Approach to Overdose pt.


History
  • who? age, weight, underlying medical problems, medications
  • what? substance and how much
  • when? time since exposure determines prognosis and need for decontamination, symptoms since
  • how? route
  • why? intention, suicidality
Principles of Toxicology
  • 5 principles to consider with all ingestions
    1. Resuscitation (ABCs)
    2. Screening (toxidrome? clinical clues?)
    3. Decrease absorption of drug
    4. Increase elimination of drug
    5. Antidote available?
 
Clinical Pearl
Suspect overdose when:
  • Altered level of consciousness/coma
  • Young patient with life-threatening arrhythmia
  • Trauma patient
  • Bizarre or puzzling clinical presentation

ABCs of Toxicology
  • Basic axiom of care is symptomatic and supportive treatment
  • Address underlying problem only once patient is stable
     
  • A = Airway (consider stabilizing the C-spine)
    B = Breathing
    C = Circulation

    D1 = Drugs

    Universal antidotes:

    • Treatments that will not harm patients and may be essential
    • Oxygen
      • Do not deprive a hypoxic patient of oxygen no matter what the antecedent medical history (i.e. even COPD with CO2 retention)
      • If depression of hypoxic drive, intubate and ventilate
      • Exception: paraquat or diquat (herbicides) inhalation or ingestion (oxygen radicals increase morbidity)
    • Glucose
      • Give to any patient presenting with altered LOC
      • Measure blood glucose prior to glucose administration if possible
      • Adults: 0.5-1.0 g/kg (1-2 mL/kg) IV of D50W
      • Children: 0.25 g/kg (2-4 mL/kg) IV of D25W
    • Thiamine (Vitamin B1)
      • 100 mg IV/IM to all patients with IV/PO glucose
      • A necessary cofactor for glucose metabolism, but do not delay glucose if thiamine
        unavailable
      • To prevent Wernicke-Korsakoff syndrome
      • Must assume all undifferentiated comatose patients are at risk
    • Naloxone
      • Antidote for Opioids: administration is both diagnostic and therapeutic (1 min onset of action)
      • used for the undifferentiated comatose patient
      • Loading dose:
        • Adults
          • 2 mg initial bolus IV/IM/SL/SC or via ETT (ETT dose = 2-2.5x IV dose)
          • If no response after 2-3 minutes, increase dose by 2 mg increments until a response or to max 10 mg
          • known chronic user, suspicious history, or evidence of track marks, give 0.01 mg/kg
        • Child
          • 0.01 mg/kg initial bolus IV/IO/ETT
          • 0.1 mg/kg if no response and narcotic still suspected to max of 10 mg
      • Maintenance dose 
        • May be required because half-life of naloxone (30-80 mins) is much shorter than many narcotics
          • Hourly infusion rate at 2/3 of initial dose that produced patient arousal
    Red Flag
    Administration of naloxone can cause opiate withdrawal in chronic users

    D2 = Draw Blood

    • Essential bloods (see Table below, for interpretation)
      • CBC, electrolytes, BUN/creat, glucose, INR/PTT, osmolality
      • ABGs, measure O2 sat
      • acetylsalicylic acid (ASA), acetaminophen, EtOH levels
    • Potentially useful bloods
      • Drug levels NOT serum drug screen
      • Ca, Mg, PO4
      • protein, albumin, lactate, ketones, liver enzymes, CK - depending on drug and clinical presentation
    • Serum Drug Levels
      • Treat the patient, not the drug level
      • Negative tox screen does not rule out a toxic ingestion - signifies only that the specific drugs tested were not detectable in the specimen
      • Specific drugs available on general screen vary by institution; check before ordering
      • Urine screens also available (qualitative only)
    Use of the Clinical Laboratory in the Initial Diagnosis of Poisoning
    Test Finding Selected Causes
    ABG Hypoventilation (increased pCO2)
    Hyperventilation (decreased pCO2)
    CNS depressants (opioids, sedative-hypnotic agents, phenothiazines, EtOH)
    Salicylates, CO, other asphyxiants
    Electrolytes Increased anion-gap metabolic acidosis
    Hyperkalemia
    Hypokalemia
    MUDPILES CAT: see Metabolic Acidosis above
    Digitalis glycosides, fluoride, potassium
    Theophylline, caffeine, beta-adrenergic agents, soluble barium salts, diuretics
    Glucose Hypoglycemia Oral hypoglycemia agents, insulin, EtOH, ASA
    Osmolality and Osmolar Gap Elevated osmolar gap MAE DIE: see Toxic above
    ECG Wide QRS complex
    Prolonged QT interval
    Atrioventricular block
    TCAs, quinidine, other class Ia and Ic antiarrhythmic agents
    Quinidine and related antiarrhythmics, terfenadine, astemizole
    Ca2+ antogonists, digitalis glycosides, phenylpropanolamine
    Abdominal X-Ray Radiopaque pills or objects CHIPES: 
    C
    alcium, Chloral hydrate, CCl4, 
    H
    eavy metals, 
    I
    ron, 
    P
    otassium, 
    E
    nteric coated Salicylates,
    & some foreign bodies
    Serum Acetaminophen Elevated level 
    (>140 mg/L or 1000 µmol/L 4 hours after ingestion)
    May be only sign of acetaminophen poisoning

    Metabolic Acidosis       
    Increased AG: MUDPILES ACT
    (* = toxic)   
         
    M
    ethanol*
    Uremia        
    Diabetic ketoacidosis/Starvation ketoacidosis        

    Phenformin*/Paraldehyde*

    Isoniazid, iron, ibuprofen        
    Lactate (anything that causes seizures or shock)     
    Ethylene glycol*     
    Salicylates*    
    Alcoholic Ketoacidosis
    Cyanide, carbon monoxide*    
    Toluene, theophylline*
    Decreased AG    
    Error    
    Electrolyte imbalance (increased Na+/K+/Mg2+)    
    Hypoalbuminemia (50% fall in albumin ~5.5 mmol/L decrease in the AG)    
    Li, Br elevation    
    Paraproteins (multiple myeloma) 
     
    Normal AG
    High K: pyelonephritis, obstructive nephropathy, renal tubular acidosis (RTA), IV, TPN
    Low K: small bowel losses, acetazolamide, RTA I, II

     
    Increased (POG): MAE DIE (if it ends in, it will likely increase the POG)

    Methanol
    Acetone
    Ethanol
    Diuretics (glycerol, mannitol, sorbitol)
    Isopropanol
    Ethylene Glycol

    Note: normal osmolar gap does not rule out toxic alcohol; only an elevated gap is helpful
    Increased O2 saturation gap
    Carboxyhemoglobin
    Methemoglobin
    Sulfmethemoglobin

    D3 = Decontamination


    D3 = D
    econtamination (decrease absorption)

    Clinical Pearl
    Substances NOT Absorbed by Activated Charcoal
    Li
    Fe
    Alcohols
    Lead
    Caustics

    OCULAR DECONTAMINATION:

    • Saline irrigation to neutralize pH; alkali exposure requires ophthalmology consult

    DERMAL DECONTAMINATION: (wear protective gear)

    • Remove clothing, brush off toxic agents, irrigate all external surfaces

    GI DECONTAMINATION:

    • Single dose activated charcoal (SDAC) 
      • Adsorption of drug/toxin to AC prevents availability
      • Contraindications: caustics, SBO, perforation
      • Dose: 10g/g drug ingested or 1g/kg body weight
      • Odourless, tasteless, prepared as slurry with H2O
    • Whole bowel irrigation
      • 500 mL (child) to 2000 mL (adult) of polyethylene glycol solution/hour by mouth until clear effluent per rectum
      • Indications
        • Awake, alert patient who can be nursed upright
        • Delayed release product
        • Drug/toxin not bound to charcoal
        • Drug packages (if any evidence of breakage = emergency surgery)
        • Recent toxin ingestion
      • Contraindications
        • Evidence of ileus,
        • Perforation, or
        • Obstruction
    • Surgical removal in extreme cases
      • indicated for drugs that are toxic, form concretions, or cannot be removed by conventional means
    • No evidence for the use of cathartics (or ipecac)


    EXTRA-CORPOREAL DRUG REMOVAL (ECDR)
    1. Urine Alkalinization:

    • May be used for: ASA, methotrexate, phenobarb, chlorpropamide
    • weakly acidic substances can be trapped in alkali urine (pH >7.5) to increase elimination

    2. Multidose Activated Charcoal (MDAC)

    • may be used for: carbamazepine, phenobarb, quinine, theophylline
       
    • for toxins which undergo enterohepatic recirculation 
    • removes drug that has already been absorbed by drawing it back into GI tract
    • various regimens: 12.5g (1/4 bottle) PO q1h or 25g (1/2 bottle) PO q2h until non-toxic

    3. Hemodialysis

    • Indictaions/Criteria for hemodialysis:
       
      • Toxins that have high water solubility, low protein binding, low molecular weight, adequate concentration gradient, small volume of distribution (Vd) or rapid plasma equilibration
      • Removal of toxin will cause clinical improvement
      • Advantage is shown over other modes of therapy
      • Predicted that drug or metabolite will have toxic effects
      • Impairment of normal routes of elimination (cardiac, renal, or hepatic)
      • Clinical deterioration despite maximal medical support
    • Useful for the following toxin blood levels:
      • Methanol
      • Ethylene glycol
      • Salicylates
      • Lithium
      • Phenobarbital:  430-650 mmol/L
      • Chloral hydrate (trichloroethanol): >200 mg/kg
    • Others include theophylline, carbamazepine, valproate, methotrexate

    E = Expose

    E = Expose (look for specific toxidromes)/Examine the Patient

    • Vital signs (including temperature), skin (needle tracks, colour), mucous membranes, pupils, odours and CNS
    • Head-to-toe survey including:
      • C-spine
      • signs of trauma, seizures (incontinence, “tongue biting”, etc.), infection
        (meningismus), chronic alcohol/drug abuse (track marks, nasal septum erosion
    • Mental status
    • Clinical Pearl
      Anticholinergics - Hot and Dry"
      Sympathomimetics - Hot and Wet"

    Specific Toxidromes:
    Note: ASA poisoning and hypoglycemia mimic sympathomimetic toxidrome 

    Toxidrome Overdose Signs & Symptoms Examples of
    Drugs
    Anticholinergics   
     
    Hyperthermia    
          - Hot as a hare
    Dilated pupils    
            -Blind as a bat    
    Dry skin             
            -Dry as a bone    
    Vasodilation       
            -Red as a beet    
    Agitation/hallucinations    
            -Mad as a hatter  
    Ileus, Urinary retention, Tachycardia   
            The bowel and bladder lose
              their tone and the heart
              goes on alone
    Antidepressants (e.g. TCAs)
    Cyclobenzaprine (Flexeril)
    Carbamazepine
    Antihistamines (e.g. diphenhydramine)
    Antiparkinsonians
    Antipsychotics
    Antispasmotics
    Belladonna alkaloids (e.g. atropine)
     
    Cholinergics   
     
    DUMBELS
    Diaphoresis, Diarrhea, Decreased blood pressure       
    Urination        
    Miosis           
    Bronchospasm, Bronchorrhea, Bradycardia       
    Emesis, Excitation of skeletal muscle       
    Lacrimation          
    Salivation, Seizures        
     
    Natural plants: mushrooms, trumpet flower

    Anticholinesterases:
    physostigmine
    insecticides (organophosphate, carbanates)
    nerve gases

     
    Extrapyramidal   
     
    Dysphonia, dysphagia        
    Rigidity and tremor        
    Motor restlessness, crawling sensation (akathisia)
    Constant movements (dyskinesia)
    Dystonia (muscle spasms, laryngospasm, trismus, oculogyric crisis, torticollis)
     
    Major tranquilizers
    Antipsychotics
     
    Hemoglobin Derangements 
     
    Increased respiratory rate
    Decreased level of consciousness    
    Seizures 
    Cyanosis unresponsive to O2
    Lactic acidosis

     
    Carbon monoxide poisoning (carboxyhemoglobin)
    Drug ingestion (methemoglobin, sulfmethemoglobin)
    Narcotics, Sedatives/
    Hypnotics,
    EtOH
    Hypothermia        
    Hypotension        
    Respiratory depression        
    Dilated or constricted pupils (pinpoint in opiate OD)    
    CNS depression        
     
    EtOH
    Benzodiazepines
    Opiates (morphine, heroin, etc.)
    Barbiturates
    GHB
     
    Sympatho-
    mimetics   

     
    Increased temperature        
    CNS excitation (including seizures)        
    Tachycardia, hypertension        
    Nausea and vomiting        
    Diaphoresis        
    Dilated pupils        
     
    Amphetamines, Caffeine, Cocaine, LSD, PCP
    Ephedrine & other decongestants
    Thyroid hormone
    Sedatives, EtOH withdrawal
     
    Serotonin Syndrome   
     
    Mental status changes, autonomic hyperactivity, neuromuscular abnormalities, hyperthermia, diarrhea, HTN
     
    MAOI, TCA, SSRI, opiate analgesics
    Cough medicine, weight reduction medications
     

    F = Full vitals


    F = Full vitals, ECG monitor, Foley, X-rays, etc.

    G = Give specific antidoote

    G = Give specific antidotes, treatments

    Urine Alkalinization Treatment for ASA Overdose

    • Urine pH >7.5
    • Fluid resuscitate first, then 3 amps NaHCO3/litre of DSW @ 1.5 x maintenance
    • Add 20-40 mEq KCl/litre if patient is able to urinate

    Table 23. Protocol for Warfarin Overdose

    INR Management
    <5.0* Cessation of warfarin administration, observation, serial INR/PT
    5.1 - 9.0* If no risk factors for bleeding, hold warfarin x 1-2 days and reduce maintenance dose
    OR
    Vitamin K 1-2 mg PO if patient at increased risk of bleeding or fresh forzen plasma (FPP) if active bleed
     
    9.1 - 20.0* Hold warfarin, Vitamin K 2-4 mg PO, serial INR/PT, additional Vitamin K if necessary or FFP if active bleed
     
    >20.0 FFP 10-15 mL/kg, Vitamin K 10 mg IV over 10 min, increase Vitamin K dosing (q4h) if needed
     


    - Go back and reassess  
    - Call Poison information
    - Obtain corroborative history from family, bystanders
     

    Disposition

    • Methanol, ethylene glycol
      • delayed onset, admit and watch clinical and biochemical markers
    • TCAs
      • prolonged/delayed cardiotoxicity warrants admission to monitored (ICU) bed
      • if asymptomatic and no clinical signs of intoxication: 6 hour ED observation adequate with proper decontamination
      • sinus tachycardia alone (most common finding) with history of OD warrants observation in ED
    • Hydrocarbons/smoke inhalation
      • pneumonitis may lag 6-8 hours
      • consider observation for repeated clinical and radiographic examination
    • ASA, acetaminophen
      • if borderline level, get second level 2-4 hours after first
    • Oral hypoglycemics
      • admit all patients for minimum 24 hours if hypoglycemic
      • observe asymptomatic patient for at least 8 hours

    Psychiatric Consultation

    • once patient medically cleared, arrange psychiatric intervention if required
    • beware - suicidal ideation may not be expressed