Pain Due to Certain Specified Procedures
Conditions
Keywords
Sucrose, Pain
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.
Interventions
DRUG24% sucrose po solution
CHEO pharmacy department will provide syringes labeled NICU Pain Relief Study containing a maximum of 1 ml dose of a 24% sucrose solution. 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. The total amount of the study solution will be divided into a maximum of 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure.
DRUGPlacebo po
CHEO pharmacy department will provide syringes labeled NICU Pain Relief Study containing a maximum of 1 ml dose of water (almost identical in color, consistency and odor placebo to the sucrose solution in identical packaging) The total amount of the study solution will be divided into 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure
Sponsors
University of Ottawa
Children's Hospital of Eastern Ontario
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Canada
Participant flow
Recruitment details
Between June 2012 and September 2015, 73 infants admitted in the NICU were assessed for eligibility, 50 (69%) were ineligible, of the 23 (32%) infants that were approached, 7 (3%) declined to participate, 16 (70%) provided consent.
Pre-assignment details
Consent was obtain for 16 infants to participate, 7 (44%) were not randomized (prior to data collection n=3 infants were weaned off fentanyl, n=3 infants were discharged/transferred, n=1 medical team refused). 9 (12%) infants were randomized. 4 infants were allocated to sucrose and 5 infants were allocated to water.
Participants by arm
| Arm | Count |
|---|---|
| Sucrose 24% po 24% sucrose solution. The CHEO pharmacy department will provide syringes labeled NICU Pain Relief Study containing a maximum dose of 1 mL of a 24% sucrose solution
24% sucrose po solution: CHEO pharmacy department will provide syringes labeled NICU Pain Relief Study containing a maximum of 1 ml dose of a 24% sucrose solution. 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. The total amount of the study solution will be divided into a maximum of 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure. | 4 |
| 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
Placebo po: CHEO pharmacy department will provide syringes labeled NICU Pain Relief Study containing a maximum of 1 ml dose of water (almost identical in color, consistency and odor placebo to the sucrose solution in identical packaging) The total amount of the study solution will be divided into 5 aliquots and administered throughout the procedure at two minutes prior to the heel lance, immediately prior to the heel lance, and two-minutely intervals until completion of the procedure | 5 |
| Total | 9 |
Baseline characteristics
| Characteristic | Sucrose 24% po | Placebo po | Total |
|---|---|---|---|
| Age, Continuous | 261.5 gestational age (days) | 236.0 gestational age (days) | 236.0 gestational age (days) |
| Duration of Procedure | 281 seconds | 380 seconds | 301 seconds |
| Previous use of sucrose No | 1 Participants | 1 Participants | 2 Participants |
| Previous use of sucrose Unknown | 2 Participants | 0 Participants | 2 Participants |
| Previous use of sucrose Yes | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 4 Participants |
| Type of opioid administered Fentanyl | 3 Participants | 4 Participants | 7 Participants |
| Type of opioid administered Morphine | 1 Participants | 1 Participants | 2 Participants |
| Type of Procedure Heel lance | 4 Participants | 4 Participants | 8 Participants |
| Type of Procedure Naso/oro gastric insertion | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 0 / 5 |
| serious Total, serious adverse events | 0 / 4 | 0 / 5 |
Outcome results
Primary
Premature Infant Pain Profile (PIPP)
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).
Time frame: Baseline, day one of blood test
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sucrose 24% po | Premature Infant Pain Profile (PIPP) | PIPP-R at 30 seconds | 9.5 score on a scale |
| Sucrose 24% po | Premature Infant Pain Profile (PIPP) | PIPP-R at 60 seconds | 9.5 score on a scale |
| Sucrose 24% po | Premature Infant Pain Profile (PIPP) | NFCS at 30 seconds | 1.5 score on a scale |
| Sucrose 24% po | Premature Infant Pain Profile (PIPP) | NFCS at 60 seconds | 2 score on a scale |
| Placebo po | Premature Infant Pain Profile (PIPP) | NFCS at 60 seconds | 0 score on a scale |
| Placebo po | Premature Infant Pain Profile (PIPP) | PIPP-R at 30 seconds | 10 score on a scale |
| Placebo po | Premature Infant Pain Profile (PIPP) | NFCS at 30 seconds | 0 score on a scale |
| Placebo po | Premature Infant Pain Profile (PIPP) | PIPP-R at 60 seconds | 9 score on a scale |
Secondary
Total Crying Time
Cry duration is a useful method to determine infant distress in general and to evaluate pain in the infant's environmental context.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sucrose 24% po | Total Crying Time | 0 seconds |
| Placebo po | Total Crying Time | 0 seconds |