OBSTETRICS

PHYSIOLOGIC CHANGES IN PREGNANT WOMEN

Cardiovascular System Changes

• Changes in the cardiovascular system during pregnancy can be summarized as

• (I) an increase in intravascular fluid volume, • (2) an increase in cardiac output, • (3) a decrease in systemic vascular resistance

INTRAVASCULAR FLUID VOLUME

Maternal intravascular fluid volume increases in the firsttrimester, and at term the plasma volume is increasedabout 45% and the erythrocyte volume about 20%. This disproportionate increase in plasma volume accounts forthe relative anemia of pregnancy. The increased intravascularfluid volume offsets the 300 to 500 mL blood lossthat accompanies vaginal delivery and the average 800 to1000 mL blood loss that accompanies cesarean section.The total plasma protein concentration is decreased as aresult of the dilutional effect of the increased intravascularfluid volume.

CARDIAC OUTPUTCardiac output increases about 10% by the 10th week ofgestation and increases 40% to 50% by the third trimester.This augmentation of cardiac output is due to an increasedstroke volume (25% to 30%) and heart rate (15% to 25%).The onset of labor is associated with further increases incardiac output, with the largest increase occurring immediatelyafter delivery, when cardiac output is increased byas much as 80%. This presents a unique postpartum riskfor patients with cardiac disease, such as fixed valvularstenosis. A regional anesthetic is capable of attenuatingthe release of catecholamines during painful labor and theresultant maternal tachycardia and systemic hypertension.Cardiac output substantially returns toward prepregnantvalues by 2 weeks postpartum.

SYSTEMIC VASCULAR RESISTANCE

Systolic blood pressure decreases by as much as 15%during an uncomplicated pregnancy. Although there is anincrease in cardiac output and plasma volume, systemicblood pressure does not increase because of a decrease insystemic vascular resistance (mean arterial pressure maydecrease slightly). Furthermore, there is no change in centralvenous pressure during pregnancy despite the increasedplasma volume because venous capacitance increases.Femoral venous pressure increases about 15%, presumablyreflecting compression of the inferior vena cava by thegravid uterus.

AORTOCAVAL COMPRESSION (SUPINE HYPOTENSION SYNDROME)

Decreases in maternal blood pressure because of aortocavalcompression by the gravid utems are associated withthe supine position. Significant aortoiliac artery compressionoccurs in 15% to 20% of pregnant women and venacava compression in all such women. Vena cava compressionmay contribute to lower extremity venous stasis andthereby result in ankle edema and varices. Diaphoresis,nausea, vomiting, and changes in cerebration may accompanythis hypotension. These symptoms are termed the"supine hypotension syndrome."

Mechanism and Compensatory Responses

The mechanism of supine hypotension syndrome is decreased venous return as a result of compression of the inferior vena cava by the gravid uterus when the pregnant woman assumes the supine position. The resulting decrease in venous return leads to a decrease in cardiac output and a decline in systemic blood pressure.

compensatory responses that prevent hypotension despite aortocaval compression:

One compensatory mechanism is increased venous pressure below the level of compression of the inferior vena cava, which serves to divert venous blood from the lower half of the body via the paravertebral venous plexuses to the azygos vein. Flow from the azygos vein enters the superior vena cava and venous return is maintained. Dilation of the epidural veins may make penetration of a vein more likely during attempted lumbar epidural anesthesia and thus could lead to accidental intravascular injection of the local anesthetic solution. This would result in a bolus delivery of local anesthetic to the heart with potentially profound consequences on the central nervous and cardiovascular systems.

Another compensatory response that prevents hypotensionwith aortocaval compression is a reflex increase inperipheral sympathetic nervous system activity. This resultsin increased systemic vascular resistance and permitssystemic blood pressure to be maintained despite decreasedcardiac output. It is important to recognize that compensatoryincreases in systemic vascular resistance are impairedby regional anesthetic techniques. Indeed, arterialhypotension is more common and profound during regionalanesthesia administered to pregnant as compared withnonpregnant women.

In addition to compression of the inferior vena cava, the gravid uterus can compress the lower abdominal aorta . Such compression leads to arterial hypotension in the lower extremities, but maternal symptoms or decreases in systemic blood pressure as measured in the arms do not occur.

RISKS: The significance of aortocaval compression is the associated decrease in

uterine and placental blood flow. Even with a healthy uteroplacental unit, prolonged maternal hypotension (approximately 90 to 100 mm Hg systolic blood pressure for an average patient) for longer than 10 to 15 minutes will most likely significantly decrease uterine blood flow and lead to progressive fetal acidosis. Venous compression by the gravid uterus diverts some blood returning from the lower extremities through the internal vertebral venous plexus to the azygos and epidural veins, thereby increasing the likelihood of epidural venous puncture with epidural or spinal techniques. Supine positioning is avoided in pregnant women during anesthetic administration in the second and third trimesters. Anesthetic techniques that interfere with increased sympathetic nervous system tone will further compromise the compensatory mechanisms for vena cava compression induced by supine positioning and potentially cause profound hypotension

Treatment

Displacing the gravid uterus can minimize the incidenceof supine hypotension syndrome, which is important forpatients undergoing regional or general anesthesia becausetheir compensatory increases in systemic vascularresistance will be impaired. Displacement of the graviduterus can be achieved by placing the pregnant woman inthe lateral position or by moving the gravid uterus to theleft and off the inferior vena cava or aorta. Displacementof the uterus to the left can be accomplished manually orby elevation of the right hip 10 to 15 cm with a blanketor wedge .

Pulmonary System Changes

• The most significant changes in the pulmonary system during pregnancy include alterations in

• (l) the upper airway,• (2) minute ventilation, • (3) lung volumes, • (4) arterial oxygenation

UPPER AIRWAY

Capillary engorgement of the mucosal lining of the upper

respiratory tract accompanies pregnancy, emphasizing

the need for careful instrumentation of the upper airway

during suctioning, placement of airways (avoid nasal

instrumentation if possible), and direct laryngoscopy. It

may be prudent to select a smaller cuffed tracheal tube

(6.5 to 7.0 mm internal diameter) because the vocal cords and arytenoids are often edematous.

Weight gain associated with pregnancy, particularly in women of short

stature or with coexisting obesity, can result in difficulty inserting the laryngoscope because of a short neck and large breasts.

MINUTE VENTILATION

Minute ventilation is increased about 50% above prepregnantlevels during the first trimester and is maintained forthe remainder of the pregnancy. This increased minuteventilation is achieved primarily by an increased tidal volume,with small increases in the respiratory rate (see 1able 32-2).Increased circulating levels of progesterone are presumedto be the stimulus for increased minute ventilation.

Resting maternal Paco2 decreases from 40 to about32 mm Hg during the first trimester as a reflection of theincreased minute ventilation. Arterial pH, however,remains near normal because of increased renal

excretionof bicarbonate ions. The pain associated with labor anddelivery results in further hyperventilation, which can beattenuated by adequate analgesia, such as lumbarepidural analgesia.

LUNG VOLUMES

Lung volumes, in contrast to the early appearance ofincreased minute ventilation, do not begin to change untilabout the third month of pregnancy.With increasing enlargement of the uterus, the diaphragmis forced cephalad, which is primarily responsible for the20% decrease in functional residual capacity (FRC)present at term. As a result, FRC can be less than closingcapacity for many small airways and may give rise toatelectasis in the supine position. Vital capacity is notsignificantly changed.

The combination of increased minute ventilation and

decreased FRC results in an increase in the rate at which

changes in the alveolar concentration of inhaled anestheticcan be achieved. This affects induction of anesthesia, emergence

from anesthesia, and changes in depth of anesthesia.

ARTERIAL OXYGENATION

Early in gestation, maternal Pao2 while breathing roomair is normally above 100 mm Hg because of the presenceof hyperventilation. Later, Pao2 becomes normal or evenslightly decreased, most likely reflecting airway closure.During induction of general anesthesia in a pregnant patient,Pao2 decreases more rapidly than in a nonpregnant patientbecause of decreased oxygen reserve (decreased FRC)and increased oxygen uptake (increased metabolic rate).For these reasons, the administration of supplementaloxygen during a regional anesthetic or "preoxygenation"(breathe oxygen for 3 minutes, four to five deep breaths,or eight maximal breaths over a I-minute period) beforeany anticipated period of apnea (such as induction ofgeneral anesthesia) is recommended.

Nervous System ChangesAnesthetic requirements (minimum alveolar concentration[MAC]) for volatile anesthetics decrease during pregnancyas demonstrated in humans and animals.s The sedativeeffects produced by progesterone may be partially responsible.The important clinical implication of decreasedMAC is that alveolar concentrations of inhaled drugs thatwould not produce unconsciousness in nonpregnantpatients may approximate anesthetizing concentrations inpregnant women. This degree of central nervous systemdepression can impair protective upper airway reflexesand subject pregnant women to pulmonary aspiration.Furthermore, the decreased FRC increases the rate at whichpotential excessive alveolar concentrations of anestheticscan be achieved.

Engorgement of epidural veins as intra-abdominal pressureincreases with progressive enlargement of the uterusresults in a decrease in the size of the epidural space anddecreased volume of cerebrospinal fluid (CSF) in thesubarachnoid space. The decreased volume of these spacesfacilitates the spread of local anesthetics. The observationof increased spread of local anesthetic solutionsplaced in the epidural space as early as the first trimestersuggests a role for biochemical as well as mechanicalchanges. Indeed, data from pregnant women demonstrateincreased peripheral nerve sensitivity to lidocaine. Thesemechanical and biochemical changes are consistent withthe decrease in dose requirements of local anestheticsnecessary for epidural or spinal anesthesia in pregnantwomen at term gestation.

Renal Changes

Renal blood flow and the glomerular filtration rate are

increased about 50% to 60% by the third month of

pregnancy. Therefore, the normal upper limits in blood urea nitrogen and serum creatinine concentrations are

decreased about 50% in pregnant women.

Hepatic Changes

Plasma protein concentrations are reduced during pregnancybecause of dilution, similar to the physiologic anemiaof pregnancy. Decreased serum albumin levels can resultin higher free blood levels of highly protein-bound drugs.Slightly elevated liver function test results do not necessarilyindicate hepatic disease. Plasma cholinesterase(pseudocholinesterase) activity is decreased about 25%from the 10th week of gestation to as long as 6 weekspostpartum. This decreased activity is unlikely to be associatedwith significant prolongation of the neuromuscularblocking effects of succinylcholine or mivacurium. Aspart of the hypercoagulable state of pregnancy, plasmaconcentrations of coagulation factors, including fibrinogen,are increased.

Gastrointestinal Changes

Gastrointestinal changes during pregnancy make pregnantwomen vulnerable to regurgitation of gastric contentsand to the development of acid pneumonitis shouldpulmonary aspiration occur. Displacement of the pyloruscephalad by the enlarged uterus retards gastric emptying,and progesterone decreases gastrointestinal motility. As aresult, gastric fluid volume tends to be increased even inthe fasting state. In addition, gastrin, which is secreted bythe placenta, stimulates gastric hydrogen ion secretionsuch that the pH of gastric fluid is predictably low inpregnant women. The enlarging uterus changes the angleof the gastroesophageal junction and thereby leads torelative incompetence of the physiologic sphinctermechanism. For this reason, gastric fluid reflux into theesophagus with subsequent esophagitis (heartburn) iscommon in pregnant women.

RISK OF ASPIRATIONRegardless of the time interval since the ingestion of food,women in labor must be treated as having a full stomach.Pain, anxiety, and drugs (especially opioids) administeredduring labor can all slow gastric emptying beyond analready prolonged transit time.The increased risk for pulmonary aspiration of gastriccontents is the reason for recommending placement of acuffed tube in the trachea of pregnant women renderedunconscious by anesthesia. The recognition that the pHof inhaled gastric fluid is important in the production andseverity of acid pneumonitis is the basis for the administrationof antacids to pregnant women before inductionof anesthesia. To obviate the hazards of inhalation ofparticulate antacids that can increase pulmonary damage,the use of a nonparticulate antacid such as sodium citrateis recommended.

H2 receptor antagonists usually increase gastric fluid pH in pregnant women without producing

adverse effects and are recommended by some. 1-12receptorantagonists, unlike antacids, do not alter the pl-l of gastricfluid already present in the stomach. Combinations of an1-12receptor antagonist and sodium citrate may be moreuseful than an antacid alone for producing a persistentincrease in gastric fluid pH.Metoclopramide can be useful for decreasing the gastricfluid volume of pregnant women in active labor whorequire general anesthesia and are considered to be at highrisk for increased gastric fluid volume (apprehension,systemic opioid analgesia, recent solid food ingestion).The gastric hypomotility associated with opioid administration,however, may be resistant to treatment withmetoclopramide.

PHYSIOLOGY OF THE UTEROPLACENTAL CIRCULATION

The placenta is a union of maternal and fetal tissue forthe purpose of physiologic exchange. Maternal blood isdelivered to the placenta by the uterine arteries, and

fetalblood arrives via two umbilical arteries. Nutrient-rich

andwaste-free blood is delivered to the fetus through a

singleumbilical vein.

Uterine Blood Flow

Uterine blood flow increases to about 700 mUmin (about10% of cardiac output) at term gestation, with about 80%of the uterine blood flow perfusing the intervillous space(placenta) and 20% the myometrium. The uterine vasculatureis not autoregulated and remains essentially maximallydilated under normal conditions during pregnancy.Though capable of marked vasoconstriction in responseto a-adrenergic drugs, pregnancy is associated with reduceduterine artery response and sensitivity to vasoconstrictors.

Uterine blood flow decreases because of decreaseduterine perfusion pressure as a result of systemic hypotension(shock; general, epidural, or spinal anesthesia). Uterineblood flow also decreases with aortocaval compression orincreased uterine venous pressure as a result of vena cavacompression (supine position) or uterine contractions(particularly uterine hyperstimulation as may occur withoxytocin administration or abruption). Epidural or spinalanesthesia does not alter uterine blood flow as long asmaternal hypotension is avoided.

ephedrinehas been considered the drug of choice for the

treatment of hypotension caused by the administration of regional

anesthesia to pregnant women.

Increased uterine vascular resistance with decreases inuterine blood flow can also result from maternal stress orpain that stimulates the endogenous release of

catecholamines. This response suggests that a regional or general anesthetic may be protective to the fetus

in certain instances. Uterine contractions also decreaseuterine blood flow secondary to increased uterine venouspressure.

PLacentaL Exchange

Placental exchange of substances occurs principally bydiffusion from the maternal circulation to the fetus andvice versa. Diffusion of a substance across the placenta tothe fetus depends on maternal-to-fetal concentrationgradients, maternal protein binding, molecular weight,lipid solubility, and the degree of ionization of thatsubstance. Minimizing the maternal blood concentrationof a drug is the most important method of limiting theamount that ultimately reaches the fetus.

The high molecular weight and poor lipid solubility ofnondepolarizing neuromuscular blocking drugs result inlimited ability of these drugs to cross the placenta.Succinylcholine has a low molecular weight but is highlyionized and therefore does not readily cross the placenta.Thus, during administration of a general anesthetic forcesarean section, the fetus/neonate is not paralyzed. Placentaltransfer of barbiturates, local anesthetics, and opioids isfacilitated by the relatively low molecular weights of thesesubstances. Drugs that readily cross the blood-brain barrieralso cross the placenta.

FETAL UPTAKEFetal uptake of a substance that crosses the placenta isfacilitated by the lower pH (0.1 unit) of fetal than maternalblood. The lower fetal pH means that weakly basic drugs(local anesthetics, opioids) that cross the placenta in thenonionized form will become ionized in the fetal circulation.Because an ionized drug cannot readily cross theplacenta back to the maternal circulation, this drug willaccumulate in the fetal blood against a concentrationgradient. This phenomenon is known as ion trapping andmay explain the higher concentrations of lidocaine foundin the fetus when acidosis secondary to fetal distress ispresent . Furthermore, conversion of lidocaineto the ionized fraction maintains the concentration gradientfrom the mother to the fetus for continued passage ofnonionized lidocaine to the fetus. Despite decreased enzymeactivity in comparison to adults, neonatal enzyme systemsare adequately developed to metabolize most drugs, withthe possible exception of mepivacaine.

UNIQUE CHARACTERISTICS OF THE FETALCIRCULATION

The unique characteristics of the fetal circulation influencethe distribution of drugs in the fetus and protect the vitalorgans of the fetus from exposure to high concentrationsof drugs initially present in umbilical venous blood. Forexample, about 75% of umbilical venous blood passesthrough the liver such that significant portions of drugscan be

metabolized before reaching the fetal arterialcirculation for delivery to the heart and brain. Moreover,drugs in the portion of umbilical venous blood thatenters the inferior vena cava via the ductus venosus willbe diluted by drug-free blood returning from the lowerextremities and pelvic viscera of the fetus.

ANESTHESIA FOR CESAREAN DELIVERY

Although the majority of cesarean deliveries are performedwith regional anesthesia, sometimes the severity of the fetalcondition (severe fetal heart rate deceleration) necessitatesthe use of general anesthesia for its rapidity, and atother times it is required when regional anesthesia iscontraindicated. Regardless, in preparation for cesareandelivery, all pregnant women should receive an oral antacid(nonparticulate such as sodium citrate) to reduce gastricfluid pH. In addition, some anesthesiologists routinelyadminister a drug to accelerate gastric emptying (metoclopramide)or an H2 receptor antagonist (ranitidine), orboth, to reduce gastric acid production.

Spinal AnesthesiaFor a pregnant woman without an epidural catheter, spinalanesthesia is the most common regional anesthetic techniqueused for cesarean delivery (Table 32-6). The blockis technically easier than an epidural anesthetic, more rapidin onset, and more reliable in providing surgical anesthesiafrom the mid thoracic level to the sacrum.Theincidence of post-dural puncture headache has becomelow with the introduction of noncutting, "pencil-point"spinal needles. However, maternal hypotension is morelikely and more profound with spinal anesthesia than withepidural anesthesia because the onset of sympathectomyis more rapid. Prehydration, avoidance of aortocavalcompression, and aggressive use of ephedrine (even as aprophylactic) may minimize the risk for hypotension.Spinal anesthesia can be safely used in patients withpreeclampsia.

Lumbar Epidural AnesthesiaEpidural anesthesia is an excellent choice for surgicalanesthesia when an indwelling, functioning epidural catheterhas been placed for labor analgesia. It is also ideal forpatients who cannot tolerate the sudden onset of sympathectomyor in some patients with cardiac disease. Thevolume and concentration of local anesthetic drugs usedfor surgical anesthesia are larger than those used for laboranalgesia; however, the technique of catheter placement,test dosing, and potential complications are similar. Typically,the anesthesiologist attempts to provide sensoryanesthesia from the T4 level to the sacrum. This level ofanesthesia may not always alleviate the visceral pain associatedwith peritoneal manipulation, and adjuvant drugsmay be necessary (see Table 32-5).

Local Anesthesia

Although cesarean delivery can be performed by localinfiltration, it is accompanied by considerable discomfortand risks the possibility of local anesthetic overdose;moreover, most obstetricians have not been trained to dothis. However, in rare circumstances of acute fetal distress,when a regional block is inadequate, and when inductionof general anesthesia is considered dangerous (morbidobesity), local infiltration can be helpful to at least deliverthe baby. General anesthesia can then be induced aftersecuring the patient's airway with appropriate techniques,which may include awake fiberoptic tracheal innlbation.

General AnesthesiaGeneral anesthesia is used in obstetric practice for cesareansection, typically when regional anesthesia is contraindicated(coagulopathy, certain cardiac lesions, hemorrhage)or for emergencies (placental abruption, uterine rupture,fetal bradycardia, prolapsed umbilical cord) because of itsrapid and predictable action (Table 32-7).After rapid-sequence induction of anesthesia and placementof a cuffed tracheal tube facilitated by the administrationof succinylcholine or a nondepolarizing neuromuscularblocking drug, anesthesia is maintained byinhalation of nitrous oxide and a volatile anesthetic, oftenin combination with sedative-hypnotics or opioids (or both).Nondepolarizing neuromuscular blocking drugs aresubsequently administered to facilitate surgery.

INDUCTION DRUGS

ThiopentalThiopental (4 to 6 mg/kg IV) is the most commonly useddrug for induction of general anesthesia in obstetricsbecause it renders the patient unconscious within 30seconds of administration. This dose of thiopental has nosignificant clinical impact on neonatal well-being. Neonataldepression may, however, occur with higher doses ofthiopental, and cardiorespiratory supportive techniquesare necessary until the neonate can excrete the drug (maytake up to 48 hours).

KetamineKetamine produces a rapid onset of anesthesia and, unlikethiopental, increases systemic blood pressure, heart rate,and cardiac output by central stimulation of the sympatheticnervous system. Increased uterine tone and decreaseduterine blood flow can accompany excessively large dosesof ketamine. In contrast to thiopental, low doses of ketamine(0.25 mglkg IV) have profound analgesic effects.The undesirable psychotomimetic side effects (hallucinations,bad dreams) associated with ketamine administrationscan be lessened by coadministration of benzodiazepines .Many anesthesiologists consider ketamine the appropriatedrug for induction of anesthesia in a pregnant woman whois actively hemorrhaging, has uncertain blood volume,and is at risk for profound hypotension in response tointravenous thiopental.

Etomidate

Etomidate, like thiopental, has a rapid onset of action because

of its high lipid solubility, and redistribution results in arelatively short duration of action. Although etomidatehas minimal effects on the cardiovascular system, unlikethiopental and ketamine, it is painful on injection, inducesextrapyramidal motor activity, and thus is rarely usedin obstetrics.

PropofoIThe need to have syringes of induction drugs ready toadminister for rapid response to urgent situations requiringinduction of general anesthesia (fetal distress) detractsfrom the value of preservative-free propofol in the obstetricsuite. For an elective cesarean section, this highly lipid solubledrug results in rapid onset of action similar to thiopental and rapid and

complete recovery with lessresidual sedative effect than is the case with thiopental.Nevertheless, propofol has not been demonstrated to besuperior to thiopental in maternal or neonata] outcome.Furthermore, propofol has been associated with maternalbradycardia when administered with succinylcholine forinduction of general anesthesia for cesarean section.

MAINTENANCE OF ANESTHESIA

Maintenance of anesthesia for cesarean section oftenincludes the inhalation of 50% nitrous oxide in combinationwith a low concentration of volatile anesthetic. Avolatile anesthetic is an important component of generalanesthesia for cesarean section because the incidence ofmaternal recall of intraoperative events without these drugsis unacceptably high. During a typical general anestheticfor cesarean delivery, opioids are administered after thebaby is delivered to avoid the concern of placentaltransfer to the neonate.

Placental transfer of volatile anesthetics is rapid becausethey are nonionized, highly lipid-soluble substances oflow molecular weight. Fetal concentrations depend onthe concentration and duration of anesthetic administeredto the mother. If excessive concentrations of volatileanesthetics are administered for prolonged periods,neonatal effects of these drugs, as evidenced by flaccidity,cardiorespiratory depression, and decreased tone, may beanticipated. It is important to recognize that if neonataldepression is due to transfer of anesthetic drugs, the infantis merely lightly anesthetized and should respond easilyto simple treatment measures such as assisted ventilationof the lungs to facilitate excretion of the inhalation anesthetic.Rapid improvement of the infant should be expected,and if it does not occur, it is important to search for othercauses of depression.

There may be confusion regarding the presence of fetal distress, the use of general anesthesia, and subsequent delivery of a depressed neonate. A depressed fetus is likely to be associated with a depressed neonate, and general anesthesia is selected because it is the most rapidly acting anesthetic technique to allow cesarean delivery. For a healthy fetus, the interval from induction to delivery is not as important to neonatal outcome as the interval from uterine incision to delivery, when uterine blood flow may be compromised and fetal asphyxia may occur. A long time from induction to delivery may result in a lightly anesthetized neonate, but not an asphyxiated neonate.

NEUROMUSCULAR BLOCKING DRUGS

Succinylcholine remains the neuromuscular blocking drugof choice for obstetric anesthesia because of its rapidonset and short duration of action. This depolarizingneuromuscular blocking drug is normally hydrolyzed inmaternal blood by the enzyme pseudocholinesterase anddoes not generally interfere with fetal neuromuscularactivity. If the hydrolytic enzyme is present either in

lowconcentration or in a genetically determined atypical form,

prolonged maternal or neonatal respiratory depressionsecondary to muscular paralysis can occur

Nondepolarizing neuromuscular blocking drugs aretitrated to response with the use of a peripheral nervestimulator. Under normal circumstances, the poorly lipidsoluble,highly ionized, non depolarizing neuromuscularblocking drugs do not cross the placenta in amounts signifIcantenough to cause neonatal skeletal muscle weakness.This placental impermeability is only relative, however,and when large doses are given over long periods, as forthe treatment of maternal tetanus or status epilepticus,neonatal neuromuscular blockade can occur.

The diagnosis of neonatal depression secondary to drug-induced neuromuscular blockade may be made on the basis of the maternal history (prolonged administration of neuromuscular blocking drugs, history of atypical pseudocholinesterase), the response of the mother to neuromuscular blocking drugs, and physical examination of the newborn. A paralyzed neonate will have normal cardiovascular function and good color, but no spontaneous ventilatory movements or reflex responses, and skeletal muscle flaccidity is present. The anesthesiologist can test the neonate with a peripheral nerve stimulator and demonstrate the classic signs of neuromuscular blockade. Treatment consists of respiratory support until the neonate excretes the drug (may take up to 48 hours). Antagonism of nondepolarizing neuromuscular blocking drugs with cholinesterase inhibitors (neostigmine, edrophonium) may be attempted, but adequate respiratory support is the mainstay of treatment.