Part 11 (1/2)
Opiates, sedatives, and tranquilizers are contraindicated in asthmatics because they cause alveolar ventilatory depression, and are a.s.sociated with respiratory arrest immediately after use (Table 5.4). Beta-adrenergic blockers and parasympathetic agents should also be avoided in asthmatics because they can cause bronchospasm.
Additionally, if prostaglandins are needed for labor induction or termination of pregnancy, prostaglandin E (PGE ), a bronchodilator, should be administered, rather than 2 2.prostaglandin F (PGF ), because it has potent bronchoconstricting effects and may 2a 2a Key references 113.
precipitate status asthmaticus (Fishburne et al et al., 1972a, 1972b; Hyman et al et al., 1978; Smith, 1973).
Chronic asthma Chronic asthma patients need additional steroid therapy for coverage during the stress of labor if they have received oral steroid therapy for more than 2 weeks within the previous year to prevent adrenal crisis. Hydrocortisone, 100 mg IM or IV every 68 h for 24 h, is usually given. Corticosteroids should be given in cases of severe or mild asthma with wheezing that is unresponsive to bronchodilators. Initially, prednisone, 3060 mg daily is given to prevent status asthmaticus. Beclomethasone dipropionate is effective and safe when prolonged steroid use is necessary.
Beta-agonist by inhalation every 34 h as needed is used for outpatient management of chronic asthma, along with inhalation steroids such as beclomethasone (Cunningham, 1994).
Cromolyn sodium can be given chronically by inhalation, and is fairly effective in improving the symptoms of an asthmatic. An added benefit with cromolyn use is a decreased requirement for other antiasthma agents. Cromolyn therapy is best begun during remissions because it requires several days to reach an effective dosing regimen.
Medications that cause bronchospasm or depress alveolar ventilation should be avoided in the pregnant woman with asthma (Table 5.4).
Key references ACOG (American College of Obstetricians and Gynecologists). Pulmonary Disease in Pregnancy. Technical Bulletin No. 224, American College of Obstetricians and Gynecologists, Was.h.i.+ngton, DC, June 1996.
Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. A Reference Guide to Fetal and Neonatal Risk, 6th edn. Philadelphia: Lippincott Williams & Wilkins, 2005: 8734.
Dombrowski, M.P. Pharmacologic therapy of asthma during pregnancy. Obstet Gynecol Clin North Am 1997; 24 24: 55974.
Jana N, Vasishta K, Saha SC, Khunnu B. Effect of bronchial asthma on the course of pregnancy, labour and perinatal outcome. J Obstet Gynaecol 1995; 21 21: 227.
Kallen B, Rydhstroem H, Aberg A. Asthma during pregnancy a population-based study. Eur J Epidemiol 2000; 16 16: 16771.
Little BB. Pharmac.o.kinetics during pregnancy. Evidence-based maternal dose formulation.
Obstet Gynecol 1999; 93 93: 85868.
Schatz M. The efficacy and safety of asthma medications during pregnancy. Semin Perinatol 2001; 25 25: 14552.
Stenius-Aarniala B, Hedman J, Teramo KA. Acute asthma during pregnancy. Thorax 1996; 51 51: 411.
Stenius-Aarniala B, Riikonen S, Teramo K. Slow-release theophylline in pregnant asthmatics.
Chest 1995; 107 107: 642.
Weinberger M, Hendeles L. Theophylline in asthma. N Engl J Med 1996; 334 334: 1380.
Wendel PJ, Ramin SM, Barnett-Hamm C, Rowe TF, Cunningham FG. Asthma treatment in pregnancy. A randomized controlled study. Am J Obstet Gynecol 1996; 175 175: 150.
Further references are available on the book's website at6.Anesthetic agents and surgery during pregnancy Anesthetic agents 117.
Inhaled anesthesia agents 119.
Local anesthetics 117.
Systemic a.n.a.lgesics 120.
General anesthetics 118.
Special considerations 121.
Neuromuscular blocking agents 118.
Key references 125.
Surgery during pregnancy is necessary among approximately 12 percent of gravidas in the USA (Brodsky, 1983; Friedman, 1988). Many surgeons are reluctant to perform operative procedures on women known to be pregnant, although emergency procedures are sometimes necessary. In addition, elective or indicated procedures may be carried out on women with an unrecognized pregnancy. Obstetrical surgery (i.e., Caesarean section) is increasingly common with a steady rise in the Caesarean section rate from 45 percent in the 1960s to rates exceeding 20 percent in contemporary practice (Gilstrap et al et al., 1984; Notzon et al et al., 1987).
General principles that the clinician should be aware of when surgery is antic.i.p.ated in a pregnant woman are based on physiologic differences between the pregnant and nonpregnant state (Box 6.1). Most importantly, two patients are involved, the mother and her fetus. Virtually all anesthetic agents and 98 percent of medications cross the placenta, exposing the fetus to medically significant levels. In addition, mild changes in maternal cardiopulmonary status (i.e., changes in blood pressure or oxygen saturation) may have physiologically important sequelae for the fetus, but are of little consequence Box 6.1 General principles regarding surgery and anesthesia Box 6.1 General principles regarding surgery and anesthesia during pregnancy during pregnancy Two patients: Mother and embrofetus a.s.sume that all anesthetics and 98 percent of medications cross the placenta, resulting in fetal levels Minor maternal cardiopulmonary status changes may have profound effects on the fetus Numerous maternal physiological changes occur during pregnancy (Table 6.1) Aspiration pneumonitis risk is increased during pregnancy Laboratory and radiologic procedures should be performed as indicated Indicated surgery during pregnancy showed be performed statim because delays increase risks of morbidity and mortality Anesthetic agents and surgery during pregnancy 115.
to the mother. Even a minimal degree of hypotension and hypoxia is to be avoided because this may result in placental hypoperfusion and fetal hypoxemia. Pregnant women being prepared for surgery should be placed on their left side, adequately hydrated, and preoxygenated prior to induction of anesthesia.
Pharmac.o.kinetics of anesthetic agents have been reported for only pancuronium, and its disposition was a pregnancy-a.s.sociated decreased half-life, and this was probably due to significantly increased clearance (Little, 1999).
Table 6.1 Physiologic changes in pregnancy Physiologic changes in pregnancy System Cardiovascular Cardiac output Increase Blood volume Increase Heart rate Increase Blood pressure Initial decreasea Peripheral resistance Decrease Hematocrit Decrease Hematologic Leukocytes Increase Fibrinogen (I) Increase Factors VIIX Increase Factors II Slow increase Factors XI, XIII Decrease Platelets Unchanged Prothrombin time/ partial thromboplastin time Slow decrease Respiratory Tidal volume Increase Vital capacity Unchanged Functional residual capacity Decrease Compliance Unchanged Minute ventilation Increase pCO Decrease 2.HCO.
Decrease 3.Renal Serum creatinine Decrease Serum blood urea nitrogen Decrease Creatinine clearance Increase Gastrointestinal Gastric emptying Decrease Cardiac valve competency Decrease Regurgitation Increase aReturns to prepregnancy levels by term.
From Little, 1999; Gilstrap and Hankins, 1988.
116.
Anaesthetic agents and surgery during pregnancy Several maternal physiologic changes occur during pregnancy (Table 6.1), and the most marked is expansion of the maternal blood volume by up to 50 percent. Increased blood volume is caused by a plasma volume increase of approximately 1000 cc and a 300500 cc increase in red cells. This usually results in lower hematocrit compared to the nonpregnant woman, and is commonly known as physiologic anemia of pregnancy.
Increased renal blood flow is a result of the increase in blood volume. Accordingly, the glomerular filtration rate increases (as measured by the endogenous creatinine clearance) because of increased blood volume. Serum creatinine and blood urea nitrogen decrease because of dilution by increased plasma volume. Other changes in the renal system include dilatation of the ureters and a relative stasis of urine, resulting in a 'relative'
hydronephrosis. The relative hydronephrosis is frequently more p.r.o.nounced on the right than on the left side.
Other cardiopulmonary changes that occur during pregnancy include a slight increase in heart rate, and decreased systolic and diastolic blood pressures in the second trimester.
Blood pressure gradually returns to prepregnancy levels by the third trimester. Most women have a systolic flow murmur by midpregnancy. Respiratory rate increases slightly during pregnancy with a decrease in physiologic 'dead s.p.a.ce' as pregnancy progresses. Tidal volume is increased during pregnancy, but minute ventilation and compliance do not change during pregnancy. Blood pCO and HCO decrease during preg-2 3.nancy, while pH is slightly increased during pregnancy. Hence, upper normal range pCO for nonpregnant women probably indicates CO retention.
2.2.Gastrointestinal system changes with pregnancy affect pregnant women that require anesthesia and/or surgery. The risk for aspiration pneumonitis in surgery on the gravid patient is increased because of pregnancy-a.s.sociated decreases in intestinal motility and gastric emptying. Hepatic function is also altered during pregnancy. Maternal alkaline phosphatase levels are increased during gestation.
Liver cytochrome P-450 (CYP) 3A4 and CYP2D6 activities increase during pregnancy. Importantly, the enzyme responsible for metabolism of 50 percent of pharmacologic agents (CYP1A2) is downregulated. This has implications for anesthesia dose management of the pregnant patient; lower doses than in the nongravid patient may achieve the desired anesthetic effect. CYP2C19 activity is upregulated in pregnant compared to nonpregnant women, but even during pregnancy its activity is not higher than normal adult male levels. Extrahepatic enzymes (e.g., cholinesterase) that also metabolize some anesthetics have diminished activity during pregnancy.
Liver fibrinogen production is also increased during pregnancy. Serum levels as high as 400 mg percent are not unusual during the third trimester and cause increased red cell sedimentation rate in pregnant women. Hematocrit is decreased during pregnancy accompanied by a relative leukocytosis (white blood cell count greater than or equal to 10 00012 000 or even higher during labor). Several hematologic measures are unchanged during pregnancy: for example, the relative percent of immature forms (i.e., 'bands'), lymphocytes, eosinophils, and platelet count.
Whole blood clotting time, prothrombin time, and partial thromboplastin time remain in normal ranges during pregnancy.
Surgery should be performed without delay when it is indicated for life-threatening maternal conditions. Indicated laboratory tests and radiologic procedures should be performed without hesitation to properly guide life-saving surgical procedures.
Local anesthetics 117.
ANESTHETIC AGENTS.
Secondary effects of anesthetic agents (hypotension, hypoxia) are important to avoid in the gravid patient as these may cause adverse fetal effects. Anesthetic adjuncts, or other 'nonanesthetic' drugs and medications during the pre-, intra-, and post-operative periods may also adversely affect the fetus.
LOCAL ANESTHETICS.
Local anesthetics may be injected in subdural or epidural s.p.a.ces for regional anesthesia (Table 6.2). Topical application results in negligible fetal exposure and minimal risk.