As required versus fixed schedule analgesic administration for postoperative pain in children
Acute postoperative pain occurs as a result of tissue damage following surgery. Administering the appropriate analgesia to children is a complex process and it is unclear whether children's postoperative pain is more successfully treated by using 'as required' (when pain occurs) (termed 'pro re nata' or PRN) or fixed scheduled 'around the clock' (ATC) analgesic administration (irrespective of pain at the time of administration).
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 years.
On 2 July 2014, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL databases. We reviewed the bibliographies of all included studies and of reviews, and searched two clinical trial databases, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform, to identify additional published or unpublished data.
We included randomised controlled trials (RCTs) comparing PRN versus ATC analgesic administration for postoperative pain in children under the age of 16 years who had undergone any surgical procedure requiring postoperative pain relief, in any setting.
Data collection and analysis
Two review authors (AH, PW) independently extracted efficacy and adverse event data, examined issues of study quality, and assessed risk of bias as recommended in the Cochrane Handbook for Systematic Reviews of Interventions.
We included three RCTs (four reports) of 246 children aged under 16 years undergoing tonsillectomy. Children were given weight‐appropriate doses of the study medication, either PRN or ATC, by a parent or carer at home for up to four days following surgery. We did not identify any studies assessing the management of postoperative pain in children in any other setting (i.e. as an inpatient). All studies included in this review were based on the use of paracetamol, and an opioid was added to paracetamol in two studies. Analgesics were administered either orally (tablet or elixir) or rectally (suppository). Reporting quality was poor and there were fewer than 50 children in each arm. Mean pain intensity scores decreased over time, as did medication use. However, children were still reporting pain at the final assessment, suggesting that no administration schedule provided adequate analgesia. There were no significant differences in pain intensity scores at any time point. The studies reported adverse events that may have been related to the study medication, such as nausea and vomiting, and constipation, but no statistically significant differences were noted between the groups. There were too few data from only three small studies and meta‐analysis was not possible. One study reported that a higher amount of analgesics was consumed in the ATC group compared with the PRN group: it would have been helpful to show that the higher volume in the ATC group led to better analgesia but we were not able to demonstrate this.
There was limited evidence available to draw any conclusions about the efficacy of PRN versus ATC analgesic administration for the management of postoperative pain in children.
Anna Erskine, Philip J Wiffen, Joy A Conlon
Plain language summary
Postoperative pain relief for children
Pain is commonly experienced after surgery. Children tend to rely on a parent or carer to give medication to help relieve the pain. Medication can either be given when the child complains of pain (as required), or 'around the clock' (fixed schedule, e.g. every four hours).
In July 2014, we found three studies (randomised controlled trials) of 246 children under the age of 16 years. All studies compared the two ways of giving medicine for pain relief after tonsillectomy (an operation to remove the tonsils). The studies were small, and generally of low quality.
One study showed that the children in the 'around the clock' group took more medication, but they did not have better pain relief. There were no differences in pain relief or side effects between the two groups. There was not enough evidence to be sure which method is better for a child's pain relief after surgery. More high quality, large studies are needed.
Anna Erskine, Philip J Wiffen, Joy A Conlon
Implications for practice
- For children under the age of 16 years with postoperative pain, we could not determine whether the 'around the clock' method was any different from the 'as required' method, for outpatients given oral or rectal analgesics.
- For clinicians, at present there is insufficient evidence to recommend one approach over another. Around the clock would appear to be a logical approach based on adult studies but we have not been able to demonstrate superiority.
- For policy‐makers and funders, there can be no implications for policy‐makers making recommendations on the management of postoperative pain based on this review.
Implications for research
- General: there is an urgent need for the adoption of a sensible pain assessment outcome for use by children that can be used both in clinical trials and in clinical practice. The outcome of mild or no pain has been suggested as being a target important to (adult) patients. It has the advantage of being useful as a dichotomous outcome to determine efficacy. Failure to attain the outcome is a marker of poor treatment.
- Design: there is a need for randomised controlled trials of large size, and using robust methods and reporting useful outcomes. These should use analgesic efficacy with known endpoints, and take into account concerns about safety and serious adverse events such as postoperative bleeding.
- Measurement (endpoints): we recommend that future studies aim to measure patient self report of pain relief or pain intensity, or both, using validated scales appropriate for use in children, ideally as a primary outcome. Parent‐reported pain (such as the Parents' Post‐operative Pain Measure (PPPM)) could also be a helpful secondary outcome, particularly in younger children as parents may have a better sense of their child's state than the child is able to report. Observer‐reported pain scores could be a primary outcome measure if self report is not available. Investigators in future studies could also consider measuring the timing of pain ratings, whether pain is provoked or not, and the location and the spread of pain.
- It is recommended that funding bodies work on three levels. First to generate agreement, based on evidence, of outcomes to be used in clinical trials of pain in children. Second, to generate agreement, based on evidence, of interventions that should be both effective and safe, and with protocols concerning how they may be used. Third, based on this, to commission several large studies in a number of different painful surgical interventions in children of various ages.