Which is Better for Pain Reduction before Venipuncture: Glucose, Lidocaine or Expressed Breast Milk?
Aim: The aim of this study was to compare effects of 2 cc oral glucose (50%), topical application of lidocaine, 2 cc of expressed breast milk (EBM), and nothing per oral for reducing of pain before painful procedures. Patients and methods: In this case-control study, 121 term neonates were included. There were 3 groups of cases and one control group. Inclusion criteria were: term neonates (38-42 weeks); stable condition; per oral feeding; five minutes APGAR>7; and no history of narcotic usage. Neonates were randomly divided in 4 groups. Two milliliter of glucose solution (50%), topical application of lidocaine, and 2 cc of expressed breast milk via syringe were used for group I, II, and III respectively. Group IV is the control group. For control group, no additional measure was done. Data analysis was performed using SPSS ver 11.0 (SPSS Inc, Chicago, IL, USA). Chi-square, t-test, and ANOVA were used for analysis. P<0.05 was considered significant. Results: Score of Douleur Aiguë Nouveau-né was significantly lower in group III compared to other group (P<0.05, Tukey). Crying time in group III was significantly lower than group IV. Respiratory rate in group II was significantly lower than group IV (P=0.018). Pulse rate was significantly lower in group III compared to other group. Conclusion: Expressed breast milk is the safe and natural agents for reducing pain of neonates. Another clinical trial study with more samples is recommended.
Keyword : Expressed breast milk; Glucose; Lidocaine; Neonate; Pain
Introduction and Aim
Newborn infants routinely undergo painful invasive procedures, even in uncomplicated situation. There is evidence that shows neonates do feel pain and even have increased sensation to pain with longer duration compared to older children.1 Also, evidence showed even premature newborns may experience pain that could unfavourably affect clinical and behavioural parameters of their present and future.2 Some research showed sucrose as the most effective while other showed breastfeeding.3,4 In the Skogsdal et al study, they found 1 ml of glucose 30% had significant effect to reduce mild pain compared to breast milk.5 In the study from Turkey, repeated doses of hindmilk administration was an effective analgesic intervention.6 But in another study from Turkey, neither hindmilk nor foremilk is superior in relieving pain compared to placebo.7
Although there are studies on pharmacologic8,9 and non pharmacologic agents which may reduce neonatal pain, more research are needed to find the most effective, and least expensive method for decreasing pain in neonates. This pharmacologic (Sucrose) or non pharmacologic agents (pacifier) may interfere with correct breastfeeding.10 So, it may be interesting, especially in developing country; to use safest, less expensive and most available method such as breast milk for analgesia. The aim of this study was to compare effects of 50% glucose 2 cc topical lidocaine, breast milk 2 cc and control for reducing pain following painful procedures.
Patients and Methods
In this case-control study, 121 term newborns (6.21±6.49 day, range:1-30 day) were included. In our study sample size was calculated according to research conducted by Mathai et al11 and Yilmaz and Arikan studies.12 Newborns were randomly placed in 4 groups: 3 groups of cases and one control group. Inclusion criteria were: term neonates (38-42 weeks); without evidence of poor feeding; stable condition; per oral feeding; five minute APGAR>7; and no history of narcotic usage. Exclusion criteria were difficult venipuncture. We included cases with 1st time venipuncture on the hand. In our cases, venipucture was done for blood sampling. Neonates were randomly divided in 4 groups. For group I (glucose), 2 cc glucose 50% was administered orally, 2 minutes before procedure. Thirteen minutes before venipuncture, 1 gr of Lidocaine gel (2%) was administered topically in group II.13,14 For group III (breast milk), 2 cc breast milk was administered orally via syringe at 2 minutes before venipuncture. For control group, routine venipuncture was performed without adding anything. Venipunctures were done in the quiet room. After 1st step, an experienced nurse who is blind to group allocation of patients came for evaluation. During venipuncture, an experienced nurse measured crying times in the 1st 3 minutes after procedure. Validated Score of DAN (Douleur Aiguë Nouveau-né) scale (primary outcome measure)15,16 was used for pain assessment (Table 1). Facial expression, limb movements, and vocal expression were evaluated by DAN scale. A score from 0 (no pain) to 10 (highest pain) was attributed to each neonates, according to intensity of pain.15,17 Data analysis was performed using SPSS ver 11.0 (SPSS Inc, Chicago, IL, USA). Two-sample t-test, ANOVA, Spearmen, and Tukey tests were used for analysis.
Of 121 cases, 83 (68.6%) were male and 38 (31.4%) were female (Chi2=33.47, P<0.0001). Male ratios in glucose, lidocaine, EBM, and control were 63.33%, 60%, 73.33%, and 77.41% respectively. There were no significant difference between groups regarding sex ratio (P=0.41). Mean±SE of age was 6.21±6.49 day. Crying time was significantly less in group III (P=0.0001, ANOVA). DAN score was significantly lower in group III (P<0.05, ANOVA). Respiratory rate was significantly lower in group I (P=0.018, ANOVA). Among the four groups, the lowest pulse rate was seen in group III (P=0.000, ANOVA). By using Tukey-test, there was significant difference between mean crying time of group III (21.600±3.138) and group IV(55.96±6.85). Mean of DAN score was significantly lower in group III compared to group I, II and IV (P<0.05, Tukey). There were no significant differences between other groups using Tukey-test. Respiratory rate in control subjects was significantly higher than EBM cases. Pulse rate was significantly lower in group III compared to other group using Tukey-test. Pulse rate was significantly higher in group IV compared to other groups (P<0.05).
In our study, crying time was significantly lesser in group III compared to control group. In the study by Olsson and Eriksson, there was no significant difference between case and controls.18 Their study was conducted on pre-term neonates while we studied term neonates. In the study by Miazzo et al on the infants 30-36 weeks of gestation, using 24% sucrose solution, significant reduction in crying subscale of the Neonatal Infant Pain scale was found.19 They didn't include breast milk in their study but we included 50% glucose, lidocaine, and EBM in our study. In our study, in term neonates, we showed that EBM is more effective than higher sucrose concentration even 50%.
In our study mean of DAN score was significantly lower in group III (EBM) compared to group I, II, and IV. In the study by Upadahyay et al, the modified Neonatal Facial Coding Scores (NFCS) was significantly lower in the EBM group compared to placebo.20 The results of two studies were similar regarding effect of EBM on reducing pain. In their study, distilled water was used as a placebo. We compared EBM with 50% glucose, lidocaine, and nothing per oral in this study.
In the study by Ors et al, 25% sucrose was superior to expressed breast milk in pain relief, especially in crying time and behavioural variable.21
In the study by Askarpour et al, authors concluded that oral glucose is the safe analgesic agent. In their study, comparison between different solutions of glucose and distilled water was performed.22 In the study by Eriksson et al, the choice of blood sampling has no impact on the pain symptom if blood glucose was given prior to sampling.23
In our study we showed that breast milk significantly reduced crying time and DAN score. In the study by Bueno et al on 113 newborns to compare EBM versus 25% glucose, they found that 25% glucose was more effective than EBM in reducing pain and crying.24 But in their study, groups were similar regarding demographics and clinical characteristics, except for birth weight at data collection day. In both studies, groups were not completely similar, and this may affect final measurement. In the study by Jatana et al, on 125 full term newborn (5 groups of 25 each), they found 10%; 25%; 50% of glucose solutions and EBM were found to reduce physiological and behavioural response in neonates undergoing painful procedures. EBM and 10% glucose solution have similar effect but less than 25% and 50% glucose solution.25
Pulse rate was significantly lower in group III case compared to other especially versus controls. In another study on the effect of expressed breast milk, changes in heart rate was significantly lower in expressed breast milk group compared to distilled water as a placebo.20 The results of the two studies were similar regarding effect of EBM on the heart rate.
In the Simonse et al study on 71 preterm neonates, they found no significant difference in Premature Infant Pain Profile in neonates receiving glucose and those receiving breast milk (either breast fed or bottle fed).26
Several studies showed superiority of glucose/sucrose for reducing pain compared to breast feeding/breast milk.24 Shah et al in a systematic review concluded, breastfeeding or breast milk should be used to alleviate pain in neonates undergoing painful procedure. Administration of sucrose/glucose had similar effect.27 In another study by Codipietro et al, on 101 term neonates undergoing heal lance using an automated device, median of Premature Infant Pain Profile was significantly lower in breast fed neonates.28
Previous studies by Skogsdal et al,5 and Ors et al,21 showed a trend toward reduction in pain with use of 1-2 ml of expressed breast milk, but their results were not statistically significant. Upadahay et al showed significant effect of 5-ml of expressed breast milk compared to placebo.20 In the current study, we showed significant effect of 2-ml of EBM compared to 50% glucose, topical lidocaine, and nothing per oral. All studies on the effect of EBM had different ages and weights of the cases. There is also differences between dose of EBM used in studies.
Dose related response may be important in the evaluation of effect of EBM. EBM has a 7% lactose which was lower than the same volume of glucose. Duration of venipucture may be important. Age of the cases varied between 1-15 days in Ors et al,21 8-9 days in Upadhyay,20 to 40-46 days in Mathai et al11 study. More studies are needed in this matter.29
In this study, there was no significant difference between effect of local anesthetic and nothing per oral group. This may be due to inappropriate anesthetic agent, and shorter duration of use. However, we assessed lidocaine gel as the most available drug in our province. Most of studies used Eutectic Mixture of Local Anesthetics with a duration more than 1 hour.30
Our results supported expressed breast milk as the safest, more effective, and inexpensive method for analgesia in neonates. Another prospective study with more sample and measurement of beta endorphin and lactose level is recommended when compared to glucose/sucrose.
In this study, however we selected cases randomly but age of the cases had significantly different, age of the cases in the EBM group was higher than other group.
This study was supported by student research committee of Ahvaz Jundishapur University of Medical Sciences (Registration no=89s71). This study was approved by ethical committee of university (Ethic code=Eth91s.5). Author's acknowledged Mrs. Kobra Moazen (Head of Nursery), Hoda Mohammadi and Mr. Mohammad Kochak Molashahi.
Conflict of Interest
There is no conflict of interest.
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