Anesthesia for the Pregnant Patient
Eveline A. M. Faure, MD
Department of Anesthesia and Critical Care (emeritius)
University of Chicago
“She is the highest nature can achieve and by her mold all beauty tests itself”
Dante Alighieri, Vita Nuova
Analgesic and Anesthetic Techniques
Society for Obstetric Anesthesia and Perinatology (SOAP)
I. PHYSIOLOGY OF PREGNANCY
A. Physiologic changes of pregnancy
1. Cardiovascular adaptation
a. Blood volume increases by 40% at term; plasma volume increases more than red cell volume, resulting in lower hemoglobin
b. Cardiac output rises during the second trimester to meet the increased oxygen consumption to a 20% increase at term. CO exceeds 50% during labor and remains elevated until the third postpartum day.
c. Heart rate increases and peripheral vascular resistance and diastolic blood pressure (BP) decrease. Central venous pressure is unchanged.
d. The growing uterus receives 20% of the cardiac output; uterine enlargement causes compression of the inferior vena cava and the aorta, resulting in maternal hypotension and fetal distress
Figure 1. Changes in blood volume, plasma volume, red cell volume, and cardiac output during pregnancy and in the puerperium. The curves were constructed from various resports in the literature and illustrate trends in percent change rather than absolute values.
Figure 2. Changes in maternal heart rate, stroke volume, and cardiac output during pregancy with the gravida in the supine position and in the lateral position. These curves are based on data derived from several studies, including Ueland, K., et al.: Am. J. Obstet. Gynecol. 104:856, 1969.
e. Clinical implications: to avoid aortocaval compression, parturients should never be allowed to rest in the supine position. Sympathetic blockade due to spinal or epidural anesthesia interferes with the compensatory vasoconstrictor reflex, resulting in profound hypotension in spite of adequate intravascular volume expansion
Figure 3. Changes in arterial blood pressure, venous pressure, and total peripheral resistance during pregnancy.
f. Definition of hypotension in obstetrics: systolic BP below 100 mm Hg or 20% from preanesthetic level (30% in hypertensive patients)
g. Clinical implications: engorgement of the epidural vasculature makes puncture of an epidural vein more likely. The decrease in epidural space by the engorged vessels leads to decreased drug requirement: pregnant patients need only two-thirds of the amount of local anesthetics used in nonpregnant patients
Figure 4. Diagram of the caval venous system and its connections with the vertebral and azygous systems. Commonest sites of compression of the inferior vena cava (IVC) are: (a) suprahepatic in lordotic position; (b) uterus at term; and (c) pressure at pelvic brim in exaggerated lordosis and term pregnancy. (Courtesy of Bromage, P.R., Epidural Analgesia: Philadelphia, W.B. Saunders, 1978.)
Figure 6. Pulmonary volumes and capacities in the nonpregant state and in the gravida at term. (Courtesy of Bonica, J.J.: Principles and Practice of Obstetric Analgesia and Anesthesia, Philadelphia, F.A. Davis Company, 1967.)
2. Respiratory adaptation
a. Upper airway: capillary engorgement of the respiratory tract leads to edema and increased friability of the mucous membranes with increased tendency to severe hemorrhage during insertion of nasogastric or endotracheal tubes. Preeclamptic patients may have vocal cord edema requiring small-diameter endotracheal tubes
b. Mechanics of respiration: the expanding uterus displaces the diaphragm cephalad, decreasing functional residual capacity (FRC). Vital capacity (VC) and inspiratory capacity remain unchanged, because of an increase in anteroposterior thoracic diameter. Tidal volume increases by 40% and respiratory rate by 15% resulting in a raise in alveolar ventilation by 70%. The elevated progesterone level has been assumed to stimulate the rise in alveolar ventilation
c. Maternal blood gas: increase in alveolar ventilation produces respiratory alkalosis with compensatory renal excretion of bicarbonate and correction of pH. Oxygenation is improved, O2 saturation is close to 100%
d. Clinical implications: due to the decreased FRC, parturients are more susceptible to hypoxia and hypercarbia during apnea while pushing and after induction of general anesthesia. The supine and lithotomy position assumed during birth aggravates the onset of hypoxia. Severe hyperventilation during pain leads to hypocarbia, causing uterine artery vasoconstriction. The decreased FRC implies that preoxygenation and induction of anesthesia with inhalation agents occur more rapidly, as does emergence. Administration of supplemental 100% oxygen is mandatory during fetal distress and prior to induction of general anesthesia
Figure 7. Changes in the outline of the heart, lungs, and thoracic cage that occur in pregnancy. The gradual migration of the uterus cephalad causes the diaphragm to move upward and thus encroach on the lungs, and causes the heart to be displaced laterally and anteriorally, but this is counterbalanced by an increase in the anterior-posterior and transvers diameters of the chest wall. (From Bonica, J. J.: Principles and Practice of Obstetric Analgesia and Anesthesia, Philadelphia, F.A. Davis Company, 1967, as modified from and courtesy of Klaften, E. and Palugvav, H. Arch.Gvnaek. 78:1, 1959.)
3. Gastrointestinal changes
a. Elevated progesterone levels decrease gastric mobility and food absorption, and lower esophageal sphincter tension at term
b. Placental secretion of gastrin results in higher gastric acidity and gastric volume
c. The enlarged uterus increases intragastric pressure and the gastroesophageal angle flattens
d. Clinical implications: these gastrointestinal changes result in an increased danger of vomiting and aspiration of gastric contents in the parturient. Regardless of the number of hours after last food intake, all parturients are considered to have a full stomach! In addition to the unpredictability of last meal prior to onset of labor, pain, anxiety, and narcotic pain medication totally block gastric emptying. It is therefore recommended that no solid food be given to parturients and that liquids be restricted to a small amount of ice chips
e. Medical control of the full stomach: although histamine2-blocking agents (cimetidine, ranitidine) have been used in elective cesarean section patients with success, the time required to change gastric acidity is unpredictable and too long to be effective in labor patients. Metoclopramide increases gastric motility and lower esophageal sphincter tone, and has central antiemetic effects. Oral clear liquid antacids (Bicitra) .3 M sodium citrate, 30 mL, is sufficient to buffer gastric acidity acutely. It may ameliorate pulmonary irritation from gastric acid, if aspiration occurs
f. Prevention of aspiration of gastric contents: whenever possible, regional anesthesia is chosen over general anesthesia. Clear oral liquid antacid, 30 mL, is administered 10 minutes prior to induction. Preoxygenate with 100% oxygen for 3 minutes; induce anesthesia with a fast-acting IV agent, followed by a muscle relaxant, with cricoid pressure and intubation, inflating the cuff immediately. If difficult intubation is anticipated, awake intubation with topical spray and mild sedation is indicated
4. Renal function
a. Renal plasma flow increases to 80% above normal by the middle of the second trimester and decreases slightly at term
b. Glomerular filtration rate (GFR) rises to 50% above prepregnant levels by the sixteenth gestational week and remains high until delivery, leading to an increase in creatine clearance
c. Glycosuria is due to the increased load of glucose presented by the increased GFR
d. Progesterone causes dilation of the renal calyces, causing an increased incidence of urinary tract infections
5. Liver function: hepatic blood flow is unchanged, but liver function test may be slightly abnormal; plasma cholinesterase is slightly decreased
6. Hematological changes
a. The increased plasma volume exceeds the increase in red cell mass, leading to a decrease in blood viscosity and “dilutional anemia”
b. Coagulation factors I, VII, X, and XII are increased and render pregnancy a “hypercoagulable state” as a protection to the parturient against bleeding at the time of delivery
B. Pain pathways
1. First stage of labor: pain from uterine contraction and cervical dilation is transmitted via efferent nerve fibers arising from the uterus together with the sympathetic chain and enters the spinal cord at the tenth thoracic level through the First lumbar segment
2. In the late first and early second stages of labor, noxious stimulation of other pelvic structures that are innervated by lower lumbar and sacral sensory fibers leads to additional pain
3. During delivery, perineal distention by the fetal presenting part, stretching and tearing of the perineum result in transmission of pain signals from the three sacral segments: S2-S4
4. During cesarean section, painful stimuli arise from the abdominal peritoneum, uterus, bladder, ureters, and rectum. Therefore, nerve fibers arising from the second thoracic level to the fourth sacral level need to be blocked
Figure 8. Peripheral parturition pain pathways. The uterus, including the cervix, is supplied by sensory (pain) fibers that pass from the uterus to the spinal cord by accompanying sympathetic nerves in the sequence summariezed in the text. The primary pathways (shown as thick lines in the inset) enter the 11th and 12th spinal segments while the secondary auxiliary pathways enter at T10 and L1. The pathways from the perineum pass to the sacral spinal cord via the pudendal nerves. (Modified from and courtesy of Bonica, J.J.: Principles and Practice of Obstetric Analgesia and Anesthesia, Philadelphia, F.A. Davis Company, 1967.)
A. Local anesthetic agents used in obstetrical anesthesia
a. Procaine (Novocain), chloroprocaine (Nesacaine)
Fast metabolism: T_ in plasma of pregnant women is 23 seconds
Disadvantage: possible allergy to the nitrogen in para-position
b. Tetracaine (Pontocaine)
Disadvantages: patchy sensory block, high toxicity
a. lidocaine (Xylocaine), bupivacaine (Marcaine)
Good sensory block at low concentrations with minimal motor block
Metabolized in the liver
Bupivacaine is highly cardiotoxic if injected inadvertently into a vein. The toxic dose is 1 mg/kg IV
Tachyphylaxis may occur after repeated doses of plain lidocaine
3. Toxicity of local anesthetic agents
a. Central nervous system: moderately elevated blood levels cause drowsiness, slurred speech, “feeling drunk,” ringing in ears. Major toxicity reactions are seizures and coma
b. Cardiovascular: irregular heart rhythm, A-V block, ventricular fibrillation leading to a fall in cardiac output and cardiovascular collapse with cardiac arrest
c. Prevention: before each therapeutic epidural dose of local anesthetic, a small test dose of 3 mL has to be administered, the patient has to be observed and questioned about any strange sensations, and blood pressure and oxygen saturation monitored. The person administering epidural anesthesia has to be trained in CPR. Appropriate resuscitation equipment must be available and functioning
d. Treatment: minor symptoms can be treated with the administration of oxygen and reassurance of the patient. In case of seizure, sodium pentothal 50 mg or diazepam 10 mg IV has to be given to interrupt the seizure. The airway has to be protected by endotracheal intubation facilitated by succinylcholine 40 mg IV, and the lungs have to be ventilated with 100% oxygen to assure oxygenation and ventilation. Cardiovascular support with vasopressors, fluid therapy including cardiac massage may be necessary. Emergency cesarean delivery of the baby may be necessary, if persistent fetal bradycardia is present
Recommended Maximum Doses of Local Anesthetics
Used in Epidural Anesthesia for Obstetrics
B. Sedatives and hypnotics
1.a. Barbiturates: pentothal and methohexital are used as induction agents for general anesthesia because of the rapid onset. All barbiturates are depressant to mother and baby, dependent on dosage and individual duration, and not used for sedation
b. Benzodiazepines: diazepam (Valium) and midazolam (Versed) are anxiolytics and anticonvulsants, and may be used in small doses (5 mg and 2 mg IV). In larger doses, both cause neonatal hypotonia, hypothermia, delayed feeding, increased jaundice, and kernicterus
c. Hydroxyzine (Vistaril) and promethazine (Phenergan) are depressant to mother and baby and have not been useful in obstetrics
d. Propofol (Deprivan) has been introduced as an induction agent for general anesthesia in doses 2-2.5 mg/kg. While maternal cardiovascular status is unchanged, neonatal irritability is noted. In smaller doses, 1-2 mg/kg, maternal awareness is possible
e. Ketamine, 1 mg/kg, produces dissociative analgesia, amnesia, and sedation, while maintaining maternal BP, and does not depress the fetus. It is contraindicated in patients with preeclampsia or hypertension and may cause a hypertensive crisis when combined with ergonovine or vasopressors
f. Scopolamine, an anticholinergic and amnestic agent, is no longer used because of its deleterious effects
C. Opioids and opioid agonist/antagonist
a. Morphine, meperidine (Demerol), fentanyl, and sufentanil are the most effective systemic analgesics. No narcotic currently available can produce effective analgesia during labor without producing respiratory depression in mother and neonate when given intravenously or intramuscularly. Other side effects include nausea and vomiting, orthostatic hypotension, delayed gastric motility, somnolence, and uncooperativeness in the mother. Epidural or subarachnoid administration of opioids alone or in combination with local anesthetics is now frequently used because the amount of local anesthetic needed for efficient analgesia is greatly reduced when combined with opioids. Systemic effects are minimal and the duration of analgesia is markedly prolonged. The more lipid-soluble the opioid, the greater the spread into the nervous tissue and the more rapid the clearance from the cerebrospinal fluid (meperidine, fentanyl, and sufentanil). Morphine is relatively non-lipid soluble and slowly penetrates the dura and nerve tissue, resulting in slow onset and long duration. Epidural morphine, 4-5 mg (onset 30-45 minutes), provides analgesia up to 24 hours postoperatively. Epidural fentanyl, 100-200 mcg, has a quick onset (5-10 min) with brief (60-140 min) satisfactory analgesia. Epidural sufentanil 10-20 mcg results in 1 hour of pain relief. Subarachnoid morphine in doses as small as 0.25 mg can provide safe analgesia for the first and second stages of labor. The slow onset can be overcome by adding 25 mcg of fentanyl. Subarachnoid meperidine 10-20 mg produces analgesia lasting approximately 2 hours. Sufentanil, 10 mcg, provides analgesia for 1-2 hours. Side effects of spinal opioids include pruritus, nausea and vomiting, and rarely, delayed respiratory depression
2. Opioid agonist/antagonist
a. Butorphanol (Stadol) and nalbuphine (Nubain): when used alone, these drugs have poor analgesic properties and may produce maternal somnolence
b. When used in addition to opioids, epidural butorphanol 4 mg with epidural morphine greatly reduces the incidence of pruritus
D. Inhalational agents
1. Nitrous oxide
a. Maternal effects: low blood solubility of nitrous oxide renders uptake and recovery very rapid. Although its analgesic effects are good, its low potency does not provide complete analgesia for delivery. Nitrous oxide administered in analgesic concentrations (50-75%) does not cause maternal cardiovascular or respiratory depression and does not affect uterine contractility
b. Neonatal effects: respiratory depression and fetal acidosis occur after long administration, especially if maternal analgesia is incomplete and maternal catecholamines are elevated
2. Halogenated agents: halothane, enflurane, isoflurane
a. Maternal effects: in anesthetic concentrations, all halogenated agents cause cardiovascular and respiratory depression. Uterine activity decreases in a dose-related fashion. In low concentrations, 0.4-0.8%, these agents are used to prevent maternal awareness during general anesthesia for cesarean section. When uterine relaxation is needed (entrapment of the second twin, the fetal head, retained placenta), rapid uterine relaxation is provided by hyperventilation of the mother under general, endotracheal anesthesia with high concentrations of these agents. Intravenous oxytocin is needed to reverse uterine relaxation after washout of the inhalational agent. Danger: maternal hyperventilation with high concentrations of a halogenated agent may result in cardiovascular collapse from cardiac depression
b. Fetal effects: low concentrations over a short period of time cause neonatal sedation. Higher concentrations and prolonged administration result in neonatal apnea and hypotension
III. ANALGESIC AND ANESTHETIC TECHNIQUES
A. Psychological preparation: Lamaze, natural childbirth classes, and self-hypnosis training are useful in decreasing the anxiety associated with labor and delivery and may reduce the amount of analgesia needed
B. Intravenous or intramuscular narcotics provide incomplete analgesia and interfere with the mother’s ability to concentrate and cooperate
C. Paracervical block
1. Injection of small amounts of local anesthetic into the cervix provides temporary pain relief. It is indicated in parturients with a history of short labor. Pudendal block may be needed for delivery
a. Short duration
b. May lead to high fetal and uterine drug levels leading to fetal bradycardia and uterine vasoconstriction
D. Pudendal block, perineal infiltration
1. Pain from uterine contraction is not blocked
2. Possible intravascular injection and maternal overdose
Figure 9. Regional anesthetic techniques used for obstetric analgesia- anesthesia. Lumbar sympathetic block is rarely used but is highly effective in relieving pain of the first stage and may be prefereable to paracervical block, especially in high risk pregnancies. (Modified from and courtesy of Bonica, J.J.: An atlas on mechanisms and pathways of pain in labor. What’s New, 217:16, 1960.)
Regional anesthesia: epidural analgesia, segmental lumbar, and caudal
Labor and delivery
Maternal effects: segmental analgesia to the 10th thoracic dermatome causes little or no change in maternal cardiovascular status or uterine blood flow with adequate, acute hydration, and prevention of aortocaval compression
Fetal effects: small amounts of local anesthetics do not effect the baby
Course of labor: uterine contractility may improve with pain relief, due to a decrease in maternal norepinephrine
Contraindication for regional anesthesia
Active neurological disease
Infection at the site of injection
Inability to communicate
Table 2. Drugs used for Epidural Anesthesia for Labor and Delivery
A. Initial block
1. Bupivacaine: 0.25%, 10 mL
2. Sufentanil: 10-15 mcg, saline 10 mL
3. Bupivacaine: 0.125, plus
a. Fentanyl: 1 mcg/mL, or
b. Sufentanil: 10-15 in saline 10 mL
B. Subsequent block
1. Intermittent as above
2. Continuous infusion rate 10-12 mL/hr
a. Bupivacaine 0.0625 plus fentanyl 1-2 mcg/mL, or
b. Bupivacaine 0.0625 plus sufentanil 0.1-0.2 mcg/mL
C. If perineal analgesia is needed for delivery, administer 10-15 mL of lidocaine 1-2% or chloroprocaine 3%
Cesarean section: higher sensory and sympathetic block to T2 results in peripheral vasodilation, capillary engorgement, decreased venous return and is associated with an incidence of hypotension of 30-50% even if prehydrated with 20 mL/kg and left lateral tilt is maintained. Administration of oxygen by face mask is mandatory
Lidocaine 2%, 20-25 m/L, with or without epinephrine, 1:200,000, and fentanyl 50 mcg
Bupivacaine 0.5%, 20-25 m/L with fentanyl 50 mcg, or
Chloroprocaine 3%, 20-30 m/L
Treatment of hypotension: increase lateral tilt, increase IV fluids, administer ephedrine 5 mg IV in increments as soon as first fall in blood pressure is noted. Ephedrine is the vasopressor of choice because it does not cause uterine vasoconstriction in clinical doses
Figure 10. Influence of vasopressors on uterine blood flow and mean arterial pressure (MABP). Note that ephedrine does not influence uterine blood flow even with doses that increas maternal MABP as much as 50%. On the other hand, other vasopressors decrease uterine blood flow, and the greater the increase in MABP (and presumably the greater the dose of the vasopressor) the greater the decrease in uterine blood flow. (Courtesy of Bromage, P.R.: Epidural Analgesia, Philadelphia, W.B.Saunders Co., 1978; developed from data by Ralston, D., Shnider, S., and deLorimier, A.: Anesthesiology 40:354, 1974.)
Spinal anesthesia for labor and delivery
Opioids are indicated in early labor
No cardiovascular effects
No motor block
Reversal of side effects may be achieved with naloxone (Narcan) 0.04 mg IV or nalbuphine (Nubain) 5 mg IV and 5 mg IM
Opioids do not provide sufficient analgesia for delivery–pudendal block is required
Local anesthetics: tetracaine 4-5 mg or lidocaine 30-40 mg are sufficient for delivery. Advantages include fast onset of complete anesthesia for operative delivery; small amount of drug does not affect the baby, provided no hypotension ensues
Spinal anesthesia for cesarean section
The use of small amounts of drugs
Tetracaine 10-12 mg in 10% dextrose
Bupivacaine 10-15 mg (7.5% in 8.5% dextrose)
Lidocaine 75-100 mg (5% in 7.5 % dextrose)
Disadvantage: sudden onset of hypotension in 50-80% of cases, even with adequate intravenous preload with 20 mL/kg crystalloid and adequate left lateral tilt. Prophylactic intramuscular ephedrine is of limited value
Complications of regional anesthesia
Intravascular injection of epidural dose local anesthetics results in maternal seizure with fetal distress
Maternal hypotension and, if untreated, fetal acidosis
Total spinal with respiratory and cardiovascular collapse
Postdural puncture headache
General anesthesia for cesarean section
Indications: rapid induction of anesthesia for emergency cesarean section (fetal distress, bleeding placenta previa, placental abruption, uterine rupture, delivery of the second entrapped twin)
Technique: preoxygenation, three deep breaths of 100% oxygen, 4 mg/kg of thiopental IV or 1 mg/kg of ketamine IV and 1.5 mg/kg succinylcholine IV while an assistant applies cricoid pressure. After 40-60 sec, the trachea is intubated and the endotracheal tube sealed by inflating the cuff. The patient’s lungs are ventilated with nitrous oxide (5 L/min) plus oxygen (5 L/min) plus either halothane 0.5%, isoflurane 0.75%, or enflurane 1%. Muscle relaxants are used as necessary. After the umbilical cord has been clamped, deepen anesthesia with nitrous oxide and narcotic. The inhalational agent may be discontinued. The patient is extubated awake
Contraindications: patient refusal
Aspiration of gastric contents is the leading cause of maternal morbidity and mortality due to anesthesia
Inability to intubate and/or ventilate the patient: obstetrical patients are 10x more at risk than nonpregnant patients due to changed anatomy (short neck, large breasts, laryngeal edema, morbid obesity, emergency)
Severe hypertension due to light anesthesia and tracheal stimulus leads to a decrease in uterine perfusion, fetal distress, and may aggravate pre-existing hypertension (preeclampsia)
Maternal awareness and recall during anesthesia
Uterine relaxation and increased blood loss
Figure 11. The effects of pain-induced stress on maternal arterial blood pressure, noradrenalin blood level, and uterine blood flow. The stress was induced by aplication of an electric current on the skin of a ewe at term. Note that the increase in arterial pressure is very transient but the decay in norephinephrine level is more protracted and is reflected by a mirror-image decrease in uterine blood flow. (Courtesy of Shnider, S.M., et al.: Anesthesiology 50:30, 1979.)
Neonatal outcome in general anesthesia vs regional anesthesia: if conducted without complications, there is no difference in neonatal outcome as measured in Apgar scores or newborn acid-base status between these anesthetic techniques
General anesthesia: induction to delivery time has to be kept under 10 minutes and uterine to delivery time shorter than 3 minutes
Regional anesthesia: induction to delivery time is not important, but uterine incision to delivery time has to be kept under 3 minutes for the baby to be vigorous at birth
Zador G, Willeck-Lund G, Nillson BA. Acid-base changes associated with labor. Acta Obstet Gynecol Scand [Suppl] 1974;34:41-49.
Abboud TK, Nagappala S, Murakawa K, David S, Haroutunian S, Zakarian M, et al. Comparison of the effects of general and regional anesthesia for cesarean section on neonatal neurologic and adaptive capacity scores. Anesth Analg 1985;64:996-1000.
Attia RR, Ebeid AM, Fisher JE, et al. Maternal, fetal, and placental gastrin concentrations. Anaesthesia 1982;37:18-21.
Bader AM, Datta S, Arthur GR, Benvenuti E, Courtney M, Hauch M. Maternal and fetal catecholamines and uterine incision-to-delivery interval during elective cesarean section. Obstet Gynecol 1990;75:600-603.
Brizgys RV, Dailey PA, Shnider SM, Kotelko DM, Levinson G. The incidence and neonatal effects of maternal hypotension during epidural anesthesia for cesarean section. Anesthesiology 1987;64:782-786.
Celleno D, Capogna G, Tomassetti M, Costantino P, DiFeo G, Nisini R. Neurobehavioral effects of propofol on the neonate following elective caesarean section. Br J Anaesth 1989;62:649-654.
Davison JM. Overview: kidney function in pregnant women. Am J Kidney Dis 1987;9:248-252.
Eckstein KL, Marx GF. Aortocaval compression: incidence and prevention. Anesthesiology 1965;40:381-384.
Gilroy RJ, Mangura BT, Lavietes MH. Rib cage and abdominal volume displacements during breathing in pregnancy. Am Rev Respir Dis 1988;137:668-672.
Glassenberg R. General anesthesia and maternal mortality. Sem Perinatol 1991;15(5):386-396.
Gutsche, BB. Prophylactic ephedrine preceding spinal analgesia for cesarean section. Anesthesiology 1976;45:462-465.
James CF, Gibbs CP, Banner TE. Postpartum perioperative risk of pulmonary aspiration. Abstracts of scientific papers, Society for Obstetric Anesthesia and Perinatology. Vancouver: May, 1983.
Jones CM, Creiss FC. The effect of labor on maternal and fetal circulating catecholamines. Am J Obstet Gynecol 1982;194:149-153.
Lind LJ, Smith AM, McIver DK, et al. Lower esophageal sphincter pressures in pregnancy. Can Med Assoc J 1968;98:571-574.
Maltau JM, Eielsen OV, Stotcke KT. Effect of stress during labor on the concentration of cortisol and estriol in maternal plasma. Am J Obstet Gynecol 1979;134:681-684.
Marx GF, Luykx WM, Cohen S. Fetal-neonatal status following caesarean section for fetal distress. Br J Anaesth 1984;56:1009-1013.
Moore DC. Spinal anesthesia: bupivacaine compared with tetracaine. Anesth Analg 1980;59:743-750.
Moya F, Morishima HO, Shnider SM, et al. Influence of maternal hyperventilation on the newborn infant. Am J Obstet Gynecol 1965;90:76-84.
O’Sullivan GM, Sutton AJ, Thompson SA, et al. Noninvasive measurement of gastric emptying in obstetric patients. Anesth Analg 1987;66:505-511.
O’Brien WF, Saba HI, Knuppel RA, et al. Alterations in platelet concentration and aggregation in normal pregnancy. Am J Obstet Gynecol 1986;155:486-490.
Palahniuic RJ, Shnider SM, Eger EI. Pregnancy decreases the requirement for inhaled anesthetic agents. Anesthesiology 1974;41:82-87.
Pernoll ML, Metcalf J, Schlenlser TL. Oxygen consumption at rest and during exercise in pregnancy. Respir Physiol 1975;22:285-292.
Prowse CM, Gaenster EA. Respiratory and acid-base changes during pregnancy. Anesthesiology 1965;26:381-384.
Ralston DH, Shnider SM, deLorimier AA. Effects of equipotent ephedrine, metaraminol, mephentermine, and methoxamine on uterine blood flow in the pregnant ewe. Anesthesiology 1974;40:354-370.
Russell GN, Smith CL, Snowdon SL, et al. Preoxygenation and the parturient patient. Anaesthesia 1987;42:346-351.
Ueland K. Maternal cardiovascular hemodynamics. VII. Intrapartum blood volume changes. Am J Obstet Gynecol 1976;126:671-676.
Wittels B, Glosten B, Faure EA, Moawad A, et al. Opioid antagonist adjuncts to epidural morphine for postcesarean analgesia: maternal outcomes. Anesth Anal 1993;77:925-932.