acute poisoning
TRANSCRIPT
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)