ACUTE POISONING SUMMARIZE Poisoning is a substance that, when introduced into the body in relatively small quantities, causes destruction or malfunction of some tissues and organs. Depending on the quantity in the body (the dose), a poison can kill. Poison is any substance that causes injury or illness or death of a living organism. Classification according to sources and usage : ① Industry ② Drugs ③ Agrochemical ④Venomous animals and plants. Classification according to the doses and time of exposure:①Acute poisoning:a high toxicant dose over a short period of time. Acute poisoning is with rush onset, serious symptom and rapid change, which will threaten life ②Chronic poisoning: a small dose of a toxicant over a long period of time. Chronic poisoning is with slow onset、long period, lack of the specificity criteria of diagnosis and lead to misdiagnosis and missed diagnosis easily. There are approximate 9 million kinds of natural and the synthesis chemical materials in the world, but insufficient 3000 kinds could cause poisoning. ETIOLOGICAL FACTORS & PATHOGENESY 1. 1.1. Etiological Factors Occupational poisoning The major causes of the poisoning accidents were lack of knowledge of prevention and protection from them. Many examples of diseases associated with specific occupations were recorded in antiquity, but they were not considered serious because the health of the workers was not a societal concern. 1.2. Living poisoning Living poisoning is the common reason of acute poisoning, including: Accidental poisoning; Non-deliberate self-poisoning: abuse or addiction; Deliberate self-poisoning: suicide; Homicidal poisoning. 2 Absorption、Metabolism、Excretion A chemical routes of administration to a body may through the gastrointestinal tract (ingestion) 、 respiratory tract (inhalation) 、 the skin (dermal absorption) and the Injection (intravenous, intramuscular). Oral administration of medications is the most common method. Other routes are rectum、urinary canal、vaginal、bladder、peritoneum and ocular. The frequent route of occupational poisoning is by respiratory tract, such as dust、smog、steam and gases. The frequent route of living poisoning is by gastrointestinal tract or skin, such as drugs 、 organophosphorous insecticides,etc. The venom could enter the body by wound after biting or nipping by venomous insects. Absorbed poison was distributed to the whole body through blood. The body generally tries to “change” a more toxic into a less toxic. This process is often called metabolism or biotransformation. Liver is the most important organ. Some toxin of poison increase after metabolism, for example, parathion is oxidated to paraoxon. 1 The body generally tries to “rid” itself of a chemical and/or its metabolites through the urine (kidneys involved), feces (liver involved), and exhaled air (lungs involved). This process is often called excretion or elimination. Water soluble products are filtered out of the blood by the kidney and excreted into the urine. Volatile compounds are exhaled by breathing. Compounds can be extracted by the liver and excreted into the bile. The bile drains into the small intestine and is eliminated in the feces. In addition, milk、sweat、saliva 3. 3.1. Mechanism of poisoning Topical corrosive stimulation Strong acid and strong alkali absorb the water in tissue, bind with protein and fat which produce cell degeneration and necrosis in exposure sites. 3.2. Hypoxia Cyanide、CO or H2S poisoning can make tissue and organs hypoxia by different ways to obstruct oxygen absorption, delivering and usage. Brain and heart are sensitive to hypoxia which leads to damage, unconsciousness and dysrhythmia or heart dysfunction. 3.3. Anesthetic action Organic solvent and anesthetic inhalation are strong fat-loving chemical. Lipide in cerebral tissue and cellular membrane is high,which can inhibit cerebral tissue while enter it. 3.4. Inhibiting the action of enzyme Many poisons or their metabolites have the toxicity by inhibiting enzyme vigor, for example, cyanide inhibites cytochrome oxydase, organophosphorous insecticides inhibite cholinesterase, heavy metals inhibite sulfhydryl in enzymes. 3.5. Interfering the physiological function of cell and organelle In vivo, CCl4 is changed to CCl3- by enzyme catalysis, which acts on unsaturated fatty acid in membrane of hepatocyte, produces lipid peroxidation, leads to mitochondria and endocytoplasmic reticulum degeneration and hepatocyte necrosis. Phenols can cause oxidative phosphorylation uncoupling, prevent triphosadenine formation and store. 3.6. Competing acceptors Atropine and curare produce alkaloids that compete successfully with acetylcholine at nerve synapses The delayed action of Paraquat poisoning can cause multiorgan failure and pulmonary fibrosis, respiratory failure will occur after 1~2 weeks. 4. Factors effect on toxic action 4.1. Physico-chemical property of poison: Volatility、solubility、particulates etc. This is important to guide you as to the appropriate advice to be given, especially therapeutic interventions. 4.2. Individual susceptibility: Age (preferably date of birth), Sex, Weight/Height (useful in some settings for indication of nutritional status, also toxic dose and doses of antidotes may be based on body weight), Past medical history such as allergies, psychiatric, conditions, hypertension, heart disease, seizure disorder, etc., Current medications, Pregnancy or lactating, (Other information that can be taken later if relevant and appropriate: marital status, ethnic origin, educational attainment, occupation, details of family doctor etc.) 2 THE DIAGNOSIS OF POISONING 1. Patient history Poisoning should be suspected in all cases of sudden, severe, and unexpected illness. You should investigate such situations by ascertaining, as quickly and thoroughly as possible, the answers to the following questions: WHO? - Patient information: This is important because patient factors can influence the effect of the poison. WHAT? - Agent information: This is important to guide you as to the appropriate advice to be given, especially therapeutic interventions HOW? - Mode of exposure: The degree and rapidity of absorption of a poison is dependent on the mode of exposure. The absorption is faster through the inhalational route or by injection compared with the oral route. WHEN? - Time of exposure This is important for the following reasons: (1) to determine the kinetic phase of the poison; (2) to interpret plasma concentrations of toxic agents; (3) to correlate signs and symptoms to the risk to poisoning; (4) to decide on appropriate management, e.g. WHERE? This is important so as to evaluate the extent of poisoning. For instance, if it occurred in the workplace, other workers may also be poisoned, or the agent involved in poisoning may be the industrial grade which is more concentrated; an exposure to a gas in a confined space may be more severe than the same exposure in an open space. WHY? This is important in the overall evaluation, especially when it concerns medical disposition. For instance, a patient who has intentionally self-poisoned may need psychiatric evaluation. A young child who accidentally swallows something will usually ingest much less than a child who has been given something orally by another person. HOW MUCH? Dosage of angent how much was there initially, and how much is there now? If possible, bring the container to the treatment facility. The label will often identify the contents and the recommended precautions and treatment. The label may also list a contact number for emergency advice. Remember, though, that other people— including you may become contaminated through contact with the container. Handle it carefully. 2. Sings and symptoms Each chemical family attacks the human body in a different way. General poisoning symptoms include the following. Mild Poisoning Headache, fatigue, weakness, dizziness, restlessness, perspiration, nausea, diarrhea, loss of appetite, loss of weight, thirst, moodiness, soreness in joints, skin irritation, eye irritation. 3 Moderate Poisoning Severe nausea, severe diarrhea, excessive saliva, stomach cramps, excessive perspiration, trembling, no muscle coordination and muscle twitches, extreme weakness, mental confusion, blurred vision, difficulty in breathing, cough, rapid pulse, flushed or yellow skin, weepy eyes. Severe Poisonings Fever, intense thirst, increased rate of breathing, uncontrollable muscle twitches, pinpoint pupils, convulsions, inability to breathe, unconsciousness. Table 1 Syndrome Commonly Encountered Toxidromes Sources Signs & Symptoms narcotic opiates, benzodiazepines, barbiturates Abeady eyes, sunglasses, decreased blood pressure, CNS and respiratory depression withdrawal alcohol, arbiturates, benzodiazepines, narcotics, sedative-hypnotics diarrhea, dilated pupils, goose bumps, increased heart rate, tearing, yawning, stomach cramps, hallucinations sympathomimetic theophylline, caffeine, LSD, PCP, amphetamine, cocaine, decongestants CNS excitation (confusion, incoordination, agitation, hallucination, delirium, seizures), increased blood pressure and heart rate anticholinergic antihistamines, atropine, scopolamine, antidepressants, anti-Parkinson, antipsychotics, antispasmodics, mush-rooms, hallucinogens, antidepressants dry skin, increased heart rate, dilated pupils, fever, urinary retention, decreased bowel sounds, CNS excitation organophosphates, carbamates, physostig-mine, neostigmine, endrophonium ASLUDGE: increased salivation, lacrimation, urination, defecation, GI cramping, emesis; CNS (headache, restless, anxiety, confusion, coma, seizures); muscle weakness and fasciculations syndrome various chemicals with delayed onset due to biotransformation, depletion of natural detoxifying agent, accumulation of dose or effect From nothing to minor complaints that initially appear to be trivial cholinergic non - syndrome Table 10-1-2 Poisoning Severity Score (PSS) 0 No symptoms or signs related to poisoning 1 None Minor: 2 Moderate: Pronounced or prolonged symptoms 3 Severe: Severe or life-threatening symptoms 4 Fatal: Death Mild, transient, and spontaneously resolving symptoms 4 3. Laboratory testing Laboratory testing is make for diagnosis, but could not identify all poisons. Urine It is easier to detect presence of the drug due to the accumulation of drug in the urine. Red(Phenindione、Rifampicin)、Blue or green(Methylene blue) 、Grey (Phenol、cresols)、 Crystalluria (Primidone、some sulphonamides) 、blood(Coagulation disorders、renal functional lesion). Blood/Serum ①Blood biochemistry: hypokalemia - Diuretic、Barium、Theophylline、β-agonists; Hyperkalemia - digoxin、fluorid、α-agonists、β-antagonist; hypoglycemia - alcohol、 β- antagonist; hyperglycosemia - β-agonists、CCB; ②Arterial blood gas:coma patients. Hypoxia – asphyxia 、 irritant gas; respiratory alkalosis – ortho-oxybenzoic acid; metabolic acidosis – alcohol、ethylene alcohol、asprin. EKG Reentrant tachycardia: fluorid、heavy metals、potassium magnesium salt、Normeperidine、 antipsychotic drug; A-V block or Bradycardia arrhythmia : β -agonists 、 CCB 、 digoxin 、 Organophosphorous insecticides X- ray Abdomen--Heavy metals :arsenic、ferri、lead、mercury、thallium; Chest—Poison gas: alkaline gas、chlorine gas、hydrogen sulfide、carbon monoxide; Smog:multimer compound、 metaloxide; Vapor:dense acid、aldehyde、mercury. Special examination toxicology analysis , such as Gastric Contents、Blood、Urine、Remaining poison, is hyperspecificity and hyposensitivity. Table 10-1-3 Identify poisons according to odors Aromatic Acetone, Alcohols, Phenols Pears Chloral Hydrate Bitter Almonds Cyanide Carrot Cowbane Garlic Arsenic, Dmso, Organophosphates Phosphates, Tellurium, Thallium Rotten Eggs Hydrogen Sulfide Checkerberry Methyl Salicylate Smell Of Fish Zine, Aluminium Phosphide Shoe Polish Nitrobenzene Rubber Methylbenzene TREATMENT OF POISONING 1. Therapeutic Principle Emergent resuscitation、stopping poison contact、antidotes usage、remove the unabsorbed poison in gastrointestinal tract、supportive treatment、preventing complication. 5 2. Treatment of acute poisoning 2.1. Emergent resuscitation ① Breathing aid. The victim's airway must be open for breathing to be restored. The airway may be blocked when a patient loses consciousness or may be obstructed by food or some other foreign object. Apply artificial respiration if breathing has stopped or is irregular. If patient is convulsing, watch his breathing and protect him from falling and striking his head. Pull his chin forward so his tongue does not block his air passage. Do not give respiratory stimulant in any form, if poison is still in body. ② Circulation aid. Hypotension and circulatory failure are common symptoms in poisoning patients. The reasons: 1) Vasomotor centre(VMC)reppression 2) Heart direct repression 3) Capacitance vessel dilation,returned blood volume reduction,cardiac output reduction 4) Permeability of capillary increasing,intravascular volume reduction. When hypotension happens, inject crystal liquid、blood plasma or its substitutes. If it is unavailable, maintain on intravenous dopamine or dobutamine for. treatment of this refractory hypotension. ③ Treatment of coma and convulsion 1) Threatment of coma: Bedside capillary blood glucose(CBG) testing is a must in unconsciousness patients. A dangerously low blood sugar (hypoglycemia) will cause weakness, unconsciousness, and eventually death. Sugar given by IV 50%glucose 40ml is an effective treatment. An unconscious patient suffered with severe malnutrition and ethanol poisoning should be treated by IM vitamin B6. Naloxone is used in opioid overdoses for countering life-threatening depression of the central nervous system and respiratory system. An initial dose of 0.01mg/kg of naloxone may be administered intravenously. If the desired degree of counteraction and improvement in respiratory functions is not obtained, it may be repeated at 2 to 3 minute intervals. If no response is observed after 10 mg of naloxone have been administered, the diagnosis of narcotic induced or partial narcotic induced toxicity should be questioned. Flumazenil is a specific and competitive antagonist at the central benzodiazepine receptor, reversing all effects of benzodiazepine agonists without tranquillising or anticonvulsant actions. Hypoxia、 hypotension 、 hypercarbia and hypoglyemia happen easily after cardiopulmonary resuscitation, aggravate encephaledema and increase intracranial pressure, which can be treated with dexamethasone and mannitol. 2)Treatment of convulsion: Diazepam is the common drug used as anti-convulsant, administered intravenously with 5~10mg of each time or 0.1~0.2mg/mg, If unavailable, instead of sodium phenytoin 15 ~ 18mg/kg (or 50mg/min) administered intravenously; or phenobarbitone 100~200mg of each time administered intravenously or intramuscularly and repeat after 4~6h. 2.2. Stopping poison contact ①Remove the victim from the scene if it is safe to do so, especially inhalation poisons involving dust, vapors, gases. ②Clear the poison in mouth immediately, remove contaminated clothing. ③Poison on the Skin: Remove contaminated clothing, wash the skin with large quantities of cold running water at least 15min.④Poison in the Eye: Hold eyelids open, wash eyes with a gentle stream of clean running water at body temperature for 15 minutes or more continuously. Keep the pH of tears at 7.0 after washing acid or alkali chemicals poison. Do not use chemicals or drugs in wash water, they may increase the extent of injury. 2.3. Antidotes An antidote is a substance which can counteract a form of poisoning, but not for uncertain or over deadline poison. Only 5% toxins have known antidote, but some antidotes 6 also have high toxicity. Attention patients’ state of illness at antidotes using. Table 10 1- 4 Common using antidotes poisons antidotes Acetaminophen (paracetamol) N-acetylcysteine Anticholinergic Physostigmine sulfate Benzodiazepine flumazenil Carbon monoxide oxygen Anticholinesterase atropine sulfate and Pralidoxime chloride 2-PAM Cyanide amyl nitrite, sodium nitrite, and thiosulfate Digoxin anti digoxin fab fragments Ethylene glycol ethanol or fomepizole Extrapyramidal signs diphenhydramine hydrochloride and benztropine mesylate chelators, calcium disodium edetate (EDTA), dimercaprol Heavy metal (BAL), penicillamine, and 2,3-dimercaptosuccinic acid (DMSA, succimer) Iron deferoxamine mesylate as Isoniazid pyridoxine Methanol ethanol or fomepizole Methemoglobinemia methylene blue Opioid naloxone hydrochloride Warfarin vitamin K phytonadione and fresh frozen plasma 2.4. Remove the unabsorbed poison in gastrointestinal tract Empty the stomach using emetic, gastric lavage, adsorbent, cathartic and/or dilute the poison by having the conscious victim drink one to two glasses of water or milk. ①Emesis 1) echanical Tickle the back of the victim’s throat with your finger or a blunt object. This procedure should induce vomiting. If it is unavailable, drink 200~300ml of warm water before do it. Repeat it until vomit clear water. 2) rugs Syrup of ipecac is the top selected drug. The usual adult dose is 15-20 cc. The dosage should be followed immediately by 200ml of water. Most people will vomit within 20 minutes, otherwise,repeat it. This way can’t be use in coma、convulsion、no vomit reflex、shock or corrosive chemicals intake patients. Induced vomiting can cause even more damage, especially if a caustic substance has been swallowed. ② Gastric lavage Gastric lavage is used infrequently in poisonings and some authorities have suggested that it not be used routinely, if ever, in poisoning situations. Lavage should only be considered if the amount of poison ingested is potentially life threatening and the procedure can be performed within 1~2h of ingestion. Contraindication: Loss of airway protective reflexes, such as in a patient with a depressed state of consciousness, unless 7 intubated tracheally; Ingestion of a corrosive substance such as a strong acid or alkali; Ingestion of a hydrocarbon with high aspiration potential; Patients who are at risk of hemorrhage or gastrointestinal perforation due to pathology, recent surgery, or other medical condition such as a coagulopathy. If the patient has a poor cough reflex, protect the lungs and the patency of the airway by inserting a cuffed endotracheal tube before passing a stomach tube. In conscious patients and even unconscious patients with intact cough and gag reflexes, a large bore stomach tube may be passed at once. Place the patient so that his mouth is lower than his trachea. Remove any dentures and keep the mouth open with a gag. Lubricate the tube with glycerine or a suitable jelly, and ease it over the tongue and down the esophagus to a distance of about 50 cm in adults. Suck out the stomach contents using gentle mechanical suction if available. If a source of continuous suction is not available, a large syringe fitted with an adaptor will help. If little or nothing is obtained, it may be that the tube is not correctly located. Proper positioning of the tube can be checked by forcing a little air down it and listening with a stethoscope over the stomach for bubbling sounds. After making a reasonable effort to remove any stomach contents and being quite certain that the end of the tube is in the stomach attach a large evacuator or funnel to the oral end of the tube. Add water or physiological saline heated to about body temperature. (300 ml for adults, or less for children). If a funnel is used, elevate the oral end of the tube and allow the water to enter the stomach by gravity. For this purpose, it may be necessary to use an adaptor and add a length of tubing between the funnel and the stomach tube so to increase the overall length and make it easier to regulate the height of the column of water. Before all the water has passed into the stomach, lower the tube into a basin or jar and allow the stomach contents to siphon off, do not use more than 300 ml for each washing, because a large volume would have more tendency to cause emptying of the stomach contents into the duodenum. Repeat the lavage until the returning fluid is clear. ③ Absorption of poisons in intestinal tract Activated charcoal is effective in decreasing absorption of a number of drugs and chemicals by binding or adsorbing these substances in the gastrointestinal tract. Its effectiveness is time-dependent with greatest benefit observed when administered within one hour of ingestion. Its administration is more favoured than the use of syrup of ipecac and gastric lavage. Activated charcoal will not adsorb alcohol, lithium, iron, lead, cyanide, strong acids or alkalis, hydrocarbons (gasoline, kerosene, lamp oil). However, it is effective for poisonings involving aminophylline, ampicillin, aspirin, carbamazepine, digoxin, doxepin, phenobarbital, acetaminophen, phenytoin, tetracycline and theophylline. Activated charcoal is often given after gastric lavage to prevent further absorption in usual dosage (Table 10-a). It may be administered through an orogastric or nasogastric tube with 150~200g every 4~8h in severe patients. That administered through an orogastric or nasogastric tube with 20~30g in 3~4h is called Moltiple-dose activated charcoal. This technique often called the “gut dialysis”. Contraindications to activated charcoal include: vomit, aspiration,constipation,small bowel obstruction. 8 Table 10-a Dosage of activated charcoal Children up to 1 year: 0.5-1 g/kg 1-12 years old: 25-50 g Adolescents and adults 25-100 g ④ Cathartics Cathartics, also known as laxatives or purgatives have been used in the belief that they decrease absorption of poisons by accelerating their expulsion from the gastrointestinal tract. However, published clinical studies did not show efficacy of cathartics, with or without activated charcoal, in reducing bioavailability of drugs or improving patient outcome. They have also been found to increase gastrointestinal motility by stimulating gastrointestinal hormones or acting on the myenteric plexus and other gastrointestinal lnerves. The common using cathartic:Sorbitol, 10% Magnesium citrate, Sodium sulphate. 10% Magnesium citrate is administrated through orogastric or nasogastric tube. Magnesium-containing cathartics are contraindicated in patients with renal impairment and central nervous system depression. Cathartics is no useful to organophosphates pesticides poisoning having treated with high dose atropine. Fluid and electrolyte imbalances are must be noted in this process. ⑤ Whole bowel irrigation Whole bowel irrigation utilizes electrolyte-balanced, inert solutions such as polyethylene glycol-electrolyte solution to induce a liquid stool. It is used to expel poisons that are poorly adsorbed by activated charcoal and also sustained-release and enteric-coated drugs. It is also useful as an enhanced elimination technique if tablets have passed beyond the pylorus. The polyethylene glycol-electrolyte solution is continuously administered with 2L/h, either orally or through a nasogastric tube until the rectal effluent is clear. 2.5. Techniques Used to Enhance Elimination of Poisons ① Urinary alkalinization or acidification therapy Urine alkalinization is a method for increasing elimination of selected toxins. Increasing the pH of tubular fluids by the administration of sodium bicarbonate increases the degree of ionization of weak acids. Through this ion trapping technique, passive reabsorption of weak acids is inhibited, thereby enhancing their elimination. Examples of these weakly acidic substances are chlorpropamide, 2,4-dichlorophenoxyacetic acid (2,4-D), diflunisal, fluoride, mecoprop, methotrexate, phenobarbital, and salicylates. 8.4% Sodium bicarbonate:225 mmol (225 mL) in adults or 25-50 mmol (25 mL) in children given intravenously over one hour. Subsequent doses are given to titrate urine pH within 7.5-8.5. Monitor arterial blood gases.Urinary acidification therapy is not recommended because it can produce metabolic acidosis, rhabdomyolysis and renal failure. ② Haemodialysis and haemoperfusion can be used to enhance elimination of poisons such as ethylene glycol and methanol. Considerations for their use would include the 9 following: Severe poisoning with depression of midbrain function; Impairment of normal excretory function in the presence of hepatic, cardiac and/or renal insufficiency; Poisoning with agents producing metabolic acidosis and/or delayed effects; Poisoning with agents that can be removed at a rate exceeding;that of endogenous elimination by the liver or the kidneys; Acute renal failure. Haemodialysis is effective for drugs that are not water soluble, with a small volume of distribution, low protein binding, and low molecular weight ( <500 daltons). Complications include: hypotension, bleeding, nosocomial infection and air embolism. Haemoperfusion involves passing blood through a filter in the form of a column or cartridge containing activated charcoal. For its efficiency, charcoal haemoperfusion is dependent on the physical process of drug adsorption, and not on water solubility. This technique is more efficient than haemodialysis in removing poisons. However, the charcoal filters are not readily available and there is a greater risk of the development of complications compared to the other methods. Complications are frequent and they include: hypotension, bleeding, nosocomial infection, air embolism, leucopenia, thrombocytopenia and hypocalcaemia. 2.6. Supportive Management Supportive care is important in the management of a poisoned patient, especially when intensive care admission is required. The following measures should be instituted: Monitor vital signs (blood pressure, heart rate, respiratory rate, temperature); Monitor fluid input and output; Monitor level of consciousness, pattern of breathing and regularity of the heart rate; Monitor oxygen saturation using a pulse oximeter; Administer intravenous fluids for maintenance and fluid loss replacement; Carry out intensive nursing care to avoid aspiration or the development of bed sores; Treat metabolic disturbances such as electrolyte abnormalities, hypoglycaemia and metabolic acidosis; Manage underlying illnesses that may be aggravated by existing problem of poisoning; Use specific antidotes if indicated. 10