Dr Kevin McCarthy talks about managing pain in children in the pharmacy setting – within a biopsychological framework
Acute and persistent pain in children are best managed within a biopsychosocial framework. One way of approaching this is to think of it as “3P’s”: pharmacological, psychological, and physical/physiological. Even pain after a surgery like tonsillectomy can be formulated like this: the use of regular simple analgesia (pharmacological), the use of cold, e.g. ice lollies (physical), and distraction, e.g. playing video games (psychological), illustrate how such an approach can provide effective acute pain management. Medications are “one leg of a stool”, and consideration must always be given to the other domains prior to escalating pharmacological management, either increasing the dose or adding another medication. Children’s nervous systems are different than adults and for the most part, pain is short-lived because of very strong anti-inflammatory responses (think of it like a very robust sprinkler system to suppress fires). This may mean that sometimes pain is under-treated with no obvious short-term consequences. However, under-treated pain in childhood can lead to changes in subsequent pain responses that can persist into adulthood. That said, where medication is concerned, the mantra will be familiar to many: “right drug, right dose, shortest duration necessary”. It is also worth emphasizing that with pain, there is something generating it and something transmitting/amplifying it: where possible, target the source, i.e. where there may be inflammation, use anti-inflammatory agents such as NSAIDs. The following is a brief outline of what may be used for mild self-limiting conditions likely managed in primary care, more intermediate conditions seen in secondary care, followed by more persistent or complex pain presentations managed in tertiary care. I have followed this with brief commentary that is a synthesis of current literature and clinical experience. As in many other contexts, the lack of high-quality evidence and off-label use of most medications in paediatrics makes it difficult to make robust recommendations.
Mild self-limiting conditions in Primary Care:
Analgesics may be administered regularly for the first 24 hours and on an ‘as needed’ or PRN basis thereafter. These measures may be augmented further by the use of physical measures or topical agents, e.g. heat/cold, topical agents and/or massage, position, and techniques such as distraction.
Paracetamol 15mg/kg/dose every 4-6 hours PO (max. 75mg/kg/day or 5 doses)
Ibuprofen 7.5mg/kg/dose every 6 hours PO (max. 30mg/kg/day or 4 doses)
Moderate acute pain post-discharge from Secondary Care:
Similar dosing of OTC agents, but given regularly every 6 hours ‘on the dot’. We expect that tissue healing can take up to two weeks. Pain will be more intense initially and then rapidly improve. Regular, ‘round the clock’, administration is to allow normal activities (i.e. eating, sleeping, toileting) to resume, as a withdrawn child may not overtly complain of pain while eating or sleeping poorly due to pain. If regular NSAIDs are being administered for longer than one week, it may be necessary to consider gastric protection, especially if there are other risk factors. Adjunct analgesics or opioids may have been commenced, but with the expectation of self-tapering. If treatment is required beyond the initial prescription, this should be flagged to the original prescriber and may require follow-up by a pain service for a short period. Opioids prescribed for children for use following discharge from hospital frequently go unused, therefore providing advice about safe storage and disposal of unused doses of opioids would be prudent.
Clonidine 1mCg/kg every 6-8 hours PO
Gabapentin 5mg/kg every 8 hours PO
Tramadol 1mg/kg up to every 6 hours PO PRN
Morphine 100-200 mCg/kg every 6 hours PO PRN
Longer-term persistent or complex pain in Tertiary Care:
In brief, the longer that pain persists, the more it becomes about the central nervous system amplifying or maintaining it, and the less it is about tissue injury or peripheral inflammation, although it may still be present. Strategies shift to target central sensitization in addiction to peripheral pain generators. General considerations would include no longer using regular or ‘round the clock’ paracetamol and reserving it for the acute pain of specific events or procedures. For rheumatological conditions, this also may mean switching from non-selective NSAIDs to selective COX-2 inhibitors. For oncology and haematology, this may mean the longer term use of adjuvants and opioids, which may also now require management of drug-induced side effects, e.g opioid-induced constipation. Long-term use of opioids may be associated with opioid tolerance. Strategies to circumvent tolerance include opioid rotation to a different opioid agonist or the use of adjuvants such as α2 agonists or NMDA antagonists.
Chronic or persistent pain without an identifiable cause is now termed a ‘primary pain’ condition, i.e. the pain is a disease in its own right. In general, in primary pain conditions, the emphasis is on non-pharmacological therapeutic modalities. However, there is still some evidence to support pharmacological and nutraceutical therapies in some specific contexts, eg. probiotics in recurrent abdominal pain or Vitamin D supplementation in children with chronic headache or musculoskeletal pain. Vitamin C prophylaxis has been shown to reduce the frequency of Complex Regional Pain Syndrome (CRPS) in at-risk adult patients, reduce opioid requirements, and reduce the incidence and severity of post-herpetic neuralgia. Along with vitamins C and D, the same principle applies to magnesium supplementation in the context of pain: low levels are associated with pain, therefore we assume that supplementation and normalization of serum levels should be beneficial. However, robust data is lacking at present. The use of tricyclic, or other, antidepressants for chronic pain should ideally be following consultation with a specialist in paediatric pain, paediatric palliative care, or child psychiatry. Children on such medication may require periodic ECGs to monitor QT interval.
Amitriptyline 0.1-0.5mg/kg nocte (Typically start at 5mg, increase in 5mg increments and max. dose of 25mg).
Non-steroidal Anti-inflammatory Drugs (NSAIDs)
The analgesic dose of several NSAIDs is less than the anti-inflammatory or anti-pyretic dose, so if solely for pain relief, it is feasible to give smaller doses more frequently. Where pain and fever co-exist, it is reasonable to default to the advice and dosing that one would give for managing a fever e.g. 6-hourly paracetamol dovetailed with 8-hourly ibuprofen. In contrast, where there is definite tissue injury as a source of pain, e.g. after surgery, pharmacokinetic modelling has suggested there is greater benefit from the co-administration of paracetamol and ibuprofen regularly every six hours (while remaining within the daily maximum dose) rather than dovetailing the two agents as one would typically do to manage a fever. NSAIDs are often under-prescribed and under-administered due to concerns about side effects. NSAIDs are not usually recommended for analgesia in neonates and infants less than 3 months of age and it is unlikely they would be prescribed in an outpatient setting for infants below 6 months of age. A small number (<5%) of children with moderate to severe asthma and nasal polyps are susceptible to NSAID-exacerbated respiratory disease. The majority of asthmatic children are not sensitive to NSAIDs and should not be denied their benefits.
Gabapentinoids (Gabapenbtin & Pregabalin)
The use of gabapentinoids for postsurgical and chronic pain has mirrored their use for similar indications in adults. Currently, there is not the same level of evidence to support their long-term use. These agents are also perceived as being relatively benign, which appears to be a consideration in assessing the risk-benefit ratio of prescribing them. However, as with several other anti-epileptics, there are reports of changes in mood and of suicidal ideation when prescribed to adolescents. Anecdotally, this is more common with Pregabalin. It is therefore of utmost importance that when used for pain, the indication and efficacy are under regular review to screen for such side effects.
Clonidine is used as an adjunct in an inpatient setting to augment the effect of opioids and local anaesthetics. α2-agonists attenuate the side effects of opioid withdrawal. They may also be used for speculative dose-sparing effects upon opioid use over the longer term. The effects on the sympathetic nervous system (similar to b-blockers) may also be beneficial in conditions like CRPS where sympathetic over-activation may be contributing to pain.
The ‘best’ opioid agonist is the one which is providing the best analgesia at the lowest dose and with the fewest side effects. It is unlikely that opioids would be initiated in an outpatient setting without some prior evidence of safe exposure in a monitored environment. Opioid-induce respiratory depression (OIRD) is rare in children but obviously potentially devastating should it occur. Drug errors or iatrogenic overdose are an important cause of OIRD. In the remaining cases, three distinct patterns are seen: morphine administration in patients with renal impairment; codeine use in patients with the cytochrome P4502D6 (CYP2D6) gene polymorphism associated with ultra-rapid metaboliser phenotype; and opioid use in patients after adenotonsillectomy for obstructive sleep apnoea. Codeine should only be used children over 12 years of age for acute pain, and not at all in children below 18 years of age undergoing adenotonsillectomy for obstructive sleep apnoea. Tramadol and morphine have been proposed as alternatives to codeine for postoperative analgesia at home. Tramadol is also metabolised by cytochrome P4502D6 and is subject to variations in pharmacokinetics due to polymorphisms of CYP2D, although respiratory depression has not been reported at doses used in clinical practice. An additional note of caution for opioids (and paracetamol) is dosing based on actual body weight in children with a high Body Mass Index (BMI), that may lead to an overestimation and a ‘staggered overdose’. Dose adjustment towards lean body weight should be considered in these children, with follow-up assessment to ensure adequate analgesia.
Topical NSAIDs may be used in chronic musculoskeletal pain, although studies of efficacy in children are lacking. A sparing effect on the consumption of oral NSAIDs may be desirable. Topical ibuprofen is licensed for children over 12 years of age and topical diclofenac for children over 14 years of age. For peripheral neuropathic pain, the use of topical TRPV1 agonists may not be tolerated by children due to the burning sensation they produce. An alternative is 1-2% menthol in aqeous cream, which is a TRPM8 agonist and produces a cooling sensation which is usually better-tolerated.