Oral Sucrose as an Effective Method of Pain Relief for Preterm Neonates - Literature review Example

?Oral Sucrose as an Effective Method of Pain Relief for Preterm Neonates: A Literature Review The use of oral sucrose in the management of pain in preterm neonates has been an important area of research in nursing and health sciences profession. Preterm neonates are more susceptible to the potential adverse effects of medications because of underdeveloped organs for metabolism and excretion of drug components. In this paper, current practices related to the use of oral sucrose in the relief of pain in preterm infants will be reviewed and compared based on the methods and validity of the results. Furthermore, implications for the current guidelines will also be discussed along with the knowledge gaps that require further research. Preterm neonates undergo several diagnostic procedures in the clinics and hospital, from vitamin K injection during the first hours after being delivered up to heel pricks for blood sampling to detect metabolic aberrations few days after being discharged. Some preterm neonates also undergo necessary resuscitation and ventilation to sustain and support life of premature vital organs. These situations warrant the administration of drugs and behavioral interventions like opioid analgesics, local and general anesthetics, sedative/ hypnotics, NSAIDS, and sucrose (Anand et al 2006, p. 11). While there are several researches performed to validate the efficiency of these agents in neonates, the issue on safety on the preterm neonates remains an active area of debate. In this review, research articles from journals in scholarly databases such as Cochrane databases and PubMed were evaluated and compared based on their relevant evidence on the practice of using oral sucrose in preterm neonates. Only the studies that utilized a randomized controlled trial designs were selected. The design and number of participants utilized in the studies will be considered and discussed in this paper. Moreover, the research articles are classified and covered under specific procedure often undergone by neonates. The Challenge of Pain Assessment New developments in the neurobiological, embryological, and developmental studies established that even the primitive forms of human life respond to noxious stimuli through a combination of distinct behaviors and physiological activity (Anand et al 2006, p. 9). Like adults, unnecessary pain and suffering of the fetus and the neonate need to be prevented to avoid short- term and long- term consequences (Haidon and Cunliffe 2010, p. 123). As with every situation, assessments always precede interventions even in the management of pain. In the actual clinic setting, the pain felt by the neonates are often overlooked as a normal pattern of their behavior. For instance, neonates undergoing procedures in the clinics and hospitals like bladder catheterization, needle sticks, surgery, mechanical ventilation, and even the administration of intravenous antibiotics are expected to cry due to discomfort and pain. Because of the ubiquitous nature of pain in preterm neonates, clinicians may fail to address the suffering in minor procedures and fail to perform necessary actions (Porter, Wolf, and Miller 1999, p. 1). Failure to acknowledge the importance of alleviating pain in the preterm and term neonates can result to serious consequences in their neurologic maturation. Therefore, more sensitive assessment tools are needed to detect the level of pain in the neonates and to validate the intervention researches in pain relief. Currently, specific tools consider multidimensional features associated with pain like cry behavior, grimace, quality of sucking, and physiological outcomes (Vani, Nimbalkar, and Thakre 2009, p. 200). Neonates may show different spectra of crying depending on each situation (Belliene et al. 2004, p. 142). Unlike adults, pain assessment of preterm neonates rely on these signs rather that an actual description and quality of pain (Lawrence et al. 1993). Although several researches were conducted to minimize the unnecessary pain, the assessment of pain in preterm infants relies on the arbitrarily accepted methods like the Premature Infant Pain Profile (PIPP) scores, Neonatal Infant Pain Score (NIPS), Neonatal Facial Coding System (NFCS), Neonatal Pain, Agitation, and Sedation Scale (N-PASS), Cry, Requires oxygen, Increased vital signs, Expression, Sleeplessness (CRIES), and COMFORT Scales (Anand et al. 2006, p.14). The PIPP is a validated pain measure that includes behavioral (three facial expressions), physiological (heart rate and oxygen saturation) and contextual (gestational age and behavioral state) indicators (Stevens et al. 2010, p. 51). While PIPP measures the heart rate, oxygen saturation, facial actions, it considers the state and gestational age of neonate. Behavioral indicators include brow bulge, eyes squeezed shut, and nasal- labial furrow. The PIPP is specifically sensitive in detecting procedural and postoperative pain. It can be used for premature neonates at 28 to 40 weeks gestational age. The NIPS aims to measure pain level through evaluation of facial expression, crying, breathing patterns, arm and leg movements, and arousal of neonates. It is sensitive only to pain associated with procedures. It can be used for preterm infants at 28 to 38 weeks gestational age (Haidon and Cunliffe 2010, p. 124). NFCS measures pain through validation of facial muscle group movements and is sensitive only to procedural pain. It is a reliable measure of pain for both preterm and term neonates and even the infants at 4 months gestational age (Haidon and Cunliffe 2010, p. 124). Another assessment tool, the N-PASS measures crying, irritability, behavioral state, facial expression, extremity tone, and vital signs that changes with pain experience. Aside from procedural and postoperative pain, it is also sensitive in identifying discomfort in ventilated neonates. CRIES evaluates crying patterns, facial expression, sleeplessness, oxygen requirement to maintain a minimum 95% saturation, and vital signs in postoperative pain (Krechel et al. 1995). Lastly, the COMFORT scale considers the movement, calmness, facial tension, alertness, respiratory rate, muscle tone, heart rate, and blood pressure changes due to pain of neonates in the postoperative and critical care settings (Grunau et al. 1990). Using Oral Sucrose for Pain Relief from Heel- Lance Oral sucrose has been an important part of neonatal pain research. Several studies back- up this practice because it is relatively safer to be used with preterm neonates compared with opioid analgesics, NSAIDS, general, regional, and local anesthetics. Heel- lance procedures among the preterm neonates are undertaken as part of newborn screening to detect metabolic compromise at an early age. Preterm neonates born from mothers with gestational diabetes and showed significant increases in their serum bilirubin levels are subject for repeated heel- prick procedures for blood sampling (Morrow, Hidinger, and Wilkinson- Faulk 2010, p. 347). The procedure is generally painful and causes a certain degree of discomfort. According to pediatric behavioral scientists (Kennedy, Luhman and Zempsky 2008, p. 130), repeated exposure to needle pricks might lead to psycho- behavioral challenges when the neonate grows older. And because of this suffering, studies in pediatrics and neonatology are geared towards testing and evaluating interventions to minimize the pain experienced especially by preterm neonates. In a recent multicenter randomized controlled trial by Cignacco et al. (2012), the analgesic effects of two non- pharmacological interventions including oral sucrose administration and facilitated tucking were compared as single interventions or used in combination. Behaviors of 71 preterm infants between 24 and 32 weeks of gestation undergoing heel- stick were rated using the Bernese Pain Scale for Neonates. Results showed the remarkable analgesic effect of oral sucrose used either alone or in combination with facilitated tucking. This effect is not limited to preterm neonates but may also apply even to those born at term. On the other hand, facilitated tucking did not show any relevant analgesic activity and therefore not suggested by the authors to be used in the clinical setting. Furthermore, in a meta- analyses study of the effect of sucrose in pain relief among preterm neonates, the authors conclude that sucrose solution administered orally may be a practical and safe alternative to analgesics (Stevens et al. 2010, p. 1). The intervention review gathered studies with randomized control group designs of preterm neonates undergoing a heel- lance procedure. Controls were set on the amount of water, breastfeeding practices, positioning, and use of pacifier. Moreover, the parameters measured were the total duration of cry, heart rate, and Premature Infant Pain Profile (PIPP) scores. The results of the review showed that preterm neonates had shorter duration of cry and significantly lower PIPP scores when given oral sucrose solution. With these research claims, the use of an opioid analgesic morphine in providing pain relief for acute procedures among preterm neonates is challenged by another research work completed by Carbajal et al. (2005). Morphine has been a standard medication in the relief of prolonged pain from surgery by term neonates. It has also been used to alleviate behavioral and hormonal stress associated with surgery. Likewise, preterm neonates may benefit from morphine in ventilator synchronization and sedation. However, in their prospective, randomized control trial, morphine was not found to have an analgesic effect in acute potentially painful procedures such as a heel- prick. Pain perception was assessed using the Dougler Aigue Nouveau- ne (DAN) scale and the Premature Infant Pain Profile (PIPP). Authors conclude that pain relief following heel- lance procedures needs to follow another intervention, such as oral sucrose instead of morphine, tested through several clinical trials and approved by the American Academy of Pediatrics. Using Oral Sucrose for Pain Relief from Venipuncture With relatively safer administration, oral sucrose has been a favorite relief measure in several procedural pains undergone by preterm neonates. In a double- blind randomized control trial of 330 neonates, the analgesic effect of sucrose and liposomal lidocaine were evaluated based on facial grimacing scores to assess pain level (Taddio et al. 2011, p.940). Compared with liposomal lidocaine, sucrose was more effective during venipuncture in newborns. In fact, the combination of both treatments did not show a significant difference and therefore not suggested in the clinical setting. On the other hand, in a randomized prospective study by Carbajal et al. (1999), pain relief from venipuncture injury was tested using sucrose, glucose, and pacifiers. In all of these trials, the behavioral acute pain rating scales recorded analgesic effects in venipuncture, with the use of pacifiers as the most effective among the three. Furthermore, the association of sucrose with pacifiers tends to be more effective rather than being used as single separate interventions. Following this study, Curtis et al. (2007) validated this finding using a double (sucrose) and single blind (pacifier), placebo- controlled random trial- factorial design which showed that oral sucrose has considerably lesser analgesic effects compared with the use of pacifier. Four groups were formed from the study population containing eighty- four infants and assigned into: group 1 to receive sucrose only, group 2 to receive sucrose and pacifier, group 3 to receive the control, or group 4 to receive control and pacifier. The major tools used were FLACC pain scale, crying time, and heart rate change. Although sucrose showed some analgesic effects, the use of pacifiers demonstrated a more remarkable result. Nevertheless, the study suggests that sucrose be used along with the pacifier to maximize pain relief from venipuncture. Although results in pain relief from venipuncture with oral sucrose are found impressive, another research utilizing a randomized control trial design still adhere to breastfeeding for analgesia based on evidence obtained (Carbajal et al. 2003, p.1). Four groups were formed and assigned whether to receive breastfeeding (group 1), held in mother's arms without breastfeeding (group 2), received placebo (group 3), or sugar water (group 4). Pain assessment utilized behavioral measurements as in Douleur Aigue Nouveau-ne scale (DAN) and the Premature Infant Pain Profile (PIPP). In both tools, breastfeeding proved to be better in the management of pain from venipuncture. Using Oral Sucrose for Pain Relief from Surgery For preterm neonates undergoing major surgery, pain relief is achieved using general, regional, and local infiltration anesthesia, opioids, and NSAIDS. Like adults, preterm neonates are also susceptible to the adverse effects of these agents. Although guidelines from the American Academy of Pediatrics and Canadian Paediatric Society (2000) do not recommend intervention to use sucrose in a major surgery, it might help to relieve the anxiety after the operation. Using Oral Sucrose for Pain Relief from Injections Injections among neonates are often associated with routine vaccination. In one study using a quasi- experimental design by Sahebihag et al. (2011), pain relief using oral sucrose, breastfeeding, or a combination of both was evaluated among 120 neonates undergoing first- time vaccination. Pain level was measured using the Neonatal infant Pain Scale (NIPS) at intervals 0, 5, and 10 minutes. Pulse rate and duration of crying were included as physiological measurements associated with pain. Results of the study showed that breastfeeding lowers pain score and decreases crying time significantly than using sucrose. The authors conclude that this might be attributed to the natural effects of holding and swaddling the neonate while breastfeeding. Skin-to-skin contact was also studied as a pain relief measure following hepatitis B vaccination in addition to sugar water. Instead of sucrose, a study by Chermont et al. (2009) utilized 25% dextrose to evaluate its efficiency in the management of pain. Specifically, the study utilized a prospective approach, random control, and partial blinding on a population of 640 neonates at 12 to 72 hours of life. Four groups were formed whether to receive oral 25% dextrose, skin-to-skin contact, a combination of both interventions, and no intervention at all (control group). The pain level was assessed using Neonatal Facial Coding System, Neonatal Infant Pain Scale, and Premature Infant Pain Profile. Results showed that newborns on both treatment groups scored a lower pain scale on three assessment tools. The study recommends the combination of both interventions to maximize the relief of pain in injections. Aside from intramuscular, injections for the preterm neonates may also come in subcutaneous routes. In a study of 285 neonates, Allen (1996) concluded that oral sucrose significantly reduced the duration of crying during and after the procedure. The set- up of the study comprised of the administration of 2 mL of 12% sucrose to the treatment group, 2 mL of sterile water to another group, and no treatment at all to the control group. The infants who received either sucrose solution or water had shorter duration of crying, but the effect of sucrose solution was found to be statistically more significant. A similar study by Mucignat (2004) aimed to determine if preterm infants respond to sucrose solution as with the infants born a full term. In this study, 33 preterm neonates with a mean gestational age of 30 weeks at birth, and 32 weeks at the time of injection, were to undergo subcutaneous injections. The study population was divided into four groups. The first group was given non- nutritive pacifier, second group was given 0.2 to 0.5 mL of 30% sucrose with pacifier, third group was given local application of EMLA with pacifier, and the last group was given 0.2 to 0.5 sucrose, pacifier and EMLA application. The perception and level of pain were measured based on the duration of crying during injection until 2 minutes after the procedure, and changes in the heart rate from the baseline records. Among the four groups, crying time was shortest in the group that received sucrose, pacifier, and EMLA. This suggests the additive effects of the treatments used in the relief of pain of preterm infants from subcutaneous injections. Heart rate changes did not record significant differences among the four groups. Using Oral Sucrose for Pain Relief from Bladder Catheterization Another procedural pain possibly undertaken by preterm neonates is the bladder catheterization. This procedure is not a routine for all newborns. In fact, this procedure is avoided if possible because of the potential risks and complications associated with insertion of a foreign body such as tissue trauma, bleeding, and obstruction. Only specific conditions that cause mechanical interruption and surgery warrant the use of a bladder catheter. Actually, bladder catheterization can cause pain and discomfort in the neonate. In a randomized controlled trial design by Rogers, Greenwald, and DeGuzman (2006), the use of oral sucrose solution in the relief of pain among neonates undergoing bladder catheterization in the emergency department was evaluated. Two minutes before the procedure, half of the neonates were given 2 mL of sucrose, while the other half received of water of the same amount. The level of pain was measured by trained ED nurses based on the presence and duration of cry, and time to return to baseline. Results of the study showed that preterm infants who received oral sucrose had lesser increases in pain score than those who received water only. In addition, results demonstrated that neonates who received the sucrose solution had shorter duration of cry compared to the control set- up. This finding supports the reduction of pain experienced by neonates during a bladder catheterization. On the other hand, older infants did not show a significant difference in any treatment. Using Oral Sucrose for Anxiety Relief in the Emergency Department Aside from pain, anxiety also plays an important role in the experience of pediatric clients in the emergency department. In the general pediatric population, unnecessary anxiety should also be avoided. The clinical report by Zempsky and Cravero (2004) from the American Academy of Pediatrics explicitly laid down the guidelines to be followed to relieve pain and anxiety among pediatric clients. In the report, oral sucrose has been suggested to decrease the response to noxious stimuli. However, the analgesic and anxiolytic effects of sucrose solution decrease gradually over the next 6 months. Using Oral Sucrose for Pain Relief from NG- Tube Insertions In some pediatric conditions that necessitate the installment of nasogastric tubes, pain cannot be avoided especially among the preterm neonates. The invasive nature of this procedure predisposes the infant not only to pain and discomfort, but also to risks of tube dislodgement and improper placement. Thus, pain management of neonates prescribed with this procedure must not be delayed to avoid secondary physical complications. In a study by McCullough (2008), preterm infants with a mean gestational age of 30.7 weeks were to undergo NG tube insertion. The set- up involved the administration of 0.5 to 2.0 mL of sterile water 2 minutes prior to the procedure as the control, and the same amount and timing with 24% sucrose as the treatment group. The amount of fluids introduced was adjusted according the weight of the individual infant. Behavioral indicators of pain included the incidence of cry while physiologic indicators were the heart rate change, oxygen saturation changes, and the NCFS system of scoring. Results showed only minor statistical significance based on the behavioral indicator. While the physiologic indicators such as heart rate, oxygen saturation, and NCFS scores displayed some differences, the figures are not intrinsically remarkable to be conclusive. Using Oral Sucrose for Pain Relief ROP Examination Preterm neonates are also susceptible to retinopathy. The disorder is routinely checked for premature neonates through retinal examinations. Unfortunately, this procedure is not free from pain, and infants subjected to this eye examination develop serious physiologic disturbances. Oral sucrose has not been shown to provide the necessary relief for preterm infants. That is, more aggressive measures are performed such as a continuous intravenous infusion of remifentanyl and use of topical anesthetics in cases of eye surgery and laser therapy (American Academy of Pediatrics 2006, p. 2236). Furthermore, the study by Boyle (2006) demonstrated that oral sucrose can provide only minimal benefits for preterm neonates undergoing eye examination for ROP compared with the use of pacifiers. The study used a randomized controlled trial approach involving 40 preterm infants with a median gestational age of 29 weeks. The study population was divided into four to represent control and treatment groups. One group received 1 mL of sterile water only while another group received 1 mL of 33% sucrose. Still another group received a combination of 1 mL sterile water and pacifier, and the remaining group received 1 mL of 33% sucrose in addition to pacifier. All the interventions were given two minutes prior to eye examination. The parameters associated with pain were assessed using the PIPP scale. Results of the study showed that the use of pacifier showed significant differences than the use of either sterile water or sucrose. In fact, no significant differences existed between using sterile water against sucrose solution. In contrast, the study by Gal (2005) showed that PIPP scores were lower in preterm infants who received sucrose solution compared to those who received only placebo. 23 neonates with a gestational age of 24 to 29 weeks were subjected to eye examination for detection of ROP. The treatments compared in the study were 2 mL sterile water, 2 mL of 24% sucrose, mydriatic eye drops, and local anesthetic eye drops. In a similar study to determine the analgesic effect of oral sucrose, Rush (2005) studied the response of 30 preterm infants, with gestational age lower than 32 weeks or weighing less than 1500 g, to eye examinations for ROP. Prior to the examination, the preterm neonates received an instillation of 0.5% procainamide, 1% tropicamide, and 2.5% phenylephrine. Control set- ups comprised of no swaddling, no pacifier, and no handling. Treatments composed of either swaddling in a warm blanket 15 minutes prior to examination, or pacifier soaked in 24% sucrose solution and held by nurse 15 minutes after the procedure. Results showed no significant differences in crying time between the control and treatment groups. Implications for Policy Amendments and Implementation Preterm neonates are subjected to a lot of procedural pain than those infants born at full term. Physiologically, the ascending sensory neural pain pathways are said to be developed in both preterm and term neonates. However, in preterm infants, the descending inhibitory pathways have not reached full maturity (Porter, Wolf, and Miller 1999, p. 1). Because this pathway develops only with time, preterm neonates experience more intense pain than their term counterparts (Kennedy, Luhman and Zempsky 2008, p. 130). Routine newborn screening and special diagnostic procedures are performed to check for metabolic alterations in all newborns. These tests require repeated heel- pricks, venipunctures, and other procedures that can inflict pain and discomfort. In some cases, preterm neonates are born with developmental compromise that requires resuscitation, ventilation, and surgery to support life. Like adults, major procedures in preterm neonates usually require the administration of general, regional, or local anesthetics, opioid drugs, NSAIDS, and insertion of endotracheal and nasogastric tubes. The current guidelines do not recommend oral sucrose as a pain relief measure in major operations. However, it might help to alleviate anxiety before and after the surgical experience. The current literature is saturated with claims and disagreements on the efficiency of using oral sucrose in the relief of pain from procedures for preterm neonates. Neurobiological studies confirm that concentrated oral sucrose solution diminishes electroencephalographic patterns attributed to pain in the neonate. However, the exact mechanism of how this effect happens is not well understood. Hoslti and Grunau (2009) from the American Academy of Pediatrics deducted from animal research articles that chronic exposure to sucrose produces an alternative amine and hormone pathways common to the processing of sucrose, attention, and motor development, thus, the calming effect of sucrose. In contrast to what is traditionally thought, the release of endorphins physiologically associated with pain is not affected by oral sucrose intake. Furthermore, the direct gastric administration of sucrose does not show any significant advantage compared when it is orally taken. Glucose, when used as an alternative to sucrose, does not decrease oxygen and energy consumption of the neonates, which suggests that a stress response is still manifested (American Academy of Pediatrics 2006, p. 2234). Although most are convinced about the analgesic effects of oral sucrose, some researchers recommend that oral sucrose be used in combination with other nonpharmacological interventions such as breastfeeding, skin- to- skin contact, swaddling, and use of pacifiers. Another area of concern in the use of oral sucrose is the possibility of side- effects. Currently, the use of oral sucrose has not been found to be associated with major side effects. Some authors described minor side effects not directly related to the solution itself, but correlated in the technique used to administer the treatment. For example, in one study by Gibbins et al. (2002), one neonate suffered from choking with the use of pacifier and placebo. Three other infants in the study also suffered a decrease in oxygen saturation. The condition stabilized within 10 minutes and did not warrant the administration of supplemental oxygen. It can be inferred that these incidences can happen in the administration of oral sucrose solution when the care giver does not perform necessary technique to prevent such accidents. There was no significant difference as to the rate of incidence of the improper administration of oral sucrose and water. Choking and oxygen desaturation occur independently to the type of solution administered. Spitting up of the solution also occurred during the administration of oral solutions. Based on the developmental stage of the preterm neonates, these incidents were easily correlated to the extrusion reflexes that do not disappear yet at this early age. In some infants as observed in the study by McCullough et al. (2008), some neonates experienced bradycardia and brief apnea. These incidents stabilized eventually even without clinical interventions performed. Thus, these side effects may be attributed to the immaturity of the functional body systems of the preterm neonates and not on the type of solution used as a pain relief measure. Guidelines set by the American Academy of Pediatrics (2006) explain that every health care facility must develop a protocol to assess pain and minimize the number of painful procedures in the preterm neonates. That is, an effective pain management among preterm neonates should call for a collaborative involvement of the parents and primary care givers (Sharek et al. 2006, p. 78). The remarkable results affirming the positive effects of behavioral interventions also prove that pain management must incorporate the value of affection and care (Anand and Hall 2008, p. 825). Most importantly, it is important to note that oral sucrose only reduces pain. It does not totally eliminate the overall discomfort experienced by preterm neonates. Therefore, the challenge of providing the optimum comfort to preterm neonates in different procedures should not rest into proving or disproving the value of sucrose (Sharek et al. 2006, p. 78). Knowledge Gaps for Future Research Several gaps in literature have surfaced on the issue of using oral sucrose in pain relief of preterm neonates. In fact, the dosage formulation of sucrose in the solution has not been studied well. While the current evidence available in scholarly databases prioritized on the proof and disproof of analgesic effects of sucrose, the dosage calculations were not highlighted. Researchers rely on a single dose of sucrose solution with only few attempts to determine if analgesic effects are affected by changes in concentrations. Most authors agree that a minimum concentration of 0.012 to 0.12 g of 24% sucrose apparently reduces pain level among the preterm neonates. Still, the dosage is arbitrarily set depending on which treatments were compared. Research studies that involved clinical comparisons of several other treatments such as local anesthetics tend to use lesser concentrations of sucrose compared to studies aimed at providing proof of analgesia alone. Furthermore, there is not enough evidence yet that investigated whether lower concentrations of sucrose led to negative findings in pain reduction. Higher concentrations of up to 33% oral sucrose have been used in some researches like Boyle et al (2006), but proved to be less effective in reducing pain as compared to pacifiers. Single and multiple doses of the solution are still being agreed upon until now. These proposals remain to be speculations and not grounded yet to comparative clinical trials. Some authors also argue on the exact timing of oral sucrose administration before, during, or after the painful procedure (American Academy of Pediatrics 2006, p. 2234). Because of the inconsistencies of the pain- reducing capacity of oral sucrose in different procedures, the timing of the administration of sucrose can be an important complicating factor subject for further studies. Oral sucrose demonstrated a remarkable pain- reducing activity in some procedures, but lesser activity in others. Conflicting data can also be observed in the results of some studies regarding the concentrations of the sucrose solution and the frequency that it should be administered to the infants. In a study by Boyle (2004), the neonates were given 0.1 to 0.3 mL of 24% sucrose solution in seven consecutive days. Results showed no remarkable implications because the salivary cortisol levels used as the quantitative parameter in detecting stress did not fluctuate as to produce a statistical difference. Again, this result may vary when the concentration of sucrose is increased or decreased. On the other hand, Gaspardo (2008) concluded that the analgesic effect of oral sucrose is limited up to three days only from the first administration. In this study, 25% sucrose solution was given to neonates undergoing a painful procedure. Facial expression and crying diminished significantly in the second and third day of treatment (Stevens, Yamada, and Ohlsson 2010, p.54). When oral sucrose becomes an accepted procedure in the relief of procedural pain in preterm neonates, precision of the amount of sucrose used for this purpose needs to be established. Randomized controlled trials are essential to compare the efficiency of different concentrations of sucrose and obtain reliable results. Sucrose, like other substances, needs to be studied not only on its apparent effects in pain relief for preterm infants but on the minimum concentrations that the solution is effective and cause only lesser side- effects, if there are any. The review posed significant areas that need further research including the identification of an optimum concentration that can provide the needed analgesia (Stevens et al. 2010, p. 1). The hypothesis behind the use of sucrose as more appropriate in low- birth weight infants due to an increased need for calorie and energy supply also warrants further evidence. Bibliography American Academy of Pediatrics 2006, 'Prevention and management of pain in the neonate: An update', in Pediatrics, vol. 118, no. 5, pp. 2231- 2241. American Academy of Pediatrics and Canadian Paediatric Society 2000, 'Prevention and Management of Pain and Stress in the Neonate', in Pediatrics, vol. 105, no. 2, pp. 454- 461. Allen, KD, White DD and Walburn JN. 1996, 'Sucrose as an analgesic agent for infants during immunization injections', Archives of Pediatrics & Adolescent Medicine, vol. 150, pp. 270- 274. Anand, KJS. and Hall, RW. 2008, 'Love, pain, and intensive care', American Academy of Pediatrics, vol. 121, no. 4, pp. 825- 827. Anand, KJS., Aranda, JV., Berde, C. et al. 2006, 'Summary Proceedings from the neonatal pain- control group'', Pediatrics, vol. 117, no. 3, pp. S9- 24. Bellieni, CV., Sisto, R., Cordelli, DM and Buonocore, G 2004, 'Cry features reflect pain intensity in term newborns: An alarm threshold', Pediatrics Research, vol. 55, no. 1, pp. 142- 147. Boyer, K., Johnston, C., Walker, CD., Filion F. and Sherrard A.. 2004, 'Does sucrose analgesia promote physiologic stability in preterm neonates?', Biology of the Neonate, vol 85, pp. 26- 31. Boyle, EM, Freer Y., Khan- Orazaki et al. 2006, 'Sucrose and non-nutritive sucking for the relief of pain in screening for retinopathy of prematurity: a randomized controlled trial', Archives of Disease in Childhood. Fetal and Neonatal Edition, vol. 91, pp. 166- 168. Bucher HU, Moser T, von Siebenthal, K et al. 1995, 'Sucrose reduces pain reaction to heel lancing in preterm infants: A placebo-controlled, randomized and masked study', Pediatric Research, vol. 38, pp. 332- 335. Carbajal, R., Lenclen, R., Jugie, M. et al. 2005, 'Morphine does not provide adequate analgesia for acute procedural pain among preterm neonates', Pediatrics, vol. 115, no. 6, pp. 1494- 1500. Carbajal, R., Veerapen, S. and Couderc S. et al. 2003, 'Analgesic effect of breast feeding in term neonates: Randomised controlled trial', BMJ, vol. 326, pp. 1-5. Carbajal, R., Chauvet, X., Couderc, S. and Oliver- Martin, M. 1999, 'Randomised trial of analgesic effects of sucrose, glucose, and pacifiers in term neonates', BMJ, vol. 319, pp. 1393- 1397. Chermont, AG., Falcao, LF., Silva, E. et al. 2009, 'Skin-to-skin contact and/or oral 25% dextrose for procedural pai relief for term newborn infants,' Pediatrics, vol. 124, no. 6, pp. e1101–e1107. Cignacco, EL., Sellam, G., Stoffel, L. et al. 2012, 'Oral sucrose and facilitated tucking for repeated pain relief in preterms: A randomised controlled trial, ' Pediatrics, vol. 129, no. 6, pp. 1- 10. Codipietro L, Ceccarelli M and Ponzone A 2008, 'Breastfeeding or oral sucrose solution in term neonates receiving heel lance: A randomized controlled trial', Pediatrics, vol. 122, pp. 716- 721. Curtis, SJ., Jou, H., Ali, S., Vandermeer, B. and Klassen, T. 2007, 'A randomized controlled trial of sucrose and/or pacifier as analgesia for infants receiving venipuncture in a pediatric emergency department', BMC Pediatrics, vol. 7, no. 27, pp. 1-9. Gal, P, Kissling, GE, Young, WO et al. 2005, 'Efficacy of sucrose to reduce pain in premature infants during eye examinations for retinopathy of prematurity', Annals of Pharmacotherapy, vol. 39, pp. 1029- 1033. Gaspardo, CM, Miyase, CI, Chimello, JT et al. 2008, 'Is pain relief equally efficacious and free of side effects with repeated doses of oral sucrose in preterm neonates?', Pain, vol. 137, pp. 16- 25. Gibbins, S. and Stevens, B. 2002, 'The influence of gestational age on the efficacy and short-term safety of sucrose for procedural pain relief', Advances in Neonatal Care, vol. 3, no. 3, pp. 241- 249. Grunau RVE and Craig KD 1990, 'Facial activity as a measure of neonatal pain expression', Advances in Pain Research Therapy, vol. 15, pp. 147- 154 Haidon, JL. and Cunliffe, M. 2010, 'Analgesia for neonates', Continuing Education in Anesthesia, Critical Care, & Pain, vol. 10, no. 4, pp. 123- 127. Holsti, L. and Grunau, RE., 2009, 'Considerations for using sucrose to reduce procedural pain in preterm infants', American Academy of Pediatrics, vol. 125, no. 5, pp. 1042- 1047. Kennedy, RM., Luhmann, J. and Zempsky, WT. 2008, 'Clinical implications of unmanaged needle- insertion pain and distress in children', Pediatrics, vol. 132, no. 3, pp. 130- 133. Krechel SW and Bildner J 1995, 'CRIES: a new neonatal postoperative pain measurement score: initial testing of validity and reliability', Pediatr Anaesth, vol. 5, pp. 53- 61. Lawrence J, Alcock, D, McGrath P et al. 1993, 'The development of a tool to assess neonatal pain', Neonatal Networks, vol. 12, pp. 59- 66. McCullough, S., Halton, T., Mowbray, D., and Macfarlane, PI. 2008, 'Lingual sucrose reduces the pain response to nasogastric tube insertion: A randomised clinical trial’, Archives of Disease in Childhood. Fetal and Neonatal Edition, vol. 93, pp. 100- 103. Morrow, C., Hidinger, A., Wilkinson- Faulk, D. 2010. 'Reducing neonatal pain during routine heel lance procedures', Lippincott Williams & Wilkins, vol. 35, no. 6, pp. 346- 354. Mucignat, V., Ducrocq, S., Mungan, N. et al. 2004, 'Analgesic effects of Emla cream and saccharose solution for ubcutaneous injections in preterm newborns: A prospective study of 265 injections', Archives of Pediatrics, vol 11, pp. 921- 925. Perreault T, Fraser- Askin D, and Liston R et al. 1989, 'Pain in the neonate', Paediatric Child Health, vol. 1997, pp. 201- 209. Porter, FL., Wolf, CM. and Miller, JP 1999, 'Procedural pain in newborn infants: The influence of intensity and development', Pediatrics, vol. 104, no. 1, pp. 1-10. Rogers, AJ., Greenwald, MH., DeGuzman, MA. et al. 2006, 'A randomized, controlled trial of sucrose analgesia in infants younger than 90 days of age who require bladder catheterization in the pediatric emergency department', Academic Emergency Medicine, vol. 13, pp. 617-622. Rush, R, Rush, S, Ighani F, et al. 2005, 'The effects of comfort care on the pain response in preterm infants undergoing screening for retinopathy of prematurity', Retina, vol. 25, pp. 59- 62. Sahebihag, MH., Hosseinzadeh, M., Mohammadpourasl, A. and Kosha, A. 2011, 'The effect of breastfeeding, oral sucrose and combination of oral sucrose and breastfeeding in infant's pain relief during the vaccination', Iranian Journal of Nursing and Midwifery Research, vol. 16, no. 1, pp. 9- 15. Stevens B, Yamada J, and Ohlsson A 2010, 'Sucrose for analgesia in newborn infants undergoing painful procedures (Review)', The Cochrane Database Library, issue no. 1, pp. 1- 112. Stevens B, Abu- Saad HH, Bours G et al. 1998, 'Assessment of pain in neonates', Semin Perinatol, vol. 22, pp. 402- 416. Sharek, PJ., Powers, R., Koehn, A. and Anand, KJS. 2006, 'Evaluation and development of potentially better practices to improve pain management of neonates', Pediatrics, vol. 118, no. 2, pp. S78-88. Taddio, A., Shah, V. and Stephens, D. 2011, 'Effect of liposomal lidocaine and sucrose alone and in combination for venipuncture pain in newborns', Pediatrics, vol. 127, pp. e940–e947. Taddio, A., Ohlsson, A., Einarson, TR. et al. 1998, 'A Systematic Review of Lidocaine-Prilocaine Cream (EMLA) in the Treatment of Acute Pain in Neonates', Pediatrics, vol. 101, no. 2, pp. 1-9. Vani, SN., Nimbalkar, S., and Thakre, R. 2009, 'Assessment and management of pain in the newborn', NNF Publications, pp. 199- 215. Zempsky, WT., Cravero, JP. et al. 2004, 'Relief of pain and anxiety in pediatric patients in emergency medical systems', American Academy of Pediatrics, vol. 114, no. 5, pp. 1348- 1356. Read More