Critical Care Obstetrics part 54 docx

Suspected overdose or poisoning in pregnancy Consider trauma Patent AWY Spontaneous breathing Pulse Altered mental status O2 + “coma cocktail” glucose, thiamine, flumazenil, naloxone Res

Suspected overdose or poisoning in pregnancy

Consider trauma Patent AWY

Spontaneous breathing Pulse

Altered mental status

O2 + “coma cocktail”

(glucose, thiamine, flumazenil, naloxone)

Response No response

Repeat doses

No response

Intensive care consult

Toxicology consult

ICU admission

H&P Monitor fetus Toxicology samples Suicide potential evaluation

Altered mental status?

Positive drug ID Negative drug ID

Supportive measures

*

I:

II:

III:

IV:

* May require restraints, sedation, and Foley catheterization

Decontamination procedures Specific antidote

• Observation/monitoring until therapeutic goals

• Psychiatry clearance

Dismiss and F/U Admit

Improvement No improvement

V:

(a)

Figure 39.2 (a) Guidelines for evaluation and

management of pregnant patients with a known or

suspected toxic exposure (b) Guidelines for the

evaluation of the unconscious pregnant patient with

a known or suspected toxic exposure During 1999

1085 suicidal toxic exposures among pregnant

women were reported to American Poison Control

Centers This represents 12% of the toxic exposures

reported during pregnancy for that year and less

than 1% of the suicide attempts by poisoning

reported to the American Association of Poison

Control Centers The substances most frequently

involved were acetaminophen (alone or in

combination with decongestants and antihistamines;

35.5%), nonsteroidal anti - infl ammatory drugs

(15.2%), selective serotonin - reuptake inhibitors

(SSRIs; 8.8%), and benzodiazepines (7.1%)

* May require restraints, sedation, and Foley

catheterization ACLS, advanced cardiac life support;

AWY, airway; CPR, cardiopulmonary resuscitation;

C/S, cesarean section; EKG, electrocardiogram; F/U,

follow - up; GA, gestational age; H & P, history and

physical; OD, overdose Reproduced with permission

from Gei AF, Saade GR Poisoning during pregnancy

and lactation In: Yankowitz J, Niebyl J Drug

Therapy in Pregnancy , 3rd edn Philadelphia:

Lippincott, Williams and Wilkins, 2001

• Some patients would require observation and management in

an intensive care setting (see Table 39.7 )

Toxic i dentifi cation

• The collection of samples for toxicology is of paramount

importance in the identifi cation of the toxic agent(s) causing the

exposure, to predict the severity and to implement and monitor specifi c treatment/antidotes As a general rule, at least one sample of all biologic fl uids should be obtained, and saved for toxicology analysis (see Tables 39.8 and 39.9 ) Depending

on the clinical circumstances, these will include blood, urine, saliva, vomit, gastric lavage fl uid, feces, cerebrospinal fl uid,

Obstructed AWY

No spontaneous

breathing

No pulse

Establish patent AWY

Assisted ventilation

CPR

ACLS protocols Stat consult with obstetrics/gynecology

Determine viability Consider emergent C/S

Continue CPR/ACLS protocols Determine GA/viability Monitor: vitals/EKG/SaO2/fetus

H&P

Drug ID/OD mechanism

ICU admission

Consider perimortem C/S

A

B

C

I:

II:

III:

IV:

(b)

Figure 39.2 Continued

amniotic fl uid if collected, and meconium if the patient delivers

soon after admission Occasionally the analysis of an arterial

blood gas and basic chemistry will detect an anion gap [AG=(N

a + +K + ) − (Cl − +HCO 3 − ); normal outside pregnancy 12 ± 4 mEq/l;

for pregnancy 8.5 ± 2.9 mEq/l; postpartum 10.7 ± 2.5 mEq/l]

or osmolar gap (normal − 5 to +15 mOsm/l) which will assist

in the differential diagnosis of acidosis and suggest the possibility

[27,28,29]

• The mainstay of treatment for all poisonings is supportive

therapy For some toxic agents, three additional strategies can be

implemented to: (a) decrease the exposure ( decontamination

pro-cedures ), (b) enhance elimination (diuresis, hemofi ltration,

hemoperfusion, hemodyalisis, and plasmapheresis), or (c)

coun-teract the toxicity of the agent (antidotes) The specifi c measures

to enhance elimination and the use of antidotes are particular for every toxic substance and will be discussed as appropriate in the corresponding section (see Tables 39.12 , 39.13 , 39.14 , 39.15 and 39.16 )

Decontamination p rocedures

Skin

Substances that can cause signifi cant systemic toxicity through transdermal absorption include: organophosphate insecticides, organochlorines, nitrates, and industrial aromatic hydrocarbons Organophosphates in particular can pass through intact skin at a remarkable speed, without causing any specifi c skin sensation of burning or itching In theory, pregnancy, as shown in Table 39.2 , predisposes to such toxicity, given the physiologic increase in skin perfusion throughout gestation

salicylates, meprobamate, barbiturates, glutethimide, or drugs that can delay the gastric emptying: tricyclics, narcotics, salicy-lates, or conditions producing adynamic ileus (see Table 39.12 ) Its use is controversial for the following reasons:

1 not immediately effective;

2 the effect may persist for 2 hours, delaying the administration

of adsorbants;

3 unlikely to be effective within several hours after the ingestion

(more than 1 – 2 hours with exceptions);

4 not proven to be better than lavage;

5 several contraindications: caustic ingestion; altered mental status; inability to protect airway, seizures or seizure potential, hemorrhagic diathesis, hematemesis, ingestion of drugs that can lead to rapid change in the patient ’ s condition (tricyclics, β blockers, PCP, isoniazid);

6 has no value in ethanol intoxication and certain hydrocarbon

ingestions;

7 in case of failure to induce emesis (about 5% of cases), the

stomach should be evacuated by other means, since ipecac can be cardiotoxic (theoretical risk)

Recently published guidelines recommend the use of ipecac syrup when in the absence of contraindications (above) it can be

Table 39.3 Altered mental status: indications for antidote treatment in pregnancy

Naloxone

(Narcan)

Altered mental status (AMS) associated with:

• miosis

• respiratory rate less than 12 or

• circumstantial evidence of opioid use/abuse

2 mg (IV, IM, ET, IL); onset of action: 1 – 3 min May repeat if no response is noted after 3 – 5 min (maximal effect is observed within 5 – 10 min)

• An IV drip or repeated doses are given as needed

• Higher doses may be necessary to reverse methadone, diphenoxylate, propoxyphene, butorphanol, pentazocine, nalbuphine, designer drugs, or veterinary tranquilizers

• Caution in cardiovascular disease; may precipitate withdrawal symptoms in patients with opiate addiction

Thiamine (vitamin B 1 ,

thiamilate)

AMS in patient with risk factors for B 1 defi ciency:

• ethanol abuse

• malnutrition

• hyperemesis gravidarum

• eating disorder

• total parenteral nutrition

• AIDS

• cancer

• dialysis requirement

100 mg daily IV/IM for up to 2 weeks

• Administer before or with dextrose - containing fl uids (100 mg/L of fl uid)

Flumazenil

(Romazicon)

AMS with:

• suspected or known benzodiazepine exposure and no contraindication for antidote use (hypersensitivity, use of benzodiazepine for control of life - threatening condition, intracranial pressure or seizure disorder), coexposure to tricyclic antidepressant or chronic benzodiazepine use

• check EKG to rule out conduction disturbances, which would suggest the presence of tricyclics

0.2 mg (2 mL) given IV over 30 s; a second dose of 0.3 mg (3 mL) can be given over another 30 s

• Further doses of 0.5 mg (5 mL) can be given over 30 s at 1 - min intervals up to

a total dose of 3 mg (although some patients may require up to 5 mg)

• If the patient has not responded 5 min after receiving a cumulative dose of

5 mg, the major cause of sedation is probably not due to benzodiazepines and additional doses of fl umazenil are likely to have no effect

• For resedation, repeated doses may be given at 20 - min intervals; no more than 1 mg (given as 0.5 mg/min) at any one time and no more than 3 mg in any 1 h should be administered

The skin should be fl ushed thoroughly with warm soapy water

It may be worthwhile to use an industrial shower (as is used for

corrosive exposure) to thoroughly rinse the entire body A rare

exception to immediate decontamination with water would be

the exposure to agents that may react violently with it (e.g the

chemical may ignite, explode, or produce toxic fumes with water)

Examples include: chlorosulfonic acid, titanium tetrachloride,

and calcium oxide

Gastrointestinal [30,31,32,33]

Several strategies can be useful, as described below

Dilution

Lacking from alternatives (see below), 200 – 300 ml of milk may

be given orally (not through gastric tubes) in caustic ingestions

(acids or alkalis)

Emesis

Considered the second choice after lavage as the preferred method

for gastric emptying The dose in adults is 30 ml of ipecac with

water and repeated in 15 – 30 minutes if vomiting is not induced

Indicated in ingestions of drugs that can form gastric concretions:

Class of drug Common signs Common causes

Anticholinergics Dementia with mumbling speech Antihistamines

Tachycardia Antiparkinsonian medications Dry fl ushed skin Atropine

Dilated pupils (mydriasis) Scopolamine Myoclonus Amantadine Temperature slightly elevated Antipsychotics Urinary retention Antidepressants Decreased bowel sounds Antispasmodics Seizures/dysrhythmias (severe cases) Mydriatics Skeletal muscle relaxants Some plants (i.e jimson weed) Sympathomimetics Delusions Cocaine

Paranoia Amphetamines Tachycardia Methamphetamines and derivatives Hypertension Over - the - counter decongestants

(phenylpropanolamine, ephedrine, pseudoephedrine)

Hyperpyrexia Diaphoresis Piloerection NB: Caffeine and theophylline overdoses have

similar fi ndings, except for organic psychiatric signs

Mydriasis Hyperrefl exia Seizures/dysrhythmias (severe cases) Opiate/sedatives Coma Narcotics

Respiratory depression Barbiturates Constricted pupils (miosis) Benzodiazepines Hypotension Ethchlorvynol Bradycardia Glutethimide Hypothermia Methyprylon Pulmonary edema Methaqualone Decreased bowel sounds Meprobamate Hyporefl exia

Needle marks Cholinergics Confusion/CNS depression Organophosphate and carbamate insecticides

Weakness Physostigmine Salivation Edrophonium Lacrimation Some mushrooms ( Amanita muscaria ; Amanita

pantherina , Inocybe spp., Clitocybe spp.) Urinary and fecal incontinence

Gastrointestinal cramping

Muscle fasciculations Bronchospasm (From Briggs GG, Freeman RK, eds Drugs in pregnancy and lactation, 4th edn Baltimore: Williams and Wilkins,

1994; and Doyon S, Roberts JR Reappraisal of the “ coma cocktail ” Dextrose, fl umazenil, naloxone and

thiamine Emerg Clin of N Am , 1994;12:301 – 316.)

Table 39.4 The most common toxic syndromes

Table 39.5 Physical fi ndings in poisoning

Pupils

Dilation

Alkaloids

Aminophylline

Anticholinergics

Antihistaminics

Barbiturates

Carbon monoxide

Cocaine

Cyanide

Ergot

Ethanol

Ethylene glycol

Glutethimide

LSD

Methaqualone

Mushrooms

Phenothiazines

Phenytoin

Quinine

Reserpine

Sympathomimetics

Toluene

Tricyclics

Withdrawal states

Constriction

Acetone

Barbiturates

Benzodiazepines

Caffeine

Chloral hydrate

Cholinergics

Cholinesterase inhibitors

Clonidine

Codeine

Ethanol

Meprobamate

Opiates (except meperidine)

Organophosphates

Phencyclidine

Phenothiazines

Propoxyphene

Sympatholytics

Breath odor Acetone: Acetone, chloroform, ethanol, isopropyl alcohol,

salicylates Acrid or pear - like: Chloral hydrate, paraldehyde Bitter almonds: Cyanide

Carrots: Cicutoxin (water hemlock) Garlic: Arsenic, organophosphates, phosphorus,

selenium, thallium Mothballs: Camphor, naphthalene, paradichlorobenzene Pungent aromatic: Ethchlorvynol (Placidyl)

Violets: Turpentine Wintergreen: Methyl salicylate

Refl exes Depressed Antidepressants Barbiturates Benzodiazepines Chloral hydrate Clonidine Ethanol Ethchlorvynol Glutethimide Meprobamate Narcotics Phenothiazines Tricyclic antidepressants Valproic acid

Hyperrefl exia Amphetamines Carbamazepine Carbon monoxide Cocaine Cyanide Haloperidol Methaqualone Phencyclidine Phenothiazines Phenytoin Propoxyphene Propranolol Strychnine Tricyclic antidepressants

(Data for “ Breath odor ” from Olson K Poisoning and drug overdose, 2nd edn Norwalk, CT: Appleton and Lange, 1994.)

administered within 30 – 90 minutes of an ingestion with a

sub-stantial risk of serious toxicity to the victim and no alternative to

decrease gastrointestinal (GI) absorption is available (or effective)

and a delay of greater than 1 hour to an emergency medical

facil-ity is anticipated [34]

Gastric l avage

Indicated when emesis is inappropriate or contraindicated, the patient is comatose or mentally altered, the substance ingested has the potential for seizures or when the substance ingested is lethal and/or rapidly absorbed (i.e delay for emesis can result in

Table 39.7 Quantitative toxicology testing

Test Time to sample postingestion Repeat sample Implication positive test

Nomogram and N - acetylcysteine Carbamazepine 2 – 4 h 2 – 4 h Repetitive doses of activated charcoal/hemoperfusion

Carboxyhemoglobin Immediate 2 – 4 h 100% oxygen

Cholinesterase blood RBC Immediate 12 – 24 h Confi rm exposure to insecticide

Digoxin 2 – 4 h 2 – 4 h Digoxin antibody fragments (Fab)

Ethanol 0.5 – 1 h Not necessary If negative, not ethanol intoxication; if positive, inconclusive (tolerance) Ethylene glycol 0.5 – 1 h 2 h Ethanol therapy, hemodialysis, sodium bicarbonate

Heavy metals First 24 h 2 – 4 h Chelation therapy, dialysis

Iron 2 – 4 h (chewable/liquid preparation

absorbed faster)

2 – 4 h Serum iron 350 µ g use deferoxamine Isopropanol 0.5 – 1 h 2 h Supportive - care hemodialysis

Methanol 0.5 – 1 h 2 h Ethanol therapy folinic acid, NaHCO 3 , hemodialysis

Methemoglobin Immediate 1 – 2 h Methylene blue

Phenobarbital 1 – 2 h 4 – 6 h Alkaline diuresis

Phenytoin 1 – 2 h 4 – 6 h Supportive care

Salicylates 2 – 4 h 2 – 4 h Serum and urine alkalinization

Theophylline 1 - h peak at 12 – 36 h 1 – 2 h Repeat activated charcoal, hemoperfusion

2 - PAM, pralidoxime; ABGs, arterial blood gases; Fab, fragment antigen - binding; PT, prothrombin time; PTT, partial thromboplastin time

(Reproduced by permission from Mowry JB, Furbee RB, Chyka PA Poisoning In: Chernow B, Borater DC, Holaday JW, et al., eds The Pharmacological Approach to the Critically Ill Patient, 3rd edn Baltimore: Williams and Wilkins, 1995.)

Supine hypotensive syndrome

Lower potential to resist acidosis in pregnancy

Need for preservation of a maternal P a O 2 of at least 60 – 70 mmHg for fetal oxygenation

Increased maternal cardiac output and oxygen consumption

Increased renal clearance of antidotes and therapeutic drugs

Different “ normal ” values of blood tests such as BUN and creatinine

Effects of various resuscitative drugs on the uteroplacental circulation and myometrium

Increased potential for gastric aspiration in pregnant women and heightened need for airway protection

Table 39.6 Factors to consider in the clinical

management of the pregnant poison patient

Barbiturates

Marijuana

(Reproduced by permission from Thorp J Management of drug dependency, overdose, and withdrawal in the

obstetric patient Obstet Gynecol Clin N Am 1995;22:131 – 142)

Table 39.8 Time intervals for detecting drugs in

urine after use

Acetaminophen Chloroquine Heptabarbital Procainamide

Amanita toxins Creatinine Meprobamate Quinalbital Ammonia Cyclobarbital Methaqualone Quinidine Amobarbital Demeton Methotrexate Salicylates Barbital Digoxin Methyprylon Secobarbital Bromide Dimethoate Nitrostigmine Theophylline Butabarbital Diquat Paraquat Thyroxine Camphor Disopyramide Parathion Tricyclic antidepressant Carbon tetrachloride Ethanol Pentobarbital Triiodothyronine Carbamazepine Ethchlorvynol Phenobarbital Uric acid Chloral hydrate Glutethimide Phenytoin

Table 39.9 Compounds for which hemoperfusion

is appropriate

Acetaminophen Chloride Gallamine Nitrofurantoin Aluminum Chromate Gentamicin Ouabain

Amanita toxin Cimetidine Glutethimide Paraquat Amikacin Cisplatin Hydrogen ions Penicillin

Amobarbital Colistin Iron desferrioxamine Phosphate Amoxicillin Creatinine Isoniazid Potassium Amphetamines Cyclobarbital Isopropyl alcohol Primidone Ampicillin Cyclophosphamide Kanamycin Procainamide Aniline Cycloserine Lactate Quinidine Arsenic Demeton Lead edetate Quinine Azathioprine Diazoxide Lithium Salicylates Barbital Dimethoate Magnesium Sodium

Bromide Diisopyramide Meprobamate Strontium Butabarbital Ethambutol Methanol Sulfonamides Calcium Ethanol Methaqualone Theophylline Camphor Ethchlorvynol Methotrexate Thiocyanate Carbenicillin Ethionamide Methyldopa Ticarcillin Carbon tetrachloride Ethylene glycol Methylprednisolone Tobramycin Cephalosporins Flucytosine Methyprylon Trichloroethylene Chloral hydrate Fluoride Metronidazole Urea

Chloramphenicol 5 - Fluorouracil MAO inhibitors Uric acid

Table 39.10 Compounds for which dialysis is an

appropriate consideration

death) It is contraindicated in ingestion of caustics and in

hem-orrhagic diathesis It has the advantages that can be performed

immediately on arrival of the patient; takes only 15 – 20 minutes

to complete and facilitates the administration of charcoal

A large gastric tube (Ewald, Lavaculator®, and others) size

36 – 40 F should be passed orally with lubricant Consideration

for intubation needs to be made in patients with depressed

mental status, altered gag refl ex, and seizures or seizure potential

The patient needs to be placed in Trendelenburg or sitting

posi-tion and aspiraposi-tion prior to lavage needs to be made to confi rm

placement of the tube (collect sample for analysis) Lavage is

made with normal saline or water in runs of 1.5 ml/kg (up to

200 ml) until clear and then with at least one more liter Some

recommend slight movement changes of the patient or position

changes to dislodge potential residues of medications or undis-olved pills

Adsorption ( a ctivated c harcoal)

Activated charcoal is a fi nely divided powder made by pyrolysis

of carbonaceous material It consists of small particles with an internal network of pores that adsorb substances It is indicated after gastric emptying procedures (successful or not) and in repeated doses (2 – 4 hours) for drugs with enterohepatic circula-tion (theophylline, digoxin, nor and amitryptiline, salicylates, benzodiazepines, phenytoin, and phenobarbital for example) This effect has been called GI dialysis Activated charcoal may be used immediately after ipecac (does not interfere with its action; some authors actually think this is the best way to give it) and

Neutralizing a gents

In some poisonings a neutralizing agent instead of charcoal is preferable for instillation (see Table 39.13 )

Cathartics

Used as adjunctive treatment with charcoal These agents should

be used only when indicated They are contraindicated in diar-rhea, dehydration, electrolyte imbalances, abdominal trauma, intestinal obstruction and ileus The agent most frequently used

in poisoning treatment is sorbitol because of the onset of action

N - acetylcysteine It is contraindicated in caustic ingestions and

ineffective in ingestion of elemental metals (iron for example),

some pesticides (malathion, DDT), cyanide, ethanol, and

methanol

The typical dose is 30 – 100 g in adults (or 1 g/kg) and is usually

given with a cathartic (50 ml of 70% sorbitol or 30 g of

magne-sium sulfate) in order to accelerate the transit time of the complex

toxin – charcoal A superactivated charcoal formulation, capable

of adsorbing two to three times the conventional capacity of the

charcoal, is available

Table 39.11 Antidotes

Acetaminophen N - Acetylcysteine 140 mg/kg PO, followed by 70 mg/kg/4 h × 17 doses

Anticholinergics (atropine) Physostigmine salicylate 0.5 – 2.0 mg IV (IM) over 2 min every 30 – 60 min prn

Anticholinesterases

(organophosphates)

Atropine sulfate 1 – 5 mg IV (IM, SQ) every 15 min prn Pralidoxime (2 - PAM) chloride 1 g IV (PO) over 15 – 30 min every 8 – 12 h × 3 doses prn Benzodiazepines Flumazenil (British data) 1 – 2 mg IV (for respiratory arrest)

Cyanide Amyl nitrite Inhalation pearls for 15 – 30 s every minute

Sodium nitrite 300 mg (10 mL of 3% solution) IV over 3 min, repeated in half dosage in 2 h

if persistent toxicity Sodium thiosulfate 12.5 g (50 mL of 25% solution) IV over 10 min, repeated in half dosage in 2 h

if persistent toxicity Digoxin Antidigoxin Fab fragments —

Ethylene glycol Ethanol 0.6 g/kg ethanol in D5W IV (PO) over 30 – 45 min, followed initially by

110 mg/kg/hr to maintain blood level of 100 – 150 mg/dL Extrapyramidal signs Diphenhydramine HCl 25 – 50 mg IV (IM, PO) prn

Benztropine mesylate 1 – 2 mg IV (IM, PO) prn Heavy metals (arsenic, copper,

gold, lead, mercury)

Calcium disodium edetate (EDTA) 1 g IV (IM) over 1 h every 12 h Dimercaprol (BAL) 2.5 – 5.0 mg/kg IM every 4 – 6 h Penicillamine 250 – 500 mg PO every 6 h Heparin Protamine 1 mg/100 units heparin and for every 60 min after heparin, halved dose Iron Desferrioxamine mesylate 1 gIM (IV at a rate of ≤ 15 mg/kg/hr if hypotension) every 8 h prn (maximum

80 mg/kg in 24 h) Isoniazid Pyridoxine Gram per gram ingested; 5 g, if INH dose unknown

Magnesium sulfate Calcium glutamate 2 – 3 g IV over 5 min (in 30 - mL D10)

Methemoglobinemia (nitrites) Methylene blue 1 – 2 mg/kg (0.1 – 0.2 mL/kg 1% solution) IV over 5 min, repeated in 1 h prn Opiates/narcotics Naloxone HCl 0.4 – 2.0 mg IV (IM, SQ, ET) prn

Warfarin Phytonadione/vitamin K 0.5 mg/min IV (in NS or D5W)

2 - PAM, pralidoxime; ET, endotracheal; IM, intramuscularly; INH, isoniazid; NS, normal saline; PO, by mouth; prn, as circumstances may require; SQ, subcutaneously (From Thorp J Management of drug dependency, overdose, and withdrawal in the obstetric patient Obstet Gynecol Clin N Am 1995;22:222 – 228; and Roberts JM Pregnancy related hypertension In: Creasy RK, Resnick R, eds Maternal - fetal Medicine: Principles and Practice, 3rd edn Philadelphia: WB Saunders, 1994:804 – 843.)

Table 39.12 Indications for ipecac syrup

Gastric concretion formation

Salicylates

Meprobamate

Barbiturates

Glutethimide

Gastric emptying delay (pregnancy)

Tricyclics

Narcotics

Salicylates

Conditions producing adynamic ileus

Table 39.13 Poisoning in which a specifi c neutralizing agent is preferable to

activated charcoal

Mercury Sodium formaldehyde (20 g) converts HgCl to

less soluble metallic mercury Iron Iodium bicarbonate (200 – 300 mL) converts

ferrous iron to ferrous carbonate Iodine Starch solution (75 g of starch in 1 L of water;

continue until aspirate is no longer blue) Strychnine, nicotine, quinine,

physostigmine

Potassium permanganate (1:10 000)

Table 39.14 Substances most frequently involved in adult exposures ( > 19

years)

Substance No % of all adult

exposures

As cause of mortality

Analgesics 92 245 13.3 1

Sedatives/hypnotics/antipsychotics 67 946 9.8 3

Cleaning substances 66 384 9.5 12

Antidepressants 55 429 8.0 2

Bites/envenomations 55 145 7.9 19

Alcohols 37 451 5.4 6

Food products, food poisoning 35 860 5.2 20

Cosmetics and personal care

products

33 511 4.8 18 Chemicals 31 738 4.6 10

Pesticides 31 285 4.5 15

Cardiovascular drugs 28 941 4.2 5

Fumes/gases/vapors 27 486 3.9 9

Hydrocarbons 27 419 3.9 16

Antihistamines 19 570 2.8 11

Anticonvulsants 17 851 2.6 7

Antimicrobials 17 683 2.5 14

Stimulants and street drugs 17 423 2.5 4

Plants 17 261 2.5 17

Cough and cold preparations 16 866 2.4 18

(From Litovitz TL, Klein - Schwartz W, White S, et al 2000 Annual report of the

American Association of Poison Control Centers Toxic Exposure Surveillance

System Am J Emerg Med 2001;19(5):337 – 95.)

Table 39.15 Stages of acetaminophen toxicity

Phase Time Symptoms

I 0 – 24 h Gastrointestinal symptoms (anorexia, nausea, vomiting),

malaise, diaphoresis

II 24 – 48 h Clinical improvement, but abnormal liver function tests III 72 – 96 h Peak hepatotoxicity with encephalopathy, coagulopathy,

and hypoglycemia

IV 7 – 8 days Death, or recovery from hepatic failure (begins within 5

days and usually progresses to complete resolution within 3 months)

Table 39.16 Criteria for consideration of admission to the intensive care unit

Mechanical ventilation required Vasopressor support necessary Arrhythmia management or need for hemodialysis Signs of severe poisoning

Worsening signs of toxicity Predisposing underlying medical conditions Potential for prolonged absorption of toxin Potential for delayed onset of toxicity Invasive procedures or monitoring needed Antidotes with potential for serious side effects Suicidal patients requiring observation

(less than an hour), duration of effect (8 – 12 hours) and no inter-action with charcoal Oil cathartics are contraindicated because they can be aspirated and can increase the absorption of hydro-carbons Complications can result from overaggressive use (fl uid and electrolyte imbalances) [35]

Whole - b owel i rrigation

tube with the purpose of cleaning the bowel of whole or undis-olved pills May be helpful in clearing the GI tract of iron, lead, zinc lithium, delayed - release formulations not adsorbed

by charcoal, very delayed onset of treatment or drug packets

of illicit drugs [36] The procedure takes 3 – 5 hours and may be complicated by bowel perforation or obstruction, ileus or GI hemorrhage

SPECIFIC AGENTS

More than 250 000 drugs and commercial products are available for ingestion [37,38] Table 39.14 lists the most frequent causes of morbidity and mortality from poisoning in adults in the USA [2] Figure 39.3 details the classes of drugs most frequently used in suicide attempts among 1085 pregnant women in 1999 [16]

Serum h alf - l ife

The serum half - life of acetaminophen in pregnancy is 3.7 hours, and the pharmacokinetics (absorption, metabolism, and renal clearance) are similar in the pregnant and nonpregnant states [41,42]

Lethal d osage

The lethal dosage is in excess of 150 mg/kg or 15 g in the healthy adult and primarily involves hepatotoxicity [40,43] The lethality

of acetaminophen is not only directly related to the dose, but to other factors such as age, nutritional status, and other com-pounds ingested Renal failure, myocardial depression, and pan-creatitis also have been observed in acute overdoses

Maternal c onsiderations

In general, the primary short - term problem of acetaminophen overdose is hepatocellular necrosis, which peaks at 72 – 96 hours Cardiac, renal, and pancreatic complications rarely occur, but appropriate monitoring should be instituted Perhaps the most serious long - term consequence is residual liver damage

Symptoms

Nausea; vomiting; anorexia; right upper quadrant pain The symptoms of acetaminophen toxicity have been divided into four stages (Table 39.15 )

Signs

Icterus; right upper quadrant abdominal tenderness; lethargy; evidence of bleeding

Diagnostic t ests

Blood: acetaminophen level (at 4 or more hours after ingestion); transaminases (elevated); lactic dehydrogenase (LDH) (elevated); prothrombin time (prolonged); amylase (elevated); lipase

The general characteristics and management of selected toxic

exposures during pregnancy are discussed in further detail in the

sections below, arranged in alphabetical order by drug name

In the USA all consults and reports of exposure can be made

to the number: +1 - 800 - 222 - 1222

Acetaminophen

Toxicology

• Common proprietary names: Alka - Seltzer ® (some

presenta-tions); Anacin ® ; Benadryl ® (some presentapresenta-tions); Comtrex ® ;

Contac ® ; Coricidin ® ; Darvocet; Dimetapp ® ; Drixoral ® ; Esgic ® ;

Excedrin (aspirin - free) ® ; Fioricet ® ; Goody ’ s Body Pain Relief ® ;

Lortab ® ; Midol ® ; Midrin ® ; Nyquil ® ; Pamprin ® ; Panadol ® ;

Parafon ® ; Percocet ® ; Phenaphen ® ; Robitussin ® ; Sudafed ® ;

Tavist ® ; Thera - Flu ® ; Triaminic ® ; Tylenol ® , Tempra ® ; Unisom ® ;

Vicodin ® ; Wygesic ®

• FDA classifi cation: B [39]

• As a cause of morbidity: 1 (other analgesics included) [2]

• As a cause of mortality: 1 (other analgesics included) [2]

• Most frequent route of exposure: ingestion

• Most frequent reason for exposure: unintentional overdose

Metabolism

Acetaminophen is metabolized in the liver to nontoxic sulfate

(52%) and glucuronide (42%) forms and then excreted by the

kidneys Approximately 4% is metabolized by the hepatic

cyto-chrome oxidase P450 system, resulting in a toxic reactive

inter-mediate This toxic metabolite is conjugated with glutathione and

excreted in the urine as nontoxic mercaptourate Two percent of

acetaminophen is excreted unchanged In an overdose, the

hepatic glutathione stores are depleted and the toxic

intermedi-ates become covalently bound to hepatic cellular proteins,

result-ing in hepatocellular necrosis [40]

Acetaminophen (alone or combination) NSAIDs

SSRIs Benzodiazepines Miscellaneous

Substances most frequently involved

15.2

33.3

35.5

Figure 39.3 Suicide attempts during pregnancy by

poisoning or overdose: report from a National Database, 1999 NSAIDs, nonsteroidal anti infl ammatory drugs; SSRIs, selective serotonin reuptake inhibitors