Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04767178 |
| Other study ID # |
Ozgul1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2020 |
| Est. completion date |
August 15, 2020 |
Study information
| Verified date |
February 2021 |
| Source |
Istanbul Medeniyet University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Abstract Background: Screening examinations for retinopathy of prematurity (ROP) is critical
to reduce ROP-related vision loss, however, the procedure is painful and uncomfortable, and
topical anesthetics do not completely suppress the painful responses. The number of safe and
effective pharmacological options to reduce pain during eye examinations for ROP screening in
preterm infants is limited.
Objective: This study compared the efficacy of oral ibuprofen and oral paracetamol in
reducing pain during screening for ROP in preterm infants.
Design: This prospective observational study was conducted at a tertiary-care neonatal
intensive care units. Forty-four preterm infants with gestational age ≤ 32 weeks undergoing
ROP screening were included. Each enrolled infant received either oral ibuprofen 10 mg/kg (n
= 22) or oral paracetamol 10 mg/kg (n = 22) one hour before eye examination. The primary
outcome measure was pain assessed by the Neonatal Pain, Agitation, and Sedation (N-PASS)
scale. Secondary outcome measures were tachycardia, bradycardia, desaturations, and crying
time.
Description:
Retinopathy of prematurity (ROP) is a physiopathological condition that develops upon
abnormal proliferation of the retinal veins in neonates, and its pathogenesis is unknown.1
With the advancements in neonate care, the survival rate of premature babies with extremely
low gestational ages and birth weights has increased significantly; however, this has also
resulted in an increasing incidence of ROP, which may lead to vision defects and/or
blindness. Early diagnosis, and timely and effective treatment may prevent vision loss and
thus improve the developmental process and the quality of life of these infants. Therefore,
recurring screening with retinal examination is essential to identify neonates who need ROP
treatment.2, 3 The American Academy of Pediatrics and American Academy of Ophthalmology
recommend ROP screening for preterm infants with a birth weight of ≤1500 g or a gestational
age of ≤30 weeks, and selected infants with a birth weight between 1500 and 2000 g or a
gestational age of >30 weeks who have received cardiopulmonary supportive therapy, or who are
considered by the attending clinician to be at risk for the development of ROP.4 The
ophthalmological examinations for screening ROP involve repeated use of mydriatic eye drops,
physical constriction, forced opening of the eyelids, insertion of the blepharostat, scleral
indentation, and dense light, all of which cause pain and stress to the infant.5, 6 The
extreme and long-term unreduced pain resulting from the interventions applied in the neonatal
intensive care units (NICU) may generally cause life-threatening effects in organs and
systems. Inadequate management of pain in preterm neonates can cause physiological changes
and may also obscure the behavior of the infant, interactions between the family and the
infant, and the adaptation of the infant to the social world, causing neurological and
behavioral disorders and negatively affecting growth.7, 8, 9, 10 Thus, determination of
optimal strategies for stress reduction and pain management related to these medical
procedures is important in order to minimize the discomfort experienced by these neonates.
In order to reduce the pain and stress related to ROP examination, non-pharmacological
methods, including the use of pacifiers, skin-to-skin touch, swaddling, kangaroo care,
positioning, musical therapy, breast milk and breast feeding, single or recurring doses of
oral sucrose, and personalized developmental care applications, have been used.5, 11, 12, 13,
14 However, a recent meta-analysis of randomized controlled studies evaluated a variety of
non-pharmacological pain-reducing interventions in addition to topical ophthalmic anesthetics
for ROP examination. Although multisensory pain treatments (e.g., oral dextrose/sucrose
solution, breast milk, swinging, singing, non-feeding suction, swaddling) may reduce the pain
to varying degrees, no specific treatment has been reported to show significant pain-relief
ability. The Premature Infant Pain Profile (PIPP) score in most of the studies was >12.11
Pharmacological methods are used for pain relief as well as non-pharmacological in neonates.
The pharmacological agents include local anesthetics, non-steroidal anti-inflammatory drugs
(NSAIDs), and opioid medications.15 Although topical anesthetics are routinely used in ROP
examination in the NICU, they do not offer complete relief from pain.12 Moreover, opioid
analgesics should be used carefully, due to their adverse effects such as respiratory
depression, apnea, bradycardia, hypotension, intestinal hypoperistalsis, and bladder
dysfunction. 16 NSAIDs are commonly used in newborns and children as antipyretic agents to
control fever and as analgesic, anti-inflammatory, and vasoactive agents to manage pain and
modulate inflammation.17 Paracetamol shows analgesic and antipyretic effects by inhibiting
the cyclooxygenase (COX)-2 enzyme.17 It can be used safely in neonates during mild to
moderately painful procedures and in the postoperative period. Malnory et al. showed that the
preoperative use of paracetamol during circumcision of late preterm and term infants reduced
pain within the first 24 h.18 Ceelie et al. reported that the intravenous use of paracetamol
in neonates and infants after major surgeries reduced the need for morphine in the first 48 h
following surgery.19 Ibuprofen, another NSAID, inhibits COX-1 and COX-2 enzymes to show
analgesic, antipyretic, and anti-inflammatory effects.17 However, the role of ibuprofen in
reducing pain in neonates has not been studied in detail. Recently, these two medications are
commonly used in NICUs for ductus closure.20 To our knowledge, no previous study has compared
the pain-reducing effect of ibuprofen and paracetamol in preterm infants during ROP
examinations. Thus, this study aimed to compare the pain-reducing effects of single-dose
ibuprofen and paracetamol in preterm infants during ROP examination by using the Neonatal
Pain, Agitation, and Sedation (N-PASS) scale.
