GENERAL MANAGEMENT OF POISONED PATIENTS Prepared by Prof

GENERAL MANAGEMENT OF POISONED PATIENTS Prepared by Prof. Dr. Yüksel KESİM Ondokuz Mayıs University Medical Faulty Department of Pharmacology 2014 -2015

General Information n n All chemicals have potential to be poisons if given a large enough dose Poisoning occurs when exposure to a substance adversely affects function of any organ system

Paracelsus (1493 -1541) ‘Grandfather of Toxicology’ "All things are poison and nothing is without poison, only the dose permits something not to be poisonous. " “The dose makes the poison” therapeutic effect increasing dose toxic effect 3

Lecture objectives n After this lecture, and further reading as required, students will be able to: • describe the manifestations of toxicity • Approach to the poisened patient n n n Toxidromes History, examination, Laboratory Studies and detective work İnitial menagement and spesialized treatment of poisining, including methods of supportive care, prevention of poison absorption, enhancement of elimination of poison and administration of antidotes

Toxicology n n n the study of the effect of poisons on the function of living systems. Toxicokinetic: denotes the absorption, distribution, excrection, and metabolism of toxines, toxic doses of therapeutic agents, and their metabolits. Toxicodynamics: is used to denote the injurious effects of toxic substances on vital function.

Toxicokinetics n Overdose of a drug can alter the usual pharmacokinetic processes, and this must be considered when applying kinetics to poisened patients, For example, dissolution of tablets or gastric emptying time may be slowed so that absorption and peak toxic effects are delayed.

Toxicokinetics n n Drugs may injure the epithelial barrier of the Gastrointestinal Tract(GIT) and thereby increase absorption. With a dramatic increase the concentration of drug in the blood, protein binding capasity may be exceeded, resulting in an increased fraction of free drug and grater toxic effect.

Toxicokinetics n If the plasma concentration is very high and normal metabolism is saturated, the rate of elimination may become fixed. This change is kinetics may markedly prolong the apperent serum half-life and increase the toxicity.

THE POISONED OR OVERDOSED PATIENT Poisonings and drug overdoses can cause quick physical and mental changes in a person. Bystanders usually are the ones who must initiate care and call a poison control center or emergency number. n The most common routes of exposure in poisoning are inhalation, ingestion, and injection. n Toxic chemical reactions compromise cardiovascular, respiratory, central nervous system, hepatic, gastrointestinal (GI), and renal systems. n 9

n n n Chemical agents that cause toxicity include: Drugs Insecticides/herbicides Plant toxins, Animal toxins Chemical weapons, Radioactive elements

Drugs n n Poisoning can occur in the health care environment when a medication normally given only by the subcutaneous or intramuscular route is given intravenously, or when the incorrect medication is injected. Poisoning by injection can also occur in the setting of substance abuse, as when a heroin addict inadvertently (without knowledge or intention) injects too much heroin.

Household cleaning products n n n Poisoning may result from the improper mixing of household cleaning products. The ingestion of poisons and toxins occurs in various settings and in different age groups. Poisoning in the home usually occurs when children ingest household cleaners or medicines. Improper storage of these items contributes to such accidents.

Household cleaning products n n Plants, pesticides, and paint products are also potential household poisons. Because of mental or visual impairment, illiteracy, or a language barrier, older adults may ingest incorrect amounts of medications.

Toxic fumes n Most exposures to toxic fumes occur in the home. Burning wood, gas, oil, coal, or kerosene produces carbon monoxide (CO). CO gas is colorless, odorless, tasteless, and nonirritating, which makes it especially dangerous.

n n Cellular hypoxia may occur in spite of adequate ventilation and oxygen administration when poising is due to carbon monoxide, cyanide, hydrogen sulfide, and other poisons that interfere with transport or utilization of oxygen. In such patients, cellular hypoxia is evident by the development of tachiycardia, hypotension, severe lactic asidosis, and ischemia

Substance Abuse and Overdose n n n Admission of most poisoned patients to a critical care unit is for an intentional or suspected suicidal overdose. As part of their histories, these patients frequently have mental illness, substance abuse problems, or both. Often, withdrawal symptoms complicate the assessment of potential toxidromes. A toxidrome is a group of signs and symptoms (syndrome) associated with overdose or exposure to a particular category of drugs and toxins. 16

n Commonly observed poisonings or drug overdoses are caused by (but certainly not limited to) carbon monoxide, salicylates, acetaminophen, nicotine, alcohol, heroin, marijuana, narcotic analgesics, benzodiazepines, tricyclic antidepressants, amphetamines, and cocaine. 17

Approach to the poisened patient n n n How does the poisoned patient die? Many toxins depress the Central Nervous System(CNS), resulting in coma. Patients under the influence of hallucinogens such as LSD may die in fights or falls from high places.

n n Comatose patients frequently lose their airway protective reflexes and their respiratory drive. Thus they may die as a result of airway obstruction by the flaccid tongue, aspiration of gastric contents into the tracheobronchial tree, or respiratory arrest. These are the most common causes of death due to overdose of narcotics and sedativehypnotic drugs.

n Cardiovascular toxicity is also frequently encountered in poising. Hypotension may be due to depression of cardiac contractility; peripheral vascular collaps due to blockade of alpha adrenoceptormediated vascular tone or cardiac arrhythmias.

n n Hypothermia or hyperthermia due to exposure as well as the temperature dysregulating effects of many drugs can also produce hypotension. Hyperthermia may result from sustained muscular hyperreactivity and can lead to muscle breakdown and myoglobinuria, renal failure, lactic asidosis, and hyperkalemia.

n Letal arrhythmias such as ventricular tachycardia and fibrillation can occur with overdoses of many cardioactive drugs such as epinephrine, amphetamines, cocaine, digitalis and theophylline; and drugs not usually concidered cardioactive, such as tricyclic antidepressants, antihistamines, and some opioid analogs.

n n n Seizures, muscular hyperactivity, and rigidity may result in death. Seizures may cause pulmonary aspiration, hypoxia, and brain demage. Drugs and poisons that often cause seizures include antidepressants, isoniazid, diphenhydramine, cocain, and amphetamines.

n n n Some organ system damage may occur after poisoning and is sometimes delayed in onset. Pulmonary fibrosis may begin sevral days after ingestion. Massive hepatic necrosis due to poisoning by acetaminophen or certain mushrooms result in hepatic encephalopaty and death 48 -72 hours or longer ingestion.

ASSESSMENT n n A health care facility’s systematic approach to the assessment of the poisoned or overdosed patient includes performing triage, A) Obtaining the patient’s history, B) Performing a physical examination, and C) Conducting laboratory studies. 25

Triage is always the first step performed in the emergency department. n Two essential questions to be considered in the triage evaluation are: 1. Is the patient’s life in immediate danger? 2. Is the patient’s life in potential danger? n 26

Initial management of the poisoned patient n n If the patient’s life is in immediate danger, the goals of immediate treatment are patient stabilization and evaluation and management of airway, breathing, circulation and dextrose (ABCDs). Stabilization; First the airway should be cleared of vomitus or any other obstruction and an oral airway or nasotracheal or endotracheal intubation may be necessary to adequately maintain and protec the patient’s airway. For many patients is sufficient to move the flaccid tongue out of the airway. 27

Breathing should be assesed by measuring arterial blood gases. Mechanical ventilation may be necessary to support the patient. Many drugs and toxins, such as heroin, depress the respiratory drive. Patients therefore may require ventilator assistance until the drugs or toxins are eliminated from the body.

Circulation n n should be assesed by continious monitoring of pulse rate, blood pressure, urinary output and evaluation of peripheral perfusion Some toxic drug ingestions impair myocardial contractility, cause cardiac conduction delays and arrhythmias and fluid overload may result because of the heart’s inability to pump effectively.

n n In these cases, fluid balance needs to be carefully controlled. Invasive monitoring (e. g. , central venous pressure, pulmonary artery catheter, Foley catheter with urometer) and drug therapy may be necessary to prevent or minimize complications such as pulmonary edema 30

n n Every patients with altered mental status should receive a concentrated Dextrose. Adults are given 25 g (50 ml of 50% dextrose solution) i. v. Children 0. 5 g/kg(2 ml/kg of 25% dextrose). Hypoglycemic patients may appear to be intoxicated , and there is no rapid and reliable way to distinguish them from poisened patients.

History and Physical examination n n Once the essantial initial ABCD interventions have been instituted , one can begin a more detailed evaluation to make a spesific diagnosis. This includes gathering any available history and performing a toxicologically oriented physical examination.

n The history of the drug(s) or toxin(s) involved may not be reliable or even known, especially when patients are found unconscious or have attempted suicide 33

A. History n A history of the patient’s exposure provides a framework for managing the poisoning or overdose. Need to obtain as much info as possible about exposure n Key points include identifying the drug(s) or toxin(s), type of exposure, the time and duration of the exposure, amount or dose, empty bottles or containers, houshold products, over the counter drug (OCD), smells or suicide not.

History First aid treatment given before arrival at the hospital, allergies, and any underlying disease processes or related injuries. This information may be obtained from the patient, family members, friends, rescuers, or bystanders. n In some cases, family or police may need to search the patient’s home for clues. n Number of exposed persons may supply additional information. n

B. Physical Examination n n Check clothing for objects or substances A quick but thorough physical examination is essential. These include vital signs and temperature, eyes and mouth, skin, abdomen and nervous system.

Toxidrome n n A toxidrome is a group of signs and symptoms associated with overdose or exposure to a particular category of drugs and toxins. Recognizing the presence of a toxidrome may help identify the toxin(s) or drug(s) to which the patent was exposed, and the crucial body systems that may be involved.

1. Vital signs n Careful evaluation of vital signs (blood pressure, pulse, respirations, and temperature) is essential in all toxicologic emergencies. The critical or potentially critical patient’s vital signs and temperature are measured frequently to track changes indicating additional problems.

Lungs n n Wheezing? Rapid respirations are typical of salicylates, CO, and other toxines that produce metabolic acidosis or cellular asphyxia.

CV system n n n rhythm, rate, regularity Hypertension and tachycardia are typical with amphetamines, cocain and anticholinergic drugs. Hypotension and bradycardia are characteristic features of overdose with calcium channel blockers, beta blockers, clonidine, and sedative hipnotics. Hypotension with tachycardia is common with tricyclic antidepressants, vasodilators and beta agonists.

n n Hyperthermia may be associated with sympathomimetics, anticholinergic, salicylates, and drugs producing seizures or muscular rigidity. Hypothermia can be caused by any CNS depressant drug.

2. Eyes n n n The eyes are a valuable source of toxicologic information. Exam eyes for pupils size, nystagmus, reactivity, increased lacramaiton Miosis is typical of opioids, cholinesterase inhibitors (e. g. Organophosphate insecticides), and deep coma due to sedative drugs.

Eyes n n Mydriasis is common with amphetamines, cocaine, LSD, atropine and other anticholinergic drugs. Horizontal nystagmus is characteristic of intoxication with alcohol and other sedative drugs. The presence of both vertical and horizontal nystagmus is strongly suggestive of phencyclidine poising.

3. Mouth n n The mouth may show signs of burns due to corrosive substances, or soot from smoke inhalation. Typical odors of alcohol or ammonia may be noted.

4. Skin n n Exam skin for hot, and dry, flushing, bruising, cyanosis, Cyanosis may be caused by hypoxemia or by methemoglobinemia. Icterus may suggest hepatic necrosis. Excessive sweeting occurs with organophosphates, nicotine and sympathomimetic drugs.

5. Abdomen n Hyperactive bowel sounds, tenderness abdominal cramping and diarrhea are common in poisoning with organophosphatase, iron, arsenic, teophylline, Amanita muscaria and phalloides.

6. Nervous system n n n A careful neurologic examination is essantial Assess general appearance n Agitation or confusion reflexes, muscle tone coordination, cognition Focal seizures or motor deficits suggest a structural lesions. Extremities: fasiculations, tremor,

n n muscular rigidity can be caused by antipsychotic agents, serotonin syndrome and by strychnine. Nystagmus and ataxia are typical of phenytoin, alcohol or other sedative intoxication.

CNS Examination n Physiologic excitation – anticholinergic, sympathomimetic, or central hallucinogenic agents, drug withdrawal Physiologic depression – cholinergic (parasympathomimetic), sympatholytic, opiate, or sedative-hypnotic agents, or alcohols Mixed state – polydrugs, hypoglycemic agents, tricyclic antidepressants, salicylates, cyanide

Mentation n n Many factors can affect the patient’s mental status. Hypoglycemia and hypoxemia; that can be life-threatening but easily addressed by administering oxygen and IV dextrose until laboratory results are available.

C. Laboratory Studies n n Relevant clinical laboratory data are vital to the assessment of the poisoned or overdosed patient. Tests that provide clues to the agent(s) taken by the patient include arterial blood gases (ABGs), electrolytes, serum osmolality tests, urinalysis, complete blood count, electrocardiography , imaging findings and hepatic function.

Acid–base balance and electrolyte homeostasis n Electrolyte abnormalities and metabolic acidosis frequently occur and may require serial measurements of electrolytes and arterial blood gases (ABGs), and other specific laboratory tests.

1. Arterial Blood Gases (ABGs) n n n Hypoventilation will result in an elevated PCO 2 (hypercapnia) and a low PO 2(hypoxia). The PO 2 may also be low with aspiration pneumonia or drug induced pulmonary edema. Signs of inadequate ventilation or oxygenation include cyanosis, tachycardia, hypoventilation, intercostal muscle retractions, and altered mental status.

2. Electrolytes n n Acute poisoning can cause an imbalance in a patient’s electrolyte levels, including sodium, potassium, chloride, bicarbonate, carbon dioxide, magnesium, and calcium. Serum level measurements are also available for carbamazepine, iron, ethanol, lithium, aspirin, and valproic acid and may be obtained if these agents are suspected in an overdose.

n n n The anion (A negatively charged ion) gap represents the difference between unmeasured anions and cations (An ion or group of ions having a positive charge ) in the blood. Anion gap = (Na + K) - (HCO 3 + Cl) The normal value for the anion gap is approximately 8 to 16 m. Eq/L.

n n An anion gap that exceeds the upper normal value can indicate metabolic acidosis caused by an accumulation of acids in the blood. Drugs, toxins, or medical conditions that can produce an elevated anion gap include iron, isoniazid (INH), lithium, lactate, carbon monoxide, cyanide, methanol, metformin, ethylene glycol, salicylates, hydrogen sulfide, , diabetic ketoacidosis, uremia, seizures, and starvation. 56

3. Serum osmolality n n n The osmolal gap is the difference between the measured osmolality and the calculated osmolality. The calculated osmolality is derived using laboratory values for the major osmotically active substances in the serum, such as sodium, glucose, and blood urea nitrogen (BUN). Like the anion gap, it is a simple, costeffective tool for evaluating the poisoned patient for certain drugs or toxins

n n n The calculated serum osmolality can be estimated from the following formula; 2 X Na(meq/L) + Glucose(mg/dl) /18 + BUN(mg/dl) / 3 This calculated value is normally 280 -290 m. Osm/L

Diagnostic tools include the following 4. Electrocardiography: can provide evidence of drugs causing arrhythmias or conduction delays (e. g. , tricyclic antidepressants).

5. Radiology Many substances are radiopaque, or can be visualized using a contrast-enhanced computed tomography (CT) scan (e. g. , heavy metals, button, batteries, some modified-release tablets or capsules, aspirin concretions, cocaine or heroin containers). Chest radiographs provide evidence of aspiration and pulmonary edema.

6. Renal function tests n n Some toxines have direct nephrotoxic, in other cases renal failure is due to shock or myoglobinuria. BUN and creatinine levels should be measured and urinanalysis performed.

7. Toxicology screens A toxicology screen is a laboratory analysis of a body fluid or tissue to identify drugs or toxins. Saliva, spinal fluid, and hair may be analyzed, blood or urine samples are used more frequently. Each screen tests for specific drugs or agents. n The sample must also be properly collected, and there must be a laboratory near enough to obtain results quickly.

n n The test sample must be collected while the drug or toxin is in the body fluid or tissue used for testing. For example, cocaine is a rapidly metabolized drug; however, its metabolite, benzoylecgonine, can be detected in the urine for several hours after cocaine use. 63

n n MANAGEMENT Management of the poisoned or overdosed patient seeks to prevent absorption of and further exposure to the agent. Treatment begins with first aid at the scene and continues in the emergency department and often the intensive care unit (ICU). Advanced general management involves further steps to prevent absorption and enhance elimination of the agent. For instance, antidotes, antivenins (the treatment of venomous bites or stings) or antitoxins may be administered. 64

General- management n n I. provision of supportive care II. prevention of poison absorption III. enhancement of elimination of poison IV. administration of antidotes

I. Supportive care n n n Vital signs, mental status, and pupil size cardiac monitoring, ECG Protect airway Intravenous access cervical immobilization if suspect trauma Rule out hypoglycaemia

II. Preventing absorption n n Decontamination; A) dermal, B) ocular, C) inhalation, and D) ingestion exposures follow.

A) DERMAL EXPOSURE n n Generally; achieved by; undressing patients and washing them thoroughly with copious amounts of lukewarm water for 15 to 30 minute All towels and clothing should be put into hazardous waste bags

n n Some toxins may require further decontamination. For example, three separate soap and water washings or showers are recommended to decontaminate organophosphate pesticides (e. g. , Malathion or Diazinon). Protective clothing should be worn to reduce the risk for toxicity while handling contaminated clothing or assisting with skin decontamination. 69

B) Eyes n n Many substances can accidentally splash into the eyes. When this happens, the eyes must be flushed to remove the agent. Immediate irrigation with lukewarm water or normal saline is recommended. Continuous flooding of the eyes with a large glass of water or low-pressure shower should be done for 15 minutes.

n n n The patient should blink the eyes open and closed during the irrigation. If necessary, the p. H of the eyes can be tested. If the p. H is abnormal, irrigation should continue until the p. H normalizes. An ophthalmologic examination is needed when ocular irritation or visual disturbance persists after irrigation.

C) INHALATION EXPOSURE n n n A victim of an inhalation exposure should be moved to fresh air as quickly as possible. The responder must also protect himself or herself from the airborne toxin. Further evaluation is needed if the patient experiences respiratory irritation or shortness of breath.

D) GI Decontamination n n Three general methods involve removing toxin from stomach via the mouth, binding it inside gut lumen, or mechanically flushing it through GI tract Each method has benefits and risks

Milk or water dilutes ingested irritants such as bleach or caustics such as drain cleaner. After such an ingestion, adults or children should drink milk or water (children based on their size). n Further evaluation is necessary after dilution if there is mucosal irritation or burns. n

n n Because of the risk of aspiration, ingestions should not be diluted when they are accompanied by seizures, depressed mental status, or loss of the gag reflex. Again, neutralization is not used because of the risk of thermal burn.

Gastrointestinal Decontamination n n 1. Vomiting, 2. Gastric lavage, 3. adsorbents (is the adhesion of molecules of gas, liquid, or dissolved solids to a surface), 4. cathartics, and 5. whole-bowel irrigation are used to prevent absorption toxins.

1. Induced Vomiting Ipecac n Risk of aspiration Emesis: achieved by using syrup of ipecac n n n Dosing: 15 ml for 1 -12 years old and 30 ml for adults; may repeat once if no emesis in 12 hr 90% vomit within 20 minutes of first dose and 97% vomit with second dose Usually 3 -5 episodes of emesis and resolve in two hours; if protracted emesis occurs consider toxin as etiology

Ipecac con’t n n n Use of Ipecac very limited Contraindications: ingestions with potential for change in mental status, active or prior vomiting, caustic ingestion, toxin with more pulmonary than GI toxicity (hydrocarbons), ingestion of toxins with potential for seizures The American Academy of Pediatrics no longer recommends the use of emetics (such as syrup of ipecac) for GI decontamination.

2. GASTRIC LAVAGE Fluid (usually normal saline) is introduced into the stomach through a large-bore orogastric tube and then drained in an attempt to reclaim part of the ingested agent before it is absorbed. n A small-bore nasogastric tube is ineffective for lavage because particulate matter such as tablets or capsules are too large to pass through the tube. If airway protection is necessary, the patient should be intubated before lavage begins. n

Orogastric lavage con’t n n n Contraindications: Not in unconscious patient unless intubated (risk aspiration) caustic ingestion or hydrocarbons with a high aspiration potential, airway integrity not secured, more toxic to lung than GI Because of the associated risks and the lack of clear evidence supporting its use, gastric lavage should be used only if the patient has ingested a life-threatening amount of a substance and the procedure is undertaken within an hour of the ingestion.

GASTRIC LAVAGE n n Complications: insertion into trachea, esophageal or gastric perforation, decreased O 2, pulmonary aspiration, electrolyte imbalance, tension pneumothorax, and hypothermia (when cold lavage solutions are used). Charcoal should be used before withdrawal of tube

GASTRIC LAVAGE n The contents of the stomach can then be collected for drug or toxin identification. n n n Drug removal range from 35 -56%. Indicated if in 1 hr of ingestion. For the lavage, the patient is positioned in the left. lateral decubitus position, with the head lower than the feet.

3. ADSORBENTS n n n An adsorbent is a solid substance that has the ability to attract and hold another substance to its surface (“to adsorb”). Activated charcoal is an effective nonspecific adsorbent of many drugs and toxins. Activated charcoal adsorbs, or traps the drug or toxin to its large surface area and prevents absorption from the GI tract.

ADSORBENTS n n Activated charcoal is a fine, black powder that is given as a slurry with water, either orally or by nasogastric or orogastric tube, as soon as possible after the ingestion. Commercially available activated charcoal products may be mixed with 70% sorbitol to decrease grittiness (composed of or covered with relatively large particles, increase palatability (Acceptable to the taste) , and serve as a cathartic. The usual dose that is given is one 50 -g bottle. 84

Activated Charcoal • • n n binds non-specifically timing - use within 1 hour Safety proven in adults and children Dose 1 g/kg

Activated Charcoal n n n Indications: any drug known to absorb it or after unknown ingestions. Activated charcoal is used cautiously in patients with diminished bowel sounds and is contraindicated in patients with bowel obstruction. Should not be given if esophageal or gastric perforation suspected or emergent endoscopy possibly needed. Complications rare; aspiration or impaction possible

Drugs/Toxins Well Adsorbed by Activated Charcoal ■ Acetaminophen ■ Amphetamines ■ Antihistamines ■ Aspirin ■ Barbiturates ■ Benzodiazepines ■ Beta blockers ■ Calcium channel blockers ■ Cocaine ■ Opioids ■ Phenytoin ■ Theophylline ■ Valproic acid Drugs/Toxins Not Well Adsorbed by Activated Charcoal ■ Acids ■ caustic alkalis ■ Alcohols ■ Iron ■ Lithium ■ Metals cyanide mineral acids, organic solvents, 87

4. CATHARTICS n n A cathartic is a substance that causes or promotes bowel movements. In theory, cathartics decrease the absorption of drugs and toxins by speeding their passage through the GI tract, thereby limiting their contact with mucosal surfaces. 88

Cathartics n n Osmotic cathartic usually given with activated charcoal 70% sorbitol (1 g/kg) or 10% Mg citrate Shown to decrease transit time of activated charcoal No definitive clinical human data suggest that a cathartic limits toxins bioavailability.

5. WHOLE-BOWEL IRRIGATION n The goal of whole-bowel irrigation is to give large volumes of a balanced electrolyte solution rapidly (1 to 2 L/hour) to flush the patient’s bowel mechanically without creating electrolyte disturbances.

n n n Commercial products used in whole-bowel irrigation include Go. LYTELY and Colyte. Both products are dispensed (To prepare and give out ) as powders and are given after adding water. Whole-bowel irrigation is contraindicated in the patient with bowel obstruction or perforation. 91

Whole-Bowel Irrigation n Common indications: Heavy metals, Iron, Lithium, n Sustained or delayed release formulations End point is clear rectal effluent n Antiemetic frequently required n Avoid phenergan (slows gut motility) n n Contraindications: absent bowel sounds or obstruction Complications: bloating, cramping, rectal irritation

n As a result, absorption is delayed, and the development of toxic effects, such as hypokalemia, metabolic acidosis, and respiratory alkalosis, may not be observed for several hours. 93

III. Enhanced Elimination of the Drug or Toxin n The absorption rate, body distribution, metabolism, and elimination must be considered when choosing methods to eliminate the drug or toxin from the body.

There are six methods of enhanced elimination: 1. Multiple-dose activated charcoal 2. Alteration of urine p. H 3. Chelation 4. Hemodialysis 5. Hemoperfusion 6. Hyperbaric oxygenation (HBO) therapy

1. Multi-Dose Charcoal n n One dose usually sufficient Indications for multi-dose activated charcoal: ingestion of large doses, substances that slow release toxins, toxins that slow gut function, toxins with enteroenteric circulation, repetitive doses useful to enhance the elimination of certain drugs (eg, theophylline, phenobarbital, carbamazepine, valproic acide, aspirin)

MULTIPLE-DOSE ACTIVATED CHARCOAL n n n Repeat dose is 0. 25 -0. 5 g/kg Multiple-dose activated charcoal is given orally, by nasogastric tube, or by orogastric tube every 2 to 6 hours. Complications of multipledose activated charcoal include aspiration and bowel obstruction.

2. ALTERATION OF URINE p. H n Alkalinization: Alkalinizing the patient’s urine enhances excretion of drugs that are weak acids by increasing the amount of ionized drug in the urine. n This form of enhanced elimination is also termed ion trapping. Alkalinization achieved by IV dose of bicarb at 1 -2 m. Eq/kg, followed by intermittent boluses or continuous bicarb drip for urine p. H 7. 5 -8. 0

n n n Used to eliminate acidic drug that mainly excreted by the kidney eg salicylates overdose. Complications of alkalinization include cerebral or pulmonary edema and electrolyte imbalances. Need expert monitoring

Acidification of Urine n n Urine acidification is no longer recommended because of low drug clearance and the risk of complications such as rhabdomyolysis. Rhabdomyolysis is the breakdown of muscle fibers resulting in the release of muscle fiber contents into the circulation. Some of these are toxic to the kidney and frequently result in kidney damage. Can somewhat enhance elimination of amphetamines, phencyclidine, and some other drugs.

3. CHELATION Chelation involves the use of binding agents to remove toxic levels of metals from the body, such as mercury, lead, iron, and arsenic. Examples of chelating agents are dimercaprol (BAL in oil), calcium disodium edetate (EDTA), and deferoxamine. n

4. HEMODIALYSIS n Hemodialysis is the process of altering the solute composition of blood by removing it from an artery, diffusing it across a semipermeable membrane (between the blood and a salt solution), then returning it into a vein.

Hemodialysis n n It is used in moderate to severe intoxications to remove a drug or toxin rapidly when more conservative methods (e. g. , gastric lavage, activated charcoal, antidotes) have failed or in patients with decreased renal function. Hemodialysis requires consultation with a nephrologist and specially trained nurses to perform the procedure and monitor the patient.

Hemodialysis n n n Drug should be dialyzable. Low molecular weight, low protein binding, and water solubility are factors that make a drug or toxin suitable for hemodialysis. may also be used temporarily or as long term if the kidneys are damaged due to the overdose. Dialysis reserved for specific toxins: salicylates, methanol, lithium, theophylline, amanita (mushrooms)

Dialysis con’t n n n Benefits: removal of toxins already absorbed by gut, ability to remove parent compound active metabolite, Dialysis rarely contraindicated No dialysis for small children, exchange transfusion should be considered

5. HEMOPERFUSION n n Hemoperfusion removes drugs and toxins from the patient’s blood by pumping the blood through a cartridge of adsorbent material, such as activated charcoal. An advantage of hemoperfusion over hemodialysis is that the total surface area of the dialyzing membrane is much greater with the hemoperfusion cartridges.

HEMOPERFUSION As in hemodialysis, drugs that have high tissuebinding characteristics and a large volume distributed outside the circulation are not good candidates for hemoperfusion because little drug is found in the blood. n Although rarely used in the poisoned and overdosed population, hemoperfusion has been used successfully in patients experiencing a theophylline overdose

6. HYPERBARIC OXYGENATION THERAPY (HBO) In HBO therapy, oxygen is administered to a patient in an enclosed chamber at a pressure greater than the pressure at sea level (e. g. , 1 atmosphere absolute). This therapy has been used in carbon monoxide and methylene chloride poisonings (methylene chloride is metabolized to carbon monoxide in the body). n

n n Complications of HBO therapy include pressure-related otalgia (ear pain), sinus pain, tooth pain, and tympanic membrane rupture. anxiety, convulsions, and tension pneumothorax also have been observed in patients receiving HBO therapy.

IV. Antidotes (Antitoxins) and Antagonists), n n n In pharmacology, an antagonist is a substance that counteracts the action of another drug. Although the general public often believes there is an antidote for every drug or toxin, the opposite is closer to the truth. There are, in fact, very few antidotes.

Antitoxins neutralize a toxin. For instance, botulism(food poisoning from ingesting botulin)(potent bacterial toxin) produced by the Clostridium botulinum that causes botulism; can be used as a bioweapon) n 111

n n n Antivenins are antitoxins that neutralize the venom of the offending snake or spider. Antitoxin trivalent (equine) is available through the Centers for Disease Control and Prevention to counteract the effects of botulism. There are several antitoxins; each is active against a specific venom. 112

Continuous Patient Monitoring n n Seriously poisoned or overdosed patients may require continued monitoring for hours or days after exposure. Physical examination, the use of diagnostic tools, and careful assessment of clinical signs and symptoms provide information about the patient’s