Transcript Toxicology - Philippe Le Fevre

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
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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
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Salicylate Poisoning
 PK Review
 Aspirin is a weak acid (pKa = 3.5).
 [ASA] dependent protein binding and metabolism
 Acidosis
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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
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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
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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
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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
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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
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>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
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Anticholinergic effects may prolong absorption
 High volume of distribution
 Protein binding > 95%
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May saturate increasing free fraction
pH dependent
 P450 Hepatic metabolism
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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
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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,
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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
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Shifts pH towards pKa
 In discussion with the Toxicologist
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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
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Beware sustained release preparations!
 D – not protein bound therefore = body water
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Equilibrium btw serum and tissues takes days to weeks
 M / E – excreted unchanged in urine
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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
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Impaired consciousness
Myoclonus
Dysarthria and ataxia
 Severe toxicity
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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
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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
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Rebound phenomenon
Need to check levels to see if further HDx needed
 CVVHD
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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
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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