Are You Ready For Tolerating Honesty ?

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06/01/09

are you ready for tolerating honesty ?

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ABC in drug Poisoning ) for education purposes only(

By Dr. Ahmed Shaker Ali Please send any comments regarding this lecture [email protected] 06/01/09

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Objectives 



General Principles in the Management of Poisoning e.g charcoal √√ Specific management options with certain substances e.g    

Paracetamol√√ Opiates )Heroin, Methadone, Morphine( NSAIDs )ibuprofen ( Tricyclic Antidepressants )

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Topics  

Introduction General guidelines regarding the exam (

  

) most slides are optional

ABC, toxidromes, decontamination, antidote Acetaminophen toxicity Heroin toxicity Optional ) Tricyclic antidepressant toxicity (

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Introduction Types of Intoxication

Acute

A sudden and severe exposure to a toxic agent

Subacute

Repeated exposures over a period of hours or days

Chronic

Repeated exposure over weeks or even years

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Assessment & management History & Evaluation, diagnosis life saving measures ) ABC .. ( General measures : o Stop Exposure:

Many steps may be performed simultaneously

o Limit GI Absorption o Hasten Elimination

o Specific antidote Further Investigations & follow up

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General Management -1    

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A )Airway( B )Breathing( C )Circulation( D )Disability-AVPU/ Glasgow Coma Scale( DEFG ) Don’t ever forget the Glucose( GET A SET OF BASIC

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History 

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Who – pt’s age, weight, relation to others What – name and dose of medication, coingestants and how much amount ingested When – time of ingestion, single vs. multiple ingestions Where – route of ingestion, geographical location Why – intentional vs. unintentional,

Also consider : Psychiatric history & other Circumstances Drug history, I identify, keep any drugs came with the patients , or empty containers

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Toxidromes =symptoms of toxicity

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Physical Examination eye { pupil size, nystagmus CNS – level of arousal, GCS, mental status, neurologic exam CVS – Blood pressure, Pulse rater, rhythm Respiration – pattern, depth, wheezing GI – bowel sounds, distention Vomiting Skin – color, temp, sweating, signs of trauma Other observations Odors :

Essential Clinical laboratory tests

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  

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U & Es, LFTs , glucose, ABG, clotting,

Drug monitoring & Toxicology screening E.g Acetaminophen , salicylate , Antiepileptic , digoxin , selective screen ) e.g drugs of abuse ( NB : Toxicology screening need urine samples+ blood samples. Other may be considered : urine analysis Serum osmolality and osmolar gap Osmolar gap = measure - calculated = 0 ± 5 ?? Calculated Os = 2 Na+ glucose + BUN ??

Summery of ABC Management 11 plan 

Supportive monitoring and management of serious life threatening problems 



Correct hypoxia, hypotension, dehydration, hypo- hyperthermia, and acidosis Control seizures

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General measures 2- Decontamination

  

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Surface Decontamination Skin : protect yourself,

remove contaminated clothes , washing, soap and shampoos for oily substances etc EYE : place the victim in supine position under tap water or use IV tubing to direct a stream of water across the nasal bridge into the medial aspect of the eye ) use at least 1L /eye ( Inhalation : remove the patient from exposure, subliminal humidified oxygen, Assist vent. If necessary , Observe closely for URT edema , and late onset pulmonary edema etc

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√GIT decontamination-3 Methods      

activated charcoal Gastric Lavage ? Whole bowel irrigation ? Emesis ???? Cathartics???? Surgery ????????

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√√√Activated Charcoal 

Indications  



Within 1 hour of ingestion Nearly all suspected toxic ingestions except ) inorganic salts, acids, alkali, heavy metals, Iron, alcohols , ethylene glycol (

Contraindications : no absolute contraindications



Complications  

Intestinal impaction if multiple doses Distension of the stomach with potential of pulmonary aspiration.

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√√√Activated Charcoal 



1g/kg PO or NG at least 10 times the ingested dose. One or two additional doses may be used at 1-2 hr intervals

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Whole bowel irrigation 

PEG in a balanced electrolyte soln. via NG at 1-2 L/h )500cc/h in peds( until effluent clear



+ activated charcoal 25-50 g / 2-3 hr Indications Large doses of SR or EC prep of dangerous drugs e.g Theophylline , carbamazepine, aspirin etc

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Contraindications    

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Ingested packets of illicit drug )stuffers, packers( Substances not adsorbed by AC Iron ingestions Ileus , Bowel perforation or obstruction, Intractable vomiting GI bleeding Unprotected airway Hemodynamic instability ??

Complications   

Nausea, vomiting, cramps Aspiration Reduce effectiveness of charcoal

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‫اكثر من‬ ‫التقيىء‬ ‫ضرر‬in ‫ربما‬ Emesis Ipecac –syrup‫????نفعه‬ ) not used hospitals (

 



Emetic – both peripherally and central acting >90% effective Dose: 30cc PO >5yrs, 15cc 1-5yrs, 10cc 6-12 mo

Indications 



Contraindications      



Unprotected or anticipated unprotected airway Hydrocarbons, crossover agent Substance likely to cause CNS depression or seizure in short time Obtunded, comatose or convulsive patients Cardiac and pulmonary patients < 6 month

Complications ) many ( 



Early pre-hospital management when activated charcoal is not available , prolonged transport time to hospital

Diarrhea, lethargy/drowsiness, prolonged vomiting, hemorrhagic gastritis s

A soapy water) dishwashing liquid or lotion , 2 teaspoonful in a glass of water ( solution may be used as alternate emetic

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Gastric Lavage 

Overview : Occasionally used in ER,, not necessary for small to moderate ingestion of most substances if activated charcoal can be given promptly



Indications   



Contraindications     



Obtunded, comatose or convulsive patients SR or enteric coated tab. Corrosives ?? Hydrocarbons Risk of GI bleed or perforation

Adverse effects :  



Recent ingestion )<1-2 hr( Massive overdose or a particularly toxic subsetance Agents not adsorbed by AC

mostly from bad manipulation mechanical injury, Aspiration pneumonia , laryngospasm, hypoxia,, fluid/electrolyte imbalances

Technique : protect airway, proper position, administer activated charcoal before starting lavage

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)Enhancing elimination) EE Overview : Application of toxic kinetics is necessary for appropriate use # 3 Q ?  Q1: Does the patient need EE?  Q2 : Is the drug accessible to the procedure ? 



this depends on PK ) vd, protein binding (

Q3: Will the method work ? 

this depends on Total CL & t-half.

Methods avialble  Urinary manipulation ) Alkalinization of urine for acidic drugs or diuretics(

   

Hemodialysis Hemoperfusion Hemofilteration Repeated dose activated charcoal

Details are optional ) Annex 2 (

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Antidotes ANTAGONISING THE EFFECTS OF THE )

POISON

Antidote

N-acetylcysteine

Poison acetaminophen

atropine

organophosphate

Ca gluconate or Ca chloride Cyanide kit

Calcium channel blockers

Deferoxamine Fab digoxin

Iron Digoxin

Dimercaprol )BAL(

Arsenic, mercury, lead

cyanide

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Antidotes poison

Antidote ethanol

MeOH, et glycol

flumazenil

Benzodiazepine

Fomepizole

MeOH

glucagon

Β-blocker, CCB

Methylene blue

methemoglobin

naloxone

opioids

physostigmine

anticholinergic

pralidoxime

organophosphate

pyridoxine

isoniazid

Sodium bicarbonate

TCA, cocaine, salicylates

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Paracetamol toxicity

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



Toxicity Little to no toxicity in therapeutic dosing With overdose: 



Hepatic toxicity progressing to fulminant hepatic failure, encephalopathy and death within days Other systemic effects

Pharmacological basis of √√√√√ Acetaminophen toxicity

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Acetaminophen O ll HN-C-CH3

Glucuronidation

Sulfation

OH

P450

N-Acetyl-p-benzoquinonamine

NAPQI Oxidant tissue damage

Glutathione

Non-toxic metabolites

Oxidant tissue damage

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

   

Overdose Normal conjugation metabolism routes are saturated More NAPQI is produced Glutathione reserves fall below 30% Unable to detoxify all NAPQI formed Cellular injury results

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Management NB in initial phases no clear symptoms. Drug monitoring is very valuable if done properly N-actylcystine is the anti-dote Use the Rumack-Matthew Nomogram to identify the potential toxicity

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Rumack-Matthew Nomogram for Acute Acetaminophen Toxicity

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Opiate Poisoning- Features    

Heroin ) addiction ( Methadone, analgesics in Elderly General toxidromes.   

‫بئس المصير‬

1. PINPOINT PUPILS 2. RESPIRATORY DEPRESSION 3.COMA

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Opiate OverdoseManagement     

INITIAL MANAGEMENT A B C D

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Opiate OverdoseManagement 2 

NALOXONE     



Opioid antagonist High Affinity for the opiate receptors Little other effects Rapid onset Effects last 2-4 hrs, may need repeated doses Give I-M or I-V

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References You may visit these sites  http://www.clintox.org  http://www.aapcc.org  TOXNET database http://toxnet.nlm.nih.gov/index.htm/  Text book : Poisoning and & drug overdose  Kent R OLSON 4th ed . LANGE P. 66-69 , 286-289

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) Optional section ) SDL

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A irway 

Assessment :



Patients awake )monitor closely ( lethargic or obtunded ) consider management (

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Management : Optimize the airway position o o o

)practical skill (

Sniffing position Jaw thrust Head down, left sided position

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Remove any obstruction or secretions

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Perform endotrachial intubations if indicated o o

Nasotrachial orotracheal

or

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B reathing 1-Ventilatory failure cause : CNS depression by opiates, barbiturates alcohol, Tricylic antidepressants, etc ) R.O other causes ( Assessment : Arterial blood gases ) PCO2 > normal values( indicate the need for assisted ventilation Treatment : Assisted ventilation : optimal programming of the ventilator

2- Hypoxia cause : sedative hypnotic , opiates ,salicylates,) R.O other causes ( Treatment : Correct hypoxia : Administer oxygen as indicated based on arterial PO2

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Breathing cont 3- Cellular hypoxia cause : CO , Cyanide & hydrogen sulfide Treatment : CO ) 100 % oxygen , consider hyperbaric oxygen ( refer to the specific guide

4- Bronchospasm

Cause : Direct irritant ) gases, aspiration of petroleum distillates ( Pharmc effects of poisons or drugs ; e.g Organophosporous , carbamates insecticides, B-blockers . Hypersensitivity : many drugs & poisons Treatment : o Administer oxygen, assist ventilation, endotrachial intubations if needed , o Administer bronchodilators o e.g albutrol 2.5-5 mg in nebulizer o ibratroprium bromide 0.5 mg 4-6 h o consider iV theophylline in case of B-blockers poisoning

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C irculation 

I-General

Check BP , pulse rate & rhythm. CRP ) cardiopulmonary resuscitation( if no pulse ACLS [ Advanced cardiac life support ] for severe arrhythmia and shock Begin cont EEG monitoring Begin IV infusion of appropriate fluids Secure venous access  II: Bradicardia & AV block no treatment unless the pt is symptomatic Treatment include : maintain airway and assists ventilation if necessary Atropine 0.01-0.03 mg/kg IV or isopreternol 1-10 mcg/min, ER pacemaker Specific antidote if appropriate o Glucogon for bet-blockers over dose o Fab digoxin for digoxin toxicity

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Circulation cont 

III-QRS INTERVAL PROLONGATION



>0.12S INDICATE POSIONING BY TCA OR OTHER MEMBRANE DEPRESSANT DRUGS eg digitalis , b-blockers



Treatment :

o

maintain airway and assists ventilation if necessary Treat hyperkalimia and hypothermia if present Treat AV block by atropine , isoppteternol and pacemaker if necessary for TCA or other sodium channel blockers give 1-2 mEq sod bicarc IV bolus, repeat as needed

o o

o

o

Other antidote if appropriate

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Circulation 

III-Tachycardia causes : many e.g sympathomimetic agents : Amphetamine ,

theophylline , cocaine Treatment observation and sedation if no chest pain or hypotension sympathomimetic induced : propranolol or esmolol If tachycardia is anticholinergic induced ; consider use of neostigmine these drugs should be avoided in case of TCA ) A systole additive depression of conduction (

V-Ventricular arrhythmia  Causes : many drugse.g exissive Sympathetic stimulation ) cocaine , amphetamine (



Treatment :

follow the standard guidelines for management of arrhythmia with exception : Procanimide and bretylium should not be used esp if TCA or B-blockers over dose is suspected.

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Circulation cont VI-Hypotension 

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Causes : many drugs. Opiates , sedative hypnotics , theophylline , TCA Treatment :usually respond to simple measures Fluid therapy and low dose of pressor drugs IF not resolved use systematic approach Which consider management of Airway, Arrhythmia, hypothermia, dopamine ) nor-epinephrine in case of TCA Specific antidote

VII-Hypertension Causes : With Tachycardia : LSD, Cocaine, Amphetamine, TCA  Treatment : it depends on other symptoms: No Tachycardia : phentolamine or nitroprusside Presence of Tachycardia : As above + propranolol or esmolol or labetolol NB : not use These drugs alone for treatment of hypertensive crisis 

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Mental Status 

Coma and stupor



Cause: many Treatment :

    

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:Generalized CNS depressants & sympatholytic

1-Maintain airway , assists ventilation, administer oxygen if necessary 2-DRUGS : Dextrose, Thiamine, Naloxone ) if respiratory depression, Flumazenil ) If Benzodiazepine alone is suspected

(

Hypothermia : follow the guidelines Hyperthermia : follow the guidelines

Key words :,, Treatment : immediate rapid cooling  1- as above, 2- Fluids, 3- Control of seizure 4-External cooling with tepid sponging and fanning 5- specific drugs , neuromuscular paralysis by vecuronium Malignant hyperthermia : Give dantrolene neuroleptic malignant syndrome : Consider bromocriptine serotonin syndrome : cryptoheptadine or methylsergide my helpful 

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Mental Status cont Seizure : 

Causes :

many drugs including adrenergic sympathomimetic agents

Antidepressants and antipsychotic 

Treatment :



1- 1-Maintain airway , assists ventilation, administer oxygen if

  





necessary 2- Nalxone : if seizure is due to narcotic 3-correct hypoglycemia : dextrose and thiamine as for coma 4- Appropriate anticonvulsant drug ) Diazepam, Lorazepam, Midazolam, phenobarbital, pentoparbital, propofol , phenytoin } 5-Specific antidote : Pralidoxime or atropine or both for organophosphate or carbamate insectside

Agitation, delirium or Psychosis follow the guideline

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Other complications      

Dystonic reactions Dyskinesia Rigidity Rhabdomylosis Anaphylaxis Anaphylactoid reactions

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Details of Enhanced elimination

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Hemodialysis   

Blood passed across membrane with countercurrent dialysate flow Toxins removed by diffusion Patient must be anticoagulated

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(

Complications      

Bleeding at venous puncture site hypotension DVT Bleeding due to systemic anticoagulation Infection Air embolus

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Hemoperfusion Overview : Blood passed through cartridge containing AC  Toxins removed by adsorption Advantages : Drug characteristics are less important  Usually greater clearance rate Disadvantages Systemic anticoagulant is required  Thrombocytopenia is a common complication



Properties required:  



Low Vd <1L/kg Low endogenous clearance <4cc/min/kg Adsorbable to AC

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Peritoneal dialysis 

  

Easer to perform than other dialysis tech. Only 10-15 % as effective , slow Cl. rate Can be performed continuously 24 hr Pr. D = 4 hr of Hemo. D.

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Alkalinization 



Enhances elimination of weak bases by ion trapping Useful for: 

  

Salicylates, phenobarbital, chlorpropamide, methotrexate, myoglobin

NaHCO3 1-2 mEq/kg IV Q3-4H Aim for Urine pH 7-8 Must replace K

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Multiple Dose Activated Charcoal 

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

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Details of Toxicity of Acetaminophen

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Phase I  

0 to 24 hours Usually asymptomatic 

“silent overdose”: 



Importance of obtaining level

Nausea, vomiting, abdominal pain

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Phase II  

24-72 hours Resolution of initial physical symptoms 



May develop right upper quadrant pain

Evolving liver injury 

Elevation of LFT, PT, Bilirubin

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Phase III  







3 to 4 days Nausea, vomiting, and abdominal pain reoccur Maximal manifestation of hepatic injury-AST/ALT in 10,000s Coagulopathy, hepatic necrosis, acidosis, encephalopathy Coma and anuria precede death

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Phase IV   



Beyond 4 days Recovery phase LFTs will decrease, but bilirubin may remain elevated for some time May take several weeks for LFTs to normalize

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Other Overdose Sequelae 

Renal toxicity 

Occasionally renal failure can occur from massive overdoses 

 

Possibly 2° to P450 activity in the kidney

Pancreatitis Pneumonitis

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



Is a guideline for determining who should be treated for a single acute ingestion Is not a representation of the elimination kinetics 



Serial levels not useful

In US, line positioned 25% lower  



The Nomogram

↑ sensitivity – no missed cases ↓ specificity

Important to use a 4-hour level whenever possible

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Ingestion of single dose 

Treatment indicated if:    

Level above 150mg/dL at 4 hours Ingestion of 150 mg/kg in children Ingestion of 7.5 g in adults Patient is unreliable or unconscious

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N-acetylcysteine

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Mechanism of N-acetylcysteine 

Restores glutathione: 

 

Allows NAPQI detoxification

Augments sulfation reaction Direct anti-oxidant:  

Directly detoxifies NAPQI Improves organ function and limits hepatocyte injury

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Unknown ingestion time 





Treat if any sign of liver injury even without history of APAP ingestion Detectable APAP level in altered patient If AST/ALT are normal 

And APAP is less than 10 µg/ml  

Do not treat Narrow window of risk

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Laboratory Assessment 

If patient is sick, one should obtain LFTs, PT, electrolytes, BUN/Cr, amylase, lipase and glucose 

 

Late presenting sick patients will not have detectable acetaminophen levels Diagnosis can be more difficult They will require treatment

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Repeat or Chronic ingestion  

Nomogram does not apply Suggested threshold:  



150 mg/kg per 24 hours in children 7.5 g per 24 hour period in adults

Obtain acetaminophen level, AST, ALT, PT, BUN/Cr and electrolytes

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Repeat or chronic ingestion 

Patients who should be treated )similar to unknown ingestion time(:   



Signs of hepatotoxicity )elevated AST( APAP level of ≈25 mcg/ml or greater Symptomatic

“Gray area”: APAP 11-25 mcg/ml and normal AST in asymptomatic patient

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Ethanol And Acetaminophen 



Ethanol is metabolized to some extent by P450 system Chronic ethanol ingestion causes increase in 2E1 P450 activity 

Acute acetaminophen ingestion is treated the same in patients who consume alcohol chronically

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N-acetylcysteine

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N-acetylcysteine 

Greatest benefit if administered within 8 hours:  





No clinical difference within the first 8 hours All patients that have a normal AST at time of NAC initiation survive Treatment within 8 hours of single ingestion completely prevents liver failure

“Too Late” does not exist 

Improved mortality even in patients with hepatic failure when initiated 2-3 days after ingestion

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Oral N-acetylcysteine 

Oral loading dose is 140 mg/kg  





Dilute 4:1 with palatable liquid Repeat doses are 70mg/kg every 4 hours Total of 17 doses for total of 72 hours

Antiemetic treatment may be required 

NAC is very foul “rotten egg” liquid

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IV N-acetylcysteine 

Can cause anaphylactoid reaction 







Rash, hypotension, bronchospasm and death Rate related; rare when given slowly

Higher, continuous blood levels obtained then oral NAC Bolus administered first, then constant infusion rate may be given

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IV vs. Oral 



 

Both have their advantages and disadvantages Each may be more appropriate in certain settings No side by side studies to date Conclusions of relative benefits are speculative