Pain Reactivity to Non-Pharmacological Interventions Across Repeated Routine Heel-Sticks in Preterm Infants in a Neonatal Intensive Care Unit
Condition: Preterm Infants
MeSH terms: Premature Birth
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Switzerland is having one of the highest premature rates in Europa and most of the preterm
      neonates need neonatal intensive care. Up to 80% of the analgesic used in neonatal intensive
      care units are either "off label used" or "non-licensed" used. As an alternative approach
      non-pharmacological interventions for pain prevention and relief are increasingly being
      recommended for the prevention and treatment of mild and moderate pain in this population.

      This multicenter pilot study will use a randomized three group,repeated measures design.

      The primary aims of this study of premature neonates are to:

      1.) Estimate effect sizes for the impact of the proposed interventions(facilitated tucking
      alone, sucrose alone and sucrose in combination with tucking)on pain reactivity.

      2.) Examine the impact of gestational age on the estimates of efficacy 3.) Examine the impact
      of the numbers of painful procedures the infant experiences and the concurrent use of
      analgesic medications on the estimates of efficacy
    

Detailed description: 
      Background and significance:

      Switzerland with its approximately 8% of premature births is having one of the highest
      premature rates in Europe and most of the preterm neonates need neonatal intensive care.
      Recur-rent neonatal pain and stress occur routinely during neonatal intensive care,
      particularly among the extremely low birth weight preterm neonates . It has become clear in
      recent years that the nervous system undergoes extensive development postnatally and there is
      increasing evidence that repeated exposure to pain, may lead to serious biobehavioral changes
      during the sensitive developmental phase of the central nervous system and that these changes
      may underlie long-term learning and behavior difficulties in this patient population. The
      frequency of exposure to pain and the adequate treatment of that pain are therefore important
      factors in later motor and cognitive development in preterm infants requiring intensive care.
      Pain treatment in infants is viewed as inadequate in the context of acute diagnostic and
      therapeutic procedures in the NICU. Up to 80% of the analgesic used in neonatal intensive
      care units (NICU) are either "off label used" or "non-licensed used". Secondary to
      significant side effects, associated with the use of analgesics drugs, health care providers
      are often reticence to administer these drugs in the NICU. As an alternative approach
      non-pharmacological interventions for pain prevention and relief are increasingly being
      recommended for the prevention and treatment of mild and moderate pain in this population.
      This type of intervention includes methods that involve reducing the sensitivity of the
      neonates during and after painful procedures, which have been shown to effectively reduce
      pain from minor procedures in neonates.

      Although non-pharmacological interventions have been shown to be efficacious when tested
      during a single painful procedure there is a lack of evidence related to their efficacy after
      infants have being exposed to a high number of painful procedures and the accompanying
      chronic stress. To improve the clinical outcomes there is a critical need for accurate and
      efficient neonatal pain management for this highly vulnerable patient population.

      Specific aims:

      To determine the sample size needed for a larger randomized clinical trial (RCT) designed to
      compare the sustained impact of three non-pharmacological approaches on the pain reactivity
      of premature neo-nates in a NICU.

      Design and methods:

      This multicenter pilot study will use a randomized three group, repeated measures design. 72
      premature infants from 24 0/7 to 32 0/7 weeks of gestation needing neonatal intensive care
      will be recruited during the first 2 days of life in three University Clinics (Bern, Basel,
      Zurich). The premature infants will be randomly assigned to one of three intervention groups
      (1) oral sucrose, (2) facilitated tucking, or (3) oral sucrose plus facilitated tucking.
      Sucrose is currently the standard of care in NICUs in Switzerland and will serve as the usual
      care control condition. The infants will be stratified into two gestational groups to examine
      the impact of gestational age on the effect size estimates. Five heel sticks across 12-14
      days will be videotaped and pain will be rated by 4 independent raters, who are blinded to
      the data collection period. Raters will use the "Bernese Pain Scale for Neonates" to measure
      pain before, during and after the heel stick procedure. The physiologic data (heart rate and
      oxygen saturation) needed to complete the Bernese Pain Scale for Neonates will be down loaded
      from the clinical database for the same time frame as the neonate is videotaped. Near
      infrared spectroscopy (NIRS) will be performed during the painful procedures in the one site
      to measure differences in somatosensory cortical activation during heel sticks in infants
      managed with the three interventions at a baseline and across repeated heel sticks.

      Expected value of the proposed project:

      Adequate and efficient pain management is an important factor in later motor and cognitive
      development in preterm infants requiring intensive care. This pilot data will provide
      information about the sample size needed for a larger RCT. That study will compare the impact
      of the mentioned non-pharmacological interventions on pain reactivity across multiple painful
      procedures. In addition to examining their individual impact, we will evaluate the impact of
      using them in combination. The larger study will contribute to a better understanding of the
      efficacy of non-pharmacological pain relieving methods and their efficacy across repeated
      pain exposures. This pilot study is a collaborative effort of the disciplines of nursing
      science and neonatal medicine.
    

Intervention name(s): 25% Sucrose; facilitated tucking; Sucrose and facilitated tucking
Intervention type(s): Procedure; Procedure; Procedure
Intervention description(s): orally administrated 25%Sucrose before, during and after heel stick; facilitated tucking before, during and after heel stick; orally administrated 25%sucrose and facilitated tucking before, during and after heel stick
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: cortisol; pain; pain management; preterm infants; sucrose; facilitated tucking