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Toxicology Tidbits Howard Burns, MD, FACEP, FACMT Toxicology Tidbits • • • • Toxidromes? New treatments?, HIET, Lipids, etc. Widened QRS, Prolonged QT Miscellaneous musings Portmanteau ? • The word toxidrome is a portmanteau portmanteau • A morph formed by the combination of two or more morphemes • ie. A word made by the combining of two or more other word’s sounds and meanings • Smoke +fog = smog, labradoodle, etc. Toxidromes • • • • Anticholinergic and Muscarinic Sympathomimetic, Opiate Hallucinogenic Sedative hypnotic Toxidromes • Taxis in Durham, NC ? • Anticholinergic (Hot as Hades, red as a beet, dry as a bone, blind as a bat, mad as a hatter). Benadryl, tricyclic antidepressants • Cholinergic- SLUDGE, organophosphates, carbamates, sarin etc. • DUMBELS Mad as a Hatter ? • Hg Mad as a Hatter Erethism? • Hg poisoning triad of Stomatitis, tremors and erethism Sympathomimetic and Opiate • Sympathomimetic- dilated pupils, elevated BP & P, diaphoresis, Temp, ? Hallucinations • Opiate- pinpoint pupils, Depressed everything, ?pulmonary edema Sedative Hypnotic and hallucinogenic • Not very helpful • Too many things cause sedation and specific signs may not show early on. • Most hallucination causing drugs have some stimulant effect also. • Beware as seizures may be next deterioration. Cannabinoid Toxidrome Cannabinoid Toxidrome • • • • Dazed look Smells like weed. Poor time space awareness Keeps asking for Doritos Seratonergic Syndrome Seratonine Syndrome • Hunter’s Criteria • Clonus plus serotonergic agent • Diaphoresis, tremor, agitation, rigidity, elevated temp Seratonine Syndrome • What do these people die from? • Acutely? Seratonine Syndrome • Hyperthermia • Rhabdomyolyses • Aggressive Care can treat these problems if they are recognized. • Cooling, treat agitation (benzos), IV’s hydration, cyproheptadine? Cyproheptadine • • • • 5-HT-2A inhibitor 12 mg (PO only) then 2mg q 2hr Mortality 2-12%, about 100 deaths per year Hyperthermia, rhabdomyolyses with renal failure, DIC (? from hyperthermia) • 0) Seratonine Syndrome • Can’t overemphasize need for close monitoring of temp (core) and liberal use of paralyses and intubation and external cooling in the more critical of these patients. • Olanzapine, thorazine (chlorpromazine), Haldol have all been used with some success. S-S vs NMS • Concerns exist about using antipsychotics for treating Seratonin Syndrome because of difficulties differentiating NMS from SS. • Benzodiazepines (valium, lorazepam, etc.) are a good starting point for any agitated delerium Drugs causing seratonine syndrome Antidepressants,(SSRI’s,SNRI’s, MAOI’s, bupropion, Li, etc. Opioids, Stimulants (cocaine, amphetamines, ie ADHD meds) Herbals (St. John’s wort, gensing, nutmeg, yohimbine) Others- dextromethorphan, odansetron NMS vs SS History of taking antipsychotic med? Onset acutely vs. gradualy? Dopaaminergic blockade vs. Seratonine excess SS vs NMS • Don’t worry about differentiating the two syndromes. • More important to recognize hyperthermia, and sedate patient adequately to control agitation and delirium (benzo’s, Haldol?, • If nothing working, paralyze and intubate, hydrate and cool pt. Libby Zion? • Who was Libby Zion? • What was the significance of her case? Libby Zion Case • Led to decrease in House Staff (MD residents in training) hours. • ? Overworked resident gave Libby (18 yo agitated psych patient on Nardil-phenelzine, MAOI) pethidine. She was thought to have died from hyperthermia from drug interaction in form of seratonine syndrome. Libby Zion • She also received Haldol to control her agitation • She also had restraints ordered • One test showed positive for cocaine • Her father was a lawyer High Dose Insulin Therapy • Also known as hyperinsulin euglycemic therapy, HIET, HDI, etc. • Doses as high as 10 Units/Kg/hr after a bolus have been used. • Glucose level is closely monitored and dextrose given as needed. When to use HDI therapy • Any overdose of BB or CCB that doesn’t respond to usual treatments or any serious OD of that type • Many toxicologists now consider this first line treatment of these OD’s • Many toxicologists are trying this on any OD where myocardial activity is suppressed in an unknown lngestion. How do I do it? • Bolus .5 to 1 unit/ kg • Drip .5 to 2 U / kg / hr • Some re commend as high as 10 U/kg/hr drip if needed • Frequently need a D10 drip along with this especially with BB OD How to do it • CCB OD’s will cause insulin resistance in pancreas and glucose levels are usually higher in these OD’s and therefore Dextrose needs lessened. • Potassium levels will be lower at times also because of insulin shifts to intracellular so replacement may be required, however these aren’t true losses and mildly depressed levels can be tolerated. Lipid Rescue • Also known as LRT (lipid rescue therapy), intralipid infusion therapy, intravenous fat emulsion, etc. • Intralipid 20% emulsion is used. • Thought to work as lipid sink (ie fat soluble drug is absorbed into fat emulsion from circulation) • Maybe works to supply lipid to cytochrome chain to allow mitochondrial function to How do we do it? • Bolus 100 ml IV slow push (1.5 ml/kg) • Drip if needed is 500 to 1 liter over 1-4 hours • This isn’t a routine therapy and is generally recommended for patients in extremis. • Fat emboli and other complication potential. • 2 cardiac arrests reported in one paper. Some clinical thoughts: Opiates • With push to get “life saving” narcan out to the masses • May see patients coming to your ED in acute withdrawal • They will be angry and want to leave The Point? (opiates) • These patients are at risk for delayed effects since almost all opiate effects will outlast narcan effects. • ie they may well arrest away from medical care and are a high liability patient, since record will show you saw them shortly before their death (hardly ever a good thing) Some Clinical Thoughts: Case Report • 44 yo female ingests 200 aspirin tablets (325 mg) 2 hours before arrival in your ED • What treatments should you do? • Your patient continues to deteriorate and needs intubated Clinical Thoughts • 1. Almost no expert these days will criticize you for not using lavage or charcoal. • 2. This patient is or soon will be acidotic • 3. You could easily have this patient arrest during intubation if you aren’t careful to keep them from worsening their acidosis • 4. Try to avoid this with careful monitoring of pH, giving bicarb, and hyperventilating patient Clinical thoughts: prolonged QRS (Na channel blockade) • We used to do this for TCA (tricyclic antidepressant OD), but has now become routine recommendation to do bicarb drip for any tox related QRS widening • With EMR it’s easier than ever to check an old EKG, especially in elderly • 2 amps bicarb in 1 L. sterile water at 150ml an hour Clinical Thoughts: QT prolongation (K channel blockade) • Check Ca and Mg levels and replace if necessary • Consider giving Magnesium 2-4 GM if worried about arrhythmia (Torsade) Last week Whats this? What is fugu • What toxin is associated with this fish? • How potent is this toxin? Tetrodotoxin • Potent Na channel blocker from puffer fish • Considered a delicacy (fugu) in Japan • Must be licensed there to prepare this fish as liver gonads etc. contain the toxin and many people have died over the years from improper preparation of this fish • LD50 is 25 mg E-Cigarettes • How toxic is nicotine? • LD 50 controversial probably around a gram for an adult • For comparison this would be similar to Arsenic and about one tenth the toxicity of strychnine E-Cigs • Unregulated at this point • No safety caps on refill cartridges,etc. • Concentrations up to 100mg/ml • ie 10 ml potentially fatal even for an adult • E-cigs also contain or give off propylene glycol, formaldehyde, glycerine, nitrosamines E-Cigs cont.’ • Already one death of a 1 yo on NY who got into a refill cartridge. • Some pet deaths have been reported also. • Siezures will be hard to control and consider early paralyses and intubation along with early aggressive antisiezure meds E-cigs • One call to PCCs in 2010 up to 1351 in 2013. • As Dr. Cantrell from California Poison Control said “its not a matter of if a child will be seriously injured or killed it’s a matter of when”