POISONING

1. POISONING

2. Epidemiology • 99% of ingestions by children under 6 are unintentional. • Approximately 40% of ingestions reported to the poison center by adolescents are intentional. • Approximately 56% of adolescent ingestions are by females.

3. Physiologic Differences • Blood brain barrier still more permeable to toxicologic substances until around 4 months. • toxicity noted with smaller doses than expected. • Higher metabolic demands. • Decreased ability to glucuronidate in the infant period. Second trimester pregnancies that were terminated showed only 10% activity of the cytocrome P-450 system. • between ages 2-4 years that glucuronidation is equivalent to adults. • Decreased glycogen stores.

4. Physiologic Differences • Increased body surface area can lead to thermoregulatory issues. • Children reside lower to the ground. This puts them at higher risk for ingesting compounds heavier than air. Often adults will NOT have the same exposure. • Inability to avoid hazards – they do not read warning labels or “Do Not Enter” signs.

5. ANTIDOTES • A common antidote is N-acetylcysteine (Mucomyst), which is used to neutralize acetaminophen, paracetamol.Acetaminophen, in normal doses, is one of the safest medications known, but after a massive overdose, the liver is damaged, and hepatitis and liver failure develop • Calcium Disodium EDTA treats lead poisoning

7. Pesticides • Specifically organophosphates and carbamates. • They work by inhibiting acetylcholinesterase. • Present with cholinergic symptoms

8.  The mechanism of toxicity is the inhibition of acetylcholinesterase, resulting in an accumulation of the neurotransmitter acetylcholine and the continued stimulation of acetylcholine receptors. The standard treatment consists of reactivation of the inhibited acetylcholinesterase with an oximeantidote and reversal of the biochemical effects of acetylcholine with atropine

9. Cholinergic Symptoms

10. Nicotinic Symptoms • Remember the days of the week ! • Mydriasis • Tachypnea • Weakness • Tachycardia • Fasiculations • Pediatric patients tend to present with a predominance of nicotinic symptoms!!!

11. First Aid Treatment of Pesticide Poisoning: General Principles • TERMINATE EXPOSURE by removing the person from thescene of contamination. Avoid further skincontact and/or inhalation of fumes or dust. • REMOVE CONTAMINATED CLOTHING quickly and completely,includingfootwear • REMOVE PESTICIDES FROM SKIN, HAIR AND EYES by usinglarge quantities of water. Pay particular attention to thewashing of the eyes, hold eyelids apart and rinse thoroughly for at least 10 minutes

12. 33 Swallowed Pesticide Induce vomiting when the chemical swallowed is highly toxicand would likely prove fatal and if medical assistance is not readily available. If the person is unconscious, the doctor will put a flexible, soft, plastic tube into the windpipe to protect the person from suffocating in his or her own vomit and to provide artificial breathing (intubation). Activated charcoal acts as a "super" absorber of many poisons, the poison cannot get absorbed into the bloodstream.

13. Treatment • Atropine 0.02 mg / Kg IV. Repeat as needed and titrate to respiratory secretions. It will likely take massive doses!! • Pralidoxime (2-Pam) 20-40 mg / Kg bolus followed by 10-20 mg / Kg /hour infusion. • Remember to send RBC and Plasma Cholinesterase levels upon arrival and daily.

14. Mushroom Poisoning Classification • according to the toxic effects of mycotoxins → there are a few syndromes caused by certain mushrooms • hepatotoxic syndromes • death cap (Amanita phalloides) • destroying angel (Amanita virosa) • spring amanita (Amanita verna) • luggies (e. g., Gyromitra esculenta) • little poison parasol mushrooms (Lepiota spec.) • Galerina spec. • nefrotoxic syndrome • Cortinarius spec.; e. g., web-cap (Cortinarius bulbosus)

15. neurotoxic syndromes • cholinomimetic (muscarinic) • some forms of fly agaric intoxication (Amanita muscaria) and panther cap intoxication (Amanita pantherina) • Inocybe spec.; e. g., fibrecap (Inocybe erubescens) • Clitocybe spec.; e. g., tawny funnel cap (Clitocybe flaccida) • cholinolytic(mycoatropine) • some forms of fly agaric intoxication (Amanita muscaria) and panther fungus intoxication (Amanita pantherina) • mixed syndromes • gastrointestinal dyspetic syndromes • gastric dyspepsia syndromes – satan´s boletus (Boletus satanas) • gastric-bowel dyspepsia syndromes • Scleroderma spec.; e. g., earthball (Scleroderma citricum) • Russula spec.; e. g., the sickener (russulas) (Russula emetica) • Lactarius spec.; hazel milkcap (Lactarius pyrogalus) • bowel dyspepsia syndromes – Ramaria spec.; e. g., beech ramaria (Ramaria botrytis)

16. vasotoxic syndrome • Coprinus spec.; e. g., common ink-cap (Coprinus atramentarius) • hallucinogenic syndrome • magic mushrooms (Psilocybe) • fly agaric (Amanita muscaria)

17. Amanita phalloides • symptoms • 6 – 24 hours (approx. 10 – 12 hours) • between the consummation and occuring symptoms • cruel abdominal pain, malaise, vomiting, profound diarrhoea (blood can be present) • fever, tachycardia, hyperglycemia, dehydration, electrolyte imbalance • latency phase (24 hours) • symptoms remit during water and electrolytic balance improving • subclinic elevation of serum transaminases • hepatorenal icteric phase (in 3 – 4 days) • fuzziness, delirium, hypoglycemia, coma, exitus in 1 week • complications • coagulopathy, metabolic acidosis, hemorrhage, sepsis, renal failure

19. Treatment • gastric lavage • up to 36 hours after consummation • repeated big doses of activated carbon • 1 gramm/1 kilogramm every 2 – 4 hours • block amatoxins and their enterohepatic cycle • water and electrolyte imbalance correction • save for glomerular filtration • danger of the brain edema! • antidote: silibinin(Legalon SIL) • start the admistration as soon as possible (for 3 – 5 days, till transaminaseachieve the normal serum level, the administration can be terminated even after 1 day use when misdiagnosed) • decreases the hepatic content of amatoxins • blocks the trasport system for amatoxins (into the hepatic cells) → prevention and diminishing of necrosis • stimulates hepatic cell RNA-polymerase and hepatic metabolism • stabilizes extra- and endoplasmatic membranes • regeneration of hepatocytes

20. antidote of the second choice: acetylcysteine (ACC INJEKT) • if silibinin is not available • for 3 days • benzylpenicilline • its administration is not recommended more (for unclear benefit) • complex and intensive supporting care! • central venous pressure monitoring • fluid resuscitation • intensive supporting care in hepatorenal failure and ecephalopathy (glucose, K1 vitamine, fresh frozen plasma in coagulopathy, lactulose) • liver transplantation, indications • severe prognosis • prothrombine time less than 20% of the normal value without any improvement after the third day • increasing creatinine level with no reactions after rehydration (in 4 days) accompanied by bilirubin level elevation

21. Muscarinic Syndromes Due To Mushroom Poisoning: Inocybe spec., Clinocybe spec. • symptoms • latency phase (very short, sometimes the symptoms occur during the meal) • muscarinic symptoms and others • sweating, salivation, lachrymation, miosis, colics, diarrhoea, hypotension, bronchoconstriction • treatment • gastric lavage • activated carbon • atropine • symptomatic treatment (and supporting care)

22. Gastrointestinal Dyspeptic Syndromes: Clitocybe Spec., yellow coral fungus (Ramaria), satan´s boletus (Boletus satanas), Scleroderma Spec. • after consuming also of unsufficiently cooked or bad stored mushrooms • symptoms • vomiting, diarrhoea • treatment • activated carbon • symptomatic treatment, supporting care

23. Hallucinogenic Syndromes: Magic mushrooms (Psilocybe) • symptoms • mydriasis, elevated heart rate and blood pressure, sweating, tremor • hallucinations • acoustic, visual • changed perception of the reality, emotions, mood, desorientation, fuzziness • danger of suicide!!! • treatment • activated carbon • sedatives (remember the risk of suicide!) • in long-term abuse averse effects on the personality and psyche! • hallucinogenic syndromes can also be caused by fly agaric (Amanita muscaria) intoxication

24. ALCOHOL POISONINGThe Stages of Intoxication • 50 mg/dL: Loss of emotional restraint, vivaciousness, feeling of warmth, flushing of skin, mild impairment of judgment • 100 mg/dL: Slight slurring of speech, loss of control of fine motor movements (such as writing), confusion when faced with tasks requiring thinking, emotionally unstable, inappropriate laughter • 200 mg/dL: Very slurred speech, staggering gait, double vision, lethargic but able to be aroused by voice, difficulty sitting upright in a chair, memory loss, vomiting • 300 mg/dL:Stuporous, able to be aroused only briefly by strong physical stimulus (such as a face slap or deep pinch), deep snoring • 400 mg/dL: Comatose, not able to be aroused, incontinent (wets self), low blood pressure, irregular breathing • 500 mg/dL: Death possible, either from cessation of breathing, excessively low blood pressure, or vomit entering the lungs without the presence of the protective reflex to cough it out

25. Intoxicated people often receive IV fluids and B complex vitamins for dehydration (alcohol is a diuretic and increases urine output) and as a precaution or treatment for vitamin deficiency. • In severe cases - those of severe stupor and coma - the person should be intubated (a breathing tube placed in the patient's airway) to support respirations (which may stop spontaneously) and to protect the lungs from filling with vomit/secretions. • Intubation involves placing a short, flexible plastic tube into the windpipe (trachea) below the vocal cords and connecting the tube to a respirator machine. The tip of the tube has a small donut-shaped balloon around it, which is inflated to seal the end of the tube to the inside of the windpipe. This accomplishes two things: • It prevents the air from the respirator from leaking out into the mouth instead of going into the lungs. • It provides a protective seal so that a large amount of vomit in the mouth is prevented from entering the lungs where it could cause damage and possible suffocation.

26. Hemodialysis is frequently required in patients with significant methanol ingestions.[13, 17] Indications for hemodialysis include (1) arterial pH < 7.10, (2) a decline of >0.05 in the arterial pH despite bicarbonate infusion, (3) pH < 7.3 despite bicarbonate therapy, (4) rise in serum creatinine level by 90 mmol/L

27. Signs and symptoms • The peripheral autonomic nervous system, central nervous system and the heart are the main systems that are affected following overdose. Initial or mild symptoms typically develop within 2 hours and include tachycardia, drowsiness, a dry mouth, nausea and vomiting, urinary retention, confusion, agitation, and headache. • More severe complications include hypotension, cardiac rhythm disturbances, hallucinations, and seizures. Electrocardiogram (ECG) abnormalities are frequent and a wide variety of cardiac dysrhythmias can occur, the most common being sinus tachycardia and intraventricular conduction delay resulting in prolongation of the QRS complex and the PR/QT intervals. Seizures, cardiac dysrhythmias, and apnea

28. Triciclic antidepressants • ingestions of 10 to 20 mg per kilogram of body weight are a risk for moderate to severe poisoning • Most of the toxic effects of TCAs are caused by four major pharmacological effects. TCAs have anticholinergic effects, cause excessive blockade of norepinephrine reuptake at the preganglionicsynapse, direct alpha adrenergic blockade, and importantly they block sodium membrane channels with slowing of membrane depolarization, thus having quinidine like effects on the myocardium

29. Treatment • gastric decontamination of the patient. This is achieved by administering activated charcoallavage • stomach pumps, ipecac induced emesis, or whole bowel irrigation are not recommended in TCA poisoning. • maintenance of the airways, along with monitoring of blood pressure, arterial pH, and continuous ECG monitoring. • intravenous sodium bicarbonate as an antidote, which has been shown to be an effective treatment for resolving the metabolic acidosis and cardiovascular complications of TCA poisoning • Seizures often resolve without treatment but administration of a benzodiazepine or other anticonvulsive

30. Benzodiazepineoverdose • Following an acute overdose of a benzodiazepine the onset of symptoms is typically rapid with most developing symptoms within 4 hours. • Patients initially present with mild to moderate impairment of central nervous system function. Initial signs and symptoms include intoxication, somnolence, diplopia, impaired balance, impaired motor function, anterograde amnesia, ataxia, and slurred speech. • The symptoms of an overdose such as sleepiness, agitation and ataxia occur much more frequently and severely in children. Hypotonia may also occur in severe cases

31. The diagnosis of benzodiazepine overdose may be difficult, but is usually made based on the clinical presentation of the patient along with a history of overdose. • Obtaining a laboratory test for benzodiazepine blood concentrations can be useful in patients presenting with CNS depression or coma of unknown origin. Techniques available to measure blood concentrations include thin layer chromatography, gas liquid chromatography with or without a mass spectrometer, and radioimmunoassay

32. Treatment • Gastric decontamination with activated charcoal is not beneficial in pure benzodiazepine overdose as the risk of adverse effects would outweigh any potential benefit from the procedure. It is recommended only if benzodiazepines have been taken in combination with other drugs that may benefit from decontamination. Gastric lavage (stomach pumping) or whole bowel irrigation are also not recommended Enhancing elimination of the drug with hemodialysis, hemoperfusion, or forced diuresis is unlikely to be beneficial as these procedures have little effect on the clearance of benzodiazepines due to their large volume of distribution and lipid solubility.[42]

33. Glasgow Coma Scale

34. Glasgow Coma Scale • Generally, comas are classified as: • Severe, with GCS ≤ 8 • Moderate, GCS 9 - 12 • Minor, GCS ≥ 13. • Highest score is 15/15.the person in this case is alert and oriented to person, place and time • Lowest score is 3/15 there’s no 0.The patient is in deep coma and is considered brain dead if he can’t breath without a ventilator

35. Hypotension is corrected with fluid replacement, although catecholamines such as norepinephrine or dopamine may be require • Flumazenil (Anexate) is a competitive benzodiazepine receptor antagonist that can be used as an antidote for benzodiazepine overdose. Its use, however, is controversial as it has numerous contraindications. • It is contraindicated in who have tachycardia, widened QRS complex on ECG, anticholinergic signs, or a history of seizures. • Due to these contraindications and the possibility of it causing severe adverse effects including seizures, adverse cardiac effects, and deathdue to increase blood pressure

36. Barbiturates • Symptoms of an overdose typically include sluggishness, incoordination, difficulty in thinking, slowness of speech, faulty judgment, drowsiness, shallow breathing, and staggering. In severe cases, coma and death can result • The treatment of barbiturate abuse or overdose is generally supportive

37. Supportive treatment often includes the following: • Activated charcoal may be given via nasogastric tube. • Intravenous administration of saline, naloxone, thiamine, and/or glucose. • NaHCO3 to alkalize the urine to increase rate of excretion • Observation in the Emergency Department for a number of hours or admission to the hospital for several days of observation if symptoms are severe. • Advise the patient about drug misuse or refer for psychiatric consult

38. Carbon Monoxide Poisoning

39. CO is found in combustion fumes, such as those produced by cars and trucks, small gasoline engines, stoves, lanterns, burning charcoal and wood, and gas ranges and heating systems. CO from these sources can build up in enclosed or semi-enclosed spaces. People and animals in these spaces can be poisoned by breathing it.

40. Carbon Monoxide Poisoning • CO prevents oxygen from attaching to the hemoglobin molecule in your blood • Oxygen cannot be delivered to the brain and other tissues • SYMPTOMS • Confusion, hallucinations, headache, nausea, fatigue, dizziness, palpitations, seizures • COMA and DEATH • Severe: Hospitalization and adminstration of 100% oxygen

42. Administering oxygen via non-rebreather mask shortens the half life of carbon monoxide to 80 minutes from 320 minutes on normal air Hyperbaric oxygen is also used in the treatment of carbon monoxide poisoning, as it may hasten dissociation of CO from carboxyhemoglobin[6]and cytochromeoxidase treatment for other complications such as seizure, hypotension, cardiac abnormalities, pulmonary edema, and acidosis