OTC and household toxins

1. OTC and household toxins • Yael Moussadji, R4 • Nov 29, 2007

2. Case • 2 y/o male found in the home eating an unknown number of tablets of adult strength ibuprofen 90 min ago • Looks well, has been asymptomatic, now sipping on charcoal (nurse obtained verbal order) • Potential ingestion of 100mg/kg • Parents called poison control and were told to come in for assessment • What would you like to do

3. NSAID Overdose • Despite the widespread use of NSAIDs, the number of reported cases of poisoning is small, and most overdoses result in a benign outcome • Of 50,614 exposures in the US in a 2-year period, 0.26% (131) had a major outcome, with 10 deaths • Isolated case reports have documented serious toxicity including seizures, coma, hypotension, respiratory depression, hepatic dysfunction and renal failure in severe poisonings

4. Pharmacology • NSAIDS exhibit anti-inflammatory, analgesic, anti-pyretic, and platelet inhibitory properties • The anti-inflammatory effects are achieved through inhibition of COX and blockade of prostaglandin production • COX-1 is located in platelets, vascular endothelial cells, gastric mucosal cells, and renal collecting tubules • COX-2 is only present in response to inflammatory stimuli • NSAIDS are completely absorbed from the small intestine and are highly bound to plasma proteins • Half-lives are short (1-4 hours) and are not prolonged in overdoses

5. NSAID Ingestion • Ingestions less than than 100mg/kg are unlikely to result in symptoms, and symptoms are not usually life-threatening until ingestions of >400mg/kg • About 50% of adults and 7% of children develop symptoms, always within 4 hours of the ingestion • Most toxicity is manifest at mild CNS or GI disturbance (nausea, vomiting, headache, drowsiness, blurred vision, dizziness) that resolves within 24 hours • Reversible renal dysfunction can occur in the presence of hypotension • Serum ibuprofen concentrations do not predict toxicity

6. Management • Supportive care is the rule for any degree of toxicity, including aggressive management of hypotension • Gastric lavage in massive OD <1 hour • Otherwise charcoal administration for large ingestions • Patients with mild toxicity can be managed with IV fluids, anti-emetics, and repeat electrolytes after 4 hours

7. Disposition • Adults and children with ingestions of <100mg/kg do not require medical evaluation • Ingestions of 100-300mg/kg need treatment only if symptoms develop • Patients who remain asymptomatic for 4 hours can be discharged from the ED • Patients with mild GI or neurologic symptoms can be observed until asymptomatic, then discharged home

8. Antitussives • Dextromethorphan, found in a number of cough and cold preparations, is a stereoisomer of codiene, is an effective cough suppressant, and has few analgesic or addictive properties • It’s generally safe, but children may experience toxicity after taking large doses • Most common effect is CNS depression (drowsiness, stupor, coma) and resp depression • Symptoms can be reversed with naloxone • Serotonin syndrome can results from concomitant ingestion with SSRIs or MAOIs

9. Decongestants • Decongestants exert their effect through sympathomimetic actions causing alpha-adrenergic stimulation and arteriolar vasoconstriction leading to relief of congestion • Hypertension is the most serious side effect, which can be potentiated by co-ingestion of antihistamines that prevent reflux reductions in heart rate • Hypertensive emergencies including mental status changes, seizures, ICH, MI and death are all possible complications • Ingestion of topical decongestants (imidazole) can produce serious toxicity from stimulation of central alpha-2-adrenergic receptors, causing decreased output from vasomotor centres and a reduction in heart rate and blood pressure

10. A Tale of Two Cases • 16 y/o f, found acting very strange at school • Silly, agitated, at times incoherent • EMS called, parents are on their way • On arrival to ED, delirious, hallucinating, agitated • VS: BP 130/80, HR 128, RR 24, SpO2 98%, T 38.4 • O/E: Flushed, warm to touch, no diaphoresis, MM dry, pupils dilated

11. First case • Your patients friends tell you that they were smoking this over lunch

12. Case 2 • 19 y/o brought in by EMS, found unresponsive by parents at home with several empty packages of benadryl • O/E: GCS 5, HR 144, BP 90/50, SpO2 97%, T 39.2 • MM dry, skin flushed and dry, absent bowel sounds, pupils markedly dilated • ECG

14. Ddx of febrile delerium • Toxic • Salicylism, sedative-hypnotic withdrawal, cocaine and amphetamine, anticholinergics, serotonin syndrome, NMS • Metabolic/endocrine • Infectious/inflammatory

15. Antihistamines • Antihistamines block H1 or H2 histamine receptors • Centrally acting, first generation H1 receptor antagonists (diphenhydramine, chlopheniramine, hydroxyzine) are also potent inhibitors of muscarinic receptors • 90% of exposures to antihistamines involve DPH; in 2004 7.4% resulted in moderate to major toxicity and 0.076% in death • Toxicity results in potent anticholinergic effects, seizures, cardiac arrythmias, and hypotension

16. Anticholinergic effects • Anticholinergics have antimuscarininc effects on smooth muscle function in the eye, intestine, and bladder, causing pupillary dilatation and loss of accommodation, GI paralysis and urinary retention • They impair sweat production, and salivary and mucosal gland activity, and cause peripheral vasodilation resulting in dry mucosal surfaces, warm flushed skin, an inability to sweat, and hyperthermia • Muscarinic inhibition on cardiac receptors and vagal nerve fibers cause tachcardia (early sign) • In the CNS, muscarinic inhibition causes disorientation, agitation, incoherent speech, choreoathetosis or repetative motor activity, perceptual and cognitive dysfunction, seizure and coma

17. Antihistamines • CNS • Central H-1 antagonists cause both stimulation and depression, restlessness, agitation, catatonic stupor, seizures (more common in children, short-lived), somnolence, lethargy, coma • Cardiac • sinus tach is the most common toxic cardiovascular effect from antihistamines with prominent anticholinergic properties • potential to cause quinine-like sodium channel blocking effect, and at high doses, a K+ channel blocking effect resulting in delayed conduction and repolarization, widened QRS, ventricular dysrhythmias (particularly second gen H-1 blockers)

18. Management • Lab: screen for ASA, APAP, EtOH and the usual including CK • Aggressive sedation with benzos, cooling, and hydration are the priorities • Decontamination • consider gastric lavage if massive OD and <1hr (not in agitated patients) • charcoal binds DPH and may be useful • patients who have smoked or ingested teas are not candidates for gastrointestinal decontamination • Treat wide complex tachycardia as you would any Na-channel blockade (NaHCO3)

19. Physostigmine • Reversible acetylcholinesterase inhibitor, crosses the blood-brain barrier, binds to central acetylcholinesterase increasing acetylcholine levels and reversing central and peripheral anticholinergic effects • Extremely effective in treating agitated anticholinergic delerium when benzos are ineffective (controlling muscle injury, acidosis, rhabdo, and hyperthermia) • Several case reports indicated that asystole developed in patients with TCA poisoning; do not use if any conduction disturbances on ECG • Generally people do well with supportive care alone, so use of physostigmine is limited to patients with pronounced agitation or delerium, intractable seizures (evidence very limited), narrow comlex SVT causing hemodynamic instability

20. Disposition • Alert patients with symptoms and VS that improve over the course of observation can be discharged home from the ED • Onset of symptoms is rapid, patients can be discharged home or medically cleared after 4 hours if asymptomatic • Patients who ingested Jimson weed should be observed for 8 hours

21. Case • A 14 mo old presents to the ED after being found with a bottle of drain cleaner (pH 13) • Mom is unsure in child drank any • Child looks well with normal vital signs, no resp distress, no stridor, no drooling, no vomiting, no oral lesions

22. Case • A 14 y/o female presents after drinking what she thought was apple juice in chemistry class • Substance is identified as potassium hydroxide, pH 12 • She is complaining of a burning sensation in her mouth and chest and is vomiting • She is able to swallow but it is extremely painful, and her mouth is blistered and erythematous

23. Case • A 2 y/o presents to the ED after drinking liquid pipe cleaner (sodium hydroxide) • Immediately after drinking the solution, the child began vomiting and choking • In the ED, the child has a decreased LOC, is drooling thick yellow secretions, and has visible burns to her tongue, face, and chest • The child is stridorous, wheezing, and continues to vomit; abdomen is non-peritoneal • VS: HR 138, RR 36, BP 121/77, T 36.4, SpO2 92%

24. Caustics • A chemical capable of causing injury on tissue contact • Strong acids (pH<3) and strong alkalis (pH>11) are of greatest concern • Severity of injury is related to pH, physical state, TAR, concentration, tissue contact time, volume of substance ingested, presence of vomiting, intentional vs accidental • Solution concentration is the most important predictor of esophageal damage

25. Caustics Products • Drain cleaners • Have high concentrations of alkali (30% KOH) or acid (93% H2SO4) • Can be in liquid or crystal form (74% NaOH) • Laundry or dishwasher detergents • Liquid detergents have pH >12 (lower titratable base content) • Granular detergents are associated with devastating injuries • Cleaners and disinfectants • Oven cleaner (NaOH) , rust remover (HF or NaOH), toilet bowl cleaners (25% HCl), swimming pool cleaners (31% HCl)

26. Principles • Acids generally cause coagulation necrosis, with eschar formation that limits substance penetration and injury depth • Alkalis denature tissue proteins and cause liquifactive necrosis and saponification allowing further penetration of substance into tissues; 30% NaOH results in a full thickness burn after 1 second of contact • Alkalis also cause blood vessel thrombosis, impairing blood flow to the affected area • Strong acid ingestions are associated with systemic complications including renal failure, liver dysfunction, DIC, hemolysis • Both penetrate esophageal tissues rapidly, potentially leading to full thickness injury, laryngeal burns, or perforation

27. Esophageal Injury • Caustic injury is categorized similarly to a thermal burn based on appearance at endoscopy • Initial depth of injury on endoscopy correlates with risk of stricture formation • Grade 1) edema and hyperemia • Grade 2) superficial ulcers, white membranes, exudates, friability, hemorrhage, deep or circumferential ulceration • Grade 3) necrosis • 15-30% of grade 2 injuries (75% if circumferential), and 90% of grade 3 injuries result in stricture

28. Tissue injury • Phase 1 • eosinophilic necrosis, swelling, hemorrhagic congestion • Phase 2 (4-7 days) • mucosal sloughing, bacterial invasion, inflammation, granulation • tensile strength low, risk of delayed perforation (1-3 weeks) • Phase 3 (1 week-1 mo) • esophageal repair, collagen deposition, re-epithelialization • Phase 4 (months-years) • esophageal stricture formation

29. Controversies • Dilutional or neutralization therapy? • Who needs endoscopy? • Steroids and antibiotics? • Who needs surgery?

30. Clinical presentation • Airway edema and esophageal or gastric perforation are the most emergent issues; tracheal necrosis is a frequent cause of death • Laryngeal edema occurs over minutes to hours • Size of ingestion does not correlate with outcome; 40% of patients who only took a “lick” will have esophageal burns • Common symptoms include vomiting, dysphagia, oodynophagia, drooling, abdo pain, chest pain, stridor, wheeze, cough, dysphonia

31. Clinical predictors • Absence of oropharyngeal injury does not exclude esophageal lesions; 12% incidence of grade 2 esophageal injury in asymtomatic patients • Drooling and dysphagia have both been highly correlated with esophageal injury, but in general clinical findings are not predictive of presence or severity of injury

32. Diagnostic evaluation • Goal is to identify the extent and severity of burn • Upright chest and abdominal films to assess for free air • CT chest/abdomen if suspicious for perforation • Early endoscopy for patients with clinical signs and symptoms or intentional ingestions • visible burns, stridor, vomiting, chest/abdo pain, drooling, dyspnea, refusal to drink • Degree of esophageal injury is an accurate predictor of systemic complications and depth

33. Management • Hemodynamic stabilization and airway assessment; early ETI for potential or suspected airway compromise (hoarseness, drooling) • Decontamination • pH neutralization - no data to support practice in humans, not currently recommended • dilution (milk or water) - no human data, not recommended because of concerns for potential of emesis, obscuring EGD evaluation, and perforation • No role for charcoal administration or lavage

34. Do corticosteroids prevent esophageal stricture after corrosive ingestion?Pelclova D, Navratil T. Toxicological Reviews. 24(2):125-29, 2005 • Were believed to attenuate inflammation, granulation and fibrous tissue formation, preventing stricture formation • A recent mata-analysis attempted to evaluate this practice by looking at all clinical reports published between 1991-2004 • Inclusion criteria were the presence of 2nd or 3rd degree esophageal injuries and management involving either at least an 8-day course of steroid or no steroid therapy • 10 studies, 572 people; 6 studies used corticosteroids, 2 studies did not, and 2 compared outcomes with and without steroids • In 305 patients treated with steroids, 35.1% developed strictures vs, 33.3% in the 267 patients not treated with steroids

35. Other • Antibiotics • There has been no prospective clinical trials evaluating the utility of antibiotics • Antibiotics may potentially mask evidence of perforation, and are not widely recommended • Surgery • Immediate surgical exploration is indicated for free air and peritonits

36. Disposition • Asymptomatic patients can undergo endoscopy in emerg or be discharged home with close follow-up • Grade 1 injuries can be safely discharged home after complete resolution of symptoms and if tolerating solids and liquids • More symptomatic patients generally need admission to an ICU

37. New case • Toddler wandered into the garage and ingested unknown amount of gasoline (was kept in a reused milk container) • Coughing, grunting, noisy resps, has been vomiting • O/E: Alert but looks uncomfortable, moderate resp distress • VS: RR 48, T 38.2, HR 142, BP 100/50, SpO2 89%

38. Case 2 • Paramedics call ahead with cardiac arrest en route • 15 y/o male, collapsed while running in gym class • Distinctive odor • Rash around mouth and nose • Friends say he was “bagging” at lunch

39. Hydrocarbons • A diverse group of organic compounds that contain hydrogen and carbon • Most are byproducts of crude oil (petroleum distillates) • Petroleum distillates are either aliphatic (straight chain hydrocarbons; propane) or aromatic (those containing benzene ring structure; toluene) • Wood distillates (turpentine) are derived from pine oil • Halogenated (eg chlorinated) hydrocarbons have multiple non-organic side chains; used as a solvent base for metals and insecticides, which usually carries greater toxicity

40. Aliphatic hydrocarbons • Gases (< 5 carbons) • Methane (natural gas), propane, butane (cigarette lighter refills) • Abused inhalents, simple asphyxiants causing hypoxia and CNS depression; “sudden sniffing death” • Liquids or solvents (5-16 carbons) • Gasoline, kerosene, mineral spirits (furniture polish) • Abused as inhalents, pnuemonitis when aspirated

41. Aromatic hydrocarbons • Cyclic structure with one or more benzene rings • Highly lipophilic, causing narcosis and CNS depressant effects similar to those of GA • Toluene (glue, acrylic spray paint), benzene (chemical intermediate in plastics, rubber, chemical and solvent industries) • Highly volatile, lung aspiration • Absorbed from GI tract • Organ toxicity; RTA, aplastic anemia, leukemia

42. Chlorinated hydrocarbons • Can cause multi-system toxicity • Found in industrial solvents, refrigerants and propellants (carbon tetrachloride), fire extinguishers, paper correction fluid and spot remover (trichloroethylene), paint strippers (methylene chloride) • Highly volatile but not flammable • Renal failure, centrilobular hepatic necrosis, prominent CNS toxicity (seizures, coma), CO poisoning (methylene chloride), sudden cardiac death

43. Hydrocarbon toxicity • Viscosity • low viscosity allows the substance to spread rapidly • Volatility • capacity for liquid to turn into gas; highly volatile substances displace alveolar oxygen (simple asphyxiants) • Surface tension • low surface tension enables a substance to disperse easily (eg turpentine • Chemical side chains • heavy metals, halogens, aromatic structures increase toxicity

44. Pathophysiology • Pulmonary disease • fatalities usually occur after aspiration; major toxicity of aliphatics (low viscosity, low surface tension) • hydrocarbons are not water soluble, and penetrate into the lower airways causing bronchospasm and an inflammatory response • Volatilized hydrocarbons displace O2 in the alveolar space (asphyxiant) and inhibit surfactant function causing alveolar collapse • Damage alveoli and capillaries causing hemorrhagic exudative alveolitis, necrotizing pneumonitis, V/Q mismatch, hypoxemia, respiratory failure, death within 24 hours

45. Pathophysiology • CNS • Most cause CNS depression via a narcotic like effect • Can also cause excitation, euphoria, agitation, hallucinations • Chronic use causes peripheral neuropathy, cerebellar degeneration, neuropsychiatric disorders, chronic encephalopathy, dementia • Cardiac • sensitizes the myocardium to endogenous and exogenous catecholamines, precipitating ventricular dysrhythmias • typically occurs with sudden physical activity after inhalation • halogenated and aromatic hydrocarbons are the worst offenders

46. Other • GI - No significant toxicity • Renal - toluene can cause RTA, chlorinated hydrocarbons can cause renal failure • Hematologic - benzene can cause bone marrow toxicity and leukemia • CO poisoning - methylene chloride • Hepatic - chlorinated hydrocarbons can cause hepatic necrosis • Dermal - Chemical burns, dermatitis

47. Management • Hydrocarbons can cause sudden decompensation in pulmonary, cardiac, and CNS function; patients should be on continuous cardiac monitoring • ABC’s • Early intubation for suspected aspiration • CPAP +/- PEEP if required • Decontamination - remove all clothes • Gastric emptying for highly toxic ingestions • ABG, CXR, labs etc

48. GI Decontamination • The safest place in the body for hydrocarbons is the duodenum • Aggressive decontamination risks converting harmless ingestion to a life-threatening aspiration • Exceptions • C - camphor (status epilepticus) • H - halogenated hydrocarbons (dysrhythmias, hepatotoxicity) • A - aromatics (bone marrow suppression, cancer) • M - metals • P - pesticides (cholinergic crisis)

49. Disposition • Patients with known, relatively benign unintentional ingestions of aliphatic hydrocarbons can be watched at home or in ED if initially asymptomatic for a period of 6 hours (no GI decontamination, watch for pulmonary complications) • Patients who present after recreational inhalation should be observed on a monitor for 4-6 hours • Admit for minimum of 24 hours if any respiratory symptoms • Any patients with ingestion of toxic additives (aromatics, halogens) must be monitored and managed in ED (gastric emptying, supportive care)

50. The End