Acute Poisoning and Drug Overdose

Dr. Rashidi AhmadMD (USM), MMED (USM), FADUSM, AM

Dept. Emergency MedicineSchool of Medical Sciences

USM Health Campus8th December 2007

Update on Medical Emergencies Course, Terengganu

Objectives

• Understanding poison

• Develop methodical approach to Poisoned Patients

• Characterize Toxidromes & its management

• Evidence-Based GI Decontamination

• Learn Antidotes

Outline

• Definition

• Relevant epidemiological data

• Risk assessment

• Treatment

Poison

“Substance that when introduced into, or absorbed by a living organism destroys life or injures

health”(Oxford Dictionary)

“Poisons and medicines are oftentimes the same substance given with different intents”

(Peter Mere Latham; 1789 – 1875)

“What is it that is not a poison?

All things are poison and nothing is without poison. It is the dose only that

makes a thing not a poison.”

Paracelsus (1493-1541), the Renaissance “Father of Toxicology,” in his Third Defense.

7 Mechanisms of Toxicity

1. Interfere with O2 transport or tissue utilization of oxygen (i.e: cyanide, CO)

2. Affect lungs (paraquat)

3. Affect cardiovascular system (TCA, Ca++ channel blockers)

4. Affect CNS (cocaine, sedatives)

5. Affect ANS (organophosphates)

6. Direct local damage (acids, bases)

7. Delayed effects on liver or kidneys(acetaminophen, metals)

Toxin Mortality Curve

Most lethal human toxic exposure

Two Sources of Data

• Data from Dr. Rozlan Ishak, Environmental Health, Unit Disease Control Division, MOH (1999)

• Data from the Occupational Health Unit of the MOH (1997-2000)

• Data from the National Poison Centre, Universiti Sains Malaysia (1995 to 2002)

Site of Exposure

1997 1998 1999 2000

HOME 357 400 684 767

WORKPLACE 83 115 136 136

OTHERS 15 20 50 68

MISSING 253 11 18 75

TOTAL 708 546 888 1,046

Age Group

1997 1998 1999 2000

< 10 76 22 161 21010-19 101 90 179 19720-29 143 177 221 26130-39 111 105 134 17240-49 35 60 72 7550-59 24 23 42 4260-69 12 16 22 1570-79 3 5 7 1779 5 0 2 14MISSING 198 48 48 60

TOTAL 708 546 888 1,046

Poisoning cases in Malaysia, 1999

1798

10291058

1794

1427

1045926

778660 566 522

355 395267 176 222

0200400600800

100012001400160018002000

1 - 4

5 - 9

10 –

14

15 - 1

9

20 -

24

25 - 2

9

30 - 3

4

35 - 3

9

40 - 4

4

45 - 4

9

50 - 5

4

55 - 5

9

60 - 6

4

65 - 6

9

71 - 7

4

> 75

Age Groups

No.

of C

ases

Poisoning cases

Ethnic Group

1997 1998 1999 2000

MALAY 229 170 393 399

CHINESE 137 106 173 175

INDIAN 254 159 177 290

OTHERS 87 110 136 159

MISSING 1 1 9 23

TOTAL 708 546 888 1,046

Ethnic difference of Chemical Poisoning in Malaysia in 1999

4843

984 91034 340

3630

952 1161

24 2830

100020003000400050006000

Malays /Bumiputra

Chinese Indians Others Missing Data

Ethnicity in Malaysia

No.

of

Cas

es

Male Female

0

200

400

600

800

1000

1200

No. of Cases

PerlisKedahPulau PinangPerakSelangorW

. P Kuala Lumpur

Negeri Sembilan

Melaka

JohorPahangTerengganuKelantanSabahSaraw

ak

States in Malaysia

Gender Difference in Poisoning in Malaysia, 1999

Male

Female

Nationality

1997 1998 1999 2000

MALAYSIAN 633 512 844 972

INDONESIAN 44 19 31 43

BANGLADESHI 14 3 2 3

PHILIPPINO 3 2 1 2

OTHERS 3 7 5 10

MISSING 11 3 5 16

TOTAL 708 546 888 1,046

Circumstances

1997 1998 1999 2000 TOTAL

OCCUPATIONAL 74 94 105 92 365 (11.5%)

SUICIDE 257 220 273 327 1077(33.8%)

HOMICIDE 9 6 8 6 29 (0.9%)

OTHERS 226 226 430 417

MISSING 14 20 72 204

TOTAL 708 546 888 1,046 3188

Chemical Poisoning in Malaysia in 1999

0

0.07

0.09

0.17

0.17

0.19

0.2

0.21

0.22

0.26

0.26

0.34

0.4

0.46

0.49

0.52

0.69

0.96

1

1.11

1.55

2.37

2.98

4.91

5.56

6.19

7.73

8.03

8.76

44.07

0 5 10 15 20 25 30 35 40 45 50

Alfatoxin and other mycotoxin

Other antibiotic

Other inorganic substances

Halogen and aromatic hydrocarbon

Agents affecting GIS

Agents affecting CVS

Narcotic

Metals

Anaesthetic

Hormones

Drugs affecting ANS

Alcohol

Noxious substances eaten as seafood

Agents affecting Muscular system

Soaps and detergents

Carbon Dioxide

Antibiotic

Haematological agents

Other gases, fumes and vapors

Other psychotropic drugs

Antiepileptic

Other and unspecified

Corrosive substances

Topical agents

Other noxious food

Organic solvents

Analgesic

Diuretic and others

Pesticides

Venomous animals

Type

of C

hem

ical

Poi

soni

ng

Percentag

Chemical PoisoningN: 13133

Type of Chemicals

1997 1998 1999 2000 Total

Pesticides 256 183 288 406 1133 (35%)Agrochemicals 29 32 17 18 96 (3%)Therapeutic Drugs 86 135 246 237 704 (22%)Chemicals 182 176 290 357 1005 (32%)Metals 6 1 1 2 10 (0.3%)Unknown 149 29 36 26 240 (7.7%)TOTAL 708 556 878 1046 3188

Data on Pesticides Availability (1996-1998)

Total number of pesticides marketed/used: 1,983

Breakdown:

Insecticides/Nematicides: 539 (27.2%)

Fungicides: 229 (11.6%)

Herbicides: 692 (34.9%)

Household, veterinary

& public health pesticides 373 (18.8%)

Rodenticides 50 ( 2.5%)

Others 100 ( 5.0%)

Type of Pesticides

1997 1998 1999 2000

Paraquat 171 92 113 187Glyphosate 6 11 19 18Organophosphate 46 43 70 69Organochlorine 0 5 8 2Pyrethroids 4 0 1 12Carbamate 0 6 7 6Others 29 26 48 45Non Pesticides 452 363 600 640Unknown/missing - - 22 67TOTAL 708 546 888 1,046

• Review of data from the National Poison Centre, USM

• Data extracted from inquiry records for the years 1995 to 2002

(n=1666)

Pesticides45.3 % Chemicals/Heavy Metals

8.6 %

Household Products 18.0 %

Natural Toxins 3.2 %

Unknown 1.2 %

Others 0.4 %

Gases 0.8 %Pharmaceuticals

22.3 %

Enquiries on specific poisoning (1995 – 2002)

MalayChineseIndian

142106280

IntentionalUnintentional

385241

IngestionInhalationCutaneousOcular

64379202

Route of exposure

Race

Type of Incidents

Types of Poisons Involved

Pesticides

• Glyphosate

• Paraquat

• Malathion

• Endosulfan

• Carbofuran

Drugs

• Paracetamol

• Calamine Lotion

• Traditional Products

• Haloperidol

Plants

• Natural rubber latex

• Datura

Animal

• Snake bite

• Spider bite

• Jellyfish sting

• Bees sting

Chemicals/Heavy Metals

• Lead• Mercury

• Formic acid• Thinner• Ammonia

Household Products

• Household insecticides• Mosquito Aerosol Spray• Vape Mat• Mosquito Coil

• Dettol• Silica gel• Mothballs

Types of Poisons Involved

GlyphosateParaquatMalathionEndosulfanCarbofuranGlufosinate AmmoniumChlorpyrifos2,4-DLindane

269671519421214168

Type of pesticides

• Home > Workplace

• Ingestion

• Suicidal attempt

• Male

• Malay

• Children

• Pesticides > Pharmaceuticals > Chemicals

Conclusions

Phases Of Poisoning

• Preclinical phase

• Toxic phase

• Resolution phase

Preclinical phase

• Follows exposure before s/sx

• History guides management

• Aim: to reduce or prevent toxicity

• Decontamination is a priority

Toxic phase

• Period from onset to peak of manifestation of

toxicity clinical or laboratory

• PE guides treatment

• Aim: to shorten or lessen the severity of toxicity

• Priority: stabilize airways, breathing and

circulation and consider antidote

Resolution phase

• From peak toxicity to recovery

• Clinical status guides management

• Major goal: shorten the duration of toxicity &

supportive care

Suspect intoxication

Cumbridge & Murray. CHEST 2003; 123:577-592

Approach to the Poisoned Patient

• ABC’s are always first !

• Most Patients Do Fine

- Majority of poisoned patients require

only supportive Rx

• But, those who don’t … often present with

undifferentiated AMS

Approach to the Poisoned Patient

• Approach to AMS

• Toxicologic History

• Toxicologic Physical Exam

• Toxicologic Labs

Think Toxins in any patient with AMS !

Approach to AMS

• A – Airway (mental status, suicidal trauma)

• B – Breathing (resp depression, pulm oedema, ARDS)

• C – Circulation (dysrhythmias, CV depression)

• D – Dysfunction CNS (hypoglycemia, alcohol, opiate

& benzodiazepine overdose, seizure control)

• E – Exposure (hyperthermia)

“Coma Cocktail” in toxin induce AMS

• Use of D50%, thiamine, nalaxone, flumazenil

• Toxin-induced LOC is generally well-tolerated and

achieving "arousal" of the patient does not

necessarily improve outcome.

• ? cost-effectiveness and risks of the coma cocktail

• D50% & thiamine should probably be given to patients with AMS from unknown causes.

• Strongly suspected opiate overdose: Naloxone is indicated. Lack of response to 10 mg of naloxone generally excludes opioid toxicity

• Flumazenil should be used mainly for reversal of therapeutic conscious sedation.

Hoffman RS, et al. The poisoned patient with altered consciousness. Controversies in the use of a "coma cocktail." JAMA 1995;274:562-9

Toxicology in ECC. Circulation. 2005;112:IV-126-IV-132

• Reversal of BZD intoxication with flumazenil is a/w significant toxicity in patients with benzodiazepine dependence or coingestion of proconvulsant medications (TCA)

• May be useful to reverse excessive sedation when BZDs are used for procedural sedation.

Toxicology history

• Risk assessment

- to predict the likely clinical course and potential

complications

- To allow the clinician to make specific decisions

about all subsequent management steps

(appropriate supportive care and monitoring; screening and

specialized testing; decontamination; enhanced elimination; antidotes and disposition)

Toxicology History

• Goal is Identification of Etiologic Agent(s)• Use all Available Resources

- Pill bottles

- Pre-hospital personnel

- Family and Friends

- Medical Records

- Past medication and medical history

• Assess for Suicidal Behavior

- Must assume suicidal until proven otherwise

- Low threshold for Psychiatric consultation

Evaluation of Toxicity

• Evaluate the SATSC– Substance– Amount– Time since ingestion– Symptoms– Co-morbid

• Regional Poison Control Center

Toxicology PE

• Vitals, Vitals, Vitals !- Measure accurately

- Measure often

- Temp, HR, BP, RR, Pulse Ox

• Assess for Signs of Trauma• “Skin” exam is critical

- Diaphoresis ?

- Trauma (scalp, elsewhere) ?

• Odor!! • Pupil examination

Odor Poison

Sweet/fruity Ketone, alcohol

Almond Cyanide

Gasoline Hydrocarbon

Garlic Organophospate

Wintergreen Methylsalicylate

Pear Chloral hydrate

John J. Marini, Arthur P. Wheeler. Critical care Medicine. The essentials – Textbook 2006

Toxicology laboratory

• Mainly to assess the severity• Asymptomatic Patients

- Acetaminophen Level – the “Silent” killer

• Toxin Identified/Strongly Suspected- Testing based on suspected toxin

- Consider acetaminophen level as well

• In any patient with Undifferentiated AMS- Blood: CBC, Chem 7, LFT’s, CPK, Serum osm

- Urine: U/A, UPT, UTox

- Tox-Specific: Acet, ASA,

Toxicology laboratory

• Most poisonings can be managed appropriately without extensive laboratory studies.

• “Tox screens" rarely helpful.- Undetected: bromide, carbon monoxide, chloral hydrate,

clonidine, cyanide, organophosphates, tetrahydrozoline, beta-blockers, calcium-channel blockers, clonidine, colchicine, digitalis, and iron.

• PCM screening helps especially in multiple medications in intentional overdose.

Importance of ancillary testing

• Wide anion gap metabolic acidosis – MUDPILES• Low anion gap metabolic acidosis – bromides, lithium,

abnormal cationic proteins

• Wide anion gap, ketone & glucose negative, osmolar gap > 10mOsm/L – methanol, ethylene glycol

• Wide anion gap, ketone & glucose negative, osmolar gap < 10mOsm/L – iron, paraldehyde, CO, cyanide

• Respiratory alkalosis – salicylate

• Plain abdominal films: CHIPES (chloral hydrate, heavy metals, iron, iodides, phenothiazines, enteric coated pills, sustained-release preparations and solvents

Iron tabletsBody packers

Nomograms

Level-guided treatment

Substance Level Rx

Carboxyhaemoglobin > 25% Hyperbaric Oxygen

Ethylene glycol > 20mcg/dL Ethanol +/-haemodialysis

Lithium > 2.5mEq/L Haemodialysis

Iron > 350mcg/dL Desferrioxamine

Methaemoglobin > 30% Methylene blue

Salicylate > 100mcg/dL Haemodialysis

Lead > 45mcg/dL Chelation

Drug Durations in the urine

Drug Duration

Amphetamines 48 hoursAlcohol 12 hoursBarbiturates 10-30 daysValium 4-5 daysCocaine 24-72 hoursHeroin 24 hoursMarijuana 3-30 daysMethaqualone 4-24 daysPhencyclidine 3-10 daysMethadone 3 days

Urine toxicology

Toxidromes

• Constellation of Physical Findings- Provides Clues- Narrows Differential Diagnosis

• Beware: Many Exceptions Exist!- Poly-drug Overdoses- Overlapping and confusing mixed syndromes

Autonomic Nervous System

• Parasympathetic (PNS)- “Rest and Digest”- Mediated by Acetylcholine- Muscarinic and Nicotinic Receptors

• Sympathetic (SNS)- “Fight or Flight” response- Mediated by Catecholamines- Sympathetic Cholinergic: Sweating

Toxidrome review

• Physiologic stimulants- Anticholinergics- Sympathomimetics (ex. cocaine)- Hallucinogens- Drug withdrawal- Miscellaneous (thyroid hormones)

• Physiologic depressants- Cholinergics- Narcotics- Symphatholytics (cyclic antidepressants)- Sedative-hypnotics- Miscellaneous (carbon monoxide)

• Serotonin Syndrome (mixed)

Serotonin Syndrome

• Hyperthermia

• Mental status changes

• Autonomic instability

• Neuromuscular abnormalities

• Examples: Antidepressants (SSRIs), Meperidine,

Dextromethorphan, Ecstasy

Toxidrome Summary

• ANTI-CHOLINERGIC- Decreased Parasympathetic- Hot…Mad…Dry…etc…

• (PRO) CHOLINERGIC- Increased Parasympathetic- SLUDGE/DUMBELS

• SYMPATHOLYTIC- Decreased Sympathetic- AMS, Decreased Respiratory, Miosis

• SYMPATHOMIMETIC- Increased Sympathetic

• SEROTONIN SYNDROME- Altered Parasympathetic and Sympathetic- Fever, AMS, Dysautonomia, NM

Points to ponder

• Anticholinergic

• Procholinergic

• Sympatholytic

• Sympathomimetic

• Serotonin Syndrome

• Think TCA toxicity

• Think Terrorism/OP

• Think Intubation

• Think Withdrawal

• Fever and AMS

“CLUB DRUGS”

• Rave parties increasing in

popularity

• Drugs meant to intensify

sensory experience of

lights/music, facilitate

prolonged dancing

MDMA “Ectasy”

• Structurally resembles amphetamine (stimulant) and mescaline (hallucinogen)

• SX: trismus, bruxism, tachycardia, mydriasis, diaphoresis, hyperthermia, hyponatremia, hepatic failure, CV toxicity (tachycardia, HTN)

• Treatment– Mainly supportive– Benzodiazepines– Calm environment– Avoid beta-blockers

Can result in unopposed alpha effect If essential consider labetolol

GHB: Date rape drug“Georgia homeboy, liquid ectasy, or grievous bodily harm”

• Developed as anesthetic agent. GABA analog

• Symptoms: bradycardia, hypothermia, hypoventilation, somnolence, vomiting, myoclonic jerking

• Treatment

– Conservative mx

– Intubation

– Careful exam for sexual assault

Ketamine: “K”, “special K”

• Developed as an anesthetic, structurally resemble PCP

• Acts on all six neurotransmitter systems– Anticholinergic: dry skin, miosis– Dopamine/norepinephrine: agitation, delusions– Opioid: pain perception alterations– Serotonin: perceptual changes– GABA receptor inhibition: excitation

• Treatment– Benzodiazepines/haloperidol

– Supportive care

– Can consider urine alkalinization

Treatment of acute poisoning

• Primary goal - keep concentration of poison as low

as possible by preventing absorption and increasing

elimination

• Secondary goal - counteract toxicological effects at

effectors site, if possible

Management principles

• GI decontamination

• Antidote

• Resources

Principle of GI decontamination

• Toxins poorly absorbed in stomach, toxins wellabsorbed in SI

• Decrease amount in stomach, therefore less presenting to SI for absorption

• Maximum benefit: present soon after the ingestion.

• Delayed presentation + without symptoms -probably does not contribute to the outcome

• Drugs with delayed absorption/reduce GI motility, activated charcoal may reduce the final amount absorbed.

?? Prehospital GI decontamination of toxic ingestions

Methods of GI decontamination

• Gastric- Ipecac

- Activated Charcoal

- Single dose vs multi-dose

- Gastric Lavage

• Gastro-Intestinal- Cathartics

- Whole Bowel Irrigation

You make the choice…

Ipecac

• Little evidence that ipecac prevents drug absorption or systemic toxicity

• No convincing data that it significantly alters the clinical outcome of patients who are awake and alert on presentation to the ED.

• Considered only in fully alert patients

• Never indicated after hospital admission

• CI: corrosives, petroleum products, or antiemetics, high risk of seizures or altered consciousness.

Vale JA, Meredith TJ, Proudfoot AT. Syrup of ipecacuanha: isit really useful? BMJ 1986; 293:1321–1322

Ipecac

• No evidence from clinical studies that ipecac improves the outcome of poisoned patients and its routine administration in the emergency department should be abandoned.

• Insufficient data to support or exclude ipecac administration soon after poison ingestion.

• Ipecac may delay the administration or reducethe effectiveness of activated charcoal, oral antidotes, and whole bowel irrigation.

Krenzelok AP et al. J Toxicol Clin Toxicol. 2004;42(2):133-43.

Single-dose activated charcoal

• Should not be administered routinely

• The effectiveness of activated charcoal decreases with time; the greatest benefit is within 1 hour of ingestion.

• Consider if a patient has ingested a potentially toxic amount of a poison: insufficient data to support or exclude its use after 1 hour of ingestion.

• There is no evidence that the administration of activated charcoal improves clinical outcome.

Chyka PA et al. J Toxicol Clin Toxicol. 1997;35(7):721-41.

Substances that are not absorb by charcoal

Mnemonic: CHARCOAL

Caustics & corrosive

Heavy metals

Alcohol & glycols

Rapidly absorbed substances

Cyanide

Other insoluble drugs

Aliphatic hydrocarbobs

Laxatives

Multiple-dose activated charcoal

• Consider only if a patient has ingested a life-threatening amount of:

- carbamazepine

- dapsone

- phenobarbital

- quinine

- theophylline

• Insufficient clinical data: salicylate, amitriptyline, dextropropoxyphene, digitoxin, digoxin, disopyramide, nadolol, phenylbutazone, phenytoin, piroxicam, and sotalol

• The need for concurrent administration of cathartics remains unproven and is not recommended.

• Cathartics should not be administered to young children because of the propensity of laxatives to cause fluid and electrolyte imbalance.

Jefrey B, et al. Clinical Toxicology, 37(6), 731–751 (1999)

Gastric lavage

• Reported complication:– Aspiration pneumonia - most

common– Laryngospasm with cyanosis– Kinking of lavage tube in

eosphagus– Esophageal perforation

Reid et al Arch Dis Child 1970

Mattew et al Br Med J 1966

“Gastric lavage should not be employed routinely, if ever, in the management of poisoned patients.”

J Toxicol Clin Toxicol 2004;42:7:933.

Evidence based protocols

• Ipecac- is effectively obsolete

• Charcoal- agent of choice for most poisons

- Best if used within one hour

• Lavage- Narrow indications

- principally for potentially serious amounts of agents not adsorbed by charcoal within half hour ingestion

Bateman DN. Gastric decontamination--a view for the millennium.J Accid Emerg Med. 1999 Mar;16(2):84-6

Cathartics

• Use alone - not recommended as a method of gut decontamination.

• Conflicting data: combine with activated charcoal:

• No clinical studies have been published to investigate the ability of a cathartic, with or without activated charcoal, to reduce the bioavailability of drugs or to improve the outcome of poisoned patients.

Donna Seger, et al. CLINICAL TOXICOLOGY. Vol. 42, No. 3, pp. 243–253, 2004

Whole bowel irrigation (WBI)

• No conclusive evidence WBI improves outcome

• Consider: potentially toxic ingestions of sustained-release or enteric-coated drugs.

• Insufficient/theoretical data for iron, lead, zinc, or packets of illicit drugs

• CI: bowel obstruction, perforation, ileus, hemodynamic instability or unprotected airways.

• A single dose of charcoal prior to WBI does notdecrease the binding capacity of charcoal

Hoffman RS. J Toxicol Clin Toxicol. 2000;38(7):689-90

Antidote

Criteria for ICU admission

Resources

Pusat Racun Negara

Emergency First-Aid Databases

Office Hours : 1-800-88-8099 / 04-6570099

Monday to Friday: 8.10am - 4.40pmSaturday: 8:10am -1.00pm

After office hours : 012-4309499[including weekends and public holidays]

Summary

• Resuscitation

– Airway

– Breathing

– Circulation

– Seizure control

– Correct hypoglycaemia

– Correct hyperthermia

– Resuscitation antidotes

• Risk assessment

Risk assessment

• Distinct cognitive step (predict the likely clinical course and potential complications for the individual patient at that particular presentation)

• Quantitative

• Takes into account:

– Agent(s)

– Dose(s)

– Time since ingestion

– Current clinical status

– Patient factors

Summary

• Supportive care and monitoring

• Investigations

– Screening (ECG, paracetamol)

– Specific

• Decontamination

• Enhanced elimination

• Antidotes

• Disposition

Conclusion

• Intoxication manifestation is very challenging (non specific, AMS, no hx of intoxication, masked by other conditions)

• Methodical approach/toxidrome helps

• Decontamination methods are vital – indications determined by type of poisons, conscious level, risk of aspiration, hemodynamic stability, time factor

• Antidote: gold standard

Build me newer molecules,

O my Soul -

As the swift seasons roll

Let each new compound

Safer than the last

Avoid the reactions observed in the past

………………..

The Pharmacologic Principles of Medical Practice (1954)