As required versus fixed schedule analgesic administration for postoperative pain in children
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To assess the efficacy of as required versus fixed schedule analgesic administration for the management of postoperative pain in children under the age of 16.
Background
Description of the condition
Acute pain occurs as a result of tissue damage either accidentally due to an injury or as a result of surgery. Acute postoperative pain is a manifestation of inflammation due to tissue injury or nerve injury, or both. The management of postoperative pain and inflammation is a critical component of patient care (Derry 2013), and if treated inadequately can significantly affect recovery (Apfelbaum 2003).
The World Health Organization (WHO) guidelines for pharmacological treatments for children's pain acknowledge that pain in children is a public health concern of major significance in most parts of the world (WHO 2012). These guidelines state that the principle for treating pain at regular intervals, for example postoperatively, is to administer analgesics 'by the clock' rather than on an 'as needed' basis. It has also been suggested that "Around‐the‐Clock" (ATC) dosing should be used when pain itself is continuous or present for 12 or more hours each day, since postoperative pain will most likely be continuous for at least 24 hours following surgery (Pasero 2010). However, there is a need to understand the risks and benefits of time‐contingent (ATC) dosing because of fears of over‐medication or unwanted side effects (Sutters 2005). Hence, it is unclear whether 'as required' or scheduled ATC analgesic administration for children's postoperative pain is the most successful at preventing or reducing pain.
A report for the Department of Health (DoH) in the United Kingdom (UK) stated that approximately half a million children and young people undergo anaesthesia and surgery each year in England and Wales (Cochrane 2007). In the United States, tonsillectomy is one of the most common surgical procedures, with more than 530,000 procedures performed annually in children younger than 15 years (Baugh 2011). Over 30 years ago, a survey on the incidence of postoperative pain in children showed that on the first postoperative day, 17% still reported severe pain (Mather 1983). More recent evaluations of the prevalence of acute pain in hospitalised children have shown that those on surgical units, for example, reported higher rates of moderate to severe pain (44%) than those on medical units (13%) (McGrath 2013). Another survey of 290 medical and surgical inpatients in Canada concluded that pain was infrequently assessed, yet occurred commonly across all age groups and services, and was often moderate or severe; analgesic therapy was largely single‐agent and intermittent (Taylor 2008). In recent years, a range of postoperative analgesic techniques have been developed to recognise, minimise, and control pain in children (Lönnqvist 2005). However, it is still reported that children remain under treated and that more research in this area is needed (Lee 2014; Schechter 2003).
Description of the intervention
Self report is the primary source of information for measuring pain intensity in children (McGrath 2013), and analgesic doses can be adjusted in response to reports of intensity (von Baeyer 2009).
Cognitive developmental factors can impact children's understanding of pain and their ability to describe it effectively, and a good measure "should accurately reflect the individual's subjective experience" (Schechter 2003). Age‐appropriate measurement tools are used to assess a child's self report, and can assist the person administering the analgesics in selecting and evaluating treatments. The numerical rating scale (NRS) and the visual analogue scale (VAS) are validated measurement scales commonly used by children over the age of eight, whereas the Faces Pain Scale ‐ Revised (FPS‐R) or the Poker Chip Tool (PCT) may be implemented for much younger children. NRS and VAS require the individual to be able to estimate quantities along a numerical or spatial dimension, hence are more appropriate for older children (von Baeyer 2013).
Administering the appropriate analgesia to paediatric patients is a complex process and multiple strategies may be required (Smyth 2011). Participation of the parents and carers, or proxy measures (e.g. observational, behavioural, or physiological), may be utilised in order to manage children's postoperative pain (APA 2012; Lee 2014; Lönnqvist 2005). Behavioural measures may be helpful when the child is sedated, in distress, or believed to be under‐reporting their pain (MacLaren Chorney 2013). Physiological biomarkers of pain, such as cortisol levels or heart rate, may also be utilised, but the process of identifying and measuring biomarkers for such a diverse and subjective experience as pain is still under development (Brummelte 2013).
'As required', or 'as needed', analgesic administration can be used to manage children's postoperative pain; this is also referred to as 'pro re nata' (PRN) administration. PRN analgesia is designed to provide flexible dosing that can be adapted to the needs of an individual (Gordon 2008). Self administration is not always possible, especially in very young children, and the patient may need to signal to the person administering the analgesic, e.g. a parent or nurse, to indicate that they are in pain and require another dose.
Scheduled ATC analgesia is also used to manage children's postoperative pain, and this can provide continuous relief by preventing the pain from recurring (Chiaretti 2013). The website for the Great Ormond Street Hospital in the UK describes planned pain relief for children after surgery, indicating that the effects of analgesics such as paracetamol, ibuprofen, or oral morphine last for four to six hours (GOSH 2014). For most patients receiving scheduled analgesia for postoperative pain, a supplemental dose is also offered on an 'as required' basis, although the route of administration and time to peak effect will dictate how often the rescue dose can be offered (Chiaretti 2013). Clinical concerns for those administering analgesics can include whether to wake children up in order to maintain scheduled ATC dosing, and whether the child's self report makes sense and can be accurately interpreted.
Regardless of the means of administering pain relief, it is acknowledged that good communication between the child, the parents and carers, and the healthcare team is vital in helping to manage a child's postoperative pain (APA 2012).
This review will compare as required analgesia and scheduled analgesic administration for postoperative pain as two distinct intervention arms.
Why it is important to do this review
This review has been commissioned by the National Institute for Health Research (NIHR) in the UK in response to a National Health Service (NHS) 'decision problem' regarding outpatient management of postoperative pain in children. This topic was identified in September 2013 during consultation with the NIHR. This review will assess the comparative benefits of as required analgesia and scheduled analgesic administration for postoperative pain in children who have recently undergone surgery, in both inpatient and outpatient settings.
The NIHR commission states: "Guidelines on postoperative management of paediatric pain recommend time‐contingent analgesic dosing to reduce or prevent pain before it begins. Potential benefits of this approach include the maintenance of therapeutic levels of opioids, the facilitation of routine postoperative activities (e.g., oral intake, activity, sleep), and the avoidance of delays in analgesic administration because of inaccurate parental assessment of children's pain behaviours. However, many clinicians and parents fear that regularly scheduled administration of analgesics may result in the administration of unnecessary and/or excessive amounts of analgesics, which may cause undesirable and potentially harmful adverse effects. As a result, children are often not given enough pain control in the post‐operative period. It is therefore necessary to evaluate the current evidence to determine the benefits and/or harms of regular dosing of analgesics versus 'when needed' following surgery in children."
This protocol replaces the original version on as required versus fixed schedule analgesic administration schedules for treating postoperative pain in children and adults (Conlon 2013). The review will assess analgesic administration for children, and has been directly commissioned for completion by March 2015.
Objectives
To assess the efficacy of as required versus fixed schedule analgesic administration for the management of postoperative pain in children under the age of 16.
Methods
Criteria for considering studies for this review
Types of studies
We will include studies if they are randomised controlled trials (RCTs) assessing participant outcomes based on validated age‐appropriate pain scales.
Types of participants
Children under the age of 16, who have undergone any surgical procedure requiring postoperative pain relief, in any setting.
Types of interventions
Interventions of interest include:
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the use of as required or 'pro re nata' (PRN) analgesia administered by any route, in any dosage and prescribed to treat pain postoperatively;
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fixed analgesic administration schedules for postoperative pain management.
We do not plan to include studies of patient‐controlled analgesia (PCA) as these are not 'PRN' in the true sense of the term and this topic will be considered for a separate review.
Types of outcome measures
We plan to include a 'Summary of findings' table as set out in the Cochrane Pain, Palliative and Supportive Care Review Group's author guide (AUREF 2011), and recommended in theCochrane Handbook for Systematic Reviews of Interventions, chapter 4.6.6 (Higgins 2011). We will justify and document all assessments of the quality of the body of evidence.
Primary outcomes
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Pain intensity and pain relief, assessed using validated tools such as numerical rating scale (NRS), visual analogue scale (VAS), Faces Pain Scale ‐ Revised (FPS‐R), Colour Analogue Scale (CAS), or any other validated numerical rating scale. We will look for participant‐reported pain, but we will accept observer‐reported outcomes if no data are available for participant‐reported pain.
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Any reported adverse events.
Secondary outcomes
We identified the following with reference to the PedIMMPACT recommendations, which suggest core outcome domains and measures for consideration in paediatric acute and chronic/recurrent pain clinical trials (PedIMMPACT 2008).
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Participant global impression, measured using the Patients' Global Impression of Change (PGIC) scale (Hurst 2004).
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Carer global impression; see above.
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Medication use.
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Requirement for rescue analgesia.
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Length of postoperative stay.
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Sleep duration and quality.
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Acceptability of treatment.
Search methods for identification of studies
Electronic searches
We will search the following electronic databases: CENTRAL (on The Cochrane Library), MEDLINE, EMBASE, and CINAHL, from inception to the latest issue. We will use Medical Subject Headings (MeSH) or equivalent and text word terms. There will be no language restrictions. We will tailor searches to individual databases. The search strategy for MEDLINE is shown in Appendix 1.
Searching other resources
We will search clinicaltrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (http://apps.who.int/trialsearch/) for ongoing trials. We plan to search the metaRegister of Controlled Trials (mRCT) (www.controlled‐trials.com/mrct) but this may not be possible as the website is currently unavailable (at November 2014). In addition, we will check reference lists of reviews and retrieved articles for additional studies and perform citation searches on key articles. We will contact authors where necessary for additional information.
Data collection and analysis
Selection of studies
Two review authors (AH, PW) will independently assess the abstract of each study identified by the search. We will eliminate studies that clearly do not satisfy the inclusion criteria. Disagreements will be resolved by discussion with the third author if necessary (JC). We will document the selection process in sufficient detail to complete a PRISMA flowchart (Liberati 2009), and 'Characteristics of included and excluded studies' tables.
Data extraction and management
We will obtain full copies of the studies and assess them against the inclusion criteria. Where available, data extraction will include study design, participants, interventions, reported postoperative pain, adverse effects, participant and carer global impressions, medication use, requirement for rescue analgesia, and length of stay. We will use a template data extraction form and check for agreement before entry into The Cochrane Collaboration's statistical software Review Manager 5.3 (RevMan 2014).
If a study has more than two intervention arms, we will only include in the review intervention groups and control groups that meet the eligibility criteria. If multi‐arm studies are included, we will analyse multiple intervention groups in an appropriate way that avoids arbitrary omission of relevant groups and double‐counting of participants.
We will include studies in the review irrespective of whether measured outcome data are reported in a 'usable' way.
Assessment of risk of bias in included studies
Two authors will independently assess risk of bias for each study, using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), and adapted from those used by the Cochrane Pregnancy and Childbirth Group, with any disagreements resolved by discussion.
We will assess the following for each study.
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Random sequence generation (checking for possible selection bias). We will assess the method used to generate the allocation sequence as: low risk of bias (i.e. any truly random process, for example random number table; computer random number generator); or unclear risk of bias (when the method used to generate the sequence is not clearly stated). We will exclude studies at high risk of bias that use a non‐random process (for example, odd or even date of birth; hospital or clinic record number).
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Allocation concealment (checking for possible selection bias). The method used to conceal allocation to interventions prior to assignment determines whether intervention allocation could have been foreseen in advance of, or during, recruitment, or changed after assignment. We will assess the methods as: low risk of bias (for example, telephone or central randomisation; consecutively numbered, sealed, opaque envelopes); or unclear risk of bias (when the method is not clearly stated). We will exclude studies that do not conceal allocation and are therefore at a high risk of bias (for example, open list).
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Blinding of outcome assessment (checking for possible detection bias). For this review, it is unlikely that these studies will be blinded to the investigators or participants. We will assess any methods used to blind the outcome assessors from knowledge of which intervention a participant received. We will assess the methods as: low risk of bias (e.g. study states that it was single‐blinded and describes the method used to achieve blinding of the outcome assessor); unclear risk of bias (study states that outcome assessors were blinded but does not provide an adequate description of how it was achieved); or high risk of bias (outcome assessors were not blinded). We will exclude studies at a high risk of bias that were not single‐blind.
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Incomplete outcome data (checking for possible attrition bias due to the amount, nature, and handling of incomplete outcome data). We will assess the methods used to deal with incomplete data as: low risk of bias (i.e. less than 10% of participants did not complete the study or used 'baseline observation carried forward' (BOCF) analysis, or both); unclear risk of bias (used 'last observation carried forward' (LOCF) analysis); or high risk of bias (used 'completer' analysis).
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Size of study (checking for possible biases confounded by small size). We will assess studies as being at low risk of bias (200 participants or more per treatment arm); unclear risk of bias (50 to 199 participants per treatment arm); or high risk of bias (fewer than 50 participants per treatment arm).
Measures of treatment effect
Where dichotomous data are available, we will calculate a risk ratio (RR) with 95% confidence intervals (CIs) and meta‐analyse the data as appropriate. We will use a fixed‐effect model unless significant statistical heterogeneity is found. We will calculate numbers needed to treat to benefit (NNTBs) where appropriate (McQuay 1998); for unwanted effects the NNTB becomes the number needed to treat to harm (NNTH) and is calculated in the same manner. Where continuous data are reported, we will use appropriate methods to combine these data in the meta‐analysis.
Assessment of heterogeneity
We will identify and measure heterogeneity as recommended in Chapter 9 of theCochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will deal with clinical heterogeneity by combining studies that examine similar conditions. We will undertake and present a meta‐analysis only if participants, interventions, comparisons, and outcomes are judged to be sufficiently similar to ensure an answer that is clinically meaningful. We will assess statistical heterogeneity visually (L'Abbé 1987), and with the use of the I² statistic. When I² is greater than 50%, we will consider the possible reasons.
Assessment of reporting biases
We will use The Cochrane Collaboration's tool for assessing the risk of reporting bias, as recommended in Chapter 8 of theCochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). The aim of this review is to use dichotomous data of known utility (Moore 2010). The review will not depend on what authors of the original studies chose to report or not, though clearly difficulties will arise in studies failing to report any dichotomous results. We will extract and use continuous data, which probably poorly reflect efficacy and utility, if useful for illustrative purposes only.
Data synthesis
We plan to use a fixed‐effect model for meta‐analysis. We will use a random‐effects model for meta‐analysis if there is significant clinical heterogeneity and it is considered appropriate to combine studies. We will conduct our analysis using the primary outcomes of pain and adverse events, and we plan to calculate the NNTHs for adverse events.
Subgroup analysis and investigation of heterogeneity
We plan to perform subgroup analyses, where data are available, according to age (two to five years, five to 12 years) and types of surgery, e.g. tonsillectomy versus other.
Sensitivity analysis
We do not intend to carry out any sensitivity analyses.
