Oral propranolol for retinopathy of prematurity: risks, safety concerns, and perspectives.
OBJECTIVE
To evaluate safety and efficacy of oral propranolol administration in preterm newborns affected by an early phase of retinopathy of prematurity (ROP).


METHODS
Fifty-two preterm newborns with Stage 2 ROP were randomized to receive oral propranolol (0.25 or 0.5 mg/kg/6 hours) added to standard treatment or standard treatment alone. To evaluate safety of the treatment, hemodynamic and respiratory variables were continuously monitored, and blood samples were collected weekly to check for renal, liver, and metabolic balance. To evaluate efficacy of the treatment, the progression of the disease (number of laser treatments, number of bevacizumab treatments, and incidence of retinal detachment) was evaluated by serial ophthalmologic examinations, and plasma soluble E-selectin levels were measured weekly.


RESULTS
Newborns treated with propranolol showed less progression to Stage 3 (risk ratio 0.52; 95% CI 0.47-0.58, relative reduction of risk 48%) or Stage 3 plus (relative risk 0.42 95% CI 0.31-0.58, relative reduction of risk 58%). The infants required fewer laser treatments and less need for rescue treatment with intravitreal bevacizumab (relative risk 0.48; 95% CI 0.29-0.79, relative reduction of risk 52 %), a 100% relative reduction of risk for progression to Stage 4. They also had significantly lower plasma soluble E-selectin levels. However, 5 of the 26 newborns treated with propranolol had serious adverse effects (hypotension, bradycardia), in conjunction with episodes of sepsis, anesthesia induction, or tracheal stimulation.


CONCLUSIONS
This pilot study suggests that the administration of oral propranolol is effective in counteracting the progression of ROP but that safety is a concern.
Neonatal Intensive Care Unit, Medical Surgical Fetal-Neonatal Department, "A. Meyer" University Children's Hospital, Florence, Italy. Electronic address: l.filippi@meyer.it.
Luca
L
Filippi
Giacomo
G
Cavallaro
Paola
P
Bagnoli
Massimo
M
Dal Monte
Patrizio
P
Fiorini
Gianpaolo
G
Donzelli
Francesca
F
Tinelli
Gabriella
G
Araimo
Gloria
G
Cristofori
Giancarlo
G
la Marca
Maria Luisa
ML
Della Bona
Agostino
A
La Torre
Pina
P
Fortunato
Sandra
S
Furlanetto
Silvia
S
Osnaghi
Fabio
F
Mosca
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007234:Infant, Premature; D008297:Male; D010865:Pilot Projects; D011433:Propranolol / Q000009:adverse effects / Q000627:therapeutic use*; D012178:Retinopathy of Prematurity / Q000188:drug therapy*; D012307:Risk Factors; D016037:Single-Blind Method
D000319:Adrenergic beta-Antagonists; D011433:Propranolol
GA; Gestational age; OIR; Oxygen-induced retinopathy; ROP; Retinopathy of prematurity; VEGF; Vascular endothelial growth factor; β-AR; β-adrenoreceptor