Toxicology Management of the Poisoned Patient Background DSP

Toxicology Management of the Poisoned Patient

Background �DSP is a big problem �Intentional self harm or suicide, was ranked 15 th 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 �AC – single vs multidose �Gastric lavage �WBI �Enhanced elimination �Ion trapping �Dialysis �MDAC Supportive care ICU admission for ABC’s Who needs intubation?

Paracetamol

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 24 hr period and duration since commencement of ingestion � NAC infusion regime

Salicylates

Salicylate Poisoning �PK Review �Aspirin is a weak acid (p. Ka = 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. 5 h Overdose = 18 -36 h �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 CO 2 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 p. H �Plasma salicylate concentration and repeat Q 2 -4 H �Q 2 H 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 p. H < 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 m. Eq/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

Tricyclic Antidepressants

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 -20 mg/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 � p. H dependent �P 450 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 a. VR > 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 p. H corrected (alkalaemic) and discussed with Toxicologist

TCA’s – Treatment 2 �Sodium bicarbonate / Systemic Alkalinisation �Multifactorial � Shifts p. H towards p. Ka �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 Na. HCO 3) � 3 -6 meq bolus (if in shock) �Titrated by ECG �Monitored ABG target p. H 7. 55 -7. 6

Lithium

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. 5 m. Eq/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. 0 m. Eq/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 � Wiki. Tox – 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 venous 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