Emergency Medicine in ToxicologyToxicology

Basics

Definitions A poison is any substance that can cause illness or death when it is absorbed into the body.

An antidote is a substance that acts against a An antidote is a substance that acts against a poison to offset its effects.

Prevention: most accidental poisonings can be prevented if the presence of poisons is recognized and proper care is takenin their use and storage.

Poisioning may be acute or chronic

Signs and symptoms vary widely and are dependent about the quantity and route of of administered poison

Types of poisons:Types of poisons:

• Ingested poisons

• Inhaled poisons

• Absorbed posions

• Injected poisons

Acute poisonings• Aimed (suicides)

• Accidental

– Self-treatment– Self-treatment

– Misuse of chemicals and drugs

• At home

• In medicine

Acute poisoning may occur despite all reasonable precautions and when it does, act quikly but do not panic. does, act quikly but do not panic.

Four basic facts should be known to give appropriate first aid for poisoning.

Four basic steps:• Identify the poisonous substance. Look for bottles, pills,

containers or remnants of poisonous material, even vomitus, that can be used to identify the toxic agent.

• Determine the quantity taken. Estimate, from the container’s size, the number of pills or amount of chemical available and, size, the number of pills or amount of chemical available and, from remaining chemical or pills, how much of poisonous substance may have been taken.

• Determine the route of entry into the body. First aid will vary according to whether the substance was ingested into the stomach, inhaled into lungs, absorbed through the skin, injected into the bloodstream, or taken by combination of two or more of these.

• Determine the time elapsed since the poisoning occurred

Intoxication with drugsEvery drug is poison if used in too high quantities.

• Trankvillisators, antidepressants

• Cardiovascular drugs

• Paracetamol, etc.• Paracetamol, etc.

Try to identify

• The poisonous substance

• Quantity taken

• Rout of entry into body

• Time elapsed since appearance of symptoms

First aid• Unresponsive patient – recovery position

• Concious patient – induce vomiting

“Restaurant method”“Restaurant method”

Patient is concious and clear-mind, provokes itself the

reflex of vomiting and is able to control the airways

Drink water and vomit

Never induce vomiting if victim has swallowed corrosive chemicals.

Emergency ward management

Decontamination:Toxic inhalation:

Air – skin decontamination = useful

Dermal (insecticide, organophosphate)Dermal (insecticide, organophosphate)

(protocol for rescuer themselves)

Gastro-intestinalDecontamination

(ipecac, charcoal, bowel irrigation) not shown to change the outcome, follow shown to change the outcome, follow regional poison center:

(National: 800-222-1222)

Investigations

Always check blood glucose.

Send blood & urine for toxicology screening.

ALWAYS measure paracetamol & salicylate ALWAYS measure paracetamol & salicylate levels

Failure to diagnose & treat is negligent.

U&Es, LFTs, glucose, ABG, clotting, bicarbonate

ECG, CXR

Specific blood levels

Management

SupportiveCorrect hypoxia, hypotension, dehydration, hypo-hyperthermia, and acidosis

Control seizures

MonitorMonitorTPR, BP, ECG, Oxygenation, GCS

General↓ Absorption

↑ Elimination

Specific antidotes

↓ Absorption

Gastric lavage

Only if within 1 hour & life-threatening amount

Never for corrosivesNever for corrosives

If ↓ LOC intubate

Activated charcoal50 g single or repeated dose (↑ elimination)

Doesn’t bind heavy metals, ethanol, acids

↑ Elimination

Multiple dose activated charcoal

Quinine, phenobarbitone

Charcoal haemoperfusion

Barbiturates, theophylline

Diuresis (fluids!, furosemide)

Urinary alkalinization

Dialysis

CVVHDFCVVHDFContinuous VenoContinuous Veno--Venous HemodiafiltrationVenous Hemodiafiltration

ReplacementReplacement

AccessAccess

ReturnReturn

DialysateDialysate

Fluid removal

Solute removal

(small and larger ReplacementReplacement

S S

EffluentEffluent

(small and larger solutes)

Diffusion

Convection

Syrup of Ipecac ???

Within 30 min of ingestion

For low risk substance

In alert, responsive victimIn alert, responsive victim

Activate Charcoal

Absorbs numerous drugs

↓ the bioavailability by

70% within 30 minutes of ingestion70% within 30 minutes of ingestion

30% within 60 minutes of ingestion

Activated Charcoal cont’d

1 gm/kg up to 1 year

25 – 50 gm 1 – 12 years

If stable airway, with protective reflex

Contraindicated if no bowel sound

(TCA – Ca blocker – Opiate)

Gastric LavageComplication – hypoxia – pneumothorax – GI perforation

Symptoms and treatment

Carbon monoxide intoxicationModerate headache initially

Disturbancies of consiousness (…unconsiousness)(…unconsiousness)

Vomiting

Death if not rescued

Treatment Oxygen

Mechanical Ventilation

Cardiovascular system`s support Cardiovascular system`s support

Hyperbaric chamber

Blood transfusion

Cocaine / Crack1/3 fatal injury in young adults

Absorbs from mucous mbr, IV – onset 1-2 minutes ½ life = 60 minminutes ½ life = 60 min

Small children ingest crack → shock “ALTE” passive inhal./breast milk → seizure

Cocaine / Crack cont’d

→ blocks reuptake of neurotransmitters on presyn, nerves (Accumulation of Epi, Nor, Dopa, Serot)Nor, Dopa, Serot)

→ and is a fast Na channel blocker (prolongs QRS) (lidocaine, ß blocker, procainamide, propranolol, quinidine, carbamazepine, doxepin)

Cocaine / Crack, Clinical

CNS: mood elevation, exhilaration, hallucination, movement disorder, tremor, hyper θ, mydriasis

Resp.CV: Hypertension, ACS (Acute Resp.CV: Hypertension, ACS (Acute Coronary Syndrome) ↑ 02 demand, coronary artery const. Myocardial infarction, chest pain. Prolonged QRS, QT, VT, VF

Platelets: Aggregation, activation

Cocaine / Crack Treatment

AW, V, O2

ECG monit (troponin)

Benzodiazepine (no

Phentolamine

0.05 mg/kg

ASA / HeparinBenzodiazepine (no phenothiazine)

“MONA” greets all patients: Morphine, O2, Nitroglycerin

0.2 – 0.5 mcg/kg/min

Na H CO3 1 – 2 mcg/Kg

No ß-blocker (antagonize cocaine ß adrenergic stimulation and vasodilation)

Ca – Channel BlockersAffect transmembrane, and intracellular

movement of Ca

↓ Conduction in slow channel (SA, AV node)↓ Conduction in slow channel (SA, AV node)

↓ Myocardial excit contract

↓ Vascular smooth muscle tone

Ca – Channel Blockers cont’d

Bradyarrhytmia / Hypotension

Pulm-edema, ↓ GI mobility – CNS (coma, syncope)(coma, syncope)

Immediate

Delayed (slow release)

Ca-Channel Blockers Treatment cont’d

AW – V – O2

ECG monit

Vascular access

CaCl 10% 20mg/kg, infusion, monitor Ca++

Insulin/Glucose (0.5 g/kg) 0.1u/kg – Glucagon 0.05-Vascular access

(treat shock)

N/S small bolus 5-10 ml/kg

High dose Epi/Nor

0.1u/kg – Glucagon 0.05-0.1mg/kg bolus, infusion 01.mg/kg/hr

Cardiac pacing, ECMO

Isopro/Abropine/Dopamine Amrinore

ß-Adrenergic Blockers

Compete with sympathetic (Epi, Nor) neurot. At receptor sites

(ß1 Cardiac, renal adipose(ß1 Cardiac, renal adipose

ß2 Lower airway, vessels, GI)

↓ intracellular CAMP (brady, ↓ contractility)

↓ release of Ca from endo retriculum

(↓ conduction)

ß-Blocker-Cardio-Vasc Toxicity

Propranolol-atenolol-metroprolol = 90%

Bradycardia, hypotension

Prolonged PR, QRS, blockProlonged PR, QRS, block

Intravent conduction defect

Acebutolol → torsade de pointe, VF- asystole

Na blocking effect (propan. – sotalol)

Prolonged QRS - QT

ß-Blocker, ClinicalCNS=altered mental status, seizures,coma

(2o to hypoperfusion, high lipid solubility (propranolol)

CV/ECG

- Brady – hypot

- Prolonged QRS, QT – block- Prolonged QRS, QT – block

- arrhythmia

- ↓ contractility

Resp bronchospasm

Hypoglycemia

ß-Blocker TreatmentAW, O2, V

ECG monitor

Vascular Access (Treat shock)

* Epinephrine infusion – high dose* Epinephrine infusion – high dose

* Glucagon 0.05 to 0.1 mg/kg up to 1 mg (∅ phenol)

* Glucose / insulin

* Nabic

* Ca?

* Cardiac pacing - ECMO

OPIOD ODRecreational

Analgesic

Morphine, codeine, hydrocodone, fentanyl patch 25-100 µg/hr (2.5mg – 100mg)patch 25-100 µg/hr (2.5mg – 100mg)

Dm cough syrup

Methadone (long ½ life)

Clonidine (central ą2 agonist)

OPIOD OD cont’d

Respiratory depression-apnea-non cardiogenic pulm edema (inhibition of medulla receptors)

Coma, seizure (meperidone)Coma, seizure (meperidone)

Miosis pin-point)

Hypotension-brady/tacky-cardiac arrest

GI delay

Potentiated by benzodiazepine-alcohol (glutamate-GABA neurotransm)

Drug / Coma / Miosis

88% narcotics88% narcotics

72% phenothiazine

35% ethanol

31% barbiturate

Heroin - symptomsSmall eye pupils

Coma

Stop of breathingStop of breathing

Signs of needle sticks

Ecstazy - symptomsRestless

Difficult, fast speech

Fever up to 41Fever up to 41

Disturbancies of conciuousness

Seizures

Amphethamine - symptoms• Hyperactivity, restless,insomnia

• Fast, disturbed, speech

• Disturbancies of consiousness• Disturbancies of consiousness

• Seizures

• Pulse is fast, high blood pressure

OPIOD OD, Treatment

AW – V – O2 (Correct CO2)

ECG monitoring (treat arrhythmia)

Vascular Access (treat shock)

Naloxone (0.1 mg/kg up to 2 mg for 2 hours) – short ½ life

Now. GO-SLOW. GO-LOW

(1)

OPIOD OD, Treatment cont’d

Naloxone (0.1 mg/kg up to 2 mg for 2 hours) –short ½ life

Now. GO-SLOW. GO-LOW

(1) Normaliza pCO2 (to prevent ↑ epinephrine)(1) Normaliza pCO2 (to prevent ↑ epinephrine)

(2) 0.01 mg/kg up to 0.4 mg Naloxone

IM, SC, IV, ET

Narcan drip 6-48 hrs (if methadone OD) watch for cyclical emesis, coma, hypo/hypertension, pupil dilation, pulm edema, arrhythmia

Paracetamol Overdose

Most common drug taken in overdose

Few symptoms or early signs

As little as 12g can be fatalAs little as 12g can be fatal

Hepatic and renal toxinCentrolobular necrosis

More toxic if liver enzymes induced or reduced ability to conjugate toxin

Paracetamol Metabolism

Management

General measures includingU&Es, LFTs, glucose, clotting ABG, bicarbonate, paracetamol and salicylate levels

Activated charcoal

<8 hours<8 hoursTake level after four hours

Start N-aceylcysteine if above treatment line

Patients are usually declared fit for discharge from medical care on completion of its administration. However, check INR, creatinine and ALT before discharge. Patients should be advised to return to hospital if vomiting or abdominal pain develop or recur

Management 2

>8 hoursUrgent action required because the efficacy of NAC declines progressively from 8 hours after the overdose

Therefore, if > 150mg/kg or > 12g (whichever is Therefore, if > 150mg/kg or > 12g (whichever is the smaller) has been ingested, start NAC immediately, without waiting for the result of the plasma paracetamol concentration

>24 hoursStill benefit from starting NAC

Treatment Graph

N-acetylcysteine

Supplies glutathione

Dosage for NAC infusion - ADULT(1) 150mg/kg IV infusion in 200ml 5% dextrose over 15 minutes, then

(2) 50mg/kg IV infusion in 500ml 5% dextrose (2) 50mg/kg IV infusion in 500ml 5% dextrose over 4 hours, then

(3) 100mg/kg IV infusion in 1000ml 5% dextrose over 16 hours

Side-effectsFlushing, hypotension, wheezing, anaphylactoid reaction

Alternative is methionine PO (<12 hours)

Aspirin Overdose

Early featureshyperventilation, sweating, tremor, tinnitus, nausea / vomiting, or hyperpyrexia

Metabolic featuresMetabolic featuresHypo- or hyper-glycaemia, hypokalaemia, respiratory alkalosis, metabolic acidosis

Othersrenal failure, pulmonary oedema, seizures, coma, death

ManagementGeneral measures

BloodsSalicylate (paracetamol) level >2 hours, and after 2hrs

>700 potentially lethal

>500 moderate-severe poisoning

U&Es, glucose, ABG, bicarbonateU&Es, glucose, ABG, bicarbonate

Activated charcoal

Rehydrate, monitor glucose, correct acidosis and K+

If levels >500mg/L alkalanize urine (HCO3-)

Levels > 700 mg/L before rehydration, renal failure or pulmonary oedema consider haemodialysis

Tricyclic Antidepressant(and other Na+ blocker)

“TCA” (Three C, A, coma, convulsion+++, cardiac arrhythmia, acidosis)

Na blocker

* Propranolol, sotalol* Propranolol, sotalol

* Procain, quinidine

* Lidocaine / cocaine

* Antiarrhythmic

* Benadryl - doxepin

2 Effects

•Anticholinergic (mad as a hatter, red as a beet, blind as a bat, hot as a hare, dry as a bone)

•Na blocker – quinide like on myocardium K blocker

First anticholin effect → CNS stim – agitation, First anticholin effect → CNS stim – agitation, confusion, hallucination. Seizure, θ↑ - coma

CV – sinus tacky, then wide complex QRS >0.1. Sec, brady, block, VF ↑ wave lead a VR > 3mm

RESP: Pulm edema

TCAs -Introduction

Potentially fatal (2.5 to 3.5g of amitriptyline)

Neurological and cardiac problems commonToxicity due to anticholinergic actions, and direct quinidine-like effect on the myocardium

Serious toxicity results from:-Ventricular dysrhythmiasVentricular dysrhythmias

Seizures

Hypotension

Respiratory depression

Initial symptoms at presentation may be trivial, and most major problems occur within 6hrs

TCAs-Features of poisoningPeripheral

Sinus tachycardia, hot dry skin, dry mouth, urinary retention, hypotension and hypothermia may occur

CNSCNSDilated pupils, ataxia, nystagmus, squint, ↓LOC, coma, seizures, respiratory depression, ↑tone, ↑↓reflexes, ↑ plantars

ECGprolonged PR and QRS interval, ↑ QT

ventricular dysrhythmias

TCAs -Management

GCS and QRS, best indicators of toxicity

Supportive do not use flumazenil if benzo taken

Check airway, maintain ventilation, correct hypoxia

Check ABG, if ↑ CO requires ventilationCheck ABG, if ↑ CO2 requires ventilation

Correct hypotension (crystalloids)

Gastric lavage if within 1 hr, and activated charcoal

Rx fits and agitation with diazepam

Rewarm slowly if hypothermic

Close monitoring for 24hrs

Tricyclic Antidepressant, Treatment

AW, V, O2

ECG monitor

Vascular Access (Shock) – EpinVascular Access (Shock) – Epin

Nabic: 1 meq/kg/bolus inusion (ph7.45-7.5)

Benzodiazepine – no physostigmine

no phenytoin

Anticholinergic: MydriasisAntihistamine

Antiparkinson

BelladoneBelladone

Jimson weed

Carbamazepine - phenothiazine

TCAs- DysrhythmiasCarful ECG monitoring is required

QRS interval is a guide to cardiac toxicity (>100ms)

Avoid antidysrhythmic drugs. They may make matters worsematters worse

Correct hypoxia and acidosis. Aim for a pH of 7.45-7.50 (no higher)

use iv boluses of sodium bicarbonate

Sodium loading may also help

Prolonged CPR may be of use

Tricyclic OD – Initial ECG

Tricyclic OD – Recovery ECG

Benzodiazepine Overdose

Deaths from poisoning with benzodiazepines alone are rare, but may be lethal in combination with other CNS depressants

Treatment is supportive and aimed at maintaining adequate ventilation whilst supporting cardiovascular adequate ventilation whilst supporting cardiovascular depression

Benzodiazepine OverdoseFlumazenil (specific benzodiazepine antidote) is not licensed (in the UK) for routine use in benzodiazepine overdoses

Flumazenil may induce seizures; particularly Flumazenil may induce seizures; particularly dangerous where tricyclic antidepressants have been taken

Flumazenil, may however, be used in the differential diagnosis of unclear cases of multiple overdoses but expert advice is ESSENTIAL.