Article Discussion

read an article, write several sentences to answer the questions, this is for discussion, so please make sure the answers are short and brief, and also come up with a specific question for people to discuss.

article and requirements are uploaded.

Contents lists available at ScienceDirect

International Journal of Nursing Studies

journal homepage: www.elsevier.com/locate/ijns

Effect of non-nutritive sucking and sucrose alone and in combination for repeated procedural pain in preterm infants: A randomized controlled trial

Haixia Gaoa,⁎, Mei Lib, Honglian Gaoc, Guihua Xua, Fang Lib, Jing Zhoub, Yunsu Zoub, Honghua Jiangb

a School of Nursing, Nanjing University of Chinese Medicine, Nanjing, China b Children’s Hospital of Nanjing Medical University, China c Binzhou Medical University Hospital, Binzhou, China

A R T I C L E I N F O

Keywords: Preterm infants Pain Analgesia Sucrose Non-nutritive sucking

A B S T R A C T

Background: Sucrose combined with non-nutritive sucking provided better pain relief than sucrose or non-nu- tritive sucking alone in a single painful procedure. However, whether the combination of non-nutritive sucking with sucrose could obtain a significant difference in analgesic effect of the repeated procedural pain than any single intervention has not been established. Objective: To compare the effect of non-nutritive sucking and sucrose alone and in combination of repeated procedural pain in preterm infants. Design: Randomized controlled trial. Setting: A level III neonatal intensive care unit of a university hospital in China. Method: Preterm infants born before 37 weeks of gestation were randomly assigned to four groups: routine care group (routine comfort through gentle touch when infants cried; n = 21), non-nutritive sucking group (n = 22), sucrose group (0.2 ml/kg of 20%; n = 21), sucrose (0.2 ml/kg of 20%) plus non-nutritive sucking group (n = 22). Each preterm infant received three nonconsecutive routine heel sticks. Each heel stick included three phases: baseline (the last 1 min of the 30 min without stimuli), blood collection, recovery (1 min after blood collection). Three phases of 3 heel stick procedures were videotaped. Premature infant pain profile (PIPP) score, heart rate, oxygen saturation and percentage of crying time were assessed by five independent evaluators who were blinded to the purpose of the study at different phases across three heel sticks. Data were analyzed by analysis of variance, with repeated measures at different evaluation phases of heel stick. Results: 86 preterm infants completed the protocol. During the blood collection and recovery phases, combi- nation group, had lower PIPP score (4.4 ± 1.5; 3.0 ± 0.8), lower heart rate (138.6 ± 7.9; 137.4 ± 4.7), higher oxygen saturation (95.2 ± 1.6; 96.0 ± 1.2), and smaller percentage of crying time (11.5 ± 8.6; 4.6 ± 3.4), compared with the group has given non-nutritive sucking (9.3 ± 1.3, 6.8 ± 1.4; 154.2 ± 9.0, 148.0 ± 9.3; 92.9 ± 2.4, 94.1 ± 1.0; 44.2 ± 9.6, 31.2 ± 10.5; respectively) or sucrose (10.1 ± 2.0, 7.4 ± 1.6; 151.6 ± 9.6, 147.9 ± 6.9; 93.5 ± 1.7, 94.5 ± 1.2; 53.8 ± 16.7, 35.2 ± 13.9; respectively) or routine care (13.3 ± 1.6, 10.6 ± 1.9; 156.8 ± 7.2, 151.7 ± 7.9; 92.9 ± 2.1, 93.8 ± 1.6; 80.6 ± 7.6, 68.2 ± 9.9; respectively). Both non-nutritive sucking and sucrose were more effective in reducing preterm infants’ PIPP score and percentage of crying time than routine care. There was no difference in PIPP score, heart rate, oxygen saturation and percentage of crying time between the non-nutritive sucking and sucrose groups. Conclusion: The combination of non-nutritive sucking with sucrose provided better pain relief during repeated painful procedures than when non-nutritive sucking or sucrose was used alone. The effect of non-nutritive sucking was similar to that of sucrose on repeated procedural pain.

What is already known about the topic?

• In an neonatal intensive care unit, preterm infants are exposed to various painful stimuli to guarantee their survival. Repeated painful

stimuli in neonates may have short- and long-term consequences on preterm infants physically and developmentally.

• Repeated exposure of preterm infants to opioid may have a detri- mental effect on child neurodevelopmental outcomes.

https://doi.org/10.1016/j.ijnurstu.2018.04.006 Received 8 August 2017; Received in revised form 4 April 2018; Accepted 5 April 2018

⁎ Corresponding author at: School of Nursing, Nanjing University of Chinese Medicine, 138 Xianlin Road, Qixia District, Nanjing, Jiangsu Province 210023, China. E-mail address: bpn456@163.com (H. Gao).

International Journal of Nursing Studies 83 (2018) 25–33

0020-7489/ © 2018 Elsevier Ltd. All rights reserved.

T

 

 

• The use of sucrose alone or combined with non-nutritive sucking has been the most frequently studied non-pharmacological intervention method for single procedural pain. However, there have been no studies comparing the effect of sucrose and non-nutritive sucking alone and in combination with repeated procedural pain for preterm infants.

What this paper adds

• The combination of sucrose and non-nutritive sucking shows better efficacy for repeated procedural pain than their single use in pre- term infants.

• The effect of non-nutritive sucking was similar to that of sucrose on repeated procedural pain.

• When both sucrose and non-nutritive sucking can be provided in a unit, the combination of them can be recommended as an analgesic alternative for repeated pain exposure in preterm infants.

1. Introduction

Preterm birth is a significant global health problem. Survival rates for preterm infants have increased markedly in recent decades due to significant advances in neonatal intensive care. However, preterm in- fants are exposed to various painful stimuli to guarantee their survival during their stay in the neonatal intensive care unit (Chen et al., 2012; Cruz et al., 2016; Jeong et al., 2014). Greater exposure to neonatal pain-related stress has been found to be associated with poorer long- term neurodevelopmental outcomes (Brummelte et al., 2012; Doesburg et al., 2013; Lax et al., 2013; Skranes et al., 2012; Smith et al., 2011; Vinall et al., 2013; Nuseir et al., 2015). Therefore, pharmacological or non-pharmacological pain management must be required for preterm infants in current neonatal practice.

Opioid analgesia is now widely used in preterm neonates. It is no- teworthy that several recent studies have demonstrated repeated ex- posure of preterm infants to opioid may have a detrimental effect on child neurodevelopmental outcomes (Nuseir et al., 2015). For example, the result from Nunes et al. study showed that repeated morphine ex- posure during early life could have intermediate and long-term adverse effects on the nociceptive responses, which included thermal hyper- algesia and mechanical allodynia (Nunes et al., 2017). Kocek et al. observed decreasing cognitive scores at 20 months corrected age in extremely low birth weight infants who had cumulative opioid ex- posure while in the neonatal intensive care unit (Kocek et al., 2016). Furthermore, Ranger et al. reported that higher cumulative doses of neonatal morphine were related with higher internalizing behaviours at school age (Ranger et al., 2014). Thus, the adverse effects of opioid analgesic are not negligible. It is very important to better understand the potential risks and benefits of repeated opioid exposure in preterm infants.

In contrast to pharmacological pain management, non-pharmaco- logical pain management may have lower risk and greater ease of use for preterm infants. Sucrose and non-nutritive sucking are the most frequently studied non-pharmacological methods for reducing a single procedural pain in preterm infants, and have been recommended by national and international guidelines to alleviate procedural pain. Furthermore, recent systematic reviews have addressed sucrose and non-nutritive sucking as effective interventions to provide analgesia and comfort for infants during painful procedures (Pillai Riddell et al., 2015; Stevens et al., 2016). However, the evidence regarding the effi- cacy and safety of repeated sucrose alone or combined with other non- pharmacological interventions across repeated procedural pain for neonates was limited (Gao et al., 2016). What’s more, there have been no studies examining whether the combined intervention of sucrose and non-nutritive sucking could obtain a significant difference in analgesic effect on repeated procedural pain compared to any single intervention for preterm infants, although several studies have reported that sucrose

combined with non-nutritive sucking provided better pain relief than sucrose or non-nutritive sucking alone in a single painful procedure (Liu et al., 2017; Naughton, 2013; Thakkar et al., 2016). It is a remarkable fact that preterm newborns could learn and react to painful experiences in the neonatal intensive care unit (Goubet et al., 2001), and the re- peated exposure to painful experiences may reduce the pain threshold and provoke hyperalgesia (Gibbins et al., 2008; Grunau, 2002). Thus, it is vital to determine if the effects of the combination of sucrose and non-nutritive sucking are better than their single-use on repeated pro- cedural pain for preterm infants. In addition, animal studies have shown that continuous consumption of sucrose can induce some be- havioral and physiological responses similar to those elicited by drugs of abuse like cocaine or amphetamine (Avena et al., 2008). Therefore, the safety of repeated administration of sucrose or non-nutritive sucking or their combination during painful procedures for preterm infants needs to be examined.

Hence, the purpose of this study was to compare the efficacy and safety of sucrose, non-nutritive sucking, and in combination with re- peated procedural pain in preterm infants. We hypothesized that: (1) Combined intervention of sucrose and non-nutritive sucking could be more effective than any single intervention across repeated procedural pain; (2) It is safe for preterm infants to use non-nutritive sucking or sucrose alone or their combination repeatedly across repeated painful procedures.

2. Methods

2.1. Design

This randomized controlled trial evaluated and compared the ef- fectiveness of sucrose and non-nutritive sucking alone and in combi- nation with repeated procedural pain across three nonconsecutive routine heel sticks in preterm infants. Preterm infants were randomly allocated before the heel stick by a research nurse using a random computer-generated table to one of the four groups: routine care group, non-nutritive sucking group, oral sucrose group, combined oral sucrose and non-nutritive sucking group.

2.2. Setting and sample

Preterm infants were recruited by convenience sampling from a level III neonatal intensive care unit (NICU) of a university hospital in China from August 2015 to February 2016. Infants were included if they met the following inclusion criteria: (1) Singleton born before 37 weeks of gestation, (2) Cared for in an incubator, (3) Anticipated re- ceiving at least three routine heel sticks for capillary blood sampling within two weeks after birth, (4) Hospitalized for the first time, (5) Non-nutritive sucking rate at a minimum of 30 times/min (Blass and Watt, 1999), and (6) Not scheduled to receive sedatives, muscle re- laxants, or analgesic drugs 24 h before a study session. Infants were excluded by these criteria: (1) Apgar Score of less than five at five minutes, (2) Required mechanical ventilation, (3) Suffered from a neurologic disorder, (4) Had congenital anomalies, (5) Undergone surgery, (6) Born to substance-abusing mother, (7) Had hyperglycemia, and (8) Nothing by mouth status for any reason.

To identify unforeseen problems and calculate the sample size, we conducted a pilot study. Our pilot study showed the average Preterm Infant Pain Profile (PIPP) score in 10 preterm infants during heel sticks were 11.7 (SD = ± 5.5) in routine care group, 10.8 (SD = ± 4.2) in non-nutritive sucking group, 9.0 (SD = ± 3.6) in oral sucrose group, 7.3 (SD = ± 2.0) in combined oral sucrose and non-nutritive sucking group. To detect a significant difference in PIPP score among the four groups, considering a power of 0.90, alpha of 0.05, and a 10% attrition rate, a sample size of 22 was required in each group.

H. Gao et al. International Journal of Nursing Studies 83 (2018) 25–33

26

 

 

2.3. Conditions in the four groups

All preterm infants, wearing only a diaper, were placed prone or in a side-lying position in the incubator and remained undisturbed for 30 min before the heel stick procedure. The assigned treatment condi- tion was administered by one researcher (the first author).

2.3.1. The condition in the routine care group The preterm infant received only routine comfort through gentle

touch when he cried after the heel stick procedure. The effectiveness of gentle touch as analgesia has been established in controlled clinical trials (Bahman Bijari et al., 2012; Herrington and Chiodo, 2014). Thus, for ethical reasons, preterm infants in the routine care group were given gentle touch to alleviate procedural pain if they were crying.

2.3.2. The condition in the non-nutritive sucking group The preterm infant was given a standard silicone newborn pacifier

to stimulate sucking in 2 min before, and throughout the recovery phase of the heel stick.

2.3.3. The condition in the sucrose group Sucrose 20% (0.2 ml/kg) was administrated to the preterm infant’s

mouth by 1 ml syringe without the needle in 2 min before the heel stick procedure (Cignacco et al., 2012).

2.3.4. The condition in the combined oral sucrose and non-nutritive sucking group

Sucrose 20% (0.2 ml/kg) was administrated to the preterm infant’s mouth by 1 ml syringe without the needle in 2 min before the heel stick procedure (Cignacco et al., 2012), and then a standard silicone new- born pacifier was given to stimulate sucking until the recovery phase of the heel stick.

2.4. Measures

Outcome variables included preterm infants’ procedural pain, phy- siological response, behavioral response, and incidence of any adverse events.

2.4.1. Measurement of procedural pain The preterm infants’ procedural pain was measured by the

Premature Infant Pain Profile (PIPP) scale. The PIPP scale is a validated seven-indicator scale for the assessment of procedural pain in pre- mature and term infants (Stevens et al., 1996). It measures pain ac- cording to two contextual indicators (gestational age and behavioral state), two physiological indicators (heart rate and oxygen saturation), and three behavioral indicators (brow bulge, eye squeeze, and nasola- bial furrow). Each indicator is numerically scaled and scored on a 4- point scale (0, 1, 2, 3), the total scores obtained for the seven indicators range from 0 to 21. Higher total scores indicate greater pain response. PIPP score < 6 means no pain, PIPP score ≥6 indicates pain, PIPP scores ≥12 signals moderate to severe pain. Validity and reliability of the PIPP instrument in infants at various gestational ages has previously been determined. For translation of PIPP scale from English into Chi- nese, the standard forward-backward procedure was applied. Transla- tion of the PIPP scale (English to Chinese) was independently per- formed by two professional translators, and then the temporary version was provided. The temporary version of the PIPP scale was backward translated into English by a native English translator who was blinded to the original instrument and not previously involved in the study. The back-translator and the expert committee evaluated the back-translated version, then the final version of the PIPP scale was provided.

Physiological indicators were continuously monitored by a pulse oximeter set on the preterm infant’s foot and videotaped by one digital camera (Canon sx30is). Behavioral indicators and behavioral state in- dicator were continuously videotaped by another digital camera (Canon

sx30is) which was in close up focus on preterm infants’ face and al- lowed for high-quality facial images. The two digital cameras (Canon sx30is) were used synchronously by the research assistant. The beha- vioral state indicator was evaluated using Prechtl’s categories of quiet sleep or quiet awake or active sleep or active awake (Prechtl, 1974; Prechtl and Beintema, 1977). Gestational age was determined ac- cording to the electronic medical record. PIPP score was measured by two trained evaluators (the second and third author) who were una- ware of the purpose of the study during the blood collection phase and recovery phase of each heel stick procedure. In order to ensure accep- table inter-rater agreement, the two evaluators respectively assessed PIPP score for each preterm infant at the blood collection phase of the first heel stick, the inter-rater reliability among evaluators was 97%. Intra-rater reliability was checked every three months, remaining more than 90%.

2.4.2. Measurement of physiological response The preterm infant’s physiological response to procedural pain was

assessed by the change in heart rate and oxygen saturation throughout repeated heel sticks. Oxygen saturation and heart rate were con- tinuously monitored by a pulse oximeter set on the preterm infant’s foot, were manually recorded every 30 s by a nurse student, and then were used to calculate the mean heart rate and oxygen saturation across the baseline, blood collection and recovery phases of each heel stick procedure.

2.4.3. Measurement of behavioral response The preterm infant’s behavioral response to procedural pain was

measured by the percentage of crying time respectively in the blood collection phase and recovery phase. Crying was defined as audible vocalization that lasted five seconds or more (Ludington-Hoe et al., 2005). Preterm infants’ voices were videotaped by a digital audio re- corder (MODEL F97), and then two assessors calculated the percentage of crying time through playing the tapes. To examine the inter-rater agreement, the two assessors, respectively calculated the percentage of crying time at the blood collection phase of the first heel stick, and the inter-rater reliability between the assessors was 98%. Intra-rater relia- bility was checked every three months, remaining more than 90%.

2.4.4. Measurement of incidence of adverse events The safety of different interventions (non-nutritive sucking, sucrose,

and combined use of them) was assessed by the incidence of adverse events during the study period. The adverse events included: (1) Choking, coughing, vomiting, abdominal distension, oral infection, necrotizing enterocolitis; (2) Sustained tachycardia (heart rate > 200 beats/min), bradycardia (heart rate < 80 beats/min), tachypnea (re- spiratory rate > 80 beats/min), dyspnea (respiratory rate < 20 beats/ min), or oxygen desaturation < 80% for > 15 s; (3) Hyperglycemia. The adverse events were monitored and recorded by two trained re- search nurses who were blind to the purpose of the study. A safety committee was established prior to study commencement. If severe adverse event such as choking or need for immediate medical inter- vention (e.g., intubation or resuscitation) following the administration of non-nutritive sucking, sucrose, or their combination occurred, the trial would be stopped by the safety committee.

2.5. Procedures

The study protocol (Fig. 1) and consent forms were approved by the institutional review board of the participating centre (approval number: 201507001-1). One research assistant screened admission log every other day in the neonatal intensive care unit, and finalized potential eligible infants, and informed the preterm infant’s parent of the purpose of the study, and obtained parental oral consent. Participating preterm infants were randomly assigned to the routine care group, non-nutritive sucking group, oral sucrose group, or combined intervention group. The

H. Gao et al. International Journal of Nursing Studies 83 (2018) 25–33

27

 

 

research assistant collected preterm infant’s characteristics, set pulse oximeter on the preterm infant’s foot at about 5 min before the heel- stick procedure. One researcher administered the intervention ac- cording to the assigned condition, and then the experienced laboratory employee performed heel stick in a standardized manner. One research nurse videotaped preterm infant’s physiological indicators in 15 s be- fore and 30 s after the heel stick, and in 15 s before and 30 s after the end of the heel stick, and videotaped preterm infant’s facial actions in 30 s after the heel stick and 30 s after the end of the heel stick. The other research nurse videotaped preterm infants’ voices occurring in the heel stick procedure by a digital audio recorder. Because the timing of blood sampling was determined by clinical needs, there were no fixed time points for data collection. Most heel-stick events took place in the morning and the intervals of them ranged from 3 to 48 h.

Each heel stick included three phases: (1) Baseline: 1 min of baseline was collected at the end of the 30 min without stimuli. (2) Blood col- lection: includes locating the site, disinfecting, sticking, squeezing, applying adhesive bandage to the site for hemostasis, which lasted about 60 s according to our previous observation. (3) Recovery: one min after blood collection. The mean heart rate and oxygen saturation during three phases of each heel stick, which displays in a pulse oxi- meter, were collected by a nurse student (see Section 2.4.2). Preterm infants’ PIPP score and percentage of crying time across the whole heel stick were evaluated by four assessors (see Sections 2.4.1; 2.4.3). All personnel was trained separately by the first author.

Study fidelity was established by the first author having separate weekly meetings with the investigators, research assistant, nursing student, and laboratory employees.

2.6. Data analysis

SPSS version 21.0 software package was used to conduct all the descriptive and comparative statistical analysis. Data were presented as means and standard deviations for continuous variables and frequencies for categorical variables. Preterm infant’s characteristics such as birth weight were evaluated for significant differences between the four groups by one-way ANOVA test or Kruskal–Wallis analysis when the assumption of normality test could not be found. For preterm infant’s characteristics such as sex and the incidence of adverse events, Chi- square test was used to determine whether there was significant dif- ference between groups. For comparisons among the different phases,

measurement parameters (PIPP score, heart rate, oxygen saturation, and the percentage of crying time) through the repeated heel sticks were averaged separately. Repeated measurement analysis of variance was performed to analyze both between- and within-groups difference in three phases, followed by the Bonferroni post-hoc test. For all com- parisons, a p- value of less than 0.05 was considered statistically sig- nificant.

3. Results

There were 137 preterm infants were screened during the data collection period. 103 were eligible for the criteria and were ap- proached, and 91 agreed to participate. The reasons for refusals in- cluded parents: did not want their infants to be videotaped due to their small size (n = 7), refused anything extra done to their infants (n = 3), were not interested (n = 2). Five infants dropped out of the study be- cause they were discharged from the unit prior to the required heel stick (Fig. 2). Preterm infant’s characteristics did not vary significantly between infants whose parents declined to participate or dropped out of the study (n = 17) and those who completed the study protocol (n = 86).

3.1. Preterm infant characteristics

The characteristics of preterm infants completed the study protocol are shown in Table 1. The sample included 86 preterm infants with a mean gestational age of 31.7 ± 0.9 weeks. The majority was male (60%) and born by cesarean delivery (71%). The preterm infants’ mean birth weight was 1732.0 ± 267.9 g, mean Apgar score at 5 min was 8.8 ± 0.7, and they had 15.7 ± 2.4 previous invasive procedures. No significant differences were noted among the four groups with regard to the preterm infants’ characteristics.

3.2. Comparison of pain measurement parameters during the three repeated heel sticks between groups

3.2.1. Between-group differences in pain measurement parameters during the repeated three heel sticks

We compared the effectiveness of routine care, non-nutritive sucking, sucrose and their combination in reducing procedural pain during repeated heel sticks. The results of repeated measurement

Fig. 1. The study protocol.

H. Gao et al. International Journal of Nursing Studies 83 (2018) 25–33

28

 

 

analysis of variance between groups revealed significant interactions of all the pain measurement parameters except PIPP score between treatment conditions and evaluation phases (PIPP score: F = 1.995, p = 0.121; heart rate: F = 11.509, p < 0.0001; oxygen saturation: F = 2.886, p = 0.016; percentage of crying time: F = 72.517, p < 0.0001). Moreover, there was a significant main effect of the treatment groups for all the pain measurement parameters (PIPP score: F = 168.360, p < 0.0001; heart rate: F = 16.983, p < 0.0001; oxygen saturation: F = 10.165, p < 0.0001; percentage of crying time: F = 275.310, p < 0.0001). Post hoc analyses were performed to compare the treatment conditions with each other (Table 2). In the baseline phase, there was no significant difference in heart rate, oxygen saturation and percentage of crying time respectively between groups with each other. Thus, all pain parameters during the blood collection phase and the recovery phase were comparable between groups. During the blood collection phase and recovery phase, regarding PIPP score, the combination group was significantly lower than the other three groups, both the sucrose group and non-nutritive group were lower than the routine care group. Regarding heart rate and oxygen satura- tion, the combination group had achieved a significant improvement compared with the other three groups, while there were no significant difference among the routine care group, sucrose group and non-nu- tritive sucking group. Regarding the percentage of crying, the combi- nation group was significantly smallest, the routine care group was significantly biggest, the non-nutritive sucking group was significantly

similar to the sucrose group.

3.2.2. Within-group differences in pain measurement parameters during the repeated three heel sticks

PIPP score, heart rate, oxygen saturation and percentage of crying time showed similar patterns in the four treatment groups, which changing significantly followed by the blood collection phase and re- covering afterwards (Table 3). In the blood collection phase, the mean PIPP scores at heel stick 1, 2, and 3 for the four treatment groups were as follows: 13.2 ± 2.1, 13.1 ± 1.7, 13.4 ± 2.6 respectively in the control group, 9.9 ± 2.4, 8.5 ± 2.7, 9.5 ± 2.6 respectively in the non-nutritive sucking group, 11.1 ± 2.1, 10.1 ± 3.9, 8.9 ± 4.0 re- spectively in the sucrose group, 4.2 ± 2.1, 4.8 ± 2.9, 4.4 ± 2.0 re- spectively in the combination group. In the recovery phase, the mean PIPP score at heel stick 1, 2, and 3 for the four treatment groups were as follows: 10.5 ± 2.5, 10.7 ± 1.9, 10.5 ± 2.5 respectively in the con- trol group, 7.6 ± 2.2, 6.0 ± 2.6, 6.9 ± 2.6 respectively in the non- nutritive sucking group, 7.9 ± 1.8, 7.3 ± 3.3, 7.1 ± 2.7 respectively in the sucrose group, 3.1 ± 2.0, 3.1 ± 1.7, 2.8 ± 1.0 respectively in the combination group. The dada above showed that preterm infants in the combination group didn’t feel pain at each heel stick, infants in the sucrose and non-nutritive sucking group felt mild pain, while infants in the control group felt moderate to severe pain.

Within-group comparison showed that significant differences in heart rate and oxygen saturation between the baseline phase and

Assessed for eligibility (n=137)

Excluded (n =46) Mee ng exclusion criteria (n =34) Refused to par cipate (n = 12)

n =91 Randomly allocated

Allocated to rou ne care group (n=23)

In all three nonconsecu ve heel s cks, infants received allocated incubator condi on Heel s ck 1 (n=23) Heel s ck 2 (n=23) Heel s ck 3 (n=21) : 2 infants discharged prior to the third heel s ck

Allocated to nonnutri ve sucking group (n=23)

In all three nonconsecu ve heel s cks, infants received allocated nonnutri ve sucking Heel s ck 1 (n=23) Heel s ck 2 (n=23) Heel s ck 3 (n=22) : 1 infant discharged prior to the third heel s ck

Allocated to sucrose group (n=23)

In all three nonconsecu ve heel s cks, infants received allocated oral sucrose Heel s ck 1 (n=23) Heel s ck 2 (n=23) Heel s ck 3 (n=21): 2 infants discharged prior to third heel s ck

Allocated to combina on group (n=22)

In all three nonconsecu ve heel s cks, infants received allocated combined treatment Heel s ck 1 (n=22) Heel s ck 2 (n=22) Heel s ck 3 (n=22)

Analyzed Repeated three heel s cks

(n=21)

Analyzed Repeated three heel s cks

(n=22)

Analyzed Repeated three heel s cks

(n=21)

Analyzed Repeated three heel s cks

(n=22)

Fig. 2. Flow diagram of the recruitment and randomization process.

H. Gao et al. International Journal of Nursing Studies 83 (2018) 25–33

29

 

 

recovery phase approached for all groups except the combination group. For the routine care group, sucrose group, non-nutritive sucking group, heart rate remained significantly quicker in recovery phase than in baseline phase, oxygen saturation remained significantly lower in recovery phase than in baseline phase. However, both heart rate and oxygen saturation in the combination group remained steady across all phases. In addition, compared to the other three group infants, com- bination group infants’ mean percentage of crying time in the recovery phase was near to the baseline phase percentage, although significant differences occurred in all groups between the baseline phase and the recovery phase.

3.3. Comparison of incidence of adverse events in the study period between groups

The incidence of adverse events in the study period was as follows: three preterm infants vomited (1 in the combination group, 1 in the routine care group, 1 in the non-nutritive sucking group); two preterm infants had abdominal distension (1 in the combination group, 1 in the routine care group). The Chi-square test exhibited that there were no statistically significant differences between groups in the incidence of adverse events (vomit: χ2 = 1.006, p = 0.800; abdominal distension: χ2 = 2.050, p = 0.562).

Table 1 Comparisons of characteristics of preterm infants between groups.

Variable Routine care group Nonnutritive sucking group Sucrose group Combination group P value

Gestational age, week 30–32a 21 16 17 18 33–34a 0 6 4 4 0.102

Gender Malea 13 15 10 14 Femalea 8 7 11 8 0.550

Method of delivery Vaginal deliverya 5 9 6 5 Cesarean deliverya 16 13 15 17 0.530

Birth weight, gb 1682.7 ± 200.2 1767.3 ± 302.7 1780.8 ± 304.6 1697.1 ± 254.7 0.547 Gestational age at birth, weekb 31.3 ± 0.6 31.9 ± 1.1 31.7 ± 0.9 32.0 ± 0.8 0.068 5 min Apgar scoreb 8.7 ± 0.6 8.8 ± 0.6 8.9 ± 0.7 8.8 ± 0.8 0.846

Postnatal days Heel stick 1b 3.2 ± 0.6 3.5 ± 0.6 3.4 ± 0.6 3.2 ± 0.7 0.262 Heel stick 2b 5.4 ± 0.6 5.4 ± 0.7 5.3 ± 0.6 5.6 ± 0.7 0.580 Heel stick 3b 9.5 ± 1.0 8.2 ± 2.0 8.5 ± 1.4 9.0 ± 2.9 0.179

Previous invasive proceduresb 15.7 ± 2.2 14.9 ± 2.9 16.1 ± 2.0 16.0 ± 2.3 0.359

Duration of blood collection phase, seconds Heel stick 1b 61.9 ± 12.5 61.5 ± 9.3 59.8 ± 9.7 57.7 ± 9.9 0.544 Heel stick 2b 65.5 ± 9.6 62.7 ± 12.8 66.9 ± 18.2 61.6 ± 13.7 0.573 Heel stick 3b 64.1 ± 9.2 58.7 ± 11.1 63.2 ± 9.0 59.1 ± 13.2 0.240

Behavioral state score at baseline phase Heel stick 1b 0.9 ± 0.7 0.8 ± 0.7 0.8 ± 0.7 0.9 ± 0.9 0.893 Heel stick 2b 1.1 ± 0.7 0.7 ± 0.6 0.8 ± 0.7 0.9 ± 0.6 0.216 Heel stick 3b 0.4 ± 0.5 0.4 ± 0.5 0.4 ± 0.5 0.3 ± 0.5 0.938

a n. b Mean (standard deviation).

Table 2 Between-group comparison of pain measurement parameters during the repeated three heel sticks.

RC group −NS group RC group −S group RC group −C group NS group-S group NS group- C group S group- C group

PIPP score Blood collectiona P < 0.0001 P < 0.0001 P < 0.0001 0.694 P < 0.0001 P < 0.0001 Recoverya P < 0.0001 P < 0.0001 P < 0.0001 1.000 P < 0.0001 P < 0.0001

Heat rate (beats/min) Baselinea 0.203 1.000 1.000 0.283 1.000 1.000 Blood collectiona 1.000 0.305 P < 0.0001 1.000 P < 0.0001 P < 0.0001 Recoverya 0.621 0.610 P < 0.0001 1.000 P < 0.0001 P < 0.0001

Oxygen saturation (%) Baselinea 1.000 1.000 1.000 1.000 1.000 1.000 Blood collectiona 1.000 1.000 0.002 1.000 0.002 0.035 Recoverya 1.000 0.602 P < 0.0001 1.000 P < 0.0001 0.001

Percentage of crying time (%) Baselinea – – – – – – Blood collectiona P < 0.0001 P < 0.0001 P < 0.0001 0.035 P < 0.0001 P < 0.0001 Recoverya P < 0.0001 P < 0.0001 P < 0.0001 1.000 P < 0.0001 P < 0.0001

Note: Data are listed as mean ± SD. PIPP: premature infant pain profile; RC: Routine care; NS: Nonnutritive sucking; S: Sucrose; C: Combination of nonnutritive sucking and sucrose.

a Bonferroni correction for multiples comparisons.

H. Gao et al. International Journal of Nursing Studies 83 (2018) 25–33

30

 

 

4. Discussion

Studies have demonstrated that preterm infants could mount both physiological and behavioral responses to painful stimuli. Repeated painful stimuli in neonates may have short- and long-term con- sequences on preterm infants physically and developmentally. Therefore, it is imperative to provide relief for preterm infants during repeated painful procedures. Sucrose and non-nutritive sucking have been established for managing a single procedural pain. However, to our knowledge, this is the first study to examine the analgesic effect of non-nutritive sucking across repeated painful procedure, and to de- termine if the combined intervention of sucrose and non-nutritive sucking could obtain a significant difference in analgesic effect on re- peated procedural pain compared to any single intervention for preterm infants.

Our study represents that both sucrose and non-nutritive sucking could reduce preterm infants’ PIPP score and percentage of crying time, but neither of them could decrease preterm infants’ physiological re- sponse during the repeated heel sticks, which is consistent with the previous studies (Table 2). Gaspardo et al. study found that preterm neonates in the sucrose group had significantly fewer facial actions and crying than the control group, but no statistical difference in the per- centage of neonates with a heart rate of > 160 beats/min between groups during repeated procedural pain (Gaspardo et al., 2008). Cignacco et al. study, using the Bernese Pain Scale for Neonates to measure preterm infants’ pain response caused by five heel sticks, re- ported that sucrose was significantly more effective in relieving re- peated procedural pain than facilitated tucking (Cignacco et al., 2012). Boyer et al. study reported routine sucrose alone had no effect on the change in cortisol level and variability of heart rate which resulted from repeated procedural pain for preterm infants (Boyer et al., 2004). However, these previous studies differed from our study in the fol- lowing respects: (1) The method of evaluating procedural pain: we assessed preterm infants’ pain not only using Preterm Infant Pain

Profile, but also using physiological and behavioral response, whereas other studies only used a pain scale, or physiological and behavioral response to measure preterm infants’ pain. (2) The methodological as- pect of study design: enough sample size used in our study, while small sample size in Gaspardo et al. study and moderate attrition rates in Boyer et al. study. These results suggest that clinicians in Neonatal Intensive Care Unit can provide non-nutritive sucking and sucrose to reduce preterm infants’ repeated procedural pain.

It is worthwhile to note that we could not find any study that compared the analgesic effects of non-nutritive sucking in preterm in- fants to the analgesic effects of sucrose during repeated painful proce- dure. Our findings indicated that the analgesic effects of non-nutritive sucking in preterm infants was similar to that of sucrose during re- peated painful procedure. These study results provide an alternative to sucrose to relieve preterm infants’ repeated procedural pain.

However, we consider that either sucrose or non-nutritive sucking is not perfect analgesics, because both of them couldn’t reduce preterm infants’ physiological response following by repeated procedural pain. This present study demonstrated that the PIPP score, percentage of crying time, and magnitude of physiological response following by re- peated painful procedures were lowest in the combination of sucrose and non-nutritive sucking group, which indicated that sucrose plus non- nutritive sucking produced the most efficacious means of pain reduc- tion for repeated painful procedures. To date, only one study has evaluated the effect of sucrose combined with non-nutritive sucking on repeated procedural pain for preterm infants, which reported PIPP score was significantly lower in the sucrose with pacifier intervention group compared with the standard care group (Stevens et al., 2005). Yet in Stevens et al. study, the Premature Infant Pain Profile (PIPP) scores were not available on all preterm infants at all fixed data collection points due to some of the infants did not receive routine painful pro- cedure at each time point, which may affect the reliability of the con- clusion. The specific contribution of our study was that we analyzed exclusively sucrose in comparison to nonnutritive sucking, their

Table 3 Within-group comparison of pain measurement parameters during the repeated three heel sticks.

Baselinea Blood collectiona Recoverya P (one-way RM ANOVA)

PIPP score Routine care group – 13.3 ± 1.6 10.6 ± 1.9 P < 0.0001 Nonnutritive sucking group – 9.3 ± 1.3 6.8 ± 1.4 P < 0.0001 Sucrose group – 10.1 ± 2.0 7.4 ± 1.6 P < 0.0001 Combination group – 4.4 ± 1.5 3.0 ± 0.8 P < 0.0001

Heat rate (beats/min) Routine care group 133.1 ± 5.8b,c 156.8 ± 7.2 151.7 ± 7.9 P < 0.0001 Nonnutritive sucking group 137.0 ± 5.8b,d 154.2 ± 9.0 148.0 ± 9.3 P < 0.0001 Sucrose group 133.4 ± 5.6b,e 151.6 ± 9.6 147.9 ± 6.9 P < 0.0001 Combination group 134.7 ± 6.1b,f 138.6 ± 7.9 137.4 ± 4.7 0.080

Oxygen saturation (%) Routine care group 95.7 ± 1.5b,c 92.9 ± 2.1 93.8 ± 1.6 P < 0.0001 Nonnutritive sucking group 95.8 ± 0.9b,d 92.9 ± 2.4 94.1 ± 1.0 P < 0.0001 Sucrose group 96.1 ± 1.5b,e 93.5 ± 1.7 94.5 ± 1.2 P < 0.0001 Combination group 96.1 ± 1.2b,f 95.2 ± 1.6 96.0 ± 1.2 0.024

Percentage of crying time (%) Routine care group 0b,c 80.6 ± 7.6 68.2 ± 9.9 P < 0.0001 Nonnutritive sucking group 0b,d 44.2 ± 9.6 31.2 ± 10.5 P < 0.0001 Sucrose group 0b,e 53.8 ± 16.7 35.2 ± 13.9 P < 0.0001 Combination group 0b,g 11.5 ± 8.6 4.6 ± 3.4 P < 0.0001

Note: Data are listed as mean ± SD. PIPP: premature infant pain profile. a Mean (standard deviation). b Bonferroni correction for multiples comparisons. c Significant difference when compared with recovery–Routine Care group (P < 0.05). d Significant difference when compared with recovery–Nonnutritive sucking group (P < 0.05). e Significant difference when compared with recovery–Sucrose group (P < 0.05). f No significant difference when compared with recovery–Combination group (P > 0.05). g Significant difference when compared with recovery–Combination group (P < 0.05).

H. Gao et al. International Journal of Nursing Studies 83 (2018) 25–33

31

 

 

combination and routine care, whereas Stevens et al. used combined sucrose plus pacifier in the same group in comparison with pacifier plus water and standard care.

Furthermore, our results found that preterm infants’ mean heart rate and oxygen saturation in the recovery phase had been back to baseline phase, and the percentage of crying time in the recovery phase had been near to baseline phase in the combination group (Table 3). The ability to recover quickly is a sign of ability to maintain homeostasis, a major task that the very preterm neonate must accomplish in order to grow and develop (Moore and Anderson, 2007). In summary, the combination of sucrose and non-nutritive sucking could have a better analgesic effect on repeated procedural pain than both methods sepa- rately. The plausible reason could be the multimodal stimulation that the preterm infant experiences when sucrose and non-nutritive sucking were administered together. These findings can guide nurses and other clinicians to combine sucrose and non-nutritive sucking to minimize preterm infants’ repeated procedural pain.

Establishing the safety of sucrose, non-nutritive sucking and their combination for repeated procedural pain might be the first priority. Our study demonstrated no significant difference in the incidence of adverse events between different groups. Thus, it indicates sucrose, non-nutritive sucking or their combination had no short-term side ef- fects on the health status of the preterm infants. Other authors have reported the similar results (Banga et al., 2016; Gaspardo et al., 2008; Stevens et al., 2005; Taddio et al., 2008).

The strengths of the present study included: (1) It was a randomized controlled trial with sufficient sample size. (2) Multiple outcome vari- ables (PIPP score, behavioral and physiological response) were used to evaluate the effect of sucrose, non-nutritive sucking, and in combina- tion on repeated procedural pain, which not only provided a detailed analysis over the entire sampling period, but also examined their ef- fectiveness on the overall changes in the summary scores. (3) Videotaping, evaluating, offering treatment conditions were performed by different persons respectively, which enhanced the internal validity of the study results.

Despite its strengths, the study had some limitations: (1) Preterm infants enrolled in the study were stable and aged more than 30 weeks. Thus, its results can not be generalized to the unstable and extremely preterm infants. (2) The study only focused on the analgesic effects of sucrose, non-nutritive sucking and their combination on repeated heel sticks, yet whether they could have the same analgesic effects on other repeated procedural pain as on repeated heel sticks had not been de- termined by the study. (3) The study examined the short-term safety of repeated sucrose, non-nutritive sucking and their combination for preterm infants, while the long-term impact of repeatedly offering a pacifier or sucrose or in combination during repeated procedural pain on preterm infants’ readiness for breastfeeding, weight gain and even neurobehavioral development had not been discussed. (4) The Premature Infant Pain Profile especially its grimacing indicator evalu- ating procedure was impossible to be completely blind, because non- nutritive sucking had to be continued until 1 min after the painful procedure. (5) The control condition for our study was routine care, which might have led to unnecessary pain for preterm infants assigned to this condition, although this limitation was minimized by offering preterm infants in this condition gentle touch.

The implications for future research and practice may be as follows: Firstly, future studies should include the preterm infants with gesta- tional age less than 30 weeks and being medically unstable, and then examine and compare the efficacy and safety of sucrose, non-nutritive sucking, and their combination for repeated procedural pain in them. Secondly, researchers can further evaluate the effects of sucrose, non- nutritive sucking, and their combination on different types of repeated procedural pain except heel stick pain in preterm infants. Thirdly, further randomized controlled trials are needed to examine the long- term impact of repeatedly offering a pacifier or sucrose or their com- bination in repeated procedural pain on preterm infants during their

stay in neonatal intensive care unit.

5. Conclusion

Both sucrose and non-nutritive sucking have a good analgesic effect for preterm infants on repeated procedural pain, but a combination of the two interventions shows better efficacy. Our results provide evi- dence supporting clinicians’ incorporation of the combined use of su- crose and non-nutritive sucking into clinical practice while preterm infants undergo repeated painful procedures. Thus, when both sucrose and non-nutritive sucking can be provided in a unit, the combination of them could be recommended as an analgesic alternative for repeated pain exposure in preterm infants.

Acknowledgments

We acknowledge the financial contribution of National Natural Science Foundation of China (81703246), the Preponderant Discipline Project of Universities in Jiangsu Province, Nursing Science Open Fund of Nanjing University of Chinese Medicine (YSHL2016-018), Top-notch Academic Programs Project of Jiangsu Higher Education Institutions (PPZY2015C258) and Project of nursing science in Nanjing University of Chinese Medicine (NZYHLXPPJG2017-54).

References

Avena, N.M., Rada, P., Hoebel, B.G., 2008. Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci. Biobehav. Rev. 32 (1), 20–39.

Bahman Bijari, B., Iranmanesh, S., Eshghi, F., Baneshi, M.R., 2012. Gentle human touch and yakson: the effect on preterm’s behavioral reactions. ISRN Nurs. 750363.

Banga, S., Datta, V., Rehan, H.S., Bhakhri, B.K., 2016. Effect of sucrose analgesia, for repeated painful procedures, on short-term neurobehavioral outcome of preterm neonates: a randomized controlled trial. J. Trop. Pediatr. 62 (2), 101–106.

Blass, E.M., Watt, L.B., 1999. Suckling- and sucrose-induced analgesia in human new- borns. Pain 83, 611–623.

Boyer, K., Johnston, C., Walker, C.D., Filion, F., Sherrard, A.l., 2004. Does sucrose an- algesia promote physiologic stability in preterm neonates. Biol. Neonate 85 (1), 26–31.

Brummelte, S., Grunau, R.E., Chau, V., Poskitt, K.J., Brant, R., Vinall, J., Gover, A., Synnes, A.R., Miller, S.P., 2012. Procedural pain and brain development in premature newborns. Ann. Neurol. 71 (3), 385–396.

Chen, M., Shi, X., Chen, Y., Cao, Z., Cheng, R., Xu, Y., Liu, L., Li, X., 2012. A prospective study of pain experience in a neonatal intensive care unit of China. Clin. J. Pain 28 (8), 700–704.

Cignacco, E.L., Sellam, G., Stoffel, L., Gerull, R., Nelle, M., Anand, K.J., Engberg, S., 2012. Oral sucrose and facilitated tucking for repeated pain relief in preterms: a rando- mized controlled trial. Pediatrics 129 (2), 299–308.

Cruz, M.D., Fernandes, A.M., Oliveira, C.R., 2016. Epidemiology of painful procedures performed in neonates: a systematic review of observational studies. Eur. J. Pain 20 (4), 489–498.

Doesburg, S.M., Chau, C.M., Cheung, T.P., Moiseev, A., Ribary, U., Herdman, A.T., Miller, S.P., Cepeda, I.L., Synnes, A., Grunau, R.E., 2013. Neonatal pain-related stress, functional cortical activity and visual-perceptual abilities in school-age children born at extremely low gestational age. Pain 154, 1946–1952.

Gao, H., Gao, H., Xu, G., Li, M., Du, S., Li, F., Zhang, H., Wang, D., 2016. Efficacy and safety of repeated oral sucrose for repeated procedural pain in neonates: a systematic review. Int. J. Nurs. Stud. 62, 118–125.

Gaspardo, C.M., Miyase, C.I., Chimello, J.T., Martinez, F.E., Martins Linhares, M.B., 2008. Is pain relief equally efficacious and free of side effects with repeated doses of oral sucrose in preterm neonates. Pain 137 (1), 16–25.

Gibbins, S., Stevens, B., McGrath, P.J., Yamada, J., Beyene, J., Breau, L., Camfield, C., Finley, A., Franck, L., Johnston, C., Howlett, A., McKeever, P., O’Brien, K., Ohlsson, A., 2008. Comparison of pain responses in infants of varying gestational ages. Neonatology 93 (1), 10–18.

Goubet, N., Clifton, R., Shah, B., 2001. Learning about pain in preterm newborns. J. Dev. Behav. Pediatr. 22 (6), 418–424.

Grunau, R.E., 2002. Early pain in preterm infants: a model of long-term effects. Clin. Perinatol. 29 (3), 373–394.

Herrington, C.J., Chiodo, L.M., 2014. Human touch effectively and safely reduces pain in the newborn intensive care unit. Pain Manag. Nurs. 15 (1), 107–115.

Jeong, I.S., Park, S.M., Lee, J.M., Choi, Y.J., Lee, J., 2014. The frequency of painful procedures in neonatal intensive care units in South Korea. Int. J. Nurs. Pract. 20 (4), 398–407.

Kocek, M., Wilcox, R., Crank, C., Patra, K., 2016. Evaluation of the relationship between opioid exposure in extremely low birth weight infants in the neonatal intensive care unit and neurodevelopmental outcome at 2 years. Early Hum. Dev. 92, 29–32.

Lax, I.D., Duerden, E.G., Lin, S.Y., Mallar, Chakravarty M., Donner, E.J., Lerch, J.P.,

H. Gao et al. International Journal of Nursing Studies 83 (2018) 25–33

32

 

 

Taylor, M.J., 2013. Neuroanatomical consequences of very preterm birth in middle childhood. Brain Struct. Funct. 218 (2), 575–585.

Liu, Y., Huang, X., Luo, B., Peng, W., 2017. Effects of combined oral sucrose and non- nutritive sucking (NNS) on procedural pain of NICU newborns, 2001 to 2016: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore) 96 (6), e6108.

Ludington-Hoe, S.M., Hosseini, R., Torowicz, D.L., 2005. Skin-to skin contact (Kangaroo Care) analgesia for preterm infant heel stick. AACN Clin. Issues 16 (3), 373–387.

Moore, E.R., Anderson, G.C., 2007. Randomized controlled trial of very early mother- infant skin-to-skin contact and breastfeeding status. J. Midwifery Womens Health 52 (2), 116–125.

Naughton, K.A., 2013. The combined use of sucrose and nonnutritive sucking for pro- cedural pain in both term and preterm neonates: an integrative review of the lit- erature. Adv. Neonatal Care 13 (1), 9–19.

Nunes, E.A., Medeiros, L.F., de Freitas, J.S., Macedo, I.C., Kuo, J., de Souza, A., Rozisky, J.R., Caumo, W., Torres, I.L., 2017. Morphine exposure during early life alters thermal and mechanical thresholds in rats. Int. J. Dev. Neurosci. 60, 78–85.

Nuseir, K.Q., Alzoubi, K.H., Alabwaini, J., Khabour, O.F., Kassab, M.I., 2015. Sucrose- induced analgesia during early life modulates adulthood learning and memory for- mation. Physiol. Behav. 145, 84–90.

Pillai Riddell, R.R., Racine, N.M., Gennis, H.G., Turcotte, K., Uman, L.S., Horton, R.E., Ahola Kohut, S., Hillgrove Stuart, J., Stevens, B., Lisi, D.M., 2015. Non-pharmaco- logical management of infant and young child procedural pain. Cochrane Database Syst. Rev. 12, CD006275.

Prechtl, H.F.R., Beintema, D., 1977. The neurological examination of the full term new- born infant. Clin. Dev. Med. 63.

Prechtl, H.F.R., 1974. The behavioral states of the newborn infant: a review. Brain Res. 76, 185–212.

Ranger, M., Synnes, A.R., Vinall, J., 2014. Internalizing behaviours in school-age children

born very preterm are predicted by neonatal pain and morphine exposure. Eur. J. Pain 18 (6), 844–852.

Skranes, J., Løhaugen, G.C., Evensen, K.A., Indredavik, M.S., Haraldseth, O., Dale, A.M., Brubakk, A.M., Martinussen, M., 2012. Entorhinal cortical thinning affects perceptual and cognitive functions in adolescents born preterm with very low birth weight (VLBW). Early Hum. Dev. 88 (2), 103–109.

Smith, G.C., Gutovich, J., Smyser, C., Pineda, R., Newnham, C., Tjoeng, T.H., Vavasseur, C., Wallendorf, M., Neil, J., Inder, T., 2011. Neonatal intensive care unit stress is associated with brain development in preterm infants. Ann. Neurol. 70 (4), 541–549.

Stevens, B., Johnston, C., Petryshen, P., Taddio, A., 1996. Premature infant pain profile: develo-pment and initial validation. Clin. J. Pain 12 (1), 13–22.

Stevens, B., Yamada, J., Beyene, J., Gibbins, S., Petryshen, P., Stinson, J., Narciso, J., 2005. Consistent management of repeated procedural pain with sucrose in preterm neonates: is it effective and safe for repeated use over time? Clin. J. Pain 21 (6), 543–548.

Stevens, B., Yamada, J., Ohlsson, A., Haliburton, S., Shorkey, A., 2016. Sucrose for an- algesia in newborn infants undergoing painful procedures. Cochrane Database Syst. Rev. 16 (7), CD001069.

Taddio, A., Shah, V., Hancock, R., Smith, R.W., Stephens, D., Atenafu, E., Beyene, J., Koren, G., Stevens, B., Katz, J., 2008. Effectiveness of sucrose analgesia in newborns undergoing painful medical procedures. CMAJ 179 (1), 37–43.

Thakkar, P., Arora, K., Goyal, K., Das, R.R., Javadekar, B., Aiyer, S., Panigrahi, S.K., 2016. To evaluate and compare the efficacy of combined sucrose and non-nutritive sucking for analgesia in newborns undergoing minor painful procedure: a randomized con- trolled trial. J. Perinatol. 36 (1), 67–70.

Vinall, J., Miller, S.P., Synnes, A.R., Grunau, R.E., 2013. Parent behaviors moderate the relationship between neonatal pain and internalizing behaviors at 18 months cor- rected age in children born very prematurely. Pain 154, 1831–1839.

H. Gao et al. International Journal of Nursing Studies 83 (2018) 25–33

33

 

  • Effect of non-nutritive sucking and sucrose alone and in combination for repeated procedural pain in preterm infants: A randomized controlled trial
    • What is already known about the topic?
    • What this paper adds
    • Introduction
    • Methods
      • Design
      • Setting and sample
      • Conditions in the four groups
        • The condition in the routine care group
        • The condition in the non-nutritive sucking group
        • The condition in the sucrose group
        • The condition in the combined oral sucrose and non-nutritive sucking group
      • Measures
        • Measurement of procedural pain
        • Measurement of physiological response
        • Measurement of behavioral response
        • Measurement of incidence of adverse events
      • Procedures
      • Data analysis
    • Results
      • Preterm infant characteristics
      • Comparison of pain measurement parameters during the three repeated heel sticks between groups
        • Between-group differences in pain measurement parameters during the repeated three heel sticks
        • Within-group differences in pain measurement parameters during the repeated three heel sticks
      • Comparison of incidence of adverse events in the study period between groups
    • Discussion
    • Conclusion
    • Acknowledgments
    • References