The cardiovascular system undergoes significant alteration under the influence of the altered hormonal milieu of pregnancy. Cardiac output begins to rise in the first trimester and continues a steady rise peaking at 30% to 50% of preexisting levels by 32 weeks’ gestation [4]. The rise in cardiac output is produced by increases in both heart rate and stroke volume which are in response to an increase in endogenous circulating catecholamines, which affect both an inotropic and a chronotropic response [5,6]. Peripheral vascular resistance is reduced secondary to a direct effect of progesterone relaxing the smooth muscle intima of the precapillary resistance vessels, resulting in vasodilatation [6]. The arterial–venous shunt of the placenta also contributes to decreased vascular resistance. In the third trimester, the enlarged uterus may compress the vena cava (particularly in the supine position) leading to decreased venous return to the heart and a decrease in cardiac output. The third-trimester pregnant patient is best positioned so that the uterus is displaced to the left, allowing adequate venal caval flow and venous return to avoid hypotension. There is a slight drop in mean arterial pressure in normal pregnancy beginning during the second trimester secondary to the reduction in peripheral resistance. Blood volume increases in pregnancy, peaking at 50% above prepregnancy levels. The maximal increase in blood volume occurs at about 32 weeks’ gestation [7,8]. This increased blood volume leads to normalization of mean arterial pressures by term.

The pulmonic and systemic circulations undergo similar alterations. There is vasodilatation with an increased volume to capacitance. However, in the pulmonic circulation the volume and capacitance changes almost equal each other. Therefore, there is virtually no change in mean pulmonic pressures [9,10]. When the pulmonic circulation is evaluated by central catheterization, no changes in pulmonary artery pressures or wedge pressures can be attributed to pregnancy [9,11]. The increased pulmonic volume with increased capacitance renders the pregnant patient susceptible to fluid overload and pulmonary edema. Pulmonary edema will occur much more readily in pregnancy secondary to these specific maternal adaptations.

Progesterone affects the hypothalamic apneustic center. Carbon dioxide sensitivity is reduced to 30 mm Hg. This results in an increased respiratory rate and an increased tidal volume. The pregnant patient is in a chronic state of respiratory alkalosis. The kidneys compensate by excreting bicarbonate to maintain normal acid–base equilibrium [12]. The normal blood gas of pregnancy is a compensated respiratory alkalosis. The normal pH is 7.44 and the bicarbonate decreases 4 mEq per L [12]. Vital capacity and maximum voluntary ventilation are not altered. The functional residual capacity is reduced as the diaphragm is elevated. The reduced bicarbonate level renders the pregnant patient much more susceptible to the development of metabolic acidosis in response to a variety of conditions [12,13].

Plasma volume in pregnancy increases by 50% for prepregnancy levels. The red cell mass will increase in pregnancy by 30% over prepregnancy levels. This leads to a dilutional effect, decreasing hemoglobin concentrations (lower normal: 10.5 to 11 g per dL) and hematocrit levels (30% to 35%). This phenomenon has been termed the physiologic anemia of pregnancy [8,14].

Increased catecholamine and steroid levels in pregnancy cause a demargination of mature leukocytes from the
endothelium. This leads to a physiologic leukocytosis of pregnancy, with the white blood cell count increasing by 5,000 to 10,000 cells per mL [8,14].

Estrogen stimulates the hepatocyte endoplasmic reticulum, leading to an increased protein production. There is also increased synthesis of several clotting factors (VII, VIII, IX, and X) throughout pregnancy. Fibrinogen increases by 20%, with an average level during gestation of 400 mg. These increases render the pregnant woman hypercoagulable [15]. Critically ill pregnant patients rendered immobile require some form of prophylaxis to prevent venous thromboembolic events as they are at higher risk secondary to the hypercoagulability of pregnancy.

Renal plasma blood flow and glomerular filtration rate increase by approximately 30% to 50% from prepregnant levels resulting in an increased creatinine, urea, and uric acid clearance, with a decrease in serum creatinine (normal: 0.5 to 0.9 mg per dL), blood urea nitrogen (normal: 10 to 15 mg per dL), and uric acid (normal: 2.5 to 3.5 mEq per L) levels [15,16,17]. When drugs with renal clearance are used in pregnancy, their dose needs to be adjusted to account for increased renal clearance. Progesterone relaxes the renal collecting system. The muscularis of the bladder is relaxed and urinary stasis occurs. The angle of the urethra to the vagina is altered, making urinary tract infections common in pregnancy. If bladder catheterization is required for more than 12 hours, antibiotic prophylaxis is needed to prevent urinary tract infection (Table 156.1).

Opiate narcotic agents administered for short periods of time have been shown to be safe in pregnancy. Morphine and meperidine administered intravenously, intramuscularly, or in patient-controlled pumps, have demonstrated no adverse fetal effects. Chronic opiate use in pregnancy has been associated with intrauterine growth restriction. Intrauterine fetal addiction with withdrawal may occur [28,29,30]. Intrauterine fetal withdrawal has been associated with intrauterine fetal demise. Oral opiates may be used with similar cautions.

Codeine-containing compounds should be avoided in the first trimester because they have a small teratogenic potential [30]. These compounds may be used in the second and third trimesters for short intervals with little fetal risk. Nonsteroidal anti-inflammatory agents may decrease fetal renal blood flow, leading to oligohydramnios. They also will lead to the in utero closure of the ductus arteriosus, producing fetal pulmonary hypertension after 32 weeks’ gestation. Short courses of indomethacin may be used with caution prior to 32 weeks’ gestation. Benzodiazepines may be used; they have not been shown to exert an adverse fetal effect. High doses near the time of delivery may lead to neonatal depression [30,31].

Penicillin, penicillin derivatives, as well as cephalosporins have no known adverse fetal effect. Erythromycin, clindamycin, and vancomycin are considered safe in pregnancy. There is some concern regarding renal toxicity with vancomycin. Aminoglycosides have been implicated with fetal ototoxicity [30]. However, only streptomycin and kanamycin have been implicated. Gentamicin has not been reported to have significant ototoxicity. Gentamicin may be used in life-threatening infections while carefully monitoring levels. Sulfonamides complete with bilirubin-binding sites and may lead to neonatal kernicterus if administered in the third trimester. Tetracycline is teratogenic, leading to brown teeth and abnormal long bone development [30,32,33] (Table 156.3).

Unfractionated heparin, because of its molecular size and ionic negative charge, has been shown not to cross the placental membrane [34]. Therefore, it is the anticoagulant of choice in all trimesters of pregnancy and may be used with relative fetal safety. Fractionated heparins also have been shown not to cross the placental membrane. They may be used throughout pregnancy as well. If fractionated heparins are used in pregnancy, it is advised to change to unfractionated heparin late in the third trimester. If surgical intervention is needed, unfractionated heparin may be reversed with protamine sulfate and the activated partial thromboplastic time is a more reliable monitor for anticoagulant effect than the activated factor Xa assessment needed to assess the activity of fractionated heparins [35,36]. Warfarin and its derivatives are contraindicated in the first trimester as these agents are teratogenic, producing midline defects such as clefts, cardiac septal defect, and limb bud abnormalities. In all trimesters, warfarin crosses the placenta and may lead to spontaneous fetal bleeding [37,38,39]. In some select cardiac patients (particularly those with mechanical valves), warfarin may be used in the second and early third trimesters. Fetal intracranial bleeding has been observed with warfarin use in the late third trimester.