Download Critical Care Toxicology - Division of Critical Care

Critical Care Toxicology
Division of Critical Care Medicine
University of Alberta
Objectives
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Approach to the poisoned patient
General treatment strategies
Common Poisonings in the ICU
Toxicology literature
Epidemiology
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Approximately 2.4million exposures
reported per year in the U.S. (2004)
True incidence unknown
91% - single substance exposures
12.8% required ICU admission
7.0% required non-critical care
1183 fatalities (0.05%)
50.6% of fatal cases were multi-substance
exposures
Immediate Stabilization
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Airway with cervical spine control
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Breathing
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Oxygen, ventilation if respiratory suppression
Circulation
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LOC, emesis, evidence of trauma
IVs, fluid resuscitation
Cardiac monitor
Decontamination
Enhance elimination
Find an antidote
Important historical information
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Often incomplete, unreliable or
unobtainable
What was ingested, how much and when
What was the patient doing when they
became ill
Past medical history
Information from family, friends, EMS
Pill containers – pill count
May need to contact pharmacy
Toxicological Physical Exam
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CNS – level of arousal, GCS, pupils, behavior,
neurological exam
CVS – rate, rhythm
Resp – pattern, depth, wheezing
GI – bowel sounds, distention
Skin – color, temp, signs of trauma
Odors
Toxidromes
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Sympathomimetics
Cholinergic
Anticholinergic
Opiate
Sedative hypnotic
Withdrawal (EtOH, BDZ, opiates)
Laboratory investigations
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General labs: CBC, lytes, BUN, Cr, glucose,
ABG, anion gap
Special laboratory investigation indicated
in following cases
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Intentional ingestion
Substance unknown
Potential for moderate to severe toxicity
Laboratory investigations
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Labs considered essential and available within 4
hrs:
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Labs available through referral center:
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EtOH, acetaminophen, salicylate, digoxin,
carbamazepine, phenobarb, phenytoin, valproate,
theophylline
Methanol, ethylene glycol, isopropyl alcohol, iron,
lithium
Tox screen – generally does not contribute to
patient management
Additional Tests
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ECG – TCA or other cardiotoxic drugs,
arrhythmias, ischemia
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Radiology
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CXR – aspiration, noncardiogenic pulmonary
edema
Abdominal films useful in screening for
ingestions of radio-opaque materials
What substances are visible on AXR?
Antidotes
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If after stabilization a toxin is identified,
there may be a specific antidote
There are approximately 18 antidotes
commonly stored in tertiary care centers
in N. America
Antidotes
antidote
poison
antidote
poison
Acetylcysteine
acetaminophen
Ethanol
MeOH, Et glycol
Crotalid
Antivenin
Crotalid snake bite
Flumazenil
BDZ
atropine
Carbamate or
organophosphate
Fomepizole
MeOH, Et glycol
Glucagon
Β-blocker, CCB
Methylene blue
methemoglobin
Naloxone
opioids
Physostigmine
anticholinergic
Pralidoxime
organophosphate
Pyridoxine
isoniazid
Sodium
bicarbonate
TCA, cocaine,
salicylate
Ca gluconate or CCB or hydrogen
Ca chloride
fluoride
Cyanide kit
cyanide
Deferoxamine
Iron
Digoxin
immune Fab
Digoxin, digitoxin
Dimercaprol
(BAL)
Arsenic, mercury,
lead
Gastrointestinal
Decontamination
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AACT/EAPCCT Position statement on
gastrointestinal decontamination
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Clinical Toxicology 2004, 2005
Ipecac
Gastric Lavage
Whole bowel irrigation
Single dose activated charcoal
Cathartics
Ipecac
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Emetic – both peripherally and central acting
>90% effective
Dose: 30cc PO >5yrs, 15cc 1-5yrs, 10cc 6-12 mo
Indications
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Contraindications
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None, really
consider in the out of hospital toxic ingestion
Unprotected or anticipated unprotected airway
Hydrocarbons, caustics
Debilitated patients
Complications
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Diarrhea, lethargy/drowsiness, prolonged vomiting
Gastric Lavage
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36-40 Fr NG, sequential instillation and removal
of small volumes of isotonic fluid
Indications
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Recent ingestion (<1-2 hr)
Substance exceeds adsorptive capacity of
initial AC dosing
Agents not adsorbed by AC
Substances likely to form concretions after
overdose
Substantial risk of toxicity, or  LOC requiring
intubation (ASA, chloroquine, colchicine, TCA,
CCBs)
Gastric Lavage
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Contraindications
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Unprotected airway
Corrosives
Hydrocarbons
Risk of GI bleed or perforation
Complications
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Aspn pneumonia, laryngospasm, hypoxia,
mechanical injury, fluid/electrolyte imbalances
Whole bowel irrigation
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PEG via NG at 1-2 L/h (500cc/h in peds) until
effluent clear
Indications
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Potentially toxic ingestion of SR or EC prep
Ingested packets of illicit drug (stuffers,
packers)
Substances not adsorbed by AC
Iron ingestions
Whole bowel Irrigation
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Contraindications
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Bowel perforation or obstruction
GI bleed
Ileus
Unprotected airway
Hemodynamic instability
Intractable vomiting
Complications
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Nausea, vomiting, aspiration, cramps
Activated Charcoal
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1g/kg PO or NG
Indications
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Contraindications
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Within 1 hour of ingestion
Nearly all suspected toxic ingestions except
May be considered more than 1 hour after ingestion but
insufficient data to support or exclude use
Unprotected airway
When AC therapy may increase risk and severity of aspiration
Intestinal obstruction
GI tract not anatomically intact (Boerhaave’s…)
Complications
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Aspiration, emesis
Enhancing elimination
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Multiple dose activated charcoal
Alkalinization
Hemodialysis
Hemoperfusion
Multiple Dose Activated Charcoal
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Improves elimination of drugs with enterohepatic
circulation
Initial dose of 1g/kg, then 1/4 - 1/2 g/kg q1h
Consider only if life-threatening amount of:
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May also increase elimination of :
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Carbamazepine
Phenobarbital
Dapsone
Quinine
Theophylline
amitriptyline, propoxyphene, digitoxin, digoxin, disopyramide,
nadolol, phenylbutazone, phenytoin, piroxicam, sotalol
Contraindications same as for single dose AC
Alkalinization
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Enhances elimination of weak bases by ion
trapping
Useful for:
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Salicylate, phenobarbital, chlorpropamide,
methotrexate, myoglobin
NaHCO3 1-2 mEq/kg IV Q3-4H
Aim for Urine pH 7-8
Must replace K in order to achieve alkaline
urine
Hemodialysis
Blood passed across membrane with
countercurrent dialysate flow
 Toxins removed primarily by diffusion
Properties required:
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Molecular weight < 500 daltons
High water solubility
Low or saturable plasma protein binding
Low Vd (<1L/kg)
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Low endogenous clearance(<4ml/min/kg)
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Hemoperfusion
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Blood passed through extracorporeal
circuit containing AC
Toxins removed by adsorption
Properties required:
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Low Vd <1L/kg
Low endogenous clearance <4cc/min/kg
Absorbable to AC
Substances amenable to
hemodialysis
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LET ME SAV P
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Lithium
Ethylene glycol
Theophylline
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MEthanol
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Salicylates
Atenolol
Valproic acid
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Potassium
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Acetaminophen
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Common overdose
Normally 90% metabolized by glucuronidation
and sulfation, 5-10% metabolized by cytP450 to
NAPQI
In overdose glutathione stores are depleted
NAPQI accumulates and directly damages
liver, kidneys…
↑ susceptibility in alcoholics, malnourished b/c
upregulated cytP450 and ↓ glutathione stores
Acetaminophen – clinical
presentation
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Stage 1: Pre-injury period– 0-24h
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Stage 2: Acute liver injury– 24-48h
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RUQ pain, ↑AST/ALT, PTT, INR, bili +/- ↑Cr
Stage 3: Maximal liver injury – 48-96h
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Asymptomatic or minor N+V
marked hepatic dysfnfulminant hepatic failure,
encephalopathy, coagulopathy, hypoglycemia,
acidosis, renal failure
Stage 4: Recovery period - 4-14 days
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Resolution of hepatic dysfunction and recovery
Acetaminophen – treatment
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N-acetylcysteine (NAC) – 20 hr IV protocol
Mechanism of action:
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Glutathione precursor
Glutathione substitute
Substrate for sulfation
Non-specific free radical binder
Rumack-Matthew Nomogram
Acetaminophen
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Obtain serum level at 4hrs post ingestion and
use Rumack-Matthew nomogram
If 8 -24 hrs, or unknown time of ingestion draw
level and start IV NAC
Efficacy of NAC decreases with time if
administered > 8 hrs post ingestion
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No documented fatalities if given within 8 hrs
If over 24 hrs and acetaminophen level
undetectable, AST and INR normal – no
treatment required
If INR > 2 after completion of 20hr protocol,
continue infusion until INR < 2
Acetaminophen – transplant
criteria
King’s College Hospital Criteria
 Metabolic acidosis persisting after
resuscitation – pH <7.3 or lactate > 3.0
 All 3 of below within 24hrs
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Progressive coagulopathy – INR >6.5
Hepatic encephalopathy – Grade 3 -4
Renal failure – Cr >300
ASA
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Toxic dose – 200 mg/kg in single ingestion
(40-45 x 325mg tab)
Pts with chronic ingestion may have
serious toxicity with remarkably low serum
salicylate concentrations
Mortality rate:
acute salicylate intoxication
1%
chronic salicylate intoxication
25%
ASA – preparations
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Aspirin 325 mg/ tab; 500 mg/ tab
Enteric coated aspirin; 325 mg/ tab
Children's aspirin 80 mg
Oil of Wintergreen (100 % Methyl
salicylate)7000 mg/ 5 ml
Ben Gay® (20 % methyl salicylate)6000
mg/ 30 ml
Pepto Bismol (Bismuth subsalicylate)650
mg/ 60 ml
Herbal products contain various amounts
ASA – clinical features
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Initial Sx
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Significant toxicity
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Hearing loss, tinnitus
Hyperventilation, N & V, dehydration,
hyperthermia, altered LOC
Serious toxicity
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Pulmonary edema, cerebral edema, renal
failure, rhabdomyolysis, seizures, coma, death
ASA – clinical features
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Acid Base disturbance
Resp. alkalosis - direct stimulation of medulla
2. Compensatory metabolic acidosis – renal
HCO3 loss
3. Inhibition Krebs cycle enzymes - lactate,
pyruvate anion gap metabolic acidosis
4. Uncoupling of oxidative phosphorylation  tissue glycolysis and BMR 
hypo/hyperglycemia, hyperpyrexia
1.
ASA - treatment
1. Prevent further salicylate absorption
 Gastric decontamination
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Activated charcoal
Whole bowel irrigation
2. Correct fluid deficits and acid-base
abnormalities
 Volume resuscitation
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Careful not to over resuscitate to prevent
precipitation of pulmonary/cerebral edema
Must replace K+
ASA -treatment
3. Enhance elimination
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Ion trapping
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Alkalinize urine: 3 amps NaHCO3 in 1L D5W
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Run @ 250cc/h to urine pH 7.5 -8.0
Urine salicylate clearance is directly
proportional to urine flow rate, but more
importantly, it is logarithmically proportional
to urine pH
ASA - treatment
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Hemodialysis
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Toxic level (>3 mmol/L) and:
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CNS toxicity – sz, coma, delirium
ARDS
Renal failure
Severe acid-base or electrolyte abnormality
Coagulopathy
Unstable or deteriorating vital signs
CHF
Acute level > 7mmol/L
Chronic level > 4 mmol/L
Cardiac drugs – clinical
presentation
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Calcium channel blockers
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Bradycardia and hypotension
Awake and alert
Hyperglycemia
Narrow QRS
May get reflex tachycardia with
dihydropyridines
Cardiac drugs – clinical
presentation
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Beta Blockers
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Bradycardia and hypotension
Depressed LOC
Hypoglycemia
Cardiac drugs
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Digoxin
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Variable HR +/- hypotension
GI and visual symptoms
Hyperkalemia
Characteristic ECG findings
Enhanced automaticity and slowed AV conduction
 Multiple PVCs – ventricular dysrhythmias
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Cardiac drugs - treatment
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Calcium channel blockers
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IV CaCl or Ca gluconate,
Fluids, pressors, pacing, IABP
Insulin/glucose - 10-20 units IV, then 0.2-1
U/kg/h, with D5W or D10W infusion
Beta blockers
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IV glucagon - 5-10 mg over 1 min, then 1-10
mg/h
milrinone/pressors, pacing, IABP
Cardiac drugs - treatment
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Digoxin – Digoxin immune Fab (Digibind)
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Indications for Digibind
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Ventricular dysrhythmia
Progressive/refractory hemodynamic instability
K > 5 with acute toxicity
Acute ingestion > 10 mg
Dosing of Digibind
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Empiric tx acute toxicity– 10 vials
Empiric tx chronic toxicity – 4-6 vials
Known dose: (dose in mg x 0.8)/0.5 = # vials
Steady state Vd at 6hrs: (serum dig level x wt)/100 = # vials
Tricyclic antidepressants
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Rapidly absorbed, large Vd, variable
protein binding, lipophilic
Mechanism of action
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Voltage dependent Na channel blockade –prolonged
QRS
Inward rectifier K channel blockade –prolonged QTc
H1 and H2 receptor blockade – mixed effects
Muscarinic receptor blockade - anticholinergic
α-adrenergic receptor blockade - hypotension
Blocks reuptake DA, NE – altered mental status
GABA receptor blockade - seizures
Tricyclic antidepressants
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Drug levels do not correlate with toxicity
ECG can be diagnostic of Na channel
blockade:
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QRS > 100 msec - 30% risk seizures
QRS > 160 msec – 50% risk arrhythmias
Right axis deviation of terminal 40 msec of
QRS – look in aVR
Prolonged QT
Sinus tachycardia
Tricyclic antidepressants – ECG
Tricyclic antidepressants treatment
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Gastric lavage and AC if indicated
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Avoid acidosis (Sz, ↓BP)
Serum alkalinization (hyperventilation, bicarb)
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Beware rapid decrease in LOC
Uncouples TCA from Na channel
Increases Na gradient (mass effect)
Increased pH decreases tissue penetration of TCA
Indications for alkalinization
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QRS > 100 msec
VT/Cardiac arrest
Seizures or hypotension
Toxic Alcohols
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Methanol
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Present in windshield washer fluid, solvents,
formaldehyde – bitter tasting
Metabolized by alcohol DH, then aldehyde DH
to formaldehyde, then formic acid
Formic acid – inhibits oxidative
phosphorylation and toxic to eyes and CNS
Clinical Presentation
Early (0-6h)– inebriation, gastritis, altered LOC
 Late (6-72h)– visual changes “snowstorm
blindness”, metabolic acidosis, seizures, ↓LOC
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Toxic alcohols
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Ethylene glycol
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Found in antifreeze, coolants – sweet tasting
Metabolized by alcohol dehydrogenase to
glycoaldehyde, glycolic acid and oxalic acid
Inhibit oxidative phosphorylation, and are
toxic to CNS, lung and kidney
Clinical Presentation
Acute neurologic stage (30min-12hrs)
 Cardiopulmonary stage (12-24hrs)
 Renal stage (24-72hrs)
 Delayed neurologic stage (6-12d)
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Toxic alcohols - treatment
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Correct acidemia
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bicarbonate, allow hyperventilation
Prevents diffusion of toxic metabolites into
tissues
Inhibit alcohol dehydrogenase
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EtOH – aim for level 22-33mmol/L
Fomepizole – easier administration, safer,
longer t1/2, but significantly more expensive
Treat if EG>3mmol/L, MeOH >6mmol/L
Documented or suspected ingestion and
OG>10
Toxic alcohols - treatment
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Enhance elimination by hemodialysis
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Serum EG > 8 or MeOH > 15
Metabolic acidosis (pH < 7.25)
End organ symptoms (i.e. visual changes)
Renal impairment, electrolyte abnormalities
Deteriorating vital signs
Continue dialysis until EG < 3 or MeOH <6
Adjunctive treatments
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Thiamine 100mg IV/IM q6H, pyridoxine 50mg
IV/IM q6h (glyoxalateglycine, other non-toxic)
Folate 50 mg IV/IM q6h (FormateC02 +H20)
Summary
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ABC’s
Supportive therapy sufficient for most
overdoses
Decontamination/enhancing elimination
Antidotes/specific treatment indicated for
certain overdoses
Questions
Pupils
Miosis
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Cholinergics/clonidine
Opiates/organophosphates
Phenothiazines,
pilocarpine, pontine bleed
Sedative hypnotics
Mydriasis
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Antihistamines
Antidepressants
Anticholinergics
Sympathomimetics
Odors
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Bitter almonds – cyanide
Fruity – DKA, isopropanol
Minty – methyl salicylates
Rotten eggs – sulfur dioxide, hydrogen
sulfide
Pears – chloral hydrate
Garlic – organophosphates, arsenic
Mothballs - camphor
Drugs that don’t adsorb to AC
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PHAILS
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Pesticides
Hydrocarbons
Acids/alkalis
Iron
Lithium
Solvents
Radiodense substances that may
be visible on AXR
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CHIPES
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Chloral hydrate
Heavy metals
Iron
Phenothiazines
Enteric coated preps
Sustained release preps
Drug Packets