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Year : 2022  |  Volume : 10  |  Issue : 3  |  Page : 118-123

Assessment 20% oral dextrose induced analgesia during screening for retinopathy of prematurity

Department of Ophthalmology, Yenepoya Medical College, Deralakatte, Karnataka, India

Date of Submission02-Jan-2022
Date of Decision10-Jul-2022
Date of Acceptance09-Aug-2022
Date of Web Publication1-Dec-2022

Correspondence Address:
Anupama Bappal
Department of Ophthalmology, Yenepoya Medical College, Deralakatte, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcor.jcor_1_22

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Aim: The aim of this study was to assess the relief from pain afforded by orally administered 20% dextrose as an analgesic for the purpose of retinopathy of prematurity (ROP) screening. Setting and Study Design: This was an observational case–control subject study design. Materials and Methods: This study was performed over a period of 19 months during the first ROP screening. The readings of clinical and behavioral parameters of preterm babies were taken at baseline and monitored continuously during the screening procedure. The right eye was examined before administration of oral dextrose (WOD) and the left eye was examined after administration of dextrose orally (WD). Babies were given 2 ml of 20% dextrose orally with syringe. ROP screening was performed under topical anesthesia with binocular indirect ophthalmoscope. Pain score was calculated by premature infant pain profile scoring system. Results: One hundred and two babies participated in this study, of which 33 (32.35%) babies had a gestational age ≤32 weeks. Statistical analysis done using Wilcoxon signed-rank test showed significant P values for pain score (P < 0.001), heart rate (P < 0.05), oxygen saturation (P < 0.05), and behavioral parameters (P < 0.001) for WOD and WD. Pain score, WOD, and WD in babies ≤32 and >32 weeks were also significant (P < 0.001) for pain score, heart rate (<0.05), and behavioral parameters except for oxygen saturation (P > 0.05) (Mann–Whitney U test). Conclusions: Oral dextrose has a significant role in reducing pain, during ROP screening, but does not alleviate pain completely. The within-subject study design ensured close to identical baseline parameters, thereby providing better internal reliability of the study.

Keywords: Oral dextrose, premature infant pain profile scoring system, preterm, retinopathy of prematurity

How to cite this article:
Singh C, Bappal A, Mithun H K. Assessment 20% oral dextrose induced analgesia during screening for retinopathy of prematurity. J Clin Ophthalmol Res 2022;10:118-23

How to cite this URL:
Singh C, Bappal A, Mithun H K. Assessment 20% oral dextrose induced analgesia during screening for retinopathy of prematurity. J Clin Ophthalmol Res [serial online] 2022 [cited 2023 Feb 9];10:118-23. Available from: https://www.jcor.in/text.asp?2022/10/3/118/362495

Retinopathy of prematurity (ROP) is one of the causes for preventable blindness in preterm babies. The World Health Organization has indicated that the third epidemic of ROP is presently occurring in “middle-income countries,” the previous two epidemics (1940 and 1970) having been confined to the more industrialized nations.[1] Screening is the first step for its early detection enabling timely intervention. To this end, validated screening protocols for early detection of ROP have been duly established for use in hospitals. ROP screening may be performed with the help of a standard binocular indirect ophthalmoscope (BIO) or the more advanced, but more expensive, RetCam.

Examination of the retina requires that the infant's eye stays open during the procedure. This is achieved by the use of an appropriately sized and designed infant eye speculum. However, the very act of inserting a speculum into the conjunctival sac and following it up with a procedure that requires bright light and scleral depression is certainly painful for the premature neonate as well as being fairly distressing for the accompanying parent. In order to alleviate the baby's stress, all such examinations are conducted under topical anesthesia as the standard of care.[2] Nevertheless, screening for ROP remains a procedure which causes extreme discomfort all around, despite the use of additional strategies including swaddling and reverse Kangaroo Mother Care. ROP screening-induced stress may manifest as an altered heart rate, a fluctuating blood pressure, a lowered oxygen saturation, and/or a depressed respiratory rate.[3] Pain scales such as premature infant pain profile (PIPP), Neonatal Infant Pain Scale, Crying Requires Increased Expression Sleeplessness, and Neonatal-Pain Agitation and Sedation Scale use these parameters to evaluate the degree of stress generated as well as to determine the efficacy of stress reduction strategies.[4]

In recent years, recommendations for the use of oral sugars have been made in an attempt to further reduce the stress to the baby. These recommendations follow the observation that oral sugars provide effective analgesia for short procedures such as heel prick and venipuncture in neonates.[5] Government guidelines also recommend the use of oral sucrose as an analgesic during ROP screening.[6] Oral sucrose is often not available; hence, 20% dextrose orally has been suggested as a suitable alternative.[7] Dextrose too has proven to be safe when used for nonophthalmic short duration painful procedures in infants. However, only a few studies have reported its efficacy in ROP screening. Most researchers have chosen a “between-subject” study design to investigate pain relief during ROP screening; the present study used a “within-subject” design to assess the relief from pain afforded by orally administered 20% dextrose as an analgesic for the purpose of ROP screening in neonates belonging to a local population.

  Materials and Methods Top

This within-subject comparison study was conducted in compliance with the existing ethical standards for biomedical research. The research protocol was approved by the institutional ethics committee vide number YUE390/2017 and performed over a period of 19 months from November 2017 to May 2019.

The study population comprised all consecutive referrals from treating neonatologists. Babies were enrolled in the study after taking informed consent from the parents/guardians. The study subjects were preterm neonates admitted in a level III neonatal intensive care unit with gestational age (GA) ≤37 weeks and/or birth weight (BW) ≤2000 g.

The study was performed during the first ROP screening before the postnatal age of 4 weeks. Data regarding GA, postnatal age, BW, and the present weight of babies were obtained from the medical records and duly entered into a predetermined pro forma. Screening was done by the same investigator, while clinical and behavioral parameters were recorded by the resident, a member of the research team.

Clinical parameters used for assessment included heart rate and oxygen saturation as measured by a Schiller Oxywave Pulse Oximeter®. In addition, sleep/wake state and behavioral features which include changes in brow bulge, eye squeeze, and nasolabial furrow were also looked for and noted. These readings were taken just before screening as well as monitored continuously during the screening procedure.

Babies received diluted Tropicacyl Plus® eye drop(combination of tropicamide 0.8% and phenylephrine 5%, diluted using distilled water in a ratio of 1:1) one drop at an interval of 15 min, ½ h prior to examination of right and left eye. ROP screening was performed under topical anesthesia (proparacaine hydrochloride ophthalmic solution 0.5%) using a BIO (Keeler) and a 20D converging lens. Babies were swaddled and the head was stabilized by the nursing staff during ROP screening. A standard ROP speculum was used to retract the lids. The eye was moved into the appropriate positions using an indenter so as to enable examination of the peripheral retina.

Babies were kept nil oral 1 h before the procedure; no intervention was performed apart from instillation of dilating drops into the right eye during this period. Baseline clinical and behavioral parameters were recorded just before examination of the right eye. Parameters were also noted (without dextrose [WOD]) during the examination of the right eye. Following this, babies were freed of their swaddling course and allowed a rest time of 1 h for parameters to return to baseline. No intervention was performed during this period, apart from instillation of dilating drops into the left eye. At the end of 1 h rest time, babies were given a single dose of 2 ml of 20% dextrose,[8] labeled, and loaded in a 2.5 ml syringe. Dextrose was slowly administered into the neonate's oral cavity by the nursing staff. Examination of the left eye was performed 2 min following administration of oral dextrose as this interval is required for the dextrose to act.[9] All parameters were recorded once again during examination of the left eye (parameters with dextrose [WD]) [Figure 1].
Figure 1: Flowchart of study methodology

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A pain score was calculated using the PIPP scoring system which includes two contextual indicators (GA and sleep/wake state), two physiologic indicators (heart rate and oxygen saturation), and three behavioral indicators (brow bulge, eye squeeze, and nasolabial furrow). PIPP scores <7 indicated no pain, 7–12 indicated intermediate pain, and >12 indicated significant pain.[10]

All data entered in an excel sheet and statistical analysis was done with SPSS version 20.0 (SPSS Inc, Chicago, Illinois, USA). Variables were analyzed using Wilcoxon signed-rank test and Mann–Whitney U test. P < 0.05 was considered to be significant, while P < 0.001 was considered to be highly significant.

Neonates on opioid analgesics, sedatives, anticonvulsants, and on mechanical ventilation were excluded at the beginning of the study.

  Results Top

One hundred and nine preterm babies were screened during this study period. Six babies were not eligible to be included in the study as they were on mechanical ventilator and one parent of the baby did not consent for the study [Figure 2]. One hundred and two babies participated in this study, of which 33 (32.35%) babies (Group A) had a GA ≤32 weeks (extremely preterm) and 69 (67.64%) babies (Group B) had a GA >32 weeks (preterm babies).[11] The profile of preterm babies screened for ROP is described in [Table 1].
Figure 2: Flowchart of babies included and excluded from the study

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Table 1: Profile of preterm babies, pain score, and clinical and behavioral variables at baseline, without dextrose, and with dextrose across gestational age (≤32 weeks and>32 weeks) in babies screened for retinopathy of prematurity

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Examination of each eye was approximately for 2–3 min. Clinical and behavioral parameters in all babies had reached baseline by 1 h of examination of the right eye. None of the babies required intervention during 1-h rest time. Statistical analysis done using Wilcoxon signed-rank test showed significant P values for changes in pain score (P < 0.001), heart rate (P < 0.05), oxygen saturation (P < 0.05), and behavioral parameters (P < 0.001) in WOD and WD readings. Pain score, heart rate, and behavioral parameters of babies, when ROP screening was performed WOD and WD in babies ≤32 and >32 weeks, were also significant, except for oxygen saturation (P > 0.05) using Mann–Whitney U test [Table 1].

  Discussion Top

The awareness that neonates feel pain began with a landmark paper published by Anand and Hickey in 1987.[12] Preterm babies are subjected to frequent ROP screening which is a painful procedure.

In studies related to pain alleviation during ROP screening, a search of reported literature, in the past 10 years, reveals that the number of subjects is quite often <50, whereas the sample size in the present study was 102 babies.

The “within-subject” design enabled each participating baby to act as his/her own control. Barring a couple of other studies, such a “within-subject” study design has not been used in ROP research on “analgesic effect of oral sugar solution during ROP screening” before. The “within-subject” studies offer the advantage that not only are all subjects exposed to all the variables, thus obviating the need for a large sample size, and reducing the duration of the study, but additionally, there is improved power of the study due to the removal of the element of interindividual differences compared to that seen in “between-subject” study designs.[13]

The dual role (control and study) by the same baby offered identical baseline states for the variables to be studied and hence avoided interindividual differences. The time interval between the right eye and left eye examination was fixed at 1 h as it takes approximately less than an hour for the physiological parameters to return to baseline states. The altered facial responses take 10 min to normalize, and the changes in the physiological parameters during ROP screening generally take 60 min to return to baseline.[3],[14] A further advantage of the “within-subject” design was that the time needed to complete the protocol was also reduced. This markedly reduced duration for each subject's participation compares favorably against the 2 weeks' time needed for each group to participate in the research by Saudamini et al.[15]

Multiple approaches have been attempted to reduce pain during ROP screening. These include administration of oral sugar solutions (sucrose/glucose/dextrose), feeding expressed breast milk, skin-to-skin care (Kangaroo Care), swaddling, and nonnutritive sucking (NNS).[16]

The strong sweet taste of sugar solutions has an analgesic and calming effect in babies exposed to procedural pain. The analgesia produced by the sugar solutions is, in general, attributed to endogenously secreted opioids activated by the sweet taste.[17],[18]

Among the sugars, sucrose a disaccharide is the most commonly used nonpharmacological analgesic. In India, dextrose use is more common because of easy availability. Dextrose (glucose) is a monosaccharide and is 0.75 times as sweet as sucrose. A comparative study to establish the efficacy of sucrose versus glucose during heel lance in neonates confirmed that analgesic effects of sucrose and glucose are almost identical.[19] The effectiveness of oral sugar solution as an analgesic in ROP screening was first validated for sucrose by Mitchel et al. in 2004 and subsequently for dextrose by Marlene et al. in 2013.

We used a 20% dextrose solution due to its easy availability in the hospital pharmacy. This study examined the analgesic effect of 20% oral dextrose solution during ROP screening of 102 preterm babies whose mean GA was 33.18 ± 2.22 weeks and mean BW was 1709 ± 12.3 g. It was seen that pain scores increased from baseline when ROP screening was performed WOD (control group), confirming that ROP screening per se is a painful procedure.

When ROP screening was performed using 20% oral dextrose WD, a significant increase in the pain scores was observed from baseline. However, pain score WD was significantly less (P < 0.001) than pain score WOD. Analysis of individual parameters in the PIPP revealed that, although oxygen saturations dropped below baseline levels and heart rates increased from baseline, irrespective of the use of 20% dextrose, these changes were significantly less when oral dextrose-induced analgesia was present. It becomes obvious that 20% dextrose oral solution is a fairly effective analgesic in these neonates. The analgesic effect of oral dextrose was alike across all GAs.

Marlene et al. and a similar study by Praveen et al. both concluded that there was a significant reduction in pain score compared to placebo if screening is assisted by 25% oral dextrose.[20],[21] Nesargi et al., in a comparative study, concluded that 0.5% proparacaine eye drops and 20% oral dextrose each produced insufficient analgesia when used alone without the other.[15]

In a study done, by Mitchell A et al babies were randomly assigned to get either oral sterile water or 24% sucrose during ROP screening. All babies in the above study received topical anesthesia and a pacifier. The difference in pain scores was statistically significant and therefore validated it as an analgesic for ROP screening.[22]

Recently, Nayak et al. compared the analgesic effects of breast milk, 10% dextrose, and sterile water during ROP screening by means of a RetCam and reported that 10% dextrose fared the best although this was not a statistically significant finding. Even so, it was observed that oral dextrose was effective in stabilizing physiological parameters. Perhaps, the lower concentration of dextrose solution (10%) was responsible for the poorer analgesia. NNS was common for all the groups during ROP screening and may have contributed to the lack of any difference between the three groups.[23]

Unlike sugar, the analgesic effect of NNS is believed to be activated by nonopioid pathways through oro-tactile and mechanoreceptors. It is presumed that there is synergism in the analgesic actions of sugar solutions and NNS. There is sufficient evidence to support the combination of NNS and oral sugars to reduce procedural pain in infants.[9],[22],[24],[25] The present study differed from Nayak's study in that a higher concentration of dextrose (20%) was used. We delivered oral dextrose with the help of a syringe and did not use NNS during the procedure to avoid a confounding factor. We used 2 ml of 20% dextrose and obtained significant analgesia similar to that reported by other researchers who used 2 ml,[26] 0.6 ml/0.2 ml of 24% sucrose.[27]

Dilli[24] and Benzer et al.[27] unlike our study did not show a statistically significant effect on individual clinical parameters, despite significantly lower pain scores with oral sucrose. Grabska et al. reported that adjusting the dose of 24% sucrose according to the baby's weight did not produce any greater beneficial analgesia nor was there any improvement in physiological parameters during ROP screening. PIPP scoring was 14 ± 3 in the study and control groups, compared to our study in which PIPP scores were 11.09 ± 2.24 and 9.42 ± 2.70 without and with oral dextrose, respectively.[28]

XSun, in a systematic review, concluded that although sucrose reduced pain during ROP screening, PIPP scores remained relatively high in all the studies.[29] We observed that pain score and physiological parameters altered significantly from baseline parameters even with the use of dextrose indicating the need for an even better mode of pain management.

  Conclusions Top

Oral dextrose has a significant role in reducing pain and stabilizing physiological parameters during ROP screening. The effect of dextrose was similar across all babies irrespective of the GA. Oral dextrose does not alleviate the pain completely as evidenced by a significant increase in PIPP score from baseline. Ergo, there is a definite need to improve the pain management during ROP screening. The within-subject study design enabled each participant to act as his/her own control and is the distinctive feature of the study. It helped reduce the duration of participation for each baby and also avoided individual differences with and without the use of dextrose resulting in better internal reliability of the study.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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Jiang JB, Zhang ZW, Zhang JW, Wang YL, Nie C, Luo XQ. Systemic changes and adverse effects induced by retinopathy of prematurity screening. Int J Ophthalmol 2016;9:1148-55.  Back to cited text no. 3
Beltramini A, Milojevic K, Pateron D. Pain assessment in newborns, infants, and children. Pediatr Ann 2017;46:e387-95.  Back to cited text no. 4
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  [Full text]  
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Dilli D, İlarslan NE, Kabataş EU, Zenciroğlu A, Şimşek Y, Okumuş N. Oral sucrose and non-nutritive sucking goes some way to reducing pain during retinopathy of prematurity eye examinations. Acta Paediatr 2014;103:e76-9.  Back to cited text no. 24
Boyle EM, Freer Y, Khan-Orakzai Z, Watkinson M, Wright E, Ainsworth JR, et al. Sucrose and non-nutritive sucking for the relief of pain in screening for retinopathy of prematurity: A randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2006;91:F166-8.  Back to cited text no. 25
Gal P, Kissling GE, Young WO, Dunaway KK, Marsh VA, Jones SM, et al. Efficacy of sucrose to reduce pain in premature infants during eye examinations for retinopathy of prematurity. Ann Pharmacother 2005;39:1029-33.  Back to cited text no. 26
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