Overdose, Poisoning and Envenomation During Pregnancy 539 gradual withdrawal of the agent [102] . An alternative treatment for seizure control is phenobarbital. Monitoring Vital signs/mental status/oxymetry/intermittent fetal heart rate monitoring. Repeat drug levels not indicated. Therapeutic g oals Asymptomatic patient; normal mental status without benzodiaz- epine antagonism (at least more than 4 hours since last dose of fl umazenil); normal bowel sounds; completed decontamination procedures; no evidence of coingestion; reassurant fetal condi- tion; consults completed. Discharge c onsiderations Investigate chronic use/abuse of benzodiazepines. Consider drug counselor, psychiatry, and social worker evaluations. As part of the patient ’ s ongoing care, drug rehabilitation should be considered. Follow - u p Notify primary care physician (obstetrician, psychiatry). Clinical follow - up with a social worker, obstetrician, and psychiatrist is warranted [102,109,113] . Carbon m onoxide Toxicology Carbon monoxide (CO) is a tasteless, colorless, odorless gas. It is a by - product of cigarette smoking (the most common source of CO exposure), automobile exhaust, opens fi res, kerosene stoves, and heating systems (heaters or furnaces) in improperly venti- lated areas. An unusual source of CO poisoning is paint removers that contain methylene chloride, which can be absorbed by the respiratory tract and be metabolized to CO over a delayed period of time. CO is absorbed rapidly through the respiratory tract. Hemoglobin ’ s affi nity for CO is 250 – 300 times greater than for oxygen. In addition it binds to myoglobin with a 40 - fold greater affi nity than that of oxygen, which may be related to some of the cardiac effects seen in this type of poisoning [114,115,116] . • Examples: fi res, motor vehicle fumes, heat stoves • As a cause of morbidity: 13 * [2] • As a cause of mortality: 9 * [2] • Main route of exposure: inhalation • Reasons for exposure: unintentional; intentional (suicide attempt) Maternal c onsiderations Maternal signs and symptoms relate to the reduction of the oxygen carrying capacity of hemoglobin as it is bound by CO Teratogenic p otential Majority of the evidence does not support it. The teratogenic potential of these agents generally falls in category C/D/Xm [39] . In one study, chlordiazepoxide (category D) was associated with a fourfold increase in congenital anomalies [103] . However, others have not found such associations [104,105] . Diazepam (category D) has been reported to be associated with oral clefts [106,107] . More recently retrospective and prospective studies have been unable to fi nd an association between diazepam use during pregnancy and facial clefts or other defects in the off- spring, even among those patients exposed to high doses [108,109,110] . Fetal d istress p otential Only in the presence of severe maternal toxicity and secondary to maternal hypovolemia or hypoxemia. Indications for d elivery Obstetric indications. Caution is suggested when interpreting fetal assessment techniques (electronic fetal monitoring and bio- physical profi le). Postnatal Potential for neonatal hypotonia, impaired temperature regula- tion, lethargy, and apnea needing resuscitation measures [111] . Risk of neonatal withdrawal may produce seizures 2 – 6 days after delivery. High - dose or recent use prior to delivery has been asso- ciated with birth depression and withdrawal stigmata in neonates, the latter occurring up to 6 days after delivery [110,112] . Management c onsiderations Wide therapeutic index; low lethal potential if isolated poison. Investigate the possibility of coingestion (particularly alcohol and tricyclics). The therapeutic goal with benzodiazepine overdose is supportive care and gradual withdrawal of the benzodiazepines in long - term abusers. Supportive Respiratory assistance may be required; crystalloid infusion to maintain adequate volume; dopamine and norepinephrine infu- sions may be required in refractory hypotension. If severe toxicity is present, respiratory and cardiovascular support may be needed. Specifi c m easures/ a ntidotes • T h e fi rst step is gastric emptying followed by activated charcoal and cathartics (50 – 60 g of activated charcoal in sorbitol: 1 g/kg) and repeated (25 – 30 g) every 4 hours (the sorbitol added only every 12 hours). Induced emesis not recommended. • Flumazenil (Romazicon ® ; category C); give if vital signs are no stable, tricyclic coingestion excluded and if no history of chronic use or abuse of benzodiazepines (possibility of inducing seizures) (see Table 39.3 ). • If the patient develops seizures, IV injection of benzodiazepine may be required to terminate withdrawal seizures, followed by a * Includes vapors, fumes, and other gases. Chapter 39 540 Fetal c onsiderations CO crosses the placenta and has a higher affi nity for fetal than adult hemoglobin. As a result, fetal concentrations of CO are 10% to 15% higher than those in the mother. Maximal concentrations of CO in fetal blood are found after about 4 hours of the expo- sure. Maternal COHb levels are a poor predictor of fetal toxicity and maternal wellbeing might be misleadingly reassuring of the fetal condition [118,119] . Signs Nonreassuring fetal condition: decreased variability; decelera- tions [120] . Teratogenic p otential Although the teratogenic potential is unclear, fetal brain damage and subsequent developmental delays may be seen [116,121] . Some cases of CO poisoning severe enough to cause maternal symptoms have been associated with premature birth, neurologic defi cits and anomalies (CNS, skeletal, clefts) in surviving infants [116,119,120,122] . Fetal d istress p otential Yes; high. Increased risk of fetal demise with chronic exposure [123] . Fetal death or permanent neurological damage can occur in the absence of severe maternal symptoms [119,120] . The fetal prognosis is diffi cult to estimate. Indications for d elivery Obstetric indications; nonreassuring fetal condition despite ade- quate maternal therapy. Management c onsiderations The half - life of CO in a healthy adult breathing 21% oxygen is 4 – 5 hours. This time is reduced to 80 – 90 minutes when breathing 100% oxygen. Hyperbaric oxygen (100%) reduces the half - life to less than 30 minutes [115] . Pulse oxymetry inaccurately refl ects oxygen saturation (cannot differentiate carboxyhemoglobin from oxyhemoglobin) [61] . Given the fetal considerations above, a more aggressive management approach is indicated during preg- nancy [117] . Specifi c m easures/ a ntidotes • Oxygen (100%) should be administered via a tight - fi tting non - rebreathing mask and continued for a period equal to fi ve times the duration that it took for the maternal CO levels to normalize [117,124] . • Hyperbaric oxygen is indicated if COHb is greater than 15% (versus more than 40% in the nonpregnant state), signs of non- reassuring fetal condition any neurologic signs in the mother (altered mental status; coma; focal neurologic defi cits; seizures) or history of loss of consciousness [56,61,118] . Monitoring Admit if COHb greater than 10% in pregnant patients; impaired mentation or metabolic acidosis with any presenting COHb level. (Table 35.24 ). Given their higher oxygen extraction ratios the heart and CNS are responsible for most of the presenting features [115] . Symptoms Depends on concentration (%COHb): headache; shortness of breath; nausea; dizziness; dim vision; weakness; chest pain (see Table 39.24 ). Signs Vasodilation; confusion; disturbed judgement; tachypnea; tachy- cardia; collapse; dysrhythmias; hypotension; non - cardiogenic pulmonary edema; myocardial ischemia; coma; seizures; Cheyne – Stokes respirations; “ cherry - red ” discoloration is clini- cally rare. Diagnostic t ests EKG: sinus tachycardia, ST depression, atrial fi brillation, pro- longed PR and QT intervals; AV or bundle branch block.; ABGs: %COHb (correlates with symptoms and signs). A metabolic aci- dosis implies signifi cant exposure with resultant tissue hypoxia Others: complete blood count, transaminases, electrolytes, creati- nine, urinalysis. Chest X - ray (if respiratory symptoms). Head CT (if coma, seizures, or focal neurologic defi cits). If the patient was rescued from a fi re, consider obtaining a cyanide level (hydrogen cyanide is a common fi re intoxicant). Short - t erm p roblems Short - term concerns with CO poisoning include myocardial isch- emia or infarction, rhabdomyolysis, renal failure, pulmonary edema, blindness, and hearing loss. Long - t erm p roblems Delayed CNS toxicity (perivascular infarction; demyelination of basal ganglia) on comatose or acidotic patients on arrival. Delayed problems include CNS toxicity due to perivascular infarction and demyelination of basal ganglia. This is usually seen in patients who are comatose or acidotic on arrival to the hospital [115,117,118] . Table 39.24 Signs and symptoms of carbon monoxide overdose. * Signs Symptoms Vasodilation Headache Disturbed judgment Shortness of breath Collapse Nausea Coma Dizziness Convulsions Visual disturbances Cheyne – Stokes respiration Weakness * Signs and symptoms will vary depending on the concentration of carboxyhemoglobin. Overdose, Poisoning and Envenomation During Pregnancy 541 • As a cause of mortality: 4 * [2] • Most frequent route of exposure: inhalation • Most frequent reason for exposure: unintentional overdose Maternal c onsiderations The fetus, infant, and pregnant woman experience slower metab- olism and elimination [127,130] . The peak effects of cocaine in nonpregnant women occur within 3 – 5 minutes IV or at 60 – 90 minutes orally. Symptoms Mild - to - moderate toxicity is manifested by nausea, vomiting, abdominal pain, headache, apprehension, dysphoria, confusion, and hallucinations [60] . Other symptoms include: anxiety, dizzi- ness, chest pain, respiratory diffi culty, and palpitations. Specifi c during pregnancy: threatened preterm labor; vaginal bleeding; preterm premature rupture of membranes [131] . Signs Agitation; altered mental status (up to frank psychosis); tachycar- dia; hypertension; hyperthermia; mydriasis; tachypnea; diapho- resis; hyperactive bowel sounds; pulmonary edema; uterine contractions (up to tetany); vaginal bleeding. Severe toxicity is manifested by psychotic behavior, seizures, coma, ventricular arrhythmias (myocardial ischemia/infarction), hypertension (severe), circulatory collapse, pulmonary edema and respiratory depression, ARDS ( “ crack lung ” ), pneumomediastinum, rhabdo- myolysis, hyperthermia, and hepatic infarction [129] . Death may occur rapidly from respiratory depression and/or circulatory collapse [114] . Diagnostic t ests Rectal and vaginal exams indicated to rule out occult drug packing. Blood: complete blood count; electrolytes and glucose; creatinine and blood urea nitrogen; creatine phosphokinase (CPK) and isofractions; myoglobin; troponin I (most specifi c in cocaine users); amylase; lipase and liver - function tests. Urine: microhematuria; myoglobinuria; EKG: tachycardia; ischemia; ST elevation (up to 43% of patients with chest pain); acute myocardial infarction. Chest X ray: pulmonary edema, pulmonary infarction. Consider other X rays surveys if history of recent traveling (possibility of body packing). CT and lumbar puncture if seizures. Cocaine is detectable in blood within 24 hours of ingestion and in urine for several days (see Table 39.8 ). Short - t erm p roblems Arrhythmias; myocardial infarction; seizures; pulmonary infarc- tion; intracranial hemorrhage or infarcts; visceral infarcts; preterm delivery; abruptio placentae. Cerebral infarction is more common among alkaloidal cocaine users, and hemorrhagic stroke is seen more frequently in IV cocaine hydrochloride use. Cerebral catastrophes can occur within minutes of the use of cocaine [132] . Any pregnant woman who is exposed to CO and has a potentially viable fetus should be monitored for a minimum of 12 hours. If cardiovascular complications are present, she should be admitted to the ICU. Such complications are expected in nonpregnant patients with a COHb greater than 15%. This level is lower in pregnant women (COHb 10%). Additionally, each patient ’ s mental state and acid - base status should be monitored. Therapeutic g oals COHb < 5% and no symptoms. Reassuring antenatal fetal condi- tion as appropriate according to the gestational age. Discharge c onsiderations Identifi cation (and avoidance) of source of exposure if not obvious (social work consult may be helpful). Suicidal potential evaluation (psychiatry consult) if circumstances suggest such possibility. Counsel on potential long - term effects on fetus. Follow - u p Establish. Consider follow - up of intrauterine growth and fetal anatomy [61,115,117,118] . Cocaine Toxicology Cocaine is a naturally occurring agent that is legally available for use as a topical anesthetic. It is more commonly used illegally as a CNS stimulant with a street - sample purity of 15 – 60% [125] . It is principally used in one of two forms: either as the hydrochlo- ride salt ( “ snorted ” intranasal or IV) or as an alkaloid ( “ crack, ” “ free base ” ). Illegally produced cocaine is frequently adulterated with foreign substances such as lactose, mannitol, lidocaine, and/ or procaine [125] . Cocaine is absorbed through mucous membranes and can be inhaled, smoked, swallowed, injected IV, IM, or subcutaneously, or placed in the vagina or rectum [126] . Lethal overdoses can be taken via any route but are more likely with parenteral use or “ freebasing ” (smoking purifi ed cocaine) or by the accidental rupture of a container of cocaine in “ body packers ” [127] . Cocaine is a sympathomimetic with direct cardiovascular stim- ulant activity that causes hypertension and vasoconstriction (see Table 39.4 ). It has both direct and indirect cardiotoxic effects (sensitizing the myocardium to epinephrine (adrenalin) and nor- epinephrine) [128] . It is detoxifi ed by liver and plasma cholines- terase. Though the biologic half - life is 0.5 – 1.5 hours vascular catastrophes can occur several weeks after its use [129] . • Examples/other names: “ crack ” ; “ rock ” ; “ blow ” ; “ snow ” ; “ liquid lady ” : alcohol+cocaine; “ speedball ” : heroine+cocaine • FDA classifi cation: X (C if used as a local anesthetic) [39] • As a cause of morbidity: 17 * [2] * Includes other stimulants and street drugs. Chapter 39 542 Cocaine has been shown to be associated with signifi cantly increased perinatal distress hypotonia and signifi cantly lower 5 - minute Apgar scores [135] . Postnatally, perinatal, or newborn cerebrovascular accidents may be found in neonates with a posi- tive cocaine screening test [135,141] . The pathology of these inju- ries may include, intraventricular hemorrhage, echodensities known to be associated with necrosis, and cavitary lesions par- ticularly in the basal ganglion, frontal lobes, and posterior fossa [69] . The risk of necrotizing enterocolitis is also higher among neonates exposed to cocaine [142,143] . Management c onsiderations The initial therapeutic goal is to stabilize and support the patient for 24 hours. In addition, most patients require symptomatic management of specifi c problems [60] . In selected circumstances, overdose victims or users will suffer from seizures, arrhythmias, hyperthermia, hypertension, hypotension, behavioral problems, and rhabdomyolysis. Supportive Hydration (forced alkaline diuresis if myoglobinuria detected or if creatinine elevated on arrival) to maintain the urine output at ≈ 3 ml/kg/h. Physical restraints may be required for patients with signifi cant psychomotor agitation as a temporizing measure to facilitate chemical sedation [129] . Admit to an ICU if seizures, ventricular arrhythmias, or hyperthermia. Specifi c m easures/ a ntidotes • Activated charcoal and whole bowel irrigation may decrease absorption if history of ingestion ( “ stuffi ng ” ). • Benzodiazepines (diazepam 5 – 10 mg IV or lorazepam 2 – 4 mg IV) are the fi rst line of treatment for supraventricular arrhyth- mias, hypertension, ischemic chest pain, behavioral problems, and seizures. • Lidocaine (1.5 mg/kg IV bolus followed by infusion of 2 mg/min) and alkalinization are the treatments of choice for ventricular arrhythmias. Defi brillation is indicated if hemodynamically unstable. Avoid use of β - blockers for the treatment of arrhythmias or hypertension (may worsen hypertension and coronary vasoconstriction, and induce seizures). • Phenobarbital (25 – 50 mg/min up to 10 – 20 mg/kg) is the second choice for seizures and propofol the third. Status epilepticus may require paralysis and ventilation. • In severe cases of hypertension (after diazepam or lorazepam), the use of nitroprusside or phentolamine may be needed for control. • Hyperthermia is managed with external cooling. This is espe- cially important in pregnancy to protect the fetus. • In cases of hypotension, treatment with IV fl uids should be initiated. For refractory hypotension, dopamine or norepineph- rine may be required. Long - t erm p roblems Malnutrition; sexually transmitted diseases; growth restriction; stillbirth; pre - eclampsia; risk for fetal neurodevelopmental delay (when cocaine is a component of a polydrug abuse). Long - term problems include the aftermath of intracranial hemorrhage or infarction and rhabdomyolysis [58,129,132] . Fetal c onsiderations Cocaine has high water and lipid solubility, a low molecular weight, and a low degree of ionization, all of which facilitate its passage across the placenta and into the fetus [130] . Cocaine infusion is associated with a decrease in uterine blood fl ow, leading to fetal hypoxic damage in the short term and to intra- uterine growth retardation over time [128,133] . In pregnancy, there is a signifi cant increase in the incidence of preterm labor (25 – 30% vs 12 – 17%) and anemia (57 vs 39%) [134] . There is also a higher incidence of pregnancy - induced hypertension (25 vs 4%) [134] and abruptio placentae [135] . Meconium aspiration, preeclampsia, premature rupture of mem- branes, and fetal distress are all increased [134,136] . Signs Fetal tachycardia; decreased beat - to - beat variability; bradycardia; late decelerations [127] . Teratogenic p otential Controversial data; there is no agreement on whether cocaine increases the risk of structural malformations. The teratogenic potential for cocaine falls into category C. For nonmedicinal use, cocaine is classifi ed as category X [39] . Urinary tract malforma- tions (hydronephrosis, hypospadias, prune - belly syndrome), congenital heart defects (transposition of the great vessels, hypo- plastic right - heart, ventricular septal defect, patent ductus arte- riosus), and skull defects (exencephaly, encephalocele) have been associated with cocaine use in pregnancy [137,138] . Potential for growth restriction and restriction of fetal brain growth [138] . Fetal d istress p otential Yes; secondary to uterine hyperstimulation, uterine vasoconstric- tion, abruption placentae, uterine rupture, and/or maternal sei- zures. Up to 13% of women who used cocaine during pregnancy develop an abruption, which may be sudden, unpredictable, and catastrophic. The incidence of abruptio placentae - related still- births in cocaine users can be 10 times higher than that of drug - free control women [130,135,139,140] . Indications for d elivery Nonreassuring fetal condition despite adequate supportive maternal care; severe abruptio placentae and severe growth restriction. Postnatal Risk of withdrawal syndrome (seizures; cardiovascular collapse); antenatal notifi cation of the neonatology service recommended. Overdose, Poisoning and Envenomation During Pregnancy 543 subject of debate [145] . Ethanol is primarily ( > 90%) eliminated by the liver via enzymatic oxidation, with 5 – 10% excreted unchanged by the kidneys, lungs, and sweat. Ethanol is metabo- lized via at least three different pathways: alcohol dehydrogenase (ADH) located in the cytosol of the hepatocytes; the microsomal ethanol - oxidizing system (MEOS or CYP2E1), located in the endoplasmatic reticulum; and the peroxidase - catalase system, associated with the hepatic peroxisomes [145] . In adults, the average rate of ethanol metabolism is 100 – 125 mg/kg/h (up to 175 in habitual drinkers). As a result of an hourly metabolism of 7 – 10 g, the concentrations of ethanol fall 15 – 20 mg/dl/h with con- siderable individual variation [145] . Clinical presentation may vary with acute and/or chronic ethanol abuse or withdrawal. In addition consumption of illegally produced ethanol ( “ moonshine ” ) can result in a methanol, lead, or arsenic poisoning [145] . Only acute overdosage is considered here. • Examples/other names: alcohol; ethylic alcohol; “ booze ” • FDA classifi cation: D (X if used in large amounts or for pro- longed periods) • As a cause of morbidity: 7 [2] • As a cause of mortality: 6 [2] • Most frequent route of exposure: ingestion • Most frequent reason for exposure: unintentional overdose Maternal c onsiderations Clinical presentation may vary with acute and/or chronic ethanol abuse or withdrawal. Will consider here the acute overdose (see Table 39.22 for treatment of alcohol withdrawal). A systematic approach to the inebriated patient will help the clinician avoid potential pitfalls as they may present to a medical facility with a broad range of diagnostic possibilities and many serious condi- tions [144] . Symptoms With acute alcohol overdosage, the signs and symptoms vary depending on the severity of intoxication and may include euphoria, incoordination, impaired judgment, and altered mental status. Social inhibitions are loosened. As such, aggressive or boisterous behavior is commonly seen. Signs As above plus fl ushed facies, diaphoresis, tachycardia, hypoten- sion, hypothermia, ataxia, abnormal refl exes, nystagmus, altered mental status, mydriasis, impaired judgment and refl exes, and a characteristic breath smell. The presence of an ethylic breath is an unreliable means of ascertaining whether a person is intoxicated or whether ethanol was recently consumed [145] . In severe overdose, bradycardia, hypotension, respiratory depres- sion, hypoglycemia, hypothermia, and coma are seen. Diagnostic t ests Blood work: complete blood count, glucose, electrolytes, blood urea nitrogen, creatinine, transaminases, lipase, prothrombin • In ischemic chest pain, may also use nitroglycerine (0.4 mg sublingually every 5 minutes and IV continuous drip thereafter) and in refractory cases: phentolamine 1 mg IV (repeat in 5 min). • Heparinize if ischemic chest pain (5000 IU IV bolus+1000 I/h infusion). • External cooling is needed to control hyperthermia (neuro - muscular blockade may be needed in severe cases). • Rhabdomyolysis is treated with maintenance and alkalinization of urine fl ow with IV fl uids and sodium bicarbonate infusion (see doses under aspirin poisoning, above). Hemodyalisis may be indicated for renal failure secondary to myoglobinuria. • N o s p e c i fi c antidote available. Monitoring Vitals/mental status/oxymetry/cardiac for at least 24 hours after the exposure. Consider repeat EKGs and cardiac enzymes every 6 hours if signifi cant exposure, risk factors for coronary artery disease or chest pain on arrival. Evaluation may include EKG, BP, temperature, blood gases, chest X - ray, renal and liver function tests, prothrombin and partial thromboplastin times and plate- lets, hemoglobin/hematocrit, and urinalysis for myoglobin. Therapeutic g oals Asymptomatic patient; normal laboratory values; no contractions or bleeding; reassuring fetal condition; more than 24 hours of observation. Consults obtained (see below). Disposition c onsiderations Drug counselor, psychiatry, and social worker consults recom- mended. Evaluate for sexually transmitted diseases. Follow - u p Establish since a high proportion of these patients do not have (or have an erratic) prenatal care. Consider follow - up of fetal growth. On discharge, the patient will need clinical follow - up with a social worker, obstetrician, or psychiatric service. Fetal follow - up will require ultrasound evaluations to monitor fetal growth and anatomy. Once the fetus is potentially viable, assess- ment of fetal well - being is warranted. In addition, evaluation of the newborn for cerebral, urologic, and GI sequelae is indicated [61,127,129] . Ethanol Toxicology Ethanol is the most frequently ingested toxin in the world [144] . Ethanol is a colorless, odorless, volatile, liquid hydrocarbon. It is fully miscible in water and is lipid - soluble. It diffuses readily across lipid membranes, accounting for its multiorgan effects [145] . It is rapidly absorbed from the GI tract with approximately 20% absorbed in the stomach and the remainder in the small intestine. No specifi c receptor for ethanol has been identifi ed and the mechanism of action leading to intoxication remains the Chapter 39 544 microcephaly. Diagnosis may be delayed until 9 – 12 months of age [148] . Fetal d istress p otential Not likely unless the acute intoxication is complicated by trauma or maternal respiratory compromise (aspiration or depression). Transient nonreactivity to fetal movements or to external stimuli has been described in acute intoxications [146] . Yet a threefold increase in the risk of stillbirth has been described for women who drink more than four drinks per week during pregnancy [149] . Indications for d elivery Obstetric indications. Allow metabolism of alcoholic load before acting upon nonreassuring tracings of electric fetal monitoring. Postnatally Postnatally, the potential for withdrawal syndrome in neonates should be considered and the infant carefully monitored [148] . Because ethanol passes freely into breast milk, there is the poten- tial for sedation and dose - related psychomotor and developmen- tal delay in breast - fed infants. For ethanol, which cannot be measured in hair or meconium, accumulation of its fatty acid ethyl esters in meconium is emerging as a promising test for heavy maternal drinking in the second part of pregnancy [150] . Maternal ethanol use during pregnancy has been associated with an increase in childhood leukemia, particularly for the develop- ment of acute nonlymphocytic leukemia [148,151] and possibly other neoplasias. Management c onsiderations With ethanol overdose, the therapeutic goal is to prevent acute complications in the fi rst 6 – 8 hours following admission. Elimination occurs at a fi xed rate. Supportive Protection of the airway because of the possibility of gastric aspi- ration or respiratory depression. Treatment of coma and seizures if they occur. If arriving with altered mental status immediate investigation for reversible causes (hypoxemia, hypoglycemia, and opioid intoxication) is warranted. Supplemental oxygen, intravenous dextrose (0.5 – 1 mg/kg), thiamine (100 mg), and nal- oxone should be administered if clinically indicated (see Table 39.3 ) [145] . Specifi c m easures/ a ntidotes • Although the fi rst step in ethanol overdose is decontamination, its use will depend on the proximity to the ingestion. Emesis is not indicated unless a substantial ingestion has occurred within minutes of presentation or other drug ingestion is suspected. Gastric lavage is indicated if intake of large amounts occurred within 30 – 45 minutes of presentation. Charcoal does not effi - ciently adsorb ethanol; it may be useful if other drugs were (or suspected to be) ingested. time, magnesium, calcium, ketones, acetone, ammonia, and alcohol level. Patients with anion gap metabolic acidosis should have urine ketones and serum lactate concentration analysis as metabolic acidosis resulting from ethanol intoxication is uncom- mon (see Table 39.20 ). A high acetone level may suggest isopro- panol intoxication. Clinically signifi cant lactic acidosis due to ethanol can be related to a seizure, infection, hypoxia, or hypo- perfusion states [144] . Consider arterial blood gases if altered mental status or respira- tory distress, depression, or hypoxemia suspected on pulse oxy- metry. Consider a drug screen if altered mental status or history of trauma. If aspiration is suspected, a chest x - ray should be obtained. History of head trauma and comatose patients with concentrations of alcohol under 300 mg/dl and those with levels above 300 mg/dl who fail to improve after a period of observation should have a head CT, followed by a lumbar puncture if needed [145] . Short - t erm p roblems The most important short - term problems of a severe overdose are respiratory depression, pulmonary aspiration, hypoglycemia, and coma. Less frequently, GI bleeding, atrial arrhythmias, or rhabdomyolysis are encountered. Long - t erm p roblems Long - term problems are both organic and social. Organic prob- lems include pancreatitis, hepatitis, cirrhosis, hepatic encepha- lopathy, portal hypertension, GI bleeding, anemia, thiamine defi ciency, alcoholic ketoacidosis, systemic hypertension, decreased resistance to infection, hypomagnesemia, hypokale- mia, and hypophosphatemia. Alcohol abuse is an important risk factor for intracerebral hemorrhage, particularly hemorrhagic stroke [58] . Alcohol is the leading cause of non - ischemic cardio- myopathy [58] . Social problems are manifested by malnutrition, isolation, depression, or suicide attempts. Fetal c onsiderations Signs Decrease in fetal heart rate accelerations and variability (non - reactivity of electronic fetal heart rate tracing); suppression of fetal breathing movements, electrocorticographic activity, and electro - oculographic activity [39,146,147] . Teratogenic p otential Fetal alcohol syndrome (FAS): (a) craniofacial dysmorphology (short palpebral fi ssures, hypoplastic philtrum, fl attened maxilla); (b) prenatal and postnatal growth defi ciencies (body length more than weight); (c) CNS dysfunction (including mental retar- dation and behavioral abnormalities); and (d) major organ system abnormalities (mainly cardiac, urogenital and hemangio- mas) in 30 – 40% and probably more of the infants exposed. Other features are: ptosis, strabismus, epicanthal folds, myopia, microphtalmia, short upturned nose, posterior rotation of ears, poorly formed concha, hypotonia, poor coordination, and Overdose, Poisoning and Envenomation During Pregnancy 545 local dysfunction of the GI, hepatic, cardiovascular and CNS [152,153] . • Examples/common names: ferrous gluconate; ferrous fuma- rate; ferrous sulfate/Chromagen ® ; Feosol ® , Fergon ® ; Ferro- Folic ® ; Ferro-Grad ® ; Ferlecit ® ; Iberet ® ; Irospan ® ; Megadose ® ; Nephrofer ® ; Nephrovite ® ; Prenate ® ; Slow Fe ® ; Trinsicon ® • FDA classifi cation: A • As a cause of morbidity: 2 * [67] • As a cause of mortality: rare • Most frequent route of exposure: ingestion • Most frequent reason for exposure: intentional overdose; sui- cidal gesture Maternal c onsiderations Four physiopathologic stages of iron overdose have been recog- nized: (a) direct corrosive insult to the intestinal mucosa; (b) a quiescent phase (which may not occur in severe overdoses); (c) systemic organ failure, characterized by a worsening of the GI hemorrhage, cardiovascular collapse, and severe metabolic acido- sis; (d) GI sequelae as a result of intestinal scarring weeks after the ingestion [152,154] . Symptoms Indigestion; abdominal pain; nausea; vomiting; hematemesis; diarrhea, hematochezia. Signs As above+bloody stools; tachycardia; fever; lethargy; shock and acidosis in severe cases. Rarely icterus, hypoglycemic symptoms, coagulopathy. Diagnostic t ests Complete blood count: leukocytosis; anemia, or hemoconcentra- tion. Serum iron levels: normal: 50 – 175 µ g/dl; mild - to - moderate toxicity generally manifests at levels of 350 – 500 µ g/dl. Hepatotoxicity usually is observed at levels higher than 500 µ g/dl. Levels higher than 1000 µ g/dl are associated with severe toxicity and potential mortality. Caveats: A single iron concentration may not represent a peak concentration; repeat every 2 hours for the fi rst 6 – 8 hours. Samples drawn too early or too late post - overdose may be unreliable. Other tests: serum electrolytes (anion gap metabolic acidosis; see Table 39.20 ); blood urea nitrogen and creatinine; glucose (mild hyperglycemia); liver function tests, including coagulation profi le; ABGs if patient ’ s mental status is altered or in shock. Abdominal X - ray: radiopaque pills may guide further GI decontamination (their absence does not exclude potential toxicity). Short - t erm p roblems Shock; hemorrhage; hepatic failure; pulmonary edema/hemor- rhage; disseminated intravascular coagulation. • If trauma is suspected cervical spine immobilization should be instituted and the injury specifi cally ruled out. • There is no specifi c antidote for ethanol; fl umazenil and nalox- one may alleviate respiratory depression in an inconsistent manner (anecdotal arousal after use of naloxone). Glucose and thiamine should be given routinely to ethanol overdose patients. • Hemodyalisis may be considered in severe ethanol intoxication associated with respiratory failure or coma. Monitoring Continuous pulse oxymetry if the patient is asleep or initial reading is abnormal. Therapeutic g oals Sobriety; no acute complications in 6 – 8 hours of observation. Ponder admission for social reasons. Other indications for hos- pital admission are: persistently abnormal vital signs, persistently abnormal mental status, mixed overdose, concomitant trauma, ethanol withdrawal or associated disease process (pancreatitis, GI hemorrhage, etc.). Discharge c onsiderations Clinical re - evaluation should be performed to avoid missing inju- ries initially masked by the intoxication. Social worker, drug counseling, and psychiatry evaluations may be helpful prior to discharge. Consider folate supplementation. On discharge, clini- cal follow - up may involve a social worker, drug counselor, obste- trician, and/or psychiatrist. Follow - u p Fetal follow - up will require ultrasound evaluations to monitor fetal growth [144,145] . Iron Toxicology Iron supplements are available as the iron salts: ferrous gluconate, ferrous sulfate, and ferrous fumarate, and as the nonionic prepa- rations carbonyl iron and polysacchararide iron. Their concen- trations of elemental iron may vary from 12 to 98%. Under normal conditions the oral bio - availability of inorganic iron is less than 10%. It is not known whether in overdoses this percentage is actually higher. In overdose peak concentrations are thought to occur 2 – 6 hours after ingestion. Toxic effects of iron poisoning occur at doses of 10 – 20 mg/kg of elemental iron. The lethal dose of elemental iron is 200 – 300 mg/kg [152,153] . Iron can generate oxidative stress and inhibit several metabolic enzymes (including mitochondrial oxidative phosphorilation) causing local caustic injury and metabolic acidosis. The damage to the GI tract allows iron ions to enter the systemic circulation, bind to circulating proteins, and eventually allowing “ free iron ” to be deposited in most major organs affecting metabolism and * Intentional overdoses during pregnancy. Chapter 39 546 lavage is ineffective in removing pill fragments or pills are seen past the stomach [152,153] . • Endoscopy or surgery may be occasionally required to remove iron tablets adherent to the gastric mucosa [153] . • Deferoxamine (category C medication) is a specifi c chelator of ferric iron ( ≈ 9 µ g of free iron per 100 mg) with resulting forma- tion of ferrioxamine, which is renally excreted (redish - brown color). It should be given at a dose of 15 mg/kg/h as an intrave- nous infusion for up to 24 hours. It is recommended for inges- tions of > 60 mg/kg of elemental iron; peak serum irons > 350 µ g/ dl; toxic appearance, lethargy, hypotension, signs of shock and metabolic acidosis. If prolonged infusion is deemed necessary, consider a hiatus of 12 hours to allow the elimination of ferrioxamine. • The use of deferoxamine may be associated to hypotension. Hypovolemia should be corrected with crystalloids before initia- tion of chelation [152] . • Hemodialysis may be required in the presence of associated or toxic renal failure. Monitoring Serum iron levels every 4 – 6 hours until within normal range. Therapeutic g oals Normal serum iron levels. Admit patients who ingested in excess of 60 mg of elemental iron; those with symptomatic ingestions of lower amounts; patients with levels in excess of 350 µ g/dl regard- less of symptoms or those with positive radiographs (if obtained) [152] . Admission to an ICU is indicated if serum iron level that exceed 1000 µ g/dl; coma, shock or metabolic acidosis. May discontinue deferoxamine when the patient is asymptomatic, the anion gap acidosis has resolved, the urine color undergoes no further change and/or with serum iron levels < 100 µ g/dl. Discharge c onsiderations Asymptomatic patients are unlikely to develop symptoms after more than 6 hours of the ingestion. Be mindful of patients that appeared to have recovered from the GI toxicity as they might be in the quiescent stage of the intoxication. Evaluate suicidal poten- tial in all patients (psychiatry consult). Follow - u p Establish multidisciplinary prenatal care if not already done (obstetrician, social worker and/or psychiatrist). A follow - up with gastroenterology may be indicated 2 weeks after the inges- tion to assess integrity of the GI tract [152,153,154,156,157] . Organophosphates (and c arbamates) Toxicology Organophosphates and carbamates are cholinesterase - inhibiting chemicals used predominantly as pesticides. Some forms are Long - t erm p roblems GI scarring; small intestine infarction; hepatic necrosis; achlorhydria. Fetal c onsiderations Signs Uterine contractions may be associated to maternal hypovolemia and shock. Teratogenic p otential None specifi c. In a review of 61 cases of obstetric iron overdose it was found that a peak iron level greater than or equal to 400 µ g/dl was not associated with increased risk of spontaneous abortion, preterm delivery or congenital anomalies. However, patients with evidence of organ failure due to iron toxicity were more likely to spontaneously abort or deliver preterm [154,155] . Fetal d istress p otential None unless associated with maternal acidosis, hypovolemia, dehydration or bleeding. Indications for d elivery Obstetric indications. Management c onsiderations Pregnancy should not alter therapy for acute iron overdose. If the patient condition is stable the need for treatment begins from the estimation the amount of ingested elemental iron [156] . When calculating the dose ingested use prepregnancy (not current) weight [157] . Deferoxamine administered in the third trimester is not associated with perinatal complications and is potentially life saving [18,158] . Supportive Initial stabilization must include supplemental oxygen, airway assessment and establishment of intravenous access. Assess hemodynamic status and start vigorous intravenous hydration through 2 large bore IVs if indicated. Consider early orogastric intubation in lethargic patients for airway protection. Specifi c m easures/ a ntidotes • Ipecac emesis recommended within the fi rst 30 – 60 minutes in the conscious patient if lavage is not available (and the patient has not started vomiting on her own). The uses of bicarbonate in the gastric lavage or enteral deferoxamine are currently not rec- ommended. Activated charcoal is ineffective in adsorbing iron [157] . • The presence and location of radiopaque pills on an abdominal radiograph can help guide lavage (see caveats above). If pills are past the pylorus a lavage will be unlikely. If lavage is performed, a post - lavage radiograph is recommended. • Whole - bowel irrigation (polyethylene glycol: at 1.5 – 2 l/h; decrease rate by 50% if not tolerated) may be required if gastric Overdose, Poisoning and Envenomation During Pregnancy 547 (intentional use can coexist with cocaine). EKG: tachycardia; bradycardia; AV block or various degrees; QT prolongation; asystole. Short - t erm p roblems Bronchorrhea, bronchospasm and respiratory failure; aspiration pneumonia; ventricular arrhythmias; pancreatitis; ARDS. Long - t erm p roblems Hepatic failure: three kinds of neurologic sequelae described: (a) prolonged memory impairment, peripheral neuropathy, person- ality change have been reported; (b) relapse after apparent recov- ery is known as “ intermediate syndrome ” has been described 24 – 96 hours after resolution of the acute cholinergic crisis and manifesting as muscular paralysis (including respiratory failure) developing after recovery from the cholinergic phase (explained by the hepatic metabolism to more toxic compounds within 72 hours of the exposure); (c) organophosphate - induced delayed neurotoxicity (OPIDN) is a sensorimotor polyneuropathy occur- ring 1 – 3 weeks after exposure and may mimic Guillain – Barre syndrome; recovery may take 12 – 15 months and might not be complete. Fetal c onsiderations These compounds cross the placenta. Signs Potential for preterm delivery [161] . Mild decreases in duration of pregnancy have been reported [163] . Teratogenic p otential Not enough evidence (one case reported of multiple anomalies after exposure to oxydemeton - methyl at 4 weeks). Association between pesticides and male genital anomalies has not been con- fi rmed [164] . Possible effects on neurobehavioral development has not been studied [165] . Fetal d istress p otential Yes; from maternal hypoxia or low placental perfusion associated to maternal bradycardia. Fetotoxicity and fetal death has been reported [166] . Organic brain dysfunction has also been described [165] . Indications for d elivery Obstetric indications. Nonreassuring fetal condition. Management c onsiderations Patients will remain clinically ill as long as there is active toxin available to bind to any free cholinesterase and depress its activity to less than 20% [159] . Organophosphates can penetrate latex gloves and health care personnel should wear nitrile or neoprene (chemical - resistant) gloves, water - resistant gowns, and eye shields to prevent a sec- ondary exposure [159] . used as nerve gases in chemical warfare (Sarin, VX) [159,160] . Collectively they are responsible for about 4 million poisonings and 300 000 deaths worldwide per year [161] . These insecticides are in general extremely well absorbed from the lungs, GI tract, skin, mucous membranes, and conjunctiva following inhalation, ingestion, or topical contact [162] . Carbamates in general (Carboryl ® and Bendiocarb ® for example) do not enter the CNS, and enzyme inhibition is reversible in minutes to hours resulting in limited toxicity. Organophosphates permanently inactivate acetylcholinesterase and penetrate the CNS leading to greater toxicity and need for antidote administra- tion [61] . Cholinergic poisoning, which can be acute or chronic, is caused by the accumulation of acetylcholine at synapses exerting delete- rious effects on three systems: muscarinic, nicotinic and CNS [61] . Although pesticide exposure is ubiquitous, special consider- ation should be taken with immigrants and seasonal farm workers, particularly in medically underserved areas. • Examples/other names: Dichlorvos ® , Diazinon ® , Dimethoate ® , Malathion ® ; Parathion ® ; Quinalphos ® , Sarban ® ; nerve gases: tabun (GA); sarin (GB); soman (GD); VX • As a cause of morbidity: 8 [2] • As a cause of mortality: 15 [2] • Most frequent route of exposure: ingestion • Most frequent reason for exposure: accidental exposure/inten- tional overdose Maternal c onsiderations The majority of agents show some signs and symptoms of toxicity within 6 – 12 hours after the exposure (exception of highly lipo - soluble: fenthion, difenthion, and chlorfenthion) [159] . The latter compounds may require several exposures before the person becomes symptomatic because the agent is stored in the adipose tissue depressing cholinesterase activity in an additive manner [159] . Symptoms Nausea; vomiting; blurred vision; headache; dizziness; respiratory diffi culty; abdominal pain (cramping usually); diarrhea; urinary incontinence; coma (see Table 39.4 ). Signs Agitation; altered mental status; fever; myosis; fasciculations or tremors; sialorrhea; bronchorrhea; bronchospasm; pulmonary edema; tachy - or bradycardia; hypo - or hypertension; respiratory arrest; coma (see Table 39.4 ). Some compounds may give a “ garlic - like ” breath smell; other may have a solvent - type smell. Diagnostic t ests Blood: complete blood count (leukocytosis possible); electrolytes and glucose (hypokalemia and hyperglycemia); amylase (might be elevated); decrease of 80 – 90% of erythrocyte cholinesterase (correlates better with synaptic inhibition). Urine: drug screen Chapter 39 548 Supportive Respiratory: administer 100% oxygen. The airway is best pro- tected by early endotracheal intubation. Only nondepolarizing neuromuscular blockers should be used due to prolonged paraly- sis with succinylcholine. Specifi c m easures/ a ntidotes • Decontamination: all forms of carbamates and organophos- phates may persist on the human body and clothing and footwear (particularly leather). They need to be removed and discarded as toxic waste [159] . Aspiration of gastric contents is indicated if ingestion occurred within the past hour and the patient is not vomiting. Activated charcoal is administered if no contraindications. • If the exposure has been cutaneous the patient needs to be washed down with copious amounts of water. Shaving the head might be necessary for oily insecticides. The water and other body fl uids should be considered potentially toxic and deactivated with chlorine bleach (4 – 5%). • Atropine (category C) 2 mg (0.05 mg/kg) IV (or IM if no IV access established yet) in repeated doses controls muscarinic effects (nausea, vomiting, bradycardia, salivation, bronchorrhea, bronchospasm) but does not reverse nicotinic effects. The dose can be repeated every 5 minutes until muscarinic fi ndings subside. Large doses of atropine may be needed in patients expose to more liposoluble compounds. A continuous infusion of atropine (0.05 mg/kg/h) can be started and titrated to effect and then slowly withdrawn. The end - point of atropinization is drying of the tracheobronchial tree and the ability to oxygenate (mydriasis is not a contraindication). • Pralidoxime chloride (2 - PAM chloride) (category C) is required for muscle weakness (nicotinic effect). 2 - PAM chloride allows for reactivation of the cholinesterases if given before irreversible binding of the toxin (time not fully known; usually within 24 – 48 hours depending on the agent, but may be attempted even later). The usual dose is 1 – 2 g IV (may be given IM if IV access not established) over 10 – 20 minutes (may cause neuromuscular blockade if administered too fast) followed by an infusion of 200 – 500 mg/h (World Health Organization - recommended doses are: 30 mg/kg or more as a bolus and more than 8 mg/kg/h as an infusion for 7 days or until recovery). • Diazepam IV can be used for seizures (phenobarbital being the second - line therapy). Monitoring Any symptomatic patient should be admitted for at least 24 hours. Any evidence of nicotinic symptoms or airway compro- mise requires an ICU setting until all signs have resolved [159] . Pulse oximetry; respiratory frequency; cholinesterase levels every 12 – 24 hours until cholinergic effects resolve. Therapeutic g oals Asymptomatic patient with normal levels of erythrocyte cholinesterase. Discharge c onsiderations More than 72 hours after signifi cant exposure and 24 hours after the last atropine; stable cholinesterase level; easy accessibility to the hospital. Caution patients about recurring symptoms: an intermediate syndrome of respiratory paralysis, weakness, and depressed refl exes has been described 24 – 96 hours after the reso- lution of the severe cholinergic crisis [61] . Follow - u p Establish multidisciplinary prenatal care if not already done (obstetrician, social worker, and/or psychiatrist; monitor acetyl- cholinesterase activity level until normal after discharge (5 weeks to 4 months in untreated patients) [159,167] . Ensure that work- place has been inspected and meet approved standards [159] . Workers should not be re - exposed to organophosphates until acetylcholinesterase levels are more than 75% [61,159,162,168] . Envenomations d uring p regnancy Venomous animals are a signifi cant health problem for rural populations in many parts of the world. The medically important venomous animals consist of six major groups: cnidarians (e.g. jelly fi sh, anemones, and corals), venomous fi sh, sea snakes, scor- pions, spiders, hymenoterans (e.g. bee, wasps, ants), and venom- ous terrestrial snakes. An animal classifi ed as venomous possesses a special apparatus for injecting venom (snakes, scorpions, etc.). Unlike venomous animals, poisonous animals possess toxins that are dispersed in their body tissues and are activated when the animal is ingested [169] . Terrestrial venomous snakes are the most important group of venomous animals. During 1999, 524 cases of bites or stings during pregnancy were reported to occur to the American Poison Control Centers. This represents 5.9% of all the toxic exposures occurring during preg- nancy reported nationally in 1999. Moderate effects (more pro- nounced or prolonged than minor effects, usually requiring some form of treatment) were seen in only 5.1%; however, the rate increased to 13.1% when the envenomation was by a spider bite. No major effects (life - threatening or resulting in residual dis- ability or disfi gurement) were reported in this series [170] . Snakebites Snakebite is a largely unrecognized public health problem that presents signifi cant challenges for medical management. It has been estimated that worldwide about 2.5 million people are envenomed per year, and over 125 000 die from this cause [171] . More than 6000 people are reported to sustain snakebites annually in the USA with nearly half from poisonous species [172] . In the USA snakebites during pregnancy are fortunately an uncommon event. In 1999, ophidic accidents represented 3.5% of all the stings and bites reported to American Poison Control Centers [173] . That year the majority of snakebites during preg- nancy arose from envenomations by snakes in the Crotalidae family (pit vipers) (see Table 39.25 ). Common pit vipers in the . psychiatry, and social worker evaluations. As part of the patient ’ s ongoing care, drug rehabilitation should be considered. Follow - u p Notify primary care physician (obstetrician, psychiatry) Investigate the possibility of coingestion (particularly alcohol and tricyclics). The therapeutic goal with benzodiazepine overdose is supportive care and gradual withdrawal of the benzodiazepines. maternal drinking in the second part of pregnancy [150] . Maternal ethanol use during pregnancy has been associated with an increase in childhood leukemia, particularly for the develop- ment