The use of oral sucrose for pain control in infants is a relatively new concept in the field of analgesia. Blass and Hoffmeyer (1991) published the first study on sucrose as an analgesic for humans in 1991, demonstrating that neonates cried significantly less during heel-lance blood collection or circumcision when given sucrose versus sterile water or no intervention. While the majority of the literature has focused on neonates, emerging evidence points to the efficacy of this intervention in the nonneonate infant. The focus of this review is to provide evidence for efficacy of oral sucrose solution as an analgesic intervention prior to painful procedures (such as immunizations and venipuncture) in infants 1–12 months of age. For instance, a recent meta-analysis determined that sucrose or glucose (sweet solutions) is effective in reducing incidence and duration of crying during immunization in this age group (Harrison et al., 2010).
The infant time period is defined as a child being less than 12 months of age. The neonate time period is defined as “beginning at birth and lasting through the 28th day following birth”—a definition in use by the American Academy of Pediatrics (AAP), World Health Organization (WHO), and American College of Obstetricians and Gynecologists (ACOGs). Gestational age (GA) is defined as the time between the woman's last menstrual period and her date of delivery (AAP, 2004).
The term “pain” can be defined in many ways. For the purpose of this review, pain will be defined using the International Association for the Study of Pain's (IASP) definition. The IASP defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (IASP, 2007, para. 33). The IASP further explains that pain is a subjective report of what the person perceives through his or her personal experience (IASP, 2007).
Infant pain modulation and oral sweet solutions
At birth, human babies are able to feel pain. By 24 weeks GA nociceptive pathways are fully developed and functioning (Helms & Barone, 2008). Shorter nerve tracts in infants means that pain impulses have less distance to travel as compared to adults (Anand, Phil, & Carr, 1989).
Limitations still exist in the prevention and treatment of unnecessary pain from anticipated painful events in infants. Many healthcare providers focus on pain management, rather than prevention of anticipated pain (AAP, 2000). This may have consequences in later years, because it has been demonstrated that repetitive nociceptive stimulation can lead to a hyperanalgesic response to pain in infants (Taddio, Shah, Gilbert-MacLeod, & Katz, 2009). This provides one rationale for investigation of oral sucrose solution as a preprocedural intervention.
The exact mechanism of action of oral sucrose solution as an analgesic remains unknown and is an area of active investigation; however, it is theorized to trigger release of endogenous endorphins. This theory is supported by animal studies in which the analgesic effects of sucrose can be reverse by naltrexone (Shide & Blass, 1989); this analgesic response occurred in the brainstem (Reboucas et al., 2005). Human infant studies have demonstrated a slower onset and offset response as compared to nonnutritive sucking (NNS; Blass & Shide, 1994). Endogenous endorphin release is further supported by a study demonstrating no analgesic response to sucrose in infants born to mothers who took methadone throughout pregnancy (pacifier orotactile response remained intact; Blass & Ciaramitaro, 1994). Thus, administration of sucrose solution may involve activation of different neurologic pathways than those activated by NNS (Blass & Watt, 1999).
The effect sucrose has on pain relief also could be linked to the sweetness of the solution. One study compared sucrose solution, aspartame solution of equivalent sweetness, and a polycose solution (soluble carbohydrate only slightly sweet). There was no significant difference shown between sucrose and aspartame indicating the pain relieving effect may be linked to the sweetness of the solution (Barr et al., 1999).
Another potentially additive effect is the oral method of administration. Ramenghi, Evans, and Levene (1999) compared the effects of sucrose solution administered orally versus through a nasogastric tube in regards to pain responses after heel sticks in preterm neonates. There was a significant reduction in crying time and behavior score for those neonates receiving sucrose solution orally.
Nonpharmacologic interventions for minor painful procedures in infants
Providers may hesitate to use pharmacological analgesia for mild pain in infants because of fear of potential drug side effects (Carbajal, Veerapen, Couderc, Jugie, & Ville, 2003). Several nonpharmacological interventions have been studied in infants and found to be effective in reducing pain response during minor painful procedures. These include NNS, swaddling, infant positioning, injection technique, parent-led distraction, nurse-led distraction, parent coaching, and oral sweet solutions. Both NNS via a pacifier and swaddling were found to be effective interventions for the outcomes measured (reduction in heart rate, crying, and alertness); however, rebound occurred more in the NNS pacifier group than in the swaddled group (Campos, 1989).
Taddio, Ilersich, Ipp, and Kikuta (2009) completed a systematic review comparing physical interventions and different injection techniques as methods to reduce pain and distress in infants and children undergoing immunization administration. The review concluded that effective measures in infants included the following: using the least painful formulation of the vaccine, having the infant sit up or be held, administering the least painful vaccination first when multiple vaccines are administered, and rapid intramuscular injection without aspiration.
Chambers, Taddio, Uman, and McMurtry (2009) completed a systematic review focusing on psychological techniques used to reduce pain and distress during immunization injection in infants and children. Results of this review found breathing exercises, child-directed distraction, nurse-led distraction (nurse directs child's attention to age-appropriate toys or videos), and combined cognitive-behavioral interventions significantly reduced pain and distress in infants and toddlers receiving immunization injections. Parent-directed distraction (parent provides age-appropriate distraction with toys or movies) and parent coaching (parents provide distraction in combination with other effective interventions such as reducing parental reassurance, empathy, and criticism) did have some benefit, but this was not significant. They suggested that because some benefit was noted, parents should be encouraged to use some of the interventions. One major finding from this review is that the use of distraction with age-appropriate toys was found to be the only intervention that can be used with all children regardless of age.
Oral glucose solution
Sweet-tasting sugar solutions that have been studied in the literature include glucose and sucrose. Glucose solution has been shown effective as an analgesic intervention for immunization pain management. Results from at least one study revealed a 44% reduction in crying time (Thyr, Sundholm, Teeland, & Rahm, 2007).
Oral sucrose solution
Multiple studies over recent years have demonstrated effectiveness in the older infant using this oral sucrose solution. In a meta-analysis for a clinical practice guideline, the most common dose of oral sucrose solution was 2 mL of 25% strength given 1-2 min prior to injection. Sucrose is available from the pharmacy, or by using grocery sugar cubes or packets with water. A simple and commonly used recipe that provides a 25% strength is dissolving one packet (or cube) of sugar in 10 mL of water (weight/volume; Taddio et al., 2010).
Numerous pain scales are available to assess pain in the infant. However, there is inconsistency with their clinical use and interpretation. In addition, variation in healthcare provider beliefs concerning infant pain may lead to inadequate assessment of infant pain (Duhn & Medves, 2004). Expert opinion holds that the first step in managing and treating pain is proper assessment (Zempsky & Cravero, 2004). Figure 1 provides information regarding the pain scales used in the oral sucrose solution studies that composed our study sample.
Other ways to assess pain
Several studies did not use formal pain scales for outcome data but instead used specific measurements of infant behaviors in response to the painful stimuli. Examples of physiological changes in response to pain include the following: changes in heart rate, respiration rate, blood pressure, and oxygen saturation and examples of behavioral changes include facial expression, body movements, and crying (AAP, 2006). In the studies that did not use formal pain scales, the most commonly used measurement was presence of cry, total crying time (audible crying vocalizations), and (or) percent crying time for the entire encounter. One study found that the power and velocity of crying to be the best predictors of infant pain. In addition, “this is the first report of these specific measures of crying and a consistent relation to an independent measure of infant pain and arousal” (Lehr et al., 2007, p. 422). One limitation to using crying as an indicator of pain is the subjective nature of analysis regarding the infant cry. Other expert opinion is that multiple responses to pain should be assessed, and reliance upon one response (such as crying) should be avoided (Lehr et al., 2007).
An integrated review of literature with healthcare reference librarian assistance through the Hunter Library (Western Carolina University) was conducted using Academic Search Premier, Cumulative Index of Nursing and Allied Health (CINAHL), Cochrane Database of Systematic Reviews, EBSCO's Electronic Journal Service (EJS), MEDLINE, Centers for Disease Control and Prevention (CDC), and National Library of Medicine (PubMed). E-mail contact with one author was made to receive a set of trial data results (prepublication, from conference). Data extraction was performed by the research team with inclusion criteria narrowing the search to derivations of the terms sucrose, sucrose analgesia, sucrose pain, infant pain, pain measurement, pain scale, infant, baby, neonate, circumcision, immunization, heel stick, heel lance, and venipuncture. The search resulted in 27 studies, of which 10 met the inclusion criteria to become the study sample. Those excluded were studies conducted on neonates or did not include sucrose as an intervention.
The study sample results are organized into tabular format (see Table 1). The primary outcome was efficacy of intervention (pain response). A discussion of these tabulated results follows.
Most clinical settings were outpatient, with procedures including immunizations and venipuncture. Immunizations are probably the most likely source of painful procedures in the infant age group, with infants receiving up to 19 immunizations before 12 months of age (Department of Health and Human Services and Centers for Disease Control and Prevention, 2009). Use of pharmacologic agents included Paracetamol (acetaminophen) prior to immunization, and comparison to standard application of an anesthetic cream (eutectic mixture of local anesthetics, EMLA). In addition to no intervention, other comparator interventions were sterile water, hydrogenated glucose (Lycasin), pacifier (NNS), or bottle (nutritive sucking), in combination or alone. In some studies, maternal contact was combined with other interventions. Between studies, there was wide variation in which interventions were allowed or studied as efficacy outcomes as well as the type and number of painful procedures. This and the use of different pain assessment methods among studies made direct comparison difficult.
Results in some studies suggested that older infants may need a higher concentration of sucrose (Allen, White, & Walburn, 1996). However, studies had conflicting results in this area.
There was a wide variation in oral sucrose solution concentration and dosing. Sucrose solution concentrations ranged from 12% to 50% (wt/vol.) with dosing ranging from 250 μL to 10 mL with the majority (seven studies) using 2 mL. One study used multiple sucrose dosing (before a single painful procedure), while the rest relied on a single dose. The number of painful procedures taking place during the study session varied (from single procedure to multiple injections). One study found that sucrose was not superior to sterile water (although sucrose or water provided a benefit as compared to no intervention; Allen et al., 1996). In evaluating oral sucrose solution as compared to anesthetic cream (EMLA), one study found no significant difference in crying time or pain scores between the two interventions (Dilli, Kucuk, & Dallar, 2009). Overall, most studies found that sucrose used prior to multiple painful procedures showed a benefit in reduction of pain (Allen et al., 1996; Barr et al., 1995; Curtis, Jou, Ali, Vandermeer, & Klassen, 2007; Dilli et al., 2009; Hatfield, 2008; L. Hatfield, personal communication, February 19, 2010; Hatfield, Gusic, Dyer, & Polomano, 2008; Lewindon, Harkness, & Lewindon, 1998; Ramenghi et al., 2002; Reis, Roth, Syphan, Tarbell, & Holubkov, 2003).
In addition to the studies discussed in our study sample, there are published reviews, meta-analyses, systematic reviews, and clinical practice guidelines available for the practitioner regarding the topic of analgesic intervention prior to or during minor painful procedures in nonneonate infants. These have been summarized in Figure 2. Overall, they all recommend the use of sweet-tasting solutions (sucrose or glucose) in this clinical setting and age group.
Preprocedural oral sucrose administration does show analgesic benefits in infants up to 12 months of age. Currently, information is available for sucrose solutions ranging from 12% to 50%, as either a single dose or multiple doses. The benefit is apparent when delivered alone or in combination with other nonpharmacological interventions such as NNS (pacifier), formula bottle, nurse-led distraction, maternal holding, and/or maternal interaction. The use of oral sucrose for this purpose is associated with very few minor adverse events (vomiting, gagging, and coughing) in a very small number of participants. Additional research is needed regarding dose response in different infant age groups, the optimal concentration of sucrose solution, the need for multiple sucrose dosing, adjustment of concentration or dose of sucrose in response to the number of painful procedures, and the addition of nonpharmacologic interventions as a combination approach.
Implications for practice
Its proven effectiveness as an analgesic intervention, as well as its low rate of minor adverse events, ease of administration, and excellent availability make sucrose a good choice for preventing and/or reducing pain in infants up to the age of 12 months during intramuscular injections and venipuncture. In agreement with the recommendations from systematic reviews, meta-analyses, and clinical practice guidelines, oral sucrose solution should be used as a pain reduction intervention in infants up to 12 months of age undergoing minor painful procedures. In addition, healthcare providers should encourage combining this with other pain reducing interventions, such as NNS, nurse-led or parent-led distraction, and/or breastfeeding. The most commonly used dose is 2 mL of 24% (weight/volume) sucrose solution administered orally 2 min prior to procedure.
The authors wish to thank Ann Hallyburton, Reference Librarian/Health Sciences Liaison, Hunter Library (Western Carolina University, NC) for her assistance with the initial literature review. The authors thank Linda Hatfield and Luca Ramenghi for their correspondence, encouragement, and copies of their studies for use in this review. The first author would like to thank her family for their support.
Allen, K., White, D., & Walburn, J. (1996). Sucrose as an analgesic agent for infants during immunization injections. Archives of Pediatric and Adolescent Medicine
American Academy of Pediatrics (AAP). (2000). Prevention and management of pain and stress in the neonate. Pediatrics
American Academy of Pediatrics (AAP). (2004). Age terminology during the perinatal period. Pediatrics
American Academy of Pediatrics (AAP). (2006). Prevention and management of pain in the neonate: An update. Pediatrics
Anand, K., Phil, D., & Carr, D. (1989). The neuroanatomy, neurophysiology, and neurochemistry of pain, stress, and analgesia in newborns and children. Pediatric Clinics of North America
Barr, R., Pantel, M., Young, S., Wright, J., Hendricks, L., & Gravel, R. (1999). The response of crying newborns to sucrose: Is it a “sweetness” effect? Physiology & Behavior
Barr, R., Young, S., Wright, J., Cassidy, K., Hendricks, L., Bedard, Y., & Treherne, S. (1995). “ Sucrose analgesia” and diphtheria-tetanus-pertussis immunizations at 2 and 4 months. Developmental and Behavioral Pediatrics
Blass, E., & Ciaramitaro, V. (1994). A new look at some old mechanisms in human newborns: Taste and tactile determinants of state, affect, and action. Monographs of the Society of Research in Child Development
Blass, E., & Hoffmeyer, L. (1991). Sucrose as an analgesic for newborn infants. Pediatrics
Blass, E., & Shide, D. (1994). Some comparisons among the calming and pain-reducing effects of sucrose, glucose, fructose and lactose in infant rats. Chemical Senses
Blass, E., & Watt, L. (1999). Suckling- and sucrose-induced analgesia in human newborns. PAIN
Campos, R. (1989). Soothing pain-elicited distress in infants with swaddling and pacifiers. Child Development
(4), 781–792, DOI: 10.1111/1467-8624.ep9676061.
Carbajal, R., Veerapen, S., Couderc, S., Jugie, M., & Ville, Y. (2003). Analgesic effect of breast feeding in term neonates: Randomized controlled trial. British Medical Journal
, 13–15, DOI: 10.1136/bmj.326.7379.13.
Chambers, C., Taddio, A., Uman, L., McMurtry, C. M., & HELPinKIDS Team. (2009). Psychological interventions for reducing pain and distress during routine childhood immunizations: A systematic review. Clinical Therapeutics
(Suppl B), S77–S103.
Crellin, D., Sullivan, T., Babl, F., O'Sullivan, R., & Hutchinson, A. (2007). Analysis of the validation of existing behavioral pain and distress scales for use in the procedural setting. Pediatric Anesthesia
Curtis, S., Jou, H., Ali, S., Vandermeer, B., & Klassen, T. (2007). A randomized controlled trial of sucrose and/or pacifier as analgesia for infants receiving venipuncture in a pediatric emergency department. BioMed Central Pediatrics
(27), DOI: 10.1186/1471-2431-7-27.
Department of Health and Human Services and Centers for Disease Control and Prevention. (2009). Recommended immunization schedule for persons aged 0 through 6 years: United States, 009
. Retrieved from http://www.aap.org/sections/infectdis/IZSchedule_Childhood.pdf
Dilli, D., Kucuk, I., & Dallar, Y. (2009). Interventions to reduce pain during vaccination in infancy. Journal of Pediatrics
Duhn, L., & Medves, J. (2004). A systematic integrative review of infant pain assessment tools. Advances in Neonatal Care
Harrison, D., Stevens, B., Bueno, M., Yamada, J., Adams-Webber, T., Beyene, J., & Ohlsson, A. (2010). Efficacy of sweet solutions for analgesia in infants between 1 and 12 months of age: A systematic review. Archives of Diseases in Childhood
, 406–413, DOI: 10.1136/adc.2009.174227.
Harrison, D., Yamada, J., & Stevens, B. (2010). Strategies for the prevention and management of neonatal and infant pain. Current Pain and Headache Report
Hatfield, L. (2008). Sucrose decreases infant biobehavioral pain response
to immunizations: A randomized controlled trial. Journal of Nursing Scholarship
Hatfield, L., Gusic, M., Dyer, A., & Polomano, R. (2008). Analgesic properties of oral sucrose during routine immunizations at 2 and 4 months of age. Pediatrics
Helms, J., & Barone, C. (2008). Physiology and treatment of pain. Critical Care Nurse
Lehr, V., Zeskind, P., Ofenstein, J., Cepeda, E., Warrior, I., & Aranda, J. (2007). Neonatal facial coding system scores and spectral characteristics of infant crying during newborn circumcision. Clinical Journal of Pain
Lewindon, P., Harkness, L., & Lewindon, N. (1998). Randomised controlled trial of sucrose by mouth for the relief of infant crying after immunization. Archives of Disease in Childhood
Merkel, S., Voepel-Lewis, T., Shayevitz, J., & Malviya, S. (1997). The FLACC: A behavioral scale for scoring postoperative pain in young children. Pediatric Nursing
Ramenghi, L., Evans, D., & Levene, M. (1999). “ Sucrose analgesia”: Absorptive mechanism or taste perception? Archives of Disease in Childhood Fetal and Neonatal Edition
Ramenghi, L. A., Webb, A. V., Shevlin, P. M., Green, M., Evans, D. J., & Levene, M. I. (2002). Intra-oral administration of sweet-tasting substances and infants' crying response to immunization: A randomized, placebo-controlled trial. Biology of the Neonate
Reboucas, E., Segato, E., Kishi, R., Freitas, R., Savoldi, M., & Morato, S., & Coimbra, N. C. (2005). Effect of the blockade of mu-1-opioid and 5HT2A-serotonergic/alpha-noradrenergic receptors on sweet-substance-induced analgesia. Psychopharmacology
Reis, E., Roth, E., Syphan, J., Tarbell, S., & Holubkov, R. (2003). Effective pain reduction for multiple immunization injections in young infants. Archive of Pediatric and Adolescent Medicine
Shah, V., Taddio, A., Rieder, M. (2009). Effectiveness and tolerability of pharmacologic and combined interventions for reducing injection pain during routine childhood immunizations: Systematic review and meta-analyses. Clinical Therapeutics
(Suppl. B), S104–S151, DOI: 10.1016/j.clinithera.2009.08.001.
Shide, D. & Blass, E. (1989). Opiodlike effects of intraoral infusions of corn oil and polycose on stress reactions in 10-day-old rats. Behavioral Neuroscience
Soetenga, D., Frank, J., & Pellino, T. (1999). Assessment of the validity and reliability of the University of Wisconsin children's hospital pain scale for preverbal and nonverbal children. Pediatric Nursing
Taddio, A., Appleton, M., Bortolussi, R., Chambers, C., Dubey, V., Halperin, S., & Shah, V. (2010). Reducing the pain of childhood vaccination: An evidence-based clinical practice guideline. Canadian Medical Association Journal
(18), E843–E855, DOI: 10.1503/cmaj.101720.
Taddio, A., Ilersich, A., Ipp, M., & Kikuta, A. (2009). Physical interventions and injection techniques for reducing injection pain during routine childhood immunizations: Systematic review of randomized controlled trials and quasi-randomized controlled trials. Clinical Therapeutics
(Suppl. B), S48–S76. DOI: 10.1016/j.clinthera.2009.07.024.
Taddio, A., O'Brien, L., Ipp, M., Stephens, D., Goldbach, M., & Koren, G. (2009). Reliability and validity of observer ratings of pain using the visual analog scale (VAS) in infants undergoing immunization injections. Pain
Taddio, A., Shah, V., Gilbert-MacLeod, C., & Katz, J. (2009). Conditioning and hyperanalgesia in newborns exposed to repeated heel lances. Journal of the American Medical Association
Thyr, M., Sundholm, A., Teeland, L., & Rahm, V. (2007). Oral glucose as an analgesic to reduce infant distress following immunization at the age of 3, 5, and 12 months. Acta Paediatrica
Zempsky, W., & Cravero, J. (2004). Relief of pain and anxiety in pediatric patients in emergency medical systems. Pediatrics