Sharyn Gibbins

Efficacy and Safety of Sucrose for Procedural Pain Relief in Preterm and Term Neonates

BackgroundPreterm and acutely ill term neonates who are hospitalized in a neonatal intensive care unit are subjected to multiple frequent invasive and painful procedures aimed at improving their outcome. Although several trials to determine the efficacy of sucrose for managing procedural pain in preterm and acutely ill term neonates have been developed, these have generally lacked methodological rigor and have not provided clinicians with clear practice guidelines. ObjectivesTo compare the efficacy and safety of three interventions for relieving procedural pain associated with heel lances in preterm and term neonates, and to explore the influence of contextual factors including sex, severity of illness, and prior painful procedures on pain responses. MethodsIn a randomized controlled trial, 190 neonates were stratified by gestational age and then randomized to receive (a) sucrose and nonnutritive sucking (n = 64), (b) sucrose alone (n = 62), or (c) sterile water and nonnutritive sucking (control) (n = 64) to evaluate the efficacy (pain response as measured using the Premature Infant Pain Profile) (Stevens, Johnson, Petryshen, & Taddio, 1996) and safety (adverse events) following a scheduled heel lance during the first week of life. Stratification was used to control for the effects of age on pain response. ResultsSignificant differences in pain response existed among treatment groups (F = 22.49, p < .001), with the lowest mean Premature Infant Pain Profile scores in the sucrose and nonnutritive sucking group. Efficacy of sucrose following a heel lance was not affected by severity of illness, postnatal age, or number of painful procedures. Intervention group and sex explained 12% of the variance in Premature Infant Pain Profile scores. Few adverse events occurred (n = 6), and none of them required medical or nursing interventions ConclusionsThe combination of sucrose and nonnutritive sucking is the most efficacious intervention for single heel lances. Research on the effects of gestational age on the efficacy and safety of repeated doses of sucrose is required.

Hair Cortisol as a Potential Biologic Marker of Chronic Stress in Hospitalized Neonates

Background: As preterm and term infants in the neonatal intensive care unit (NICU) undergo multiple stressful/painful procedures, research is required that addresses chronic stress. Objectives: To determine whether (a) hair cortisol levels differed between term and preterm infants exposed to stress in the NICU and (b) an association exists between hair cortisol levels and severity of illness or indicators of acute stress. Methods: Hair cortisol levels were determined using the ELISA method (solid-phase enzyme-linked immunoassay, Alpco Diagnostics, Windham, N.H., USA) in 60 infants >25 weeks gestational age at birth. Results: No significant differences were found between the hair cortisol levels of term infants compared to preterm infants in the NICU. When compared to a group of healthy term infants, hospitalized infants had significantly higher hair cortisol levels (t (76) = 2.755, p = 0.004). A subgroup analysis of the term NICU infants showed a statistically significant association between total number of ventilator days and hair cortisol levels. For every extra day on the ventilator, hair cortisol levels increased on average by 0.2 nmol/g (p = 0.03). 21% of the variance in hair cortisol levels was explained by the total number of days on the ventilator. Conclusions: Hair cortisol is influenced by days of ventilation in NICU term infants. This is a potentially valid outcome for chronic neonatal stress in these infants and warrants further investigation.

Procedural pain in newborns at risk for neurologic impairment

In the past decade, our knowledge of pain in newborn infants has advanced considerably. However, infants at significant risk for neurologic impairment (NI) have been systematically excluded from almost all research on pain in neonates. The objectives of this study were to compare: (a) the nature, frequency and prevalence of painful procedures, (b) analgesics and sedatives administered, and (c) the relationship between painful procedures and analgesia for neonates at risk for NI. One hundred and ninety‐four infants at high (cohort A, n=67), moderate (cohort B, n=59) and low (cohort C, n=68) risk for NI from two tertiary level Neonatal Intensive Care Units in Canada were included in a retrospective cohort study on the first 7 days of life. Data were collected from medical records and analyzed using chi‐square, ANOVA and regression approaches. All cohorts had a mean of >10 painful procedures per day during the first 2 days of life. There was an interaction effect between cohort group and day of life (F5,188=2.13, P<0.06) with cohort A having significantly more painful procedures on day 1 (F2,191=4.79, P<0.009). There was no statistical difference in the number of infants who received continuous infusion (F2,20=1.9, P=0.13) or bolus (F2,20=1.3, P=0.25) opioids or sedatives (F2,20=0.45, P=0.84) by cohort over the 7 day period. There was a statistical difference in bolus opioid administration for days 1 (P<0.05) and 2 (P<0.001) with less than 10% of infants in cohort A receiving bolus opioids compared with approximately 22–33% of infants in cohorts B and C. There was a statistically significant correlation between painful procedures and analgesic use (r=0.29, P<0.001), although significant associations existed for cohorts B and C only. The number of painful procedures and study site primarily accounted for the variance (61% in cohort B and 35% in cohort C) in analgesic use, while in cohort A, only study site contributed to the variance (16%). Neonates at the highest risk for NI had the greatest number of painful procedures and the least amount of opioids administered during the first day of life. There was no relationship between painful procedures and analgesic use in this group. As these infants are vulnerable to pain and its consequences, the rational underlying health professional strategies regarding painful procedures and analgesic use for procedural pain in this population urgently awaits exploration.

Consistent management of repeated procedural pain with sucrose in preterm neonates: Is it effective and safe for repeated use over time?

Objective:Preterm neonates undergo numerous painful procedures in the neonatal intensive care unit (NICU). Sucrose, with and without pacifiers, is effective and safe for relieving pain from single painful events. However, repeated use of sucrose for multiple painful procedures has not been adequately evaluated. The study objectives were to: 1) determine the efficacy and safety of consistent management of repeated procedural pain with sucrose; and 2) explore the impact of consistent pain management on clinical outcomes and neurobiological risk status. Methods:Sixty-six preterm infants were randomized to receive standard care (positioning and swaddling; n = 21), sterile water plus pacifier (n = 23), or 24% sucrose plus pacifier (n = 22) prior to all painful procedures in the NICU during the first 28 days of life. Also, at a routine heel lance at 7, 14, 21, and 28 days of life, data were collected to determine efficacy and immediate and long-term adverse events. Data on clinical outcomes and neurobiological risk status were collected at 28 days or NICU discharge. Results:There was no intervention by time interaction (P = 0.60). There was a significant main effect of intervention (P = 0.03) between the sucrose plus pacifier group, and the standard care group (P = 0.01), but there was no main effect of time (P = 0.72). No group differences existed for adverse events, clinical outcomes, or neurobiological risk status. Discussion:Consistent management of painful procedures with sucrose plus pacifier was effective and safe for preterm neonates during their stay in the NICU. Further exploration of consistent pain management with sucrose on clinical, developmental, and neurobiological outcomes is required.

TREATMENT OF PAIN IN THE NEONATAL INTENSIVE CARE UNIT

Pain is a disruptive influence on infants in the NICU. The most obvious and effective strategy to decrease infant pain in the NICU is to stringently limit the frequency of painful procedures, especially those that are most commonly reported (i.e., heel lances and endotracheal suctioning), and have these performed on infants that are most unstable or critically ill by the most experienced person available. Organizational concerns over the cost of NICU care have forced a re-evaluation of the necessity of certain diagnostic and care procedures and a limiting of procedures to those that can be documented to positively affect clinical outcome. Pharmacologic and nonpharmacologic strategies are essential to the prevention and management of neonatal pain, and these should be considered for complementary use for every infant. Research has shown the safety and effectiveness of some of the strategies in reducing mild pain caused by brief invasive procedures; however, many of the studies had methodologic limitations. Therefore, more research is required to determine the comparative efficacy of the various strategies and to document additive or synergistic effects when combined.

The premature infant pain profile: evaluation 13 years after development.

ObjectiveTo review the (1) reliability, validation, feasibility, and clinical utility and (2) the use of the Premature Infant Pain Profile (PIPP) from 1996 to 2009 to determine the effectiveness of pain management strategies. MethodsData sources included MEDLINE, CINAHL, EMBASE, PsycINFO, and the Web of Science. Published studies evaluating the measurement properties of the PIPP and intervention studies using the PIPP as an outcome measure of acute pain were included. One reviewer screened studies for relevance and inclusion. Four reviewers rated intervention studies for methodological quality and extracted data for the evidence tables. ResultsOf the 62 studies included, 14 focused on the measurement properties of the PIPP. Reliability of the PIPP was supported in 5 studies and construct validation was supported in 13 studies. The feasibility of the PIPP was addressed in 4 studies, whereas clinical utility was discussed in 2 studies. Twenty-seven of the 48 studies that were considered to have high methodological quality used the PIPP as the major outcome to evaluate the effectiveness of pain management interventions in infants. DiscussionThe PIPP continues to be a reliable and valid measure of acute pain in infants with numerous positive validation studies. There is substantial support for the use of the PIPP as an effective outcome measure in pain intervention studies in infants. Further research with health professionals is required to better support the feasibility and clinical utility of this measure.

Comparison of Pain Responses in Infants of Different Gestational Ages

Background: There is a plethora of infant pain measures; however, none of them have been validated for extremely low for gestational age (ELGA) infants (<27 weeks’ gestation). To date, clinicians, researchers and parents use information gleaned from more mature infants to make inferences about pain in ELGA infants. Using physiological or behavioral pain indicators derived from more mature infants may lead to inaccurate assessments and management. Objectives: To compare physiological (heart rate, oxygen saturation) and behavioral (9 facial activities, cry) pain indicators of ELGA infants with infants of varying more mature gestational ages (GAs). Methods: The aim was to determine the effects of GA on pain response. GA was categorized into four mutually exclusive strata: <27 6/7 weeks, 28–31 6/7 weeks, 32–35 6/7 weeks and >36 weeks. Physiological data during four phases of a routine heel lance were collected by placing disposable ECG electrodes and pulse oximetry probes on the infant’s chest. Behavioral data were collected by videotaping facial activities, and cry data were collected by audio recording. Results: Four facial activities (brow bulge, eye squeeze, nasolabial furrow, vertical mouth stretch) in response to acute pain were present in ELGA infants. Facial activities increased following painful procedures and the magnitude of responses was proportional to GA with the youngest infants (<27 6/7 weeks GA) showing the least amount of change. Decreased oxygen saturation and increased heart rate were associated with the most invasive phase of the heel lance; however, the differences were neither clinically or statistically significant across age groups. Cry was not a sensitive pain indicator in ELGA infants, due to the presence of endotracheal tubes in this high-risk population. Discussion: ELGA infants have similar pain responses to older infants, but the responses are dampened. Other factors such as severity of illness, frequency of painful procedures or medication use should be examined, as they may influence the pain responses in ELGA infants.

Clinical utility and clinical significance in the assessment and management of pain in vulnerable infants

Pain in vulnerable populations unable to provide verbal report is challenging in terms of measurement and treatment. Clinicians strive to provide the best possible pain management for infants in the NICU, yet they are often hindered due to paucity of measures that are not only reliable and valid but also clinically useful. Clinical utility of measures is difficult to establish due to a lack of consistent definition of the construct, varied methods of determination, and the secondary importance afforded to this issue in relation to the establishment of reliability and utility. Without clinically useful pain measures, however, clinicians are unable and unlikely to assess the infants pain or the effectiveness of pain-relieving interventions. Furthermore, even when the clinician is able to assess pain using a valid measure with a minimum of time, cost, and instruction, the clinical significance of any reduction in pain scores needs to be interpreted in terms of the infant and his/her care provider. The issue of defining the extent of change in pain scores that is clinically significant or important remains unclear. Clarity will involve assigning meaning to particular changes in pain scores for vulnerable infants across a broad array of situations and severities of pain. Although research on this topic in children and adults provides some guidance to this dilemma, only through innovative and creative methods will we be able to address these issues.

The influence of gestational age on the efficacy and short-term safety of sucrose for procedural pain relief.

BACKGROUNDPhysiologic and behavioral responses to procedural pain are influenced by gestational age (GA). Compared with term neonates, hospitalized preterm neonates are subjected to more painful procedures aimed at improving their clinical outcome. Although several trials to determine the efficacy of sucrose for managing procedural pain have been conducted, none have examined the influence of GA. OBJECTIVESTo examine the influence of GA on the efficacy and short-term safety of oral sucrose for relieving procedural pain associated with heel lances. To explore GA differences in behavioral and physiologic indicators of pain. METHODSAs part of a larger randomized controlled trial (RCT) to examine the efficacy and safety of sucrose during heel lance, 190 neonates were stratified by GA: (a) 27 to 31 6/7 weeks (group 1; n = 63), (b) 32 to 35 6/7 weeks (group 2; n = 63), and (c) >36 weeks (group 3; n = 64). They were then randomized to receive (a) oral sucrose and non-nutritive sucking (NNS), (b) sucrose alone, or (c) sterile water and NNS (control) for a heel lance. The influence of GA was determined by examining the short-term safety, as defined by the number of associated adverse events (choking, coughing or vomiting, sustained tachycardia, sustained tachypnea or dyspnea, or sustained oxygen desaturation). The efficacy was measured by changes in a validated pain measure, scored during each phase of the intervention and analyzed according to GA groups. RESULTSSignificant differences in pain response existed in each GA group, with the lowest mean pain scores in the sucrose and NNS group. Significant GA differences in behavioral and physiologic responses were found, with the most mature neonates demonstrating the greatest magnitude of pain response. The greatest number of short-term adverse effects to treatment occurred in the lowest GA group. CONCLUSIONSIn a secondary analysis of a larger RCT, sucrose and NNS was the most efficacious intervention for single heel lances in each of 3 GA groups. However, infants of lower GA experienced more adverse events. Research on the efficacy and safety of repeated doses of oral sucrose, tested in infants from a wide range of GA, is required.

Mechanisms of Sucrose and Non-Nutritive Sucking in Procedural Pain Management in Infants

The administration of sucrose with and without non-nutritive sucking (NNS) has been examined for relieving procedural pain in newborn infants. The calming and pain-relieving effects of sucrose are thought to be mediated by endogenous opioid pathways activated by sweet taste. The orogustatory effects of sucrose have been demonstrated in animal newborns, and in preterm and full term human infants during painful procedures. In contrast to sucrose, the analgesic effects of NNS are hypothesized to be activated through nonopioid pathways by stimulation of orotactile and mechanoreceptor mechanisms. Although there is uncertainty as to whether the effects of sucrose and NNS are synergistic or additive, there is sufficient evidence to support the efficacy of combining the two interventions for procedural pain relief in infants. In this review article, the underlying mechanisms of sucrose and NNS, separately and in combination for relieving procedural pain in preterm and full term infants, are examined. Clinical and research implications are addressed.