Effect of multisensory stimulation on analgesia in term neonates: a randomized controlled trial

Many attempts have been made to obtain safe and effective analgesia in newborns. Oral glucose-water has been found to have analgesic properties in neonates. We investigated whether other sensory stimulation added to oral glucose provided more effective analgesia than oral glucose alone. In a randomized prospective double-blind trial, we studied 120 term newborns during heel prick. The babies were divided randomly into six groups of 20, and each group was treated with a different procedure during heel prick: A) control; B) 1 mL 33% oral glucose given 2 min before the heel prick; C) sucking; D) 1 mL 33% oral glucose plus sucking; E) multisensory stimulation including 1 mL 33% oral glucose (sensorial saturation); F) multisensory stimulation without oral glucose. Sensorial saturation consisted in massage, voice, eye contact, and perfume smelling during heel prick. Each heel prick was filmed and assigned a point score according to the Douleur Aigu? du Nouveau-né (DAN) neonatal acute pain scale. Camera recording began 30 s before the heel prick, so it was impossible for the scorers to distinguish procedure A (control) from B (glucose given 2 min before), C (sucking water) from D (sucking glucose), and E (multisensory stimulation and glucose) from F (multisensory stimulation and water) from the video. Procedure E (multisensory stimulation and glucose) was found to be the most effective procedure, and the analgesia was even more effective than that produced by procedure D (sucking glucose). We conclude that sensorial saturation is an effective analgesic technique that potentiates the analgesic effect of oral sugar. It can be used for minor painful procedures on newborns.     

Analgesic effects of breast-feeding or pacifier use with maternal holding in term infants.

OBJECTIVES: First, to compare analgesic effects of breast-feeding versus pacifier use in newborn infants undergoing blood collection via heel sticks. Second, to compare analgesic effects of pacifier use with maternal holding versus nonmaternal holding. DESIGN: A prospective, randomized, controlled trial. SETTING: Normal newborn nursery at academic teaching hospital. PARTICIPANTS: Full-term breast-feeding infants scheduled for routine newborn screening blood test via heel stick (n = 96). Interventions.-Infants randomized to 3 groups for analgesia: 1) breast-feeding, 2) pacifier use while held by mothers, 3) pacifier use while held by research assistants (nonmothers). OUTCOME MEASURES: Primary outcome was crying (percent of infants who cried during the procedure and mean percent of procedure time that infants cried). Secondary outcomes were physiologic measures. RESULTS: Fewer breast-feeding infants cried than infants using a pacifier while held by nonmothers both during the procedure (69% vs 100%, P < .01) and after the procedure (28% vs 60%, P = .03). Those infants crying during the procedure cried for less time if held by their mothers either breast-feeding (33%, P < .01) or using a pacifier (45%, P = .03) than those using a pacifier while being held by nonmothers (66%). CONCLUSION: Breast-feeding is more analgesic than pacifier use with nonmaternal holding. Maternal holding with either breast-feeding or pacifier use is more analgesic than nonmaternal holding with pacifier use, suggesting that maternal holding itself has an analgesic effect. Breast-feeding and maternal holding should be considered as pain-control measures for the neonate during heel-stick procedures.     

Analgesia with saccharose during heel capillary prick. A randomized study in 37 newborns of over 33 weeks of amenorrhea]

BACKGROUND: To evaluate the efficiency of intraoral saccharose administration for analgesia among neonates born after at least 33 weeks of gestation. POPULATION AND METHOD: Thirty-seven neonates from two neonatal units were tested using an objective scale of infants' pain. A double blind study of the heel prick response after saccharose vs. water administration was performed. RESULTS: Prior administration of saccharose significantly reduced the pain reaction (1.24 vs. 2.24, P < 10(-5)). CONCLUSION: The analgesia obtained after an intraoral saccharose administration can be useful for repeated punctures for which common procedures of analgesia are ineffective. Beyond its use for heel prick, this procedure could be proposed for venous punctures when ELMA analgesia is not possible.     

Pain-relieving effect of sucrose in newborns during heel prick

We assessed the effect of sucrose as a pain reliever in a population of newborns when cuddled and comforted during heel prick for diagnosis of phenylketonuria. In addition, the influences of gender, gestational age, postnatal age, ponderal index and behavioural state of the infant before the heel prick were studied, as judged by the neonatal infant pain scale (NIPS) score, on crying time (CT) and subsequent NIPS score. 100 healthy full-term infants were enrolled in this double-blind, randomized controlled trial. Before the heel prick, the newborns, when cuddled by the parent(s), were either given 2 ml 50% sucrose solution or 2 ml sterile water. The sessions were videotaped and analyzed for determination of CT and NIPS scores. The frequency distribution of CT showed a bimodal pattern in both the sucrose and the placebo groups. Sucrose significantly reduced CT and NIPS scores after the heel prick. No influence of gender, gestational age, postnatal age or ponderal index on CT was found. NIPS scores before the heel prick correlated significantly and positively with CT and subsequent NIPS scores in both the sucrose and the placebo groups. Intra-orally administered sucrose given before heel prick can be recommended as a useful pain reliever. Furthermore, the findings indicate that factors calming the newborn and creating low NIPS scores before the procedure can reduce the pain reaction equivalently and additively to sucrose administration.     

Comparison of two doses of breast milk and sucrose during neonatal heel prick

Background: The aim of the present study was to test analgesic effects of double‐ versus single‐dose breast milk and compare this effect with efficacy of double‐ versus single‐dose sucrose in a group of healthy term newborns during heel prick blood sampling. Methods: Healthy newborns (n= 142) were consecutively allocated to one of the six groups: group 1, single‐dose breast milk; group 2, single‐dose sterile water; group 3, single‐dose 12.5% sucrose; group 4, two doses breast milk; group 5, two doses sterile water; and group 6, two doses 12.5% sucrose before the heel prick. The medians for crying time and the pain scores according to the neonatal facial coding system were recorded. Results: Crying times were 117 s, 126 s, 82 s, 128 s, 117 s, and 95 s in groups 1–6, respectively (P= 0.053). The mean pain scores were 4.60, 5.82, 3.91, 4.94, 5, and 4.05 in groups 1–6, respectively (P= 0.068). There was a significant difference between the groups for mean pain scores at 1 min and 3 min. There was a significant difference between the single‐dose sucrose group and single‐dose sterile water group at 1 min (P= 0.002). The babies in the sucrose group were active awake, whereas the ones in the breast milk group were asleep before heel prick. Conclusion: Two doses of sucrose solution were not superior to single‐dose sucrose. Neither single nor double doses of breast milk were effective in relieving pain in neonates. Two milliliters breast milk does not reduce response to pain during minor painful procedures in term neonates even when two doses have been given. Further studies are needed.     

Can topical lignocaine reduce behavioural response to heel prick?

In a randomised, double blind, controlled study the ability of 5% lignocaine ointment to reduce the behavioural response to heel lance in 30 healthy neonates was assessed. Five per cent lignocaine ointment applied to the heel under an occlusive dressing for one hour before heel prick did not reduce the infants'' behavioural response to the heel prick procedure.     

Food intake and oral sucrose in preterms prior to heel prick

To investigate the soothing effect of feeding on infants in distress, the effects of 2 mL 15% and 1 mL 25% sucrose given orally 2 min before heel prick in fasting preterms to reduce the pain response were assessed. The effects of milk intake by nasogastric tube were also assessed once during the last hour before heel prick, and the effects of milk intake by nasogastric tube once during the last hour before heel prick together with 1 mL 25% sucrose given orally 2 min before heel prick. The pain response was measured as changes in crying time, behavioural state, skin conductance and heart rate. Each group included 12 healthy preterm infants with a median gestational age of 32 wk and a median postnatal age of 14 d. These infants were randomly studied twice; one in connection with the intervention and once after being given sterilized water. Differences in the measured variables before and during heel prick showed that only the crying time was reduced when the infants received milk or 25% sucrose prior to heel prick (p < 0.05). If the infants received milk and 25% sucrose before heel prick, the crying time and the level of behavioural state were reduced (p < 0.05). The increase from before to during heel prick in skin conductance (number and amplitude of the waves) and heart rate correlated with the crying time (p < 0.01).     

Oral sucrose compares favourably with lidocaine-prilocaine cream for pain relief during venepuncture in neonates

To compare the relative efficacy of oral sucrose versus EMLA cream for pain relief during venepuncture, 51 full-term newborns (38M, 13F; postnatal age <4 d) in a stable condition were randomly allocated to one of four treatment groups: placebo (2 ml spring water); 2 ml sucrose 24% w/v; 1 g lidocaine-prilocaine 5% cream (EMLA); or EMLA plus sucrose. Water or a single dose of sucrose solution was administered orally 2 min before venepuncture. EMLA cream was applied in the antecubital fossa 45-60 min before venepuncture and covered by a Tegaderm dressing. A pacifier was given before skin puncture, but it was not actively held or replaced during the procedure or observation periods. In total, 55 venepunctures were performed blindly, always for clinical reasons. As indicators of pain, the total crying time was recorded and heart rate, respiratory rate and arterial oxygen saturation were measured blindly at baseline, immediately post-venepuncture, and 2 and 4 min afterwards. The main effects observed were: (i) time spent crying decreased significantly in the sucrose alone (p = 0.001) and EMLA plus sucrose (p = 0.008) groups; (ii) the above treatments attenuated significantly (p < 0.05) the immediate heart rate response to pain; and (iii) the concomitant use of EMLA did not increase further the analgesic efficacy of sucrose. Conclusion: This study shows that a 24% oral sucrose solution compares favourably with EMLA cream as a safe and cheap analgesic procedure to decrease pain responses to venepuncture in newborns.     

Pain assessment and procedural pain management practices in neonatal units in Australia

OBJECTIVE: To identify current pain assessment and procedural pain management practices in neonatal units in Australia. METHODS: Postal survey conducted during December 2003 and January 2004. The survey comprised questions relating to pain assessment scores, pain reduction strategies for minor painful procedures and the use of articulated policies relating to procedural pain management. Participants were the Nurse Unit Managers or their nominees of neonatal intensive care units, special care units and newborn emergency transport services in Australia. RESULTS: Surveys were sent to 181 eligible organizations, and 105 of these were returned (58%). Six units (6%) used pain assessment scores on a regular basis, and 16 units (15%) had an articulated policy directing pain management practices during painful procedures. Non-nutritive sucking and various nursing comfort measures were the pain reduction strategies most frequently used during minor painful procedures. Twenty-four units (23%) used sucrose or other sweet-tasting solutions during procedures; however, the reported frequency of their usage was low. Breast-feeding during venepuncture, heel lance and intramuscular or subcutaneous injection was infrequently practised and topical anaesthetic agents were rarely used. CONCLUSION: This survey demonstrates that the majority of Australian neonatal units have no articulated policy to guide pain management during painful procedures and do not regularly undertake pain assessments. Current evidence-based strategies to reduce procedural pain in hospitalized infants are used infrequently.     

Topical amethocaine gel for pain relief of heel prick blood sampling: a randomised double blind controlled trial

BACKGROUND: Heel prick blood sampling is a commonly performed and painful procedure in the newborn infant. Use of a topical local anaesthetic does not relieve this pain. A 4% w/w amethocaine gel (Ametop) reduces the pain of venepuncture in the newborn but has not been tried with heel pricks. AIM: To investigate the effect of topical amethocaine gel on the pain of heel prick in the newborn infant. DESIGN: Randomised, double blind, placebo controlled trial. SUBJECTS: Sixty newborn infants, gestation 28-42 weeks (median 36), postnatal age 1-16 days (median 5) undergoing routine heel prick blood sampling. METHODS: A 1.5 g portion of 4% w/w amethocaine gel or placebo was applied to the skin under occlusion for one hour, then wiped away. Heel prick blood sampling with a spring loaded lance was performed five minutes later. The procedure was videotaped and pain assessed at one second intervals using an adaptation of the neonatal facial coding system (NFCS). No or minimal pain was defined as a cumulative score of less than 5 (out of 15) in the three seconds after firing of the lance and as lack of a cry in the first five seconds. RESULTS: In terms of a low NFCS core and lack of cry (p = 0.12) 20 of 30 (67%) in the amethocaine group and 13 of 29 (45%) in the placebo group had no or minimal pain in response to the heel prick. The median cumulative NFCS score over the three seconds after firing the lance was 3 (interquartile range 0-6) in the amethocaine group compared with 5 (interquartile range 1-10) in the placebo group (p = 0.07). These differences are not significant. CONCLUSIONS: Topical amethocaine gel does not have a clinically important effect on the pain of heel prick blood sampling and its use for this purpose cannot therefore be recommended. Alternative approaches to the relief of pain from this procedure should be explored.     

Effect of sucrose on crying in response to heel stab.

It has been suggested that sucrose acts as an analgesic in the neonatal period. To evaluate this further, 52 infants received either 2 ml of 7.5% sucrose or 2 ml of sterile water before heel stab blood sampling. The duration of crying in response to sampling did not differ in the two groups but was related to level of arousal at the time of stimulation.     

Effect of sucrose on crying in response to heel stab

It has been suggested that sucrose acts as an analgesic in the neonatal period. To evaluate this further, 52 infants received either 2 ml of 7.5% sucrose or 2 ml of sterile water before heel stab blood sampling. The duration of crying in response to sampling did not differ in the two groups but was related to level of arousal at the time of stimulation.     

"Sucrose analgesia": absorptive mechanism or taste perception?

It remains unclear whether "sucrose analgesia" is related to a pre- or postabsorptive mechanism. In a double blind cross over study sucrose reduced the pain response of preterm infants exposed to heel prick blood samples only when it was administered into the mouth. It was ineffective when administered intragastrically.     

Pain management and the effect of guidelines in neonatal units in Austria, Germany and Switzerland

BACKGROUND: Painful invasive procedures are frequently performed on preterm infants admitted to a neonatal intensive care unit (NICU). The aim of the present study was to investigate current pain management in Austrian, German and Swiss NICU and to identify factors associated with improved pain management in preterm infants. METHODS: A questionnaire was sent to all Austrian, German and Swiss pediatric hospitals with an NICU (n = 370). Pain assessment and documentation, use of analgesics for 13 painful procedures, presence of written guidelines for pain management and the use of 12 analgesics and sedatives were examined. RESULTS: A total of 225 units responded (61%). Pain assessment and documentation and frequent analgesic therapy for painful procedures were performed more often in units using written guidelines for pain management and in those treating >50 preterm infants at <32 weeks of gestation per year. This was also the case for the use of opioid analgesics and sucrose solution. Non-opioid analgesics were used more often in smaller units and in units with written guidelines. There was a broad variation in dosage of analgesics and sedatives within all groups. CONCLUSION: Pain assessment, documentation of pain and analgesic therapy are more frequently performed in NICU with written guidelines for pain management and in larger units with more than 50 preterm infants at <32 weeks of gestation per year.     

Development and validation of the ABC pain scale for healthy full-term babies

AIM: We developed and validated a pain scale (ABC scale) for term babies based on acoustic features of crying. METHODS: The scale consisted of three different cry parameters: (a) pitch of the first cry; (b) rhythmicity of the crying bout; (c) constancy of crying intensity. These parameters were previously found to distinguish between medium and high levels of pain measured by spectral analysis of crying. We validated the scale using healthy term babies undergoing routine heel prick. Concurrent validity was assessed comparing pain values obtained with our scale with those obtained with another pain scale; this relationship was also used to assess the sensitivity of the scale. To assess specificity we compared the ABC scores during a painful event (heel prick) with two non-painful events (preliminary phase of prick in the same group of babies, and heel prick with analgesia in another group). RESULTS: Specificity: (a) analgesic/non-analgesic comparison, p < 0.0001; (b) pain/sham comparison, p < 0.0001). Sensitivity: a high correlation between scores of the ABC scale and the Douleur Aigue du Nouveau-Né scale indicates good sensitivity. Concurrent validity: Spearman rho = 0.91. Internal consistency: Cronbach's alpha = 0.76. Inter-rater reliability: Cohen's kappa for multiple raters = 0.83. Intra-rater reliability: Cohen's kappa = 0.85. Practicality: All nurses who used it scored the scale as "good". CONCLUSION: The ABC scale proved to be simple and reliable for assessing pain in healthy, non-intubated term newborns.     

Effect of non-sucrose sweet tasting solution on neonatal heel prick responses.

A substance commercially described as ''sugar free,'' used as a sweetener for paracetamol suspension, was evaluated on measures of neonatal pain. Sixty infants were randomly allocated to receive one of four solutions before heel stab blood sampling: sterile water (placebo); 25 or 50% sucrose (weight/volume); and the commercial sweet-tasting solution. There was a significant reduction in crying time and pain score 3 minutes after the painful stimulus in all groups compared with the controls. It is concluded that this sweet-tasting solution has analgesic effects as potent as those of concentrated sucrose solutions.     

Venepuncture is preferable to heel lance for blood sampling in term neonates

BACKGROUND: The analgesic effect of oral sucrose in newborn infants undergoing painful procedures is generally accepted. For blood sampling, some studies have shown that venepuncture (VP) is less painful than heel lance (HL). OBJECTIVE: To determine the least painful and most effective method among blood sampling by VP or HL with or without sucrose. DESIGN: Randomised, double blind, placebo controlled trial. SUBJECTS: A total of 100 healthy, full term newborn infants being screened for inborn errors of metabolism were randomly allocated to one of four experimental groups (25 infants in each).Intervention and OUTCOME MEASURE: Seven specially trained nurses took turns to carry out blood sampling two minutes after administration of oral sucrose or water. Neonatal pain was assessed by the neonatal facial coding system (NFCS), as well as by crying. RESULTS: Without sucrose, the NFCS score was higher in the HL group than the VP group during blood sampling (median 58 v 23, p<0.001). Oral sucrose significantly reduced the score of the HL group (58 v 47, p<0.01) and also tended to reduce the score of the VP group (23 v 2, p<0.1). However, the HL with sucrose group still had a higher score than the VP without sucrose group (47 v 23, p<0.01). Crying and the total procedure time showed the same trends as the NFCS score. CONCLUSIONS: VP is less painful and more effective than HL for blood sampling in newborn infants. Although oral sucrose may have an additive analgesic effect, it is not necessarily required if VP is used for blood sampling.     

Sugaring the pill: ethics and uncertainties in the use of sucrose for newborn infants

Sucrose is widely used for the management of procedural pain in newborn infants, including capillary blood sampling, venepuncture, and vascular cannulation. Multiple randomized controlled trials have demonstrated that sweet-tasting solutions reduce behavioral responses to acute painful stimuli. It has been claimed that sucrose should be a standard of care in neonatal units and that further placebo-controlled trials of sucrose are unnecessary and unethical. However, recently published data cast doubt on the analgesic properties of sucrose. We review this new evidence and analyze the philosophical and ethical questions that it raises, including the "problem of other minds." Sugar may be better understood not as an analgesic, removing or relieving pain, but as a compensating pleasure. There is a need for further research on the mechanism of sucrose's effect on pain behavior and on the long-term effects of sucrose treatment. Such trials will require comparison with placebo or with other interventions. Given uncertainty about the benefit of sucrose, it may be wise to use alternative analgesics or nonpharmacological interventions where these are available and appropriate. Sucrose may not be the answer to procedural pain in newborns.     

Variability in pain response to a non-pharmacological intervention across repeated routine pain exposure in preterm infants: a feasibility study

Aim: To explore the variability in pain response in preterm infants across time who received sucrose during routine heel stick.
Method: Single group, exploratory repeated measures design.
Setting: Two tertiary level neonatal intensive care units (NICU) in Switzerland.
Subjects: Nine preterm infants born between 28 2/7 and 31 4/7 weeks of gestation during their first 14 days of life.
Measurements: Pain was assessed by the Bernese Pain Scale for Neonates (BPSN), the Premature Infant Pain Profile (PIPP) and the Visual Analogue Scale (VAS). Salivary cortisol was analysed.
Results: 72–94% of the variability was within-subject variability, indicating inconsistency of pain responses across the 5 heel sticks. Interrater agreement was highest during heel sticks 1–3 and decreased during heel stick 4 and 5, indicating a possible alteration of pain patterns. No significant differences in the amount of cortisol could be detected before and after the heel sticks (p = 0.55), indicating no stress-induced peak after the painful intervention. However, a general gradual decrease of cortisol levels across time could be detected.
Conclusion: A high variability in pain response among preterm neonates across time could be described. Consistency of cortisol levels before and after the heel sticks could indicate the effectiveness of sucrose across time.     

Randomised controlled trial of paracetamol for heel prick pain in neonates

AIM: To evaluate the effectiveness of paracetamol in decreasing the pain from heel prick. METHODS: A prospective randomised double blind placebo controlled trial was conducted of 75 term neonates undergoing heel prick. Sixty to 90 minutes before the procedure neonates received paracetamol orally in a dose of 20 mg/kg (group 1) or an equal volume of placebo (group 2). Heel prick was performed in a standardised manner. Pain assessments were made using per cent facial action (brow bulge, eye squeeze, and nasolabial fold (range 0-300%) and per cent of time spent crying (range 0-100%). RESULTS: Thirty eight neonates were enrolled in group 1 and 37 neonates in group 2. There were no significant differences in the demographic characteristics between groups. Mean gestational age was 39 (SD 1.4) vs 39.4 (SD 1.2) weeks, p = 0.86, mean birthweight 3.45 (SD 0.45) vs 3.44 (SD 0.42) kg; p = 0.31 for groups 1 and 2, respectively. Facial action pain scores did not differ between groups (143.5 (SD 54.2)% vs 131.1 (SD 59.6)%; p = 0.38). Cry scores also did not differ (29.4 (SD 19.9)% vs 26.8 (SD 20.2)%; p = 0.60). No adverse effects were observed. CONCLUSION: Paracetamol is ineffective for decreasing the pain from heel prick in term neonates.