Strategies for Managing Pediatric Fracture Pain: Assessment, Pharmacological, and Non-Pharmacological Interventions

Introduction

The International Association of 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 [1]. Due to a lack of specialized training in pediatric pain management and insufficient attention from pediatric medical professionals, pain in children is often under-recognized and inadequately treated [2]. This oversight contributes to severe anxiety or depression among children, leading to increased catabolism, immunosuppression, and hemodynamic instability [3]. The management of pediatric fracture pain is complex and challenging, and there is a paucity of high-quality research studies on management strategies. In the current pain treatment approach, physicians primarily emphasize pharmacological interventions as an effective means of relieving pain in children. However, non-pharmacological treatments, including physical therapy, relaxation techniques, psychological interventions, home care, and residential care, also hold significant importance in pain management [4]. Therefore, this article aimed to review the evaluation and management of pain in children with bone fracture, including pharmacological and non-pharmacological treatments.

Characteristics of Pain in Children with Fracture

Pediatric pain accompanied by fractures belongs to the category of acute pain, which is characterized by severe pain and significantly affected limb mobility. It is often challenging to provide timely analgesic treatment after the occurrence of a fracture, which leads to prolonged pain duration and high pain scores. Following hospitalization, most patients require closed reduction and cast immobilization, while some patients can require multiple manual reductions, resulting in intense pain that generates a strong sense of fear in children. In cases of unstable fractures, movement can cause displacement, leading to persistent pain. Severe and persistent pain can lead to a profound sense of fear and anxiety in children.

Pain in children differs from that in adults for physiological, cognitive, developmental, and social reasons. Therefore, assessment tools developed for adults should not be applied to children directly [5,6]. The most important characteristic of pain in children is the difficulty in accurately assessing it. This is because of the child’s developmental processes, which lead to important and continuously changing differences in age, perception, ability to express feelings and pain, as well as cognition and educational level [7]. Younger children can have difficulty expressing their pain using words, relying more on non-verbal cues such as crying, whimpering, or screaming, or facial expressions such as grimacing, furrowing their brows, or tightening their facial muscles. Older children can provide more detailed descriptions of their pain, including its intensity, location, and quality. These visual cues can provide insight into the severity and discomfort the child is experiencing. Without standardized, validated pain assessment tools for children, pain management cannot be performed accurately and effectively.

Pain can elicit not only physiological change but also psychological changes, with adverse effects in children [8]. In infants and toddlers, pain can lead to difficulty sleeping, eating, and self-soothing, or to changes in appetite. It can also make them irritable, withdrawn, and fearful. In preschool-aged children, pain can cause anxiety, sadness, and anger. It can also lead to behavioral problems such as tantrums, aggression, and withdrawal. Acute pain can make children fearful of medical institutions and lead to non-compliance with treatment. It is important to assess and treat pain in children as early as possible. Early intervention can help to reduce the severity of the pain and its long-term consequences.

Pain Assessment Tools According to Patient Age

Assessment Tools for Patients 0 to 3 Years Old

ASSESSMENT TOOLS FOR PATIENTS 0 TO 3 YEARS OLD:

Infants and toddlers lack the ability to communicate verbally, rendering self-assessment scales unsuitable for this age group. The symptoms of body rigidity, facial overexpression, crying, sleep disorders, resistance, and changes in appetite can serve as indicators [10]. Based on these symptoms, a number of behavioral scales have been developed. Among them, the Comfort Behavior Scale and the Face, Legs, Activity, Cry and Consolability (FLACC) scale are widely used and highly regarded.

COMFORT BEHAVIOR SCALE: The Comfort Behavior Scale (Comfort B) is a modified version of the Comfort Scale developed by van Dijk et al [11]. It has been adapted by removing physiological assessment items, such as average arterial blood pressure and heart rate, while retaining 6 behavioral assessment items. These items include alertness, calmness-agitation, crying, physical movement, muscle tone, and facial tension. The observation period lasts for a full 2 min, and the assessment is concluded with a gentle touch to the infant’s arm or leg to assess muscle tension. The Comfort B scale is specifically designed to assess the intensity of pain in young children aged from 0 to 3 years. Initially, it was primarily used for patients in critical care settings. However, Andersen et al pointed out that the Comfort B can also contribute to the overall clinical assessment of sedation, pain, and distress in toddlers before and after surgery [12]. In the Comfort B, each indicator is rated on a scale of 1 to 5, as shown in Table 1. The total score ranges from 6 to 30, with scores of 6 to 17 indicating no or mild pain, scores of 18 to 27 indicating moderate pain, and scores of 28 to 30 indicating severe pain. It is important to note that moderate and severe pain require intervention (Table 1).

FACE, LEGS, ACTIVITY, CRY AND CONSOLABILITY SCALE: The FLACC scale [13] incorporates 5 categories of pain behaviors: facial expression, leg movement, activity, crying, and consolability. This scale is used to assess the intensity of postoperative pain in young children aged from 2 months to 7 years. During assessment, it is recommended that the patients remain asleep, with their body and limbs exposed. The observation period should last between 2 and 5 min. Each parameter is evaluated on a scale from 0 to 2. The total score is interpreted as follows: 0 indicates the child is relaxed and comfortable, 1 to 3 indicates mild discomfort, 4 to 6 indicates moderate pain, and 7 to 10 indicates severe discomfort or pain. A score exceeding 3 points indicates the need for analgesic management [14] (Table 2).

ASSESSMENT TOOLS FOR PATIENTS 4 TO 7 YEARS OLD:

At the preschool age, children possess the ability to communicate with their parents or medical staff to describe the severity, location, and perception of pain. At this stage, behavioral scales and self-assessment scales are used. The Modified Objective Pain Scale (MOPS) [15,16] and Oucher Scale [17] are commonly used scales in practical settings.

MODIFIED OBJECTIVE PAIN SCALE: The Objective Pain Scale (OPS), originally developed by Broadman et al [16], incorporates physiological parameters and standardized behavioral observations to assess pain, including blood pressure, crying, agitation, movement, and verbal evaluation. In developing the MOPS, Wilson and Doyle [15] made modifications to the OPS by replacing blood pressure with posture, to evaluate pain in children aged 8 months to 13 years (Table 3). Each item on the MOPS is scored on a scale from 0 to 2, resulting in a total score ranging from 0 to 10. According to research conducted by Wilson and Doyle [15], the MOPS is particularly suitable for parents to assess postoperative pain in children, especially in day-case surgery scenarios. The score ranges from 0 to 10, with 0 indicating no pain and 10 indicating the most severe pain. Pain management should begin when mild pain is detected.

OUCHER SCALE: The Oucher Scale (www.oucher.org), developed by Beyer et al [17] is a pain assessment tool designed to assist children between the ages of 3 and 12 years in evaluating the intensity of their pain. It consists of 2 scales: a number scale for older children and a picture scale for younger children. The advantage of this scale is that there are different ethnic and gender versions, presenting examples for Caucasian, Hispanic, Asian, African American, and First Nations individuals. It is important to note that only the children themselves should rate their own pain using the Oucher Scale. Adults should refrain from comparing the child’s facial expression with the faces depicted on the Oucher. Children who are capable of counting to 100 by ones or tens and who understand that 71 is greater than 43 can effectively use the numerical scale. In scoring, 0 indicates no pain, 1 to 3 indicates a little pain, 4 to 6 indicates mild pain, and 7 to 10 indicates severe pain. Treatment should start from mild pain.

ASSESSMENT TOOLS FOR PATIENTS 8 TO 14 YEARS OLD:

School-age children demonstrate good verbalization and comprehension abilities, making self-assessment scales the criterion standard for pain assessment in this age group. The most commonly used scales for school-age children include the visual analog scale (VAS) [15,18] and the numeric rating scale (NRS) [18,19]. In clinical practice, it is important to select one or more suitable pain assessment scales based on the child’s age and specific circumstances in order to obtain a comprehensive evaluation of their pain condition.

VISUAL ANALOG SCALE: The VAS is a pain assessment tool that typically consists of a line, usually 10 cm long, with verbal anchors at each end. The left end is labeled as “no pain,” and the right end is labeled as “the most severe pain” [20]. On the scale, the far-left represents no pain, while the far-right indicates the most severe pain (Figure 1). The VAS is generally more suitable for children aged 8 years and above, as it requires a certain level of abstract thinking and comprehension. To use the VAS, the patient places a mark on the line that corresponds to their subjective rating of pain intensity. The VAS has been supported by significant empirical evidence, demonstrating its reliability in terms of inter-rater reliability (consistency across different raters) and test-retest reliability (consistency over repeated assessments) [21,22].

NUMERIC RATING SCALE: The NRS is a pain assessment tool that typically consists of a series of numbers with verbal anchors representing the entire range of pain intensity (Figure 2). The scale ranges from 0, indicating no pain at all, to 10, representing the worst imaginable pain [18]. Children between the ages of 7 and 17 years rate their pain on an 11-point numerical scale. The NRS has well-documented validity and has shown positive correlations with other measures of pain. It is also sensitive to treatments that are expected to impact pain levels [19]. Studies have indicated that the composite scoring system, which includes assessing the best, worst, and current levels of pain experienced over the past 24 h, is sufficient to detect changes in pain intensity, with a high level of reliability. In summary, the NRS is a reliable and valid pain assessment tool that allows children to rate their pain on a numerical scale, facilitating effective pain monitoring and evaluation [23].

Types of Interventions

Non-Pharmacological Intervention

NON-PHARMACOLOGICAL INTERVENTION:

Pain management necessitates a comprehensive, interdisciplinary, and integrated approach. It is imperative not to overlook the role of non-pharmacological treatments in alleviating pain, complementing traditional pharmacological interventions. Embracing the biopsychosocial model of pain is crucial, as it recognizes pain as a multifaceted experience resulting from the interplay of biological, psychological, and social factors [24]. When addressing families and caregivers, it is essential to adopt a biopsychosocial perspective, recognizing that pain should not be treated solely as a biomedical issue [6,25]. A wide range of non-pharmacological therapies for managing children’s pain are available and are categorized as physical techniques, cognitive-behavioral techniques, and complementary therapies [26]. Many of these therapies adopt a “child-centered” approach, focusing on alleviating the anxiety, depression, and fear associated with each child’s pain. Fracture pain, characterized by its high intensity, demands careful management. Non-pharmacological therapies are generally considered safe, with few contraindications for children with fractures. The choice of a specific non-pharmacological method depends on factors such as the child’s age, behavioral traits, coping abilities, levels of fear and anxiety, and the type of pain experienced. Drawing from the biopsychosocial model, this section will delve into non-pharmacological treatment methods in detail, with the primary aim of reducing the reliance on analgesic drugs, enhancing patient pain management, and improving the overall quality of pain management in healthcare settings.

PHYSICAL THERAPY:

Strong support now exists for the use of non-pharmacological approaches to alleviate children’s pain. Several physical strategies, such as comfort positioning, non-nutritive sucking, oral sucrose, and massage, have demonstrated both effectiveness and safety in managing pediatric pain. These physical strategies are designed to alleviate pain and reduce the need for analgesics in hospital and home settings. Additionally, they contribute to lowering the overall stress and anxiety levels associated with pediatric fracture pain. These techniques are particularly valuable for young children and can be easily implemented with the collaboration of parents. However, it is important to note that despite the promise of these physical interventions, there remains a scarcity of evidence and concerns about the overall quality of existing studies. This is particularly true for interventions like massage, acupuncture, and transcutaneous electrical nerve stimulation, which require further clarification regarding their effectiveness in treating pediatric orthopedic injury pain. In this section, we will delve into the appropriate physical interventions for managing pediatric fracture pain.

CASTING AND IMMOBILIZATION: The cornerstone of pain management during a fracture is immobilization and casting, which can also be categorized as a component of fracture treatment. Achieving stable fixation through casting is crucial, as it helps prevent secondary displacement, which can lead to persistent and intense pain [27]. For patients who require surgery, the use of temporary casting or immobilization is also necessary before the surgical procedure to prevent severe pain caused by movement. In cases in which non-surgical treatment is the chosen approach for home care, stable immobilization remains a fundamental therapy for pain relief. Caregivers play a vital role in helping children find a comfortable position to alleviate discomfort and pain resulting from the fracture [28]. Additionally, the use of appropriate mattresses and pillows can be valuable in facilitating changes in position and enhancing overall comfort during the healing process.

DETUMESCENCE: Furthermore, it is important to address swelling, as it is a significant contributor to pain during fractures. This applies to both surgical and non-surgical patients, making detumescence treatment a crucial aspect of pain management. Pain in these patients primarily occurs during the swelling stage, with a significant reduction in pain once the swelling subsides. Limb evaluation is instrumental in promoting blood circulation, reducing local congestion around the fracture site, and facilitating the regression of swelling. Traditionally, cold therapy has been used to treat acute injuries associated with swelling. Parents can be advised to apply ice packs during the initial 48 to 72 h following a fracture. However, after the first 72 h, there is limited evidence to support continued benefit [29]. In cases where necessary, swelling-dispersing drugs can also be used to promote detumescence and alleviate pain.

FOOD AND SOOTHE: Breastfeeding and non-nutritive sucking are valuable methods to soothe and calm infants with fractures. Combining breastfeeding with other effective pain-relief strategies, such as sucking, can produce sufficient analgesic effects during painful procedures. A prospective randomized controlled trial conducted by Peng et al [30] demonstrated that the combined use of sucking and breastfeeding effectively reduced mild pain and moderate to severe pain in preterm infants during heel-stick procedures. For infants and preschool-aged children, oral sucrose is a suitable and effective non-pharmacological analgesic that has been used to mitigate pain responses. Multiple reviews have discussed the literature supporting the use of oral sucrose and non-nutritive sucking for managing procedural pain in infants [31–34]. During episodes of intense pain resulting from fractures, providing a small amount of a 24% sucrose solution orally to patients can offer pain relief.

COGNITIVE-BEHAVIORAL THERAPY: In the 1960s, Aaron Beck developed cognitive-behavioral therapy (CBT), which has proven to be highly effective in numerous outcome studies for various psychiatric disorders, including depression, anxiety disorders, eating disorders, substance abuse issues, and personality disorders [35]. Additionally, CBT has demonstrated its effectiveness as an adjunctive treatment alongside medication for chronic pain and serious mental disorders. It is essential for physicians and nurses to recognize that CBT is often used in conjunction with pharmacological therapy to achieve the best outcomes. The research of Uhl et al indicated that, in the management of pediatric cancer-related pain, CBT significantly and meaningfully increased the chronic pain acceptance questionnaire scores, reduced anxiety in youth with chronic pain, and diminished anxiety and fear of movement [26]. Cognitive therapies play a vital role in pain control, because effective treatment should address all the factors contributing to a child’s pain and suffering. When children receive accurate information about what to expect and how they may feel, they can enhance their understanding, gain a greater sense of control, reduce distress, and alleviate their pain. Among non-pharmacological pain therapies for children, cognitive interventions stand out as the most powerful and versatile. While there are numerous categories of cognitive-behavioral therapy, this section will focus exclusively on those categories with a clear effect on managing fracture pain in children, with the aim of promoting improved fracture pain treatment.

GUIDED IMAGERY:

Guided imagery, as well as distraction and focused attention techniques, are valuable tools that healthcare professionals and parents can regularly use when children are experiencing pain. Genuine distraction and focused attention involve fully engaging the child’s mind in an activity or topic unrelated to their pain. This active process can effectively reduce neuronal responses triggered by tissue damage. Parents and healthcare staff can play a crucial role in helping children divert their attention away from their pain. Various stimuli can be used to capture a child’s attention, particularly in young children, including music, lights, colorful objects, tactile toys, sweet tastes, and interactions with other children. For older children and adolescents, engaging in conversation, playing games, using computers, or watching interesting movies can be effective distracters. Guided imagery, on the other hand, involves teaching a child to create mental images in their mind. This practice can help children learn how to modify the way their body senses and responds to pain. It provides a constructive means for children to cope with pain by using their imagination to visualize a different, more comfortable experience.

Distraction techniques can serve as valuable supplementary approaches for managing pain in preschool- and school-aged children. Clown therapy stands out as one of the most commonly used techniques in the non-pharmacological management of acute pediatric pain. The act of laughter, induced through clown therapy, has a physiological impact, stimulating the production of beta-endorphins. These substances have effects similar to those of opiates, contributing to pain relief. In 6 randomized controlled trials involving a total of 517 pediatric participants, it was found that children undergoing clown therapy during procedures such as venipuncture or peripheral vein cannulation reported experiencing less pain than did those who received the standard of care. This underscores the effectiveness of clown therapy as a means to alleviate pediatric pain and highlights the importance of non-pharmacological interventions in enhancing the overall well-being of pediatric patients [36].

Animal-assisted treatment has been shown to have a positive impact on reducing children’s pain and behavioral distress to a certain extent. It can also influence various physiological parameters, such as respiratory rate, heart rate, diastolic blood pressure, oxygen saturation, and cerebral oxygenation. This non-pharmacological intervention method is relatively safe and demonstrates practicality for implementation among pediatric patients [37]. Another noteworthy non-pharmacological pain relief method that has gained traction in recent years is the use of virtual reality for acute and chronic pain management. In a randomized controlled trial that compared acute pain outcomes of pediatric patients undergoing burn wound care, the virtual reality treatment group exhibited benefits over those who watched a movie or received standard care without distraction [38]. This highlights the potential of virtual reality as an effective tool in alleviating pain and enhancing the overall experience of pediatric patients undergoing medical procedures.

BREATHING EXERCISE: Deep breathing exercises are a straightforward yet potent relaxation technique with a significant impact on pain reduction [39,40]. Deep breathing helps trigger the body’s relaxation response, leading to a slower heart rate and lower blood pressure. This, in turn, can result in decreased pain levels and an improved overall sense of well-being. Encouraging children to focus on deep diaphragmatic breathing, with or without the use of imagery, can help relax them and divert their attention from a painful procedure. There is substantial evidence supporting the effectiveness of these practices. Most physiotherapists are familiar with the principles and mechanisms of effective relaxation and deep breathing techniques. For brief and non-stressful procedures, it can be helpful to teach these breathing techniques separately from the painful treatment. Whenever possible, it is beneficial to encourage the practice of the technique before the painful procedure. In a crossover randomized clinical trial conducted by Bahrololoomi et al [41], using a bubble blower for breathing exercises was found to be an effective distraction and relaxation method for reducing pain in 7 to 10-year-old children with moderate to severe anxiety. Incorporating deep breathing exercises into daily life can be done in various ways. Regardless of the approach taken, consistent practice of these breathing exercises can provide ongoing benefits for pain management.

RELAXATION TRAINING: Research has compellingly demonstrated that relaxation techniques can have a profound impact on the physical and emotional aspects of pain. These techniques have been effective in reducing pain intensity, increasing pain tolerance, and enhancing overall well-being. Moreover, integrating these techniques into a pain management plan can empower individuals to regain a sense of control over their pain, which, in turn, reduces feelings of helplessness and despair. Relaxation is a state of being calm and at ease. The process of learning to relax involves identifying and letting go of tension in the body and mind. Relaxation techniques are particularly valuable in relieving muscle tension and reducing stress [42]. A meta-analysis was conducted to evaluate the effectiveness of relaxation techniques in decreasing postoperative pain and improving perioperative clinical care in orthopedic surgery. The results showed that relaxation techniques consistently produced positive effects, benefiting patients in terms of pain reduction, anxiety reduction, and overall recovery [43]. However, it is important to note that the quality of evidence is generally considered low. Future studies with larger sample sizes, especially in pediatric populations, may help resolve any inconsistencies and provide more robust support for the use of relaxation training in orthopedic procedures.

POSITIVE REINFORCEMENT: In operant conditioning, positive reinforcement entails adding a reinforcing stimulus following a behavior, which increases the likelihood of that behavior occurring again in the future. When used appropriately, positive reinforcement can be a highly effective tool for learning and behavior modification. A study conducted by He et al [44] demonstrated statistically significant improvements in participants’ reported use of various pain relief methods, including imagery, positive reinforcement, thermal regulation, massage, and positioning, to alleviate postoperative pain in children. Additionally, another study found a statistically significant relationship between an increase in nurses’ use of positive reinforcement and postoperative pain relief in children in pre- and post-test results [45]. These findings highlight the positive impact of positive reinforcement techniques in enhancing pain management for pediatric patients. Numerous studies have shown that memories of past painful procedures strongly influence a child’s distress and coping during subsequent medical procedures. Encouragingly, there is evidence to suggest that memories of painful experiences can be reframed to reduce pain and distress during subsequent procedures. This has significant implications for medical staff and parents, as they can potentially help children cope with future procedures by reviewing and rewarding them for their coping strategies during current procedures. By reinforcing positive behaviors and coping mechanisms, medical professionals and caregivers can contribute to better pain management and reduced distress in pediatric patients.

Complementary Therapy

THERAPEUTIC PLAY:

Play therapy techniques have proven to be valuable in alleviating anxiety and guiding children’s behavior, especially in the context of elective surgery [46]. A comprehensive review of 8 studies provided significant evidence for the role of play in reducing anxiety and pain and enhancing the overall well-being of pediatric patients [47]. Based on these findings, it is safe to conclude that therapeutic play interventions are effective in mitigating negative emotional manifestations in children, reducing preoperative anxiety and pain, improving compliance with anesthesia induction, and decreasing postoperative anxiety and pain. Furthermore, dramatic puppetry has been identified as an effective preoperative care and preparation strategy for reducing anxiety in children undergoing surgery. The use of the “bubble breath” exercise, a technique from the realm of play therapy, has also proven highly effective for psychologists to engage and manage highly anxious children. Play therapy revolves around providing objects or situations in the form of games, thus establishing communication. For children, toys are their words, and play is their conversation [48]. In the context of pediatric fractures, implementing play therapy, with a focus on parent education so that the therapy can be conducted by parents, can significantly contribute to the reduction of anxiety and pain in children. This approach also helps decrease the reliance on analgesic drugs and reduces the fear of pain, ultimately promoting a smoother fracture recovery process.

MUSIC THERAPY:

Music therapy has demonstrated positive effects in alleviating anxiety and pain, improving sleep quality, reducing the use of analgesic drugs, and promoting physiological rehabilitation in various pediatric studies, including those involving injection and surgical pain [49,50]. While the exact mechanism of action is not entirely clear, it is believed that music exerts its analgesic effect through distraction. The therapeutic effects of music for pain reduction have yielded mixed results in some studies, with many lacking rigorous or high-quality methodologies. However, a meta-analysis of 7 randomized controlled trials indicated that listening to music modestly reduced pain intensity and opioid requirements, which are often seen as physiological analogs to pain [51]. It is worth noting that the magnitude of the opioid-sparing effect of music was found to be lower than the effect produced by commonly used pain relievers, such as acetaminophen or over-the-counter nonsteroidal medications. Therefore, while music should not be considered the primary method for pain treatment, it does show promise as a valuable adjunct for managing acute musculoskeletal pain.

Additionally, providing emotional support with the comforting and reassuring presence of caregivers involved in daily activities and the creation of a comfortable environment are considered useful non-pharmacological techniques for pain management. These approaches can contribute to a holistic and comprehensive approach to pediatric pain care.

Pharmacological Intervention

Nonsteroidal Anti-Inflammatory Drugs

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS:

NSAIDs received their initial approval in 1989 for short-term pain management. Over the past few decades, numerous orthopedic surgery trials have demonstrated the safety and efficacy of NSAIDs [56]. Due to their distinct mechanism of action from that of opioids, NSAIDs possess the potential to provide sufficient pain relief while reducing overall opioid requirements [38]. Some surgeons avoid the use of NSAIDs due to concerns regarding bone healing, and a meta-analysis indicates a negative impact of NSAIDs on bone healing [57]. NSAIDs function by inhibiting peripheral and central cyclooxygenase. The 2 primary forms of cyclooxygenase are COX-1 and COX-2. The concept of selectively inhibiting COX-2 while leaving COX-1 uninhibited has been long recognized for potentially yielding an NSAID with a higher therapeutic index. The introduction of highly-selective COX-2 inhibitors, such as celecoxib, has generated considerable enthusiasm, due to their significantly improved safety, compared with that of nonselective COX inhibitors. The common NSAIDs ibuprofen, naproxen, diclofenac, acetaminophen, and celecoxib will be described, including their appropriate usage, age recommendations, and dosages (Table 4). These are only suggestions, and the European Society for Paediatric Anaesthesiology assumes no legal responsibility for these recommendations. Please consult the pharmacopoeia of your country before implementing these dosage suggestions, including the maximum drug doses. It is essential to note that certain analgesic drugs or formulations may not be available in all countries [58].

IBUPROFEN: Ibuprofen is the most commonly used NSAID for treating inflammation, mild to moderate pain, and fever in children. It is available in various pediatric formulations and is associated with minimal adverse effects. Notably, it is the only NSAID approved for use in children aged ≥3 months, due to its proven efficacy and safety profiles [59]. As per the British National Formulary for Children, ibuprofen is recommended for use in infants as young as 1 month, with a dosage of 5 to 10 mg/kg/dose, administered 3 to 4 times daily, up to a maximum dose of 40 mg/kg/day.

NAPROXEN:

Naproxen is an anti-inflammatory agent with analgesic and antipyretic properties, which is commonly used in the treatment of juvenile rheumatoid arthritis, fever, and pain in children and adolescents [60]. Its elimination half-life of 12 to 14 h is longer than that of most other NSAIDs, making it an effective analgesic option for children. A randomized controlled study demonstrated the efficacy of preoperative oral naproxen (10 mg/kg), which significantly reduces the need for rescue analgesics after adenoidectomy in children [61]. The dosing of naproxen is typically 5 to 10 mg/kg every 8 to 12 h, up to a maximum daily dose of 20 mg/kg.

DICLOFENAC: Diclofenac is a phenylacetic acid derivative commonly used in the form of the sodium salt to treat pain and inflammation. Standing et al [62] demonstrated that 1 mg/kg of diclofenac produces similar exposure in children aged 1 to 12 years as does 50 mg in adults, making it an acceptable dosage for clinical practice. Higher doses are unlikely to provide additional benefits to patients. An open-label study [63,64] revealed that oral diclofenac exhibited a favorable pharmacokinetic and safety profile in patients aged 12 to 17 years, with no new safety concerns in this pediatric population and good gastrointestinal tolerability. In 2018, the European Society for Paediatric Anaesthesiology Pain Committee published guidelines suggesting oral and suppository diclofenac at a dosage of 1 mg/kg, 3 times daily, to enhance postoperative pain management in children [65].

ACETAMINOPHEN: Acetaminophen, developed in the 1980s, is the most widely used analgesic and antipyretic drug. Although it lacks anti-inflammatory actions, acetaminophen is often grouped with NSAIDs. Acetaminophen is considered a first-line treatment for fever and pain in children, due to its perceived safety profile. Acetaminophen’s effects are believed to be exclusively mediated by central COX inhibition, thus avoiding the negative effects of peripheral COX inhibition commonly associated with NSAIDs. However, there is growing evidence suggesting that acetaminophen use in children is associated with an increased risk of developing asthma and related atopic diseases, and more attention should be paid when clinicians meet patients with these diseases [66,67] Please refer to Table 4 for detailed recommended drug dosages.

CELECOXIB:

Celecoxib belongs to a novel group of agents that selectively inhibit COX-2, making it an important class of drug, due to its lower incidence of adverse effects, compared with traditional nonsteroidal anti-inflammatory drugs. Celecoxib is the most commonly used analgesic medication in adults with osteoarthritis. In a double-blind randomized controlled study conducted by Murto et al in children aged 2 to 18 years undergoing pediatric adenotonsillectomy, a 3-day course of oral celecoxib was found to reduce early pain and co-analgesic consumption. However, for sustained pain relief in the pediatric setting, a longer duration of treatment can be required [68]. Another randomized controlled trial demonstrated that high-dose celecoxib (5 mg/kg) effectively controls pain after tonsillectomy, without any adverse effects in this relatively small sample. It also reduces narcotic consumption, with a greater effect observed in children experiencing higher degrees of pain. Therefore, celecoxib can be considered an effective alternative to ibuprofen after tonsillectomy [69].

Opioids

MORPHINE:

Morphine is a naturally occurring opioid derived from the poppy straw of the opioid poppy. It is known for providing excellent analgesia and sedation, making it a highly effective agent for postoperative systemic analgesia. Morphine serves as the prototypical opioid, against which the potency of all other opioids is measured. There are numerous formulations available, including intravenous, oral, buccal, sublingual, intranasal, subcutaneous, intramuscular, and neuraxial routes. When administered intravenously, the peak effect of morphine is observed at 20 min, while oral dosages peak around 30 to 60 min. For pediatric pain management, oral dosage is recommended as the first-line choice, due to its specific characteristics and potential for addiction. Morphine is primarily metabolized in the liver, with a much smaller portion undergoing metabolization in the kidneys and brain through glucuronidation. In neonates and individuals with a reduced glomerular filtration rate, there is a possibility of metabolite accumulation, particularly in the form of respiratory issues. Therefore, careful consideration and monitoring are essential when using morphine in these populations.

HYDROMORPHONE:

Hydromorphone is a hydrophilic hydrogenated ketone synthesized from morphine. It is approximately 5 times more potent than morphine and has a decreased incidence of nausea and vomiting [78]. This medication is commonly used to treat acute pain, either as an intravenous bolus or infusion (including PCA), and can be administered epidurally in children. The recommended dose of hydromorphone is 0.03 to 0.08 mg/kg/dose every 3 to 4 h orally and 0.01 to 0.02 mg/kg/dose every 3 to 4 h intravenously. When used with PCA, hydromorphone bolus doses of 2 to 4 μg/kg with a lockout period of 8 to 15 min are suggested, along with an optional basal infusion rate of 1 to 5 μg/kg/h. It is important to note that hydromorphone has a low oral bioavailability, and when administered orally, the dosage needs to be increased by a factor of approximately 4 [79]. The metabolite of hydromorphone is inactive, but it can accumulate in individuals with renal or hepatic insufficiency, potentially leading to neuroexcitatory adverse effects, including allodynia and seizures. Careful monitoring is necessary when using hydromorphone in patients with compromised renal or hepatic function.

MEPERIDINE:

Meperidine is indicated for preoperative medication, supporting anesthesia, providing obstetrical analgesia, and managing severe pain that requires an opioid analgesic and for which alternative treatments are insufficient. However, it should not be used to relieve chronic (long-lasting or recurrent) pain. In children, meperidine use is recommended only as a single dose to treat shivering in the post-anesthesia care unit. In a retrospective comparison of 35 years of sedation experiences by Nathan [80], meperidine was found to be the most effective and safe option for overcoming the need for restraint in cases of moderate and severe levels of anxiety. In another study, by Alhashemi and Daghistani, a randomized double-blind study revealed that meperidine provided adequate analgesia, less sedation, and earlier readiness for recovery room discharge in pediatric patients undergoing tonsillectomy [81]. The recommended dose of meperidine is usually 1.1 to 1.8 mg/kg per dose, given every 3 or 4 h as needed in children older than 1 year old. However, it is important to note that reports in the literature suggest meperidine has a slower elimination rate in neonates and young infants, putting them at higher risk of experiencing respiratory depressant effects. Due to the lack of evidence supporting its use in children and its potential risks, meperidine should not be licensed as the first-line treatment for pediatric pain management. Alternative options with better safety profiles should be considered in this population.

FENTANYL:

Fentanyl is the most widely used synthetic opioid in medicine, boasting a potency 100 times that of morphine and a strong affinity for μ-opioid receptor agonism. It has a wide therapeutic index, allowing for safe use in various medical settings requiring strong analgesia. The rapid onset and short duration of action make fentanyl ideal for situations in which a high level of analgesia is needed for a brief period. The highly lipophilic nature of fentanyl enables it to cross cell membranes rapidly, leading to its successful use in various administration routes, including intravenous, epidural, intrathecal, transdermal, intranasal, and other transmucosal applications [82]. Intranasal fentanyl has proven effective in treating acute moderate to severe pain, causing minimal distress to children during administration [83]. Studies have indicated that intranasal fentanyl at a dose of 1.5 μg/kg is safe and effective in managing acute severe pain in children, offering an attractive alternative to oral and intravenous opiates [84]. Crellin et al [85] reported statistically significant reductions in pain scores among children with upper limb injuries when using the 50 μg/mL concentration at a dose of 1.5 μg/kg. However, caution should be exercised with larger doses in small infants unless they are ventilated or closely monitored postoperatively. Infants older than 3 months of age may be less sensitive to fentanyl-induced ventilatory depression and metabolize the drug more rapidly. As a result, intravenous fentanyl is routinely considered an intraoperative anesthetic or used in postoperative PCA at a dose of 1 to 2 μg/kg. Careful consideration of dosing and patient factors is crucial to ensuring safe and effective use of fentanyl in pediatric populations.

METHADONE:

Methadone is a synthetic opioid with a potency roughly equivalent to that of morphine. It is increasingly used in infants and children due to its prolonged duration of action, inactive metabolites, and lipophilicity. In the acute setting, methadone can effectively manage moderate to severe pain, with its analgesic properties, respiratory depression, and sedation persisting for 12 to 36 h after a single dose. A study by Sadhasivam et al [86] demonstrated that multiple small perioperative methadone doses resulted in sustained analgesia, safe lower blood methadone levels, and no respiratory depression. Another scoping review on intraoperative methadone for postoperative pain control showed that it decreased postoperative opioid consumption and resulted in superior reported pain scores, compared with that of other opioids, with similar frequency of adverse events between the groups [87]. The elimination half-life for the racemate form of methadone is 15 to 60 h. Common adverse effects are similar to those of other opioids and can include apnea, nausea and vomiting, and sedation. Oral methadone is not recommended as an as-needed analgesic, due to the increased risk of overdose and death with this long-acting opioid. Instead, its use is limited to chronic pain management. For intravenous dosing, methadone should be initiated at 0.05 to 0.1 mg/kg, given every 30 min, and titrated to achieve the desired effect. Once the desired analgesia is obtained, the maintenance dosage is typically 0.05 to 0.1 mg/kg every 12 h. During initial titration, it is advised to avoid methadone dosages higher than 30 mg/day. Methadone can lead to QT prolongation; therefore, careful dosing and monitoring are essential to ensure safe and effective use of methadone in pediatric patients.

OXYCODONE:

Oxycodone is a semi-synthetic derivative of opioid alkaloid commonly used to relieve severe pain that requires opioid treatment following an operation, often in combination with other pain-relief medicines, such as NSAIDs [88]. This medication exerts full agonism at the μ receptor and partial κ and δ activity, with a potency approximately 1.5 times that of morphine. Oxycodone offers several advantages, including high bioavailability, stable hemodynamics, and few adverse effects. In a recent study, oxycodone at a dosage of 0.1 mg/kg, in combination with sufentanil, was used for preemptive analgesia to reduce postoperative pain in children undergoing tonsillectomy [88]. Oxycodone is available in various forms, including oral solution, suppositories, immediate-release and extended-release tablets, and tamper-resistant formulations. In August 2015, the FDA approved the use of extended-release oxycodone for children between 11 and 16 years old with severe pain that is inadequately controlled by alternative treatment options [89]. The effects of oxycodone pharmacogenetics on postoperative analgesia and related clinical outcomes have been investigated in a pilot prospective study [90]. The suggested doses based on weight are listed in Table 4 for reference.

Future Directions

The management in pain from childhood fractures, which is similar to cancer-related pain, requires an interdisciplinary, stepwise approach to reduce the physiological and psychological effects, following the 3-step pain management ladder (Figure 3). In this process, healthcare professionals and caregivers must collaborate closely, each fulfilling their respective roles to reduce reliance on analgesic drugs, improve pain management, and enhance the overall quality of care for childhood fractures.

Conclusions

Childhood fractures can cause severe pain, leading to physical and psychological effects. Effective pain management requires a multidisciplinary approach, incorporating non-pharmacological and pharmacological treatments. Accurate assessment of fracture-related pain, combined with timely and appropriate treatment, can better manage pain, reduce complications, and promote fracture healing.