REVIEW ARTICLE

Interventional Procedures for Chronic Pain in Children and Adolescents: A Review of the Current Evidence Ravi D. Shah, MD*; Dario Cappiello, MD†; Santhanam Suresh, MD* *Department of Pediatric Anesthesiology, Ann & Robert H. Lurie Children’s Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois, U.S.A.; †Department of Anesthesiology, Pain and Intensive Care Medicine, University School of Medicine Campus Bio-Medico of Rome, Rome, Italy

& Abstract: This review discusses the role of interventional procedures in the treatment of chronic pain in children and adolescents. Due to lack of scientific evidence, significant controversy surrounds the utility of invasive techniques for managing pediatric chronic pain states. Interventional procedures are a widely accepted modality for pain management in adults. The use of such techniques in children is supported only by case reports, case series, and very few randomized controlled studies. In addition, the potential for severe complications leaves open a debate on the safety of these invasive procedures, which must be confirmed by more extensive and accurate prospective studies. & Key Words: pediatric pain, nerve block, interventional pain procedures, evidence-based medicine, review

INTRODUCTION Chronic pain is a significant yet underreported problem in the pediatric population1 that carries psychological,

Address correspondence and reprint requests to: Ravi D. Shah, MD, Assistant Professor of Anesthesiology, Ann & Robert H. Lurie Children’s Hospital of Chicago, 225 E. Chicago Ave, Box 19, Chicago, IL 60611, U.S.A. E-mail: [email protected]. Submitted: October 5, 2014; Revision accepted: December 9, 2014 DOI. 10.1111/papr.12285

© 2015 World Institute of Pain, 1530-7085/16/$15.00 Pain Practice, Volume 16, Issue 3, 2016 359–369

emotional, and social repercussions for the child and the family.2,3 The potential for such consequences to negatively impact a child’s quality of life has, in recent years, fostered the development of a multidisciplinary approach to treat pediatric pain.4,5 A variety of behavioral, pharmacological, and physical therapies are employed in pediatric chronic pain treatment regimens. Unlike in the adult cohort, where it is used as an initial diagnostic and therapeutic modality, interventional procedures are often introduced after patients fail other treatment approaches.6 The purpose of this review is to examine the role of interventional procedures in managing pediatric chronic pain. Regional anesthetic techniques and other interventional procedures are performed in children for therapeutic, diagnostic, and prognostic purposes.7,8 Regional anesthesia may also be performed in children to facilitate participation in physical therapy. The indications for such approaches in pediatric chronic pain management remain unclear; we conducted a literature review to determine the prevalence and reported efficacy of interventional techniques in children and adolescents who suffer from chronic pain. Chronic Pain Syndromes in Children The International Association for the Study of Pain defines chronic pain as pain lasting more than

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3 months.9 Chronic pain is more common than is reported in childhood and adolescence and prevalence rates vary substantially between data from different studies.10 Children experiencing persistent or recurrent chronic pain may miss school or withdraw from social activities, and are at risk of developing internalizing symptoms in response to their pain. Given these consequences, researchers and clinicians are working to enable the development of effective multidisciplinary strategies to ameliorate chronic pain in children and adolescents.

DISCUSSION Literature Review We analyzed a total of 133 studies, of which 25 prospective studies almost entirely focused on the use of baclofen; there were 7 retrospective studies, 17 case series, and 84 case reports (Table 1). We will extensively discuss the use of each of the procedures in pediatric syndromes and specific procedures based on our review of the literature (Table 2). Role of Imaging for procedures

METHODS References included in the literature review were identified by searching PubMed and OVID for articles published between January 1970 and March 2013 using various combinations of the following search terms: chronic pain; children; interventional procedures; regional anesthesia; anesthetic; imaging; epidural; subarachnoid; nerve block; plexus block; intrathecal baclofen; sympathetic block; and Bier block. Prospective and retrospective studies, case reports, and case series were all considered for inclusion, without language restrictions.

The potential for anatomic variation can lead to high failure rates when performing landmark-based interventional procedures.11 Radiological image-based guidance optimizes performance of several procedures for the treatment of chronic pain in children.12 Fluoroscopic guidance, CT guidance, ultrasound guidance, or a combination of these techniques are commonly used to improve success rates and to reduce procedure-associated risks. When necessary, these modalities can also aid in establishing pain-related diagnoses.13,14 For these reasons, we will also discuss the use of image-guidance in our review of interventional procedures.

Table 1. Interventional Procedures and Indications for Pediatric Patients Included in Literature Review Procedures

Studies

No. of Cases

Neuraxial blocks

Case report Case series Prospective study Retrospective study Case report Case series Prospective study Retrospettive study

12 7 2 2 51 4 2 1

Case report Case series Prospective study Case reports Case series Prospective study Retrospective study Case report Case series Prospective study Case series Case report Case series Prospective study Case report Retrospective study. Prospective study

14 2 2 1 1 1 2 1 1 1 1 4 1 15 1 2 2

Peripheral blocks

Sympathetic blocks Bier block

Neurolysis

Neurostimulation Intrathecal baclofen

Intra-articular steroids

Indications

Imaging Guidance

Refractory pain, cancer pain, excessive sedation, phantom limb pain, CRPS

Fluoroscopy Ultrasound CT

6,16–23,25,99

Refractory pain, cancer-related pain, excessive sedation, phantom limb pain, neuralgia, CRPS, slipping rib syndrome, myofascial pain syndrome, chronic abdominal wall pain Unexplained abdominal pain, CRPS, herpes zoster

Ultrasound

6,8,41,42,51–53,55, 61,66,81,83,88–90, 92–95

Fluoroscopy Ultrasound CT

11–13,61,97,99,101, 102,103–105,107–112

CRPS, neuropatic pain

Refractory pain, cancer pain, spasticity

Spasticity and dystonia

Juvenile idiopathic arthritis, osteitis condensans

References

113, 114, 116,117, 119

Fluoroscopy Ultrasound CT Fluoroscopy Fluoroscopy

32, 82

132 26–30

127–131

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Table 2. Chronic Pain Symptoms and Syndromes Treated with Interventional Procedures Areas Affected by Chronic Pain Head

Abdomen

Chest pain

Back pain

Limb pain

Clinical Symptoms and Syndromes

Interventional Procedures

Migraine Persistent neuropatic headache Cystic fibrosis Neuropathic pain after surgery Cystic fibrosis (recurrent pancreatitis) Cancer pain (visceral pain)

Peripheral nerve blocks (trigeminal and occipital) Peripheral nerve blocks (trigeminal, occipital, and C2 nerve root) Supraorbital nerve block Peripheral nerve blocks (rectus sheath blocks or transversus abdominis plane blocks) Thoracolumbar nerve roots blocks Peripheral nerve blocks (ilioinguinal and perineural catheters) Celiac plexus block Long-standing epidural administration with tunneled catheter Intrathecal analgesia and continuous intrathecal analgesia Intercostal nerve blocks Thoracic epidural analgesia

Costochondritis Tietze’s syndrome Slipping rib cage syndrome Cystic fibrosis Spondylolysis, spondylolisthesis, disk degeneration, disk herniation, spinal cord tumors, sickle cell disease Myofascial pain syndrome Fibromyalgia Juvenile arthritis Phantom limb pain and cancer pain Sickle cell crisis pain (VOC) Meralgia paresthetica CRPS I and II (allodynia, hyperalgesia, edema, changes in skin blood flow)

Central Neuraxial Blocks Epidural and Continuous Epidural Analgesia. These techniques may be utilized to decrease pain intensity and improve quality of life in several conditions, including cancer-related pain,15 back pain, and sickle cell crisis pain.16 Epidural analgesia may also be performed to enable successful participation in physical therapy and desensitization exercises for patients with complex regional pain syndrome (CRPS) types I and II of the lower extremity.17 The epidural block is generally performed as a “single-shot” or as continuous epidural analgesia through an epidural catheter. The catheter for continuous analgesia may be tunneled in children to avoid accidental displacement during physical therapy.18–21 Epidural placement via the caudal and lumbar approaches are the most common; however, thoracic placement is also feasible when indicated.18 Local anesthetic solutions may be combined with adjuvant medications such as alpha-2 agonists or opioids. Dexmedetomidine and clonidine have been shown to enhance and prolong analgesia (more so than opioid adjuvants), ultimately allowing a decrease in the local anesthetic dose requirement.22–32 To our knowledge, no

Epidural analgesia Trigger point infiltrations

Trigger point Joint infiltration Spinal, epidural, and regional blocks Epidural and regional blocks Lateral Femoral Cutaneous nerve block Bier block (guanethidine, bretilium, lidocaine-ketorolac) Sympathetic chain blocks (stellate ganglion blocks, lumbar sympathetic blocks) Neuromodulation via spinal cord stimulation Continuous peripheral nerve blocks (brachial plexus catheters), sciatic nerve catheters

data are available to support the use of epidural steroid injections in children or adolescents.33 Intrathecal and Continuous Intrathecal Analgesia. Intrathecal drug delivery can be effective in treating pain states that are refractory to epidural analgesia.34 In the pediatric population, intrathecal infusions have been successfully utilized to treat severe cancer pain15 and CRPS I.21 Intrathecal administration of both opioids and local anesthetics has been described in children.35 Farid and Heiner successfully treated an 8-year-old girl with chronic left foot pain by placing an intrathecal catheter at the L4-5 spinal space and infusing 0.2% ropivacaine at 0.03 mg/kg/h for 1 week.34 Intrathecal clonidine administration, which is commonly performed in adults, has also been reported in a terminally ill child.36 Baclofen has been administered intrathecally to manage refractory spasticity and dystonia in children with multiple sclerosis, cerebral palsy, traumatic brain injury, spinal cord injury, transverse myelitis, and other conditions.37 This technique has also been effectively utilized to manage pain and improve muscle tone in patients with Friedrich’s ataxia and spinocerebellar

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ataxia.38–41 Subarachnoid neurolysis has been reported as an effective last resort to alleviate pain secondary to terminal cancer.42 Fluoroscopic and CT-guided approaches have been described for epidural and intrathecal catether placement.43,44 Ultrasound imaging for neuraxial blockade is easier to perform in the pediatric population compared to adults because of the shallower depth to structures of interest, which permits use of higher-frequency ultrasound probes with superior imaging resolution.45,46 Although some studies demonstrate an advantage of using ultrasound guidance for spinal anesthesia in adults,47–49 ultrasound guidance is primarily used for limb, epidural, and caudal blockade in children.50,51 No published reports exist that describe ultrasound guidance for intrathecal injection in pediatric patients for management of chronic pain.15,45 Peripheral Nerve Blocks and Continuous Regional Blocks Peripheral nerve blockade has become an important therapeutic measure for the management of several pediatric pain syndromes. Serial peripheral nerve blocks and continuous peripheral nerve blocks (CPNBs)52 have been reported as effective in facilitating physical therapy53 and controlling pain in both inpatient and outpatient settings.52 Peripheral nerve blocks may be utilized as adjunctive therapy in children with CRPS, migraine, neuropathic pain, cancer pain, phantom limb pain, musculoskeletal pain, and sickle cell crisis pain.6,54–57 These procedures are traditionally performed using either landmarks or nerve stimulators; however, the evolution of ultrasound-guided techniques has led to safer practices with improved success rates.58 Head and Neck Blocks. Peripheral head and neck blocks are most commonly performed in patients with chronic daily headaches, including migraine, tensiontype, and persistent neuropathic headaches.59 Trigeminal nerve blocks for frontal headaches and occipital nerve blocks for persistent posterior headaches and occipital neuralgia have been shown to be effective in children.55 These procedures may be performed serially and can be easily performed in the outpatient setting with topical anesthesia.60 Supraorbital and supratrochlear nerve blocks are performed at the level of the supraorbital foramen after careful aspiration (0.5 to 1 mL of 0.25% bupivacaine with 1:200,000 epinephrine).61 The occipital nerve block may be conducted

using landmark-based techniques or with ultrasound guidance.62,63 Ultrasound-guided occipital nerve blockade requires that a linear probe be placed over the C2 spinous process and tilted laterally until the obliquus capitis muscle is identified. The occipital nerve, which is located superficial to the muscle, can easily be blocked using an in-plane approach. This approach to the occipital nerve allows easy access to the C2 nerve root, thereby providing a more robust blockade when compared to landmark-based subcutaneous injection.64 Local anesthetics are typically co-administered with steroids such as betamethasone, methylprednisolone, and dexamethasone in a ratio of 2:1 to 3:1.65,66 Upper Extremity Blocks: Brachial Plexus Block. Brachial plexus blockade is frequently utilized to provide intraoperative and postoperative analgesia in children.67,68 These techniques may be successfully applied to the treatment of chronic pain states, including adjuvant management of CRPS I, neuropathic pain of the upper extremity,69 phantom limb pain, and cancerrelated pain.56 The brachial plexus may be approached at the supraclavicular, infraclavicular, interscalene, and axillary levels for single or continuous regional anesthesia.70–74 Although some controversy exists about ideal catheter location for continuous regional anesthesia,75,76 an infraclavicular catheter is likely to be more secure while performing physical therapy.77 Local anesthetics (0.1% to 0.25% bupivacaine or 0.2% ropivacaine with epinephrine 1:200,000) and adjuvants such as clonidine can be used for a “single-shot block” and for continuous regional blockade.78 Ultrasound guidance is imperative when performing brachial plexus blocks in children, as it is associated with improved success and fewer complications.79,80 Tobias et al. demonstrated the utility of continuous peripheral nerve blockade for the treatment of CRPS type I in a 10-yearold girl; such techniques can enable patients to participate fully in physical therapy and exercise regimens. In this case, the catheter was removed after 60 hours and the patient was discharged from the hospital 4 days after catheter placement with minimal swelling, improved color, and improved mobility.69 Lower Extremity Blocks: Sciatic, Lateral Femoral Cutaneous, Obturator, and Other Nerves. Sciatic, obturator, and lateral femoral cutaneous nerve blocks may be performed to treat chronic lower limb pain in children.53,81–83 Sciatic nerve catheters have been demonstrated as an effective means to achieve long-term

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analgesia in children with chronic pain.84 Femoral nerve blockade has been described for treatment of intractable pain in an adolescent with chronic hip dislocation.85 The fascia iliaca compartment block, which is used to manage surgical and traumatic hip pain in children, has not been described for the treatment of chronic pain.86 Sciatic nerve block: This block has been described as an effective therapeutic option for reducing CRPS Irelated neuropathic pain81,82, cancer-related pain, and lower extremity phantom limb pain.83 Single-shot blockade can be performed; however, continuous regional analgesia by perineural catheter placement is preferred for long-term analgesia and facilitation of physical therapy.84,87–90 Currently, the most widely used approach for chronic pain treatment is via the popliteal fossa, in which the nerve is identified with ultrasound guidance, followed by administration of local anesthetic at various concentrations—along with possible adjuvants such as alpha-2 agonists—based on the nature and intensity of pain.85,91,92 Lateral femoral cutaneous nerve block: Meralgia paresthetica is a syndrome that has been well-described in both adults and children93,94 and is best treated with a multidisciplinary approach.95 The lateral femoral cutaneous nerve block can be effectively employed as adjunctive therapy for this chronic condition.96 Ultrasound guidance allows for greater accuracy and effectiveness compared to landmark-based techniques.97,98 In most cases, the nerve is identified between the tensor fascia lata and the sartorious muscle in the superior part of the thigh and blocked by 4 to 5 mL of bupivacaine 0.25% or mepivacaine 1% to 2% and corticosteroids.97,98 The obturator nerve can be blocked to treat obturator neuralgia in children by either landmark or ultrasound-based guidance. In addition, neurolysis of the obturator nerve has been described for treatment of spasticity in children with cerebral palsy.99–101 The femoral nerve block has been described as an effective means of providing analgesia to the lower limb in order to facilitate participation in physical therapy for patients with CRPS type I.69 In addition, it has been successfully used to treat refractory pain in a child with chronic hip dislocation after failed medical management.85 Truncal Blocks: Paravertebral, Intercostal, Rectus Sheath, Transversus Abdominis Plane (TAP), and Ileoinguinal Nerve Blocks. The paravertebral block

has been validated in adults as an effective modality for providing perioperative analgesia102–104 and treating various chronic pain syndromes;105 however, pediatric data remain limited. Intercostal nerve blocks may be performed to manage pain related to costochondritis or slipping rib syndrome, or after chest tube placement.106,107 Other regional blocks of the trunk have been used to provide analgesia in children with chronic abdominal pain as well as pain in the inguinal region. The utilization of ultrasound guidance has made these techniques more popular and effective.108,109 The TAP block has been described for the treatment of pediatric patients with refractory abdominal neuropathic pain.110 Ultrasound guidance allows visualization of the virtual space between the internal oblique muscle and the transversus abdominis muscles where the thoracolumbar nerve roots (T8-L1) lie. An indwelling catheter may be left in the space for continuous analgesia. Serial rectus sheath blocks have be described as a means of providing analgesia for children with chronic abdominal wall pain.111 Postsurgical anterior cutaneous nerve entrapment syndrome (ACNES) has been successfully managed with serial TAP blocks.112 Blockade of the ilioinguinal nerve, which provides sensation to the groin area, can be used for therapeutic purposes in patients suffering from chronic pain after previous surgical procedures in the inguinal area. We have demonstrated the utility of performing ilioinguinal nerve blockade in adolescents with persistent groin pain following inguinal hernia repair.113 For refractory pain, we have placed a continuous infusion catheter in this space with good results. Sympathetic Blockade Sympathetic blockade is an interventional treatment option for the management of CRPS I and CRPS II and can be used to control pain and facilitate physical therapy and restoration of normal limb movement.114 Other indications for sympathetic blockade include acute and chronic pancreatitis, herpes zoster, visceral cancer pain, peripheral vascular disease, Reynaud’s disease, and to reverse the effects of accidental intraarterial drug injection. These indications have been wellstudied in adults, but data are lacking to support their use in children.115,116 Stellate Ganglion Block. The stellate ganglion has been successfully blocked in children to manage CRPS I of the

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upper extremity,117,118 headache,65 herpes zoster,119,120 and painful events caused by ischemia and thrombosis associated with Klippel–Trenaunay–Weber Syndrome.121 In children, blockade may be performed with either fluoroscopic or ultrasound guidance, which minimize the risk of vascular injuries or esophageal puncture.122 Lumbar Sympathetic Block. This block has been described for the treatment of various pediatric pain syndromes, including CRPS I, recurrent migratory sympathetically maintained pain syndrome,123 and cutis marmorata telangiectatica congenita.124 Several authors have suggested that utilization of a lumbar indwelling catheter is more effective in reducing pain intensity compared to repeated blocks.125 This procedure is routinely performed under fluoroscopy or with CT guidance.13 The lumbar sympathetic ganglia are identified anterior and medial to the lateral border of the second and third lumbar vertebral bodies and are blocked by administering a bolus of local anesthetic, resulting in increased skin temperature and vasodilatation with reduced pain in the ipsilateral limb.126 Celiac Plexus Block. The celiac plexus is located in the retroperitoneum at the T12-L1 level and is composed of both sympathetic fibers and parasympathetic fibers from the vagus nerve. The celiac plexus has been successfully blocked in anesthetized children with fluoroscopy, 3D-fluoroscopic reconstruction,127 and CT guidance.128 Local anesthetic and neurolytic blockade of the celiac plexus have been effectively utilized in children for treatment of chronic visceral pain secondary to malignancy, chronic pancreatitis, or inflammatory bowel disease.129–131 Dramatic pain relief can be achieved and opioid requirements may decrease. The celiac plexus block is technically challenging and must be performed by qualified and experienced personnel. Many complications have been reported, including somatic nerve damage, hypotension (orthostatic), diarrhea (unopposed parasympathetic activity), inadvertent intravascular injection, vascular embolism or thrombosis, aorto-duodenal fistula formation, renal injury, peritoneal abscess formation, retroperitoneal bleeding, and even paraplegia or death. Contraindications include patients on anticoagulant therapy, patients with coagulopathy, and local/intra-abdominal infection or sepsis and bowel obstruction. It is therefore important to limit

celiac plexus blockade as a last resort to achieve comfort in terminally ill patients.132–134 Intravenous Regional Anesthesia (IVRA) The Bier Block. IVRA has been effectively used to manage pain and facilitate active physical therapy in children with sympathetically mediated pain.84,132,133 A combination of local anesthetic and nonsteroidal antiinflammatory medications has been described as effective in treating CRPS type I.134 Guanethedine, which has been described for use in IVRA for management of CRPS I in adults, is rarely used in children.135 Other Interventional Procedures Myofascial pain syndrome112 is well-known in children and adolescents136 and is often refractory to traditional therapeutic approaches. Trigger point injections may be used for this syndrome and have also been used in pediatric patients with headache.55,65 Trigger point injections with botulinum toxin have been described in refractory adult cases of myofascial pain.136,137 In the pediatric population, botulinum toxin injections are primarily used to treat spasticity and dystonia.138–140 Several studies have demonstrated the safety and feasibility of performing intra-articular steroid injections in children with juvenile idiopathic arthritis (JIA) and osteitis condensans without significant side effects.141–144 These procedures can be performed under fluoroscopic guidance; however, ultrasound guidance may reduce radiation exposure and confirm successful injection.145 Gekht et al.146 described a case in which a 17-year-old male who sustained a traumatic fracture of the right L3-4 facet joint underwent neurolytic blockade of the right medial branch of the L2 dorsal ramus, which completely resolved his pain. Spinal cord stimulation is rarely performed in children, but can be attempted after other therapeutic measures have failed. Olsson et al.147 reported an effective application of spinal cord stimulation for the treatment for CRPS type I in adolescents; however, there are no other data that support this approach in children.

COMPLICATIONS Despite the development of new and safer interventional techniques to manage pediatric chronic pain, such procedures are not devoid of complications, which range from mild (dural puncture, local infection, vascu-

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lar puncture, or nerve injury) to severe (subdural and epidural abscesses, spinal cord injury, hemorrhage, intra-arterial or intravenous injection, chemical meningitis, paralysis, or pneumothorax). Therefore, it is important to critically evaluate the necessity of performing an interventional procedure in pediatric patients and to consider these procedures as a last resort at the end of the therapeutic algorithm.148,149

CONCLUSION Interventional procedures can serve as useful adjuncts to managing chronic pain conditions in children, especially in cases that are refractory to noninvasive treatments. In this review, we have summarized the current knowledge and reported practices of interventional management in children with chronic pain. The majority of literature on this topic consists of case reports and retrospective studies. This review serves as starting point from which we can generate a larger evidence base about the benefits or potential risks of performing such procedures in children and adolescents. Although more prospective, randomized controlled trials are needed to better answer these questions, we encourage clinicians to consider regional approaches as an important option when systemic management is limited or ineffective.

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