention Adult education. Double-check dosage before administration. Vigilance by health professionals to recognise the early signs of abuse and potential suicide. Put all medicines and household chemicals in a locked child-proof cupboard >1.5 metres off the ground. Safely dispose of medicines, chemicals which are not needed or out of date. Keep all medicines and chemicals in their original containers with clear label