Racepinephrine hydrochloride

What it is

Racepinephrine hydrochloride is epinephrine supplied as an equal mixture of its two mirror-image forms, rather than the single natural l-form. In the United States it is sold two quite different ways. One is an over-the-counter nebuliser solution whose Drug Facts label gives 11.25 mg of racepinephrine per 0.5 mL vial and describes its purpose as a bronchodilator. The other, and the one with the real trial literature, is nebulised racemic epinephrine given in emergency departments and hospitals for croup and for bronchiolitis in small children. These are separate uses with separate evidence, and the hospital evidence does not transfer to the home product.

What the research says

The hospital evidence is genuinely good and mostly modest. For croup, two systematic reviews agree it improves the croup score about half an hour after a nebulised dose and that the improvement is no longer statistically significant at two hours; the newer of the two says its own two-hour result remains inconclusive, and found no significant shortening of hospital stay. For bronchiolitis, a Cochrane review found fewer same-day admissions among outpatients but no difference in length of stay for inpatients, a later systematic review found the epinephrine-plus-steroid combination ineffective for admissions or length of stay, and a 2026 trial in 26 infants needing respiratory support did not detect a difference in oxygen requirement, though its own authors say it was too small for that to mean the treatments are equivalent. For asthma, a randomised trial in children found no clinical advantage over salbutamol, and a four-person pilot held back until 2014 found the over-the-counter nebulised form gave less bronchoprotection than albuterol. For post-extubation stridor in newborns, a Cochrane review last updated in 2002 found no eligible trials at all.

Evidence grade: Limited evidence.

How it works

Drug class: Non-selective alpha- and beta-adrenergic agonist (catecholamine); a 50:50 mixture of the two mirror-image forms of epinephrine

Racemic epinephrine works on two fronts at once in a swollen airway. A 2025 mini-review describes it as acting through alpha-1 adrenergic vasoconstriction, which shrinks the swollen lining of the upper airway, together with beta-2 mediated relaxation of airway muscle, and reports that this produces a clinically meaningful fall in the Westley croup score within about thirty minutes. The same review stresses that the therapeutic window is transient, roughly 90 to 120 minutes, which is why a steroid is given alongside it. (Source 1)

What it is used for

• Two systematic reviews find a real but short-lived improvement in croup score 30 minutes after a dose. The 2013 Cochrane review found the effect no longer significant at two and six hours; the 2026 update found it no longer statistically significant at two hours but says in its own conclusion that the sustained effect remains inconclusive because its sensitivity analysis was unstable. On hospital stay the two disagree: the 2013 review's single contributing trial found a significantly shorter stay (mean difference -32.0 hours), while the 2026 update pooling 12 studies found no significant reduction (mean difference -25.1 hours, 95% CI -52.34 to 2.15, P = 0.07). Both reviews say the trials are few and small. This is the hospital or emergency-department nebulised use, not the indication on the over-the-counter label. Evidence: limited. (Source 2)
• A Cochrane review found fewer admissions on the day of the emergency visit but not a week later, no difference in length of stay for children already admitted, and no evidence of effectiveness for repeated or prolonged dosing among inpatients. A 2017 systematic review of five trials found the epinephrine-plus-corticosteroid combination ineffective for hospital admission and length of stay, though it did report a statistically significant secondary benefit on oxygen saturation. A 2026 single-blind trial in 26 infants needing respiratory support did not detect a difference in oxygen requirement, but its own authors say an unpowered null must not be read as equivalence. An older randomised trial found racemic epinephrine relieved respiratory distress better than nebulised salbutamol without shortening the stay. Evidence: disputed. (Source 3)
• This is the labelled over-the-counter use: 21 CFR 341.16 lists racepinephrine hydrochloride among the bronchodilator active ingredients permitted without a prescription, under a rule dated 2 October 1986. The trial evidence is weak and indirect. A randomised double-blind trial in 120 children aged 1 to 17 with mild to moderate acute asthma, all of whom also received oral steroids, found no significant clinical benefit of nebulised racemic epinephrine over salbutamol and concluded salbutamol remains the treatment of choice in children with known asthma - a hospital comparison of two nebulised drugs, not a test of buying a product to self-treat. A separate unrandomised four-subject pilot found the approximate non-prescription dose gave less protection against methacholine-induced airway narrowing than albuterol and said it may be less effective in treating acute bronchospasm. We found no trial of the over-the-counter product in its labelled setting. Evidence: not-supported. (Source 4)
• The current version of a Cochrane review, updated in 2002 with searches run to September 2001, found no trials that met its criteria and concluded there is no evidence either supporting or refuting the practice. Its own background records that the practice is routine in some neonatal units and is recommended for neonates with post-extubation tracheal obstruction and stridor in neonatal and respiratory textbooks and reviews. A single case report shows the practice in use in a newborn and describes localised facial blanching as a complication. The absence of evidence is a position dated 2002, not a current search. Evidence: unknown. (Source 5)

Interactions

• Monoamine oxidase inhibitors (MAOIs) (label): The over-the-counter label says not to use it at all while taking a prescription MAOI, or within two weeks of stopping one. MAOIs slow the breakdown of catecholamines, so adding a catecholamine drug risks an exaggerated cardiovascular response. (Source 6)
• Caffeine in food and drink (label): The label tells people to avoid caffeinated food and drink while using the product. The concern is additive stimulant effect. This is labelling, not the result of an interaction study. (Source 7)
• Dietary supplements with stimulant ingredients (label): The label tells people to avoid supplements whose ingredients are reported or claimed to be stimulants. No individual supplement is named, so this is a class-level caution rather than evidence about a particular product. (Source 7)
• Other medicines containing phenylephrine, pseudoephedrine, ephedrine or caffeine (label): The label directs anyone taking a medicine with these ingredients, for allergy, cough and cold or pain, to ask a doctor or pharmacist first, because they act on the same adrenergic system. (Source 8)
• Prescription asthma, weight-control and psychiatric medicines (label): The label directs anyone already taking prescription drugs for asthma, obesity, weight control, depression or psychiatric or emotional conditions to ask a doctor or pharmacist before using it. (Source 8)
• Corticosteroids given at the same time (a deliberate combination, not a clash) (clinical trial): In croup a steroid is normally given alongside, because the epinephrine effect is short. A 2025 mini-review frames the combination as necessary for sustained symptom control and says the transient window makes careful monitoring necessary. What the combination does in bronchiolitis is a separate question and is reported under findings with its own source. (Source 1)

Stopping it

• The main stopping issue is that the effect wears off rather than that the drug is hard to come off. The croup score benefit is no longer statistically significant at two hours in both systematic reviews, and the newer one calls the sustained effect inconclusive; a 2025 mini-review puts the therapeutic window at roughly 90 to 120 minutes, which is why children are watched afterwards and given a steroid. (Source 1)
• How long a child is observed after a dose before going home appears to matter. A retrospective chart review found treatment failure - defined by its authors as needing a second racemic epinephrine treatment and/or returning to the emergency department for croup symptoms within 24 hours of discharge - in 16.7% of children observed for 2.1 to 3 hours against 7.1% of those observed for 3.1 to 4 hours. (Source 9)
• No withdrawal syndrome, rebound or dependence has been described for nebulised racemic epinephrine in the trial literature we searched. The Cochrane croup review could not even report adverse effects, because none of its trials collected them, so the absence of a withdrawal signal reflects an absence of measurement as much as an absence of effect. (Source 2)

What goes wrong

A case report describes a small myocardial infarction in a child given multiple nebulised doses of racemic epinephrine for severe croup, with ventricular tachycardia during one treatment. (Source 10)

• Case report, Very low certainty.
• Size: 1 child.
• Who: a paediatric patient with croup syndrome and severe respiratory distress in an emergency department.
• How long: multiple doses during a single emergency department visit.
• Result: Ventricular tachycardia and chest discomfort during a treatment, persistently abnormal ECGs and raised CPK-MB, with a stress nuclear study showing a small myocardial infarct in an anatomically normal heart.
• Funding: not stated.

The patient developed ventricular tachycardia and mild chest discomfort during one treatment

A case report describes localised facial blanching in a newborn treated with nebulised racemic epinephrine for post-extubation stridor, from the drug being absorbed through the skin. (Source 11)

• Case report, Very low certainty.
• Size: 1 term infant.
• Who: a term newborn treated for post-extubation stridor.
• How long: single episode.
• Result: Localised facial blanching; local application of heat restored circulation to the afflicted area.
• Funding: not stated.

A term infant treated for post-extubation stridor with nebulized racemic epinephrine developed localized facial blanching

The croup evidence base contains no adverse-effect data at all, because none of the included trials looked for it, so the apparent safety record for that use rests on an absence of measurement. (Source 2)

• Systematic review, Low certainty.
• Size: eight studies, 225 participants.
• Who: children with moderate to severe croup.
• How long: not applicable.
• Result: No adverse-effect data available from any included trial.
• Funding: not stated in the abstract (Cochrane review)

None of the studies sought or reported data on adverse effects.

The over-the-counter label carries the same cardiovascular warning as the epinephrine inhaler: blood pressure or heart rate may rise, which it says could increase the risk of heart attack or stroke and may cause death. (Source 7)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: people buying the nebuliser solution over the counter in the US.
• How long: label version published 28 January 2026.
• Result: No rate given on the label.
• Funding: not applicable.

Your blood pressure or heart rate may go up. This could increase your risk of heart attack or stroke, which may cause death. Your risk of heart attack or stroke increases if you: Have a history of high blood pressure or heart disease Take this product more frequently or take more than the recommended dose.

A retrospective chart review of children discharged after racemic epinephrine for croup found treatment failure more than twice as likely when the observation period before discharge was shorter. (Source 9)

• Cohort study, Very low certainty.
• Size: retrospective chart review; the primary analysis compared two observation windows.
• Who: children given racemic epinephrine for croup and managed as outpatients.
• How long: observation of 2.1 to 3 hours versus 3.1 to 4 hours, with failure counted within 24 hours of discharge.
• Result: Treatment failure 16.7% after 2.1 to 3 hours of observation against 7.1% after 3.1 to 4 hours (odds ratio 2.44, P < .01); no total number of charts and no confidence interval for the odds ratio is given in the abstract.
• Funding: not stated in the abstract.

Limit of this finding: "Treatment failure" here is a composite the authors defined as needing a second racemic epinephrine treatment and/or returning to the emergency department for croup symptoms within 24 hours of discharge, so the 24-hour window applies only to the return limb. The abstract gives no total number of charts and no confidence interval, so the precision of the 2.44 cannot be judged from it.

The patients in the 2.1- to 3-hour group had a higher rate of treatment failure

The over-the-counter label tells anyone who is pregnant or breast-feeding to ask a health professional before using it. (Source 12)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: people buying the nebuliser solution over the counter in the US.
• How long: label version published 28 January 2026.
• Result: No rate or outcome given; the label states only that a health professional should be asked first.
• Funding: not applicable.

If pregnant or breast-feeding, ask a health professional before use.

The same label's Warnings section tells people to keep it out of reach of children and, in case of overdose, to get medical help or contact a Poison Control Center right away. (Source 13)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: households where the nebuliser solution is kept.
• How long: label version published 28 January 2026.
• Result: No rate given; the label treats overdose as a reason for immediate medical help.
• Funding: not applicable.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away.

What the evidence supports

A Cochrane review found nebulised epinephrine improved the croup score 30 minutes after treatment, with no heterogeneity between the three contributing trials. (Source 2)

• Systematic review, Low certainty.
• Size: eight studies, 225 participants in total; the 30-minute result came from three randomised trials.
• Who: children with moderate to severe croup, average age under two in most of the included studies, mostly inpatients.
• How long: single treatments, outcomes at 30 minutes, two hours and six hours.
• Result: Standardised mean difference -0.94 (95% CI -1.37 to -0.51), I-squared 0%; shorter hospital stay in one trial, mean difference -32.0 hours (95% CI -59.1 to -4.9)
• Funding: not stated in the abstract (Cochrane review)

Nebulized epinephrine was associated with croup score improvement 30 minutes post-treatment (three RCTs, standardized mean difference (SMD) -0.94; 95% confidence interval (CI) -1.37 to -0.51; I(2) statistic = 0%).

In the bronchiolitis literature, where adverse events were recorded, the reviews report no important differences from comparators. (Source 3)

• Systematic review, Low certainty.
• Size: 19 studies, 2256 participants (Cochrane 2011)
• Who: children under two with acute viral bronchiolitis.
• How long: across included trials.
• Result: No important differences in adverse events reported.
• Funding: not stated in the abstract (Cochrane review)

There were no important differences in adverse events.

What the evidence does not support

In its Authors' conclusions the same review calls the reduction transient, says the evidence does not favour racemic over L-epinephrine or positive-pressure delivery over simple nebulisation, and warns that the analysis rested on very few, very small studies with most outcomes coming from single studies. (Source 14)

• Systematic review, Low certainty.
• Size: eight studies, 225 participants.
• Who: children with moderate to severe croup.
• How long: outcomes at two and six hours after treatment.
• Result: No effect estimate is given in this section. The two- and six-hour non-significance and the racemic-versus-L-epinephrine comparison at 30 minutes (SMD 0.33; 95% CI -0.42 to 1.08) are reported in the review's Main results and are carried by the sibling reference cochrane2013-croup-main, not here.
• Funding: not stated in the abstract (Cochrane review)

The authors note that data and analyses were limited by the small number of relevant studies and total number of participants and thus most outcomes contained data from very few or even single studies.

That review found no statistically significant shortening of hospital stay and said routine use for that purpose is not supported. (Source 15)

• Systematic review, Low certainty.
• Size: 12 studies, 672 patients in total.
• Who: children with croup.
• How long: hospital stay.
• Result: Mean difference -25.1 hours (95% CI -52.34 to 2.15), P = 0.07, confidence interval crossing zero.
• Funding: not stated in the abstract.

No significant reduction in hospital stay was observed (P = 0.07). Routine use for shortening hospital stay is not supported by current evidence, although it remains a valuable early intervention in moderate-to-severe acute settings.

The same review concluded there is no evidence of effectiveness for repeated dosing or prolonged use of epinephrine, or of epinephrine and dexamethasone combined, among children already admitted to hospital. (Source 16)

• Systematic review, Low certainty.
• Size: 19 studies, 2256 participants.
• Who: inpatient children under two with bronchiolitis.
• How long: repeated and prolonged dosing.
• Result: No effectiveness demonstrated for repeated dose or prolonged use.
• Funding: not stated in the abstract (Cochrane review)

There is no evidence of effectiveness for repeated dose or prolonged use of epinephrine or epinephrine and dexamethasone combined among inpatients.

A 2017 systematic review of five randomised trials found adding a corticosteroid to epinephrine did not reduce hospital admission or length of stay in infants with bronchiolitis. (Source 17)

• Systematic review, Moderate certainty.
• Size: 5 randomised controlled trials, 1,157 patients.
• Who: infants under 24 months with bronchiolitis.
• How long: hospital admission rate and length of stay as primary outcomes.
• Result: No significant difference in the primary outcomes; hospitalisation reduced in only one of five studies, with pooled data showing no benefit over epinephrine plus placebo; oxygen saturation mean difference -0.70 (95% CI -1.17 to -0.22, p = 0.004)
• Funding: not stated in the abstract.

Limit of this finding: One number in this review is printed in a way that reads backwards: it reports that "combination therapy was more effective at improving oxygen saturation level (mean difference: -0.70; 95% confidence interval: -1.17 to -0.22, p = 0.004)", pairing a negative mean difference with an improvement. That is the review's own sign convention, which we have not altered. The primary outcomes - hospital admission and length of stay - were null; the oxygen-saturation result is a secondary outcome.

Combination treatment of epinephrine and dexamethasone was ineffective in reducing hospital admission and length of stay among infants with bronchiolitis.

A 2026 randomised, single-blind, placebo-controlled trial in 26 infants needing respiratory support did not detect a difference in oxygen requirement, oxygen saturation, respiratory rate or heart rate; the trial was unpowered and its analyses exploratory, and its authors say the null must not be read as equivalence. (Source 18)

• Randomized trial, Very low certainty.
• Size: 26 infants (13 per arm)
• Who: infants aged 0 to 12 months with moderate-to-severe bronchiolitis requiring respiratory support.
• How long: outcomes at baseline, day 3 and day 6.
• Result: Adjusted day-6 difference in inspired oxygen fraction -0.43 percentage points (95% CI -3.43 to 2.57; p = 0.772); non-significant for oxygen saturation (p = 0.058), respiratory rate (p = 0.093) and heart rate (p = 0.487)
• Funding: independent (the paper's Funding Statement reads "This research received no external funding." and its Conflicts of Interest section reads "The authors declare no conflicts of interest.")

Limit of this finding: This trial randomised 26 infants at one centre, was only single-blind, was not prospectively registered, and its own abstract says the outcome hierarchy was not chosen in advance. Its authors write that non-significant findings should not be interpreted as proof of equivalence. The oxygen-saturation result it folds into "no difference" was p = 0.058, which is borderline rather than flat. It is reported here because it is the most recent placebo-controlled test and points the same way as the larger reviews, not as a demonstration that the drug does nothing.

Nebulized racemic epinephrine did not improve the trajectories of oxygen requirement, SpO2, RR, or HR compared with placebo; improvements over time were observed in both groups.

A randomised double-blind trial in 120 children aged 1 to 17 with mild to moderate acute asthma, all of whom also received oral steroids, found no clinical benefit of nebulised racemic epinephrine over salbutamol, and more minor side effects in the epinephrine group. (Source 19)

• Randomized trial, Moderate certainty.
• Size: 120 patients randomised.
• Who: children aged 1 to 17 with mild to moderate acute asthma in an emergency department, all given oral steroids.
• How long: nebulised treatments at 0, 20 and 40 minutes.
• Result: No significant difference in change in pulmonary index score, length of stay, hospital admission or relapse rate; significantly more minor side effects in the epinephrine group, such as excess or brownish nasal discharge.
• Funding: not stated in the abstract.

Limit of this finding: The trial reports no effect sizes, confidence intervals or p values for these outcomes - only the words "no significant difference" - so this is an unquantified null in 120 children and is not evidence that the two treatments are equivalent. It also compared two nebulised drugs in an emergency department in children who all received oral steroids as well, which is a different setting, comparator and co-treatment from buying a product off a shelf to self-treat mild asthma.

There was no significant difference between treatments in the change in PIS, length of stay, admission to hospital, or relapse rate. The epinephrine-treated group had significantly more minor side effects (such as excess or brownish nasal discharge).

A four-subject unrandomised pilot, run in 2001 and published only in 2014 once the over-the-counter nebuliser product reached the market, found the approximate non-prescription dose gave less protection against methacholine-induced airway narrowing than albuterol, and its authors said it may be less effective in treating acute bronchospasm. (Source 20)

• Case series, Very low certainty.
• Size: 4 subjects completed the pilot; no randomisation and no parallel control group.
• Who: adults aged 18 to 45 with mild stable asthma, each tested without pretreatment and then on separate days after albuterol and after each of four ascending racepinephrine doses.
• How long: methacholine challenges on separate days, 15 minutes after each treatment.
• Result: Geometric mean provocative methacholine concentration causing a 20% fall in FEV1 was 44 mg/mL (95% CI 23 to 85) after albuterol versus 10.2 mg/mL (95% CI 3.5 to 30) after the 10 mg racepinephrine dose closest to the non-prescription dose (P = .001); no adverse effects.
• Funding: not stated in the abstract; the authors note the study was conducted in 2001 and never published until the product was promoted as a Primatene replacement.

Limit of this finding: This was a four-person open-label dose-ranging pilot using a methacholine challenge as a surrogate, not a test of symptom relief during an asthma attack, and PubMed types it a Clinical Trial rather than a Randomized Controlled Trial. No value on our design list describes an unrandomised, uncontrolled interventional crossover of this kind, so it is recorded as case-series, the closest non-randomised human-study value, and the real design is spelled out here.

RE provides less bronchoprotection from methacholine than does albuterol and may be less effective in treating acute bronchospasm.

The current version of a Cochrane review of nebulised racemic epinephrine after extubation in newborn infants, updated in 2002, found that no study met its inclusion criteria, despite the practice being routine in some neonatal units. (Source 21)

• Systematic review, Very low certainty.
• Size: no studies met the inclusion criteria.
• Who: newborn infants weaned from intermittent positive pressure ventilation and extubated.
• How long: searches run to September 2001.
• Result: No evidence either supporting or refuting the practice.
• Funding: not stated in the abstract (Cochrane review)

Limit of this finding: This is a dated position, not the current state of the evidence. The newest version of this review is from 2002 and its searches ran only to September 2001, so "no evidence" means no trial had been published by then. The 2000, 2001 and 2002 versions all share one DOI, which resolves to the 2002 version; that version spells "nebulized" the American way, which is what is quoted here.

There is no evidence either supporting or refuting

A retrospective single-centre comparison did not observe any statistically significant difference between l-epinephrine by metered-dose inhaler and nebulised racemic epinephrine for croup; with 38 inhaler encounters and no stated non-inferiority margin, that is not evidence the two are equivalent. (Source 22)

• Cohort study, Very low certainty.
• Size: 325 patients analysed, of which 38 encounters used the metered-dose inhaler; the two arms are very unequal.
• Who: children aged 1 to 10 diagnosed with croup at a single centre between March 2020 and July 2023; the study was retrospective but the l-epinephrine data were collected prospectively, so the two arms were not ascertained the same way.
• How long: outcomes including repeat dosing, heart rate change, return to care within 48 hours and admission.
• Result: No statistical difference in need for repeat dosing, change in heart rate, return to care within 48 hours or hospital admission. The paper prints the inhaler group's 30-minute Westley Croup Score change as an improvement "of 2 (IQR: -3, -2)" - see the caveat on that interval.
• Funding: not stated in the abstract.

Limit of this finding: Two things to hold in mind. First, the paper prints an interval that cannot be right: a median improvement of 2 with an interquartile range of -3 to -2 puts the median outside its own interval. Both Europe PMC and NCBI return exactly that text, so the inconsistency is the journal's; the authors appear to have meant a median change of -2, that is a 2-point improvement. We have kept the source's words and do not restate the figure as fact. Second, the study was not powered or designed as an equivalence trial - its stated aim was to show l-epinephrine by inhaler is effective and safe - so finding no significant difference across 38 inhaler encounters does not show the two formulations are the same.

we did not observe any statistically significant differences compared to nebulized racemic epinephrine in the treatment of croup.

That trial's own conclusion is bounded: it says there is no significant clinical benefit of nebulised epinephrine over salbutamol in children aged 1 to 17 with MILD TO MODERATE acute asthma, and that salbutamol remains the treatment of choice in children with KNOWN asthma. (Source 23)

• Randomized trial, Moderate certainty.
• Size: 120 patients randomised.
• Who: children aged 1 to 17 with mild to moderate acute asthma in an emergency department, all of whom also received oral steroids.
• How long: nebulised treatments at 0, 20 and 40 minutes.
• Result: No numbers are given in this section; the conclusion is a statement bounded by severity and by known asthma.
• Funding: not stated in the abstract.

Limit of this finding: The restrictions in this sentence matter. The trial was in children with already-diagnosed, mild to moderate asthma, treated in an emergency department with two nebulised drugs while also receiving oral steroids. The over-the-counter indication is self-treatment of mild intermittent asthma at home, so reading this trial across to that setting is an extrapolation across setting, comparator and co-treatment.

There is no significant clinical benefit of nebulized epinephrine over salbutamol in children 1-17 years old with mild to moderate acute asthma. Salbutamol remains the treatment of choice in children with known asthma.

Where the evidence is mixed

An updated 2026 systematic review reproduced the 30-minute croup score benefit; at two hours the between-group difference was no longer statistically significant. (Source 24)

• Systematic review, Low certainty.
• Size: 12 studies, 325 patients in treatment groups and 347 in control groups.
• Who: children treated with nebulised epinephrine for croup.
• How long: outcomes at 30 minutes and 2 hours, plus hospital stay.
• Result: SMD -1.48 (95% CI -2.83 to -0.13) at 30 minutes; SMD -0.51 (95% CI -1.11 to 0.09) at 2 hours.
• Funding: not stated in the abstract; protocol registered with PROSPERO (CRD420251160013)

Limit of this finding: The review's Results section says the 30-minute effect "was not sustained", but its own Conclusion is more cautious: it says the sustained effect at 2 hours "remains inconclusive due to unstable sensitivity analysis". Read this as the effect not being demonstrated at two hours, not as a demonstration that it has gone.

The meta-analysis revealed that nebulised epinephrine significantly improved croup severity score at 30 min post-administration (SMD = -1.48, 95% CI [-2.83, -0.13]). However, this effect was not sustained. At 2 h, the between group difference was no longer statistically significant (SMD = -0.51, 95% CI [-1.11, 0.09]).

A Cochrane review of epinephrine in bronchiolitis found fewer admissions on the day of the emergency visit but not a week later, and no difference in length of stay for children already in hospital. (Source 3)

• Systematic review, Low certainty.
• Size: 19 studies, 2256 participants.
• Who: children under two years old with acute viral bronchiolitis, outpatients and inpatients analysed separately.
• How long: admissions at day 1 and day 7; length of stay for inpatients.
• Result: Risk ratio 0.67 (95% CI 0.50 to 0.89) for admission at day 1 versus placebo among outpatients; no difference at day 7; no difference in length of stay for inpatients.
• Funding: not stated in the abstract (Cochrane review)

Epinephrine versus placebo among outpatients showed a significant reduction in admissions at Day 1 (risk ratio (RR) 0.67; 95% confidence interval (CI) 0.50 to 0.89) but not at Day 7 post-emergency department visit. There was no difference in LOS for inpatients.

The largest single trial reported absolute admission rates that look modest beside its relative risk, and the one apparently significant result did not survive adjustment for multiple comparisons. (Source 25)

• Randomized trial, Moderate certainty.
• Size: 800 infants aged 6 weeks to 12 months.
• Who: infants with bronchiolitis seen in paediatric emergency departments, randomised to four groups.
• How long: hospital admission within 7 days of enrolment.
• Result: Admitted by day 7: 34 (17.1%) epinephrine plus dexamethasone, 47 (23.7%) epinephrine alone, 51 (25.6%) dexamethasone alone, 53 (26.4%) placebo; relative risk 0.65 (95% CI 0.45 to 0.95, P=0.02) unadjusted, P=0.07 after adjustment for multiple comparisons; no serious adverse events.
• Funding: not stated in the abstract.

By the seventh day, 34 infants (17.1%) in the epinephrine-dexamethasone group, 47 (23.7%) in the epinephrine group, 51 (25.6%) in the dexamethasone group, and 53 (26.4%) in the placebo group had been admitted to the hospital. In the unadjusted analysis, only the infants in the epinephrine-dexamethasone group were significantly less likely than those in the placebo group to be admitted by day 7 (relative risk, 0.65; 95% confidence interval, 0.45 to 0.95, P=0.02). However, with adjustment for multiple comparisons, this result was rendered insignificant (P=0.07).

A randomised trial in hospitalised infants found racemic epinephrine relieved respiratory distress better than nebulised salbutamol - there was no placebo arm - and did not shorten the hospital stay. (Source 26)

• Randomized trial, Low certainty.
• Size: 62 children, mean age 6.4 months, 80% with respiratory syncytial virus.
• Who: previously well children aged 6 weeks to 2 years admitted with bronchiolitis, randomised against nebulised salbutamol, with no placebo group.
• How long: treatments every one to four hours during the admission, with parental follow-up one week after discharge.
• Result: Significant improvement in wheezing and total RDAI score on day 2 and over the stay (p < 0.05); mean length of stay 2.6 days (95% CI 2, 3.2) versus 3.4 days on salbutamol (95% CI 2.6, 4.2) (p > 0.05); adverse events not significantly different.
• Funding: not stated in the abstract.

Racemic epinephrine relieves respiratory distress in hospitalized infants with bronchiolitis and is safe but does not abbreviate hospital stay.

The authors of that 2026 trial state in their own limitations that it had no formal prior sample-size calculation, had limited power, and that its non-significant findings should not be interpreted as proof of equivalence. (Source 27)

• Randomized trial, Very low certainty.
• Size: 26 infants at a single centre.
• Who: infants aged 0 to 12 months with moderate-to-severe bronchiolitis requiring respiratory support, in one paediatric intensive care unit.
• How long: outcomes at baseline, day 3 and day 6.
• Result: No a priori power calculation; endpoint hierarchy and analysis plan not prospectively prespecified; trial not prospectively registered; single-blind design with clinician-directed supportive care; chance baseline imbalances in age and breastfeeding status.
• Funding: independent (the paper's Funding Statement reads "This research received no external funding." and its Conflicts of Interest section reads "The authors declare no conflicts of interest.")

This single-center trial included only 26 participants and had no formal a priori sample-size calculation; consequently, it had limited power to detect modest treatment effects, and non-significant findings should not be interpreted as proof of equivalence.

In that study "failure of treatment" was a composite: needing a second racemic epinephrine treatment, or returning to the paediatric emergency department for croup symptoms within 24 hours of discharge, or both. (Source 28)

• Cohort study, Very low certainty.
• Size: retrospective chart review; no total stated in the abstract.
• Who: children with croup who required racemic epinephrine at one paediatric emergency department.
• How long: failure counted up to 24 hours after discharge.
• Result: Definition only; no numbers in this section.
• Funding: not stated in the abstract.

Failure of treatment was defined as requiring a second RE treatment and/or returning to the pediatric emergency department for croup symptoms within 24 hours of discharge.

The same retrospective study reported a 30-minute improvement in the Westley Croup Score in the metered-dose-inhaler group, but the interval it prints beside that figure is internally inconsistent, so the size of the improvement cannot be taken from it. (Source 29)

• Cohort study, Very low certainty.
• Size: 325 patients analysed, 38 encounters treated with the metered-dose inhaler.
• Who: children aged 1 to 10 with croup at a single centre; median age 2.6 years, 75% male, 14% positive for SARS-CoV-2.
• How long: score measured 30 minutes after administration.
• Result: The paper prints "an improvement in Westley Croup Score (WCS) of 2 (IQR: -3, -2) at 30 minutes post-administration"
• Funding: not stated in the abstract.

Limit of this finding: The paper prints the 30-minute Westley Croup Score change as an improvement of 2 with an interquartile range of -3 to -2, which places the median outside its own interval. Both Europe PMC and NCBI return exactly that text, so the inconsistency is the journal's and not ours; the authors appear to have meant a median change of -2, that is a 2-point improvement. The figure is quoted as printed and is not restated here as fact.

Patients that received LEM showed an improvement in Westley Croup Score (WCS) of 2 (IQR: -3, -2) at 30 minutes post-administration.

Where the research disagrees

Whether racemic epinephrine belongs on a shop shelf as a non-prescription asthma treatment

• US Food and Drug Administration, over-the-counter bronchodilator monograph, regulatory monograph, source note [51 FR 35339, Oct. 2, 1986]; a position, not trial evidence: "The active ingredients of the product consist of any of the following when used within the dosage limits established for each ingredient:" with racepinephrine hydrochloride listed at paragraph (g) (Source 30)
• Mondal and colleagues, Journal of Allergy and Clinical Immunology: In Practice (2014), unrandomised, open-label, four-subject ascending-dose crossover pilot using a methacholine challenge as a bioassay, conducted in 2001 and published only when the product reached the market: "RE provides less bronchoprotection from methacholine than does albuterol and may be less effective in treating acute bronchospasm." (Source 20)

Whether nebulised epinephrine shortens hospital stay in croup

• Bjornson and colleagues, Cochrane Database of Systematic Reviews (2013), systematic review, but the hospital-stay result comes from a single randomised trial: "Nebulized epinephrine was associated with significantly shorter hospital stay than placebo (one RCT, MD -32.0 hours; 95% CI -59.1 to -4.9)." (Source 2)
• Authors of the 2026 updated systematic review, Frontiers in Pediatrics, updated systematic review and meta-analysis of 12 studies, PROSPERO-registered: "Routine use for shortening hospital stay is not supported by current evidence, although it remains a valuable early intervention in moderate-to-severe acute settings." (Source 15)

How much

• Reference intake: For the hospital use the amount is decided by the treating clinician and the trials differ; the doses individual trials gave are recorded under studied, each with its own source. For the over-the-counter product the amount is fixed by the Drug Facts label, which states 1 to 3 inhalations not more often than every 3 hours for adults and children 4 and over, and says children under 4 should ask a doctor. Recorded as labelling, not advice. (Source 31)
• Upper limit: The over-the-counter label's ceiling is 12 inhalations in 24 hours, and its Asthma alert treats needing more than that, or more than 9 inhalations a day on three or more days a week, as a reason to see a doctor rather than a higher permitted dose. (Source 31)
• Studied: In the 800-infant bronchiolitis trial one of the four groups received two nebulised treatments of 3 mL of epinephrine in a 1:1000 solution per treatment together with six oral doses of dexamethasone (1.0 mg per kilogram of body weight in the emergency department and 0.6 mg per kilogram for an additional 5 days). A second group received nebulised epinephrine with oral placebo, a third oral dexamethasone with nebulised placebo and a fourth placebo only, so only about a quarter of the 800 infants received the combined regimen. (Source 32)
• Studied: The over-the-counter nebuliser vial contains 11.25 mg of racepinephrine in 0.5 mL; the 2014 pilot tested 2.5, 5, 10 and 20 mg against 1.25 mg of nebulised albuterol, treating 10 mg as the approximate non-prescription dose. (Source 33)
• Studied: The 2026 placebo-controlled trial allocated 26 infants 1:1 to nebulised racemic epinephrine or isotonic saline placebo in a single-blind, single-centre design, with outcomes at baseline, day 3 and day 6; its abstract states the outcome hierarchy was not prospectively prespecified. The treatment itself was 0.02 mL/kg of a 1% solution diluted to 6 mL with normal saline every 6 hours, continued through day 6, so the drug was still being given at both follow-up assessments. (Source 34)

A common belief, and what the research shows

The belief: A nebulised dose of racemic epinephrine fixes croup.

What the research shows: It buys about half an hour. The 2013 Cochrane review's own conclusion is that "Nebulized epinephrine is associated with clinically and statistically significant transient reduction of symptoms of croup 30 minutes post-treatment." The 2026 update agrees and adds that "At 2 h, the between group difference was no longer statistically significant (SMD = -0.51, 95% CI [-1.11, 0.09])." Its conclusion is careful about what that means, saying the sustained effect at two hours "remains inconclusive due to unstable sensitivity analysis". That is why a steroid is given with it and why children are observed afterwards: a retrospective chart review found treatment failure - a second dose or a return within 24 hours of discharge - in 16.7% of children observed for 2.1 to 3 hours.

Questions and answers

What is it?

Racepinephrine hydrochloride is epinephrine made as an equal mixture of its two mirror-image forms rather than the single natural form. One version is a small vial of solution, 11.25 mg in 0.5 mL, sold over the counter in the US to be breathed in from a nebuliser. The other, and the one with the real evidence behind it, is the nebulised solution used in hospitals for croup and bronchiolitis in small children. (Source 33)

What does it do in the body?

In a swollen airway it does two things at once. Through alpha-1 receptors it constricts blood vessels, which shrinks the swollen lining of the upper airway, and through beta-2 receptors it relaxes the muscle around the airways. A 2025 mini-review reports this producing a fall of two to three points in the Westley Croup Score within about thirty minutes of administration. (Source 1)

Is it good or bad for you?

Good in the right place, poor value in the wrong one. For a child with moderate or severe croup in an emergency department it reliably buys about half an hour of easier breathing while a steroid starts working. Beyond that the picture thins out fast: the 2026 systematic review found the 30-minute improvement no longer statistically significant at two hours and calls its sustained effect inconclusive, found no significant reduction in hospital stay, and says routine use for shortening hospital stay is not supported. The bronchiolitis evidence is largely null, and for asthma a randomised trial in 120 children found no clinical benefit over salbutamol while a four-person pilot found the approximate non-prescription dose gave less protection against methacholine-induced airway narrowing than albuterol. (Source 15)

How do you get more of it?

There is no food or supplement route; it is a manufactured drug solution. The nebuliser vials are sold over the counter in US pharmacies - the regulatory basis for that is recorded separately in this entry, citing 21 CFR 341.16 - and the hospital form is given by a clinician. The label states the labelled amount and frequency, recorded here as the manufacturer's position rather than advice. (Source 31)

If it is harmful, what reduces it?

Nothing is needed to clear it. The effect itself is short - the figure for the therapeutic window is recorded under what it does, from a 2025 mini-review - and what the evidence focuses on is watching the child while it wears off rather than removing the drug. For the over-the-counter product the label's position is that needing it repeatedly is a reason to stop and see a doctor, not to take more. (Source 35)

Why might someone be low in it or missing it?

This does not apply in the usual sense. Epinephrine is a hormone the body makes; nobody is deficient in the molecule, and the racemic mixture is a manufactured formulation that only exists in a medicine. What does vary is access to it: a 2025 mini-review notes important disparities in global accessibility and cost-effectiveness between the racemic and single-isomer formulations. (Source 1)

Which whole foods contain it or feed it?

None. No whole food contains racepinephrine hydrochloride and nothing in the diet feeds it, because it is a synthetic drug solution. The only food-related instruction on the label points the other way: avoid caffeinated food and drink, and stimulant supplements, while using it. (Source 7)

We searched: Europe PMC searches for racemic epinephrine and racepinephrine with dietary or food sources, plus the complete Drug Facts label; no food source is described anywhere, and the only food content on the label is a caffeine caution.

What happens if you do not have it?

Not having it is not a deficiency. For croup, what it provides is a short bridge before steroids take effect, so going without means a child with severe croup has nothing acting in the first half hour. For bronchiolitis the primary outcomes were null: a 2017 systematic review of five trials found no significant differences in hospital admission or length of stay for epinephrine plus a corticosteroid. That review did report a statistically significant secondary benefit on oxygen saturation (p = 0.004) and improvement in clinical severity scores in each of the five trials assessed individually, so saying nothing at all is lost would overstate it. (Source 36)

How can you test for it?

There is no blood test for whether you have enough of it, and none is used. What is measured instead is the child's breathing, scored on a croup severity scale: a 2025 mini-review describes a clinically significant fall of two to three points in the Westley Croup Score within about thirty minutes as the expected response, and the croup reviews pool severity scores of that kind. Those scores are observer-rated. The 2013 Cochrane review judged six of its eight studies at low risk of bias and the remaining two unclear, but warned that most of its outcomes rested on very few or even single studies - neither review attaches a GRADE certainty rating. (Source 1)

References

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2. The Cochrane database of systematic reviews. Nebulized epinephrine for croup in children — Main results section of the abstract. 2013. PMID 24114291, DOI 10.1002/14651858.cd006619.pub3. Read the source
3. The Cochrane database of systematic reviews. Epinephrine for bronchiolitis — Main results section of the abstract. 2011. PMID 21678340, DOI 10.1002/14651858.cd003123.pub3. Read the source
4. DailyMed (US National Library of Medicine), SPL submitted by Nephron Pharmaceuticals Corporation; label version published 28 January 2026. Drug Facts label, S2 racepinephrine hydrochloride inhalation solution — the complete "Uses" section. 2026. Read the source
5. The Cochrane database of systematic reviews. Nebulized racemic epinephrine for extubation of newborn infants (2002 update, the current version) — Main results section of the abstract. 2002. PMID 11869578, DOI 10.1002/14651858.cd000506. Read the source
6. DailyMed (US National Library of Medicine), SPL submitted by Nephron Pharmaceuticals Corporation; label version published 28 January 2026. Drug Facts label, S2 racepinephrine hydrochloride inhalation solution — the complete "Do not use" subsection of Warnings. 2026. Read the source
7. DailyMed (US National Library of Medicine), SPL submitted by Nephron Pharmaceuticals Corporation; label version published 28 January 2026. Drug Facts label, S2 racepinephrine hydrochloride inhalation solution — the complete "When using this product" subsection of Warnings. 2026. Read the source
8. DailyMed (US National Library of Medicine), SPL submitted by Nephron Pharmaceuticals Corporation; label version published 28 January 2026. Drug Facts label, S2 racepinephrine hydrochloride inhalation solution — the complete "Ask a doctor or pharmacist before use if you are" subsection of Warnings. 2026. Read the source
9. Clinical pediatrics. Failure of Outpatient Management With Different Observation Times After Racemic Epinephrine for Croup — Results section of the abstract. 2018. PMID 29034735, DOI 10.1177/0009922817737075. Read the source
10. Pediatrics. Pediatric myocardial infarction after racemic epinephrine administration — Abstract. 1999. PMID 10390295, DOI 10.1542/peds.104.1.e9. Read the source
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12. DailyMed (US National Library of Medicine); labeller Nephron Pharmaceuticals Corporation. Drug Facts label, S2 racepinephrine hydrochloride inhalation solution — the complete pregnancy or breast-feeding subsection of Warnings (SPL section code 53414-9). 2026. Read the source
13. DailyMed (US National Library of Medicine); labeller Nephron Pharmaceuticals Corporation. Drug Facts label, S2 racepinephrine hydrochloride inhalation solution — the complete keep-out-of-reach-of-children and overdose subsection of Warnings (SPL section code 50565-1). 2026. Read the source
14. The Cochrane database of systematic reviews. Nebulized epinephrine for croup in children — Authors' conclusions section of the abstract. 2013. PMID 24114291, DOI 10.1002/14651858.cd006619.pub3. Read the source
15. Frontiers in pediatrics. Nebulized epinephrine for croup in children: an updated systematic review — Conclusion section of the abstract. 2026. PMID 42719212, DOI 10.3389/fped.2026.1886410. Read the source
16. The Cochrane database of systematic reviews. Epinephrine for bronchiolitis — Authors' conclusions section of the abstract. 2011. PMID 21678340, DOI 10.1002/14651858.cd003123.pub3. Read the source
17. Frontiers in pharmacology. Systematic Review and Meta-Analysis of the Efficacy and Safety of Combined Epinephrine and Corticosteroid Therapy for Acute Bronchiolitis in Infants — Conclusions section of the abstract. 2017. PMID 28690542, DOI 10.3389/fphar.2017.00396. Read the source
18. Children (Basel, Switzerland). Nebulized Epinephrine Versus Placebo in Infants with Moderate-to-Severe Bronchiolitis: A Randomized Controlled Trial — Conclusions section of the abstract. 2026. PMID 42794274, DOI 10.3390/children13091254. Read the source
19. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. The efficacy of nebulized racemic epinephrine in children with acute asthma: a randomized, double-blind trial — Results section of the abstract. 2000. PMID 11015240, DOI 10.1111/j.1553-2712.2000.tb01258.x. Read the source
20. The journal of allergy and clinical immunology. In practice. Nonprescription racemic epinephrine for asthma — Conclusion section of the abstract. 2014. PMID 25213051, DOI 10.1016/j.jaip.2014.02.014. Read the source
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23. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. The efficacy of nebulized racemic epinephrine in children with acute asthma: a randomized, double-blind trial — Conclusions section of the abstract. 2000. PMID 11015240, DOI 10.1111/j.1553-2712.2000.tb01258.x. Read the source
24. Frontiers in pediatrics. Nebulized epinephrine for croup in children: an updated systematic review — Results section of the abstract. 2026. PMID 42719212, DOI 10.3389/fped.2026.1886410. Read the source
25. The New England journal of medicine. Epinephrine and dexamethasone in children with bronchiolitis — Results section of the abstract. 2009. PMID 19439742, DOI 10.1056/nejmoa0900544. Read the source
26. BMC pediatrics. Racemic epinephrine compared to salbutamol in hospitalized young children with bronchiolitis; a randomized controlled clinical trial [ISRCTN46561076] — Conclusion section of the abstract. 2005. PMID 15876347, DOI 10.1186/1471-2431-5-7. Read the source
27. Children (Basel, Switzerland). Nebulized Epinephrine Versus Placebo in Infants with Moderate-to-Severe Bronchiolitis: A Randomized Controlled Trial — Limits of the Study paragraph of the full text. 2026. PMID 42794274, DOI 10.3390/children13091254. Read the source
28. Clinical pediatrics. Failure of Outpatient Management With Different Observation Times After Racemic Epinephrine for Croup — Methods section of the abstract. 2018. PMID 29034735, DOI 10.1177/0009922817737075. Read the source
29. The Journal of emergency medicine. Delivery of L-Epinephrine by Metered-Dose Inhaler Compared to Racemic Epinephrine by Nebulizer for the Treatment of Croup — Results section of the abstract. 2025. PMID 41138556, DOI 10.1016/j.jemermed.2025.08.015. Read the source
30. Code of Federal Regulations, US Government Publishing Office (govinfo). 21 CFR 341.16 Bronchodilator active ingredients (2024 annual revision). 2024. Read the source
31. DailyMed (US National Library of Medicine), SPL submitted by Nephron Pharmaceuticals Corporation; label version published 28 January 2026. Drug Facts label, S2 racepinephrine hydrochloride inhalation solution — the complete "Directions" section. 2026. Read the source
32. The New England journal of medicine. Epinephrine and dexamethasone in children with bronchiolitis — Methods section of the abstract. 2009. PMID 19439742, DOI 10.1056/nejmoa0900544. Read the source
33. The journal of allergy and clinical immunology. In practice. Nonprescription racemic epinephrine for asthma — Background section of the abstract. 2014. PMID 25213051, DOI 10.1016/j.jaip.2014.02.014. Read the source
34. Children (Basel, Switzerland). Nebulized Epinephrine Versus Placebo in Infants with Moderate-to-Severe Bronchiolitis: A Randomized Controlled Trial — Methods paragraph of the full text on the treatment given. 2026. PMID 42794274, DOI 10.3390/children13091254. Read the source
35. DailyMed (US National Library of Medicine), SPL submitted by Nephron Pharmaceuticals Corporation; label version published 28 January 2026. Drug Facts label, S2 racepinephrine hydrochloride inhalation solution — the complete "Asthma alert" subsection of Warnings. 2026. Read the source
36. Frontiers in pharmacology. Systematic Review and Meta-Analysis of the Efficacy and Safety of Combined Epinephrine and Corticosteroid Therapy for Acute Bronchiolitis in Infants — Results section of the abstract. 2017. PMID 28690542, DOI 10.3389/fphar.2017.00396. Read the source