Clinical Reference · Pulmonology & Critical Care

Managing Respiratory & Critical Illness
During Pregnancy

A practical reference for pulmonologists, intensivists, and obstetric teams covering medication safety tiers, physiologic lab targets, PFT changes, and ventilator management in the pregnant patient.

💊

Medication Safety in Pregnancy

Guiding principle: Uncontrolled disease is almost always more dangerous than the medication used to treat it. Neither necessary medications nor diagnostic imaging should be withheld from a pregnant woman because of fetal concerns.
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Tier 1 — Safe to Use
Extensive human data; no known teratogenicity; standard of care in pregnancy.
Bronchodilators
Albuterol (SABA)
Preferred rescue inhaler; extensive safety data.
[1][2]
Levalbuterol
Less data than albuterol but considered safe.
[1]
Ipratropium
No known teratogenicity.
[1]
Inhaled Corticosteroids
Budesonide
Most pregnancy safety data of any ICS — preferred agent.
[1][2]
Other ICS
Fluticasone, beclomethasone, mometasone
No data suggesting harm; do not switch a well-controlled patient.
[1][2]
LABA / ICS-LABA
Formoterol, Salmeterol, ICS-LABA combos
Safe; do not de-escalate during pregnancy.
[1][2]
Mast Cell Stabilizer
Cromolyn
Excellent safety profile.
[2]
Anticoagulants
LMWH
Enoxaparin, dalteparin
Preferred anticoagulant — does not cross the placenta.
[3][4]
Unfractionated Heparin (UFH)
Does not cross placenta; risk of HIT and osteoporosis with prolonged use.
[3][4]
Antibiotics
Beta-lactams
Penicillins, cephalosporins, carbapenems
No teratogenicity.
[5]
Azithromycin
Preferred macrolide in pregnancy.
[5]
Clindamycin
No increased risk of birth defects.
[5]
Anti-TB (First-line)
Isoniazid
Not teratogenic; monitor LFTs monthly (increased hepatotoxicity risk in pregnancy).
[5][6]
Rifampin
Not teratogenic in humans.
[5][6]
Ethambutol
No evidence of teratogenicity in humans.
[5][6]
Antifungals
Amphotericin B
Including liposomal formulation
Treatment of choice for invasive fungal infections in pregnancy.
[7][8]
Topical antifungals
Minimal systemic absorption.
[7]
Antihypertensives
Labetalol
First-line antihypertensive in pregnancy.
[9]
Nifedipine ER
First-line antihypertensive in pregnancy.
[9]
Alpha-methyldopa
Long track record of safety.
[9]
Hydralazine
Safe.
[9]
Metoprolol
Safe.
[9]
Vasopressors
Norepinephrine
Preferred vasopressor in pregnancy; monitor fetal status.
[10][11]
Phenylephrine
Commonly used in obstetric anesthesia.
[10]
Sedation / Analgesia
Propofol
Preferred sedative; caution near delivery (neonatal depression).
[10]
Acetaminophen
Safe in all trimesters.
Cardiac / GI / Supportive
Digoxin
Safe; may cause low birth weight.
[9]
Proton pump inhibitors
Safe in all trimesters.
Ondansetron
Widely used; limited 1st trimester data.
Insulin
Preferred agent for glycemic control.
Magnesium sulfate
Used for preeclampsia and tocolysis.
Corticosteroids (Fetal Lung Maturity)
Betamethasone / Dexamethasone
Standard of care at 24 0/7 – 33 6/7 weeks.
NMBAs
Cisatracurium
Does not cross placenta — preferred paralytic.
Succinylcholine
Minimal clinical effects on neonate.
⚠️
Tier 2 — Mild Concern: Use with Awareness
Limited data or minor theoretical concerns; generally safe when clinically indicated.
Asthma
Montelukast (LTRA)
Animal data reassuring; continue if well-controlled pre-pregnancy.
[1][2]
Theophylline
Requires monitoring (target 5–12 mcg/mL); narrow therapeutic index.
[1][2]
Systemic corticosteroids
Prednisone, methylprednisolone
Use for exacerbations; possible association with preeclampsia/prematurity (may be confounded by disease severity).
[1][2]
Pulmonary Hypertension
Epoprostenol (IV)
Benefit outweighs risk; most studied prostacyclin in pregnancy.
[3][4][5]
Treprostinil
IV / SC / inhaled
Benefit outweighs risk.
[3][4]
Iloprost (inhaled)
Benefit outweighs risk.
[3][4]
Sildenafil / Tadalafil
Benefit outweighs risk.
[3][4]
CCBs
Vasodilator-responsive PAH
May continue.
[3]
Sedation
Dexmedetomidine
No significant adverse fetal events in available data.
[6]
Opioids
Fentanyl, morphine
Caution near delivery (neonatal respiratory depression); prolonged use may cause neonatal abstinence syndrome.
[6]
Antibiotics
Vancomycin
Limited 1st trimester data; no neonatal renal or ototoxicity reported.
[7]
Linezolid
Not teratogenic in animals; limited human data.
[7]
Antihypertensives
Amlodipine
Second-line; less data than labetalol or nifedipine.
[3]
Furosemide / Diuretics
Monitor for volume depletion and oligohydramnios.
[3]
NMBAs
Rocuronium
Acceptable for RSI; crosses placenta but no adverse fetal events reported.
Anti-TB
Pyrazinamide
WHO recommends routine use; US guidelines suggest case-by-case risk-benefit assessment.
[7][8]
🟠
Tier 3 — Moderate Concern
Meaningful risk signals or very sparse data. Use only when no safer alternative exists.
Asthma Biologics
Omalizumab
Registry data show no increased risk of major malformations; weigh against risk of uncontrolled asthma.
Registry data only
[1]
Mepolizumab, dupilumab, other biologics
Very limited pregnancy data; case-by-case basis.
Very sparse data
[1]
Sedation
Midazolam / Benzodiazepines
Conflicting data on teratogenicity; neonatal depression near delivery.
Conflicting teratogenicity data
[2]
Ketamine
Less favorable safety profile than propofol or dexmedetomidine.
Vasopressors
Vasopressin
Theoretical interaction with oxytocin receptors; limited data.
Theoretical risk
[2]
Epinephrine
May reduce placental blood flow; use when clearly indicated.
Antibiotics
Fluoroquinolones
Arthropathy in immature animal models; human studies generally reassuring. Reserve for serious infections with no safer alternative.
Reserve for serious infections only
[3]
Aminoglycosides
Gentamicin, tobramycin
Theoretical risk of fetal renal and 8th nerve damage.
[3]
TMP-SMX
Folate antagonist; avoid in 1st trimester if possible.
Antifungals
Fluconazole (≤150 mg single dose)
Debated; teratogenic at doses ≥400 mg. Low single doses remain controversial.
Dose-dependent risk
[4][5]
Anticoagulants
Warfarin (2nd/3rd trimester only)
May be used for mechanical valves with careful risk-benefit discussion; switch to heparin by 36 weeks.
Requires MFM consultation
[6][7]
Anti-TB
Bedaquiline
Limited data; increased frequency of low birth weight reported.
Sparse data, growth concerns
[3]
🚫
Tier 4 — Contraindicated
Known teratogenicity, fetal toxicity, or strong contraindication. Avoid in pregnancy.
Pulmonary HTN — Endothelin Receptor Antagonists
Bosentan
Teratogenic (mandibular/cardiac defects); reduces efficacy of hormonal contraceptives.
Teratogenic
[1][2][3]
Ambrisentan
Teratogenic
[1][2][3]
Macitentan
Teratogenic
[1][2][3]
Riociguat
Teratogenic
[1][2][3]
Anticoagulants
Warfarin (1st trimester)
Embryopathy risk (weeks 6–12).
Embryopathy
[4][5]
DOACs
Apixaban, rivaroxaban, edoxaban
Cross placenta; insufficient safety data; excluded from pregnancy trials.
Crosses placenta, no safety data
[5][6]
Antihypertensives
ACE Inhibitors
Teratogenic: oligohydramnios, renal and skeletal malformations.
Teratogenic
[1]
ARBs
Same teratogenic risks as ACE inhibitors.
Teratogenic
[1]
Sacubitril/valsartan (ARNI)
Contains ARB component.
Contains ARB
[1]
Spironolactone / Eplerenone
Antiandrogenic effects on fetus.
Antiandrogenic
[1]
SGLT2 inhibitors
Renal changes in animal studies; no human pregnancy data.
No human data, animal signal
[1]
Atenolol
Associated with intrauterine growth restriction.
IUGR risk
[1]
Ivabradine
Contraindicated.
Contraindicated
[1]
Analgesics
NSAIDs after 20 weeks
Ibuprofen, ketorolac
Risk of premature ductus arteriosus closure and oligohydramnios.
Premature DA closure
Antibiotics
Clarithromycin
Increased risk of birth defects in animal studies; possible spontaneous abortion.
Teratogenic signal
[7]
Doxycycline / Tetracyclines
Hepatotoxicity; staining of fetal teeth and bones.
Fetal bone/tooth staining
[7]
Telavancin (1st trimester)
Limb malformations in animal studies.
Animal malformation data
[7]
Antifungals
Fluconazole (high dose / prolonged)
Teratogenic in 1st trimester at ≥400 mg.
Teratogenic at high dose
[8][9]
Voriconazole
Fetal abnormalities in animal models — contraindicated.
Contraindicated
[8][9]
Echinocandins
Caspofungin, micafungin, anidulafungin
Teratogenic in animal studies; no human data.
Teratogenic animal data
[8][9]
Flucytosine
Teratogenic (converted to 5-FU) — contraindicated.
Contraindicated — metabolized to 5-FU
[8][9]
Anti-TB
Streptomycin
~10% risk of fetal ototoxicity.
~10% ototoxicity risk
[7]
Kanamycin
~2% risk of fetal ototoxicity.
~2% ototoxicity risk
[7]
🧪

Lab Values: Pregnant vs. Non-Pregnant

Arterial Blood Gas (ABG)

Parameter Non-Pregnant Pregnant (3rd Trimester) Change Clinical Pearl
pH7.35–7.457.40–7.47Compensated respiratory alkalosis is normal in pregnancy
PaCO₂ (mm Hg)35–4528–32↓↓A "normal" PaCO₂ of 40 mm Hg in pregnancy signals impending respiratory failure
PaO₂ (mm Hg)90–100100–107 (↓ slightly toward term)↑ earlyEven mild PaO₂ reduction may signify pathology
HCO₃⁻ (mEq/L)22–2618–21Renal compensation for chronic respiratory alkalosis; reduced buffering capacity
Base Excess (mEq/L)−2 to +2−3 to −4Reflects compensatory metabolic adjustment
A-a Gradient (mm Hg)5–155–15 (unchanged)No significant change despite other ABG shifts
P₅₀ (mm Hg)2730 (maternal); fetal P₅₀ = 19↑ maternalRight-shifted maternal OxyHb curve; higher PaO₂ needed for same SpO₂. Fetal curve is left-shifted (facilitates O₂ transfer)

Venous Blood Gas (VBG)

Parameter Non-Pregnant (Peripheral VBG) Pregnant (Estimated VBG) Change Clinical Pearl
pH7.30–7.437.35–7.42↑ slightVBG pH is ~0.03–0.05 lower than arterial; in pregnancy, still reflects compensated respiratory alkalosis
PvCO₂ (mm Hg)38–5833–37 (estimated)↓↓VBG pCO₂ is ~5–6 mm Hg higher than arterial; a VBG pCO₂ of 45 mm Hg in pregnancy signals impending respiratory failure
PvO₂ (mm Hg)19–65Not clinically usefulVBG pO₂ does NOT reliably reflect arterial oxygenation; use SpO₂ or ABG
HCO₃⁻ (mEq/L)22–3019–23~1 mEq/L higher than arterial; still reflects reduced buffering capacity in pregnancy
Base Excess (mEq/L)−1.9 to +4.5−3 to −2↓ slightSimilar to arterial trend
Lactate (mmol/L)0.4–2.20.4–2.2 (↑ in labor)→ (↑ labor)VBG lactate correlates well with arterial; rises during active labor — not pathologic in that context
SvO₂ / peripheral (%)23–93% (wide range)Not clinically usefulPeripheral venous O₂ sat varies widely by site; not a substitute for SpO₂

Comprehensive Metabolic Panel (CMP) — Electrolytes

Parameter Non-Pregnant Pregnant (3rd Trimester) Change Clinical Pearl
Sodium (mEq/L)136–145130–140 (↓ 3–6 mEq/L)Reset osmostat; lower ADH threshold. Do not correct mild hyponatremia in pregnancy
Potassium (mEq/L)3.5–5.03.2–4.7 (↓ ~0.3 mEq/L)↓ mildProgesterone counteracts aldosterone-driven K⁺ wasting; increased predilection for rhabdomyolysis with hypokalemia
Chloride (mEq/L)98–10697–105↓ mildFollows sodium trend
CO₂/Bicarbonate (mEq/L)22–2618–21Renal compensation for respiratory alkalosis; reduced buffering capacity
Calcium, total (mg/dL)8.5–10.58.0–9.5Dilutional + reduced albumin; ionized Ca²⁺ generally unchanged — use ionized measurement
Magnesium (mg/dL)1.7–2.21.5–2.0↓ mildMild decrease common; important to monitor closely if patient is on MgSO₄
Phosphate (mg/dL)2.5–4.52.5–4.5 (unchanged)Generally stable throughout pregnancy
Plasma Osmolality (mOsm/kg)275–295270–285 (↓ 5–10 mOsm/kg)Reset osmostat; lower thirst and ADH thresholds — physiologic, do not over-interpret

CMP — Renal Function

Parameter Non-Pregnant Pregnant (3rd Trimester) Change Clinical Pearl
BUN (mg/dL)7–205–12GFR increases 40–50% → increased urea clearance
Creatinine (mg/dL)0.6–1.20.4–0.8↓↓ (~25%)A "normal" Cr of 1.0 mg/dL in pregnancy may indicate renal impairment. Cr >0.8 warrants attention
eGFR~90–120 mL/min~120–180 mL/min↑↑ (40–50%)Standard CKD-EPI formulas not validated in pregnancy; use creatinine clearance if precise measurement needed
Uric Acid (mg/dL)2.5–6.02.0–5.0 (T1/T2); rises toward term↓ then ↑Falls early due to increased GFR; rises in 3rd trimester. Elevated uric acid associated with preeclampsia

CMP — Glucose

Parameter Non-Pregnant Pregnant (3rd Trimester) Change Clinical Pearl
Fasting Glucose (mg/dL)70–10060–90Fetal glucose consumption + increased insulin production; accelerated starvation physiology
Random Glucose (mg/dL)70–140May be higher postprandially↑ postprandialInsulin resistance increases in 2nd/3rd trimester (human placental lactogen effect)

CMP — Hepatic Function

Parameter Non-Pregnant Pregnant (3rd Trimester) Change Clinical Pearl
ALT (IU/L)0–356–32 (unchanged)Any elevation should be evaluated — ALT does NOT rise in normal pregnancy
AST (IU/L)0–4010–30 (unchanged)Same as ALT; elevation suggests pathology (HELLP, AFLP, viral hepatitis)
Alkaline Phosphatase (IU/L)30–150T1: 32–100 / T2: 43–135 / T3: 133–418↑↑↑Placental origin; fractionation confirms source. ALP is not a useful liver marker in pregnancy
GGT (IU/L)7–333–43 (unchanged to ↓)→ to ↓Decreases in 2nd/3rd trimester; useful to differentiate hepatic vs. placental ALP elevation
Total Bilirubin (mg/dL)0.1–1.20.1–0.8Lower due to hemodilution; any elevation warrants workup
Albumin (g/dL)3.5–4.62.8–3.7↓↓Hemodilution; affects total calcium interpretation and drug binding — use ionized Ca²⁺
Total Protein (g/dL)6.0–8.35.5–7.5Hemodilution; decreases progressively through gestation

Hematologic & Coagulation

Parameter Non-Pregnant Pregnant (3rd Trimester) Change Clinical Pearl
Hemoglobin (g/dL)12.0–16.010.0–14.0Dilutional anemia: plasma volume ↑ ~50%, RBC mass ↑ ~25%
Hematocrit (%)36–4631–41Same mechanism as Hgb reduction
WBC (×10⁹/L)4.5–11.06.0–16.0 (up to 30 in labor)Predominantly neutrophilia; do not reflexively attribute elevated WBC to infection
Platelets (×10⁹/L)150–400130–400↓ mildGestational thrombocytopenia (dilutional); count <100 warrants workup
Fibrinogen (mg/dL)200–400300–600+↑↑Reflects hypercoagulable state of pregnancy
D-dimer (μg/mL FEU)<0.50T1: 0.95 / T2: 1.29 / T3: 1.70↑↑↑Standard non-pregnant cutoff is unreliable; use trimester-specific thresholds
PT (seconds)11–13.59.5–12.5Shortened due to elevated clotting factors
aPTT (seconds)25–3523–33Same mechanism as PT shortening

Other Pulmonary-Relevant Labs

Parameter Non-Pregnant Pregnant Change Clinical Pearl
BNP (pg/mL)<100Generally <100 (mildly elevated)→ / ↑Elevated BNP + PE should raise concern for RV strain
NT-proBNP (pg/mL)<125Can be mildly elevated→ / ↑No validated pregnancy-specific cutoffs; interpret with caution
Procalcitonin (ng/mL)<0.10Generally unchangedRemains useful for bacterial infection assessment in pregnancy
Lactate (mmol/L)0.5–2.00.5–2.0 (↑ in active labor)→ (↑ labor)Rises during active labor; not pathologic in that context
Serum Bicarbonate (mEq/L)22–2618–21↓ ~25%Reduced buffering capacity → faster onset of DKA and starvation ketoacidosis
Plasma Ketones (mmol/L)~0.13~0.43↑↑Starvation ketoacidosis can occur after just 16 hours of fasting in 2nd/3rd trimester
🫁

PFT Physiology in Pregnancy

Key Takeaway: The hallmark of pregnancy PFT physiology is a reduced FRC with preserved spirometry (FEV₁, FVC). The decreased FRC combined with increased O₂ consumption creates a critically reduced oxygen reserve — explaining the rapid desaturation seen with apnea or hypoventilation in pregnant patients.
Parameter Non-Pregnant Pregnant (3rd Trimester) Change Mechanism
Tidal Volume (mL)~500~700 (↑ 30–40%)↑↑Progesterone-driven increase in ventilatory drive
Minute Ventilation (L/min)~6–8~9–11 (↑ 30–50%)↑↑Driven by increased tidal volume; respiratory rate unchanged
Respiratory Rate12–2012–20 (unchanged)Increased minute ventilation is entirely from increased TV
FRC (mL)~2400~1800–2000 (↓ 10–25%)↓↓Diaphragm elevation by gravid uterus
ERV (mL)~1200~800 (↓ 15–20%)Component of FRC reduction
RV (mL)~1200~1000 (↓ 5–15%)↓ mildComponent of FRC reduction
IC (mL)~2500~2800–3000 (↑ 15–20%)Compensatory increase via increased tidal volume and IRV
TLC (mL)~5900~5600–5700 (↓ 0–5%)↓ minimalIC increase partially offsets FRC decrease
VC (mL)~3500~3500 (unchanged)Preserved despite mechanical changes
FEV₁NormalUnchangedNo airflow obstruction from pregnancy itself
FVCNormalUnchangedNo true restriction despite reduced FRC
FEV₁/FVCNormalUnchangedRatio preserved
DLCONormalNormal to mildly ↑→ / ↑Increased cardiac output and pulmonary blood flow
O₂ Consumption (mL/min)~250~300–330 (↑ 20–33%)↑↑Combined fetal and maternal metabolic demands
⚙️

Ventilator Goals in Pregnancy

Parameter Non-Pregnant (Standard ARDS) Pregnant Rationale
Tidal Volume6–8 mL/kg IBW6–8 mL/kg IBW
Use pre-pregnancy weight
Lung-protective ventilation applies equally
Plateau Pressure≤30 cm H₂O≤30 cm H₂OSame barotrauma prevention goals
Driving Pressure≤15 cm H₂O≤15 cm H₂OSame as non-pregnant
PEEPTitrate per FiO₂/PEEP tableCautious titrationExcessive PEEP may reduce venous return (already compromised by IVC compression)
PaCO₂ Target35–45 mm Hg28–32 mm HgMust maintain maternal respiratory alkalosis for fetal CO₂ clearance
pH Target7.35–7.457.40–7.47Avoid maternal acidosis (fetal acidosis risk)
SpO₂ Target≥88–92% (ARDS)≥92–95%Higher target needed due to right-shifted maternal OxyHb curve; fetal oxygenation depends on maternal PaO₂
PaO₂ Target≥55–80 mm Hg≥70 mm HgFetal well-being requires higher maternal PaO₂
Permissive HypercapniaAccepted in ARDSAvoid if possibleElevated maternal PaCO₂ reduces fetal CO₂ gradient → fetal acidosis
FiO₂Lowest to maintain SpO₂Lowest to maintain SpO₂ ≥92%Hyperoxygenation may reduce fetal cardiac output
PositioningProne for severe ARDSSemi-prone or lateral
Feasible up to ~30 wks; modified prone with abdominal support later
Left lateral tilt ≥15° to relieve aortocaval compression

Critical Pearls

PaCO₂ of 40 mm Hg is NOT normal in pregnancy. In a pregnant patient, a PaCO₂ at the low end of the non-pregnant normal range signals impending respiratory failure and should prompt urgent reassessment.
Permissive hypercapnia is poorly tolerated. Unlike standard ARDS management, elevated maternal CO₂ impairs the transplacental CO₂ gradient and risks fetal acidosis. Target pregnant-normal PaCO₂ (28–32 mm Hg) on the ventilator.
Rapid desaturation risk. The reduced FRC and increased O₂ consumption mean pregnant patients desaturate extremely rapidly after apnea. Preoxygenation before intubation is essential. The failed intubation rate in obstetrics is approximately 1 in 224 — roughly 8× higher than in the general population.

Universal Clinical Reminders

⚖️Uncontrolled disease is almost always more dangerous than the medication used to treat it.
🏥Neither necessary medications nor diagnostic imaging should be withheld from a pregnant woman because of fetal concerns.
💉Pregnancy alters pharmacokinetics (increased GFR, plasma volume, cardiac output; decreased gastric emptying) — dose adjustments may be needed.
👥Always consult pharmacy and maternal-fetal medicine when managing critically ill pregnant patients.

References

  1. [1]Sigelko AD, Strek ME, Wolfe KS. Asthma in Pregnancy. Obstet Gynecol. 2025;146(1):39-58. PubMed
  2. [2]NAEPP Expert Panel Report. Managing Asthma During Pregnancy: 2004 Update. J Allergy Clin Immunol. 2005;115(1):34-46. PubMed
  3. [3]Greer IA. Pregnancy Complicated by Venous Thrombosis. N Engl J Med. 2015;373(6):540-7. NEJM
  4. [4]ACOG Practice Bulletin No. 196: Thromboembolism in Pregnancy. Obstet Gynecol. 2018;132(1):e1-e17. DOI
  5. [5]Benson C, Brooks J, Dhanireddy S, et al. Guidelines for OI Prevention and Treatment in Adults with HIV. IDSA/OARAC 2025. PDF
  6. [6]Nahid P, Dorman SE, Alipanah N, et al. ATS/CDC/IDSA Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis. 2016;63(7):e147-e195. PMC
  7. [7]Gaultier S, Tazi A, Charre C, et al. Infectious Diseases in Pregnant Women With Haematological Malignancies. Lancet Haematol. 2025;12(10):e836-e849. PubMed
  8. [8]Pappas PG, Kauffman CA, Andes DR, et al. IDSA Guideline for Management of Candidiasis: 2016 Update. Clin Infect Dis. 2016;62(4):e1-50. PMC
  9. [9]Halpern DG, Weinberg CR, Pinnelas R, et al. Medication for Cardiovascular Disease During Pregnancy. J Am Coll Cardiol. 2019;73(4):457-476. PubMed
  10. [10]Gewarges M, Cao A, Alexopoulos K, et al. Management of the Critically Ill Cardiac Patient During Pregnancy. JACC Adv. 2025;4(10):102037. PubMed
  11. [11]Shields AD, Plante LA, Pacheco LD, Louis JM. SMFM Consult Series #67: Maternal Sepsis. Am J Obstet Gynecol. 2023;229(3):B2-B19. ScienceDirect