Sucrose Analgesia: Identifying Potentially Better Practices
OBJECTIVE. The objectives of this study were to review the use of oral sucrose for procedural pain management in NICUs, develop potentially better practice guidelines that are based on the best current evidence, and provide ideas for the implementation of these potentially better practices.
METHODS. A collaboration of 12 centers of the Vermont Oxford Network worked together to review the strength of the evidence, clinical indications, dosage, administration, and contraindications and identify potential adverse effects for the use of sucrose analgesia as the basis of potentially better practices for sucrose analgesia guidelines. Several units implemented the guidelines.
RESULTS. Through reviews and inputs from all centers of the evidence, consensus was reached and guidelines that included indication, dosage per painful procedure, age-related dosage over 24 hours, method of delivery, and contraindications were developed.
CONCLUSIONS. Guidelines now are available from a consensus group, and suggestions for implementation of guidelines, based on implementation of other pain management strategies, were developed.
Infants who are treated in NICUs across the United States can range from 24 weeks’ gestational age to 12 months or older. Although technologic and medical advances have improved the outcomes for these hospitalized newborns, they also have created an increase in painful procedures for the infants with estimates of the average number of tissue-damaging procedures exceeding 10 per day.1–5 There has been considerable concern about the potential adverse effects of medications that are used to treat pain in neonates.6 This fear has contributed to the delay in procedural and surgical pain management in this patient population.
On the basis of many studies and a Cochrane review of the efficacy of sucrose as an analgesic for procedural pain in neonates,7 sucrose became the focus of a potentially better practice for the pain and analgesia group. These studies show efficacy in reducing pain behaviors in infants with the use of oral sucrose by pacifier or via syringe drops that are administered onto the tongue or the cheek. The consensus statement came out of the work of the “I Feel Good” focus group as a result of the wide variation in focus group practices and a goal of standardization of best practice for general reference.
In 2002, a group of Vermont Oxford Network sites began a collaborative project to identify potentially better practices for reducing pain in hospitalized infants. The goal was to standardize recommendations for sucrose analgesia. The first step was to review the scientific evidence and determine the clinical indications, administration recommendations, and implementation strategies. The American Academy of Pediatrics has endorsed oral administration of sucrose to reduce pain that is associated with procedures.8
Evidence to Support Sucrose Analgesia
The use of oral sucrose to decrease pain during painful or stressful procedures is the most extensively studied pharmacologic intervention in neonates. The Cochrane review of randomized, controlled trials of sucrose in neonates by Stevens et al,7 including updates through September 2003, found 24 published studies that included >1800 infants with gestational ages from 25 to 42 weeks.7 Significant decreases in crying, grimacing, heart rate, and pain scores have been reported in neonates who were given sucrose solution before a procedure when compared with water,7 and repeating the dose every 2 minutes up to 3 times increases the effect.9
An earlier study investigated whether the effects of sucrose were attributable to the sweet taste or the carbohydrate content, and it was determined to be attributable to effect of sweetness, with any solution 12% or higher being effective. There was no sweetness dose response above 24%.10 The mechanism of action of lingual sucrose is markedly different from that of other systemic analgesics that are used in the NICU. Administration of sucrose to the stomach by nasogastric tube is not an effective analgesic.11 The onset of action (10 seconds) is so rapid that there is not time for oral absorption to occur.12 The peak action is 2 minutes, and the duration of action is ∼5–10 minutes and therefore cannot be related to clearance from the circulation of any measurable agent.12
Diagnostic and therapeutic procedures are a part of everyday life in the NICU, where neonates routinely experience pain that is associated with invasive procedures. There now is sufficient evidence to support the administration of sucrose, often in conjunction with additional pharmacologic and nonpharmacologic interventions, for relief of procedural pain.13 Successful use of sucrose surrounding heel lance and venipuncture is well documented.9,14–24
Other clinical indications for the administration of sucrose include suctioning, nasogastric or orogastric tube insertion, intravenous insertion, subcutaneous or intramuscular injections, dressing changes, and eye examinations.13 Sucrose also is an effective adjunct to pharmacologic pain management during percutaneous venous catheter insertion, percutaneous arterial catheter insertion, central venous line placement, peripherally inserted central catheter placement, lumbar puncture, chest tube insertion, and circumcision.13
Precise sucrose dosing and age parameters are not well defined. Sucrose volumes ranging from 0.05 mL to 2 mL have been identified as effective in providing pain relief in neonates.7 However, it is the neonate’s detection of a sweet substance, not the volume, that produces the analgesic effect. As a result, studies report that 0.05 mL to 0.5 mL is an adequate volume of 24% to 25% sucrose or glucose for reducing procedural pain in neonates.7 Age parameters also are unclear. Sucrose is effective when used in neonates as young as 25 weeks’ gestation, yet recent concerns have been raised surrounding developmental outcomes for those who are <32 weeks’ corrected gestational age.7,16,25 It is interesting that as the infant matures, the effect seems to disappear. In examining the use of oral sucrose during immunizations in 2-, 4-, and 6-month-olds, sucrose was found to be less effective in infants as old as 4 months.26
If clinicians understand that the sweet taste is the salient factor, then potential problems from administering excessive dose volumes or giving the solution by nasogastric tube or to the wrong part of the mouth should be minimized. If the 2-minute peak effectiveness is recalled by clinicians, then it will be easier to remember to give the sucrose just before the painful stimulus. If clinicians understand that the duration of sucrose action is temporary and analgesic, not sedative, then sucrose will not be used in an ineffective attempt to sedate irritable infants.
Studies have evaluated the effectiveness of administering 24% sucrose orally via a syringe onto the tongue by dipping a pacifier in the solution and allowing the infant to suck on it or by administering the sucrose into the infant’s mouth followed by nonnutritive sucking (NNS) on a pacifier. NNS, either on a pacifier that is dipped in the 24% sucrose solution24 or on a pacifier that is offered immediately after the administration of the sucrose onto the tongue,25 has been shown to reduce significantly pain behaviors in infants who undergo painful procedures. To enhance the effects of the sucrose further, comfort measures, such as facilitated tucking, rocking, kangaroo care, and swaddling, may be used in conjunction with the sucrose.
Adverse Effects of Oral Sucrose in the Neonate
Although many studies have shown the efficacy of oral sucrose in the management of procedural pain in neonates, few have described adverse effects. In a randomized, double-blind, controlled trial, Johnston et al27 found no differences in outcomes between infants who were <31 weeks’ postconceptional age and received 0.1 mL of a 24% oral sucrose solution and those who received water for invasive procedures during the first week of life.
They did describe lower scores on certain components of the Neurobehavioral Assessment of the Preterm Infant in infants who received higher numbers of doses of sucrose than those who received fewer doses.27 The infants who received more doses also had higher Neurobiologic Risk Scores at 2 weeks’ postnatal age but not at discharge. Because of the possible long-term effects suggested by these findings, judicious use of sucrose analgesia and, perhaps, limiting the number of doses in infants who are <32 weeks’ postconceptional age is advocated.
Two other studies described short-term effects of oral sucrose or glucose administration. Carbajal16 observed slight, transient oxygen desaturations (85%–88%) during 7 of 54 administrations of 0.3 mL of a 30% oral glucose solution for subcutaneous injections in preterm infants, and although not statistically significant, none of the 24 placebo (sterile water) administrations elicited oxygen desaturations. Gibbins et al25 evaluated the efficacy and short-term safety of oral sucrose during heel lance. Infants were stratified into 3 groups according to gestational age: 27 weeks to 31 weeks, 6 days (n = 63); 32 weeks to 35 weeks, 6 days (n = 63); and 36 to 43 weeks (n = 64). The infants within each group were randomly assigned to receive 0.5 mL of oral 24% sucrose alone, oral sucrose and a pacifier for NNS, or placebo (water) and NNS.
Adverse effects were described as those that occurred immediately after administration of the solution, such as choking, coughing, or vomiting; sustained tachycardia, or bradycardia. Of the infants who received sucrose alone, adverse effects were noted most often in the most immature infants (4 of 23). In the older age groups, 1 infant in each group exhibited adverse effects (1 of 19 and 1 of 20, respectively). The short-term adverse effects that were demonstrated by these infants were not considered to be clinically significant. None of the infants who received sucrose and NNS had any adverse effects noted.
Other possible adverse effects that have been suspected include alterations in glucose homeostasis, specifically hyperglycemia, and necrotizing enterocolitis (NEC). Currently, hyperglycemia is more of a theoretical adverse effect than a well-documented one. In fact, sucrose has not been proved to cause any of these adverse effects.
Sucrose is a disaccharide that is composed of glucose and levulose, which further limits the immediate absorption of carbohydrate. It is possible to calculate the amount of carbohydrate that is presented to the patient using various combinations of sucrose concentration and volume. These calculations help clinicians compare the dose of carbohydrate administered through sucrose solution with that administered through feedings or intravenous dextrose. One common sucrose analgesia regimen is a pacifier dipped in 24% sucrose. Two independent measurements of the volume of 24% sucrose that is administered when a pacifier is dipped found this value to be no more than 0.2 mL.
An additional area of concern surrounds the osmolarity of sucrose solutions (Table 1) and risk for NEC as a result of oral administration of sucrose. The 24% sucrose solutions have a labeled osmolarity of 700 mOsm/L, which clearly is hypertonic but not the most concentrated or irritating drug product used in the NICU. Emphasis on lingual administration of small volumes provides 1 method of protecting infants from this potential problem. Using sucrose analgesia only for procedural pain is another method of minimizing concerns over the risk for NEC.
Ten of 11 units had written guidelines for the use of sucrose in neonates. Three of those 10 units were in the early stages of implementation, and 7 had used sucrose in their pain management protocols from 4 months to 2 years. Barriers and controversies in implementation of the use of sucrose are presented as well as literature review to guide units in the process of successful implementation.
Sucrose guidelines are presented in Tables 2 and 3. Implementation of oral sucrose for procedural pain will be unique in each NICU depending on the culture of the institution. Some units have been concerned regarding the negative neurodevelopmental results of the study of repeated administrations.27 Infants in that study who showed poorer scores received >20 doses in 24 hours, some >30 doses (C. Johnston, RN, DEd, verbal communication, 2003), and they were <31 weeks when they entered the study for the week. They spent more time in the NICU after the study in which they did not receive analgesia of any sort for painful procedures. The sudden withdrawal of the sucrose analgesia may have been as important as the number of doses. If our guidelines are followed and there is no abrupt cessation of care, then the likelihood of neurodevelopmental problems is decreased.
The team should decide early in the process whether they regard this therapy as a food, a nutritional supplement, or a medication. The key is that no matter which approach is chosen, its use for pain management be taken seriously as a pain intervention. Because sucrose is used in the NICU to relieve pain, the most sensible approach is to treat the therapy as we would other analgesics, most of which are medications. If organizations treat this therapy as they would any medication, then many questions related to implementation are much easier to answer. Table 2 offers examples to illustrate this.
These types of questions help to guide the introduction and implementation of sucrose use into a unit. Within the collaborative, sucrose was introduced in different yet equally successful ways. Some units wrote policies or procedures, whereas others wrote guidelines, protocols, or algorithms. No matter which form the introduction took, most centers included the same basic information: indications and contraindications for use (patients and procedures), precautions, potential adverse effects, personnel who should administer sucrose, equipment needed, dosing guidelines, the procedure for giving the sucrose, documentation of the dose, and references to support the practice. In addition, some centers included pain assessments written into the process. Monitoring clinical response to sucrose during and after a procedure is important to assess whether additional doses are needed.
Once the process was written on how sucrose would be administered, implementation steps also were similar within the collaborative. The next step for most units was in-service education for staff on the use of sucrose. This took many different forms, including staff meetings, storyboards, skills labs, and in-service education that was specific to sucrose. Keeping the practice visible and reinforcing it with staff is a critical step.
Centers are different, and what works with 1 staff may not work with another, so it is important to know which learning style is most effective for each individual unit. Another important step for successful implementation is follow-up on the practice. Shortly after sucrose was introduced, most units collected data on how the process was working, to detect and resolve any problems that might have arisen. This data review helped to minimize any staff frustration and resulted in successful implementation. This is important to do fairly soon after implementation. Most units had some revisions or clarifications that needed to be made, but for the most part, implementation went smoothly.
One key to success for many units has been having a nurse-focused policy. In these units, administration of sucrose is based on clinical assessment of a pain, not necessarily a written physician order. In units that treat this intervention as another medication, the as-needed order for oral sucrose has been added to an “Admission Order Set.” The nurse then transcribes the order onto the medication administration record and administers it as needed for the indication of procedural pain. Units that approached the use of sucrose this way have guidelines in place for administration.
Another key to successful implementation has been the mindset of the unit that introduces it. With a goal to alleviate neonatal pain, most units and disciplines within the collaborative have been very receptive to the introduction of sucrose, especially when they see how effective this simple intervention is. Ongoing communication among direct caregivers and members of the implementation team is critical. Stocking and tracking sucrose was an issue for units.
One of the first questions to ask when introducing sucrose is the form to use. Will the center use prepackaged sucrose or have it compounded in their pharmacy? Prepackaged sucrose is easy to use but creates a dilemma in deciding who will stock and track it. In most of the participating units, the pharmacy has assumed this responsibility. Once key issues were addressed, sucrose administration was introduced easily as a treatment for procedural pain. Multidisciplinary teams that worked together were successful in developing and implementing this well-received practice.
- Accepted July 18, 2006.
- Address correspondence to Linda Lefrak, RN, MS, Children’s Hospital and Research Center, 747 52nd St, Neonatology, Oakland, CA 94609. E-mail:
The authors have indicated they have no financial relationships relevant to this article to disclose.
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- ↵American Academy of Pediatrics, Committee on Fetus and Newborn, Committee on Drugs, Section on Anesthesiology, Section on Surgery; Canadian Paediatric Society, Fetus and Newborn Committee. Prevention and management of pain and stress in the neonate. Pediatrics.2000;105 :454– 461
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- ↵Carbajal R. Crossover trial of analgesic efficacy of glucose and pacifier in very preterm neonates during subcutaneous injections. Pediatrics.2002;110 :389– 393
- Carbajal R, Chauvet X, Couderc S, Olivier-Martin M. Randomised trial of analgesic effects of sucrose, glucose, and pacifiers in term neonates. BMJ.1999;27 :319:1393– 1397
- Deshmukh LS, Udani RH. Analgesic effect of oral glucose in preterm infants during venipuncture: a double-blind, randomized, controlled trial. J Trop Pediatr.2002;48 :138– 141
- Ramenghi LA, Griffith GC, Wood CM, Levene MI. Effect of nonsucrose sweet tasting solution on neonatal heel prick responses. Arch Dis Child Fetal Neonatal Ed.1996;74 :F129– F131
- Copyright © 2006 by the American Academy of Pediatrics