Scolaris Content Display Scolaris Content Display

Forest plot of comparison: 3 Heel lance: sucrose 20‐50% vs. control (sterile water), outcome: 3.1 Duration of first cry (s).
Figuras y tablas -
Figure 1

Forest plot of comparison: 3 Heel lance: sucrose 20‐50% vs. control (sterile water), outcome: 3.1 Duration of first cry (s).

Forest plot of comparison: 3 Heel lance: sucrose 20‐50% vs. control (sterile water), outcome: 3.2 Total crying time (s).
Figuras y tablas -
Figure 2

Forest plot of comparison: 3 Heel lance: sucrose 20‐50% vs. control (sterile water), outcome: 3.2 Total crying time (s).

Forest plot of comparison: 2 Heel lance: sucrose 25‐33% vs. control (sterile water), outcome: 2.1 % change in heart rate one minute after heel lance.
Figuras y tablas -
Figure 3

Forest plot of comparison: 2 Heel lance: sucrose 25‐33% vs. control (sterile water), outcome: 2.1 % change in heart rate one minute after heel lance.

Forest plot of comparison: 2 Heel lance: sucrose 25‐33% vs. control (sterile water), outcome: 2.2 % change in heart rate three minutes after heel lance.
Figuras y tablas -
Figure 4

Forest plot of comparison: 2 Heel lance: sucrose 25‐33% vs. control (sterile water), outcome: 2.2 % change in heart rate three minutes after heel lance.

Forest plot of comparison: 2 Heel lance: sucrose 25‐33% vs. control (sterile water), outcome: 2.3 Heart rate at three minutes after heel lance.
Figuras y tablas -
Figure 5

Forest plot of comparison: 2 Heel lance: sucrose 25‐33% vs. control (sterile water), outcome: 2.3 Heart rate at three minutes after heel lance.

Forest plot of comparison: 1 Heel lance: sucrose (sucrose or sucrose+NNS) vs. control (NNS+water, water or positioning and containing intervention), outcome: 1.1 Premature Infant Pain Profile (PIPP) at 30 seconds after heel lance.
Figuras y tablas -
Figure 6

Forest plot of comparison: 1 Heel lance: sucrose (sucrose or sucrose+NNS) vs. control (NNS+water, water or positioning and containing intervention), outcome: 1.1 Premature Infant Pain Profile (PIPP) at 30 seconds after heel lance.

Forest plot of comparison: 1 Heel lance: sucrose (sucrose or sucrose+NNS) vs. control (NNS+water, water or positioning and containing intervention), outcome: 1.2 Premature Infant Pain Profile (PIPP) at 60 seconds after heel lance.
Figuras y tablas -
Figure 7

Forest plot of comparison: 1 Heel lance: sucrose (sucrose or sucrose+NNS) vs. control (NNS+water, water or positioning and containing intervention), outcome: 1.2 Premature Infant Pain Profile (PIPP) at 60 seconds after heel lance.

Forest plot of comparison: 7 ROP examination: sucrose 24‐33% (sucrose or sucrose+NNS) vs. control (water or water+NNS), outcome: 7.1 Oxygen saturation (%) during eye examination.
Figuras y tablas -
Figure 8

Forest plot of comparison: 7 ROP examination: sucrose 24‐33% (sucrose or sucrose+NNS) vs. control (water or water+NNS), outcome: 7.1 Oxygen saturation (%) during eye examination.

Comparison 1 Heel lance: sucrose (sucrose or sucrose+NNS) vs. control (NNS+water, water or positioning and containing intervention), Outcome 1 Premature Infant Pain Profile (PIPP) at 30 s after heel lance.
Figuras y tablas -
Analysis 1.1

Comparison 1 Heel lance: sucrose (sucrose or sucrose+NNS) vs. control (NNS+water, water or positioning and containing intervention), Outcome 1 Premature Infant Pain Profile (PIPP) at 30 s after heel lance.

Comparison 1 Heel lance: sucrose (sucrose or sucrose+NNS) vs. control (NNS+water, water or positioning and containing intervention), Outcome 2 Premature Infant Pain Profile (PIPP) at 60 s after heel lance.
Figuras y tablas -
Analysis 1.2

Comparison 1 Heel lance: sucrose (sucrose or sucrose+NNS) vs. control (NNS+water, water or positioning and containing intervention), Outcome 2 Premature Infant Pain Profile (PIPP) at 60 s after heel lance.

Comparison 2 Heel lance: sucrose 25‐33% vs. control (sterile water), Outcome 1 % change in heart rate 1 min after heel lance.
Figuras y tablas -
Analysis 2.1

Comparison 2 Heel lance: sucrose 25‐33% vs. control (sterile water), Outcome 1 % change in heart rate 1 min after heel lance.

Comparison 2 Heel lance: sucrose 25‐33% vs. control (sterile water), Outcome 2 % change in heart rate 3 min after heel lance.
Figuras y tablas -
Analysis 2.2

Comparison 2 Heel lance: sucrose 25‐33% vs. control (sterile water), Outcome 2 % change in heart rate 3 min after heel lance.

Comparison 2 Heel lance: sucrose 25‐33% vs. control (sterile water), Outcome 3 Heart rate at 3 min after heel lance.
Figuras y tablas -
Analysis 2.3

Comparison 2 Heel lance: sucrose 25‐33% vs. control (sterile water), Outcome 3 Heart rate at 3 min after heel lance.

Comparison 3 Heel lance: sucrose 12.5‐50% vs. control (sterile water), Outcome 1 Duration of first cry (s).
Figuras y tablas -
Analysis 3.1

Comparison 3 Heel lance: sucrose 12.5‐50% vs. control (sterile water), Outcome 1 Duration of first cry (s).

Comparison 3 Heel lance: sucrose 12.5‐50% vs. control (sterile water), Outcome 2 Total crying time (s).
Figuras y tablas -
Analysis 3.2

Comparison 3 Heel lance: sucrose 12.5‐50% vs. control (sterile water), Outcome 2 Total crying time (s).

Comparison 4 ROP examination: sucrose 24‐33% (sucrose or sucrose+NNS) vs. control (water or water+NNS), Outcome 1 PIPP score during (L) eye examination.
Figuras y tablas -
Analysis 4.1

Comparison 4 ROP examination: sucrose 24‐33% (sucrose or sucrose+NNS) vs. control (water or water+NNS), Outcome 1 PIPP score during (L) eye examination.

Comparison 4 ROP examination: sucrose 24‐33% (sucrose or sucrose+NNS) vs. control (water or water+NNS), Outcome 2 PIPP score for ROP examinations.
Figuras y tablas -
Analysis 4.2

Comparison 4 ROP examination: sucrose 24‐33% (sucrose or sucrose+NNS) vs. control (water or water+NNS), Outcome 2 PIPP score for ROP examinations.

Comparison 5 ROP examination: sucrose 24‐33% (sucrose or sucrose+NNS) vs. control (water or water+NNS), Outcome 1 Oxygen saturation (%) during eye examination.
Figuras y tablas -
Analysis 5.1

Comparison 5 ROP examination: sucrose 24‐33% (sucrose or sucrose+NNS) vs. control (water or water+NNS), Outcome 1 Oxygen saturation (%) during eye examination.

Table 1. Trials assessing pain during heel lances

Study

Participants

Procedure

Interventions

Outcomes

Metrics used

Results

Altun‐Koroglu 2010

 

 

75 full‐term infants

Heel lance

3 mL of hind milk (N = 25)

3 mL of 12.5% sucrose solution (N = 25)

3 mL of distilled water (N = 25)

NFCS, crying time, duration of crying, HR

 

Median and IQR

Median crying time, duration of first cry and tachycardia, and time needed to return to baseline = longest in the distilled water group. Significantly shorter in the hind milk group when compared to distilled water group (P = 0.022, P = 0.008, P 0.009 and P = 0.038, respectively)

No statistically significant differences observed between the hind milk and sucrose group

Maximum HR in hind milk group was significantly lower than distilled water group (184 bpm vs. 196 bpm, P = 0.031)

Significant reduction in average NFCS score. 1st minute NFCS score and 5th minute NFCS score in the hind milk group compared to the distilled water group (P = 0.006, P = 0.017 and P = 0.021, respectively)

Blass 1997

72 infants, 22 to 40 h old

Heel lance

2 mL of either of the following solutions:

water       

12% sucrose    

protein mixture

7% lactose   

dilute fat (coconut and soy oil)    

concentrated fat    

fat and lactose mixture RSF (water, protein, lactose, fat)

milk

N = 8 for all groups

Crying time (%) during blood collection and 1, 2 and 3 min after heel lance   

Mean % of crying time per min at 1, 2 and 3 min after heel lance (recovery period)

Mean proportions 

   

Graphically reported

Significantly less crying time during blood collection in the sucrose group (47%) compared to the water group (92%, P = 0.015)

Blass 1999

40 term newborn infants, 34 to 55 h old

Heel lance

2 mL of 12% sucrose over 2 min via syringe (N = 10)

2 mL of water via syringe over 2 min (N = 10)

Pacifier dipped every 30 s in 12% sucrose solution for 2 min (N = 10)

Pacifier dipped in water every 30 s for 2 min (N = 10) prior to heel lance

% time crying 3 min after heel lance

Mean change in HR

% time grimacing

Mean percentage

Mean change (bpm)

Mean percentage

2 mL of 12% (0.24 g) sucrose alone diminished cry duration from heel lance compared to water (8% vs. 50%, P = 0.003) and water with pacifier (8% vs. 35%, P = 0.002). Pacifier with 12% sucrose more effective in reducing cry duration compared to water with pacifier (5% vs. 35%, P = 0.001) or water alone (50%, P = 0.002)

Mean HR increased significantly from treatment to heel lance in infants receiving water alone (mean increase of 17 bpm, P = 0.002) and water with pacifier (mean increase of 20 bpm, P = 0.005). Mean increase in HR also increased for the 2 mL of 12% (0.24 g) sucrose and pacifier group (mean difference of 7.4 bpm, P = 0.05) but not for infants receiving 2 mL of 12% (0.24 g) sucrose alone (mean difference of 5.9 bpm, P = 0.142)

2 mL of 12% (0.24 g) sucrose reduced grimacing compared to water (P = 0.0003). 12% (0.24 g) sucrose with pacifier reduced grimacing compared to water (P = 0.001) and pacifier alone (P = 0.04)

Bucher 1995

16 preterm infants, 27 to 34 weeks' GA, postnatal age approximately 42 days

Heel lance

2 mL of 50% sucrose via syringe into the mouth 2 min before heel lance

2 mL of distilled water via syringe into the mouth 2 min before heel lance (N = 16, cross‐over design)

% time crying

Recovery time until crying stopped

Increase in HR

Recovery time for HR

TcpO2 (max increase ‐ kPa); TcpO2 (max decrease ‐ kPa); TcpO2 (difference between baseline and 10 min after end of intervention ‐ kPa); TcpCO2 (max decrease ‐ kPa); TcpCO2 (difference between baseline and 10 min after the end of intervention), recovery time for respirations

Not reported

Median, IQR

Median, IQR

Cry duration (% of total duration of intervention) significantly reduced in 2 mL of 50% (1.0 g) sucrose group (71.5%) compared to control group (93.5%, P = 0.002)

Median increase in HR (bpm) after heel lance were significantly reduced in the 2 mL of 50% (1.0 g) of sucrose group (35 bpm) compared to water (51 bpm), P = 0.005

No significant differences between groups with respect to measures for TcpO2 (P = 0.05) and TcpCO2 (P = 0.21)

Codipietro 2008

101 term infants, 39.3 to 39.4 weeks GA

Heel lance

Breastfeeding prior to heel lance (N = 51)

1 mL 25% sucrose via syringe (N = 50)

Duration of first cry, % crying time in first 2 min, and % crying time during blood sampling

HR increase from baselines at 30 s following commencement of procedure

SpO2 decrease

PIPP during blood sampling, 2 min after heel lance

Median, range

Median duration of first cry: breastfeeding group (3 (0 to 12)) compared to sucrose (21 (0 to 120)), P = 0.004

% crying during first 2 min: breastfeeding group (4 (0 to 100) compared to sucrose (45 (0 to 100) (P < 0.001)

% crying during sampling: breastfeeding group (8 (0 to 100) compared to sucrose (56.5 (0 to 100) (P = 0.0003)

Median increase in HR from baseline to 30 s after start of heel lance was significantly lower in breastfeeding group (13 (‐12 to 54)) compared to sucrose group (22 (‐32 to 65)) (P = 0.005)

Median decrease in SpO2 from baseline to 30 s after start of heel lance was significantly greater in sucrose group (‐3 (‐30 to 1)) compared to breastfeeding group (‐1 (‐14 to 2)) (P= 0.001)

Median PIPP scores significantly lower in breastfeeding group (3.0) compared to sucrose group (8.5) (P < 0.0001)

Gibbins 2002

190 preterm and term infants, mean GA of 33.7 weeks, < 7 days postnatal age

Heel lance

0.5 mL of 24% sucrose via syringe to the anterior surface of the tongue followed by pacifier (N = 64)
0.5 mL 24% sucrose without pacifier (N = 62)
0.5 mL sterile water with pacifier (N = 64)
2 min prior to heel lance

PIPP scores at 30 and 60 s after heel lance

Reported means, SD

Statistically significant difference in mean PIPP scores at both 30 s (F = 8.23, P < 0.001) and 60 s (F = 8.49, P < 0.001) after heel lance in favour of 0.5 mL of 24% (0.12 g) sucrose group and 0.5 mL of 24% (0.12 g) sucrose with pacifier group. Post‐hoc Tukey tests showed infants who received sucrose and pacifier had significantly lower PIPP scores after heel lance at 30 s (mean 8.16, SD 3.24) compared to infants receiving sucrose alone (mean 9.77, SD 3.04, P = 0.007) and water with pacifier (mean 10.19, SD 2.67, P < 0.001). At 60 s after heel lance, PIPP scores were significantly lower for 0.5 mL of 24% (0.12 g) sucrose with pacifier group (mean 8.78, SD 4.03) compared to the 0.5 mL of 24% (0.12 g) sucrose alone group (mean 11.20, SD 3.25, P = 0.005) and water with pacifier group (mean 11.20, SD 3.47, P = 0.007). No significant differences in PIPP scores found between 0.5 mL of 24% (0.12 g) sucrose alone group or water with pacifier group at both follow‐up times

Gormally 2001

94 term newborns, mean GA 39.4 weeks on 2nd or 3rd day of life

Heel lance

No holding and sterile water given by pipette (N = 21)

No holding and 0.250 mL of 24% sucrose solution given by pipette (N = 22)

Holding and sterile water given by pipette (N = 20)

Holding and 0.250 mL of 24% sucrose solution by pipette (N = 22)

All solutions given 3 times at 30‐s intervals

% time crying 1, 2, 3 min after heel lance

Mean HR before intervention, 1, 2, 3 min after heel lance, mean vagal tone index before intervention, 1, 2, 3 min after heel lance

Pain concatenation scores for facial activity before intervention, 1, 2, 3 min after heel lance

Not reported

Crying decreased over time (F(2,80) = 10.0, P < 0.001) but no significant interaction noted for time with holding, taste or holding and taste. Effect of taste on crying was significant (F(1,81) = 4.1, P < 0.05) in favour of 0.25 mL of 24% (0.18 g) sucrose. Effect of holding not statistically significant (F(1,81) = 3.0, P = 0.09)). No statistically significant interaction between taste and holding to reduce crying (F(1,81) = 0.80, P = 0.37). Effect of combined interventions was additive

Although no significant differences in mean HR due to holding or sucrose as main effects, there was significant interaction between holding and taste (F(1,61) = 8.89, P < 0.004), indicating synergistic effect that was also dependent on pre‐intervention HR (F(1,61) = 9.23, P < 0.004). No significant main effects noted for vagal tone; as with HR, effect of vagal tone was dependent on pre‐intervention vagal tone for both holding and taste interventions (F(1,60) = 4.82, P < 0.03). Pre‐intervention levels interacted to decrease HR and vagal tone in infants who had higher rates before interventions

Pain concatenation scores measuring facial expressions of pain decreased over time (F(1,65) = 28.5, P < 0.001). Only the effect of holding reduced pain scores (F(1,65) = 5.6, P <0.02). No difference as to whether infant received sucrose (taste main effect F(1,65) 0.17, P = 0.68

Greenberg 2002

84 term newborns, approximately 17 to 19 h old

Heel lance

Sugar‐coated pacifier (N = 21)

water‐moistened pacifier (N = 21)

2 mL of 12% sucrose (n =21)

routine care (N = 21)

Duration of cry from procedure phase to 3 min post‐procedure

Vagal tone and vagal tone index

Salivary cortisol levels

Not reported

Significant decrease in duration of cry for the sugar‐coated pacifier group compared to the control group (P = 0.001) and the water‐moistened pacifier group (P = 0.001).

Lower vagal tone during heel lance in the sugar‐coated pacifier group compared to the control group (P = 0.008) and oral sucrose group (P = 0.018). Lower vagal tone index in the sugar‐coated pacifier group compared to control group at heel lance (P = 0.019), and 6 to 10 min after (P = 0.007) and 11 to 15 min (P = 0.049) after heel lance

No significant differences were found in salivary cortisol levels across groups (no P value reported).

Guala 2001

140 term, 38 to 41 weeks' GA

Heel lance

Nothing (N = 20) Water (N = 20) 5% Glucose (N = 20) 33% Glucose (N = 20 50% Glucose (N = 20) 33% Sucrose (N = 20) 50% Sucrose (N = 20)

HR before, during and 3 min after heel lance

Mean, SD

No significant differences were found between groups for differences in HR at each of the 3 phases of the heel lance (P value reported for 3 min after heel lance, P = 0.087; the difference between 3 min after heel lance and during heel lance, P = 0.068)

Haouari 1995

60 term infants, 37 to 42 weeks' gestation, 1 to 6 days of age

Heel lance

2 mL of 12.5% sucrose 2 min prior to heel lance (N = 15)

2 mL of 25% sucrose 2 min prior to heel lance (N = 15)

2 mL of 50 % sucrose 2 min prior to heel lance (N = 15)

2 mL of sterile water 2 min prior to heel lance (N = 15)

All solutions were given by syringe on the tongue over < 1 min

Total time crying over 3 min. Time of first cry after lance

% change in HR at 1, 3, 5 min after heel lance

Median, IQR

Reported Means and SEM

After heel lance, significant decreases in total crying time and duration of first cry in 2 mL of 50% (1.0 g) sucrose group compared with water (P = 0.02). Significant reduction in median time crying at end of first minute (P < 0.02) in 2 mL of 50% (1.0 g) sucrose group (35 s; range 14 to 60) compared with water (60 s; range 50 to 60). In second minute, duration of cry was significantly less in 2 mL of 50% (1.0 g) sucrose group (0 s; range 0 to 25) and in 2 mL of 25% (0.5 g) sucrose group (18 s; range 0 to 55) compared to water (60 s; range 40 to 60), P = 0.003 and P = 0.02, respectively

Significant decrease in % change in HR 3 min after heel lancing (P = 0.02) in the 2 mL of 50% (1.0 g) sucrose group (mean 0.1%, SEM 3.3) compared to water group (mean 17.5%, SEM 6.0)

Harrison 2003

99 sick hospitalised infants, mean (SD) gestation age 36.7 weeks (3.3) (treatment), 36.8 weeks (3.7) (control) (author provided data on a subset of infants from a larger study (N = 128) that fulfilled our inclusion criteria)

Heel lance

1 mL of water (N = 46)

1 mL of 25% sucrose (N = 53)

For infants weighing ≤ 1500 g the dose was reduced to 0.5 mL

Duration of cry until 5 second pause, incidence and duration of crying time during the heel lance and squeeze and during the 3‐minute recovery period

HR at baseline, heel lance, during heel lance and 1, 2, 3 min post heel lance

SpO2 at baseline, heel lance, during heel lance and 1, 2, 3 min post heel lance

4‐point subset of the NFCS (brow bulge, eye squeeze, nasolabial furrow, stretch mouth) at heel lance, during heel lance and 1, 2, 3 min post heel lance

Mean, SD (collected from authors)

Mean length of first cry was higher in the water group (70.5 (83.6)) compared to the sucrose group (46.8 (63.1)). The sucrose group cried 57.1% of the procedure time compared to 58.8% in the water group. The mean total duration of cry during the heel lance was 84.7 s (68.8) in the sucrose group and 87.4 s (87.1) in the water group.

The mean (SD) HR upon heel lance was 163.0 (17.9) bpm in the sucrose group and 159.5 (19.2) bpm in the water group. HR at 30 s from the beginning of the procedure was 175.4 (22.2) and 172.8 (23.6) bpm in the sucrose and water groups, respectively. The HR in both groups decreased after the procedure to 152.1 (22.5) bpm in the sucrose group and 154.2 (29.1) bpm in the water group 2 min post heel lance

Results of SpO2 were similar between the 2 groups

Mean facial scores were significantly reduced at heel lance (2.74 (1.8)) in the sucrose group compared to the water group (2.94 (1.6)) (P = 0.02) and at 1 min (P = 0.04) and 2 min (P = 0.046) post‐heel lance. No significant differences occurred at 3 min post heel lance

Isik 2000a

113 healthy term newborns GAs 37 to 42 weeks, median post natal age 2 days, range 2 to 5 days

Heel lance

2 mL of 30% sucrose (N = 28)

2 mL of 10% glucose (N = 29)

2 mL of 30% glucose (N = 28)

2 mL of distilled water (N = 28)

syringed into the anterior third of the tongue for 1 and 2 min prior to heel lance

Mean cry time during 3 min after lance

Mean maximum HR 3 min from heel lance

Mean recovery time for HR

% change in HR at 1, 2, 3 min after heel lance

Reported means, SD

Reported means and SEM

Infants who received 2 mL of 30% (0.6 g) sucrose (mean crying time of 61 s) cried significantly less than those who received 30% glucose (mean crying time of 95 s), 10% glucose (mean crying time of 103 s) or sterile water (mean crying time of 105 s)(P = 0.02)

No significant difference between groups with respect to maximum HR after heel lance (P = 0.71), or mean recovery time (P = 0.09). No significant difference found in % change in HR at 1 or 3 min after heel lance (P = 0.14, P = 0.53, respectively). At 2 min after heel lance, % change in HR favoured group receiving sucrose (P = 0.05) compared to other groups

Johnston 1997a

85 preterm infants, 25 ‐ 34 weeks' GA, 2 to 10 days of age

Heel lance

0.05 mL of 24% sucrose via syringe into the mouth just prior to heel lance (N = 27)
0.05 mL of 24% sucrose via syringe into the mouth just prior to heel lance and simulated rocking 15 min prior to heel lance (N = 14)
0.05 mL of sterile water via syringe into the mouth just prior to heel lance and simulated rocking 15 min prior to heel lance (N = 24)
0.05 mL of sterile water via syringe into the mouth just prior to heel lance

HR at baseline and 3 x 30‐second blocks

Behavioural facial actions (NFCS) at baseline and 3 x 30‐second blocks

Not reported

Although HR increased across all phases of procedure (F(3,59) = 2.94, P < 0.04), there was no significant differences noted between groups (F(3,59) = 0.682, P = 0.566)

Decrease in % facial action in 0.05 mL of 24% (0.012 g) sucrose alone group and combined 0.05 mL of 24% (0.012 g) sucrose and rocking group compared to water group (F(6, 150) = 2.765, P < 0.02)

Johnston 1999a

48 preterm neonates mean GA of 31 weeks, range 25 to 34 weeks, within 10 days of birth

Heel lance

0.05 mL of 24% sucrose as a single dose, followed by 2 doses of sterile water (N = 15)
3 doses of 0.05 mL of 24% sucrose (N = 17)
3 doses of 0.05 mL of sterile water (N = 16)
given by syringe to anterior surface of the tongue at:
2 min prior to heel lance,
just prior to lancing and
2 min after lancing

PIPP scores in 5 x 30 second blocks

Reported means, SD

Statistically significant difference between groups (F = 9.143, P < 0.0001) for mean PIPP scores. Post‐hoc analysis found significantly lower PIPP scores with repeated doses of 0.05 mL of 24% (0.012 g) sucrose compared to placebo groups across all blocks of time, P < 0.05. PIPP scores for repeated doses of 0.05 mL of 24% (0.012 g) sucrose were significantly lower compared to single doses of 0.05 mL of 24% (0.012 g) sucrose (8.25 vs. 6.25) only at last block of time, P < 0.05. PIPP scores for single doses of 0.05 mL of 24% (0.012 g) sucrose compared to placebo showed trend towards statistical significance in favour of 0.05 mL of 24% (0.012 g) sucrose (F = 3.465, P = 0.07)

Mathai 2006

104 term neonates, postnatal age > 24 h,

sucrose group mean postnatal age 48 h,

distilled water groups mean postnatal age 44 h

Heel lance

 

2 mL 20% sucrose instilled into mouth via a dropper (N = 17)

2 mL distilled water instilled into mouth via a dropper (N = 15)

Rocking (N = 17)

Massage (N = 17)

Expressed breast milk (N = 18)

NNS (N = 18)

Time of first cry in seconds, total cry in seconds

HR before heel lance, 2 min after heel lance and 4 min after heel lance

SpO2 before heel lance, 2 min after heel lance and 4 min after heel lance

DAN scale before the heel lance and 30 s, 1 min, 2 min, 4 min after heel lance

Reported means, SD

Not reported

Mean, SD

No significant difference between sucrose group and any other group for time of first cry

NNS and rocking significantly reduced total duration of cry, P < 0.05

No significant difference in HR between the groups at any time point

No significant difference in SpO2 between the groups at any time point

Significantly reduced DAN scores at 30 s after the heel lance for the sucrose group (mean 7.6, SD 14, P < 0.05);  however, this was not sustained at 1, 2 and 4 min 

NNS and rocking significantly decreased the DAN scores at 2 and 4 min post heel lance, P < 0.05

Okan 2007

31 healthy preterm newborns, mean GA 30.5 weeks, mean postmenstrual age 32.3 weeks

Heel lance

2 mL of 20% sucrose

2 mL of 20% glucose

2 mL of water

Infants received all 3 interventions at different times

Duration of first cry and total crying time

HR at baseline, during heel lance and 1, 2, 3, 4 and 5 min post heel lance

SpO2 and respiratory rate at baseline, during heel lance and 1, 2, 3, 4 and 5 min after heel lance

NFCS scores during heel lance and 1, 2, 3, 4 and 5 min post heel lance

Mean, SD

Significantly increased duration of first cry and total crying time in the water group compared to the sucrose and glucose groups (P = 0.005 and P = 0.007, respectively). No significant differences in cry characteristics were observed between the sucrose and glucose groups

Significantly higher HR in the water group (mean 175, SD 20.8) compared to the sucrose (mean 166, SD 17.6) and glucose groups (mean 165, SD 17.5) at 1 min following heel lance (P = 0.007). No significant differences between the sucrose and glucose groups

Significantly higher NFCS score in the placebo group in the 4th minute following heel lance (mean 1.3, SD 2.0) and 5th minute following heel lance (mean 1.0, SD 1.0) compared to the sucrose (mean 0.5, SD 1.7; mean 0.3, SD 1.3, respectively) and glucose groups (mean 0.2, SD 0.5; mean 0.1, SD 0.3, respectively) (P = 0.009 at 4th minute and P = 0.049 at 5th minute. There were no significant differences between the sucrose and glucose groups

Ors 1999

102 healthy term infants, GA 37 to 42 weeks, median postnatal age 1.6 days, range 1 to 15 days

Heel lance

2 mL of 25% sucrose (N = 35)

2 mL of human milk (N = 33)

2 mL of sterile water (N = 34)

All solutions syringed onto anterior part of tongue for 1 min

Heel prick performed 2 min after intervention

Median cry time during 3 min after lance

% change HR 1, 2 and 3 min after heel lance

Median, IQR

Significant decrease in crying times for 2 mL of 25% (0.5 g) sucrose group (median 36, IQR 18 to 43) compared to human milk (median 62, IQR 29 to 107) and sterile water [(median 52, IQR 32 to 158) (P = 0.0009). Recovery time for crying was significantly reduced in 2 mL of 25% (0.5 g) sucrose group (median 72, IQR 48 to 116) compared to human milk (median 112, IQR 72 to 180) and sterile water (median 124, IQR 82 to 180) (P = 0.004)

% change in HR after heel lance was significantly lower in the group receiving 2 mL of 25% (0.5 g) sucrose compared to groups receiving human milk and sterile water at 1, 2 and 3 min (P = 0.008, P = 0.01, P = 0.002, respectively)

Overgaard 1999

100 newborn term infants, mean age 6 days, range 4 to 9

Heel lance

2 mL of 50% sucrose solution via syringe into the mouth over 30 s 2 min prior to heel lance

2 mL of sterile water via syringe into the mouth over 30 s 2 min prior to heel lance

Median crying time during heel lance, fraction of crying during sampling, crying time during first minute after end of sampling, total crying time

Change HR 0 and 1 min

SpO2 at 0 and 1 min

NIPS scores 1 min after heel lance and 1 min after blood sampling

Median, 5th and 95th percentiles

Median duration of first cry in group receiving 2 mL of 50% (1 g) sucrose was significantly lower (18 s (2 to 75)) compared to placebo group (22 s (11 to 143)) (P = 0.03). Median crying time during heel lance in the sucrose group was lower (26 s (2 to 183)) compared to placebo group (40 s (12 to 157)) (P = 0.07). Median fraction of crying during sampling in 2 mL of 50% (1 g) sucrose group was significantly lower (43% (4 to 100)) compared to placebo group (83% (20 to 100)) (P = 0.004). Median crying time during first minute after end of sampling in 2 mL of 50% (1 g) sucrose group was significantly lower (3 s (0 ‐ 58)) compared to placebo group (16 s (0 to 59)) (P = 0.004). Median total time crying in 2 mL of 50% (1 g) sucrose group was significantly lower (30 s (2 to 217)) compared to placebo group (71 s (13 to 176)) (P = 0.007)

No significant in HR differences between groups (P = 0.05)

No significant differences between groups with respect to changes in SpO2 (P = 0.8)

Median NIPS scores 1 min after heel lance were lower in 2 mL of 50% (1.0 g) sucrose group compared to placebo group (3 (0 to 7) and 6 (0 to 7), respectively; P = 0.04). Median NIPS scores 1 min after end of blood sampling were lower in 2 mL of 50% (1.0 g) sucrose group (0 (0 to 7)) compared to placebo group (2 (0 to 7)) (P = 0.05)

Ozdogan 2010

142 healthy term newborns

Heel lance

6 groups

Single‐dose breast milk

Single‐dose sterile water

Single‐dose 12.5% sucrose

2 doses breast milk

2 doses sterile water 2 doses 12.5% sucrose

Median crying time; NFCS

Medians

Significant difference between single‐dose sucrose vs. water (P = 0.002) in favour of sucrose. Double doses of sucrose were not superior to single doses; single doses or double doses of breast milk were not effective in reducing pain

No significant differences between groups on crying time

Ramenghi 1996a

15 preterm infants, 32 to 34 weeks' gestation, > 24 h of age

Heel lance

1 mL of 25% sucrose
1 mL of sterile water

Duration of first cry and % time crying 5 min after lance

HR (at ‐2, 0, 1, 3 and 5 min from heel lance)

Behavioural scores (4 facial expressions and the presence of crying) ‐2, ‐1 , 0, 1, 2, 3 and 5 min

Quality/intensity of sucking

Median, IQR

Not reported

Not reported

Significant decrease in total % of time crying over 5 min (median 6%, IQR 3.3 to 15.3) in the 1 mL of 25% (0.25 g) sucrose group compared with water group (median 16.6%, range 5 to 27.3) (P = 0.018). Duration of first cry was significantly decreased in the 1 mL of 25% (0.25 g) sucrose group (median 12 s, IQR 8 to 22) compared to control group (median 23 s, IQR 15 to 45) (P = 0.004)

No significant differences in HR between groups, P value not reported

Mean pain scores were significantly lower in the groups receiving 1 mL of 25% sucrose (0.25 g) of sucrose at both 1 and 3 min after heel lance (P = 0.01, P = 0.03, respectively)

The clinical interpretation of the quality of sucking was significantly more intense in the 1 mL of 25% (0.25 g) sucrose group than in the water group (P = 0.04)

Ramenghi 1996b

60 term infants, 37 to 42 weeks GA, 2‐ to 5‐day old

Heel lance

2 mL of 25% (0.5 g) sucrose

2 mL of 50% (1.0 g) sucrose

Calpol

Single‐dose sterile water

Duration of first cry after lance,

% time crying over 3 min after heel lance

% change in HR over 5 min (at ‐2, 0, 1, 3 and 5 min from heel lance)

Behavioural scores (4 facial expressions and the presence of crying) ‐2, ‐1, 0, 1, 2, 3 and 5 min

Median, IQR

Not reported

Median, IQR

Significant decrease in duration of first cry and % crying during 3 min after heel lance in the 2 mL of 25% (0.5 g) sucrose, 2 mL of 50% (1.0 g) sucrose and Calpol groups (P = 0.02) (data in graph form only)

Significant increase in HR for 3 min after heel lance in water group compared with 2 mL of 50% (1.0 g) sucrose group and Calpol group (P = 0.009)

Pain score (0 to 5) was significantly higher in water group (score = 2, range 1 to 5) than in other 3 groups: 2 mL of 50% (1 g) sucrose group (score = 0, range 0 to 3); 2 mL of 25% (0.5 g) sucrose group (score = 0, range 0 to 2); Calpol group (score = 0, range 0 to 1) (P = 0.05)

Ramenghi 1999

30 preterm infants, GA 32 to 36 weeks, postnatal age < 24 h

Heel lance

25% sucrose solution (volume not reported) was given via syringe into the mouth or via NG tube 2 min prior to first heel lance (N = 15), and via the alternate route for the second heel lance within 48 h

Sterile water via syringe into the mouth or via NG tube 2 min prior to first heel lance and for the second heel lance the alternate route within 48 h (cross‐over design, N = 30)

% cry over 5 min after sampling

Behavioural scores (4 facial expressions and the presence of cry) at 1, 3 and 5 min after the lance for a total behavioural score

Median, IQR

Median % cry in intraoral water group was 22% (IQR 10.6 to 40) and 27% (IQR 11.6 to 47) for infants in NG tube water group. Median % cry in intraoral 25% sucrose group was 6% (IQR 0.6 to 15) and 18.3% (IQR 11.6 to 41.6) for NG tube 25% sucrose group. Significant reduction in crying time (P = 0.006) noted in the 25% sucrose group compared with water group when infants received 25% sucrose intraorally, not via NG‐tube route. For infants in 25% sucrose group, significant reduction in crying time noted (P = 0.008) when solution given intraorally compared to NG tube route

Behavioural scores for the intraoral water group was 9 (IQR 6 to 12) and 10 (IQR 6 to 14) for NG tube water group. Behavioural scores for intraoral 25% sucrose group was 5 (IQR 3 to 6) and 9 (IQR 8 to 10) for NG tube sucrose group. Significant reduction in behavioural scores noted in 25% sucrose group (P = 0.002) compared with water group when infants received 25% sucrose intraorally but not via NG route. For infants in 25% sucrose group, there was significant reduction in behavioural score (P = 0.001) when solution was given intraorally compared to via NG tube

Rushforth 1993

52 term infants, 37 to 42 weeks, GA, 2 to 7 days of age

Heel lance

2 mL of 7.5% sucrose administered by a dropper into the mouth over a 1‐minute period prior to heel lance (N = 26)

2 mL of sterile water administered by dropper into the mouth over a 1‐minute period prior to heel lance (N = 26)

% cry over 3 min after sampling

Median only

No significant differences in median % time crying between group receiving 2 mL of 7.5% (0.15 g) sucrose (74.3%) compared to group receiving water (73.2%). No significant differences between groups in duration of cry after 1 min (P = 0.65), 2 min (P = 0.52) and 3 min (P = 0.72). No difference in time to cessation of crying (P = 0.16)

Slater 2010

44 term infants, 37 to 43 GA, < 8 days old

Heel lance

0.5 mL of 24% sucrose given via syringe (N = 20)

0.5 mL of sterile water (N = 24)

HR change, PIPP score, nociceptive‐specific brain activity, latency to change in facial expression (s), facial non‐responders, nociceptive reflex withdrawal activity

Mean, SD, mean weight

Only mean baseline HR given: 0.5 mL of 24% sucrose 132. 6 bpm (124.3 to 140.9); 0.5 mL of sterile water 131.8 (122.2 to 141.5) (P = 0.90)

Only mean baseline SpO2 given: 0.5 mL of 24% sucrose 99.4 (98.8 to 100.1); 0.5 mL of sterile water 97.4 (95.0 to 99.8) (P = 0.13)

PIPP score during insertion: baseline PIPP score: 0.5 mL of 24% sucrose 1.3 (0.8 to 1.7), 0.5 mL of sterile water 1.3 (0.8 to 1.8) (P = 0.13); PIPP during procedure: 0.5 mL of 24% sucrose 5.8 (3.7 to 7.8), 0.5 mL of sterile water 8.5 (7.3 to 9.8) (P = 0.02)

No significant differences in nociceptive‐specific brain activity (P = 0.46) latency to change in facial expression (P = 0.86), mean nociceptive reflex withdrawal activity (P = 0,49) or mean latency to nociceptive reflex withdrawal activity (P = 0.56); significant difference in facial non‐responder (P < 0.0001).

Stevens 1999

122 neonates, 27 to 31 weeks' GA, < 28 days of age

Heel lance

Prone positioning 30 min prior to heel lance

Pacifier dipped in sterile water and placed into the mouth 2 min prior to heel lance

Pacifier dipped in 24% sucrose and placed into the mouth 2 min prior to heel lance

Control: Containment in SnuggleUp device (N = 122)

NB: all infants were contained in SnuggleUp device

PIPP scores at 30 and 60 s

Reported means, SD

Main effect of treatment for mean PIPP scores (F(16.20), P < 0.0001). Post‐hoc analysis revealed significant reduction in PIPP scores 30 s after heel lance in sucrose group (pacifier dipped in 24% sucrose ‐ estimated at 0.02 g), (mean 7.87, SD 3.35), compared to control group (mean 9.80, SD 3.55) (F(24.09), P < 0.0001). Statistically significant reduction in PIPP scores in pacifier and water group (mean 8.44, SD 3.55) compared to control group (mean 9.80, SD 3.55) (F(9.00), P = 0.003). Trend towards lower PIPP scores with sucrose and pacifier group compared to water and pacifier group (F(3.62), P < 0.05)

Stevens 2005

66 preterm infants, 26 to 30 weeks, postnatal age 72 h

Heel lance

Standard care‐positioning and swaddling (N = 21)

Standard care‐positioning and swaddling  and 0.1 mL sterile water via syringe into the mouth immediately followed by a pacifier 2 min prior to painful procedure (N = 23)

Standard care‐positioning and swaddling  and 0.1 mL 24% sucrose via syringe into the mouth immediately followed by a pacifier 2 min prior to painful procedure (N = 22)

These interventions were given every time there was a painful procedure during the first 28 days of life

PIPP at day 7, 14, 21 and 28 at routine heel lance

Not reported

Significant main effect of group (P = 0.03) with differences occurring between the sucrose + pacifier group and standard care group (t(60) = ‐2.54; P = 0.01). Mean PIPP scores were generally higher in the standard care group

No significant main effect of time

Adverse effects: no group differences for adverse events, clinical outcomes or neurobiological risk status

Storm 2002

48 preterm, median GA of 32 weeks, median postnatal age of 14 days

Heel lance

2 mL of 15% sucrose, N = 12
1 mL of 25% sucrose, N =12
Milk via NG tube N = 12
Milk via NG tube + 25% sucrose, N = 12
All infants were given water prior to a second heel lance

Differences in crying time for pre‐heel lance to heel lance procedure

Changes in HR from pre‐heel lance to heel lance procedure

Difference in skin conductance from pre‐heel lance to heel lance procedure

Not reported

Significantly less crying in infants receiving 1 mL of 25% sucrose (P < 0.05) and food (milk) + 1 mL of 25% sucrose (P < 0.05)

No significant differences between groups in changes in HR from pre‐heel lance to heel lance procedure (P value not reported)

No statistically significant smaller increase in skin conductance variables compared to their water control session (P value not reported)

Unceta‐Barranechea 2008

150 term infants

Heel lance

Facilitated tucking

NNS + water

NNS + 2 mL 24% sucrose

Mean crying time between groups

Modified NFCS

Mean, SD

Statistically significant differences in crying time between control group and 2 intervention groups (P < 0.001). No significant difference between sucking with placebo and sucking with sucrose groups (P = 0.735).

Statistically significant differences in pain score between control group and 2 intervention groups (P < 0.001). No significant difference between sucking with placebo and sucking with sucrose groups (P = 0.105)

Yilmaz 2011

120 infants GA 37 to 42 weeks

Control group (N = 30): mean GA (SD) = 39.67 (0.80)

Mother’s milk group (N = 30): mean GA (SD) = 39.10 (1.03)

Sucrose group (N = 30): mean GA (SD) =39.10 (0.71)

Pacifier group (N = 30): mean GA (SD) = 39.20 (0.93)

Heel lance

Control group: newborns were in their mothers’ lap; no interventions were made before the painful procedure

Mother's milk group: 2 mL mother’s milk 2 min before the procedure by using a syringe with the needle removed and avoiding contact of the syringe with the mouth and lips

Sucrose group: 2 mL sucrose of 20% by using a syringe 2 min before the procedure

Pacifier group: given a pacifier

NIPS score, HR, respiratory rate, crying time

Mean, SD

No differences in HR and O2 saturation between groups

After the procedure, the mean crying time of the sucrose group was shorter than those of the other groups. Comparing the crying times of the control and experimental groups according to the procedure time showed no statistically significant differences between the values for before and during the procedure (F = 1.50, P > 0.05); (F = 2.43, P > 0.05)

Before the procedure, the lowest NIPS mean was in the sucrose group and the highest NIPS mean was in the pacifier group. During the procedure, no statistically significant differences were found between the groups for NIPS means (P > 0.05). After the procedure, the sucrose group showed the lowest response to pain, while the mother's milk group had the highest response. Comparing the NIPS means of the control and experimental groups according to the procedure times, statistically significant differences were found between the groups for values obtained before and after the procedure (F = 3.49, P < 0.05); (F = 6.71, P < 0.05)

bpm: beats per minute; DAN: Douleur Aigue du Nouveau‐ne; GA: gestational age; HR: heart rate; IQR: interquartile range; NFCS: Neonatal Facial Coding System; NG: nasogastric; NIPS: Neonatal Infant Pain Scale; NNS: non‐nutritive sucking; PIPP: Premature Infant Pain Profile; RSF: Ross Special Formula; SD: standard deviation; SEM: standard error of the mean; SpO2: oxygen saturation; TcpO2: transcutaneous oxygen pressure.

Figuras y tablas -
Table 1. Trials assessing pain during heel lances
Table 2. Trials assessing pain during venipunctures

Study

Participants

Procedure

Interventions

Outcomes

Metrics used

Results

Abad 1996

28 preterm, 29 to 36 weeks' GA, infants, postnatal age 1 to 26 days

Venipuncture

2 mL of 12% sucrose via syringe (N = 8)

2 mL of 24% sucrose via syringe (N = 8)

2 mL of spring water via syringe (N = 12) 2 min prior to venipuncture

Time crying for 3 min after venipuncture

HR: pre solution, post solution, 5 min after venipuncture

Mean SpO2 and respiratory rate pre solution, post solution, 5 min after venipuncture

Median, IQR

Mean, SEM

Mean, SD

Significant group effect noted, (F(2, 25) = 4.26; P = 0.0256) for cry duration 3 min after venipuncture. Cry duration was significantly reduced in 2 mL of 24% (0.48 g) sucrose group (19.1 sec) compared to 2 mL of 12% (0.24 g) sucrose (63.1 sec) and water (72.9 sec) groups (P < 0.05)

Significant group effect for HR, F(2, 25) = 6.37, P = 0.006. Overall time effect, F(2, 50) = 14.15, P < 0.001. No significant interaction between treatment group and time. Post hoc Tukey test showed that group receiving 2 mL of 12% sucrose (0.24 g) had lower HR compared to the 2 mL of 24% sucrose group (0.48 g) or water group at all 3 time points (pre solution, P = 0.048; post solution, P = 0.010; 5 min after, P = 0.007)

No significant differences noted between groups over time for SpO2 and respiratory rates (no P values reported)

Acharya 2004

39 preterm neonates, mean 30.5 weeks' GA, mean postnatal age 27.2 days

Venipuncture

2 mL of 25% (0.5 g) sucrose administered by syringe into front of infant's mouth over 2 min, 4 min prior to venipuncture

Duration of first cry (beginning to end of first cry); total duration of crying (onset of first cry to cessation of all crying)

Mean change in HR from pre‐procedure, procedure and post‐procedure phase of venipuncture

Mean SpO2 (%) at pre‐procedure, procedure and post‐procedure

NFCS changes across 3 phases of venipuncture

Mean (SD)

Mean duration of first cry lower in infants who received sucrose (18.6 s (24.4)) compared to infants who received water (52.3 s (56)) (estimated treatment effect = 33.7, P < 0.001). Mean total duration of crying was significantly lower in infants who received sucrose (31.9 s (41.9)) compared to infants who received water (72.5 s (66.7)) (estimated treatment effect = 40.6, P < 0.001)

Mean change in HR from pre‐procedure to procedure was lower in the infants receiving sucrose compared to water (estimated treatment effect = 7.5, P = 0.003). Mean change in HR from pre‐procedure to post‐procedure was lower in the infants who received sucrose compared to water (estimated treatment effect = 4.16, P = 0.036)

No significant differences between groups with respect to changes in SpO2 from pre‐procedure to procedure phase (P = 0.17)

Changes in mean NFCS scores were significantly lower in the sucrose group compared to water group from pre‐procedure to procedure phase (estimated treatment effect = 1.08, P = 0.013) and between the pre‐procedure and post‐procedure phase (estimated treatment effect = 2.39, P < 0.001)

Alsaedi 2009

36 preterm infants, median (range): GA 32 (27 to 46), mean (SD) GA 32.4 (2.0) ‐ 2 different mean GA reported in the article

Venipuncture

Babies randomly allocated to 6 different regimens (0.5 mL sterile water with pacifier, 0.5 mL sterile water without pacifier, 0.5 mL sucrose 24% with pacifier, 0.5 mL sucrose 24% without pacifier, pacifier alone and control group) during a stay in intensive care of up to 15 days

HR, SpO2, PIPP, respiratory rate, blood pressure, glucose check

Range, mean

PIPP score: significantly different between treatment groups P = 0.0005, over time P < 0.0005

24% sucrose + pacifier resulted in lowest pain scores  (P < 0.05)

No difference in respiratory rate (P = 0.193), no difference in blood pressure (P = 0.246); no difference in glucose check (P = 0.227)

Basnet 2010

50 term infants between 12 h to 8 days of life; 59.92 h of life non‐sucrose, 68.76 h of life sucrose group

Venipuncture

No treatment (N = 25)

Treatment group: did not report method of administration (i.e. pacifier/syringe; N = 25)

Duration of cry, DAN scale

Percentage for duration of cry, IQR for DAN scale

13 (52%) infants in sucrose group did not cry compared to 4 (16%) in no treatment group, P = 0.001, mean duration of cry was not significant between groups (P = 0.65)

HR increased during procedure (P = 0.008) followed by decrease post procedure (P = 0.001) in control group; no significant changes in sucrose group (P = 0.39). Decrease in SpO2 in control group (P = 0.001) during procedure; no significant changes in sucrose group (P = 0.03)

Significantly lower DAN scores in the 30% sucrose group (score of 3 (1.5 to 5.5) compared to the control group (score of 7 (5 to 9.5) (P = 0.0001)

Biran 2011

76 preterm infants, mean GA (S group): 32.6 (2.33) weeks, mean GA (S + E group): 32.3 (2.01) weeks

Venipuncture

S group: 0.5 mL of 30% sucrose solution orally and placebo cream (N = 37)

S + E group: 30% sucrose solution orally + EMLA on the skin (N = 39)

DAN scale, PIPP

Median, IQR

Mean (SD) DAN pain scores for the S group and the SE group were 7.7 (2.1) and 6.4 (2.5), respectively, during venipuncture and 7.1 (2.8) and 5.7 (3.3) during the post‐injection period.

Significant time effect (P = 0.047) and treatment effect (P = 0.018) effect in favour of S + EMLA group; no significant differences using PIPP

Carbajal 1999

150 term newborn infants, 3 or 4 days old

Venipuncture

No treatment (N = 25)

2 mL of sterile water via syringe over 30 s (N = 25)

2 mL of 30% glucose via syringe (N = 25)

2 mL of 30% sucrose (N = 25)

Pacifier alone (N = 25) 2 min prior to venipuncture

2 mL of 30% sucrose via syringe followed by sucking a pacifier (N = 25)

DAN scale

Median, IQR

Median pain scores with IQRs during venipuncture were: no treatment 7 (5 to 10); sterile water group 7 (6 to 10); 30% glucose group 5 (3 to 7); 2 mL of 30% sucrose (0.6 g) group 5 (2 to 8); pacifier alone group 2 (1 to 4); 2 mL of 30% (0.6 g) sucrose with pacifier group 1 (1 to 2). All groups had significantly lower pain scores compared to sterile water group: 30% glucose (P = 0.005), 2 mL of 30% (0.6 g) sucrose (P = 0.01), pacifier (P < 0.0001), 2 mL of 30% (0.6 g) sucrose with pacifier (P < 0.0001). Pacifier alone group had significantly lower pain scores than infants receiving 30% glucose (P = 0.0001) or 2 mL of 30% (0.6 g) sucrose (P = 0.001). Trend towards lower pain scores for infants receiving 2 mL of 30% (0.16 g) sucrose with pacifier compared to pacifier alone (P < 0.06)

Gaspardo 2008

33 preterm infants. Median (range) GA of intervention group  30 (25 to 33). Median (range) GA of control  group  31 (27 to 33)

Pain assessed at venipuncture phases (baseline, antisepsis, puncture, dressing, recovery). Sucrose administered before every minor painful procedure (venipuncture, arterial puncture, heel‐lance, intravenous cannulation, endotracheal tube introduction, endotracheal tube suctioning, gavage insertion for feeding, removal of electrode leads and tape)

0.5 mL/kg of sterile water 2 min prior to procedure

0.5 mL/kg  25% sucrose 2 min prior to procedure

Volume of solution was adjusted for current body weight

Incidence of cry

HR

NFCS score

ABS score

Percentage

Percentage with rate > 160 bpm

Percentage attaining score ≥ 3

Percentage attaining score ≥ 4

Cry on the second day there was a significant difference between the sucrose and control groups in the antisepsis phase (P = 0.04) and puncture phases (P = 0.009) in favour of the sucrose group. On day 3, there was a significant difference between groups in the dressing phase (P = 0.04) in favour of the sucrose group. On day 4, significant differences existed between groups at the puncture phase (P = 0.03) in favour of the sucrose group

No significant differences in HR were observed

NFCS: significant difference was seen between sucrose and control groups on day 2 at the puncture phase (P = 0.05) favouring the sucrose group. Significant difference was also observed on day 3 at the antisepsis phase (P = 0.02) in favour of the sucrose group. No significant differences were observed on day 4, but a trend favouring the sucrose group was noted in the  puncture (P = 0.08) and dressing (P = 0.09) phases

ABS: significant difference between sucrose and control groups on day 2 at the puncture phase (P = 0.05) favouring the sucrose group. Significant difference observed on day 3 at the antisepsis phase (P = 0.02) in favour of sucrose group. At the dressing phase, the trend favoured the sucrose groups, but this result was not significant (P = 0.09). No significant differences were observed on day 4, but a trend favouring the sucrose group was noted in the  puncture (P = 0.08) and dressing (P = 0.09) phases

Montoya 2009

111 neonates (55 in treatment group and 56 in control group)

Venipuncture

5 min before venipuncture: 1 mL of 12% sucrose (treatment group) or distilled water (control group)

Overall NIPS score

Means

NIPS scores significantly lower for infants who received sucrose (2.9 (SD 2.3)) versus water (3.8 (SD 2.6)) (t = ‐2.063, P = 0.041)

Taddio 2011

330 infants, mean GA (SD) 39.5 (1.2),

liposomal lidocaine group (N = 110), mean GA (SD) 39.6 (1),

sucrose group (N = 110), mean GA (SD) 39.6 (1.3),

sucrose liposomal lidocaine group (N = 110), mean GA (SD) 39.6 (1.3)

Venipuncture

Liposomal lidocaine group: 1 g of liposomal lidocaine 4% cream to the dorsum of the hand, occluded by a dressing (Tegaderm) for 30 to 40 min

Sucrose group: 2 mL of 24% sucrose solution, administered by mouth using a syringe over 1 to 2 min

Sucrose liposomal lidocaine group: both sucrose and liposomal lidocaine

Placebos were used for liposomal lidocaine and sucrose (i.e. double‐dummy design), so that all infants received a topically administered cream (liposomal lidocaine or placebo cream) and oral solution (sucrose or placebo water)

Non‐randomised group of healthy neonates undergoing venipuncture were administered water

Facial grimacing, cry duration (seconds), Observer‐rated pain using a VAS (0 to 10 cm), HR(bpm), SpO2 (%)

Mean, 95% CI

The mean facial grimacing score differed among the randomised groups (P < 0.001). Post‐hoc analyses demonstrated a significantly lower score for the sucrose group compared with liposomal lidocaine (mean difference 27; 95% CI ‐36 to ‐19; P < 0.001) and for the sucrose plus liposomal lidocaine group compared with the liposomal lidocaine group (mean difference 23; 95% CI 31 to 14; P < 0.001). No evidence of different between the sucrose and sucrose plus liposomal lidocaine groups

Cry duration differed among groups (P < 0.001). Infants in the sucrose and sucrose plus liposomal lidocaine groups cried less than infants in the liposomal lidocaine group (mean difference: 38 s; 95% CI ‐52 to ‐25; P < 0.001; and mean difference: 39 s; 95% CI ‐ 52 to ‐ 25; P < 0.001, respectively). There was no evidence of a difference in cry duration between the sucrose and sucrose plus liposomal lidocaine group (mean difference: 0 s; 95% CI ‐13 to ‐14; P = 0.95)

No difference in VAS, HR or SpO2

When compared with the non‐randomised placebo‐control group, the liposomal lidocaine group had significantly lower facial grimacing (mean difference 17; 95% CI ‐27 to ‐7; P < 0.001) and VAS scores (1.7 cm; 95% CI 2.5 to 0.9; P < 0.001). HR, SpO2 and procedure duration were significantly higher in the liposomal lidocaine group compared to the control group. Cry duration and procedure success rate did not different beyond chance.

No significant adverse events reported

ABS: Activated Behavioural State; bpm: beats per min; CI: confidence interval; DAN: Douleur Aigue du Nouveau‐ne; EMLA: eutectic mixture of local anaesthetics; GA: gestational age; HR: heart rate; IQR: interquartile range; NFCS: Neonatal Facial Coding System; NIPS: Neonatal Infant Pain Scale; PIPP: Premature Infant Pain Profile; SD: standard deviation; SEM: standard error of the mean; SpO2: oxygen saturation; VAS: visual analogue scale.

Figuras y tablas -
Table 2. Trials assessing pain during venipunctures
Table 3. Trials assessing pain during heel lances and venipunctures

Study

Participants

Procedure

Interventions

Outcomes

Metrics used

Results

Ogawa 2005

100 healthy full‐term infants

Heel lance group GA 40 weeks (range 38‐42 weeks)

Heel lance + sucrose group GA 39 weeks (range 37 to 41 weeks)

Venipuncture group GA 39 weeks (range 37 to 41 weeks)

Venipuncture + sucrose group GA 39 weeks (range 37 to 41 weeks)

 

Heel lance or venipuncture

Heel lance + 0.1 mL of sterile water on infant's tongue via syringe 2 min before procedure (N = 25)

Heel lance + 0.1 mL of 50% sucrose on infant's tongue via syringe 2 min before procedure (N = 25)

Venipuncture + 0.1 mL of sterile water on infant's tongue via syringe 2 min before procedure (N = 25)

Venipuncture + 0.1 mL of 50% sucrose on infant's tongue via syringe 2 min before procedure (N = 25)

Duration of first cry (sec), first crying time/total procedure time (%) and the ration of crying: no crying

NFCS score 1 min after oral administration of water/sucrose (1), disinfection of skin before heel lance or venipuncture (2), during skin puncture (3), during blood sampling (4), during compression to stop bleeding (5), during application of plaster (6) and 1 min after application of plaster (7)

Reported medians, range and mean, SD

Reported in graph form, median and IQR

Significant reduction in duration of first cry in heel lance group given sucrose compared to heel lance alone (P < 0.05)

Significantly reduced NFCS scores in sucrose group during heel lance (median 47, IQR 31 to 60) and during compression to stop bleeding (median 32, IQR 8 to 54) compared to the water group (median 58, IQR 54 to 65, median 52, IQR 41 to 61, respectively) (P < 0.01)

Sucrose did not significantly reduce NFCS scores during or after venipuncture

GA: gestational age; IQR: interquartile range; NFCS: Neonatal Facial Coding System; SD: standard deviation.

Figuras y tablas -
Table 3. Trials assessing pain during heel lances and venipunctures
Table 4. Trials assessing pain during ROP examinations

Study

Participants

Procedure

Interventions

Outcomes

Metrics used

Results

Boyle 2006

40 preterm infants, median GA 29 weeks (24 to 34 weeks)

Sterile water group: median GA 27 weeks, median postnatal age 45 days

Sucrose group: median GA 29 weeks, median postnatal age 43 days

Water and pacifier group: median GA 30 weeks, median postnatal age 41 days

Sucrose and pacifier group: median GA 29 weeks, median postnatal age mean 42 days

Eye examination for ROP

1 mL sterile water via a syringe into the mouth (group 1; N = 10)

1 mL sucrose 33% via a syringe into the mouth (group 2; N = 10)

1 mL sterile water via a syringe into the mouth and pacifier (group 3; N = 9)

1 mL sucrose 33% via a syringe into the mouth and pacifier (group 4; N = 11)

*all were given 2 min before start of  the eye examination*

 

 

PIPP during examination of eye

Mean, SD, 95% CI

PIPP scores of Mean (SD)were: 15.3 (1.9), 14.3 (1.6), 12.3
(2.9), and 12.1 (3.4) for groups 1, 2, 3, and 4

Significant differences in PIPP scores between the groups, P = 0.023

Infants in pacifier groups scored significantly lower than groups without pacifiers, P = 0.003 (95% CI ‐4.23 to ‐0.96)

No significant differences between groups receiving sucrose vs. groups receiving water

 

Gal 2005

23 neonates, GA 24 to 29 weeks, postnatal age 28 to 93 days

Eye examination for ROP

2 mL of sterile water

2 mL of 24% sucrose (N = 23, cross‐over design)

Mydriatic eye drops (phenylephrine HCl 1%, cyclopentolate HCl 0.2%) and local anaesthetic eye drops (proparacaine HCl 0.5%; 2 drops) given to both groups prior to examination

Decreased SpO2 by ≥ 10% pre‐examination, at eye speculum insertion and post‐examination

PIPP scores at 5 and 1 min pre‐examination, eye speculum insertion, and 1 and 5 min post‐examination

Percentage of population

Means, SD reported

No significant difference in SpO2 between water group and sucrose group

PIPP score at the eye examination significantly lower in the group given sucrose (mean 8.3, SD 4.5) compared to the placebo group (mean 10.5, SD 4.0), P = 0.01); however, this effect was not sustained at 1 and 5 min post‐examination

Grabska 2005

32 preterm infants, mean GA 28 weeks, mean postnatal age 50.8 days

 

Eye examination for ROP

Sterile water delivered either directly into the mouth or via a nipple 2 min prior to eye examination (N = 16)

24% oral sucrose was delivered either directly into the mouth via a nipple 2 min prior to eye examination (N = 16)

Doses were adjusted by weight:

< 1 kg = 0.5 cm3 (0.12 g); 1 to 1.5 kg = 1.0 cm3 (0.24 g); 1.5 to 2 kg = 1.5 cm3 (0.36 g); > 2 kg = 2.0 cm3 (0.48 g)

All infants were swaddled and offered a pacifier

All infants received tropicamide 0.5% and phenylephrine 2.5% eye drops approximately 30 min before examination. Topical tetracaine was instilled into the eyes just prior to the examination

% of the eye examination the infant spent crying 

 

Mean HR, at baseline, post‐eye drop instillation, post‐study drug, during eye examination and post‐eye examination*

RR and SpO2 at baseline, post‐eye drop instillation, post‐study drug, during eye examination and post‐eye examination*

PIPP at  baseline, during eye examination, post‐eye examination*

*measures were taken at 1‐min intervals and were means for each study period ‐ study period times (in min) were not defined

Mean, SD

No significant difference in crying time between the sucrose and water groups.

Significant increases in HR, in both groups from baseline (P < 0.01)

No differences between the sucrose and placebo groups in HR at any time point

Significant reduction in SpO2 in infants receiving sucrose after the study drug (mean 95%, SD 4%) compared to the water group (mean 97%, SD 3%)

Significant reduction in SpO2 in infants receiving sucrose during the eye examination (mean 93%, SD 5%; P < 0.05) compared to the water group (mean 96%, SD 3%; P < 0.05)

No significant difference in RR and SpO2 at 2 min post‐examination.

No significant differences in PIPP scores between the sucrose and placebo groups before, during and after eye examinations

Mitchell 2004

30 preterm infants

Water group: mean GA 27.3 weeks, mean postnatal age 8.2 weeks

Sucrose group: mean GA 26.5 weeks, mean postnatal age 8.5 weeks

 

 

Eye examination for ROP

Pacifier and 3 doses of 0.1 mL sterile water via syringe into the mouth (N = 15)

Pacifier and 3 doses of 0.1 mL 24% sucrose via syringe into the mouth (N = 15)

*1st dose given 1.5 min before local anaesthetic eye drops, 2nd dose right at placement of the eye speculum, 3rd dose 120 s after 2nd drop*

All infants received proparacaine hydrochloride 0.5% eye drops and were swaddled before the eye examination

 

PIPP at baseline, at eye drop instillation, at examination of left eye and at 30, 60, 90 and 120 s after the examination

Mean, SEM

Statistically significant differences in mean PIPP scores were found between sucrose group (mean 8.8, SEM 0.7) and the water group (mean 11.4, SEM 0.6) during the eye examination (P = 0.0077). However, this was not sustained after the eye examination

 

 

Rush 2005

30 preterm infants < 32 weeks' GA or weighing < 1500 g

 

Control group: mean GA 28.88 weeks (range 25 to 31 weeks)

 

Treatment group: mean GA of 29.57 weeks (range 26 to 32 weeks)

Eye examination for ROP

Prior to examination: instillation of 0.5% proparacaine and 1% tropicamide,  then 15 min later eye drop instillation of 0.5% tropicamide, 2.5% phenylephrine and 0.5% tropicamide

Control group: no swaddling, no pacifier and no holding (N = 16)

Treatment group: swaddled in warm blanket 15 min prior to examination; given pacifier soaked in 24% sucrose solution and held by nurse until 15 min after examination (N = 14)

Total crying time out of 5 min starting at the onset of the ROP examination

HR 30 min before eye drop instillation and 5 min before ROP examination, during examination, 5 min after examination

SpO2 and RR at 30 min before eye drop instillation and 5 min before the ROP examination, SpO2 and RR at ROP (3 measurements) and SpO2 and RR 5 min after ROP examination

Reported means and SEM

Not reported

SpO2 means and SEM reported

RR not reported

No significant differences in crying time between treatment and control groups

 

There was no significant difference in HR between groups.

No significant differences between treatment group and the control group for SpO2 and respiratory rate at any point

O'Sullivan 2010

40 preterm infants

corrected age: mean = 33.0 ± 1.1 weeks

Eye examination for ROP

Treatment group: 0.2 mL of sucrose with pacifier soaked in 24% sucrose solution (N = 20)

Water group: 0.2 mL of sterile water by mouth (N = 20)

N‐PASS, HR and SpO2 at baseline, # of bradycardia and desaturation, adverse events

Median, range

Significantly lower N‐PASS score at speculum insertion in sucrose compared to control group (6.5 vs. 5.0; P = 0.02); during procedure (9.5 vs. 7.5; P = 0.03). No differences between treatment group and the control group for number of bradycardia or oxygen desaturation

CI: confidence interval; GA: gestational age; HR: heart rate; N‐PASS: Neonatal Pain, Agitation and Sedation Scale; PIPP: Premature Infant Pain Profile; ROP: retinopathy of prematurity; RR: respiratory rate; SD: standard deviation; SEM: standard error of the mean; SpO2: oxygen saturation.

Figuras y tablas -
Table 4. Trials assessing pain during ROP examinations
Table 5. Trials assessing pain during subcutaneous injections

Study

Participants

Procedure

Interventions

Outcomes

Metrics used

Results

Allen 1996

285 term infants

 

Various age groups based on required immunisations. Age groups were:

2 weeks, 2 months, 4 months, 6 months, 15 months and 18 months

 

Only data for neonates at 2 weeks of age are included in this review

 

 

Subcutaneous injection

2 mL 12% sucrose

 

2 mL sterile water

 

No treatment

 

 

Cry duration (during and after procedure)

Mean, SD

 

% time crying

The overall P value for % time crying was significant (F = 5.92, P < 0.005). Pairwise comparisons of the % time spent crying of sucrose and water groups versus the no treatment group show significant differences (P < 0.01 for both comparisons)

 

This was the only age group in which significant differences were observed between sucrose, water and no treatment groups

Mucignat 2004

33 preterm neonates, mean (SD) GA at birth 30 weeks (6 days), GA at injection 32 weeks (6 days)

Subcutaneous injections

Non‐nutritive pacifier sucking (41 injections)

0.2 to 0.5 mL of 30% sucrose with pacifier (86 injections)

local application of EMLA with pacifier (71 injections)

0.2 to 0.5 mL of sucrose with EMLA and pacifier (67 injections)

Duration of cry from needle introduction until to 2 min after its removal

HR before injection, during injection and after injection

SpO2 before injection, during injections and after injection

DAN and NFCS scores during injection

Mean, SD

Crying time was significantly lower in the sucrose + EMLA + pacifier group (P = 0.0002). The mean (SD) crying time in each group was as follows: 3.93 s (2.97) in the pacifier only group, 2.81 s (4.81) in the EMLA + pacifier group, 2.32 s (7.51) in the sucrose + pacifier group and 0.89 s (2.66) in the sucrose with EMLA + pacifier group

There were no significant differences in HR between the 4 groups

The only significant difference in SpO2 between groups occurred during injection, which was lower in the NNS group (P = 0.02)

Significant reduction in DAN and NFCS scores in EMLA + NNS, sucrose + NNS, and sucrose + EMLA + pacifier groups compared to NNS alone

DAN: Douler Aigue Du Nouveau‐ne; EMLA: eutectic mixture of local anaesthetics; GA: gestational age; HR: heart rate; NFCS: Neonatal Facial Coding System; NNS: non‐nutritive sucking; SD: standard deviation.

Figuras y tablas -
Table 5. Trials assessing pain during subcutaneous injections
Table 6. Trials assessing pain during nasogastric intubations

Study

Participants

Procedure

Interventions

Outcomes

Metrics used

Results

McCullough 2008

20 infants,

mean (SD) GA 30.7 weeks (2.3)

 

NG tube insertion

0.5 ‐ 2 mL of sterile water 2 min prior to procedure

 

0.5 ‐ 2 mL 24% sucrose 2 min prior to procedure

 

Volume of solution was adjusted for current body weight

 

> 2 kg = 2 mL

1.5 to 2 kg = 1.5 mL

< 1.5 kg = 0.5 mL

Incidence of cry

Baseline HR and change in HR from baseline during NG tube insertion

Baseline SpO2 and change in SpO2 from baseline during NG tube insertion

NFCS during NG tube insertion and after insertion

%

Mean, SD

Median

There was a non‐significant trend (P = 0.069) for fewer sucrose‐treated infants to cry during NG tube insertion (8/26), compared with the placebo group (14/25)

Infants in the sucrose group had higher mean pre‐treatment baseline HR than placebo group but showed no change in HR during NG tube insertion (mean change ‐0.7 bpm). The HR of the placebo group increased during NG tube insertion (mean change +11). This difference approached statistical significance (P = 0.055)

No significant changes in mean SpO2 occurred in either groups

Sucrose group had a significant lower median NFCS score during NG tube insertion compared with the water group (1 (range 0 to 4) vs. 3 (range 0 to 4), median difference 1 (95% CI 0 to 2); P = 0.004)

After NG tube insertion, the NFCS scores fell to a median of 0 in both groups

To see if NFCS is specific for pain, authors analysed the 4 components on their own. Nasolabial folds showed a significant inhibition in the sucrose group (present in 4/26 (15%) compared with 12/25 (48%) in the placebo group; P = 0.012)

Kristoffersen 2011  

24 preterm infants. 28 to 32 weeks GA, cross‐over designs

NG tube insertion

6 interventions:

pacifier, no pacifier, combined, with no fluid, 0.2 mL sterile water, or 0.2 mL 30% sucrose

PIPP scores

Median, range

Median PIPP score during the procedure was 9 and decreased gradually towards 4 after 5 min. The lowest PIPP score in pacifier with oral sucrose combination compared to no treatment (P < 0.001). Highest pain score in sterile water group

bpm: beats per minute; GA: gestational age; HR: heart rate; NFCS: Neonatal Facial Coding Score; NG: nasogastric; PIPP: Premature Infant Pain Profile; SD: standard deviation; SpO2: oxygen saturation.

Figuras y tablas -
Table 6. Trials assessing pain during nasogastric intubations
Table 7. Trials assessing pain during circumcision

Study

Participants

Procedure

Interventions

Outcomes

Metrics used

Results

Herschel 1998

120 healthy male newborns, ≥ 38 weeks

Circumcision

Control group ‐ no treatment (N = 40)

DPNB: 0.8 mL of 1% lidocaine without epinephrine injected into dorsolateral penile root 3 min before procedure (N = 40)

Pacifier dipped in 50% sucrose with a gauze pad moistened with sucrose inside the nipple 2 min before procedure (N = 39)

HR at baseline, restraint, skin preparation for procedure, lateral clamping, lysis of adhesions, dorsal clamping, dorsal cut, retraction, application of Gomco bell and clamp, tightening of clamp, excision of foreskin, removal of clamp, removal of bell, placement of dressing and overall change in HR from baseline

SpO2 at baseline and throughout procedure; change from baseline during the circumcision procedure

Mean, SD, mean differences and 95% CI

Mean change in HR from baseline through all follow‐up times were significantly different between groups (P < 0.001)

Mean (95% CIs) HR differences: control vs. DPNB: 27.1 bpm (17.6 to 36.6), control vs. sucrose: 9.7 bpm (0.1 to 19.3) and sucrose vs. DPNB: 17.4 bpm (7.8 to 27.0)

Sucrose had statistically significant effect compared to the no treatment controls (P < 0.001)

Significant differences between groups in changes in SpO2 from baseline to circumcision (P < 0.001)

Mean (95% CI) SpO2 differences between the 3 groups from baseline: ‐2.5 (‐15.8 to 3.12) for the control group, ‐0.8 (‐4.3 to 5.5) for the DPNB group, 0.7 (‐6.8 to 12.5) for the sucrose group

Differences between both the DPNB and sucrose groups compared to control were significant (P < 0.05)

Control vs. sucrose: ‐3.3 (‐5.0 to ‐1.6) was statistically significant (P < 0.001)

Kaufman 2002

57 term infants, mean age at time of procedure 30 to 43 h

Circumcision

Gomco method and pacifier dipped in water (N = 14)

Gomco method and pacifier dipped in 24% sucrose (N = 14)

Mogen method and pacifier dipped in water (N = 15)

Mogen method and pacifier dipped in 24% sucrose (N = 14)

All infants had EMLA cream applied 1 to 3 h before procedure

Time spent crying during procedure

Time spent grimacing

Procedure stages:

1) Table ‐ restraint

2) Restraint ‐ forceps

3) Forceps ‐ excision

4) Excision ‐ unrestraint

5) Unrestraint ‐ end

Median and means, graphically

Not reported

Cumulative mean time crying for forceps to unrestraint interval in the Gomco‐sucrose group was 56 s (median = 53 s) compared to 86 s (median = 78 s) in the Gomco‐water group (P = 0.0001). Crying time in Mogen‐sucrose and Mogen‐water groups were not significantly different

Overall, mean crying time significantly decreased in infants treated with sucrose compared to infants treated with water (P = 0.0001)

Significantly less time spent grimacing in the Gomco‐sucrose group compared to the Gomco‐water group (P = 0.0001)

No significant differences between Mogen‐sucrose and the Mogen‐water groups

Overall, mean time grimacing was significantly reduced in infants treated with sucrose compared to infants treated with water (P = 0.0001)

Stang 1997

80 healthy term newborn male infants, mean GA 39.5 weeks

Circumcision

DPNB (0.8 mL lidocaine and 0.2 mL saline) plus pacifier dipped in water and using new padded restraint chair

DPNB with buffer (0.8 mL of lidocaine and 0.2 mL of sodium bicarbonate) and pacifier dipped in water

DPNB (0. 8 mL lidocaine and 0.2 mL saline) and pacifier dipped in 24% sucrose

Control: DPNB (0.8 mL lidocaine and 0.2 mL saline) and pacifier dipped in water

Plasma cortisol level 30 min after beginning circumcision

Mean, SD

Plasma cortisol levels not significantly different between groups

CI: confidence interval; DPNB: dorsal penile nerve block; EMLA: eutectic mixture of local anaesthetics; GA: gestational age; HR: heart rate; SD: standard deviation.

Figuras y tablas -
Table 7. Trials assessing pain during circumcision
Table 8. Trials assessing pain during bladder catheterisation

Study

Participants

Procedures

Intervention

Outcomes

Metrics used

Results

Rogers 2006

80 infants ≤ 90 days of age requiring bladder catheterisation

Subgroup analysis performed: infants 1 to 30, 31 to 60 and 61 to 90 days of age

Bladder catheterisation

2 mL of sterile water via syringe 2 min before procedure (N = 40)

2 mL of 24% sucrose via syringe 2 min before procedure (N = 40)

% of subjects crying at maximal insertion

Change in DAN scores

%

Youngest subgroup of infants (1 to 30 days) showed smaller changes in DAN score compared to water group (2.86 vs. 5.29; P = 0.035)

Subgroup analysis of infants (1 to 30 days) receiving sucrose were significantly less likely to cry during maximal catheter insertion compared to water group (28.6% vs. 78.6%; P = 0.008)

DAN: Douler Aigue Du Nouveau‐ne.

Figuras y tablas -
Table 8. Trials assessing pain during bladder catheterisation
Table 9. Trials assessing pain during multiple procedures

Study

Participants

Procedure

Interventions

Outcomes

Metrics used

Results

Boyer 2004

103 infants, GA < 31 weeks (57 infants included in this analysis)

All painful procedures during the 1st week of life

Before every painful procedure, up to 3 doses of:

0.1 mL of 24% sucrose (N = 27)

0.1 mL of sterile water (N = 30)

Salivary cortisol levels at baseline, 30 min after painful procedure at days 1,3,5,7

Mean, SD

No significant differences between groups for mean cortisol levels at baseline or post painful procedures

Johnston 2002

103 infants

Sucrose: 51 infants, mean GA 28.18 (1.72)

Water (control): 52 infants, mean GA 28.05 (2.06)

Every time the infant was to undergo an invasive (e.g. heel lance, intravenous cannulation,
arterial puncture, injection) or non‐invasive but presumably
uncomfortable procedure (e.g., endotracheal tube suctioning, tape/
lead removal, gavage insertion for feeding)

Sucrose group: 0.1 mL of 24% sucrose were drawn up into sterile syringes and placed in the unit medicine refrigerator

Water group: 0.1 mL of water were drawn up into sterile syringes and placed in the unit medicine refrigerator

Neurobehavioural development assessed by the subscales of alertness and orientation and motor development and vigour of theNAPI, SNAP and NBRS

Beta, CI (multiple regression)

No group differences or factors associated with SNAP over each day, with day 7 being of interest because it was calculated on the final 24 h of the intervention and would be most reflective of cumulative physiological effects of the intervention (sucrose 3.72 (3.33), water 4.10 (3.18); F(1,101) 0.093, P = 0.761). On the basis of analysis of covariance with PCA at birth and number of invasive procedures as covariates, there were no group differences on any of the secondary outcomes of NBRS scores at 2 weeks; postnatal age (sucrose 1.42 (1.32), water 1.68 (1.58); F(1,101) 0.640, P = 0.426) or at discharge (sucrose 2.29 (2.68), water 2.31 (2.47); F(1,100) = 0.002, P = 0.965)

Taddio 2008

240 newborn infants born to non‐diabetic and diabetic mothers, GA ≥ 36 weeks

3 heel lances, venipuncture and intramuscular vitamin K injection

2 mL of 24% sucrose given to infants of non‐diabetic mothers (N = 60)

2 mL of 24% sucrose given to infants of diabetic mothers (N = 60)

2 mL of sterile water given to infants of non‐diabetic mothers (N = 60)

2 mL of sterile water given to infants of diabetic mothers (N = 60)

PIPP scores overall, during intramuscular injection, during venipuncture and all 3 heel lances

Mean, SD, 95% CI

Overall PIPP scores significantly lower among newborns given sucrose (mean 6.8, SD 2.9) compared to placebo (mean 8.1, SD 2.5) (mean difference ‐1.3, 95% CI ‐2.0 to ‐0.6; P < 0.001)

PIPP scores during intramuscular injection did not differ between the sucrose and placebo group for non‐diabetic or diabetic mothers

PIPP scores during venipuncture was significantly lower among infants of non‐diabetic mothers who received sucrose compared to placebo (mean score 5.7, 95% CI 4.7 to 6.7 vs. mean score 8.9, 95% CI 7.9 to 9.9; P < 0.001). Similar results were found among infants of diabetic mothers (sucrose: mean score 6.8, 95% CI 5.7 to 7.9 vs. placebo: mean score 9.2, 95% CI 8.4 to 10.1; P < 0.001)

During first 3 heel lances, newborns from diabetic mothers receiving sucrose or placebo did not have significantly different PIPP scores

CI: confidence interval; GA: gestational age; NAPI: Neurobehavioral Assessment of the Preterm Infant; NBRS: Neuro‐Biological Risk Score; PCA: postconceptional age; PIPP: Premature Infant Pain Profile; SD: standard deviation; SNAP: Score for Neonatal Acute Physiology.

Figuras y tablas -
Table 9. Trials assessing pain during multiple procedures
Table 10. Trials assessing pain during multiple procedures during heel stroke

Study

Participants

Procedure

Interventions

Outcomes

Metrics used

Results

Fernandez 2003  

34 term infants

Water group: mean GA 39 weeks (1)

Sucrose group: mean GA 38 weeks (2)

Heel stroke

Water group: 2 mL of water

Sucrose group: 2 mL of 12% sucrose

The pipette containing the liquid was placed towards the front and centre of the mouth, and the solution was then released in small amounts

Crying behaviours, EEG, ECG and facial expressions

Mean, SD

Infants who received water (mean 33%, SD 37) cried more than those who received sucrose (mean 14%, SD 24) (t [28] = 1.66, P = 0.05) and also grimaced more (mean 39%, SD 35) than the sucrose infants (mean 19%, SD 25) during the heel stroke procedure (t [28] = 1.74, P < 0.05). One‐tailed t‐tests for HR revealed that the HR for the infants in both the sucrose (t [18] = 3.68, P < 0.01) and water groups (t [6] = 2.49, P < 0.05) increased from the pre‐heel stroke phase (mean 144 bpm, SD 13, sucrose; mean 146 bpm, SD 9, water) to the heel stroke phase (mean 153 bpm, SD 10, sucrose; mean 154 bpm, SD 10, water)
One‐tailed t‐tests for HR revealed (Figure 2) that the HR for the infants in the sucrose group decreased from the heel stroke phase (mean 155 bpm, SD 11) to the post‐heel stroke phase (mean 143 bpm, SD 13) (t [18] = 4.35, P < 0.001), whereas the HR for the infants in the water group remained elevated from heel stroke phase (mean 154 bpm, SD 11) to post heel stroke (mean 152 bpm, SD 15) (t [6] = 0.43, P > 0.50).

bpm: beats per minute; ECG: electrocardiography; EEG: electroencephalography; GA: gestational age; HR: heart rate; SD: standard deviations.

Figuras y tablas -
Table 10. Trials assessing pain during multiple procedures during heel stroke
Comparison 1. Heel lance: sucrose (sucrose or sucrose+NNS) vs. control (NNS+water, water or positioning and containing intervention)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Premature Infant Pain Profile (PIPP) at 30 s after heel lance Show forest plot

4

264

Mean Difference (IV, Fixed, 95% CI)

‐1.76 [‐2.54, ‐0.97]

2 Premature Infant Pain Profile (PIPP) at 60 s after heel lance Show forest plot

3

195

Mean Difference (IV, Fixed, 95% CI)

‐2.05 [‐3.08, ‐1.02]

Figuras y tablas -
Comparison 1. Heel lance: sucrose (sucrose or sucrose+NNS) vs. control (NNS+water, water or positioning and containing intervention)
Comparison 2. Heel lance: sucrose 25‐33% vs. control (sterile water)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 % change in heart rate 1 min after heel lance Show forest plot

2

86

Mean Difference (IV, Fixed, 95% CI)

0.90 [‐5.81, 7.61]

2 % change in heart rate 3 min after heel lance Show forest plot

2

86

Mean Difference (IV, Fixed, 95% CI)

‐6.20 [‐15.27, 2.88]

3 Heart rate at 3 min after heel lance Show forest plot

2

154

Mean Difference (IV, Fixed, 95% CI)

‐0.98 [‐8.29, 6.32]

Figuras y tablas -
Comparison 2. Heel lance: sucrose 25‐33% vs. control (sterile water)
Comparison 3. Heel lance: sucrose 12.5‐50% vs. control (sterile water)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Duration of first cry (s) Show forest plot

3

192

Mean Difference (IV, Fixed, 95% CI)

‐8.99 [‐20.07, 2.10]

2 Total crying time (s) Show forest plot

2

88

Mean Difference (IV, Fixed, 95% CI)

‐39.26 [‐44.29, ‐34.24]

Figuras y tablas -
Comparison 3. Heel lance: sucrose 12.5‐50% vs. control (sterile water)
Comparison 4. ROP examination: sucrose 24‐33% (sucrose or sucrose+NNS) vs. control (water or water+NNS)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 PIPP score during (L) eye examination Show forest plot

3

82

Mean Difference (IV, Fixed, 95% CI)

‐1.27 [‐2.29, ‐0.25]

1.1 Sucrose via syringe vs. control (sterile water via syringe)

2

52

Mean Difference (IV, Fixed, 95% CI)

‐0.65 [‐1.88, 0.59]

1.2 Sucrose + pacifier vs. control (sterile water + pacifier)

1

30

Mean Difference (IV, Fixed, 95% CI)

‐2.60 [‐4.41, ‐0.79]

2 PIPP score for ROP examinations Show forest plot

2

52

Mean Difference (IV, Fixed, 95% CI)

‐0.65 [‐1.88, 0.59]

Figuras y tablas -
Comparison 4. ROP examination: sucrose 24‐33% (sucrose or sucrose+NNS) vs. control (water or water+NNS)
Comparison 5. ROP examination: sucrose 24‐33% (sucrose or sucrose+NNS) vs. control (water or water+NNS)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Oxygen saturation (%) during eye examination Show forest plot

2

62

Mean Difference (IV, Fixed, 95% CI)

‐2.58 [‐4.94, ‐0.23]

Figuras y tablas -
Comparison 5. ROP examination: sucrose 24‐33% (sucrose or sucrose+NNS) vs. control (water or water+NNS)