Toxidromes & Overdoses!

Accidental & intentional poisonings or drug overdoses have a significant impact on health care expenditure and on patient morbidity and mortality. Although, the overall mortality rate from drug overdose and poison exposure is ~0.05%, the mortality rate may be as high as 1-2% among patients that are hospitalized from their poisoning and/or overdose.

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Overall Approach

-Recognition, identification of agents, assessment of severity, and striving to predict toxicity and adverse effects

-Supportive care, prevention of absorption, administration of antidotes, & eliminate the poison

Initial Evaluation & Treat

General Principles: ABC, O2, IV access, continuous cardiac monitor, vital signs (SpO2, BP, HR, RR, Temperature), stat AccuCheck (blood glucose), urgent stabilization if hemodynamically unstable, monitored setting, check GCS level, stabilize C-spine is concern for trauma 

·       Altered LOC: trial of "universal antidotes"- DONT (dextrose, O2, naloxone, thiamine)

o   Thiamine 100 mg IV, followed by 25 g of dextrose (50 mL of a 50% dextrose solution): for ? Wernicke’s encephalopathy & hypoglycemia

o   O2

o   Naloxone (narcan): 0.2-.04 mg IV (is ? opiate OD)

NOTE: there is a notion that thiamine must be given prior to dextrose to avoid precipitating Wernicke’s encephalopathy.

History: generally brief, and often unreliable!

•  Obtain collateral history if possible (family, friends, partner, call pharmacy re: meds, look at med bottles found), review of environment from which the patient was found (clues!)
• Psychiatric history: personality disorder, depression, anxiety, previous suicide attempts or a history of self-harm behaviour 

Physical Examination:

•   Mental Status, VS, GCS, neuroVS, pupillary examination
• Assess for Physiological Excitation: CNS +à tachycardic, HTN, tachypneic, elevated temperature
•  Symathomimetics, anti-cholinergics, drug WD (i.e. opiate, EtOH), or central hallucinogens
• Assess for Physiological Depression: depressed mental status, hypotension, bradycardic, reduced RR, hypothermic
•  Cholinergic (PSNS), sympatholytic, opiate, sedative-hypnotic, EtOH
• Mixed Physiological Effects: with poly-drug overdose or after exposures to certain metabolic poisons (i.e. salicylate, cyanide), membrane-active agents (i.e. inhalants), heavy metals, or agents with multiple mechanisms of action (i.e. TCA)
• Examine for particular toxidromes!

Investigations:

CBC, lytes, ext’d lytes, Cr, urea, albumin, INR/PTT, bilirubin, AST, ALT, GGT, ALP, glucose, B-hcg, lactate, carboxyHB

 EtOH level, salicylate level, Acetaminophen level; own med levels (Lithium, Digoxin, etc)

 ABG, anion gap, serum osmolality,  calculate Osmol Gap *(correct for EtOH if present!), CK

Consider volatile alcohols (methanol, ethylene glycol)

Urine: UA, Urine Drug Screen (TCA, cannabis, benzo, opioids, cocaine, amphetamine), ketones

12 lead

Imaging: CXR (aspiration), CT head

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        Anion Gap Metabolic Acidosis (AGMA):

o   Ketones: starvation, alcohol, DKA

o   Lactic acidosis

o   Uremia

o   Toxin: methanol, EG, salicylates

o   Rhabdomyolysis

NOTE: UA for toxins—not perfect! A negative result may reflect a drug concentration below the threshold for the limit of detection

Anti-Cholinergic

 Causes: TCA, anti-histamines, anti-psychotics, anti-Parkinson meds, amantadine, anti-spasmodic agents, skeletal muscle relaxants

Clinical: commonly fever, tachycardia, HTN, dry/flushed skin*, delirium, hallucination, mydriasis, urinary retention, decreased BS

o   SERIOUS: seizure, coma, respiratory failure, arrhythmia, CDV collapse

o   ECG: sinus tachycardia, prolonged PR, QRS/QT interval changes, ST elevation V1-V3, RBBB

·       Tx: Supportive measures; consider charcoal & HCO3 is arrhythmia

·       Sedation with benzos prn

Cholinergics

Causes: organophosphate, insecticides, pilocarpine, physostigmine, edrophonium, some mushrooms

Clinical: commonly, delirum, SLUDGE (salivation, lacrimation, urinary incontinence, diaphoresis, GI-diarrhea, emesis)

o   SERIOUS: pulmonary edema, seizures, coma

Tx: supportive, Atropine

NMS

An idiosyncratic reaction d/t DA RC blockade, usually with typical and sometimes with atypical anti-psychotics; can develop with withdrawal of dopaminergic agents (i.e. PD meds-levodopa). Often occurs within a few days of treatment, with drug levels usually in the therapeutic range

•  Clinical: TETRAD- high fever, ANS instability (HTN, tachycardia), NM rigidity, AMS. CK may be elevated with rigidity

·         Dx: Hx, physical, & elevated CK

·         Tx: Discontinue any anti-dopaminergic agents. Supportive measures, IVF, monitored setting

o   Dantrolene (skeletal muscle relaxant), bromocriptine (DA +)

Opiates

 Causes: narcotics

Clinical: decrease in VS, hypothermia, decreased LOC, dry skin, urinary retention, miosis, hyporeflexiaà can progress to respiratory depression, coma

Tx: supportive measures, naloxone (if opiates; short half life—may need continuous infusion)

• Naloxone (Narcan: consider IV infusion for a patient with exposure to long-acting opioids (i.e. methadone), sustained release (SR) products, and body packers, AFTER they have initially responded to a small dose of Naloxone. Use 2/3 of the initial effective Naloxone bolus, and administer that dose per hour. One half (1/2) of the initial bolus dose should be re-administered 15 minutes after initiation of the continuous infusion to prevent a drop in naloxone levels.

Sedative-Hypnotic

• Flumazenil (consider if benzo OD)
• Urinary alkalinization (if barbiturate OD)

Serotonin Syndrome

Over-stimulation of central and peripheral 5HT RC, usually d/t OD of SSRIs, or drug interactions that increase serotonergic neurotransmission (i.e. SSRIs, in combination with MAOI, TCAs)

• Clinical: TRIAD—ANS instability, NM rigidity, AMS; CK may be elevated

o   Similar to NMS, but only in SS should do you see hyper-reflexia, myoclonus, shivering, ataxia

Dx: history and physical

·       Tx: discontinue all serotonergic meds!

o   Sedation: Benzodiazepines—lorazepam 1-2 mg IV (goal: eliminate agitiaton, clonus, HTN, tachycardia, tremor)

o   IVF, Cardiac Monitor, O2 to keep SpO2 94%

o   If Benzo/Supportive care failsà consider Cyprohetadine in select cases    

§  H1 antagonist, weak anti-cholinergic, 5HT 1a, 2a blocker

o   Tx fever with cooling measures, if T>41.1à immediate sedation, paralysis, intubation, cool (avoid acetaminophen)

Sympathomimetic Syndromes

 Causes: cocaine, amphetamines, LSD, PCP, methamphetamine, ephedrine, etc

Clinical: commonly fever, tachycardia, HTN, diaphoresis, delusions, paranoia, mydriasis, hyper-reflexia; serious—seizures, coma, arrhythmias, CDV collapse

Tx: supportive; sedation with benzodiazepines, and AVOID BB---unopposed alpha effect!

GENERAL TREATMENT APPROACH FOR THE OVERDOSE PATIENT

Supportive care, decontamination, anti-dotes, enhanced elimination

 ACUTE: ABC, IV, O2, universal antidotes (Dextrose, O2, Naloxone, Thiamine), IVF, monitor VS

1. Decontamination: the sooner, the better. Copious IVF irrigation for topical exposures and activated charcoal for ingestion  -Activated Charcoal: 50g PO with 60 mL sorbitol; ideally within 1-2 h of ingestion

 -Gastric Lavage, WBI

2. Enhanced Elimination: forced diuresis, urine ion trapping, hemodialysis, hemoperfusion

a.     Forced alkaline diuresis will accelerate excretion of acids (ASA, barbituates)

                                               i.     3 amp NaHCO3 in 1 L D5W at 250 ml/h

                                              ii.     monitor u/o, volume, alkalosis, and for hypokalemia

b.     Goal pH: 7.5-8 (urine), 7.5-7.6 (blood)

c.      Consider Hemodialysis (HD) if toxic with: Barbituate, alcohols (acetone, EG, methanol), Li, Salicylates, etc

       3.  Specific Anti-dote: reduce M&M for certain intoxications

a.     Opiates: Naloxone 0.4-2mg IV, may need infusion (2/3 effective dose); half life 0.5-1.5h

b.     Tylenol: N-acetylcysteine (NAC)

c.      Benzodiazepines: Flumazenilà may precipitate seizures and worsen clinical course if TCA were co-ingested!

d.     Methanol/EG: Fomepizole 15 mg/kg IV, then 10mg/kg q12h

e.     Digitalis: Digibind

f.      Anticholinergics: lorazepam 2-10 mg IV q5min, physostigmine

g.     Cholinergics: atropine 0.5-1 mg IV q5 min

h.     TCA: NaHCO3—1^st line for vent tachycardias with wide QRS

       4.  Supportive care: most important

a.     Airway protection and intubation with ETT early if needed (i.e. if altered mental status, not protecting airway, concern for laryngeal edema)

b.     Hypotension: IVF, if refractory to high IVF volume, start vasopressors (NE)

c.      HTN in agitation patients: best treated with non-selective sedatives (i.e. benzodiazepines)

                                               i.     End-organ dysfunction associations: labetolol* (AVOID BB In cocaine OD or sympathetic hyperactivity—unopposed alpha adrenergic simulation and enhanced VC; consider BB + nitroprusside, a VD, in these cases )

d.     Overdrive pacing with isoproterenol or a temporary pacemaker may be effective in patients with drug-induced torsades de pointes and prolonged QTc

e.     Brady-arrhythmias  associated with hypotension:

                                               i.     Atropine or temporary pacing

                                              ii.     If CCB/BB intoxicationà Ca and glucagon may obviate the need for further measures

f.      Seizures: benzodiazepines, then barbituates if needed

g.     Drug-associated agitation: benzodiazepine or Haldol prn

Disposition

• At the very least: monitor for a defined period
•  Any signs of instability: monitored unit or ICU
• All patients should have a Psychiatry assessment and follow-up plan before D/C
• Always call Poison Control!!!!

RESOURCES

CHEST Article- Adult Toxicology in Critical Care: Part II: Specific Poisonings