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Less than 1% of pregnant women will become critically ill and require admission to an intensive care unit (ICU).1-8 Between 47% and 93% of ICU admissions result from an obstetric complication, primarily hemorrhage and hypertensive disorders. Other common causes include respiratory failure and sepsis. Common non-obstetric indications for ICU admission include maternal cardiac disease, trauma, anesthetic complications, cerebrovascular accidents, and drug overdosage. In many series, most obstetric ICU admissions occur in the immediate postpartum period and are most likely caused by complications of acute hemorrhage.1,4-6,9

An intimate understanding of the physiologic changes of pregnancy is essential in managing critically ill patients. This chapter addresses basic critical care monitoring in obstetrics and discusses conditions in which more intensive management of the pregnant patient may be indicated.

Maternal MortalityEpidemiologyMaternal mortality is defi ned as the number of maternal deaths (direct and indirect) per 100,000 live births. Direct obstetric deaths result pri-marily from thromboembolic events, hemorrhage, hypertensive dis-orders of pregnancy, and infectious complications. Indirect obstetric deaths arise from preexisting medical conditions, including diabetes, systemic lupus erythematosus, pulmonary disease, and cardiac disease aggravated by the physiologic changes of pregnancy. Figure 57-1 shows specifi c causes of pregnancy-related mortality for three time periods as reported by the Centers for Disease Control and Prevention.10-12

Maternal mortality rates are periodically surveyed by various local, state, and national agencies. Because these data are primarily collected from death certifi cates, some have suggested that the numbers under-estimate the mortality rate by as much as 20% to 50%.13 Variations in the defi nition of maternal death, medicolegal concerns, and physicians untrained in the proper completion of death certifi cates further confuse these investigations. To address these concerns, the Division of Reproductive Health at the Centers for Disease Control and Preven-tion, in collaboration with the American College of Obstetricians and Gynecologists (ACOG) and state health departments, began in 1987 to systematically collect these data in the Pregnancy-Related Mortality Surveillance System.

Mortality rates have declined precipitously in the United States over the past century, but a slight increase has been observed in more recent years, as shown in Figure 57-2.11 Some of this increase has been attributed to better ascertainment of data collected prospectively and to the use of multiple source documents. Although this trend is exhib-ited for all races, wide discrepancies still exist between white and non-white populations, even when controlling for age and use of prenatal care (Fig. 57-3).12 The reasons for this discrepancy remain unclear. Geographic differences in maternal mortality rates are also apparent and are likely infl uenced by racial disparities. States with higher per-centages of births to African-American women are also those with the highest maternal mortality rates. The data on pregnancy-related mor-tality in the United States between 1990 and 1997 indicate a rate of 11.8 deaths per 100,000 pregnant women (8.1 deaths per 100,000 whites, 30.0 deaths per 100,000 African Americans).12 Advancing maternal age and lack of education are also associated with an increased risk for death in pregancy.12 Potential explanations for this increased risk include a higher incidence of underlying or undiagnosed chronic disease.

Prediction of Maternal MortalityPredicting the risk of mortality for pregnant patients remains a chal-lenge. The overall maternal mortality rate for critically ill gravidas admitted to an ICU ranges from 0% to 20%, with most series reporting maternal mortality rates of less than 5% for all obstetric ICU admis-sions.1,3-5,8 Several scoring systems are routinely employed in critical care settings in an attempt to objectively describe the severity of the critical illness and accurately predict mortality risks. The Acute Physi-ologic and Chronic Health Evaluation (APACHE) scoring system,14,15 Simplifi ed Acute Physiologic Score (SAPS),16 and Mortality Prediction Model (MPM)17 are three widely used methods that track a variety of variables in nonpregnant patients.

Several authors have evaluated the applicability of the scoring systems in critically ill pregnant patients.18-20 In a study of obstetric ICU patients, the APACHE III score did not accurately predict mater-nal mortality.18 In the largest series, 93 gravidas were compared with 96 nonpregnant women. The overall mortality rate in the obstetric population was 10.8%. The APACHE II, SAPS II, and MPM II scoring systems each performed well in predicting mortality (14.7%, 7.8%, and 9.1%, respectively).19 The predicted mortality rate was signifi -cantly higher among obstetric patients compared with non-obstetric

Chapter 57

Intensive Care Monitoring of the Critically Ill Pregnant Patient

Stephanie Rae Martin, DO, and Michael Raymond Foley, MD

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1168 CHAPTER 57 Intensive Care Monitoring of the Critically Ill Pregnant Patient

patients for each of the three scoring tools, despite no difference in actual mortality between the two groups (10.8 versus 10.4%).

None of the scoring systems includes adjustments for normal obstetric physiologic changes such as decreased blood pressure and increased respiratory rate. Laboratory abnormalities such as elevated liver function test results and low platelet counts, which are common in obstetric disorders such as HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), are not included in the assessments and may limit their potential applicability. In summary, although the available critical care mortality scoring systems can possibly be applied

to the obstetric population, they have the potential to overestimate the mortality risk for critically ill gravidas.

Invasive Central Hemodynamic MonitoringBackground and Insertion TechniquePlacement of a central venous catheter may be indicated to provide central venous access for fl uid replacement, medication administra-tion, or hemodynamic measurements. Since its introduction in the early 1970s,21 invasive hemodynamic monitoring with a pulmonary artery catheter (PAC) has become quite common in critically ill patients. The most commonly available Swan-Ganz catheters are multilumen devices that enable direct monitoring of central venous pressure (CVP, right ventricular preload), pulmonary capillary wedge pressure (PCWP, left ventricular preload), cardiac output (CO), sys-temic vascular resistance (SVR, left ventricular afterload), pulmonary artery pressures, and mixed venous oxygen saturation. CO and mixed venous oxygen saturation can be measured in the conventional manner by thermodilution and direct distal port aspiration, respectively, or by newer fi beroptic technology that allows continuous monitoring of CO and mixed venous oxygen saturation.

PACs (i.e., Swan-Ganz catheters) are typically inserted percutane-ously through an introducer sheath and in a sterile manner through the left subclavian or right internal jugular veins and advanced into the right heart. The right internal jugular vein is usually preferred because it offers the shortest and most direct entry into the right heart. Access through the femoral vein offers the advantage of com-pressibility in a patient with a coagulopathy, but it is most distant from the right heart and may require fl uoroscopic guidance. As the catheter is advanced, characteristic oscilloscopic pressure waveforms are used to establish the catheter’s location within the heart. A 1.5-mL balloon is positioned close to the tip of the catheter. Infl ation of the balloon allows the catheter to be carried through the heart by fl owing blood.

After the infl ated balloon reaches the pulmonary artery, it travels distally until it wedges in a smaller-caliber artery and occludes blood fl ow. This results in a nonpulsatile waveform from which the PCWP is measured. When the balloon is defl ated, return of an identifi able

FIGURE 57-1 Causes of maternal mortality for three time periods. Obstetric deaths are caused by thromboembolic events, hemorrhage, hypertension, infections, and preexisting medical conditions, such as diabetes, systemic lupus erythematosus, pulmonary disease, and cardiac disease aggravated by the physiologic changes of pregnancy. CVA, cerebrovascular accident; HTN, hypertension. (From Berg CJ, Chang J, Callaghan WM, et al: Pregnancy-related mortality in the United States, 1991-1997. Obstet Gynecol 101:289-296, 2003.)

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FIGURE 57-2 Maternal mortality ratios in the United States by year for 1967 to 1996. Ratios are the number of maternal deaths per 100,000 live births. The term ratio is used instead of rate because the numerator includes some maternal deaths that were not related to live births and therefore were not included in the denominator. (From Centers for Disease Control and Prevention: Maternal Mortality—United States, 1982-1996. MMWR Morb Mortal Wkly Rep 47:705-707, 1998.)

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FIGURE 57-3 Pregnancy-related mortality ratios by age and race in the United States for 1991 to 1999. The mortality ratios are the number of deaths per 100,00 live births.

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1169CHAPTER 57 Intensive Care Monitoring of the Critically Ill Pregnant Patient

pulmonary artery systolic and diastolic pressure tracing should occur. A portable chest radiograph is indicated after placement of a PAC to verify appropriate catheter positioning and exclude pneumothorax.

Indications for Pulmonary Artery CatheterizationThe most common indications for PAC placement in the obstetric population include the following22:

� Hypovolemic shock unresponsive to initial volume resuscitation attempts

� Septic shock with refractory hypotension or oliguria� Severe preeclampsia with refractory oliguria or pulmonary

edema� Ineffective intravenous antihypertensive therapy� Adult respiratory distress syndrome (ARDS)� Intraoperative or intrapartum cardiac failure� Severe mitral or aortic valvular stenosis� New York Heart Association (NYHA) class III or IV heart

disease in labor� Anaphylactoid syndrome of pregnancy (i.e., amniotic fl uid

embolism)

Although use of the PAC in nonpregnant critically ill patients is widespread, until recently, randomized trials demonstrating a clear benefi t of PAC-directed care were lacking. Several small studies suggested a decrease in mortality when PACs are used to direct thera-pies,23-25 while others reported an increase in mortality associated with the use of PACs26-29 or no benefi t.30-32 The large Canadian Critical Care Clinical Trials Group study prospectively randomized 1994 high-risk surgical patients to receive a PAC to direct therapy or standard therapy and reported no survival benefi t when therapy was directed by a PAC (7.8% versus 7.7% for controls).33 A British trial randomized more than 1000 critically ill patients to management with or without a PAC and failed to demonstrate a survival benefi t (68.4% versus 65.7% for controls).34 The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE trial) also demonstrated no difference in mortality or length of stay for 433 patients with congestive heart failure randomized to PAC or no catheter.35

A meta-analysis of 13 trials published since 1985 included 5051 patients randomized to a PAC or to no PAC to guide management. No difference was identifi ed in mortality or length of hospital stay. Conversely, the use of a PAC was signifi cantly associated with more frequent use of inotropes and vasodilators.36 In summary, although placement of PACs remain widespread, the available data do not support the routine use of PACs for all critically ill patients. Data addressing the role of PACs in pregnant critically ill patients are lacking.

Complications of Central Venous Catheters

Common complications associated with initial venous access, advance-ment, and maintenance of a PAC are listed in Table 57-1.37 Some complications, such as pulmonary infarction and pulmonary artery rupture, are specifi c to placement of a PAC and do not occur with central venous access alone. Minimal available data address specifi c complication rates associated with PAC use in pregnant women. Initial

complication rates decline as operator experience increases, and only properly trained personnel should insert catheters for invasive hemo-dynamic monitoring.38 Several studies have also demonstrated that ultrasound-guided placement results in fewer failed attempts at place-ment, fewer complications such as hematoma or arterial puncture, and less time for placement.39

Complications encountered at initial insertion include arterial puncture, pneumothorax, and air embolism. Pneumothorax risks are highest with a subclavian approach. Transient cardiac arrhythmias are commonly encountered during placement and advancement of the PAC. The majority consist of premature ventricular contractions or nonsustained ventricular tachycardia, and they resolve with withdrawal or advancement of the catheter. The overall incidence of transient minor arrhythmias during advancement of a PAC exceeds 20% in most studies.37 Signifi cant arrhythmias such as sustained ventricular tachy-cardia or fi brillation are less common, occurring in less than 4% of patients in most series, and they are more likely to be encountered in patients with cardiac ischemia.37

Infections related to central venous catheters are common and may involve a superfi cial skin infection, colonization, or a more serious bacteremia. Skin fl ora, particularly Staphylococcus species, are most commonly involved. Positive cultures from the tip of a PAC are common and are considered evidence of colonization. However, for bacteremia or sepsis to be diagnosed, the patient must also have posi-tive blood cultures with the same organism and clinical evidence of systemic infection, such as fever or hypotension.40 The risk of bactere-mia is approximately 0.5% per catheter day, and the risk increases with each day the catheter remains indwelling. Bacteremia resulting from central venous catheters accounts for 87% of bloodstream infections in critically ill patients.41 Infectious complications can be minimized by adherence to strict sterile technique, placement in the subclavian site, use of antimicrobial-coated catheters, avoiding antibiotic oint-ments that can increase fungal colonization, avoiding empiric catheter changes, and removing the catheter as soon as possible.42

Venous thrombosis risk can be minimized by placement at the sub-clavian site and by limiting the duration of catheter placement. Pulmo-nary infarction may occur as a result of direct occlusion of a pulmonary artery branch caused by drifting of the catheter or thromboembolic events. Catheter knotting can be avoided during placement if the opera-tor remains aware of the centimeter markings on the advancing cathe-ter. The right ventricle usually is reached when the catheter has been inserted 25 to 30 cm from the jugular vein site. Few patients require more than 50 cm of catheter to reach the pulmonary artery. Infl ated catheter balloons should be checked before insertion to reduce the risk of air leakage and balloon rupture. Overinfl ation of the balloon with air (>1.5 mL) should be avoided. A pressure-release balloon has been described that limits overinfl ation and thereby minimizes pulmonary

TABLE 57-1 POTENTIAL PULMONARY ARTERY CATHETER COMPLICATIONS

At Insertion After Placement

Pneumothorax Pulmonary infarctionThrombosis Pulmonary artery ruptureArterial puncture InfectionAir embolization Balloon ruptureCatheter knotting Endocardial or valvular damageCardiac arrhythmias (transient,

sustained)

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vessel injury. Pulmonary artery rupture is a rare but often fatal compli-cation that occurs more commonly in patients with pulmonary artery hypertension or who are anticoagulated. Valvular damage can occur from chronic catheter irritation or during insertion when the catheter balloon is not defl ated before retrograde movement.

CVP monitoring alone should not be considered equivalent to PAC monitoring. Preeclampsia and its complications, such as oliguria and pulmonary edema, may prompt central venous access. However, several investigators have described poor correlation between the central venous catheter and PCWP in gravidas with pregnancy-induced hypertension (Fig. 57-4).43,44 If an accurate assessment of left ventricu-lar preload is deemed important in the management of the patient’s cardiovascular complications, insertion of a PAC may be indicated. Whether this holds true for pregnant women with critically ill disease states other than pregnancy-induced hypertension remains unknown.

Hemodynamic ConsiderationsWith a PAC, the following hemodynamic variables can be directly measured in the patient:

� Heart rate (beats/min)� CVP (mm Hg)� Pulmonary artery systolic and pulmonary artery diastolic

pressures (mm Hg)� PCWP (mm Hg)� CO (L/min)� Mixed venous oxygen saturation (%)

By use of a sphygmomanometer or by peripheral artery catheteriza-tion, direct measurements of systemic arterial pressures can also be

obtained. Table 57-2 lists formulas for calculating selected hemody-namic variables.

Hemodynamic variables often are expressed in an “indexed” fashion (i.e., cardiac index). To do this, the original nonindexed CO value must be divided by body surface area. Because standard body surface area calculations have never been established specifi cally for pregnancy, this traditional way of expressing hemodynamic data is somewhat contro-versial in obstetrics. Those who argue for its use point out that index-ing allows direct comparison of hemodynamic parameters for pregnant women of different sizes, a critical issue when interpreting these values.

Mean hemodynamic measurements for pregnant and nonpregnant patients are presented in Table 57-3. They are paired data from 10 healthy subjects, taken between 36 and 38 weeks’ gestation and between 11 and 13 weeks after delivery.45 Using the noninvasive technique of M-mode echocardiography, other investigators have demonstrated that many of these physiologic alterations in hemodynamics begin in the early phases of pregnancy.46 Position changes late in pregnancy signifi cantly infl uenced central hemodynamic stability. The standing position increased pulse by 50%, left ventricular stroke work index by 21%, and pulmonary vascular resistance by 54%.47 Compared with the nonpregnant state, the pregnant state seemed to result in a buffering of orthostatic-related hemodynamic changes. The investigators specu-lated that the increased intravascular volume during pregnancy accounted for this stabilizing effect.

Hemodynamics of Specifi c Conditions during Pregnancy

Mitral Valve StenosisMitral stenosis is the most common rheumatic valvular lesion encoun-tered in pregnancy (see Chapter 39). When the valve area falls below 1.5 cm2, fi lling of the left ventricle during diastole is severely limited, resulting in a fi xed CO. Prevention of tachycardia and maintenance of adequate left ventricular preload is essential in these patients. As the heart rate increases, less time is allowed for the left atrium to ade-quately empty and fi ll the left ventricle during diastole. The left atrium may become overdistended, resulting in dysrhythmias (primarily atrial

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FIGURE 57-4 Relationship of central venous pressure (CVP) to pulmonary capillary wedge pressure (PCWP) in severe pregnancy-induced hypertension. If an accurate assessment of left ventricular preload is deemed important in the management of the patient’s cardiovascular complications, insertion of a pulmonary artery catheter may be indicated. (From Cotton DB, Gonik B, Dorman K, et al: Cardiovascular alterations in severe pregnancy-induced hypertension: Relationship of central venous pressure to pulmonary capillary wedge pressure. Am J Obstet Gynecol 151:762, 1985.)

TABLE 57-2 FORMULAS FOR CALCULATING HEMODYNAMIC VARIABLES

SVR = [(MAP − RAP)]/CO × 80PVR = (PAP − PCWP/CO) × 80CO = VO2/(CaO2 − CvO2)DO2 = CO × CaO2 × 10VO2 = (CaO2 − CvO2) × CO × 10CaO2 = (1.34 × Hb × SaO2) + (0.003 × PaO2)CvO2 + (1.34 × Hb × SvO2) + (0.003 × PvO2)O2 extraction = VO2/ DO2

Qs/Qt = CcO2 − CaO2/CcO2 − CvO2

CaO2, arterial oxygen concentration; CcO2, end capillary O2 content;

CO, cardiac output; CvO2, venous oxygen concentration; DO2, oxygen

delivery; Hb, hemoglobin; MAP, mean arterial pressure; O2, oxygen;

PaO2, arterial partial pressure of oxygen; PAP, pulmonary artery

pressure; PCWP, pulmonary capillary wedge pressure; PvO2, venous

partial pressure of oxygen; PVR, pulmonary vascular resistance;

Qs/Qt, shunt fraction; RAP, right atrial pressure; SaO2, arterial oxygen

saturation; SvO2, venous oxygen saturation; SVR, systemic vascular

resistance; VO2, oxygen consumption.

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fi brillation, which increases the risk of thromboembolic complica-tions) or pulmonary edema. Adequate preload, however, is essential to maintain left ventricular fi lling pressure. Alternatively, if preload is excessive, pulmonary edema and atrial dysrhythmias may result. Medical management of these patients involves activity restriction, treatment of dysrhythmias, β-blockers to control heart rate, and careful diuretic use. The goal of diuretic therapy is to treat pulmonary edema, with care not to overly reduce left ventricular preload. Adequate anal-gesia and anesthesia during labor and delivery also reduce excessive cardiac demands associated with pain and anxiety.

The other important hemodynamic consideration for patients with mitral valve stenosis relates to the potential for misinterpretation of the invasive monitoring data. Because of the stenotic mitral valve, PCWP readings do not accurately refl ect left ventricular diastolic pressure. In some instances, very high PCWP values are recorded (and are needed to maintain an adequate CO). Overt pulmonary edema is usually not associated with these high readings. During attempts at maintaining a relatively constricted intravascular volume, the CO should be concomitantly monitored and maintained. For each indi-vidual patient, optimal PCWP and CO values (i.e., values that maintain blood pressure and tissue perfusion) should be determined.

Aortic StenosisThe major problem encountered with aortic stenosis is the patient’s potential inability to maintain CO because of severe obstruction or in the setting of decreasing left ventricular preload (see Chapter 39). Unlike mitral valve stenosis, aortic valve stenosis requires that attempts be made to maintain the patient in a relatively hypervolemic state, although the fi xed CO may lead to pulmonary edema. The time sur-rounding labor and delivery is particularly risky for these patients. To maintain an adequate CO, adequate venous return to the heart is crucial. Decreased venous return can result from excess blood loss, hypotension, and ganglionic blockade from a regional anesthetic or even vena caval occlusion in the supine position. Pulmonary artery catheterization may be indicated in patients with signifi cant aortic stenosis to accurately estimate intravascular volume and guide fl uid replacement.

Pulmonary HypertensionPulmonary artery hypertension may arise as a primary lesion or result from an underlying cardiac abnormality (see Chapter 39). Primary pulmonary hypertension is characterized by an unexplained elevation in pulmonary artery pressures (>25 to 30 mm Hg). Prognosis is grim

for patients with primary pulmonary hypertension; mean survival is 2.8 years from the diagnosis. Maternal mortality rates for patients with pulmonary hypertension have been as high as 50%.48-50 These patients are at increased risk for complications from placement of a PAC. Pulmonary hypertension may also result from unrepaired congenital intracardiac shunts such as a ventricular septal defect, atrial septal defect, or patent ductus arteriosus, which lead to chronic over-perfusion of the pulmonary vasculature. Over time, pulmonary arterial pressures may become signifi cant enough to reverse the direction of fl ow across the shunt. This reversal of shunt fl ow to a right-to-left pattern defi nes Eisenmenger syndrome. The estimated maternal mor-tality rate for Eisenmenger syndrome is between 30% and 40%.50,51 In a review of 73 patients with Eisenmenger syndrome, the overall mor-tality rate was 36%, which has been essentially unchanged during the past 2 decades.50

The underlying problem in patients with this condition is obstruc-tion to right ventricular outfl ow caused by a fi xed and elevated pulmonary vascular resistance. This can ultimately lead to right-to-left shunting of deoxygenated blood with resultant hypoxemia. Reductions in blood return to the heart can decrease right ventricular preload so that the pulmonary vasculature is further hypoperfused. The resultant hypoxemia has been associated with sudden death. Intrapartum man-agement requires maintenance of a relatively hypervolemic state, and any interventions that may lead to signifi cant reduction in preload or decrease in SVR should be avoided. Placement of a PAC may be quite challenging in these patients, and many experts believe the risks of placement may outweigh any potential benefi t.

Anaphylactoid Syndrome of PregnancyAnaphylactoid syndrome of pregnancy (i.e., amniotic fl uid embolus) is a rare but devastating complication of pregnancy characterized by acute onset of hypoxia, hypotension or cardiac arrest, and coagulopa-thy occurring during labor, during delivery, or within 30 minutes after delivery.52,53 This same constellation of fi ndings may have other causes, such as hemorrhage, uterine rupture, or sepsis, and each should be excluded before assigning a diagnosis of amniotic fl uid embolism. The combination of sudden cardiovascular and respiratory collapse with a coagulopathy is similar to that observed in patients with anaphylactic or septic shock. In each of these settings, a foreign substance (e.g., endotoxin) is introduced into the circulation. This initiates a cascade of events resulting in activation and release of mediators such as his-tamines, thromboxane, and prostaglandins, which lead to dissemi-nated intravascular coagulation (DIC), hypotension, and hypoxia. The

TABLE 57-3 NORMAL CENTRAL HEMODYNAMIC PARAMETERS IN HEALTHY NONPREGNANT AND PREGNANT PATIENTS

Hemodynamic Parameter Nonpregnant Values Pregnant Values

Cardiac output (L/min) 4.3 ± 0.9 6.2 ± 1.0Heart rate (beats/min) 71 ± 10 83 ± 10Systemic vascular resistance (dyne × cm × sec−5) 1530 ± 520 1210 ± 266Pulmonary vascular resistance (dyne × cm × sec−5) 119 ± 47 78 ± 22Colloid oncotic pressure (mm Hg) 20.8 ± 1.0 18.0 ± 1.5Colloid oncotic pressure − pulmonary capillary wedge pressure (mm Hg) 14.5 ± 2.5 10.5 ± 2.7Mean arterial pressure (mm Hg) 86.4 ± 7.5 90.3 ± 5.8Pulmonary capillary wedge pressure (mm Hg) 6.3 ± 2.1 7.5 ± 1.8Central venous pressure (mm Hg) 3.7 ± 2.6 3.6 ± 2.5Left ventricular stroke work index (g × m × m−2) 41 ± 8 48 ± 6

From Clark SL, Cotton DB, Lee W, et al: Central hemodynamic assessment of normal term pregnancy. Am J Obstet Gynecol 161:1439, 1989.

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inciting factor is presumed to be present in amniotic fl uid that is introduced into the maternal circulation, but the precise factor that initiates the sequence have not been identifi ed. It is a commonly held misconception that the presence of fetal debris in the pulmonary cir-culation is diagnostic of an amniotic fl uid embolus. Fetal debris can be found in the pulmonary circulation in most normal laboring patients, and it is identifi ed only in 78% of patients who meet the criteria for the diagnosis of amniotic fl uid embolism.52,53

Management of amniotic fl uid embolism is entirely supportive. Replacement of blood and clotting factors, adequate hydration and blood pressure support, ventilatory support, and invasive cardiac mon-itoring in addition to resuscitation efforts usually are required for these patients. The data suggest mortality rates approach 61% or higher. Most patients do not survive the initial course and die within 5 days. For those who survive, neurologic impairment is common.52

Hypertensive Disorders of PregnancyMost clinical hemodynamic monitoring studies in obstetrics have enrolled patients with hypertensive disorders of pregnancy (see Chapter 35). From a purely clinical perspective, clear indications for this inva-sive technology have not been established. Arguments for its use center on reports demonstrating a broad spectrum of hemodynamic fi ndings in this group of patients. For patients identifi ed to be relatively hypo-volemic, optimizing intravascular volume status should improve uteroplacental perfusion, reduce SVR, and blunt hypotensive compli-cations associated with conduction anesthesia and antihypertensive therapy. Oliguria (particularly if unresponsive to fl uid therapy) and refractory pulmonary edema, both recognized complications of severe preeclampsia, may also be better defi ned and managed with invasive monitoring.

Vasospasm is a central feature of preeclampsia. In one series of 51 untreated preeclamptic patients, an elevated SVR value was identifi ed with invasive monitoring.54 Preeclampsia likely represents an overall vasoconstrictive condition that is frequently infl uenced by underlying disease processes such as chronic hypertension, duration and severity of illness, and various therapeutic modalities.

Using ventricular function curves that correlate PCWP (i.e., left ventricular preload) with left ventricular stroke work index (i.e., myo-cardial contractility), investigators found that most preeclamptic and eclamptic patients fall into a relatively hyperdynamic range.55 The values shown in Figure 57-5 are superimposed on ventricular function graphs derived from nonpregnant subjects. The preeclamptic patient probably has at least a normal and probably a somewhat hyperdynamic functioning heart during pregnancy. As expected, this cardiac function, as estimated by CO, appears to be inversely related to SVR.

Some investigators have recommended that patients with preg-nancy-induced hypertension be classifi ed by different hemodynamic subsets so that management protocols can be tailored to individual needs. Clark and associates56 fi rst reported the use of this approach for dealing with the oliguric preeclamptic patient. They found that these patients had low PCWP values (i.e., hypovolemic) and elevated SVR (i.e., severe vasoconstriction) or were volume replete with normal to elevated vascular resistances. A third group had markedly elevated PCWP and SVR readings with depressed cardiac function.56 Manage-ment of these groups of oliguric patients varies. In the fi rst subset, patients respond favorably to volume expansion therapy. The next two groups of patients are best managed with vasodilators and aggressive afterload reduction therapy.

Another important issue in the management of oliguric patients with preeclampsia is the use of standard urinary diagnostic indices, such as urine-to-plasma ratios of osmolality, urea nitrogen, and creati-

nine or fractional excretion of sodium. Although these urinary param-eters are routinely used in non-obstetric patients to differentiate prerenal and renal causes of oliguria, they have proved to be unreliable in patients with preeclampsia. In preeclampsia complicated by oliguria, urinary diagnostic indices may suggest a prerenal cause despite normal intravascular volume, demonstrated by invasive pressure measurement determinations. From a physiologic standpoint, it is postulated that the kidney misinterprets local renal artery vasospasm to indicate a volume-depleted state.

Septic ShockSeptic shock refers to the systemic infl ammatory response syndrome associated with infection, persistent hypotension, and major organ dysfunction despite initial fl uid resuscitation.57 Although the hemody-namic effects of septic shock have been well described in the non-obstetric literature, limited information is available for obstetric patients. One study described the hemodynamic profi les of 10 obstet-ric patients at various gestational ages, who were identifi ed to have septic shock and required invasive monitoring. In this small series, SVR and myocardial function were depressed but improved with therapy.58 Mabie and coworkers59 described similar fi ndings in a more recent series of 18 obstetric patients with septic shock. The main hemody-

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FIGURE 57-5 Ventricular function in pregnancy-induced hypertensive patients. On plots of ventricular function curves that correlate pulmonary capillary wedge pressure with left ventricular stroke work index, most preeclamptic and eclamptic patients fall into a relatively hyperdynamic range. (Combined data from Benedetti TK, Cotton DB, Read JC, et al: Hemodynamic observations in severe pre-eclampsia with a fl ow-directed pulmonary artery catheter. Am J Obstet Gynecol 136:465, 1980; Hankins GDV, Wendel GP, Cunningham FG, et al: Longitudinal evaluation of hemodynamic changes in eclampsia. Am J Obstet Gynecol 15:506, 1984; Phelan JP, Yurth DA: Severe preeclampsia. I. Peripartum hemodynamic observations. Am J Obstet Gynecol 144:17, 1982; and Rafferty TD, Berkowitz RL: Hemodynamics in patients with severe toxemia during labor and delivery. Am J Obstet Gynecol 138:263, 1980.)

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namic characteristics of those who succumbed to septic shock included lower blood pressure, stroke volume, and left ventricular stroke work index than survivors.59 Sepsis and septic shock are addressed in more detail later in this chapter.

Noninvasive Hemodynamic AssessmentThe PAC is the gold standard for measurement of hemodynamic status in the critically ill patient. However, according to available data, use of the PAC to guide therapy does not favorably affect survival and carries substantial risks.

Transesophageal echocardiography (TEE) has emerged as a nonin-vasive tool for the bedside assessment of the hemodynamic status of nonpregnant, critically ill adults. In an anesthetized patient, a small transducer is introduced into the esophagus and real-time data collected. TEE can accurately measure left ventricular preload, left ventricular fi lling pressure, CO, left ventricular ejection fraction, and severe right ventricular dysfunction.60-62 TEE is often used in hypoten-sive patients to determine the cause of the hypotension, such as inad-equate fi lling or depressed contractility (Table 57-4). TEE can detect other abnormalities, including left ventricular obstruction, structural abnormalities, proximal pulmonary emboli, and valvular disease. It is also useful in evaluating the left atrium and mitral valve because of the proximity of these structures to the transducer, and it appears to be superior in evaluating congenital cardiac defects.

Only a few small series have compared data derived from a PAC with two-dimensional transthoracic and Doppler echocardiography in obstetric patients. In one report of 12 patients requiring PAC for pre-eclampsia management, CO measured by Doppler echocardiography correlated well with CO assessed by thermodilution using a PAC.63 Another study of 16 obstetric patients found good correlation between thermodilution assessment of CO and Doppler echocardiography.64 In a study of 11 critically ill obstetric patients, Belfort and colleagues65 demonstrated no difference between Doppler echocardiographic and PAC-derived estimation of stroke volume, CO, cardiac index, left ven-tricular fi lling pressure, pulmonary artery systolic pressure, and right atrial pressure.65 The data from these reports are encouraging, but echocardiographic estimation of pulmonary artery pressure was sig-nifi cantly overestimated in 32% of obstetric patients with suspected pulmonary artery hypertension.66 The technique appears to be well-tolerated, but further study is warranted.

Respiratory FailureSubstantial anatomic and physiologic changes occur over the course of pregnancy that impact respiratory function (see Chapter 7). Minute ventilation increases in a normal pregnancy and is determined by respiratory rate and tidal volume. The 40% increase in tidal volume (i.e., amount of air exchanged during a cycle of inspiration and expira-tion) primarily drives the increase in minute ventilation. As a result, the levels of CO2 decline, creating an alkalotic state. To accommodate for the decrease in CO2, the kidneys excrete bicarbonate (HCO3

−). An arterial blood gas determination in a normal pregnant woman there-fore refl ects a slightly increased pH, decreased PCO2, and decreased serum HCO3− (i.e., respiratory alkalosis with compensatory metabolic acidosis), as outlined in Table 57-5. As the pregnancy progresses, increasing abdominal girth leads to an upward displacement of the diaphragm, widening of the subcostal angle by 50%, and increased chest circumference. The end result is a decrease in the functional residual capacity by 20%. The functional residual capacity refl ects the amount of air remaining in the alveoli at the completion of expiration. As the functional residual capacity decreases, the alveoli collapse, and gas exchange decreases.67

Common causes for respiratory failure in pregnancy include pulmonary edema, asthma, infection, and pulmonary embolus.68,69 In a series of 43 gravidas requiring mechanical ventilation while undelivered, 86% delivered during the admission, and of these, 65% underwent cesarean section, with an associated mortality rate of 36% for those delivered by cesarean section. Overall maternal and perinatal mortality rates were high (14% and 11%, respectively).68

Debate continues about whether delivery improves respiratory status in these patients. Tomlinson and coworkers70 described their experience with 10 patients who delivered while mechanically venti-lated. In all but one patient, the cause of respiratory failure was pneu-monia.70 The only demonstrable benefi t after delivery was a 28% reduction in FIO2 in the ensuing 24 hours. The investigators concluded that routine delivery of these patients was not recommended. This is the only study published that was designed specifi cally to address this question. However, data from other series support the conclusion that delivery does not uniformly result in signifi cant maternal improve-ment. Mortality rates after delivery while requiring ventilatory support range from 14% to 58%, and cesarean section may further increase this risk.68,69,71

TABLE 57-4 ORIGIN OF HYPOTENSION

End-Diastolic

Cross-Sectional

Area Ejection Fraction Cause

Decreased >0.8 HypovolemiaIncreased <0.2 Left ventricular failureNormal >0.5 Low SVR or severe MR,

AR, or VSD

AR, aortic regurgitation; MR, mitral regurgitation; SVR, systemic

vascular resistance; VSD, ventricular septal defect.

From Cahalan MK: Intraoperative Transesophageal Echocardiography:

An Interactive Text and Atlas. New York, Churchill Livingstone, 1996.

TABLE 57-5 CHANGES IN ARTERIAL BLOOD GAS MEASUREMENTS IN PREGNANCY

Measurements Pregnant Values Nonpregnant Values

pH 7.4-7.46 7.38-7.42PCO2 (mm Hg) 26-32 38-45PO2 (mm Hg) 75-106 70-100HCO3

− (mEq/L) 18-21 24-31O2 saturation (%) 95-100 95-100

Modifi ed from Dildy G, Clark SL, Phelan JP, et al: Maternal-fetal blood

gas physiology. In Critical Care Obstetrics, 4th ed. New York,

Blackwell, 2004.

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Acute Respiratory Distress SyndromeAcute respiratory distress syndrome (ARDS) is characterized by rapid onset of progressive respiratory distress. Evaluation reveals bilateral pulmonary infi ltrates without evidence of cardiac failure or increased hydrostatic pressure (i.e., PCWP < 18 mm Hg). These patients require high concentrations of oxygen and frequently need intubation. ARDS is also defi ned by a diminished ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FIO2 � 200). If the ratio falls between 200 and 300, acute lung injury is present that is not severe enough to be called ARDS.

In pregnant women, infections with varicella or herpes simplex virus, severe preeclampsia, eclampsia, and hemorrhage most com-monly precipitate respiratory failure.68,72 Septic patients are at par-ticular risk for developing acute pulmonary injury and ARDS as a consequence of pulmonary vascular damage that facilitates the leakage of intravascular fl uid into the pulmonary interstitial spaces. Mortality rates are quite high, and patients who survive often have pulmonary function compromised by fi brosis and scarring of pulmonary tissue.

The treatment of ARDS focuses on identifying and treating under-lying causes such as infection and then providing respiratory, hemo-dynamic, and nutritional support to facilitate lung healing. Respiratory support may precipitate additional lung injury, and efforts to maintain adequate oxygen delivery should also minimize lung trauma in an effort to facilitate healing of the lungs.

Management of respiratory failure in nonpregnant, critically ill patients has historically used a goal of maintaining a tidal volume of 10 to 15 mL/kg. In ARDS, high tidal volumes may lead to alveolar overdistention or repeated recruitment and collapse of alveoli, predis-posing to alveolar damage and release of infl ammatory mediators that worsen pulmonary damage. In 2000, the ARDSNet published results of 861 patients with ARDS randomized to traditional tidal volumes (12 mL/kg) or to a low tidal volume of 6 mL/kg.73 The traditional tidal volume group also maintained a goal of 50 cm of H2O or less, com-pared with lower peak pressures of 30 cm of H2O in the low tidal volume group. Low tidal volumes and lower peak pressures were asso-ciated with lower mortality rates (31% versus 40%) and shorter periods of intubation compared with conventional tidal volumes and peak pressure goals. Increased tidal volume and other normal changes in pulmonary physiology may affect the utility of this approach in preg-nant women.

Prone VentilationMechanical ventilation in the prone position has improved oxygen-ation in up to 80% of patients with ARDS and acute lung injury. Approximately 50% of patients maintain improved oxygenation after they return to the supine position.74 Mechanical ventilation in the prone position is believed to achieve several benefi cial physiologic changes: improved aeration of well-perfused dorsal atelectatic lung areas, improved alveolar recruitment, relief of cardiac compression on the lung posteriorly, and improved mobilization of secretions.

Several randomized trials have compared supine with prone posi-tioning in nonpregnant patients with ARDS and acute lung injury. In one randomized trial of 304 patients, prone positioning maintained for an average of 7 hours daily was not associated with a decrease in mortality, but signifi cant improvement in oxygenation was observed in 70% of patients, with most of the benefi t occurring in the fi rst hour of prone positioning.75 Another multicenter, randomized trial of 791 patients with hypoxemic respiratory failure with multiple causes, including ARDS, found similar results. In addition to improved oxy-genation with prone positioning at least 6 hours daily, a decrease in

ventilator-associated pneumonia was observed. However, no difference in mortality was demonstrated by prone positioning.76 Only one study has shown a mortality benefi t with early and prolonged prone posi-tioning of ARDS patients. The major difference in this study was the length of time patients were maintained prone—on average 17 hours daily for a mean of 10 days. The 136 patients were randomized within 48 hours of intubation.77

Prone positioning can be accomplished manually or with a special bed designed to rotate the patient. Complications related to prone positioning include pressure sores, endotracheal tube displacement or obstruction, loss of venous access, vomiting, and edema. Data on prone ventilation in the pregnant patient are lacking. Anticipated problems include the gravid abdomen and diffi culties in accomplishing fetal monitoring while prone.

Pulmonary EdemaPregnant women are predisposed to developing pulmonary edema for various reasons, including increased plasma volume and CO in con-junction with decreased colloid oncotic pressure (COP), which occurs normally over the course of pregnancy. Alterations in the balance of hydrostatic and oncotic pressure between the pulmonary vessels and the interstitial spaces can lead to an egress of fl uid from the vascular space into the interstitium and manifest clinically as pulmonary edema. Approximately 1 in 1000 pregnancies is complicated by pulmonary edema. In a review of almost 63,000 pregnancies, Sciscione and coworkers78 reported pulmonary edema occurring most often during the antepartum period (47%), with 39% occurring in the postpartum period and the remaining 14% in the intrapartum period.78 In this series, the two most common attributable causes of pulmonary edema were cardiac disease and tocolytic use (25.5% each). The remaining cases of pulmonary edema were caused by fl uid overload (21.5%) and preeclampsia (18%). The management of patients with pulmonary edema is focused on establishing the diagnosis, determining the cause, and improving oxygenation.

Colloid Oncotic Pressure AbnormalitiesFour forces affect fl uid balance between vascular and interstitial spaces. The COP is the force exerted primarily by albumin and other proteins within the capillary, which holds fl uid within the vascular space. The oncotic pressure within the interstitial space also works to hold fl uid in the interstitium. Hydrostatic forces within the vessel and the inter-stitium exert the opposite effect.

COP decreases over the course of pregnancy, and by term, it approximates 22 mm Hg.79 This is approximately 3 mm Hg lower than pre-pregnancy values as a result of the dilutional effect from plasma expansion. An isolated decrease in oncotic pressure, as may occur in pregnancy or in patients with nephrotic syndrome, is usually well compensated and does not lead to pulmonary edema unless compli-cated by additional factors such as increased intravascular pressure or pulmonary injury resulting in vascular permeability.80 Excessive intra-venous fl uids, blood loss, decreasing COP after delivery, and the post-partum autotransfusion effect can place patients at further increased risk for pulmonary edema.

Hydrostatic or Cardiogenic Pulmonary EdemaPulmonary edema due to primary cardiac issues with or without alter-ations in COP is referred to as hydrostatic or cardiogenic pulmonary

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edema. CO is controlled through continuous adjustments in heart rate and stroke volume. At some point, the heart is no longer able to increase the CO in response to increasing preload because of intrin-sic cardiac abnormalities or excessive fl uid administration, resulting in overload. If left ventricular outfl ow is restricted, blood intended to empty into the left atrium remains in the pulmonary vasculature, which is refl ected by the increased PCWP, left ventricular end-diastolic pressure, and pulmonary artery pressure. The net result is an increase in the pulmonary intravascular hydrostatic pressure. When this pres-sure exceeds the interstitial pressures, fl uid is forced out of the pulmo-nary vasculature into the interstitial spaces, resulting in pulmonary edema.

A transthoracic or transesophageal echocardiogram can distinguish whether pulmonary edema is cardiogenic in origin. Evidence of poor ventricular systolic function is identifi ed by a decreased ejection frac-tion, as seen in patients with a cardiomyopathy. Echocardiography may also identify valvular abnormalities that may lead to compromised cardiac function and predispose patients to pulmonary edema, such as aortic or mitral stenosis.

Pulmonary Edema in the Setting of PreeclampsiaPulmonary edema develops in approximately 2.5% of patients with preeclampsia, most commonly in the postpartum period.43,81,82 The cause is not completely understood, but it likely results from a combi-nation of problems. Impaired left ventricular function may be a result of chronic hypertension, particularly if it develops in the antepartum period. Substantially increased SVR may also impair left ventricular function and lead to pulmonary edema, especially in the setting of iatrogenic fl uid overload. Preeclamptic patients often lose signifi cant amounts of albumin through the urine and exhibit decreased albumin production, both of which can lower the COP. In preeclamp-tic patients, the COP can decrease to 18 mm Hg by term and drop further after delivery to 14 mm Hg.43 Endothelial damage also leads to increased capillary permeability. Preeclamptic patients with pulmo-nary edema that fails to respond to oxygen, diuresis, and fl uid restric-tion, especially when combined with oliguria, may require pulmonary artery catheterization to guide further therapy. In a series of 10 patients with severe preeclampsia who underwent placement of a PAC, the fi ndings varied. Five patients demonstrated a decreased gradient between the COP and PCWP, but two patients had a cardiac explana-tion for the pulmonary edema, and three patients had increased pul-monary vascular permeability.83

Tocolytic-Induced Pulmonary EdemaIn the past, the use of parenteral β-agonists such as terbutaline and ritodrine was more common and became associated with the develop-ment of pulmonary edema.78,84 However, as the use of intravenous β-agonists for tocolysis has decreased, the incidence of pulmonary edema related to tocolytic use appears to have diminished. Magne-sium does not appear to independently increase the risk of pulmo-nary edema.85

ShockShock is the physiologic response to impaired tissue oxygenation. Oxygen defi ciency at the cellular level may result from inadequate delivery of oxygen, such as in hypovolemic states, cardiac failure, and hemorrhage or from improper uptake or use of oxygen, as in septic

states and neurogenic shock. In obstetric patients, shock most commonly results from hemorrhage and sepsis. Regardless of the cause, therapy is directed at restoring tissue oxygenation by eliminating the originating cause, providing adequate volume replacement, and improving cardiac function and circulation. Diffi culty in reversing this phenomenon explains the high mortality rates for patients with shock.

Sepsis and Septic Shock

Incidence and MortalitySepsis accounts for 9.3% of deaths occurring in the United States and complicates approximately 1 in 8000 deliveries.86 Fortunately, only a small percentage of these deaths can be attributed to gynecologic or obstetric problems. Bacteremia is not uncommon in obstetric pati-ents, but these patients appear to be less likely to progress to septic shock.59,87,88 An epidemiologic review of sepsis in the United States gathered discharge data on more than 10 million cases of sepsis over a 22-year period ending in 2000.89 According to this study, the inci-dence of sepsis in the population is increasing at a rate of 8.7% annu-ally. However, the percentage of pregnant women diagnosed with sepsis in that period decreased by 50%, from 0.6% to 0.3%. African Americans and men appear to be at higher risk for developing sepsis, but mortality rates did not appear to differ from those of whites and women, respectively.

Mortality rates overall have declined signifi cantly to approximately 17%, but the marked increase in sepsis diagnosis in the population accounts for tripling of the rate of hospital death from sepsis. Between 1987 and 1997, infectious causes accounted for 13% of maternal deaths.10,11 Mortality rates associated with septic shock in pregnancy are uncertain and are derived primarily from older, small series of cases, but they generally appear to be much lower than for the non-pregnant population. Estimates range from 12% to 28% for obstetric septic patients58,59,87,90 to 40% to 80% for the nongravid population.91 Improved outcomes for pregnant patients have been attributed to a younger patient population, type of organisms, sites of infection more easily accessed and treated, and lower rates of coexistent diseases.

Defi nitionsThe American College of Chest Physicians and the Society of Critical Care Medicine published consensus guidelines in 1991 that were designed to create consistency in the defi nitions used to describe septic conditions. Updated guidelines were published in 2003.57 These defi ni-tions represent the understanding that these conditions exist along a continuum of increasing severity while sharing a common patho-physiology. This continuum begins after the body develops a systemic response to an infection and may progress to multiorgan dysfunction with hemodynamic instability and even death.

The later classifi cation system questions the utility of the diagnosis of systemic infl ammatory response syndrome (SIRS), suggesting that the criteria previously set forth are too sensitive and nonspecifi c. SIRS was defi ned as the clinical response to infection manifested by two or more of the following: temperature of 38° C or higher or 36° C or lower; pulse of 90 beats/min or higher; respiration rate of 20 breaths/min or higher or a PaCO2 less than 32 mm/Hg; or a white blood cell count of 12,000 or more or 4000 or less or more than 10% immature neutrophils. When SIRS criteria are met and infection is confi rmed or suspected, the patient is then considered to be septic. The latest guide-lines expanded on this concept in the defi nitions (Table 57-6). These defi nitions do not take into account the physiologic changes of preg-nancy and therefore may overdiagnose sepsis.

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Gram-positive organisms have surpassed gram-negative organisms as the most common cause of sepsis in the general population, unlike the situation for pregnant patients. Common organisms isolated from pregnant patients in septic shock include Escherichia coli, groups A and B streptococci, Klebsiella species, and Staphylococcus aureus.59 The source of infection in pregnant women is typically the genitourinary tract and includes lower urinary tract infections, pyelonephritis, cho-rioamnionitis, endometritis, and rarely, septic abortion, necrotizing fasciitis, and toxic shock syndrome.58,59,87,88,92

Pathophysiology of SepsisSepsis is a complex phenomenon that originates with invasion of the host by an offending organism. After infection, macrophages are recruited, bind to the organism, and initiate a collection of responses resulting in the activation of the infl ammatory and coagulation cas-cades. Initially, the sepsis response was postulated to be the result of an exaggerated infl ammatory response. Initial pharmacologic approaches therefore targeted suppression of the infl ammation process, including corticosteroids and agents to block cytokines such as tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β).93 These approaches have been largely unsuccessful, a testament to the complexity of the sepsis syndromes. The roles of anti-infl ammatory mediators and genetics in the sepsis cascade has been increasingly appreciated.94 Activation of the infl ammatory cascade after infection causes release of interleukins, tumor necrosis factors, interferons, pros-taglandins, platelet-activation factor, oxygen free radicals, nitric oxide, complement, and fi brinolysins.95

Hemostatic mechanisms are also affected in severe sepsis. Initiation of the clotting cascade results from macrophages and monocytes involved in production of infl ammatory mediators. Endothelial damage also contributes to the procoagulant effect, causing platelet activation and suppression of protein C activity. These derangements in the hemostatic balance lead to clotting factor consumption, fi brin deposi-tion, thrombin generation, and decreased platelet levels.96 The resultant microthrombi are thought to negatively affect end-organ damage and contribute to the clinical features of severe sepsis and septic shock, such as oliguria, ARDS, and hepatic dysfunction. In severe cases, consump-tion of clotting factors is substantial enough to cause hemorrhagic complications from DIC. Figure 57-6 outlines the sepsis cascade.

Clinical ManifestationsSeptic shock has been classifi ed as three progressive clinical stages: warm shock, cold shock, and irreversible (secondary) shock, which are

summarized in Table 57-7. The initial phase is characterized by vaso-dilation, increased capillary permeability, and endothelial damage. Clinically, the patient may have evidence of infection or fever and may have positive blood cultures. Peripheral vasodilation causes fl ushing and warm extremities. It also leads to a decrease in blood pressure with diminished cardiac preload, which leads to a tachycardic response in an effort to maintain or increase the CO. Initial laboratory fi ndings vary. An elevated white blood cell count may be followed by neutro-penia. Hyperglycemia is typical as a result of altered adrenal respon-siveness, insulin resistance, and increased levels of catecholamines and cortisol.

If uninterrupted, sepsis progresses and is characterized by intense vasoconstriction. This leads to poor perfusion, which is manifested by cool extremities and altered organ function as a result of inadequate oxygenation (i.e., cold shock). Oliguria is typical, as are respiratory failure and ARDS. The CO decreases as a result of inadequate venous return and increasing peripheral resistance. In the advanced stages of septic shock (i.e., secondary or irreversible shock), symptoms progress and refl ect the global effects of inadequate tissue perfusion and oxy-genation: hypotension, respiratory failure, renal failure, DIC, myocar-dial depression, electrolyte disturbances, obtundation, and metabolic acidosis.

ManagementIf the patient is at a viable gestational age and is undelivered with evi-dence of sepsis or septic shock, the fetal status should be monitored closely with continuous fetal heart rate monitoring and ultrasound evaluation to estimate fetal weight, assess amniotic fl uid volume, and confi rm gestational age. Uterine perfusion and oxygenation are adversely affected as the sepsis progresses. Contractions are often encountered, possibly as a result of decreased uterine perfusion and decreased oxygen delivery to the myometrium. Tocolysis should be undertaken with caution because the side effects of the medications (e.g., tachycardia, vasodilation) may impair physiologic adaptations to sepsis. If maternal status can be corrected and fetal status remains reassuring, delivery can be avoided. The decision about whether to proceed with delivery may be challenging, particularly if maternal status is deteriorating. The fetus may not tolerate labor because of poor uterine perfusion and maternal hypoxemia; conversely, the mother may be too unstable to safely undergo a surgical procedure. If the source of infection is the uterus, as in septic abortion or chorioamnio-nitis, evacuation of the uterus is necessary.

Sepsis management has several goals:

� Identifi cation of the source of infection� Institution of empiric antibiotic therapy� Early, aggressive improvement in circulating volume� Optimization of hemodynamic performance� Maintenance of oxygenation� Volume resuscitation

Aggressive fl uid replacement to improve circulating intravascular volume is a mainstay of sepsis management and has improved CO, oxygen delivery, and survival. Studies have demonstrated a survival benefi t for patients with septic shock managed with protocol-driven, early, aggressive volume resuscitation. Early goal-directed therapy (EGDT) involves tailoring treatments and resuscitative efforts to achieve specifi ed endpoints, which include normal mixed venous oxygen saturation, arterial lactate concentration, base defi cit, and pH in an effort to reduce end-organ dysfunction and ultimately reduce mortality.

TABLE 57-6 DIAGNOSTIC CRITERIA OF SEPSIS SYNDROMES

Condition Defi nition

Infection Pathologic process caused by the invasion of normally sterile tissue or fl uid or body cavity by pathogenic or potentially pathogenic microorganisms

Bacteremia Presence of bacteria in the bloodstreamSepsis Systemic infl ammation accompanied by infectionSevere sepsis Sepsis complicated by major organ dysfunctionSeptic shock Persistent unexplained arterial hypotension in the

setting of severe sepsis

Data from Levy MM, Fink MP, Marshall JC, et al: 2001 SCCM/ESICM/

ACCP/ATS/SIS International Sepsis Defi nitions Conference. Crit Care

Med 31:1250-1256, 2003.

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In 2001, Rivers and colleagues97 published the results of a prospec-tive, randomized trial of EGDT compared with standard therapy for patients in septic shock in a single institution. Therapy for patients in the EGDT group was initiated in the emergency room setting before transfer to the intensive care unit and included placement of central venous catheters with the ability to measure continuous venous oxygen saturation (SCvO2). An elevated SCvO2 value refl ects inadequate perfusion and uptake of oxygen in the tissues. Red blood cell transfusions were administered to maintain the hematocrit at 30% or higher, and inotropic agents were added if the SCvO2 level was inadequately corrected (<70%). The protocol called for a 500-mL crystalloid bolus every 30 minutes until the CVP reached 8 to

12 mm Hg. The volume of fl uid administered to both groups of patients was similar in the fi rst 72 hours (>13 L), but the EGDT group received more volume in the initial 6 hours of therapy (5 versus 3.5 L). This aggressive approach decreased the mortality rate by 16% (30.5% versus 46.5%).

Clinicians have questioned whether modifi cation of this protocol, particularly elimination of continuous venous oxygen saturation (SCvO2), could produce similar results. In 2006, Lin and coworkers98 randomized patients to EGDT without measurement of SCvO2 and confi rmed survival benefi t. Patients randomized to receive modifi ed EGDT were signifi cantly less likely to die (71.6% versus 53.7%), spent fewer days in the hospital, were intubated for a shorter time, and were

Bacterial productsand components

Activation of coagulationand complement system

Tissue factor releaseFibrinolytic activity

TNF-aIL-1IL-6PAFNOetc.

Neutrophil activation,aggregation,

degranulationRelease of O2 radicals

and proteases

Platelet activation,aggregation

Metabolism ofarachidonic acid

Release ofthromboxane A,

PGS, LTS

T-cell release ofIL-2, INF-g,GM-CSF

Endothelial damage

Tissue injury

Organ dysfunction

Macrophage

FIGURE 57-6 The sepsis cascade. Hemostatic mechanisms are affected in patients with severe sepsis, and derangements in the hemostatic balance lead to clotting factor consumption, fi brin deposition, thrombin generation, decreased platelets, tissue injury, and organ dysfunction. GM-CSF, granulocyte-macrophage colony-stimulating factor; IL, interleukin; LTS, leukotrienes; NO, nitric oxide; PAF, platelet-activating factor; PGS, prostaglandin synthesis; TNF-α, tumor necrosis factor α. (Modifi ed from Bone RC: The pathogenesis of sepsis. Ann Intern Med 115:457-469, 1991.)

TABLE 57-7 STAGES OF SHOCK

Warm (Early) Shock Cold (Late) Shock Secondary (Irreversible) Shock

FlushingWarm extremitiesRapid capillary refi llDecreased mental statusHypotensionIncreased cardiac outputTachycardiaTachypnea

CyanosisCool extremitiesDelayed capillary refi llIncreased vascular resistanceDecreased cardiac outputRespiratory failure or adult respiratory distress syndromeOliguria

Renal failureDisseminated intravascular coagulopathyMyocardial failureRefractory hypotensionObtundation

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at less risk for developing sepsis-associated central nervous system and renal dysfunction compared with controls.

Because of the encouraging survival and morbidity data, EGDT is being widely adopted in the management of severe sepsis, but it remains to be confi rmed whether this approach will produce similarly improved outcomes in a pregnant population. The precise goals to appropriately guide therapy in a pregnant population also must be defi ned.

Optimization of Hemodynamic PerformanceIn addition to replacing intravascular volume to improve perfusion and cardiac preload, early pharmacologic interventions to improve vascular tone, cardiac contractility, and cardiac preload confer a considerable survival advantage.97,98 If the patient fails to respond appropriately to aggressive fl uid resuscitation efforts, vasopressors are indicated to improve vascular tone, resulting in improved cardiac return and CO, peripheral perfusion, and oxygen delivery. In the initial publication on EGDT, the requirement for vasopressors was signifi -cantly diminished by early, aggressive fl uid resuscitation (37% versus 51%), but there was no difference in the requirement for inotropic agents between the two groups (9% versus 15%).97 In this study, vaso-pressors were initiated to maintain mean arterial pressure above 65 mm Hg. Use of a similar protocol minimized the delay in initiation of vasopressors and reduce mortality.98

Dopamine hydrochloride is the most commonly employed fi rst-line vasopressor in the intensive care setting. Dopamine’s α- and β-adrenergic effects are dose dependent. Low doses (<10 μg/kg/min) improve myocardial contractility, CO, and renal perfusion without negatively affecting myocardial oxygen consumption. As the dose increases (>20 mg/kg/min), α-adrenergic effects predominate, result-ing in increasing SVR in addition to increased CO. In a viable gestation requiring vasopressor support, fetal monitoring is essential because dopamine has decreased uterine perfusion in an animal model.99 Dobutamine is similar to dopamine, but it has primarily β1-adrenergic effects. Dobutamine therefore improves CO with minimal impact on heart rate or vascular resistance. In the EGDT protocol, dobutamine was used to improve oxygen consumption in patients who failed to respond to fl uid resuscitation, dopamine infusion to improve mean arterial pressure, and red cell transfusion to correct anemia.97 Table 57-8 lists other commonly used vasopressor agents for the manage-ment of severe sepsis and septic shock.

Source Control and Antimicrobial TherapyPrompt identifi cation of the probable source of infection is essential to initiate appropriate antimicrobial therapy and improve outcomes for septic patients. In an obstetric population, common sources of

infection are the uterus and genitourinary tract, and gram-negative bacteria constitute the primary organisms. In the non-obstetric popu-lation, gram-positive organisms represent most of the organisms iso-lated in septic patients, followed closely by gram-negative bacteria.89 Cultures should be collected from blood and any suspected site, includ-ing the uterus if necessary, for identifi cation of the organism and determination of antibiotic sensitivities. Empiric antimicrobial therapy targeted at the suspected organism should not be delayed pending culture results.100-103

In an obstetric and postpartum population, antibiotic coverage usually consists of β-lactam antibiotics (i.e., penicillins, cephalospo-rins, carbapenems, and monobactams) with or without an aminogly-coside (see Chapter 38). Monotherapy with a carbapenem or third- or fourth-generation cephalosporin is as effective as a β-lactam antibiotic in combination with an aminoglycoside in non-neutropenic patients with severe sepsis.104 In undelivered patients, tetracycline derivatives and quinolones should be avoided. When culture results become avail-able, antibiotic therapy can be adjusted if necessary.

After appropriate antibiotic therapy has been initiated and the process of stabilization of the patient has begun, attention should be directed to source control. This entails removal of indwelling lines and catheters, with replacement if necessary. Indications for more aggres-sive surgical approaches are less clearly defi ned. Generally, more inva-sive surgical approaches are not emergent and can be accomplished after the condition of the patient has stabilized.105 Exceptions are infec-tions involving clostridia and group A streptococci, such as necrotizing fasciitis. In this scenario, delay in excision of affected tissues can have a dramatic negative effect on the patient’s condition.106 Evaluation of the abdomen by ultrasound or computed tomography (CT) can assist in identifi cation of an intra-abdominal abscess. When drainage of an intra-abdominal abscess is necessary, the percutaneous approach is preferable. In obstetric conditions, evacuation of the uterus by suction curettage in septic abortion or delivery of the neonate in viable gesta-tions should occur after initiation of antibiotics and stabilization of the patient. Postpartum hysterectomy may be necessary if the patient fails to respond to antibiotics and the uterus is the suspected source.

Adjunctive Therapies in Sepsis ManagementINSULIN THERAPYIn the critically ill population, hyperglycemia is a common phe-

nomenon attributable to insulin resistance and escalations in glucagon, cortisol, and catecholamine levels, which promote glycogenolysis and gluconeogenesis.107 In 2001, Van den Berghe and colleagues108 pub-lished a large, prospective, randomized trial that demonstrated that tight glycemic control (blood glucose level of 80 to 110 mg/dL) in critically ill patients decreased overall mortality by 34%. Septic patients exhibited an even more impressive 76% reduction in mortality as a result of aggressive euglycemia with insulin therapy.108 Other signifi -cant benefi ts of tight glycemic control included fewer ventilator days, less time in the ICU, decrease risk for developing septicemia, and a reduced need for dialysis.

Pregnant women demonstrate insulin resistance and to have higher circulating insulin levels than their nonpregnant counterparts. They are also predisposed to developing fasting hypoglycemia because of higher levels of insulin and continuous delivery of glucose to the fetus. However, the impact of aggressive euglycemia in the critically ill preg-nant patient remains to be studied.

CORTICOSTEROIDSEmpiric administration of corticosteroids in high doses does not

improve survival of unselected septic patients and may worsen out-

TABLE 57-8 INOTROPIC DRUGS FOR MANAGEMENT OF SHOCK

Agent Dose Hemodynamic Effect

Dopamine Low dose <10 μg/kg/min ↑ CO, vasodilation of renal

arteries High dose 10-20 μg/kg/min ↑ CO, ↑ SVRDobutamine 2.5-15 μg/kg/min ↑ CO, ↓ SVR or ↑ SVRPhenylephrine 40-180 μg/min ↑ SVRNorepinephrine 2-12 μg/min ↑ CO, ↑ SVRIsoproterenol 0.5-5 μg/min ↓ CO, ↑ SVR

CO, cardiac output; SVR, systemic vascular resistance; ≠, increase; Ø,

decrease.

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comes because of secondary infection.109,110 However, as the patho-physiology of sepsis has become more clearly understood, the contribution of relative adrenal insuffi ciency in critically ill patients and the potential benefi t of lower-dose, selective corticosteroid replace-ment have reemerged.

Stresses such as pain, fever, hypovolemia, or severe illness normally stimulate marked increases in cortisol levels. In the patient with septic shock, the adrenal gland may not respond to adrenocorticotropic hormone (ACTH) stimulus appropriately and fail to mount adequate corticosteroid production. In the setting of septic shock, however, the levels of cortisol may be increased overall, but the magnitude of increase after ACTH administration may be blunted. This phenome-non is described as relative adrenal insuffi ciency.111,112 This group of patients is being evaluated for potential benefi t from lower doses of corticosteroids. A randomized trial conducted by Annane and col-leagues113 demonstrated a survival benefi t (mortality rate of 37% versus 47% for controls) for patients with septic shock treated with low-dose hydrocortisone and fl udrocortisone. Patients who had documented blunted adrenal responsiveness also benefi ted from a reduced need for vasopressor support. All of these patients had elevated baseline cortisol levels. A 2004 meta-analysis of 16 trials that included more than 2000 patients suggested similar benefi t from lower-dose steroid replace-ment in patients with severe sepsis and septic shock.114 Steroids did not appear to confer a mortality benefi t when all data were included. However, inclusion of only studies utilizing low-dose (300 mg of hydrocortisone or an equivalent), longer-duration (5 to 11 days) therapy did demonstrate a decrease in overall mortality rates. The investigators recommended initiation of low-dose glucocorticoid replacement in septic patients with blunted adrenal responsiveness confi rmed by an ACTH stimulation test.

The degree of adrenal suppression in pregnant or postpartum septic shock patients and the effect of low-dose steroids on outcomes in this population are unknown. If the patient remains undelivered, care should be taken in the choice of corticosteroids. Betamethasone and dexamethasone cross the placenta and have improved neonatal outcomes for premature infants. However, both can negatively impact neonatal outcomes when administered in large doses.115

ACTIVATED PROTEIN C THERAPY FOR

SEVERE SEPSISOne of the pathophysiologic mechanisms thought to contribute to

morbidity and mortality in sepsis patients is inappropriate activation of the coagulation system. As a result, many trials have been performed involving various antithrombotic agents, including antithrombin III and tissue factor-pathway inhibitor, without successfully identifying a treatment to reduce mortality among septic shock patients.116 In con-trast, activated protein C (APC, drotrecogin alfa) has been approved by the U.S. Food and Drug Administration (FDA) for use in severely septic patients at high risk for death as evidenced by an APACHE II score greater than 25.

Patients with severe sepsis have an acquired defi ciency of protein C and are limited in their ability to convert protein C to its active form. These low protein C levels have been associated with poorer outcomes for severe sepsis patients.117,118 APC is believed to mediate the effects of severe sepsis in several ways. APC stimulates fi brinolysis and inacti-vates factors Va and VIIIa, resulting in inhibition of thrombin forma-tion.94,119 Decreased thrombin formation then leads to decreased infl ammation by inhibiting platelet activation, neutrophil recruitment, and mast cell degranulation. Two trials have evaluated APC’s effect on mortality in patients with severe sepsis. In the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS)

trial, a multicenter, randomized trial, APC administration to patients in septic shock decreased the 28-day mortality rate from 30.8% in the placebo group to 24.7% (P = .005) in the study group. This represents a 6.1% absolute reduction in overall mortality due to septic shock and a 13% reduction in the groups with the highest predicted mortality based on APACHE II scores.120 A subsequent single-arm trial (Extended Evaluation of Recombinant Human Activated Protein C [ENHANCE] trial) using APC in severe sepsis patients demonstrated a mortality rate (25.3%) similar to that seen in the PROWESS trial (24.7%). Patients who received the therapy in the fi rst 24 hours after diagnosis of major organ dysfunction had the lowest mortality rate (22.9%).121

The most signifi cant complication resulting from the use of APC is hemorrhage. In the PROWESS trial, 3.5% of patients receiving APC suffered a signifi cant hemorrhagic event such as intracranial hemorrhage or need for transfusion, compared with a 2% incidence in the control group. The risk of bleeding appears to be greatest during the infusion period, because APC has a very short half-life. Because of this risk, APC is not indicated for all patients with septic shock, and its use should be limited to patients with greatest risk of mortality (i.e., APACHE II scores �25 and one major organ dysfunction). APC is contraindicated if the risk of bleeding is increased (i.e., active internal bleeding, hemorrhagic stroke in the preceding 3 months, intracranial or intraspinal surgery, severe head trauma in the preceding 2 months, trauma, or epidural catheter). The role of APC in managing obstetric patients has not been established. Signifi cant changes in the coagula-tion cascade occur, including elevated factor VIII levels. The impact of these changes on the responsiveness to APC is unknown; however, pregnancy is not a contraindication to its use.

Hemorrhagic Shock

Incidence and EtiologyObstetric hemorrhage is the leading cause of maternal death after an intrauterine gestation. The overall incidence of maternal death from hemorrhage is 1.4 per 100,000 live births. When ectopic gestations are excluded, placental abruption is the most common cause of death (18.5%).122 The cause of hemorrhage varies by pregnancy outcome; maternal deaths after a live birth are most likely associated with post-partum hemorrhage. Stillbirths are most likely to be associated with death from placental abruption, and undelivered pregnancies occur most often with lacerations or uterine ruptures.122 A signifi cant increase in risk of death from hemorrhage is seen in nonwhite women and with advancing age. In an analysis of maternal morbidity and mortality, hemorrhage accounted for 39% of near-miss morbidities. The inves-tigators estimated that 46% of these near-miss events were preventable and were related to communication issues, policies and procedures, failure to identify high-risk status, failure to transfer to a higher level of care, or inappropriate care. The presence of a signifi cant disease state, such as preeclampsia, was also a contributor.123

Causes of obstetric hemorrhage associated with an intrauterine gestation include placental abruption or previa, uterine rupture, surgi-cal lacerations, invasive placentation, uterine inversion, and postpar-tum hemorrhage, usually caused by atony or retained products of conception. The source of hemorrhage can usually be determined by assessment of the patient. Concealed hemorrhage (e.g., abruption, liver capsule rupture in HELLP syndrome) is also possible and should be considered in a patient with evidence of shock and no obvious source of hemorrhage.

Obstetric hemorrhage has been arbitrarily defi ned as an estimated blood loss of more than 500 mL in a vaginal delivery and greater than

Ch057-X4224.indd 1179 8/26/2008 4:14:44 PM


1000 mL for cesarean section.124 Other defi nitions describe a decrease in the hematocrit by 10% or the need for transfusion.125 However, estimates of blood loss are inaccurate and can vary widely. The true incidence of obstetric hemorrhagic shock is unknown.

Clinical Staging of HemorrhageBecause of the normal blood volume expansion in pregnancy, clinical evidence of hypovolemia becomes evident much later than expected. Relatively minor symptoms such as orthostatic hypotension and tachy-cardia typically do not appear until at least 20% to 25% of the blood volume is lost. Table 57-9 outlines the clinical staging of hemorrhagic shock, depending on severity.

ManagementThe goal of management of hemorrhagic shock is to identify and control the bleeding source while restoring circulating blood volume and clotting factors. Baseline laboratory evaluation is recommended on recognition of the hemorrhage and should include a complete blood cell count, blood type and crossmatch, fi brinogen level, pro-thrombin time (international normalized ratio), and activated partial thromboplastin time. A basic metabolic panel is potentially useful to assess renal function and electrolyte disturbances. These laboratory tests should be repeated at regular intervals until the situation is resolved. The Lee-White whole-blood clotting time test can be used as a crude method to assess for the presence of DIC. Whole blood is col-lected in an unheparinized tube and observed. A stable clot should form between 5 and 15 minutes.

VOLUME REPLACEMENT THERAPYAdequate and timely replacement of circulating volume is essential

in the management of hemorrhagic shock. This is accomplished by administering crystalloid solutions such as normal saline or colloids such as albumin or blood products. Controversy exists about the most appropriate combination of fl uids to replace circulating volume. Crystalloid solutions appear to be as effective as colloid solutions in most settings.126 The Advanced Trauma Life Support (ATLS) course has proposed widely accepted standards for management of the trauma patient. For the patient in hemorrhagic shock, initial resuscitation with 2 L of crystalloid solution is followed by packed red cell transfusions.127 The degree of volume resuscitation is also a matter of debate. Histori-cally, aggressive, early fl uid resuscitation was thought to result in improved outcomes. However, later data suggest that excessive fl uid

resuscitation may destabilize clot formation and stability, worsen hypothermia, and contribute to hemodilution without providing the expected benefi t in survival. Some physicians recommend resuscita-tion to allow for permissive hypotension (i.e., systolic blood pressure >80 mm Hg).127

COLLOID SOLUTIONSColloid solutions are intravenous fl uids containing particles larger

than 10,000 daltons. Packed red cells are considered a colloid, but this discussion focuses on additional colloid products. The major advan-tage provided by a colloid solution is the signifi cant increase in plasma volume compared with a crystalloid solution. Colloid solutions increase intravascular COP and draw fl uid into the intravascular space. In achieving this effect, extravascular volume can become depleted, and fl uid resuscitation should include adequate administration of crystal-loids. The degree of plasma expansion depends on the availability of extravascular fl uid. In certain clinical settings such as sepsis, surgical trauma, or preeclampsia, vascular permeability is altered, and colloid solutions can escape into extravascular spaces, particularly the lungs, and lead to pulmonary edema. Available colloid solutions include albumin, dextran, and hetastarch. Table 57-10 compares the effects of these agents.

Albumin solutions are available in concentrations of 5% or 25%. A 25-g infusion of albumin temporarily increases intravascular volume by roughly 450 mL over 60 minutes as a result of its considerable oncotic activity. Albumin is cleared rapidly from the circulation, par-ticularly in patients with shock or sepsis.

Dextran solution contains large glucose polymers with mean molecular weights of 40,000 daltons (dextran 40) or 70,000 daltons

TABLE 57-9 CLINICAL STAGING OF HEMORRHAGIC SHOCK BY VOLUME OF BLOOD LOSS

Severity of Shock Findings Blood Loss (%) Volume (mL)*

None None Up to 20 Up to 900Mild Tachycardia (<100 beats/min) 20-25 1200-1500

Mild hypotensionPeripheral vasoconstriction

Moderate Tachycardia (100-120 beats/min) 30-35 1800-2100Hypotension (80-100 mm Hg)RestlessnessOliguria

Severe Tachycardia (>120 beats/min) >35 >2400Hypotension (<60 mm Hg)Altered consciousnessAnuria

*Based on an average blood volume of 6000 mL at 30 weeks’ gestation.

TABLE 57-10 COLLOID INFUSIONS

Colloid Dose (mL)

Crystalloid Volume

Expansion

Equivalent

Estimated

Duration of

Effect (hr)

Albumin 5% solution 500-700 Similar to crystalloid 24 25% solution 100-200 3.5 times crystalloid 24Hetastarch 500-1000 Similar to crystalloid 24-36Dextran (70) 500 1050 mL over 2 hours 24

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(dextran 70). Dextran 40 is rarely used for the purposes of volume expansion. A 500-mL infusion of 6% dextran 70 should rapidly expand intravascular volume by more than 1000 mL. Adverse effects of dextran administration include increased bleeding risk and allergic reaction. Anaphylactic reactions affect 1 in 3300 patients receiving dextran. In higher doses (>20 mL/kg/24 hr), dextran may negatively affect platelet function and clotting factor activation, and it may interfere with fi brin function. It also may interfere with laboratory cross-matching of blood. Dextran should be used cautiously in patients with hypovole-mia due to hemorrhage who may already have a coagulo pathy and require further cross-matching of blood.

Hydroxymethyl starch (i.e., hetastarch) is a synthetic molecule available in a 6% solution in normal saline (Hespan) or lactated elec-trolyte solution (Hextend). Like the other available colloid solutions of albumin and dextran, hetastarch also induces intravascular volume expansion by increasing oncotic pressure. The effects of hetastarch can persist for 24 to 36 hours. As with dextran, hetastarch may negatively affect the clotting system. Hetastarch can prolong prothrombin and partial thromboplastin times, decrease platelet counts, and reduce clot tensile strength, and it should be used with caution in patients who may have a coagulopathy. Hextend is a newer hetastarch formulation with smaller-molecular-weight particles in addition to electrolytes and lactate similar to plasma levels. It may have less effect on the coagula-tion profi le compared with other colloids and therefore offer a theo-retical advantage in the setting of hemorrhage.128

BLOOD COMPONENT THERAPYBlood product replacement is the cornerstone of successful manage-

ment of hemorrhagic shock. The variety of blood product components available for transfusion is summarized in Table 57-11, along with anticipated effects. Whole blood has not been separated into the various components and therefore offers a theoretical advantage because it contains clotting factors and platelets in addition to red blood cells. The major limitation to the use of whole blood is the inability to store the product beyond 24 hours. After 24 hours of extravascular storage, plate-lets and granulocytes are completely lost and 2,3-diphosphoglycerate is depleted, signifi cantly compromising the oxygen carrying capacity of the red blood cells. Prolonged storage results in depletion of clotting factors and increasing levels of potassium and ammonia. For these reasons, whole blood is typically separated into its individual compo-nents and stored for later use; it is essentially unavailable in the United States. Individual components can then be administered to address specifi c derangements according to clinical indications. The routine

administration of clotting factors after every 4 to 6 units of packed red blood cells has not been demonstrated to improve outcomes.129

A single unit of packed red cells has a hematocrit of approximately 80% and can increase the hemoglobin level by 1 g/dL in a 70-kg indi-vidual. Removal of white blood cells from the unit of blood (i.e., leu-kocyte-poor blood) decreases the risk of febrile transfusion reactions. Patients with evidence of acute hemorrhage (>30% blood volume loss), hemoglobin level between 6 and 10 g/dL with evidence of tachy-cardia and hypotension, or hemoglobin concentration less than 6 g/dL should be considered candidates for transfusion.130,131

Dilutional thrombocytopenia can occur as a result of massive transfusion in a hemorrhaging patient. After replacement of one blood volume, 35% to 40% of a patient’s platelets usually remain, and platelet replacement is recommended in the setting of bleeding and signifi cant thrombocytopenia. Platelet counts equilibrate within 10 minutes and can be assessed immediately after completion of the transfusion.

Fresh-frozen plasma (FFP) is plasma that is extracted from whole blood within 6 hours of collection and frozen. A single unit of FFP contains 700 mg of fi brinogen in addition to factors II, V, VII, IX, X, and XI. It is indicated for the replacement of multiple clotting factors in patients with acute hemorrhage and evidence of DIC. The goal is to correct clotting factor defi ciencies and to achieve a post-transfusion serum fi brinogen level of approximately 100 mg/dL.

Cryoprecipitate is obtained from FFP and contains factor VIII (80 to 120 units), fi brinogen (200 mg), von Willebrand factor, and factor XIII. One unit of cryoprecipitate and one unit of FFP have similar effects on the fi brinogen level (increase of 10 to 15 mg/dL). However, because of its smaller volume, cryoprecipitate more effi ciently raises the fi brinogen level compared with FFP.

COMPLICATIONS OF TRANSFUSIONComplications resulting from blood component transfusion vary

from infections to immunologic responses. Table 57-12 outlines the frequency of various transfusion-related complications.

Minor transfusion reactions are relatively common occurrences and are not caused by hemolysis. Common clinical fi ndings include low-grade fever, urticaria, or hives, and they result from exposure to incompatible platelet or white blood cell antigens. The use of leuko-cyte-poor packed red cells minimizes these types of reactions. Nonhe-molytic reactions do not require discontinuation of the transfusion. Symptoms can be managed with antipyretic agents and antihistamines, as needed.

TABLE 57-11 BLOOD COMPONENTS

Component Contents Indications Volume Shelf Life Expected Effect

Packed RBCs Red cells, some plasma, few WBCs

Correct anemia 300 mL 21 days Increase HCT 3%/unit, Hgb 1 g/unit

Leukocyte-poor blood RBCs, some plasma, few WBCs

Correct anemia, reduce febrile reactions

250 mL 21-24 days Increase HCT 3%/unit, Hgb 1 g/unit

Platelets Platelets, some plasma, RBCs, few WBCs

Bleeding due to thrombocytopenia

50 mL Up to 5 days Increase total platelet count 7500 μL/unit

Fresh-frozen plasma Plasma, clotting factors V, XI, XII

Treatment of coagulation disorders

250 mL 2 hours thawed, 12 months frozen

Increase total fi brinogen 10-15%/unit

Cryoprecipitate Fibrinogen, factors V, VIII, XIII, von Willebrand factor

Hemophilia A, von Willebrand disease, fi brinogen defi ciency

40 mL 4-6 hours thawed

Increase total fi brinogen 10-15 mg/dL per unit

HCT, hematocrit; Hgb, hemoglobin; RBCs, red blood cells; WBCs, white blood cells.

Ch057-X4224.indd 1181 8/26/2008 4:14:44 PM


Severe reactions after transfusion are usually the result of a hemo-lytic reaction to the administration of an incompatible unit of blood. Historically, administration of ABO-incompatible blood was thought to occur at a rate of 1 in 600,000 units, but a later report suggests it occurs with much greater frequency (1 in 25,000 units). Administrative error is the culprit in most of these events, underscoring the need for accurate accounting of transfused units, particularly in an emergent situation.132 Cardiovascular decompensation with DIC, fever, and renal failure usually develop rapidly after initiation of an incompatible transfusion. Treatment entails immediate discontinuation of the trans-fusion and supportive care.

ADDITIONAL SUPPORTIVE MEASURESRed Blood Cell–Saving Devices. In patients anticipated to be at

risk for excessive intraoperative blood loss, such as suspected placenta accreta, use of an autologous transfusion device (Cell Saver) should be considered.124,133 Theoretical risks of inducing amniotic fl uid embolism have caused some concern regarding the use of intraoperative cell salvage during cesarean section. However, several reports have vali-dated its safety in this arena.134-137 After delivery of the fetus and clear-ing the operating fi eld of amniotic fl uid, the suction device is changed, and blood is collected into the Cell Saver. In approximately 3 minutes, a unit of blood with a hematocrit of 50% is generated. In one study comparing patients who received blood salvage and autotransfusion during cesarean section with those receiving allogeneic blood transfu-sions, no differences in the rates of infection, coagulation abnormali-ties, or respiratory problems could be identifi ed.135 This technology may be particularly valuable for patients who have the potential for severe blood loss or who have religious preferences mandating the avoidance of transfused blood products.

Acute Normovolemic Hemodilution. Acute normovolemic hemodilution offers an additional option for patients at signifi cant risk for intraoperative hemorrhage. The principle behind this approach is to dilute the patient’s circulating volume so that when bleeding occurs, it has a lower hematocrit. This is accomplished by collecting blood from the patient preoperatively and placing it into special storage bags that can be obtained from the blood bank. Simultaneously, the patient is given crystalloid solution in a 3 : 1 ratio, resulting in a dilutional effect and a decrease in the maternal hematocrit. Intraoperatively, after achieving control of the blood loss, or at the discretion of the surgeon, the patient’s blood is then reinfused, resulting in an increase in the hematocrit.

Potential advantages include preservation of clotting factors, a decreased likelihood of allogeneic transfusion, and therefore a

decreased risk of infectious morbidity, alloimmunization, and immu-nologic complications. Adverse fetal effects have not been described during this process.138,139 Acute normovolemic hemodilution is a time-consuming process and is not appropriate for an acutely hemorrhaging patient. Suggested criteria for acute normovolemic hemodilution include an increased likelihood of transfusion; preoperative hemoglo-bin level of 12 g/dL or higher; absence of clinically signifi cant coronary, pulmonary, renal, or liver disease; absence of severe hypertension; and absence of infection and risk of bacteremia.140

Other Measures. Supplemental oxygenation and elevation of the lower extremities are recommended for patients with hemorrhage. The use of antishock (MAST) trousers has fallen out of favor after publication of a randomized trial that failed to demonstrate survival benefi t.141

Massive transfusion and blood loss place the patient at signifi cant risk for concomitant abnormalities that can compromise successful resuscitation. Maintenance of the airway and ventilation cannot be ignored. Management of the hemorrhaging patient should include regular assessment for coagulation abnormalities and recurrent bleed-ing, correction of electrolyte abnormalities, particularly calcium and potassium, and maintenance of temperature above 35° C. After control of bleeding is achieved, resuscitation is considered complete if the following goals are met142:

� Normal or hyperdynamic vital signs� Hematocrit higher than 20% (transfusion threshold

determined by the patient’s age)� Normal serum electrolyte levels� Normal coagulation function, with a platelet count of at least

50,000� Restoration of adequate microvascular perfusion, as indicated

by a pH of 7.40 with a normal base defi cit, normalized serum lactate level, normal mixed venous oxygenation, normal or high CO, and normal urine output.

DEFINITIVE THERAPY FOR HEMOSTASISControl of obstetric hemorrhage must take into consideration the

apparent cause of the hemorrhage. For example, the most likely cause of postpartum hemorrhage is uterine atony, which would be expected to respond to uterine massage and uterotonic agents as fi rst-line therapy. Hemorrhage due to placenta accreta or previa requires surgi-cal intervention. Recombinant factor VIIa (rFVIIa, NovoSeven) is approved for the management of bleeding in hemophiliacs, but its role is emerging as an off-label adjunctive therapy for the control of cata-strophic, coagulopathic bleeding. Recombinant factor VIIa functions by activating factor X, thereby enhancing thrombin production and formation of a stable clot. It is not intended as fi rst-line therapy for control of hemorrhage, and most physicians recommend use of rFVIIa only after other attempts to control hemorrhage have failed. This includes any necessary surgical approach, appropriate replacement of blood products, and correction of severe acidosis, hypothermia, and hypocalcemia.143,144 rFVIIa has been employed for the control of obstetric hemorrhage.145-148 Table 57-13 outlines pharmacologic agents useful in controlling hemorrhage from an atonic uterus.

Hemorrhage after a vaginal delivery should prompt a thorough evaluation for and repair of cervical or vaginal lacerations, particularly if an instrumented delivery was performed. If uterine atony fails to respond to uterine massage and uterotonic agents, evaluation for potential retained placental fragments should be performed. Ultra-sound may be of assistance in this assessment process, particularly if uterine curettage is necessary. Intrauterine pressure packs to control

TABLE 57-12 TRANSFUSION-RELATED RISKS

Disease or Disorder Risk

Hepatitis B 1/137,000Hepatitis C <1/1,000,000Human immunodefi ciency virus type 1

(HIV-1)<1/1,900,000

Bacterial contamination 1/38,565Acute hemolytic reaction 1/250,000-1/1,000,000Delayed hemolytic reaction 1/1,000Transfusion-related acute lung injury 1/5,000

Adapted from Goodnough LT, Brecher ME, Kanter MH, et al:

Transfusion medicine. Part 1. Blood transfusion. N Engl J Med 340:438-

447, 1999; and the American Association of Blood Banks 2002.

Available at www.aabb.org.

Ch057-X4224.indd 1182 8/26/2008 4:14:44 PM


life-threatening postpartum hemorrhage have been successful accord-ing to some reports.149,150 However, the technique used to place the packing is integral to its success and can be challenging. Other physi-cians have attempted to provide packing by modifying various infl atable devices such as Foley catheters or Sengstaken-Blakemore tubes.151,152 The SOS Bakri tamponade balloon has been introduced specifi cally to provide intrauterine compression in the management of postpartum hemorrhage.153 The SOS Bakri tamponade balloon has been placed vaginally and at cesarean section.

Surgery to Control Obstetric Hemorrhage. If uterine hemor-rhage after vaginal delivery fails to respond to the previously described measures, exploratory laparotomy should be performed. If the bleed-ing is encountered at cesarean section, the same techniques for control of hemorrhage may be applied. The B-Lynch uterine body compres-sion suture has been performed successfully to control hemorrhage due to unresponsive uterine atony, and it is demonstrated in Figure 57-7.154,155 The B-Lynch suture has been performed in conjunction with placement of an SOS Bakri balloon to achieve hemostasis.156

Suture ligation of the ascending uterine arteries (i.e., O’Leary suture) is another option and is technically straightforward to perform in most scenarios. O’Leary and O’Leary157,158reported the successful use of this technique (Fig. 57-8) in controlling postpartum and postcesar-ean bleeding. The uterine artery can be visualized and accessed ante-riorly or posteriorly. The uterine arteries are readily accessible with uterine manipulation, and minimal or no vessel dissection is necessary for uterine artery ligation. Hypogastric artery ligation is more techni-cally challenging, requiring dissection of the retroperitoneal space through the broad ligament. Bilateral ligation usually is necessary to achieve adequate reduction in pulse pressure. The surgeon must be familiar with pelvic vascular anatomy to avoid ureteral injury or in -advertent ligation of the common or exterior iliac artery, which will

obstruct blood fl ow to the lower extremity. If possible, ligation of the vessel should occur below the branch of the superior gluteal artery, as demonstrated in Figure 57-9. Because of the technical challenges and questionable effi cacy of the procedure (hemorrhage controlled in approximately 40% of cases), hypogastric artery ligation is not com-monly performed.159

The incidence of emergent peripartum hysterectomy for obstetric hemorrhage is less than 0.8%.160-164 Cesarean delivery, prior cesarean delivery, and multiple gestation are signifi cant risk factors.164,165 Other indications for peripartum hysterectomy include uterine rupture, extension of the uterine incision, infection, and myomas. A study reported peripartum hysterectomy data from a national database between 1998 and 2003 and included more than 18,000 hysterectomies. Although some case series have suggested that invasive placentation appears to be supplanting uterine atony as the leading indication for peripartum hysterectomy, other data suggest they may be equally common.160,161,164,166 Complications from emergency peripartum hys-terectomy include excessive blood loss and the need for blood product replacement, fever, wound infection, ureteral injury, thromboembolic events, cardiac arrest, and death.160,162,163,166 Supracervical and total hysterectomy have been described for the management of obstetric hemorrhage, although data are lacking to determine whether one approach is superior to the other.

Pelvic Artery Embolization. Interventional radiologists have become profi cient in arteriography for a variety of diagnostic and therapeutic approaches. It is no surprise then that selective pelvic artery embolization for the management of obstetric hemorrhage is gaining in experience. Many case series have described its effectiveness in this scenario, with success rates exceeding 90%.167-170 In addition to avoiding the added morbidity of surgical exploration, it preserves future fertility.170,171

TABLE 57-13 PHARMACOLOGIC AGENTS USEFUL FOR CONTROLLING UTERINE ATONY

Agent Dose Considerations/Side Effects

Oxytocin (Pitocin) 10-40 units/L IV10 units IM

IV bolus may cause PVCs and hypotension

Methylergonovine (Methergine) 0.2 mg IM every 2-4 hours, maximum of 5 doses

Increased SVR, increased MAP, increased CVPSide effects include pulmonary edema, seizures, intracranial

hemorrhage, retinal detachment, and coronary vasospasm.Avoid in patients with hypertension

Prostaglandin 15-methyl F2α (Hemabate)

0.25 mg IM every 15-90 minutes, maximum dose of 2 mg

DiarrheaBronchoconstrictionIncreased CO, increased heart rate, and increased right heart pressureIncreased PVRDecreased SVRDecreased coronary artery perfusionAvoid in patients with asthma

Dinoprostone (prostaglandin E2) 20 mg per rectum or vagina every 2 hours

Diarrhea, nausea, vomitingTachypnea, pyrexia, tachycardiaDecreased SVRDecreased MAPIncreased CO

Misoprostol (Cytotec, prostaglandin E1)

800-1000 μg per rectum Diarrhea, vomitingAbdominal painHeadache

Recombinant factor VIIa (NovoSeven)

200 μg/kg initial dose; may repeat with 100 μg/kg at 1 and 3 hours after the fi rst dose

Indicated with persistent bleeding despite adequate fi rst-line therapiesMay increase risk for thromboembolic events

CVP, central venous pressure; CO, cardiac output; IM, intramuscular; IV, intravenous; MAP, mean arterial pressure; PVC, premature ventricular

contraction; PVR, pulmonary vascular resistance; SVR, systemic vascular resistance.

Ch057-X4224.indd 1183 8/26/2008 4:14:44 PM


The procedure is performed in the interventional radiology suite. The femoral artery is accessed and diagnostic arteriography performed with fl uoroscopic imaging to localize the target arteries for emboliza-tion. A variety of options are available for arterial occlusion, including an absorbable gelatin sponge (Gelfoam) or another type of particulate material.

Potential adverse results from the procedure include ischemia or tissue necrosis, infection, nephrotoxicity due to contrast medium, and bleeding at the access site or failure of the embolization. Failure of this approach does not preclude a subsequent surgical attempt at hemorrhage control. Conversely, after hypogastric artery ligation is performed, successful arteriographic embolization is much more dif-fi cult to achieve.

Trauma in PregnancyTrauma is a leading cause of non-obstetric deaths in the United States, and it is estimated to complicate 6% to 7% of all pregnancies.172 About 4000 fetuses are lost annually due to complications from trauma in pregnancy.173 Most incidents are considered minor, and less than 0.4% of patients require hospitalization. Of those requiring admission, 24% proceed to delivery during the hospitalization.174,175 Motor vehicle accidents and falls account for most traumatic events affecting

pregnant women, followed by domestic violence, assault, and suicide attempts.172,176-178 Domestic violence escalates during pregnancy and is estimated to affect as many as 20% of pregnant patients.179 A high index of suspicion for domestic violence is warranted for any pregnant woman presenting for evaluation after a traumatic event.

Blunt Abdominal TraumaThe gravid uterus is particularly vulnerable to blunt trauma from motor vehicle accidents, assaults, and falls. When a pregnant woman is injured severely, it most likely involved a motor vehicle accident. Three-point restraint seatbelts are safe for use by pregnant women, they signifi cantly decrease the risk of serious maternal injury and fetal loss, and they are recommended by ACOG.180-183 Proper use of seatbelts appears to be a signifi cant predictor of maternal and fetal out-comes.181,184 Approximately one third of pregnant women do not wear seat belts because of discomfort, inconvenience, or fears about hurt-ing the fetus. Prenatal education regarding seat belt use signifi cantly improves proper seat belt use.173 The addition of airbags does not appear to be problematic for pregnant patients and may further reduce risk of injury.182

A B

C

Roundligament

Roundligament

Ovarianligament

Fallopiantube Fallopian

tube

Broadligament

FIGURE 57-7 B-Lynch surgical technique. A, Anterior view of the B-Lynch stitch placement. B, Posterior view of the B-Lynch stitch placement. C, Anterior view of the completed procedure. (From B-Lynch C, Coker A, Lawal AH, et al: The B-Lynch surgical technique for the control of massive postpartum haemorrhage: An alternative to hysterectomy? Five cases reported. BJOG 104:372, 1997. Reprinted with permission.)

Uterine artery

Cervical branch

Ureter

FIGURE 57-8 Anterior approach to the uterine artery ligation technique for postpartum obstetric hemorrhage.

Externaliliac artery Common

iliac artery

AortaSuperior

gluteal artery

Hypogastric arteryligation site

Internalpudendal trunk

Obturatorartery

Uterineartery

Ureter

FIGURE 57-9 Localization of the hypogastric artery along the right pelvic side wall.

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Placental abruption is a particularly serious complication after blunt trauma and motor vehicle accidents, because it may lead to pre-mature labor and delivery, concealed hemorrhage, consumptive coagu-lopathy, fetomaternal hemorrhage, fetal distress, and death. Detection of an abruption in the patient without vaginal bleeding presents a challenge. Abruption occurs in approximately 7% of patients after trauma, but the severity of the injury does not appear to correlate with the presence of an abruption or to predict outcome. Most placental abruptions occur in patients after relatively minor trauma without evidence of serious injury.172,178,185-187 Unfortunately, a negative ultrasound result does not reliably exclude the possibility of a placental abruption. At best, the sensitivity of ultrasound to detect abruption is 25%.188 However, the sonographic identifi cation of an abruption cor-relates with a higher likelihood of adverse outcome.188,189

The Injury Severity Score (ISS) is often used to quantify the risk of adverse outcomes for nonpregnant patients.190 Unfortunately, the ISS does not translate well to the pregnant population and has not been shown to reliably predict outcomes in this group. El-Kady and col-leagues174 published a large, population-based study of more than 10,000 trauma evaluations in pregnant women.174 Patients were divided into those delivering during the admission for trauma and those dis-charged to deliver at a later date. Falls were most common among women requiring delivery, followed by motor vehicle accidents. The likelihood of abruption, uterine rupture, maternal death, and adverse neonatal outcomes, including fetal and neonatal death, was signifi -cantly higher for the group that delivered during the trauma admis-sion. Those women discharged undelivered after trauma had improved maternal outcomes compared with the delivered patients, but they remained at increased risk for preterm delivery, abruption, and the need for blood products compared with uninjured controls. These risks could not accurately be predicted by the ISS. Adverse fetal and neonatal outcomes were not increased after discharge. In contrast, for the group of patients who delivered during the trauma admission, a high ISS (>10) was associated with the highest risk for adverse out-comes. However, a lower ISS score (<10) was still associated with a signifi cant increase in serious adverse events, including abruption, uterine rupture, and maternal or fetal death. The Revised Trauma Score (RTS), which includes the Glasgow Coma Scale, also appears to be limited in its ability to accurately predict pregnancy outcome after trauma.191

External monitoring of the fetal heart rate and contraction moni-toring are recommended after blunt trauma in a viable gestation. Pearlman and associates178 performed a prospective study monitoring patients for a minimum of 4 hours after blunt trauma. Eighty-eight percent of the patients had no visible trauma; 2.4% were critically injured. Most patients had contractions, and 70% required admission beyond the initial 4-hour observation period. Of these, 19% went on to deliver, with one fetal death. The abruption incidence in this sub-group was 9.4%. No adverse events occurred in the group of patients for whom contractions did not occur more frequently than every 15 minutes. However, all women suffering an adverse perinatal outcome had contractions every 2 to 5 minutes at some point during the initial 4-hour observation period. The severity of injury did not predict abruption or adverse outcomes.178 Other investigators have since vali-dated the concept that less than one contraction every 15 minutes is not associated with adverse outcomes after blunt trauma in pregnant patients.172,185,192 A minimum of 4 hours of fetal heart rate and contrac-tion monitoring is recommended after blunt trauma in pregnant women, regardless of injury severity. Beyond the initial observation period, the recommended duration for monitoring is not clear, par-ticularly for patients with evidence of contractions. Most physicians

recommend at least 24 hours because most serious complications occur shortly after the traumatic event.

Fetomaternal hemorrhage is another potential concern after blunt trauma in pregnancy. A Kleihauer-Betke test can provide an estimate of the amount of fetal blood within the maternal circulation, which is particularly important in determining if additional doses of RhoGAM are necessary in Rh-negative women. The test is based on the detection of fetal hemoglobin. If the presence of fetal hemoglobin within mater-nal red cells, such as in a hemoglobinopathy, is detected, the result will be falsely elevated. Figure 57-10 describes how to interpret a Kleihauer-Betke result and calculate volume of fetomaternal hemorrhage. Spon-taneous fetomaternal hemorrhage can occur throughout pregnancy in the absence of any identifi ed precipitating event, but the volumes appear to be low.193 Fetomaternal hemorrhage is thought to occur with greater frequency after blunt trauma, and Kleihauer-Betke testing is often recommended. However, the available data suggest that a positive Kleihauer-Betke result does not alter management. In four studies of 730 pregnant women who had Kleihauer-Betke testing performed after blunt trauma, 95 (13%) had evidence of fetomaternal hemor-rhage.172,178,192,194 Of these, in only two cases (0.02%) did the result potentially alter management; one patient had signifi cant hemorrhage requiring delivery as a result of fetal distress, and one underwent umbilical cord blood sampling but did not require transfusion or delivery. For the remainder, the result did not appear to affect manage-ment. In another study, no difference was found in the frequency of positive Kleihauer-Betke tests between normal controls and pregnant women being evaluated for trauma.194

Because of the gravid uterus, patterns of traumatic injury are some-what different in pregnant patients after blunt abdominal trauma, particularly motor vehicle accidents. Upper abdominal injury to the spleen and liver are more common, whereas bowel injuries occur less frequently.192,195 Traumatic uterine rupture has been reported, but it is rare with minor trauma.174,196 The risk increases with increasing sever-ity of trauma and the size of the uterus. Most ruptures occur in the fundal or posterior regions. With traumatic rupture of the uterus, fetal mortality approaches 100%.

Pelvic fractures are typically related to trauma as a result of a motor vehicle accident. The presence of a pelvic fracture should raise concern

Fetal red blood cells � MBV maternal Hct % fetal cells (KB)

If KB result is 0.9% : 0.9% of maternal blood volume (MBV) is fetalorigin.MBV is assumed to be 5000 mL for an average-size woman at term.Maternal hematocrit (Hct) should be measured; assumeapproximately 35%.Normal Hct for term newborn infant can be assumed to be 50%, ifthe patient is undelivered.

Therefore, the fetus has hemorrhaged 31.5 mL of red cells into thematernal circulation. At term, the neonatal blood volume is 125 mL/kg.If the Hct is assumed to be approximately 50% at term, the actualamount of blood lost is 63 mL. In a term infant assumed to weigh3500 g, the blood volume is approximately 438 mL, and the fetushas lost 7% of its blood volume.

Newborn Hct

Fetal red blood cells � 5000 0.35 0.009 � 31.5 mL0.5

FIGURE 57-10 Calculation of the volume of fetomaternal hemorrhage using the Kleihauer-Betke results.

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about signifi cant bleeding risk and coexistent intra-abdominal trauma, such as splenic or hepatic laceration or urinary tract injury. Pelvic fracture is not a contraindication to vaginal delivery. The decision should be based on the stability of the fracture and presence of pelvic deformities. Fetal head injuries are also more common if a pelvic fracture is sutained.197

Penetrating Abdominal TraumaGunshot and stab wounds are the most common penetrating injuries in pregnant women, usually as a result of assault or suicide attempt. The enlarged uterus increases the likelihood that the uterus and fetus will sustain injury, and the prognosis is generally less favorable for the fetus. Penetrating trauma to the lower abdomen carries a lower likeli-hood of maternal bowel injury. The impact of gunshot wounds is less predictable and varies according to the entry site and angle, size of uterus and distance from the gun. Visceral injuries occur in 19% of pregnant patients, compared with 82% in nonpregnant patients. Mortality rates are correspondingly lower in pregnant victims (3.9% versus 12.5%).198 Stab wounds are more likely to involve the upper abdomen during pregnancy, and in these cases, bowel injury should be considered.198,199

Evaluation of the patient after penetrating abdominal trauma should include an assessment of the likelihood of intra-abdominal bleeding. Ultrasound and CT are useful in this regard, and exploratory laparotomy is recommended if there is suspicion of bowel perforation or active hemorrhage. Diagnostic peritoneal lavage can help determine if bleeding is likely in hemodynamically stable patients with equivocal fi ndings on abdominal ultrasound or CT. Lavage is performed by entering the abdomen through a small incision and infusing a saline wash. The presence of blood in the recovered lavage fl uid supports the presence of intra-abdominal bleeding and warrants exploration. Tetanus toxoid prophylaxis should be used for the same indications as in the nonpregnant patient.

Trauma Management IssuesOn initial presentation, the pregnant trauma patient should be evalu-ated similar to the nonpregnant patient. Assessment and stabilization of the airway, breathing, and circulation are the primary steps, followed by systematic evaluation for evidence of traumatic injuries. If the patient is pregnant, rapid confi rmation of gestational age and assess-ment of fetal well-being are necessary. This evaluation can be per-formed simultaneous to any required maternal stabilization efforts.

Care should be taken to provide displacement of the gravid uterus off the aorta and vena cava. Compression of the great vessels occurs after the uterus reaches a size consistent with 20 weeks’ gestation, and it decreases the CO. Displacement can be accomplished manually, by moving the patient to a lateral position, or by placing a wedge under the hip.

Evaluation of a pregnant trauma patient must take into consider-ation the physiologic changes of pregnancy that affect the clinical pre-sentation. Pregnant women near term have expanded their circulating blood volume by 40% to 50%. As a result, signifi cant intra-abdominal or intrauterine blood loss can occur with minimal change in maternal vital signs. Prognosis is worse if the patient develops hypotension and tachycardia.187 In a viable gestation, a reassuring fetal heart rate tracing demonstrates adequate uterine perfusion and acts as a barometer of maternal status. As maternal cardiovascular status deteriorates, uterine perfusion suffers and manifests as contractions and fetal heart rate abnormalities. Fibrinogen levels decrease in the setting of hemorrhage

as a result of consumption. In pregnancy, fi brinogen levels are substan-tially elevated, and low and even normal-range fi brinogen should raise concern about the pregnant patient.

Delivery timing and route are dictated by maternal and fetal status and need to be individualized. If laparotomy is necessary, hysterotomy is not automatically indicated. If there is evidence of uterine injury, delivery may be necessary. Pregnancy should not preclude the use of diagnostic testing thought to be otherwise indicated for a pregnant trauma patient. No single diagnostic radiologic imaging study exists that can provide enough radiation exposure to adversely affect a devel-oping fetus. Radiation exposure of less than 5 rads has not been associ-ated with fetal abnormalities or pregnancy loss, and the radiation associated with abdominal and pelvic CT scans falls substantially below this threshold.200 Magnetic resonance imaging (MRI) does not produce ionizing radiation, and no adverse fetal effects have been reported from in utero exposure. However, because of theoretical con-cerns, ACOG states that the “National Radiological Protection Board arbitrarily advises against its use in the fi rst trimester.”200 Table 57-14 lists anticipated dose of radiation exposure to the fetus from examina-tions commonly required for a trauma patient.

Burns in PregnancyBackgroundAccording to the American Burn Association, 40,000 people require hospitalization because of burns each year. Of these, 60% are admitted to one of the 125 specialized burn centers in the United States. These centers admit 200 patients per year on average, compared with the average of three burn admissions to nonspecialized burn centers.201,202 Although current U.S. statistics are not available, burn injuries appear to be more common in developing countries, as evidenced by fewer case reports from the United States In two larger series of burns in pregnancy collected in India and Iran, approximately 7% of burn victims were pregnant patients. Burns resulting from fl ames or scalds account for 78% of cases; the remainder resulted from hot object contact (8%) or electrical (4%), chemical (3%), or other (6%) causes.203

Classifi cationBurns are characterized by the depth and size of the involved area. Partial-thickness burns (formerly classifi ed as fi rst-degree and second-degree burns) involve superfi cial skin layers and are capable of re-

TABLE 57-14 ESTIMATES OF FETAL RADIATION EXPOSURE FROM COMMON RADIOLOGIC PROCEDURES IN A TRAUMA PATIENT

Radiologic Examination

Fetal Radiation Exposure

(cGy)

Chest (posteroanterior, lateral) <<0.1Abdomen 0.15-0.26Pelvis 0.2-0.35Hip 0.13-0.2Computed tomography of head <<0.1Computed tomography of abdomen 0.04Computed tomography of pelvis 2.5

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epithelialization. These burns are painful, blistering injuries that can be red, white, or pink. These wounds are usually managed with topical agents and dressings. If healing does not occur within 3 weeks, man-agement converts to that for more serious burns. Full-thickness burns (formerly called third-degree burns) are the most severe, and epithe-lium does not regenerate. These burns are not blistering and are pain-less. They can be gray, white, or brown.

Early surgical excision of the eschar is the standard of management in the United States. Full-thickness wounds hold the greatest potential for scarring, contractures, and infection and should be referred to a burn center.204,205 The prognosis for pregnant and nonpregnant patients is directly related to the percentage of body surface area involved. Figure 57-11 shows one method of estimating the percentage of total body surface burned in nonpregnant adults. A modifi cation for the pregnant patient has not been created, but the gravid abdomen should be taken into account when estimating body surface area involvement. The severity of the burn increases in proportion to the degree of involvement, as outlined in Table 57-15.

OutcomesSevere burns are morbid events with signifi cant short-term and long-term consequences. The pregnancy does not appear to negatively affect the outcome after a burn, but the burn has the potential to signifi cantly affect the pregnancy outcome. Maternal and fetal survival depends most on the severity of the burn itself.201,202,206 In one of the largest series of burns in pregnancy, Maghsoudi and colleagues202 prospec-tively collected data on 51 pregnant burn victims admitted to a referral burn center in Iran over a 9-year period. The overall maternal mortal-ity rate was 39%, and the fetal mortality rate was 45%. The most sig-nifi cant predictor of maternal and fetal mortality was total body surface area involvement exceeding 40% and the presence of inhalation injury. These patients suffered severe burns; the mean burn surface area was 38%. In nonsurvivors, the mean burn surface area was 69%. Other studies have found similar results.201

ManagementManagement of the pregnant burn patient is similar to that of a nonpregnant patient. Acute management of the burn victim should address aggressive fl uid resuscitation, evaluation for inhalation injury and airway maintenance, assessment of carbon monoxide poisoning, anemia, prevention of infection, and wound management.

The initial priority is recognition of smoke inhalation injury, carbon monoxide poisoning, and airway management. Carbon monoxide crosses the placenta easily, and fetal hemoglobin has a higher affi nity for carbon monoxide than adult hemoglobin. Hyper-baric oxygen may play a role in treating carbon monoxide poison-ing.207 Early intubation should be considered to maximize oxygen delivery in a patient with inhalation injury and to protect against aspiration.

Fluid losses after a serious burn are substantial as a result of third spacing due to edema and evaporative loss from damaged skin. The fl uid defi cit is easily underestimated in a pregnant patient. The normal physiologic adaptations of pregnancy, including up to 40% increase in blood volume, 40% increase in CO, and 20% decrease in SVR, are not refl ected in the fl uid replacement strategies recommended for non-pregnant burn patients. One commonly used formula, the Parkland formula, recommends replacement with Ringer’s lactate at a rate of 4 mL/kg of body weight per percent of body surface area burned. Fifty percent of the calculated replacement volume is administered over the initial 8 hours and the remainder over the subsequent 16 hours. In one report, 208 the Parkland formula underestimated fl uid requirement in a pregnant burn patient by almost 10 L. Given the lack of guidelines for pregnant patients, fl uid resuscitation should be individualized to achieve hemodynamic stability, adequate urine output, and uterine perfusion. Electrolyte disturbances should also be anticipated and addressed.

Burns are associated with a signifi cant hypermetabolic state and markedly increased nutritional requirements. Hypermetabolism can be minimized by providing adequate pain relief; supplying aggressive wound management with excision, grafting, and occlusive dressings; and managing temperature and adequate fl uid replacement. Attention to adequate nutrition is essential and usually requires enteral and par-enteral feeds.209

Wound infection and sepsis are signifi cant risks after burn injury. Bacteremia results from colonization of the burn area. The most common organisms encountered are S. aureus, Pseudomonas aerugi-nosa, and Candida albicans.210 Aggressive management of the wound with excision of the eschar, grafting, and occlusive dressings, in addi-

4.5

4.5 4.5 4.5 4.5

1818

9 9 9 9

4.5

FIGURE 57-11 Body surface area diagram depicts the relative percentage of the total body surface area of defi ned anatomic areas in nonpregnant adults. (From Wolf SE, Hernon DN: Burns. In Townsend CM, Beauchamp RD, Evers BM, et al [eds]: Sabiston’s Textbook of Surgery, 17th ed. Philadelphia, Elsevier Saunders, 2004.)

TABLE 57-15 CLASSIFICATION OF BURN SEVERITY

Classifi cation Defi ned Body Surface Areas

Minor <15% partial thickness<2% full thickness

Moderate 15-25%2-10% full thickness

Major >25%>10% full thicknessAny burn involving the face, eyes, ears, feet, or

perineumInhalation injury or electrical injury

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tion to topical and systemic antibiotics, helps to prevent infectious complications. The patient may be at increased risk for venous throm-boembolic events.

Assessment of fetal well-being in a viable gestation should not be overlooked. Intravascular depletion, hypoxemia, hypermetabolism, and infection can adversely affect the fetus. Continuous monitoring is recommended in a viable gestation, particularly during the early stages of management. If the abdomen is involved with burn, direct ausculta-tion may be limited and continuous fetal heart rate monitoring not feasible. Sterile coverings are available for the heart rate monitor and ultrasound probes to minimize infection risk. Vaginal ultrasound assessment may also be considered in some settings.

Contractions and preterm labor are to be expected, particularly in a severely burned pregnant patient, although the frequency is unknown. Few data are available to guide the use of tocolytic medications. Tocoly-sis should therefore be undertaken cautiously and judiciously, with an appreciation of the hemodynamic effects and other side effects of the drug. Hypovolemic patients may not tolerate β-agonists such as terbu-taline, because they may already be in a high output state. Given the high fetal mortality rates with severe burns, delivery may be the most judicious alternative in a viable gestation. Most physicians recommend cesarean section for the usual obstetric indications. Delivery by cesar-ean section through a burned abdomen and vaginal delivery through a burned perineum have been reported.208,211-213

Cardiopulmonary Resuscitation and Perimortem Cesarean SectionCardiac arrest in a pregnant patient is a rare event. According to the most recent available data on United States maternal mortality, the most likely neonatal outcome in the setting of a maternal death is a live birth.12 The data do not refl ect the frequency of arrest occurring before delivery. In a review of 38 patients delivered perimortem by cesarean section, the causes included trauma, cardiac abnormalities, embolism, magnesium overdose, sepsis, intracranial hemorrhage, anesthetic complications, eclampsia, and uterine rupture.214 The causes of cardiac arrest in pregnant women are more likely to be acute and therefore may be more amenable to aggressive interventions. Several physiologic changes of pregnancy negatively affect attempts at cardio-pulmonary resuscitation (CPR):

� Increased CO and requirement for uterine perfusion� Aortocaval compression by the gravid uterus in the supine

position� Reduced functional residual capacity and increased oxygen

consumption� Reduced chest wall compliance� Delayed stomach emptying and decreased esophageal sphincter

tone, which increase the aspiration risk

Aortocaval obstruction should be relieved by placing the patient in a more lateral recumbent position or by manually displacing the uterus. CPR can provide only 30% of the CO when the patient is supine.215 The effectiveness of compressions increases dramatically when the patient is tilted in the lateral position.214 Early intubation is recommended to minimize aspiration risk. The use of sodium bicar-

bonate to correct maternal acidosis should be undertaken with caution because of the potential for worsening fetal acidosis. Electrocardiover-sion can be performed in a pregnant patient; the recommendations are the same as for nonpregnant patients.216

Rapid restoration of maternal circulation and reversal of hypoxia are the most effective ways to minimize negative effects on the fetus. If this is not possible, attention must then be directed to evacuation of the uterus by cesarean section. Cesarean section in the setting of mater-nal cardiac arrest can improve the likelihood of an intact neonatal outcome and simultaneously improve maternal resuscitative efforts. In 1986, Katz and colleagues217 initially advocated performing a cesarean section at 4 minutes after instituting CPR.217 This recommendation was based on the theory that emptying the uterus would improve CO generated by chest compressions after the obstructing uterus was emptied. Maternal neurologic injury could be avoided if cerebral per-fusion improved by 6 minutes, the time at which cerebral injury occurs after cessation of blood fl ow. They then reviewed the literature and reported neonatal outcomes at various time intervals after delivery. From these data, delivery within 5 minutes of arrest was most likely to result in good neonatal outcomes.52,217

Subsequently, Katz and coworkers214 reviewed 34 published cases of perimortem cesarean section performed between 1985 and 2004 to assess whether the “4-minute rule” was valid. In this series, 79% deliv-ered live infants (30 of 38; 3 sets of twins and 1 set of triplets). Data were available regarding the arrest-to-delivery interval for 25 infants and are presented in Table 57-16. Similar to data presented in earlier series, prolonging the arrest-to-delivery interval decreased the likeli-hood of intact survival, although apparently normal neonates were delivered even after more than 15 minutes.

Data were also provided about perimortem cesarean section potentially negatively impacting maternal survival. Twenty (59%) of 34 cases provided information regarding maternal hemodynamic status and indicated a benefi cial effect on maternal resuscitation efforts after perimortem cesarean. None of the cases had worsening maternal

TABLE 57-16 PERIMORTEM CESAREAN DELIVERIES WITH SURVIVING INFANTS WITH REPORTS OF TIME FROM MATERNAL CARDIAC ARREST TO DELIVERY OF THE INFANT, 1985-2004

Time (min)

Gestational Age

(wk) Number of Patients

0-5 25-42 8 (normal infant)1 (retinopathy of prematurity and

hearing loss)3 (condition not reported)

6-10 28-37 1 (normal infant)2 (neurologic sequelae)1 (condition not reported)

11-15 38-39 1 (normal infant)1 (neurologic sequelae)

>15 30-38 4 (normal infants)2 (neurologic sequelae)1 (respiratory sequelae)

Total 25

From Katz V, Balderston K, DeFreest M: Perimortem cesarean delivery:

Were our assumptions correct? Am J Obstet Gynecol 192:1916-1920,

2005.

Ch057-X4224.indd 1188 8/26/2008 4:14:46 PM


status as a result of perimortem cesarean section; 12 women had “sudden” and “profound” improvement at the time of emptying the uterus.214

The following guidelines are being suggested for the management of maternal cardiac arrest with a viable gestation:

1. Begin maternal CPR immediately. 2. Establish an airway.3. Establish intravenous access simultaneously.4. Institute cesarean delivery if there is no evidence of a maternal pulse

by 4 minutes.5. Sterile technique is not necessary, and the patient need not be

moved to an operating room.6. Continue CPR efforts during and after delivery.7. Continuous fetal monitoring is not possible because of interference

from resuscitative efforts. The maternal condition dictates whether perimortem cesarean section is necessary.

Cesarean section is not recommended in an unstable patient because of anticipated cardiac arrest. This may inadvertently precipi-

tate a worse maternal outcome. If CPR is effective at restoring circula-tion, perimortem cesarean section is not recommended.

Brain Death and Somatic Support during PregnancyBrain death is defi ned as the complete absence of brain function, which is determined clinically by lack of consciousness, movement, respira-tory effort, and most refl exes. It is confi rmed by the lack of activity on electroencephalogram. It is considered distinct from coma and persis-tent vegetative state (Table 57-17).218

Maternal brain death has been rarely reported in the obstetric and critical care literature. Two reviews on the topic identifi ed only 12 reported cases since 1982.218,219 Two additional cases were identi-fi ed.220,221 The most common reason for brain death was subarachnoid hemorrhage, followed by trauma and infection.

After brain death occurs, the options include immediate delivery, withdrawal of maternal support, or prolongation of maternal life to

TABLE 57-17 FEATURES OF COMA, PERSISTENT VEGETATIVE STATE, AND BRAIN DEATH

Feature PVS Coma Brain Death

Self-awareness Absent Absent AbsentSuffering No No NoMotor function No purposeful movement No purposeful movement None or only refl ex spinal movementsSleep-wake cycles Intact Absent AbsentRespiratory function Normal Depressed, variable AbsentElectroencephalographic activity Polymorphic delta or theta,

sometimes slow alphaPolymorphic delta or theta Electrocerebral silence

Cerebral metabolism Reduced by 50% or more Reduced by 50% or more, variable

Absent

Life expectancy Usually 2-5 yr Varies Death within 2-4 wk (Harvard criteria)Neurologic recovery Nontraumatic: rare after 3 mo

Traumatic: rare after 12 moUsually recovery, PVS, or

death in 2-4 wkNo recovery

PVS, persistent vegetative state.

Adapted from Ashwal S, Cranford R: Medical aspects of the persistent vegetative state—fi rst of two parts. The Multi-Society Task Force on PVS.

N Engl J Med 330:1499-1508, 1994.

TABLE 57-18 INTENSIVE CARE MANAGEMENT OF PREGNANT PATIENTS WITH SEVERE NEUROLOGIC INJURY

Condition Therapy Physiologic Goal

Respiratory failure Controlled hyperventilation, PEEP Physiologic hypercarbia, decrease intracranial pressure, avoid neurogenic pulmonary edema

Fluid-resistant hypotension Left lateral position, vasopressors Maintain uteroplacental circulationHypothermia Warming blankets Prevent fetal bradycardia and IUGRHyperthermia Cooling blankets Prevent fetal deathNutritional support Enteral or parenteral insulin Maintain positive nitrogen balance (energy intake of

126-147 kJ/kg of ideal body weight), avoid hyperglycemia

Panhypopituitarism DDAVP, thyroxine, cortisol Adjust for central diabetes insipidus and adrenocortical insuffi ciency

Infection prevention Frequent cultures, catheter line changes Prevent sepsisDeep venous thrombosis prophylaxis Heparin Prevent pulmonary embolismPreterm labor Betamethasone or dexamethasone, consider

tocolysisProlong gestation

General condition Expert nursing care

DDAVP, L-deamino-8-D-arginine vasopressin; IUGR, intrauterine growth restriction; PEEP, positive end-expiratory pressure.

Ch057-X4224.indd 1189 8/26/2008 4:14:46 PM


improve the neonatal prognosis by advancing gestational age. The challenges in providing life support to the brain-dead gravida cannot be underestimated and include hemodynamic instability, panhy-popituitarism, ventilatory support, temperature regulation, nutrition, infectious complications, hypercoagulability, and premature contrac-tions (Table 57-18).215 Given these challenges, it is surprising that two patients experienced a latency exceeding 100 days, with a mean latency of longer than 50 days from the diagnosis of brain death.218-220,222,223 Delivery timing is based on assessment of fetal well-being or maturity unless there is evidence of maternal deterioration. Preparation for immediate bedside cesarean section should be made. Discussion of the ethical and legal considerations that surround these cases is beyond the scope of this chapter.

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