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Craig Sims, Dana Weber and Chris Johnson (eds.) A Guide to Pediatric Anesthesiahttps://doi.org/10.1007/978-3-030-19246-4_9

9. Acute Pain Management in Children

Priya Thalayasingam¹ and Dana Weber¹

(1)

Department of Anaesthesia and Pain Management, Perth Children’s Hospital, Nedlands, WA, Australia

Priya Thalayasingam (Corresponding author)

Email: Priya.Thalayasingam@health.wa.gov.au

Dana Weber

Email: dana.weber@health.wa.gov.au

Keywords

Pediatric pain toolsMorphine metabolism childrenOpioid infusions childrenParacetamol in neonatesNurse controlled opioid infusionsPatient controlled analgesia in children

The International Association for the Study of Pain defines pain as ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage’. However, the inability to communicate does not negate the possibility an individual is experiencing pain. The safe and effective management of pain in children includes the prevention, recognition and assessment of pain, the early and individualized treatment of pain and the evaluation of the effectiveness of treatment. This goal is the responsibility of all health care providers caring for children. This chapter describes the assessment of pain in children, and the management options available. Regional analgesia is also appropriate for children and is covered in Chap. 10.

9.1 Pain Assessment

Children’s pain may be difficult to recognize and to measure reliably. Many pain assessment tools (PAT) have been developed to measure ‘pain scores’ (Table 9.1). These tools must be age and developmentally appropriate because children’s understanding and ability to describe pain will change as they grow older. Additionally, the tools should be sensitive, specific and validated. There are three types of tools used for assessment of pain in children:

1.

Self-report: The preferred approach, which can be used in children older than 3–4 years who are not cognitively impaired.
2.

Observational or behavioral: An objective assessment by the carer or parent of signs of distress caused by pain.
3.

Physiological: measures physiological parameters of the pain arousal response. It is best combined with a behavioral assessment of pain. The measured parameters can be confounded by underlying illness (e.g. sepsis causing tachycardia) and have wide inter-individual variability

Table 9.1

Examples of pain assessment tools (PAT) validated in children

Assessment tool	Age range	Assessment	Notes/limitations
Premature Infant Pain Profile (PIPP)	<33 weeks	Gestational age, behavioral state, HR, oxygen saturation, brow bulge, eye squeeze, nasolabial furrow	For procedural and postoperative pain
Neonatal Pain Assessment Tool	>33 weeks	Behavioral indicators: posture, tone, sleep pattern, facial expression, color, cry Physiological indicators: respiratory rate, HR, oxygen saturation, BP	Behavioral and physiological PAT and observation
The Faces, Legs, Activity, Cry and Consolability (FLACC) scale	0–7 years	Facial expression, leg position, activity, cry, consolability	Behavioral PAT May be adapted for cognitively impaired children
The Revised Faces Pain Scale	4–12 years	Six faces with the first face scoring 0/10 and the last scoring 10/10 pain	Self-report PAT
Visual Analogue Scale (VAS)	7–8 years to adult	A line expressing an increasing continuum of pain	Self-report PAT
Numerical Rating Scale (NRS)	7–8 years to adult	0/10 = no pain 10/10 = worst pain	Self-report PAT

Of the available tools, the revised faces scale is commonly used for school aged children, whereas the FLACC scale is commonly used for preschool aged and cognitively impaired children. Although these are generally used, different institutions may have their own preferred tools. Pain scores form only one component of pain assessment. Holistic pain assessment accounts for factors influencing a child’s perception of pain, which contribute to different pain experiences in different children undergoing the same procedure (Table 9.2).

Table 9.2

Factors influencing a child’s perception of pain

Physiological factors—site or severity of surgery

Psychological and cognitive factors— age, gender and maturity

Behavioral factors—child’s coping style and parental response

Socio-cultural beliefs

Past health and hospitalization experiences

Keypoint

Pain assessment appropriate to the child’s age needs to be performed regularly so pain is treated early and effectively. Because pain is dynamic, regular pain assessments provide a trend for the patient’s progress.

9.2 Management Strategies

Anesthetists most often encounter children with acute pain related to surgery, medical conditions, cancer or trauma. Acute pain management includes a combination of pharmacological and non-pharmacological strategies.

9.2.1 Non-pharmacological Strategies

These strategies are techniques used to supplement analgesic drugs and are especially useful for procedural pain. They can be as simple as comforting an injured child, while others include physical methods such as massage, heat therapy and transcutaneous electrical nerve stimulation (TENS). The most important psychological technique is distraction with toys or electronic games and devices, while others include breathing techniques, imagery, play therapy and hypnosis. These techniques need to be appropriate to the child’s development, personality and circumstances, and ideally should be familiar to the child before they are used.

9.2.2 Pharmacological Strategies

Drug treatment is modelled on the 3-step analgesic ladder, starting with simple oral analgesia and progressing to opioid and regional analgesia if required. As in adults, simple analgesics reduce opioid use and side effects. Systemic analgesia is usually given by the oral or IV routes, but rectal, transdermal, intranasal, transmucosal or inhalational routes are alternatives. Intramuscular injections are avoided in children because of pain and erratic drug absorption.

Postoperative pain relief and side effects should be discussed preoperatively with the parents, child (if plausible) and surgeon. It should be safe, efficacious, titratable and appropriate for the surgery and patient age (for example, an ilio-inguinal block may be preferable to a caudal in an ambulating 5 year old for inguinal hernia repair). Regional techniques are useful but an alternative plan is needed if they fail, and parental education about analgesia when the block wears off is important.

Children’s analgesic needs fluctuate during the day—more analgesia is required whilst mobilizing, participating in physiotherapy or undergoing therapeutic procedures such as dressing changes. Thus, effective analgesic regimens need background analgesia and a pro-active plan for managing break-through pain, especially in preverbal or cognitively impaired children.

9.3 Analgesic Agents

9.3.1 Paracetamol

Paracetamol has a central analgesic effect mediated through activation of descending serotonergic pathways. The analgesic and antipyretic plasma concentration in children is the same as adults and is 10 mg/mL. Higher plasma concentrations only modestly increase efficacy but increase the risk of hepatotoxicity.

9.3.1.1 Metabolism

Paracetamol undergoes glucuronidation and to a lesser extent, sulfation, in the liver. In neonates, sulfation is the main mechanism. Clearance increases with post menstrual age, but in a term neonate it is still only about a third that of an older child (Fig. 9.1). Unconjugated hyperbilirubinemia is a crude measure of hepatic conjugating ability and is a reason to reduce the dosage of paracetamol.

../images/467929_2_En_9_Chapter/467929_2_En_9_Fig1_HTML.png — Fig. 9.1

Schematic representation of metabolism of paracetamol with age. Metabolism of paracetamol in neonates is only 30–40% of the adult level, but reaches nearly 80% by 6 months of age as the enzymes responsible for glucuronidation mature. Modified from Anderson and Holford, Pediatr Anesth 2018

Keypoint

Children taking maximal doses of paracetamol for several days are at risk of hepatotoxicity. The risk is even higher if they are malnourished or dehydrated.

9.3.1.2 Oral Administration

Paracetamol is most often given orally. Absorption is rapid in children, though slower in neonates. Oral paracetamol undergoes 10–40% first pass elimination. Plasma concentration is maximal 30–60 min after oral administration, but the brain concentration rises slowly. Maximum analgesia develops up to 2 h after administration. Doses at various ages are shown in Table 9.3. The manufacturer’s dose of 60 mg/kg/day in children is often replaced by a dose of 90 mg/kg/day for the first 48 h, either by using a larger loading dose or using 20 mg/kg 6 hourly.

Table 9.3

ORAL paracetamol dose in neonates and children

Age	Oral dose (mg/kg)	Interval (h)	Maximum daily dose (mg/kg)	Maximum duration at maximum dose (h)
28–32 weeks PMA	10–15	8–12	30	48
32–52 weeks PMA	10–15	6–8	60	48
3–6 months	15	6	90^a	48
>6 months	15	6	90^a	48

Some suggest a loading dose of 20 mg/kg in children older than 32 weeks. Dose adjustment is required in overweight and obese patients. Paracetamol dose must be reviewed every 48 h; beware of risk factors for paracetamol toxicity. If treatment >1 week, use minimum dosing interval of 6 h, and consider lowering maximum daily dose and monitoring LFT’s. PMA Post menstrual age

^aMaximum 4 g in 24 h for 48 h. After 48 h reduce dose to 60 mg/kg/24 h

9.3.1.3 Intravenous Administration

IV paracetamol is more effective than oral paracetamol because there is no first pass metabolism or delay in absorption. The dose in children is 15 mg/kg infused over 15 min. The dose is reduced in neonates and is adjusted in obese children based on their ideal body weight (Table 9.4).

Table 9.4

INTRAVENOUS paracetamol dose in neonates and children

Age	Maintenance dose	Maximum daily dose (mg/kg per day)
32–40 weeks PMA	7.5 mg/kg 8 hourly	30
40–44 weeks PMA	10 mg/kg 6 hourly	40
44 weeks PMA–18 years	15 mg/kg (up to 1 g) 6 hourly	60

9.3.1.4 Rectal Administration

Rectal administration has slow and variable absorption, with typical doses failing to give a therapeutic plasma level. The smallest suppository commercially available is 125 mg, but cannot be cut to reduce the dose because the paracetamol may not be evenly distributed through it. IV paracetamol is preferable in clinical practice.

9.3.1.5 Toxicity of Paracetamol

A small amount of paracetamol is oxidized by the cytochrome P450 CYP2E1 enzymes to the reactive metabolite NAPQI. This metabolite binds to glutathione and is excreted. As sulfation and glucuronidation pathways become saturated, more paracetamol is shunted into the oxidative NAPQI pathway. However, once glutathione stores are depleted, hepatotoxicity develops from unbound NAPQI. Neonates have reduced P450 oxidation, but they can still form the reactive metabolite. This reduced oxidation paired with increased glutathione synthesis protects them from hepatotoxicity and gives paracetamol a high therapeutic ratio in neonates. The effect of liver disease on paracetamol metabolism is variable and difficult to determine in any given patient. Paracetamol may still be used in hepatic impairment, usually as a single dose or smaller, infrequent doses.

Although safe when used alone or in combination with other analgesics, severe or fatal hepatotoxicity can occur with analgesic doses of paracetamol. Children at risk are those who are malnourished, dehydrated, obese (and dosed with actual rather than ideal body weight), or have been receiving maximal doses for several days. Such conditions may exist in children after surgery who are not well hydrated and have been taking regular, maximal dose paracetamol for several days. In these groups of children, the dose must be reduced after a few days, and liver function tests performed regularly. When neonates and infants are given IV paracetamol, the volume of drug is small and they are at high risk of a ten times overdose. Prescribing in both mLs and mGs has been suggested as a way of avoiding overdose. It has also been recommended by the Safe Anesthesia Liaison Group to use 50 mL vials (where available) for children weighing less than 33 kg. The dose of IV paracetamol should be drawn up in a syringe and given, rather than hanging a full bag of paracetamol.

Paracetamol toxicity is treated with IV N-Acetylcysteine (NAC), which restores hepatic glutathione. The nomograms used for the management of paracetamol toxicity refer to oral overdose. The UK National Poisons Information Service advises NAC after a single IV dose of paracetamol larger than 60 mg/kg, and advise against waiting for a serum paracetamol level before NAC is started. If the dose of IV paracetamol is unknown, a level should be taken 4 h after the IV paracetamol dose and NAC started if the plasma paracetamol level is above 50 mg/L.

9.3.2 Non-steroidal Anti-inflammatory Drugs (NSAIDs)

NSAIDs are effective analgesics and antipyretics in children. As in adults, they reduce morphine requirements by approximately 30%. Although many NSAIDs are available for use in adults, few are marketed in a liquid form or in a suppository dose suitable for children. NSAIDs uncommonly exacerbate asthma in children younger than 10 years, and can be used in young asthmatic children unless there has been past sensitivity. Renal dysfunction is also uncommon in children, although dehydration is a predisposing factor as it is in adults. NSAIDs are not recommended for neonates—they reduce GFR by 20% and may affect cerebral and pulmonary blood flow. Aspirin is rarely used in children because of its association with Reye’s syndrome.

Ibuprofen is the most commonly used oral NSAID in children. The dose is 10 mg/kg every 6–8 h in children greater than 3 months old. It is not recommended for children under 3 months of age. It does not need to need to be taken with food in children. Ibuprofen is unlikely to increase the risk of bleeding after tonsillectomy and provides useful analgesia, however its use in this setting is surgeon and institution specific. An intravenous form of Ibuprofen is available and is dosed at 10 mg/kg (max daily dose 40 mg/kg or 2400 mg whichever is less) in children younger than 17 years. It must be diluted before administration and infused over 10 min. It may cause hemolysis if given undiluted and cannot be given intramuscularly.

Diclofenac is available orally, rectally and intravenously. The doses are 0.3 mg/kg IV, 0.5 mg/kg rectally and 1 mg/kg orally, usually 8–12 hourly. It is rapidly and well absorbed from the rectum with peak levels reached faster than either oral or rectal paracetamol. Parecoxib has not been extensively studied in children and is not approved for use in children younger than 16 years. However, its pharmacokinetics in children have been reported, and it is an effective analgesic in children after tonsillectomy.

9.3.3 Opioids

Although many different opioids are used for analgesia in adults, only a few are used in children because few have oral, liquid forms available and because experience with many opioids in children is limited. Neither transcutaneous patches nor opioid agonist-antagonist preparations are made in pediatric doses.

9.3.3.1 Morphine

Morphine is the most widely studied and used opioid in children. It is available in an immediate release elixir (dose 0.2–0.5 mg/kg, 3–4 hourly PRN) or as a controlled-release preparation (MS Contin suspension or tablets). Morphine is the only opioid with a liquid, sustained release preparation suitable for small children who can’t swallow tablets. (Controlled-release tablets should never be crushed or chewed, as an unpredictably large dose of morphine is released immediately, resulting in opioid toxicity).

Morphine metabolism is reduced in neonates and infants (Fig. 9.2). Furthermore, a larger proportion of morphine is metabolized to the active metabolite M6G in neonates. These pharmacokinetic differences place neonates at risk of respiratory depression compared to children and adults—the incidence of respiratory depression from opioids is almost ten times more in neonates than adults. Differences in the blood-brain barrier between neonates and children are minor and unlikely to be clinically important. Respiratory depression is the same in neonates and children at equivalent plasma concentrations of morphine, but the plasma concentration is reached in neonates with much smaller doses than in children (Table 9.5).

../images/467929_2_En_9_Chapter/467929_2_En_9_Fig2_HTML.png — Fig. 9.2

Metabolism of morphine and tramadol in neonates and young children. Tramadol undergoes phase I metabolism by CYP iso-enzymes that mature quickly. Morphine undergoes phase II glucuronidation, which matures more slowly. Modified from Anderson and Holford, Pediatr Anesth 2018

Table 9.5

Typical infusion rates for morphine infusions in children of different ages

Age	Typical infusion rate of morphine (μg/kg/h)
Neonate	5–10
Infant	10–20
Child	10–40

The lower rates in neonates and infants reflect pharmacokinetic differences

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Pain Management in Children