Epidemiology

Since 1981, official advisories have warned against the use of alcohol by pregnant women or women considering pregnancy. Yet, the 2015 National Survey on Drug Use and Health noted that 9.3% of pregnant women 15 to 44 years of age reported past-month alcohol use, 4.6% reported binge drinking, and 0.8% reported heavy drinking. Not all of these women have alcohol use disorder or are drinking alcohol recklessly. Some may not be aware that they are pregnant, or may not be knowledgeable of the ill effects on their pregnancy.

Pharmacology

Alcohol is absorbed through the gastrointestinal tract, primarily within the small intestine, and is then metabolized by alcohol and acetaldehyde dehydrogenases. This process leads to the production of acetaldehyde and the reduction of nicotinamide adenine dinucleotide (NAD ⁺ ) to NADH. The intracellular accumulation of NADH relative to NAD ⁺ results in metabolic derangements, including the inhibition of fatty acid oxidation, resulting in a fatty liver and the inhibition of gluconeogenesis, leading to hypoglycemia or lactic acidosis. A small residual amount (2% to 8%) of alcohol is excreted via the lungs, urine, and sweat.

Systemic Effects

Legally defined “intoxication” implies a blood alcohol level of at least 80 to 100 mg/dL, although behavioral, cognitive, and psychomotor changes can occur at levels of 20 to 30 mg/dL (e.g., after one to two drinks) ( Table 53.3 ).

Alcohol has complex effects on the central nervous system (CNS); it acts as both a depressant and a stimulant through a variety of neurotransmitter pathways. Consuming alcohol in conjunction with barbiturates or benzodiazepines compounds these effects. Endogenous opioids interact with alcohol to “reinforce” further alcohol use; this effect is blunted by opioid antagonists such as naltrexone, which can be used in the treatment of alcohol use disorder.

Alcohol and its metabolites (e.g., acetaldehyde) can be directly toxic to brain tissue. Chronic alcoholism is associated with brain atrophy that results in impairment of memory, abstract problem-solving, verbal learning, and visual-spatial processing. Additional adverse neurologic effects result from vitamin (e.g., thiamine, vitamin B ₁₂ ) deficiencies.

Heavy alcohol consumption can result in hepatic cirrhosis, which, in turn, can lead to encephalopathy, coagulopathy, and esophageal varices ( Table 53.4 ). Gastrointestinal mucosa injury, pancreatitis, and cardiomyopathy may also occur. In a retrospective cohort study of the Nationwide Inpatient Sample database, women with a diagnosis of alcohol use disorder undergoing cesarean delivery were twice as likely as women without alcohol use disorders to develop a hospital-acquired infection, including urinary tract infection or sepsis. The underlying pathophysiology was not reported but could involve an immunocompromised state in chronic alcohol users.

Symptoms of acute alcohol withdrawal (e.g., nausea, vomiting, tachycardia, hypertension, arrhythmias, tremor, hallucinations, agitation, seizures) usually occur within 6 to 48 hours after cessation of chronic consumption ( Table 53.5 ). Pharmacologic therapy to minimize the signs and symptoms of alcohol withdrawal includes the use of benzodiazepines and alpha ₂ -adrenergic receptor agonists (e.g., clonidine). Dexmedetomidine, a potent alpha ₂ -adrenergic receptor agonist, has also been investigated as an adjunct therapy. The most severe form of withdrawal symptoms, delirium tremens, manifests as agitation, disorientation, hallucinations, and fever combined with autonomic instability. Delirium tremens, though rare in pregnant women, can lead to maternal and fetal death if untreated.

Effects on Pregnancy and the Fetus

Intrauterine alcohol exposure is the leading cause of preventable birth defects in the United States. No safe level of alcohol consumption by pregnant women has been identified as studies investigating minimal to moderate prenatal alcohol exposure during pregnancy have been limited by confounding variables. According to the National Organization on Fetal Alcohol Syndrome, fetal alcohol spectrum disorders (FASD) is the “umbrella term describing the range of effects that can occur in an individual whose mother drank alcohol during pregnancy. These effects include physical, mental, behavioral, and/or learning disabilities with possible lifelong implications.” Fetal alcohol syndrome (FAS) refers to a clinical diagnosis and is based on the presence of particular neonatal facial features (e.g., small palpebral fissures, flat mid-face with a short upturned nose, thin upper lip) and significant impairment in neurodevelopment and physical growth. A recent meta-analysis identified a range of complications that occur with a high prevalence in children affected by FAS including disorders of conduct and language disorder, chronic serous otitis media, and peripheral nerve abnormalities. Education and screening for prenatal alcohol exposure can facilitate treatment and improve pregnancy outcomes by encouraging cessation of alcohol consumption as soon as pregnancy is recognized.

Anesthetic Management

Alcohol-intoxicated parturients are at increased risk for behavioral problems, electrolyte abnormalities, greater gastric acid secretion, and co-intoxication with other substances. Determining whether the patient can protect her airway is of paramount importance because acute intoxication increases the risk for pulmonary aspiration of gastric contents. In addition, these patients may have intravascular volume depletion secondary to vomiting, inadequate oral intake, diuresis, and hypoalbuminemia. Significant alcohol ingestion in the setting of poor oral intake may also manifest as severe hypoglycemia.

Neuraxial analgesia or anesthesia can be safely administered for labor or cesarean delivery in patients with alcohol use disorders provided that (1) the patient is cooperative, (2) there is no evidence of coagulopathy (as a result of liver disease), (3) the patient is volume replete, and (4) baseline neurologic deficits (e.g., peripheral neuropathy, cognitive deficits) are assessed and documented.

If emergency delivery is required and the patient is either uncooperative or too sedated to protect her airway, general anesthesia will be necessary. The patient should receive pharmacologic aspiration prophylaxis (e.g., nonparticulate antacid, histamine-2 (H ₂ )-receptor antagonist, metoclopramide) and should undergo a rapid-sequence induction of general anesthesia.

Evidence from published reports is inconclusive about predictable differences in anesthetic requirements in patients with acute and chronic alcohol use. Acute alcohol intoxication is believed to decrease anesthetic requirement, in part because of the additive effect of alcohol and other CNS depressants. The notion that chronic alcoholics require more anesthesia than their non–alcohol-using counterparts is based primarily on data from an abstract published by Han in 1969, who demonstrated that the mean minimum alveolar concentration (MAC) for halothane in six chronic, nonpregnant, heavy alcohol users was significantly greater than that for six healthy adults. Subsequently, Swerdlow et al. assessed the response to thiopental in 11 nonpregnant, chronic alcohol users. After eliminating potential confounders such as acute intoxication, withdrawal, polysubstance use, and end-organ dysfunction, they found that chronic alcohol intake did not alter thiopental dose requirements, pharmacokinetics, or pharmacodynamics. No large population studies have assessed dose requirements for volatile anesthetic agents or hypnotic agents in patients who chronically use alcohol.

Short-term consumption of alcohol inhibits the metabolism of drugs by the liver (through competition for cytochrome P450), which results in higher plasma concentrations of hepatically metabolized drugs. Long-term consumption of alcohol increases the activity of cytochrome P450, resulting in decreased levels of medications such as diazepam and labetalol, and increased levels of toxic metabolites that occur from hepatic degradation of illicit drugs such as cocaine. Both pregnancy and liver disease can lead to decreased plasma concentrations of pseudocholinesterase; however, this does not seem to have a clinically significant effect on the degradation of succinylcholine or ester local anesthetics.

Pregnant women who regularly consume large amounts of alcohol and undergo general anesthesia for cesarean delivery may be at high risk for awareness under anesthesia. The high doses of volatile anesthetics often recommended in nonpregnant, chronic alcohol-using patients can lead to significant uterine atony and potential increased blood loss. Therefore, a balanced anesthetic technique that combines induction with generous doses of a hypnotic agent with succinylcholine, followed by maintenance with a volatile anesthetic agent (limited to 0.5 to 0.8 MAC after delivery to prevent uterine atony), nitrous oxide, and an opioid and a benzodiazepine (for analgesia and amnesia), should be considered. Withholding additional muscle relaxation after induction and adding a brain function monitor if time and circumstance permit may help identify patients who could benefit from additional anesthesia.

Epidemiology

On a daily basis, 80% to 98% of women drink caffeine-containing beverages. The prevalence of consumption of caffeine-containing beverages during pregnancy is unknown.

Pharmacology

Caffeine (1,3,7-trimethylxanthine) is a naturally occurring alkaloid found in coffee, tea, cocoa, and some soft drinks and medicines. The primary sources of caffeine in the adult diet are coffee (56 to 100 mg/100 mL if brewed) and tea (20 to 73 mg/100 mL). Caffeine is readily absorbed through the gastrointestinal tract with maximum blood concentrations 1 to 1.5 hours after ingestion. Caffeine undergoes hepatic metabolism and is then excreted in the urine. In pregnancy, the half-life increases from 4 hours in the first trimester to 11.5 to 18 hours by the third trimester. Caffeine crosses the placenta and can also be found in breast milk. The half-life in the neonate is prolonged compared with that in children and in nonpregnant women. Habitual use of caffeine at levels greater than 500 to 600 mg/day is defined in some studies as abuse.

Systemic Effects

Caffeine acts as an antagonist at the adenosine receptor. In the absence of the inhibitory effects of adenosine, the neurotransmitters norepinephrine, dopamine, and serotonin are released in increased concentrations. Systemic effects of caffeine include CNS stimulation, changes in blood pressure and metabolic rate, and diuresis (see Table 53.3 ). The side effects attributed to caffeine vary among individuals, in part related to the doses ingested and the chronicity of use. Studies of the effects of caffeine on alertness, vigilance, mood, and memory have produced inconsistent results.

Moderate caffeine intake (less than or equal to 400 mg/day or less than or equal to 4 cups of coffee/day) does not seem to negatively affect cardiovascular health in most people. Although some people who ingest caffeine report tachycardia and palpitations, doses lower than 450 mg/day do not appear to increase significant cardiac arrhythmias in healthy patients or those with ischemia or ventricular ectopy. Caffeine doses as low as 250 mg have been reported to have a hypertensive effect after acute ingestion (an increase in systolic blood pressure of 5 to 15 mm Hg and an increase in diastolic blood pressure of 5 to 10 mm Hg), particularly in caffeine-naïve individuals; however, epidemiologic studies have produced inconsistent results. Caffeine appears to affect bladder function in women. Moderate caffeine intake may exacerbate preexisting bladder symptoms, and excessive intake (greater than 400 mg/day) increases the risk for bladder dysfunction.

Evidence suggests that caffeine is not a human carcinogen. The lethal dose of caffeine in humans has been estimated to be 10 g; however, only a few such cases have been reported.

Caffeine withdrawal is associated with headache, anxiety, depressed mood, and fatigue (see Table 53.5 ). Typically, symptoms begin 12 to 24 hours after cessation of use, peak at 20 to 48 hours, and last up to 7 days. The severity and likelihood of symptoms are not predictable.

Effects on Pregnancy and the Fetus

Caffeine readily crosses the placenta. Whereas animal studies have shown a teratogenic effect with very high doses, moderate doses do not appear to result in teratogenesis in humans. There is some evidence that caffeine at doses greater than 300 mg/day may result in fetal growth restriction and decreased birth weight, particularly in women who also smoke or drink significant amounts of alcohol, although previous studies have not shown an association between low or moderate caffeine intake (less than 300 mg/day) and greater risk for spontaneous abortion or preterm delivery. Weng et al. found that caffeine consumption greater than 200 mg/day was associated with an increased risk for miscarriage, particularly among pregnant women who did not have a previous history of miscarriage.

Moderate first-trimester caffeine intake was found to have either no significant effect or to have a protective effect on the development of maternal gestational diabetes mellitus, depending on the population studied. Moderate intake of caffeine in lactating women does not adversely affect postnatal development.

Anesthetic Management

Caffeine may enhance the side effects of beta-adrenergic receptor agonists such as epinephrine and albuterol. Caffeine may also increase the risk for a hypertensive crisis in patients taking monoamine oxidase inhibitors (MAOIs). Chronic caffeine use causes an increase in CYP1A2 activity, which can have potential effects on medications degraded by this enzyme. The elimination of theophylline and acetaminophen can be slowed by habitual caffeine consumption, resulting in higher serum drug concentrations. In contrast, serum concentrations of lithium may be decreased secondary to caffeine-enhanced elimination.

Perhaps of greatest significance to the anesthesia provider is the potential for caffeine withdrawal headache when caffeine intake is abruptly stopped during labor and delivery. Caffeine withdrawal should be considered in a postpartum patient with a nonspecific, nonpositional headache without associated lateralizing neurologic findings (see Chapter 30 ). Evidence for the efficacy of caffeine in the treatment of post–dural puncture headache is scant (see Chapter 30 ).

Epidemiology

As public awareness has grown regarding the hazards of smoking during pregnancy, the prevalence of cigarette smoking during pregnancy has declined; an estimated 18% of pregnant women reported smoking (in the past month) in 2003, compared with 13.6% in 2015. The percentage of young pregnant and nonpregnant female smokers 18 to 25 years of age was equivalent (23%), but fewer older pregnant women (26 to 44 years of age) reported smoking than nonpregnant women of the same age range (8.1% versus 23.3%). Among the approximately 40% of patients who stop smoking when they discover that they are pregnant, 60% to 80% return to smoking by 6 months postpartum.

Pharmacology

More than 4000 chemicals are found in tobacco, including nicotine, carbon monoxide, and cyanides. Tobacco is most often smoked, but it can also be chewed or sniffed. Nicotine, the principal component of tobacco, acts at peripheral and central nicotinic (acetylcholine) receptors throughout the body to affect the release of catecholamines. Nicotine’s effects begin immediately on exposure, and the half-life is typically a few hours; it is then rapidly metabolized in the liver and the lungs and excreted by the kidneys. Nicotine’s acute effects are of shorter duration in heavy smokers than in light smokers.

Carbon monoxide, another key component, interferes with oxygen delivery to the cells by competitively binding to hemoglobin, decreasing the latter’s oxygen-binding capacity and shifting the oxyhemoglobin dissociation curve to the left. Depending on the extent of smoke inhalation, carbon monoxide may occupy 3% to 15% (or more) of the oxygen-carrying capacity of the blood.

Systemic Effects

Smoking alters maternal physiology through tobacco’s acute pharmacologic action and its contribution to comorbid disease. Peripherally, nicotine increases sympathetic tone, thereby increasing maternal heart rate, blood pressure, and cardiac work (see Table 53.3 ). Nicotine affects neurotransmitter release in different areas of the brain, producing feelings of alertness, euphoria, and, ultimately, dependence.

Increased production of carboxyhemoglobin is thought to be a major factor in the impaired wound healing observed in smokers. Smoking also promotes atherosclerosis. The pulmonary effects of tobacco smoking include changes in the increased volume of mucus, impaired mucociliary clearance, and an increased incidence of bronchitis and chronic obstructive pulmonary disease (see Table 53.4 ).

Tobacco is addictive, and cessation of its use produces withdrawal symptoms of cravings, irritability, headache, cough, and insomnia (see Table 53.5 ). Smoking cessation interventions include counseling and therapy, hypnosis, acupuncture, and pharmacologic therapy. There is insufficient evidence to recommend nicotine replacement therapy (e.g., nicotine patch) in pregnancy ; the American College of Obstetricians and Gynecologists (ACOG) recommends that it be used only when nonpharmacologic interventions have failed.

Effects on Pregnancy and the Fetus

Nicotine has a low molecular weight and readily crosses the placenta, eventually yielding higher fetal than maternal nicotine concentrations. Smoking may result in decreased fetal oxygenation as a result of increased concentrations of carboxyhemoglobin and reduced uteroplacental perfusion. This compromised state can lead to decreased uptake of nourishing amino acids by the placenta. Smoking also adversely affects fetal growth. Salihu et al. documented that infant mortality was 40% higher in the offspring of women who smoked than in the offspring of nonsmoking women; this risk increased in a dose-dependent fashion for infants that were small for gestational age (SGA). In a more recent study, smoking cessation in early pregnancy was associated with a greater reduction in risk for fetal growth restriction compared with cessation later in pregnancy.

Smoking is also associated with higher incidences of spontaneous fetal loss, preterm labor, placental abruption, and sudden infant death syndrome (SIDS). Paradoxically, smoking has been associated with a reduced risk for preeclampsia, although this may be related to the higher rates of early pregnancy loss among pregnant smokers (see Chapter 35 ).

Although the negative impact of fetal tobacco exposure on growth appears to resolve by 2 years of age, there may be other long-term effects. A growing number of studies indicate that prenatal smoking exposure may be associated with an increased risk for attention deficit/hyperactivity disorder, although it is not clear whether the relationship is causal. Holz et al. examined offspring exposed to prenatal smoking using functional magnetic resonance imaging in a prospective 25-year study. After controlling for confounders, including adversity and sex, prenatal smoking exposure appeared to have long-term effects on neural activity and development. A recent study by Quinn et al. suggested this association may be caused by confounding effects of other lifestyle and genetic issues; when cousins and siblings discordant on prenatal smoking and severe mental illness were compared, there was no increased risk for severe mental illness in the smoking-exposed newborns.

Anesthetic Management

Smoking is a risk factor for several perioperative complications, including respiratory sequelae and impaired wound healing. Smoking results in increased airway secretions, decreased ciliary motility, and impaired gas exchange. Smoking is also associated with an increase in nonspecific airway reactivity, and tracheal intubation may provoke bronchospasm. Smokers may be more likely to cough following emergence from general anesthesia, but the data are mixed and may be related to the specific volatile agent used.

The physiologic benefits of smoking cessation are progressive. Even brief smoke-free intervals can result in a reduction in the carboxyhemoglobin concentration, some improved ciliary function, and decreased small airway obstruction. However, 6 months of abstinence may be required before the function of alveolar macrophages and pulmonary cytokines during and after general anesthesia in former smokers is similar to that of nonsmokers. Neuraxial anesthesia avoids airway manipulation and is typically preferred in parturients who smoke.