Pilot Study of Sucrose to Reduce Pain in Sick Babies

Phase 4

Terminated

Conditions: Pain Due to Certain Specified Procedures

Interventions: Drug: 24% sucrose po solution
Drug: Placebo po

Registration Number: NCT01438008

Lead Sponsor: Children's Hospital of Eastern Ontario

Brief Summary: Small amounts of sweet tasting sugar water reduces pain in babies during painful blood tests and injections. The investigators do not know if sugar also reduces pain in babies already receiving a continuous infusion of opioid analgesics. This project will help determine if small amounts of sugar water reduce pain in babies already receiving a continuous infusion of opioid analgesic during a heel lance procedure or nasogastric/orogastric (NG/OG) tube insertions. The investigators hypothesize that infants who are receiving opioid analgesics will have lower pain scores during their blood tests (heel lance) or NG/OG tube insertion, when sucrose is given, compared to when water is given.

Detailed Description: Background: Sick infants nursed in Neonatal Intensive Care Units (NICU) are exposed to large numbers of repeated painful procedures during their hospitalization \[1-6\]. Effectively reducing pain during these frequently performed and repeated painful procedures minimizes short term behavioural and physiological responses to pain, and has the potential to reduce long term adverse effects, including altered responses to subsequent pain \[7\] and increased risk of adverse neurodevelopmental, behavioural, and cognitive outcomes \[8\] The effectiveness of sucrose and other sweet solutions in the reduction of pain during painful procedures in infants has been well established. Despite the large numbers of randomized controlled trials (RCTs) of sweet solutions for procedural pain reduction in infants, there remain significant knowledge and research gaps. One of the key unanswered questions is whether sweet solutions reduce pain when given with concomitant opioid analgesics \[9\].

Rationale: Sick infants in hospital need to have blood tests as part of their medical care. Oral sucrose and glucose has shown to effectively reduce behavioural responses to pain and pain scores during commonly performed painful procedures in preterm and term newborn infants and infants up to 12 months of age. However, the investigators do not know if this also works for infants already receiving a continuous infusion of opioid analgesics. The aim is to establish preliminary evidence of the effectiveness of oral sucrose in reducing pain during heel lancing or NG/OG tube insertion when concomitant opioid analgesics are being administered, and to use the pilot data to inform a full scale RCT.

Hypothesis: Infants who are receiving opioid analgesics will have lower pain scores during their blood tests (heel lance) or NG/OG tube insertion, when sucrose is given, compared to when water is given.

Primary Objective: To obtain preliminary data about the effectiveness of sucrose and concomitant opioid analgesics compared to opioid analgesics alone during the painful procedure of heel lancing or NG/OG tube insertion to inform a full scale RCT.

Secondary Objectives: To determine the acceptability of the interventions to infants' parents and to use these results to help us calculate sample size for a subsequent full trial.

Methods: A single-center, randomized, double-blind, placebo controlled pilot trial will be conducted in an urban tertiary care pediatric university-affiliated hospital NICU. The study population is all infants who are inpatients in the Neonatal Intensive Care Unit (NICU) who are receiving a continuous infusion of opioid analgesics and who require a heel lance for the purpose of medically-required capillary blood sampling or a NG/OG tube insertion. Study participants will be randomly allocated to receive 24% sucrose solution or a placebo solution (water). The maximum amount of the study solution will be administered according to the infant's gestational age and according to the hospital's Sucrose policy:

\<28 weeks gestation = maximum dose of 0.1 mL; 28-31 weeks gestation = maximum dose of 0.3 mL; 32-35 weeks gestation = maximum dose of 0.5 mL; \>36 weeks gestation = maximum dose between 0.5-1.0 mL.

The primary outcome measure is the difference in pain levels during the heel lance procedure or NG/OG tube insertion in the study population as assessed by the Premature Infant Pain Profile (PIPP).

Secondary outcomes will include; i) total crying time; ii) skin conductance activity, a valid, non-invasive, physiological measure of pain and stress in infants.

Statistical analysis: PIPP scores, crying time, and skin conductance activity will be summarized using mean and standard deviation if normally distributed, and median and interquartile range (IQR) if non-normally distributed. An intention to treat analysis will be performed.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 9

Inclusion Criteria

Infants who are inpatients of the NICU:

Who are receiving a continuous intravenous infusion of an opioid analgesic such as morphine or fentanyl at a maximum dose equivalent to 20 mcg/kg/hr of morphine and;
Who require heel lance for medically required blood sampling or nasogastric/orogastric (NG/OG) tube insertions and;
Who are eligible to receive sucrose as per the hospital's Sucrose policy for infants.

Exclusion Criteria

Infants less than 25 weeks gestation
Infants with any injury to the skin where the probe needs to be placed
Infants with an implanted defibrillator or pacemaker
Infants with an injury affecting sympathetic nerve conduction
Infants exposed to antenatal methadone
Infants who, aside from being on opioid analgesics, are ineligible to receive sucrose as per the hospital's Sucrose policy38
If the infant's mother wishes to breastfeed during the procedure
Infants with known or suspected fructose intolerance
Infants with spinal cord malformation (e.g. myelomeningocele and sacral teratoma) since these infant's response, and sensitivity to pain may differ from infants without spinal cord malformations
Infants who are unconscious, heavily sedated and those with absent gag and/or swallow reflex
Infants who are in isolation with only essential personnel caring for them
To ensure there is no interaction effect of muscle relaxants, which may impact on infants' ability to mount a behavioural response to pain, assessments will not be conducted until a period of 24 hours since the previous muscle relaxant dose
Parental language barrier (if unable to speak/understand French and/or English)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sucrose 24% po	24% sucrose po solution	24% sucrose solution. The Children's Hospital of Eastern Ontario (CHOE) pharmacy department will provide syringes labeled "NICU Pain Relief Study" containing a maximum dose of 1 mL of a 24% sucrose solution
Placebo po	Placebo po	The CHEO pharmacy department will provide a syringe labeled "NICU Pain Relief Study" containing a maximum of 1 ml dose of water (contents almost identical in color, consistency and odor to the sucrose solution) in identical packagings

Primary Outcome Measures

Name	Time	Method
Premature Infant Pain Profile (PIPP)	Baseline, day one of blood test	The Premature Infant Pain Profile (PIPP), a validated seven-indicator multidimensional pain assessment tool which is extensively used in neonatal pain research. The scale consists of seven indicators including assessment of gestational age and behavioural state (contextual indicators), heart rate and oxygen saturation (physiological indicators), and facial actions-brow bulge, eye squeeze, and nasolabial furrow (behavioural indicators), which are scored on a 0-3 scale and added for a total score of 0-21 Facial expression scores were also recorded on a 0-4 scale using a modified Neonatal Facial Coding System (NFCS) at 30, and 60 seconds following the beginning of the procedure. The modified NFCS coded for the presence (1) or absence (0) of the 4 most common facial expressions in response to acute pain (brow bulge, eye squeeze, nasolabial furrow, and stretch open mouth). High values on both of these scales represent worse outcome (i.e higher pain intensity).

Secondary Outcome Measures

Name	Time	Method
Total Crying Time	Total crying time were recorded as a proportion of the time spent crying over the total length of procedure and/or in the 3 minutes that followed.	Cry duration is a useful method to determine infant distress in general and to evaluate pain in the infant's environmental context.