acute poisoning
DESCRIPTION
Acute Poisoning. Michael Eddleston NPIS Edinburgh SpR in Clinical Toxicology, RIE. NPIS Edinburgh. THE IMPORTANCE OF PHARMACOLOGY. - PowerPoint PPT PresentationTRANSCRIPT
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Acute PoisoningAcute Poisoning
Michael Eddleston
NPIS Edinburgh
SpR in Clinical Toxicology, RIE NPIS
Edinburgh
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THE IMPORTANCE OF PHARMACOLOGYTHE IMPORTANCE OF PHARMACOLOGY
“You may experience a difficulty in remembering the antidotes for the various poisons. If so, rest assured that your knowledge of pharmacology is defective. All rational treatment of cases of poisoning is founded on a correct appreciation
of the physiological action of drugs.”
What to do in cases of poisoning, William Murrell, 1925
NPIS
Edinburgh
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EPIDEMIOLOGYEPIDEMIOLOGY
• most common cause of medical presentation accounting for 10-20% of acute medical admissions (RIE 3000 of 15000/annum)
• females > males, but male rate rising NPIS
Edinburgh
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APPRAISAL OF THE POISONED APPRAISAL OF THE POISONED PATIENTPATIENT
• history from patient
• tablets / circumstances found
• clinical features (“TOXIDROMES”)» Opiate» anticholinergic» stimulant» metabolic acidosis
NPIS
Edinburgh
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Gastric lavageWard 3, Royal Infirmary of Edinburgh, 1973
(courtesy of Alex Proudfoot)
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PREVENTION OF ABSORPTIONPREVENTION OF ABSORPTION
• activated charcoal
• binds non-specifically
• binds about 1/10 of charcoal weight
• (charcoal dose 50 g in an adult)
• Slow release products
NPIS
Edinburgh
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Christophersen et al, Br J Clin Pharmacol 2002; 53: 312-7.
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ACTIVATED CHARCOALACTIVATED CHARCOAL
• timing - use within 1 hour
• airway - don’t if problems
• agent - eg iron, lithium, hydrocarbons NOT bound
NPIS
Edinburgh
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PARACETAMOLPARACETAMOL
NPIS
Edinburgh
PROBLEMS
• Indications for treatment
• Staggered overdose
• Late presentations
• Reactions to antidote
• Interpretation of results in poisoning
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NPIS
Edinburgh
Paracetamol Quantity
Activity
Quantity
RISK FACTORS IN PARACETAMOL OD
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PARACETAMOL: RISK FACTORSPARACETAMOL: RISK FACTORS
NPIS
Edinburgh
Nutritional deficiencyEating disordersAlcoholism Malabsorption syndromesAIDS?? Acute starvation
(CLUE: Blood urea)
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PARACETAMOL: RISK FACTORSPARACETAMOL: RISK FACTORS
NPIS
Edinburgh
Enzyme inducers: carbamazepinephenytoin
barbituratesrifampicin
St Johns wortchronic ethanol
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PARACETAMOL: RISK FACTORSPARACETAMOL: RISK FACTORS
NPIS
Edinburgh
Enzyme inducers: carbamazepinephenytoinbarbituratesrifampicinSt Johns wortchronic ethanol
CLUE: Gamma GT
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Schmidt et al Hepatol 2002; 35: 876-882.
The cumulative survival rates for every time to acetylcysteine for each alcohol subgroup. There was a significant difference between the chronic and other subgroups (p < 0.0001 by Cox’s F test)
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NPIS
Edinburgh
Paracetamol Quantity
Activity
Quantity
RISK FACTORS IN PARACETAMOL OD
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NPIS
Edinburgh
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Outcome – ALT >1000 related to original plasma level and time of ingestion- ORAL NAC
Rumack 2002 Clin Toxicol 40: 3-20.
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Current use of Acetylcysteine
NPIS
Edinburgh
• Before 4 hours - WAIT until 4 hours• 4-8 Hours - Blood sample and wait **• 8- 24 Hours - Treat on history, do bloods• After 24 hours - Do bloods unless toxic
• STAGGERED INGESTION – use first dose time for treatment decisions
**ASSUMES RESULT SOON
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What to do if patient presents >20hWhat to do if patient presents >20h post ingesionpost ingesion
NPIS
Edinburgh
• Do bloods (U&E, LFTs, INR, pcm)
• If transaminase less than 2x elevated, INR < 1.4, creatinine normal, and paracetamol is not detected:
• The patient has not been poisoned and can be safely discharged home
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PARACETAMOL: ANTIDOTEPARACETAMOL: ANTIDOTE
NPIS
Edinburgh
Acetylcysteine IV
Adverse effects Vomiting flushinghypotensionbronchospasm Anaphylactoid reaction - treat with antihistamines
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Intravenous acetylcysteineIntravenous acetylcysteine
NPIS
Edinburgh
• adverse reactions common • Treatment is symptomatic: antihistamine and beta agonists.
NOT ANAPHYLAXIS• fatalities uncommon (usually miscalculation), caution in
asthmatics • Patients with a late presentation seem to have a higher
incidence of anaphylactoid reactions that relates to lower paracetamol levels.
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Risk factors for ADRs to acetylcysteine Risk factors for ADRs to acetylcysteine
NPIS
Edinburgh
• asthmatics 2.9 (95% CI 2.1, 4.7) more likely to develop ADR
• allergy to other medicines not a risk factor
Schmidt and Dalhoff. BJCP 2001:51; 87-91)
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What to do after 20 hours antidote??What to do after 20 hours antidote??
NPIS
Edinburgh
• Transaminase, sensitive. If normal or less than 2x elevated risk of hepatotoxicity is low
• INR more specific, if above 1.3
• ALWAYS also check creatinine
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STIMULANTSSTIMULANTS
• amphetamine• ecstasy• cocaine• LSD• psilocybe mushrooms• phencyclidine
NPIS
Edinburgh
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STIMULANTSSTIMULANTS
• Key issue is control of central excitation and hyperthermia
• Use of judicious HIGH DOSES of diazepam and cooling
• Watch for coronary spasm and infarction
• Caution with antipsychotics and flumazenil
NPIS
Edinburgh
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CALCIUM ANTAGONIST CALCIUM ANTAGONIST POISONINGPOISONING
• cardiac effects - diltiazem, verapamil
• peripheral effects - dihydropyridines (eg nifedipine, amlodipine)
Both seen in overdose
Beware bradycardic hypotensive patient NPIS
Edinburgh
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MANAGEMENT OF CALCIUM MANAGEMENT OF CALCIUM ANTAGONIST POISONINGANTAGONIST POISONING
• CNS effects often seen late
• hypotension and rhythm disturbance
• hyperglycaemia and lactic acidosis
• beware slow release preparations
NPIS
Edinburgh
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TREATMENT OF CALCIUM TREATMENT OF CALCIUM ANTAGONIST POISONINGANTAGONIST POISONING
• atropine
• calcium
• glucagon
• catecholamines
• cardiac pacing
• insulin and glucose
NPIS
Edinburgh
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INSULIN-GLUCOSE AS ADJUNCTIVE INSULIN-GLUCOSE AS ADJUNCTIVE THERAPY FOR CALCIUM CHANNEL THERAPY FOR CALCIUM CHANNEL ANTAGONIST POISONINGANTAGONIST POISONING
• insulin 10-30 u/hr with dextrose (mean 0.5 IU/kg/hr) in five patients:
4 verapamil
1 amlodipine and atenolol
Yuan et al. Clin Tox 1999; 37, 463-74
NPIS
Edinburgh
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ANTIDEPRESSANTSANTIDEPRESSANTS
Tricyclics amitriptyline dosulepinSNRI venlafaxineSSRIs paroxetine fluoxetine
sertraline citalopramNRI reboxetine
Presynaptic -2 antgst mirtazepine
MAOI phenelzineSMAOI moclobemide
NPIS
Edinburgh
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TRICYCLICSTRICYCLICS
ACTIONS
Amine reuptake inhibitors
Anticholinergics
Membrane effects (Na channel blockade)
Antihistamine
TOXICITY
Arrythmias and fits
NPIS
Edinburgh
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ANTIDEPRESSANTSANTIDEPRESSANTS
ECG of patient at risk:QRS > 100ms possible arrythmia
(higher risk for fits) > 160ms definite arrythmia
Dosulepin (Dothiepin ) most toxic
NPIS
Edinburgh
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ANTIDEPRESSANTSANTIDEPRESSANTS
Treatment of patient at risk:Monitor using serial 12 lead ECGsConsider Bicarbonate IV if risk factors (QRS >100, and decreased conscious level) are present
Magnesium additionally if torsade NPIS
Edinburgh
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Metabolic acidosis
• Definition: process that lowers serum HCO3-
• Occurs when H+ ion production exceeds body’s ability to compensate adequately via buffering or ventilation
Mechanisms of metabolic acidosis in poisoning
• Increased acid production• Impaired acid elimination
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Mechanisms of increased acid production
• Poisons are acids (eg HCl vs. sulphuric acid) • Poisons have acid metabolites (eg metabolism
of alcohols to acids)• Poisons affect ATP consumption/production in
mitochondria (eg pcm, valproate, ARVs, metformin, CO, cyanide, formate, +++ adrenergic stimulation)[uncoupling oxidative phosphorylation or inhibiting cytochromes of the electron transport chain]
• Poisons create ketoacids (eg ethanol, isoniazid)
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Mechanisms of impaired acid elimination
• Toxic metabolites damage kidneys (ethylene glycol)
• Poison causes distal RTA (eg toluene)
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Calculations
• Note the low pH (or high H+)
• Then calculate Anion Gap (AG) AG = [Na+] – ([Cl-] + [HCO3
-])Usual range = 12 +/- 4 m/Eq/L (more recently 7 +/- 4)
• If toxic alcohols suspected, calculate osmolality:2 x [Na+] + [glucose] + [urea] andrequest a measured osmolality on a blood sample
Osmol Gap = measured osmolality – calculated osmolality
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AG & metabolic acidosis
• High AGOccurs when an acid is paired with an unmeasured anion (eg lactate, formate)
• Normal AGOccurs with gain of both H+ and Cl- ions, or a loss of HCO3
- and retention of Cl-, preserving electroneutrality
• However, AG can be affected by errors of calculation or assay and by many disease states.So the lack of a high AG does not exclude any particular cause
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Use of the osmol gap in patients with a high AG metabolic acidosis
• Osmol gap may provide extra information if a toxic alcohol is suspected.
• However, be aware that other medical conditions such as ketoacidosis and renal failure also cause a raised OG
• Normal osmol gap = less than 10 +/- 6 mOsm/L
• However, normal range has problems due to wide variability between people and assays
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Toxins associated with a high osmol gap
• Mannitol• Alcohols: ethanol, etylene glycol, isopropanol,
methanol, propylene glycol• Diatrizoate (amidothizoate)• Glycerol• Acetone• Sorbitol
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Metabolism of toxic alcohols
• Ethylene glycol
• Glyceraldehyde
• Glycolate
• Glyoxylate
• Oxalate
• Methanol
• Formaldehyde
• Formate
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The mountain
Mycyk & Aks, 2003
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METHANOL & ETHYLENE GLYCOLMETHANOL & ETHYLENE GLYCOL
• action - CNS depressantsmetabolic toxicity secondary to
metabolites - formic acid, aldehydes - renal failure, blindness
• Treatment - block metabolic production- ethanol- fomepizoleincrease removal- dialysis
NPIS
Edinburgh
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Metabolism of toxic alcohols
• Ethylene glycol
• Glyceraldehyde
• Glycolate
• Glyoxylate
• Oxalate
• Methanol
• Formaldehyde
• Formate
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DELIBERATE RELEASEDELIBERATE RELEASE
• Irritant gases- Chlorine• Toxic chemicals- Cyanide• Nerve agents- sarin, VX
• Infective agents- anthrax NPIS
Edinburgh
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NERVE AGENTSNERVE AGENTS
Cholinesterase inhibitors– Bronchorrhoea– Increased gut motility– Small pupils– CNS activity, Fits
Atropine
Oximes
NPIS
Edinburgh
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CARE AFTER RECOVERYCARE AFTER RECOVERY
NPIS
Edinburgh
1. psycho-social assessment
2. approximately 15% of patients have
psychiatric illness
3. most never re-attend with self harm