Critical Care Obstetrics part 56 docx

Fetal d istress p otential Only in the presence of severe maternal toxicity and secondary to maternal hypovolemia or hypoxemia.. Maternal COHb levels are a poor predictor of fetal toxi

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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

• The 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

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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]

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]

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

Obstetric indications; nonreassuring fetal condition despite ade-quate maternal therapy

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]

• 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 and symptoms will vary depending on the concentration of

carboxyhemoglobin

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• As a cause of mortality: 4 * [2]

• Most frequent route of exposure: inhalation

• Most frequent reason for exposure: unintentional overdose

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]

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 )

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

COHb < 5% and no symptoms Reassuring antenatal fetal

condi-tion as appropriate according to the gestacondi-tional age

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]

* Includes other stimulants and street drugs

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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]

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

• 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

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]

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]

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]

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

stillbirths in cocaine users can be 10 times higher than that of drug

free control women [130,135,139,140]

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

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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

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

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

• No specifi 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

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

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microcephaly Diagnosis may be delayed until 9 – 12 months of age [148]

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]

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

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]

• 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]

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 - 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

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]

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

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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 mortality: rare

• Most frequent reason for exposure: intentional overdose; sui-cidal gesture

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

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)

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

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.)

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

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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 chelainitia-tion [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

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

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

GI scarring; small intestine infarction; hepatic necrosis;

achlorhydria

Signs

Uterine contractions may be associated to maternal hypovolemia

and shock

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]

None unless associated with maternal acidosis, hypovolemia,

dehydration or bleeding

Obstetric indications

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

• 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

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(intentional use can coexist with cocaine) EKG: tachycardia; bradycardia; AV block or various degrees; QT prolongation; asystole

Bronchorrhea, bronchospasm and respiratory failure; aspiration pneumonia; ventricular arrhythmias; pancreatitis; ARDS

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

These compounds cross the placenta

Signs

Potential for preterm delivery [161] Mild decreases in duration

of pregnancy have been reported [163]

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]

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]

Obstetric indications Nonreassuring fetal condition

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 reason for exposure: accidental

exposure/inten-tional overdose

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

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

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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

• 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

Asymptomatic patient with normal levels of erythrocyte

cholinesterase

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 venomvenom-ous 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

Tiêu đề	Overdose, Poisoning and Envenomation During Pregnancy
Trường học	University of Medicine
Chuyên ngành	Obstetrics
Thể loại	bài luận
Thành phố	Hanoi

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