GENERAL MANAGEMENT OF POISONED PATIENTS

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

2. General Information • 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

3. toxic effect therapeutic effect increasing dose 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”

4. Lecture objectives • After this lecture, and further reading as required, students will be able to: • describe the manifestations of toxicity • Approach to the poisened patient • 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

5. Toxicology • 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.

6. Toxicokinetics • 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.

7. Toxicokinetics • 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.

8. Toxicokinetics • 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.

9. 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. • The most common routes of exposure in poisoning are inhalation, ingestion, and injection. • Toxic chemical reactions compromise cardiovascular, respiratory, central nervous system, hepatic, gastrointestinal (GI), and renal systems.

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

11. Drugs • 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.

12. Household cleaning products • 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.

13. Household cleaning products • 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.

14. Toxic fumes • 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.

15. 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

16. Substance Abuse and Overdose • 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.

17. 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.

18. Approach to the poisened patient • 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.

19. 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 sedative-hypnotic drugs.

20. 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 adrenoceptor-mediated vascular tone or cardiac arrhythmias.

21. 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.

22. 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.

23. 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.

24. 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.

25. ASSESSMENT • 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.

26. Triage • Triage is always the first step performed in the emergency department. • 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?

27. Initial management of the poisoned patient • 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.

28. Breathing 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.

29. Circulation • 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 arrhythmiasand fluid overload may result because of the heart’s inability to pump effectively.

30. 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

31. Every patients with altered mental status should receive a concentrated Dextrose. Adults are given 25g (50ml of 50% dextrose solution) i.v. Children 0.5g/kg(2ml/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.

32. History and Physical examination • 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.

33. 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

34. A.History • 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 • 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.

35. 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. • In some cases, family or police may need to search the patient’s home for clues. • Number of exposed persons may supply additional information.

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

37. Toxidrome • 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.

38. 1.Vital signs • 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.

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

40. CV system • 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.

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

42. 2.Eyes • 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.

43. Eyes • 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.

44. 3. Mouth • 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.

45. 4.Skin • 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.

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

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

48. muscular rigidity can be caused by anti-psychotic agents, serotonin syndrome and by strychnine. • Nystagmus and ataxia are typical of phenytoin, alcohol or other sedative intoxication.

49. CNS Examination • 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

50. Mentation • 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.