Pain Management During Screening for Retinopathy of Prematurity

February 20, 2021 updated by: Ozgul Bulut, Istanbul Medeniyet University

Oral Ibuprofen Versus Oral Paracetamol in Pain Management During Screening for Retinopathy of Prematurity: A Prospective Observational Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Observational

Enrollment (Actual)

44

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Turkey
      • Istanbul, Turkey, 34674
        • Medeniyet University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 months to 7 months (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

The present study enrolled preterm infants with a gestational age of ≤32 weeks or birth weight ≤ 1500 g who were screened for ROP.

Description

Inclusion Criteria:

  • Preterm infants of ≤32 weeks of gestational
  • Preterm infants ≤ 1500 gram of birth weight

Exclusion Criteria:

  • Major congenital abnormalities
  • Neurological dysfunction
  • Infants who were mechanically ventilated and/or sedated, hemodynamically unstable
  • Infants > 32 weeks of gestational
  • The infants whose parents denied consent were also not included.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Ibuprofen group
Infants that received oral ibuprofen were categorized into the ibuprofen group
Drug: Ibuprofen (Sanofi, Istanbul, Turkey)
Each enrolled infant received oral ibuprofen at a dose of 10 mg/kg 60 min before the onset of the eye examination.
Other Names:
  • Dolven
Paracetamol group
Infants that received oral paracetamol were categorized into the paracetamol group
Drug: Paracetamol (GlaxoSmithKline, Istanbul, Turkey)
Each enrolled infant received oral paracetamol at a dose of 10 mg/kg 60 min before the onset of the eye examination.
Other Names:
  • Parol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Neonatal Pain, Agitation, and Sedation scale
Time Frame: 8 month
The mean of the Neonatal Pain, Agitation, and Sedation score (A score >+3 indicates pain)
8 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istanbul Medeniyet University

Investigators

  • Principal Investigator: Ozgul Bulut, Medeniyet University Goztepe Training and Research Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 1, 2020

Primary Completion (ACTUAL)

July 30, 2020

Study Completion (ACTUAL)

August 15, 2020

Study Registration Dates

First Submitted

February 14, 2021

First Submitted That Met QC Criteria

February 20, 2021

First Posted (ACTUAL)

February 23, 2021

Study Record Updates

Last Update Posted (ACTUAL)

February 23, 2021

Last Update Submitted That Met QC Criteria

February 20, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Ozgul1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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