Racemic Epinephrine vs Nebulized Saline for Croup
Nebulized racemic epinephrine is significantly superior to nebulized saline for treating moderate to severe croup, providing clinically meaningful symptom reduction within 10-30 minutes, while normal saline nebulization is not recommended as a primary treatment for croup. 1, 2
Evidence for Racemic Epinephrine
Nebulized epinephrine demonstrates clear superiority over saline in the acute treatment of croup. A double-blind RCT showed that racemic epinephrine produced significantly improved clinical scores at 10 minutes (P < 0.01) and 30 minutes (P < 0.05) compared to nebulized saline, though this effect was not sustained at 120 minutes. 2 A Cochrane systematic review confirmed that nebulized epinephrine is associated with clinically and statistically significant transient reduction of croup symptoms 30 minutes post-treatment (SMD -0.94; 95% CI -1.37 to -0.51). 3
Evidence Against Nebulized Saline
Current guidelines explicitly recommend against using normal saline nebulization as a primary treatment for croup. The American Academy of Pediatrics and other major societies support nebulized epinephrine and oral corticosteroids instead, with no role identified for saline nebulization in the treatment algorithm. 1 The British Thoracic Society guidelines note that normal saline may be tried to loosen tenacious secretions in palliative care settings, but acknowledge there is no supporting scientific evidence for this practice. 4
Clinical Application Algorithm
For mild croup: No nebulized treatments are needed—only oral corticosteroids and observation for 2-3 hours. 1
For moderate to severe croup (stridor at rest or respiratory distress):
- Administer nebulized epinephrine 0.5 mL/kg of 1:1000 solution (maximum 5 mL) 1, 5
- Always give oral corticosteroids concurrently 1
- Observe for at least 2 hours after the last epinephrine dose to monitor for rebound symptoms 1, 5
Critical Timing Considerations
The therapeutic effect of nebulized epinephrine is short-lived, lasting only 1-2 hours. 1, 6, 5 This transient benefit explains why the superiority over saline disappears by 120 minutes post-treatment. 2, 3 The Cochrane review found no significant difference in croup scores at two and six hours post-treatment. 3
Essential Pitfalls to Avoid
Never use nebulized epinephrine in outpatient settings where immediate return is not feasible or discharge patients within 2 hours of administration. 1, 6, 5 The risk of rebound symptoms after the 1-2 hour therapeutic window makes premature discharge dangerous. 1, 5
Never use nebulized epinephrine without concurrent corticosteroids. 5 Corticosteroids provide sustained benefit while epinephrine provides rapid but temporary relief. 1
Consider hospital admission if three or more doses of nebulized epinephrine are required. 1, 6, 5 This threshold can reduce hospitalization rates by 37% without increasing revisits or readmissions. 1, 6
Racemic vs L-Epinephrine
There is no clinically significant difference between racemic epinephrine and L-epinephrine. The Cochrane review found no difference in croup scores at 30 minutes (SMD 0.33; 95% CI -0.42 to 1.08), and while L-epinephrine showed statistical superiority at two hours in one RCT, the evidence does not favor one formulation over the other. 3