Multisensory stimulation as a non-pharmacological intervention for neonates undergoing painful procedures: A scoping review

Abstract

AIM:

The aim of this review is to identify available evidence on MSS practices as a pain-relieving intervention among neonates undergoing a repetitive painful procedure.

METHODS:

Searches were performed in the following databases: PubMed/ MEDLINE, SCOPUS, CINAHL, and the physiotherapy evidence database (PEDro). A total of eight studies were identified, among them; studies related to MSS in relieving neonatal procedural pain were conducted only in three countries only.

RESULTS:

Data collected from the identified studies were extracted by two independent reviewers, and were synthesized quantitatively, and qualitatively. Eight studies involving six hundred and eighty-six neonates in three countries were identified in the search. Among them, six were randomized controlled trials, and two were observational studies. The study results highlighted that implementation of MSS as a non-pharmacological pain-relieving intervention follows a similar protocol among the reviewed articles, but varies by who administers MSS (Physiotherapists/ Nurses/Mothers) in neonates undergoing repetitive painful procedures.

INTERPRETATION:

Standardized MSS protocol should be followed globally along with its implementation for reducing procedural pain among neonates and also to promote good clinical practice in neonatal intensive care unit (NICU) settings. Future research could determine the effects of standardized MSS protocol either with or without other non-pharmacological interventions among neonates undergoing painful procedures.

Keywords

Analgesia neonates procedural pain physiotherapy

1 Introduction

Pain in neonates is difficult to assess due to their inability to express pain verbally. Repeated painful procedures are very common in newborns that require neonatal intensive care [1]. They are exposed to significant painful procedures when their nervous system is developing. Neonates undergo 7 to 17 painful procedures per week when they are admitted to neonatal intensive care unit (NICU) [2]. Neonatal procedural pain has detrimental effects on future pain response, neurodevelopmental maturity, and sensory processing. Acute painful stimuli lead to alterations in behavioral responses, and physiological parameters in neonates undergoing repetitive painful procedures [3]. Painful procedures commonly performed in NICU are mainly for investigatory, remedial, and surgical purposes. Among them, investigatory (Heel pricking/ lancing, venipuncture, lumbar puncture, and arterial puncture) and remedial (Intramuscular injection, chest physiotherapy, and dressing change) painful procedures are routinely performed in NICU [3]. The top three common procedures performed in NICU are heel blood sampling, endotracheal aspiration, and intravenous cannula [4].

Untreated procedural pain leads to short- and long-term consequences. Short-term consequences include altered behavior responses (grimacing, crying, and withdrawal), and autonomic responses (increase in Heart rate, respiratory rate, Blood pressure, and oxygen saturation), which further leads to an increase in excitability in the spinal cord [5]. Over-excitability of the spinal cord due to repetitive painful stimuli leads to long-term consequences. These long-term consequences are mainly associated with sensory processing, future pain response, behavior alterations, sensorimotor and cognitive development, which may persist into adolescence and young adulthood [6]. Chronic pain due to repetitive painful stimuli stimulates the hypothalamic pituitary axis, which causes apoptosis of neural cells, and ultimately leads to intraventricular hemorrhage, and periventricular leukomalacia [7].

Neonatal pain management techniques are standard of care and provide analgesic effects to the neonates undergoing repetitive painful procedures in NICU [8]. Pain caused by minimally-invasive painful procedures can be reduced effectively by pharmacological (topical anesthetics, fentanyl) and non-pharmacological interventions (massage therapy, multisensory stimulation (MSS), oral glucose, and sucrose, facilitated tucking, non-nutritive sucking, aromatherapy, and music therapy) [9, 10]. Non-pharmacological pain-relieving interventions are considered ideal for routine pain management in NICU as compared to pharmacological pain-relieving interventions because they do not triggers drug-related side effects [11]. MSS is acknowledged as a potential pain-relieving strategy when administered in combination or without combination with any other non-pharmacological intervention. MSS provides different developmental sensory inputs consisting of visual, auditory, olfactory, tactile, gustatory, and kinesthetic sensations [12, 13]. it helps in releasing oxytocin, which is an anti-stress hormone and has longer pain reduction effects [5]. This scoping review aims to identify existing evidence on MSS practices as a pain-relieving intervention in neonates undergoing painful procedures.

2 Methodology

This scoping review followed the Arksey and O’Malley methodological framework, refined by Levac and O’Brien, and also following JBI methodology [14, 15]. This scoping review is the initial process of a systematic review registered under PROSPERO with unique reference no. CRD42022296248. This scoping review is also registered under Open Science Framework (OSF) on 15th July 2022, https://doi.org/10.17605/OSF.IO/AZ2WM

2.1 Need for this scoping review

This scoping review describes the current ongoing practices of MSS as a non-pharmacological intervention in decreasing procedural pain among preterm neonates. The ultimate need of this scoping review is to describe and facilitate complete reporting of MSS as an intervention, and standardized outcome measures used for assessing procedural pain.

2.2 Stage 1: Identifying the research question

The research question for scoping review has been drafted based on the PICOT(S) method by Sackett and colleagues [16] which was implemented for formulating the search strategy for this scoping review.

P (Population): Preterm and Term neonates experiencing procedural pain in NICU

I (Intervention): Multi-sensory stimulation/ Sensorial saturation

C (Comparator): Any/ No Comparator

O (Outcomes): Procedural pain

T (Time): Considered studies were not limited up to time to follow-up

S (Study design): Any type of study design was considered for this scoping review

2.2.1 Scoping Review question

What are the current practices of MSS globally on reducing procedural pain among preterm neonates admitted to NICU?

2.3 Stage 2: Identifying relevant studies

2.3.1 Search strategy and keywords

A comprehensive search strategy was conducted in the following databases: PubMed/ MEDLINE, SCOPUS, CINAHL, and Physiotherapy evidence database (PEDro). MeSH (Medical Subject headings) Keywords were searched using truncation and phrase symbols. The MeSH keywords used in combination were, neonate, preterm neonate, term neonate, infant, newborn, multisensory stimulation, multimodal stimulation, Sensorial saturation, Pain, and analgesia. All the potential keywords were linked with Boolean terms “AND” and “OR”. The databases were searched from inception to 6th June 2021. The search strategy was created and applied to PubMed/MEDLINE (Supplementary file 1), and then applied to other (PEDro, CINAHL, and SCOPUS) databases. Searches were limited to humans, filters related to age group (1–28 days of life), and articles in English languages were applied.

2.4 Stage 3: Study selection

The sources considered for this scoping review contains observational and experimental studies.

2.4.1 Selection criteria of studies for inclusion

PCC criteria, P: Population, Concepts, and Context was considered for formulating search strategy, and selection criteria for this scoping review. Inclusion criteria for study selection are displayed in Table 1.

Table 1
Inclusion criteria for study selection

Participants Concept Context

This scoping review examined all studies focused on the use of multisensory stimulation in preterm and term neonates undergoing painful procedures in NICU. This scoping review focused on implementation of MSS by health care professionals (Physicians, Nurses, and Physiotherapists) on preterm and term neonates. Preterm and term neonates undergoing painful procedures in NICU were considered as context for this scoping review.

Participants	Concept	Context
This scoping review examined all studies focused on the use of multisensory stimulation in preterm and term neonates undergoing painful procedures in NICU.	This scoping review focused on implementation of MSS by health care professionals (Physicians, Nurses, and Physiotherapists) on preterm and term neonates.	Preterm and term neonates undergoing painful procedures in NICU were considered as context for this scoping review.

Two team members (NS and AJS) reviewed the title and abstract independently, which is the first stage of screening. Study selection and extraction were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist [17] (Supplementary file 2). Rayyan software [18, 19] was used for data extraction. All the relevant and identified articles were uploaded to Rayyan for screening and data extraction. The scoping review process was displayed in a PRISMA flow diagram (Fig. 1). Full-text articles in English were identified and screened independently by the two reviewers. Hand searching was undertaken for retrieval articles to verify comprehensiveness.

Fig. 1

Flowchart of included studies.

2.5 Stage 4: Charting the data

Extracted data from the identified relevant studies were included in this scoping review by NS and AJS using a data extraction format [18] developed by reviewers for charting the data. The data extraction format was adapted from JBI guidelines [15] for scoping reviews to collect data from the included studies. The data extraction format included participant details, aim, and type of the study, intervention, and outcome details. Data were extracted by NS and then checked by AJS to ensure preciseness.

2.6 Stage 5: Collating, summarizing, and reporting

After data extraction a numerical (Quantitative) and thematic (Qualitative) analysis [20, 21] were undertaken to describe the included studies in terms of the study design, target population, interventions delivered, outcomes assessed, and also country information, where the study was performed. Overall, this endeavor is to describe the available literature/ evidence, and also to identify the research gaps in the current literature base.

3 Results

3.1 Literature search

The initial search produced 389 articles from the targeted databases. After removing duplicates, 81 articles were included for screening. Of these 24 were excluded after the title and abstract screening. The remaining 57 articles were retrieved for full-text. Of these, 49 articles were excluded and the reasons for their exclusion are mentioned in Fig. 1. The remaining 8 articles met eligibility criteria and were included in this scoping review.

3.2 Type of studies included

A total of 8 studies were included in this scoping review. Among them, 6 were randomized controlled trials (RCTs), and the other 2 were comparative studies. The studies were conducted in only 3 countries (6 in Italy, 1 in Iran, and 1 in Indonesia), and 2 continents (2 in Asia, 6 in Europe), Global representation of data is displayed in Fig. 2. Publication years ranged from 2001 and 2021. The painful procedures performed on neonates were heel stick/ prick, venipuncture, intramuscular injection (IMI), and screening for retinopathy. The identified studies focused on relieving procedural pain with sensorial saturation (SS)/MSS along with and without other pharmacological (fentanyl/topical anesthetic cream (TAC) and non-pharmacological measures (oral sucrose, glucose, distilled water and facilitated tucking).

Fig. 2

Global representation of current practices of MSS as a non-pharmacological intervention in NICU.

3.3 Participant characteristics

There were total of 686 neonates in the included studies for this scoping review. The neonates in these studies were preterm (4 studies) and full-term neonates (4 studies), with gestational ages of 27–41 weeks, and birth weight of 1000–4000 grams.

3.4 Outcome measures details

The included studies used the premature pain profile (PIPP), premature pain profile-revised (PIPP-R), crying requires increased oxygen administration, increased vital signs, expression, and sleeplessness (CRIES) Scale, ABC pain scale, and Douleur Aiguë Nouveau-né (DAN) Scale.

3.5 Comparators

Comparators in identified articles included non-pharmacological interventions such as oral glucose and sucrose, distilled water, facilitated tucking, breast milk, and pharmacological interventions such as fentanyl, and TCA. Pharmacological interventions have been included as a comparator in two studies, along with MSS and other non-pharmacological interventions among 8 selected studies. Out of 8, six studies have compared other non-pharmacological interventions with MSS.

3.6 Effects of SS/MSS on procedural pain among neonates

The terms used varied in the included studies: sensorial saturation (SS), and multisensory stimulation (MSS). Despite all included studies including SS/MSS as part of the pain-relieving intervention, a significant number of articles did not properly describe the SS/MSS input in sufficient detail. In most of the studies, SS was performed by mothers (n = 2), nurses (n = 1), physiotherapists (n = 3), and both nurses and parents (n = 2). In all studies, MSS/SS approaches were shown beneficial and positive effects on reducing pain in preterm and full-term neonates. Several studies compared SS/MSS with pharmacological (fentanyl/TCA), and non-pharmacological approaches (sucrose, glucose, distilled water, and facilitated tucking). SS shows a decrease in pain scores when compared with other non-pharmacological interventions (10% oral glucose and sucking, and distilled water). One study (n = 1) showed improvement in pain scores when treating neonates with fentanyl and SS [22]. SS combined with breast milk and sucrose has shown a significant reduction in pain scores (p < 0.001) when compared with 24% of sucrose only [23]. SS without any combination of other non-pharmacological interventions has shown a significant decrease in pain scores (p < 0.001) in neonates undergoing screening for retinopathy [24]. In most of the studies, SS consisted of auditory, tactile, taste, visual, and olfactory (ATTVO) sensations. A detailed summary of included studies is displayed in Table 2.

Table 2
Data extraction from included studies

Sr. No. Authors Country Purpose Population Procedure Intervention Outcomes Study design Findings

1. Carlo Valerio Bellieni et al. (2001) [25] Italy To determine the effects of SS and Oral glucose combined with sucking in relieving procedural pain 17 Preterm neonates Heel prick No intervention, 10% oral glucose and sucking, SS, oral distilled water, 10% Oral glucose without sucking PIPP Prospective randomized trial SS is more effective in relieving procedural pain

2. Carlo Valerio Bellieni et al. (2002) [12] Italy To determine the effects of SS along with oral glucose in relieving procedural pain 120 Term neonates Heel prick Glucose 33 %, Distilled water, 33% Glucose and sucking, SS, SS without sugar, No analgesia DAN Scale Randomized controlled trial SS given along with oral glucose potentiates analgesic effects

3. Carlo Valerio Bellieni et al. (2007) [26] Italy To identify analgesic effects of SS provided by mothers and nurses in relieving procedural pain 66 Term neonates Heel prick Glucose and sucking, SS by mothers, SS by nurses ABC Scale Randomized prospective trail SS provided by both mothers and nurses are effective

4. Eloisa Gitto et al. (2011) [22] Italy To test the utility of pharmacological and non- pharmacological interventions to relieve procedural pain due to heel-lancing 150 Preterm neonates Heel lance Fentanyl, Facilitated tucking, SS CRIES Prospective Randomized controlled trial SS and FE shows decrease in pain scores

5. Carlo Valerio Bellieni et al. (2013) [27] Italy To determine effects of pharmacological and non-pharmacological interventions in relieving pain caused by Intramuscular injections 62 Term neonates IMI Oral glucose, SS, Topic anesthetic cream DAN scale Observational study SS and Oral glucose reduces procedural pain

6. Hossein Zeerati et al. (2016) [29] Iran To determine the effects of MSS during eye examination for retinopathy screening 80 Preterm neonates Eye examination for retinopathy screening MSS (Visual, tactile, taste, and olfactory), No intervention PIPP Randomized controlled trial MSS is safe and beneficial in reducing pain

7. S. Perrone et al. (2017) [30] Italy To analyze the effects of SS and oral glucose in neonates undergoing heel pricking 83 Term neonates Heel pricking 1 ml of 10% glucose solution, SS ABC pain scale Observational study SS decreases pain scores along with oxidative stress

8. Siti Yuyun Rahayu Fitri et al. (2020) [23] Indonesia To compare the analgesic effects of SS with oral glucose, sucrose, and breast milk 108 Preterm and term neonates Venipuncture SS with Sucrose, SS with breast milk, Oral glucose alone PIPP-R Randomized controlled trial SS given along with sucrose and breast milk is more effective than glucose only

Sr. No.	Authors	Country	Purpose	Population	Procedure	Intervention	Outcomes	Study design	Findings
1.	Carlo Valerio Bellieni et al. (2001) [25]	Italy	To determine the effects of SS and Oral glucose combined with sucking in relieving procedural pain	17 Preterm neonates	Heel prick	No intervention, 10% oral glucose and sucking, SS, oral distilled water, 10% Oral glucose without sucking	PIPP	Prospective randomized trial	SS is more effective in relieving procedural pain
2.	Carlo Valerio Bellieni et al. (2002) [12]	Italy	To determine the effects of SS along with oral glucose in relieving procedural pain	120 Term neonates	Heel prick	Glucose 33 %, Distilled water, 33% Glucose and sucking, SS, SS without sugar, No analgesia	DAN Scale	Randomized controlled trial	SS given along with oral glucose potentiates analgesic effects
3.	Carlo Valerio Bellieni et al. (2007) [26]	Italy	To identify analgesic effects of SS provided by mothers and nurses in relieving procedural pain	66 Term neonates	Heel prick	Glucose and sucking, SS by mothers, SS by nurses	ABC Scale	Randomized prospective trail	SS provided by both mothers and nurses are effective
4.	Eloisa Gitto et al. (2011) [22]	Italy	To test the utility of pharmacological and non- pharmacological interventions to relieve procedural pain due to heel-lancing	150 Preterm neonates	Heel lance	Fentanyl, Facilitated tucking, SS	CRIES	Prospective Randomized controlled trial	SS and FE shows decrease in pain scores
5.	Carlo Valerio Bellieni et al. (2013) [27]	Italy	To determine effects of pharmacological and non-pharmacological interventions in relieving pain caused by Intramuscular injections	62 Term neonates	IMI	Oral glucose, SS, Topic anesthetic cream	DAN scale	Observational study	SS and Oral glucose reduces procedural pain
6.	Hossein Zeerati et al. (2016) [29]	Iran	To determine the effects of MSS during eye examination for retinopathy screening	80 Preterm neonates	Eye examination for retinopathy screening	MSS (Visual, tactile, taste, and olfactory), No intervention	PIPP	Randomized controlled trial	MSS is safe and beneficial in reducing pain
7.	S. Perrone et al. (2017) [30]	Italy	To analyze the effects of SS and oral glucose in neonates undergoing heel pricking	83 Term neonates	Heel pricking	1 ml of 10% glucose solution, SS	ABC pain scale	Observational study	SS decreases pain scores along with oxidative stress
8.	Siti Yuyun Rahayu Fitri et al. (2020) [23]	Indonesia	To compare the analgesic effects of SS with oral glucose, sucrose, and breast milk	108 Preterm and term neonates	Venipuncture	SS with Sucrose, SS with breast milk, Oral glucose alone	PIPP-R	Randomized controlled trial	SS given along with sucrose and breast milk is more effective than glucose only

Abbreviations: SS; Sensorial saturation, MSS: Multisensory stimulation, IMI; Intramuscular Injections, PIPP: Premature infant pain profile, PIPP-R; Premature infant pain profile-revised, CRIES; Crying requires increased oxygen administration, increased vital signs, expression and sleeplessness, DAN; Douleur Aiguë Nouveau-né Scale.

4 Discussion

This scoping review aimed to identify existing literature on current practices of SS/MSS as a non-pharmacological intervention to manage procedural pain among neonates admitted in NICU. The use of MSS/SS as a non-pharmacological intervention for relieving procedural pain has been studied previously by many experts [25 –27]. However, the protocol for using MSS as a non-pharmacological intervention varies for the term and preterm neonates. Oral glucose and sucrose were already considered a non-pharmacological interventions for managing procedural pain among neonates when administered alone [28]. It is included in the MSS program for stimulating taste sensation. Studies examining the effectiveness of oral glucose and sucrose compared with any other comparator other than MSS were not included in this scoping review because of the difficulty in isolating the effects of oral glucose/sucrose as non-pharmacological intervention on pain perception.

A total of 8 articles met the inclusion criteria for this review. According to the review of included articles, MSS is the most commonly used method for managing procedural pain among neonates. Although, 7 studies mentioned that they undertook MSS in combination with other methods such as breast milk, sucrose, glucose, and sucking, which are already considered as a part of MSS (taste sensation), and individually also as a non-pharmacological pain-relieving intervention. The previous reviews have already documented that MSS can produce pain reduction effects among neonates [2]. Hence, combining MSS with other non-pharmacological interventions can increase the analgesic effects as they target various sensory sensations, which can reduce procedural pain among neonates [2]. The terms used for MSS as an analgesic varied from study to study. An appropriate MSS protocol for managing procedural pain among neonates will reduce the adverse effects of MSS intervention. However, MSS is safer and beneficial in treating procedural pain among preterm and term neonates.

The protocol for implementing MSS was almost similar in every included study, but administration of sensory stimulation varies in terms of olfactive and taste sensory stimulation. Among 8 included studies, 4 studies have administered Auditory, Tactile, Taste, Visual and Olfactive stimulation (ATTVO). For olfactive stimulation, 0.64 g of vanilla 99% distilled in 100 ml of water solution have been used in one study [29], a baby perfume fragrance (Colonia Anal colica humana) was used in another study [13], and a baby oil fragrance (Babygella, Guieu Labs) was used in two studies [22, 25]. Other 4 included studies [23 , 30] out of 8, have administered ATTV only, without olfactive sensory stimulation. Taste sensory stimulation was administered in all included studies, but the percentage of glucose varies. Four studies used 1 ml of 33% glucose [13 , 29], three studies have used 1 ml of 10% glucose, [22 , 30] and one study have used 24% of sucrose for one group, and breast milk for another group as a taste sensory stimulation [23].

In most of the studies, the intervention was implemented for 15 min., 2 min.,and 30 s before the beginning of the painful procedure, and was continued throughout the procedure [26 , 29]. Procedural pain scales commonly used for assessing procedural pain are PIPP/PIPP-R, CRIES, DAN pain scale, and ABC pain scale, which are reliable and validated scales for measuring procedural pain in NICU. Among the 8 included studies, three studies have used PIPP/PIPP-R [23 , 29], two studies have used the ABC pain scale [26, 30], other two studies have used the DAN Pain scale [13, 27], and only one study has used the CRIES scale [22]. In most of the studies [26 , 29], the outcome assessment was evaluated through video-based observation and was done at the time of the painful procedure.

4.1 Effects of MSS on preterm neonates undergoing painful procedures in NICU

Out of 8 studies, four [22 , 29] studies have included preterm neonates with the gestational age of 27–36 weeks and 6 days. All four studies were RCTs. In all four studies, MSS consisted of ATTV administered. Along with ATTV, olfactory stimulation was administered in 3 studies, while in one study, only ATTV was administered. Olfactory stimulation was provided with vanilla essence (in 1 study), and baby oil (in 2 studies). Taste sensory stimulation was administered in all four studies. It was provided with 1 ml of 10% glucose (in 2 studies), 1 ml of 33% glucose (in 1 study), and 24% of sucrose in another (1) study. Among 4 studies, MSS was administered by mothers (in 1 study), therapists (in 2 studies), and by nurses (in 1 study). Outcome measures were assessed through PIPP/PIPP-R (in 3 studies), which is most reliable and valid scale for the preterm population, and with CRIES (in another 1 study). The result findings revealed that MSS protocol varies in all four studies performed on preterm neonates, in terms of olfactory, and taste sensory stimulations. Along with the interventions, outcome measures were also varied. PIPP/PIPP-R is the most common, reliable, and valid scale used in NICU for measuring procedural pain among preterm neonates. MSS helps in decreasing pain scores among preterm neonates during their NICU stay, but there is a definite need to establish a standardized protocol in terms of olfactory and taste sensory stimulations for relieving procedural pain among preterm neonates undergoing repetitive painful procedures.

4.2 Effects of MSS on term neonates undergoing painful procedures in NICU

Out of 8 studies, Another 4 studies [13 , 30] have recruited term neonates with the gestational age of 37 to 41 weeks. Two studies were RCTs, and another two were observational studies. MSS consisted of ATTV was administered in three studies, but only in one study, olfactory stimulation with baby perfume fragrance was provided. Taste sensory stimulation was common and administered in all four studies. It was provided with 1 ml of 33% glucose (in 3 studies), and 1 ml of 10% glucose (in 1 study). MSS administration also varies among the four included studies. It was administered by a therapist (in 1 study), by the mother (in 1 study), and by both mothers and nurses (in 2 studies). Outcomes were common and assessed with the DAN pain scale (in 2 studies), and the ABC pain scale (in 2 studies). The result findings revealed that the MSS protocol and its implementation varies from study to study, along with the outcome measures. MSS helps in decreasing pain scores among term neonates, but still, there is a definite need to establish standardized MSS protocol for promoting best clinical practice, and improving procedural pain among term neonates undergoing repetitive painful procedures.

4.3 Physiological aspects of MSS in reducing procedural pain among neonates

The sensory development occurs between 15 weeks -32 weeks of gestation [31]. Studies [12, 23] have shown the beneficial effects of MSS in reducing pain intensity among neonates undergoing repetitive painful procedures. The mechanism of pain reduction by MSS is still not clear, but some previous studies have tried to explain the mechanism of pain reduction by MSS. According to the American Academy of Pediatrics [8], MSS is more effective in reducing procedural pain than unimodal sensory stimulation, because MSS works through the mechanism of competition between painful stimuli and non-painful stimuli [12], which is also described as distraction strategies [23]. Stimulation of various sensory channels (auditory, tactile, visual, olfactory, taste, and vestibular) prevents nociceptive transmission in the spinal cord by the activation of gate control mechanisms to block nociceptive transmission [12]. Unimodal sensory stimulation did not provide an analgesic effect; rather they cause agitation in the neonate. Sensory stimulations given in combination potentiate analgesic effects of each other [12].

Sensory stimulation given in combination such as taste stimulation, leads to opioid release [23]. Taste stimulation given with breast milk or glucose leads to extensive cortical activation during a painful procedure confirmed by near infrared spectroscopy [23]. Breast milk contains tryptophan, which is a precursor of melatonin. Melatonin leads to opioid release of Beta-endorphin, which causes nociception blockade [23]. Also, olfactory stimulation provided with breast milk or vanilla increases the hemoglobin-oxygen bond in the orbitofrontal cortex of the brain, which further causes an increase in cerebral blood flow and relieves pain [23, 32]. MSS also deactivates the hypothalamic pituitary adrenal axis, which causes a decrease in serum cortisol (stress hormone) levels and an increase in Beta-endorphin levels [33].

Another study also demonstrated the effectiveness of MSS in pain and stress reduction among infants undergoing painful procedures [34, 35]. The mechanism of pain and stress reduction by MSS involves the secretion of the hypothalamic hormone, oxytocin, which releases during social interaction, and produces anti-stress effects. It is released when MSS is provided with touch or massage (tactile stimulation), interaction with neonate involving eye contact (visual stimulation), speaking with neonate (auditory stimulation), and feeding the neonate with breast milk (taste and olfactory) [34, 35]. Implementation of MSS through interaction with neonates helps in reducing pain and stress levels, confirmed by salivary cortisol levels in blood tests among neonates [34, 35].

Along with MSS, the use of other non-pharmacological approaches is also practiced nowadays for managing neonatal procedural pain in NICU. One recent review suggested that neonatal aquatic physiotherapy (NAPT) helps in decreasing pain and stress among admitted neonates [36]. It helps in normalizing muscle tone, improving sleep quality and patterns, and also helps in weight gain. It also promotes active movements, and postural organization [36]. NAPT is a flexible, and simple method for improving physical activity, and decreasing pain and stress among admitted neonates in NICU, and can be given along with MSS as a good clinical physiotherapy practice for promoting neuromotor behavior development, and reducing procedural pain and stress among neonates.

A recent RCT reported that MSS given along with movement therapy has beneficial effects on neuromotor behavior and pain among hospitalized preterm neonates [37]. Total of 32 preterm neonates with gestational age of 28 to 32 weeks were recruited in the trial. Intervention protocol consisted of multisensory stimulation (ATTVO) and movement therapy (Passive movements, antigravity movements, and upright positioning) were provided for 5 consecutive days of NICU stay [37]. The study results highlighted that MSS given in combination with movement therapy helps in improving neuromotor behavior, and weight gain, and also reduces pain among preterm neonates admitted in NICU [37].

4.4 Strengths and limitations

This scoping review applied a systematic search strategy that retrieves several articles to answer the review question and objectives. Standardized methodological frameworks by Arksey and O’Malley, Levac and O’Brien, and JBI guidelines were adapted for framing the methodological framework for this review. Search strings were framed according to the PICOTS method suggested by Sackett and colleagues [16]. However, some relevant articles published in other languages might be omitted. Peer-reviewed articles were only considered without assessing, whether their evidence existed in the grey literature.

4.5 Study Implication

Our review highlights that there is a definite need for more studies to conduct and demonstrate the effectiveness of MSS in relieving procedural pain among neonates admitted to NICU. This will help in establishing standardized protocol, and documenting good clinical practices that can be easily implemented in NICU settings.

5 Conclusion

This scoping review illustrates the global presentation of current practices of MSS as a non-pharmacological approach to managing procedural pain among neonates. The review reveals that MSS protocol varies in terms of olfactory and taste sensory stimulations, and also at the time of protocol administration. Outcome measures were also varied among included studies. However, this all included studies showed positive results for MSS in reducing procedural pain intensity. Future studies must establish more specific, detailed, and appropriate MSS protocol for reducing procedural pain among neonates undergoing painful procedures during NICU stay, and also for promoting best clinical practices in NICU settings.

Conflict of interest

None of the authors have competing interest declared.

Author’s contributions

N. Sharma contributed to the Collection of intellectual content, manuscript preparation and manuscript review. A.J. Samuel structured the concepts, design, and definition of intellectual content and manuscript review. Both the authors approved the manuscript.

Footnotes

Acknowledgments

NS is being supported by a five year “Innovation in Science Pursuit for Inspired Research (INSPIRE)” fellowship by Department of Science and Technology, Government of India (Ref No: IF190481) and registered for the structured PhD program (Roll no. 1820742) under the supervision of second author, AJS, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, Haryana, India 133207.

The supplementary material is available in the electronic version of this article: .

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