Nonpharmacological interventions for needle‐related procedural pain and post‐operative pain in neonates and infants.
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
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To assess the efficacy of nonpharmacological interventions for the management of needle‐related procedural and postoperative pain and distress in neonates, infants and children up to three years of age.
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To formulate an evidence base regarding the role of nonpharmacological strategies/techniques enacted in conjunction with pharmacological treatments.
Background
Evolving conceptualizations of pain in infancy
Despite the vigorous responses that result when an infant is subjected to a painful procedure, the premise that infants were insensitive to pain was only recently rejected by the general scientific community (McClain 2005), although exceptions in the literature still remain (e.g. Derbyshire 1999). Early studies suggested that infants did not possess a cortex well developed enough to perceive or localize pain (McGraw 1943). Moreover, initial misinterpretations of common infant pain outcomes, for example, the lack of declarative memory for painful experiences during infancy (Field 1995), the muted responses of premature infants after a barrage of painful procedures (Johnston 1993) and unacceptable rates of cardiac arrest or death due to poor knowledge of infant morphokinetics during the 1950's to 70's (Berde 2005), all perpetuated widespread neglect of infant pain treatment until the last three decades.
Current research supports that infants possess the anatomical and functional requirements to perceive pain (Anand 1987; Fitzgerald 2005) and respond behaviourally during tissue insult in a manner unequivocally interpretable as pain (Grunau 1987). However, despite evidence of the long‐term implications of unrelieved pain during infancy (Anand 2000; Grunau 1996; Grunau 2000; Howard 2003; Taddio 1997), evidence that infant pain is still under managed and unmanaged is clearly evident (Alexander 2003; Simons 2003). A comprehensive and systematic review of pain management strategies will be integral in appropriate infant pain management.
Managing infant pain
Generally speaking, pain management can be subdivided into two categories: pharmacological (Barber 2004; treatments that deal with the uses, effects, and modes of action of drugs) and non‐pharmacological (any treatments [contextual, psychological, and behavioural strategies] that do not deal with uses, effects and modes of action of drugs).
In a recent prècis of infant nonpharmacological pain management strategies, pain management was defined as any strategy or technique administered to an infant in pain with the intention of lessening pain sensation, pain perception or both (Pillai Riddell 2006). However, research has almost exclusively focused on the context of infant acute‐procedural or acute‐prolonged pain such as pain from heel sticks or surgical incisions with little research focusing on chronic pain during infancy (Pillai Riddell 2005).
One of the important principles in infant pain management is to recognize that pain is most effectively managed by avoiding, preventing or limiting exposure to pain provoking stimuli (Joint Committee 2000). Accordingly, pain management during infancy must be multifaceted and integrated within every step of the decision‐making process; from deciding whether a particular procedure is warranted to determining the safest and most efficacious pain relieving strategy.
There are comprehensive reviews which summarize assessment and management techniques for painful procedures in neonates or infants, or both which have recently been published (Anand 2001; Johnston in press), to our knowledge, there has been no comprehensive, systematic meta‐analysis conducted on the efficacy or effectiveness of nonpharmacological interventions for managing acute pain and distress in infants and young children up to three years of age. Therefore, this review will take a broader and more sensitive developmental approach and a summary statistical approach (meta‐analysis) to synthesize the current evidence on nonpharmacological strategies for procedural pain.
Objectives
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To assess the efficacy of nonpharmacological interventions for the management of needle‐related procedural and postoperative pain and distress in neonates, infants and children up to three years of age.
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To formulate an evidence base regarding the role of nonpharmacological strategies/techniques enacted in conjunction with pharmacological treatments.
Methods
Criteria for considering studies for this review
Types of studies
Only randomized controlled trials (RCTs) involving the management of acute procedural pain in infants and children up to three years of age will be included in this review (studies on children three years and older will be excluded). No language restriction will be used during the search. Due to existing work completed or currently underway by other Cochrane review authors, this review will exclude:
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studies that solely focus on sucrose (Stevens 2005) or breastmilk (Shah 2006) as a pain management strategy. Note that multi‐modal studies would be included (e.g. breastmilk and lullaby condition), if a relevant research design is utilized (i.e. breastmilk and lullaby condition versus lullaby condition);
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studies that examine pain management for the following types of acute pain stimuli and age groups: circumcision procedure for boys aged zero to three years (Brady‐Fryer 2004; Cyna 2005) and blood sampling via heel lance or venepuncture in neonates up to 28 days (Shah 2005);
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studies that relate to needle‐related or procedural pain in children older than three years (Uman 2006).
Types of participants
Participants will include all young children who are undergoing painful acute procedures. Term and preterm neonates will also be included in the review. Given that research in the area of infant pain management began in the late 1980's, a broad mandate of 'procedural pain' was selected rather than any particular type of procedure. However, in order to provide general parameters regarding procedures that would be under the review, sample procedures are provided. Based on two comprehensive references that outline painful procedures in either neonates or older children (Anand 2001; Uman 2006), the following non‐exhaustive list is provided as a sample of procedures that would fall under the umbrella of this review (see 'Table 1'). Definitions were derived from two online medical encyclopedic reference sources (i.e. MedLine Plus Medical Encyclopedia: www.nlm.nih.gov/medlineplus/mplusdictionary.html; The Merck Manual of Diagnosis and Therapy, 17th Edition, www.merck.com]; and by consulting with medical professionals in the area of infant pain.
| Name | Description |
| Vaccinations involving needles / immunization (also known as immunisation) | The creation of immunity usually against a particular disease or treatment of an organism for the purpose of providing immunity to subsequent attack by a particular pathogen; the introduction into humans or domestic animals of microorganisms that have previously been treated to make them harmless for the purpose of inducing the development of immunity |
| Venipuncture (also known as venepuncture) | Surgical puncture of a vein especially for the withdrawal of blood or for intravenous medication (only on infants older than 28 days) |
| Lumbar Punctures (also known as spinal tap) | Puncture of the subarachnoid space in the lumbar region of the spinal cord to withdraw cerebrospinal fluid (diagnostic) or inject anesthetic drugs (therapeutic) |
| Heel Lance (also known as heel puncture) | Heel puncture involves lancing of the lateral aspect of the infant's heel, squeezing the heel, and collecting the pooled capillary blood (only on infants older than 28 days) |
| Injection | The act of forcing a liquid into tissue, the vascular tree or an organ |
| Inserting or removing a central line or central venous catheter | Insertion/removal of a catheter into the large vein above the heart, usually the subclavian vein, through which access to the blood stream can be made for drugs and blood products to be given and blood samples withdrawn |
| Suture (also known as laceration repair) | A stitch made with a suture; a strand or fiber used to sew parts of the living body. Also the removal of sutures |
| Surgery (also known as operation) | Any invasive procedure that may involve cutting, abrading, lasering, or otherwise physically changing body tissues or organs |
Types of interventions
Nonpharmacological interventions
Nonpharmacological interventions can be clustered into three different categories based on their hypothesized mechanism of action (Pillai Riddell 2006).
Contextual strategies
Contextual strategies can refer to strategies that impact:
a) The intra‐individual context of the infant (such as reducing the number of painful procedures, based on an individual infant's past pain experiences that day or week; (e.g. Johnston 1996) or;
b) The environmental context (such as reducing the presence of stressful elements in the infant's environment; using a less painful technique to conduct a painful procedure (e.g. Kaufman 2002), or both a and b. The context in which a painful procedure is conducted modifies behavioural and physiological expression of infant pain. Preliminary research suggests that infants who are cared for in a developmentally sensitive manner (i.e. low noise and lighting, clustering procedures to avoid over handling, soothing smells) have lower pain reactivity (Stevens 1996a). Contextual strategies are often considered the standard of care in NICUs around the world (Johnston in press).
Cognitive strategies
Although less extensively studied than contextual strategies, infants' abilities to cognitively modulate the pain experience are beginning to receive attention.
a) Distraction: a cognitive technique designed to shift attention away from painful stimulus by encouraging attention to another non‐painful stimulus is used in infancy by using developmentally appropriate distractor's. Two types of distraction have been seen in the literature:
i.e visual e.g. mobile or mirror (Cohen 2002),
ii. auditory e.g. music / lullabies (Bo 2000).
b) Signalling: another cognitive technique that has successfully managed infants' pain is signaling (e.g. Derrickson 1993). This technique allows an infant to predict the occurrence of painful and invasive procedures by conditioning the infant to anticipate a painful experience only after a certain signal is made. In essence, "non‐invasive" (e.g. non‐physical infant attention from caregiver) versus "invasive" periods (e.g. tracheal suctioning, injections, medication administration) are made clear to the infant in advance of the procedure. Taddio 2002 verify that even infants not subjected to experimenter‐designed signaling procedures become conditioned to expect painful experiences.
Behavioural strategies
These strategies involve either direct (e.g. rocking) or indirect (e.g. non‐nutritive sucking; caregiver provides soother) manipulation of the infant's body by a caregiver. Much research on nonpharmacological pain management strategies has been conducted within this domain. Accordingly, a number of strategies will be covered in this review. These strategies include:
a) Non‐nutritive sucking (NNS): placing an object (e.g. pacifier, non‐lactating nipple) into an infant's mouth to stimulate oro‐tactile or sucking behaviours during a painful event;
b) Skin‐to‐skin contact with mother (also known as maternal kangaroo care): an infant is placed on their mother's bare chest during a painful procedure or for soothing after a painful procedure (e.g. Johnston 2003);
c) Rocking and holding: an infant is held by a caregiver during the painful procedure and after the procedure the infant is gently moved up and down or side to side (e.g. Campos 1994);
d) Swaddling: an infant is wrapped in a light cloth to keep limbs close to the trunk and prevent the child from moving around excessively (e.g. Fearon 1997);
e) Positioning: containment through positioning and blanket rolls to provide the infant with physical boundaries and help in maintaining a flexed position (e.g. Stevens 2000);
f) Facilitative tucking: a caregiver uses their hands to swaddle the infant in a fetal position by placing a hand on the infant's head and feet while providing flexion and containment (e.g. Corff 1995);
g) Multisensory saturation: the administration of strategies (could be combination of contextual, cognitive, behavioural) that concurrently stimulate different sensory pathways and involves some combination of the above strategies (e.g. massage, eye contact, gentle vocalization, soothing smell, sucrose; e.g. Bellieni 2002; NNS with sucrose or breastmilk, e.g. Gray 2002; Stevens 1999).
The above interventions can be administered by any qualified health‐care professional (i.e., MD, nurse, psychologist, technician) or family member involved in the care of the infant.
Management versus additive benefit studies
The role of nonpharmacological interventions (contextual, behavioural, cognitive; see specific examples above) will be the main focus of the review. In order to accomplish the main objectives, interventions that are specifically addressing the adjuvant value of nonpharmacological interventions will be handled separately (e.g. studies examining a music group versus non‐music group, will be analyzed separately than a study examining a music plus topical lidocaine group versus a lidocaine‐only group).
Types of outcome measures
Due to the limited verbal capacity of the infant it is important to recognize that pain measures are limited in distinguishing between infant pain and infant distress (Craig 2002). However, due to the presence of an objectively painful stimulus in all studies selected for this review, all pain measures will be considered an indicator of an infant's pain.
Based on a recent comprehensive review in infant pain assessment (Stevens in press), there are at least 25 infant pain and general distress measures with preliminary reliability and validity (as evidenced by a study in at least one peer reviewed journal). To help limit non‐treatment variance from the outcome measures, only measures with preliminary reliability and validity will be included. The following is a list of potential variables for analysis based on the aforementioned review
Primary outcomes
1) Unidimensional measures: these measurement tools or approaches include either one indicator (e.g. cortisol) or multiple indicators from one particular domain (e.g. measuring different discrete facial actions to produce a facial action score).
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Visual Analog Scales (VAS).
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Numerical Rating Scales (NRS).
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Baby Facial Action Coding System (Rosenstein 1988)
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Infant Body Coding System (Craig 1993).
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Maximally Discriminative Facial Movement Coding System (Izard 1979).
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Neonatal Facial Coding System (Grunau 1987).
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Cry (presence, latency to cry, amplitude, pitch, vigour, fundamental frequency).
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Heart Rate (variability, vagal tone).
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Cortisol (plasma, salivary).
Secondary outcomes
2) Multidimensional measures: a multidimensional measure generally refers to any measure that combines different indicators of pain within a particular domain (e.g. behavioural domain that includes facial action, body movement, cry) or a composite approach across domains (e.g. behavioural, physiological and contextual indicators) into a single score.
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Behavioral Pain Score (Robieux 1991).
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Behavioral Pain Score (Pokela 1994).
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Children's and Infants Postoperative Pain Scale (Buttner 2000).
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Douleur Aiguë du Nouveau‐né (DAN; Carbajal 1997, Bellieni 2002; Carbajal 2005).
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Modified Behavioral Pain Scale (MBPS; Taddio 1995).
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Face, Legs, Activity, Cry and Consolability Scale (FLACC; Merkel 1997; Manworren 2003).
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Clinical Scoring System (Barrier 1989).
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Modified Postoperative Comfort Score (Guinsburg 1998).
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Echelle Douleur inconfort nouveau‐Né (EDIN ; Debillon 2001).
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Liverpool Infant Distress Scale (LIDS; Horgan 1996; Horgan 2002).
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Neonatal Pain, Agitation and Sedation Scale (N‐PASS ; Hummel 2003).
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Riley Infant Pain Scale (RIPS; Schade 1996).
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Pain Assessment Tool (PAT, Hodgkinson 1994).
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Scale for Use in Newborns (SUN, Blauer 1998).
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Distress Scale for Ventilated Newborn Infants (DSVNI, Sparshott 1996).
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The Comfort Scale (Ambuel 1992, Van Dijk 2000).
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Crying, Requires increased oxygen, Increased vital signs, Expression, Sleeplessness, (CRIES, Krechel 1995).
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Neonatal Infant Pain Scale (NIPS; Lawrence 1993).
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Pain Assessment in Neonates Scale (PAIN; Hudson‐Barr 2002).
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Modified Infant Pain Scale (MIPS; Bucholz 1998).
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Premature Infant Pain Profile (PIPP, Stevens 1996b).
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Cardiac Analgesic Assessment Scale (CAAS; Suominen 2004).
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Nepean Neonatal Intensive Care Unit Pain Assessment Tool (NNICUPAT; Marceau 2003).
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Bernese Pain Scale (Cignacco 2004).
Search methods for identification of studies
Electronic searches
In terms of published studies, a unique search strategy for each of the five databases was designed in conjunction with a librarian affiliated with The Cochrane Collaboration. Moreover, using the auto‐updating feature offered by MEDLINE, PSYCINFO, EMBASE and CINAHL, we will receive weekly abstract updates using our review strategy, up until four months before the final copy of the review is submitted to the Cochrane database. Finally, we will use the reference lists of recently published reviews and meta‐analyses to ensure completeness (e.g. Anand 2001; Johnston in press).
Electronic search (Published studies):
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MEDLINE (1966 to present);
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PSYCINFO (1887 to present);
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EMBASE (1974 to present);
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Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to present);
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ProQuest Dissertations and Theses (1861 ‐ 1996 (citations only); 1997 ‐ (full text);
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The Central Register of Controlled Trials (CENTRAL) The Cochrane Library;
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Pain, Palliative Care and Supportive Care Group Register.
The search strategy we will be using with MEDLINE 1966 can be found in Appendix 1.
A similar search strategy will be adapted for searches of the other databases.
Searching other resources
Unpublished studies
Unpublished studies (unpublished manuscripts, dissertations not yet in the abstract database, etc) for possible inclusion in this review will be obtained by two methods:
a) general emails to international list serves including: Pain in Child Health list‐serve, Society of Pediatric Psychology list‐serve, Developmental Psychology list‐serve, Pediatric Nursing List‐serve.
b) tailored emails, sent to researchers who have published in the area of infant pain management or who have registered a nonpharmacological infant pain management RCT with The Cochrane Collaboration. A list of names will be generated from authors who have published in the area of infant pain management (as generated by our search strategy).
Data collection and analysis
1. Selection of trials
Three review authors (RPR, LU, AG) will independently screen abstracts of trials from literature searches for inclusion in the review. Review authors will not be blind to authors, institutions, journals, or results. A fourth review author (BS) will be brought in if any disagreements cannot be resolved.
2. Data extraction
Data extraction will be conducted by three review authors (RPR, LU & AG) using a data extraction form designed for this specific review. A fourth review author (BS) will be brought in to resolve any disagreements. The following information will be extracted, if available:
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Number of subjects (total and in each treatment group);
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Gender, age, and race of subjects;
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Study design (e.g., parallel design, cross‐over design);
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Procedure they are undergoing (e.g., immunization);
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Type of intervention (e.g., distraction);
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When intervention was administered (i.e., pre‐procedure, during procedure, following procedure);
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Type(s) of outcome measures (e.g., NFCS, PIPP);
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Results from outcome measures (i.e., means, standard deviations [noting when transformations from standard error will be necessary], number of subjects);
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Participant refusal rate for the study;
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Reasons for refusal to participate;
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Number of randomized subjects who withdrew and reasons;
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Whether study was a management study or an additive benefit study. If this information is not included in the article, we will attempt to contact authors to obtain the information;
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Adverse events for any treatment condition.
All data will be recorded directly into electronic data extraction forms by two review authors (LU, AG) and the other review authors (RPR, BJS) will independently re‐record the data from 30% of the studies to establish inter‐rater reliability using Kappa coefficients. Once all forms are completed they will be entered into a computer spreadsheet by two of the review authors (LU, AG) and once again, 30% will be independently verified for accuracy by a second review author (RPR).
3. Losses to follow‐up
If more than 20% of the originally randomized participants were not available for the outcome analysis, the data will not be incorporated in the statistical analysis.
4. Study quality
Each study included in the review will be scored for quality by one author (RPR, LU) using the Quality of Study Design and Methods Scale (Yates 2005). The original scale is comprised of eight multi‐part questions. The scale for item responses range from zero to one or zero to two, with a maximum score of 26 points. Although this scale could be used for a broad array of research areas, this scale was specifically validated with nonpharmacological treatments (psychological treatments). Two minor modifications will be made to the Yates scale based on lack of relevance to the present review. Item four has a part that relates to treatment expectations (i.e. patient expectations) and will not be scored due to age of patient (less than three years). Second, item six (in the original scale) was completely omitted due to the focus of current review on brief procedural pain interventions. In the original scale this item related to following up the patient for at least six months post‐treatment. The maximum scale on the revised Yates will be 24 points.
Scale questions
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Are the inclusion and exclusion criteria clearly specified (two parts)?
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Sample criteria: zero to one;
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Evidence that criteria was met: zero to one.
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Is there evidence that CONSORT guidelines for reporting attrition have been followed (two parts)?
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Attrition: zero to two;
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Rates of Attrition zero to one.
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Is there a good description of the sample (two parts)?
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Sample characteristics: zero to one;
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Group equivalence: zero to one.
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Adequate steps to minimise bias (three parts)?
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Randomisation: zero to two;
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Allocation bias: zero to one;
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Measurement bias: zero to one.
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5. Are the outcomes that have been chosen appropriate (three parts)?
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Justification of outcomes: zero to two;
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Validity of outcomes for context: zero to two;
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Reliability and Sensitivity: zero to two.
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Are the statistical analyses adequate (five parts)?
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Power calculation: zero to one;
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Sufficient sample: zero to one;
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Planned analysis: zero to one;
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Statistics reporting zero to one;
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Intention to treat: zero to one.
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Has a good, well‐matched alternative treatment group been used (one part)?
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Control group: zero to two.
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5. Statistical analyses
Guiding principles
Three main guiding principles will guide the meta‐analysis of the data collected for this review:
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An attempt will be made to analyze results separately for infants of different age categories. These age categories will be: preterm neonates (of extremely low birth weight), term neonates to eight months, eight to 18 months, 18 to 36 months.
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All data will be kept in its continuous form to increase power and avoid loss of data.
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Analyses will be conducted for each pain measure separately.
Analyses will be conducted in relation to the combination of four dimensions: infant age, infant pain measure, pain management intervention, and source of procedural pain (e.g. an analysis will be conducted in preterm infants, using the Premature Infant Pain Profile, for the treatment of swaddling during a heel lance procedure). While complex, this type of separation of results is seen to be an appropriate analysis structure because
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it adheres to one of the most basic principles of meta‐analysis [not combining studies that differ on key points relevant to the analysis];
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it will result in a clearer summary of evidence for clinicians; and
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it will elucidate gaps in the evidence for researchers.
6. Analysis
The main type of analysis presented in this review will be the mean difference (MD) with the assumption of a fixed effects model (Deeks 2005). In essence, the MD offers readers the magnitude of the treatment effect relative to the variability observed in the study. The mean difference refers to the difference between the treatment group and one of the control groups described above. Using this statistical methodology, an index of the variability of the sample (standard deviation) and the number of participants in the sample (sample size) are used to determine how influential each study will be to the final meta‐analytic statistic. The greater the variability (generally associated with small sample sizes), the less a particular study will be weighted in the final analysis. Given our strategy that only certain studies (i.e. utilizing infants of a similar age group, the same measurement tool, a similar painful procedure, and pain management strategy) will be analyzed together and assuming a priori that the individual analyses will meet the statistical assumption of homogeneity, we believe that the use of MD is a valid choice. In addition to the MD, we will also report a 95% confidence interval (CI) (which incorporates the standard error of the pooled treatment effect) for the treatment effect.
7. Heterogeneity
Although we have outlined a statistical analysis plan that is respectful of what we hypothesize to be four major contributors to the heterogeneity of the treatment studies (infant age, source of pain, pain measurement tool, and pain management procedure), we believe that the existence of heterogeneity between studies is inevitable. Given our primary interest in the impact of the heterogeneity rather than the presence of heterogeneity, we will utilize the I2 statistics which measures the impact, rather that the presence of, heterogeneity (as cited in Deeks 2005). In cases where substantial heterogeneity is found, strategies to clarify the source (using additional information from data extraction sheets), minimize the impact or both combined will be utilized.
8. Sensitivity analyses
Factors that may affect the results from individual studies will be investigated using sensitivity analyses. In order to examine how the types of decisions made for this review may have impacted the results, each separate data analysis (i.e. the MD statistic) will be run twice to see if a significant change to the results occurs. The first time will involve only studies that met our inclusion criteria and the second time will involve all studies found.
Statistical analyses will be conducted using RevMan 4.2 software.
| Name | Description |
| Vaccinations involving needles / immunization (also known as immunisation) | The creation of immunity usually against a particular disease or treatment of an organism for the purpose of providing immunity to subsequent attack by a particular pathogen; the introduction into humans or domestic animals of microorganisms that have previously been treated to make them harmless for the purpose of inducing the development of immunity |
| Venipuncture (also known as venepuncture) | Surgical puncture of a vein especially for the withdrawal of blood or for intravenous medication (only on infants older than 28 days) |
| Lumbar Punctures (also known as spinal tap) | Puncture of the subarachnoid space in the lumbar region of the spinal cord to withdraw cerebrospinal fluid (diagnostic) or inject anesthetic drugs (therapeutic) |
| Heel Lance (also known as heel puncture) | Heel puncture involves lancing of the lateral aspect of the infant's heel, squeezing the heel, and collecting the pooled capillary blood (only on infants older than 28 days) |
| Injection | The act of forcing a liquid into tissue, the vascular tree or an organ |
| Inserting or removing a central line or central venous catheter | Insertion/removal of a catheter into the large vein above the heart, usually the subclavian vein, through which access to the blood stream can be made for drugs and blood products to be given and blood samples withdrawn |
| Suture (also known as laceration repair) | A stitch made with a suture; a strand or fiber used to sew parts of the living body. Also the removal of sutures |
| Surgery (also known as operation) | Any invasive procedure that may involve cutting, abrading, lasering, or otherwise physically changing body tissues or organs |
