Clinical Policy Title: Parenteral treatment for complex regional pain syndrome

Clinical Policy Title: Parenteral treatment for complex regional pain syndrome Clinical Policy Number: CCP.1011 Effective Date: June 1, 2013 Initial Review Date: March 21, 2013 Most Recent Review Date: August 1, 2018 Next Review Date: August 2019 Related policies: Policy contains: Ketamine hydrochloride. Intravenous regional sympathetic nerve blockade. Complex regional pain syndrome. Reflex sympathetic dystrophy. CCP.1101 CCP.1098 CCP.1093 Hierarchy of chronic pain management Spinal cord stimulators for chronic pain Intrathecal opioid therapy for chronic pain ABOUT THIS POLICY: Prestige Health Choice has developed clinical policies to assist with making coverage determinations. Prestige Health Choice s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peer-reviewed professional literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of medically necessary, and the specific facts of the particular situation are considered by Prestige Health Choice when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. Prestige Health Choice s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. Prestige Health Choice s clinical policies are reflective of evidencebased medicine at the time of review. As medical science evolves, Prestige Health Choice will update its clinical policies as necessary. Prestige Health Choice s clinical policies are not guarantees of payment. Coverage policy Prestige Health Choice considers the use of intravenous ketamine hydrochloride to be clinically proven and, therefore, medically necessary for the treatment of severe complex regional pain syndrome that has not responded to other treatments (Cossins, 2013; Hayes, 2017; O Connell, 2013; Xu, 2016). Prestige Health Choice considers the use of intravenous regional sympathetic nerve blockade using any drug for the treatment of complex regional pain syndrome to be investigational and, therefore, not medically necessary. Limitations: 1

Coverage determinations are subject to benefit limitations and exclusions as delineated by the state Medicaid authority. The Florida Medicaid website may be accessed at http://ahca.myflorida.com/medicaid/. This policy does not address ketamine used for anesthesia. Alternative covered services: Oral pharmacotherapy with analgesics, antidepressants, anticonvulsants, anti-inflammatory medications, corticosteroids, and bone loss medications. Physical therapy, occupational therapy, or other covered manipulation therapy, excluding chiropractic care. Spinal cord stimulators. Behavioral health services. Background Complex regional pain syndrome is a neuropathic pain pathology of the peripheral and central nervous systems (International Association for the Study of Pain, 2011). It usually develops after an initiating noxious event, and is not limited to the distribution of a single peripheral nerve. Other causes may include nonsurgical procedures, drug exposure, stroke with hemiplegia, and cervical spondylosis. The causative mechanism that triggers complex regional pain syndrome from an injury is not completely understood, but may involve inflammation, altered sympathetic and catecholaminergic function, altered somatosensory representation in the brain, genetic factors, and psychophysiological interactions (Bruehl, 2010). There is no cure for complex regional pain syndrome, and the chronic nature of the disease, combined with the expectancy that the pain will worsen over time, adds to the burden of effective pain management. The pain is regional, with neither a specific nerve territory nor dermatome, and usually affects the extremities with a progressive burning sensation. It may display a distal predominance of abnormal sensory, motor, sudomotor, vasomotor edema, or other trophic manifestation. The pain may be a continuing evoked or spontaneous occurrence disproportionate to the initiating event in terms of the time or degree of pain related to the usual course of recuperation after the noxious event. In the later stages of complex regional pain syndrome, persons may experience bone mineral loss. Currently, there are two recognized types of complex regional pain syndrome. Type 1, previously known as reflex sympathetic dystrophy syndrome, occurs most often after an illness or injury that did not directly damage the nerves in the affected limb. It may develop after any type of trauma, especially a fracture. The majority of people with complex regional pain syndrome have type 1. Type 2, once referred to as causalgia, follows any identified injury to a nerve. There is no uniformly accepted list of diagnostic criteria or a single test that can definitively diagnose complex regional pain syndrome. This disease occurs in both genders of all ages, though literature suggests 2

that complex regional pain syndrome may be more common between the ages of 40 and 60. The onset of complex regional pain syndrome symptoms usually occurs within one month of the noxious event (Harden, 2001). Clinical findings are the gold standard for the diagnosis of complex regional pain syndrome, based on individual physical examination and medical history. Skin surface temperature recordings have been proposed but are unable to discriminate between complex regional pain syndrome 1 patients, thus limiting their clinical use (Niehof, 2008). Other diagnostic tests may provide important adjunctive information to assist in a diagnosis of complex regional pain syndrome. However, these procedures have a low sensitivity and a low predictive value, yielding an incomplete clinical picture and borderline diagnosis (Schürmann, 2007): Bone scan to detect changes in the bone. Sympathetic nervous system tests to detect changes in the sympathetic nervous system of the affected limbs; differences in results between limbs may indicate complex regional pain syndrome. X-rays to detect the loss of bone mineral content. Magnetic resonance imaging to detect changes within the affected tissues. Treatment for complex regional pain syndrome: Therapeutic approaches to complex regional pain syndrome are not uniform and, in some cases, are controversial. Some of the difficulty lies in the incomplete knowledge surrounding the causative factors for complex regional pain syndrome types 1 and 2. This lack of knowledge has slowed the progress of research for effective complex regional pain syndrome treatments. General consensus in professional literature supports early diagnosis with aggressive treatment for complex regional pain syndrome. Ideally, early treatment will stem the scale and scope of the symptoms, with possible containment of the progression of the syndrome, or even remission (Schwartzman, 2000). Individuals presenting with severe pain are less likely to have successful pain amelioration or resolution than those presenting with moderate pain. Rehabilitation may be extended due to a delay in the initiation of treatment. In the absence of treatment, permanent tissue damage, impairment, and living with chronic pain may occur (Atkin, 2003). Treatment of complex regional pain syndrome should be directed toward pain management and functional recovery in the affected extremity or body region, often requiring a combination of therapies. Conservative treatment options may include physical therapy, occupational therapy, pain relief through over-the-counter or prescription pain relievers, antidepressants, anticonvulsants, corticosteroids, bone-loss medications, percutaneous sympathetic nerve blocks and, in limited cases, sympathectomy. Intravenous sympathetic nerve blocks, spinal cord stimulation, and intrathecal infusion of analgesic medications have been used when conservative treatment has failed, but in general, these alternatives lack strong evidence of durable effectiveness from research or clinical experience (Harden, 2001; O Connell, 2016; Henson, 2010). Recent conclusions from an interdisciplinary expert panel encourage continued research and development, including the development of new drugs, devices, and safety recommendations to improve the care of patients with chronic pain (Deer, 2012). 3

Ketamine is a well-known, rapid acting anesthetic drug granted New Drug Application approval more than 40 years ago for intramuscular or intravenous use (Food and Drug Administration, 2017). It has both antinociceptive and antihyperalgesic effects primarily based on the antagonism of the N-methyl-Daspartate receptor. Central N-methyl-D-aspartate receptors activated by excitatory amino acid glutamate are involved in pain processing, neuronal plasticity, and central sensitization. As an N-methyl-D-aspartate antagonist, ketamine has been purported to reduce continuous and evoked pain when given in prolonged, subanesthetic doses to individuals with injuries of both the peripheral and central nervous systems, representing an off-label use; ketamine has been administered topically and intranasally in some cases (Hocking, 2003). Because of its analgesic and psychological effects (e.g., inducing dream-like states), it is a well-known drug of abuse. Intravenous regional block is designed to introduce a concentration of medication into a finite area at the sympathetic nerve endings in a particular region of the body. The intent is to produce a sympathetic denervation without disrupting motor activity. Intravenous regional block has been proposed using several substances. Professional literature suggests that ethical reasons should allow individuals to undergo a welldefined trial of a finite number of nerve blocks if attempts at functional restoration have been unsuccessful (Harden, 2001). Searches Prestige Health Choice searched PubMed and the databases of: UK National Health Services Centre for Reviews and Dissemination. Agency for Healthcare Research and Quality s National Guideline Clearinghouse and other evidence-based practice centers. The Centers for Medicare & Medicaid Services. We conducted searches on May 16, 2018. Search terms were: complex regional pain syndromes/drug therapy (MeSH), complex regional pain syndromes/therapy (MeSH), reflex sympathetic dystrophy, and ketamine (MeSH). We included: Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies. Guidelines based on systematic reviews. Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple cost studies), reporting both costs and outcomes sometimes referred to as efficiency studies which also rank near the top of evidence hierarchies. Findings 4

Sigtermans (2009) conducted a double-blind, randomized placebo-controlled trial with 60 participants with severe pain. Each participant received either ketamine or saline infused over four days at an inpatient facility. Ketamine was titrated at regular intervals to a maximum dosage of 30 milligrams per hour for a 70- kilogram patient. Infusion rates were increased when pain relief was deemed insufficient. Blood pressures were monitored, and liver function studies were conducted daily. Pain scores over the 12-week monitoring period were significantly lower than those in patients receiving placebo (p < 0.001); however, the significance was not present between the groups at week 12 (p = 0.07). Patients receiving the drug experienced more psychotomimetic side effects than controls (93 percent versus 17 percent, p < 0.001). Ketamine treatment did not cause functional improvement in either group. The authors suggested that a four-day treatment with low-dose ketamine is safe, with psychotomimetic side effects acceptable to most patients. Schwartzman (2009) conducted a double-blind, randomized placebo-controlled trial with 21 participants diagnosed with refractory complex regional pain syndrome. Nine participants were placed in the ketamine group and 10 in the placebo group. All participants were subjected to daily four-hour infusions with either ketamine or normal saline according to their respective group for 10 days (five days on, two days off, five days on). The maximum ketamine rate was 0.35 mg/kg/hour, not to exceed 25 mg/hour over a four-hour period; this was a sub-anesthetic dose of ketamine. All participants were monitored at two weeks, and then monthly for a period of three months. After treatment, the ketamine group showed a 21.4 percent reduction in pain to 6.01 ± 0.6 (p < 0.01), with both a sensory and affective component demonstrated of a decrease in pain that lasted for the threemonth follow-up period. The placebo group demonstrated a nonsignificant 3.1 percent reduction to 6.98 ± 0.5 (p > 0.05), with no demonstrable treatment effects. There was no change in participant activity in either the pre- or post-treatment phase. Side effects were described as nausea, headache, tiredness, or dysphoria in four out of nine patients in the ketamine group and in two out of 10 patients in the placebo group. The authors also noted two points in relation to the addition of midazolam and clonidine with the dose of ketamine: the apparent lack of psychotomimetic side effects and that, in their experience, only a five-day course of intravenous ketamine at anesthetic doses with midazolam and clonidine would provide complete, lasting remission of complex regional pain syndrome symptoms for over five years. The trial was terminated prematurely as the researchers found that ketamine at doses of 50 mg/hour provided a much larger relief from pain that lasted for a longer period of time with the absence of complications. However, the authors noted the necessity for larger, randomized, placebo-controlled trials using higher doses of ketamine, with lengthier follow-up periods. Although the rationale for using ketamine seems appropriate, studies to date have not yet validated its benefit using objective outcome parameters with double-blind, randomized control trial (RCT) methodology. Questions of safety remain regarding the use of repeat infusion of ketamine for the return of complex regional pain syndrome pain. Additionally, multiple researchers have not been able to determine optimal treatment regimens for the use of ketamine in complex regional pain syndrome (Sunder, 2008; Azari, 2012). A summary of the main issues are as follows: 5

The optimal duration and dosing of ketamine infusions. The effectiveness of the setting for the infusions (inpatient versus outpatient). Using ketamine on its own or as an adjunct to regional anesthetic blocks. Ketamine usage in diagnosed refractory cases of complex regional pain syndrome. The use of ketamine prior to an established diagnosis of complex regional pain syndrome. Extended use of ketamine at anesthetic dosages ("ketamine coma") remains a controversial and unproven treatment for complex regional pain syndrome. Policy updates: In 2015, one additional systematic review (Cossins, 2013) and one meta-analysis, which was a Cochrane synthesis of available systematic reviews (O Connell, 2013), were identified for this policy. No economic analyses were identified. For treatment with intravenous ketamine, the available evidence is insufficient to support its effectiveness in patients with either type 1 or type 2 complex regional pain syndrome. The available evidence from RCTs is limited by small sample sizes, variable administration, and short duration. Reporting of adverse effects was notably lacking given that ketamine is toxic and a drug of abuse. While intravenous ketamine appears effective for short-term pain relief, both authors cite the need for independent confirmation in larger studies of longer duration that incorporates systematic evaluation of adverse effects. For treatment with intravenous regional block in general, there is strong evidence that guanethidine is not effective in treating complex regional pain syndrome and appears to be associated with the risk of significant adverse events. Results from studies of intravenous regional block using ketanserin, bretylium, atropine, or droperidol are inconclusive. Recent evidence-based guidelines further cite the lack of goodquality supportive outcome studies of intravenous regional block for treatment of complex regional pain syndrome to inform clinical practice (Harden, 2013). In 2017, we added one new systematic review of intravenous therapies for complex regional pain syndrome (Xu, 2016) and one update of a previously included systematic review (Hayes, 2017) to this policy. Hayes (2017) added a longitudinal study of intravenous ketamine in a pediatric cohort (Sheehy, 2015). Xu, et. al., found low-quality evidence suggesting intravenous ketamine and intravenous regional block with ketorolac (when used with lidocaine) or with lidocaine alone can provide short-term pain relief for persons with refractory complex regional pain syndrome. Anecdotal evidence suggests a potential risk for liver injury associated with prolonged use of ketamine or repeated administration in the short term. The evidence base continues to lack systematic data collection on long-term safety and effectiveness, and rigorous comparisons with alternative active treatments. However, because intravenous ketamine in low doses may offer temporary pain relief for persons with refractory complex regional pain syndrome, the policy was modified in 2018 to consider intravenous ketamine medically necessary for the treatment of refractory complex regional pain syndrome. We did not identify any additional guidelines/other or peer-reviewed literature in 2018. Policy ID changed from 00.02.01 to CCP.1011. 6

Summary of clinical evidence: Citation Hayes (2017; update of 2015) Intravenous ketamine for chronic nonmalignant pain Xu (2016) Intravenous therapies for complex regional pain syndrome (only ketamine and intravenous regional block reported) Cossins (2013) Content, Methods, Recommendations Key points: Systematic review of two RCTs and a longitudinal study (Sheehy, 2015) of a pediatric cohort. RCT results show short-term pain relief, but need long-term outcome data. Limited evidence suggests an increased risk of ketamine-induced liver injury if the infusion is prolonged and/or repeated within a short period. Longitudinal study of 63 consecutive children and adolescents (median age 15, interquartile range 12 17 years) over a 15-month period at doses of 0.1 0.3 mg/kg/h that lasted for 4 8 hours per day, up to a maximum of 16 total hours over a maximum of three consecutive days. Subanesthetic doses of intravenous ketamine on an outpatient basis appear safe, are not associated with psychotropic effects or hemodynamic perturbations, and reduce pain intensity (p < 0.001); also yielded greater pain reduction in patients with complex regional pain syndrome than in patients with other chronic pain syndromes (p = 0.029). Key points: Systematic review of 63 studies of mixed designs. Overall quality: low. Most studies preceded establishment of Budapest criteria. Evidence grading as follows: 2B+ one RCT with methodologic weaknesses demonstrating effectiveness. The benefits closely balanced with risk and burdens. 2C+ Effectiveness only demonstrated in observational studies. Given no conclusive evidence of the effect, benefits closely balanced with risk and burdens. 2 B- one RCT with methodologic weaknesses, or large observational studies not indicating any superiority to controls. Given no positive clinical effect, risk and burdens outweigh the benefit. 2 A- RCT of a good quality demonstrating no clinical effect. Given no positive clinical effect, risk and burdens outweigh the benefit. Recommended treatments: Intravenous ketamine for selected patients with refractory complex regional pain syndrome (2B+/2C+). IVRB with ketorolac (when used with lidocaine) for short-term pain reduction (2B+/2C+). IVRB lidocaine at 5 mg/kg/h for thermal pain (2B+/2C+). Inconclusive evidence: intravenous regional block with clonidine, phenoxybenzamine, or labetalol (2C+). Not recommended: intravenous regional block with guanethidine, reserpine, or droperidol (2A-/2B-). Key points: Treatment of complex regional pain syndrome in Systematic review of two RCTs for intravenous ketamine, two RCTs of intravenous regional block with methylprednisolone, parecoxib, or ketorolac. 7

Citation Content, Methods, Recommendations adults Quality of evidence: low to moderate for low-dose intravenous ketamine infusion in long-standing complex regional pain syndrome; low-to-high for intravenous regional block studies; studies were small and of short duration. Intravenous infusion of low-dose ketamine (4.5 days of continuous treatment or 10 consecutive working days of outpatient treatment) significantly reduced pain, which reverted back to normal more slowly than the short ketamine half-life would have demanded. Systematic reporting of adverse effects is lacking; anecdotal evidence of liver failure with prolonged or repeated treatment has been reported. Intravenous regional block with 5 mg of parecoxib, 1 mg/kg lignocaine, and 30 mg clonidine in 10 ml normal saline, plus systemic normal saline decreased pain more than either intravenous parecoxib (20 mg) with intravenous regional lidocaine and clonidine, or a control group in long-standing complex regional pain syndrome (one high-quality RCT). Intravenous regional block of 40 mg methylprednisolone in 10 ml of 2% lidocaine, given as one block per week for three weeks were no more effective than saline blocks in early complex regional pain syndrome (one low-quality RCT). Intravenous regional block lignocaine (50 ml 0.5%), either alone or together with ketorolac one week apart in random sequence, was not effective in reducing pain versus lignocaine injection (one high-quality RCT). Overall, limited evidence of effectiveness of intravenous ketamine or intravenous regional block in persons with complex regional pain syndrome. O Connell (2013) Key points: Cochrane review Interventions for treating pain and disability in adults with complex regional pain syndrome Meta-analysis of two RCTs of intravenous ketamine. Trials were small, short-duration with high risk of bias. Low-quality evidence that intravenous ketamine may be effective for pain versus placebo; effects not sustained beyond four to 11 weeks post-treatment. Meta-analysis of three systematic reviews of intravenous regional block. Trials were small with high risk of bias. Moderate-quality evidence that intravenous regional block with guanethidine is not effective in complex regional pain syndrome and appears to be associated with the risk of significant adverse events. Very low-quality evidence that intravenous regional block ketanserin and intravenous regional block bretylium may be effective. Very low-quality evidence that intravenous regional block atropine and intravenous regional block droperidol are not effective. Results are inconclusive. References Professional society guidelines/other: Harden RN, Oaklander AL, Burton AW, et al. Complex regional pain syndrome: practical diagnostic and treatment guidelines, 4th edition. Pain Med. 2013 Feb; 14(2): 180 229. 8

Perez RS, Zollinger PE, Dijkstra PU, et al. CRPS I task force. Evidence based guidelines for complex regional pain syndrome type 1. BMC Neurol. March 2010; 31 (10): 20. BMC website. http://www.biomedcentral.com/1471-2377/10/20. Accessed June 30, 2017. The International Association for the Study of Pain (IASP). Classification of chronic pain. Original 1986. Revised 2011. IASP website. Available at: http://www.iasppain.org/publicationsnews/content.aspx?itemnumber=1673. Accessed June 30, 2017. Peer-reviewed references: Azari P, Lindsay DR, Briones D., et al. Efficacy and safety of ketamine in patients with complex regional pain syndrome: a systematic review. CNS Drugs. 2012 Mar 1; 26(3): 215 228. Bruehl S. An update on the pathophysiology of complex regional pain syndrome. Anesthesiology. 2010 Sep; 113(3): 713 725. Cheng J, Ji RR. Intracellular signaling in primary sensory neurons and persistent pain. Neurochem Res. 2008 October; 33(10): 1970 1978. Cossins L, Okell RW, Cameron H, et al. Treatment of complex regional pain syndrome in adults: a systematic review of randomized controlled trials published from June 2000 to February 2012. Eur J Pain. 2013 Feb; 17(2): 158 173. Deer TR, Prager J, Levy R, et al. Polyanalgesic Consensus Conference 2012: recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel. Neuromodulation. 2012 Sep Oct; 15(5): 436 464; discussion 464-6. Epub 2012 Jul 2. Drugs@FDA: FDA Approved Drug Products searched using the term ketamine. FDA website. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed June 30, 2017. Harden RN. Complex regional pain syndrome. Br J Anaesth. 2001; 87: 99 106. Hayes, Inc. Hayes Medical Technology Report. Intravenous ketamine for chronic nonmalignant pain. Lansdale, Pa. Hayes, Inc.; March 24, 2017. Henson P, Bruehl S. Complex regional pain syndrome: state of the art update. Curr Treat Options Cardiovasc Med. 2010: 12(2): 156 167. Hocking G, Cousins MJ. Ketamine in chronic pain management: an evidence-based review. Anesth Analg. 2003 Dec 9; 7(6): 1730 1739. 9

National Institute of Neurological Disorders and Stroke (NINDS). Complex regional pain syndrome fact sheet. Last updated January 2017. NINDS website. https://www.ninds.nih.gov/disorders/patient-caregiver- Education/Fact-Sheets/Complex-Regional-Pain-Syndrome-Fact-Sheet. Accessed June 30, 2017. Niehof SP, Beerthuizen A, Huygen FJ, Zijlstra FJ. Using skin surface temperature to differentiate between complex regional pain syndrome type 1 patients after a fracture and control patients with various complaints after a fracture. Anesth Analg. 2008; 106(1): 270 277. Oaklander A, Rissmiller J, Gelman L, et al. Evidence of focal small-fiber axonal degeneration in complex regional pain syndrome-i (reflex sympathetic dystrophy). Pain. 2006 Feb; 120: 235 243. O'Connell NE, Wand BM, Gibson W, et al. Local anaesthetic sympathetic blockade for complex regional pain syndrome. Cochrane Database Syst Rev. 2016; 7: Cd004598. O'Connell NE, Wand BM, McAuley J, Marston L, Moseley GL. Interventions for treating pain and disability in adults with complex regional pain syndrome. Cochrane Database Syst Rev. 2013; 4: Cd009416. Perez RS, Zollinger PE, Dijkstra PU, et al. CRPS I task force. Evidence based guidelines for complex regional pain syndrome type 1. BMC Neurol. March 2010. 31; 10: 20. Rowbotham MC. Pharmacologic management of complex regional pain syndrome. Clin J Pain. 2006 Jun; 22(5): 425 429. Schürmann M, Zaspel J, Löhr P, et al. Imaging in early posttraumatic complex regional pain syndrome: a comparison of diagnostic methods. Clin J Pain. 2007; 23(5): 449 457. Schwartzman R. New treatments for reflex sympathetic dystrophy. N Engl J Med. 2000; 343: 654 656. Schwartzman R, Alexander G, Grothusen J, et al. Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain. 2009; 147: 107 115. Sheehy KA, Muller EA, Lippold C, et al. Subanesthetic ketamine infusions for the treatment of children and adolescents with chronic pain: a longitudinal study. BMC Pediatr. 2015; 15: 198. Sigtermans MJ, van Hilten JJ, Bauer MC, et al. Ketamine produces effective and long-term pain relief in patients with complex regional pain syndrome type 1. Pain. 2009; 145(3): 304 311. Sunder RA, Toshniwal G, Dureja G. Ketamine as an adjuvant in sympathetic blocks for management of central sensitization following peripheral nerve injury. J Brachial Plex Peripher Nerve Inj. Oct 25, 2008; 3: 22. Xu J, Yang J, Lin P, Rosenquist E, Cheng J. Intravenous therapies for complex regional pain syndrome: a systematic review. Anesth Analg. 2016; 122(3): 843 856. 10

CMS National Coverage Determinations (NCDs): No NCDs identified as of the writing of this policy. Local Coverage Determinations (LCDs): No LCDs identified as of the writing of this policy. Commonly submitted codes Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill accordingly. CPT Code Description Comments 64505 Injection, anesthetic agent; sphenopalatine ganglion 64510 Injection, anesthetic agent; stellate ganglion (cervical sympathetic) 64508 Injection, anesthetic agent; carotid sinus (separate procedure) 64520 Injection, anesthetic agent; lumbar or thoracic (paravertebral sympathetic) 64517 Injection, anesthetic agent; superior hypogastric plexus 64530 Injection, anesthetic agent; celiac plexus, with or without radiologic monitoring ICD-10 Code Description Comments G56.40 Causalgia of unspecified upper limb G56.41 Causalgia of right upper limb G56.42 Causalgia of left upper limb G57.70 Causalgia of unspecified lower limb G57.71 Causalgia of the right lower limb G57.72 Causalgia of the left lower limb G90.5 Complex regional pain syndrome I, (CRPS I) G90.50 Complex regional pain syndrome I, unspecified G90.511 Complex regional pain syndrome I of right upper limb G90.512 Complex regional pain syndrome I of left upper limb G90.513 Complex regional pain syndrome I of upper limb bilateral G90.519 Complex regional pain syndrome I of unspecified limb G90.521 Complex regional pain syndrome I of right lower limb G90.522 Complex regional pain syndrome I of left lower limb G90.523 Complex regional pain syndrome I of lower limb bilateral G90.529 Complex regional pain syndrome I of unspecified lower limb G90.59 Complex regional pain syndrome I of other specified site G90.8 Other disorders of autonomic nervous system 11

ICD-10 Code Description Comments M89.00 Algoneurodystrophy, unspecified site M89.011 Algoneurodystrophy, right shoulder M89.012 Algoneurodystrophy, left shoulder M89.019 Algoneurodystrophy, unspecified shoulder M89.021 Algoneurodystrophy, right upper arm M89.022 Algoneurodystrophy, left upper arm M89.029 Algoneurodystrophy, unspecified upper arm M89.031 Algoneurodystrophy, right forearm M89.032 Algoneurodystrophy, left forearm M89.039 Algoneurodystrophy, unspecified forearm M89.041 Algoneurodystrophy, right hand M89.042 Algoneurodystrophy, left hand M89.049 Algoneurodystrophy, unspecified hand M89.051 Algoneurodystrophy, right thigh M89.052 Algoneurodystrophy, left thigh M89.059 Algoneurodystrophy, unspecified thigh M89.061 Algoneurodystrophy, right lower leg M89.062 Algoneurodystrophy, left lower leg M89.069 Algoneurodystrophy, unspecified lower leg M89.071 Algoneurodystrophy, right ankle and foot HCPCS Level II Code J3490 Description Ketamine, IV Comments 12