Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download THE MANAGEMENT OF DRUG OVERDOSE
Document related concepts
Transcript
Acute Poisoning Michael Eddleston NPIS Edinburgh SpR in Clinical Toxicology, RIE NPIS Edinburgh THE 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 NPIS of the physiological action of drugs.” What to do in cases of poisoning, William Murrell, 1925 Edinburgh EPIDEMIOLOGY • 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 APPRAISAL OF THE POISONED PATIENT • history from patient • tablets / circumstances found • clinical features (“TOXIDROMES”) » Opiate » anticholinergic » stimulant » metabolic acidosis NPIS Edinburgh Gastric lavage Ward 3, Royal Infirmary of Edinburgh, 1973 (courtesy of Alex Proudfoot) PREVENTION OF ABSORPTION • activated charcoal • binds non-specifically • binds about 1/10 of charcoal weight • (charcoal dose 50 g in an adult) NPIS • Slow release products Edinburgh Christophersen et al, Br J Clin Pharmacol 2002; 53: 312-7. ACTIVATED CHARCOAL • timing - use within 1 hour • airway - don’t if problems • agent - eg iron, lithium, hydrocarbons NOT bound NPIS Edinburgh PARACETAMOL PROBLEMS • Indications for treatment • Staggered overdose • Late presentations • Reactions to antidote • Interpretation of results in poisoning NPIS Edinburgh Paracetamol Quantity Activity Quantity NPIS RISK FACTORS IN PARACETAMOL OD Edinburgh PARACETAMOL: RISK FACTORS Nutritional deficiency Eating disorders Alcoholism Malabsorption syndromes AIDS ?? Acute starvation (CLUE: Blood urea) NPIS Edinburgh PARACETAMOL: RISK FACTORS Enzyme inducers: carbamazepine phenytoin barbiturates rifampicin St Johns wort chronic ethanol NPIS Edinburgh PARACETAMOL: RISK FACTORS Enzyme inducers: carbamazepine phenytoin barbiturates rifampicin St Johns wort chronic ethanol NPIS CLUE: Gamma GT Edinburgh 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) Schmidt et al Hepatol 2002; 35: 876-882. Paracetamol Quantity Activity Quantity NPIS RISK FACTORS IN PARACETAMOL OD Edinburgh NPIS Edinburgh Outcome – ALT >1000 related to original plasma level and time of ingestion- ORAL NAC Rumack 2002 Clin Toxicol 40: 3-20. Current use of Acetylcysteine • • • • Before 4 hours 4-8 Hours 8- 24 Hours After 24 hours - WAIT until 4 hours - Blood sample and wait ** - Treat on history, do bloods - Do bloods unless toxic • STAGGERED INGESTION – use first dose time NPIS for treatment decisions **ASSUMES RESULT SOON Edinburgh What to do if patient presents >20h post ingesion • 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 NPIS Edinburgh PARACETAMOL: ANTIDOTE Acetylcysteine IV Adverse effects Vomiting flushing hypotension bronchospasm NPIS Anaphylactoid reaction - treat with antihistamines Edinburgh Intravenous acetylcysteine • 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. NPIS Edinburgh Risk factors for ADRs to acetylcysteine • asthmatics 2.9 (95% CI 2.1, 4.7) more likely to develop ADR • allergy to other medicines not a risk factor NPIS Schmidt and Dalhoff. BJCP 2001:51; 87-91) Edinburgh What to do after 20 hours antidote?? • 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 NPIS Edinburgh STIMULANTS • • • • • • amphetamine ecstasy cocaine LSD psilocybe mushrooms phencyclidine NPIS Edinburgh STIMULANTS • 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 CALCIUM ANTAGONIST POISONING • cardiac effects - diltiazem, verapamil • peripheral effects - dihydropyridines (eg nifedipine, amlodipine) Both seen in overdose Beware bradycardic hypotensive patient NPIS Edinburgh MANAGEMENT OF CALCIUM ANTAGONIST POISONING • CNS effects often seen late • hypotension and rhythm disturbance • hyperglycaemia and lactic acidosis NPIS • beware slow release preparations Edinburgh TREATMENT OF CALCIUM ANTAGONIST POISONING • • • • • • atropine calcium glucagon catecholamines cardiac pacing insulin and glucose NPIS Edinburgh INSULIN-GLUCOSE AS ADJUNCTIVE THERAPY FOR CALCIUM CHANNEL ANTAGONIST POISONING • insulin 10-30 u/hr with dextrose (mean 0.5 IU/kg/hr) in five patients: 4 verapamil 1 amlodipine and atenolol NPIS Yuan et al. Clin Tox 1999; 37, 463-74 Edinburgh ANTIDEPRESSANTS Tricyclics SNRI SSRIs NRI amitriptyline dosulepin venlafaxine paroxetine fluoxetine sertraline citalopram reboxetine Presynaptic -2 antgst mirtazepine NPIS MAOI SMAOI phenelzine moclobemide Edinburgh TRICYCLICS ACTIONS Amine reuptake inhibitors Anticholinergics Membrane effects (Na channel blockade) Antihistamine NPIS TOXICITY Arrythmias and fits Edinburgh ANTIDEPRESSANTS ECG of patient at risk: QRS > 100ms possible arrythmia (higher risk for fits) > 160ms definite arrythmia Dosulepin (Dothiepin ) most toxic NPIS Edinburgh ANTIDEPRESSANTS Treatment of patient at risk: Monitor using serial 12 lead ECGs Consider Bicarbonate IV if risk factors (QRS >100, and decreased conscious level) are present NPIS Magnesium additionally if torsade Edinburgh 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 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) Mechanisms of impaired acid elimination • Toxic metabolites damage kidneys (ethylene glycol) • Poison causes distal RTA (eg toluene) 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] and request a measured osmolality on a blood sample Osmol Gap = measured osmolality – calculated osmolality AG & metabolic acidosis • High AG Occurs when an acid is paired with an unmeasured anion (eg lactate, formate) • Normal AG Occurs 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 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 Toxins associated with a high osmol gap • Mannitol • Alcohols: ethanol, etylene glycol, isopropanol, methanol, propylene glycol • Diatrizoate (amidothizoate) • Glycerol • Acetone • Sorbitol Metabolism of toxic alcohols • Ethylene glycol • Methanol • Glyceraldehyde • Formaldehyde • Glycolate • Formate • Glyoxylate • Oxalate The mountain Mycyk & Aks, 2003 METHANOL & ETHYLENE GLYCOL • action - CNS depressants metabolic toxicity secondary to metabolites - formic acid, aldehydes - renal failure, blindness • Treatment - block metabolic production - ethanol NPIS - fomepizole increase removal- dialysis Edinburgh Metabolism of toxic alcohols • Ethylene glycol • Methanol • Glyceraldehyde • Formaldehyde • Glycolate • Formate • Glyoxylate • Oxalate DELIBERATE RELEASE • Irritant gases• Toxic chemicals• Nerve agents- Chlorine Cyanide sarin, VX • Infective agents- anthrax NPIS Edinburgh NERVE AGENTS Cholinesterase inhibitors – Bronchorrhoea – Increased gut motility – Small pupils – CNS activity, Fits NPIS Atropine Oximes Edinburgh CARE AFTER RECOVERY 1. psycho-social assessment 2. approximately 15% of patients have psychiatric illness 3. most never re-attend with self harm NPIS Edinburgh
