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

Summary: 
      INTRODUCTION AND JUSTIFICATION

      The use of sucrose has been well studied for certain procedures in neonatal intensive care
      unit patients 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 behavioural pain responses
      when compared with those receiving placebo.

      In Emergency Departments (ED), children undergo many painful procedures, such as bladder
      catheterization, capillary blood tests, venipuncture and lumbar puncture. Only two studies
      have examined the effectiveness of sweet solutions as an analgesic in the ED. A randomized
      controlled trial in an emergency setting of sucrose and/or pacifier for infants receiving
      venipuncture conducted by Curtis and al among infants of 0 to 6 months demonstrated a trend
      in reducing pain among the sub-group of infants of 0 to 3 months. However, this study showed
      no difference in pain scales after 3 months of age. Also, in a study examining the effect of
      sucrose during bladder catheterization, the subgroup of infants 1 to 30 days old who received
      a sweet solution showed smaller changes in pain scores, were less likely to cry during
      catheterization and returned to baseline more quickly, in comparison with the placebo group.
      However, among children of 31 to 90 days, there was no statistically significant difference
      in pain scores. In this study, they used a sucrose solution of only 24% and as they said in
      the discussion, it is possible that older infants, who on average received a smaller dose (in
      milligrams per kilogram), were in fact underdosed.

      Finally, the painful procedure chosen for this study is bladder catheterization. Bladder
      catheterizations are frequently performed in the ED in this age group.

      HYPOTHESIS The investigators believe that providing an oral sucrose solution during bladder
      catheterization will decrease pain levels in infants 1 to 3 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
      1 to 3 months during bladder catheterization in the ED. The investigators secondary objective
      is to asses changes in pain levels as per the NIPS score. The investigators will also measure
      variations in heart rate and crying time. All side effects will also be reported.
    

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 procedures. 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 behaviour,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 neonatal intensive care
      unit patients 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 behavioural 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.

      A Cochrane systematic review concluded that sucrose is safe and effective in reducing
      procedural pain from single short procedural events in neonates, but an optimal dose could
      not be identified due to inconsistency in effective sucrose dosage among studies. A review of
      published studies reported that sucrose or glucose in healthy term or preterm infants during
      single episodes of heel lancing, venipuncture or intramuscular injection is effective.
      However, uncertainties remain beyond the neonatal period, given the limited number of
      published studies.

      In Emergency Departments (ED), children undergo many painful procedures, such as bladder
      catheterization, capillary blood tests, venipuncture and lumbar puncture. Only two studies
      have examined the effectiveness of sweet solutions as an analgesic in the ED. A randomized
      controlled trial in an emergency setting of sucrose and/or pacifier for infants receiving
      venipuncture conducted by Curtis and al among infants of 0 to 6 months demonstrated a trend
      in reducing pain among the sub-group of infants of 0 to 3 months. However, this study showed
      no difference in pain scales after 3 months of age. Also, in a study examining the effect of
      sucrose during bladder catheterization, the subgroup of infants 1 to 30 days old who received
      a sweet solution showed smaller changes in pain scores, were less likely to cry during
      catheterization and returned to baseline more quickly, in comparison with the placebo group.
      However, among children of 31 to 90 days, there was no statistically significant difference
      in pain scores. In this study, they used a sucrose solution of only 24% and as they said in
      the discussion, it is possible that older infants, who on average received a smaller dose (in
      milligrams per kilogram), were in fact underdosed. Moreover, they use the Douleur Aiguë du
      Nouveau-né (DAN) pain scale, which is less recognized than the FLACC scale to evaluate pain
      in such a study population. Finally, there were not enough participants between 30 and 90
      days of age to obtain statistical significance for this age group.

      Also, studies have used varieties of concentrations of sucrose (e.g. Rogers had used sucrose
      24%, Curtis had used sucrose 44% and Lewindon had used sucrose 75%). Systematic reviews of
      the current literature have been unable to demonstrate superiority of one concentration of a
      sweet solution over another, but many studies suggest that higher concentrations of sweet
      solutions seem 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 3 months
      of age and it is safe (e.g. prednisone syrup is made using this syrup). A 2 ml dose of 88%
      sucrose contains the same amount of carbohydrates as 25 ml of infant milk formulas which
      contain approximately 7,5g/100 ml. Also, 88% sucrose has the same concentration of sugar as
      many other medications which are commonly used in infants, such as oral antibiotics, oral
      steroid solutions and other pain medications. This syrup is of particular interest as it is
      of low cost ($9,58 for a bottle of 2000 ml), universally available, stable and viable for
      approximately three months. Therefore, the intervention studied here would be easy to apply
      in most clinical settings.

      Finally, the painful procedure chosen for this study is bladder catheterization. Bladder
      catheterizations are frequently performed in the ED in this age group.

      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 5 categories, from 0 to 2 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 2 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 1 to 3 months old. Furthermore, the Neonatal Infant Pain Scale (NIPS) is a
      well validated pain scale for newborns up to 1 month of age. This pain scale was chosen as a
      secondary outcome. The investigators estimate that using one pain scale validated in infants
      up to 1 month of age and another validated in infants older than 2 months of age will allow
      us to assess pain in infants from 1 to 3 months of age best, given current available tools.
      Furthermore, other patient parameters such as heart rate and crying time will be used to
      corroborate findings.

      HYPOTHESIS THe investigators believe that providing an oral sucrose solution during bladder
      catheterization will decrease pain levels in infants 1 to 3 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
      1 to 3 months during bladder catheterization in the ED. The investigators secondary objective
      is to asses changes in pain levels as per the NIPS score. The investigators will also measure
      variations in heart rate and crying time. All side effects will also be reported.
    

Intervention name(s): 88% sucrose po solution; 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; bladder catheterization