Trial of an Oral Sucrose Solution Versus Placebo in Children 1 to 3 Months Old Needing Nasopharyngeal Aspiration
Condition: Pain
Study type: Interventional
Phase: Phase 4

Summary: 
      Background: Early recognition and treatment of pain among children is important for their
      cognitive development and their future response to pain throughout their life. Oral sweet
      solutions have been accepted as effective pain reducing agents for procedures in the neonatal
      population. To date, there have been a limited number of published clinical trials in an
      emergency setting studying this type of intervention among infants undergoing venous puncture
      and bladder catheterization. These studies have reported conflicting results. No previous
      studies have evaluated the utilization of sucrose to manage pain during nasopharyngeal
      aspiration.

      Objective: To compare the efficacy of an oral sucrose solution versus placebo in reducing
      pain in children one to three months of age during nasopharyngeal aspiration in the Emergency
      Department.
    

Detailed description: 
      INTRODUCTION AND JUSTIFICATION

      Acute pain is one of the most common adverse stimuli experienced by children, occurring as a
      result of injury, illness, and necessary medical procedures1. The American Academy of
      Pediatrics (AAP) and the American Pain Society (APS) have jointly issued a statement
      promoting the responsibility of paediatricians as leaders and advocates to ensure the humane
      and competent treatment of pain and suffering in all infants, children, and adolescents.

      Long-term effects of unmanaged pain in human infants have been shown to include permanent
      impairment of elements of cognitive development, such as learning, memory, and behavior, and
      increased somatisation in childhood. The plasticity of the developing brain and the changes
      that occur in response to painful stimuli also contribute to altered perceptions of pain
      later in life. Early painful experiences affect children's future responses to analgesia.
      Weisman et al found that inadequate analgesia in young children during procedures diminished
      the effects of adequate analgesia during subsequent procedures. Many studies have suggested
      that the prompt and accurate recognition and treatment of pain in young infants is important
      for their immediate comfort and for their best possible lifelong development. Despite the
      recent interest in paediatric pain assessment, prevention and treatment, many children do not
      receive adequate management to alleviate pain. The ideal pre-procedural analgesic agent for
      minor invasive procedures would be a cost-effective, inexpensive, short-acting agent with few
      associated risks.

      The use of sucrose has been well studied for certain procedures in the patients of the
      neonatal intensive care unit and in the newborn nursery settings, particularly for venous
      blood draws, capillary blood tests and circumcision. In these studies, infants receiving oral
      sucrose solutions before procedures cried less and had overall decreased behavioral pain
      responses when compared with those receiving placebo. Furthermore, sucrose has been shown to
      be a safe intervention with no serious life-threatening adverse events and only few reported
      side effects consisting of minimal coughing with administration. Sucrose is inexpensive,
      short acting, non-sedating, easily administered and non-invasive. Administration of sucrose
      does not require additional training and does not expose the infant to risks greater than
      those associated with breast or bottle feeding.

      Nasopharyngeal aspiration (NPA) is a common procedure in the Emergency Department (ED),
      especially during wintertime. It is also a recognized way to support small children with
      bronchiolitis or upper respiratory viral illness. There is currently a paucity of literature
      about the perception of pain or discomfort during nasopharyngeal aspiration. Macfarlane and
      al. compared nasal swab versus nasopharyngeal aspirate for RSV testing in children of 1 month
      to 20 months. Infant distress was measured using a facial, cry, and movement scoring scale
      (FLACC). A median score of six was obtaining in the group of nasopharyngeal aspirate in
      comparison of median score of cinq for nasal swab (p<0,0001).

      Sucrose administered by non-nutritive sucking two minutes prior to the procedure is now
      recognized as a safe16 and efficient way to relieve pain for minor procedures in the neonatal
      intensive care unit (NICU). It can contribute to decrease the physiologic response to a
      painful stimulus (heart rate, respiratory rate and decrease in oxygensaturation) as well as
      attenuate pain behaviors and decrease the overall score in pain scales. Since 1998, the
      Cochrane Database Review recommends the use of sucrose for procedural pain in the neonatal
      population. The latest edition (2010) provides sufficient evidence to recommend the use of
      sucrose for single heel lance punctures and its consideration for venipuncture. Authors
      conclude that further studies are needed to extend the use of sucrose to some other neonatal
      common but painful procedures such as bladder catheterization, nasogastric tube insertion and
      suctioning.

      Studies about the use of sucrose for relieving pain in routine immunizations suggest that
      analgesic properties can have an effect beyond infancy, despite upper age of this limit and
      appropriate concentration or quantity of sucrose are unknown for this age group. Randomized
      controlled trials in EDs introduced the use of sucrose for venipuncture or bladder
      catheterization for older infants. Curtis and al demonstrated a trend toward reducing pain in
      children of zero to six months of age using sucrose during venipuncture. However the benefit
      seemed to be limited to infants less than three months old with no significant variation in
      pain scale scores beyond this age (three to six months). In a second study, Rogers and al.
      showed that using sucrose while an infant undergoes bladder catheterization reduced
      variations in pain scale scores and enhanced a quicker return to baseline for infants of 1 to
      30 days of life, while infants in the group of 30 to 90 days failed to demonstrate this
      relation. No specific study was found about pain management during nasopharyngeal aspiration
      in infants in ED.

      Also, studies have used varieties of concentrations of sucrose ranging from 24% to 75%.
      Systematic reviews of the current literature have been unable to demonstrate superiority of
      one concentration of a sweet solution over another21-25, but many studies suggested that
      higher concentrations of sweet solutions seemed more effective. Therefore, the investigators
      chose to study the effect of a sweet solution named syrup B.P. (product by Laboratoire Atlas
      inc.) which contains 88% of sucrose. This solution is already commonly used in the population
      of infants up to three months of age and it is safe (e.g. prednisone syrup or codeine syrup
      are made using this syrup). A two milliliters dose of 88% sucrose contains the same amount of
      carbohydrates as 25 milliliters of infant milk formulas which contain approximately 7,5g/100
      milliliters 30. Also, 88% sucrose has the same sugar concentration as many other medications
      which are commonly used in infants, such as oral antibiotics, oral steroid solutions and
      other pain medications (e.g. codeine syrup). This syrup is of particular interest as it is of
      low cost ($9,58 for a bottle of 2000 milliliters), universally available, stable and viable
      for approximately three months. Therefore, the procedure studied here would be easy to apply
      in most clinical settings.

      Finally, the painful procedure chosen for the study is nasopharyngeal aspiration. This
      procedure is frequently performed in the ED in this age group, particularly in the winter
      either as a therapeutic or diagnostic procedure.

      To date, there are no pain scales which have been validated precisely for the age group
      studied in this project. However, the Face, Legs, Activity, Cry and Consolability (FLACC)
      scale is recommended by the IMMPACT group (Initiative on Methods, Measurement and Pain
      Assessment in Clinical Trials). FLACC is an easily applicable pain scale in which the
      observer scores a patient on five categories, from zero to two points, for a total score of
      maximum 10 points. The validity and reliability of this pain scale has been established in
      the past for children from 2 months to 7 years. Validity was evaluated by comparing the FLACC
      scale with the Objective Pain Scale and demonstrated that both tools showed similar
      behaviours (r=0.80; p<0.001). The interrater reliability between two observers was considered
      good (r[87]=0.94; p<0.001) with a kappa value greater than 0,50 for each category. Therefore,
      this pain scale was chosen as the measure of the investigators primary outcome, in this
      population of infants from one to three months old. Furthermore, the Neonatal Infant Pain
      Scale (NIPS)is a well validated pain scale for newborns up to one month of age. This pain
      scale was chosen as a secondary outcome. The investigators hypothesize that using one pain
      scale validated in infants up to 1 month of age and another validated in infants older than
      two months of age will allow us to assess pain in infants from one to three months of age
      best, given current available tools. Furthermore, several other patient parameters will be
      used to corroborate findings.

      HYPOTHESIS

      The investigators believe that providing an oral sucrose solution during nasopharyngeal
      aspiration will decrease pain levels in infants one to three months of age.

      OBJECTIVES

      The investigators primary objective is to compare the efficacy an oral 88% sucrose solution
      to a placebo solution in reducing pain as assessed by the FLACC scale in children of one to
      three months during nasopharyngeal aspiration in the ED. The investigators secondary
      objectives are to asses changes in pain levels as per the NIPS scores. The investigators will
      also measure variations of heart rate and crying time. Any side effects will also be
      reported.
    

Intervention name(s): 88% sucrose po; placebo po
Intervention type(s): Drug; Drug
Intervention description(s): 88% sucrose solution (Syrup B.P.); sterile water
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: pediatrics; emergency medicine; pain; nasopharyngeal aspiration