Lecture presented by Dr Mohamed Khaled at the Egyptian African Critical Care Summit 2017 held at Cairo, Egypt

1. Assistant Professor of Critical Care
Cairo University

2.  Respiratory physiology in pregnancy
 Causes of respiratory failure in pregnancy
 ICU management during pregnancy

3. Pollock et al, Int Care Med 2010,36:1465
Characteristics of included studies according to
country level of development

4.  0.2 – 0.4% of deliveries require ICU
 Respiratory failure accounts for 40 - 50%
 i.e. about 1-2 per 1000 deliveries
 Account for about 1% of ICU admissions
 Vast majority admitted postpartum

6. The gravid woman undergoes a number of
respiratory adaptations, some of which increase her
risk for respiratory compromise.
Progesterone stimulates a 30% increase in minute
ventilation, which is achieved by an increase in tidal
volume; respiratory rate does not change significantly.
Because the respiratory rate remains constant across
gestation, tachypnea often is a sign of underlying
pathology.

7. Three noteworthy changes occur in the thorax during
pregnancy:
1 Increase in the circumference of the lower chest wall
2Increases in anteroposterior and transverse diameters
3Elevation of the diaphragm with cephalad displacement
of 4 cm to 5 cm.
Reducing functional residual capacity by 10% to 25%; and
as much as a 50% widening of the costal angle.

8. These changes peak at the 37th week of pregnancy
and normalize within 6 months of delivery, translating to an
overall reduced respiratory reserve and putting the
pregnant woman at risk for precipitous drops in
oxygenation during significant illness.
Pregnant women have reduced capacity for respiratory
compensation in response to metabolic acidosis. All this
can lead to more rapid development of hypoxia,
hypercarbia, and acidosis.

9. Increased estrogen levels can produce mucosal
edema, hyperemia, mucus hypersecretion, capillary
congestion, and increased fragility in the upper respiratory
tract, most markedly during the third trimester.
Hormonally mediated rhinitis affects 30% of pregnant
women
Thus, placement of endotracheal tubes, and nasogastric
tubes in these women may be more difficult and smaller
tubes may be required.

10. airway edema, friability
widened AP and
transverse diam.
elevated diaphragm
widened subcostal
angle
enlarging uterus
Anatomic effects Functional effects

11. Anatomic effects Functional effects
airway edema,
friability
widened AP and
transverse diam.
elevated
diaphragm
widened subcostal
angle
enlarging uterus
increased
respiratory
drive
minimal change in
TLC increased Vt
reduced FRC
normal
diaphragmatic
function
increased O2
consumptionand
CO2 production

12. Anatomic effects Functional effects
• airway edema,
friability
• WidenedAP and
transverse diam.
• Elevated diaphragm
• Widenedsubcostal
angle
• Enlarging uterus
increased
respiratory
drive
minimal change in
TLC increased Vt
reducedFRC
normal
diaphragmatic
function
increased O2
consumption and CO2
production

13. Maternal partial pressure of carbon dioxide (PaCO2)
drops from a range of about 36 mm Hg to 44 mm Hg
to a range of 28 mm Hg to 32 mm Hg, but renal
compensation helps maintain arterial pH between 7.40
and 7.47.
Because of this change in PaCO2, established normal
ranges in nonpregnant patients do not apply during
gestation.

14. Thus, a minor increase in PaCO2 above 40 mm Hg
may reflect significant respiratory compromise in the
gravid woman.
Maternal PaO2 increases slightly to an average of 100
mm Hg to 105mm Hg at sea level. Oxygen
consumption during pregnancy increases by 15% to
20% because of increased maternal metabolism and
the needs of the growing fetus.

15. % change
from
baseline
16
Weeks Delivery

16. Determinants
 Placental function
 Uterine oxygen delivery

17. Determinants

 uterine oxygen delivery
• Maternal oxygen content
• Uterine blood flow
- Normally maximally dilated
- Decreased by o Catecholamines
o Alkalosis
o Hypotension
o Contractions

18.  Pregnancy specific
 Aggravated by pregnancy
 Other

19.  Pregnancy specific:
 Preeclampsia and pulmonary edema
 Amniotic fluid embolism
 Tocolytic induced pulmonary edema
 Aggravated by pregnancy
 Gastric acid aspiration
 Venous thromboembolism
 Sepsis and ARDS
 Cardiac failure
 Other
 Pneumonia
 Asthma
 Neuromuscular disease

20. Selected causes of respiratory failure
Modifiedfrom: Deblieux PM,et al.,

21. Although estimates vary, amniotic fluid embolism,
also referred to as anaphylactoid syndrome of
pregnancy, occurs in from 1 in 40,000 to 1 in 60,000
deliveries, with a reported mortality rate reaching
86%.

22. Amniotic fluid embolism usually occurs during
labor or delivery, but has been reported as early as
20 weeks' gestation and as late as 48 hours
postpartum, as well as after a first- or second-
trimester abortion, amniocentesis, and
abdominal/uterine trauma.

23. Predisposing factors include
 The presence of amniotic fluid meconium,
 Advanced maternal age,
 Multiparity,
 Intrauterine fetal death
 Complicated course of labor.

24. The major clinical findings are the abrupt and
fulminant onset of hypotension caused by
cardiogenic shock, hypoxic RF, and disseminated
intravascular coagulopathy.

25. Less severe presentation of amniotic fluid
embolism in which only some major symptoms and
signs occur.
Such patients generally present with the sudden
onset of mild dyspnea and hypotension.
The clinical course tends to be abbreviated, and the
prognosis is better than in those with full syndrome.

26. In general, experts consider this condition
to be unpredictable and unpreventable.

27. Pulmonary edema occurs when fluid is filtered into
the lungs faster than it is removed, which interferes
with alveolar gas exchange.
Pregnant women are particularly at risk given their
already increased circulating volume and alterations in
sodium metabolism and water retention.

28. Tocolytics, particularly the beta-adrenergics, are associated with
iatrogenic pulmonary oedema and are more common in pregnancies
involving;
multiple gestation,
maternal infection, or
simultaneous use of multiple tocolytic agents.

29. Tocolytic-associated pulmonary oedema is
multifactorial and reflects enhanced vasodilation
and tachycardia in response to these medications, as
well as increased sodium and fluid resorption after
stimulation of antidiuretic hormone. Iatrogenic fluid
loading is a contributing factor.

30. Preeclampsia can be associated with pulmonary oedema.
In this situation:
 Pulmonary oedema again is thought to be multifactorial
and related to fluid overload,
 Decreased plasma oncotic pressure,
 Increased capillary permeability,
 Increased pulmonary capillary hydrostatic pressure,
and possibly to the use of magnesium.

31. Peripartum cardiomyopathy (PP CDM) accounts for a
substantial proportion of reported pregnancy-related
deaths, with a mortality rate reaching 19%.
Diagnostic criteria for PP CDM include:
Onset of heart failure in the last month of pregnancy or
within 5 months of delivery;
Absence of other determinable causes for cardiac
failure; and
Absence of demonstrable heart disease before the final
month of pregnancy.

32. Some experts have proposed a fourth criterion: left
ventricular systolic dysfunction demonstrated by classic
echocardiographic findings, such as depressed shortening
fraction (less than 30%), ejection fraction less than 45%,
Cardiomegaly almost always is present on chest xray.
Etiology of the disease is unknown. In contrast to PP CDM,
heart failure from underlying structural heart disease usually
presents in the second trimester when hemodynamic changes
are most appreciable.

33. Prevalence and hospitalization rates for pneumonia
are similar in pregnant and non-pregnant women.
However, RF due to pneumonia was the third leading
indication for intubation during pregnancy and accounted
for 12% of intubated obstetric patients in one series.
Severe pneumonia and RF lead to more preterm
deliveries and higher fetal mortality related to prematurity.

34. Pneumonia in pregnancy most often is community-acquired.
In as many as two-thirds of cases, the offending microbe is
not recovered. Comorbid illnesses play an important
pathological role.

35. Immunologic and physiologic changes that occur during
pregnancy place women at increased risk for severe viral
infections. Secondary bacterial infections, frank RF, and acute
respiratory distress syndrome which frequently complicate viral
pneumonias.

36. The recent H1N1 influenza pandemic raised
awareness of the potential for catastrophic illness during
pregnancy. During the 2009 flu season in New York City,
pregnant women were 7 times more likely to be
hospitalized than non -pregnant reproductive-age women
and 4 times more likely to develop severe infection.

37. Severe infection Defined as a need for admission to the
intensive care unit (ICU) or ultimate death. This latter
finding suggested that pregnant women experienced
more severe disease .

38. A large database accumulated by the US Centers for
Disease Control and Prevention (CDC) showed that
between April and August 2009, 65% of 788 pregnant
women with proven H1N1 infection were hospitalized.
Of those hospitalized, nearly one-quarter developed
severe disease necessitating ICU-level care and one-fifth
required intubation.

39. Approximately half of pregnant women diagnosed with H1N1
had an underlying comorbid condition, such as
 Obesity,
 Asthma, or
 Diabetes (both pregnancy-related and Nonpregnancy-
related).
Influenza infection had a significant impact on the fetus as
well; one-third of live-born babies were delivered prematurely.
Pregnant women accounted for 5% of influenza-related
deaths reported to the CDC in the same period.

40. The study also highlighted the importance of early
recognition and treatment; pregnant women given
oseltamivir within 48 hours did well as indicated by a
0.5% maternal mortality rate. Among survivors, earlier
treatment was associated with less severe disease .

41. Embolic diseases are the primary cause worldwide of
acute hemodynamic and respiratory collapse during
gestation. Contributing factors include changes in clotting
protein profiles, inhibition of the fibrinolytic system, and
venous stasis.
Risk of venous thromboembolism (VTE) begins to
increase in the first trimester and continues through the
postpartum period.

42. Other conditions that increase the risk of VTE include:
 Prolonged bed rest,
 Instrumentation or cesarean delivery,
 Hemorrhage,
 Sepsis,
 Multiparity, and
 Increased maternal age.
Diagnosis is confirmed by imaging (computed tomography
pulmonary angiography or low-dose ventilation perfusion
scanning).

43. If suspicion of VTE is high, anticoagulation therapy
instituted before completion of the diagnostic evaluation is
appropriate, as is maintaining adequate maternal and
fetal oxygenation and circulation.

44. Venous air embolism (VAE) is a rare but potentially
fatal condition that manifests after the introduction of air
into the vasculature.
Typically, air enters the venous circulation through the
subplacental myometrial veins, travels to the right side of
the heart, and lodges within the pulmonary circulation,
where it can cause endothelial damage and mechanical
obstruction.

45. Increases in fibrin deposition, clot formation, and
platelet aggregation occur in the vasculature as a result of
turbulent blood flow.
While release of histamine and serotonin in the lung lead
to pulmonary vasoconstriction and increased capillary
permeability.
The result is pulmonary hypertension and pulmonary
edema. Incidence likely is underestimated.

46. Although most cases of air embolism are
asymptomatic and often undetected, presentation may
include acute hemodynamic instability and neurologic
symptoms.
Factors that increase risk include cesarean delivery,
trauma, and uterine rupture.

47. Asthma is the respiratory disorder that most often
complicates pregnancy. Incidence is reported at between
0.4% to 7%, and prevalence is increasing. Acute
exacerbations rarely occur during labor and delivery,
however.

48. During an asthma attack, severity is best judged by
clinical appearance and by forced expiratory volume in 1
second (FEV1); physical examination and chest x-rays
are poorer measures of disease severity.

49.  Important cause of maternal death
 Pregnant women appear more susceptible:
 Reduced serum albumin
 Increased blood volume
 Upregulation of components of the inflammatory
response in the lung
Smith, et al. West J Med 1990,153:508
Catanzarite,ObstetGynecolSurvey1997,52:381

50.  Pre-eclampsia
 Obstetric sepsis
 Amniotic fluid embolism
 Aspiration
 TRALI
 Placental abruption

51.  Parenchymal disease
 eg. IPF, sarcoid, connective tissue disease
 Chest wall abnormalities
 eg. kyphoscoliosis, osteogenesis imperfecta
 Neuromuscular disease
 eg. myopathy, spinal muscular atrophy

54. The actual number of obstetric patients who require
ICU admission for RF is low. Little data exist on optimal
management of these patients.
The most appropriate management strategy is to
apply those practices used to manage RF in
nonobstetric populations while keeping in mind the
anatomic and physiologic changes of pregnancy that
affect respiratory goals.

55. Other
consultants:
Hematology
Rheumatology
Cardiology
Dietitian
Clinical Pharmacy
Obstetrician/Maternal-Fetal Medicine
0.2 to 0.5% of patients require ICU
Intensivist
1 – 2% of patients are OB
0.1% are pregnant

56.  ICU must be prepared

57.  ICU must be prepared:
 Drugs: oxytocin, coagulant & vasoactive drugs
 Equipment:
 Vaginal delivery
 Caesarean delivery
 Neonatal resuscitation
 Decisions: fetal resuscitation status
 Contact details: OB, anesthesia, neonatology

58. Fetal monitoring should be performed by an obstetric
nurse in the ICU at least every 4 to 8 hours while the
patient is critically ill and more frequently if the degree
and/or acuity of respiratory compromise increases.
Continuous fetal monitoring is appropriate in the most
serious situations.
Urgent cesarean delivery may become necessary.

59. For hypoxic RF, the goal is to improve arterial
oxygenation and maintain a PaO2 of greater than 60 mm
Hg and an arterial blood oxygen saturation (SaO2) of
greater than 90%. Administration of supplemental
oxygen improves oxygenation in most clinical situations
except those involving anatomic shunts.
Low-flow oxygen can be delivered using a nasal
cannula or a face mask.

60. The maximum fraction of inspired oxygen (FiO2) that can be
delivered via this route is approximately 0.4.
Adding a reservoir bag to a face mask achieves a higher FiO2
by minimizing admixture of the supplemental oxygen with room
air.
Noninvasive positive pressure ventilation and mechanical
ventilation via an endotracheal tube are additional approaches
for providing supplemental oxygen as well as partial or total
support for minute ventilation.

61. In hemodynamically stable patients with mild or moderate
RF, noninvasive positive pressure ventilation may decrease the
need for intubation and mechanical ventilation and reduce the
length of stay in ICU.
Ideal candidates for this mode of ventilation have intact
mental status, can protect their airway, are hemodynamically
stable, and are at low risk of aspiration.
The presence of copious airway secretions is considered a
relative contraindication.

62.  Advantages
 Avoids the upper airway
 Avoids sedation
 Concerns
 Nasal congestion
 Reduced lower esophageal sphincter tone
 Aspiration

63.  Acute respiratory failure
 Pulmonary edema (preeclampsia, cardiogenic)
 Other (eg. asthma, pneumonia)
 Chronic respiratory failure
 Neuromuscular disease
 Kyphoscoliosis
 Bronchiectasis
Bach.Am J Phys Med Rehabil 2003; 82:226

64. In hypercarbic RF, the primary goal of treatment is to
maintain arterial pH at greater than 7.30 with a PaCO
appropriate for the pH, but less than 45 mm Hg in the
gravid patient.
Bronchodilators can be delivered via metered dose
inhalers or nebulizers; however, patients with respiratory
distress and tachypnea may not be able to use metered
dose inhalers.

65. Long-acting beta-adrenergic agonists should not be
used to treat acute exacerbations of chronic
bronchospasm.
Corticosteroids often are used to treat acute
exacerbations of disease related to airway inflammation
(eg, asthma and chronic obstructive pulmonary
disease).

66. Aerosolized steroids may not improve the
episode in its acute phase, but are useful for
maintenance.
Although systemic absorption of aerosol steroids is
not significant, some degree of adrenal suppression
may occur.
Patients who experience change in the production or
color of sputum may benefit from a short course of
antibiotic therapy.

67. Goals of respiratory support

68. RF necessitates intubation;
Slowed gastrointestinal motility,
Progesterone-mediated loss of lower esophageal
sphincter tone,
Higher intraabdominal pressures from the gravid uterus
Increase risk of aspiration during intubation.
Patients should be kept semi-recumbent while preparing
for intubation to reduce compression of the inferior vena
cava and to decrease pressure on the diaphragm.

69.  Indications
 Remember normal PaCO2 levels
 Tube size
 eg. 6.5 to 7.5
 Airway friability
 Avoid nasal route
 Aspiration
 Delayed gastric emptying, increased abdominal pressure
 Oxygen desaturation
 Reduced O2 reserves

70.  Oxygenation
 optimize: PaO2 > 60 mmHg
 Ventilation
 normal PaCO2 30 mmHg
 permissive hypercapnia ?
 avoid alkalosis
 Pressure
 respiratory system compliance
 adequate PEEP

71.  CO2 goal in pregnancy
 Limited animal and human data
 Maternal PaCO2 < 25 mmHg is associated with fetal hypoxia
and acidosis, due to reduced uterine blood flow
 Mild hypercapnia produces fetal acidemia secondary to
maternal acidemia, but NOT fetal hypoxemia
 Mild  CO2 associated with better APGARs than CO2.
Peng et al, Br J Anasth 1972,44:1173 Buss Am J Physiol 1975;228:1497
Clark AnesthAnalg 1971;50:713
Hollmen,Acta AnaesthScan 1972,221 Ivankovic et al, Am J ObstetGynecol1970

72.  Oxygenation
 optimize: PaO2 > 60 mmHg
 Ventilation
 normal PaCO2 30 mmHg
 permissive hypercapnia ?
 avoid alkalosis
 Pressure
 respiratory system compliance
 adequate PEEP

73.  Prone positioning
 no data on maternal or fetal effects
 Nitric oxide
 little data, case reports in Pulm HTN
 HFO
 Recent experience during H1N1
 ECMO
 Australian case-series during H1N1

74.  No completely “safe” drugs
 Opiates: most OK
 Benzodiazepines: cross placenta, potential problems.
 Midazolam
 Propofol: short term OK?
 Propofol syndrome in mother and fetus?
 Neuromuscular blockers: cross placenta
 Delivery: warn neonatologist!

75. Loop diuretics : Potential maternal complications of loop diuretic use are
similar to those of nonpregnant patients and include volume contraction,
metabolic alkalosis, decreased carbohydrate tolerance, hypokalemia,
hyponatremia, hyperuricemia, and pancreatitis. Potential risks to the fetus
are relatedto the potential for intravascular volume contraction and
reduced placental perfusion.
Thiazide diuretic : In addition to the general risks associated with diuretic
use described above, a bleeding diathesis and hyponatremia have been
reported in neonates of patients who have taken thiazide diuretics during
pregnancy
Aldosterone antagonists: Spironolactone in animal studies caused
feminizationof the male fetus.There are neither data nor clinical
experience to support the safety of these agents (Spironolactone and
eplerenone)during pregnancy

76. Safe : cephalosporins, penicillins, erythromycin, azithromycin, and clindamycin
Relative safety : Aminoglycosides (risk of fetal (and maternal) ototoxicity and
nephrotoxicity) , Macrolides (Clarithromycin produces adverse pregnancy outcome
in animal studies)
Avoid : Doxycycline (transient suppression of bone growth and with staining of
developing teeth) , Fluoroquinolones ( toxic to developing cartilage in experimental
animal studies) , Trimethoprim in first trimester (folic acid antagonist),
nitrofurantoin in first trimester (associated with birth defects), Sulfonamides in first
trimester and near delivery ( associated with birth defects , and risk of kernicterus
respectively )

77. Heparins : Safer than other anticoagulants(unfractioned heparin and LMWH) for
most patients who require anticoagulation during pregnancy .
Warfarin : Generally avoided during pregnancy, or, rarely, restricted to the second
and early third trimester.
NOAC : are not used during pregnancy due to increased reproductive risks in
animal studies and insufficient human safety and efficacy data
Fondaparinux: are generally not used during pregnancy unless there is a
contraindication to heparins (eg, heparin-induced thrombocytopenia) or an inability
to use injections . The American College of Chest Physicians (ACCP) suggests limiting
the use of fondaparinux during pregnancy to women with severe reactions to
heparin (eg, HIT)

78.  Review of 93 pregnant women admitted to ICU
(Mayo Clinic 1995 -2005)
 Fetal loss
 1st trimester: 65% spontaneous abortion
 2nd trimester: 43% fetal loss
 3rd trimester: 5% fetal loss
 Risk factors for fetal loss:
 Maternal shock
 Maternal transfusion
 Lower gestational age
Cartin-Ceba et al, Crit Care Med 2008; 38:2746

79.  Fetal risk
 oncogenicity
 increased incidence of childhood leukemia (RR 1.5 – 2.0)
 associated with 1 – 5 rads
 1 childhood cancer death per 1,700 exposures
 Teratogenicity
 fetal exposure 10 to 50 rads
 10 – 20 in first 6 weeks gestation
 Neurological development
 5-30 rad at 8-15 weeks
Fetal exposure (rad)
chest XR 0.001
V/Q 0.060
CT angio 0.100
CT pelvis/abdo 5.0
Lowe 2004, Austr NZ J ObstetGynaecol National Radiological
Protection Board, 1998 Ratnapalan et al, CMAJ 2008; 179:1293

80. Lowe 2004, Austr NZ J ObstetGynaecol National Radiological
Protection Board, 1998 Ratnapalan et al, CMAJ 2008; 179:1293
 Consider risk-benefit
 Don’t avoid necessary studies, eg. CT angio
 Don’t do unnecessary, eg. daily CXR, lateral
 Remember contrast for CT angio may carry risk
 Screen abdomen
 Reduce exposure by 50%
 Use Barium swallow?
 Discuss with mother and father
 Perceived risk very high (parents and family doc)
 Can be a major source of concern

81.  Given the physiological changes, it may be considered
that delivery of the pregnant women with respiratory
failure is beneficial to the mother
 NOT always the case:
 Some oxygenation improvement
 Little change in compliance or PEEP requirement
Tomlinson MW, et al. Obstet Gynecol. 1998; 91:108-11.
Mabie WC, et al. Am J Obstet Gynecol 1992; 167:950-7

82.  Pregnancy-related anatomic and physiologic changes
increase the risk for RF.
 Many causes of RF are not unique to pregnancy,
including pneumonia, influenza, pulmonary embolism,
cardiogenic pulmonary edema, and asthma.
 Pregnancy-specific etiologies include amniotic fluid
embolus, pulmonary edema secondary to tocolytic
therapy, preeclampsia/eclampsia, and PP CDM.

83.  Diagnostic evaluation and management of gravid
women is similar to that in nonpregnant women;
however, special attention to maintaining appropriate
oxygenation is essential for both mother and fetus.
 Good knowledge and understanding of the
physiologic changes and pathologic processes that
occur in pregnancy.
 Optimizing maternal outcome ultimately ensures
fetal and maternal well being.