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Objectives. Approach to the poisoned patientGeneral treatment strategiesCommon Poisonings in the ICUToxicology literature. Epidemiology. Approximately 2.4million exposures reported per year in the U.S. (2004)True incidence unknown91% - single substance exposures12.8% required ICU admission7.
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1. Critical Care Toxicology Division of Critical Care Medicine
University of Alberta
2. Objectives Approach to the poisoned patient
General treatment strategies
Common Poisonings in the ICU
Toxicology literature
3. Epidemiology 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 Poisonings are common
Very few are fatal and fatal poisonings often involve more than one drug
WA Watson et al, 2004 AAPCC Annual ReportPoisonings are common
Very few are fatal and fatal poisonings often involve more than one drug
WA Watson et al, 2004 AAPCC Annual Report
4. Immediate Stabilization Airway with cervical spine control
LOC, emesis, evidence of trauma
Breathing
Oxygen, ventilation if respiratory suppression
Circulation
IVs, fluid resuscitation
Cardiac monitor
Decontamination
Enhance elimination
Find an antidote
Failure to secure the airway is most lethal toxicological complication Failure to secure the airway is most lethal toxicological complication
5. Important historical information 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
6. Toxicological Physical Exam 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
Brief, but detailed physical exam, hyperalert look for anticholinergic toxidrome, nystagmus PCP, phenytoin GI may alert to toxidrome or to contraindication to decon methods Brief, but detailed physical exam, hyperalert look for anticholinergic toxidrome, nystagmus PCP, phenytoin GI may alert to toxidrome or to contraindication to decon methods
7. Toxidromes Sympathomimetics
Cholinergic
Anticholinergic
Opiate
Sedative hypnotic
Withdrawal (EtOH, BDZ, opiates)
After PE may be alerted to one of the more common toxidromes
Can quiz residents on these or notAfter PE may be alerted to one of the more common toxidromes
Can quiz residents on these or not
8. Laboratory investigations General labs: CBC, lytes, BUN, Cr, glucose, ABG, anion gap
Special laboratory investigation indicated in following cases
Intentional ingestion
Substance unknown
Potential for moderate to severe toxicity
Numerous studies in both adult and pediatric populations demonstrate that tox screen does not contribute to management of ptNumerous studies in both adult and pediatric populations demonstrate that tox screen does not contribute to management of pt
9. Laboratory investigations Labs considered essential and available within 4 hrs:
EtOH, acetaminophen, salicylate, digoxin, carbamazepine, phenobarb, phenytoin, valproate, theophylline
Labs available through referral center:
Methanol, ethylene glycol, isopropyl alcohol, iron, lithium
Tox screen generally does not contribute to patient management
10. Additional Tests ECG TCA or other cardiotoxic drugs, arrhythmias, ischemia
Radiology
CXR aspiration, noncardiogenic pulmonary edema
Abdominal films useful in screening for ingestions of radio-opaque materials
What substances are visible on AXR?
11. Antidotes 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
12. Antidotes
If, after your history, physical and lab investigations youve idd a toxin there may be a specific antidote
There are approximately 18 antidotes commonly stocked in tertiary care centers in N. AmericaIf, after your history, physical and lab investigations youve idd a toxin there may be a specific antidote
There are approximately 18 antidotes commonly stocked in tertiary care centers in N. America
13. Gastrointestinal Decontamination AACT/EAPCCT Position statement on gastrointestinal decontamination
Clinical Toxicology 2004, 2005
Ipecac
Gastric Lavage
Whole bowel irrigation
Single dose activated charcoal
Cathartics
14. Ipecac Emetic both peripherally and central acting
>90% effective
Dose: 30cc PO >5yrs, 15cc 1-5yrs, 10cc 6-12 mo
Indications
None, really
consider in the out of hospital toxic ingestion
Contraindications
Unprotected or anticipated unprotected airway
Hydrocarbons, caustics
Debilitated patients
Complications
Diarrhea, lethargy/drowsiness, prolonged vomiting
Historical value onlyHistorical value only
15. Gastric Lavage
36-40 Fr NG, sequential instillation and removal of small volumes of isotonic fluid
Indications
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)
16. Gastric Lavage Contraindications
Unprotected airway
Corrosives
Hydrocarbons
Risk of GI bleed or perforation
Complications
Aspn pneumonia, laryngospasm, hypoxia, mechanical injury, fluid/electrolyte imbalances
17. Whole bowel irrigation PEG via NG at 1-2 L/h (500cc/h in peds) until effluent clear
Indications
Potentially toxic ingestion of SR or EC prep
Ingested packets of illicit drug (stuffers, packers)
Substances not adsorbed by AC
Iron ingestions
18. Whole bowel Irrigation Contraindications
Bowel perforation or obstruction
GI bleed
Ileus
Unprotected airway
Hemodynamic instability
Intractable vomiting
Complications
Nausea, vomiting, aspiration, cramps
19. Activated Charcoal 1g/kg PO or NG
Indications
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
Contraindications
Unprotected airway
When AC therapy may increase risk and severity of aspiration
Intestinal obstruction
GI tract not anatomically intact (Boerhaaves)
Complications
Aspiration, emesis
Produced by pyrolysis of carbonaceous materials to incr surface area, first demonstrated in 1930 by touery who took several times lethal dose of strychnine in front of the Academie Francaise , chased it with charcoal and survived. A number of questions remain to be answered charcoal vs. nothing, symptomatic patients presenting in first hour after ingestion of agents that slow gastric emptying, sustained release preps, massive or life threatening ingestions, what to do for caustic ingestions,
Single-dose activated charcoal should not be administered routinely in the management of poisoned patients. Based on volunteer studies, the administration of activated charcoal may be considered if a patient has ingested a potentially toxic amount of a poison (which is known to be adsorbed to charcoal) up to one
hour previously. Although volunteer studies demonstrate that the reduction of drug absorption decreases to values of questionable clinical importance when charcoal is administered at times greater than one hour, the potential for benefit after one hour cannot be excluded. There is no evidence that the administration
of activated charcoal improves clinical outcome. Unless a patient has an intact or protected airway, the administration of charcoal is contraindicated.
Produced by pyrolysis of carbonaceous materials to incr surface area, first demonstrated in 1930 by touery who took several times lethal dose of strychnine in front of the Academie Francaise , chased it with charcoal and survived. A number of questions remain to be answered charcoal vs. nothing, symptomatic patients presenting in first hour after ingestion of agents that slow gastric emptying, sustained release preps, massive or life threatening ingestions, what to do for caustic ingestions,
Single-dose activated charcoal should not be administered routinely in the management of poisoned patients. Based on volunteer studies, the administration of activated charcoal may be considered if a patient has ingested a potentially toxic amount of a poison (which is known to be adsorbed to charcoal) up to one
hour previously. Although volunteer studies demonstrate that the reduction of drug absorption decreases to values of questionable clinical importance when charcoal is administered at times greater than one hour, the potential for benefit after one hour cannot be excluded. There is no evidence that the administration
of activated charcoal improves clinical outcome. Unless a patient has an intact or protected airway, the administration of charcoal is contraindicated.
20. Enhancing elimination Multiple dose activated charcoal
Alkalinization
Hemodialysis
Hemoperfusion Hemodialysis has been discussed, hemoperfusion is accomplished by running the venous blood through a charcoal hemoperfusion cartridge
The advantage of hemodialysis over hemoperfusion is that HD can also correct met acidosis/alkalosis, hyperkalemia, and fluid overloadHemodialysis has been discussed, hemoperfusion is accomplished by running the venous blood through a charcoal hemoperfusion cartridge
The advantage of hemodialysis over hemoperfusion is that HD can also correct met acidosis/alkalosis, hyperkalemia, and fluid overload
21. Multiple Dose Activated Charcoal 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:
Carbamazepine
Phenobarbital
Dapsone
Quinine
Theophylline
May also increase elimination of :
amitriptyline, propoxyphene, digitoxin, digoxin, disopyramide, nadolol, phenylbutazone, phenytoin, piroxicam, sotalol
Contraindications same as for single dose AC
22. Alkalinization Enhances elimination of weak bases by ion trapping
Useful for:
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 Not to be confused with forced alkaline diuresis
Acidification of urine for weak bases was performed in the past, but not shown any benefit and causes met acidosisNot to be confused with forced alkaline diuresis
Acidification of urine for weak bases was performed in the past, but not shown any benefit and causes met acidosis
23. Hemodialysis Blood passed across membrane with countercurrent dialysate flow
Toxins removed primarily by diffusion
Properties required:
Molecular weight < 500 daltons
High water solubility
Low or saturable plasma protein binding
Low Vd (<1L/kg)
Low endogenous clearance(<4ml/min/kg)
24. Hemoperfusion Blood passed through extracorporeal circuit containing AC
Toxins removed by adsorption
Properties required:
Low Vd <1L/kg
Low endogenous clearance <4cc/min/kg
Absorbable to AC Can also perform hemoperfusion/hemodialysis in seriesCan also perform hemoperfusion/hemodialysis in series
25. Substances amenable to hemodialysis LET ME SAV P
Lithium
Ethylene glycol
Theophylline
MEthanol
Salicylates
Atenolol
Valproic acid
Potassium Atenolol is only b-blocker with low VdAtenolol is only b-blocker with low Vd
27. Acetaminophen 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
28. Acetaminophen clinical presentation Stage 1: Pre-injury period 0-24h
Asymptomatic or minor N+V
Stage 2: Acute liver injury 24-48h
RUQ pain, ?AST/ALT, PTT, INR, bili +/- ?Cr
Stage 3: Maximal liver injury 48-96h
marked hepatic dysfn?fulminant hepatic failure, encephalopathy, coagulopathy, hypoglycemia, acidosis, renal failure
Stage 4: Recovery period - 4-14 days
Resolution of hepatic dysfunction and recovery
29. Acetaminophen treatment N-acetylcysteine (NAC) 20 hr IV protocol
Mechanism of action:
Glutathione precursor
Glutathione substitute
Substrate for sulfation
Non-specific free radical binder
30. Rumack-Matthew Nomogram
31. Acetaminophen 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
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
32. Acetaminophen transplant criteria Kings College Hospital Criteria
Metabolic acidosis persisting after resuscitation pH <7.3 or lactate > 3.0
All 3 of below within 24hrs
Progressive coagulopathy INR >6.5
Hepatic encephalopathy Grade 3 -4
Renal failure Cr >300
33. ASA 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%
34. ASA preparations 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
35. ASA clinical features Initial Sx
Hearing loss, tinnitus
Significant toxicity
Hyperventilation, N & V, dehydration, hyperthermia, altered LOC
Serious toxicity
Pulmonary edema, cerebral edema, renal failure, rhabdomyolysis, seizures, coma, death
36. ASA clinical features Acid Base disturbance
Resp. alkalosis - direct stimulation of medulla
Compensatory metabolic acidosis renal HCO3 loss
Inhibition Krebs cycle enzymes -? lactate, ?pyruvate ?anion gap metabolic acidosis
Uncoupling of oxidative phosphorylation - ? tissue glycolysis and BMR ? hypo/hyperglycemia, hyperpyrexia
37. ASA - treatment 1. Prevent further salicylate absorption
Gastric decontamination
Activated charcoal
Whole bowel irrigation
2. Correct fluid deficits and acid-base abnormalities
Volume resuscitation
Careful not to over resuscitate to prevent precipitation of pulmonary/cerebral edema
Must replace K+
Absorption is rapid with therapeutic doses, but may be significantly delayed in overdose (concretion formation)Absorption is rapid with therapeutic doses, but may be significantly delayed in overdose (concretion formation)
38. ASA -treatment 3. Enhance elimination
Ion trapping
Alkalinize urine: 3 amps NaHCO3 in 1L D5W
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
39. ASA - treatment Hemodialysis
Toxic level (>3 mmol/L) and:
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
40. Cardiac drugs clinical presentation Calcium channel blockers
Bradycardia and hypotension
Awake and alert
Hyperglycemia
Narrow QRS
May get reflex tachycardia with dihydropyridines CCBs interfere with activity of insulinCCBs interfere with activity of insulin
41. Cardiac drugs clinical presentation Beta Blockers
Bradycardia and hypotension
Depressed LOC
Hypoglycemia
B-blockers block B-blockers block
42. Cardiac drugs Digoxin
Variable HR +/- hypotension
GI and visual symptoms
Hyperkalemia
Characteristic ECG findings
Enhanced automaticity and slowed AV conduction
Multiple PVCs ventricular dysrhythmias
GI N and V, visual yellow-green halos around lights
Dig effect does not correlate with toxicityGI N and V, visual yellow-green halos around lights
Dig effect does not correlate with toxicity
43. Cardiac drugs - treatment Calcium channel blockers
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
IV glucagon - 5-10 mg over 1 min, then 1-10 mg/h
milrinone/pressors, pacing, IABP
Insulin/glucose - J.A. Kline et al. Cardiovascular Research 34(1997)289298
Insulin thought to improve myocardial carbohydrate utilization in CCB overdose (acts as an inotrope), insulin release is also a Ca channel dependent processInsulin/glucose - J.A. Kline et al. Cardiovascular Research 34(1997)289298
Insulin thought to improve myocardial carbohydrate utilization in CCB overdose (acts as an inotrope), insulin release is also a Ca channel dependent process
44. Cardiac drugs - treatment Digoxin Digoxin immune Fab (Digibind)
Indications for Digibind
Ventricular dysrhythmia
Progressive/refractory hemodynamic instability
K > 5 with acute toxicity
Acute ingestion > 10 mg
Dosing of Digibind
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
45. Tricyclic antidepressants Rapidly absorbed, large Vd, variable protein binding, lipophilic
Mechanism of action
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
a-adrenergic receptor blockade - hypotension
Blocks reuptake DA, NE altered mental status
GABA receptor blockade - seizures
46. Tricyclic antidepressants Drug levels do not correlate with toxicity
ECG can be diagnostic of Na channel blockade:
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
47. Tricyclic antidepressants ECG
48. Tricyclic antidepressants - treatment Gastric lavage and AC if indicated
Beware rapid decrease in LOC
Avoid acidosis (Sz, ?BP)
Serum alkalinization (hyperventilation, bicarb)
Uncouples TCA from Na channel
Increases Na gradient (mass effect)
Increased pH decreases tissue penetration of TCA
Indications for alkalinization
QRS > 100 msec
VT/Cardiac arrest
Seizures or hypotension
49. Toxic Alcohols Methanol
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
50. Toxic alcohols Ethylene glycol
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) Stages
Acute neurol inebriation, N/V, seizures, coma, osmolar gap
Cardiopulmonary HTN, tachycardia, met acidosis +/- pulmonary edema, shock
Renal crystalluria, hematuria, proteinuria, ATN and flank pain
Delayed Neurologic cranial n. palsies, deafness, cognitive and motor abnormalities, personality changesStages
Acute neurol inebriation, N/V, seizures, coma, osmolar gap
Cardiopulmonary HTN, tachycardia, met acidosis +/- pulmonary edema, shock
Renal crystalluria, hematuria, proteinuria, ATN and flank pain
Delayed Neurologic cranial n. palsies, deafness, cognitive and motor abnormalities, personality changes
51. Toxic alcohols - treatment Correct acidemia
bicarbonate, allow hyperventilation
Prevents diffusion of toxic metabolites into tissues
Inhibit alcohol dehydrogenase
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
52. Toxic alcohols - treatment Enhance elimination by hemodialysis
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
Thiamine 100mg IV/IM q6H, pyridoxine 50mg IV/IM q6h (glyoxalate?glycine, other non-toxic)
Folate 50 mg IV/IM q6h (Formate?C02 +H20)
when alcohol DH blocked, t1/2 MeOH = 45hrs, Ethylene glycol =19hrs
With EG watch calcium as oxalate will bindwhen alcohol DH blocked, t1/2 MeOH = 45hrs, Ethylene glycol =19hrs
With EG watch calcium as oxalate will bind
53. Summary ABCs
Supportive therapy sufficient for most overdoses
Decontamination/enhancing elimination
Antidotes/specific treatment indicated for certain overdoses
54. Questions
55. Pupils Miosis
Cholinergics/clonidine
Opiates/organophosphates
Phenothiazines, pilocarpine, pontine bleed
Sedative hypnotics
Mydriasis
Antihistamines
Antidepressants
Anticholinergics
Sympathomimetics
56. Odors Bitter almonds cyanide
Fruity DKA, isopropanol
Minty methyl salicylates
Rotten eggs sulfur dioxide, hydrogen sulfide
Pears chloral hydrate
Garlic organophosphates, arsenic
Mothballs - camphor
57. Drugs that dont adsorb to AC PHAILS
Pesticides
Hydrocarbons
Acids/alkalis
Iron
Lithium
Solvents
58. Radiodense substances that may be visible on AXR CHIPES
Chloral hydrate
Heavy metals
Iron
Phenothiazines
Enteric coated preps
Sustained release preps
Drug Packets