Pulmonary Edema 349 pressure increase. There is a redistribution of intravascular volume from the systemic circulation to the pulmonary circula- tion resulting in alveolar fl ooding. With backward failure of the right heart, there is decreased emptying of the right ventricle and elevated central venous pressure (CVP) resulting in peripheral edema, neck vein distension, hepatojugular refl ux, hepatic congestion, and jaundice. Clinical manifestations of forward failure result from an inad- equate discharge of blood into the arterial system. If left ventricu- lar forward output is decreased, blood pressure falls. The kidneys sense decreased effective blood volume and increase renin, angio- tensin, and aldosterone production resulting in salt and water retention and increased systemic vascular resistance (SVR). With forward failure of the right heart, there is an interventricular septal shift to the left compromising the left ventricular cavity and decreasing stroke volume. This results in increased left ventricu- lar fi lling pressure, decreased blood fl ow through the lungs Table 25.1 Clinical setting of pulmonary edema in pregnancy. Tocolytic therapy Pre - eclampsia/eclampsia Cardiac disease Obesity, chronic hypertension, diastolic dysfunction Sepsis/acute lung injury Thyroid storm Renal failure Profound anemia Acute myocardial infarction Intravenous heroin Intracranial hemorrhage Amniotic fl uid embolism Multifactorial Alveolar epithelial surface Airway epithelium Apical domain Cotransporters H 2 O H 2 O AQP AQP 4 5 ATINa + Na,K-ATPase Na + Na + K + AT II Figure 25.1 Schematic representation of alveolar epithelial cells types I and II, depicting the apical Na + channels, the basolaterally located Na,K - ATPase, the aquaporins (AQPs) and some of the cotransporters. Sodium enters through the apical membrane via Na + channels and is extruded by the Na,K - ATPase with water following isosmotically. Also shown is an airway epithelial cell with associated basolateral aquaporins. (Reproduced by permission of the publisher, Springer - Verlag, from Dematte JE, Sznajder JI. Mechanisms of pulmonary edema clearance: from basic research to clinical implication. Intensive Care Med 2000; 26: 477 – 480.) Chapter 25 350 the heart has undergone dimorphic adaptation. Obesity results in chamber dilatation while hypertension results in concentric hypertrophy [7,8] . During pregnancy, the valvular heart disease which commonly results in pulmonary edema is rheumatic mitral stenosis. Pregnancy complicates mitral stenosis in two ways: (i) an increase in blood volume; and (ii) an increase in heart rate, shortening diastolic fi lling time. The pregnant patient with mitral stenosis has a shorter time interval to get an increased amount of blood across a stenotic valve than a non - pregnant patient with mitral stenosis. This results in increased left atrial pressure and, since there are no valves in the pulmonary circulation, increased pres- sure in the entire pulmonary circuit manifested by elevated pul- monary artery pressure and right ventricular afterload. Thus, the pregnant patient with mitral stenosis is closer to being in pulmo- nary edema when she is pregnant than when she is not pregnant. These women are apt to go into pulmonary edema postpartum after autotransfusion from the contracting uterus. This autotransfusion is associated with an approximately 10 mmHg increase in the PAWP. Heart rate control with β - blockers and judicious diuresis using Swan – Ganz catheter measurements for guidance has been discussed in an original paper by Clark et al. in 1985 [9] . Colloid osmotic pressure (COP) refers to the pressure resulting from the effect of albumin and globulins that hold water in the vascular space. Intravascular COP opposes hydrostatic pressure and interstitial COP which tend to pull water from the vascula- ture into the interstitium. The normal intravascular COP in the non - pregnant state is 25 mmHg. Normal PAWP is 6 – 12 mmHg. Therefore, the normal COP - wedge gradient is about 12 mmHg. Low albumin can occur with liver disease, renal losses, and mal- nutrition. In normal pregnancy at term, because of increased plasma volume and dilution of albumin, intravascular COP falls to 22 mmHg. With blood loss and crystalloid replacement postpartum, COP falls to 15 mmHg [10] . In patients with pre - eclampsia and hypoalbuminemia, COP may fall from 18 antepar- tum to 13 mmHg postpartum [11] . Pulmonary edema has been shown to occur when the COP - wedge gradient is less than 4 mmHg. This narrowing of the COP - wedge gradient refl ects pre- disposition to pulmonary edema. The situation is not so simple, however. When COP falls, the intravascular and interstitial COP decrease in parallel, so that the next fl ux across the membrane should be zero. In addition, patients with nephrotic syndrome and low COP are not more prone to pulmonary edema. Decreased COP is rarely responsible for pulmonary edema on its own, but it can exaggerate the edema that occurs when some other precipi- tating factor is present [12] . Permeability e dema In permeability pulmonary edema (the second mechanism out- lined in Table 25.2 ), the tight junctions between the endothelial cells open up allowing water, proteins, and cells into the intersti- tial and alveolar space. The spectrum of severity for permeability edema ranges from acute lung injury (ALI) to the acute respira- returning to the left atrium, and decreased left ventricular output and systemic blood pressure [2] . Despite the usefulness of these concepts, the ventricles are interdependent. If one ventricle fails, the other will fail. One of the most interesting developments in cardiology during the last 25 years has been the discovery of congestive heart failure in the absence of systolic dysfunction. Largely based on echocar- diographic fi ndings, it is now recognized that, depending on the population studied, about half of patients with heart failure have normal systolic function and presumed diastolic dysfunction [6] . This is particularly common in patients with chronic hyperten- sion and left ventricular hypertrophy. Diastolic relaxation is an active energy - requiring process. The echocardiographic diagnosis of diastolic dysfunction is complex, still evolving, and beyond the scope of this discussion. Some of the parameters measured echo- cardiographically are the E wave to A wave peak velocity ratio of transmitral fi lling, the rate of left ventricular posterior wall thin- ning, and tissue Doppler imaging to calculate myocardial veloc- ity. Many obstetric patients have been found to have diastolic dysfunction as a cause of pulmonary edema, particularly those with both exogenous obesity and chronic hypertension in which Table 25.2 Mechanisms of pulmonary edema. Hydrostatic Cardiogenic Systolic dysfunction (e.g. peripartum cardiomyopathy) Diastolic dysfunction (e.g. chronic hypertension) Valvular disease (e.g. mitral stenosis) Decreased COP Hypoalbuminemia secondary to pre - eclampsia, renal, liver, intestinal disease or malnutrition Increased negative interstitial pressure Rapid expansion of pneumothorax Acute airway obstruction Permeability (ARDS) Pneumonia (bacterial or viral) Severe sepsis (e.g. pyelonephritis, ruptured appendix) Aspiration Inhaled toxins (e.g. “ crack ” cocaine, smoke, chlorine gas) Burns Non - thoracic trauma Pancreatitis Lymphatic insuffi ciency Lymphangitic carcinomatosis Fibrosing lymphangitis (e.g. silicosis) Post lung transplant Unknown or incompletely understood Tocolytic induced Pre - eclampsia Narcotic overdose (e.g. intravenous heroin) Neurogenic (e.g. head trauma) High altitude Pulmonary Edema 351 Unknown or p oorly u nderstood m echanisms of p ulmonary e dema The fourth category (Table 25.2 ) includes diseases in which the mechanisms of pulmonary edema are incompletely understood. Tocolytic - induced pulmonary edema is associated with open fetal surgery, twin gestation, maternal anemia, low maternal weight, use of intravenous ritodrine or terbutaline for more than 24 hours, simultaneous use of two or three tocolytic agents, and corticosteroid therapy to accelerate fetal lung maturity. Several mechanisms have been proposed for the development of toco- lytic - induced pulmonary edema. These include antidiuretic hormone release, underlying heart disease, fl uid overload, occult chorioamnionitis, hypokalemia, myocardial ischemia, mineralo- corticoid effect of corticosteroids, catecholamine injury to the myocardium, and permeability edema. The most plausible expla- nation is that catecholamine tocolytics increase antidiuretic hormone release from the posterior pituitary causing oliguria. This has been confi rmed clinically by fi nding an hematocrit fall of 6 – 8 points after a 24 - hour infusion of β - agonist tocolytics. Many times occult abruption has been suspected because of this hematocrit fall. The mineralocorticoid effect of steroid therapy is now thought to be too small to be contributing to pulmonary edema. With the switch from catecholamine tocolytics to magne- sium sulfate as the fi rst agent of choice for tocolysis and the limi- tation of intravenous therapy to 24 hours, the incidence of tocolytic - induced pulmonary edema has decreased [14 – 16] . Preeclampsia should also be considered in the unknown or incompletely understood category. Preeclamptic patients fre- quently have multiple abnormalities including increased capillary permeability due to endothelial cell injury, hypoalbuminemia, afterload - induced left ventricular dysfunction, and increased hydrostatic pressure due to delayed postpartum mobilization of extravascular fl uid [17 – 20] . Narcotic overdose pulmonary edema has been thought to be due to contaminants. Neurogenic pulmonary edema, as seen in tory distress syndrome (ARDS). The recommended criteria for ALI are acute onset, bilateral infi ltrates on chest radiograph, PAWP of 18 mmHg or less or no clinical evidence of left atrial hypertension, and a ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen (Pa0 2 /F 1 0 2 ) of 300 mmHg or less. The criteria for ARDS are the same for timing, chest radio- graph, and PAWP, but ARDS requires a Pa0 2 /F 1 0 2 of 200 mmHg or less [13] . The mechanisms for this edema formation are numerous. Bacterial or viral pneumonia cause release of prostaglandins, cytokines, and complement components. Septic shock acts simi- larly by releasing a myriad of mediators including myocardial depressant factor. Aspiration causes a chemical acid injury to the lung as well as bacterial and obstructive components of injury. Inhaled toxins cause direct injury to the alveoli and vasculature (e.g.chlorine gas, smoke). Finally, burns, nonthoracic trauma, and pancreatitis act by systemic transport of a locally - initiated cytokine cascade. Permeability edema can be substantiated by obtaining edema fl uid (e.g. suctioned from an endotracheal tube) and measuring the edema fl uid to plasma protein ratio. In hydrostatic pulmo- nary edema, there should be a low protein content in the edema fl uid; whereas, in permeability pulmonary edema, there should be a high protein content. Thus, the edema fl uid protein to plasma protein ratio is ≥ 0.6 in permeability pulmonary edema. Another way to look at the difference between hydrostatic pulmonary edema and permeability edema is to consider the histologic picture of the lung. In hydrostatic pulmonary edema, one sees nice, lacy alveoli fi lled with salt water. In permeability edema (particularly in ARDS), one sees “ chopped chicken liver. ” Distorted alveoli are fi lled with infl ammatory cells, protein, blood, hyaline membranes due to fi brin deposition, and collagen. Hydrostatic pulmonary edema clears in a few hours with aggressive diuresis, whereas permeability edema takes days or weeks to clear, because polymorphonuclear leukocytes have to ingest and eliminate the protein and debris in the lung. One may also use a pulmonary artery catheter to differentiate hydrostatic from permeability edema. Hydrostatic pulmonary edema is accompanied by a PAWP > 18 mmHg. Permeability edema is thus associated with a normal PAWP (6 – 12 mmHg) or at least a PAWP < 18 mmHg. There are problems with trying to document an elevated wedge pressure. There may be “ fl ash ” pul- monary edema where the wedge pressure goes to 35 mmHg and then falls because of decompression of the pulmonary vasculature with alveolar fl ooding, delay in inserting the pulmonary artery catheter, or partial treatment with diuretics. Table 25.3 summa- rizes the differences between cardiogenic and non - cardiogenic pulmonary edema. Lymphatic i nsuffi ciency The third mechanism of pulmonary edema in Table 25.2 is lym- phatic insuffi ciency. This is rarely seen in pregnancy and will not be discussed further. Table 25.3 Cardiogenic versus non - cardiogenic pulmonary edema. Cardiogenic Non - cardiogenic Hydrostatic Permeability related Left ventricular systolic or diastolic dysfunction, interstitial fl uid overwhelms lymphatics, alveolar fl ooding, interference with gas exchange Injury to semipermeable alveolar - capillary membrane, leakage of proteinaceous fl uid into interstitium even at normal hydrostatic pressures, alveolar fl ooding, disrupted gas exchange Decreased compliance Decreased compliance Clears rapidly Clears slowly Recovery – nearly normal lung function or fi brosis, inability to wean, eventual death Chapter 25 352 size, peripheral distribution of edema, normal central vascula- ture, and air bronchograms. Arterial blood gases are measured less frequently now, because non - invasive pulse oximetry allows continuous oxygen satura- tion measurement. If the patient is critically ill or has comorbid conditions such as renal disease, chronic obstructive pulmonary disease, or sepsis, an arterial blood gas measurement may be needed to check for acidosis or carbon dioxide retention. Typical blood gases in pulmonary edema reveal hypoxemia with low or normal P a CO 2 . With fl orid pulmonary edema, carbon dioxide retention and respiratory acidosis may develop. A 12 - lead electrocardiogram should be performed to detect chamber hypertrophy, ischemia, infarction, conduction defects, or arrhythmias. A recent development in the diagnosis of congestive heart failure has been the measurement of plasma brain natriuretic peptide (BNP) in patients who present with acute dyspnea. BNP was initially identifi ed in the brain, but it is also synthesized by the cardiac ventricles in response to increased wall stress. Like atrial natriuretic peptide which is released by atrial myocardial cells, BNP has diuretic, natriuretic, and hypotensive effects. Both hormones inhibit the renin – angiotensin system, endothelin secretion, and systemic and renal sympathetic activity. The BNP level is most useful if the value is below 100 pg/mL, a level at which congestive heart failure is unlikely. Concentrations higher than 500 pg/mL are likely to be associated with heart failure. BNP levels cannot be used to distinguish between systolic and diastolic heart failure [28] . In pregnancy, median BNP values are less than 20 pg/mL and do not change signifi cantly between trimesters. In severe pre - eclampsia, however, median BNP levels are elevated to around 100 pg/mL, possibly refl ecting increased ventricular wall stress due to hypertension [29] . The role of BNP levels in the diagnosis of heart failure in pregnancy has not been adequately studied. An extremely useful diagnostic test in pulmonary edema is the echocardiogram. This allows non - invasive evaluation of cardiac structure and function. In a prospective study of pregnant women with pulmonary edema, Mabie et al. used echocardiography to differentiate between cardiogenic and non - cardiogenic forms of pulmonary edema, determine the type of cardiac dysfunction (systolic, diastolic, or valvular), and plan long - term therapy [25] . It is important to recognize that the echocardiogram does not have to be done acutely while the patient is in pulmonary edema. The underlying cardiac abnormalities do not change rapidly despite therapy. A pulmonary artery catheter (PAC) may be needed for diag- nosis and/or management of patients with pulmonary edema. The PAC can be used to diagnose hypovolemia; hydrostatic pul- monary edema (PAWP > 18 mmHg); severe mitral regurgitation (V wave); pulmonary hypertension; low, normal, or high cardiac output state; cardiac tamponade (equalization of pressures PAWP, CVP, pulmonary artery diastolic), and ventricular septal rupture (step - up in oxygenation). Many of these diagnostic uses have been replaced by echocardiography. The PAC is primarily head trauma or intracranial hemorrhage, has been thought to be due to a massive sympathetic discharge with an acute rise in PAWP. High altitude pulmonary edema is thought to be caused by hypoxic pulmonary vasoconstriction. The wedge pressure is normal, but pulmonary artery pressures are high. The pulmonary edema fl uid has a high protein content, however, suggesting cap- illary leak [12] . Several physiologic changes of pregnancy may predispose to the development of pulmonary edema. These include increased cardiac output, increased blood volume, decreased plasma colloid osmotic pressure, increased heart rate, and decreased functional residual capacity in the lung [21] . A chronological review of some of the advancements in our knowledge of pulmonary edema in pregnancy is found in Table 25.4 [7,17 – 20,22 – 27] . Lung m echanics and g as e xchange Pulmonary edema reduces the distensibility of the lung and edematous alveoli shrink in size. Perfusion of partially fl uid - fi lled or fl ooded alveoli results in ventilation – perfusion mismatching or an absolute shunt. Hypoxic pulmonary vasoconstriction reduces the ventilation - perfusion mismatch, but pulmonary vas- cular resistance rises thereby increasing the right ventricular work load. Airway resistance is increased, especially if the large airways are fi lled with fl uid. Rapid, shallow breathing occurs early in the course of pulmonary edema because of stimulation of J receptors in the alveolar walls. This breathing pattern minimizes the high elastic work of breathing. Arterial hypoxemia is an additional stimulus to breathing [12] . Diagnosis The diagnosis of pulmonary edema is summarized in Table 25.5 . In the history, one seeks the onset and duration of symptoms, precipitating factors, comorbidity (e.g. anemia, underlying heart, lung, kidney, or liver disease), and any medication the patient is taking. Symptoms of pulmonary edema include dyspnea, orthop- nea, paroxysmal nocturnal dyspnea, Cheyne – Stokes or periodic respiration, and decreased exercise tolerance. Signs include tachy- pnea, upright posture, air hunger, sweating, rales, use of accessory muscles of respiration, resting tachycardia, displaced point of maximal impulse, third heart sound, neck vein distension, hepa- tojugular refl ux, hepatomegaly, jaundice, and peripheral edema. The chest X - ray usually shows bilateral air space disease more prominent in the bases (Figure 25.2 ). Chest radiography cannot reliably distinguish hydrostatic from permeability edema, although claims to the contrary have been made. Features sug- gesting cardiogenic or hydrostatic pulmonary edema are increased heart size, “ bat - wing ” or perihilar distribution of edema, promi- nence of the upper lobe veins, pleural effusions, and septal lines or B - lines of Kerley. On the other hand, non - cardiogenic pulmo- nary edema is more likely if the radiograph shows normal heart Pulmonary Edema 353 Table 25.4 Selective literature review of pulmonary edema in obstetrics. Year Authors Cardiac monitoring Signifi cant fi ndings 1980 Berkowitz, Rafferty [22] Swan – Ganz Used in 20 obstetric patients over 3 years. Differentiated cardiogenic from non - cardiogenic pulmonary edema. Followed patients with multiple organ system failure. Early detection of loss of cardiac reserve and effectiveness of therapeutic manipulations. 1980 Strauss et al. [17] Swan – Ganz Three cases of pre - eclampsia with pulmonary edema. Elevated PAWP (22 – 33 mmHg). Simultaneous CVP normal. Isolated left ventricular dysfunction was primarily the result of increased afterload and responded to vasodilators (sodium nitroprusside, hydralazine). Cardiac output nearly doubled without a signifi cant change in heart rate or blood pressure. Limit nitroprusside therapy to 30 minutes if fetus still in utero . 1981 Keefer et al. [18] Swan – Ganz Four cases of non - cardiogenic pulmonary edema treated with supportive care with mechanical ventilation and positive end - expiratory pressure. Pulmonary artery catheter allowed documentation of normal wedge pressure. 1984 Hankins et al. [19] Swan – Ganz Eight primigravid women with eclampsia. Initial hemodynamic fi ndings: low CVP and PAWP, high cardiac output, and elevated SVR. Postpartum, women without spontaneous diuresis had elevated PAWP and cardiac output. Proposed concept of delayed mobilization of extravascular fl uid occurring 24 – 72 hours postpartum. 1985 Benedetti et al. [20] Swan – Ganz Ten pre - eclamptic patients with pulmonary edema. Eight of 10 developed pulmonary edema postpartum. Five patients had COP - wedge gradient ≤ 4. Three had fi ndings consistent with pulmonary capillary leak. Two had left ventricular failure. CVP did not correlate with PAWP. Eight of 10 received colloidal fl uid before onset of pulmonary edema, raising the possibility that colloid was contributory. 1986 Cotton et al. [23] Swan – Ganz Used intravenous nitroglycerin to drop mean arterial pressure by 20% in three pre - eclamptic women with pulmonary edema. Mean PAWP decreased from 27 ± 4 to 14 ± 6 mmHg, resulting in a COP - wedge gradient change from − 10 to 2 mmHg. There was no change in heart rate, CVP or cardiac output. 1987 Sibai et al. [24] None Retrospective chart review of 37 patients. Incidence of pulmonary edema 2.9% among 1290 severe pre - eclampsia/eclampsia patients. Incidence was higher in older, multiparas with chronic hypertension. Seventy per cent of cases occurred postpartum. Four maternal deaths. Perinatal mortality 530/1000. Sick patients with much comorbidity: 18 had disseminated intravascular coagulation, 17 sepsis, 12 abruptio placentae, 10 acute renal failure, 6 hypertensive crisis, 5 cardiopulmonary arrest, 2 liver rupture, and 2 ischemic cerebral damage. 1988 Mabie et al. [7] Echocardiography Used the concept of diastolic dysfunction to explain pulmonary edema in four obese, chronically hypertensive pregnant women. 1993 Mabie et al. [25] Echocardiography Prospective study of 45 obstetric patients with pulmonary edema. Three therapeutically and prognostically distinct groups were identifi ed: (i) systolic dysfunction (n = 19); (ii) diastolic dysfunction (n = 17); and (iii) normal heart (n = 9). Two patients with systolic dysfunction died and one underwent cardiac transplantation. Patients with systolic dysfunction required short - and long - term treatment with digoxin, diuretics, and angiotensin - converting enzyme inhibitors. Those with diastolic dysfunction received diuretics and long - term antihypertensive therapy. Women with normal hearts required acute therapy only. Because clinical and roentgenographic fi ndings do not accurately differentiate patients with respect to the presence and type of cardiac dysfunction, echocardiography was recommended to evaluate all pregnant women with pulmonary edema. 1998 DiFederico et al. [26] None Retrospective chart review of pulmonary edema in obstetric patients(1985 – 1995). Eighty - six cases out of 16 810 deliveries (prevalence about 1/200 deliveries). Associated clinical conditions were pre - eclampsia 28%, preterm labor 24%, fetal surgery 17%, and infection 14%. Forty - fi ve per cent of patients required intensive care unit admission; 15% required mechanical ventilation. Sixty - nine patients (80%) received tocolysis; 37 patients (41%) received multiple, simultaneous tocolytics. An interesting subgroup was found. Fifteen of 65 patients (23%) undergoing open fetal surgery developed pulmonary edema. Most received intravenous nitroglycerin as a tocolytic. The increased severity and delayed resolution of pulmonary edema in the open fetal surgery group suggested permeability edema. 2003 Sciscione et al. [27] None Ten - year retrospective chart review of acute pulmonary edema in pregnancy (1989 – 99). The main causes were tocolytic agents, underlying heart disease, fl uid overload, and pre - eclampsia. Fifty - one cases among 62 917 consecutive deliveries (prevalence 8/10 000 deliveries). Chapter 25 354 be given by nasal cannula at rates of up to 4 L/min. Flow rates above this do not increase the inhaled oxygen fraction and cause nasal irritation. Face - mask oxygen can be given with a non - rebreathing mask using fl ow rates up to 15 L/min. Non - invasive positive - pressure ventilation may be given with a nasal mask or the better tolerated oronasal mask. Either a portable pressure - limited or a standard mechanical ventilator may be used. This increases intra - alveolar pressure, reduces transudation of fl uid from alveolar capillaries, and impedes venous return to the thorax. It is most useful as a temporizing measure to maintain oxygenation until furosemide - induced diuresis clears the lungs. Intubation and mechanical ventilation may be required for patient exhaustion or refractory hypoxemia. Mechanical ventila- tion decreases the work of breathing, allows delivery of increased inhaled oxygen fractions, and permits the use of positive end - expiratory pressure to recruit atelectatic alveoli or to maintain partially expanded alveoli. The route of oxygen administration depends on the severity of the pulmonary edema and the response to initial therapy. The goal is to maintain the arterial partial pres- sure of oxygen > 60 mmHg and the oxygen saturation > 90%. Furosemide may be given in a dose of 40 mg intravenously. This causes venodilation, decreasing preload, and blockage of chloride and sodium reabsorption in the ascending limb of the loop of Henle. The aim should be to obtain roughly a 2000 mL diuresis over a few hours. This is often associated with radio- graphic clearing of the pulmonary edema. Morphine (2 – 5 mg intravenously) is also a venodilator and will decrease the patient ’ s anxiety. Frequently in obstetrics, these mainstays of therapy are all that are needed. Further management will depend on the cause of the pulmo- nary edema. If it is tocolytic - induced, consideration should be given to stopping tocolysis and allowing delivery to occur. A recent review of pulmonary edema associated with magnesium sulfate tocolysis advocated continuing the tocolytic once pulmonary edema has been treated [36] . The present author disagrees with this advice for several reasons: (i) pulmonary edema may be a life - threatening complication; (ii) frequently labor does not progress even after tocolysis is stopped; (iii) actual fetal weight may exceed 1800 g; (iv) occult chorioamnionitis or placental abruption may be present; (v) there may be a maternal contraindication to tocoly- sis such as pre - eclampsia, appendicitis, or hyperthyroidism; and (vi) there may be a fetal contraindication to tocolysis such as an anomaly or intrauterine growth restriction. If pulmonary edema occurs antepartum in a patient with pre - eclampsia, delivery will usually be indicated. When pulmonary edema is associated with severe hypertension, antihypertensive therapy with intravenous hydralazine, labetalol, or nicardipine will reduce afterload and improve cardiac performance. Oral short - acting nifedipine is also effi cacious for severe hypertension, but may produce overshoot hypotension. Sodium nitroprusside, a balanced arterial and venular vasodilator, can be used for min- ute - to - minute titration of blood pressure; however, it is rarely used in pregnancy because of the risk of fetal cyanide and thio- cyanate toxicity. Nitroglycerin is primarily a venular vasodilator useful for management to obtain CVP, PAWP, intermittent or continuous cardiac output, mixed venous oxygen saturation, and right ventricular ejection fraction – depending on the type of catheter used. The author has found the PAC most useful in treating pregnant patients with tight mitral stenosis (valve area < 1 cm 2 ), a “ white out ” on chest X - ray, and those patients who do not respond to aggressive diuresis with furosemide. The PAC provides information that one could not obtain by history, physical examination, and chest X - ray [30] . Nevertheless, it has become highly controversial with calls for a moratorium on its use [31] . Problems are lack of physician ability to interpret hemodynamic waveforms and non - randomized trials showing increased length of stay with increased cost and mortality in patients undergoing Swan – Ganz monitoring [32,33] . It has been suggested that use of the right heart catheter is a marker for a more aggressive and morbid style of care [30] . This controversy has stimulated recent prospective, randomized trials which have shown that use of the PAC is relatively safe, but it does not improve outcome [34,35] . Therefore, its role in critical care is diminishing. Treatment The treatment of acute pulmonary edema in pregnancy depends on whether the excessive accumulation of extravascular lung water is due to increased hydrostatic pressures (e.g. left ventricu- lar failure, mitral stenosis, volume overload); to increased capillary permeability (e.g. sepsis - induced ARDS, pneumonia, trauma); or to one of the poorly understood causes such as toco- lytic - induced pulmonary edema or pre - eclampsia. Although the algorithm for diagnosis is stepwise, providing care is a dynamic process requiring simultaneous diagnosis and treatment. In the absence of contraindications, initial management can proceed as outlined in Table 25.5 for suspected hydrostatic pulmonary edema [3] . Initial treatment includes sitting the patient upright and administering oxygen, furosemide, and morphine. Oxygen may Table 25.5 Diagnosis and treatment. Diagnosis History Physical Pulse oximetry ± blood gas Chest radiograph Electrocardiogram Brain natriuretic peptide Echocardiogram Initial management Sit patient upright Oxygen Furosemide Morphine Pulmonary Edema 355 (a) (b) (c) (d) Figure 25.2 Pulmonary edema induced by 48 hours of tocolysis with intravenous and then oral ritodrine. (a) Roentgenogram of the chest taken at the onset of pulmonary edema showing bilateral perihilar and basilar infi ltrates. (b) Postpartum fi lm taken 22 hours after (a) shows worsening infi ltrates despite fl uid restriction and furosemide - induced diuresis. (c) Portable AP fi lm taken 50 hours after the onset of pulmonary edema demonstrating some resolution of the infi ltrates. Notice air bronchograms and normal pulmonary vasculature. (d) Standard PA fi lm taken 30 days after the onset of pulmonary edema demonstrating a normal cardiac silhouette and clear lungs. (Adapted from: Mabie WC, Pernoll ML, Witty JB, and Biswas MK. Pulmonary edema induced by betamimetic drugs. S Med J. 1983;76:1354 – 60.) Chapter 25 356 includes: (i) attention to contraindications to tocolytic therapy (e.g. pre - eclampsia, infection); (ii) careful intake and output with total fl uid administration limited to 2500 mL/day; (iii) recogni- tion of predisposing factors (e.g. twins, anemia, low maternal weight); and (iv) use of magnesium sulfate as the tocolytic agent of fi rst choice. Other strategies to prevent pulmonary edema include: (i) inva- sive hemodynamic monitoring in patients with New York Heart Association class III or IV cardiac disease, particularly mitral stenosis with a valve area less than 1.0 cm 2 ; and (ii) close monitor- ing of the patient undergoing “ conservative ” management of severe pre - eclampsia. References 1 Dematte JE , Sznajder JI . Mechanisms of pulmonary edema clearance: from basic research to clinical implication . Intens Care Med 2000 ; 26 ( 4 ): 477 – 480 . 2 Ingram RH Jr , Braunwald E . Dyspnea and pulmonary edema . In: Kasper DL , Braunwald E , Fauci AS , et al., eds. Harrison ’ s Principles of Internal Medicine , 16th edn . New York : McGraw - Hill , 2005 : 201 – 205 . 3 Ware LB , Matthay MA . Acute pulmonary edema . N Engl J Med 2005 ; 353 : 2788 – 2796 . 4 Heider AL , Kuller JA , Strauss RA , Wells SR . Peripartum cardiomy- opathy: a review of the literature . Obstet Gynecol Surv 1999 ; 54 ( 1 ): 526 – 531 . 5 Pearson GD , Veille JC , Rahimtoola S , et al. Peripartum cardiomyopa- thy: National Heart, Lung, and Blood Institute and Offi ce of Rare Diseases (National Institute of Health) workshop recommendations and review . JAMA 2000 ; 283 ( 9 ): 1183 – 1188 . 6 Gandhi SK , Powers JC , Nomeir AM , et al. The pathogenesis of acute pulmonary edema associated with hypertension . N Engl J Med 2001 ; 344 ( 1 ): 17 – 22 . 7 Mabie WC , Ratts TE , Ramanathan KB , Sibai BM . Circulatory conges- tion in obese hypertensive women: a subset of pulmonary edema in pregnancy . Obstet Gynecol 1988 ; 72 ( 4 ): 553 – 558 . 8 Desai DK , Moodley J , Naidoo DP , Bhorat I . Cardiac abnormalities in pulmonary edema associated with hypertensive crises in pregnancy . Br J Obstet Gynaecol 1996 ; 103 ( 6 ): 523 – 528 . 9 Clark SL , Phelan JP , Greenspoon J , Aldahl D , Horenstein J . Labor and delivery in the presence of mitral stenosis: central hemodynamic observations . Am J Obstet Gynecol 1985 ; 152 ( 8 ): 984 – 988 . 10 Cotton DB , Gonik B , Spillman T , Dorman KF . Intrapartum to post- partum changes in colloid osmotic pressure . Am J Obstet Gynecol 1984 ; 149 ( 2 ): 174 – 177 . 11 Benedetti TJ , Carlson RW . Studies of colloid osmotic pressure in pregnancy - induced hypertension . Am J Obstet Gynecol 1979 ; 135 ( 3 ): 308 – 311 . 12 West JB . Pulmonary edema . In: Pulmonary Physiology and Pathophysiology , 2nd edn . Philadelphia, PA : Wolters Kluwer Lippincott, Williams and Wilkins , 2007 : 94 – 104 . 13 Bernard GR , Artigas A , Brigham KL , et al. and the Consensus Committee. The American - European Consensus Conference on ARDS: defi nitions, mechanisms, relevant outcomes, and clinical trial coordination . Am J Respir Crit Care Med 1994 ; 149 : 818 – 824 . that has arterial vasodilator effects when given in higher intrave- nous doses. Although it crosses the placenta, nitroglycerin is safe for the fetus. It is the drug of choice in hypertension associated with acute coronary syndromes such as myocardial infarction or unstable angina; however, symptomatic coronary artery disease is uncommon in pregnancy. The treatment of cardiogenic or non - cardiogenic pulmonary edema is complex and may be thought of in terms of how cardi- ologists or pulmonary/critical care physicians handle their spe- cialty patients. Table 25.6 summarizes the cardiologist ’ s options for the treatment of systolic heart failure [37] . The indications and details of this treatment are beyond the scope of this chapter. Angiotensin - converting enzyme inhibitors, angiotensin receptor blockers, amiodarone, and coumadin are contraindicated in pregnancy. Hydralazine and isosorbide dinitrate may be substi- tuted for angiotensin - converting enzyme inhibitors or angioten- sin receptor blockers in the treatment of systolic heart failure during pregnancy. Treatment for diastolic heart failure consists of diuretics, treating the underlying etiology by controlling hypertension, and rate control with β - blockers to allow time for diastolic fi lling. The pulmonary/critical care approach to permeability edema includes supportive care until the lung can heal and a lung - pro- tective strategy for mechanical ventilation (tidal volume 6 mL/kg) [38] . Management of severe sepsis and septic shock includes early goal - directed therapy, antibiotics and source control, activated protein C, replacement - dose hydrocortisone, and tight glucose control [39] . Prevention Tocolytic - induced pulmonary edema is the etiology most ame- nable to prevention by the obstetrician. A strategy for prevention Table 25.6 Treatment of systolic heart failure. Angiotensin - converting enzyme inhibitors Angiotensin receptor blockers Other vasodilators Diuretics Aldosterone blockers β - blockers Digoxin Amiodarone Calcium channel blockers Inotropic agents Nesiritide Acute hemodialysis and ultrafi ltration Anticoagulants Implantable cardioverter - defi brillators Biventricular pacemakers (cardiac resynchronization therapy) Ventricular assist devices Cardiac transplantation Pulmonary Edema 357 28 Mueller C , Scholer A , Laule - Kilian K , et al. Use of B - type natriuretic peptide in the evaluation and management of acute dyspnea . N Engl J Med 2004 ; 350 : 647 – 654 . 29 Resnik , JL , Hoag C , Resnik R , et al. Evaluation of B - type natriuretic peptide (BNP) levels in normal and preeclamptic women . Am J Obstet Gynecol 2005 ; 193 : 450 – 454 . 30 Connors AF , Speroff T , Dawson NV , et al. for the SUPPORT (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments) Investigators. The effectiveness of right heart catheter- ization in the initial care of critically ill patients . JAMA 1996 ; 276 ( 11 ): 889 – 897 . 31 Dahlen JE , Bone RC . Is it time to pull the pulmonary artery catheter? JAMA 1996 ; 276 ( 11 ): 916 – 918 . 32 Iberti TJ , Fischer EP , Leibowitz AB , Panacek EA , Silverstein JH , Albertson TE , and the Pulmonary Artery Catheter Study Group . A multicenter study of physicians ’ knowledge of the pulmonary artery catheter . JAMA 1990 ; 264 ( 22 ): 2928 – 2932 . 33 Dahlen JE . The pulmonary artery catheter – friend, foe, or accom- plice? JAMA 2001 ; 286 ( 3 ): 348 – 350 . 34 Richard C , Warszawski J , Anguel N , et al. Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respira- tory distress syndrome: a randomized trial . JAMA 2003 ; 290 : 2713 – 2720 . 35 National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network . Pulmonary - artery versus central venous catheter to guide treatment of acute lung injury . N Engl J Med 2006 ; 354 : 2213 – 2224 . 36 Samol JM , Lambers DS . Magnesium sulfate tocolysis and pulmonary edema: the drug or the vehicle? Am J Obstet Gynecol 2005 ; 192 : 1430 – 1432 . 37 Hunt SA , Abraham WT , Chin MH , et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult – summary article . J Am Coll Cardiol 2005 ; 46 : 1116 – 1143 . 38 Acute Respiratory Distress Syndrome Network . Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome . N Engl J Med 2000 ; 342 : 1301 – 1318 . 39 Dellinger RP , Carlet JM , Masur H , et al. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock . Crit Care Med 2004 ; 32 : 858 – 873 . 14 Pisani RJ , Rosenow EC 3rd . Pulmonary edema associated with toco- lytic therapy . Ann Intern Med 1989 ; 110 ( 9 ): 814 – 818 . 15 Lampert MB , Hibbard J , Weinert L , Briller J , Lindheimer M , Lang RM . Peripartum heart failure associated with prolonged tocolytic therapy . Am J Obstet Gynecol 1993 ; 168 ( 2 ): 493 – 495 . 16 Leduc D , Naeije K , Leeman M , Homans C , Kahn RJ . Severe pulmo- nary edema associated with tocolytic therapy: case report with hemo- dynamic study . Intens Care Med 1996 ; 22 ( 11 ): 1280 – 1281 . 17 Strauss RG , Keefer JR , Burke T , Civetta JM . Hemodynamic monitor- ing of cardiogenic pulmonary edema complicating toxemia of preg- nancy . Obstet Gynecol 1980 ; 55 ( 2 ): 170 – 174 . 18 Keefer JR , Strauss RG , Civetta JM , Burke T . Non - cardiogenic pulmo- nary edema and invasive cardiovascular monitoring . Obstet Gynecol 1981 ; 58 ( 1 ): 46 – 51 . 19 Hankins GDV , Wendel GD , Cunningham FG , Leveno KJ . Longitudinal evaluation of hemodynamic changes in eclampsia . Am J Obstet Gynecol 1984 ; 150 ( 5 pt1): 506 – 512 . 20 Benedetti TJ , Kates R , Williams V . Hemodynamic observations in severe preeclampsia complicated by pulmonary edema . Am J Obstet Gynecol 1985 ; 152 ( 3 ): 330 – 334 . 21 Zlatnik MG . Pulmonary edema: etiology and treatment . Semin Perinatol 1997 ; 21 ( 4 ): 298 – 306 . 22 Berkowitz RL , Rafferty TD . Invasive hemodynamic monitoring in critically ill pregnant patients: role of Swan – Ganz catheterization . Am J Obstet Gynecol 1980 ; 137 ( 1 ): 127 – 134 . 23 Cotton DB , Jones MM , Longmire S , Dorman KF , Tessem J , Joyce TH 3rd . Role of intravenous nitroglycerin in the treatment of severe pregnancy - induced hypertension complicated by pulmonary edema . Am J Obstet Gynecol 1986 ; 154 ( 1 ): 91 – 93 . 24 Sibai BM , Mabie BC , Harvey CJ , Gonzales AR . Pulmonary edema in severe preeclampsia - eclampsia: analysis of 37 consecutive cases . Am J Obstet Gynecol 1987 ; 156 ( 4 ): 1174 – 1179 . 25 Mabie WC , Hackman BB , Sibai BM . Pulmonary edema associated with pregnancy: echocardiographic insights and implications for treatment . Obstet Gynecol 1993 ; 81 ( 2 ): 227 – 234 . 26 DiFederico EM , Burlingame JM , Kilpatrick SJ , Harrison M , Matthay MA . Pulmonary edema in obstetric patients is rapidly resolved except in the presence of infection or of nitroglycerin tocolysis after open fetal surgery . Am J Obstet Gynecol 1998 ; 179 : 925 – 933 . 27 Sciscione AC , Ivester T , Largoza M , Manley J , Schlossman P , Colmorgen GHC . Acute pulmonary edema in pregnancy . Obstet Gynecol 2003 ; 101 : 511 – 515 . 358 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 26 The Acute Abdomen During Pregnancy Howard T. Sharp Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, UT, USA Introduction Effective communication between physicians and medical ser- vices is critically important in the treatment of the pregnant patient with an acute abdomen. Caring for two patients, both with unique vulnerabilities, is optimally performed with the coordination of appropriate obstet- ric, surgical, radiological, and in later gestational ages, neonatal services. Proper communication with radiologists can help to minimize exposure to ionizing radiation, while maternal and fetal recommendations to the surgical team can help maximize intra- operative safety if surgery is necessary. Timely communication can also help avoid treatment delay, which can ultimately be the greatest risk for maternal and fetal morbidity and mortality. As a general rule, the acute abdomen during pregnancy should be treated as it would in the non - pregnant state. It is important for physicians caring for obstetric patients with acute surgical issues to be aware of the unique cir- cumstances associated with each trimester of pregnancy, in par- ticular organogenesis in the fi rst trimester and preterm labor issues in the later part of the second and the third trimesters. Lastly, with the popularization of laparoscopy, surgical approaches are evolving, the limits of which are currently being investigated for safety and effi cacy. This chapter will review contemporary diagnostic and surgical modalities available for patients with the acute abdomen in pregnancy. The morbidity and mortality associated with these surgical conditions will also be reviewed. The vast majority of data regarding the acute abdomen in pregnancy are based upon case reports and case series, and are therefore con- sidered level III data as outlined by the US Preventive Services Task Force. Laparoscopy d uring p regnancy The refi nement of operative laparoscopy has allowed for a signifi - cant shift in the way many surgeries are performed during preg- nancy. There remain questions about the potential for decreased maternal uterine blood fl ow due to increased intra - abdominal pressures from insuffl ation, and possible fetal carbon dioxide absorption. Some data from animal models suggest that the risk of fetal acidosis may be higher than expected [1] . Other possible drawbacks of laparoscopic surgery during pregnancy include injury to the pregnant uterus, and the technical diffi culty of lapa- roscopic surgery due to the growing mass of the gravid uterus. The most commonly performed laparoscopic surgeries during pregnancy are cholecystectomy and appendectomy. Laparoscopy is routinely performed during the second trimester at most hos- pitals, and is becoming more common during the fi rst and third trimesters [2] . In a review of appendectomy and cholecystectomy during pregnancy at a tertiary care hospital, one group reported an increase in the use of laparoscopy from 54% in 1998 to 97% in 2002 with no signifi cant differences in preterm delivery rates, birth weights, or 5 - minute Apgar scores compared to a control group of pregnant women who underwent laparotomy [3] . Most evidence for the use of laparoscopy during pregnancy comes from case series demonstrating feasibility and reporting favorable outcomes from surgeons with signifi cant interest and skill in laparoscopy [4,5] . Therefore, their results may not accu- rately refl ect complication rates at other centers. Some groups are less enthusiastic about the use of laparoscopy during pregnancy and caution that the broad application and acceptance of lapa- roscopy in pregnancy should follow favorable outcomes from high - quality evidence [6] . Due to the limited amount of high - quality studies, data on laparoscopic surgery during pregnancy are insuffi cient to draw fi rm conclusions on its safety and com- plication rate [7] . However, the trend of the cumulative experi- ence over the past 10 years suggests that laparoscopic surgery is becoming more widely used and may be performed safely during pregnancy in most cases. Though preliminary evidence on . cardi- ologists or pulmonary /critical care physicians handle their spe- cialty patients. Table 25.6 summarizes the cardiologist ’ s options for the treatment of systolic heart failure [37] . The indications. blockers to allow time for diastolic fi lling. The pulmonary /critical care approach to permeability edema includes supportive care until the lung can heal and a lung - pro- tective strategy. GHC . Acute pulmonary edema in pregnancy . Obstet Gynecol 2003 ; 101 : 511 – 515 . 358 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy.