Part 12 (1/2)

Non.o.bstetric surgery Non.o.bstetric surgery is sometimes necessary during pregnancy, and ranges from 1 in 500 to 1 in 635 (Affleck et al et al., 1999). Maternal mortality non.o.bstetric surgery is no greater than mortality in the nonpregnant patient. Risks to the fetus from surgery are probably related more to the specific condition requiring the surgery than to the surgery itself. Among 2565 women who underwent surgery during the first or second trimester compared to controls, the frequency of spontaneous abortion in women undergoing surgery with general anesthesia was greater for gynecologic procedures compared to surgery in other anatomic regions (risk ratio of 2 versus 1.54). The frequency of congenital anomalies was not different (Duncan et al et al., 1986).

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Anaesthetic agents and surgery during pregnancy Appendicitis is the most common nontrauma indication for non.o.bstetric surgery during pregnancy, at approximately 1 in 3000 (Affleck et al et al., 1999), and occurs with equal frequency in all three trimesters (Black, 1960).

Cholecyst.i.tis and biliary tract disease are the most common surgical conditions following appendicitis and occur in approximately 110 per 10 000 pregnancies (Affleck et al et al., 1999; Hill et al. et al. , 1975). Laparoscopic surgery morbidity and mortality was no different from the open cholecystectomy (Affleck , 1975). Laparoscopic surgery morbidity and mortality was no different from the open cholecystectomy (Affleck et al et al., 1999; Barone et al et al., 1999).

Surgical procedures for intestinal obstruction, inflammatory bowel disease, breast disease, and diseases of the ovary are also relatively common. Surgery for cardiovascular disease during pregnancy is less common, but procedures such as mitral valvotomy (el-Maraghy et al et al., 1983) valve replacement, and cardiopulmonary bypa.s.s (Bernal and Miralles, 1986) have been performed in pregnant women with reasonably good results.

Anesthesia for non.o.bstetrical surgery may be delivered via either general endotracheal or regional techniques. The choice depends on: (1) procedure to be performed; (2) emergent nature of the procedure; (3) length of time the patient has been fasting; and (4) preferences of the surgeon and the patient. General anesthesia should be accomplished through a balanced technique using nitrous oxide, oxygen, thiopental, succinylcholine, and a halogenated agent. As surgical patients, pregnant women should receive antacid prophylaxis to prevent aspiration pneumonia. The patient should also fast for 1012 h prior to antic.i.p.ated surgery, but this may not be possible in all cases (e.g., emergency procedures). Endotracheal intubation with timely extubation when reflexes have returned will help prevent aspiration complications. High-concentration oxygen should be used and hypotension should be avoided in the pregnant surgical patient.

Choice of anesthetic depends on length of the procedure and preference of the anesthesiologist. To prevent maternal hypotension and decreased uteroplacental blood flow, adequate preload with a balanced salt solution is recommended prior to initiation of the actual block. Regional anesthetic techniques have some complications (Box 6.4), but they can be minimized using preventative techniques to decrease the incidence and severity of hypotension from regional blocks (Box 6.5).

Anesthesia for Caesarean section: the uncomplicated patient Regional anesthesia is the preferred method of anesthesia for the uncomplicated patient undergoing Caesarean section. Subarachnoid (spinal) or epidural block, or a combination, are suitable anesthetic techniques for these patients. The various agents which can Regional anesthesia is the preferred method of anesthesia for the uncomplicated patient undergoing Caesarean section. Subarachnoid (spinal) or epidural block, or a combination, are suitable anesthetic techniques for these patients. The various agents which can Box 6.4 Complications of regional anesthesia Box 6.4 Complications of regional anesthesia Subarachnoid block Total spinal block Arachnoiditis Epidural block Bladder dysfunction Hematoma or infection Headaches Hypotension Hypotension Subarachnoid or intravascular injection Meningitis From Gilstrap and Hankins, 1988.

Special considerations 123.

Box 6.5 Prevention and treatment of hypotension from regional anesthesia anesthesia Positioning Ephedrine Left lateral position 2550 mg IM prophylactically Left uterine displacement 1015 mg IV for hypotension Preanesthetic hydration 5001000 cc balanced salt solution From Gilstrap and Hankins, 1988.

Box 6.6 Anesthetic agents for regional anesthesia for Caesarean section section Subarachnoid block Bupivacaine (Marcaine, spinal), 7.510.5 mg Lidocaine (Xylocaine) 5% in 7.5% glucose, 6075 mg Tetracaine (Pontocaine) 1%, 810 mg Epidural block Bupivacaine (Marcaine) 0.5% Chloroprocaine (Nesacaine) 23% Lidocaine (Xylocaine) 12% be utilized in these patients are listed in Box 6.6. Hypotension is the most common complication of these techniques and the one that has the greatest impact on the fetus (Box 6.5).

A potentially serious complication resulting from the inadvertent intravascular injection of local anesthetic is central nervous system (CNS) toxicity. Epidural veins are engorged and large during pregnancy, and may be punctured with a needle or catheter.

Symptoms of CNS toxicity include: slurred speech, dizziness, metallic taste in the mouth, ringing in the ears, paresthesias of the face, seizures, and syncope. Epinephrine to detect intravascular injection has been discussed. Treatment of CNS toxicity is primarily supportive care: airway and ventilation support, oxygen, prevention and treatment of seizures (thiopental, diazepam), and treatment for hypotension (fluid, ephedrine, and lateral uterine displacement) (Gilstrap and Hankins, 1988).

General anesthesia is used even for uncomplicated Caesarean section. The estimated rate of general anesthesia is 2126 percent (Shroff et al et al., 2004). The previously described balanced general technique of nitrous oxide, oxygen, thiopental, succinylcholine and a halogenated agent provides satisfactory anesthesia for uncomplicated Caesarean sections. Patients should be preoxygenated and placed in the lateral position with left lateral uterine displacement. While avoiding hypotension, general anesthesia provides reliable and expeditious anesthesia. Aspiration pneumonitis is the major maternal risk and neonatal cardiorespiratory depression is the major fetal risk. As a precautionary rule, all pregnant women undergoing Caesarean section should be treated as if they have 'full stomachs,' hence the importance of endotracheal intubation.

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Anaesthetic agents and surgery during pregnancy Anesthesia for Caesarean section: The complicated patient Many women who require Caesarean section have other medical complications, such as hypertension, diabetes, or heart disease. It is, therefore, imperative for the obstetrician and anesthesiologist to communicate. Importantly, this is the critical path where communication frequently breaks down (Shroff Many women who require Caesarean section have other medical complications, such as hypertension, diabetes, or heart disease. It is, therefore, imperative for the obstetrician and anesthesiologist to communicate. Importantly, this is the critical path where communication frequently breaks down (Shroff et al et al., 2004).

Pregnancy-induced hypertension (PIH) occurs among about 5 percent of pregnancies and presents a significant challenge with regard to anesthesia when Caesarean section is required (Lopez-Jaramillo et al et al., 2005). Severe PIH, blood pressure 160/110 mmHg, is a.s.sociated with several cardiovascular changes, the most important of which is changes in blood volume. Blood volume in women with severe PIH generally does not expand much above the nonpregnant state, unlike the normotensive pregnant woman.

Severe PIH patients typically have low colloidal osmotic pressures and 'leaky vessels.'

Hence, they are more likely to develop pulmonary edema following the intravenous infusion of crystalloid solutions. A small percentage of women with PIH may also have hematologic abnormalities (thrombocytopenia, hemolytic anemia). Anesthetic choice for Caesarean section in women with severe PIH is controversial. General anesthesia, preferred by some, is not without risk. Significant hypertension may develop during intubation or extubation, with increased risk of cerebral hemorrhage or cardiac failure.

Hypertensive response to endotracheal intubation for general anesthesia may be damp-ened through antihypertensives such as nitroglycerin (Hodgkinson et al et al., 1980; Snyder et al et al., 1979). The efficacy and safety of general anesthesia in these patients is shown in one study of 245 cases of eclampsia in which no cases of cerebral hemorrhage, pulmonary edema, or mortality were observed (Pritchard et al et al., 1984).

Hypotension is a major problem with conduction anesthesia (spinal or epidural), secondary to sympathetic blockade. Hypotension is difficult to treat in women with severe PIH because they may be overly sensitive to pressor agents. Preloading with crystalloid solutions must be done with great caution, being careful to prevent fluid overload in a vasoconstricted but not underfilled vascular tree. The general consensus is that spinal block is contraindicated in women with severe PIH, but many clinicians do advocate epidural anesthesia for these women (Jouppila et al et al., 1982; Marx, 1974; Moir et al et al., 1972; Newsome and Branwell, 1984). Careful attention to fluid preload, prevention of hypotension, and test of coagulation status are of paramount importance if epidurals are to be used in these gravidas. Epidural or general anesthesia is effective for women with mild PIH.

Diabetes mellitus complicates approximately 2 percent of pregnancies and many of these women require Caesarean section. When necessary among pregnant diabetics, Caesarean section should be scheduled as the first case in the morning with blood glucose well controlled prior to surgery. General anesthesia or regional techniques (including spinal) may be used. If preload is required for regional techniques, a nondextrose solution should be used to prevent neonatal hypoglycemia.

No single anesthetic technique is ideal for women with heart disease during pregnancy. Anesthetic technique choice will depend on the specific type of heart lesion present and the patient's functional cardiac status (New York Heart a.s.sociation Cla.s.sification; Dunselman et al et al., 1988). Epidural anesthesia is preferred in pregnant women requiring surgery with most varieties of heart disease, and close attention must be paid to preload and hypotension.

Key references 125.

General anesthesia is indicated for certain cardiac lesions. Pregnant women with aortic stenosis are at significant risk for hypotension and hypovolemia, and are better served by general anesthesia when Caesarean section is required. Women who have pulmonary hypertension and diminished venous return to the heart are especially at risk for hypotension and hypovolemia. Hence, they do not receive regional anesthesia when surgery is required. For women with recent myocardial infarctions, epidural or general anesthesia is efficacious.

Key references Affleck DG, Handrahan DL, Egger MJ, Price RR. The laparoscopic management of appendicitis and cholelithiasis during pregnancy. Am J Surg 1999; 178 178: 523.

Barone JE, Bears S, Chen S et al. Outcome study of cholecystectomy during pregnancy. Am J Surg 1999; 177 177: 232.

Little BB. Pharmac.o.kinetics during pregnancy. Evidence-based maternal dose formulation.

Obstet Gynecol 1999; 93 93: 85868.

Lopez-Jaramillo P, Garcia RG, Lopez M. Preventing pregnancy-induced hypertension. Are there regional differences for this global problem? J Hypertens 2005; 23 23: 1121.

Shroff R, Thompson ACD, McCrum A, Rees SGO. Prospective multidisciplinary general anesthesia in a district general hospital. J Obstet Gynaecol 2004; 24 24: 641.

Further references are available on the book's website at7.Antineoplastic drugs during pregnancy Alkylating agents 129.

Special considerations 142.

Antibiotics 136.

Summary 148.

Plant alkaloids 138.

Key references 148.

Miscellaneous agents 139.

Cancer is uncommon during pregnancy and occurs in approximately one in 10006000 pregnant women (Haas, 1984; Kennedy et al et al., 1993; Pepe et al et al., 1989). It can be estimated that one in 118 women with cancer will be pregnant, because 12.8 percent of all cancers in women occur in the 1544 age group (Third National Cancer Survey, 1975).

Population- and hospital-based studies show that the most frequently occurring cancers that present during pregnancy are cervix, breast, and ovary (Haas, 1984; Pepe et al et al., 1989). The frequencies of nongenital-type cancers during pregnancy are shown in Table 7.1. The frequencies of the various forms of genital cancers in pregnancy are shown in Table 7.2, with cervical cancer being the most common.

Table 7.1 Frequencies of nongenital cancers in pregnancy Malignancy type Frequencies of nongenital cancers in pregnancy Malignancy type Incidence (per number Source of gestations) Malignant melanoma 1:100010 000 Pavlidis (2002) Breast carcinoma 1:30001:10 000 Lymphoma 1:10001:6000 Leukemia 1:75 0001:100 000 Colon cancer 1:13 000.

Hodgkin's lymphoma 1 in 6000 Others, see below Non-Hodgkin's lymphomas Extremely rare (< 1=”” in=”” 100=”” 000)=”” acute=”” leukemia=”” 1=”” in=”” 75=”” 000=”” to=”” 1=”” in=”” 100=”” 000=”” gastrointestinal=”” (colon,=”” gastric,=”” up=”” to=”” 1=”” in=”” 10=”” 000=”” pancreatic,=”” carcinoid,=”” hepatic)=”” renal=”” cell=”” rare=”” thyroid=”” rare=”” compiled=”” from=”” pavlidis,=”” 2002=”” and=”” others=”” (donegan,=”” 1983,=”” 1986;=”” koren=”” et=”” al.,=”” 1990;=”” mclain,=”” 1974;=”” orr=”” and=”” s.h.i.+ngleton,=”” 1983;=”” parente=”” et=”” al.,=”” 1988;=”” smith=”” and=”” randal,=”” 1969;=”” yazigi=”” and=”” cunningham,=””>

Antineoplastic drugs during pregnancy 127.

Table 7.2 Frequency of genital cancers in pregnancy Type Frequency of genital cancers in pregnancy Type Frequency Cervix Carcinoma in situ 1.3 in 1000 to 1 in 770 Others Carcinoma of the cervix 1:200010 000 Pavlidis, 2002 Invasive carcinoma 0.5 in 1000 to 1 in 2200 Others Ovarian 1 in 18 000 to 1 in 25 000 Others Ovarian carcinoma 1:10 0001:100 000 Pavlidis, 2002 Data compiled from Pavlidis, 2002 and Others (Chung and Birnbaum, 1973; Hacker et al., 1982; Munnell, 1963; Yazigi and Cunningham, 1990).

When cancer is present during pregnancy, several dilemmas arise. Perhaps most important is whether the pregnancy should be continued or terminated. Several factors must be considered in this discussion: (1) the gestational age of the pregnancy; (2) the patient's desire to continue the pregnancy; (3) whether pregnancy per se per se affects the cancerous progression; and (4) the ultimate prognosis for the mother and infant. In general, pregnancies close to viability (i.e., 2428 weeks gestation) may be continued with mild to moderate adverse effects on the fetus. Of the various therapeutic modalities available, none are known to be safe for use during pregnancy. Some patients with pregnancies less than 24 weeks gestational age may best be managed by pregnancy termination. affects the cancerous progression; and (4) the ultimate prognosis for the mother and infant. In general, pregnancies close to viability (i.e., 2428 weeks gestation) may be continued with mild to moderate adverse effects on the fetus. Of the various therapeutic modalities available, none are known to be safe for use during pregnancy. Some patients with pregnancies less than 24 weeks gestational age may best be managed by pregnancy termination.

Decisions regarding pregnancy termination between 24 and 28 weeks are more difficult.

Management is most often dependent upon the patient's wishes, as well as the type and stage of the woman's cancer.

Available data suggest that pregnancy affects neither the progression nor prognosis for most cancers; the exception to this is the critical period of neural plate development (1018 days postconception). However, pregnancy may interfere with the diagnostic procedures for some types of malignancies.

The pharmac.o.kinetics of neoplastics is poorly studied, with only sufficient information to speculate on the effects of pregnancy on metabolism and clearance of cyclophosphamide. Of the five cytochrome P-450 enzymes that metabolize cyclophosphamide (Matalon et al et al., 2004), the activity of one, CYP3A4 (Little, 1999), is significantly increased during pregnancy. This implies that dose size or dose frequency should be adjusted for pregnant women by monitoring levels, and adjusting these parameters to maintain therapeutic levels.

A major consideration in treating cancer during pregnancy is finding the optimal regimen. This must include consideration of: (1) the effects of diagnostic tests; (2) surgical procedures; (3) radiotherapy; and (4) chemotherapy (Gilstrap and Cunningham, 1996; Koren et al et al., 1990; Yazigi and Cunningham, 1990). It is important to minimize the amount of fetal exposure to ionizing radiation. Many diagnostic tests can be performed safely during pregnancy because most diagnostic X-ray procedures expose the fetus to low doses of radiation, i.e., less than 1 rad per procedure; this holds true even for pelvic neoplasms. General 'rule of thumb' suggests that a fetal or embryonic radiation exposure of less than 5 'skin' rads is a.s.sociated with little to no risk the exception to this is the critical period of neural plate development (days 1018 postconception) with the threshold for significant risk being as high as 1520 'skin' rads (Brent, 1987). Skin rads 128 128 Antineoplastic drugs during pregnancy are the amount of radiation delivered to the mother's skin surface. Thus, procedures such as barium enemas, pyelography, chest films, and nonpelvic computerized tomography can be safely performed if deemed necessary during the initial diagnosis of malignancies during pregnancy. Other diagnostic modalities, such as magnetic resonance imaging and ultrasonography, can often provide the same diagnostic information as X-ray studies and carry no known risk to the fetus or embryo. Until the end of the second trimester, diagnostic techniques such as cystoscopy and sigmoidoscopy may be performed safely (Pentheroudakis and Pavlidis, 2006).

Most surgical oncology techniques can be used during pregnancy to treat life-threatening disease, especially if they do not involve the pelvis or pelvic organs (Miller and Bloss, 1995). Ovaries can generally be removed after 10 weeks gestational age (8 weeks postconception) without apparent adverse effects on pregnancy. However, progestational agents should be utilized if ooph.o.r.ectomy is necessary prior to this time (Gilstrap and Cunningham, 1996; Pentheroudakis and Pavlidis, 2006; Yazigi and Cunningham, 1990).