Special Feature

Pregnancy and Critical Care Medicine — Part 1I: Acute Respiratory Failure and Pregnancy

By Andrew M. Luks, MD, Pulmonary and Critical Care Medicine, University of Washington, Seattle, is Associate Editor for Critical Care Alert.

Dr. Luks reports no financial relationship to this field of study.

INTRODUCTION

In Part 1 of this two-part series on Pregnancy and Critical Care Medicine (see Critical Care Alert, March 2011, p. 89-93), we reviewed the normal physiologic changes that occur during pregnancy, examining changes occurring across multiple organ systems that affect our management of these patients as well as the ability of the pregnant woman to respond to various forms of stress, such as acute hemorrhage. In the second part of this series, we build on this understanding of pregnancy physiology and examine one of the major reasons critical care physicians are asked to evaluate women around the time of pregnancy — acute respiratory failure. After reviewing some basic frameworks that can be used to sort through the differential diagnosis of women with respiratory failure around the time of pregnancy and other key issues involved in managing these patients, we will consider important issues in airway and ventilator management and then discuss the presentation and management of the most common forms of respiratory failure in this patient population.

DON'T OVERLOOK THE "POSSIBLY PREGNANT" PATIENT

The topics of interest in this Special Feature will be discussed in the context of the woman who is known to be pregnant, actively delivering a baby, or known to have recently delivered a baby. It is important to remember, however, that pregnancy status may not be known to the physician, the patient's family, or possibly even the patient at the time of presentation. This may be due to comorbid conditions, such as morbid obesity, that mask the presence of pregnancy or the fact that the patient has not told any family members about their expected delivery. A recent case report1 of an obese patient not known to be pregnant who presented with acute pulmonary edema and was subsequently found to be pregnant and suffering from preeclampsia serves as a strong reminder that many of the items on the differential presented in Table 1 must be considered in any woman of child-bearing age who presents with respiratory failure, even if she is not known to be pregnant at that time.

SORTING THROUGH THE DIFFERENTIAL DIAGNOSIS

A basic differential diagnosis for acute respiratory failure in the possibly pregnant patient is provided in Table 1. There are additional ways that this differential diagnosis can be laid out. For example, as shown in Table 2, the causes of respiratory failure in pregnancy can be grouped according to whether the patient has diffuse bilateral opacities on chest imaging. The causes of respiratory failure in pregnancy can also be grouped according to timing relative to delivery (see Table 3), as some disorders, such as pulmonary embolism, can occur at any time relative to delivery, while other disorders, including tocolytic-induced pulmonary edema or amniotic fluid embolism, typically occur around the time of delivery. Patients with decompensated pulmonary hypertension may present up to 1 week following delivery while peripartum cardiomyopathy may present for the first time several months following delivery. It is important to remember, however, that these are somewhat artificial distinctions and items should not be taken off the differential diagnosis solely based on timing relative to delivery if other features of the clinical presentation are suggestive of the diagnosis.

Table 1. Differential Diagnosis for Acute Respiratory Failure in the Possibly Pregnant Patient

  • Acute asthma exacerbation
  • Amniotic fluid embolism
  • Aspiration pneumonitis
  • Decompensated cardiomyopathy (e.g., aortic stenosis)
  • Peripartum cardiomyopathy
  • Pneumomediastinum/pneumothorax
  • Preeclampsia with pulmonary edema
  • Pulmonary embolism
  • Pulmonary hypertension
  • Tocolytic-induced pulmonary edema
  • Venous air embolism

Table 2. Differential Diagnosis for Acute Respiratory Failure in Pregnancy Grouped by Chest X-ray Findings

Typically Associated with Diffuse Bilateral Opacities on Chest X-ray

  • Amniotic fluid embolism
  • Aspiration pneumonitis
  • Decompensated cardiomyopathy
  • Peripartum cardiomyopathy
  • Preeclampsia with pulmonary edema
  • Tocolytic-induced pulmonary edema

Typically Presents with Clear Lung Fields

  • Acute asthma exacerbation
  • Pulmonary embolism
  • Decompensated pulmonary hypertension
  • Venous air embolism

Table 3. Breakdown of Causes of Acute Respiratory Failure in Pregnancy Based on Timing Relative to Delivery

May Occur at Any Time Prior to or Following Delivery

Risk Increased in Last Trimester of Pregnancy

Typically Occurs Near the Time of Delivery

May Occur Following Delivery of the Fetus

Acute asthma exacerbation

Decompensated cardiomyopathy

Amniotic fluid embolism

Peripartum cardiomyopathy

Venous thromboembolism

Decompensated pulmonary hypertension

Pneumomediastinum/Pneumothorax

Pulmonary embolism

Preeclampsia with pulmonary edema

Decompensated pulmonary hypertension

Tocolytic-induced pulmonary edema

Venous air embolism

CAN I IMAGE THE PATIENT?

There often is reluctance to image pregnant patients for fear of exposing the fetus to harmful radiation. In cases of acute respiratory failure, this concern should not lead to withholding of necessary imaging tests. With abdominal shielding, the average radiation dose of a chest CT or CT pulmonary angiogram, for example, is 0.02 mGy, while that of a PA chest x-ray is < 0.01 mGy. These levels are well below the threshold above which the fetus may be at risk for injury (> 50-100 mGy). Fluoroscopy is associated with significantly higher doses of up to 20-100 mGy/min depending on the procedure and duration of each imaging period.2

WHAT'S GOOD FOR THE MOTHER IS USUALLY GOOD FOR THE FETUS

Caring for the pregnant patient is different from most situations critical care physicians face, as they are actually caring for two patients at the same time, the mother and the fetus. Decisions about which antibiotics or other medications to use must take into account the possible effects on the fetus and efforts should always be made to include the obstetrician caring for the patient in the decision-making process about these and other major decisions. In general, however, when it comes to managing most critical care issues, a useful principle to remember is that what is good for the mother is usually good for the fetus. For example, improving oxygenation in a severely hypoxemic pregnant mother will improve oxygen delivery to the placenta as will aggressive hemodynamic support in pregnant patients with sepsis. Aggressive management during an acute asthma exacerbation will also prevent possible fetal compromise. The particular tactics used may vary compared to the non-pregnant patient given the fetal concerns, and consultation with the obstetrician can help in such decisions; in general, however, interventions on behalf of the mother are of benefit to the fetus.

AIRWAY AND VENTILATOR MANAGEMENT IN PREGNANT PATIENTS

Depending on the cause and severity of respiratory failure, patients may require more than supplemental oxygen by nasal cannula or face mask in order to maintain adequate respiratory status. Although pregnancy is not an explicit contraindication to use of non-invasive ventilation and numerous case reports document its safe application in pregnant women with pneumonia or during cesarean delivery, for example, extreme care must be used when applying non-invasive techniques of mechanical ventilatory support. As noted in Part 1 of this series, pregnant women are at increased risk of aspiration due to upward pressure of the gravid uterus on the stomach as well as progesterone-induced decreases in lower esophageal sphincter tone. High distending pressures used during non-invasive ventilation may overcome the already less-competent lower esophageal sphincter, increase gastric distention, and further increase the risk of aspiration.

In those patients who require invasive mechanical ventilation, it is important to remember that airway management is fraught with risk in this patient population. Due to their low functional residual capacity and increased oxygen consumption, pregnant women will rapidly develop hypoxemia following cessation of spontaneous ventilation, particularly in the setting of an abnormal lung parenchyma.3 Multiple factors, including increased mucosal edema, weight gain, and increased breast size, also contribute to difficult airway visualization.4 Tactics that can be of use in dealing with these issues include ensuring adequate preoxygenation and proper patient positioning, as well as use of short-handled laryngoscopes, smaller endotracheal tubes, and rigid adherence to the principles of rapid sequence intubation. Nasal intubation should be avoided due to an increased risk of epistaxis as a result of capillary engorgement. Further details about managing airways in pregnant women are beyond the scope of this special feature and have been reviewed elsewhere.4,5

There is no evidence that one mode of mechanical ventilation is better for pregnant women than another. Because pregnant women have a compensated respiratory alkalosis at baseline, regardless of the mode that is used, minute ventilation should be adjusted to target the typical PaCO2 in a pregnant woman of 28-32 mmHg.3 Overventilation and increased respiratory alkalosis should be avoided as this has the potential to impair uterine blood flow and fetal oxygen delivery, although pregnant women and the fetus tend to tolerate modest degrees of hypercarbia (PaCO2 < 60 mmHg) without difficulty.3 Finally, static pressures may be elevated in late pregnancy as a result of the large, parturient abdomen, a fact that must be considered when interpreting pressure measurements on the ventilator and deciding how far to lower the tidal volume in pregnant women with acute respiratory distress syndrome.

SPECIFIC CAUSES OF RESPIRATORY FAILURE IN PREGNANCY

Several of the leading items to consider in the differential diagnosis of acute respiratory failure around the time of pregnancy are considered in the following section.

Acute Asthma Exacerbation — Roughly 20%-30% of asthmatic patients have worsening control of their disease in pregnancy, and up to 18% of pregnant asthmatic patients will seek emergency care for an exacerbation.6 The care of patients who present in exacerbation is largely the same as for nonpregnant patients, including aggressive administration of bronchodilator aerosols, systemic corticosteroids, and supplemental oxygen, but there are several notable differences in management. Systemic epinephrine is avoided if possible as this may cause uterine artery vasoconstriction and impaired fetal oxygen delivery.6 If arterial blood gases are performed, the clinician's interpretation of those gases must account for the fact that pregnant women have a compensated respiratory alkalosis at baseline. Worsening of that alkalosis can decrease uterine blood flow while the development of maternal respiratory acidosis may impair elimination of carbon dioxide from the fetal circulation by lowering the diffusion gradient across the placenta.

Women who develop progressive respiratory failure despite the measures noted above need mechanical ventilation. Given the increased risk of aspiration in late pregnancy, non-invasive positive pressure ventilation should be avoided and the patient should instead be started on invasive mechanical ventilation. In rare cases that are refractory to aggressive support, termination of the pregnancy can be considered as this may improve the patient's respiratory mechanics in the latter stages of pregnancy, decrease oxygen consumption, and allow use of additional therapies such as systemic epinephrine or permission hypercapnia.6

Amniotic Fluid Embolism — This rare but potentially catastrophic complication typically occurs around the time of labor and delivery or in the immediate postpartum period, but it has been described in association with trauma and other forms of uterine manipulation. Cardinal features of the presentation include sudden onset of hypoxemia, cardiovascular collapse, altered mental status, and disseminated intravascular coagulation, with less common presenting signs and symptoms including seizures, constitutional symptoms, agitation, and signs of fetal distress.7 Although identification of fetal squamous epithelial cells in aspirated pulmonary artery blood has been described as a diagnostic tool, these are nonspecific findings and amniotic fluid embolism remains a clinical diagnosis,3 with the key feature being the sudden decompensation of the patient in the peridelivery period. Once other potential sources of decompensation such as pulmonary embolism, venous air embolism, and severe preeclampsia have been ruled out, treatment is largely supportive. Aggressive use of fluids and vasopressors is indicated for hemodynamic support, and the degree of respiratory support will vary from oxygen by high flow face mask to invasive mechanical ventilation depending on the degree of hypoxemia and the overall stability of the patient. If onset occurs in the predelivery period, immediate delivery is indicated to prevent further hypoxic insults to the fetus. If the mother suffers a cardiac arrest at any point, standard ACLS protocols are followed and resuscitative medications should not be withheld for fear of harming the fetus.7

Peripartum Cardiomyopathy — This entity is defined as the onset of heart failure between the last month of gestation and 5 months following delivery, in the absence of other identifiable causes of heart failure.8 It can occur at any age and race and with the first pregnancy although it is more common in older, multiparous women. Presentation is similar to other forms of cardiomyopathy, although in the predelivery or immediate postpartum periods, dyspnea, weight gain, and peripheral edema may be difficult to distinguish from normal pregnancy-related changes. Diagnosis is confirmed using echocardiography and treatment is similar to that used in other forms of acute and/or chronic cardiomyopathy, with acute management varying based on the adequacy of systemic perfusion. Those patients with adequate perfusion can be managed with diuretics and vasodilator therapy, while those with evidence of impaired perfusion will require inotropic support.8 Continuous positive airway pressure (CPAP) therapy, a commonly used modality for acute cardiogenic edema in nonpregnant individuals, can be considered in peripartum cardiomyopathy but must be used cautiously in the predelivery period due to the increased aspiration risk. Pregnancy usually is continued through term in those patients who present in the last month of gestation and termination is reserved for those with severe hemodynamic instability.

It should also be remembered that not all cardiomyopathy that presents in pregnancy will be of the peripartum type. Patients with known or previously unrecognized stenotic valvular lesions will also develop problems during pregnancy as they do not tolerate the large increases in plasma volume that occur during pregnancy.3 Given that plasma volume reaches its peak levels around 24 weeks gestation, decompensated cardiomyopathy secondary to such problems will tend to present earlier than peripartum cardiomyopathy, which tends to be seen in the last month of gestation.

Pneumonia — Pregnant women are at risk for developing pneumonia just like the nonpregnant population. The presentation is similar to that in nonpregnant patients, including the causative bacterial organisms, although the physiologic reserve and tolerance of these infections is decreased due to the physiologic demands of pregnancy. Fungal pneumonia is rare in pregnancy, but viral pneumonia should remain on the differential diagnosis, with varicella and influenza being leading considerations.9 Varicella is of particular concern due to the risk of fetal effects including preterm birth, intrauterine infection, and fetal congenital varicella syndrome. The typical empiric antibiotic therapy used to treat community-acquired pneumonia in nonpregnant patients — ceftriaxone plus azithromycin — is safe in pregnancy but fluoroquinolones should be avoided, if possible, due to concerns about effects on fetal cartilage development.9

As noted earlier, pregnant women are at increased risk for aspiration due to decreased lower esophageal sphincter tone and upward pressure on the stomach from the uterus. Aspiration pneumonitis and pneumonia should therefore be considered in pregnant women presenting with focal opacities, particularly in the lower lung zones. Because most aspiration will be gastric in nature, antibiotics may be held unless the patient develops persistent fevers, worsening opacities or hypoxemia, and leukocytosis or other signs of clinical deterioration.

Preeclampsia with Pulmonary Edema — Typically occurring in the third trimester of pregnancy, preeclampsia is defined by the presence of hypertension (SBP > 140 mmHg or DBP > 90 mmHg) and proteinuria (> 300 mg/24 hours)10 and may be accompanied by peripheral edema, headaches, hepatitis, thrombocytopenia, seizures, and the HELLP syndrome (Hemolysis, Elevated Liver enzymes and Low Platelets).3 About 3% of patients who develop preeclampsia also develop pulmonary edema.11 While milder cases of preeclampsia may be managed with blood pressure control alone using hydralazine or labetalol, the presence of pulmonary edema indicates the patient has severe preeclampsia, which warrants delivery of the fetus, provided it is of viable gestational age. Diuretics can be given prior to surgery, although they are often avoided in other cases of preeclampsia due to the fact that many patients have intravascular volume depletion. Magnesium sulfate is typically administered as prophylaxis for seizures while dexamethasone is administered with preterm deliveries to assist with fetal lung maturation.

Pulmonary Embolism — Venous thromboembolism is more common in pregnant women than in the general population and pulmonary embolism remains a leading source of morbidity and mortality in these patients. Of all the disorders described in this review, pulmonary embolism should be considered over the widest time frame relative to delivery, as pregnant women are considered to be at risk from the first trimester well into the post-partum period. Clinical suspicion for the diagnosis must always be high because many of the signs and symptoms of venous thromboembolism, including dyspnea, tachypnea, tachycardia, and lower extremity edema, are common features of normal pregnancy. Diagnosis is made the same way as in non-pregnant patients. Despite the common reluctance to image these patients, CT angiography is a safe modality, as the administered radiation doses are below those felt to create risk to the fetus at all stages of pregnancy.2 Ventilation-perfusion scanning is also considered safe. Heparin remains the standard treatment for pulmonary embolism in pregnant women. Unfractionated and low molecular weight heparin do not cross the placenta and are not associated with increased bleeding risk or teratogenicity. Warfarin, on the other hand, is relatively contraindicated due to concerns about fetal teratogenicity and risk of fetal hemorrhage. Thrombolytics are also relatively contraindicated, and should only be considered in cases of massive pulmonary embolism where the life of the mother, and therefore the fetus, is at risk.

Pulmonary Hypertension — Regardless of the underlying etiology, pulmonary hypertension and pregnancy are a bad combination. The basic physiologic problem is that in the setting of high pulmonary artery pressures, the right heart is unable to pump the increasing blood volumes seen at different stages of pregnancy through the high resistance pulmonary circulation. Pregnancy itself does not cause pulmonary hypertension, but preexisting pulmonary hypertension will get worse in pregnancy while previously unrecognized disease may manifest itself for the first time during pregnancy. The risk of decompensated right heart failure rises substantially at around 24 weeks of gestation when circulating blood volume reaches its peak level and persists through the remainder of pregnancy. Labor and delivery also causes problems as uterine contractions lead to auto-transfusion of several hundred milliliters of blood, thereby causing acute increases in right ventricular preload. Importantly, the risk of decompensated right heart failure persists in the first 1-2 weeks following delivery as the pregnant woman mobilizes significant volumes of extracellular fluid into the systemic circulation.12 The risk of complications and maternal mortality appear to be a function of the stage of the patient's disease with those patients in higher New York Heart Association (NYHA) classes (III and IV) having worse outcomes.13

Evidence-based management guidelines are lacking, as the literature consists largely of case reports and small case series of various approaches. The mainstay of therapy remains the use of pulmonary vasodilators with reports in the literature documenting the use of epoprostenol, inhaled iloprost, sildenafil, and nifedipine. Diuresis also may be needed to manage the high intravascular volume. Cesarean and vaginal deliveries are both feasible based on the documented reports, during which care must be given to anesthetic management. Single-shot spinal anesthesia is contraindicated due to a risk of provoking hypotension while epidural anesthesia is preferred due to the lack of significant hemodynamic effects. If patients require general anesthesia, laryngoscopy can transiently raise pulmonary artery pressures while initiation of mechanical ventilation may have a negative impact on right ventricular preload. Mortality risk remains high for these patients with the largest case series reporting maternal mortality of 30%-56%.12,13 Interestingly, if the mother can be supported through the pregnancy, fetal outcomes are higher than one might expect, with survival ranging from 72% to 88%.12,13

Tocolytic-Induced Pulmonary Edema — Patients receiving terbutaline or other β2-agonists for management of preterm labor may develop pulmonary edema either during therapy or within 12 hours of its discontinuation.3 The presentation is similar to that of other forms of pulmonary edema in nonpregnant patients, including development of hypoxemia and diffuse bilateral opacities on chest radiography, with the key historical features being the onset of these symptoms in close temporal proximity to use of the medication and lack of other complications such as hemodynamic instability or disseminated intravascular coagulation. Treatment involves supplemental oxygen administration, discontinuation of the medication, and diuretic therapy. CPAP would be a reasonable consideration in those patients who remain hypoxemic despite high flow face mask but are otherwise hemodynamically stable and have an empty stomach. Failure to respond to these measures or onset of symptoms outside the time frame described above should lead to consideration of other potential etiologies for the patient's respiratory failure.

Venous Air Embolism — Air can gain entry to the venous circulation under different circumstances in pregnancy and cause obstruction of pulmonary blood flow and, in certain cases, complete right ventricular outflow tract obstruction. Most cases occur during cesarean section with the peak risk occurring between delivery of the infant and closure of the incision. Cases have also been described with tumultuous labor, uterine rupture, and sexual activity in pregnancy.7 The presentation will vary based on the amount of air that enters the circulation and the degree of obstruction to pulmonary flow. Because many of the symptoms, including chest pain, dyspnea, and hypoxemia, are non-specific and seen with many of the other disorders described above, the key feature that should alert to the possibility of this diagnosis will be the sudden onset of symptoms, including possibly hemodynamic compromise, around the time of a procedure or during labor and delivery. In the operating room, a major clue to the diagnosis may be a decline in end-tidal carbon dioxide tensions, but outside of this arena, diagnosis is difficult and largely relies on a high clinical suspicion.7 Echocardiography can sometimes be used to visualize the air collections. When the diagnosis is suspected, the patient should be placed in the left lateral decubitus position and started on high flow oxygen with an FIO2 of 1.0. In severe cases, consideration can be given to having interventional radiology attempt to aspirate air from the right ventricle or hyperbaric therapy; in less severe cases, treatment with supplemental oxygen alone should lead to slow resolution of the air collection and associated effects.

CONCLUSIONS

Acute respiratory failure is a challenging issue in pregnancy as the unique physiologic and clinical aspects of pregnancy affect the evaluation and management of these patients. The fact that there are actually two patients being cared for at the same time adds an additional layer of complexity and concern. With careful consideration of the broader differential diagnosis for respiratory failure in this patient population, extreme care during airway management, and effective communication with the obstetricians, it is possible to ensure a safe outcome for both the mother and the fetus.

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