Transcript Management of overdose and poisoning

Management of
overdose and poisoning
Paula Jerrard-Dunne
Pharmacology & Therapeutics 2006
General- evaluation
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recognition of poisoning
identification of agents involved
assessment of severity
prediction of toxicity
General- management
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provision of supportive care
prevention of poison absorption
enhancement of elimination of poison
administration of antidotes
Supportive care
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ABC
Vital signs, mental status, and pupil size
Pulse oximetry, cardiac monitoring, ECG
Protect airway
Intravenous access
cervical immobilization if suspect trauma
Rule out hypoglycaemia
Naloxone for suspected opiate poisoning
History
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Pill bottles
Alcohol
Drug history including access
Remember OTC drugs
Suicide note
National Poisons Information Centre *
Examination
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Physiologic excitation –
anticholinergic, sympathomimetic, or central
hallucinogenic agents, drug withdrawal
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Physiologic depression –
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cholinergic (parasympathomimetic), sympatholytic,
opiate, or sedative-hypnotic agents, or alcohols
Mixed state –
polydrugs, hypoglycemic agents, tricyclic
antidepressants, salicylates, cyanide
Drug detection
Drug levels
Preventing absorption
Gastric lavage
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Not in unconscious patient unless intubated (risk aspiration)
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Flexible tube is inserted through the nose into the stomach
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Stomach contents are then suctioned via the tube
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A solution of saline is injected into the tube
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Recommended for up to 2 hrs in TCA & up to 4hrs in Salicylate OD
Induced Vomiting
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Ipecac - Not routinely recommended
Risk of aspiration
Preventing absorption
Activated charcoal
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Adsorbs toxic substances or irritants, thus inhibiting GI
absorption
Addition of sorbitol →laxative effect
Oral: 25-100 g as a single dose
repetitive doses useful to enhance the elimination of certain
drugs (eg, theophylline, phenobarbital, carbamazepine,
aspirin, sustained-release products)
not effective for cyanide, mineral acids, caustic alkalis, organic
solvents, iron, ethanol, methanol poisoning, lithium
Elimination of poisons
Renal elimination
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Medication to stimulate urination or defecation may be given to try to
flush the excess drug out of the body faster.
Forced alkaline diuresis
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Infusion of large amount of NS+NAHCO3
Used to eliminate acidic drug that mainly excreted by the kidney eg
salicylates
Serious fluid and electrolytes disturbance may occur
Need expert monitoring
Hemodialysis or haemoperfusion:
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Reserved for severe poisoning
Drug should be dialyzable i.e. protein bound with low volume of
distribution
may also be used temporarily or as long term if the kidneys are damage
due to the overdose.
Antidotes
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Does an antidote exist?
Does actual or predicted severity of
poisoning warrant its use?
Do expected benefits of therapy
outweigh its associated risk?
Are there contraindications?
Specific overdoses
Opiates
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Antidote – naloxone
MOA: Pure opioid antagonist competes and
displaces narcotics at opioid receptor sites
I.V. (preferred), I.M., intratracheal, SubQ: 0.4-2 mg
every 2-3 minutes as needed
Lower doses in opiate dependence
Elimination half-life of naloxone is only 60 to 90
minutes
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Repeated administration/infusion may be necessary
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S/E BP changes; arrhythmias; seizures; withdrawal
Benzodiazepines
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Antidote – flumazenil
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MOA: Benzodiazepine antagonist
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IV administration 0.2 mg over 15 sec to max 3mg
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S/E N&V; arrhythmias; convulsions
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C/I concomitant TCAD; status epilepticus
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Should not be used for making the diagnosis
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Benzodiazepines may be masking/protecting
against other drug effects
Tricyclic antidepressants
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PHARMACOLOGY —
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TCAs have several important cellular effects, including inhibition of:
Presynaptic neurotransmitter reuptake
Cardiac fast sodium channels
Central and peripheral muscarinic acetylcholine receptors
Peripheral alpha-1 adrenergic receptors
Histamine (H1) receptors
CNS GABA-A receptors
TCAD overdose
clinical features
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Arrhythmias
- widening of PR, QRS, and QT intervals;
heart block; VF/VT
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Hypotension
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Anticholinergic toxicity
- hyperthermia, flushing, dilated pupils,
intestinal ileus, urinary retention, sinus tachycardia
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Confusion, delirium, hallucinations
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Seizures
Diagnosis
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History
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Blood/urine toxicology screen
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Levels not clinically useful
TCAD overdose -Treatment
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ABC – many require intubation
Consider gastric lavage if taken < 2hrs
Activated charcoal
Treatment of hypotension with isotonic saline
Sodium bicarbonate for cardiovascular toxicity
Alpha adrenergic vasopressors (norepinephrine)
for hypotension refractory to aggressive fluid
resuscitation and bicarbonate infusion
Benzodiazepines for seizures
Sodium Bicarbonate in TCA overdose
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Hypertonic sodium bicarbonate (NaHCO3)
- QRS widening >100 msec; ventricular
arrhythmias, and/or refractory hypotension
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↑ serum pH promotes protein binding and ↓ free drug
concentrations; narrows the QRS complex, ↑ systolic blood
pressure, and controls ventricular arrhythmias
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1 to 2 meq/kg (two to three 100 mL ampules of 8.4 percent
NaHCO3) rapid IV push large bore IV then infusion if working
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reasonable goal pH is 7.50 to 7.55 then taper dose
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S/E Volume overload, hypernatreamia, and metabolic alkalosis
Special Cautions in TCAD overdose
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Class IA and IC antiarrhythmic agents are
contraindicated eg quinidine;disopyramide,
flecainide; propafenone
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Class IB Lignocaine, phenytoin used
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Phenytoin may precipitate arrhythmias
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Magnesium may be useful
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Flumazenil must not be given
Salicylate overdose
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Aspirin (acetylsalicylic acid)
Methyl salicylate (Oil of Wintergreen)
5 ml = 7g salicylic acid
Herbal remedies
Fatal intoxication can occur after the
ingestion of 10 to 30 g by adults and as
little as 3 g by children
Salicylate levels
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Plasma salicylate concentration
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Rapidly absorbed; peak blood levels usually occur
within one hour but delayed in overdose 6-35 hrs
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Measure @ 4 hrs post ingestion & every 2 hrs until
they are clearly falling
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Most patients show signs of intoxication when the
plasma level exceeds 40 to 50 mg/dL (2.9 to 3.6
mmol/L)
Salicylate overdose
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Inhibition of cyclooxygenase results in decreased synthesis of
prostaglandins, prostacyclin, and thromboxanes
Stimulation of the chemoreceptor trigger zone in the medulla
causes nausea and vomiting
Direct toxicity of salicylate species in the CNS, cerebral
edema, and neuroglycopenia
Activation of the respiratory center of the medulla results in
tachypnea, hyperventilation, respiratory alkalosis
Uncoupled oxidative phosphorylation in the mitochondria
generates heat and may increase body temperature
Interference with cellular metabolism leads to metabolic
acidosis
Clinical features
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Early symptoms of aspirin toxicity include tinnitus,
fever, vertigo, nausea, hyperventilation, vomiting,
diarrhoea
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More severe intoxication can cause altered mental
status, coma, non-cardiac pulmonary oedema and
death
Metabolic abnormalities
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Stimulate the respiratory center directly, early fall in the PCO2
and respiratory alkalosis
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An anion-gap metabolic acidosis then follows, due to the
accumulation of organic acids, including lactic acid and ketoacids
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Mixed respiratory alkalosis and metabolic acidosis with ↑ anion
gap
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Arterial Ph variable depending on severity
Metabolic abnormalities
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Metabolic acidosis increases the
plasma concentration of protonated
salicylate
thus worsening toxicity by allowing
easy diffusion of the drug across cell
membranes
Salicylate overdose - treatment
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directed toward increasing systemic pH by the administration
of sodium bicarbonate
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IV fluids +/- vasopressors
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Avoid intubation if at all possible (↑ acidosis)
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Supplemental glucose (100 mL of 50 percent dextrose in
adults) to patients with altered mental status regardless of
serum glucose concentration to overcome neuroglycopaenia
Hemodialysis
Alkalinization of plasma and urine
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Alkalemia from a respiratory alkalosis is not a contraindication
to sodium bicarbonate therapy
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A urine pH of 7.5 to 8.0 is desirable
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Blood gas analysis every two hours
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Avoid severe alkalemia (arterial pH >7.60)
Haemodialysis - indications
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Altered mental status
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Pulmonary or cerebral edema
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Renal insufficiency that interferes with salicylate excretion
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Fluid overload that prevents the administration of sodium
bicarbonate
A plasma salicylate concentration >100 mg/dL (7.2 mmol/L)
Clinical deterioration despite aggressive and appropriate supportive
care
Paracetamol
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Widely available
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Potential toxicity underestimated
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Toxicity unlikely to result from a single dose of less than 150
mg/kg in child or 7.5 to 10 g for adult
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Toxicity is likely with single ingestions greater than 250 mg/kg
or those greater than 12 g over a 24-hour period
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Virtually all patients who ingest doses in excess of 350 mg/kg
develop severe liver toxicity unless appropriately treated
Factors influencing toxicity
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Dose ingested
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Excessive cytochrome P450 activity due to induction by
chronic alcohol or other drug use eg carbamazepine,
phenytoin, isoniazid, rifampin
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Decreased capacity for glucuronidation or sulfation
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Depletion of glutathione stores due to malnutrition or chronic
alcohol ingestion
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Acute alcohol ingestion is not a risk factor for hepatotoxicity
and may even be protective by competing with
acetaminophen for CYP2E1
Clinical features
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Stage I (0.5 to 24 hours)
No symptoms; N&V Malaise
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Stage II (24 to 72 hours)
Subclinical elevations of hepatic aminotransferases (AST, ALT)
right upper quadrant pain, with liver enlargement and tenderness.
Elevations of prothrombin time (PT), total bilirubin, and oliguria and
renal function abnormalities may become evident
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Stage III (72 to 96 hours)
Jaundice, confusion (hepatic encephalopathy), a marked elevation in
hepatic enzymes, hyperammonemia, and a bleeding diathesis
hypoglycemia, lactic acidosis, renal failure 25%, death
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Stage IV (4 days to 2 weeks)
Recovery phase that usually begins by day 4 and is complete by 7
days after overdose
Paracetamol overdose
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The risk of toxicity is best predicted by relating the time of
ingestion to the serum paracetamol concentration
The dose history should not be used as studies have found no
correlation
Peak serum concentrations reached within 4 hrs following
overdose of immediate-release preparations
May be delayed with extended releases preparations or drugs
that delay gastric emptying (eg, opiates, anticholinergic
agents) are coingested
Check level at >= 4 hrs
Paracetamol overdose treatment
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Activated charcoal within four hours of
ingestion
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May reduce absorption by 50 to 90 percent
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Single oral dose of one gram per kilogram
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Inhibits absorption of oral methionine
N-acetylcysteine
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Antidote – MOA: a glutathione precursor
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Limits the formation and accumulation of NAPQI
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Powerful anti-inflammatory and antioxidant effects
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IV infusion or oral tablets (also oral methionine)
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150mg/Kg over 15 min; 50mg/Kg over next 4 hrs; 100mg/kg over
next 16 hrs up to 36hrs
Beyond 8 hours, NAC efficacy progressively decreases
S/Es nausea, flushing, urticaria, bronchospasm, angioedema, fever,
chills, hypotension, hemolysis and rarely, cardiovascular collapse
Paracetamol overdose treatment
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At the end of NAC infusion, a blood sample should be taken
for determination of the INR, plasma creatinine and ALT. If
any is abnormal or the patient is symptomatic, further
monitoring is required and advice sought from the NPIS
Patients with normal INR, plasma creatinine and ALT and who
are asymptomatic may be discharged from medical care. They
should be advised to return to hospital if vomiting or
abdominal pain develop or recur
Indications for liver transplantation
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Liver transplantation is life-saving for fulminant hepatic necrosis
The indications for liver transplantation are:
1 - Acidosis (pH < 7.3), or
2 - PT > 100 sec
3 - Creatinine > 300 mcg/l
4 - Grade 3 encephalopathy (or worse)
It is better to contact the local liver transplant centre earlier than this.
Grossly abnormal prothrombin times should trigger referral:
PT > 20 sec at 24 hr
PT > 40 sec at 48 hr
Alcohol poisoning
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Clinical features of acute alcohol poisoning include:
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Ataxia and anaesthesia leading to accidental injury
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Dysarthria and nystagmus
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Drowsiness which may progress to coma
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Inhalation of vomit which can be fatal & should be prevented
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Hypoglycaemia in children and some adults
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Check BM stix and give 50% glucose i.v. if required
Coma (alcohol induced)
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In cases of alcohol induced coma exclude:
Coincident head injury
Hepatic failure
Meningitis
Wernicke’s encephalopathy
Other associated drug ingestion
A blood test will confirm substantial levels of alcohol
Rule out alcoholic hypoglycaemia
The airway and circulation must be maintained
But glucose- containing fluids may precipitate Wernicke's
encephalopathy
Thiamine should given to all
Intravenous naloxone has reversed coma in a proportion of cases