Respiratory Distress Syndrome Differential Diagnoses

  • Author: Arun K Pramanik, MD, MBBS; Chief Editor: Ted Rosenkrantz, MD   more...
 
Updated: Mar 9, 2012
 
 

Diagnostic Considerations

Conditions to consider in the differential diagnosis of respiratory distress syndrome include the following:

  • Metabolic problems
  • Hematologic problems
  • Pulmonary air leaks
  • Congenital anomalies of the lungs

Differential Diagnoses

Proceed to Workup
 
 
Contributor Information and Disclosures
Author

Arun K Pramanik, MD, MBBS  Professor of Pediatrics, Director of Neonatal Fellowship, Louisiana State University Health Sciences Center

Arun K Pramanik, MD, MBBS is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, National Perinatal Association, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD  Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine

Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

David A Clark, MD Chairman, Professor, Department of Pediatrics, Albany Medical College

David A Clark, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Pediatric Society, Christian Medical & Dental Society, Medical Society of the State of New York, New York Academy of Sciences, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References

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Chest radiographs in a premature infant with respiratory distress syndrome before and after surfactant treatment. Left: Initial radiograph shows poor lung expansion, air bronchogram, and reticular granular appearance. Right: Repeat chest radiograph obtained when the neonate is aged 3 hours and after surfactant therapy demonstrates marked improvement.
Microscopic appearance of lungs of an infant with respiratory distress syndrome. Hematoxylin and eosin stain shows hyaline membranes (pink areas).
Schematic outlines the pathology of respiratory distress syndrome (RDS). Infants may recover completely or develop chronic lung damage, resulting in bronchopulmonary dysplasia (BPD). FiO2 = fraction of inspired oxygen; HMD = hyaline membrane disease; V/Q = ventilation perfusion.
Bar chart demonstrates the composition of lung surfactant. About 1% of the 10% protein component comprises surfactant apoproteins; the remaining proteins are derived from alveolar exudate.
Schematic show surfactant metabolism, with a single alveolus is shown and the location and movement of surfactant components. Surfactant components are synthesized from precursors in the endoplasmic reticulum and transported through the Golgi apparatus by multivesicular bodies. Components are ultimately packaged in lamellar bodies, which are intracellular storage granules for surfactant before its secretion. After secretion (exocytosis) into the liquid lining of the alveolus, surfactant phospholipids are organized into a complex lattice called tubular myelin. Tubular myelin is believed to generate the phospholipid that provides material for a monolayer at the air-liquid interface in the alveolus, which lowers surface tension. Surfactant phospholipids and proteins are subsequently taken back into type II cells, in the form of small vesicles, apparently by a specific pathway that involves endosomes, and then are transported for storage into lamellar bodies for recycling. Alveolar macrophages also take up some surfactant in the liquid layer. A single transit of the phospholipid components of surfactant through the alveolar lumen normally requires a few hours. The phospholipid in the lumen is taken back into type II cell and is reused 10 times before being degraded. Surfactant proteins are synthesized in polyribosomes and extensively modified in the endoplasmic reticulum, Golgi apparatus, and multivesicular bodies. Surfactant proteins are detected in lamellar bodies or secretory vesicles closely associated with lamellar bodies before they are secreted into the alveolus.
Bottom curve reflects findings from lungs obtained at postmortem from an infant with hyaline membrane disease (HMD). Lungs with HMD require far more pressure than to achieve a given volume of inflation than do lungs obtained from an infant dying of a nonrespiratory cause. Arrows indicate inspiratory and expiratory limbs of the pressure-volume curves. Note the decreased lung compliance and increased critical opening and closing pressures, respectively, in the premature infant with HMD.
Effects of early treatment with low-dose inhaled nitric oxide (iNO) on brain injury (ie, grade 3-4 intracranial hemorrhage [ICH], periventricular leukomalacia [PVL], ventriculomegaly) in premature infants according to birth weight strata. iNO reduced ultrasonography findings of brain injury for the overall group (n = 793), with the largest effect in the 750-g to 999-g group (n = 280). Control = □; iNO = ■.
Effects of early treatment of preterm infants with low-dose inhaled nitric oxide (iNO) on bronchopulmonary dysplasia (BPD) incidence by birth weight strata. No difference in reduction was reported in infants weighing less than 1000 g (n = 129). Control = &#9633;; iNO = &#9632;.
Effects of inhaled nitric oxide (iNO) survival without bronchopulmonary dysplasia (BPD) for infants aged 7-21 days. iNO increased survival without BPD in infants who were treated before age 14 days (n = 727).
Table 1. Meta-Analysis of Early Versus Delayed Surfactant Treatment of RDS
OutcomeNumber of



Trials



Relative Risk



(95% CI)



Relative Difference



(95% CI)



Pneumothorax30.70 (0.59, 0.82)-5.2% (-7.5%, -2.9%)
Bronchopulmonary dysplasia (BPD)30.97 (0.88, 1.06)-1.2% (-4.6%, 2.2%)
Mortality40.87 (0.77, 0.99)-2.8% (-5.5%, 0.0%)
BPD or death30.94 (0.88, 1.00)-3.7% (-7.2%, 0.0%)
Table 2. Surfactant Preparations: Type, Source, Composition, Dosages, and Other Information
TypeSourceCompositionDosingComments
Beractant (Survanta)Bovine lung minceDipalmitoyl phosphatidylcholine (DPPC), tripalmitin, SP-B < 0.5%, SP-C 99% of TP wt/wt4mL/kg (100mg/kg), 1-4 doses every 6hRefrigerate
Surfactant-TA (Surfacten)
Bovactant (Alveofact)Bovine lung lavage99% PL, 1% SP-B and SP-C45mg/mLFrom the Federal Republic of Germany
Bovine lipid extract surfactant (bLES)Bovine lung lavage75% phosphatidylcholine (PC) and 1% SP-B and SP-C135mg/kg/dose (5mL/kg), 1-4 doses every 12hCanadian
InfasurfCalf lung lavageDPPC, tripalmitin, SP-B 290g/mL, SP-C 360g/mL3mL/kg (105mg/kg), 1-4 doses every 6-12h6mL vials, refrigerate
Calf lung surfactant extract (CLSE)Similar to Infasurf
Poractant alpha (Curosurf)Minced pig lungPhospholipids (DPPC, phosphatidylglycerol [PG]), neutral lipids, fatty acids; SP-B and SP-C; 80mg/mL of PL/mL [54mg PC (30.5mg DPPC and 1mg protein includes 0.3mg of SP-B)] Initially 2.5mL/kg (200mg/kg), followed by 1.25mL (100mg)/kg1.5 and 3mL
Colfosceril palmitate (Exosurf)Synthetic85% DPPC, 9% hexadecanol, 6% tyloxapol5mL/kg (67.5mg/kg),



1-4 doses every 12h



No longer available; lyophilized, dissolve in 8mL
Lucinactant (Surfaxin)SyntheticProtein: KL4 (sinapultide) resembles SP-B; Phospholipids: DPPC, palmitoyloleoyl phosphatidylcholine (POPG)175 mg/kg/dose phospholipidFDA-approved March 2012; warmed for 15min at 44°C on a heating block, followed by vigorous shaking until a uniform, free-flowing suspension forms
Artificial lung expanding compound (ALEC)Synthetic70% DPPC, 30% unsaturated phosphatidylglycerolNo dataDiscontinued
Table 3. Results of a Meta-Analysis of Separate Clinical Trials of the Treatment of Respiratory Distress Syndrome With Natural or Synthetic Surfactant Preparations
Natural Surfactant TreatmentSynthetic Surfactant Treatment
OutcomeNumber of TrialsRelative Risk (95% Confidence Interval [CI])



Relative Difference (95% CI)



Number of TrialsRelative Risk (95% CI)



Relative Difference (95% CI)



Pneumothorax120.43 (0.35, 0.52)



-17% (-21%, -13%)



50.64 (0.55, 0.76)



-9% (-12%, -6%)



Bronchopulmonary dysplasia (BPD)90.94 (0.72, 1.22)



-2% (-9%, 4%)



50.75 (0.61, 0.92)



-4% (-6%, -1%)



Mortality120.68 (0.57, 0.80)



-9% (-13%, -5%)



60.73 (0.61, 0.88)



-5% (-7%, -2%)



BPD or death100.76 (0.65, 0.90)



-14% (-21%, -7%)



40.73 (0.65, 0.83)



-8% (-11%, -5%)



Table 4. Results of a Meta-Analysis of Separate Clinical Trials of the Prophylactic Use of Natural or Synthetic Surfactant Preparations
Natural ProphylaxisSynthetic Prophylaxis
OutcomeNumber of TrialsRelative Risk (95% CI)



Relative Difference (95% CI)



Number of TrialsRelative Risk (95% CI)



Relative Difference (95% CI)



Pneumothorax80.35 (0.26, 0.49)



-13% (-20%, -11%)



60.67 (0.50, 0.90)



-5% (-9%, -2%)



BPD70.93 (0.80, 1.07)



-4% (-9%, -3%)



41.06 (0.83, 1.36)



1% (-4%, 6%)



Mortality70.60 (0.44, 0.83)



-7% (-12%, -3%)



70.70 (0.58, 0.85)



-7% (-11%, -3%)



BPD or death70.84 (0.75, 0.93)



-10% (-16%, -4%)



40.80 (0.77, 1.03)



-4% (-10%, 1%)



Table 5. Results of a Meta-Analysis of Head-to-Head Trials With Natural Versus Synthetic Surfactants
OutcomeNumber of



Trials



Relative Risk



(95% CI)



Relative Difference



(95% CI)



Pneumothorax50.68 (0.56, 0.83)-4.1% (-6.3%, -2.0%)
BPD40.97 (0.88, 1.07)-1.2% (-5.4%, -2.9%)
Mortality70.88 (0.76, 1.02)-2.2% (-4.7%, 0.4%)
BPD or death20.94 (0.87, 1.01)-3.6% (-8.0%, 0.8%)
Table 6. Meta-Analysis of Clinical Trials Comparing Prophylactic Use of Surfactant Versus Rescue Treatment of Infants With Respiratory Distress Syndrome
OutcomeNumber of



Trials



Relative Risk



(95% CI)



Relative Difference



(95% CI)



Pneumothorax60.62 (0.42, 0.89)-2.1% (-3.7%, -0.55)
BPD70.95 (0.81, 1.11)-0.9% (-3.5%, 1.7%)
Mortality60.59 (0.46, 0.76)-4.6% (-6.8%, -2.5%)
BPD or death70.85 (0.76, 0.95)-4.5% (-7.4%, -1.5%)
Infants < 30 wk of gestation
Mortality60.60 (0.47, 0.77)-6.5% (-9.6%, -3.4%)
BPD or death70.86 (0.77, 0.96)-5.5% (-9.6%, -1.5%)
Table 7. Results of a Meta-Analysis of Clinical Trials to Compare Multiple Doses With a Single Dose of Surfactant
OutcomeNumber of



Trials



Relative Risk



(95% CI)



Relative Difference



(95% CI)



Pneumothorax20.51 (0.30, 0.88)-8.7% (-15.4%, -2.0%)
BPD11.10 (0.63, 1.93)1.2% (-5.8%, 8.3%)
Mortality20.63 (0.57, 1.11)-7.0% (-14%, 0%)
BPD or death10.80 (0.57, 1.11)-6.6%, (-16.2%. 3%)
Table 8. Inhaled Nitric Oxide Therapy in Preterm Infants and Outcome Measures
StudyNumber EnrolledMean



Gestational Age (wk)



Mean



Birth Weight (g)



Mean



Oxygen Index



Placebo



Death Rate



Therapy



Duration (d)



Maximum



Dose



% Change in Death/BPD
Kinsella et al[60] 802710003053%75 ppm-15%
Schreiber et al[61] 20127.29701022.5%710 ppm-15%
Van Meurs et al[62] 420268392244%310 ppm-2%
Ballard et al[63] 5872676076%2420 ppm-11%
Kinsella et al[64] 79325792525%145 ppm-4%
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