Overdose, Poisoning and Envenomation During Pregnancy 519 Suspected overdose or poisoning in pregnancy Conscious Unconscious ABC Consider trauma Patent AWY Spontaneous breathing Pulse Altered mental status O 2 + “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? No Yes 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, Chapter 39 520 Obstructed AWY No spontaneous breathing No pulse Establish patent AWY Assisted ventilation CPR ACLS protocols Stat consult with obstetrics/gynecology Stable Unstable Determine viability Consider emergent C/S Continue CPR/ACLS protocols Determine GA/viability Monitor: vitals/EKG/SaO 2 /fetus H&P Drug ID/OD mechanism ICU admission Response No response 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 of a poisoning or overdose (see Tables 39.10 and 39.11 ) [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. Overdose, Poisoning and Envenomation During Pregnancy 521 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: Chapter 39 522 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 Emesis Diarrhea Diaphoresis 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. Overdose, Poisoning and Envenomation During Pregnancy 523 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 Chapter 39 524 Table 39.7 Quantitative toxicology testing. Test Time to sample postingestion Repeat sample Implication positive test Acetaminophen 4 h None Blood level 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 Lithium 2 – 4 h 4 h 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 Repeated activated charcoal; hemoperfusion Phenytoin 1 – 2 h 4 – 6 h Supportive care Repeated activated charcoal Salicylates 2 – 4 h 2 – 4 h Serum and urine alkalinization Repeated activated charcoal, hemodialysis 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. Drug Detectable after use Alcohol 24 h Amphetamines 48 h Barbiturates Short - acting 48 h Long - acting 7 days Benzodiazepines 72 h Cocaine 72 h Marijuana Single use 72 h Chronic use 30 days (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. Overdose, Poisoning and Envenomation During Pregnancy 525 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 Ammonia Citrate Iodide Phenobarbital 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 Borate Diquat Mannitol Streptomycin 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 Chlorate Fosfomycin Neomycin Water 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 aspiration 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 Chapter 39 526 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. Poison Antidote Dosage 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) Carbon monoxide Oxygen 100%, hyperbaric 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) Chelator 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) Methanol Ethanol See ethylene glycol 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.) Overdose, Poisoning and Envenomation During Pregnancy 527 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 Consists of the administration of polyethylene - glycol at a rate of 500 – 2000 ml/hour orally or through a nasogastric 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] . Chapter 39 528 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 (ele- 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 presentations); 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 8.8 7.1 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. . 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 . 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. spontaneous breathing No pulse Establish patent AWY Assisted ventilation CPR ACLS protocols Stat consult with obstetrics/ gynecology Stable Unstable Determine viability Consider emergent C/S Continue CPR/ACLS