Alimohammad Alimohammadi Clinical Toxicologist & Forensic Medicine Approach to the Poisoned Patient اصول كلي مسموميت‌ها و چگونگي برخورد با آن Alimohammad Alimohammadi Clinical Toxicologist & Forensic Medicine

Definitions of terms Poisoned patient : to injure or kill with poison Poison : a substance that through its chemical action usually kills , injures , or impairs a organism Poisoning :exposure to poison is accidental Overdose : exposure to poison is intentional

Definitions of terms Accidental poisonings(children-elderly) Over dose( Nonsuicidal Patient) secondary to drug abuse Occupational Environmental Attempt poisonings (adults) Over dose(suicidal Patient) Over dose(Homiside)

Any Pt who comes with abrupt alteration In consciousness level in overall a clinical toxicologist should brings in mind following points if he has suspicion of overdose in comatose Pt : Any Pt who comes with abrupt alteration In consciousness level Any young Pt with arrhythmia Any Pt with suicidal and psychic records . Any Pt with drug abuse record. Any Pt who bring in ED with multi system failure of unknown etiology should be suspected of poisoning until proved otherwise Any Pt who had recent familial or social problem especially in young`s. Any Pt who has metabolic acidosis without clear base . Any Pt who was rescued from fire accident Any Pt who was found unconscious in work environment

How to diagnose a poisoned patient It may be : 1) To easy to ascertain like a child poisoning with his/her mothers iron tablets ingestion. or an elderly Pt who misreads label , or misuse a drink. 2) To difficult like a youth who was found unconscious in deserted place with unclear history.

IMPORTANT OR SERIOUS AFFAIR suddenly acute Chronic dealy

IMPORTANT OR SERIOUS AFFAIR

The initial approach to the poisoned patient (1) resuscitation and stabilization; (2) history and physical examination, including evaluation for a specific toxidrome; (3) appropriate decontamination of the gastrointestinal tract, skin, and eyes; (4) judicious use of laboratory tests, electrocardiograms, and radiographic studies; (5) administration of specific antidotes, if indicated (6) utilization of enhanced elimination techniques for selected toxins.

RESUSCITATION AND STABILIZATION the same as with all patients. The patency of the airway must be ensured, followed by assistance of breathing and support of circulation. Cardiac monitoring, pulse oximetry, and intravenous access should be established as indicated by the patient’s clinical condition.

should focus on correcting: Airway management should focus on correcting: hypoxia respiratory acidosis avoiding pulmonary aspiration. Acid, opium, hydrocarbon

Acidemia due to respiratory depression can exacerbate the toxicity of drugs, such as cyclic antidepressants and salicylates. severe upper airway injury that occurs following a caustic ingestion may preclude routine endotracheal intubation, necessitating surgical management of the airway. The use of succinylcholine for rapid-sequence intubation can result in prolonged paralysis in patients with organophosphate toxicity.

Standard ACLS doses of atropine are inadequate for organophosphate-induced cholinergic symptoms. The use of procainamide is contraindicated for ventricular dysrhythmias caused by cyclic antidepressants and other myocardial sodium channel–blocking agents. Intravenous calcium can be lifesaving in a patient poisoned with hydrofluoric acid, a calcium channel–blocking agent, or magnesium. Sodium bicarbonate may be lifesaving in resuscitation of the patient poisoned with cyclic antidepressants or salicylates

In patients with altered mental status, administration of naloxone, dextrose, and thiamine should be considered, flumazenil should be administered cautiously in cases of benzodiazepine overdose with significant respiratory depression

The indications generally fall into the following categories •    Failure to maintain reasonable gas exchange    •    Failure to maintain a patent airway    •    Failure to adequately protect the airway against aspiration (which may be especially problematic in the toxicologic patient prone to vomiting)    •    To provide a route for pulmonary toilette    •    To facilitate patient and symptom control

history accidental poisonings Over dose Nonsuicidal Patient

history Accurate identification of ingestants is particularly important in the patient exposed to agents that have delayed onset of toxic effects, such as acetonitrile, which is metabolized to cyanide, or monoamine oxidase inhibitors

Focused Physical Examination/Toxidromes VITAL SIGNS NEUROLOGIC MANIFESTATIONS OF TOXINS DERMATOLOGIC MANIFESTATIONS OF TOXINS GASTROINTESTINAL MANIFESTATIONS OF TOXINS

Focused Physical Examination/Toxidromes Examples include the respiratory depression of barbiturate or opioid poisoning and the tachycardia and hypertension of poisoning with sympathomimetic agents. Characteristic “toxidromes” indicate the presence of agents with cholinergic, anticholinergic, sympathomimetic, and opioid effects. Less specific findings, such as nystagmus, myoclonus, asterixis, and tremor, also suggest various toxins. Characteristic odors suggest the presence of toxins, such as cyanide (almond odor) or ethchlorvynol (vinyl odor).

DECONTAMINATION Dermal decontamination is best accomplished with copious amounts of water. However, the use of water on skin contaminated with metallic sodium, metallic potassium, or phosphorus (white, yellow) may result in further skin injury owing to heat generation and explosive injury. Irrigation of phenol burns with low molecular weight polyethylene glycol is effective. Other therapies, such as topical calcium salts for hydrofluoric acid burns, may be indicated following initial water decontamination. Ocular decontamination can be accomplished with water or normal saline irrigation

Gastrointestinal Decontamination SYRUP OF IPECAC GASTRIC LAVAGE ACTIVATED CHARCOAL ALONE CATHARTICS OBSERVATION ALONE WHOLE BOWEL IRRIGATION THE BODY PACKER/BODY STUFFER PATIENT

activated charcoal primary method of gastrointestinal decontamination, and it should be administered within 1 hour of toxin ingestion whenever possible. Multiple doses of activated charcoal may be beneficial in patients ingesting life-threatening amounts of carbamazepine, dapsone, phenobarbital, quinine, theophylline bezoar

Laboratory Testing in Emergency Toxicology TOXICOLOGY SCREENS (3,000,000 toxin) SERUM QUANTITATION OF OVERDOSED DRUGS Electrocardiograms Radiology

DIAGNOSTIC TESTING Many toxic agents are not detected on routine screening, while false-positive results are commonly reported. Other tests, such as serum electrolytes, calculated anion gap, glucose, arterial blood gases, serum creatinine, and liver function tests, can assist in the indirect evaluation of the end-organ effects of a toxin. Electrocardiograms should be obtained in patients ingesting toxins known to produce cardiac dysrhythmias or conduction delays, or in significantly poisoned patients as an aid to the diagnosis of an unknown toxin.

Radiographs Routine radiographs may be indicated to evaluate potential adverse effects of toxins, such as pulmonary injury due to inhalation of chlorine gas or aspiration of a hydrocarbon. Routine abdominal radiographs may be unreliable for evaluation of toxins thought to be radiopaque MRI, CT, brain damage,

ANTIDOTES Antidote Indication for Use Antivenom (equine)  Crotalid (Crotalidae polyvalent antivenin) Crotalids: Rattlesnakes (Crotalus spp. and Sistrurus spp.), cottonmouth (Agkistrodon spp.), copperhead (Agkistrodon spp.)  Elapid Eastern (Micrurus fulvius fulvius) and Texas (Micrurus fulvius tenere) coral snakes Antivenom (Fab) * Crotalids Antivenom, latrodectus (equine) Black widow spider (Latrodectus spp.) Antivenom, loxosceles (rabbit) Brown recluse spider (Loxosceles reclusa) Antivenom, scorpion (goat) Scorpions (Centruroides spp.) Botulinum antitoxin (equine) Clostridium botulinum Calcium Calcium channel antagonists Hydrofluoric acid Hyperkalemia (except cardiac glycosides) Hypermagnesemia Hypocalcemia (e.g., ethylene glycol) Calcium disodium edetate Lead Cyanide antidote kit: Cyanide  Amyl nitrite    Sodium nitrite  Thiosulfate Deferoxamine Iron Dextrose Ackee fruit (hypoglycin) Insulin Sulfonylureas Other (e.g., salicylates, pentamidine) Digoxin-specific antibody fragments (Fab) Digoxin Digitalis Other cardiac glycosides, e.g., bufodienalides (Bufo toads) Oleander Dimercaprol Arsenic Mercury Ethanol Diethylene glycol Ethylene glycol Methanol Experimental: sodium monofluoroacetate Flumazenil Benzodiazepines Venlafaxine Folic acid/tetrahydrofolic acid (leucovorin) Methotrexate Fomepizole Glucagon Beta-adrenergic receptor antagonists Hyberbaric oxygen Carbon monoxide Experimental: carbon tetrachloride Cyanide, hydrogen sulfide Methylene blue Methemoglobin-producing agents N-Acetylcysteine Acetaminophen Experimental: carbon tetrachloride, chloroform, pennyroyal oil Naloxone, nalmefene, naltrexone Opioids Physostigmine Anticholinergic agents, e.g., diphenhydramine, Jimsonweed (Datura spp.), scopalamine Pralidoxime Organophosphates Protamine Heparin Pyridoxine Ethylene glycol (theoretical efficacy) Isoniazid Monomethylhydrazine mushrooms (Gyrometra esculenta) Sodium bicarbonate Myocardial sodium channel blockers, e.g., cyclic antidepressants, cocaine, norpropoxyphene, class Ia and Ic antidysrhythmics, piperidine phenothiazines (thioridazine, mesoridazine) Altered tissue distribution/enhanced elimination: chlorophenoxy herbicides, chlorpropamide, formic acid (methanol), methotrexate, phenobarbital, salicylates Neutralization: inhaled chlorine gas, hydrogen chloride, phosgene Succimer Vitamin K Anticoagulants, e.g., warfarin, long-acting anticoagulant rodenticides

Extracorporeal Removal of Drugs and Toxins Hemodialysis charcoal hemoperfusion Plasmapheresis exchange transfusion continuous ultrafiltration

DRUGS AND TOXINS COMMONLY REMOVED BY EXTRACORPOREAL THERAPY Barbiturates - hemoperfusion or hemodialysis Ethylene Glycol - hemodialysis Lithium - hemodialysis Methanol - hemodialysis Salicylates - dialysis, at toxic levels Theophylline - Hemoperfusion

COMPLICATIONS AND LIMITATIONS OF EXTRACORPOREAL REMOVAL OF TOXINS Vascular Access Hypotension Bleeding

Advanced Life Support in the Poisoned Patient (TOX ACLS) BASIC LIFE SUPPORT ADVANCED LIFE SUPPORT BRAIN DEATH AND ORGAN DONATION CRITERIA

Adult Basic Life Support Immediate recognition of sudden cardiac arrest (SCA) Activation of the emergency response system Early cardiopulmonary resuscitation (CPR) Rapid defibrillation With an automated external defibrillator (AED) Initial recognition and response to heart attack and stroke are also considered part of BLS.

Advanced Life Support in the Poisoned Patient (TOX ACLS) Standard supportive care for critically ill patients often follows the advanced cardiac life support (ACLS) algorithms published by the American Heart Association (AHA). Evidence suggests that standard supportive care may not be adequate for critically ill poisoned patients Synthetic or semisynthetic opioid poisoning may be more resistant to opioid antagonistsAs much as 10 mg of naloxone has been required for adequate reversal in rare cases

BASIC LIFE SUPPORT (poisoned patient) Prolonged Resuscitation good neurologic outcome has been reported in cases of severe poisoning requiring prolonged CPR that extended to periods of up to 3 to 5 hours

Adult Advanced Cardiovascular Life Support Continuous quantitative waveform capnography is recommended for confirmation and monitoring of endotracheal tube placement. Cardiac arrest algorithms are simplified and redesigned to emphasize the importance of high-quality CPR (including chest compressions of adequate rate and depth, allowing complete chest recoil after each compression, minimizing interruptions in chest compressions and avoiding excessive ventilation).

Adult Advanced Cardiovascular Life Support Atropine is no longer recommended for routine use in the management of pulseless electrical activity (PEA)/asystole. There is an increased emphasis on physiologic monitoring to optimize CPR quality and detect ROSC. Chronotropic drug infusions are recommended as an alternative to pacing in symptomatic and unstable bradycardia. Adenosine is recommended as a safe and potentially effective therapy in the initial management of stable undifferentiated regular monomorphic wide-complex tachycardia .

ADVANCED LIFE SUPPORT ( poisoned patient ) Hyperadrenergic States (Tachycardia and Hypertension) Bradycardias Ventricular Dysrhythmias (Tachycardia and Fibrillation) Pacing Hypertonic Saline and Systemic Alkalinization Potassium

Hyper adrenergic States (Tachycardia and Hypertension) physostigmine (Antilirium) is indicated for hemodynamically significant tachycardia associated with pure anticholinergic poisoning. Benzodiazepines such as diazepam or lorazepam are generally safe and effective for chest pain, hypertension, or tachycardia associated with drug-induced hyperadrenergic states. nitroglycerin and phentolamine have been shown to reverse cocaine-induced vasoconstriction, whereas labetalol had no effect and propranolol worsened it.

Bradycardias In the ACLS bradycardia algorithm, atropine, pacing, dopamine, epinephrine, and isoproterenol are recommended in sequence for hemodynamically significant or “symptomatic” bradycardia. In bradycardias due to severe poisoning by digoxin, calcium channel antagonists, or β-adrenergic receptor antagonists, atropine may be ineffective even in high doses In drug-induced, symptomatic bradycardia, many authors have cautioned that isoproterenol (a nonselective β-adrenergic receptor agonist) may induce or aggravate hypotension (β2 effect) and ventricular dysrhythmias (β1 effect In massive β-adrenergic receptor antagonist poisonings, very high-dose isoproterenol therapy has been effective ]Drug-induced, symptomatic bradycardia refractory to atropine is an indication for cardiac pacing (electrical).

Bradycardias In a case of severe insecticide poisoning (organophosphate or carbamate), approximately 20 g of atropine over 24 h was required Atropine cannot reverse the severe nicotinic effects seen with organophosphate insecticides (i.e., muscle paralysis and fasciculations), and pralidoxime will be required. Digoxin-specific Fab antibody fragments have been shown to be extremely effective therapy for severe digoxin and cardiac glycoside poisoning.

Ventricular Dysrhythmias (Tachycardia and Fibrillation) Magnesium has been recommended for polymorphic ventricular tachycardia, even when magnesium levels in the blood are normal polymorphic ventricular tachycardia and monomorphic ventricular tachycardia respond to lidocaine Hypokalemia is a risk factor for ventricular dysrhythmias and even with normal potassium levels, potassium supplementation has been recommended in torsades de pointes

Shock Vasopressor Agents Usual Starting Dose Amrinone 0.75–2.0 mg/kg SIVP Calcium 1–3 g SIVP Glucagon 5–10 mg IVP Insulin Pump or Glucose-Insulin-Potassium (GIK)  Glucose (D50W) 1 g/kg  Insulin (regular) 1.5 U/kg  Potassium chloride 10 mEq Isoproterenol 2–20 μg/min SIVP, slow intravenous push.

BRAIN DEATH AND ORGAN DONATION CRITERIA Electroencephalograms and neurologic examinations do not provide valid criteria for proof of brain death during acute toxic encephalopathy and can be applied only when drug levels are no longer toxic. In the presence of toxic drug levels, the only valid criterion for ascertaining brain death is the absence of cerebral blood flow

SUMMARY Utilization of standard AHA ACLS protocols for critically poisoned patients may not result in optimal outcomes. a more toxicology-oriented type of ACLS (TOX ACLS) may be effective. Elements of TOX ACLS not usually included in standard ACLS protocols include higher doses of standard drugs, nonstandard drugs (amrinone , calcium, esmolol , glucagon, glucose-insulin-potassium (GIK), metoprolol , phenylephrine , physostigmine , and sodium bicarbonate) and nonstandard techniques such as prolonged CPR and circulatory assist devices. Proper application of TOX ACLS techniques requires basic understanding of the pathophysiology of acute poisonings. Care of critically poisoned patients can be enhanced through consultation with a medical toxicologist or a regional poison information center

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