Pain Management During Screening for Retinopathy of Prematurity
Condition: Retinopathy of Prematurity; Pain Management
MeSH terms: Retinal Diseases; Retinopathy of Prematurity; Premature Birth
Study type: Observational

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.
    

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.
    

Intervention name(s): Ibuprofen (Sanofi, Istanbul, Turkey); Paracetamol (GlaxoSmithKline, Istanbul, Turkey)
Intervention type(s): Drug; Drug
Intervention description(s): Each enrolled infant received oral ibuprofen at a dose of 10 mg/kg 60 min before the onset of the eye examination.; Each enrolled infant received oral paracetamol at a dose of 10 mg/kg 60 min before the onset of the eye examination.
Other intervention name(s): Dolven; Parol
Intervention MeSH terms: Acetaminophen; Ibuprofen
Observational model: Cohort
Time perspective: Prospective
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.
      
Keywords: Analgesia; ibuprofen; N-PASS; pain management; paracetamol; preterm infant; retinopathy of prematurity