Role of Repeated Painful Procedures in Preterm Neonates on Short Term Neurobehavioural Outcome
Condition: Pain
Study type: Interventional
Phase: Phase 3

Summary: 
      Procedural pain in neonates is recently acknowledged entity and many studies on the use of
      pharmacological as well as non pharmacological interventions for alleviation of this pain
      have been done. Of these, sucrose with or without non nutritive sucking has been the most
      widely studied and accepted form of pain relief. Its analgesic effect is thought to be
      mediated by endogenous opioid pathways activated by sweet taste (orogustatory effect).

      Although, guidelines based on systematic reviews and meta-analysis for pain management
      recommend the use of sucrose solutions for pain relief during procedures, the use of repeated
      doses of sucrose with preterm neonates requires further investigation.

      Pain may have profound consequences for preterm neonates during a critical time of brain
      development. Data derived from animal models suggests that repeated painful stimuli may
      result in structural and functional reorganization of the nervous system and alteration in
      future pain response. Early pain experience during this critical period in development are
      thought to have immediate and long term consequences that could influence physiological,
      behavioral and developmental outcomes. Early repetitive procedural pain related stress in
      very preterm neonates is associated with poorer neurobehaviour in first 2 years of life.1
      This study aims to assess the effect of repeated painful stimuli on short term neurobehaviour
      of preterm infants and the efficacy of repeated doses of sucrose used for pain relief.
    

Detailed description: 
      DEFINITION OF PAIN - an unpleasant sensory and emotional experience with actual or potential
      damage or described in terms of such damage (note that the inability to communicate verbally
      or non verbally does not negate the possibility that an individual is having pain and is in
      need of appropriate pain relieving treatment)

      HISTORICAL BACKGROUND- we as clinicians have emerged from a period of relative neglect of
      neonatal pain and are now recognizing the immediate and long term impact of pain on the
      neonatal development as well as the need to alleviate pain effectively. Neonatal pain has
      been acknowledged and Paediatric societies such as American Academy of Paediatrics and
      Canadian paediatric society (2000) have adopted specific guidelines on pain relief in
      neonates .

      LONG TERM EFFECTS OF CHRONIC PAIN -Early repeated procedural pain in NICU has been proposed
      as one of the factors that may contribute to altered development of cognition ,motor function
      and behaviour in infants and children born preterm.The vulnerability of preterms is well
      established due to their lower pain threshold ,sensitization from repeated pain and immature
      systems for maintaining homeostasis .For infants with extremely immature physiological and
      neurobehavioural systems ,continual adaptation to repeated challenges induces long term
      alterations in pain sensitivity, might affect generalized stress arousal systems and
      potentially affect the developing cytotexture of the brain. The physiologic perturbations
      associated with early prolonged exposure to episodic pain appear to contribute to altering
      the rapidly developing stress systems .Exposure to painful procedures in early neonatal
      period affects the long term neurobehavioural outcome.

      .

      SCALE USED TO ASSESS SHORT TERM NEUROBEHAVIOUR

      NAPI (NEUROBEHAVIOURAL ASSESSMENT OF PRETERM INFANT) -The NAPI is appropriate for infants
      between 32 weeks post conceptional age and term. It assesses the relative maturity of
      functioning of preterm infants,with higher scores reflecting higher maturity , and can
      differentiate 2 weeks PCA . The clinical validity and sensitivity of NAPI were established
      using an index of medical complications based on a 1-5 classification range of degrees of
      complications21 The items in the motor development cluster include ventral suspension, prone
      head raising ,the crawling reflex ,forearm recoil ,power of active movements , and vigor of
      spontaneous movements .The alertness and orientation items include percent of time in an
      alert state ,duration and quality of alertness , quantitative response to inanimate and
      animate visual and auditory stimulation and qualitative ratings that express the nature of
      response.

      LACUNAE IN KNOWLEDGE -Preterm infants are more prone to undergo multiple painful procedures
      due to their prolonged stay in the neonatal intensive care unit and their typical vulnerable
      clinical profile.It has now been proved that painful procedures lead to long term changes in
      the pain reactivity and also affect the long term neurobehavioural outcome in these preterm
      infants.When a medline search was carried out on the subject it did not return any
      result.Currently there is no study which has tried to explore the short term neurobehavioural
      outcome in preterm babies >32 weeks - <37 weeks of gestation who undergo multiple painful
      procedures during their NICU stay.The present study was thus planned to evaluate the role of
      sucrose analgesia in alleviating the pain caused by the routine NICU procedures over a period
      of 7 days and to assess the early neurobehavioural outcome in these babies with the help of a
      well designed double blinded randomized controlled trial.
    

Intervention name(s): 24% Sucrose; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): The enrolled neonates will be administered either a sterile solution of 24 % sucrose or double distilled water orally for a period of 7 days from enrollment. At the beginning of each potentially painful procedure namely, venepuncture, venous and arterial cannulation, heel lance,orogastric tube insertion, suprapubic aspiration of urine and any other skin breaking procedure,0.5ml of solution marked with patients serial number will be administered by a prefilled syringe to the patient on the anterior aspect of the tongue , avoiding spillage , by the personnel carrying out the procedure; The patient will be enrolled into the study only after an informed written consent has been obtained from either of the parent/caregiver. At the beginning of each potentially painful procedure namely, venepuncture, venous and arterial cannulation, heel lance,orogastric tube insertion, suprapubic aspiration of urine and any other skin breaking procedure,0.5ml of solution marked with patients serial number will be administered by a prefilled syringe to the patient on the anterior aspect of the tongue , avoiding spillage , by the personnel carrying out the procedure
Other intervention name(s): Sucrose; Distilled Water
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Screening
Keywords: Pain; Neonate; Procedure; Neurobehavioural outcome