Sucrose analgesia for heel-lance procedures in neonates

Abstract

Background: Sucrose has been examined for calming and pain-relieving effects in neonates for invasive procedures such as heel lance. Objectives: To assess the effectiveness of sucrose for relieving pain from heel lance in neonates in terms of immediate and long-term outcomes. Search methods: We searched (February 2022): CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and three trial registries. Selection criteria: We included randomised controlled trials where term and/or preterm neonates received sucrose for heel lances. Comparison treatments included water/placebo/no intervention, non-nutritive sucking (NNS), glucose, breastfeeding, breast milk, music, acupuncture, facilitated tucking, and skin-to-skin care. Data collection and analysis: We used standard Cochrane methods. We reported mean differences (MD) with 95% confidence intervals (CI) using the fixed-effect model for continuous outcome measures. We assessed heterogeneity by the I2 test. We used GRADE to assess certainty of evidence. Main results: We included 55 trials (6273 infants): 29 included term neonates, 22 included preterm neonates, and four included both. Heel lance was investigated in 50 trials; 15 investigated other minor painful procedures in addition to lancing. Sucrose vs control. The evidence suggests that sucrose probably results in a reduction in PIPP scores compared to the control group at 30 seconds (MD -1.74 (95% CI -2.11 to -1.37); I2 = 62%; moderate-certainty evidence) and 60 seconds after lancing (MD -2.14, 95% CI -3.34 to -0.94; I2 = 0%; moderate-certainty evidence). The evidence is very uncertain about the effects of sucrose on DAN scores compared to water at 30 seconds after lancing (MD -1.90, 95% CI -8.58 to 4.78; heterogeneity not applicable (N/A); very low-certainty evidence). The evidence suggests that sucrose probably results in a reduction in NIPS scores compared to water immediately after lancing (MD -2.00, 95% CI -2.42 to -1.58; heterogeneity N/A; moderate-certainty evidence). Sucrose vs NNS. The evidence is very uncertain about the effect of sucrose on PIPP scores compared to NNS during the recovery period after lancing (MD 0.60, 95% CI -0.30 to 1.50; heterogeneity not applicable; very low-certainty evidence) and on DAN scores at 30 seconds after lancing (MD -1.20, 95% CI -7.87 to 5.47; heterogeneity N/A; very low-certainty evidence). Sucrose + NNS vs NNS. The evidence is very uncertain about the effect of sucrose + NNS on PIPP scores compared to NNS during lancing (MD -4.90, 95% CI -5.73 to -4.07; heterogeneity not applicable; very low-certainty evidence) and during recovery after lancing (MD -3.80, 95% CI -4.47 to -3.13; heterogeneity N/A; very low-certainty evidence). The evidence is very uncertain about the effects of sucrose + NNS on NFCS scores compared to water + NNS during lancing (MD -0.60, 95% CI -1.47 to 0.27; heterogeneity N/A; very low-certainty evidence). Sucrose vs glucose. The evidence suggests that sucrose results in little to no difference in PIPP scores compared to glucose at 30 seconds (MD 0.26, 95% CI -0.70 to 1.22; heterogeneity not applicable; low-certainty evidence) and 60 seconds after lancing (MD -0.02, 95% CI -0.79 to 0.75; heterogeneity N/A; low-certainty evidence). Sucrose vs breastfeeding. The evidence is very uncertain about the effect of sucrose on PIPP scores compared to breastfeeding at 30 seconds after lancing (MD -0.70, 95% CI -0.49 to 1.88; I2 = 94%; very low-certainty evidence). The evidence is very uncertain about the effect of sucrose on COMFORTneo scores compared to breastfeeding after lancing (MD -2.60, 95% CI -3.06 to -2.14; heterogeneity N/A; very low-certainty evidence). Sucrose vs expressed breast milk. The evidence suggests that sucrose may result in little to no difference in PIPP-R scores compared to expressed breast milk during (MD 0.3, 95% CI -0.24 to 0.84; heterogeneity not applicable; low-certainty evidence) and at 30 seconds after lancing (MD 0.3, 95% CI -0.11 to 0.71; heterogeneity N/A; low-certainty evidence). The evidence suggests that sucrose probably may result in slightly increased PIPP-R scores compared to expressed breast milk 60 seconds after lancing (MD 1.10, 95% CI 0.34 to 1.86; heterogeneity N/A; low-certainty evidence). The evidence is very uncertain about the effect of sucrose on DAN scores compared to expressed breast milk 30 seconds after lancing (MD -1.80, 95% CI -8.47 to 4.87; heterogeneity N/A; very low-certainty evidence). Sucrose vs laser acupuncture. There was no difference in PIPP-R scores between sucrose and music groups; however, data were reported as medians and IQRs. The evidence is very uncertain about the effect of sucrose on NIPS scores compared to laser acupuncture during lancing (MD -0.86, 95% CI -1.43 to -0.29; heterogeneity N/A; very low-certainty evidence). Sucrose vs facilitated tucking. The evidence is very uncertain about the effect of sucrose on total BPSN scores compared to facilitated tucking during lancing (MD -2.27, 95% CI -4.66 to 0.12; heterogeneity N/A; very low-certainty evidence) and during recovery after lancing (MD -0.31, 95% CI -1.72 to 1.10; heterogeneity N/A; very low-certainty evidence). Sucrose vs skin-to-skin + water (repeated lancing). The evidence suggests that sucrose results in little to no difference in PIPP scores compared to skin-to-skin + water at 30 seconds after 1st (MD 0.13, 95% CI -0.70 to 0.96); 2nd (MD -0.56, 95% CI -1.57 to 0.45); or 3rd lancing (MD-0.15, 95% CI -1.26 to 0.96); heterogeneity N/A, low-certainty evidence for all comparisons. The evidence suggests that sucrose results in little to no difference in PIPP scores compared to skin-to-skin + water at 60 seconds after 1st (MD –0.61, 95% CI -1.55 to 0.33); 2nd (MD -0.12, 95% CI -0.99 to 0.75); or 3rd lancing (MD-0.40, 95% CI -1.48 to 0.68); heterogeneity N/A, low-certainty evidence for all comparisons. Minor adverse events required no intervention. Authors' conclusions: Sucrose compared to control probably results in a reduction of PIPP scores 30 and 60 seconds after single heel lances (moderate-certainty evidence). Evidence is very uncertain about the effect of sucrose compared to NNS, breastfeeding, laser acupuncture, facilitated tucking, and the effect of sucrose + NNS compared to NNS in reducing pain. Sucrose compared to glucose, expressed breast milk, and skin-to-skin care shows little to no difference in pain scores. Sucrose combined with other nonpharmacologic interventions should be used with caution, given the uncertainty of evidence.