MANAGEMENT OF ACUTE POISONING

Kent R. Olson, MDMedical 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

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:• 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• 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• 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

Negative InotropicEffects

Negative InotropicEffects

DecreasedAutomaticity& Conduction

DecreasedAutomaticity& Conduction

Dilated VascularSmooth Muscle

Dilated VascularSmooth Muscle

SVRSVRCOCOHRHRAV BlockAV Block

SHOCKSHOCKSHOCKSHOCK

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

Reduces brain pyridoxal 5-phosphate, a cofactor for glutamic acid decarboxylase:

Seizures common; acidosis often severe Antidote: Pyridoxine (Vitamin B-6)

GlutamateGlutamate GABA GABA GAD

(excitatory) (inhibitory)

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:• Ethanol• Methanol & Ethylene Glycol• Other alcohols, also aldehydes, ketones

Osm = 2 (Na) + BUN/2.8 + Glucose/18

Gap = Measured - Calculated Osm = 0 + 5

METHANOLMETHANOL

FORMALDEHYDEFORMALDEHYDE

FORMIC ACIDFORMIC ACIDANION GAPACIDOSIS

ANION GAPACIDOSIS

ELEVATEDOSMOLAR GAP

ELEVATEDOSMOLAR GAP

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)

Glucuronidation(non toxic)

Sulfation(non toxic)

NAPQI

P-450

~ 5%

Glutathione + NAPQInontoxic product

Liver cell damage

NAC

++

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, butnot 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”