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Management of the Poisoned Patient Background DSP is a big problem Intentional self harm or suicide, was ranked 15th of all deaths registered in Australia in 2007 Poisoning accounted for ~ 25% of these deaths The primary aim in the treatment of poisoned patients is to reduce mortality and early and late morbidity The first priority in the assessment of patients is the adequacy of ABC Simultaneous investigation and treatment So many drugs but so little time... Paracetamol Salicylates TCA’s Lithium Other... But first – some general principles General Principles The first priority in the assessment of patients is to ascertain the adequacy of their Airway Ventilation Circulation Subsequent management determined by the risk to the patient from the poisoning. Need to know information regarding the toxin, the exposure, and the patient. General Principles History Examination Investigations Differential Diagnosis General and Supportive Management Specific Interventions Core Info History What drug, how much, when Sources of info? Prev DSP’s – what, when, where, treatment Targeted Examination Identify Toxidromes / life threatening abnormalities Investigations Routine bloods inc ABG Drug levels UDS ECG Treatment GI decontamination Supportive care AC – single vs multidose ICU admission for ABC’s Gastric lavage Who needs intubation? WBI Enhanced elimination Ion trapping Dialysis MDAC Paracetamol Common Really common Primarily an ED managed thing Mostly won’t need ICU involvement if single agent but may be involved in polysubstance ingestions Guideline changed in 2008 Paracetamol 2 What changed? Acute ingestion One line nomogram Above the line treat Below the line don’t treat Chronic ingestion Based on dose per 24hr period and duration since commencement of ingestion NAC infusion regime Salicylate Poisoning PK Review Aspirin is a weak acid (pKa = 3.5). [ASA] dependent protein binding and metabolism Acidosis Increased Vd Increased CNS penetration Hepatic clearance Zero Order Kinetics / capacity limited elimination Normal T(1/2) = 2-4.5h Overdose = 18-36h Renal excretion more important in overdose Salicylates – Effects Respiratory alkalosis Salicylates directly stimulate the respiratory centre leading to hyperventilation and a respiratory alkalosis Major feature is a Metabolic acidosis. Raised AGMA – (acronyms anyone?) This triggers An increase in metabolic rate Increased oxygen consumption Increased CO2 formation Increased heat production Increased glucose utilisation Salicylates – Effects Other effects CNS effects – mild / mod / severe Electrolyte imbalances Potassium depletion Dehydration Hepatic effects Glucose metabolism GIT disturbance Salicylates – Investigations FBC, EUC, Coags, Calcium, Glucose Arterial blood gas Urinalysis and urine pH Plasma salicylate concentration and repeat Q2-4H Q2H ABG’s for acidaemia, electrolytes and glucose Salicylates – Treatment 1 Patients should be admitted to ICU if they fulfill any of the following criteria An acute ingestion > 300 mg/kg Moderate or severe clinical severity Acid-base disturbances where pH < 7.4 Salicylate concentration > 4 mmol/L Treatment consists of monitoring and correction of Hydration Metabolic acidosis Hypokalaemia Hypoglycaemia Salicylates – Treatment 2 Correct acidaemia, potassium deficit and dehydration. Urinary alkalinisation The patient should be commenced on 1 mEq/kg/hour of bicarbonate added to the IV fluid. Bolus doses may be required in severe acidosis. Causes ion trapping and increases excretion Haemodialysis Ion Trapping Salicylates – Dialysis Indications for haemodialysis Pre-existing cardiac or renal failure Pulmonary oedema Intractable acidosis or severe electrolyte imbalance Salicylate concentrations >9.4 mmol/L in ACUTE ingestions (when the concentration has been taken within 6 hours of ingestion) >4.5 mmol/L in CHRONIC intoxication Clinically serious toxicity regardless of concentration TCA’s In Australia they are the number one cause of fatality from drug ingestion and 90% of successful TCA suicides do not reach hospital but die at home (Buckley et al, 1995). The ingestion of 15-20mg/kg of tricyclics is potentially fatal. TCA’s – PK Highly lipid soluble weak bases Rapidly absorbed Anticholinergic effects may prolong absorption High volume of distribution Protein binding > 95% May saturate increasing free fraction pH dependent P450 Hepatic metabolism Saturated in overdose therefore renal excretion vital TCA – Toxicity 3 features Anticholinergic toxidrome Red / hot / mad / blind / dry CNS toxicity CVS toxicity TCA’s – CNS Toxicity Psychosis Decreased level of consciousness / coma Seizures May trigger acute deterioration Associated with increased mortality Anticholinergic delirium during recovery TCA’s – CVS Toxicity Tachycardia Bradycardia Hypotension Arrhythmia Prolonged QRS TCA’s – from bad to worse Predictors of severe toxicity QRS > 100 milliseconds or more in a limb lead Ventricular arrhythmia Seizures R in aVR > 3 mm ECG in TCA overdose 1 ECG in TCA overdose 2 TCA’s – Treatment Supportive care – airway, aggressive IV Fluids resuscitation, continuous ECG monitoring for at least 6 hours post ingestion GI Decontamination – for conscious patients who present within 1-2/24. for unconscious patients via OGT post intubation. Avoid acidaemia. Treat seizures promptly and beware of CVS collapse post seizure Extended Resuscitation – until pH corrected (alkalaemic) and discussed with Toxicologist TCA’s – Treatment 2 Sodium bicarbonate / Systemic Alkalinisation Multifactorial Shifts pH towards pKa In discussion with the Toxicologist 1-3 meq/kg bolus (if not in shock) 1-3 mls/kg of 8.4% solution (1 minijet of NaHCO3) 3-6 meq bolus (if in shock) Titrated by ECG Monitored ABG target pH 7.55 -7.6 Lithium Narrow therapeutic range Predominately CNS effects in toxicity CVS toxicity is bad sign Acute toxicity well tolerated Treat those with renal failure or sodium depletion Chronic toxicity is more severe than acute toxicity Death and long term disability each occur in ~10% of chronic poisonings Lithium – PK review A – well absorbed orally. Peak [Li] in 2-3/24 Beware sustained release preparations! D – not protein bound therefore = body water Equilibrium btw serum and tissues takes days to weeks M / E – excreted unchanged in urine Filtered, reabsorbed in PCT ↓ Na reabsorption means ↑ Li reabsorption Prolonged half-life in overdose Lithium – Effects Lithium has dose related toxicity in therapeutic use Initial symptoms include tremor, polyuria. Later symptoms Impaired consciousness Myoclonus Dysarthria and ataxia Severe toxicity Coma / seizures / ARF / death CVS – ventricular dysrhythmias, prolonged QT common Lithium – Treatment Admission anyone with CNS symptoms or level > 1.5mEq/L ICU for those needing Dialysis or with ECG changes GI decontamination AC ineffective WBI – in patients who present early following large OD Enhanced Elimination Indications for dialysis Seizures or coma Renal failure in acute or chronic poisoning [Li] > 2.5-3.0mEq/L Hypotension despite adequate fluid resuscitation Lithium – Treatment Dialysis - Intermittent VS Continuous Intermittent HDx Rebound phenomenon Need to check levels to see if further HDx needed CVVHD No rebound Useful in haemodynamically compromised where IHDx not appropriate As ongoing treatment post initial HDx Slower clearance than IHDx Toxidromes Summary Toxicology is about doing the simple things Supportive care most of the time Treatment should be commenced in ED ABC’s Dialysis and alkalinisation are important and are ICU stuff. TCA’s are bad. Lithium and Aspirin aren’t great either. References Hypertox WikiTox – online reference http://curriculum.toxicology.wikispaces.net Oh’s Intensive Care Manual Katzung, Basic and Clinical Pharmacology Beckmann, U. et al (2001) Efficacy of continuous venovenous hemodialysis in the treatment of severe lithium toxicity. Journal of Toxicology, Clinical toxicology; 39(4): 393-397. The Clinical Toxicology Dept at CMN ABS Zimmerman, J. (2003) Poisonings and overdoses in the intensive care unit: General and specific management issues. Critical Care Medicine; 31(12): 27942801. Daly et al. (2008) Consensus Statement: Guidelines for the management of paracetamol poisoning in Australia and New Zealand. Medical Journal of Australia; 188: 296–301