Respiratory Failure in Pregnancy (ARDS [acute respiratory distress syndrome] during pregnancy; ALI [acute lung injury] during pregnancy; Ventilatory failure during pregnancy; Severe pneumonia during pregnancy; pulmonary embolus [PE] during pregnancy; Amniotic fluid embolus)

Respiratory Failure during Pregnancy

Synonyms

ARDS (acute respiratory distress syndrome) during pregnancy

ALI (acute lung injury) during pregnancy

Ventilatory failure during pregnancy

Severe pneumonia during pregnancy

Pulmonary embolus (PE) during pregnancy

Amniotic fluid embolus

Related Conditions

Status asthmaticus during pregnancy

Mechanical ventilation during pregnancy

1. Description of the problem

What every clinician needs to know

Pregnancy imposes a significant challenge to management of the patient with respiratory failure, and providers must consider both maternal and fetal well-being at all stages of care.

• An understanding of the normal physiologic circulatory and respiratory changes of pregnancy is critical in approaching the critically ill pregnant patient.

• There are 2 main types of respiratory failure encountered during pregnancy: ventilatory failure (due to severe asthma, PE, circulatory shock, or neuromuscular disorders) and hypoxemic (due to pneumonia, aspiration, heart failure, ALI/ARDS, or amniotic fluid embolus).

• Special considerations of oxygen delivery to the fetus (determined by maternal cardiac output, hemoglobin, and oxygen saturation) and oxygen consumption (driven by metabolic demands of both mother and fetus, and significantly increased during labor or cesarean birth) factor into decision-making in this population.

• The critical care team caring for a pregnant patient must include the obstetrician and neonatologist, and should have a detailed plan regarding fetal monitoring, labor monitoring, acceptable pharmacotherapy during pregnancy, and contingency plans if delivery is imminent.

• This section will provide an approach to the pregnant patient with hypoxemic or ventilatory failure.

Clinical features

• Increased work of breathing

• Tachypnea

• Fatigue

• Hypoxemia — often mild in ventilatory failure, profound if hypoxemic failure

• CO2 retention — often underrecognized since the normal PCO2 in pregnancy = 30 mmHg. A POC2 of 40, especially when the respiratory rate is high, indicates respiratory failure during pregnancy.

• Mental status changes due to exhaustion

• Abnormal chest imaging

  Asthma: hyperlucency, hyperinflated

  PE: detected by perfusion lung scan, ventilation-perfusion (VQ) scan, or chest computed tomography (CT)

  Pulmonary edema, due to either increased hydrostatic pressure or increased capillary leak (Figure 1, Figure 2,
  Figure 3 and Figure 4)

• Signs of fetal distress on monitoring

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Key management points

• Unload work of breathing / Minimize oxygen consumption

  Aggressively bronchodilate patients who manifest severe airflow obstruction

  Consider non-invasive ventilation (NIV) if:

  Respiratory rate is under 40

  Mentation appears adequate

  Circulation is adequate / no shock

  Patient is not actively having emesis

  You expect a rapid (2 – 12 hour) improvement in maternal condition

  If there is no significant improvement after 30-60 minutes of NIV, INTUBATE.

  Non-invasive ventilation may be especially effective for 2 conditions:

  Obstructive lung disease / hypercapnea

  Cardiogenic / high-pressure pulmonary edema, including beta-agonist-induced pulmonary edema

  Non-invasive ventilation has a high rate of failure for pneumonia or ALI.

  Intubation is indicated for refractory hypoxemia, ongoing high work of breathing, airway obstruction, or shock.

  Intubation is more complicated in pregnancy (see Emergency Management below), but can be done safely and rapidly by experienced personnel.

• Maintain adequate maternal cardiac output, as oxygen delivery to the fetus is proportional to cardiac output.

  The physiologic response to pregnancy is a 50% increase in maternal cardiac output by full term.

  Inadequate maternal cardiac output can have drastic consequences for the fetus.

• Maintain adequate maternal oxygenation.

  The fetal environment is hypoxic at baseline, and adapts with a high fetal cardiac output and fetal hemoglobin to maximally extract oxygen.

  It is generally accepted that a higher maternal oxygen saturation (>95%, corresponding to PaO2 > 67) is favorable to optimize maternal oxygen delivery to the placenta.

  Fetus and placenta increase resting oxygen consumption by 20%, and may double O2 consumption in the setting of active labor and delivery.

  Minimizing oxygen consumption by ventilatory support — invasive or non-invasive — as well as tocolysis or anesthesia (for labor) can have an important effect on maternal (and thus fetal) oxygenation.

• Involve maternal medicine experts immediately and establish a plan for fetal monitoring if appropriate based on gestational age.

• If appropriate based on fetal age, consideration of the timing and route of delivery must be entertained.

• Diagnose and treat the underlying cause of respiratory failure.

2. Emergency Management

Stabilizing the patient

• Ensure A, B, Cs

• Airway: Intubation if impaired

  Pregnancy diminishes the oxygen reserve. Pregnant patients will desaturate more quickly and may be more difficult to pre-oxygenate given their lower O2 reserve, higher resting O2 consumption, and reliance on a high minute ventilation at baseline.

  A rapid sequence induction with cricoid pressure and orotracheal intubation is generally recommended.

  Anesthetists should be alert to the increased risk of aspiration due to impaired gastric emptying in the gravid patient.

  Given the propensity to desaturate, if a difficult airway is anticipated, awake intubation with adequate topical anesthesia is recommended.

• Breathing

  Patients with severe airflow obstruction should be given maximal bronchodilator therapy along with parenteral corticosteroids to improve bronchoconstriction.

  Non-invasive ventilation can be considered for pregnant patients with a high work of breathing provided the following:

  Patient is conscious

  Oxygen deficit is modest (FiO2 < 60% to maintain SaO2 > 95%)

  Patient’s condition is expected to improve rapidly (< 24 hours)

  Patient is not in shock

  Patient does not require transfer (ie, for imaging studies or to another healthcare facility)

  Patient has adequate ventilatory drive

  The best evidence for NIV is for hypercapneic ventilatory failure (asthma, emphysema) or for cardiogenic pulmonary edema without active ischemia.

  If the patient shows no reduction in work of breathing after a 30- to 60-minute trial of NIV, patient should be intubated and mechanically ventilated.

  Invasive Mechanical Ventilation

  Achieve adequate sedation and analgesia to tolerate the endotracheal tube, achieve ventilator synchrony, and minimize oxygen consumption / CO2 production.

  Goal O2 sat > 95% ; Goal PaO2 > 67 mmHg

  If the patient meets ALI criteria (acute onset; bilateral; PaO2/FiO2 < 300; not due to elevated left atrial pressure), low-stretch ventilation has been shown to reduce mortality.

  Initial Vt 6 ml / kg IDEAL BODY WEIGHT= 45.5 kg + 2.3 kg for each inch over 5 feet in a woman. This formula does not change for pregnant vs non-pregnant status.

  Plateau pressure maintained <= 30 cm H2O

  Modest maternal hypercapnea (PaCO2 < 60 mmHg) may be tolerated in order to achieve low-stretch ventilation if the biophysical profile of the fetus remains reassuring, given the rationale that follows.

  The effects of hypercapnea on the human fetus are not known.

  Data abstracted from animal studies with gradual rise in PaCO2 (analogous to that observed with low-stretch ventilation) found no significant change in uterine blood flow up to maternal PaCO2 of 60 mmHg, but uterine blood flow decreased as maternal PaCO2 rose above 60.

  Fetal PCO2 would be expected to be higher than maternal PaCO2, and thus there exists risk for fetal acidosis, increased intracranial pressure, and a rightward shift in the O2-Hb dissociation curve.

  It is unclear whether bicarbonate infusion adequately crosses the placental barrier to buffer fetal pH.

  PEEP — positive end-expiratory pressure — is an effective modality to increase functional residual capacity and thus oxygen reserve.

  PEEP improves oxygenation in alveolar flooding processes.

  However, PEEP can diminish venous return to the right ventricle, causing inadequate cardiac output and potentially hypotension or decreased oxygen saturation via venous admixture.

  If the patient becomes hypotensive or hypoxemic or develops signs of hypoperfusion while being mechanically ventilated, ensure adequate circulating volume and consider lowering the PEEP until an intravenous volume challenge is given. PEEP may then be reinitiated at the higher level.

  Circulation

  Ensure adequate perfusion, titrating to blood pressure (MAP > 65), urine output, mentation (as appropriate), pH / lactate, SVO2, and fetal monitoring (as appropriate).

  Intubation and sedation often result in hypotension, given the blunting of the patient’s endogenous catecholamine secretion and by uncovering a relative hypovolemia with the institution of positive pressure ventilation / PEEP.

  Fluid resuscitate prior to / with intubation

  Vasoactive support as necessary tailored to the patient’s condition

  Vasoconstrictive agents: norepinephrine, vasopressin, dopamine, or phenylephrine if in septic or vasodilatory shock with a wide pulse pressure

  Ionotrope support (dobutamine or milrinone) if patient has ventricular failure (CHF, right ventricular failure with PE)

  ICU monitoring with fetal monitoring if appropriate by gestational age

Management points not to be missed

• Ensure mother’s airway, breathing, and circulation

  If CPR is necessary, recommend left lateral tilt to keep gravid uterus from impairing venous return

• Fetal monitoring if appropriate for gestational age

• All medications should be considered in the context of pregnancy.

3. Diagnosis

Diagnostic criteria and tests

Specify the type of respiratory failure — hypoxemic vs. ventilatory failure — using the following tests.

• History: asthma, heart disease, cystic fibrosis, sickle cell anemia, immunocompromise?

• Arterial blood gas

  Normal during pregnancy = pH 7.37 / PaCO2 30 mmHg / PaO2 70 mmHg

  If intubated, ABG within 30 minutes to ensure adequate oxygenation and ventilation

• Chest X-ray (CXR): shield abdomen, though radiation exposure with a plain film is minimal

  Is there alveolar flooding? If yes: pneumonia, cardiogenic edema, or permeability edema?

  If edema, presence of an enlarged cardiac silhouette, a wide vascular pedicle, or pleural effusion(s) suggests increased hydrostatic (cardiogenic) pressure.

  If no or minimal airspace disease, consider asthma / airflow obstruction, pulmonary embolism, or (with history) sickle cell disease. Septic shock, especially before volume resuscitation, can also be a cause for ventilatory failure despite a normal or near-normal initial CXR.

• Infectious workup if any signs of pneumonia, sepsis, or if endemic virus in season

  Blood cultures

  Respiratory cultures

  Nasal swab for influenza subtypes, +/- other viruses

  Urine antigen testing for
  Streptococcus pneumoniae and Legionella

• Consider echocardiogram if new murmur or signs suggesting heart failure

• If considering PE:

  Lower extremity Dopplers are specific but less sensitive during pregnancy given the possibility of pelvic vein clot origin

  If CXR is relatively normal, a normal perfusion lung scan can obviate need for further testing with the lowest dose of radiation to mother and fetus.

  Adding ventilation scans to the perfusion scan increases the radiation exposure slightly, but improves ability to find isolated perfusion deficits.

  Chest CT scan with shielding of the abdomen has an excellent diagnostic ability but does expose the mother to significant radiation to her breast tissue, which has been cited as an increased risk for breast cancer. Nonetheless, chest CT is considered an acceptable risk for a pregnant patient suspected of having PE. Due to the mother’s high cardiac output, timing of the injection bolus may be problematic and can lead to suboptimal studies. It is recommended to discuss the case with the radiologist prior to scan.

• Hemodynamic monitoring with a central venous catheter may be helpful for patients with hypoxemic respiratory failure. There is no evidence to support a pulmonary artery catheter over a standard central venous catheter.

  In a normal term pregnancy, right heart catheterization reveals:

  Increased cardiac output and increased heart rate

  Decreased systemic and pulmonary vascular resistance, and colloid oncotic pressure

  Unchanged central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), and mean arterial pressure

  Central venous O2 saturation (SVO2), an indicator of adequate oxygen delivery, is expected to be normal or high in uncomplicated pregnancy (> 65%).

• Ventilator waveform monitoring

  Peak vs. plateau pressure can indicate airflow obstruction (higher delta between peak and plateau) compared to a process flooding the lungs (high plateau).

  Expiratory pressure tracing can also indicate auto-PEEP, when patients with airflow obstruction / asthma have inadequate time to exhale their tidal volume.

  Waveform monitoring can also confirm adherence to low-stretch ventilation parameters and gauge a patient’s synchrony with the ventilator.

Normal lab values

Normal ABG in term pregnancy: 7.37 / 30 / 70

In a normal term pregnancy, right heart catheterization reveals:

• Increased cardiac output, increased heart rate

• Decreased systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR), and colloid oncotic pressure

• Unchanged central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), and mean arterial pressure (MAP). Central venous O2 saturation is normal or high in uncomplicated pregnancy (> 65%).

Chest x-rays in pregnant women without pulmonary disease will be normal or show slightly reduced lung volumes. In comparison, Figure 1 demonstrates the radiograph of a woman with severe ARDS from a viral pneumonia, and Figure 3 demonstrates a woman with hypoxemic respiratory failure from an amniotic fluid embolism.

How do I know this is what the patient has?

Respiratory failure is present if the patient is unable to perform the work of breathing comfortably. Respiratory failure can be present even if the arterial blood gas is underwhelming, as the work of breathing may be excessive.

Differential diagnosis

There is a very broad differential causing respiratory failure, as discussed above. In addition, rarer conditions that may affect pregnant patients and may mimic ALI / ARDS or CHF include:

• Cardiac valvular disease (especially mitral stenosis) presenting with hydrostatic pulmonary edema

• Peripartum cardiomyopathy with pulmonary edema

• Alveolar hemorrhage, typically observed in patients with connective tissue disease and pulmonary vasculitis

• Acute eosinophilic pneumonia

• Pneumocystis pneumonia caused by P. jiroveci in patients with compromised T-cell immunity (HIV, organ transplant recipients on anti-rejection medications)

• Fungal pneumonia such as blastomycosis in endemic areas such as the US Upper Midwest or coccidioidomycosis in the Southwest, or zoonoses (babesiosis) in the appropriate location

• Cryptogenic organizing pneumonia presenting in an acute fashion

• Acute hypersensitivity pneumonitis

Tests that may be helpful to distinguish these entities from pulmonary edema caused by CHF or ALI include echocardiography, bronchoalveolar lavage with cell count and differential, pathology review for hemosiderin-laden macrophages or eosinophilic matter, or serologic tests.

For patients with respiratory failure and a clear CXR, in addition to asthma or embolism of clot or amniotic material, one should consider:

• Neuromuscular disease (myasthenia gravis, multiple sclerosis, post-poliomyelitis syndrome, or amyotrophic lateral sclerosis

• Problems with respiratory drive (obstructive sleep apnea, obesity hypoventilation syndrome, narcotic and/or benzodiazepine use, or central apneas)

• Paradoxical vocal cord dysfunction, which frequently coexists in patients with asthma, but is distinguished from asthma by inspiratory stridor, squaring off of the inspiratory loop on pulmonary function tests, and abnormal abduction of the vocal cords on inspiration (seen on direct laryngoscopy)

Confirmatory tests

All patients should have basic laboratory testing, chest X-ray, infectious workup and consideration of an echocardiogram if critically ill.

• Bronchoscopy is reserved for patients who do not have an obvious source for ALI, whose basic microbiologic investigation (including tracheal aspirate) is unrevealing, or for whom there is suspicion of either an atypical pathogen (PCP, fungal pneumonia), a subacute course (COP, HP), or an underlying idiopathic lung condition (AEP, COP, HP, alveolar hemorrhage).

• Surgical lung biopsy tends not to change treatment in the majority of critically ill patients with respiratory failure, but is occasionally considered. Risks include persistent air leak / pneumothorax, worsening of respiratory failure, especially during single-lung ventilation, and circulatory compromise with general anesthesia.

• Infectious disease consultation may be helpful when unusual pathogens are entertained.

4. Specific Treatment

First-line and other therapies

Treatment is specific to the type of respiratory failure, and is largely supportive.

• Hypercapneic failure due to asthma or COPD:

  Bronchodilators (albuterol, +/- anticholinergic if COPD)

  Corticosteroids — parenteral until an improvement in airflow is noted

  Leukotriene modifiers have some data to support their use in critically ill asthmatic patients.

  Non-invasive ventilation (CPAP or BiPAP) to decrease work of breathing. This is best achieved by working with the patient to ensure a comfortable mask fit and allowing the patient to acclimate to the interface before increasing the pressure. For a patient in severe distress, typical target settings would be either CPAP 10 – 13 cm H2O, or BiPAP of 15-18 / 8 – 12.

  Anxiolysis and pain control: the sensations of dyspnea and bronchoconstriction are profoundly uncomfortable and exacerbate dynamic hyperinflation by prompting the patient to hyperventilate. The goal is slow, deep respirations with adequate time to exhale, and judicious use of morphine or a low-dose benzodiazepine may help achieve this.

  Mechanical ventilation: if the patient is unable to ventilate successfully with CPAP/BiPAP, she should be intubated and ventilated, with careful attention to limiting inspiratory time and allowing maximal time to exhale.

  For Assist Control Volume Control ventilation, the goal is to allow ventilation while bronchodilator therapy takes effect, and to keep the patient from becoming dangerously hyperinflated (auto-PEEP). Minimize I-time with normal or high flow rate and a steep or even square waveform. Peak pressure is less important an endpoint than plateau pressure, which will indicate auto-PEEP.

  Provide adequate PEEP to counterbalance the high positive pleural pressure (auto-PEEP) and prevent an early “choke point” or airway collapse. In general, the extrinsic PEEP should be set to be within 2 cm H2O of the measured auto-PEEP.

  Ensure adequate sedation – young asthmatics are typically quite strong and have a huge drive and thus may require very high levels of sedative and analgesic to achieve synchrony with the ventilator. Neuromuscular blockade with cisatracurium, in addition to analgosedation, is sometimes required.

  An alternative strategy is to allow large slow breaths on pressure support (Rate 6 – 8, tidal volume 800 mL – 1.2 L) if the patient is breathing spontaneously and not paralyzed. PEEP recommendations are unchanged — matching extrinsic to intrinsic PEEP — in this mode.

  Moderate permissive hypercapnea (allowing the PCO2 to rise to 60 mm Hg) appears to be tolerated by the fetus. See discussion above.

  If respiratory workload remains very high, consider delivery as this will decrease CO2 production / ventilatory workload.

• Hypercapneic failure due to PE

  If a clot has been documented or clinical suspicion is high, initiate heparin therapy. Low-molecular-weight heparins are approved for use in pregnancy and may have a favorable risk profile (lower risk of heparin-induced thrombocytopenia and decreased osteoporosis) but heparin is generally recommended during the acute ICU setting while making decisions about possible delivery or need for invasive procedures. Goal PTT is 1.5 – 2 times baseline PTT.

  Unload work of breathing with non-invasive or invasive mechanic ventilation as dictated by patient status.

  Support circulation with adequate circulating volume and / or vasoactive or inotropic support as necessary.

  Consider alternative therapies (thrombolysis, embolectomy) if the patient is in shock despite heparin.

  Temporary vena caval interruption devices may be considered but are more technically challenging in a pregnant patient and require some radiation dosing to the midabdomen, so are not routine.

• Hypoxemic respiratory failure due to CHF

  Support ventilation with non-invasive ventilation (preferred if not in shock) or invasive mechanical ventilation if necessary.

  CPAP goal 8 – 12 cm H2O or BiPAP 12 – 15 / 7-10

  If intubating, maintain Vt < 9 ml/kg IBW to decrease risk of ventilator-induced lung injury.

  Adequate PEEP and oxygen to maintain PaO2 > 67 mm Hg or SaO2 > 95%

  Ventilation can usually be achieved with assist control volume control ventilation, but consider pressure control if patient is highly dyssynchronous or pressure support if oxygenation is not critical and circulation is intact.

  Diurese as tolerated by circulation

  Afterload reduce: hydralazine is first line, with amlodipine as second line. Avoid ACE inhibitors and angiotensin-receptor blockers given their potential fetal complications.

  If refractory, consider delivery as this will decrease the circulating volume, improve colloid oncotic pressure, diminish edema formation, and decrease metabolic demand. If delivering, careful discussion with anesthesia as general anesthesia may be poorly tolerated with impaired circulation.

• Hypoxemic respiratory failure due to ALI/ARDS

  Support oxygenation and ventilation with mechanical ventilation.

  Recommend low-stretch ventilation parameters: initial tidal volume 6 ml/kg IDEAL body weight — not adjusted for pregnancy — and plateau pressure <= 30 cm H2O.

  Permissive hypercapnea tolerated to a PCO2 of approximately 60 mmHg; above this level, would liberalize tidal volume to prevent further hypercapnea

  Oxygenation goal: PaO2 >= 67 mm Hg, SaO2 >= 95%

  Fetal monitoring if age appropriate

  Discuss a delivery plan and / or tocolysis plan with maternal fetal medicine with a focus on limiting maternal oxygen consumption.

  If patient is in shock, fluid and vasoactive support as with non-pregnant patients

  If patient is not in shock, seek the lowest filling pressures to maintain adequate circulation.

  In the ARDSnetwork Fluid and Catheter Treatment Trial, subjects who had aggressive diuresis to keep overall I/O status matched or up to 1 L negative over the first 5 days in the ICU had a reduced time on the ventilator and in the ICU compared to those with a liberal fluid strategy, without increases in renal failure or shock.

  Sedation goals are unchanged from the nonpregnant state: sedate and provide analgesia to allow tolerance of low-stretch ventilation; titrate sedation using a validated sedation scale such as the RASS; and interrupt sedation to assess ongoing needs for sedation on a daily basis once the patient has no contraindication to interruption.

  If respiratory workload and oxygen deficit remain high, consider delivery as this will decrease O2 consumption and CO2 production.

Drugs and dosages

Treatment is specific to the type of respiratory failure.

• Hypercapneic failure due to asthma or COPD:

  Parenteral corticosteroids (mg/kg dose of Solu-medrol or equivalent) x 2-3 doses to saturate the glucocorticoid receptor and then can change to daily prednisone, approximately mg/kg

  Inhaled beta-agonist therapy, nebulized or via MDI, at least every 4 hours

  Inhaled anticholinergic therapy, nebulized or via MDI, every 4 – 6 hours

  Treat any precipitating factor (removal from allergens, antibiotics if a pulmonary infection is suspected).

  Consider leukotriene modifier therapy, and continue this therapy if patient already uses leukotriene modifiers.

  Consider magnesium sulfate, IV or nebulized, for a patient with severe asthma (FEV1 < 35% predicted) or if the exacerbation is very severe.

• Hypercapneic failure due to PE

  Weight-based bolus and infusion of heparin targeted to PTT 1.5 – 2 times baseline PTT

  Consider thrombolysis (tPA or alteplase, 100 mg over 2 hours, then resume heparin) if patient is in shock due to PE.

  Supportive care as discussed in the relevant chapter on PE

• Hypoxemic respiratory failure due to CHF

  Diuresis once not in shock: loop diuretics dosed to renal function

  Afterload reduction with hydralazine +/- amlodipine

  Consider beta-blockade if not in an acutely decompensated heart failure exacerbation.

• Hypoxemic respiratory failure due to ALI/ARDS

  No specific pharmacologic therapy

  Supportive care with analgosedation as described above and diuresis once not in shock

Refractory cases

For severe, refractory cases of maternal ventilatory failure, consultation should take place with maternal-fetal medicine, anesthesia, and neonatology regarding the possible need for urgent delivery or pregnancy termination. The fetus exerts an additional ventilatory demand on the mother that can be alleviated with delivery, but even cesarean births with general anesthesia temporarily increase oxygen consumption.

• Refractory obstructive lung disease (asthma)

  After deep sedation, consider muscle relaxation / paralysis to obliterate patient effort and minimize CO2 production.

  Extracorporeal support (ECMO or ECCO2R) is an option in the most refractory cases.

• Refractory heart failure

  If due to a valvular problem, consultation with cardiovascular surgery and/or interventional cardiology may be helpful.

  Cardiopulmonary bypass (CPB) has similar maternal complications as in the nonpregnant population, but fetal outcomes are reported to be suboptimal. Intra-aortic balloon pump (IABP) has also been reported in pregnancy, and may complement CPB in that it provides pulsatile flow.

  Ventricular assist devices have been reported in pregnancy as a bridge to delivery and/or heart transplantation.

• Refractory hypoxemic respiratory failure (ARDS)

  As in nonpregnant patients, there are a number of options to improve refractory hypoxemia, including:

  Muscle relaxation / paralysis once patient is adequately sedated

  Inhaled nitric oxide (iNO) or inhaled prostaglandin (Flolan) to selectively vasodilate ventilating alveoli

  High-frequency oscillatory ventilation

  Extracorporeal membrane oxygenation (ECMO) or short-term cardiopulmonary bypass

  Unlike nonpregnant patients, prone positioning is not recommended in pregnancy.

5. Disease monitoring, follow-up and disposition

Expected response to treatment

• Respiratory failure due to airflow obstruction (asthma, COPD)

  Asthma is typically responsive to therapy, and many patients will have an excellent quality of life in between asthma exacerbations.

  Patients should follow up with a pulmonologist to monitor symptoms and response to treatment, and to review and remove precipitants where possible.

• Respiratory failure due to CHF

  Peripartum cardiomyopathy can worsen with subsequent pregnancies and in the post-partum period, so patients should be followed closely with a cardiologist.

  Valvular disease may also worsen over time, and should be followed by cardiology.

• Respiratory failure due to ALI/ARDS

  Survival of young patients is approximately 40%.

  Survivors can expect significant functional disability — reduced 6-minute walk time, more difficulty with independent acts of daily living — at one year even though lung function usually returns to normal.

  Approximately half of survivors return to work at one year after ARDS, and the majority of young patients return to work within 5 years.

  Most patients will require some form of rehabilitative therapy –physical and occupational — to improve their functional capacity following ARDS.

Incorrect diagnosis

Mimics of ARDS are relatively rare in pregnancy, but may be more common in patients with pre-existing autoimmune disease (alveolar hemorrhage) or in patients with immunodeficiency like HIV (Pneumocystis pneumonia). If neither of these conditions is present, consider a more broad differential for hypoxemic respiratory failure beyond ARDS when:

• The case is more subacute than acute (cryptogenic organizing pneumonia)

• There is no clear precipitant of ALI/ARDS (sepsis, pneumonia, aspiration, pancreatitis, trauma, blood transfusion)

• The case has unusual features, such as hematuria (pulmonary-renal syndromes like Goodpasture’s syndrome or ANCA-associated vasculitis); unusual travel (eosinophilic pneumonia); history of exposure to organic compounds or birds (hypersensitivity pneumonia); unusual rashes or arthralgias (babesiosis coexistent with Lyme disease or autoimmune disease with rapidly progressive interstitial lung disease)

• Testing for these may include serologic testing for autoimmune disease, expanded microbiologic testing (thin blood smears for parasites; bronchoalveolar lavage for PCP), or lung biopsy (video-assisted) to obtain the diagnosis.

Follow-up

• Respiratory failure due to airflow obstruction (asthma,COPD)

  Patients should follow up with a pulmonologist to monitor symptoms and response to treatment, potential complications, and to review and remove precipitants where possible.

• Respiratory failure due to CHF

  Peripartum cardiomyopathy can worsen with subsequent pregnancies and in the post-partum period, so patients should be followed closely by a cardiologist.

  Valvular disease may also worsen over time, and should be followed by cardiology.

• Respiratory failure due to ALI/ARDS

  Most patients will require some form of rehabilitative therapy –physical and occupational — to improve their functional capacity following ARDS.

  Follow-up with a pulmonologist is recommended early in the recovery as patients regain lung function. This can also be helpful for providing the patient with anticipatory guidance about what to expect following ALI/ARDS.

Pathophysiology

• Asthma

  Airway inflammation and variable narrowing of the airway lumen are the pathologic hallmarks of asthma.

  Inflammatory cells are generally those that participate in allergic reactions, including mast cells, eosinophils, basophils, Th2 lymphocytes, natural killer cells, and members of the innate immune system such as dendritic cells.

  Chronic inflammation promotes thickening and edema of the airway epithelium and smooth muscle hyperplasia, which narrows the airway lumen.

  Bronchoconstriction due to smooth muscle contraction further narrows the airway lumen, causing significant airflow obstruction and potentially dynamic hyperinflation, where the air cannot effectively exit portions of the lungs.

  The effect of pregnancy on asthma is variable.

  The increased minute ventilation that is normal in pregnancy may superimpose a larger burden on a patient with moderate to severe airflow obstruction at baseline.

  Airway mechanics and thus flow measurements during pregnancy do not change appreciably compared to the non-pregnant state.

  Airway hyperresponsiveness (as measured by a methacholine challenge, or bronchoprovocation study) was found to improve slightly during pregnancy in one small study. In general, bronchoprovocation testing is not recommended in pregnancy.

• CHF

  Hydrostatic pressure within the pulmonary capillaries increases due to elevated LVEDP (left ventricular end-diastolic pressure) or elevated LAP (left atrial pressure).

  Elevated hydrostatic pressure drives fluid out of the vessels and into the pulmonary interstitium, overcoming lymphatic drainage (leading to pleural effusion), and then into alveolar space (pulmonary edema).

  In pregnancy, a few specific forms of cardiogenic edema are occasionally observed:

  Tocolytic-associated pulmonary edema, which is presumed to be secondary to fluid overload and/or cardiac toxicity superimposed on the reduced colloid oncotic pressure of pregnancy. This generally resolves within 24 hours of withholding the beta-agonist.

  Pre-existent heart disease that is worsened by the increased circulating volume, high metabolic demand, and diminished colloid oncotic pressure of pregnancy. The most common entities in this category are:

  Rheumatic heart disease / mitral stenosis

  Cardiomyopathy

  Atrial septal defect

• ALI / ARDS

  In non-cardiogenic or increased permeability edema, hydrostatic pressure is normal but the barrier itself is leaky. The pulmonary-capillary barrier consists of both endothelium (vessel) and epithelium (respiratory lining), and both have defects in ARDS.

  Many specific molecular mechanisms contribute to vascular and epithelial barrier dysfunction, including:

  Neutrophilic inflammation

  Activation of the complement cascade

  Disordered coagulation and fibrinolysis

  Biomechanical (shear stress) toxicities from repetitive opening and closing of flooded or collapsed airspaces

  Oxygen toxicity may also contribute.

  Oxygen fractions over 60% have been show to damage healthy lung tissue.

  The degree to which oxygen toxicity contributes injury to the already-injured lung is not clear.

  Increased permeability allows protein-rich fluid to leak into the alveolar airspace.

  In response to injury, alveolar type II cells proliferate but remain functionally impaired.

  Regenerating type II cells have abnormal fluid/ion transport.

  Regenerating type II cells do not produce adequate surfactant.

  Inadequate surfactant production favors alveolar collapse and makes it more difficult to recruit partially flooded airspaces.

  Flooded and collapsed airspaces decrease the number of effective gas exchange units, which then increases the shunt fraction (the fraction of blood that shunts through the lungs without becoming oxygenated).

  Severe hypoxemia causes global hypoxic vasoconstriction, which in turn significantly elevates pulmonary vascular resistance.

  Right ventricular strain is common in ALI/ARDS.

  If the RV is failing (as viewed on echocardiogram or evidenced by a low central venous saturation), the combination of profound shunt and venous admixture due to high oxygen extraction will exacerbate the patient’s hypoxemia.

• Embolism: thrombotic, amniotic, or air

  The pathophysiology of venous thromboembolic disease (VTE) is unchanged compared to the non-pregnant state, but the hormonal milieu of pregnancy and the tendency for increased venous stasis due to relative pelvic obstruction can increase the risk for VTE.

  Amniotic fluid embolism (AFE) and air embolism happen most commonly during active labor and delivery (Figure 3 and Figure 4).

  Either AFE or air embolism can precipitate respiratory failure, hypoxemia, hemodynamic instability, or even maternal death.

  The mechanism by which fetal / amniotic material or air crosses into the maternal circulation seems to require open uterine or cervical veins, lack of integrity of fetal membranes, and a gradient favoring flow from the amnion to the maternal circulation. These conditions are met during vaginal or cesarean delivery.

  The relative contribution of mechanical obstruction of the pulmonary circulation versus a generalized reaction to a foreign circulating substance (anaphylactoid response, with cardiotoxicity) is debated.

  Many practitioners espouse a biphasic model of pathophysiology in AFE, where phase I is dominated by right ventricular failure and high PVR (with clear lungs and hypotension), followed by a left ventricular failure and high pulmonary permeability (dominated by severe hypoxemia, and frequently complicated by coagulopathy / DIC).

Epidemiology

Respiratory insufficiency is among the leading causes of ICU admission for pre-partum pregnant patients, and accounts for up to 30% of maternal deaths.

• Asthma is the most common pulmonary disorder during pregnancy, and may occur in up to 8% of pregnant women.

  In one cohort of asthma during pregnancy, approximately one third of the cohort had stable asthma, one third worsened, and one third improved during pregnancy.

  The course of asthma during one pregnancy seems to predict the likely course for subsequent pregnancies.

  Between 20% and 30% of women with asthma will have an acute exacerbation during pregnancy.

• Cardiac disease complicates approximately 4% of pregnancies.

  Cardiac disease accounts for approximately 15% of obstetric ICU admissions

  However, cardiac entities inflict a high maternal morbidity, and may account for up to 50% of maternal deaths in the ICU.

• ALI/ARDS in pregnancy has been estimated to complicate 1 in 1,500 to 1 in 7,000 deliveries in the United States, for an estimated incidence of 16 to 70 cases per 100,000 population.

  Notable epidemics such as pandemic H1N1 influenza in 2009 seem to have inflicted a higher burden on pregnant patients relative to the overall population.

  In Australia and New Zealand, pregnant women had a 7-fold higher risk of being critically ill with H1N1 compared to non-pregnant women of child-bearing age, and the relative risk climbed to 13-fold after 20 weeks’ gestation.

  Previous influenza pandemics had been reported to extract a higher mortality in pregnancy.

• Embolic disease

  PE is common in pregnancy, complicating up to 0.05% to 0.1% of pregnancies.

  PE is currently the leading cause of maternal death in the US.

  Amniotic fluid embolism is rare — 1 in 21,000 deliveries in one population-based study — but may be fatal.

  Historic reports describe a maternal mortality of 26% to 61%.

  Most practitioners believe the historic data reflect only the most severe cases, and it is likely that milder cases of AFE often go unrecognized.

Prognosis

Prognosis for both mother and fetus depends on the clinical entity and case-specific features.

• Critical illness during pregnancy is associated with a 200-fold increase in maternal mortality ratio compared to the overall US mortality ratio of 12 deaths per 100,000 live births.

• One multicenter survey reported a maternal mortality of 14% and neonatal mortality of 11% for pregnant women in respiratory failure requiring intubation.

• Asthma

  Maternal complications: one prospective cohort of women with asthma enrolled in their first trimester found that 36% of women had at least one severe exacerbation during pregnancy.

  Severe exacerbations were defined as requiring a change in medication and/or unscheduled contact with health care (emergency visit, ED visit, or hospitalization).

  Increasing asthma severity was associated with an increased rate of exacerbations.

  The majority (62%) of severe asthmatic patients at baseline had at least one severe exacerbation during pregnancy.

  Hospitalizations were more common during pregnancy than prepregnancy.

  Perinatal complications: poorly controlled asthma is associated with increased perinatal mortality, pre-eclampsia, very low birth weight infants, and preterm delivery compared to pregnancies in non-asthmatic women.

• Cardiac disease causing respiratory failure

  Cardiac disease associated with pregnancy accounts for a large fraction of obstetric ICU deaths.

  The following characteristics have been identified as associated with high risk for maternal or fetal complications. Multiple risks are more than additive.

  Any prior cardiac event or arrhythmia

  NYHA functional class > II

  Ventricular dysfunction (LVEF < 40%)

  Pulmonary hypertension (PA systolic > 50% pressure)

  Left heart obstruction

  Severe aortic stenosis (valve area < 1 cm2 or velocity > 4 m/s)

  Severe or symptomatic mitral stenosis

  Severe or symptomatic aortic or mitral regurgitation (NYHA Class III – IV)

  Dilated cardiomyopathies carry a risk of arrhythmia, heart failure, stroke, and death, especially when LVEF < 40% or NYHA Class is > II.

  Hypertrophic cardiomyopathies carry the risk of sudden cardiac death.

  Perinatal complications:

  Infants born to mothers with pre-existing cardiomyopathies reportedly have higher complication rates, including low birth weight and prematurity.

• ALI / ARDS

  In non-pregnant patients, the mortality for patients with ARDS ranges from 28% to 40%.

  Mortality is generally better in younger patients.

  The mortality among pregnant women in the 2009 H1N1 outbreak was 11% in the largest registry.

  Perinatal mortality is significantly higher when mothers have ARDS.

• Embolism: PE / AFE

  Acute PE presenting with hemodynamic instability or shock has a very high mortality, reportedly as high as 65%.

  In-hospital mortality for acute PE in one registry of unselected adult patients was 3%, with a significantly increased risk of subsequent mortality. The 5-year cumulative mortality for the cohort was 35%, and 40% of deaths were classified as cardiovascular.

  PE remains the most commonly reported cause of maternal death in the US according to the CDC.

  In a Spanish registry of acute VTE (DVT and PE), there were no maternal deaths among 72 pregnant patients diagnosed with DVT or PE, though bleeding risk was increased.

  AFE is reported to carry high maternal and fetal mortality rates.

  Maternal mortality has been cited as 26-61%.

  Fetal mortality has been reported to be 21%.

Special considerations for nursing and allied health professionals.

Recommended: “High risk and critical care intrapartum nursing” by Lisa K. Mandeville and Nan H. Troiano (Lippincott)

What's the evidence?

Asthma and airway obstruction

Namazy, JA, Schatz, M. “Pregnancy and asthma: recent developments”. Curr Opin Pulm Med Jan . vol. 11. 2005. pp. 56-60.

Murphy, VE, Gibson, P, Talbot, PI, Clifton, VL. “Severe asthma exacerbations during pregnancy”. Obstet Gynecol. vol. 106. 2005. pp. 1046-54.

Lapinsky, SE. “Cardiopulmonary complications of pregnancy”. Crit Care Med . vol. 33. 2005. pp. 1616-22.

Lapinsky, SE, Kruczynski, K, Slutsky, AS. “Critical care in the pregnant patient”. Am J Respir Crit Care Med . vol. 152. 1995. pp. 427-55.

Strek, ME, O’Connor, MF, Hall, JB, Hall, JB, Schmidt, GA, Wood, LDH. “Critical Illness in Pregnancy”. Principles of Critical Care. 2005. pp. 1593-614.

Jenkins, TM, Troiano, NH, Graves, CR, Baird, SM, Boehm, FH. “Mechanical ventilation in an obstetric population: characteristics and delivery rates”. Am J Obstet Gynecol . vol. 188. 2003. pp. 549-52.

Cardiac Disease Causing Respiratory Failure

Stergiopoulos, K, Shiang, E, Bench, T. “Pregnancy in patients with pre-existing cardiomyopathies”. J Am Coll Cardiol . vol. 58. 2011. pp. 337-50.

Lapinsky, SE. “Cardiopulmonary complications of pregnancy”. Crit Care Med . vol. 33. 2005. pp. 1616-22.

Lapinsky, SE, Kruczynski, K, Slutsky, AS. “Critical care in the pregnant patient”. Am J Respir Crit Care Med . vol. 152. 1995. pp. 427-55.

Jenkins, TM, Troiano, NH, Graves, CR, Baird, SM, Boehm, FH. “Mechanical ventilation in an obstetric population: characteristics and delivery rates”. Am J Obstet Gynecol . vol. 188. 2003. pp. 549-52.

Strek, ME, O’Connor, MF, Hall, JB, Hall, JB, Schmidt, GA, Wood, LDH. “Critical Illness in Pregnancy”. Principles of Critical Care. 2005. pp. 1593-614.

ALI/ARDS

Jenkins, TM, Troiano, NH, Graves, CR, Baird, SM, Boehm, FH. “Mechanical ventilation in an obstetric population: characteristics and delivery rates”. Am J Obstet Gynecol . vol. 188. 2003. pp. 549-52.

“Critical illness due to 2009 A/H1N1 influenza in pregnant and postpartum women: population based cohort study”. BMJ. vol. 340. pp. c1279

Lapinsky, SE. “Cardiopulmonary complications of pregnancy”. Crit Care Med . vol. 33. 2005. pp. 1616-1622.

Lapinsky, SE, Kruczynski, K, Slutsky, AS. “Critical care in the pregnant patient”. Am J Respir Crit Care Med . vol. 152. 1995. pp. 427-55.

Mabie, WC, Barton, JR, Sibai, BM. “Adult respiratory distress syndrome in pregnancy”. Am J Obstet Gynecol. vol. 167. 1992. pp. 950-7.

Catanzarite, V, Willms, D, Wong, D, Landers, C. “Acute respiratory distress syndrome in pregnancy and the puerperium: causes, courses, and outcomes”. Obstet Gynecol. vol. 97. 2001. pp. 760-4.

Herridge, MS, Cheung, AM, Tansey, CM. “One-year outcomes in survivors of the acute respiratory distress syndrome”. N Engl J Med . vol. 348. 2003. pp. 683-93.

Herridge, MS, Tansey, CM, Matte, A. “Functional disability 5 years after acute respiratory distress syndrome”. N Engl J Med . vol. 364. 2011. pp. 1293-304.

Wiedemann, HP, Wheeler, AP, Bernard, GR. “Comparison of two fluid-management strategies in acute lung injury”. N Engl J Med . vol. 354. 2006. pp. 2564-75.

Pulmonary Embolus

Blanco-Molina, A, Trujillo-Santos, J, Criado, J. “Venous thromboembolism during pregnancy or postpartum: findings from the RIETE Registry”. Thromb Haemost . vol. 97. 2007. pp. 186-90.

Ng, AC, Chung, T, Yong, AS. “Long-term cardiovascular and noncardiovascular mortality of 1023 patients with confirmed acute pulmonary embolism”. Circ Cardiovasc Qual Outcomes. vol. 4. pp. 122-8.

Kearon, C, Kahn, SR, Agnelli, G, Goldhaber, S, Raskob, GE. “Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)”. Chest. vol. 133. 2008. pp. 454S-545S.

Heit, JA, Kobbervig, CE, James, AH, Petterson, TM, Bailey, KR, Melton, LJ. “Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study”. Ann Intern Med . vol. 143. 2005. pp. 697-706.

Greer, IA. “Thrombosis in pregnancy: maternal and fetal issues”. Lancet . vol. 353. 1999. pp. 1258-65.

Ginsberg, JS, Bates, SM. “Management of venous thromboembolism during pregnancy”. J Thromb Haemost . vol. 1. 2003. pp. 1435-42.

Ginsberg, JS, Hirsh, J. “Use of anticoagulants during pregnancy”. Chest. vol. 95. 1989. pp. 156S-60S.

Ginsberg, JS, Hirsh, J. “Anticoagulants during pregnancy”. Annu Rev Med . vol. 40. 1989. pp. 79-86.

Amniotic fluid embolism

Clark, SL, Montz, FJ, Phelan, JP. “Hemodynamic alterations associated with amniotic fluid embolism: a reappraisal”. Am J Obstet Gynecol . vol. 151. 1985. pp. 617-21.

Clark, SL, Hankins, GD, Dudley, DA, Dildy, GA, Porter, TF. “Amniotic fluid embolism: analysis of the national registry”. Am J Obstet Gynecol. vol. 172. 1995. pp. 1158-67.

Gilbert, WM, Danielsen, B. “Amniotic fluid embolism: decreased mortality in a population-based study”. Obstet Gynecol . vol. 93. 1999. pp. 973-7.

Gei, AF, Vadhera, RB, Hankins, GD. “Embolism during pregnancy: thrombus, air, and amniotic fluid”. Anesthesiol Clin North Am . vol. 21. 2003. pp. 165-82.

Moore, J, Baldisseri, MR. “Amniotic fluid embolism”. Crit Care Med. vol. 33. 2005. pp. S279-85.

Mortality

“Surveillance Summaries, February 21, 2003”. MMWR. vol. 52. 2003.

MacKay, AP, Berg, CJ, Duran, C, Chang, J, Rosenberg, H. “An assessment of pregnancy-related mortality in the United States”. Paediatr Perinat Epidemiol . vol. 19. 2005. pp. 206-214.

Berg, CJ, Chang, J, Callaghan, WM, Whitehead, SJ. “Pregnancy-related mortality in the United States, 1991-1997”. Obstet Gynecol . vol. 101. 2003. pp. 289-96.

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