Racemic Epinephrine - a Literature Review

							                       Racemic Epinephrine – a Literature Review

Introduction
Racemic epinephrine is a mixture of the D- and L- isomers of epinephrine. Historically, it
has been given to pediatric patients with stridor, presumed to be caused by croup
(laryngotracheobronchitis), a viral infection of the upper airway.
Epinephrine is a potent stimulant of both alpha- and beta- adrenergic receptors.
Epinephrine is believed to exert its beneficial effect by reducing bronchial secretions and
mucosal edema (alpha) and also through smooth muscle relaxation and inhibition of mast
cell mediated inflammation (beta). Traditionally, it had been thought that the D-isomer
blocked the chronotropic effects of epinephrine on the heart, and that was why racemic
epinephrine became the preferred drug for croup.
The peak effect of epinephrine in patients with croup has been documented at 30 minutes
with duration of effect of 120 minutes, after which a return to baseline may occur quite
precipitously. It was believed that giving racemic epinephrine to children with croup
mandated a hospital admission due to the “rebound” phenomenon, this same return to
baseline or worse after the temporary relief from the treatment. It has since been
determined that careful observation for at least 2 hours after treatment and the use of
corticosteroids in children with croup severe enough to require nebulized epinephrine
make for safe, outpatient treatment of croup.

Methodology
A literature search was conducted on Medline/Pubmed using the keywords “racemic
epinephrine”. The list of articles was scanned for relevance to pre-hospital or emergency
department management of respiratory distress in young children, specifically in regards
to croup or bronchiolitis. Articles were then selected and pulled for further review.

Racemic Epinephrine vs L-epinephrine

Waisman Y, Klein BL, Boenning DA et al: Prospective randomized double-blind study
comparing L-epinephrine and racemic epinephrine aerosols in the treatment of
laryngotracheitis (croup). Pediatrics 1992. Feb; 89(2): 302-6.
Children 6mo-6 yrs of age with a croup score of >/= 6 were assigned to receive either
racemic (n=16) or L- epinephrine (n=15) aerosols. Patients in both groups showed
significant transient reduction of croup score and respiratory rate following treatment and
there were differences in croup score or VS over time. The authors concluded that L-
epinephrine is at least as effective as racemic epinephrine in the treatment of croup and
does not carry the risk of additional adverse effects. L-epinephrine is also more readily
available worldwide and is less expensive.

Safety and cost-effectiveness of outpatient treatment of croup
The following studies have demonstrated that children who are treated with nebulized
racemic epinephrine in the emergency department can be safely discharged home after an
adequate period of observation, usually after steroids have also been administered.
Kelly PB, Simon JE. Racemic epinephrine use in croup and disposition. Am J Emerg
Med. 1992;10:181-3.
Prendergast M, Jones JS, Hartman D. Racemic epinephrine in the treatment of
laryngotracheitis: can we identify children for outpatient therapy? Am J Emerg Med.
1994; 12:613-6.
Ledwith CA, Shea LM, Mauro RD. Safety and efficacy of nebulized racemic epinephrine
in conjunction with oral dexamethasone and mist in the outpatient treatment of croup.
Ann. Emerg. Med. 1995; 25:331-7
Kunkel NC, Baker MD. Use of racemic epinephrine, dexamethasone and mist in the
outpatient management of croup. Pediatr Emerg Care 1996; 12:156-9.
Rizos JD, DiGravio BE, Sehl MJ et al. The disposition of children with croup treated
with racemic epinephrine and dexamethasone in the emergency department. J Emerg
Med 1998; 16: 535-539.

Racemic epinephrine vs albuterol in bronchiolitis
Albuterol (salbutamol) and epinephrine have been compared for effectiveness in
suspected bronchiolitis. Most studies have compared albuterol with racemic epinephrine.

Menon K, Sutcliffe T, Klassen TP. A randomized trial comparing the efficacy of
epinephrine with salbutamol in the treatment of acute bronchiolitis. J Pediatr 1995;
126(6):1004-7.
Mean O2 saturation at 60 minutes was significantly higher in the epinephrine group. 33%
of the patients in the epinephrine group were admitted as compared with 81% of the
salbutamol group (p = 0.003). The authors concluded that nebulized epinephrine is more
efficacious than salbutamol for infants with acute bronchiolitis seen in an ED.

Reijonen T, Korppi M, Pitkakangas S et al. The clinical efficacy of nebulized racemic
epinephrine and albuterol in acute bronchiolitis. Arch of Pediatr and Adoles Med 1995;
149(6):686-92.
Randomized, placebo-controlled, double-blind study comparing the effects of racemic
epinephrine and albuterol in 100 consecutive infants <24 months treated as inpatients for
acute bronchiolitis. Infants received either placebo first and one of the drugs next or vice
versa. Only in the racemic epinephrine then placebo group was there significant
improvement in scores in at 15 minutes.

Racemic Epinephrine vs Albuterol (Salbutamol) in Asthma
Plint AC, Osmond MH, Klassen TP. The efficacy of nebulized racemic epinephrine in
children with acute asthma: a randomized, double-blind trial. Acad Emerg Med 2000 Oct;
7(10):1097-103. 120 patients were randomized to receive either salbutamol or racemic
epinephrine by nebulization at 0, 20 and 40 minutes. All patients received oral steroids.
There was no significant difference between treatments in the change in pulmonary index
score, length of stay, admission to hospital or relapse rate. The epinephrine-treated group
had significantly more minor side effects. The authors concluded that there is no
significant benefit of nebulized epinephrine over salbutamol in children 1-17 yrs old with
mild to moderate acute asthma.
Recommendations

Croup
In children 6 months-6 years of age with significant respiratory distress and stridor, use 5
mL of L-epinephrine, 1:1000, nebulized or racemic epinephrine 0.5 mL in 3 mL NS.

Bronchiolitis
In children </= 24 months of age with respiratory distress and the first known episode of
wheezing, use 5 mL of L-epinephrine, 1:1000, nebulized.

Asthma
In children with known asthma, use albuterol, unit-dose and ipratropium, as per asthma
protocol.