Non‐pharmacological interventions for the prevention of pain during endotracheal suctioning in ventilated neonates

Sofie Pirlotte; Katrien Beeckman; Isabel Ooms; Filip Cools

doi:10.1002/14651858.CD013353.pub2

. 2024 Jan 18;2024(1):CD013353. doi: 10.1002/14651858.CD013353.pub2

Non‐pharmacological interventions for the prevention of pain during endotracheal suctioning in ventilated neonates

Sofie Pirlotte ^1,^✉, Katrien Beeckman ², Isabel Ooms ³, Filip Cools ^1,^4,⁵

Editor: Cochrane Neonatal Group

PMCID: PMC10795104 PMID: 38235838

Abstract

Background

Pain, when treated inadequately, puts preterm infants at a greater risk of developing clinical and behavioural sequelae because of their immature pain system. Preterm infants in need of intensive care are repeatedly and persistently exposed to noxious stimuli, and this happens during a critical window of their brain development with peak rates of brain growth, exuberant synaptogenesis and the developmental regulation of specific receptor populations.

Nearly two‐thirds of infants born at less than 29 weeks' gestation require mechanical ventilation for some duration during the newborn period. These neonates are endotracheally intubated and require repeated endotracheal suctioning. Endotracheal suctioning is identified as one of the most frequent and most painful procedures in premature infants, causing moderate to severe pain. Even with improved nursing performance and standard procedures based on neonatal needs, endotracheal suctioning remains associated with mild pain.

Objectives

To evaluate the benefits and harms of non‐pharmacological interventions for the prevention of pain during endotracheal suctioning in mechanically ventilated neonates. Non‐pharmacological interventions were compared to no intervention, standard care or another non‐pharmacological intervention.

Search methods

We conducted searches in June 2023 in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, Embase, CINAHL and three trial registries. We searched the reference lists of related systematic reviews, and of studies selected for inclusion.

Selection criteria

We included randomised controlled trials (RCTs), quasi‐RCTs and cluster‐RCTs that included term and preterm neonates who were mechanically ventilated via endotracheal tube or via tracheostomy tube and required endotracheal suctioning performed by doctors, nurses, physiotherapists or other healthcare professionals.

Data collection and analysis

Our main outcome measures were validated composite pain scores (including a combination of behavioural, physiological and contextual indicators). Secondary outcomes included separate physiological and behavioural pain indicators.

We used standard methodological procedures expected by Cochrane. For continuous outcome measures, we used a fixed‐effect model and reported mean differences (MDs) with 95% confidence intervals (CIs). For categorical outcomes, we reported the typical risk ratio (RR) and risk difference (RD) and 95% CIs. We assessed risk of bias using the Cochrane RoB 1 tool, and assessed the certainty of the evidence using GRADE.

Main results

We included eight RCTs (nine reports), which enroled 386 infants, in our review. Five of the eight studies were included in a meta‐analysis. All studies enrolled preterm neonates.

Facilitated tucking versus standard care (four studies)

Facilitated tucking probably reduces Premature Infant Pain Profile (PIPP) score during endotracheal suctioning (MD −2.76, 95% CI 3.57 to 1.96; I² = 82%; 4 studies, 148 infants; moderate‐certainty evidence).

Facilitated tucking probably has little or no effect during endotracheal suctioning on: heart rate (MD −3.06 beats per minute (bpm), 95% CI −9.33 to 3.21; I² = 0%; 2 studies, 80 infants; low‐certainty evidence); oxygen saturation (MD 0.87, 95% CI −1.33 to 3.08; I² = 0%; 2 studies, 80 infants; low‐certainty evidence); or stress and defensive behaviours (SDB) (MD −1.20, 95% CI −3.47 to 1.07; 1 study, 20 infants; low‐certainty evidence).

Facilitated tucking may result in a slight increase in self‐regulatory behaviours (SRB) during endotracheal suctioning (MD 0.90, 95% CI 0.20 to 1.60; 1 study, 20 infants; low‐certainty evidence).

No studies reported intraventricular haemorrhage (IVH).

Familiar odour versus standard care (one study)

Familiar odour during endotracheal suctioning probably has little or no effect on: PIPP score (MD −0.30, 95% CI −2.15 to 1.55; 1 study, 40 infants; low‐certainty evidence); heart rate (MD −6.30 bpm, 95% CI −16.04 to 3.44; 1 study, 40 infants; low‐certainty evidence); or oxygen saturation during endotracheal suctioning (MD −0.80, 95% CI −4.82 to 3.22; 1 study, 40 infants; low‐certainty evidence).

No studies reported SRB, SDB or IVH.

White noise (one study)

White noise during endotracheal suctioning probably has little or no effect on PIPP (MD −0.65, 95% CI −2.51 to 1.21; 1 study, 40 infants; low‐certainty evidence); heart rate (MD −1.85 bpm, 95% CI −11.46 to 7.76; 1 study, 40 infants; low‐certainty evidence); or oxygen saturation (MD 2.25, 95% CI −2.03 to 6.53; 1 study, 40 infants; low‐certainty evidence).

No studies reported SRB, SDB or IVH.

Authors' conclusions

Facilitated tucking / four‐handed care / gentle human touch probably reduces PIPP score. The evidence of a single study suggests that facilitated tucking / four‐handed care / gentle human touch slightly increases self‐regulatory and approach behaviours during endotracheal suctioning.

Based on a single study, familiar odour and white noise have little or no effect on any of the outcomes compared to no intervention. The use of expressed breast milk or oral sucrose suggests that there is no discernible advantage of one method over the other for reducing pain during endotracheal suctioning. None of the studies reported on any of the prespecified secondary outcomes of adverse events.

Keywords: Humans; Infant; Infant, Newborn; Cerebral Hemorrhage; Gestational Age; Infant, Premature; Pain; Pain/etiology; Pain/prevention & control; Respiration, Artificial; Respiration, Artificial/adverse effects

Plain language summary

Medicine‐free management of neonates' pain during endotracheal suctioning

Key messages

— Gently holding the infant in a flexed posture (facilitated tucking, which is the gentle positioning of an infant's arms and legs in a bent, midline position close to the infant's body while the infant is lying on their side, lying on their back with their face upwards (supine), or lying on their tummy with their head to one side (prone)) is probably effective in reducing pain during endotracheal suctioning in ventilated newborn infants

What is endotracheal suctioning?

An endotracheal tube is a flexible plastic tube placed in the windpipe (trachea), through either the nose or mouth, to maintain an open airway in mechanically ventilated newborn infants (a mechanical ventilator is a machine to help the baby breathe).

The tip of the endotracheal tube is suctioned to keep it clean, open and free of secretions, enabling the infant to breathe oxygen. Endotracheal suctioning is a standard nursing procedure. It is painful and uncomfortable for the infant.

What did we want to find out?

We wanted to find out how to reduce infants' pain during endotracheal suctioning without using medicines.

What did we do?

We searched medical databases for clinical studies looking at ways to reduce infants' pain during endotracheal suctioning.

What did we find?

We found eight studies of 386 infants.

We assessed six different ways of reducing infants' pain during endotracheal suctioning without using medicines, such as:

– gently holding the infant in a facilitated tucking position;

– familiar odour (breast milk smell);

– use of a sugar solution (sucrose);

– use of expressed breast milk;

– white noise;

– swaddling.

Main results

In ventilated newborn infants

Facilitated tucking probably reduces pain during endotracheal suctioning.

Familiar odour and white noise have little or no effect during endotracheal suctioning. The use of expressed breast milk or oral sucrose suggests that there is no real advantage of one method over the other for reducing pain during endotracheal suctioning.

What are the limitations of the evidence?

There were not enough studies to be certain about the results in the review, and the staff were aware of which method was used to reduce pain. More studies are needed to support these results.

How up to date is this evidence?

The evidence is up to date to 21 June 2023.

Summary of findings

Summary of findings 1. Facilitated tucking / four‐handed care / gentle human touch compared with standard care for pain during endotracheal suctioning.

Facilitated tucking / four‐handed care / gentle human touch compared with standard care for pain during endotracheal suctioning
Patient or population: neonates with mechanical ventilation Settings: NICU Intervention: facilitated tucking / 4‐handed‐care / gentle human touch Comparison: standard care
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Standard care	Facilitated tucking / 4‐handed‐care / gentle human touch
Validated pain scales
PIPP during endotracheal suctioning Range of scale 0 to 21. Lower score = less pain	The mean PIPP during endotracheal suctioning in the control groups was 11.5, it ranged across control groups from 8.97 to 13.75	The mean PIPP during endotracheal suctioning in the intervention groups was 2.59 lower (8.02 to 9.75)	MD −2.76 (95% CI −3.57 to −1.96)	148 (4)	⊕⊕⊕⊝ Moderate^a	Facilitated tucking / 4‐handed care / gentle human touch probably reduces PIPP score during endotracheal suctioning.
Physiological indicators
Heart rate	The mean heart rate during endotracheal suctioning in the control group was 159.1 bpm	The mean heart rate during endotracheal suctioning in the intervention groups was 3.2 bpm lower	MD −3.06 bpm (95% CI −9.33 to 3.21)	80 (2)	⊕⊕⊝⊝ Low^a,b	Facilitated tucking / 4‐handed care / gentle human touch probably has little or no effect on heart rate during endotracheal suctioning.
SaO ₂ during endotracheal suctioning	The mean SaO ₂ during endotracheal suctioning in the control group was 90.5%	The mean SaO ₂ during endotracheal suctioning in the intervention group was 0.87% higher	MD 0.87% (95% CI −1.33 to 3.08)	80 (2)	⊕⊕⊝⊝ Low^a,b	Facilitated tucking / 4‐handed care / gentle human touch probably has little or no effect on SaO ₂ during endotracheal suctioning.
Behavioural indicators
SDB during endotracheal suctioning Range: 1 to 12 Higher number = more SDB	The mean SDB during endotracheal suctioning in the control group was 2.70	The mean SDB during endotracheal suctioning in the intervention group was 1.20 lower	MD −1.20 (95% CI −3.47 to 1.07)	20 (1)	⊕⊕⊝⊝ Low^a,b	Facilitated tucking / 4‐handed care / gentle human touch probably has little or no effect on SDB during endotracheal suctioning.
SRB during endotracheal suctioning Range: 1 to 12 Higher number = more SRB	The mean SRB during endotracheal suctioning in the control group was 0.30	The mean SRB during endotracheal suctioning in the intervention group was 0.90 higher	MD 0.90 (95% CI 0.20 to 1.60)	20 (1)	⊕⊕⊝⊝ Low^a,b	Facilitated tucking / 4‐handed care / gentle human touch may result in a slight increase in SRB during endotracheal suctioning.
Intraventricular haemorrhage
—	—	—	—	—	—	No studies reported this outcome.
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). Coping with stress was considered as terminating the physical stress due to suctioning in infant, as characterised by achieving scores of 1 or 0 based on the Neonatal Infant Pain Scale. bpm: beats per minute; CI: confidence interval; MD: mean difference; NICU: neonatal intensive care unit; PIPP: Premature Infant Pain Profile; SaO ₂ : oxygen saturation; SDB: stress and defensive behaviours; SRB:** self‐regulatory and approach behaviours.
GRADE Working Group grades of evidence High certainty: further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: we are very uncertain about the estimate.

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^a Downgraded one level because of severe study limitations (lack of blinding). ^b Downgraded one level because of imprecision of the estimate.

Summary of findings 2. Familiar odour (breast milk smell) compared with standard care for pain during endotracheal suctioning.

Familiar odour (breast milk smell) compared with standard care for pain during endotracheal suctioning
Patient or population: neonates with mechanical ventilation Settings: NICU Intervention: familiar odour (breast milk smell) Comparison: standard care
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Standard care	Familiar odour (breast milk smell)
Validated pain scores
PIPP during endotracheal suctioning Range of scale 0 to 21. Lower score = less pain	The mean PIPP during endotracheal suctioning in the control group was 11.4	The mean PIPP during endotracheal suctioning in the intervention group was 0.30 lower	MD −0.30 (95% CI −2.15 to 1.55)	40 (1)	⊕⊕⊝⊝ Low^{a, b}	Familiar odour probably has little or no effect on PIPP score during endotracheal suctioning.
Physiological indicators
Heart rate	The mean heart rate during endotracheal suctioning in the control group was 153.9 bpm	The mean heart rate during endotracheal suctioning in the intervention group was 2.8 bpm higher	MD −6.30 bpm (95% CI −16.04 to 3.44)	40 (1)	⊕⊕⊝⊝ Low^{a, b}	Familiar odour probably has little or no effect on heart rate during endotracheal suctioning.
SaO ₂ during endotracheal suctioning	The mean SaO ₂ during endotracheal suctioning in the control group was 87.5%	The mean SaO ₂ during endotracheal suctioning in the intervention group was 0.80% lower	MD −0.80% (95% CI −4.82 to 3.22)	40 (1)	⊕⊕⊝⊝ Low^{a, b}	Familiar odour probably has little or no effect on SaO ₂ during endotracheal suctioning.
Behavioural indicators
—	—	—	—	—	—	No studies reported this outcome.
Intraventricular haemorrhage
—	—	—	—	—	—	No studies reported this outcome.
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). Coping with stress was considered as terminating the physical stress due to suctioning in infant, as characterised by achieving scores of 1 or 0 based on the Neonatal Infant Pain Scale. bpm: beats per minute; CI: confidence interval; MD: mean difference; NICU: neonatal intensive care unit; PIPP: Premature Infant Pain Profile; SaO ₂ :** oxygen saturation.
GRADE Working Group grades of evidence High certainty: further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: we are very uncertain about the estimate.

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^a Downgraded one level because of severe study limitations (lack of blinding). ^b Downgraded one level because of imprecision.

Summary of findings 3. White noise compared with standard care for pain during endotracheal suctioning.

White noise compared with standard care for pain during endotracheal suctioning
Patient or population: neonates with mechanical ventilation Settings: NICU Intervention: white noise Comparison: standard care
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Standard care	White noise
Validated pain scores
PIPP during endotracheal suctioning Range of scale 0 to 21 Lower score = less pain	The mean PIPP during endotracheal suctioning in the control group was 11.4	The mean PIPP during endotracheal suctioning in the intervention group was 0.65 lower	MD −0.65 (95% CI −2.51 to 1.21)	40 (1)	⊕⊕⊝⊝ Low^a,b	White noise probably has little or no effect on PIPP score during endotracheal suctioning.
Physiological indicators
Heart rate	The mean heart rate during endotracheal suctioning in the control group was 159.3 bpm	The mean heart rate during endotracheal suctioning in the intervention group was 1.85 bpm lower	MD −1.85 bpm (95% CI −11.46 to 7.76)	40 (1)	⊕⊕⊝⊝ Low^a,b	White noise probably has little or no effect on heart rate during endotracheal suctioning.
SaO ₂	The mean SaO ₂ in the control group was 87.5%	The mean SaO ₂ in the intervention group was 2.25% higher	MD 2.25 (95% CI −2.03 to 6.53)	40 (1)	⊕⊕⊝⊝ Low^a,b	White noise probably has little or no effect on SaO ₂ during endotracheal suctioning.
Behavioural indicators
—	—	—	—	—	—	No studies reported this outcome.
Intraventricular haemorrhage
—	—	—	—	—	—	No studies reported this outcome.
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). Coping with stress was considered as terminating the physical stress due to suctioning in infant, as characterised by achieving scores of 1 or 0 based on the Neonatal Infant Pain Scale. bpm: beats per minute; CI: confidence interval; MD: mean difference; NICU: neonatal intensive care unit; PIPP: Premature Infant Pain Profile; SaO ₂ :** oxygen saturation.
GRADE Working Group grades of evidence High certainty: further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: we are very uncertain about the estimate.

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^a Downgraded one level because of severe study limitations (lack of blinding). ^b Downgraded one level because of imprecision.

Background

Description of the condition

Neonates, especially when preterm, are more sensitive to nociceptive stimuli than older children; this is because the functional ascending pain pathways capable of transmitting noxious impulses are present by 24 weeks' gestation, whilst the neurotransmitters that modulate the ascending impulse are absent until approximately 48 weeks' gestation ( Anand 2000a ; Hatfield 2014 ). Neuronal and synaptic organisation may be permanently altered by repetitive painful experiences in preterm neonates. The cerebral cortex is affected by neonatal pain and stress through multiple mechanisms. Pain causes neuronal cell death, and indirectly causes changes to the set‐point of stress‐sensitive endocrine systems. Pain, when treated inadequately, results in the immature pain system predisposing preterm infants to greater clinical and behavioural sequelae ( Anand 2000a ). Both animal experiments and human studies have shown that the immature nervous system is highly responsive to tactile and noxious stimuli. Neurophysiological recordings in newborn infants undergoing clinically required skin‐breaking procedures reveal strong spinal nociceptive reflex activity and distinct nociceptive cortical potentials in response to these procedures ( Cornelissen 2013 ; Fabrizi 2011 ; Slater 2010a ). The younger the postnatal age of the infant, the more prolonged this noxious‐evoked activity is ( Fitzgerald 1984 ; Hatfield 2014 ).

With advances in perinatal services and neonatal intensive care technology, the survival of extremely premature and critically ill infants has increased substantially ( Glass 2015 ). However, despite medical advances, a considerable number of these infants have long‐term sequelae, such as cerebral palsy, neurosensory impairments, learning disabilities and respiratory diseases ( Glass 2015 ; Younge 2017 ). In neonatal intensive care units (NICUs), preterm infants are repeatedly and persistently exposed to noxious stimuli, which results in profound and long‐lasting changes in nociceptive neural pathways ( Slater 2010a ). Preterm infants are exposed to these noxious stimuli during a critical window, towards the end of human gestation, where the relatively mature foetus undergoes an important period of brain development, peak rates of brain growth, exuberant synaptogenesis and the developmental regulation of specific receptor populations ( Anand 2000b ; Bhutta 2002 ; Brummelte 2012 ).

Nearly two‐thirds of infants born at less than 29 weeks' gestation require mechanical ventilation for some duration during the newborn period ( Giaccone 2014 ). These neonates are endotracheally intubated and require repeated endotracheal suctioning ( Cignacco 2009 ). Endotracheal suctioning is identified as one of the most frequent and most painful procedures in premature infants ( Hadian 2013 ; Ward‐Larson 2004 ). It causes moderate‐to‐severe pain. Endotracheal suctioning still causes mild pain in premature neonates, despite improvement of nursing performance and performing a standard procedure based on neonatal need ( Hadian 2013 ).

To manage pain in neonates validly and reliably, pain assessment is necessary. Many multidimensional pain assessment tools are available, yet pain remains insufficiently recognised and therefore often undertreated ( Manworren 2016 ; Walker 2014 ). There is a need not only to reduce acute behavioural responses to pain in neonates, but also to protect the developing nervous system from persistent sensitisation of pain pathways and avoid potential damaging effects of altered neural activity on central nervous system development ( Walker 2014 ).

Description of the intervention

The most obvious and effective strategy to reduce pain from repeated endotracheal suctioning is to reduce the frequency of suctioning. In addition, many different non‐pharmacological interventions aimed at reducing stress during painful procedures have been described and studied ( Attarian 2014 ). These include: sucrose and breast milk; non‐nutritive sucking; maternal holding or skin‐to‐skin; facilitated tucking, swaddling or cuddling; rocking or holding; touch or massage; familiar odour; video distraction and developmental care (limiting environmental stimuli, lateral positioning, the use of supportive bedding and attention to behavioural clues) ( Riddell 2015 ).

How the intervention might work

Studies have shown that behavioural and physiological responses to single acute noxious stimuli are reduced by non‐pharmacological interventions ( AAP 2016 ; da Motta Gde 2015 ; De Lima 2010 ; Johnston 2017 ; Ohlsson 2020 ; Riddell 2015 ; Stevens 2016 ). The use of these non‐pharmacological interventions not only seems to provide effective management of neonatal distress, but also gives greater satisfaction to both parents and clinical staff ( De Lima 2010 ).

Non‐pharmacological interventions have been shown to be useful in reducing pain from a heel prick, venipuncture, and intramuscular and subcutaneous injections in preterm and term neonates. They are generally more effective when used in combination than when used alone. According to the American Academy of Pediatrics (AAP) and a Cochrane review, no adverse events have been reported when using any non‐pharmacological interventions ( AAP 2016 ; Riddell 2015 ). A summary of how these interventions might work is outlined below.

Skin‐to‐skin care or kangaroo‐care is effective and safe in reducing pain for a single procedure, measured by both physiological and behavioural indicators. One Cochrane review reported no adverse effects ( Johnston 2017 ).
Facilitated tucking, swaddling or cuddling is the gentle containment of limbs near the trunk by bending the lower extremities and aligning the midline of the upper limbs bent. Placing the hand near the mouth promotes physiological and behavioural stability. Benefits of facilitated tucking, when the infant is wrapped in a blanket or nest and contained during painful procedures, include: decreased cry duration, stabilised sleep–wake cycle and fewer changes in heart rate. This practice also helps to maintain stability in the autonomic and motor systems and behavioural states. Studies have reported no adverse effects ( da Motta Gde 2015 ; Liaw 2012 ).
Non‐nutritive sucking on a pacifier or a gloved finger may decrease hyperactivity, regulate neonates' discomfort, and may reduce the intensity and duration of acute pain in neonates. The effect of non‐nutritive sucking is associated with increased oxygenation, improvement in respiratory and gastrointestinal functions, and decreased heart rate and energy expenditure. During rhythmic suction, the benefits occur with a possible rebound effect after interruption. Studies have reported no adverse effects ( da Motta Gde 2015 ; Liaw 2012 ).
According to one Cochrane review, sucking‐related interventions, swaddling/tucking‐related interventions, rocking/holding, touch/massage, familiar odour and video distraction have all been shown to be potentially effective, with no adverse effects documented; however, further research is necessary due to the poor quality of studies and lack of replication ( Riddell 2015 ).
Oral sucrose reduces procedural pain during venipuncture and intramuscular injection. Studies have reported minimal to no adverse effects. Small doses (0.01 g to 0.02 g) of 24% sucrose are effective in reducing pain in preterm infants. Cry‐time of term infants is reduced by larger doses of sucrose (0.24 g to 0.50 g) ( Stevens 2016 ). Although observed pain behaviour is reduced by oral sucrose, the magnitude of spinal nociceptive reflexes or the acute activation of pain networks in the brain showed no effect of oral sucrose during heel lance. It seems that oral sucrose does blunt facial expression activity rather than reducing direct nociceptive activity in central sensory circuits ( Slater 2010b ).
Oral sucrose and sucking eliminates the electroencephalographic changes associated with a painful procedure in neonates. However, the mechanism of pain relief from sucking oral sucrose remains unknown. There is a wide dosage range of sucrose for reducing pain in neonates from 0.012 g to 0.12 g administered orally, two minutes before the procedure. Studies have reported no serious adverse effects. An optimal dose and the long‐term safety of multiple doses has not yet been established ( AAP 2016 ; Stevens 2016 ).
Acupuncture, transcutaneous electrical nerve stimulation and non‐invasive electrical stimulation of acupuncture points (NESAP) are a group of interventions which activate endorphins and the descending pain inhibitory pathways. They are safe in neonates. Acupuncture is accepted worldwide in the treatment of acute and chronic pain in adults ( Han 2004 ). Transcutaneous electrical nerve stimulation, due to activation of the descending pain‐inhibitory pathway, has also led to pain reduction in adults ( Choi 2016 ). However, it is ineffective against heel‐prick pain in neonates ( Mitchell 2016 ).
Multisensorial stimulation combines auditory, gustative, tactile, vestibular and visual stimuli and has been described as pain relieving during the heel‐prick test. However, it did not demonstrate any pain relief during endotracheal suction, and it might even have led to possible overstimulation of the preterm infant ( Bellieni 2001 ).
White noise has been described as effective as pain relief during heel lance procedures ( Kahraman 2020 ) and vaccinations ( Kucukoglu 2016 ).

Why it is important to do this review

Review articles have reported the role of non‐pharmacological interventions during procedural pain in neonates ( Bueno 2013 ; Carbajal 2005 ; Cignacco 2007 ; Johnston 2017 ; Ohlsson 2020 ). The effect of these interventions exists for many different acute procedures. The role of non‐pharmacological interventions during endotracheal suction in ventilated neonates has not yet been appraised. Endotracheal suctioning is often administered by a nurse or a respiratory therapist ( Gardner 2009 ). Although there is an increase of adherence to national or international pain guidelines, infant pain remains undertreated. Reducing painful stimuli and identifying effective pain‐reducing interventions is an obligation of researchers and healthcare providers in the NICU. By performing this review, we hope to determine which types of non‐pharmacological interventions are effective in pain management during endotracheal suctioning in mechanically ventilated neonates.

Objectives

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs), quasi‐RCTs and cluster‐RCTs investigating non‐pharmacological interventions applied during the procedure of endotracheal suctioning, with the specific aim of reducing pain or stress caused by the suctioning procedure. We excluded studies about pain management for other procedures.

Types of participants

We included:

term and preterm neonates who were mechanically ventilated via endotracheal tube and required endotracheal suctioning conducted by doctors, nurses, physiotherapists or other healthcare professionals during their stay in the NICU;
term and preterm neonates who had a tracheostomy and required suctioning conducted by doctors, nurses, physiotherapists or other healthcare professionals during their stay in the NICU.

We classified term neonates as those whose gestational age at birth was from 37 completed weeks to a maximum of 44 weeks.

We classified preterm neonates using the World Health Organization (WHO) criteria ( WHO 2022 ).

Extremely preterm (less than 28 weeks' gestation)
Very preterm (28 to 32 weeks' gestation)
Moderate to late preterm (32 to 37 weeks' gestation)

Types of interventions

Interventions

We included non‐pharmacological interventions applied during the procedure of endotracheal suctioning, with the specific aim of reducing pain or stress caused by the suctioning procedure.

Environmental strategies: these included modifying the environment, such as low noise and lighting, clustering procedures and soothing smells, which may have influenced behavioural and physiological expressions of infants' pain ( Riddell 2015 ).
Behavioural strategies: these involved manipulation of the infant's body, either directly (e.g. holding) or indirectly (e.g. non‐nutritive sucking). It is within this domain that most research on non‐pharmacological interventions has been conducted ( Riddell 2015 ).

Comparators

Comparators included no intervention, standard care and another non‐pharmacological intervention.

Comparisons

Comparison 1: facilitated tucking / four‐handed care / gentle human touch

Facilitated tucking / four‐handed care / gentle human touch versus standard care
Facilitated tucking / four‐handed care / gentle human touch versus familiar odour (breast milk smell)
Facilitated tucking / four‐handed care / gentle human touch versus white noise

Comparison 2: familiar odour (breast milk smell)

Familiar odour (breast milk smell) versus standard care
Familiar odour (breast milk smell) versus white noise

Comparison 3: expressed breast milk

Expressed breast milk versus standard care
Expressed breast milk versus oral sucrose
Expressed breast milk versus swaddling

Comparison 4: white noise

White noise versus standard care

Comparison 5: swaddling

Swaddling versus standard care
Swaddling versus oral sucrose

Types of outcome measures

Primary outcomes

Pain and discomfort measured, using at least one of the following methods, during endotracheal suctioning ( Hadian 2013 ).

Validated composite pain scores (including a combination of behavioural, physiological and contextual indicators) measured during the painful procedure. Those assessed in one Cochrane review as being valid for neonates undergoing procedural pain included the following ( Stevens 2016 ).
- Premature Infant Pain Profile (PIPP; Stevens 1996 ): continuous scale, ranges from 0 to 21, the higher the score the more pain, included items are heart rate, oxygen saturation (SaO ₂ ), tightly closing the eyes, changes in nose‐lip and chin shape, bulging of the brow between the eyes, gestational age, mode of behaviour for pain assessment.
- PIPP revised (PIPP‐R; Stevens 2014 ): revision of the PIPP to address validity and feasibility issues; the minor revisions include changes to the physical layout, detailed instructions for use, and clarification of scoring gestational age and behavioural state indicators for preterm and term infants.
- Douleur Aiguë du Nouveau‐né Scale (DAN; Carbajal 1997 ): continuous scale, ranges from 0 to 10, the higher the score the more pain, included items are facial responses, limb movements and vocal expression of pain.
- Neonatal Infant Pain Scale (NIPS; Lawrence 1993 ); continuous scale, ranges from 0 (minimum pain) to 7 (maximum pain), included items are facial expression, crying, activity of arms, activity of legs, state of arousal and breathing pattern.
- Neonatal Facial Coding System (NFCS; Grunau 1987 ); an anatomically based measure in which the occurences of 10 different facial actions are individually coded, ranges from 0 (minimum pain) to 10 (maximum pain).
- Neurobehavioral Assessment of Preterm Infants (NAPI; Snider 2005 ): is a standardised neurodevelopmental assessment of the progression of early neurobehavioural performance in preterm infants from 32 weeks to term age of 38 to 40 weeks, including the following seven clusters: scarf sign (assessment of the tone of the shoulder girdle), motor development and vigour, popliteals angle, alertness and orientation, irritability, quality of cry and percent sleep ratings. Measurement in each cluster ranges from 0 to 100 points.
- Neonatal Pain Agitation and Sedation Scale (N‐PASS; Hummel 2010 ): continuous scale, ranges from −10 (deep sedation) to +10 (highest level of pain); items included are crying and irritability, behaviour state, facial expression, extremities and tone, and vital signs.
- Bernese Pain Scale for Neonates (BPSN; Cignacco 2004 ): a multidimensional pain assessment tool; included items are sleeping, crying, consolation, skin colour, facial expression, posture, breathing, heart rate and SaO ₂ .
- Astrid Lindgren Children's Hospital Pain Scale Neonates (ALPS‐Neo; Lundqvist 2014 ): continuous scale, ranges from 0 to 10, the higher the score the more pain; included items are facial expression, pattern of respiration, tone of the organs, activity of the hands and feet and level of activity.
Physiological indicator changes from baseline , final value outcomes or changes between groups in: heart rate, respiratory rate, SaO ₂ /transcutaneous oxygen tension (tcPO ₂ ), and near‐infrared spectroscopy (NIRS). These measures should be reported before, during and in the time to recovery following endotracheal suctioning.
Behavioural indicators , measured during the painful procedure, besides the known and validated pain and comfort scales (proportion of time of total procedure that had predefined facial actions reflecting grimace, e.g. brow bulge, eye squeeze, nasolabial furrow; proportion of time that had predefined body movements, e.g. limb thrashing, fisting, finger splaying, limb and torso flexion).

We recorded both changes from baseline values and differences in absolute scores between intervention and control groups. We included scores within 10 minutes of the painful intervention.

Secondary outcomes

All secondary outcome were assessed during hospitalisation. All studies were screened for reporting of adverse events.

Short‐term outcomes (occurring during endotracheal suctioning)
- Pulmonary
  - Gross air leak (pneumothorax, pneumomediastinum, pneumopericardium)
  - Atelectasis confirmed by X‐ray
  - Pulmonary hypertension confirmed by echocardiography
  - Ventilator‐associated pneumonia (VAP), as defined by the study investigators
  - Duration of mechanical ventilation (days)
  - Duration of need for supplemental oxygen (days)
  - Need for supplemental oxygen at 36 weeks' postmenstrual age
  - Moderate or severe bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age, as defined by the National Institute of Child Health and Human Development (NICHD) Workshop ( Jobe 2001 )
- Haemodynamic
  - Hypotension, as defined by the study investigators
  - Hypertension, as defined by the study investigators
- Neurological
  - Any grade intraventricular haemorrhage (IVH) ( Papile 1987 )
  - Severe IVH (Grade III and IV according to the Papile classification) ( Papile 1987 )
  - Cystic periventricular leukomalacia: presence of multiple echolucent cysts in the periventricular white matter
- Mortality
  - At 28 days' postnatal age
  - At 36 weeks' postmenstrual age
  - During hospitalisation
- Other
  - Nausea/vomiting
  - Duration of hospitalisation (total length of hospitalisation from birth to discharge home or death) (days)
  - Hormonal indicators (salivary cortisol, serum beta‐endorphins) obtained from body fluids (saliva, serum) with description of analyses (e.g. radioimmunoassay techniques)
Long‐term outcomes
- Cerebral palsy at 18 to 24 months' corrected age
- Neurological development at 18 to 24 months' corrected age
- Neurological development at school age (five to eight years)
Other adverse events

Search methods for identification of studies

Electronic searches

We searched the following databases on 21 June 2023 without date or language limits:

Cochrane Central Register of Controlled Trials (CENTRAL) via CRS Web (21 June 2023);
PubMed (1996 to 23 June 2023);
Ovid Embase (1980 to 21 June 2023);
CINAHL via EBSCOhost (1982 to 21 June 2023).

Search strategies are presented in Appendix 1 .

We searched the following clinical trial registries (June 2023).

US National Institutes of Health ClinicalTrials.gov ( clinicaltrials.gov) .
WHO International Clinical Trials Registry and Platform ICTRP ( trialsearch.who.int/Default.aspx );
ISRCTN Registry ( www.isrctn.com ).

Searching other resources

Additionally, we searched the reference lists of all identified articles, at the full‐text stage, for relevant articles not identified in the primary search.

We reviewed the reference list of one systematic review "Non‐pharmacological management of infant and young child procedural pain" ( Riddell 2015 ), for relevant articles not identified in the primary search.

We contacted study authors for additional or missing information. We excluded editorials, commentaries, reviews, lecture abstracts and letters to the editor because they did not contain original data.

We searched for errata or retractions from included studies published in full‐text on PubMed ( www.ncbi.nlm.nih.gov/pubmed ), and reported the date this was performed within the review.

Data collection and analysis

We used the standard methods of Cochrane and Cochrane Neonatal.

Selection of studies

We managed search results using EndNote . Two review authors (SP, KB) independently assessed titles and abstracts retrieved from the search for inclusion in this review according to prespecified selection criteria. Two review authors (SP, KB) screened the full‐text of papers requiring assessment. At any point in the screening process, we resolved disagreements through discussion. If not resolved, we consulted a third review author (FC). We entered and cross‐checked data using RevMan Web 2022 .

We collated multiple reports of the same study, so that each study rather than each report was the unit of interest in the review. The selection process was recorded in sufficient detail to complete a PRISMA flow diagram ( Moher 2009 ), and Characteristics of excluded studies table.

Data extraction and management

Two review authors (SP, IO) independently extracted data from the full‐text articles using a specifically designed spreadsheet including the following details.

Authors
Date and place of publication
Study design: methods of randomisation, number of arms in the trial, cross‐over design, number of centre
Inclusion and exclusion criteria
Number of participants in each arm (including dropouts)
Setting
Summary of study participant characteristics: gestational age and weight at birth, postmenstrual and postnatal age at time of enrolment, sex
Details of intervention (type of intervention, description of non‐pharmacological actions, duration of intervention) and control
Adverse events
Outcome measurements and assessment time points
Risk of bias
Any relevant additional comments reported by the study authors

We compared extracted data for any differences. We resolved differences through discussion. If necessary, we consulted a third review author (FC) to reach consensus.

Assessment of risk of bias in included studies

Two review authors (SP, KB) independently assessed the risk of bias (low, high, or unclear) of all included trials using the Cochrane RoB 1 tool ( Higgins 2017 ), for the following domains.

Sequence generation (selection bias)
Allocation concealment (selection bias)
Blinding of participants and personnel (performance bias)
Blinding of outcome assessment (detection bias)
Incomplete outcome data (attrition bias)
Selective reporting (reporting bias)
Any other bias

We resolved any disagreements by discussion or by consulting with a third review author (FC). See Appendix 2 for a more detailed description of risk of bias for each domain.

Measures of treatment effect

We used RevMan Web 2022 to analyse treatment effects in the individual trials.

Continuous data

We reported continuous data as mean difference (MD) with 95% confidence intervals (CI).

Dichotomous data

We reported dichotomous data using a risk ratio (RR) and risk difference (RD), with respective 95% CIs. For those outcomes with a statistically significant RD for the pooled estimate from the meta‐analysis, we calculated the number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH), and 95% CIs.

Unit of analysis issues

For parallel‐group studies with individual randomisation, the unit of analysis is the individual participant.

Data from cluster‐RCTs, where groups of participants were randomised instead of individuals, were only included in a meta‐analysis if a measure of effect (e.g. odds ratio with 95% CI) was available from an analysis that accounted properly for clustering ( Higgins 2021 ).

For cross‐over trials, where study participants underwent more than one study intervention, meta‐analyses was only based on data from the first allocation period (if those data were available) ( Higgins 2021 ), and only for the very short‐term treatment effects (i.e. measured during the suctioning procedure). We did not include treatment effects measured during allocation periods after cross‐over, and longer‐term treatment effects, in the analyses because of the risk of 'carry over' effect ( Higgins 2021 ).

Dealing with missing data

We contacted the study authors to request missing data. In the case of missing data, we presented the number of participants with the missing data in the results section and Characteristics of included studies table. We presented only the results for the available participants. We discussed the implications of the missing data in the Discussion .

Assessment of heterogeneity

We used the formal statistics described below.

The Chi ² test for homogeneity (P value less than 0.1) to calculate whether statistical heterogeneity was present. Since this test has low power when the number of studies included in the meta‐analysis was small, the probability was set at the 10% level of significance.
The impact of statistical heterogeneity using the I ² statistic available in Review Manager Web ( RevMan Web 2022 ), which describes the percentage of total variation across studies due to heterogeneity rather than sampling error. This value is interpreted based on thresholds as identified in the Cochrane Handbook for Systematic Reviews of Interventions ( Higgins 2021 ): less than 25% as no heterogeneity; 25% to 49% as low heterogeneity; 50% to 74% as moderate heterogeneity and 75% and above as high heterogeneity. Where there was evidence of apparent or statistical heterogeneity, we assessed the source of the heterogeneity using sensitivity and subgroup analyses looking for evidence of bias or methodological differences between trials.

Assessment of reporting biases

We planned to investigate reporting and publication bias by examining the degree of asymmetry of a funnel plot if the number of trials included in the meta‐analysis was 10 or more. We were unable to do so because we included eight RCTs (nine reports) in our review.

Where bias was suspected, we attempted to contact study authors to ask them to provide missing outcome data. Where this was not possible, and the missing data were thought to introduce serious bias, we explored the impact of including such studies in the overall assessment of results using a sensitivity analysis.

Data synthesis

We used the statistical package Review Manager Web ( RevMan Web 2022 ). For meta‐analyses, we reported an MD with 95% CI using a fixed‐effect model for continuous outcome measures. For categorical outcomes, we reported the typical RR, RD and, if the RD was statistically significant, we planned to report the NNTB or NNTH. All values were reported with their 95% CIs.

For cluster‐RCTs, we used the generic inverse variance method.

Subgroup analysis and investigation of heterogeneity

If the information was available, we conducted the following subgroup analyses for the primary outcome.

Term versus preterm neonates (see Types of participants for definitions)
Endotracheal intubation versus tracheostomy

We assessed differences in effect between subgroups by examining the overlap of the CIs of the summary effect estimates for the subgroups, and by performing a Chi ² test for homogeneity and calculating an I ² value for between‐subgroup differences.

Sensitivity analysis

Sensitivity analyses explored the impact of:

the choice of statistical model (fixed‐effect versus random‐effects);
methodological quality, by excluding studies with a high risk of bias.

Summary of findings and assessment of the certainty of the evidence

We used the GRADE approach, as outlined in the GRADE Handbook to assess the certainty of evidence for the following (clinically relevant) outcomes ( Schünemann 2013 ):

validated composite pain scores:
- PIPP;
physiological indicators;
- heart rate;
- SaO ₂ ;
behavioural indicators;
IVH.

Two review authors (SP, FC) independently assessed the certainty of the evidence for each outcome. We considered evidence from RCTs as high certainty, but downgraded the evidence one level for serious (or two levels for very serious) limitations based on the following: design (risk of bias), consistency across studies, directness of the evidence, precision of estimates and presence of publication bias. We used GRADEpro GDT to create three summary of findings tables to report the certainty of the evidence for the following comparisons.

Facilitated tucking / four‐handed care / gentle human touch compared with standard care for pain during endotracheal suctioning ( Table 1 ).
Familiar odour (breast milk smell) compared with standard care for pain during endotracheal suctioning ( Table 2 ).
White noise compared with standard care for pain during endotracheal suctioning ( Table 3 ).

The GRADE approach results in an assessment of the certainty of a body of evidence as one of four grades.

High certainty: further research is very unlikely to change our confidence in the estimate of effect.
Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low certainty: we are very uncertain about the estimate.

Results

Description of studies

See the Characteristics of included studies and Characteristics of excluded studies tables.

Results of the search

Searches identified 581 articles for possible inclusion in the review (277 PubMed; 209 Embase; 12 CINAHL; 83 CRS Web). After removing 17 duplicates, 564 records were available for title and abstract screening. We eliminated 517 records based on title and abstract, and reviewed 47 full‐texts. We excluded 38 records and included eight studies (represented by nine reports) in our review. Only five of the eight studies could be included in a meta‐analysis ( Figure 1 ).

Included studies

We included eight studies (nine reports) that enroled 386 preterm infants. Full details of the eight included studies are given in the Characteristics of included studies table.

Participants

All studies included preterm infants (29 to 37 weeks' gestation) having an endotracheal tube for mechanical ventilation in need of regular endotracheal suctioning. All studies examined responses to the painful procedure of endotracheal suctioning ( Alinejad‐Naeini 2014 ; Axelin 2006 ; Cone 2013 ; Desai 2017 ; Fatollahzade 2022 ; Niaraki 2022 ; Taplak 2021 ; Ward‐Larson 2004 ).

Birth weight was 1200 g or more in two studies ( Alinejad‐Naeini 2014 ; Fatollahzade 2022 ), 1000 g or more in two studies ( Niaraki 2022 ; Taplak 2021 ), and 1500 g or less in one study ( Ward‐Larson 2004 ). Three studies did not report birth weight ( Axelin 2006 ; Cone 2013 ; Desai 2017 ).

Three studies included infants less than seven days of life ( Cone 2013 ; Niaraki 2022 ; Taplak 2021 ). In one study, infants were 28 days of life or less ( Ward‐Larson 2004 ). Four studies did not report infant age ( Alinejad‐Naeini 2014 ; Axelin 2006 ; Niaraki 2022 ; Ward‐Larson 2004 ).

Diagnostic criteria

Five studies reported infants did not receive analgesics four hours before intervention ( Alinejad‐Naeini 2014 ; Axelin 2006 ; Fatollahzade 2022 ; Niaraki 2022 ; Taplak 2021 ). In four studies, infants did not receive sedatives four hours before intervention ( Alinejad‐Naeini 2014 ; Fatollahzade 2022 ; Niaraki 2022 ; Taplak 2021 ). In one study, infants did not receive sedatives or analgesics within 12 hours before data collection ( Ward‐Larson 2004 ). One study mentioned infants not receiving paralytics, analgesics or sedating medications at all ( Cone 2013 ). One study mentioned absence of any painful procedure one hour prior to endotracheal suctioning ( Fatollahzade 2022 ), one study mentioned absence of any painful procedure 30 minutes prior to the intervention ( Alinejad‐Naeini 2014 ), and one study mentioned infants having no major physiological stress within 12 hours prior to the intervention ( Ward‐Larson 2004 ).

Two studies mentioned infants having no diagnosis of seizures and no chest tubes ( Alinejad‐Naeini 2014 ; Fatollahzade 2022 ). Three studies mentioned infants having no intracranial haemorrhage higher than Grade II ( Alinejad‐Naeini 2014 ; Fatollahzade 2022 ; Ward‐Larson 2004 ). Seven studies mentioned infants having no chromosomal or congenital malformations ( Alinejad‐Naeini 2014 ; Axelin 2006 ; Cone 2013 ; Desai 2017 ; Fatollahzade 2022 ; Niaraki 2022 ; Ward‐Larson 2004 ). One study mentioned infants having no severe encephalopathy ( Desai 2017 ). One study included infants with no metabolic disease and no skin disease ( Fatollahzade 2022 ). In one study, infants with no congenital heart disease were included ( Cone 2013 ). One study included infants with no hearing problems ( Taplak 2021 ).

Specific interventions

Four studies examined the effect of facilitated tucking on pain during endotracheal suctioning ( Alinejad‐Naeini 2014 ; Axelin 2006 ; Taplak 2021 ; Ward‐Larson 2004 ), and three other studies investigated a similar intervention, namely 'four‐handed‐care' ( Cone 2013 ; Niaraki 2022 ), and gentle human touch ( Fatollahzade 2022 ). Because the nature of the procedure is essentially the same as facilitated tucking, we combined the results. One study examined the use of expressed breast milk administered two minutes before suctioning ( Desai 2017 ), and another study investigated the effect of breast milk smell (breast milk was dropped on a pet/filter paper and placed 10 cm away from the infant's nose) and white noise ( Taplak 2021 ). Other interventions studied were: swaddling ( Desai 2017 ), and oral sucrose ( Desai 2017 ).

Outcome measures

Outcome measures varied amongst studies, often including more than one outcome. Physiological measures included heart rate and SaO ₂ before, during and after the painful procedure ( Axelin 2006 ; Cone 2013 ; Niaraki 2022 ; Taplak 2021 ); and salivary cortisol levels ( Cone 2013 ). One study used behavioural state measured by the 'Anderson Behavioural State Scales' (ABSS) ( Cone 2013 ). All studies reported validated composite pain measures that included both physiological and behavioural indicators ( Alinejad‐Naeini 2014 ; Axelin 2006 ; Cone 2013 ; Desai 2017 ; Fatollahzade 2022 ; Niaraki 2022 ; Taplak 2021 ; Ward‐Larson 2004 ). Five studies used the PIPP ( Alinejad‐Naeini 2014 ; Desai 2017 ; Fatollahzade 2022 ; Taplak 2021 ; Ward‐Larson 2004 ), one study used the NIPS ( Axelin 2006 ), and one study used the ALPS‐Neo Scale ( Niaraki 2022 ).

Excluded studies

We excluded 38 studies.

Seven used pharmacological interventions ( Anand 1999 ; Anand 2008 ; Cignacco 2008 ; Pokela 1994 ; Saarenmaa 1996 ; Saarenmaa 2001 ; Välitalo 2017 ).
One used a non‐pharmacological intervention that was not related to reducing pain ( Cardoso 2017 ).
Three mainly focused on pulmonary outcomes instead of pain measurement ( Beeram 1992 ; Nangia 2016 ; Pouraboli 2019 ).
One focused on cerebral circulation ( Shah 1992 ).
Three did not have endotracheal tube suctioning ( Miller 1993 ; Sweet 2017 ; Tekgündüz 2019 ).
Twenty‐three were not RCTs ( Adams 2018 ; Anand 2005 ; Barker 1995 ; Bernert 1997 ; Chen 2012 ; Chettri 2015 ; Cury 2013 ; Fanconi 1987 ; Gjerstad 2008 ; Grunau 2000 ; Hadian 2013 ; Hartley 2015 ; Hough 2014 ; Jeong 2014 ; Karpe 2013 ; Pitetti 2003 ; Pölkki 2014 ; Shorten 1991 ; Tison 2009 ; Treluyer 2005 ; Välitalo 2016 ; van Veenendaal 2009 ; Wilson 1991 ).

See Characteristics of excluded studies table.

Studies awaiting classification

No studies are awaiting classification.

Ongoing studies

We identified no ongoing studies.

Risk of bias in included studies

For the risk of bias for each study, see Characteristics of included studies table and Figure 2 , and as percentage across all included studies, see Figure 3 .

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Allocation

One study used computer‐generated randomisation (low risk of bias; Desai 2017 ). Seven studies mentioned randomisation, but the method of random sequence generation was not adequately described (unclear risk of bias; Alinejad‐Naeini 2014 ; Axelin 2006 ; Cone 2013 ; Fatollahzade 2022 ; Niaraki 2022 ; Taplak 2021 ; Ward‐Larson 2004 ).

Allocation concealment was adequate in three studies (low risk of bias; Axelin 2006 ; Desai 2017 ; Niaraki 2022 ). In five studies, information regarding the randomisation procedure was insufficient to adequately assess allocation concealment (unclear risk of bias; Alinejad‐Naeini 2014 ; Cone 2013 ; Fatollahzade 2022 ; Taplak 2021 ; Ward‐Larson 2004 ).

Blinding

Given the nature of the interventions, blinding of caregivers was not possible in all eight studies (high risk of bias). In one study, where blinding theoretically would have been possible, there were no measures taken to overcome performance bias ( Desai 2017 ).

Measures to overcome detection bias (i.e. blinding of outcome assessment) were inadequate in seven studies (high risk of bias; Alinejad‐Naeini 2014 ; Axelin 2006 ; Cone 2013 ; Desai 2017 ; Fatollahzade 2022 ; Niaraki 2022 ; Ward‐Larson 2004 ). In one study, blinding of outcome assessors was mentioned, but it seemed unfeasible for one of the intervention groups (facilitated tucking) ( Taplak 2021 ).

Incomplete outcome data

All eight studies had complete outcome data (low risk of bias).

Selective reporting

Reporting was adequate in six studies (low risk of bias). One study was reported in two publications, but with different outcome variables, suggesting that reporting might have been based on post‐hoc choice of outcome measure (high risk of bias; Alinejad‐Naeini 2014 ). One study only reported the outcome of the PIPP scale, no data on other physiological parameters were reported (high risk of bias; Fatollahzade 2022 ).

Other potential sources of bias

Four studies had no other source of possible bias (low risk of bias; Axelin 2006 ; Niaraki 2022 ; Taplak 2021 ; Ward‐Larson 2004 ). Three studies did not perform a power calculation (high risk of bias; Alinejad‐Naeini 2014 ; Cone 2013 ; Fatollahzade 2022 ). In one study, there was no hypothesis on anticipated effect on primary outcome (high risk of bias; Alinejad‐Naeini 2014 ). In one study, there was no comparative table of demographics presented, making assessment of comparability of the two groups impossible and no baseline PIPP score presented (high risk of bias; Fatollahzade 2022 ). In another study, the primary outcome was not clearly defined (high risk of bias; Cone 2013 ). In one study, infants could be included multiple times, suctioning episodes were randomised instead of infants; in the statistical analyses, correlation between observations was not taken into account; however, the impact of this is unclear because only 12 infants (out of 118) were included twice (unclear risk of bias; Desai 2017 ).

Effects of interventions

See: Table 1; Table 2; Table 3

For all included pain and behaviour measures, a lower score indicates a lower level of pain, except for self‐regulatory and approach behaviours (SRB) where a higher score indicates a higher level of self‐regulation, thus less stress.

Comparison 1: facilitated tucking / four‐handed care / gentle human touch

See Table 1 .

Cone 2013 and Niaraki 2022 described facilitated tucking as "four‐handed‐care" and Fatollahzade 2022 as "gentle human touch" instead of "facilitated tucking". Both interventions were considered to be sufficiently similar to "facilitated tucking" in order to be combined in one meta‐analysis.

Primary outcomes

Validated pain scale

Premature Infant Pain Profile during endotracheal suctioning

Four studies comparing facilitated tucking / four‐handed care / gentle human touch to standard care reported PIPP ( Alinejad‐Naeini 2014 ; Fatollahzade 2022 ; Taplak 2021 ; Ward‐Larson 2004 ). Facilitated tucking / four‐handed care / gentle human touch probably reduces PIPP score, compared to standard care, during endotracheal suctioning (MD −2.76, 95% CI −3.57 to −1.96; I² = 82%; 4 studies, 148 infants; moderate‐certainty evidence; Analysis 1.1 ; Figure 4 ).

1.1 — Comparison 1: Facilitated tucking / four‐handed care / gentle human touch, Outcome 1: PIPP during endotracheal suctioning

One study comparing facilitated tucking / four‐handed care / gentle human touch to familiar odour (breast milk smell) reported PIPP ( Taplak 2021 ). Familiar odour probably has little or no effect on PIPP score, compared to facilitated tucking / four‐handed care / gentle human touch, during endotracheal suctioning (MD −1.35, 95% CI −3.72 to 1.02; 1 study, 40 infants; low‐certainty evidence; Analysis 1.1 ; Figure 4 ).

One study comparing facilitated tucking / four‐handed care / gentle human touch to white noise reported PIPP ( Taplak 2021 ). White noise probably has little or no effect on PIPP score, compared to facilitated tucking / four‐handed care / gentle human touch, during endotracheal suctioning (MD −1.00, 95% CI −3.38 to 1.38; 1 study, 40 infants; low‐certainty evidence; Analysis 1.1 ; Figure 4 ).

Astrid Lindgren Children's Hospital Pain Scale Neonates Scale score during endotracheal suctioning

One study comparing facilitated tucking / four‐handed care / gentle human touch to standard care reported ALPS‐Neo Scale score ( Niaraki 2022 ). Facilitated tucking / four‐handed care / gentle human touch probably has little or no effect on ALPS‐Neo Scale, compared to standard care, during endotracheal suctioning (MD −0.15, 95% CI −1.27 to 0.97; 1 study, 40 infants; low‐certainty evidence; Analysis 1.2 ).

1.2 — Comparison 1: Facilitated tucking / four‐handed care / gentle human touch, Outcome 2: ALPS‐Neo Scale during endotracheal suctioning

No studies compared facilitated tucking / four‐handed care / gentle human touch to familiar odour (breast milk smell) or white noise.

Physiological indicators

Heart rate during endotracheal suctioning

Two studies comparing facilitated tucking / four‐handed care / gentle human touch to standard care reported heart rate ( Taplak 2021 ; Niaraki 2022 ). Facilitated tucking / four‐handed care / gentle human touch probably has little or no effect on heart rate, compared to standard care, during endotracheal suctioning (MD −3.06 beats per minute (bpm), 95% CI −9.33 to 3.21; I² = 0%; 2 studies, 80 infants; low‐certainty evidence; Analysis 1.3 ; Figure 5 ).

1.3 — Comparison 1: Facilitated tucking / four‐handed care / gentle human touch, Outcome 3: Heart rate during endotracheal suctioning (bpm)

One study comparing facilitated tucking / four‐handed care / gentle human touch to familiar odour (breast milk smell) reported heart rate ( Taplak 2021 ). Familiar odour probably has little or no effect on heart rate, compared to facilitated tucking / four‐handed care / gentle human touch, during endotracheal suctioning (MD 2.80 bpm, 95% CI −6.83 to 12.43; 1 study, 40 infants; low‐certainty evidence; Analysis 1.3 ; Figure 5 ).

One study comparing facilitated tucking / four‐handed care / gentle human touch to white noise reported heart rate ( Taplak 2021 ). White noise probably has little or no effect on heart rate, compared to facilitated tucking / four‐handed care / gentle human touch, during endotracheal suctioning (MD −0.75 bpm, 95% CI −10.25 to 8.75; 1 study, 40 infants; low‐certainty evidence; Analysis 1.3 ; Figure 5 ).

Oxygen saturation during endotracheal suctioning

Two studies comparing facilitated tucking / four‐handed care / gentle human touch to standard care reported SaO ₂ ( Niaraki 2022 ; Taplak 2021 ). Facilitated tucking / four‐handed care / gentle human touch probably has little or no effect on SaO ₂ , compared to standard care, during endotracheal suctioning (MD 0.87%, 95% CI −1.33 to 3.08; I² = 0%; 2 studies, 80 infants; low‐certainty evidence; Analysis 1.4 ; Figure 6 ).

1.4 — Comparison 1: Facilitated tucking / four‐handed care / gentle human touch, Outcome 4: Oxygen saturation during endotracheal suctioning (%)

One study comparing facilitated tucking / four‐handed care / gentle human touch to familiar odour (breast milk smell) reported SaO ₂ ( Taplak 2021 ). Familiar odour probably has little or no effect on SaO ₂ , compared to facilitated tucking / four‐handed care / gentle human touch, during endotracheal suctioning (MD 3.25%, 95% CI −0.37 to 6.87; 1 study, 40 infants; low‐certainty evidence; Analysis 1.4 ; Figure 6 ).

One study comparing facilitated tucking / four‐handed care / gentle human touch to white noise reported SaO ₂ ( Taplak 2021 ). White noise probably has little or no effect on SaO ₂ , compared to facilitated tucking / four‐handed care / gentle human touch, during endotracheal suctioning (MD 0.20%, 95% CI −3.70 to 4.10; 1 study, 40 infants; low‐certainty evidence; Analysis 1.4 ; Figure 6 ).

Behavioural indicators

Stress and defensive behaviours

One study comparing facilitated tucking / four‐handed care / gentle human touch during endotracheal suctioning to standard care reported SDB ( Cone 2013 ). Facilitated tucking / four‐handed care / gentle human touch probably has little or no effect on SDB, compared to standard care, during endotracheal suctioning (MD −1.20, 95% CI −3.47 to 1.07; 1 study, 20 infants; low‐certainty evidence; Analysis 1.5 ).

1.5 — Comparison 1: Facilitated tucking / four‐handed care / gentle human touch, Outcome 5: Stress and defence behaviours (SDB) during endotracheal suctioning

No studies compared facilitated tucking / four‐handed care / gentle human touch to familiar odour (breast milk smell) or white noise.

Self‐regulatory behaviours

One study comparing facilitated tucking / four‐handed care / gentle human touch during endotracheal suctioning to standard care reported SRB ( Cone 2013 ). Facilitated tucking / four‐handed care / gentle human touch may result in a slight increase in SRB, compared to standard care, during endotracheal suctioning (indicating less stress) (MD 0.90, 95% CI 0.20 to 1.60; 1 study, 20 infants; low‐certainty evidence; Analysis 1.6 ).

1.6 — Comparison 1: Facilitated tucking / four‐handed care / gentle human touch, Outcome 6: Self‐regulatory behaviours (SRB) during endotracheal suctioning

No studies compared facilitated tucking / four‐handed care / gentle human touch to familiar odour (breast milk smell) or white noise.

Secondary outcomes

No studies reported on any of the secondary outcomes.

Comparison 2: familiar odour (breast milk smell)

See Table 2 .

Primary outcomes

Validated pain scores

Premature Infant Pain Profile during endotracheal suctioning

One study comparing familiar odour (breast milk smell) to standard care reported PIPP ( Taplak 2021 ). Familiar odour probably has little or no effect on PIPP score, compared to standard care, during endotracheal suctioning (MD −0.30, 95% CI −2.15 to 1.55; 1 study, 40 infants; low‐certainty evidence; Analysis 2.1 ).

2.1 — Comparison 2: Familiar odour (breast milk smell), Outcome 1: PIPP during endotracheal suctioning

One study comparing familiar odour (breast milk smell) to white noise reported PIPP ( Taplak 2021 ). Familiar odour probably has little or no effect on PIPP score, compared to white noise, during endotracheal suctioning (MD −0.35, 95% CI −1.90 to 2.60; 1 study, 40 infants; low‐certainty evidence; Analysis 2.1 ).

Physiological indicators

Heart rate during endotracheal suctioning

One study comparing familiar odour (breast milk smell) to standard care reported heart rate ( Taplak 2021 ). Familiar odour probably has little or no effect on heart rate, compared to standard care, during endotracheal suctioning (MD −6.30 bpm, 95% CI −16.04 to 3.44; 1 study, 40 infants; low‐certainty evidence; Analysis 2.2 ).

2.2 — Comparison 2: Familiar odour (breast milk smell), Outcome 2: Heart rate during endotracheal suctioning (bpm)

One study comparing familiar odour (breast milk smell) to white noise reported heart rate ( Taplak 2021 ). Familiar odour probably has little or no effect on heart rate, compared to white noise, during endotracheal suctioning (MD −3.55 bpm, 95% CI −14.56 to 7.46; 1 study, 40 infants; low‐certainty evidence; Analysis 2.2 ).

Oxygen saturation during endotracheal suctioning

One study comparing familiar odour (breast milk smell) to standard care reported SaO ₂ ( Taplak 2021 ). Familiar odour probably has little or no effect on SaO ₂ , compared to standard care, during endotracheal suctioning (MD −0.80%, 95% CI −4.82 to 3.22; 1 study, 40 infants; low‐certainty evidence; Analysis 2.3 ).

2.3 — Comparison 2: Familiar odour (breast milk smell), Outcome 3: Oxygen saturation during endotracheal suctioning (%)

One study comparing familiar odour (breast milk smell) to white noise reported SaO ₂ ( Taplak 2021 ). Familiar odour probably has little or no effect on SaO ₂ , compared to white noise, during endotracheal suctioning (MD −3.05%, 95% CI −6.69 to 0.59; 1 study, 40 infants; low‐certainty evidence; Analysis 2.3 ).

Behavioural indicators

No studies reported on behavioural outcomes.

Secondary outcomes

No studies reported on any of the prespecified secondary outcomes.

Comparison 3: expressed breast milk

Primary outcomes

Validated pain scale

Premature Infant Pain Profile during endotracheal suctioning

No studies compared expressed breast milk to standard care .

One study comparing expressed breast milk to oral sucrose reported PIPP ( Desai 2017 ). Expressed breast milk probably has little or no effect on PIPP score, compared to oral sucrose, during endotracheal suctioning (MD 0.77, 95% CI −0.95 to 2.49; 1 study, 72 infants; moderate‐certainty evidence; Analysis 3.1 ).

3.1 — Comparison 3: Expressed breast milk, Outcome 1: PIPP during endotracheal suctioning

One study comparing expressed breast milk to swaddling reported PIPP ( Desai 2017 ). Expressed breast milk probably has little or no effect on PIPP score, compared to swaddling, during endotracheal suctioning (MD 1.41, 95% CI −0.17 to 2.99; 1 study, 72 infants; moderate‐certainty evidence; Analysis 3.1 ).

Physiological indicators

No studies reported on physiological indicators.

Behavioural indicators

No studies reported on behavioural indicators.

Secondary outcomes

No studies reported on any of the prespecified secondary outcomes.

Comparison 4: white noise

See: Table 3 .

Primary outcomes

Validated pain scale

Premature Infant Pain Profile during endotracheal suctioning

One study comparing white noise to standard care reported PIPP ( Taplak 2021 ). White noise probably has little or no effect on PIPP score, compared to standard care, during endotracheal suctioning (MD −0.65, 95% CI −2.51 to 1.21; 1 study, 40 infants; low‐certainty evidence; Analysis 4.1 ).

4.1 — Comparison 4: White noise, Outcome 1: PIPP during endotracheal suctioning

Physiological indicators

Heart rate during endotracheal suctioning

One study comparing white noise to standard care reported heart rate ( Taplak 2021 ). White noise probably has little or no effect on heart rate, compared to standard care, during endotracheal suctioning (MD −1.85 bpm, 95% CI −11.46 to 7.76; 1 study, 40 infants; low‐certainty evidence; Analysis 4.2 ).

4.2 — Comparison 4: White noise, Outcome 2: Heart rate during endotracheal suctioning (bpm)

Oxygen saturation during endotracheal suctioning

One study comparing white noise to standard care reported SaO ₂ ( Taplak 2021 ). White noise probably has little or no effect on SaO ₂ , compared to standard care, during endotracheal suctioning (MD 2.25%, 95% CI −2.03 to 6.53; 1 study, 40 infants; low‐certainty evidence; Analysis 4.3 ).

4.3 — Comparison 4: White noise, Outcome 3: Oxygen saturation during endotracheal suctioning (%)

Behavioural indicators

No studies reported on behavioural indicators.

Secondary outcomes

No studies reported on any of the prespecified secondary outcomes.

Comparison 5: swaddling

Primary outcomes

Validated pain scale

Premature Infant Pain Profile during endotracheal suctioning

No studies compared the effects of swaddling versus standard care .

One study comparing swaddling to oral sucrose reported PIPP ( Desai 2017 ). Swaddling probably has little or no effect on PIPP score, compared to oral sucrose, during endotracheal suctioning (MD −0.64, 95% CI −2.29 to 1.01; 1 study, 72 infants; moderate‐certainty evidence; Analysis 5.1 ).

5.1 — Comparison 5: Swaddling, Outcome 1: PIPP during endotracheal suctioning

Physiological indicators

No studies reported on physiological indicators.

Behavioural indicators

No studies reported on behavioural indicators.

Secondary outcomes

No studies reported on any of the prespecified secondary outcomes.

Discussion

Summary of main results

Eight studies including 386 mechanically ventilated newborn infants investigated the effects of non‐pharmacological interventions for the prevention of pain during endotracheal suctioning. The interventions were facilitated tucking / four‐handed care / gentle touch, familiar odour (breast milk smell), white noise, expressed breast milk, oral sucrose and swaddling. Several studies had multiple treatment arms, comparing the intervention with standard care and other interventions. The effect on pain was generally assessed using validated pain assessment scales (PIPP and ALPS‐Neo scale) before, during and after the suctioning procedure.

The results are summarised in Table 1 ; Table 2 ; and Table 3 . We included only results from the most validated pain assessment scales (PIPP, ALPS‐Neo Scale), and provided GRADE assessments for the certainty of evidence.

Facilitated tucking / four‐handed care / gentle human touch probably reduces PIPP score compared with standard care. The evidence of a single study suggests that facilitated tucking / four‐handed‐care / gentle human touch slightly increases self‐regulatory and approach behaviours (i.e. reduces stress) during endotracheal suctioning.

When different interventions were directly compared to one another, none of the interventions proved to be superior to another (low‐certainty evidence).

Overall completeness and applicability of evidence

The interventions that were studied are all easily applicable in current practice. However, studies included only preterm infants, making it difficult to draw any conclusions about the effectiveness of these interventions in mechanically ventilated term infants. Generally, studies had a small sample size, resulting in considerable imprecision in the effect estimates. In addition, due to the small number of studies and the large heterogeneity in the interventions studied, only five studies could be combined in a meta‐analysis.

Quality of the evidence

The certainty of the evidence is summarised in Table 1 ; Table 2 ; and Table 3 , and varied from low to moderate.

Most studies were small (sample size varying between 10 and 108 infants), and only one study reported on more than 100 infants ( Desai 2017 ).

All studies used validated measuring instruments. Despite this, measurement of pain remains a subjective matter where the scores depend on the observer. Only one study examined the reliability of the coders by calculating the correlation between their scoring methods using the Kappa coefficient, which was acceptable ( Niaraki 2022 ). In other studies, it was not shown whether the observer was qualified to measure pain. Most trials focused on pain during the procedure; the length of observation and return to baseline was not considered.

Preventing and reducing pain or stress in neonates starts with adaptations of procedural techniques or practices. Strategies such as reducing light and noise, minimising patient handling and tailored nursing techniques could be very powerful in the prevention of pain ( Allegaert 2013 ). Four studies mentioned considering environmental factors ( Alinejad‐Naeini 2014 ; Axelin 2006 ; Fatollahzade 2022 ; Ward‐Larson 2004 ). Two studies minimised environmental stimuli such as light and noise ( Alinejad‐Naeini 2014 ; Fatollahzade 2022 ), one study covered the incubator with a blanket ( Axelin 2006 ), and one study mentioned (without further details) that environmental factors were controlled during the study period ( Ward‐Larson 2004 ).

There were important differences in the conditions of the endotracheal suctioning procedure. One study prevented the infants from being subjected to any painful procedures from 15 minutes before to five minutes after the suctioning procedure ( Taplak 2021 ). One study performed no other procedures for at least one hour before recording ( Axelin 2006 ). Axelin 2006 , in addition to applying suction to the endotracheal tube, suctioned the throat, mouth and nose, which could strongly affect pain scores. Two studies applied hyperoxygenation before suctioning ( Cone 2013 ; Taplak 2021 ). Only one study mentioned using saline instillation ( Taplak 2021 ). None of the studies mentioned whether the insertion depth of the aspiration probe during endotracheal suctioning was taken into account. Only two studies described a maximum suctioning pressure of 100 mmHg ( Niaraki 2022 ; Taplak 2021 ).

Nurses performed endotracheal suctioning in seven studies ( Axelin 2006 ; Cardoso 2017 ; Desai 2017 ; Fatollahzade 2022 ; Hadian 2013 ; Ward‐Larson 2004 ; Niaraki 2022 ), a researcher in one study ( Alinejad‐Naeini 2014 ), and a clinician was the sole operator in one study ( Cone 2013 ). Two studies followed a specific protocol for endotracheal suctioning ( Cardoso 2017 ; Taplak 2021 ), and one study trained nursing and respiratory teams in the endotracheal suctioning technique ( Cardoso 2017 ). Three studies mentioned that endotracheal suctioning was based on the infant's needs ( Alinejad‐Naeini 2014 ; Desai 2017 ; Fatollahzade 2022 ). One study used the parents to perform facilitated tucking ( Axelin 2006 ), whereas the other studies did not mention the parents' involvement. One study mentioned that the total suction duration did not exceed 10 seconds and that the suction might be repeated up to three times with an interval of 30 seconds ( Niaraki 2022 ). Previous research has shown that theoretical and practical education of nurses, implementation of guidelines on endotracheal suctioning and learning to assess patients' needs for endotracheal suctioning could reduce the number of procedures and decrease pain and complications ( Hadian 2013 ; Wood 1998 ). Also, newer techniques in respiratory management, such as less‐invasive surfactant administration and non‐invasive respiratory support, have greatly reduced the need for endotracheal suctioning. A reduction in the number of procedures is one of the most effective strategies to relieve pain during neonatal intensive care ( Allegaert 2013 ).

Potential biases in the review process

We are not aware of any biases in the review process. Two review authors (SP, KB) selected the trials from the literature searches and there was complete agreement. Two review authors (SP and IO) completed predesigned forms for data abstraction. Two review authors (SP and FC) performed risk of bias assessments. We discussed any discrepancies and resolved them by consensus.

Discrepancies that could cause potential bias included the following.

One of the outcomes was originally facilitated tucking. Post hoc we have added 'four‐handed care' and 'gentle human touch' because they emerged in two studies ( Cone 2013 ; Fatollahzade 2022 ), and they fit best in this category.
Post hoc analysis groups were grouped according to experimental intervention against different types of comparators (both no intervention and active comparators), due to the occurrence of some studies with multiple arms of comparison.
"Prioritisation of data from multiple time points": for certain studies with multiple time points of measurement, it was decided to select one specific time point for the data extraction, namely during the intervention.

Agreements and disagreements with other studies or reviews

This systematic review with meta‐analysis is the first to evaluate non‐pharmacological pain‐reducing interventions during endotracheal suctioning. Previous systematic reviews assessing non‐pharmacological interventions for pain management in neonates have focused on pain during heel stick, venipuncture, intramuscular injection or vaccination ( Johnston 2017 ; Riddell 2015 ; Shah 2012 ). Interventions for prevention of pain described in this review have already been thoroughly described in other reviews regarding procedural pain ( Riddell 2015 ). Facilitated tucking, swaddling, non‐nutritive sucking, the use of sucrose or breast milk, kangaroo or skin‐to‐skin care have all been shown to be potentially effective, but confidence is limited due to poor quality and lack of replication ( Riddell 2015 ; Stevens 2016 ). The most established evidence for managing procedural pain in preterm and term neonates was for facilitated tucking, swaddling and non‐nutritive sucking ( Riddell 2015 ).

Authors' conclusions

Implications for practice.

Facilitated tucking / four‐handed care / gentle human touch probably reduces PIPP score compared to standard care. The evidence of a single study suggests that facilitated tucking / four‐handed‐care / gentle human touch slightly increases self‐regulatory and approach behaviours (indicating reduced stress) during endotracheal suctioning.

Implications for research.

Based on the results of this review, there are significant gaps in the existing literature on prevention of pain during endotracheal suctioning.

One of the highest priorities is the need for well‐designed trials that study the following.

Facilitated tucking and swaddling during endotracheal suctioning. They have been shown to be potentially effective but due to poor certainty of evidence, confidence is limited.
The use of expressed breast milk has no advantage over sucrose administered orally for the prevention of pain during endotracheal suctioning. However, this is based on one small trial of moderate‐certainty evidence.
While the use of expressed breast milk has no advantage over sucrose administered orally, it does not imply that there are no benefits to using expressed breast milk, since the research has not been compared to standard care.
Preliminary work from other studies suggests that interventions such as kangaroo or skin‐to‐skin care are promising non‐pharmacological interventions for the prevention of pain, yet they have never been studied regarding pain during endotracheal suctioning.
It is important that researchers ensure an increase in the quality of randomised controlled trials by, amongst other things, using larger sample sizes and replicating trials.

History

Protocol first published: Issue 6, 2019

Acknowledgements

The methods section of this review was based on a standard template used by Cochrane Neonatal.

Thank you to the following members of Cochrane Neonatal: Roger Soll and William McGuire, Co‐ordinating Editors; Michelle Fiander and Jane Cracknell, Managing Editors, for editorial support.

We acknowledge Bart Van Rompaey's contribution to the protocol ( Pirlotte 2019 ).

Thank you to the following peer reviewers: Vishakha Nanda, Attending Neonatologist, John H Stroger Hospital of Cook County, Chicago, Illinois, USA; Nanthida Phattraprayoon, MD, FAAP Princess Srisavangavadhana College of Medicine Chulabhorn Royal Academy Bangkok, Thailand.

We would also like to thank Anne Lawson, Cochrane Central Production Service, for copy editing the review.

Appendices

Appendix 1. Search strategies

PubMed:

searched 23 June 2023

(((((((infant, newborn[MeSH] OR newborn*[TIAB] OR “new born”[TIAB] OR “new borns”[TIAB] OR “newly born”[TIAB] OR baby*[TIAB] OR babies[TIAB] OR premature*[TIAB] OR prematurity[TIAB] OR preterm*[TIAB] OR “pre term”[TIAB] OR “low birth weight”[TIAB] OR “low birthweight”[TIAB] OR ELBW[TIAB] OR VLBW[TIAB] OR LBW[TIAB] OR infant[TIAB] OR infants[TIAB] OR infantile[TIAB] OR infancy[TIAB] OR neonat*[TIAB])))) AND ((((((("Intubation, Intratracheal"[Mesh]) OR intubat*[tiab]) OR endotrach*[tiab]) OR intratrach*[tiab]) OR "Tracheostomy"[Mesh]) OR tracheost*[tiab]) OR tracheal[tiab])) AND (((("Suction"[Mesh]) OR suction[tiab]) OR suctioning[tiab]) OR aspiration[tiab]))) AND (((((“Pain Measurement”[MeSH] OR Pain[MeSH] OR pain*[TIAB] OR Crying[MeSH] OR crying[TIAB] OR cries[TIAB] OR Anxiety[MeSH] OR anxiety[TIAB] OR Fear[MeSH] OR fear*[TIAB] OR Panic[MeSH] OR panic*[TIAB] OR “Facial Expression”[Mesh] OR ((facial[TIAB] OR face[TIAB]) AND expression*[TIAB]) OR Gestures[MeSH] OR gesture*[TIAB] OR distress*[TIAB] or discomfort*[TIAB] or fright*[TIAB] or anxious[TIAB])))))

Embase:

searched 21 June 2023

1	exp infant/
2	exp newborn/
3	exp prematurity/
4	exp low birth weight/
5	#1 OR #2 OR #3 OR #4
6	exp respiratory tract intubation/
7	exp tracheostomy/
8	exp respiratory tract aspiration procedure/
9	exp suction/
10	exp aspiration/
11	#6 OR #7
12	#8 OR #9 OR #10
13	exp procedural pain/
14	exp pain measurement/
15	exp crying/
16	exp fear/
17	exp panic/
18	exp facial expression/
19	exp gesture/
20	exp discomfort/
21	exp distress tolerance/
22	#13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21
23	#5 AND #11 AND #12 AND #22
24	(#5 AND #11 OR #12) AND #22
25	#11 OR #12
26	#5 AND #22 AND #25

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CINAHL:

searched 21 June 2023

S1	(MH "Pain+")
S2	(MH "Treatment Related Pain")
S3	(MH "Crying")
S4	(MH "Facial Expression")
S5	(MH "Anxiety+") OR (MH "Anticipatory Anxiety")
S6	(MH "Fear+")
S7	(MH "Suffering")
S8	(TX panic OR distress* OR discomfort* OR fright* OR anxious)
S9	S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8
S10	endotracheal n2 suction*
S11	(infan* OR newborn OR neonat* OR premature OR low birth weight OR VLBW OR LBW)
S12	S9 AND S10 AND S11

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CRS WEB:

searched 21 June 2023

1	MESH DESCRIPTOR Pain Measurement EXPLODE ALL AND CENTRAL:TARGET
2	MESH DESCRIPTOR Pain EXPLODE ALL AND CENTRAL:TARGET
3	MESH DESCRIPTOR Crying EXPLODE ALL AND CENTRAL:TARGET
4	MESH DESCRIPTOR Anxiety EXPLODE ALL AND CENTRAL:TARGET
5	MESH DESCRIPTOR Fear EXPLODE ALL AND CENTRAL:TARGET
6	MESH DESCRIPTOR Panic EXPLODE ALL AND CENTRAL:TARGET
7	MESH DESCRIPTOR Facial Expression EXPLODE ALL AND CENTRAL:TARGET
8	MESH DESCRIPTOR Gestures EXPLODE ALL AND CENTRAL:TARGET
9	(pain measurement pain assessment or pain or distress* or discomfort* or fright* or anxious or cries or crying or anxiety or fear* or panic* or facial expression* or gesture*):TI,AB,KW AND CENTRAL
10	#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 AND CENTRAL:TARGET
11	endotracheal NEAR suction* AND CENTRAL:TARGET
12	(endotracheal* or intratracheal) AND (suction or aspiration*):TI,AB,KW AND CENTRAL:TARGET
13	#11 OR #12 AND CENTRAL:TARGET
14	(infan* or newborn or neonat* or premature or preterm or very low birth weight or low birth weight or extreme low birth weight or ELBW or VLBW or LBW) AND CENTRAL:TARGET
15	#10 AND #13 AND #14 AND CENTRAL:TARGET

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Appendix 2. Risk of bias tool

We used Cochrane's RoB 1 tool, and the standard methods of Cochrane and Cochrane Neonatal to assess the methodological quality of the trials. For each trial, we sought information regarding the method of randomisation, blinding and reporting of all outcomes of all the infants enrolled in the trial. We assessed each criterion as being at a low, high, or unclear risk of bias. Two review authors separately assessed each study. We resolved any disagreement by discussion. We added this information to the Characteristics of excluded studies table. We evaluated the following issues and entered the findings into the risk of bias table:

Sequence generation (checking for possible selection bias). Was the allocation sequence adequately generated?

For each included study, we categorised the method used to generate the allocation sequence as:

low risk (any truly random process, e.g. random number table; computer random number generator);
high risk (any non‐random process, e.g. odd or even date of birth; hospital or clinic record number); or
unclear risk.

Allocation concealment (checking for possible selection bias). Was allocation adequately concealed?

For each included study, we categorised the method used to conceal the allocation sequence as:

low risk (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes);
high risk (open random allocation; unsealed or non‐opaque envelopes, alternation; date of birth); or
unclear risk.

Blinding of participants and personnel (checking for possible performance bias). Was knowledge of the allocated intervention adequately prevented during the study?

For each included study, we categorised the methods used to blind study participants and personnel from knowledge of which intervention a participant received. Blinding was assessed separately for different outcomes or class of outcomes. We categorised the methods as:

low risk, high risk or unclear risk for participants; and
low risk, high risk or unclear risk for personnel.

Blinding of outcome assessment (checking for possible detection bias). Was knowledge of the allocated intervention adequately prevented at the time of outcome assessment?

For each included study, we categorised the methods used to blind outcome assessment. Blinding was assessed separately for different outcomes or class of outcomes. We categorised the methods as:

low risk for outcome assessors;
high risk for outcome assessors; or
unclear risk for outcome assessors.

Incomplete outcome data (checking for possible attrition bias through withdrawals, dropouts, protocol deviations). Were incomplete outcome data adequately addressed?

For each included study and for each outcome, we described the completeness of data including attrition and exclusions from the analysis. We noted whether attrition and exclusions were reported, the numbers included in the analysis at each stage (compared with the total randomised participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes. Where sufficient information was reported or supplied by the trial authors, we re‐included missing data in the analyses. We categorised the methods as:

low risk (less than 20% missing data);
high risk (20% or greater missing data); or
unclear risk.

Selective reporting bias. Are reports of the study free of suggestion of selective outcome reporting?

For each included study, we described how we investigated the possibility of selective outcome reporting bias and what we found. For studies in which study protocols were published in advance, we compared prespecified outcomes versus outcomes eventually reported in the published results. If the study protocol was not published in advance, we contacted study authors to gain access to the study protocol. We assessed the methods as:

low risk (where it is clear that all of the study's prespecified outcomes and all expected outcomes of interest to the review have been reported);
high risk (where not all the study's prespecified outcomes have been reported; one or more reported primary outcomes were not prespecified outcomes of interest and are reported incompletely and so cannot be used; study fails to include results of a key outcome that would have been expected to have been reported); or
unclear risk.

Other sources of bias. Was the study apparently free of other problems that could put it at a high risk of bias?

For each included study, we described any important concerns we had about other possible sources of bias (for example, whether there was a potential source of bias related to the specific study design or whether the trial was stopped early due to some data‐dependent process). We assessed whether each study was free of other problems that could put it at risk of bias as:

low risk;
high risk; or
unclear risk

If needed, we planned to explore the impact of the level of bias through undertaking sensitivity analyses.

Data and analyses

Comparison 1. Facilitated tucking / four‐handed care / gentle human touch.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 PIPP during endotracheal suctioning	4		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
1.1.1 Facilitated tucking / four‐handed care / gentle human touch versus standard care	4	148	Mean Difference (IV, Fixed, 95% CI)	‐2.76 [‐3.57, ‐1.96]
1.1.2 Facilitated tucking / four‐handed care / gentle human touch versus familiar odour (breast milk smell)	1	40	Mean Difference (IV, Fixed, 95% CI)	‐1.35 [‐3.72, 1.02]
1.1.3 Facilitated tucking / four‐handed care / gentle human touch versus white noise	1	40	Mean Difference (IV, Fixed, 95% CI)	‐1.00 [‐3.38, 1.38]
1.2 ALPS‐Neo Scale during endotracheal suctioning	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
1.2.1 Facilitated tucking / four‐handed care / gentle human touch versus standard care	1	40	Mean Difference (IV, Fixed, 95% CI)	‐0.15 [‐1.27, 0.97]
1.3 Heart rate during endotracheal suctioning (bpm)	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
1.3.1 Facilitated tucking / four‐handed care / gentle human touch versus standard care	2	80	Mean Difference (IV, Fixed, 95% CI)	‐3.06 [‐9.33, 3.21]
1.3.2 Facilitated tucking / four‐handed care / gentle human touch versus familiar odour (breast milk smell)	1	40	Mean Difference (IV, Fixed, 95% CI)	2.80 [‐6.83, 12.43]
1.3.3 Facilitated tucking / four‐handed care / gentle human touch versus white noise	1	40	Mean Difference (IV, Fixed, 95% CI)	‐0.75 [‐10.25, 8.75]
1.4 Oxygen saturation during endotracheal suctioning (%)	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
1.4.1 Facilitated tucking / four‐handed care / gentle human touch versus standard care	2	80	Mean Difference (IV, Fixed, 95% CI)	0.87 [‐1.33, 3.08]
1.4.2 Facilitated tucking / four‐handed care / gentle human touch versus familiar odour (breast milk smell)	1	40	Mean Difference (IV, Fixed, 95% CI)	3.25 [‐0.37, 6.87]
1.4.3 Facilitated tucking / four‐handed care / gentle human touch versus white noise	1	40	Mean Difference (IV, Fixed, 95% CI)	0.20 [‐3.70, 4.10]
1.5 Stress and defence behaviours (SDB) during endotracheal suctioning	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
1.5.1 Facilitated tucking / four‐handed care / gentle human touch versus standard care	1	20	Mean Difference (IV, Fixed, 95% CI)	‐1.20 [‐3.47, 1.07]
1.6 Self‐regulatory behaviours (SRB) during endotracheal suctioning	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
1.6.1 Facilitated tucking / four‐handed care / gentle human touch versus standard care	1	20	Mean Difference (IV, Fixed, 95% CI)	0.90 [0.20, 1.60]

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Comparison 2. Familiar odour (breast milk smell).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 PIPP during endotracheal suctioning	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
2.1.1 Familiar odour (breast milk smell) versus standard care	1	40	Mean Difference (IV, Fixed, 95% CI)	‐0.30 [‐2.15, 1.55]
2.1.2 Familiar odour (breast milk smell) versus white noise	1	40	Mean Difference (IV, Fixed, 95% CI)	0.35 [‐1.90, 2.60]
2.2 Heart rate during endotracheal suctioning (bpm)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
2.2.1 Familiar odour (breast milk smell) versus standard care	1	40	Mean Difference (IV, Fixed, 95% CI)	‐6.30 [‐16.04, 3.44]
2.2.2 Familiar odour (breast milk smell) versus white noise	1	40	Mean Difference (IV, Fixed, 95% CI)	‐3.55 [‐14.56, 7.46]
2.3 Oxygen saturation during endotracheal suctioning (%)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
2.3.1 Familiar odour (breast milk smell) versus standard care	1	40	Mean Difference (IV, Fixed, 95% CI)	‐0.80 [‐4.82, 3.22]
2.3.2 Familiar odour (breast milk smell) versus white noise	1	40	Mean Difference (IV, Fixed, 95% CI)	‐3.05 [‐6.69, 0.59]

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Comparison 3. Expressed breast milk.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 PIPP during endotracheal suctioning	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
3.1.1 Expressed breast milk versus oral sucrose	1	72	Mean Difference (IV, Fixed, 95% CI)	0.77 [‐0.95, 2.49]
3.1.2 Expressed breast milk versus swaddling	1	72	Mean Difference (IV, Fixed, 95% CI)	1.41 [‐0.17, 2.99]

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Comparison 4. White noise.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 PIPP during endotracheal suctioning	1	40	Mean Difference (IV, Random, 95% CI)	‐0.65 [‐2.51, 1.21]
4.2 Heart rate during endotracheal suctioning (bpm)	1	40	Mean Difference (IV, Random, 95% CI)	‐1.85 [‐11.46, 7.76]
4.3 Oxygen saturation during endotracheal suctioning (%)	1	40	Mean Difference (IV, Random, 95% CI)	2.25 [‐2.03, 6.53]

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Comparison 5. Swaddling.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 PIPP during endotracheal suctioning	1	72	Mean Difference (IV, Random, 95% CI)	‐0.64 [‐2.29, 1.01]

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

Alinejad‐Naeini 2014.

*Study characteristics*
Methods	Study design : randomised cross‐over trial Total study duration : 5 months (January 2013 to May 2013) Setting : Tehran University of Medical Sciences, level II NICU Country : Iran
Participants	Total number : 34 Diagnostic criteria : aged 29–37 weeks' gestation, birth weight ≥ 1200 g, having an endotracheal tube, no congenital anomalies, no seizures diagnosis, no chest tubes, no intracranial haemorrhage higher than Grade II, not receiving opiates and sedatives 4 hours before intervention, not receiving any painful procedure ≥ 30 minutes before intervention Age Minimum: not reported Maximum: not reported Mean: not reported SD: not reported Sex Boys: 18 Girls: 16
Interventions	Total number of intervention groups : 1 Control group description : no intervention Total number of participants randomised to each of the groups : 17 Specific intervention : facilitated tucking Intervention details : infant was placed on his/her side, his/her back was gently bent, the legs were flexed at an angle greater than 90°, the shoulders were also constricted up to 90° and the researcher's hands were placed over the head close to the mouth or on the neonate's face Suctioning was performed based on the infant's needs. The researcher measured data, performed suctioning and intervened. Neonates were kept in a quiet environment during the intervention, environmental stimuli such as light and sound were minimised at all stages of the study and kept constant.
Outcomes	Primary outcomes Pain outcomes, time points when measured, and scale limits: PIPP Recording pain score, immediately after suction Upper limit: 21 Lower limit: 0 High score = more pain 0–6: lack of pain 7–12: mild pain > 12: moderate‐to‐severe pain Continuous Included items Heart rate SaO ₂ Closing the eyes Change in nose‐lip chin shape Bulging of the brow between the eyes Gestational age Mode of behaviour for pain assessment Monitor and pulse oximeter Recorded 30 seconds before and after suctioning: SaO ₂ (recently calibrated pulse oximetry probe was attached to the infant's right foot) Heart rate values
Notes	Conflicts/declarations of study authors : none reported Adverse reactions : none reported Key conclusions of study authors : the facilitated tucking position can be used as a safe non‐pharmacological method for procedural pain management.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Randomly received," not specified.
Allocation concealment (selection bias)	Unclear risk	No details concerning allocation method.
Blinding of participants and personnel (performance bias)  All outcomes	High risk	Not possible: intervention was (quote): "placing the neonate in facilitated tucking position."
Blinding of outcome assessment (detection bias)  All outcomes	High risk	Not possible: outcome was PIPP score, assessed by watching videorecording. 2 researchers independently assessed each video.
Incomplete outcome data (attrition bias)  All outcomes	Low risk	Outcome data were complete, no attrition and no exclusions from the analysis. 34 infants were randomised and described in Table 1 of the publication. All infants were assessed for PIPP score.
Selective reporting (reporting bias)	High risk	Study reported twice, but with different outcome variable; so, it seems that reporting was based on post‐hoc choice of outcome measure.
Other bias	High risk	No hypothesis on anticipated effect on primary outcome. No power calculation. Cross‐over design.

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Axelin 2006.

*Study characteristics*
Methods	Study design : randomised cross‐over trial Total study duration : 10 months (2003–2004) Setting : Turku University Hospital, NICU Country : Finland
Participants	Total number : 20 Diagnostic criteria : ≤ 37 weeks' gestation, no major congenital anomalies, a need for regular endotracheal/pharyngeal suctioning, no analgesics for 4 hours before the procedures Gestational age Minimum: 24 weeks' gestation Maximum: 33 weeks' gestation Mean: not reported (median 28 weeks' gestation, 15 days) SD: not reported Age Minimum 6 days Maximum 37 days Mean: not reported SD: not reported Sex Boys: 8 Girls: 12
Interventions	Total number of intervention groups : 1 Control group description : no intervention, the nurse was allowed to talk to and pat the infant Total number of participants randomised to each of the groups : 20 Specific intervention : facilitated tucking Intervention details : facilitated tucking by parents, who had been taught the procedure in advance Suctioning by bedside nurse, the nurse put saline to both nostrils and suctioned the throat and the mouth of the infant and the endotracheal tube. The incubator was covered with a blanket, infant's position was supported by nesting, each laid on their right side
Outcomes	Primary outcomes Pain outcomes, time points when measured, and scale limits: NIPS After suctioning, pain was measured every 10 seconds Lower limit: 0 (minimum amount of pain) Upper limit: 7 (maximum amount of pain) High score = more pain Continuous Behavioural items: facial expression crying arms legs state of arousal Physiological items: breathing pattern Physiological indicators Recorded in 1‐minute intervals SaO ₂ was recorded at the end of each minute Heart rate values were computed by averaging the 12 most recent beats‐per‐minute values
Notes	Conflicts/declarations of study authors : none reported Adverse reactions : 1 infant developed septicaemia after the intervention Funding sources : the South‐Western Finnish Foundation of Neonatal Research Key conclusions of study authors : facilitated tucking by parents is an effective and safe pain management method during suctioning of preterm infants
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Cross‐over design in which the (quote): "order of conditions was randomised." No information on random sequence generation.
Allocation concealment (selection bias)	Low risk	Infants were randomised by (quote) "an outside assistant." So caregivers were not involved in the allocation procedure.
Blinding of participants and personnel (performance bias)  All outcomes	High risk	Not possible. The parents applied the facilitated tucking during the procedure, so visible for doctors and nurses.
Blinding of outcome assessment (detection bias)  All outcomes	High risk	NIPS score was assessed on videorecording by 2 independent scorers. They were blinded to the order of the conditions, but not to the intervention itself.
Incomplete outcome data (attrition bias)  All outcomes	Low risk	All the randomised suctioning episodes were analysed without any loss to follow‐up and none were excluded from the final analysis.
Selective reporting (reporting bias)	Low risk	No reason for concern.
Other bias	Low risk	Cross‐over design, but no carry‐over effect detected.

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Cone 2013.

*Study characteristics*
Methods	Study design : randomised cross‐over trial Total study duration : not reported Setting : single‐family‐room‐designed NICU at an academic health centre; Virginia Country : USA
Participants	Total number : 10 Diagnostic criteria : < 37 weeks' gestation at birth; aged < 1 week; intubated, on conventional ventilation; receiving inline suctioning; no chromosomal or genetic abnormalities; no congenital heart disease; no dysmorphic syndrome; not receiving paralytics, analgesics or sedating medications Age Minimum: 24 weeks' gestation Maximum: 37 weeks' gestation Mean: 27 (SD 4.3) weeks' gestation Sex Boys: 6 Girls: 4 Ethnicity : non‐Hispanic
Interventions	Total number of intervention groups : 1 Control group description : no specific suctioning protocols dictated how supportive care was provided during endotracheal tube suctioning. Routine suctioning was the only care procedure that occurred during the observation period Total number of participants randomised to each of the groups : 10 Specific intervention : 4‐handed care Intervention details : the research assistant warmed her hands, opened the incubator porthole doors and placed her hands in the incubator. Infant's attempts at self‐regulation were assessed and, if the infant was disorganised, supportive care (supporting positioning with hands to promote flexion, or assisting the infant in achieving a calm and regulated state by allowing finger grasp or plantar grasp to aid in motor regulation) was provided. The research assistant remained with the infant until an assessment of self‐regulation had been achieved. Endotracheal suctioning by bedside nurse, hyperoxygenation prior to suctioning, thus increasing the percentage of inspired oxygen to 100%
Outcomes	Primary outcomes Pain outcomes, time points when measured, and scale limits: Anderson Behavioural State Scale Obtained prior to handling the infant, at the start of both observation conditions, just prior to the initiation of suctioning, and at 5 other times occurring over a 10‐minute time span, 2 minutes apart Upper limit: 12 Lower limit: 1 From regular quiet sleep to hard crying 1 = regular quiet sleep 2 = irregular quite sleep 3 = active sleep 4 = very active sleep 5 = drowsy 6 = alert inactivity 7 = quiet awake 8 = active 9 = very active 10 = fussing 11 = crying 12 = hard crying Counts of SDB Higher number = more stress and defensive behaviour hiccoughs facial grimace eye clinch gaze aversion tongue protrusion finger splay struggling movements crying whining fussing a cry face spitting up or vomiting halt hand hunger posture Counts of SRB Higher number = more SRB eye widening facial brightening raising of eyebrows and face opening hand opening fingers lightly flexed searching eye movements grasping and holding on efforts and successes at tucking trunk and limbs together Physiological responses Heart rate SaO ₂ Reported in time sequenced vignettes: presuctioning observation lasting 10 minutes, during suctioning observation lasting from the initiation of suctioning to the completion of suctioning, and postsuctioning observation lasting an additional 10 minutes Secondary outcomes Hormonal indicators Obtained 30 minutes after suctioning event salivary cortisol
Notes	Conflicts/declarations of study authors : none reported Adverse reactions : none reported Funding : not mentioned Key conclusions of study authors : 4‐handed care during suctioning was associated with a decrease in stress and defence behaviours and an increase in self‐regulatory behaviours.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Cross‐over design with intervention/control in random order in 1 day. No information on sequence generation.
Allocation concealment (selection bias)	Unclear risk	There is an inadequate description of attempts to deal with potential allocation bias.
Blinding of participants and personnel (performance bias)  All outcomes	High risk	No, not possible. Intervention was (quote): "four‐handed suctioning."
Blinding of outcome assessment (detection bias)  All outcomes	High risk	Primary outcome not clearly defined. Stress assessed using Anderson Behavioural State Scale before, during and after suctioning, but unclear who performed the assessment. Unlikely that outcome assessment was blinded due to the nature of the intervention.
Incomplete outcome data (attrition bias)  All outcomes	Low risk	All included infants were analysed.
Selective reporting (reporting bias)	Low risk	No selective outcome reporting.
Other bias	High risk	Primary outcome not clearly defined. No sample size calculation, convenience sample of 10 infants. So, risk of lack of power.

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Desai 2017.

*Study characteristics*
Methods	Study design : randomised controlled trial Total study duration : 6 months Setting : level III NICU in a public hospital Country : India
Participants	Total number : 108 Diagnostic criteria : preterm neonates on assisted ventilation requiring suctioning, no major congenital anomalies, no severe encephalopathy Age Minimum: not reported Maximum: not reported Mean: expressed breast milk group: 32.76 (SD 3.96) weeks' gestation; sucrose group: 33.17 (SD 4.86) weeks' gestation; swaddling group: 32.19 (SD 3.45) weeks' gestation Sex : not reported
Interventions	Total number of intervention groups : 3 Control group description : it was ethically unacceptable to include a non‐intervention control group based on the evidence that exposure of preterm infants to pain procedures without treatment is harmful Total number of participants randomised to each of the groups : 36 Specific intervention 1: expressed breast milk Intervention details: 2 mL expressed breast milk was administered to the neonate 2 minutes before suctioning Specific intervention 2: swaddling Intervention details: the neonate was swaddled for 10–15 minutes before suctioning Specific intervention 3: sucrose Intervention details: 2 mL sucrose was administered to the neonate 2 minutes before suctioning 2 senior residents performed suctioning. The procedure of suctioning was only carried out when needed by the neonate and was assessed by a trained senior resident.
Outcomes	Primary outcome Pain outcomes, time points when measured, and scale limits: PIPP Recording pain score: 1 minute before, during and 5 minutes after endotracheal tube suctioning Upper limit: 21 Lower limit: 0 High score = more pain 0–6: lack of pain 7–12: mild pain > 12: moderate‐to‐severe pain Continuous Included items: Heart rate SaO ₂ Closing the eyes Change in nose‐lip chin shape Bulging of the brow between the eyes Gestational age Mode of behaviour for pain assessment
Notes	Conflicts/declarations of study authors : none Adverse reactions : none reported Key conclusions of study authors : suctioning is painful for preterm neonates on assisted ventilation. There was no difference between expressed breast milk, swaddling, and sucrose in relieving pain associated with suctioning.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation by a computer‐generated randomisation sequence. Randomisation performed in variable random blocks of 3 or 6.
Allocation concealment (selection bias)	Low risk	Treatment allocation was inserted in sequentially numbered opaque envelopes and were sealed. Just before suctioning, a senior resident opened the sequentially numbered envelope and allocated the group.
Blinding of participants and personnel (performance bias)  All outcomes	High risk	No. Would theoretically have been possible for the groups expressed breast milk versus sucrose, but not for the group swaddling.
Blinding of outcome assessment (detection bias)  All outcomes	High risk	No. Primary outcome assessed with PIPP score, which was conducted by the investigator using video recordings that were taken during endotracheal tube suction (also by the investigator).
Incomplete outcome data (attrition bias)  All outcomes	Low risk	Outcome data were complete, no attrition and no exclusions from the analysis, no loss to follow‐up. 36 participants included per group, all were analysed according to their assigned group.
Selective reporting (reporting bias)	Low risk	No selective outcome reporting.
Other bias	Unclear risk	Infants could be included multiple times since endotracheal tube suction episodes were randomised, and not the infants. In the statistical analysis, correlation between observations was not taken into account. However, only 12/118 infants were included twice. The impact of this is unclear.

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Fatollahzade 2022.

*Study characteristics*
Methods	Study design : randomised cross‐over trial Total study duration : 17 months (June 2018 to December 2019) Setting : level III NICU Country : Iran
Participants	Total number : 34 Diagnostic criteria : hospitalised in the NICU, aged 27–34 weeks' gestation, ≥ birth weight 1200 g, having an endotracheal tube, no congenital anomalies, no seizures, no metabolic disease, no chest tubes, no intracranial haemorrhage higher than Grade II, no skin disease, not receiving opiates and sedatives within 4 hours before intervention and not receiving any painful procedures ≥ 1 hour before the intervention Age Minimum: 27 weeks' gestation Maximum: 34 weeks' gestation Sex Boys: 19 Girls: 15
Interventions	Total number of intervention groups : 1 Control group description : no intervention Total number of participants randomised to each of the groups : 25 Specific intervention : gentle human touch Intervention details : gentle human touch was provided by cupping 1 hand around the infants' head while cupping the other hand around the infant's bottom. All suctioning was performed by the same nurse, based on infant's need. Neonates were kept in a quiet environment, environmental stimuli such as light and sound were minimised and kept constant during the entire procedure.
Outcomes	Primary outcome Pain outcomes, time points when measured, and scale limits: PIPP‐R (revision of the PIPP to address validity and feasibility issues; the minor revisions include changes to the physical layout, detailed instructions for use, and clarification of scoring gestational age and behavioural state indicators for preterm and term infants). Recording pain score: during endotracheal tube suctioning Upper limit: 21 Lower limit: 0 High score = more pain 0–6: lack of pain 7–12: mild pain > 12: moderate‐to‐severe pain Continuous Included items: Heart rate SaO ₂ Closing the eyes Change in nose‐lip chin shape Bulging of the brow between the eyes Gestational age Mode of behaviour for pain assessment
Notes	Conflicts/declarations of study authors : authors declared no conflict of interest in this study Adverse reactions : none reported Key conclusions of study authors : gentle human touch can be considered effective in reducing pain during endotracheal suctioning.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Cross‐over design. Purposeful sampling method. (Quote) "Randomly received," not specified.
Allocation concealment (selection bias)	Unclear risk	They used (quote) "number cards." It is not mentioned if and how the group allocation on those cards was concealed from the researchers or caregivers (or both) (e.g. closed envelopes?).
Blinding of participants and personnel (performance bias)  All outcomes	High risk	1 nurse/researcher assistant performed all the suctions and interventions, and also performed all measurements. The regular nurses performed the routine suctions, observed by the researcher.
Blinding of outcome assessment (detection bias)  All outcomes	High risk	No, not possible. Gentle human touch during endotracheal suctioning.
Incomplete outcome data (attrition bias)  All outcomes	Low risk	6/40 participants were excluded before randomisation. There were no postrandomisation exclusions. Analyses of the primary outcome contained 100% of included participants (34).
Selective reporting (reporting bias)	High risk	Only PIPP was reported. No data on other physiological parameters were reported.
Other bias	High risk	Comparability of the 2 groups could not be assessed (no comparative table of demographics) No baseline PIPP score No power calculation Cross‐over design without information on the timing between both suction episodes

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Niaraki 2022.

*Study characteristics*
Methods	Study design : randomised cross‐over trial Total study duration : not reported Setting : NICU Country : Iran
Participants	Total number : 40 Diagnostic criteria : infants aged 29–37 weeks' gestation and postnatal age < 1 week, birth weight ≥ 1000 g, having an endotracheal tube, absence of congenital anomalies, and having consumed no opioids or sedatives 4 hours before suctioning Age Minimum: 29 weeks' gestation Maximum: 37 weeks' gestation Sex Boys: 16 Girls: 24
Interventions	Total number of intervention groups : 1 Control group description : routine method (2‐handed care) Total number of participants randomised to each of the groups : 20 Specific intervention : 4‐handed care Intervention details : in 4‐handed suctioning, it started 2 minutes before the videorecording began. The researcher began to support the infant with washed and warm hands after 2 minutes and continued until the suction began. The neonatal support and touch stopped with suctioning. The suctioning was performed by the responsible nurse trained in the field. The nurse washed her hands and manually ventilated the infant for 2 minutes to maintain the necessary pulmonary volume during suctioning. Pressure of the suction was adjusted between 60 mmHg and 100 mmHg, then the length of the suction catheter was measured. The catheter was inserted into the endotracheal tube, suction was performed according to the amount of discharge. Total suction duration did not exceed 10 seconds. If the discharge did not come out with 1 suction, the suction might be repeated up to 3 times. The time interval was 30 seconds.
Outcomes	Primary outcome: ALPS‐Neo scale: Recording pain score: during endotracheal tube suctioning Upper limit: 10 Lower limit: 0 High score = more pain 0–4: lack of pain 5–7: moderate pain 8–10: severe pain Physiological and behavioural responses, using the ALPS‐Neo scale, were recorded 5 times for 30 seconds: 2 minutes before the suctioning, at the start of the neonatal touch, during suctioning, after suction and every 2 minutes for 4 times Included items Facial expression Pattern of respiration Tone of the organs Activity of the hands and feet Level of activity The reliability for the coders of the ALPS‐Neo scale was obtained from scoring 25 samples simultaneously in a pilot form. The correlation between their scoring methods was examined by the Kappa coefficient, which was acceptable (90.48%).
Notes	Conflicts/declarations of study authors : authors declared no potential conflicts of interest Adverse reactions : none reported Key conclusions of study authors : 4‐handed suctioning method can prevent an increase in the heart rate during and 2 minutes after suctioning, but it does not seem to affect behavioural responses and SaO ₂ of the infants.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Cross‐over design, in which the (quote): "order of conditions was randomised." The infants who needed suctioning were selected by convenience sampling.
Allocation concealment (selection bias)	Low risk	Randomisation was performed using closed letters. Accordingly, 1 of the letters was randomly selected, and the infants were assigned to 1 of the 2 groups. 1 of the group was first suctioned by the routine method and then by the 4‐handed method. The other group was other way around.
Blinding of participants and personnel (performance bias)  All outcomes	High risk	Not possible. 4‐handed care during endotracheal suctioning.
Blinding of outcome assessment (detection bias)  All outcomes	High risk	2 individual independently observed and assessed the physiological and behavioural status of the infants as well as the videorecordings.
Incomplete outcome data (attrition bias)  All outcomes	Low risk	There were no postrandomisation exclusions. Analyses of the primary outcome contained 100% of included participants (40).
Selective reporting (reporting bias)	Low risk	No reason for concern.
Other bias	Low risk	Cross‐over design, but no carry‐over effect detected.

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Taplak 2021.

*Study characteristics*
Methods	Study design : randomised controlled experimental trial Total study duration : 12 months (August 2015 to August 2016) Setting : NICU of a University Hospital Country : Turkey
Participants	Total number : 80 Diagnostic criteria : preterm infants who were admitted to the NICU, received mechanical ventilation in the Synchronised Intermittent Mandatory Ventilation mode; had ventilator between 1 and 7 days, aged ≥ 26 weeks' gestation, bodyweight ≥ 1000 g, an endotracheal tube inserted, and no hearing problem; and did not receive any opioid or sedative drug therapy up to 4 hours before the procedure Age Minimum: 26 weeks' gestation Maximum: 35.6 weeks' gestation Mean: not reported SD: not reported Sex Boys: 37 Girls: 43
Interventions	Total number of intervention groups : 3 Control group description : preterm infants were placed on the right side and aspirated using an open suctioning system. Total number of participants randomised to each of the groups : 20 Specific intervention 1 : breast milk smell Intervention details : 1 mL of breast milk was dropped on a pet/filter paper and placed 10 cm away from the infant's nose. Specific intervention 2 : white noise Intervention details : expert opinion was obtained for the selection of music to be played. It was composed of the mother's uterine environment and real heartbeat sounds and relaxing music. An MP3 player and 2 mini loudspeakers were used. The speakers were placed near the infant's feet, maximum volume was set at 45 dB. Specific intervention 3 : facilitated tucking Intervention details : the preterm infants were held in the facilitated tucking position by a nurse working in the service. Infants were laid on their right side with the arms and legs flexed and the knees and elbows tucked to midline The endotracheal suctioning procedure was performed according to the NICU protocol, between 10.00 a.m. and 12.00 a.m. by the same nurse working in the 8:00 a.m. to 16:00 p.m. shift. Preterm infants were aspirated using an open suctioning system, placed on the right side and the suctioning pressure was maximum 100 mmHg. The endotracheal suctioning procedure was always performed on the same time during the morning shift (10.00 a.m. to 12.00 a.m.), by the same nurse. It was performed according to the NICU protocol. An open suctioning system was used. Maximum pressure was 100 mmHg. Saline was applied in 2 preterm infants in each group. Hyperoxygenation administration was not required. Neonates were not subjected to any painful procedure from 15 minutes before to 5 minutes after suctioning procedure. Neonates were installed on the right side.
Outcomes	Primary outcome Pain outcomes, time points when measured, and scale limits: PIPP Recording pain score: before (5, 3 and 1 minute), during and after (1, 3, and 5 minutes) Upper limit: 21 Lower limit: 0 High score = more pain 0–6: lack of pain 7–12: mild pain > 12: moderate‐to‐severe pain Continuous Included items Heart rate SaO ₂ Closing the eyes Change in nose‐lip chin shape Bulging of the brow between the eyes Gestational age Mode of behaviour for pain assessment Physiological indicators Recorded : before (5, 3 and 1 minutes), during and after (1, 3 and 5 minutes) SaO ₂ Heart rate
Notes	Conflicts/declarations of study authors: the authors declared no potential conflicts of interest with respect to the research, authorship or publication of this article Adverse reactions : none reported Key conclusions of study authors : white noise and facilitated tucking were effective in relieving pain before procedure. Facilitated tucking was effective during recovery of preterm infants after the endotracheal suctioning.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Allocation was performed (quote): "using the simple randomisation method," but the method of random sequence generation is not reported.
Allocation concealment (selection bias)	Unclear risk	The observers and the other researchers were blinded to the allocation. No information on how allocation was concealed.
Blinding of participants and personnel (performance bias)  All outcomes	High risk	It mentioned that (quote) "only the one who video‐recorded the procedure knew to which group the infants were assigned; The observers and other researchers were blinded to the allocation, and thus, they did not know to which group the infants were assigned." However, it seems difficult to blind the caregivers from the interventions due to the nature of the interventions (sound, filter paper with breast milk, facilitated tucking).
Blinding of outcome assessment (detection bias)  All outcomes	Unclear risk	Low for 2 groups: 3 observers assessed outcomes who were (quote): "blinded for group allocation." This seems feasible for the groups "smell," "sound" and control. High for 1 group: 3 observers assessed outcome who were (quote) "blinded for group allocation." This does not seem feasible for "facilitated tucking," where the position of the baby must be obvious on video.
Incomplete outcome data (attrition bias)  All outcomes	Low risk	Exclusions for analysis: 4/64 in the intervention groups and 2/20 in the control group; no concern.
Selective reporting (reporting bias)	Low risk	Primary outcome was PIPP, as reported.
Other bias	Low risk	No, planned sample size achieved.

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Ward‐Larson 2004.

*Study characteristics*
Methods	Study design : randomised cross‐over trial Total study duration : not reported Setting : NICU Country : USA
Participants	Total number : 40 Diagnostic criteria : birth weight ≤ 1500 g, appropriate for gestational age as determined by Ballard Score, ≤ 28 days of life at study entry, requiring mechanical ventilation, parental permission to participate, no congenital anomalies, no major physiologic stress within 12 hours of data collection, did not receive opioid or non‐opioid analgesia or sedative within 12 hours before data collection, no intraventricular haemorrhage greater than Grade II Age Minimum: 23 weeks' gestation Maximum: 32 weeks' gestation Mean: 27.31 (SD 2.43) weeks' gestation Sex Boys: 22 Girls: 18 Ethnicity African American: 23 Caucasian (assumed to be white people): 16 Hispanic: 1
Interventions	Total number of intervention groups : 1 Control group description : infants were placed in a Snuggle Up, no hands were on the infant Total number of participants randomised to each of the groups : 40 Specific intervention : facilitated tucking Intervention details : the infant was turned to the side, back curled gently, legs flexed > 90° and brought to midline, and shoulders brought to midline with elbows flexed > 90° with hands near the mouth or on the infant's face Suctioning by bedside nurse, normal routine of endotracheal suctioning
Outcomes	Primary outcomes Pain outcomes, time points when measured, and scale limits: PIPP Recording pain score: preprocedural and procedural. Baseline data were collected 15 seconds before each suctioning episode. The investigator then observed the infant for 30 seconds immediately following the suctioning episode. Upper limit: 21 Lower limit: 0 High score = more pain 0–6: lack of pain 7–12: mild pain > 12: moderate‐to‐severe pain Continuous Included items: Heart rate SaO ₂ Closing the eyes Change in nose‐lip chin shape Bulging of the brow between the eyes Gestational age Mode of behaviour for pain assessment
Notes	Conflicts/declarations of study authors : the authors declared no potential conflicts of interest Adverse reactions : none Funding sources : not mentioned Key conclusions of study authors : facilitated tucking is a developmentally sensitive, non‐pharmacological comfort measure that can relieve procedural pain in very low birth weight infants.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomisation was mentioned, but there was no adequate description of the methods used.
Allocation concealment (selection bias)	Unclear risk	There was no adequate description of attempts to deal with potential allocation bias, non‐probability sampling technique.
Blinding of participants and personnel (performance bias)  All outcomes	High risk	Not possible. Intervention was (quote:) "tucking," performed by 1 research assistant while suctioning performed by nurse assigned for care of infant.
Blinding of outcome assessment (detection bias)  All outcomes	High risk	No: outcome was PIPP, assessed by investigator immediately after suctioning, with infant still in (quote) "tucking" position.
Incomplete outcome data (attrition bias)  All outcomes	Low risk	All infants enrolled remained through the duration of data collection; however, exact number of participants analysed was not mentioned in table. So presumed there was no loss of follow‐up.
Selective reporting (reporting bias)	Low risk	No. Planned primary outcome was PIPP score, as is reported in the paper.
Other bias	Low risk	No. Planned sample size achieved.

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NICU: neonatal intensive care unit; NIPS: neonatal‐infant pain scale; PIPP: Premature Infant pain profile; PIPP‐R: Premature Infant Pain Profile – Revised; SaO ₂ : oxygen saturation; SD: standard deviation; SDB: stress and defensive behaviours; SRB: self‐regulatory behaviours.

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Adams 2018	Not an RCT
Anand 1999	Pharmacological interventions: use of analgesia (morphine) and sedation (midazolam)
Anand 2005	Review
Anand 2008	Pharmacological interventions: use of analgesia (morphine)
Barker 1995	Not an RCT
Beeram 1992	Effects of saline instillation during tracheal suction rather than the effect of endotracheal suctioning on pain was measured. Outcome was pulmonary compliance and airway resistance
Bernert 1997	Not an RCT
Cardoso 2017	Not a non‐pharmacological intervention for reducing pain
Chen 2012	Not an RCT
Chettri 2015	Comparison between endotracheal suction and no endotracheal suction in neonates born through meconium‐stained amniotic fluid
Cignacco 2008	Pharmacological interventions: use of analgesia (morphine)
Cury 2013	Not an RCT
Fanconi 1987	Not an RCT
Gjerstad 2008	Not an RCT
Grunau 2000	Not an RCT
Hadian 2013	Not an RCT
Hartley 2015	Review
Hough 2014	Prospective observational clinical study
Jeong 2014	Not an RCT, prospective study
Karpe 2013	Not an RCT
Miller 1993	Not pain measurement during endotracheal suction, pain observed during insertion of intravenous catheter
Nangia 2016	Comparison between endotracheal suction and no endotracheal suction in neonates born through meconium stained amniotic fluid
Pitetti 2003	Not an RCT; population aged 0–21 years
Pokela 1994	Pharmacological interventions: use of meperidine
Pouraboli 2019	Primary outcome was not measured. Outcome was respiratory rate before and after suctioning
Pölkki 2014	Instrument development and psychometric analysis
Saarenmaa 1996	Pharmacological interventions: use of alfentanil
Saarenmaa 2001	Pharmacological interventions: use of ketamine
Shah 1992	Outcome was cerebral circulation
Shorten 1991	Factorial‐within‐subjects‐design
Sweet 2017	No endotracheal tube, suctioning; nasal continuous positive airway pressure
Tekgündüz 2019	No endotracheal tube, suctioning; during nasal continuous positive airway pressure
Tison 2009	Author reply
Treluyer 2005	Dose‐finding study
van Veenendaal 2009	Not an RCT
Välitalo 2016	Not an RCT
Välitalo 2017	Pharmacological interventions: use of analgesia (morphine)
Wilson 1991	Not an RCT, examination of existing practice

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RCT: randomised controlled trial.

Differences between protocol and review

We made the following changes to the protocol ( Pirlotte 2019 ).

We were unable to conduct the following comparisons due to a lack of research on the use of these interventions during endotracheal suctioning:
- skin‐to‐skin care of kangaroo‐care versus no intervention or standard care;
- rocking/holding versus no intervention or standard care;
- touch/massage versus no intervention or standard care;
- video distractions versus no intervention or standard care;
- acupuncture: transcutaneous electrical nerve stimulation and non‐invasive electrical stimulation of acupuncture points versus no intervention or standard care;
- multisensorial stimulation (MSS) versus no intervention or standard care
Some interventions were not specified in the protocol:
- facilitated tucking / four‐handed care / gentle human touch compared to familiar odour;
- facilitated tucking / four‐handed care / gentle human touch compared to oral sucrose;
- use of expressed breast milk;
- white noise intervention;
- closed system use versus open system use.
One validated pain scale was not specified in the protocol but used in one study:
- Astrid Lindgren Children's Hospital Pain Scale Neonates (ALPS‐Neo; Lundqvist 2014 ).
The protocol outcomes stated that pain and discomfort would be measured "from five minutes before, during and until 10 minutes after endotracheal suctioning." In the review, we only measured pain during endotracheal suctioning to accurately reflect the review title and objectives.
No studies measured the following secondary outcomes: neurological outcomes (such as any grade of IVH or periventricular leukomalacia); mortality; nausea/vomiting; duration of hospitalisation; hormonal indicators; long‐term outcomes such as cerebral palsy; and neurological development at 18 months, 24 months and at school age.
We made the following edit to the 'Unit of analysis issues'. The protocol stated that short‐term treatment effects would be measured during and immediately after the suctioning procedure. In the review, we stated that short‐term treatment effects would be measured during the suctioning procedure to accurately reflect the review title and objectives.
We initially planned to use a random‐effects model to perform the meta‐analyses, but to be in line with what Cochrane Neonatal prescribes, we used a fixed‐effect model in the review.
Following peer reviewer comments: we made the following change to the 'Types of participants': postmenstrual age was changed to gestational age.
Bart Van Rompaey withdrew himself from the review.

Contributions of authors

Generated the idea of conducting this systematic review: SP and FC.

Title registration and development of the protocol: SP and FC.

Search: SP.

Screening title, abstract and full‐text: SP and KB.

Data‐extraction: SP and IO.

Risk of bias assessment: SP and KB.

GRADE analyses: SP and FC.

Development of the systematic review: SP and FC.

Critical review: IO and KB.

Sources of support

Internal sources

New Source of support, Other

The authors received no internal sources of support.

External sources

Vermont Oxford Network, USA

Cochrane Neonatal Reviews are produced with support from Vermont Oxford Network, a worldwide collaboration of health professionals dedicated to providing evidence‐based care of the highest quality for newborn infants and their families.

Declarations of interest

SP: none.

FC: none.

IO: none.

KB: none.

New

References

References to studies included in this review

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PERMALINK

Non‐pharmacological interventions for the prevention of pain during endotracheal suctioning in ventilated neonates

Sofie Pirlotte

Katrien Beeckman

Isabel Ooms

Filip Cools

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Summary of findings 1. Facilitated tucking / four‐handed care / gentle human touch compared with standard care for pain during endotracheal suctioning.

Summary of findings 2. Familiar odour (breast milk smell) compared with standard care for pain during endotracheal suctioning.

Summary of findings 3. White noise compared with standard care for pain during endotracheal suctioning.

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Interventions

Comparators

Comparisons

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Continuous data

Dichotomous data

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Summary of findings and assessment of the certainty of the evidence

Results

Description of studies

Results of the search

1.

Included studies

Participants

Diagnostic criteria

Specific interventions

Outcome measures

Excluded studies

Studies awaiting classification

Ongoing studies

Risk of bias in included studies

2.

3.

Allocation

Blinding

Incomplete outcome data

Selective reporting

Other potential sources of bias

Effects of interventions

Comparison 1: facilitated tucking / four‐handed care / gentle human touch

Primary outcomes

Validated pain scale

Premature Infant Pain Profile during endotracheal suctioning

1.1. Analysis.