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Common Toxicology

sukit wipusattayaEmergency Medicine

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Common poison exposure Ramathibodi Poison Center: 2001-2005

กลุ่��ม จํ�านวน %

สารป้�องก�นก�าจํ�ดศั�ตร�พื�ช (pesticides) 9,327 39.9

สารใช�ในบ้�านเร�อน(household products) 4,421 18.9

ยา (pharmaceutical products) 4,397 18.8

สารใช�ในงานอ�ตสาหกรรม (occupational products) 2,527 10.9

พื�ชม�พื ษ(plant toxins/poisonous plants) 977 4.2

ส�ตว"ม�พื ษ (poisonous animals) 621 2.7

รวม 23,368

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Case

PI : 6 “ ” ช�#วโมงก�อน ก นน%ายาลุ่�างห�องน�&า เป้'ดโป้ร ป้ระมาณ 50 ml. หลุ่�งก นม�อาการแสบ้คอมาก แลุ่ะป้วด

ท้�องโดยเฉพืาะบ้ร เวณลุ่ &นป้.#

PE : P 110/min, BP 90/60, RR 24/min, T 37.8 Erythema or soft palate and posterior pharynx, no stridor Lung : clear Abdomen : tender at epigastrium, no guarding or rigidity, normal bowel sound

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Acid

Sulfuric acidHydrochloric acidHydrofluoric acidFormic acid Acetic acid

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Alkali

Sodium hydroxideCalcium hydroxideLithium hydroxideAmmonium hydroxideSodium hypochloriteSodium tripolyphosphate

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determinants of damaging potential

•Volume •Concentration•Physical state•pH

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Alkali burn•Liquefaction necrosis•Protein dissolution, collagen destruction, fat saponification and cell membrane emulsification•Facilitate penetration of the alkali•often injure oropharynx and proximal esophagus

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Liquefaction necrosis

•Coagulation necrosis •protein precipitation and eschar formation•tend to be protective against deep injury

Acid Ingestion

Pathology

• Ingestion:

• Squamous epithelium

• Erythema, edema, erosion, ulcer

• Lowest tensile strength of the esophagus: Day 3-14

• Collagen organization and epithelial repair in months

• Shortening and dysmotility

• Increase risk of squamous cell CA x 20-40

Clinical manifestations

•Drooling --> oropharyngeal injury •Odynophagia ,dysphagia --> esophageal injury•Abdominal pain,GI bleed --> stomach injury •Dysphonia,stridor,resp distress --> laryngotracheal injury •Retrosternal chest pain --> mediastinitis•Signs of complication:

•GI hemorrhage•Laryngeal involvement•Esophageal perforation

TREATMENT

1. Initial Stabilization

2. Clinical Evaluation

3. Decontamination

4. Diagnostic tests

5. Enhance Elimination

6. Specific antidotes

7. Supportive care

Initial stabilization

• Personal protective equipment

• Airway: indications for early intubation• Stridor

• Dyspnea

• Oropharyngeal obstruction

• Blind nasotracheal intubation is contraindicated

Clinical Evaluation

• History

• type and amount of caustic ingested

• intentional or unintentional ingestion

• Physical examination

• determine hemodynamic stability

•etiology of shock (GI bleed , volume deplete)

• examine peritoneal sign & mediastinitis

• examine eye & skin

Decontamination

• contraindicated• No role of dilution or neutralization

Diagnostic test

•arterial blood gas•electrolyte•liver function•complete blood count•coagulation profile•calcium & magnesium ( HF acid)•Chest x-ray•EKG

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Enhance elimination

No role of enhance elimination

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Antidote

•Some agents need specific antidote•Hydrofluoric acid •Phenol

: calcium gluconate

: isopropyl alcohol

: ethyleneglycol

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Hydrofluoric acid

Hydrofluoric acid

Apply 2.5% calcium gluconate gel (10% calcium gluconate 10 ml in KY gel 60 ml ) on skin until pain resolves (usually within 10 minutes)

+

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Supportive care

Endoscopy•Benefits: treatment plan, disposition and prognosis•Timing:

• 4-6 hours post-ingestion: avoid underestimation• Not later than 48 hours post-ingestion

•Indications:• All intentional ingestion • Presence of symptom or sign of corrosive injury

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• Grade 0: Normal• Grade I: Mucosal edema or hyperemia• Grade II: Ulceration

• IIa: superficial ulceration• IIb: deep discrete or superficial ulceration

• Grade III: Necrosis• IIIa: small, scattered areas of necrosis• IIIb: extensive necrosis

Grading of Esophageal injury

Pathologic severity of injury

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Supportive care

Corticosteroid•Aim: minimizing stricture in second degree (II, IIb) burns with plans for dilation•Controversial issues

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Disposition

• Grade 0 – I can be discharge if tolerate well to eating and drinking

• Grade IIb-III need ICU admission.

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Question

1. ผู้��ป้0วยชาย 30 ป้. chronic alcohol drinking น�&าหน�ก50 kg 30 นาท้�ก�อนมาโรงพืยาบ้าลุ่ ก น paracetamol 10 เม1ด

• ท้�านจํะให�การร�กษาแก�ผู้��ป้0วยอย�างไรต�อไป้

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Acetaminophen

Paracetamol

Sulfation Glucuronidation CYP2E1

Renal excretion

NAPQI

Reduced glutathione

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CYP2E1

NAPQI

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Clinical symptoms

Stage I : 0.5-24 hrs nausea, vomiting

Stage II : 24-72 hrs RUQ pain , liver enzyme , bilirubin , prolong PT

Stage III : 72-96 hrsjaundice, hepatic encephalopathy , renal failure

Stage IV : 96 hrs -2 wksrecovery phase

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Diagnosis

1.History of ingestion > 150 mg/kg•Exception

•chronic alcohol•inducible agent : phenytoin, phenobarbital, isoniazid•eating disorder e.g. anorexia nervosa, starvation

2.Serum paracetamol level (normogram)•at 4-24 hr

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Overdose estimation: amount > 150 mg/kg

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Treatment

Paracetamal level

N-acetylcysteine

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NAC therapy : Routes of administration

•Oral : 18 doses over ~70 hours

•140 mg/kg for loading

•70 mg/kg for maintenance every 4 hours x 17 doses

•Vomiting

•Intravenous : ~ 21 hours

•150 mg/kg in 1 hours

• 50 mg/kg in 4 hours

•100 mg/kg in 16 hours

•Anaphylactoid reaction 35

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Management of Anaphylactoid reactions from IV NAC

•Flushing: continue treatment

•Urticaria:

•Diphenhydramine 50 mg IV

•Continue treatment

•Angioedema

•Stop NAC

•Diphenhydramine 50 mg IV

•Restart if no symptoms after 1 hour

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Disposition

Follow up• LFT at 48 hrs , PT• BUN/Cr at day 7

If liver enzyme >1000 •PT , BUN/Cr•NAC 150 mg/kg/day •until clinical improve , PT normal 3

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Case• ผู้��ป้0วยชายอาย� 47 ป้. มาด�วยอาการหมดสต ไม�ค�อยร� �ส3กต�ว

ตรวจํร�างกายพืบ้ RR=8 , BP=80/50 , PR=60 T=36 O2sat = 85% E1V1M5 , pupil 1mm SRTL ,

• lung clear , absent bowel sound , no sweating , DTX=141

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OpioidOpioid

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Opioid

1.Natural derived from opium• Morphine, Codeine

2.Semi-synthetics• Heroin

3.Synthetics• Fentanyl, Meperidine, Methadone

Diphenoxylate (Lomotil)

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Opioid Toxidrome

•CNS depression•Miosis•Respiratory depression

Miosis

hypoventilation

hypothermia

CNS depression

Bradycardia ,hypotension

Ileus

Hyporeflexia

Needle mark

Treatment

1. Initial Stabilization

2. Clinical Evaluation

3. Decontamination

4. Diagnostic tests

5. Enhance Elimination

6. Specific antidotes

7. Supportive care

urine toxicology

Naloxone

Initial stabilization

•Airway : oral airway , bag-mask valve , ETT

•Breathing : Improve oxygenation

•Circulation :

• Hypotension : typically orthostatic --> supine , rise legs

•R/O hypoglycemia, hypoxia, hypothermia•cardiac monitoring

Decontamination

•No role of ipecac syrup

•NG lavage : not necessary

•Activated charcoal 1 gm/kg in moderate

to large dose after ingestion within 1 hr

•Sustained release product (Oxycodone) ,

body packer --> whole-bowel irrigation

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Enhance elimination

•No role of cathartic alone

•Multiple dose activated charcoal may be

useful in Lomotil overdose

•no role of dialysis (due to large volume

distribution)

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Naloxone

•Opioid antagonist : reverses almost all adverse effects mediated through opioid receptors

•Empiric use may assist in diagnosis

•Can administered IV , IM , ETT•Onset of action (iv) 1-2 mins•Duration of action 20-90 mins

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Naloxone

Dosage Minimal resp depression Markly resp depression

Opioid dependent

0.2 mg iv

2 mg iv Non-opioid dependent

0.4 mg iv

Repeat dose q 2-3 min until •respiratory is reversed •maximum dose of 10 mg

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Case

• ผู้��ป้0วยชายอาย� 50 ป้. มาด�วยอาการหมดสต ไม�ค�อยร� �ส3กต�ว• PE : RR=14 , BP=120/80 , PR=60 T=36 O2sat = 92% • a man with drownsiness , hypersalivation• heart : regular• lung : wheezing and rhonchi both lung • abdomen : hyperactive bowel sound • extremities: sweating • E2V2M5 , pupil 1 mm SRTL

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Organophosphate/Carbamate

Organophosphate : parathion, malathion Carbamate : methamyl, methyl carbamate

Inhibit acetylcholine esterase enzyme

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MnemonicsDUMBELS

D – DiarrheaU – UrinationM – MiosisB – bradycardia,

bronchospasm, bronchorrhea

E – EmesisL – LacrimationS – Salivation

Days of the Week:M – MydriasisT – TachycardiaW – WeaknessH – HypertensionF – Fasciculations

Sign and Symptom

Treatment

plasma cholinesterase level , gastric content

atropine , 2-PAM

1. Initial Stabilization

2. Clinical Evaluation

3. Decontamination

4. Diagnostic tests

5. Enhance Elimination

6. Specific antidotes

7. Supportive care

Atropine

•Atropine 0.02 - 0.05 mg/kg (1-3 mg) q 5 min

until

•Control of mucous membrane hypersecretion

•Airway clear

•May require 200 - 500 mg in 1st hr

•Not active at nicotinic sites

Pralidoxime (2-PAM)

•Pralidoxime 1-2 g bolus (20-50 mg/kg) Then 500 mg/hr (10-25 mg/kg/hr)•Monitor clinical and AChE level

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Paraquat

Trade name:

Gramoxone

Herboxone

Dextron

Color: Blue - green

Toxicodynamic Mechanism

PQ2+ PQ+

NADP+NADPH

O2 O2

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PQ reductase

Pentose phosphate pathway

Cell death : (lung , liver , kidney)

Oropharyngeal ulceration and corrosion

Ocular injury

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Clinical symptoms

• GI : like corrosive agent

• Cardiovascular : Hypovolemia, shock, dysrhythmias

• Renal : acute tubular necrosis , renal failure

• Hepatobilliary : hepatitis , hepatic necrosis

• Respiratory : mediastinitis, pneumothorax, hemoptysis, pulmonary edema, and hemorrhage, pulmonary fibrosis

Paraquat Lung

Day 1 Day 28

Treatment

No oxygen until PaO2<50 , resp distress

lavage , fuller’s earth

urine for paraquat

hemoperfusion

1. Initial Stabilization

2. Clinical Evaluation

3. Decontamination

4. Diagnostic tests

5. Enhance Elimination

6. Specific antidotes

7. Supportive care

InvestigationsInvestigations

•Serum paraquat level

•Urine paraquat level

•Bedside : 1% Na-dithionate in NaOH 2 ml + urine 10 ml (blue = positive = paraquat 1 ppm)

•BUN, Cr, UA, arterial blood gas, pulmonary function test

Paraquat

alkaline sodium dithionate

- antioxidant: Vit C, Vit E, NAC

- Immunosuppressive

Cyclophosphamide 5mg/kg/day IV

Dexamethazone 10 mg IV q 8 hrs

Specific treatment

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Case เด1กผู้��ชาย 5 ป้.

CC. ก นแชมพื�30 นาท้�ก�อนมาโรงพืยาบ้าลุ่PI. 30 นาท้� ก�อนมารพื. ผู้��ป้0วยก นแชมพื�สระผู้มป้ระมาณ 5 อ3ก

หลุ่�งก นม�อาการป้วดชาลุ่ &นเลุ่1กน�อย มารดาพืยายามลุ่�วงคอผู้��ให� อาเจํ�ยน แต�ไม�อาเจํ�ยน จํ3งมารพื. ผู้��ป้0วยร� �ส3กต�วด� ไม�ส�าลุ่�ก ไม�ป้วด

ท้�อง อาการอ�#นป้กต PH. ไม�ม�โรคป้ระจํ�าต�วใดๆ ไม�เคยแพื�ยาใดๆ

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ผู้ลุ่ ตภั�ณฑ์"ท้�าความสะอาด (cleaner)

• ท้�าความสะอาดร�างกาย• สบ้��อาบ้น%า•แชมพื�สระผู้ม

• ท้�าความสะอาดเส�&อผู้�า• ผู้งซั�กฟอก•น�&ายาซั�กผู้�าน�&ายาขจํ�ดคราบ้

• ท้�าความสะอาดอ�#นๆ ท้�#วไป้• น�&ายาลุ่�างจําน•น�&ายาท้�าความสะอาดพื�&น

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Detergent

Surfactant Builder

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Surfactant

•Nonionic surfactant

•Anionic surfactant

•Cationic surfactant

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Nonionic surfactant

Condensation products of fatty alcohols + ethylene oxide

• Alkyl phenol polyglycol

• Alkylphenyl polyethoxyethanol

• Alkylpolyethoxylates

• Ethoxylated alcohols

• Nonoxynol

• PEG stearates

Polyalkaline glycol, fatty acid alkanolamide amide

Polyethylene glycol alkyl aryl ethers

• Polyoxyethylene alkyl ethers

Anionic surfactant

Sodium, potassium, or ammonium salts of fatty acids

• Alkyl sulfonate

• Alkylbenzene sulfonates

• Alkyl sulfate

• Dialkyl sulfosuccinate

• Linear alkylate sulfonate

• Phosphorylated hydrocarbons

• Sulfonated hydrocarbons

Cationic surfactant

Pyridinium compounds• Cetalkonium chloride

• Cetrimide

• Cetrimonium bromide

• Cetylpyridinium chloride

• Stearalkonium chloride

Quaternary ammonium compoundsBenzalkonium chloride

• Benzethonium chloride

• Quinolinium compound• Dequalinium chloride

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Example• Sodium lauryl ether sulfate 14% w/w

• Sodium lauryl sulfate 6%w/w

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•Sodiumdodecylbenzenesulphonate 6.7%w/w •Nonyl phenol ethoxylated 9% w/w•Sodium lauryl ether sulfate 5% w/w

Example

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•Sodium lauryl ether sulfate 2.12% w/w•Sodium dodecyl benzene sulphonate 14.88% w/w

Example

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Example• C12-C15 alcohol ethoxylated 1.2% w/w

• Sodium lauryl ether sulfate 3.92% w/w

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Example

• Alkoxylated linear alcohol 8%w/w

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•Anionic surfactant -Sodium linearalkyl benzenesulfonate -Polyoxyethylene alkyl ether•Sodium tripolyphosphate•Zeolite•Sodium carboxymethyl cellulose•Fluorescer

Example

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Example•Dialkyl Dimethyl Ammonium Chloride

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Builder

•sodium phosphate

•sodium carbonate

•sodium metasilicate 85

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Symptoms

•Nonionic / Anionic surfactant •mild irritation•mild GI symptoms : N/V , abdominal pain --> dehydrate

•Cationic surfactant• like corrosive agent• upper airway edema , respiratory distress• hypotension, metabolic acidosis, CNS depression

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GASTROINTESTINAL

Nausea, vomiting diarrhea --> metabolic alkalosis

Oral, pharyngeal,esophageal burns

Esophageal stricture

irritation of mucous membranes

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1. ผู้ลุ่ ตภั�ณฑ์"ความสะอาดร�างกาย (toilet articles and cosmetics):

แชมพื�สระผู้ม, สบ้��อาบ้น%า, คร�ม/ โฟมลุ่�างหน�า : nonionic and anionic surfactant

คร�มนวดผู้ม : cationic detergent

2. ผู้ลุ่ ตภั�ณฑ์"ซั�กผู้�า(laundry products):

ผู้งซั�กฟอก, น�&ายาซั�กผู้�า : nonionic and anionic surfactant

น�&ายาป้ร�บ้ผู้�าน��ม : cationic detergent

น�&ายาขจํ�ดคราบ้ไคลุ่ : anionic surfactant

3. ผู้ลุ่ ตภั�ณฑ์"ลุ่�างจําน (dishwashings):

น�&ายาลุ่�างจําน, น�&ายาลุ่�างขวดนม : nonionic and anionic detergent

น�&ายาลุ่�างจําน(เคร�#อง) : cationic detergent

4. น�&ายาท้�าความสะอาดพื�&น (floor cleaners) : nonionic and anionic detergent

5. น�&า ยาท้�าความสะอาดห�องน�า�บ้างส�ตร (toilet cleaners) : nonionic, anionic and cationic

6. น%ายาท้�าความสะอาดเอนกป้ระสงค" (All-purpose cleaner) : nonionic, anionic and

cationic

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TREATMENT

1. Initial Stabilization

2. Clinical Evaluation

3. Decontamination

4. Diagnostic tests

5. Enhance Elimination

6. Specific antidotes

7. Supportive care

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• Nonionic or anionic is generally self-limiting•requiring no treatment•maybe dilute with 120 - 240 ml of water or milk

•Cationic detergent should treat as corrosive agent•Do not induce vomiting•If signs or symptoms of esophageal irritation or burns are present, consider endoscopy •Activated charcoal - unnecessary

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Supportive care

• Treat dermal irritation / burns with standard topical drug

• Dermal hypersensitivity reactions Rx. with systemic / topical corticosteroids / antihistamines

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Summary•No activated charcoal•Nonionic / anionic surfactant•dilution by water/milk•may NG lavage •improve in 24 hr

•Cationic surfactant • treat as corrosive agent --> endoscopic 9

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Case

ผู้��ป้0วยหญิ งไท้ยโสด อาย� 20 ป้. ป้ฏิ เสธโรคป้ระจํ�าต�วCC: พื�นยาไบ้กอน(spray) ฉ�ดย�งเข�าป้าก 3 คร�&ง 5 นาท้�ก�อนมารพื.

PI: 5 นาท้�ก�อนท้ะเลุ่าะก�บ้แฟน จํ3งน�า สเป้รย"ฉ�ดย�งย�# ห�อไบ้กอนส�เหลุ่�องมาฉ�ดเข�าป้าก 3 คร�&ง แฟนน�า

ส�งรพื.ท้�นท้�PE: WNL ม�กลุ่ #นยา บ้ร เวณป้าก

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Pyrethrines & Pyrethroids•Pyrethrins: compounds extracted from chrysanthemums•Pyrethroids: synthetic derivatives of pyrethrins

•greater chemical stability•Type II pyrethroid

•Contain a cyano substituent•More toxic formulation•Potential danger to human

•Common as aerosals in automate insect spray•Less toxic and safer than other compound

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Toxicodynamics

• affect sodium channel in nerve cell• depolarization and hyperexcitability• Type I pyrethroid

• briefer , repetitive nerve discharge

• Type II• longer repetitive nerve discharge• inhibit Cl in GABA receptor --> seizure

• allergic : true IgE-mediated anaphylatic100

PyrethrinesPyrethrines

• Pyretrum extract• Pyrethrine I• Pyretrhrine II• Cinerin I• Cinerin II• Jasmolin I• Jasmolin II

AllethineBarthrineBioallethrineBioresmethrineCismethrineCymethrineCypermethrineDecamethrineDeltamethrineFenothrinFenvalerateFuramethrinetetramethrin

PyrethroidsPyrethroids

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ยาจํ�ดก�นย�งแลุ่ะผู้ลุ่ ตภั�ณฑ์"ก�นย�งใช�ก�บ้เคร�#องไฟฟ�า

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Mechanism of toxicity

1. Hypersensitivity

•immediate rhinitis and bronchial hyperreactivity

•uncertain mechanisms

2. Increase sodium influx into neurons

• Increase neurotransmitter release

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Clinical manifestation• Allergic and hypersensitivityAllergic and hypersensitivity

• Allergic rhinitisAllergic rhinitis

• Contact dermatitisContact dermatitis

• AsthmaAsthma

• AnaphylactoidAnaphylactoid• Dermal and systemic manifestationsDermal and systemic manifestations

• Abdominal pain, nausea, vomiting within 10 minutes to 1 Abdominal pain, nausea, vomiting within 10 minutes to 1 hourshours

• Paresthesia, numbness: onset hours, duration: less than Paresthesia, numbness: onset hours, duration: less than 24 hours24 hours

• Weakness and muscle fasciculationWeakness and muscle fasciculation

• SeizureSeizure

• In cases of ingestion, beware of hydrocarbon pneumonitisIn cases of ingestion, beware of hydrocarbon pneumonitis105

Respiratory mildly irritate rhinitis , bronchitis , bronchospasm , asthma

Cardiovascular not direct effect

Nervous type I : T-syndrome (tremor)type II : CS-syndrome ( choreoathetosis salivation seizure)

skin & mucous membrane

allergic contact dermatitisallergic conjunctivitis

Gastrointestinal salivation , N/V , abdominal pain , diarrhea

Liver effected due to prolong hypoxemia

Genitourinary effected due to prolong hypoxemia

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Decontamination

Respiratory

Remove from sourceadequate ventilation with 100% oxygeninhaled beta-agonist

Skin remove all contaminated clothing ,jewelrywash affected area with water and liquid detergent

Eye irrigate with water at least 20 minsMorgan lenses with ophthamic local anesthetics

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Primary survey and resuscitation

Airway open airway , intubate if necessary

Breathing

adequate oxygenation high flow O2 15 LPM via nonrebreathing reservoir maskBMV in inadequate spontaneous ventilationendotracheal intubation

Circulation

cardiac monitoring , ALCL guidelinestart IV NSS

Disability

assess level of conscious continuallyIV diazepam if seizure despite adequate O2 and glucose

Exposure

undress and decontaminated

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Poisoning treatment paradigm

Alter Absorption

Remove from the poison

Antidote non

Basic continue reassess ABCtreat anaphylactic

Change catabolism

not applicable

Enhance Elimination

not applicable

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Treatment

•Typical GI decontamination•Be careful in case of hydrocarbon media•Treat allergic symptoms with antihistamine•Symptomatic•Observe for 6 hrs and d/c if asymptomatic