MANAGEMENT OF ACUTE POISONING Kent R. Olson, MD Medical Director California Poison Control System San Francisco Division

Lessons from history A young princess ate part of an apple given to her by a wicked witch She was found comatose and unresponsive, as if in a deep sleep Airway positioning and mouth to mouth ventilation were performed, and she recovered fully

Best antidote is good supportive care Lesson: Best antidote is good supportive care (Love’s first kiss)

Case 1: Young woman found unconscious, several empty pill bottles nearby Unresponsive to painful stimuli Shallow breathing

Initial management: ABCDs Airway Breathing Circulation Dextrose, drugs, decontamination

Airway issues Risks: Major cause of morbidity in poisoned patients Floppy tongue can obstruct airway Loss of protective reflexes may permit pulmonary aspiration of gastric contents Major cause of morbidity in poisoned patients

Assessing the airway “Gag” reflex Alternatives Indirect measure May be misleading Can stimulate vomiting Alternatives

Breathing Assess visually pCO2 reflects ventilation - ABG useful pulse oximetry provides convenient, noninvasive evaluation of O2 saturation

Pitfalls pO2 measures dissolved oxygen can be normal despite abnormal hemoglobin states, eg COHgb, MetHgb Pulse oximetry also fails to detect CO poisoning

Interventions Endotracheal intubation Reverse coma? Protects airway Allows for mechanical ventilation Reverse coma? Naloxone: note T½ = 60 min Flumazenil?

Don’t forget GLUCOSE “A stroke is never a stroke until it’s had 50 of D50” – Dr. Larry Tierney, 1976 “Well, you could just do an Accuchek” - ibid, 2002 Give Thiamine 100 mg IM or in IV

Case, continued… The patient has no gag reflex, and does not resist intubation. She remains unconscious and on a ventilator overnight Awakens and extubated the next day Dx: mixed sedative drug overdose

Case 2 47 year old man calls 911, suicidal BP 70/50, HR 50/min Junctional rhythm Hx: uses an antihypertensive

Circulation = plumbing Pump working? Enough volume (is it primed)? Adequate resistance (no leaks)?

Management of Hypotension Hypovolemia? IV fluid challenge Pump? Dopamine Inadequate vascular resistance? Norepinephrine, phenylephrine

Antihypertensives Diuretics Beta blockers Calcium channel blockers ACE Inhibitors Centrally acting agents Vasodilators

Calcium channel blockers Bad ODs!! Low Toxic:Therapeutic ratio High mortality

SHOCK Decreased Automaticity & Conduction Negative Inotropic Effects Dilated Vascular Smooth Muscle SVR HR CO AV Block SHOCK

Calcium antagonists - treatment Calcium: most effective High doses may be needed Glucagon – variable results Insulin plus glucose? (experimental)

Case 3: An 18 month old takes some of his grandmother’s “sleeping pills” Brought to the ER after a seizure HR 150/min Pupils dilated, skin flushed, mucous membranes dry

Common causes of seizures Amphetamines/cocaine Tricyclic and other antidepressants Isoniazid (INH) Diphenhydramine Alcohol withdrawal Many others . . .

30 minutes later, the ECG shows:

Tricyclic antidepressants Anticholinergic syndrome Seizures Cardiotoxicity

TCA overdose treatment (similar tox possible w/ massive diphenhydramine) Stop the seizures Benzodiazepines, phenobarbital Treat cardiotoxicity Sodium bicarbonate 1 mEq/kg IV IV fluids Dopamine and/or NE

Case 4: metabolic acidosis Young man had a seizure at home In ED: obtunded, another seizure pH 6.94, pCO2 32 Recent immigrant, lives with extended family Uncle being treated for TB

Metabolic Acidosis: MUDPILES Methanol Uremia DKA Phenformin (whaa?) Isoniazid, Iron Lactic acidosis Ethylene Glycol Salicylate

Isoniazid overdose  GABA Glutamate Reduces brain pyridoxal 5-phosphate, a cofactor for glutamic acid decarboxylase: Seizures common; acidosis often severe Antidote: Pyridoxine (Vitamin B-6) (excitatory) (inhibitory) Glutamate  GABA  GAD

Case 5: another acidosis 44 year old man, obtunded BP 110/80 HR 110 RR 24 pH 7.47 pCO2 22 pO2 92 Na 140 K 3.8 Cl 104 HCO3 18 EtOH 0.18 gm/dL (180 mg/dL)

Salicylate poisoning Typical mixed acid-base disturbance Respiratory alkalosis Metabolic acidosis Large OD or enteric coated tablets may delay peak level Treatment: Urinary alkalinization, hemodialysis

Case 6: more acidosis 30 yo woman found comatose T 92 F, pH 6.9 Na 147, K 4.9, Cl 105, Bicarb 5 (AG 37) Glucose 166, BUN 16, Cr 1.5 Measured Osm 331 (calculated 308) EtOH: none detected

The Osmolar Gap Common causes of Osm Gap: Osm = 2 (Na) + BUN/2.8 + Glucose/18 Gap = Measured - Calculated Osm = 0 + 5 Common causes of Osm Gap: Ethanol Methanol & Ethylene Glycol Other alcohols, also aldehydes, ketones

METHANOL FORMALDEHYDE FORMIC ACID ELEVATED OSMOLAR GAP ANION GAP ACIDOSIS FORMIC ACID

Methanol or Ethylene Glycol: Elevated Osm Gap Anion gap Low lactate, does not account for gap Anion gap may be absent early after OD Other clues (may be unreliable): Methanol: blindness, visual disturbance EG: urine crystals, fluorescence

Methanol or Ethylene Glycol: Main DDx: alcoholic ketoacidosis Anion and Osm gaps Low lactate Clues to AKA: Gets better quickly w/ IV fluids, dextrose [Ketones] +/- (mainly -hydroxybutyrate)

Case 7: now we’re cookin’ 24 year old man with Hx depression Agitated, confused BP 110/70 HR 120 RR 20 T 40.4 C Muscle tone increased, LE clonus Tox screen negative for cocaine, amphetamines

Drug-induced Hyperthermia Heat Stroke Malignant Hyperthermia Neuroleptic Malignant Syndrome Serotonin Syndrome

Drug-induced “heat stoke” Altered judgment leads to excessive sun/heat exposure Anticholinergic drugs prevent sweating Excessive muscle hyperactivity from seizures, or from extreme agitation

Malignant hyperthermia Rare, familial myopathy Triggered by general anesthesia Succinylcholine Inhalational agents (eg, Halothane) Muscle rigidity, hypermetabolic state Treatment: dantrolene

Neuroleptic Malignant Syndrome Patient on dopamine-blocking drugs Haloperidol classic cause Also with newer agents (eg, clozapine) Rigidity (lead-pipe) Autonomic instability Hyperthermia

Serotonin Syndrome Current “hot” diagnosis Serotonin-enhancing Rx SSRIs in OD or multiple combos MAOI + serotonin-ergic drug Hypertonicity/clonus (esp. lower extr.) Autonomic instability Hyperthermia

Hyperthermia treatment Act quickly! Remove clothing spray and fan Sedation and anticonvulsants PRN Neuromuscular paralysis if T >40 C Dantrolene if NM paralysis ineffective Consider bromocriptine, cyproheptadine

One more common one A 17 year old boy takes a bottle of “aspirin” after he gets his SAT score Next morning, he is vomiting In the ED, normal vital signs Aspirin (salicylate) = negative

Acetaminophen Very common overdose May be overlooked “It’s just aspirin” (OTC’s can’t kill you..?) Hidden ingredient in many drug combos No specific findings after OD Delayed illness/lab abnormalities

Acetaminophen (APAP) NAPQI NAC ++ Glucuronidation Sulfation (non toxic) Sulfation (non toxic) ~ 5% NAPQI NAC ++ Glutathione + NAPQI nontoxic product Liver cell damage

N-acetylcysteine (NAC) Start within 8 hrs if possible Vomiting often interferes w/oral dosing Antiemetics (ondansetron, etc) Can dribble in by NG tube IV form now available (Acetadote™) Caution: hypotension w/rapid infusion

Gut decontamination after OD Goal: reduce systemic absorption Induce vomiting? Pump the stomach? Activated charcoal

Ipecac-induced emesis Easy to perform, but not very effective Contraindicated: Comatose/convulsing Ingested corrosive or hydrocarbon Bottom line: nobody uses it anymore

Pumping the stomach Cooperation not required MD sense of “control” Punitive value?

Gastric lavage May stimulate gagging, vomiting Risky if airway reflexes dulled Lack of proven efficacy Bottom line: used only rarely

Activated charcoal Finely divided powdered material Huge surface area Binds most drugs/poisons Exceptions: Lithium Iron

Activated charcoal More effective than SI, GL First choice for most ODs

Whole bowel irrigation Mechanical flush Balanced salt solution with PEG No net fluid gain/loss Good for: Iron Lithium Sustained-release pills, foreign bodies

Antidotes: The best antidote is supportive care Examples of antidotes: Digoxin-specific antibodies Atropine & 2-PAM N-acetylcysteine Vitamin B-6 (pyridoxine)

Call the Poison Center 1-800-222-1222 - 24 hours Immediate consultation by clinical pharmacists Back-up by MD toxicologists Identify pills, discuss diagnosis & Rx

“I don’t think we should go up there, especially without a paddle”