Critical Care Obstetrics part 36 doc

Acute Lung Injury and Acute Respiratory Distress Syndrome (ARDS) During Pregnancy 339 II cells in ALI/ARDS can disrupt removal of alveolar fl uid and impair normal surfactant production and turnover, contributing to the alveolar collapse, gas exchange abnormalities, and loss of lung compliance characteristic of this syndrome [9,13 – 15] . A number of human and animal studies have implicated the neutrophil as one of the key cellular mediators of this early phase of acute lung injury. Histological examinations and analysis of bronchoalveolar lavage fl uid from lungs of patients with ARDS have demonstrated increased numbers of neutrophils. Neutrophils are thought to contribute to lung injury through release of pro- teases, reactive oxygen species, leukotrienes, platelet - activating tachypnea, and tachycardia, and physical examination signs of pulmonary edema (bilateral crackles and/or wheezes on chest auscultation) without signs of left - sided heart failure (e.g. absent S3, elevated jugular venous pressure, and peripheral edema). Chest radiography will show diffuse bilateral alveolar and/or interstitial infi ltrates, typically without cardiomegaly. Although plain chest radiographs in ALI/ARDS suggest a diffuse process, studies utilizing computed tomography of the chest (CT scans) have shown that in fact lung involvement in ALI and ARDS is inhomogeneous, with alveolar infi ltrates, consolidation, and atel- ectasis that are worst in the dependent lung zones while other areas of the lung may appear to be spared [8,9] . Figure 24.1 shows examples of typical fi ndings on plain chest radiography and CT scan of the chest in ARDS. It should be noted that studies of bronchoalveolar lavage fl uid from patients with ARDS have shown that even areas of the lung that appear relatively clear on radiographic examinations may have signs of signifi cant infl am- mation [10] . A detailed review of the pathogenesis of ALI and ARDS has been published recently by Ware and Matthay [9] . ALI and ARDS are characterized by three distinct stages, although not all patients will progress through all stages. The initial stage is an acute exuda- tive phase , which again presents clinically as acute onset of respi- ratory distress and hypoxemia refractory to supplemental oxygen, most often resulting in respiratory failure requiring mechanical ventilation. The term “ non - cardiogenic pulmonary edema ” has also been applied to this clinical picture, and the radiographic fi ndings may be indistinguishable from those of congestive heart failure. This acute phase is characterized by increased permeabil- ity of the alveolar – capillary barrier leading to leakage of protein - rich edema fl uid into the alveolar spaces, accompanied by a pattern of diffuse alveolar damage with increased numbers of neutrophils, macrophages, and erythrocytes, and varying degrees of hyaline membrane formation [9,11,12] . Injury to the alveolar epithelium is a key step in the pathogenesis of ALI and ARDS, and a greater degree of alveolar epithelial injury has been corre- lated with worse outcomes. Injury to type I alveolar epithelial cells (which make up the majority of alveolar surface area) contributes to alveolar fl ooding following endothelial injury and increased vascular permeability. Alveolar type II epithelial cells normally function to produce surfactant, transport ions, and differentiate into type I cells as part of recovery from any injury. Injury to type Table 24.1 Diagnostic criteria for acute lung injury ( ALI ) and adult respiratory distress syndrome ( ARDS ). Acute onset of respiratory distress Bilateral pulmonary infi ltrates on chest X - ray PAOP ≤ 18 mmHg or absence of clinical evidence of left atrial hypertension P a O 2 /F i O 2 ratio of ≤ 200 for ARDS or ≤ 300 for ALI, regardless of PEEP PAOP, pulmonary artery occlusion (wedge) pressure; PEEP, positive end - expiratory pressure. (a) (b) Figure 24.1 (a) Chest radiograph of a woman at 26 weeks gestation with pre - eclampsia and acute non - cardiogenic pulmonary edema (ALI), showing the typical fi ndings of bilateral alveolar and interstitial infi ltrates in a perihilar distribution as well as bilateral pleural effusions. (b) Chest CT scan image from the same patient demonstrating the atelectasis/consolidation and small pleural effusions in a predominantly dependent lung zone distribution bilaterally, with areas of relatively normal - appearing lung above. Note that many of the same radiographic fi ndings may be seen with primarily cardiogenic pulmonary edema (see text). Chapter 24 340 aspiration, drowning, or inhalation exposures of smoke or irri- tant chemicals, all of which may cause direct injury to the lung. In contrast, the extrapulmonary causes trigger a systemic infl am- matory cascade that in turn mediates the lung injury; some common extrapulmonary causes include sepsis, acute pancreati- tis, massive trauma, burns, and shock of any cause. Some clinical and radiographical differences have been noted between ARDS due to direct versus indirect lung injury, including differences in responsiveness to PEEP and the presence of more lung consolida- tion on CT scans of the chest in ARDS due to direct lung injury versus a more diffuse pattern of ground glass opacifi cation and pulmonary edema in ARDS due to indirect lung injury. The most common cause of ARDS is sepsis (from pulmonary or extrapul- monary sources), accounting for up to 50% of all cases [9,21] . The risk of developing ARDS has been shown to increase with the presence of multiple risk factors, as well as with concomitant chronic alcohol abuse and chronic lung disease [22,23] . The same conditions mentioned above that predispose to the development of ALI and ARDS in non - pregnant patients can also lead to these complications in the obstetric population, but there are also several conditions unique to pregnancy that have been associated with the development of ALI/ARDS. Among the more frequently reported causes of respiratory distress during preg- nancy are sepsis - induced ARDS, pre - eclampsia and eclampsia, pulmonary edema associated with tocolytic therapy, gastric aspi- ration, and amniotic fl uid embolism (Table 24.2 ). Severe sepsis , particularly septic shock, is the most common cause of ARDS described in obstetric patients [24] . Acute pyelo- nephritis seems to be an especially important cause of sepsis - related ARDS in pregnancy, perhaps because this is one of the more common infections that may complicate pregnancy [25,26] . Acute respiratory failure has been reported as a complication in up to 7% of pregnant women with pyelonephritis [24 – 26] . factor, and other proinfl ammatory molecules in the pulmonary capillary bed and alveolar spaces. On the other hand, ALI and ARDS can develop in severely neutropenic patients, and neutro- phil - independent animal models of ALI also have been devel- oped; thus, whether neutrophils are truly a cause of lung injury in ALI/ARDS or in fact part of the host response is not entirely clear [9] . Other mechanisms implicated in the development of ALI/ ARDS include a number of proinfl ammatory cytokines (such as interleukin - 8 and tumor necrosis factor α ) that may be produced locally in the lung and also may be regulated by extrapulmonary factors [9] . Disruption of the balance between proinfl ammatory and anti - infl ammatory mediators is likely also important in the development of acute lung injury. Some of the important endog- enous inhibitors of these proinfl ammatory molecules include IL - 1 receptor antagonist, autoantibodies against IL - 8, and the anti - infl ammatory cytokines IL - 10 and IL - 11 [9] . Other pathways which may be important in the propagation of acute lung injury include secondary abnormalities of the coagulation system which can result in formation of platelet – fi brin thrombi in small vessels and impaired fi brinolysis, leading to further disruption of the pulmonary capillary bed and contributing to the gas exchange abnormalities seen clinically [9,16] . In many patients, the acute phase of ALI/ARDS resolves com- pletely, but in a subset of cases it progresses into a so - called fi broproliferative phase (also described as fi brosing alveolitis by some authors), typically beginning 5 – 7 days after the initial insult. This phase may be characterized by persistent hypoxemia, further increase in physiologic dead space, and worsening lung compliance, often associated with pulmonary hypertension secondary to obliteration of the pulmonary capillary bed. Histopathology in this stage may reveal interstitial fi brosis with acute and chronic infl ammation [9,11,12,17] . Patients who survive this phase typically go on to a recovery phase , which is perhaps the least well - characterized of the phases of ALI/ARDS [9] . In this phase, there is gradual recovery of lung function, with improvements in lung compliance and hypoxemia. Radiographic abnormalities often resolve completely in survivors, although data on the degree of histologic resolution is limited. Some studies of pulmonary function tests in survivors of ARDS have found return to near - normal pulmonary function after 6 – 12 months [18] , but other investigators have shown that the major- ity has residual abnormalities of diffusing capacity, while 20% have restrictive ventilatory defects and 20% signs of airfl ow obstruction [19,20] . Etiology A number of conditions can result in the injury to the alveolar – capillary interface that is characteristic of ALI and ARDS. These are frequently divided into direct, or pulmonary, and indirect, or extrapulmonary, causes of lung injury. Examples of pulmonary causes of ALI/ARDS include pneumonia, lung contusion, gastric Table 24.2 Causes of acute lung injury and adult respiratory distress syndrome in pregnancy. Independent of pregnancy Specifi c to pregnancy Sepsis Pre - eclampsia and eclampsia Pneumonia Tocolytic - induced pulmonary edema Aspiration of gastric contents Aspiration pneumonitis (Mendelson ’ s syndrome) Lung contusion Amniotic fl uid embolism Acute pancreatitis Placental abruption Inhalational injury Chorioamnionitis Fat embolism Endometritis Severe trauma Retained placental products Transfusion - related acute lung injury (TRALI) Other infections more frequent or more severe in pregnancy (e.g. pyelonephritis, varicella pneumonia, malaria) Drug overdoses Burns Acute Lung Injury and Acute Respiratory Distress Syndrome (ARDS) During Pregnancy 341 changes), myocardial dysfunction due to prolonged exposure to catecholamines, increased capillary permeability due to occult infection, and aggressive volume resuscitation in response to maternal tachycardia or hypotension. Possible risk factors for the development of tocolytic - induced acute pulmonary edema include multiple gestation, maternal infection, and corticosteroid therapy [30 – 32] . In part due to this complication of β 2 - adrenoceptor agonist use, magnesium sulfate has increasingly been used in place of these agents for tocolysis. Management of tocolytic - induced pulmonary edema includes immediately stop- ping the drug, followed by supportive care and diuresis. Most cases resolve rapidly, usually within 12 hours; however, in cases of delayed resolution consideration must be given to possible alternate causes of acute pulmonary edema. Aspiration of gastric contents is another important cause of ARDS during pregnancy. While this complication is not unique to pregnancy, pregnant patients are at increased risk of pulmo- nary aspiration of gastric contents because of some of the physi- ologic and anatomic changes occurring during pregnancy and immediately postpartum. Reduced gastroesophageal sphincter tone, increased intragastric pressure due to the enlarged uterus, reduced gastric motility, and reduced gastric emptying during labor all predispose to aspiration. When it occurs during obstetric anesthesia, aspiration of gastric acid resulting in acute lung injury has been termed Mendelson ’ s syndrome, after the classic descrip- tion of 66 cases published in 1946 [33] . Mendelson reported an incidence of 1 case per 668 deliveries, with only two fatalities attributed to pulmonary aspiration. A more recent study of peri- operative aspiration pneumonitis in pregnant patients reported an incidence of 0.11% for cesarean deliveries and 0.01% for vaginal deliveries [34] . The diagnosis of acid aspiration - induced acute lung injury may be straightforward in cases of witnessed aspiration, but it is important to remember that aspiration may also occur unwitnessed. Occasionally, the only clue for aspiration may be the visualization of gastric contents in the pharynx during laryngoscopy at the time of endotracheal intubation. The degree of lung injury due to aspiration is positively correlated with higher volume and lower pH of aspirated material, and with more particulate matter aspirated. Amniotic fl uid embolism (AFE) is a pregnancy - specifi c cause of ALI/ARDS which carries a high mortality rate. This condition is discussed in detail in another chapter, and thus will be only men- tioned briefl y here. The mechanisms underlying AFE are still not fully understood, but it is thought to occur when elements from amniotic fl uid enter the maternal circulation, most often at the time of labor or delivery. This can lead to mechanical disruption of pulmonary blood fl ow as a result of the embolic events and can also trigger release of proinfl ammatory cytokines that lead to disruption of the alveolar – capillary interface and produce a sys- temic infl ammatory response. The classic clinical presentation of AFE includes acute hypoxemic respiratory distress, hemody- namic collapse (often resulting in cardiac arrest), and dissemi- nated intravascular coagulation, occurring most often during labor or delivery. Reported mortality rates with AFE are generally Pregnancy - associated dilatation of the ureters and increased collecting system volume have been suggested as reasons for the increased frequency of acute pyelonephritis resulting from untreated bacteruria during pregnancy [24] . Besides pyelone- phritis, other infections linked to development of ALI and ARDS during pregnancy include viral and bacterial pneumonias, liste- riosis, fungal infections with blastomycosis and coccidioidmyco- sis, and malaria [21] . Chorioamnionitis is another important pregnancy - specifi c infectious complication to consider in the dif- ferential diagnosis of the obstetric patient with ALI/ARDS and clinical suspicion of sepsis without a clear source. Clinical indica- tions of chorioamnionitis include fever, fetal tachycardia, uterine tenderness, and foul - smelling amniotic fl uid, but the presenta- tion may be more subtle, and diagnostic amniocentesis should be considered in pregnant patients with ALI/ARDS without a clear cause [21,24] . Preeclampsia , characterized by hypertension, proteinuria, and edema, occurs in up to 8% of pregnancies [24] . Pulmonary edema has been reported to occur in about 3% of patients with severe pre - eclampsia, with most cases (70%) occurring in the immediate postpartum period [27] . Risk factors include older age, multiple prior pregnancies, pre - existing chronic hyperten- sion, and infusion of excessive volumes of crystalloid or colloid [21,27] . A combination of reduced plasma oncotic pressure, altered permeability of pulmonary capillary membranes, and elevated pulmonary vascular hydrostatic pressure have been implicated as factors contributing to the development of pulmo- nary edema complicating pre - eclampsia/eclampsia [28,29] . Details on the management of pre - eclampsia and eclampsia are discussed in a separate chapter. However, when pulmonary edema complicates these conditions, management is similar to that for pulmonary edema due to other causes, and includes supplemental oxygen, mechanical ventilation when needed, and judicious use of diuretics. Invasive hemodynamic monitoring using a pulmonary artery catheter may be helpful in distinguish- ing fl uid overload and cardiogenic pulmonary edema from ALI/ARDS, but does not seem to impact the outcome of these patients. Therefore, the decision to place these catheters must be individualized. Tocolytic - induced pulmonary edema is another important preg- nancy - specifi c cause of non - cardiogenic pulmonary edema. The β 2 - adrenoceptor agonists terbutaline and ritodrine were until recently used frequently for tocolysis, and their use has been associated with various adverse effects including hyperglycemia, hypokalemia, sodium and water retention, tachycardia, and arrhythmias. In addition, acute pulmonary edema can complicate up to approximately 10% of cases where a β 2 - adrenoceptor agonist is used for inhibition of premature labor. This complica- tion can occur during the infusion of these agents or up to 12 hours after their discontinuation [21,24] . The mechanism of tocolysis - related pulmonary edema is not fully understood, but several contributing factors have been suggested, including a combination of medication - induced increases in heart rate and cardiac output (on top of pregnancy - related cardiovascular Chapter 24 342 randomized study of a specifi c strategy of mechanical ventilation to demonstrate convincingly an improvement in mortality in ARDS, and this method of ventilation has now become the stan- dard against which all new ventilatory modes for ALI/ARDS must be compared. Unfortunately, there are no randomized trials in obstetric patients with ALI/ARDS to guide our approach to mechanical ventilation (or other aspects of management) in this population; indeed, pregnancy has been an exclusion criterion in almost all the clinical trials of therapies for ALI/ARDS. Since maintaining the best environment for the fetus generally requires optimizing intrauterine conditions by supporting the hemodynamic and other organ function of the mother until delivery is feasible, the overall approach to management of ARDS in pregnancy closely parallels the management in non - pregnant patients [24] . There are, however, some important aspects of maternal physiology that may dictate modifi cations of the targets of mechanical ventilation in this group. During pregnancy, driven in part by progesterone production by the placenta, maternal minute ventilation increases by 50% compared with the non - pregnant state due to increased tidal volume and to a lesser extent increased respiratory rate. The result is mild chronic (compensated) respiratory alkalosis, with P a CO 2 dropping from 35 – 45 mmHg at baseline to the 27 – 34 mmHg range during pregnancy. The renal compensatory response is to increase bicarbonate excretion to maintain normal pH, resulting in normal serum bicarbonate levels in the 18 – 21 mEq/L range during pregnancy. Lung volumes are also affected by pregnancy, with total lung capacity, functional residual capac- ity, expiratory reserve volume, and residual volume all decreasing by 4% to 20% from baseline, or non - pregnant values [43,44] . The general approach to mechanical ventilation in the obstetric patient with ARDS is the same as in the general population, aiming to optimize blood gas parameters while preventing ventilator - induced lung injury. However, although volume - controlled mechanical ventilation using the low - tidal volume (target 6 mL/kg ideal body weight) approach should be the goal given the proven mortality benefi t in non - pregnant populations, the degree of respiratory acidosis that may be tolerated during pregnancy may be lower as compared with the general popula- tion. In fact, the effect of maternal hypercapnia on uteroplacental blood fl ow is not well understood. Animal studies suggest that with maternal P a CO 2 > 60 mmHg, uterine vascular resistance increases and uterine blood fl ow decreases. However, these animal models generally examined the impact of acute increases in maternal P a CO 2 , whereas with the controlled hypoventilation strategy in ALI/ARDS the effect on P a CO 2 is usually more gradual. In ventilating obstetric patients with ALI/ARDS, maintaining maternal P a CO 2 < 45 – 50 mmHg has been suggested as a general rule [24] . Excessive maternal hyperventilation and hypocapnia also should be avoided when managing mechanical ventilation in pregnancy, as these have been associated with uteroplacental vasoconstriction, decreased uteroplacental blood fl ow, and fetal hypoxia and acidosis [45 – 47] . Thus, respiratory alkalosis beyond what is normal in pregnancy also should be avoided. very high (up to 80%), although more recent reports have dis- puted this [24] . Management of ALI and ARDS Mechanical v entilation The management of patients with acute lung injury and ARDS is largely supportive, in combination with specifi c therapies directed toward the underlying cause whenever possible. Especially impor- tant is identifying infections when present, and treating them expeditiously with appropriate antimicrobials and, if necessary, surgical intervention (e.g. abscess drainage). The mainstay in supportive care for patients with ALI/ARDS is positive - pressure ventilation. Soon after the initial descriptions of ARDS, investiga- tors made the observation that application of positive end - expi- ratory pressure (PEEP) could produce dramatic improvements in oxygenation [35] . More recently, the application of ventilatory support in ALI and ARDS has evolved further with increased understanding of the potential adverse effects of alveolar overdis- tention due to the use of excessively high tidal volumes. Ample evidence from animal models has shown that mechanical ventila- tion using large tidal volumes and high airway pressures can produce lung injury characterized by increased capillary perme- ability and non - cardiogenic pulmonary edema, even in previ- ously normal lungs [36,37] . This type of lung injury has been termed ventilator - induced lung injury (VILI). In addition to alveo- lar overdistention, evidence suggests that repetitive opening and closing of surfactant - depleted atelectatic alveoli during mechani- cal ventilation can itself contribute to VILI, and furthermore can initiate the release of a cascade of proinfl ammatory cytokines that contributes to a systemic infl ammatory response and resulting multiorgan failure [38 – 40] . A “ lung protective ” ventilation strat- egy which aims to avoid both overdistention of alveoli and the repetitive opening and closing of atelectatic lung units has been associated with reductions in this pulmonary and systemic cyto- kine response [41] . A number of early trials in small numbers of patients using either low tidal volume ventilation or pressure control modes with low target airway pressures in ARDS produced confl icting results as to effect on clinical outcomes. However, the benefi t of a low tidal volume approach was clearly demonstrated in the landmark NIH - sponsored ARDS Network randomized trial using volume - controlled mechanical ventilation with 12 mL/kg tidal volumes as compared with 6 mL/kg tidal volumes in 861 patients with ALI and ARDS. This study demonstrated a 22% relative risk reduction in mortality rate in the low tidal volume group (absolute mortality rates 39.8% versus 31.0%, p = 0.007) [42] . In this study a detailed algorithm was used to titrate F i O 2 and PEEP, and plateau pressures were maintained below 30 cmH 2 O, with use of sodium bicarbonate infusions if needed to manage severe respiratory acidosis resulting from the controlled hypoventilation caused by low tidal volume ventilation. The ARDS Network trial of low tidal volume ventilation was the fi rst Acute Lung Injury and Acute Respiratory Distress Syndrome (ARDS) During Pregnancy 343 ARDS; in the FACTT protocol, the conservative fl uid strategy targeted a CVP < 4 mmHg or a PAOP < 8 mmHg, as long as the patient was not in shock and maintained adequate renal perfu- sion and effective circulation (defi ned for the protocol as mean arterial pressure > 60 mmHg without vasopressors, urine output ≥ 0.5 mL/kg/h, and cardiac index ≥ 2.5 L/min/m 2 or capillary refi ll time < 2 s and the absence of cold, mottled skin). While this study excluded pregnant patients with ALI/ARDS, it suggests that avoidance of volume overload, together with judicious diuresis and fl uid restriction, should be the approach to fl uid manage- ment in this population as well. At the same time, avoidance of maternal hypotension and careful attention to end - organ perfu- sion parameters as suggested by the FACTT protocol is critical to avoid compromising uteroplacental blood fl ow. Prone p ositioning Studies have shown improved oxygenation in as many as 70 – 80% of patients with ALI when ventilated in the prone position [54] . Several factors may be involved in producing the improvement in gas exchange, which interestingly may be sustained for several hours even after return to the supine position. Reduced ventro- dorsal pleural pressure gradient and removal of the effects of compression by heart and mediastinum on dorsal lung units leading to increased recruitment of these previously atelectatic areas of lung, increased functional residual capacity due to the unsupported abdomen in the prone position, and better mobili- zation of secretions are among the proposed mechanisms for the improvement in oxygenation described with prone positioning [55,56] . However, no randomized trials have demonstrated an impact on mortality or other clinically important outcomes with this approach. Special beds and other devices have been devel- oped to aid in prone positioning of patients, but extreme caution is warranted in order to avoid inadvertent loss of the artifi cial airway or other support catheters or monitoring equipment, and to prevent the development of pressure ulcers [21] . For obvious reasons, prone positioning is not likely to be a very practical option in the obstetric patient with ARDS, at least not in later stages of pregnancy. In cases where the mother is close to term, maintaining the patient in the left lateral decubitus position will be more important in order to limit the hemodynamic conse- quences of vena caval compression by the gravid uterus. Inhaled n itric o xide Inhaled nitric oxide (NO) has been used in several studies in patients with ARDS and shown to produce improvements in oxygenation. NO is a potent vasodilator, and when administered via the inhaled route produces fairly selective pulmonary vasodilation with minimal effects on systemic blood pressure. Improvement in oxygenation in ALI/ARDS following inhaled NO administration results from improvements in ventilation – perfu- sion matching through greater vasodilation in the well - ventilated areas of lung [57] . Unfortunately, randomized multicenter trials in adults with ALI and ARDS have failed to show any improve- ment in mortality or other clinically important outcomes with For the most part, providing positive - pressure ventilatory support in pregnant patients with ALI/ARDS will require estab- lishing an artifi cial airway fi rst (i.e. endotracheal intubation). Non - invasive positive - pressure ventilation (NIPPV), where ven- tilatory support is provided by means of a tight - fi tting nasal or full - face mask, has only a limited role in the management of care- fully selected hemodynamically stable patients with ALI/ARDS [48,49] . Studies in other forms of respiratory failure have shown reduced complications with NIPPV as compared with invasive positive - pressure ventilation (principally reduced nosocomial pneumonias, and also reduced mortality rates in patients with hypercarbic respiratory failure due to COPD). However, NIPPV should not be used in hemodynamically unstable patients or in those with impaired respiratory drive or in patients at increased risk of aspiration, and there are no studies evaluating NIPPV in the management of hypoxemic respiratory failure during preg- nancy. In the obstetric population, a trial of NIPPV may be con- sidered in carefully selected patients with a rapidly reversible cause for the pulmonary edema, but close monitoring is always war- ranted due to the increased risk of gastric aspiration during preg- nancy. In general, early endotracheal intubation by a clinician experienced in the management of the obstetric airway will be preferable in most cases, especially given the increased risk of encountering a diffi cult airway in this population. Fluid m anagement Optimal fl uid management in patients with ALI/ARDS has been another area of controversy over the years, with advocates of fl uid restriction pointing to improvements in pulmonary edema and oxygenation with this approach and opponents emphasizing the potential detrimental effects of fl uid restriction on cardiac output, renal and other organ perfusion [50,51] . The role of invasive hemodynamic monitoring using pulmonary arterial catheters in this population also has been debated extensively. In an attempt to answer these questions, the NIH ARDS Network undertook the Fluid and Catheter Treatment Trial (FACTT), a randomized multicenter trial involving 1000 patients with ALI and ARDS, which compared a conservative versus liberal fl uid management strategy and hemodynamic monitoring with a pulmonary artery catheter (PAC; using primarily the pulmonary artery occlusion pressure, or PAOP, and cardiac index, or CI) versus monitoring with a central venous catheter (CVC; measuring central venous pressure, or CVP) [52,53] . This trial demonstrated that PAC - guided therapy was not associated with any improvements in survival or organ function as compared with CVC - guided therapy, but rather with more catheter - related complications than seen with CVC - guided therapy [53] . In addition, the com- parison of fl uid management strategies revealed no signifi cant difference in 60 - day mortality (the primary outcome), but the conservative fl uid strategy was associated with improvement in oxygenation and reduction in ventilator - free days as compared with the liberal fl uid strategy without any adverse effect on non - pulmonary organ function [52] . These results lend support to a conservative strategy of fl uid management in patients with ALI/ Chapter 24 344 Fetal m onitoring and p otential e ffects of m aternal ARDS on p regnancy The potential effects of maternal ARDS on a pregnancy include: (i) fetal distress due to maternal hypoxemia, (ii) premature labor triggered by the stress of the maternal condition, (iii) fetal expo- sure to medications used in management of ARDS, and (iv) inter- ference with assessment of fetal well - being by therapies used to treat the mother [21] . Fetal assessment should be part of the management of any pregnant woman with ALI/ARDS. If the fetus is not yet at the gestational age of viability (at least 24 – 26 weeks in most centers), assessment may be limited to periodic Doppler auscultation or ultrasonography to determine if the fetal heart tones are still present. However, later in pregnancy, more fre- quent fetal assessment is needed to help guide decisions regarding the possible need for delivery, especially in the event of changes in the maternal condition such as worsening maternal hypoxemia or acidosis or addition of therapies which may adversely affect the fetus such as use of high doses of vasopressors. Typically such ongoing fetal assessment will be done using continuous fetal heart rate monitoring and periodic ultrasonography with biophysical profi le scoring [21,24] . It is important to remember that fetal movements may be affected by sedatives and other medications given to the mother. Furthermore, the mother ’ s critical illness may trigger premature labor, and uterine contractions may in turn worsen maternal hypoxia due to the resulting increased maternal oxygen consumption; in this case, pharmacologic sup- pression of contractions may be necessary. In cases of maternal ARDS where the fetus is potentially viable, decisions regarding optimal timing of delivery and mode of delivery must be indi- vidualized based on the condition of the mother and fetus, and in general the indications for delivery will be the usual obstetric indications [24] . Prognosis of ALI and ARDS Most epidemiologic studies suggest improvements in survival of patients with ALI/ARDS since the syndrome was fi rst recognized. This is thought to be due to improvements in supportive critical care. Stapleton and colleagues, in a retrospective single - institution study of mortality in patients with ARDS using a uniform defi nition, describe an overall reduction in mortality rate from 68% in 1981 – 1982 to a low of 29% in 1996 [69] . Sepsis with multiple organ failure was the most common cause of death (30 – 50%) and respiratory failure accounted for a smaller propor- tion (13 – 19%) of deaths. The ARDS network low tidal volume trial found an overall mortality rate of 31% in the intervention group, and multiple other studies have shown reductions in mor- tality rates from 50 – 60% up until the 1980s, down to the 30 – 40% range since the 1990s [42,70,71] . Several investigators have shown that the mortality for sepsis - related ARDS is higher than that from ARDS associated with trauma and other non - sepsis risk factors [69,72] . Older age ( > 65), higher elevations in dead space ventilation, and presence of other comorbidities are also impor- inhaled NO use despite short - term improvements in oxygenation [58 – 60] . Thus, there is no evidence to support its use in the routine management of patients with ALI/ARDS [61] . Surfactant t herapy Surfactant therapy has been another potential intervention of great interest in the management of ALI and ARDS. Pulmonary surfactant contains a combination of phospholipids and apopro- teins and is produced by alveolar type II epithelial cells. It nor- mally lines the alveoli and respiratory bronchioles and serves to reduce surface tension and stabilize the alveoli, preventing alveo- lar collapse at low lung volumes. As discussed earlier, loss of surfactant in ALI and ARDS contributes to the atelectasis, gas exchange abnormalities, and reduced lung compliance seen in this syndrome. Exogenous surfactant is routinely used in managing respiratory distress syndrome (RDS) in premature infants, having been shown to improve outcomes in this popula- tion. However, a large multicenter randomized trial of exogenous surfactant administered by aerosolization in adults with ARDS failed to show any improvement in outcomes [62] . More recently, small studies suggesting benefi ts when surfactant preparations were instilled directly into the lower airways using bronchoscopy have revived interest in this therapy for acute lung injury [63,64] . However, larger randomized trials using newer preparations of surfactant and bronchoscopic delivery are still ongoing [21] . Systemic c orticosteroids Because of the prominent role of acute infl ammation in the pathology of acute lung injury and ARDS, there was also early interest in potential benefi t of anti - infl ammatory therapies, in particular corticosteroids. Several studies of high - dose corticoste- roids given early in acute - phase ARDS showed no improvement in outcomes including survival, with some suggesting increased rates of infection following early high - dose corticosteroid use [65,66] . However, recent small clinical trials focusing on the administration of corticosteroids in late - phase ARDS (the so - called fi broproliferative phase) reported favorable results, includ- ing one small randomized trial which showed improved survival in the steroid - treated group [67] . The ARDS Network recently published results of a multicenter double - blind, placebo - con- trolled, randomized trial of corticosteroids (methyprednisolone) in persistent ARDS, defi ned in this study as at least 7 days after the onset of ARDS. The mean duration of ARDS prior to enrol- ment in this study was 11 days. There was no signifi cant differ- ence in the primary endpoint of 60 - day mortality between the placebo and corticosteroid - treated groups, and when begun more than 14 days after onset of ARDS, methylprednisone was associated with signifi cantly increased 60 - and 180 - day mortality. No signifi cant difference in infectious complications was seen, but rates of neuromuscular weakness were higher in the corticosteroid - treated group [68] . Thus, the routine use of corticosteroids in the treatment of late - phase ARDS is no longer recommended. Acute Lung Injury and Acute Respiratory Distress Syndrome (ARDS) During Pregnancy 345 4 Goss CH , Brower RG , Hudson LD , Rubenfeld GD . Incidence of acute lung injury in the United States . Crit Care Med 2003 ; 31 ( 6 ): 1607 – 1611 . 5 Catanzarite V , Willms D , Wong D , Landers C , Cousins L , Schrimmer D . Acute respiratory distress syndrome in pregnancy and the puerpe- rium: causes, courses, and outcomes . 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Long - term assess- ment of lung function in survivors of severe ARDS . Chest 2003 ; 123 ( 3 ): 845 – 853 . 21 Bandi VD , Munnur U , Matthay MA . Acute lung injury and acute respiratory distress syndrome in pregnancy . Crit Care Clin 2004 ; 20 ( 4 ): 577 – 607 . tant independent risk factors for death in patients with ARDS [3,73,74] . While there are no established registries or studies involving large numbers of cases of ALI and ARDS in pregnancy, data from published series suggest outcomes in obstetric patients with this complication can be expected to be similar or perhaps slightly more favorable than outcomes in the general population. In one of the more recent published series, Catanzarite and colleagues reported a mortality rate of 39% in a cohort of 28 pregnant patients with ARDS, but other investigators reported mortality rates ranging from a low of 24% up to 44% [5 – 7,75] . The most common cause of death in pregnancy - associated ALI/ARDS cases has been multiple organ system failure [5] . Summary Acute lung injury (ALI) and ARDS can complicate the course of pregnancy and may result from a number of different causes, which may be unrelated to the pregnancy (such as sepsis, trauma, severe pancreatitis, or inhalation injury, to name only a few) or may be unique to pregnancy (such as pre - eclampsia or amniotic fl uid embolism). Management of these complications is directed to the prompt treatment of the underlying precipitating cause, and to supportive care in an intensive care unit. In the absence of pregnancy - specifi c data to guide supportive care, the existing recommendations are based on evidence from studies in non - obstetric populations with ALI and ARDS. Mechanical ventila- tion is the mainstay of supportive management in severe ALI/ ARDS, and a low tidal volume approach with attention to mater- nal P a CO 2 and acid – base status to avoid both excessive hypercar- bia and excessive hyperventilation should be utilized. Fluid management, appropriate hemodynamic support, and imple- menting measures to avoid nosocomial infections also should be part of the routine critical care management of these patients. Unfortunately, none of the specifi c therapies which have been studied (such as inhaled NO, surfactant, and corticosteroids) have proven to be benefi cial in improving outcomes of ALI and ARDS in adults. References 1 Ashbaugh DG , Bigelow DB , Petty TL , Levine BE . Acute respiratory distress in adults . Lancet 1967 ; 2 ( 7511 ): 319 – 323 . 2 Bernard GR , Artigas A , Brigham KL , Carlet J , Falke K , Hudson L , et al. The American - European Consensus Conference on ARDS. 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Am J Obstet Gynecol 1987 ; 156 ( 4 ): 797 – 807 . 2 6 H i l l J B , S h e f fi eld JS , McIntire DD , Wendel GD Jr . Acute pyelonephri- tis in pregnancy . Obstet Gynecol 2005 ; 105 ( 1 ): 18 – 23 . 27 Sibai BM , Mabie BC , Harvey CJ , Gonzalez AR . Pulmonary edema in severe preeclampsia - eclampsia: analysis of thirty - seven consecutive cases . Am J Obstet Gynecol 1987 ; 156 ( 5 ): 1174 – 1179 . 28 Gottlieb JE , Darby MJ , Gee MH , Fish JE . Recurrent noncardiac pul- monary edema accompanying pregnancy - induced hypertension . Chest 1991 ; 100 ( 6 ): 1730 – 1732 . 29 Benedetti TJ , Kates R , Williams V . Hemodynamic observations in severe preeclampsia complicated by pulmonary edema . Am J Obstet Gynecol 1985 ; 152 ( 3 ): 330 – 334 . 30 Bader AM , Boudier E , Martinez C , Langer B , Sacrez J , Cherif Y , et al. Etiology and prevention of pulmonary complications following beta - mimetic mediated tocolysis . 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N Engl J Med 1987 ; 317 ( 25 ): 1565 – 1570 . 6 6 L u c e J M , M o n t g o m e r y A B , M a r k s J D , Tu r n e r J , M e t z C A , M u r r a y J F . Ineffectiveness of high - dose methylprednisolone in preventing paren- chymal lung injury and improving mortality in patients with septic shock . Am Rev Respir Dis 1988 ; 138 ( 1 ): 62 – 68 . 348 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 25 Pulmonary Edema William C. Mabie University of South Carolina, Greenville, SC, USA Introduction The clinical circumstances in which pulmonary edema is seen during pregnancy are summarized in Table 25.1 . The pathophysi- ologic mechanism of the pulmonary edema may sometimes be gleaned from the history, physical examination, laboratory data, and chest radiograph. For example, pulmonary edema occurring in the setting of acute pyelonephritis suggests non - cardiogenic or permeability edema. On the other hand, even using echocardiog- raphy and pulmonary artery catheterization; we have been unable to fully understand the mechanisms involved in tocolytic - induced pulmonary edema or that associated with pre - eclampsia, two of the more common causes of pulmonary edema in pregnancy. Two stages in the formation of pulmonary edema are recog- nized: interstitial and alveolar. The physiology of lung fl uid clear- ance will be reviewed briefl y. The lung is divided into alveoli, interstitium, and vessels. Fluid enters the lung interstitium and is pumped out by the lymphatics to the thoracic duct at about 20 mL/h at rest. With strenuous exercise, interstitial edema may be cleared at a rate up to 200 mL/h. In patients with mitral ste- nosis or chronic congestive heart failure, compensatory hypertro- phy of the pulmonary lymphatics and vasculature prevents alveolar fl ooding even with elevated hydrostatic pressure (e.g. pulmonary artery wedge pressure [PAWP] > 18 mmHg) and interstitial edema formation rates. If the fl uid clearance mechanisms are exceeded and alveolar edema results, type I and type II alveolar epithelial cells actively transport fl uid back into the interstitium. Fluid enters the cells via the apical sodium channel and is extruded at the base of the cells via the Na,K - ATPase pump with water following isosmoti- cally (Figure 25.1 ). There are also water channels called aquaporins within cells and between cells. Aquaporins presumably have a role in water homeostasis as evidenced by their increased expression in the neonatal period during rapid fl uid absorption following the ini- tiation of alveolar respiration [1] . Pathophysiology Nearly all cases of pulmonary edema may be classifi ed under one of four mechanisms: hydrostatic, permeability, lymphatic insuf- fi ciency, and unknown or poorly understood (see Table 25.2 ) [2] . In perhaps 10% of cases, more than one mechanism may be operating (e.g. fl uid overload in a septic patient with permeability edema) [3] . Hydrostatic p ulmonary e dema Hydrostatic pulmonary edema includes cardiogenic causes, colloid osmotic pressure (COP) problems, and rare states result- ing in negative interstitial pressure such as rapid reexpansion of a pneumothorax or acute airway obstruction (e.g. blocked endo- tracheal tube). Excessive intravenous infusions of saline, plasma, or blood can lead to a rise in PAWP and pulmonary edema. Cardiogenic pulmonary edema can be further divided into disease resulting from systolic dysfunction (decreased myocardial squeeze, ejection fraction < 45%), diastolic dysfunction (impaired ventricular muscle relaxation resulting in high fi lling pressures), or valvular disease (either stenosis or insuffi ciency). Systolic dysfunction is one of the major causes of pulmonary edema in pregnancy (e.g. peripartum cardiomyopathy) and is the classic pathophysiologic mechanism of congestive heart failure [4,5] . Congestive heart failure may be thought of from different points of view – backward failure versus forward failure, or left heart failure versus right heart failure. Discussing these viewpoints illustrates pathophysiologic mechanisms for the development of the signs and symptoms of heart failure. With backward failure there is accumulation of excess fl uid behind the failing ventricle. In backward failure of the left heart, the ventricle does not empty normally. Left ventricular end - diastolic pressure, wedge pressure, and pulmonary artery . underlying precipitating cause, and to supportive care in an intensive care unit. In the absence of pregnancy - specifi c data to guide supportive care, the existing recommendations are based on. support, and imple- menting measures to avoid nosocomial infections also should be part of the routine critical care management of these patients. Unfortunately, none of the specifi c therapies. mortality in patients with septic shock . Am Rev Respir Dis 1988 ; 138 ( 1 ): 62 – 68 . 348 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy.