ge to management of poisoning

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G ETO MANAGEMENT OF POISONING SECOND EDITION

ABDULAZIZ SADDIQUE PHARM.D. ADAM LEE CAFAGE PHARM.D.

©

Abdulaziz Saddique, 1995

King Fahd National Library cataloging-In-Publication Data Saddique, Abdulaziz Guide to the management of poisoning .. p, .. em ISBN: 9960-27-656-2 !-Poisoning

2-Poison and poisoning

615.9 de

1515115

Legal Deposit no: 1515/15 ISBN: 9960-27-656-2

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King Saud University Press

!-Title

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vii

CONTENTS PREFACE Chapter I General Management of Poisoning

I

Assessment of Toxicity

I

Supportive Care

2

Preventi50mg'

2-Ethylene glycol level> 2Dmg%

2-Severe acid-base andlor fluid

(3.2 mmoiiL) 3-Symptomatlc patient with a history of ethylene glycol Ingestion

electrolyte dlsturban·ces desp treatment 3-Renal failure (may develop In

4-Ethylene glycol level unavailable with suspicion of concurrent EtoH and ethylene glycol Ingestion

1-

+

I DURATION OF 1THERAPY: Continue for a minimum of dialysis or until: 1-Ethylene glycol level< 10mg% 2-Giycolic acid metabolite not detectable. . 3-Ethylene glycolmduced acidosis CNS finding and ' ' osmolal gap have resolved

ETHANOL THERAPY {see treatment section in METHANOL POISONING Page 391

I Monitor blood glucose .... (especially children)

( AciQOSIS)

I

Patients such as these may have a normal acid-base profile and urinalysis despite high ethylene glycol levels. Determine blood ethanol level before beginning ethanol therapy and modifying '--------------'the loading dose.

1

oi/L) :lve ;}

Monitor: 1-ABGs 2-Determine base deficit to calculate replacement with NaHC03

T_

_ ETHANOL THERAPY WITH HEMODIALYSIS (see treatment section in methanol poisoning)

Monitor blood glucose (especially children)

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Do any of the following conditions exist?

THERAPY: . . . One day when d1alys1s 1s performed or until clinical findings resolve, whichever is longer.

NaHC03: 1-lnitial dose of 1-2 mEq/kg per liter of fluid may be needed. 2-~onitor ABGs to gu1de frequency & amount of NaHC03 replacement

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DANTROLENE

Amphetamines Poisoning .TREATMENT FLOWSHEET FOR AMPHETAMINES POISONING

(

I

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SEIZURES. ) See management Page 20

(VENTRICULAR ARRHYTHMIAS )

...

(SUPRAVENTRICULAR ARRHYTHMIAS

UDOCAINE Treatment range: 1.5- 5mgll AdUlt 50-100mg IV • bolus at25

~

r

PROPRANOLOL

to 50mgtmln; may repeat

Monitor: HR

In 5mln. at 1!2 Initial dose to a max. cA 300mg In 1hr

Adult 1mg over 1min;

Simultaneously start infl6ion at 1-4mglmln. Child: 1mglkg IV bolus (same

rate as adult); may repeat Q5-10mln prn until a max. of 5mglkg. Follow with Infusion of 20-40mcglkg/

J

may repeat Q2-5mln. until response Is

achieved or a max. or 5mg Is given. Child: 0.01 to 0.1mglkg IV over 10min. to a max.

at 1mg per dose

min. aGive loNer dose to elder1y, light weight patients, In CHF and liver dysfunction.

AJernatlve

+

CALCIUM CHANNEL BLOCKERS -Use verapamU if hypopetfusion is

present

45

46 Angiotensin Converting Enzyme Inhibitors (ACE/)

Range of Toxicity Patients have ingested up to 7.5 gm of Captopril, 300 mg ofEnalapril, and 420 mg ofLisinopril with only mild hypotension. Mechanism of Toxicity These agents are specific inhibitors of peptidyldipeptide carboxyhydrolase, the enzyme which converts angiotensin I to angiotensin II; thus preventing vasoconstriction. These agents are believed to have direct toxic effect on the kidneys. Characteristic Signs and Symptoms Cardiovascular

• Hypotension • Bradycardia Respiratory

• Bronchospasm (Captopril) • Cough(Captopril, Enalapril) Gastrointestinal • Taste loss (Agensia) Hepatic

• Hepatitis(Captopril) Genitourinary

• Nephrotic Syndrome • Proteinuria Metabolism

• Elevated Bradykinin and /or Prostaglandins

ACEI Poisoning Fl~id

and Electrolytes • Hyperkalemia • Hyponatremia

Dermatologic (4 times more with Captopril than with enalapril) • Pemphigus • Exfoliative dermatitis • Lichenoid eruptions • Lupus-like eruption (Captopril) Hematologic • Neutropenia (Captopril) • Agranulocytosis Patient disposition Children aged I to 5 years old who accidentally ingested no more than an adult daily therapeutic dose (up to I 00 mg of Captopril or 30 mg of enalapril) were safely managed at home. Hypotension effects of a pure ACE! ingestion should manifest within one hour. Maximal effect, following a single therapeutic dose, occurs within 1 to 2, 4, to 6 and 6 hours, for Captopril, enalapril, and Lisinopril, respectively. Duration of action may be dose dependent.

Monitoring parameters • BUN and Creatinine • Urea and Electrolytes (Na+ and K~ • Vital signs(Pulse and Blood pressure) • Cardiac Monitor

47

. 48

Chapter III TREATMENT FLOWSHEET FOR ANGIOTENSIN CONVERTING ENZYME POISONING Refer to GENERAL MANAGEMENT Algqrithm on page 17

MOHIIQB· 1-BUN /Cr 2-l)tes-Na, K 3-VS-BP X24-36 post-lngestlcn

.

I HYPOTENSION \.

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•

problem

•

Systolic BP ( 100 mmHg DBPnormal

......... ~

NOTES: 1-Fiuid bolus of 250-500ml NS should be tried. If no response consider sympathomimetics. 2-NOREPINEPHRINE: Add 4mg to 250ml D5w/NS (concentratiorF 16mcg/ml. (base). Avoid running with alkaline solutions. 3-DOPAMINE: Add 400mg to 250ml D5w (concentration) =1600mcg/ml.) for fluid restricted patients. 800mg in 250ml D5w(32oomcg/ml.). Avoid confusion with Sodium Bicarbonate.

Dobutamine 2-20mcglkg/min. IV. (add dopamine when BP improves. Avoid dobutamine when SBP 20 meg/ ml (79.3 mcmol/L). Ataxia at level> 30 mcg/ml (118.9 mcmol/L), and mental changes at levels> 40 mcg/ml (158.5 mcmol/L).

Mechanism of Toxicity

Phenytoin alters neuronal ion fluxes, increasing refractory periods and decreasing repetitive neuronal firing. Toxic levels usually cause central nervous system depression. Meanwhile, the diluent Propylene glycol also is a toxic substance and can cause cardiac arrest when infused rapidly (>40-50 mg/min [0.5-1 mg/ kg/ min)). Characteristic Signs and Symptoms HEENT

• Nystagmus Cardiovascular

• Bradycardia • Arrhythmia's Neurologic

• Cerebellar Ataxia- Monoplegia • Cerebellar atrophy- Neuroleptic Malignant Syndrome • Nystagmus • Coma • CNS depression • Hyperreflexia • Drowsiness

~'

58

Chapter III • Lethargy • Encephalopathy • Seizures

Gastrointestinal

• Nausea • Vomiting Hepatic

• Hepatitis • Chronic inflammation along with cholangitis • Liver Function Test changes Respiratory

• Apnea • Respiratory depression Metabolism

• Hyperglycemia Fluid and Electrolytes

• Hypematremia Dermatologic

• Erythema multiform Musculoskeletal

• Hyperreflexia Endocrine

• Hypothyroidism Psychiatric

• Hallucinations • Confusion

Phenytoin Poisoning Patient Disposition

All patients of Phenytoin overdosage should be admitted, accidental overdoses may be admitted to the medical flopr, however suicidal cases should be admitted to the intensive care. Cardiac monitoring is not necessary following accidental ORAL overdose in adults. Generally the patient's conditions, amount ingested and other underlying diseases will determine the patient's admission area and other requirements for care. Monitoring Parameters :

• Phenytoin blood level (normal 10-20 mcg/ml) • Urea and electrolytes • Liver Function Test • ABG's • EKG

59

60

Chapter III TREATMENT FLOWSHEET FOR PHENYTOIN POISONING

PHENYTOIN

:\ •

___,__________.

Refer to GENERAL MANAGEMENT Algorithm on page17

._

(Normal serum level: 10-20mgfllp_

I

!Monitoc VS. EKG 1.;;: ! Symptoms of over do~e may last 7-10days

I

Nystagmds (>20mgll} Ataxia (>30mg/l) Mental changes (>40mg/1)

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I HYPOTENSION

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I Supportive care I

I IPump problem_ I

IVolume problem J •

1-Fiuids(1)!Trenderlenberg position. 2-Cause specific interventions 3-Consider vasopressors if needed

What is the blood pressure? (BP)

I

...

I

Systolic BP 20mcg/kg/min.) Stop norepinephrine When BP improve

...

Systolic BP >100 mmHg DBP normal

Systolic BP 70-100mmHg(1)

... "''IIII

NOTES: 1-Fiuid bolus of 250-SOOml NS should be tried. If no response consider sympathomimeties. 2-NOREPINEPHRINE: Add 4mg to 250m I DSw/NS (concentration= 16mcg/ml. (base). Avoid running with alkaline solutions. 3-DOPAMINE: Add 400mg to 250m I 05w (concentration) =1600mcg/ml.) for fluid restricted patients. 800mg in 250ml 0Sw(3200mcg/ml.). Avoid confusion with Sodium Bicarbonate.

Dobutamine 2-20mcg/kg/min. IV. ...._ (add dopamine when Ill" BP improves. Avoid dobutamine when SBP-3 "!!j

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71

ANTIDEPRESSANTS (CYCLIC)

Range of Toxicity I. Ingestion of (for most antidepressants) 10- 20 mg/kg- moderate to serious exposure 35- 50 mglkg- fatal 2. Children are more sensitive to antidepressants. Mechanism of toxicity Cyclic antidepressants toxicity affects primarily the cardiovascular and central nervous systems. The anticholinergic effects of these drugs and inhibition of neuronal reuptake of catecholamines result in tachycardia and mild hypertension. Where its peripheral alpha-adrenergic blockade induces vasodilatation. Also cyclic antidepressants have a membrane-depressant effects (quininelike), which cause myocardial depression and cardiac conduction disturbances by inhibition of the fast sodium channel that initiates the cardiac cell action potential. Metabolic acidosis may contribute to cardiotoxicity by further depressing the fast sodium channel. Meanwhile, the CNS manifestations are partially caused by the anticholinergic toxicity (e.g. sedation and coma) but seizures are probably a result of inhibition of reuptake of norepinephrine or serotonin in the CNS or other central effects. Available forms There are four different groups of cyclic antidepressants (bicyclics, tricyclics, tetracyclics and a miscellaneous group) with each group showing slightly different symptomatologies upon overdosing. Tetracyclics Bicyclics Tricvclics Amitripty lin +* Maprotiline *+ Viloxazine Zimelidine Amoxapine • Mianserin

Miscellaneous Trazodone

Clomipramine• Desipramine*+ Doxepin'+ Imipramine*+ Loxapine • Nortriptyline*+ Protripty line *+ Trimipramine*+ • CNS Toxicity

+ Cardiovascular toxicity

72

Chapter III Characteristic Signs and Symptoms A. TRICYCLICS (excluding Amoxapine)

GENERAL • Hypotension • Convulsions • Coma • Arrhythmia's Onset within 4 hours after ingestion Cardiovascular

• Supraventricular tachycardia • Multifocal PVC's (may develop 5 days after exposure) • Ventricular tachycardia, flutter and fibrillation • EKG changes • Prolonged P-R interval • Widening of QRS complex • Q-T .prolongation • T -wave flattening or inversion • S-T segment depression • Right-bundle branch block • Complete heart block • Cardiac standstill •

Quinidine-like effect

• Hypertension followed by significant hypotension (hypertension should not be treated) •

Cardiopulmonary arrest

Respiratory

• Respiratory depression • Pulmonary edema • ARDS (Adult Respiratory Distress Syndrome) • Hyperventilation

Antidepressants Poisoning Acid base

• Acidemia Gastrointestinal

• Decreased gastric motility . • Delayed gastric emptying • Delayed movement through intestinal tract • Hepatitis Musculoskeletal

• Muscle twitching • Decreased deep tendon reflexes Neurologic

• CNS depression with lethargy • Disorientation • Hallucinations • Coma • Fever followed by hypothermia • Choreoathetosis • Myoclonus • Ataxia • Seizures Ophthalmic

• Dilated pupils usually responsive to light Urogenital

• Urinary retention AMOXAPINE (Loxapine shares similar toxicities) • Symptoms differ from other tricyclic antidepressant overdoses • Increased incidence of seizures and coma • Decreased cardiovascular toxicity

73

74

Chapter III Other symptoms include

• Seizures I coma associated with sinus tachycardia • Status epilepticus • Metabolic acidosis • Cerebral anoxia • Renal failure with or without rhabdomyolysis • Pancreatitis • Coma B.TETRACYCLICS • Decreased incidence and severity of cardiovascular toxicity when compared to tricyclics • Neurologic toxicity similar to tricyclics • Seizures C.BICYCLICS • Insufficient data to accurately characterize bicyclic overdosing • Incidence of cardiovascular, neurological and respiratory toxicity appear to be lower than tricyclics and tetracyclics • Seizures • Drowsiness • Miosis • Decreased reflexes • Hypotension • Tachycardia D.MISCELLANEOUS Trazodone Minimal cardiovascular and CNS toxicity following overdose Symptoms include • Drowsiness • Lethargy • Nausea

· Antidepressants Poisoning • Dizziness • Shivering • Stage 0-1 coma without significant cardiovascular toxicity Patient Disposition All patients must be obseiVed and monitored for at least 6 hours. The patient should be admitted to the ICU if symptomatic. There have been reports that suggest that delayed to?cicity and death from arrhythmia occur after an asymptomatic inteiVal, up to 5 days after ingestion. Monitoring Parameters • Blood pressure • Heart rate • Temperature • Arterial blood gases • EKG. Look for • Conduction defects - prolonged P-R and Q-T intervals and widened QRS · • Ventricular arrhythmia's - multifocal PVC's, ventricular tachycardia, flutter, fibrillation • Supraventricular arrhythmia's • Serum electrolytes* • Bowel sounds • Deep tendon reflexes CAUTION Hyper)>alemia may aggravate antidepressant induced cardiac · arrhythmia's. Exercise caution with potassium replacement.

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75

TREATMENT FLOWSHEET FOR CYCLIC ANTIDEPRESSANTS POISONING

I

Emesis Contraindicated

•

GASTRIC LAVAGE & ACTIVATED CHARCOAL according to GENERAL MANAGEMENT.

f-1---

Algorithm, page. 17

Multiple dose activated charcoal may be considered 02-Shrs. Give CATHARTIC with first dose only of activated charcoal.

~

1-Vital signs 2-ABGs 3-EKG 4-Eiectrolyles (esp.K+) Monitor for 4Bhrs in symptomatic patients. DO NOT DISCHARGE until patient remains asymptomatic for 24h1S.

Hyperkalemia may aggravate antidepressant induced Cardiac arrhythmias.

~----

Symptoms usually develop within 4hrs.

~

Asymptomatic patients should be observed for at least 6hrs, for all suspected overdose cases. If symptomatic, admit to ICU.

I VENTRICULAR ARRHYTHMIAS) (multifocal PVCs, V.Tach, V. flutter)

(

SEIZURES ) See management Page

SUPRAVENTRICULAR ) ARRHYTHMIAS

20

I

May need to treat if rate>= 160 beats per min. or Patient shows signs and symptoms of hemodynamic instability.

May respond to normalization of acid-base status to physiologic pH or slightly above (pH 7.45- 7.55)

•

I Monitor: .~K_~· & Serum levels Adult Load with 15mg/kg IV to max. of 1Gm inNS at50mg/min.; then maintain with 100mg IVJPO Q S-BH to reach serum levels between 1 0-20mgll Child: Load with 15-20mg/kg IV at 50mg/min.; then maintain with 4-Smg/kg IV/PO divided 012H.

(

I

PROPRANOLOL: Monitor: HR Adult 1mg IV over 1min; may repeat Q 2-Smin 1 until response is achieved or a max. of Smg is given. Child: 0.01 to 0.1 mg/kg IV over 10min.; to a max. of 1mg/dose.

II I

~sponsive LIDOCAINE (Theraj;!eutic serum level:1.55mg/Ll Adult50-100mg IV bolus at 25-SOmg/min.; may repeat in 5 min. at 112 initial dose. Do not exceed 300mg total bolus in 1 hour. nresponsive Simultaneously begin infusion at 14mg/min. Child: 1mg/kg IV bolus; may repeat 05-10 min prn until max. of 3-4.5mg/kg. Follow with infusion of 20-40mcg/kg/min. N.B. Give 1/2 this amount to elderly, lightweight patients, in CHF, liver dysfunction

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BRETYLIUM TOSYLATE Adult 5-10mglkg IVJIM over 10min. with additional doses of 1Omg/kg repeated pm to a max. of 40mg/kg Maintenance of 5-10mg/kg IV/1M Q 6hrs or an IV infusion of 1-2mg/min. "CONTRAINDICATED in patients with hypotension and fixed cardiac output

Note: AVOID 1-DISOPYRAMIDE 2.QUINIDINE 3-PROCAINAMIDE

I I

Antidepressants Poisoning TREATMENT FLOWSHEET FOR CYCLIC ANTIDEPRESSANTS POISONING (Cont.)

HYPOTENSION See management

ACIDOSIS

CONDUCTION DEFECTS

Page 19

NaHC03: 1-lnitial dose of 1-2mEq/kg per liter of fluid may be needed. 2-Monitor ABGs and determine base deficit to guide frequency and amount of NaHC03 replacement

Prolonged QRS interval may be best indication of overdose and

risk of sudden death.

PHENYTOIN (see dosage guidelines in Part I)

May also respond to NaHC03 therapy or

mechanical hyperventilation.

77

78

Chapter III

ANTllliSTAMINES POISONING Range of Toxicity Variable and unpredictable. Clinical evaluation is more important than attempting to determine the amount ingested or injected. Mechanism of Toxicity The toxicity of antihistamines is related to their anticholinergic (antimuscarinic) activity. The-action of Acetylcholine at muscarinic receptors is blocked. ·

Substances included/ Synonymous. A. Ethylenediamine Derivatives I.

Antazoline

2.

Methapyrilene

3.

Tripelennamine (PBZ)

4.

Thenyldiamine

5.

Pyrilamine

B. Ethanolamine Derivatives I.

Bromodiphenhydramine

2.

Carbioxamine

3.

Clemastine

4.

Dimenhydrinate

5.

Diphenhydramine

6.

Diphenylpyraline

7.

Doxylamine

8.

Phenyltoloxamine

C. Alkylamine Derivatives I.

Brompheniramine

2.

Chlorpheniramine

3.

Dexbrompheniramine

4.

Dexchlorpheniramine

5.

Dimethidene

6.

Pheniramine

7.

Pyrrobutamine

8.

Triprolidine

Antihistamines Poisoning D. Phenothiazine Derivatives I . Methdilazine 2.

Promethazine

3.

Trimeprazine

E. Piperazine Derivatives I. Buclizine 2.

Chlorcyclizine

3.

Cyclizine

4.

Meclizine

5.

Hydroxyzine

F. Others I. Astemizole 2.

Azatadine

3.

Cyproheptadine

4.

Phenindamine

5.

Teifenadine

Characteristic Signs and Symptoms GENERAL I. Young children • CNS stimulation • Symptoms of anticholinergic overdose 2.

Adults • · CNS depression • Drowsiness • Excitement • Seizures • Postictal depression

3.

Severe toxicity in children and adults may result in cerebral edema, deep coma, cardiorespiratory collapse or death. Onset of symptoms may occur within 30 min to 2 hours after ingestion.

79

80

Chapter III

HEENT • Anticholinergic effects " dryness of the mouth, nasal stuffiness etc .. " Cardiovascular

• Tachycardia • Extrasystoles • Hypotension or hypertension Neurological

• CNS stimulation and /or depression • Restlessness • Nervousness • Difficulty sleeping • Acute Dystonic reactions • Dyskinesias Temperature

• Hyperthermia Musculoskeletal

• Rhabdomyolysis Psychiatric

• Hallucination • Toxic psychosis Monitoring Parameters

Blood/Plasma/serum concentrations are not useful for guiding therapy. Monitoring the signs and symptoms as they develop and their management is the key of the treatment.

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Was AMOUNT INGESTED greater than three times the maximal dally dose?

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VENTRICULAR TACHYCARDIA, FREQUENT, PVC'S, See management Page 22

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YES

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HYPOTENSION See management Page 19

Does patient present wkh considerable ANTICHOLINERGIC symptoms?

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PHYSOSTIGMINE {see guidlines, page 51)

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SEIZURES

NO

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I YSTONIC REACTION {Especially with Chlorpheniramine & Diphenhydramine)

--.-

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DIAZEPAM: Adult· 5-10mg IV a 10-15min to max. 30mg at Smg/min. May repeat a3-4hr prn. Child: 0.25-0.4mg/kg IV to max. 5mg {Syr)

mav repeat a

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Refer to GENERAL MANAGEMENT Algorithm page 17

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MONITOR: 1-EKG 2-VS

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DIAZEPAM: Adult 5-10mg IV p.r.n. Child: 0.1-0.3mg/kg IV

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SIG]FICANT ANTICHOLINERGIC SYMPTOMS (arrhythmias, seizures, deep coma, severe hallucination, HTN)

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PHYSOSTIGMINE (see guidelines, page 51)

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See management Page 19

•...:s Unresponsive or Severe Reaction

... PHYSOSTIGMINE (see guidlines, page 51)

Refer to GENERAL MANAClEMENT Algorithm page t7

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MONITOR: 1-EKG 2-VS

NO

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DIAZEPAM: Adult: 5-10mg IV Q 10-15m;n to max. 30mg at 5mg/min. May repeat Q3-4hr prn. Child: 0.25-0.4mg/kg IV to max. Smg (5yr) ma"y repeat 2-4hr prn

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.l l'bYSTONIC REACTION (Especially With Chlorpheniramine.& Diphenhydramine)

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DIAZEPAM: Adult: 5-10mg IV p.r.n. Ch;ld: 0 1-0.3mg/kg IV

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SIGNIFICANT ANTICHOLINERGIC SYMPTOMS (arrhythmias, seizures, deep coma, severe hallucination, HTN)

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PHYSOSTIGMINE (see guidelines, page 51)

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83 BARBITURATES Range of Toxicity

Estimated lethal dose for adult (in absence of tolerance) • Short, intermediate acting barbiturates 3-5 gms, Children 5-8 mg/Kg • Long acting barbiturates 5 gms, Children 8 mg/Kg Potentially fatal plasma levels~ (in absence of tolerance) • Short, intermediate acting barbiturates 3.5 mg/dl • Long acting barbiturates 8-12 mg/dl

* Plasma levels are not usually clinically

useful except to identify presence of barbiturate in which case urine toxicologic screens will suffice. One should treat symptoms and not levels. Addiction may result after ingestion of 300 - 700 mg/d for one to two months. List of Short/Long Acting Barbiturates Long Acting Barbiturates Barbital Mephobarbital Metharbital Hexobarbitone Phenobarbital Primidone

Short acting Barbiturate Butabarbital Cyclobatbitone Heptabarbitone Methohexital Pentobarbitone Quinalbarbi tone Secobarbital Thiamylal Tiopentone

The long acting barbiturates have elimination half lives> 48 hours. Mechanism of Toxicity

Barbiturates depress the central nervous system and they differ widely in dosage, duration of action and in margin of safety between the therapeutic dose and the toxic dose. They are metabolized by the liver and excreted partially unchanged or conjugated hydroxyl compounds.

84

Chapter III Characteristic Signs and Symptoms GENERAL Respiratory depression, profound shock; hypothermia, coma. Alcohol and antihistamines enhance the toxic effects. Cardiovascular • Hypotension

• Peripheral vascular collapse • Cardiac arrest Neurologic · • Ataxia, lethargy and coma are frequently reported following overdose.

• Depression and coma may be classified by the following system 0 - Asleep, but can be aroused and can answer questions L Comatose, does withdraw from painful stimuli; reflexes intact. 2. Comatose, does not withdraw from painful stimuli; most reflexes are intact without respiratory or circulatory depression 3. Comatose, most or all reflexes are absent but without depression of respiration or circulation 4. Comatose, reflexes absent, respiratory depression with cyanosis circulatory failure or shock. Respiratory

• Respiratory depression (more commonly with short-acting barbiturates).

-

.

Pulmonary edema (with severe toxicity)

**Neonatal withdrawal also may occur in infants born of abusing mothers. Neonatal withdrawal may be significantly delayed up to 14 days or may be observed shortly after delivery. Hyperirritability and seizures may continue for several months following neonatal withdrawal. Dermatology

• Erythematous hemorrhagic blisters on hands and buttocks and between the knees.

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Barbiturates Poisoning Patient's Disposition

All patients should have serum level drawn, and have vital signs monitored. Because of the slow and frequently delayed absorption, asymptomatic patients should be monitored for at least 6 hours. The onset of toxic effects is usually within 2 hours. Peak toxicity may not occur for 18 or more hours. Monitoring Parameters • Serum barbiturate levels/Urine toxicologic screen

• Body temperature • Vital signs • Reflexes - response to painful stimuli • Respiratory rate • Neurologic symptomatology

85

'

. TREATMENT FLOWSHEET FOR BARBITURATES POISONING

r---

Refer to GENERAL MANAGEMENT

Algorithm on page 17

Induction or emesis should be avoided in short-acting barbiturate overdoses.

l Multiple-dose activated charcoal (MDAC) may be helpful for PHENOBARBITAL and other long acting Barbiturates {also see urine alkalinization below)

I MONITOR: 1-Vital signs 2-Respiratory rate 3-Neurological status

!4-Reflexes ~5-Serum level (barb.)

I PATIENTS WITH LITTLE OR NO CLINICAL SYMPTOMATOLOGY

~

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Supportive care

,,. Observe for at least6hrs

PATIENTS WITH SEVERE CLINICAL SYMPTOMATOLOGY) (Coma Ill or IV)

)

COMA. SEVERE INTOXICATION

I

I

I

HYPOTIENSION I SHOCK See page 19

I

other treatment

I

ALKALINE DIURESIS FOR PHENOBARBITAL ONLY: -Refer to general management of poisoning section. !-Precautions: hypernatremia, fluid overload. pulmonary 'edema. -Obta.1n UOs hourly, electrolyte stab.Js, unne pH. -Assure adequate hydration and renal function prior to alkalinization. Do not give K+ to oliguric I anuric patients.

!

I :

OR CHARCOAL HEMOPERFUSION: -May be of value in patients in stage IV coma with high levels of phenobarbital in serum. -Will not correct electrolyte imbalances. -Has been associated with platelet consumption, hypothermia, hypotension, and hypocalcemia. -Generally preferred to hemodialysis for Adults -May also be helpful in severe short-acting barbiturate overdoses.

I

HEMODIALYSIS: -Consider for patients who are OR cardiovascularly 1--~ unstable or in deep coma and unresponsive to supportive care. -Effective for PHENOBARBITAl. -Less effective for SHORT-ACTING BARBITURATES than hemoperfusion.

I

87 BENZODIAZEPINES Range of Toxicity

No fatalities have been documented as being solely due tobenzodiazepines agents alone ingested orally. Ingestion of up to 1500 mg has resulted in only minor toxicity. Substances included-Synonyms • Brotizolam • Chlordiazepoxide. • Clobazam. • Clonazepam. • Clorazepate. • Diazepam • Estazolam • Flunitrazepam. • Flurazepam. • Lorazepam. • Malazepam. • Midazolam • Nitrazepam. • Oxazepam. • Prazepam. • Temazepam. • Triazolam.

Characteristic Signs & Symptoms

Ataxia, lethargy and slurred speech are common. Nystagmus has been seen following over dose of Chlordiazepoxide and ethanol. HEENT

• Dilated pupils • Nystagmus (chlodiazepoxide, ethanol). Cardiovascular

• Tachycardia. • Hypotension. Gastrointestinal

•

Absent bowel sounds.

88'

Chapter III Respiratory

• Respiratory depression (Midazolam, Nitrazepam, Triazolam) Neuralgic

• Ataxia. • Lethargy. • Sleepiness. • Slurred sp.eech. • Stage 0 to I coma. • CNS depression. • Dyskinesia. Musculoskeletal

• Dysarthria. Otber

• Hypothermia. • Bullae. • Hallucination • Confusion • Seizure Monitoring Parameters

No specific laboratory work is needed, monitor the development of symptoms. Flumazenil

Flumazenil is a benzodiazepine antagonist which antagonizes the effect of centrally active benzodiazepines and non-benzodiazepine substances that interact with benzodiazepines receptors. In patients with coma due to acute benzodiazepine intoxication, administration of Flumazenil intravenously has been observed to reverse benzodiazepine-induced central nervous system depression within 1 to 2 minutes after injection. Coma may recur in most patients within I to 4 hours. The dose of Flumazenil, should be titrated according to the amount ingested and the level of coma. The starting dose should be 0. 2 mg administered I. V. over 15 seconds. If the desired degree of consciousness is not obtained within 60 seconds a second dose (O.lmg) can be injected, this dose could be repeated every 60 seconds where necessary up to a total dose of 1 mg. The usual dose is 0.3 - 0.6 mg.

Benzodiazepines Poisoning TREATMENT FLOWSHEET FOR BENZODIAZEPINES POISONING

Refer to GENERAL MANAGEMENT

Algorithm on page 17

I MONITOR: 1-RR, BP 2-EKG 3-Menta.l status

I

I

(

HYPOTENSION See management

Page 19

I

r• COMA

Supportive Care

I )

~

.,.,l,.

~..,,of

Do" hm TCA overdose or have

known s e J disorder? I

....

NO

I

I

(RESPIRATORY) DEPRESSION

Ventilatory support and Flumazenil (see guidelines)

I

Y.S Ventilatory support with or without multipledose activated charcoal

(

DYSTONIA

)

1.01phenhydramine Adult 25-SOmg IVIIM then 25-SOmg PO TID X 2-3 days. Child:6-25mg IV/1M then 6-25mg TlD 2-3days.

I 2-Benztroplne Adult1-2mg IVIIM cont. with Diphenhydramine Child: 0.25-0.Smg IV/IM cont with Diphenhydramine.

89

90 CALC~

CHANNEL BLOCKERS

Range of Toxicity Verapamil One case resulted in fatality from ingestion of 2.5 g of a sustained rele!ise preparation. Diltiazem Survival was reported with oral ingestion of 1.5 grn·, with good supportive care. Nifedipine Overdose of 900 mg produced profound hypotension and coma. Mechanism of Poisoning Calcium antagonists selectively inhibit membrane transport of calcium during the slow inward excitation contraction coupling phase in smooth muscle leading to coronary and peripheral vasodilatation. They have negative inotropic (contractility) effect on the myocardium, this effect is not manifested with therapeutic doses because of the compensation of the sympathetic nervous system. Some of the group members (Veraparnil) depresses sinus node discharge and inhibit conduction velocity through the atrioventricular node. Nifedipine decreases afterload. In overdose it decreases the preload and increase heart rate. Meanwhile, Veraparnil inhibit Insulin response to glucose. Substances included I synonyms I. Cinnarizine. 2.

Di ltiazem He!.

3.

Flunarizine He!.

4.

Nifedipine.

5.

Nimodipine.

6.

Perhexilin.

7.

Verapamil He!.

Characteristic signs and symptoms Cardiovascular • Hypotension. • Bradycardia. • Asystole. • Arrhythmia. • AV dissociation.

Calcium Channel Blockers Poisoning · 91 • Sinus arrest • Myocardial ischemic events. • Peripheral edema. Respiratory

• Pulmonary edema. • Kussmaul breathing . . _,.

Neuralgic

• Confusion. • Drowsiness. • Mental status changes. • Nightmares. • Headache. • Flushing. • Light headedness • Seizures. Gastrointestinal

• Nausea. • Vomiting. Hepatic

• Hepatotoxicity. Dermatologic

• Skin rash. Endocrine

• Hyperglycemia • Gynecomastia. Psychiatric

• Psychosis. • Parkinsonism.

Nifedipine.

92

Chapter III Acid-Base

• Mild acidosis. Fluid-Electrolyte

• Hypo I or Hyperkalemia.

Summary Signs and Symptoms Specific agents. Virapamii/Diltiazem

Cardiac effects are frequent, usually developing 1 to 5 hrs past ingestion. May persist for as long as 7 days after sustained-release preparations. a.

Hypotension.

b.

Junctional Bradycardia.

c.

Asystole.

d.

Heart Block.

Other effects commonly include

a.

Acidosis.

b.

Seizures.

c.

Pulmonary Edema.

d.

Thrombocytopenia(Diltiazem)

Nifedipine

Cardiac effect may occur rapidly following over dose and include • Hypotension. • Reflex tachycardia. • Bradycardia (Less Common). • Heart Block. Other effects commonly include

• Hyperglycemia. • Pulmonary edema.

Calcium Channel Blockers Poisoriirig 93

Flunarizine • Aggravation of parkinsonism. • Depression. • Tremor. • Extrapyramidal reactions.

Cinnarizine • Hyperthermia. • Tremor. • Extrapyramidal reactions.

Patients disposition All patients with history of calcium antagonist ingestion should have a baselirie EKG, and should be monitored for a minimum of 8 hours. Longer monitoring period is required for patients ingested sustairied release preparation. Patients presented to the Emergency room with any of the following symptoms • Cardiovascular [hypotension, bradycardia, tachycardia, heart block, A- V dissociation .. etc.] • Gastrointestinal [ nausea and vomiting] or • Neurologic [ seizures, altered mental status] Irrespect of the irigested dose, should be admitted to iritensive care where continuous monitoring is available for at least 24 hours, for observation and treatment.

Monitoring parameters • Electrolyte (Ca,Mg,K,Na). • Glucose & calcium antagonists level. • ABG's. • EKG. • Vital .Signs.

94

Chapter III TREATMENT FLOWSHEET FOR CALCIUM CHANNEL BLOCKERS POISONING

Gastric lavage

.

1

Significant Ingestion 1

(Ipecac may produce vagal stirrulation and worsen overdose and increase risk of seizures)

~

Monitor:

1-EKG- min. 81YS. 2-Vital signs. 3-ABG.

~

Activated charcoal 'Ni1h ca1hartic (see gtidlines,111der General Management)

I

4-Bectrolyte profile (Ca. Mg. K Na)

5-Serum glucose. S-FII.id status (pulmonary edema)

~

I

Observe hypotensive and bra.dycardic patients for at least 241YS.

(

(

)

HYPOTENSION

1 IV fluids I Trenclelentu'"g position 1

•

Does patlmllu.ve hypertrophle ClVdlomyopalhy7 (IHSS, Ischemic heart dls;eue)

'f

•

Yes.

All!ha-ag~miet

15 Acidosis pre1ent?

I

No

Calcium chloride 10'&

(chest pain, SOB, decreased LOG)?

I

No

... ...

J

Serious signs {low BP. shock. pulmonary congestion, CHF, acute MJ) or symptoms

urvesponslve

heart disease)

BRADYCARDIA

-Metaraminol

I

-Me1hoxamine

v..

...

-Phen~eptvine

~0

Calcium gluconata 101/,

AduH: 10-20mllV,

0.2-D.5rnlll::~~~f~-

..., g;j Refer to GENERAL MANAGEMENT Algorithm on page 17

_

.

r

~

Refer to NSAIO MANAGEMENT Algorithm on page 108

~

I (

~

I

Was AMOUNT Ingested: )

(

'o:l

6

Was SERUM LEVEL at one hr (see nomogram)

I 1

< 100mglkg

I May manage at home.

1, oo-2oomg/kg 1

I

J

I

Administer IPECAC See guidelines,

• • page

May dilute with milk or H20 to decrease Gl upset.

1 2oo-•oomg/kg

3

Observe for 4 hrs

Administer IPECAC or GASTRIC LAVAGE (if obtunded)

Il

1 , •oomg/kg

l

l

1 200mcg/ml 1

•

72% incidence of toxicity; 28% chance of severe toxic it'(.

'

;..., 00

'o:l

0

1:1:1

;

~

l

Refer to NSAID MANAGEMENT Algorithm on page 108

l

~

. ~

0

'o:l

..,~0

.... 00

~

z

U2

;J> ;J> ~

'"0

9.

"'0 ::s

s·

OCl

-

0

\0

··.

11 0

Chapter III ffiUPROFEN NOMOGRAM

1 All units converted to mcg/mL

p

a B

m

Probable Toxicity

a L

Not Valid

v

After 12

e

Hours

150 m

c Toxicity Unlikely

9

I m10 L

5L--+--~--~--4---+---+---~~---4---+--~--~ 10 11 12 9 B 2 J ~ 5 6 7

Hours

(C)Ann Emerg Ned 1986 15:1308-1313.

Used with permission.

·1.:

:

~~:--_·_

111 NON TOXIC INGESTION Definition Materials that have been ingested and generaily have not produced significant acute toxicity except in very large doses. Range of Toxicity

Most of these agents are considered not to be a toxic hazard in the quantities available through normal exposure or package size. Available forms/ sources Abrasives Antacids Antibiotics Baby products cosmetics Ballpoint pen inks Bathtub floating toys Body conditioners Calamine lotion Candles (bees wax or paraffm) Corticosteroids Cosmetics Crayons (marked A.P.,C.P.) Carboxymethyl cellulose Chalk (calcium carbonate) Clay (modeling) Dehumidifying Packets( silica or charcoal) Deodorants Deodorizers (spray and refrigerator) Elmer's glue Etch-A-Sketch Eye Makeup Fish bowl additives Glues and pastes (water soluble) Glycerol Golf ball (core may cause mechanical injury) Greases Gums Hair products (dyes, sprays, tonics) Hand lotions and Creams

112

Chapter III Indelible markers Ink (black, blue) Kaolin Lanolin Linoleic Acid Linseed Oil Lipstick Lubricant Lubricating oil Magic Markers Magnesium Silicate Makeup (eye, liquid facial) Motor oil Newspaper Paint- Indoor or latex Paraffin Pencil (lead-graphite, coloring) Petroleum jelly (vaseline) Play-Doh Polaroid picture coating fluid Porous-tip ink-marking pens Prussian Blue (ferricy anide) Putty (less than 2 oz) Rouge Sachets (essential oils, powder) Sesame oil Shoe polish (most do not contain aniline dyes) Silica Silly putty (99% silicones) Spackles Suntan preparations Sweetening agents (saccharin, cyclamate) Teething rings (water-sterility ?) Thermometers (mercury) Titanium Oxide Tooth paste (without fluoride) Vaseline Water colors Zinc Oxide Zirconium Oxide

,,~

,_ '.•••.._ ·;:

,.

c Non Toxic Ingestion CLINICAL EFFECTS

Non toxic ingestions occur when the victim conswnes a non-edible product which almost never produces symptoms. ¥aterials referenced to this management have been considered very unlikely to produce any toxicity except in very large doses.

TREATMENT

Dilution with small ,amount of water, followed by vomiting, may be performed if there is a question of simultaneous ingestion with a product which may be more dangerous. In such cases, the management on the more toxic agent should be continued. In such ingestions patients should be a symptomatic. For symptomatic patients, history should be evaluated to completeness and thoroughness. For product to be listed as a " Non toxic ingestion", it must have the following requirements. I.

Absolute identification of the product, its ingredients, and its concentration.

2. 3.

Absolute assurance that this was the only product ingested. No signal words on the container which would indicate a more potentially toxic agent.

4. 5.

A good approximation of the amount involved. A victim which is free of symptoms.

6.

The ability to follow-up the case.

Monitoring Parameters In most cases it is not necessary to perform laboratory tests. However, one must remember to treat the patient and not the poison.

113

114

OPIATES AND RELATED COMPOUNDS Range of Toxicity •

Ingestion of 7 - 14 mglkg codeine estimated lethal dose in ADULT (oral)

• •

5 mglkg codeine has caused respiratory arrest in CHILDREN I mglkg codeine mild to moderate symptoms in 51% of CHILDREN within 30- 60 minutes

•

I 0 mg of Methadone lethal dose in children

•

2.5mg ofHydrocodone lethal dose in infants

List of Opiates and Opiate Antagonists with Equivalent Dosages IMoriV (mg) PO (mg) No Data· Alfentanil No Data Alphaprodine 40-60 No Data 0.40 0.4-0.8 Buprenorphine Butorphanol 2.00 8.00 Codeine 200.00 120.00 Dihydrocodeine 60.00 300.00 Ethoheptazine No Data 1000.00 Fentanyl 0.1-0.2 No Data Hydromorphone 1.50 7.50 3-5 60.00 Heroin Levorphanol 2.00 4.00 Meperidine 75-100 300.00 Methadone 8-10 20.00 Morphine 10.00 60.00 Nalbuphine 10.00 50-60 Oxycodone 20-30 15.00 Oxymorphone 1.50 6.00 Pentazocine 30-60 180-250 Pethidine 75.00 300.00 Propoxyphene 130.00 No Data Sufentanil 0.01-0.02 No Data Example 200 mg PO codeine= 15 mg PO methadone= 10 mg 1M methadone= 130 mg 1M codeine Dru~s

!If• ~-:-:

1:1 _·,·:t

~:

·,\

~,:~

··;' \''

Opiates Poisoning Mechanism of Toxicity

Opiates and its derivatives depress the central nervous system, thereby producing coma and cessation of respiration. All these agents are highly addictive and withdrawal symptoms can result following their termination. Characteristic signs and symptoms GENERAL

Hypotension, coma, respiratory depression, hyperpyrexia. Skeletal muscle flaccidity, cold clammy skin, apnea. Cardiovascular

• Hypotension • Bradycardia • Pulmonary hypertension Gastrointestinal

• Delay of gastric emptying • Constipation Genitourinary

• Urinary retention • Acute tubular necrosis • Glomerulonephritis Metabolism

• Hyperamylasemia • Metabolic acidosis Temperature

• Hyperthermia Musculoskeletal

• Rhabdomyolysis Neurologic

• Hyperpyrexia • Muscle spasm • Cyclical coma

'

115

116 · Chapter III • Opiates delay gastric emptying so that revival of the patient may result in re institution of peristalsis and further absorption of drug which results in cyclical coma. • Seizure • Parkinson's like syndrome Ophthalmic

• Pinpoint pupils (common) • Pupils may be dilated in • Severe Acidemia, • Hypoxia, • Hypotension, • Bradycardia, • Respiratory Depression With Meperidine. Respiratory *

• Hypoxia • Respiratory depression • Respiratory arrest • Pulmonary edema • Pneumonitis

*In METHADONE OVERDOSE, prolonged toxicity including respiratory depression of24- 48 hours duration may occur. Patient' disposition

Any patient with significant opioid overdose merits close observation and supportive care for 24 to 48 hours. Monitoring Parameters

• Vital signs • Plasma opiate levels are not clinically useful • Respiratory rate • Temperature • Pupil size • Bowel sounds • Neurologic symptomatology • Urine output

/:

11:-~:: -~--

1§;:_... :.

Opiates Poisoning TREATMENT FLOWSHEET FOR OPIATES POISONING

Refer to GENERAL MANAGEMENT Algorithm on page 17

Emesis indicated n severe, substantial overdcr. es: avoid in PROPOXYPHENE overdoses

~---

I

I

For significant overdoses, observe patient closely for 24-48 hours

I Monitor: 1. Vital signs 2.Respiratory rate 3.Pupil size 4.Bowel sounds S.Neurological status 6. Urine output

r

I

I

I

SEIZURES

Patients Manifesting ModerateSevere symptomatology

)

See l'lUnagemenl

Page 20

-Coma -Respiratory depression -Hypotension

I If overdose caused by

If overdose caused by

LONG-ACTING OPIATE (Propoxyphene, methadone).

SHORT ACTING OPIATE

I I

consider:

.

NALOXONE I CONTINUOUS INFUSION METHOD: 1.Give initial dose of naloxone to achieve reversal of narcotic effects and then start on continuous infusion. 2.0ose: Use 213 of the initial bolus on an hourly basis. Add 10 times this dose to each liter and infuse at 100ml/hour. Readminister 1/2 the initial bolus dose over 15min. after the start of the infusion to prevent a drop in naloxone levels. Use mixture up within 24hrs. 3.Administratlon: Increase rate as needed to ensure adequate ventilation. Adjust both rate and concentration to achieve desired effect without fluid overload.

.

NALOXONE Adutt 0 4 to 2mg IV, IM, SC, or lntralingually; may repeat as needed to achieve clinical effect. If no response after 1Omg, question diagnosis of opioid overdose. Neonate-Child < S~r. or < 20kg: 0.1 mg/kg IV or IT, may repeat to a total of 10mg.

'

... ~

''

Monitor: 1. Vital signs I 2. Dosage requirements ' 3. Fluid status

I

...

Admit to ICU and monitor for at least 24hrs. Prominent signs of naloxone efficacy include: 1.Dtration of pupils 2.1ncrease in depth and rate of respirations . 3.Reversal of hypotension 4.Reversal of coma

117

hli:nterm · .· ·

TREATMENT FLOWSHEET OPIATES POISONING (Cont.)

H'I'POTENSION See management Page 19 External cooling with cool (not cold) water.

Maintain adequate

\entilation & OX)Yenation with 02 mask or mechanical \€ntilation.

Consider PEEP in (intubated patient) or CPJIP (non-intubated patient)

ifP02 cannot be maintained at 50mmHg with inspiration of60% 02 by face mask or mechanical \€ntilation.

If BP, HR, and heart rhythm are normal, PEEP is the treatment of choice. For patients who are hypotensi~.e, see ne>d: column.

'"'

,, I

·"·I ~Y·: r~

;_,.,;-:

. !.

,~Jr

119

::~-

~:-

:"~

ORAL CONTRACEPfiVES Range of Toxicity Acute toxicity is unlikely following overdose unless the oral contraceptives contains Iron (see management oflron) Characteristics signs and symptoms Gastrointestinal . • Nausea • Vomiting • Fluid retention Endocrine • Withdrawal bleeding may occur in young girls. Neurologic • Headache Liver • Jaundice Monitoring Parameters • Oral contraceptive levels are not clinically useful.

'·,

'12() . PARACETAMOL (ACETAMINOPHEN) Range of Toxicity _ ·Ingestion of 140 mg/kg or 7.5 grn associated with liver injury Four Hour post-ingestion levels of >150 mcg/ml (15 mg/dl) or (992.4 mmol/L) associated with liver IlljUry

Paracetanwl Pkzsma Levels Should Be Determined Four Hours Post Ingestion, As levels obtained prior may not represent peak pkzsma levels.

Levels obtained four hours post ingestion should be assessed using Rumack-Matthew nomogram, to check for the possibility of liver toxicity. Mechanism Of Toxicity Acetaminophen is metabolized in the liver by cytochrome P-450 mixed oxidase system , one of its metabolites is hepatotoxic. Normally, this reactive metabolite is rapidly detoxified by glutathione in the liver; however, in overdose, production of the toxic metabolite exceeds glutathione capacity, and the metabolite reacts directly with hepatic macromolecules, causing liver injury. Renal damage may occur by the same mechanism owing to renal metabolism. Characteristics Signs and Symptoms Gastrointestinal

(6-14 hours after ingestion)

• Nausea • Vomiting • Anorexia • Pancreatitis Hepatic (1-4 days after ·ingestion) • Liver necrosis • Right-sided abdominal pain and tenderness • Hypoglycemia • Increased SQOT, SGPT and serum bilirubin • Abnormal prothrombin levels

Paracetamol Poisoning Renal (rare)

• Antidiuretic hoiTilone effect • Acute tubular necrosis Other

• Hypophosphatemia • HypotheiTilia • Hyperglycemia • Metabolic acidosis • Myocardial damage • Thrombocytopenia Monitoring Parameters

The following laboratory analysis should be performed upon admission for baseline, and daily for 7 days and on day 14 • Liver function tests • Serum electrolytes • BUN and Serum Creatinine • Serum glucose

.

• Complete Blood Count • Prothrombin time • WBC and differential Indications of N-acetylcystine

I.

Plasma level is in toxic range

2.

Ingestion of> 7. 5 mg/d

3.

Delay to treatment > 8 hours

4.

Best treatment between 8-16 hours.

121

4

8

12

16

20

24

Hours after ingestion Semilogarithmic plot of plasma acetaminophen levels vs. time RumackMatthew Nomogram for acetaminophen poisoning Cautions For Use Of This Chart 1.

The time coordinates refer to time of ingestion.

2.

Serum levels drawn before 4 hours may not represent peak levels.

3.

The graph should be used only in relation to single acute ingestion.

4.

A half-life of greater than 4 hours indicates a high likelihood of significant hepatic injury.

·Paracetamol Poisoning TREATMENT FLOWSHEET FOR PARACETAMOL POISONING

Estimated TIME since ingestion and AMOUNT Ingested

I I < 4 HOURS and I or > 7.5 Gm or> 150 mglkg ingested

•

)

Refer to GENERAL MANAGEMENT Algorithm on page 17

> 4 HOURS and ) > 7.5 Gm or> HiO mglkg

> 24HOURS WITH

. .

DETECTABLE LEVELS OR SIGNS OF LIVER DAMAGE

ingested

•

If serum levels not readily available, start N-acetylcysteine therapy (NAG) and draw level.

Consider therapy with NAC

Obtain 4 hours post-ingestion plasma level and plot it on nomogram to determine need for ... RUMACK-MATIHEW NAG treatment. (levels should be draw AFTER 4 hours

and BEFORE 24hours

'

i y

I

I Level treatment well BELOW lower I line

...

r

.

LIVER DAMAGE UNLIKELY

.

I

l

[

Level ABOVE lower treabnent line

•

LIVER DAMAGE LIKELY

•

I

I No treatment needed I r

NACTherapy (see guidelines)

•

I

Monitoring Parameters: Monitor LFTs and PT daily X 3 days OR until lab values begin to return to normal. The following parameters may also be followed as cJinically indicated: Cr, BUN,• UJA, electrolytes, glucose, CBC, amYlase, EKG.

'

',

'

I

123

124

PROPOXYPHENE (Dextropropoxyphene) Range of toxicity

• •

As little as l 0 mglkg can cause toxic symptoms in children.

•

Death has been associated with acute ingestion of 900-1300 mg

•

Co-ingestion of alcohol or other sedative hypnotics will potentiate toxic effects

35 mg/kg may result in cardiac and respiratory arrest

Available forms Propoxyphene

Propoxyphene+ Acetaminophen

Darvon DolcncPronacet LarcetWv11:esic

Darvocet Darvon Compound Distalgcsic

Propoxyphene+ Salicylates DarvonN

-

Mechanism of toxicity Propoxyphene has weak opioid agonist activity, which is responsible for the sedation and respiratory depression. Meanwhile, Propoxyphene has membrane stabilizing activity (MSA) which is more than other opioid. The MSA in overdosage is responsible for the acute cardiac failure which did not respond to naloxone. The attribution of cardiac conduction defects and central nervous symptoms to its MSA leads us to suggest that MSA is the major factor responsible for the severe cardiac depressant effect of Dextropropoxyphene. Characteristic signs and symptoms Cardiovascular • Cardiac arrhythmia • Pulmonary edema • Right bundle branch block • Nonspecific.ST and T wave changes • Prolonged QRS complex • Heart block • Ventricular fibrillation

Propoxyphene Poisoning

125

Gastrointestinal • Nausea

• Vomiting • Constipation and abdominal pain HEENT • Miotic pupils • Blurred vision Metabolic

• Hypoglycemia of a recurrent nature in nephrogenic diabetes insipidus occur infrequently Neurologic

• Drowsiness • Dizziness • Headache • Euphoria • Minor visual disturbances • Seizures • Stupor and Coma Respiratory

• Respiratory arrest can occur within 30 minutes to one hour after ingestion • Respiratory Depression occur within 1-2 hours Other

• Rhabdomyolysis • Hypoglycemia Monitoring Parameters

• Cardiac and respiratory function • Neurological assessment • Blood sugar

ti6

Qhapter III

TREATMENT FLOWSHEET FOR PROPOXYPHENE POISONING

I

Refer to GENERAL MANAGEMENT Algorithm on page 17

Monitor:

I

•

-cardiac and respiratory function.

I I

I

SEIZURES)

I

•

NALOXONE IV: -As a trial -See dosage guidelines in next column

! !

~

ESPIRATORY DEPRESSION' COMA? MIOTIC PUPILS?

•

IV NALOXONE: Adult Initial dose of 0.4-2.0mg IV. May repeat every 2-3minutes to a maximum of 1Om g. Child: Initial dose of0.1mg/kg IV. may repeat, to a total of 1Omg continuous IV infusion : May be beneficial. Add 4-8mg in 1L DSW;

I I i

Refractory?

Infusion at 1 OOmUhr to deliver

IV DIAZEPAM: Adult IV slow push (Smg/min.) 5-10mg initially. May repeat, if necessary, at 5 minute intrervals to a total of 30mg Child: 0.1-0.3mg/kg IV slow push, may repeat at 5 min. interval to a total dose of 10 mg.

. ~

0.4-0.Smgfhr. Titrate to assure adequate ventilation. Use within 24hours. Avoid FLUID OVERLOAD

Admit to ICU and monitor for 24hours . Prominent signs of naloxone efficacy include: 1. Dilation of pupils 2. Increase in depth and rate of respirations 3. Reversal of hypotension 4. Reversal of comatose state

..... ~

'

I'

.. ,~­ .. i

~f'" :~':.'-

127

SALICYLATES Range of Toxicity

I Acute Ingestion Ingestion of !50 mglkg to 300 mg/kg may produce mild to moderate poisoning. Ingestion of greater than 300 mglkg may produce severe poisoning. 2.Chronic Ingestion Chronic ingestion of greater than I 00 mg/kg/24 hours over two or more days may produce toxicity. Severe symptomatology may be associated with salicylate levels as low as 15 mg/dl. Clinical findings, not salicylate blood levels, are more useful as an indicator of the severity of the poisoning. J.Salicylate Serum Levels DONE NOMOGRAM This nomogram attempts to elucidate the relationship between the serum salicylate levels, time since acute SINGLE ingestion and expected clinical severity of poisoning. Salicylate levels should be drawn at least 6 hours post ingestion. Two or more levels should be obtained to assure all data is in the postabsorptive phase. The utility of the Done nomogram is questionable in cases of acute ingestion or sustained release preparations.

Severity ofpoisoning could he assessed according to the following table Symptomatology Severity Salicylates Serum level 110 >160

Not intoxicated Occasional subjective, but no objective manifestations Mild Mild to moderate hyperpnea, sometimes with lethargy Moderate Severe hypetpnea, prominent neurological disturbances (marked lethargy or excitability) Severe Same as moderate but no convulsions or coma Usually lethal Severe hyperpnea, coma or semi coma, sometimes with convulsions

The peak serum salicylate level can be determined from a nomogram developed by Done.

'

128 · Chapter III Mechanism of Toxicity

Salicylates have a variety of toxic effects a. · Central stimulation of the respiratory center results in hyperventilation, leading to respiratory alkalosis and compensatory metabolic acidosis and contributing to dehydration. b.

Intracellular effects include uncoupling of oxidative_phosphorylation and interruption of glucose and fatty acid metabolism.

c.

The mechanism by which cerebral and pulmonary edema occur is not known but may be related to alteration in capillary integrity.

d.

Salicylates alter platelet function and bleeding time and may also prolong the prothrombin time.

Characteristic Signs & Symptoms Gastrointestinal

• Nausea and vomiting may develop in 3 - 8 hours • Hepatitis HEENT

• Tinnitus • Mucosal bum Hematologic

• Hemorrhagic disorders (rare) • Increased bleeding time Metabolic

• Acute ingestion, hyperthermia, acid-base imbalance, dehydration, electrolyte disturbances • Severe anion gap metabolic acidosis, respiratory alkalosis (adults-common), metabolic acidosis (children-common), hyperglycemia (adult), hypoglycemia (children) (May develop in 12-24 hours.) • Chronic ingestion -metabolic acidosis (adults and children) Neurologic

• Confusion • Coma

Salicy lates Poisoning

129

• Seizures • Cerebral edema • Disorientation • Lethargy Respiratory • Hyperpnea • Hyperventilation • Non-cardiogenic pulmonary edema Patient's Disposition Patients with major symptoms (i.e. tachypnea secondary to acidosis, dehydration, mental status changes, seizures) should be admitted to the intensive care unit regardless of serum salicylate level. Patients with minor symptoms only (i.e. nausea, Tinnitus) following acute overdose may be managed in the emergency department with alkaline diuresis if the salicylate level is less that 65 milligrams/ deciliter six hours after acute overdose and is shown to declining. Admission should be considered regardless of the salicylate level in the very young and very old in chronic overdose and when the ingested tablets are enteric coated. Monitoring Parameters • Serum Salicylate level (6 hours post ingestion) • Temperature • Arterial blood gases • Electrolytes • Renal Function • Blood sugar • Respiratory rate • Complete blood count • Prothrombin time

130

Chapterm

SERUM SALICYLATE LEVEL AND SEVERITY OF INTOXICATION SINGLE DOSE ACUTE INGESTION NOMOGRAM

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180 160 140 120 100

L

Probably Lethal

80 60

m

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20

1 0 '--0

12

24

36

48

60

Hours since ingestion

Nomogram relating serum salicylate concentration and expecxted severity of intoxication at varying intervals following the ingestion of a single dose of salicylate. From Done AK, "Aspirin. Overdosage: Incidence, Diagnosis, and manage ment" Pediatrics, 1978, 62:890-7

'

Ipecac and/or Activated charcoal; 24hrs, follow-up

/

I

II

.

>3hrs ago

I

I

Activated charcoal & cathartic; clinical evaluation

= 150-300mg/kg (MODERATE)

I

I

(

Gastric lavage followed by Activated charcoal (MDAC Q 2-6hr may be helpful)

I

> 300mg/kg (SEVERE)

Determine AMOUNT ingested. ) (one time dose)

~

General home managernf:lnt; fluids and phone follow-up

< 150mg/kg (MILD)

r--.

>= 80mg% -100mg%

----. .I>= 130mg%

)

Patients in shock may require faster infusion rates. ACIDOSIS will require NaHC03 administration.

Fluid replacement at a rate of at least 10-15 ml/kglhr over 1-2hrs until good urine flow is established

~ 1-Vital signs 2-IlO's (fluid status)

DEHYDRATION

.

r-

< 80mg % ~

-----.1

Consider HEMODIALYSIS or PERITONEAL DIALYSIS

Supportive measure; consider urine alkalinization (see acidosis below)

Supportive measures

Consider: 1- Isotonic NaHC031avage with E.G. tablets 2-Surgical removal obtain surgical consult

+

Contrast media followed by abdominal X-ray and serial Salicylate levels.

(_ CONCRETIONS )

MONITOR: 1-Piasma salicylate levels 2-Serum elctrolytes 3-ABGs 4-Biood glucose 5-CBC 6-PT, PTT 7 -RR 8-Temperature

Refer to GENERAL MANAGEMENT Algorithm on page 17

SERUM SALICYLATE LEVEL AT 6 HOURS POST INGESTION. Refer to Done nomogram to assess severity of toxicity. Check serum levels every 2 to 4hrs until level within normal limits. (Note: for SR or EC tabs, a 6 hr postingestion level may not reflect peak serum concentration).

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133 SYMPA1HOMIMETICS Range of toxicity

Phenylpropanolamine 8-10 mg/Kg has been reported as minimal toxic dose in children; 17.5 mg/Kg generally result in symptoms. Pseudoephedrine 4-5 times the single therapeutic dose can cause hypertension. Isometheptene mucate, the maximum recommended adult dose is 325 mg in 12 hours. Mechanism of Toxicity

Sympathomimetics stimulate both alpha and beta adrenergic receptor, and in large doses can elevate both blood pressure and heart rate. Phenylpropanol amine acts primarily on the peripheral alpha adrenergic receptors. The most common toxicity is hypertension due to vasoconstriction of peripheral vasculature. Reflex bradycardia may be seen. Characteristic signs and symptoms

Most patients overdoses require only observation for a period of 4-8 hours. Pharmacologic intervention is required only in severely symptomatic patients. HEENT Eyes

• Mydriasis was reported with Salbutamol overdose but not with Terbutaline overdoses. Cardiovascular • Tachycardia! Bradycardia {Phenylpropanolamine has been reported to cause bradycardia with atrioventricular block.} • Cardiac arrhythmias • Pericardia! pain • Hypertension • Myocardial ischemia Neurologic

• Tremors • Anxiety, nervo\lsness • Insomnia • Muscle tremors • Convulsions • Change in mental status

134

Chapter III • Intracranial I Subarachnoid hemorrhage • Cerebral infarction

Gastrointestinal • Vomiting • Anorexia Genitourinary • Interstitial nephritis • Acute tubular necrosis • Renal failure Acid Base

• Metabolic acidosis Hematologic • Leukocytosis Musculoskeletal • Rhabdomyolysis Endocrine • Hyperglycemia Psychiatric • Paranoid psychosis • Psychotic episodes • Acute mania • Hallucination • Psychosis (reported with Ephedrine overdose) Monitoring parameters • Urea and Electnilytes • Vital Signs • EKG

• Complete Blood Count

.

'

Refer to GENERAL MANAGEMENT Algorithm on page 17

MONITOR: 1-VS 2-EKG HYPERTENSION

AGITATION, DISORIENTATION, HALLUCINATIONS

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j

Observe at least 4-8hrs and longer for sustained· release products

supportive care

)-

See management Page 22

VENTRICULAR TACHYCARDIA FREQUENT PVCs

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See management Page 18

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See management Page 20

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ANm;~N 1

Trivalent (A. 8, E) 6ml vial contains: A- 7,5001U B-5,5001U E-8,5001U Antitoxin binds circulating

toxin and prevents progression of neurologic symptoms. It does not inhibit or decrease paralysis once toxin is inside neiVe terminal. .Q.Q§g;. One vial is given IV and one vial IM; dose is repeated in 2-4 hrs if symptoms persist Before administering. Skin test for sensitivity to horse serum.

Mechanical ventilation

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165

ARSENIC POISONING Range of Toxicity Trivalent Arsenic is more toxic than pentavalent Arsenic. The oral lethal dose of arsenic compounds is variable acute ingestion of 200 mg is likely fatal in an adult Mechanism of Poisoning Arsenic inactivates sulfhydryl-containing enzymes such as lactic dehydrogenase in heart muscle, thereby producing toxicity. Similar effects occur in the gastrointestinal tract and in neurologic tissues leading to the observed clinical toxicity. The severe gastroenteritis may not be due to a direct corrosive effect but secondary to the effects of absorbed arsenic on the vascular beds. Comptjtition for sulfhydryl binding by 2,3 dimercaprol (BAL) or D-penicillamine has resulted in successful reversal of arsenic poisoning. Characteristic Signs and Symptoms Onset: Acute ingestion generally produce symptoms within 30 to 60 minutes, but may be delayed for several hours if ingested with food. General Metallic taste, vomiting, abdominal pain, Dysphagia, and profuse water (Rice like) and sometimes bloody diarrhea and garlic odor of breath and feces are noted. Dehydration, intense thirst and fluid -electrolyte disturbances are common. Hypovolemia from capillary leaking (i.e. third spacing) is a common early sign. HEENT

Eye. • Copper like pigmentation of the eyes • Conjectivitis • Photophobia • Dimness of vision • Diplopia • Lacrimation

Nose. • Sensation of burning dryness and constriction of the oral and nasal cavities.

Throat. • Garlic like odor in breath.

166

Chapter VI

Cardiovascular • Ventricular fibrillation I VTachycardia • Increase QT interval • Heightened T-Wave ·

Neurologic • Numbness and tingling of the extremities • Intense thirst • Muscle cramps • Marked peripheral neuropathy • Delirium • Encephalopathy • Vertigo and coma • Seizures • Delayed peripheral neuropathy • Altered mental status

Gastrointestinal · • Nausea • Vomiting • Watery or bloody diarrhea • Abdominal pain

Genitourinary • Hematuria • Acute tubular necrosis

Hepatic • Jaundice may occur within 24 hrs.

Hematologic • Acute hemolysis • Decreased hematocrit • Decreased hemoglobin

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Arsenic Poisoning

·':·

Dermatology

• Flushing of the skin • Mees Lines (with transverse bands across the finger and toenails may occur within 4-6 weeks after exposure) Chronic Poisoning

Several months to years may take to produce symptoms. Malaise and fatigue are common. Malaise and fatigue are common. Most symptoms are of CNS and peripheral nervous system toxicity. Peripheral neuropathy, gait difficulty and myelopathy was reported .. Laboratory

Quantitative 24 hrs urine collections are the only way reliable laboratory measure arsenic poisoning. Others

Arsenic has been demonstrated in hair and nails within 30 minutes after exposure.

Monitoring parameters

• Serum I Blood arsenic level • Serum level are not considered useful in either diagnosis or therapy. • Urine arsenic level. It is used as a monitoring for end of the therapy. Level should fall below 5 meg per 24 hrs urine collection. • Complete Blood Count • Urea and Electrolytes. • Liver function test • Renal function

16T

168

Chapter VI TREATMENT FLOWSHEET FOR ARSENIC POISONING

Monitor. - Serum/ blood arsenic level - urine arsenic level -CBC - LFT -Renal function

Refer to GENERAL MANAGEMENT Algorithm on page 17

I (

HYPOTENSION See management )

(

ARRHYTHMIA) (

I

Page 19

I

f

TACHYCARDIA

II

. •

SEIZURES See management

Page 20.

•

VENTRICULAR ARRHYTHMIA

Prepare for Immediate

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cardloverslon

Lidocaine

1-1.5mg/kg IV push

Lidocaine

I

I

J

•

Dimercaprol:

3-Smgfkg IM every 4-12hr until symptoms resolve

•

0-Penlclllamlne 25mg/kg/dose 4 times daily up to 1gm /d

I

Procainamlde !20-30mg/min., max. total17mg/kg

(

FLUID& ELECTROLITE IMBALANCE

..

Monftor: 1-V~I signs 2-IlO's (fluid status)

Fluid replacement at a rate of at least 10-15mllkgfhr over 1-2hrs until good urine flow is established

•

0.5-0. 75mg/kg IV push max. total 3mg/kg

,

I

I CAHELATION THERAPY if urine arsenic level 200mcg/l

l

Patients in shock may require faster infusion rates. ACIDOSIS will require NaHC03 administration.

I

'

. .' .

t;c.

i(?/-'-

169 LEAD POISONING Range of Toxicity Fatal ingestion (adult) SOO mg of absorbed lead or as little as 10 g of a lead salt. Provisional tolerable weekly intake (adult) 3 mg or SO meg/kg Blood levels 40 mcg/dl (1.9 mcmol/L) considered normal, no symptomatology SO- 79 mcg/dl (2.4- 3.8 memo IlL) slight to moderate symptomatology (impaired hemesynthesis) 80- lOOmcg/dl (3.9- 4.8 mcmol/L) serious intoxication >I 00 mcg!dl (4.8 mcmol/L) encephalopathy

Sources of lead High content lead sources • Lead pigment paint

• Retention of metallic lead objects (shot, curtain weight, etc.) • Contaminated acidic foods and beverages by improper storage in lead-glazed ceramic ware folk medicines • Inhalation of fumes of leaded gasoline Luw content lead sources

• Lead contaminated dust and soil Characteristic Signs and Symptoms GENERAL Chronic low-level intoxication Adult Develops over several weeks. Personality changes, headache, metallic taste, anorexia, abdominal discomfort, vomiting, constipation. Encephalopathy rare in adults.

Child Onset of symptomatology usually abrupt (1-S days). Persistent vomiting, ataxia, seizures, alterations in state of consciousness, coma. Manifestations of acute encephalopathy may be preceded by several weeks of irritability and decreased play activity. Bone Lead lines (densities)in the radius, tibia and femur with chronic poisoning

I 70

Chapter VI

Gastrointestinal

• Anorexia • Nausea • Constipation Hematologic • Hypochromic, microcytic anemia

• Basophilic stippling on peripheral smear Neurologic

• Ataxia • Irritability • Lethargy • Stupor • Coma • Clumsiness • Behavioral Disturbances • Convulsions • Encephalopathy Secondary To Cerebral Edema (More frequent in Children than Adults) RENAL (rare) • Glucosuria • Aminoaciduria Monitoring Parameters

• Blood lead level (PbB) • . 24 hour total lead output in urine with chelation therapy (Diagnosis is confirmed if ratio of meg of lead excreted/mg CaEDTA is greater than!) • X-rays- abdomen, wrists, knees for lead lines • Complete blood count with peripheral smear • Urinary coproporphyrin (UCP) • Urinary aminolevulinic acid (ALA) • Neurologic exam (lumbar puncture contraindicated unless absolutely necessary for differential diagnosis) *Blood and urine samples must be collected witb lead free equipment.

-1.· 1~ y;-. .

·~·

'

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Lead Poisoning Guidelines for use of chelating agents A-simultaneous BAL And CaEDTA Administration 1- High-dose therapy Indications • Encephalopathy • PbB > 70mcg/dL (with or without symptoms) Dosage • BAL 4mg/kg or 75- 83mg/m 2 IM Q 4HR X 5 days. • CaEDTA 250mg/m2 IM Q 4hr X 5 days. Administration For the first dose inject BAL by deep IM injection only; then4 hrs later (but not until adequate urine flow is established) and Q 4 hrs, thereafter, for 5 days, inject BAL and CaEDTA simultaneously at separate injection sites. Rotate injection sites. If PbB rebounds to 45mcg/dL or higher within 5 to 7 days after the initial course, a second course, using CaEDTA Alone, may be required. 2- Moderate - dose therapy

Indications • Symptomatic lead poisoning (without encephalopathy) • Asymptomatic children with PbB > 70mcg/dL Dosage BAL 50mg/m2 IM Q 4hr X 5 daysCaEDTA !Gm /m2 /day (by continuous infusion in a single dose or in divided doses OR IM in divided doses Q 4 hrs.) X 5 days. Administration As above . If PbB decreases to less than 50mcg/dL after the first 3 days, BAL (but not CaEDTA) may discontinued. NOTE Children may requir~ more than 2 courses of therapy. However, it is generally inadvisable to administer more than 2 course to adults. At least two to four days, preferably 2 to 3 weeks should elapse between of treatment

171

172

Chapter VI B- CaEDTA Administration Alone Indications

• Mild symptomatology • Asymptomatic children with PbB of 45 to 69mcg/dL. • Positive CaEDTA provocation test. Dosage

CaEDTA lg/m2/day by continuous or divided- intermittent IV infusion X 3-5 days. Administration

A second course of CaEDTA may be required if PbB rebounds to 45mcgldL within 7 to 14 days after the initial course. C- CaEDTA Provocation (Mobilization) test. Indications

• Suspected lead poisoning when uncertainty exists whether to give chelation therapy or not. • PbB of 25 to 44mcg/dL Dosage 1. 24 hrs mobilization test

Adult 500mg/m 2 (maximum dose of !g) by IV infusion over a period of I hour or by 1M injection. Collect urine in a special lead-free collection apparatus for 24 hours beginning with administration of the drug and analyze for lead content Collection periods of 3-4 days may be required in individuals with renal dysfunction. Child 500mglm2 (maximum dose of lgm) by IV infusion over I hr. OR IM as a single injection, or two 1M doses of 500mg/m2 each at 12 hrs intervals. 2. 8 hrs. Mobilization test Adult/Child SOmg/kg as a single 1M dose. Collect urine in a special lead-free collection apparatus for 6-8hrs beginning with administration of the drug and analyze for lead content.

Interpretation of Test Results 1.

24br mobilization test

If the ratio of meg of lead excreted in urine to mg of CaEDTA administered is greater than I, the test positive.

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Lead Poisoning 2.

8 hrs. Mobilization test

If the ratio of meg of lead excreted in urine to mg of CaEDTA administered is greater than 0.5 ORurine lead concentration is greater than lmg/L, the test is positive. D.SUCCIMER Indications

• Children with PbB > 45mcg/dL • Alternative to parenteral therapy in patients with PbB > 45mcg/dL AND < 70 mcg/dl. Dosage • Child !Omglkg or 350mg/m2 Q8hr X 5 days. After the initialS days of therapy, reduce dosage to !Omglkg or 350mg/m 2 Ql2 hrs. for an additional2 weeks of therapy. Administration • Contents of capsules may be sprinkled on soft food just prior to administration or they may be placed on a spoon for administration and taken with fruit juice. • Intervals of not less than 2 weeks are recommended between courses of succimer therapy unless clinical conditions require more prompt therapy. • Patients who have received CaEDTA, with or without B AL, receive succimer after an interval of 4 weeks.

may

E- Suggested CaEDTA Regimen For Adults With Lead Nephropathy

Serum Creatinine 4mg/dL

Dosage Regimen * lg/day x 5 days SOOmg Q24 hrs. x 5 days SOOmg Q48 hrs. x 3 days SOOmg Q weekly

* Some clinicians recommend that these regimens may be repeated at 1-month intervals until lead excretion is reduced toward normal.

173

174

Chapter VI TREATMENT FLOWSHEET FOR LEAD POISONING

rl10-24mcg!dL~

Refer to GENERAL MANAGEMENT Algorithm on page 17

---{_25-44mcg/dl

1 Obtain SERUM LEAD LEVEL

I

I

.

-

I

Monitor:

1-Serum lead levels (PbB) 2-Erythrocyte protoporphoryn level (EP) 3-C8C 4-Serum Fe. TIBC 5-X-rays of abdomen, Ytfist. knees 6-Fiuid balance

Administer C:.DTA ) provocation test

~

-

Establish adfquate FWID BALANCE with urine fiowc11-2ml/kglhr. Do not f01re fiuids, beyond this rate.

Neurdcgical exam \W:h particular emphasis on encephalopathy; spinal tap dangerous in presence of increased Ia>.

Medical monttofing and environmental evaluation

~

>45rncg/dl or positive C:.ETA provocation test

>69mcg/dl or encep,alopathy or protracted Gl symptoms

f------1

H

Q-IELATIO THERAPY (see

bel""'

HOSPITALIZE

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Lead Poisoning

':~~.

TREATMENT FLOWSHEET FOR LEAD POISONING (CONT.)

(

(CHELATION THERAPY)

CEREBRAL ) EDEMA

' (

Hyperventilate

vnth 10o% 02 via endotracheal tube to maintain arterial pC02 eves 0

Treatment of cerebral edema must be concurrent with CHELATION therapy

Lead encephalopathy and/or PbS> 70mcg/dl (with or without symptoms)

Symptomatic Pb poisoning (without encephalopathy) or Asymptomatic children with PbS

.

~ BAL and CaEDTA (use of higher doses may be indicated)

Simultaneous

I

J

If PbS decrease to < 50mcg/dl within first 3days of therapy, BAL may be discontinued. ....

------~------

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I

Depending on blood lead )ncentratlon, BAL..( 1erapy may be follo1 I lth:

l

SUCCIMER P.O. (see guidlines)

I

J

I

(more moderate doses may be used)

r~bounds

wtthln 5 to 7 days Parenteral fluids of therapy, then: should be limited to 213 to 314 of normal maintenance CaEDTA alone (second course) Withhold spinal tap until status of ICP I I fully considered

~ CaEDTA alone

BAL and CaEDTA

to >= 45mcgldl

Adjunctive therapy may include: -mannitol -urea -glycerol -steroids consult neurologist

I Asymptomatic children with PbB of 45 to 69 mcg/dl or position CaEDTA povocation test

>70mcg/dl

Simultaneous

If PbB

SEIZURE See management Page20 ~

__

If PbB rebound

>=45mcgldl within 7 to 14dai, then

I

Repeat CaEDTA

I

ALTE~NATIVELY, give:

I

SUCCIMER PO (see guidlines)

I

17 5

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179

Fish Sting Range of Toxicity Any Sting by poisonous fish may result in poisoning, however, the severity of poisoning varies according to the type of the fish and the amount of the poison injected.

Mechanism of poisoning The venom of the fishes vary considerably in their chemistry and pharmacology. The venom components of marine fishes have not been purified or characterized. The more deleterious fractions appear to be relatively large proteins; small polypeptieds have not yet been associated with lethal activity. All the marine fish venoms so far studied have a common property the lethal factor is very unstable and rapidly destroyed by heating; the pain producing activity is also destroyed by heating. Hypotension and shock following envenomation in human is relatively rare, although primary shock may be caused by the intense pain. Stingrays as well as stonefish venoms affect the heart directly causing cardiac standstill.

Substances included Approximately 225 species of marine fishes are known to be venomous. These include • Stingrays • Scorpionfishes • Lion or Zebra-fishes • Stonefishes • Weever fishes • Toadfishes • Stargazers • Certain Catfishes • Ratfishes • Sharks • Surgeonfishes

Characteristic Signs and Symptoms The sting of all fishes are painful, the pain is far out of proportion to similar mechanical wounds and may persist for hours.

'.j

:~t

180

Chapter VII

Cardiovascular • Arrhythmia • Bradycardia • Hypotension • Cardiac Failure • Cardiac Standstill

Respiratory • Respiratory distress

Neurologic • Weakness • Paresthesia • Seizure • Severe pain • Paralysis

Dermatologic • Swelling • Tenderness • Discoloration • Elevated skin temperature • Edema • Ulcers • Cellulitis • Vesication

Gastrointestinal • Nausea • Vomiting • Abdominal pain

Hematologic • Hemolysis (Stone fish) • Hemorrhage( Stingray)

~",·.

Fish Sting Musculoskeletal • Muscle contraction • Fasciculations · • Infection Monitoring Parameters • EKG • Blood pressure • Temperature • Wound Care • Wound X-Ray

181

182

Chapter VII TREATMENT FLOWSHEET FOR FISH STING

I

Support respiration and create an artificial airway, if needed.

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,

....

: l)cr? STINGRAY/ SCORPION FISH

I

•

Irrigate with sterile saline using a needle and syringe

~Keep patient warm and rested

I

STONE FISH )

Symptoms usually mild; last few hours

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,

(

+

Irrigate wound with fresh water and remove sting.

--.

Submerge injured part in HOT WATER, as hot as the patient can tolerate without causing injury for 30 to 90 mins ..

~

I

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.

1- Aspirin. or 2- Aspirin Wllh cor.llene. or 3- OemeroiiM /IV (depending on severity of pa1n)

-

~

1

Determine TETANUS STATUS and vaccinate accordingly.

i

i I

I Give ANTIBIOTIC: S1rinqray: Cover Vibrio species, Enterobacteriaceae Tetracycline or Co-trimoxazole, Ciprofloxacin (po) or Ceftriaxane (IV/IM). Stone fish: Co-trimoxazole

I

..

(HYPOTENSION

See management Page 19

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183

SCORPIONS STING Range of toxicity This management deals with general or unknown stings from scmpions, as well as stings from certain specific scorpions. A single sting may be fatal for a child or a debilitated or hypertensive adult.

Mechanism of Poisoning Scorpion venom consists of ten or more basic neurotoxic proteins and at least six nonproteins. Most scorpion toxins affect the sodium channel of excitable cells by retarding inactivation (alpha toxins) or enhancing activation (beta toxins). A few of these toxins affect the potassium channel. Other toxins has a particular effect on the peripheral nervous system causing a block in the neuromuscular transmission. The bradycardia caused by these venoms is thought to be due to the release of acetylcholine by the action on vagal ganglia and postganglionic nerve endings found in the heart. The venom has a powerful arrhythmogenic activity which stimulates the autonomic sympathetic nervous system and adrenals, including dramatic hemodynamic increases in the left ventricular systolic and diastolic pressures and left ventricular contractility. Most of the venoms produce sympathomimetic effects on the heart demonstrated a massive discharge of catecholamines into the blood. The clinical picture of scorpion sting simulates in most cases adrenergic crisis. However the symptoms may vary according to the species of the scorpion. Characteristic Signs and Symptoms Sympathetic effects • Tachycardia • Hypertension • Hyperglycemia • Dilated pupils • Piloerection • Sweating

Parasympathetic effects • Salivation • Tearing • Urination • Defecation • Bradycardia • Hypertension /Hypotension • Gastric distension • Constricted pupils

184

Chapter VII Other effects

• Pain at site • Hyperactivity • Hyperesthesia near the sting • Respiratory difficulties • Increased secretions • Irritability • Prosthotonos and opisthatonos accompanied by muscle twitching • Blurred vision • Slurred speech • Arrhythmias • Nystagmus and even temporary blindness Monitoring parameters

• Complete Blood Count • Urea and Electrolytes • Vital Signs • Coagulation profile* NOTE * Despite the fact that coagulopathy development is rarely reported with scorpion sting, but the author have had experience with five cases of scorpion sting where patients developed severe coagulopathy similar to that reported with snake bite. Our experience is limited to scorpions from Saudi Arabia, but there are similar observations from South America. MedicaUy Important Scorpions Genus Androctonus Species Buthus Species Buthotus Species Centruroides Species Heterometrus Species Leiurus Species Mesobuthus Species Parabuthus Species Tityus Species

Distrjbution North Africa, Middle East and Turkey France and Spain to Middle East and North Africa, Mongolia and China Africa, Middle East and Central Asia North, Central and South America Central and South East Asia North Africa, Middle East and Turkey Turkey Southern Africa Central and South America

-: 1 '

'

~r .i_.::·

- Scorpion Sting

I 85

TREATMENT FLOWSHEET FOR SCORPION STING

..

Support respiration and create artlfiaclal airway, If ne~ded. Complete bedrest during acute phase

~

~

y

..

Withold food first 8 to 12 hrs due to

HYPERTENSION See Managment '-. Page 18

J

Consider ANTISCORPION VENOM SERUM.

Refer to manufacturer's instructions for more information.

~

possibility of depressed gag reflex

MONITOR: 1-HR, BP 2-ABGs 3-SERUM Ca++ 4- PT& PTT

0

I

I

SUPRAVENTRICULAR_) TACHYCARDIAS

SEIZURES See management Page 20

ADENOSINE:

I(See Adenosine guidelines page 23)

. CALCIUM GLUCONATE

~ Adult 10m!

Vagal maneuvers (carotid massage contraindicated in patient with carotid bruits)

I

I

(MUSCLESPASMS)

Child: 0.1 mllkg

•

I

I I

DIAZEPAM: Adult 5- 10mg IV/PO Q 4-6HR prn , Child: 0.1 mg/kg IV/PO Q 4-6HR prn

!86 SNAKEBITE Range of Toxicity

There are a wide variety of snakes most of which are nonvenomous, while a very small group are·venomenous. Knowing the type of the snake makes it easier to treat. Non venomenous snakes bites should be treated as simple puncture wounds, employing the appropriate anti titanous agent. About 50% of the bites by venomenous snakes do not result in envenomation, that is the snake may bite but do not inject venom, or may inject it onto the skin as in very superficial bite. Therefore, treatment should be based on the victims symptoms rather than number of strikes. Mechanism of Poisoning

Snake venom secrete a highly concentrated mixture of toxins. These include anticoagulants, coagulants, neurotoxins, cholinesterase, cardiotoxins, bacteriocidins and hyaluronidase. Venom usually demonstrate affinity for a particular system, but a spectrum of effects often occurs. Thus, for instance cardiotoxicity or vasculotoxicity might accompany neurotoxicity. Furthermore, different species have venom delivery systems of varying efficiency. Vary from species to species, enzymes can cause coagulation, anticoagulation and hemorrhage as well as lysis and destruction of cellular organelles. Characteristic signs and symptoms Local

• Punctures, Pain, Edema, Erythema, Bleeding , Ecchymosis and Lymphangitis. General • Weakness, sweating, chills, fasciculations, tachycardia, bradycardia or hypotension. Gastrointestinal

• Nausea • Vomiting • Dysphagia • Taste changes Cardiovascular

• EKG ST and T wave changes • Circulatory collapse • Hypotension • Tachycardia or Bradycardia

, 1 '~

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Snake Bite

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Temperature regulation • Low grade fever

Neurologic • Neurotoxicity

Genitourinary • Proteinuria • Hematuria

Hematology • Various types of hemorrhage • Arterial thrombosis • Cerebral or subarachnoid hemorrhage • DIC • Increase Prothrombin time and Partial thromboplastin time • Decrease Fibrinogen • Increase Fibrinogen degregate products • Decrease coagulation factors II, V, VIII,X and XIII

Dermatologic • Local swelling • Blistering • Bruising • Necrosis

Musculoskeletal • Aero-osteolysis in bitten digits

Acid Base • Metabolic acidosis

Immunologic • Activation of complements

187

188

Chapter VII Patient's Disposition

Symptomatic patients should be observed overnight, or until stable with no evidence of CNS manifestations, shock or coagulopathies. Monitoring Parameters

Baseline laboratory studies should be drawn including • Complete Blood Count

• PT (Prothrombin time) • PIT (Partial thromboplastin time) • Fibrinogen • Fibrinogen degregate products (FOP) • Electrolytes • BUN and Creatinine • Blood sugar • Blood Group • Urinalysis • EKG • ABG's Estimation of Grade of Envenomation bv Vipers Grade Characteristics 0 None 1-Minimal Local swelling. No systemic reaction II- Moderate Swelling progressing beyond area of bite. Systemic reaction and I or laboratory abnormalities III- Severe Very marked local reaction and severe generalized symptoms and sings. Markedly" abnormal laboratories studies.

'

"

)-:

Snake Bite

TREATMENT FLOWSHEET FOR SNAKE BITE POISONING

FIRST AID (Wthln 30 min.) Snake~

I

Arabia:

-E. carinatus -Cerastes c&rastes -Naja Haje ..s!Us anetans

~y bBildage oter bite; Wind it prad~ly up the-lrrtl. Do nd. release until arriw.l a1: hospital

&thm rdeaseV«ysloNiy.

ATMEIXdAL FACIUTY

.......

Monitor: 1-Vtal signs

-

r start IV line

I

2-EKG 3-Circumference c:l bitten

eldremely hwr1y 4-U/0 5- Coagulation Prdile PTIPIT, FIB .. FDP

...

... ~

•

~

BASELINE lAB STUOI§S· 6-FOP 1-CBC 2-PTIPIT 7-Fit:rilogen level 3-BUN 8-Biood t}pe 4-Serum glucose 9-Bectrd)tes 5-UA 10-ABG

Actnintstration of ANTI-SNAKE VENOM SERUM (Pesteur,Behring- Near and Mict:le East) 1-Premedicatev.i\h Dipheoh~amile IV. 2-Keep Epinephme (1:1000 a 1:10,000) Cll hand in cased anap~adic reectioo. 3-Start second IV ~ne. if possible, so STAT treatment can be given rr ansphyiaxis occurs.

Follow dosage guidlines in package insert. !!QIE;_If usa of anti-venom Is not possible due to unavailability or severe allergic response, soma clinicians administer NEOSTIGMINE to reverse neurotoxicity. Muscarinic e"ects can be blocked by admlnlsterlng atropine.

'

1-BioodtrBnsfusioo 2-Cenlralline placement Bnd measurement d CVP is hdpful.

• lransfusiCil

ENICILUN AND ETANUS PERIMMUNE OBULIN AND ETANUS TOXOID OOSTER. IF NEEDED

~

...

Coosider HYPERBI\RIC OXYGEN, if awileble

189

190 RABIES

Range of Toxicity Human rabies is almost always fatal viral encephalitis, transmitted by the bite of a rabid anirrial. Most cases in Saudi Arabia have been due to exposure to dogs or wolves. Characteristic Signs and Symptoms General There are phases in human rabies First phase, or PRODORMAL phase { 1- 3 Days up to 2 Weeks} Non specific symptoms, including malaise, anorexia, initability, vomiting, tingling, pain or numbness at the site of the bite, and low grade fever. Second Phase, Acute Neurological Phase (2-7 Days} • Restlessness • Dysarthric • Agitation •· Dysphagia • Hydrophobia • Excessive salivation with abnormal biting or chewing • Visual and/or auditory hallucinations • Manic behavior • Vertigo • Nystagmus • Polyneuritis • Diplopia • Strabismus • Hyperactive deep tendon reflexes· • Positive Babinski sign • Nuchal (nick) rigidity Third Phase, final stage, {7-10 Days} • Painful contractions of the Pharyngeal muscles • Convulsions • Prolonged apnea • General flaccid paralysis • Coma

·Rabies

HEENT • Retinal damage • Cheroiditis • Focal nongranulomatous cyclitis • Inner retinal necrosis

Cardiovascular • Myocarditis • Hypotension • Arrhythmia • ST segment depression

Respiratory • ARDS

Temperature regulation • Hyperthermia (Prodromal Phase) • Hypothermia

Musculoskeletal • Myoedema

Hematology • Leukocytosis ~nitourinary

• Proteinuria • Glucosuria

Monitoring Parameters • The best test available for rapid diagnosis is the fluorescent rabies antibody test (FRA). • Complete Blood Count (Complete Blood Count) • Urinalysis • CSF

191

192 · Chapter VII

TREATMENT FLOWSHEET FOR RABIES

I ·

Animal BHe

I

Wound Cleansing ""Copious flushing and Cleansing with soap and water. Wound itriQation with a 19 Gage needle and 20 mi. syringe. Use mild antiseptic solution or normal saline. • 1 or 20% Virucide quaternary ammonium Solution. irrigate wound thoroughly. ·Wash all exposed areas with Iodine or soap solution.

Puncture Wound

..1

cf

I..Yf I

!

Punctur~ Wound Cats, Wolves, etc. Infection may occur 30- 50 : % of the cases. Antibiotics must j be started immediately Cloxacilline 1 gm I.V .. then 500 mg 06 hrs. for seven days.

!

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I

I

Administer Tetanus Toxoid

I

I

I I

Antirabies Prophylaxis

.I I

Previous Vaccination

1

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•

Yes

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I

• Give 2 Booster doses; day 0 & 3 '* Rabies Immune Globulin is contraindicated

.

I

No

I

1

l

Rabies Immune Globulines

Active Immunization

20 IU/Kg or 91U /Lb. Half of the dose should be infiltrated around the wound site with the balance administered IM in the Gluteal Area. Note: Use different s;te for the RIG and Vaccine

5, 1 mi. doses into deltoid muscle, days: 0 ,3,7,14 &28

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195

CARBON MONOXIDE Range of Toxicity Carboxyhemoglobin (COHb)* levels • Above 30% toxic • Below 30% May Produce Severe Toxicity CO toxicity best determined by mental status and pH. *COHb levels usually do not correlate well with toxicity, therefore treat symptoms and not levels.

Mechanism of Poisoning The exact mechanism by which CO causes its toxicity have not been established. However, there are number of possible mechanism. a- CO reduces the oxygen-carrying capacity of hemoglobin by binding to hemoglobin forming Carboxyhemoglobin and preventing the binding of oxygen. b- The affinity with which CO bind to hemoglobin is more than 200 times that of oxygen. It is not known to which degree the formation of COHb is a factor in the pathogenesis of CO poisoning. c-· CO reduces the release of oxygen to the tissue, leading to tissue anoxia. d- CO binds to cytochrome oxidase system to reduce cellular utilization of oxygen and it is possible that this is a major site of CO action, since tissues most sensitive to oxygen deprivation (CNS, Myocardium) are most sensitive to CO toxicity.

Characteristic Signs and Symptoms Cardiovascular • EKG changes- ST segment depression, T wave abnormalities • Atrial fibrillation • Intraventricular block • Increase in serum transaminase

Gastrointestinal • Nausea • Vomiting

Hematologic • High COHb levels The following symptoms can appear after a week or more has elapsed following exposure:

196 Chapter VIII • Hemorrhagic Tendency • Erythema Of Skin • Edema • Patchy Alopecia • Leukocytosis • Albuminuria • Glucosuria Neurologic

• Headache • Dizziness • Fainting • Convulsions • Coma • Cerebral Edema • Death Ophthalmic

• Retinal Hemorrhages • Retrobulbar Neuritis With Neurotendinal Edema Psychiatric

• Personality Changes • Memory Impairment Monitoring Parameters

• COHb level- initially upon admission then 12-16 hours after treatment • Cardiac function (EKG) • Neurological Assessment • LDH, CPK, SGOT Note The use of N-Acetylcystine for the management of CO poisoning was reported in the litertaure by Howard et a!. Our experience with the use of this method of managment was very rewarding. Ten cases of CO poisoning with refractory coma for up to 72 hours despite the use of hyperbaric oxygen. We used N-acetylcystine in the dose same as for treatment of Acetaminophen poisoning. Specially for patients with HbCO > 20%.

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f" Carbon Monoxide Poisoning 197

TREATMENT FLOWSHEET FOR CARBON MONOXIDE

Do any of the following

CARBON MONOXIDE EXPOSURE

cll.nlcal s~atlons exist? -loss of consciousness -neurological symptoms -cardiovascular symptoms -COHb> 25% -pulmonary edema -severe metabolic acidosis (pH< 7.25)

Remove patient to trash air; administer 100% oxygen by tlght..flttlng mask Immediately

~

1 MONITOR: 1~o Hb levels 2-EKG-cardlac function 3-
CONSIDER HYPERBARIC OXYGEN

~ental

SEIZURES See management

I

.

I PULMONARY EDEMA

CEREBRAL EDEMA AND INCREASE I.C.P.

Page20

r

I Hyperventilate with 100~. oxygen via endotracheal tube

I

I REFRACTORY COMA ) COHb >20%

l

Consider N·ACETYLCYSTINE Dose: See guidelines under Paracetamol poisoning.+ Give Allopurlnol100 mg by N.G. Tube dally for 14 days.

1 Consider PEEP In (intubated patient) or CPAP (non intubated patient) If P02 cannot be maintained at:> 5DmmHg with inspiration of 60"/i 02 by face mask or mechanical ventilation.

levels at 2S-30mmHg

I Parenteral fluids should be limited to 2/3 to 3/4 of · normal maintenance.

Adjunctive therapy may include: -mannitol -urea -glycerol -steroids CONSULT NEUROLOGIST

)

Fluid restriction

to maintain arterial PC02

l

status

6-bicarbonate levels 7-neurological status (consider CT scan)

Determine COHb levels inftlally, then Q2-4hr until< 15% level is reached.

I

I

'

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I II

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i

198

·Cyanide Poisoning Range of Toxicity Ingestion of 200 mg- estimated adult lethal dose; not well~defmed

Blood levels. 0.2 mg/L- usually no symptoms 0.5-1.0 mg/L- flushing/tachycardia · 1.0 - 2.5 mg/L - obtundation Toxic dose Exposure to hydrogen cyanide gas (HCN) at low levels (150 200ppm) can rapidly fatal.

Mechanism of Poisoning Cyanide inhibits cytochrome oxidase and produces cytotoxic anoxia, but also causes hypotension through its effects on the heart. However, the main toxic mechanism is the effect on cytochrome oxidase. Cyanide forms a stable complex with ferric iron (Fe3+) in the cytochrome oxidase enzyems, thereby inhibiting cellular respiration. Cyanide also directly stimulates the chemoreceptors of the carotid and aortic bodies with a resultant hyperpnea. Death is due to respiratory arrest of central origin.

Characteristic Signs and Symptoms

GENERAL Death may occur within minutes Initial symptoms may include

• • • • •

Flushing

•

Stupor

• •

Coma

Tachycardia Tachypnea Headache

Dizziness Symptoms may progress to: • Agitation

Generalized Convulsions and Death

v~~ ~..

Cyanide Poisoning , Cardiovascular • Hypotension/hypertension And Bradycardia I Tachycardia • CardiacArrhythmias • S-T segment elevation or depression Metabolic • High anion gap (lactic acidemia) • Metabolic acidosis blood gases • Arterial-Venous oxygen differences almost absent Neurologic • Headache • Vertigo, • Agitation • Combative Behavior • Stupor • Generalized Convulsions • Death Ophthalmic • Equally red retinal arteries and veins on funduscopic examination Respiratory • Almond odor breath • Rapid respirations, initially • Labored breathing • ·Apnea • Pulmonary edema Monitoring Parameters • Determine Hgb • Electrolytes (check for anion gap) • Arterial and Venous blood gases • Blood pressure • Heart rate • Serum cyanide, thiocyanate level • Respiratory rate

199

200 Chapter VIII TREATMENT FLOWSHEET FOR CYANIDE POISONING

Avoid: 1-0irect dermal contact with patients 2-Mouth-to-mouth resuscitation in CPR 3-lnduction ·at emesis

100% OXYGEN lHERAPY

-

I

I

Be prepared for ENDOTRACHEAL INTUBATION

I I

Administer LILLY CYANIDE ANTIDOTE KIT

{for symptomatic patients· impaired consciousness. seizures, acidosis, unstable vital signs)

...

AMYL NITRATE !INHALATION! Break ampule in handkerchief & hold in front of patienrs mouth for 15 sec. rest for 15 sec. then reapply until SODIUM NITRITE can be given

Monitoring

Parameters:

1-Vital signs 2-Anion gap 3-ABGs 4-Venous 02 5-electrolytes 6-Serum lactate 7-Cyanide levels (whole blood) 8-Venous 02 Sat.

f-1-=-~

Alternatively, Inhale for 15 to 30 sec. every 2

to 3 min.

Follotwith: SODIUM NITRATE 3'.1 Adult 300mg in 10m\ IV over5min. Child: 6-8ml/m2 (0.2ml/kg, not to exceed 10m\) over5min. -Can also dilute with 50 to 1OOml NaCL 0.9% and infuse slowly "IMMEDIATELY THERE AFTER" SODIUM THIOSULFATE 2Sli Adult 12.5gm in 50miiV over 10m in. Child: 7gm/m2 {not to exceed 12.5gm} or 1.65mUkg over 10min.

,.

+

Watch closely for 24 to 46 hours. If symptoms persist, give both drugs at half the original dose.

i I SEIZURES See ) manage;;nt Page

(

HYPOTENSION ) See management Page 19

NaHC03: 1-lnitial dose of 1-2mEq/kg per liter of fluid may be needed. _ 2-Monitor ABGs to guide frequency and amount of NaHC03 replacement

._____

(ACIDOSIS)

Monitor: 1-ABGs 2-Determine base deficit to calculate replacement with NaHC03 3--Difficult to correct prior to ANTIDOTE

-

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Cyanide Poisoning

TREATMENT FLOWSHEET FOR CYANIDE POISONING (Cont.)

Do any of the follov.Ong clinical conditions exist?

l •

9;111l!oms include: ___ Blue skin, and roocous membranes, vorriting,

shock. ccma

1.Cama, Seizures. 2.Unrespanslve to normal supportive and antidotal

therapy. 3.1'1soned by cyanide and carbon monoxide {due to inhalation exposure). 4.Severe methemoglobinemia. 'tY.iceWthsoap and Ytater.

Emergency exchange

transfusion 'Mth v.tlole fresh blood.

lfSEVffiE. foUCM~treatinent

If symptoms a EXCESSIV

METHEMOGLOBINEMIA de.telop. Consider giving 1%~BLUEIV,

a_,

dose of 1-2rrg/kg 5-1 Omin .. May repeat after 1OOur, if necessary.

CNf!l

as in oral/ inhalation ecposure

201

- 202 -Chapter VIII ORGANOPHOSPHATE Range of Toxicity

•

Most toxic (LDSO 1- 50 mglkg) for organophosphates used in agriculture

•

Moderately toxic (LDSO 30 - 500 mg/kg) for organophosphates used in animal husbandry

•

Least toxic (LDSO 60 - 1300 mg/kg) for organophosphates used for household pest control List of Organophosphate compounds according to their toxicity Moderately Toxic Bromophos Chlorpyrifos Coumaphos Crotoxyphos Cyanophos. Cythioate DEF

Other Midithion Ami ton Athidathion Azi nphos-ethyl Azothoate Butonate Chlorphoxim

Demeton Dialifor Dicrotophos Disulfoton EPN Fenamiphos Fenitrothion Fenophosphon Fesulfothion

Least Toxic Acephate Bromophos-ethyl Etrimphos Iodophenphos Malathion Merphos Propylthiopyrophosphate Dimethoate Phoxim Demeton-methyl Pirimiphos-methyl Diaxathion Temephos lazinon(Dimpylate) Tetrachlorvinphos Dichlofenthion Dichlorvos EPBP Ethion Ethoprop

Fonofos lsofenphos Methamidophos Methidathion Mevinphos Monocrotophos Parathion-ethyl Parathion-methyl Ph orate Phosfolan Phosphamidon Prothoate

Famphur Fenitrothion Fenthion Formothion Heptenophos Isoxathion Leptophos Mevinphos _ Naled Phenkapton Phenthoate Phosalone

Chlorprazophos Chlorpynfos-methyl Coumithoate Crufomate Cyanthoate Demephion Demephion-0 Demephion-S Dimethyl Phosphorodithioic Acid Demeton-0 Demeton-0-methyl Demeton-S Demeton-S-methyl Demeton-S-methyl Sulphone Dialifos Dimefox Dimethoate Dioxathion Endothion Ethoate-methyl

Highly Toxic Azinphosmethyl Bomyl Carbophenothion Chlorfeninphos Chlormephos Chlorthiophos Cyanophenfos

"',,.¥~

t

Organophosphate Poisoning 203 Moderately Toxic Phosmet Profenofos Sulfotep Tensulfathion Propetamphos TEPP (tetraethyl Pyradiphenthion pyrophosphate) Terbufos Pyrazophos Trichloronate Quinalphos Sulprofos Thiometon Triazophos Trichlorphon (Metriphonate)

Least Toxic

Highly Toxic Schradan-

Other Ethoprophos Fenchlorphos (Ronnel) Fenpropalthrin Los pirate .

Lythidathion Mazidox Mecarbam Mecarphon Menazon Mephosfolan

--

Methacrifos Methocrotophos Mipafox Morphothion Omethoate Oxydemeton-methyl Oxydisulfoton Phosnichlor Phoxim-methyl Pirimiphos-ethyl Prothidathion Quinothion Quintiofos Sophamide Thionazin Vamidothion ----

-

Mechanism of Poisoning Organophosphates inhibit the enzyme acetYlcholinesterase, allowing the accumulation of excessive acetylcholine at muscarinic receptors (cholinergic effector cells) at nicotinic receptors (skeletal neuromuscular junctions and autonomic ganglia) and in the central nervous system. Characteristic Signs and Symptoms GENERAL

Toxic exposure to organophosphates generally results in CHOLINERGIC SYMYfOMATOLOGY which include miosis, vomiting, sweating, salivation, involuntary urination, defecation and lacrimation. These chemicals are rapidly absorbed across the skin, lungs and gut

.R .~

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204

Chapter VIII Oral Exposure MUSCARINIC EFFECTS • Increased bronchial secretions • Bronchospasm • Salivation • Sweating • Bradycardia • Lacrimation • Vomiting • Diarrhea • Miosis • Seizures Dermal Exposure NICOTINIC EFFECTS • Tachycardia • Hypertension • Muscle cramps • Twitching of eyelids, tongue, face and neck • Respiratory depression • Weakness • Pallor Cardiovascular • Bradycardia • Hypotension or hypertension • Arrhythmias (severe poisonings) Dermal • Sweating (consistent occurrence) Endocrine • Hyperglycemia (poisonings) • Glucosuria (severe poisonings) Gastrointestinal • Nausea e

Vomiting

f: ~-··

Organophosphate Poisoning 205 ·• Anorexia • Abdominal cramps • Diarrhea (sev.\lfe poisonings) • Salivation Genitourinary • Urinary incontinence (severe poisonings)

HEENT • Miosis (very common, but pupils may also be normal or dilated) • Blurred vision • Lacrimation Musculoskeletal • Weakness • Muscular twitching of eyelids, tongue, face and neck • Fasciculation Neurologic • Restlessness • Anxiety • Dizziness • Drowsiness • Tremor • Ataxi;1 • Depression • Confusion • Coma (severe poisonings) • Convulsions (severe poisonings) • Headache • Slurred speech • Absent or weak deep tendon reflexes (DTR)

206 · Chapter VIII Respiratory

• Increased bronchial secretions • Bronchospasm • Dyspnea • Tachypnea • Pulmonary edema Other

• Metabolic acidosis • Fever • Bleeding Monitoring•Parameters

• Plasma pseudocholinesterase (ChE) activity usually recovers in a few days or weeks* • RBC acetylcholinesterase (ACHE) activity - usually recovers in a few days to four months • Cholinergic symptomatology • Neurologic status • Vital signs • Cardiac function • Respiratory status (presence of rales)

• PI &PIT *Depressions in these parameters in excess of 50% of preexposure values is associated with symptomatology. Treatment Guidelines

a.

ATROPINE Useful for treatment of MUSCARINIC effects but will not reverse NICOTINIC effects.

I.

Diagnostic Dose Adult- l.Omg IVliM. Child- 0.25mg (0.01 mg!kg) IVliM. Following administration of these doses, if patient exhibits toxic effects of atropine (drymouth, rapid pulse, dilated pupils, etc.), then patient is probably not seriously poisoned.

2.

Dosage Adult- 2-Smg IVliM. Child- O.OSmg/kg IV liM. Repeat doses every I0-30mins. as needed

'

OrgWiophosphate Poisoning 207 to achieve full atropinization (indicated by complete clearing of rates/drying of pulmonary secretions). This is the preferred indication of adequate atropinization rather than heart rate, or pupil size as tachycardia and mydriasis can be a nicotinic effect. In seriously poisoned individuals, consider appropriateness of a continuous atropine infusion, using preservative - free atropine, at a rate of 0.02 - 0.08mglkglhr. 3. Therapeutic Endpoint Administer until ATROPINIZATION is achieved (dry mouth, clearing of rates, etc.). Maintain some degree of atropinization for at least 24 hrs after resolution of acute symptoms, withdraw slowly to prevent symptom rebound Wid recurrence. b- PRALIDOXIME

Effective against NICOTINIC effects. Used as an ADJUNCT to but not as a substitute for atropine. More effective if given in the first 24 to 48 hrs although it has produced clinical improvement when administered up to 2 to 6 days after exposure. I.

Dosage Adult- l-2Gm IV infused at a rate of0.5Gm /min; or mix in 250m! normal saline Wid infuse over 30 min. If IV not possible, give l-2GmiM. Child- 25 to 50mglkg in normal saline (a 5 percent solution) over 5 to 30mins.May repeat doses lhr after initial dose, and every 6 to 12 hrs, thereafter if muscle or diaphragmatic weakness or coma are not relieved. May be needed up to 4 to 6 days or longer.

2.

Therapeutic Endpoint Determine efficacy of treatment by monitoring blood cholinersterase activity.

3.

Adverse Effects Drowsiness, dizziness, visual disturbWices, nausea, tachycardia, headache, hyperventilation and muscular weakness. When atropine Wid pralidoximine are given together, the signs of atropinization may occur earlier than wi)en atropine is used alone. Use with CAUTION in patients with Myasthenia Gravis or Impaired Renal Function (reduce dose).

208 TREATMENT FLOWSHEET FOR ORGANOPHOSPHATE POISONING

Refur to GENERAL MANAGEMENT Algorithm on page 17

I ' Inducing EMESIS Is CONTRAINDICATED due to potential for ear1y coma. seizures, and risk of aspiration

I MONITOR: 1-plasma ChE activity*

2-RBC AChE activity•

I

3.i:h~linergic

symptomatology 4-neurological status

5-EKG- cardiac function 6-respiratory status *If possible, obtain prior to PARALIOOXIME therapy.

DECONTAMINATION: Contaminated clothing should be removed. Wash skin and hair three times; first dy soap, then by 95% ethanol, and then by soap again,

Avoid leather clothing in the presence of pesticides, as leather absorbs pesticides.

1 SEVERE SMPTOMATOLOGY with OR wfthout

(

-weakness -bronchospasm -respiratory insufficiency -muscle Witching -plasma ChEIRBC AChE activity Clin Toxicol 1988; 26 233-248

4.

Katona B & Wason S Superwarfarin poisoning. J Emerg Med 1989; 7 627631 Mount ME Diagnosis and therapy of anticoagulant rodenticide intoxications. Vet Clin N Am Small An Pract 1988; 18 115-130

5.

Anticonvulsants I.

Abdulhadi MH, Notrnan DD, Cardon GC et al Phenytoin toxicity A casue of reversible monoplegia. Cleve Clin J Med 1987; 54 438-439

2.

Albertson Te, Fisher CJ, Shragg TA et al A prolonged severe intoxication after ingestion of phenytoin and phenobarbital. West J Med 1981; 135 418422

3.

Baehler RW, Work J, Smith Wet al Cahrcoal hemoperfusion in the therapy for methsuximide and phenytoin overdose. Arch Intern Med 1980; 140 1466-1468

4.

Campbell WW Jr, Periodic alternating nystagmus in phenytoin intoxication. Arch Neurol 1980; 37 178-180

5.

Curtis DL, Piibe R, Ellenboro MJ et al Phenyton toxicity predictors of clinical course. Vet Hum Tox 1989; 31 162-163 Weichbrodt GD & Elliott DP Treatment of phenytoin toxicity with repeated doses of activated charcoal. Ann emerg Med 1987; 16 1387-1389

6.

Antidepressants I.

Banahan BF Jr & Schelkun PH Tricyclic antidepressant overdose Conservative management in a community hospital with cost-saving implications. J Emerg Med 1990; 8 451-461

'

REFERENCES

221

2.

Biggs IT, Spiker DG, Petit JM eta! Tricyclic antidepressant overdose. Incidence of symptoms JAMA 1977; 238 135

3.

Boehnert MT & Lovejoy"FH Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants. N Eng!J Med 1985; 313 47 4-4 79

4.

CallahanM Admission criteriafortricyclic antidepressant ingestion. West J Med 1982; 137 425-429

5.

Cassidy S & Henry J Fatal toxicity of antidepressant drugs in overdose. Br Med J 1987; 295 1021-1024

6.

Comstock TJ, Watson WA & Jennison TA Severe Amitriptylin intoxication and the use of charcoal hemoperfusion. Clin Pharm 1983; 2 85-88

7.

Crome P, Adams R, Ali C eta! Activated charcoal in tricyclic antidepressant poisoning Pilot controlled clinical trial. Hum Toxicol1983; 2 205-209

8.

Fasoli RA & Glauser FL Cardiac arrhythmias and ECG abnormalities in tricyclic antidepressant overdose. Clin Toxocol1981; 18 !55-163

9.

Pentel P & Sioris L Incidence of late arrhythmias following tricyclic antidepressant overdose. Clin Toxicol I 981; 18 543-548

10. Peterson CD Seizures induced by acute Loxapine overdose. Am J Psychiatry 1981; 138 1089-1091 I I. Swartz CM & Sherman A The treatment of tricyclic antidepressant overdose with repeated charcoal. J Clin Psychopharmaco! I 984; 4 336-340 Antihistamines I.

Freedberg RS, Friedman GR, Palu RN et al Cardiogenic shock due to antihistamine overdose reversal with intra-aortic balloon counterpulsation JAMA 1987; 257 660-661

2.

Richmond M & Seger D central anticholinergic syndrome in a child a case report. JEmergMed 1985; 3 453-456.

3.

Thach BT, Chase TN & Bosma JF oral facial dyskinesia associated with prolonged use of antihistaminic decongestants. N Eng! J Med 197 5; 293 486-487

4.

Jacobsen D, Frederichsen PS, Knutsen KM et a! Clinical course in acute self poisoning a prospective study of 1125 consecutively hospitalized adults. Human Toxicol 1984; 3 107-116

5 . Csillage ER & Landauer AA Alleged hallucinogenic effect of a toxic overdose of an antihistamine preparation. Med J Aust I 973; I 653-654 Barbiturates I.

Amitai Y & Degani Y Treatment of phenobarbital poisoning with multiple dose activated charcoal in an infant. J Em erg Med 1990; 8 449-450

'·•. 222

REFERENCES 2.

Beveridge GW, Lawson AAH Occurrence of bullous lesions in acute barbiturate poisoning. Br Med J 1965; I 835-837

3.

DeBroc MEet a! Hemoperfusion a useful therapy for the severely poisoned patient. Hum Toxicoll986; 5 11-14

4.

Hadden Acute barbiturate intoxication. JAMA 1969; 209 893-900

5.

McCarron MM, Schulze BW, Walberg CB et al Short acting barbiturate overdosage. Correlation of intoxication score with serum barbiturate concentration. JAMA 1982; 248 55-61

6.

Zawada ET, Nappi J, Done Get al Advances in the hemodialysis management of Phenobarbital overdose. South Med J 1983; 76 6-8

Benzodiazepines I.

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2.

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Carbon Monoxide I.

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235 ·INDEX A Abrasives Ill ACEI 46 Acetaminophen 120 Acid Diuresis 8 Acidification 8 Acids 143 Activated Charcoal 6 Acute Dystonic Reactions 50 Adsorbents l, 6 Agensia 46 Alfentanil 114 Alkaline 147 Alkaline Diuresis 9 Alphaprodine 114 Alteration OfUrinepH I Amitriptylin 71 Ammonium Chloride 8 Amoxapine 71 Angiotensin Converting Enzyme Inhibitors 46 Angiotensin I 46 Angiotensin II 46 Aniline 213 Antacids Ill Antibiotics Ill Anticholinergic 50 Anticoagulants 54 Anticonvulsants Drugs 57 Antidepressants 7l Antihistamines 78 Antipsychotics 49 Aqua Regia 143 Arrhythmias 2 Azinphos-ethyl 202 Azinphosmethyl 202 B Baby Products Cosmetics Ill Ballpoint Pen Inks Ill Barbiturates 83 Bathtub Floating Toys Ill Belladonna 13 Benzene 213 Bicyclics 73 Bleeding Diathesis 54 Blood Ethylene Glycol 33 Body Conditioners Ill Bomyl 202 Botulism 159 Bradykinin 46

Bromophos 202 Buprenorphine 114 Butorphanol ll4

c

Calamine Lotion Ill Calcium Carbonat 111 Calcium Channel Blockers 90 Candles (Bees Wax Or Paraffin) Ill Captopril 46 Carbamazepine 68 Carbon Tetrachloride 213 Carbophenothion 202 Carboxyhydrolase 46 Carboxymethyl Cellulose Ill Cardiac Glycosides 96 Cathartics I, 6 Caustics 3, 143, 147 Cerebellar Atrophy 57 Chalk Ill Charcoal Empyema 4 Charcoal Lighter Fluid 213 Chlorfeninphos 202 Chlormephos 202 Chlorpyrifos 202 Chlorthiophos 202 Cinnarizine 90 Clay 111 Clomipramine 71 Clostridium Perfringens 153 CNS Depression 5 Codeine 114 Comatose 4 Complications of gastic lavage 4 Contraindications to gastic lavage 4 Contraindications To Emesis 3 Corrosives 5 Corticosteroids 111 Cosm~tics Ill Coumaphos 202 Crayons 111 Crotoxyphos 202 Cyanophenfos 202 Cyanophos 202 Cyclic Antidepressants 71 Cythioate 202 D

Darvocet 124 Darvon 124 Darvon Comp. 124 Darvon N 124

236 Deadly Nightshad 12 DEF 202 Deferoxamine 103 Deferoxamine Guidelines 103 DehumidifYing Packets Ill Demeton 202 Demeton-methyl 202 Demeton-0 202 Demeton-0-methyl 202 Demeton-S 202 Demeton-s-methyl 202 Deodorants Ill Deodorizers Ill Desipramine 71 Dextropropoxyphene 124 Dialifor 202 Dialifos 202 Dialysis I Diaxathion 202 Diazepam 2 Dichlofenthion 202 Dichlorvos 202 Dicrotophos 202 Diethylene Glycol 31 Digitoxin 96 Digoxin 96 Digoxin F ab F ragmen! 98 Dihydrocodeine 114 Dilated Fixed Pupils II Dilated Pupils II Diltiazem 90 Dimefox 202 Dimethoate 202 Dimethyl Phosphorodithioic Acid 202 Dioxathion 202 Distalgesic 124 Disul foton 202 Diuresis I Dolene Propacet 124 Done Nomogram 127 Doxepin 71 Drugs 25 Dysrhythmias 4 E Elmer's Glue Ill Emesis I Emetic 3 Emetics 3 Enalapril 46 Endothion 202 Endotracheal Intubation 4

INDEX . Enhancement Of Excretion 8 EPBP 202 EPN 202 Epsom Salt 6 Erythema Multiform 58 Esophageal Perforation 4 Etch-a-sketch Ill Ethanol Concentrations 27 Ethanol Therapy 39 Ethion 202 Ethoate-methyl 202 Ethoheptazine 114 Ethoprop 202 Ethoprophos 202 Ethosuximid 61 Ethylene Glycol 31 Eye Makeup Ill F Famphur 202 Fenamiphos 202 Fenchlorphos (Ronnel) 202 Fenitrothion 202 Fenophosphon 202 F enpropalthri n 202 Fentanyl 114 F enthion 202 Ferric Phosphate 101 Ferric Pyrophosphate 101 F erricyanide Ill Ferrocholinate 101 Ferroglycine Sulfate 101 Ferrous Carbonte, Anhydrous 101 Ferrous Fumarate 101 Ferrous Gluconate 101 Ferrous Sulfate 101 F esulfothion 202 Fish Bowl Additives Ill Flavoxate 49 Fluids Used For Gastric Lavage 5 Flunarizine 90 Fonofos 202 Food-born Disease !53, !56, !59 Forced Diuresis 8 Formaldehyde 36 Formic Acid 36 Formothion 202 G

GABA 64 Gama-aminobutyric Acid 64 Gasoline 213

237

INDEX Gastric Lavage 1, 4 General Management Of The Poisoned Victim 17 Glasgow Coma Scale 11,14 Glauber's Salts 7 Glia 64 Glues And Pastes 111 Glycerol Ill Go! f Ball 111 Greases 111 Gum Hypertrophy 61 Gums 111 H

Hair Products 111 Hand Lotions And Creams 111 Hemodialysis 40 Hemoperfusion 1 Heroin 114 Hydrocarbon 5,211 Hydromorphone 114 Hyoscyamine l3 Hyperactivity Syndrome 11 Hyperammonemia 65 Hypematremia 58 Hypertension 2,18 Hypoprothrombinemia 54 Hypotension 2,19 Hypothyroidism 58 I

Iazinon(Dimpylate) 202 Ibuprofen 105,110 Idiosyncratic Reaction 50 Imipramine 7l Indelible Markers Ill Ink 111 Iodophenphos 202 Ipecacuanha Syrup 3 Iron 101 Isofunphos 202 Isometheptene 133 Isoxathion 202 J JimsonWeed 12 K

K 1-2,3-epoxide Reductase 54 K l Epoxide 54 Kaolin Ill K-dependent Clotting Factors 54 Kerosene 213 Kussmaul Breathing 91

L

Lanolin ll1 Larcet Wygesic 124 Laryngospasm 4 Leptophos 202 Levorphanol 114 Lighter Fluid (Petroleum Naphtha) 213 Linoleic Acid Ill Linseed Oil Ill Lipstick 111 Liquid Corrosives 147 Lisinopril 46 Lospirate 202 Loxapine 71 Lubricant Ill Lubricating Oil Ill Lythidathion 203 M

MagicMarkers 111 Magnesium Silicate Ill Magnesium Sulfate 6 Makeup Ill Malathion 202 Mannitol 8 Maprotiline 71 Matthew nomogram122 Mazidox 203 MDAC6 Mecarbam 203 Mecarphon 203 MefenamicAcid 106 Membrane Stabilizing Activity (MSA)l24 Menazon 203 Meperidine 114 Mephosfolan 203 Mercury Ill Merphqs 202 Methacrifos 203 Methadone 114 Methamidophos 202 Methanol 36 Methidathion 202 Methocrotophos 203 Methsuxi mide 61 Methylene Chloride 213 Mevinphos 202 Mianserin 71 Midithion 202 Mineral Seal Oil 213

238

INDEX

Mipafox 203 Monocrotophos 202 Monoplegia 57 Morphine 114 Morphothiori 203 Motor Oil 111 MSA 124 Multiple Dose Activated Charcoal 6

N

.

N-acetylcystine 121 Nalbuphine 114 Naled 202 Naproxen 1OS Neuroleptic Malignant Syndrome 56 Newspaper 111 Nifedipine 90 Nimodipine 90 Nitrobenzene 213 Nomogram For Acetaminophen Poisoning 122 Non Steroidal Anti Inflammatory Drugs 105 Non Toxic Ingestion 111 Nortriptyline 71 Nystagmus 13 0

Oculogyric Movements 50 Omethoate 203 Opiates 114 Oral Contraceptives 119 Organophosphate 202 Orofacial Spasms 50 Osmolar Gap 32, 38 Oxycodone 114 Oxydemeton-methyl 203 Oxydisulfoton 203 Oxymorphone 114 p Paint- Indoor Or Latex 111 Paracetamol 120 Paraffin 111 Parathion-ethyl 202 Parathion-methyl 202 Partial Thromboplastin Time 55 Penci! (Lead-graphite, Coloring Ill Pentazocine 114 Peptidyldipeptide 46 Perhexilin 90 Pethidine 114 Petroleum Distillates 5,213

Petroleum Ether (Benzine) 213 Petroleum Jelly 111 Phenkapton 202 Phensuximide 61 Phenthoate 202 Phenylpropanolamine 133 Phenytoin 2,57 Phorate 202 Phosalone 202 Phosfolan 202 Phosmet 202 Phosnichlor 203 Phosphamidon 202 Phoxim 202 Phoxim-methyl 203 Physostigmine 51 Pine Oil 216 Pinpoint Pupils l 0 Pirimiphos-ethyl 203 Pirimiphos-methyl 202 Piroxicam 105 Plasma Osmolarity 32 Play-Doh 111 Polaroid Picture Coating Fluid 111 Porous-tip Ink-marking Pens Ill Prevention Of Absorption 3 Prevention Of Absorption 1 Profenofos 202 Propetamphos 202 Propoxyphene 124 Propoxyphene 114 Propylthiopyrophosphate 202 Prostaglandins 46 Prothidathion 203 Prothoate 202 Prothrombin 53 Protri ptyl ine 71 Prussian Blue ·Ill Pseudoephedrine 133 PTT 55 Pupils 12 Putty 111 Pyradiphenthion 202 Pyrazophos 203 Q Quinalphos 203 Quinothion 203 Quintiofos 203 R

Rectal Enema 7

';.

INDEX Rouge 111 Rumack 122

s

Saccharin, Cyclamate Ill Sachets Ill Salicylates 127 Salmonella 153 Schradiui 202 Seizures 2,20 Serum Iron I 0 I Sesame Oil Ill Shigella 154 Shoe Polish Ill SI 103 Signal Oil 213 Silica lll Silly Putty (99% Silicones) Ill Size Of The Tube 4 Sodium Bicarbonate 9 Sodium Sulfate 7 Solanaceous 13 Sophamide 203 Sorbitol 7 Spackles Ill Staphylococcus !53 Streptococcus 153 Subepidermal Bulla 69 Succinimides 61 Sufentanil 114 Sulfotep 202 Sulphone 202 Sui profos 203 Suntan Preparations Ill Supportive Care I ,2 Sweetening Agents Ill Sympathomimetics 133 Syndrome Of Anticholinergic 49 T

Teething Rings Ill Temephos 202 Tensulfathion 202 Tepp (Tetraethyl Pyrophosphate) 202 Terbufos 203 Tetrachlorvinphos 202 Tetracyclics 74 Theopljylline 136 Thermometers Ill Thermoregulation 51 Thiometon 203 Thionazin 203

239 TIBC 103 Titanium Oxide lll Toluene 213 Tooth Paste Ill Torticollus 50 Total Iron Binding Capacity 101 Trazodone 71,74 Treatment Flowsheet For Cardiac Arrhythmias Using Adenosine 23 Treatment Flowsheet For Hypertension 18 Treatment Flowsheet For Hypotension 19 Treatment Flowsheet For Seizures 20 Treatment Flowsheet For Unknown Ingestions 21 Treatment Flowsheet For Ventricular Arrhythmia 22 Triazophos 203 Trichloroethane 213 Trichloroethylene 213 Trichloronate 203 Trichlorphon (Metriphonate) 203 Trimipramine 71 Turpentine 213

u Unilateral Pupil Dilation 13 Urinary Ph 8

v

Valproic Acid 64 Vamidothion 203 Vaseline Ill Verapamil 90 Viloxazine 71

w Water Colors Ill Withdrawal Bleeding 119 Withdrawal Syndrome 12 X

Xylene 213

z

Zimelidine 71 Zinc Oxide Ill Zirconium Oxide Ill