Clinical Policy Title: Continuous intrathecal infusion of drugs

Clinical Policy Title: Continuous intrathecal infusion of drugs Clinical Policy Number: 03.02.05 Effective Date: February 1, 2018 Initial Review Date: November 16, 2017 Most Recent Review Date: January 11, 2018 Next Review Date: January 2019 Policy contains: Chronic pain. Pain control. Continuous intrathecal infusion. Related policies: CP# 03.03.04 CP# 18.04.02 CP# 03.03.01 CP# 03.03.02 CP# 03.02.02 CP# 03.02.07 CP# 00.02.01 CP# 03.03.05 CP# 10.02.06 Spine pain epidural steroid injection Hierarchy of chronic pain management Spinal cord stimulators for chronic pain Intrathecal opioid therapy for chronic pain Radiofrequency ablation treatment for spine pain Spine pain - facet joint injections Parenteral treatment for complex regional pain syndrome Spine pain-trigger point injections Ambulatory continuous peripheral nerve block 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 evidence-based 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 continuous intrathecal infusion of drugs for chronic, perioperative, and malignant pain control to be clinically proven and, therefore, medically necessary when the following criteria are met (Mariano, 2017; Health Quality Ontario, 2016; American Society of Regional Anesthesia and Pain Medicine [ASRAPM], 2010; Prager, 2014; Moore, 2013; Khan, 2013; Ilfeld, 2010; Paul, 2010; Wegener, 2011): 1

Continuous intrathecal infusion of drugs for pain control is used in a multimodal approach to pain control. Continuous intrathecal infusion of drugs is desirable (e.g., lower opioid dosing requirements in patients taking methadone or buprenorphine [Appendix A], morbidly obese patients). Limitations: 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/. Pain control regimens should be tailored to the needs of the individual patient, taking into account the patient's age, medical and physical condition, level of fear or anxiety, personal preferences, type of surgical procedure, and response. Screening criteria to identify appropriate candidates for timely intrathecal opioid therapy include (Deer, 2010): Chronic pain results in significant interference with activities of daily living, including ability to work, and overall quality of life. Chronic pain is refractory to conservative medical or surgical therapy. Pre-existing medical comorbidities are well controlled, and appropriate disease-specific guidelines are followed before and after implantation. Patients are not at high risk for infection or do not present with an active infection. Patients can comply with the medication refill schedule. Patients present without any severe or uncontrolled psychological conditions. Patients for whom oral opioid therapy is not contraindicated (e.g., a patient who has difficulties managing their medications or an individual with certain comorbid conditions in which oral opioids have the potential for severe adverse effects). Alternative covered services: Routine patient evaluation and management by a network health care provider. Background The worldwide crisis in the prescription of opioids has led investigators to explore novel approaches to pain control and to explore new routes of administering analgesia that minimize the potential for abuse while successfully achieving the goals of relief of suffering, early mobilization following surgery, and durable patient satisfaction. 2

Neuraxial anesthetics (i.e., spinals and epidurals) are effective regional approaches for chronic, perioperative, and malignant pain control, and may provide superior analgesia while avoiding some of the side effects and complications of systemic opioid administration (Mariano, 2017). Devices that allow self-administered infusion of analgesics via lightweight elastomeric pumps first appeared around the turn of the millennium. The U.S. Food and Drug Administration (FDA, 2017a) has approved several implantable programmable and nonprogrammable infusion pumps as Class III devices for continuous intrathecal administration of opioid drug therapy. Preservative-free morphine sulfate is the only opioid granted approved indication by the FDA for intrathecal delivery to treat chronic pain at a maximum approved concentration of 25 mg/ml and only as monotherapy; intrathecal morphine used in combination with other drugs is considered an off-label use (FDA 2017b). The introduction of these devices has further advanced an already-existing trend of avoiding systemic opioids in the management of chronic, perioperative, and malignant pain, and of minimizing the substantial risk of abuse and complication associated with the use of narcotics. Today these small, portable pumps are credited with a major role in advancing a preference for multimodal analgesic techniques for a variety of pain-related diagnoses and surgical procedures. 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 (CMS). We conducted searches on September 28, 2017. Search terms were: pain control, analgesia, and narcotics. 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 3

A consensus on best practices in intrathecal infusion therapy for pain (Prager, 2014) noted this technology is a valuable adjunct appropriate for use in selected patients with severe chronic or end-oflife pain. While device-related complications (mostly with catheters) and surgical-site infections can occur, the main therapy-related safety issues associated with intrathecal drug delivery arise primarily with inadequate patient monitoring (e.g., respiratory depression), inflammatory mass (e.g., high doses and concentrations of opioids), wound healing, dosing errors (e.g., medication concentration and pump programming), pump fills or refills (e.g., pocket fills), and interaction with concomitant systemic medications (e.g., opioids and benzodiazepines). Many of the reported adverse events and complications of intrathecal drug delivery can be prevented by adequate clinician training, implementation of best practices, and experience to assure safety and efficacy of the modality. A contemporary health technology assessment from Health Quality Ontario (2016) evaluated the comparative effectiveness, harms, and cost-effectiveness of intrathecal drug delivery of opioids for chronic pain compared to oral administration or rehabilitation. The authors concluded that while intrathecal delivery resulted in some pain relief, it did not translate into improved quality of life or patient-reported well-being, and that there is insufficient current evidence to proclaim superiority or cost-effectiveness of intrathecal drug delivery systems for managing chronic refractory nonmalignant pain. Professional society-based guidelines (American Society of Regional Anesthesia and Pain Medicine [ASRAPM], 2010) acknowledge that the evidence for intrathecal drug delivery of opioids for nonmalignant pain is less robust than the evidence for cancer pain. The ASRAPM findings are consistent with a recent systematic review (Duarte, 2017) inclusive of seven unique studies that considered intrathecal drug delivery as an option in a number of pain management situations, including those for chronic non-cancer pain, cancer pain, and spasticity. With the exception of one study, the studies found intrathecal drug delivery to be either cost-saving or cost-effective compared to conventional medical pain management; however, the medical evidence on the effectiveness of intrathecal drug delivery in non-cancer pain was limited. Traditional postoperative pain management strategies include opioid analgesics administered orally or via epidural catheter, patient-controlled anesthesia, or intramuscular injection. A review of the literature (Ilfeld, 2010; Kardash, 2007; Paul, 2010; Wegener, 2011) supports its use over traditional intramuscular dosing in postoperative management of pain (i.e., total knee arthroplasty). Patientcontrolled anesthesia has been shown to provide more effective analgesia than intramuscular dosing, and patient-controlled anesthesia administration is preferred over intramuscular dosing by both patients and nurses. Continuous infusion of bupivacaine via pain pump is also an effective modality for reducing postoperative pain and decreasing postoperative consumption of opioid analgesics. A study (n = 30) of intravenous-based versus epidural-based techniques for anesthesia and postoperative analgesia in elderly patients undergoing laparoscopic cholecystectomy expounded on postoperative pain, adverse events, and patient satisfaction (Nishikawa, 2007). The quality of postoperative analgesia was judged similar in the two groups. The incidences of intraoperative 4

hypotension and bradycardia and postoperative hypotension were significantly lower in the intravenous-based group than in the epidural-based group (P < 0.05). A significantly higher level of patient satisfaction was found in the intravenous-based group compared with that in the epidural-based group (P < 0.05). The major contributor to dissatisfaction in the epidural-based group was anxiety or discomfort associated with the epidural procedures. The authors concluded that modified neuroleptic anesthesia with pentazocine and postoperative intravenous-based analgesia with buprenorphine were superior to epidural-based techniques, in terms of hemodynamic stability and patient satisfaction, in elderly patients undergoing laparoscopic cholecystectomy. A narrative review (Moore, 2013) highlights regional anesthesia techniques with focus on outpatient orthopedics. The authors discuss "multimodalities" addressing postoperative nausea and vomiting prophylaxis, perioperative analgesia (including perineural analgesia), and sedation-hypnosis, which are all central to timely recovery using now-available suitable recovery criteria. A narrative review (Mirza, 2011) discusses the utility of ultrasound-guided regional anesthesia to increase the comfort level for many anesthesiologists performing blocks and other advances, including better monitoring and expedited same-day discharge. As part of an Enhanced Recovery After Surgery protocol, epidural analgesia may facilitate early return of bowel function (Khan, 2013) and improve pain control (Turunen, 2009). Rawal speaking at the 2010 Gaston Labat Lecture noted that, "The challenge of adequate postoperative analgesia has come to the fore as previously inpatient surgical procedures of increasing number and complexity are becoming ambulatory. In recent years, availability of improved elastomeric and other lightweight pump devices, the general trend of avoiding strong opioids and the preference for nonopioid analgesic techniques has led to increasing use of this technique after a variety of ambulatory surgical procedures. Current evidence suggests that both are effective, although comparative studies are lacking." A narrative review (Ilfield, 2017) noted there are an increasing number of disposable infusion pumps with functionality to adjust basal rates, bolus volume, and lockout times. The authors noted that these devices suggest a promising era of communicating with and controlling pumps remotely via the Internet. The authors cited large prospective studies demonstrating relatively few major complications during ambulatory continuous peripheral nerve block. The authors also noted adductor canal catheters induced less quadriceps femoris weakness and improved mobilization and ambulation compared to femoral infusion, and the incidence and severity of chronic, persistent postsurgical pain was diminished with short-term postoperative continuous peripheral nerve block. A narrative review (Dadure 2013) considers regional anesthesia in the child in terms of morphine consumption and quality of postoperative analgesia, and warns that the use of single-shot regional anesthesia seems to induce an exacerbation of pain upon returning home. For management of prolonged postoperative pain from major orthopedic surgery, continuous peripheral nerve blocks are 5

recommended as the best options. The quality of analgesia obtained from different pediatric studies is excellent with a low incidence of adverse events. The authors opine that the use of elastomeric disposable pumps for infusion allows early and easy ambulation and greater satisfaction to parents and children. A small treatment-only study (n = 16) of iliac crest bone graft donors was performed by on-site infiltration of local anesthetics with a disposable elastomeric pump versus parenteral rescue with morphine (Ouaki, 2009). Single injections or continuous infusions of local anesthetics proved their efficacy in adults, but the result was not repeatable in children. Patients with obstructive sleep apnea are at increased risk of respiratory depression when opioids and sedatives are administered. For morbidly obese surgical patients, Mariano (2017) suggests regional analgesic techniques when possible and appropriate to minimize the use of opioids and sedatives, particularly in those with a history of obstructive sleep apnea. For morbidly obese patients with obstructive sleep apnea, it may be prudent to use local anesthetic (e.g., bupivacaine 0.125 percent) without opioid for continuous epidural analgesia, although this decision depends on the individual patient, surgery, and epidural coverage. The opioid-dependent patient will require an individualized plan of regional analgesia for peri- and postoperative pain control (Mariano, 2017). Opioid requirements for these patients can be higher than anticipated by body weight and unpredictable because of opioid tolerance. When possible, a plan for postoperative pain management should be made in advance of surgery, including possible consultation with a pain management specialist. Patients presenting for surgery who use methadone for drug dependency or chronic pain should continue the usual dose of methadone through the perioperative period. The usual dose of methadone may be administered orally, or, if necessary, half the usual dose can be given intravenously (Mariano, 2017). Postoperative breakthrough analgesic requirements may be met with additional opioids as needed via the oral route, intravenous nurse-administered bolus, or patient-controlled anesthesia. The patient taking buprenorphine may present a challenge for postoperative pain control (Mariano, 2017). Buprenorphine is a semisynthetic opioid that acts as a partial mu-opioid receptor agonist (1,000 times greater affinity compared with morphine) and antagonist at the kappa-opioid receptor. It is available in two preparations: one contains buprenorphine alone; the other buprenorphine with naloxone, an opioid antagonist. These drugs are increasingly used to treat opioid addiction and chronic pain. Because of their high affinity for opioid receptors, buprenorphine may reduce the effectiveness of other opioids. Mariano (2017), writing in UpToDate, offers the following guidance: "For patients having extremity surgery expected to produce moderate to severe postoperative pain, we regularly perform peripheral nerve blocks to provide 6

several hours of postoperative pain relief (e.g., brachial plexus block for upper extremity surgery) or insert a perineural catheter to provide two to three days of pain relief with a continuous local anesthetic infusion. For a patient having minimally invasive abdominal (e.g., laparoscopic) surgery or abdominal wall surgery (e.g., inguinal herniorrhaphy) under general anesthesia, we employ transversus abdominis plane blocks either preoperatively or prior to emergence, in addition to administering systemic opioid and nonopioid analgesics. For the patient having total knee replacement, we insert a catheter for continuous peripheral nerve block and administer a perineural local anesthetic infusion, in addition to systemic opioid and nonopioid pain medications in the perioperative period. We prefer to perform spinal anesthesia for the surgery, or general anesthesia in cases when spinal anesthesia is contraindicated or refused by the patient." Summary of clinical evidence: Citation Duarte (2017) Intrathecal drug delivery systems for the management of chronic noncancer pain: a systematic review of economic evaluations. Wegener (2011) Value of single-injection or continuous sciatic nerve block in addition to a continuous femoral nerve block in patients undergoing total knee arthroplasty: a prospective, randomized, controlled trial Health Quality Ontario (2016) Content, Methods, Recommendations Intrathecal drug delivery systems are one of a limited number of management options for chronic non-cancer pain, cancer pain, and spasticity. Concerns over their effectiveness and high initial costs led England to decommission the use of these treatments for patients with chronic non-cancer pain. A systematic review inclusive of 4,464 unique studies, of which seven met the inclusion criteria, found, with the exception of one study, the studies found intrathecal drug delivery to be either cost-saving or cost-effective compared to conventional medical management. There is limited evidence on the effectiveness of intrathecal infusion therapy in noncancer pain; however, the available economic evidence controverts arguments to refute the treatment on economic grounds. Peripheral nerve blocks may be used to provide surgical anesthesia. They can also be used for postoperative pain relief by injecting a long-acting local anesthetic when performing the block or by inserting a catheter to allow continuous infusion of medication. Peripheral nerve blocks are typically performed using ultrasound guidance to locate the nerve or by using a nerve stimulator, or both. For perineural infusions used for postoperative pain relief, low doses of a long-acting local anesthetic (e.g., 0.2% ropivacaine) at rates of 4 to 10 ml/hour are commonly used. 7

Citation Intrathecal drug delivery systems for non-cancer pain Turunen (2009) Epidural analgesia diminished pain but did not otherwise improve enhanced recovery after laparoscopic sigmoidectomy: a prospective randomized study Paul (2010) Femoral nerve block improves analgesia outcomes after total knee arthroplasty: a metaanalysis of randomized controlled trials Ouaki (2009) Continuous infusion of ropivacaïne: an optimal postoperative analgesia regimen for iliac crest bone graft in children Nishikawa (2007) Content, Methods, Recommendations Health technology assessment included four systematic reviews, one prospective cohort study, one retrospective study for evidence of effectiveness and harms, and four economic evaluations of intrathecal drug delivery systems, all versus standard care. Overall quality: very low. Patients had lower pain scores with intrathecal drug delivery systems but did not seem to feel pain less or to be happier with treatment compared with patients who received only oral opioids or a rehabilitation program. No studies compared problems with intrathecal drug delivery systems and routine care. No reliable estimates of cost-effectiveness were found. From the perspective of the Ontario Ministry of Health and Long-Term Care, the annual budget impact of publicly funding intrathecal drug delivery for this population would be between $1.5 and $5.0 million per year; much uncertainty in the calculations. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used as part of a multimodal approach to analgesia; and may be part of a regimen as adjuncts to other modalities, such as regional analgesia. A systematic review comparing the use of acetaminophen alone or in combination with NSAIDs for postoperative pain showed that the combination was more effective than NSAIDs alone in 64 percent of the studies. As part of an Enhanced Recovery After Surgery protocol, epidural analgesia may facilitate early return of bowel function and improve pain control. Peripheral nerve blocks may be used to provide surgical anesthesia. They can also be used for postoperative pain relief by injecting a long-acting local anesthetic when performing the block or by inserting a catheter to allow continuous infusion of medication. Peripheral nerve blocks are typically performed using ultrasound guidance to locate the nerve or by using a nerve stimulator, or both. For perineural infusions used for postoperative pain relief, low doses of a long-acting local anesthetic (e.g., 0.2% ropivacaine) at rates of 4 to 10 ml/hour are commonly used. A small treatment-only study (n = 16) of iliac crest bone graft donors was performed by on-site infiltration of local anesthetics with a disposable elastomeric pump versus parenteral rescue with morphine. Single injections or continuous infusions of local anesthetics proved their efficacy in adults, but the result was not repeatable in children. A comparison of intravenous-based and epidural-based techniques for anesthesia and postoperative analgesia in elderly patients undergoing A study (n = 30) of intravenous-based and epidural-based techniques for anesthesia and postoperative analgesia in elderly patients undergoing laparoscopic cholecystectomy elucidated postoperative pain, adverse events, and patient satisfaction. The quality of postoperative analgesia was judged similar in the two groups. 8

Citation laparoscopic cholecystectomy Moore (2013) Regional anesthesia and ambulatory surgery Mirza (2011) Ultrasound-guided regional anesthesia for procedures of the upper extremity Mei (2011) Bilateral ultrasound-guided transversus abdominis plane block combined with ilioinguinal-iliohypogastric nerve block for cesarean delivery anesthesia Martinez (2017) Non-opioid analgesics in adults after major surgery: systematic review with network meta-analysis of randomized trials Mariano (2017) Management of acute perioperative pain Content, Methods, Recommendations The incidences of intraoperative hypotension and bradycardia and postoperative hypotension were significantly lower in the intravenous-based group than in the epidural-based group (P 0.05). A significantly higher level of patient satisfaction was found in the intravenous-based group compared with that in the epidural-based group (P 0.05). The major contributor to dissatisfaction in the epidural-based group was anxiety or discomfort associated with the epidural procedures. The authors concluded that modified neuroleptic anesthesia with pentazocine and postoperative intravenous-based analgesia with buprenorphine were superior to epidural-based techniques, in terms of hemodynamic stability and patient satisfaction, in elderly patients undergoing laparoscopic cholecystectomy. A narrative review highlights regional anesthesia techniques with focus on outpatient orthopedics. The authors discuss 'multimodalities,' addressing postoperative nausea and vomiting prophylaxis, perioperative analgesia (including perineural analgesia), and sedationhypnosis, which are all central to timely recovery using now-available suitable recovery criteria. A narrative review discusses the utility of ultrasound-guided regional anesthesia to increase the comfort level for many anesthesiologists performing blocks and other advances, including better monitoring and expedited same-day discharge. Mei offers the following guidance: "Although not recommended for first-line use, in rare circumstances, peripheral nerve blocks (e.g., transverse abdominis plane blocks, together with ilioinguinal block), have been used for anesthesia for cesarean delivery. Supplementation with sedatives, opioids, and local anesthetic infiltration by the surgeon may be required with these techniques." NSAIDs are often used as part of a multimodal approach to analgesia, and may be part of a regimen as adjuncts to other modalities, such as regional analgesia. The addition of acetaminophen to NSAIDs can improve pain control. Mariano, writing in UpToDate, offers the following guidance: "For patients having extremity surgery expected to produce moderate to severe postoperative pain, we regularly perform peripheral nerve blocks to provide several hours of postoperative pain relief (e.g., brachial plexus block for upper extremity surgery) or insert a perineural catheter to provide two to three days of pain relief with a continuous local anesthetic infusion. 9

Citation Content, Methods, Recommendations For a patient having minimally invasive abdominal (e.g., laparoscopic) surgery or abdominal wall surgery (e.g., inguinal herniorrhaphy) under general anesthesia, we employ transversus abdominis plane blocks either preoperatively or prior to emergence, in addition to administering systemic opioid and nonopioid analgesics. Khan (2013) Effect of epidural analgesia on bowel function in laparoscopic colorectal surgery: a systematic review and meta-analysis Ilfeld (2010) A multicenter, randomized, triple-masked, placebocontrolled trial of the effect of ambulatory continuous femoral nerve blocks on discharge-readiness following total knee arthroplasty in patients on general orthopedic wards Ilfeld (2017) Continuous peripheral nerve blocks: an update of the published evidence and comparison with novel, alternative analgesic modalities Prager (2014) For the patient having total knee replacement, we insert a catheter for continuous peripheral nerve block and administer a perineural local anesthetic infusion, in addition to systemic opioid and nonopioid pain medications in the perioperative period. We prefer to perform spinal anesthesia for the surgery, or general anesthesia in cases when spinal anesthesia is contraindicated or refused by the patient. NSAIDs are often used as part of a multimodal approach to analgesia; and may be part of a regimen as adjuncts to other modalities, such as regional analgesia. The addition of acetaminophen to NSAIDs can improve pain control. A systematic review comparing the use of acetaminophen alone or in combination with NSAIDs for postoperative pain showed that the combination was more effective than NSAIDs alone in 64 percent of the studies. As part of an Enhanced Recovery After Surgery protocol, epidural analgesia may facilitate early return of bowel function and improve pain control. Peripheral nerve blocks may be used to provide surgical anesthesia. They can also be used for postoperative pain relief by injecting a long-acting local anesthetic when performing the block or by inserting a catheter to allow continuous infusion of medication. Peripheral nerve blocks are typically performed using ultrasound guidance to locate the nerve or by using a nerve stimulator, or both. For perineural infusions used for postoperative pain relief, low doses of a long-acting local anesthetic (e.g., 0.2% ropivacaine) at rates of 4 to 10 ml/hour are commonly used. A narrative review noted there are an increasing number of disposable infusion pumps with functionality to adjust basal rates, bolus volume, and lockout times. The authors noted that these devices suggest a promising era of communicating with and controlling pumps remotely via the Internet. The authors cited large prospective studies demonstrating relatively few major complications during ambulatory continuous peripheral nerve block. The authors also noted adductor canal catheters induced less quadriceps femoris weakness and improved mobilization and ambulation compared to femoral infusion; and the incidence and severity of chronic, persistent postsurgical pain was diminished with short-term postoperative continuous peripheral nerve block. 10

Citation Best practices for intrathecal drug delivery for pain Deer (2010) Consensus guidelines for the selection and implantation of patients with noncancer pain for intrathecal drug delivery Fredrickson (2010) Postoperative analgesia for shoulder surgery: a critical appraisal and review of current techniques Fowler (2008) Content, Methods, Recommendations Consensus on best practices in three areas related to safe intrathecal therapy for pain: safety and monitoring, patient and device management, and patient selection and trialing. Intrathecal drug delivery is a valuable alternative drug delivery system for many patients with severe chronic or end-of-life pain. While device-related complications (mostly with catheters) and surgical-site infections can occur, the main therapy-related safety issues associated with intrathecal drug delivery arise primarily with inadequate patient monitoring (e.g., respiratory depression), inflammatory mass (e.g., high doses and concentrations of opioids), wound healing, dosing errors (e.g., medication concentration and pump programming), pump fills or refills (e.g., pocket fills), and interaction with concomitant systemic medications (e.g., opioids and benzodiazepines). Many of the reported adverse events and complications of intrathecal drug delivery can be prevented by adequate clinician training, implementation of best practices, and experience. In adopting the therapy, providers must inform patients of its risks and benefits. Providers and patients must partner to achieve both safety and effectiveness. Screening criteria to identify appropriate candidates for timely intrathecal opioid therapy include: Chronic pain results in significant interference with activities of daily living, including ability to work, and overall quality of life. Chronic pain is refractory to conservative medical or surgical therapy. Preexisting medical comorbidities are well controlled, and appropriate disease-specific guidelines are followed before and after implantation. Patients are not at high risk for infection or do not present with an active infection. Patients can comply with the medication refill schedule. Patients present without any severe or uncontrolled psychological conditions. Patients for whom oral opioid therapy is not contraindicated (e.g., a patient who has difficulties managing their medications or an individual with certain comorbid conditions in which oral opioids have the potential for severe adverse effects). Peripheral nerve blocks may be used to provide surgical anesthesia. They can also be used for postoperative pain relief by injecting a long-acting local anesthetic when performing the block or by inserting a catheter to allow continuous infusion of medication. Peripheral nerve blocks are typically performed using ultrasound guidance to locate the nerve or by using a nerve stimulator, or both. For perineural infusions used for postoperative pain relief, low doses of a long-acting local anesthetic (e.g., 0.2% ropivacaine) at rates of 4 to 10 ml/hour are commonly used. Epidural analgesia compared with peripheral nerve blockade after major Peripheral nerve blocks may be used to provide surgical anesthesia. 11

Citation knee surgery: a systematic review and meta-analysis of randomized trials Dadure (2013) Regional anesthesia for postoperative analgesia at home in children Coffman (2016) Transversus abdominis plane and ilioinguinal/iliohypogastric blocks for cesarean delivery in a patient with type II spinal muscular atrophy Chin (2010) Content, Methods, Recommendations They can also be used for postoperative pain relief by injecting a long-acting local anesthetic when performing the block or by inserting a catheter to allow continuous infusion of medication. Peripheral nerve blocks are typically performed using ultrasound guidance to locate the nerve or by using a nerve stimulator, or both. For perineural infusions used for postoperative pain relief, low doses of a long-acting local anesthetic (e.g., 0.2% ropivacaine) at rates of 4 to 10 ml/hour are commonly used. A narrative review considering regional anesthesia in the child in terms of morphine consumption and quality of postoperative analgesia; warns that the use of single-shot regional anesthesia seems to induce an exacerbation of pain upon returning home. For management of prolonged postoperative pain from major orthopedic surgery continuous peripheral nerve blocks are recommended as the best options. The quality of analgesia obtained from different pediatric studies is excellent with a low incidence of adverse events. The authors opine that the use of elastomeric disposable pumps for infusion allows early and easy ambulation and greater satisfaction to parents and children. Coffman offers the following guidance: "Although not recommended for first-line use, in rare circumstances, peripheral nerve blocks (e.g., transversus abdominis plane blocks together with ilioinguinal block) have been used for anesthesia for cesarean delivery. Supplementation with sedatives, opioids, and local anesthetic infiltration by the surgeon may be required with these techniques." Infraclavicular brachial plexus block for regional anesthesia of the lower arm Peripheral nerve blocks may be used to provide surgical anesthesia. They can also be used for postoperative pain relief by injecting a long-acting local anesthetic when performing the block or by inserting a catheter to allow continuous infusion of medication. Peripheral nerve blocks are typically performed using ultrasound guidance to locate the nerve or by using a nerve stimulator, or both. For perineural infusions used for postoperative pain relief, low doses of a long-acting local anesthetic (e.g., 0.2% ropivacaine) at rates of 4 to 10 ml/hour are commonly used. References Professional society guidelines/other: American Society of Anesthesiologists Task Force on Chronic Pain Management, American Society of Regional Anesthesia and Pain Medicine. (ASRAPM) Practice guidelines for chronic pain management: an updated report by the American Society of Anesthesiologists Task Force on Chronic Pain Management 12

and the American Society of Regional Anesthesia and Pain Medicine. Anesthesiology. 2010;112(4): 810 833. Health Quality Ontario. Intrathecal Drug Delivery Systems for Noncancer Pain: A Health Technology Assessment. Ont Health Technol Assess Ser. 2016;16(2): 1 77. U.S. Food and Drug Administration. FDA Pre-Market Approval Database. Available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm. Searched product code LKK on October 24, 2017.(a) U.S. Food and Drug Administration. Preservative-free duramorph (morphine sulfate injection, USP). Product label. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/018565s014lbl.pdf. Accessed October 24, 2017.(b) Rawal N. American Society of Regional Anesthesia and Pain Medicine 2010 Gaston Labat Lecture: Perineural catheter analgesia as a routine method after ambulatory surgery--effective but unrealistic. Reg Anesth Pain Med. 2012;37(1):72-8. Peer-reviewed references: Chin KJ, Singh M, Velayutham V, Chee V. Infraclavicular brachial plexus block for regional anaesthesia of the lower arm. Cochrane Database Syst Rev. 2010; :CD005487. Coffman JC, Fiorini K, Ristev G, et al. Transversus abdominis plane and ilioinguinal/iliohypogastric blocks for cesarean delivery in a patient with type II spinal muscular atrophy. Int J Obstet Anesth. 2016; 25:79. Dadure C, Macq C, Sola C, Raux O. Regional anesthesia for postoperative analgesia at home in children. Ann Fr Anesth Reanim. 2013;32(1):e17-20. Deer TR, Smith HS, Cousins M, et al. Consensus guidelines for the selection and implantation of patients with noncancer pain for intrathecal drug delivery. Pain Physician. 2010;13(3): E175 213. Duarte RV, Lambe T, Raphael JH, Eldabe S, Andronis L. Intrathecal drug delivery systems for the management of chronic non-cancer pain: a systematic review of economic evaluations. Pain Pract. 2017. doi: 10.1111/papr.12650. [Epub ahead of print] Fowler SJ, Symons J, Sabato S, Myles PS. Epidural analgesia compared with peripheral nerve blockade after major knee surgery: a systematic review and meta-analysis of randomized trials. Br J Anaesth. 2008; 100:154. 13

Fredrickson MJ, Krishnan S, Chen CY. Postoperative analgesia for shoulder surgery: a critical appraisal and review of current techniques. Anaesthesia. 2010; 65:608. Ilfeld BM. Continuous Peripheral Nerve Blocks: An Update of the Published Evidence and Comparison With Novel, Alternative Analgesic Modalities. Anesth Analg. 2017;124(1):308-335. Ilfeld BM, Mariano ER, Girard PJ, et al. A multicenter, randomized, triple-masked, placebo-controlled trial of the effect of ambulatory continuous femoral nerve blocks on discharge-readiness following total knee arthroplasty in patients on general orthopaedic wards. Pain. 2010;150:477. Khan SA, Khokhar HA, Nasr AR, et al. Effect of epidural analgesia on bowel function in laparoscopic colorectal surgery: a systematic review and meta-analysis. Surg Endosc. 2013; 27:2581. Mariano E. Management of acute perioperative pain. In: Crowley M, ed. UpToDate. Waltham, Mass.: UpToDate; 2017. www.uptodate.com. Accessed August 23, 2017. Martinez V, Beloeil H, Marret E, et al. Non-opioid analgesics in adults after major surgery: systematic review with network meta-analysis of randomized trials. Br J Anaesth. 2017; 118:22. Mei W, Jin C, Feng L, et al. Bilateral ultrasound-guided transversus abdominis plane block combined with ilioinguinal-iliohypogastric nerve block for cesarean delivery anesthesia. Anesth Analg. 2011; 113:134. Mirza F, Brown AR. Ultrasound-Guided Regional Anesthesia for Procedures of the Upper Extremity. Anesthesiology Research and Practice. 2011;2011:579824. Moore JG, Ross SM, Williams BA. Regional anesthesia and ambulatory surgery. Curr Opin Anaesthesiol. 2013;26(6):652-60. Nishikawa K, Kimura S, Shimodate Y, Igarashi M, Namiki A. A comparison of intravenous-based and epidural-based techniques for anesthesia and postoperative analgesia in elderly patients undergoing laparoscopic cholecystectomy. J Anesth. 2007;21(1):1-6. Ouaki J, Dadure C, Bringuier S, et al. Continuous infusion of ropivacaïne: an optimal postoperative analgesia regimen for iliac crest bone graft in children. Paediatr Anaesth. 2009;19(9):887-91. Paul JE, Arya A, Hurlburt L, et al. Femoral nerve block improves analgesia outcomes after total knee arthroplasty: a meta-analysis of randomized controlled trials. Anesthesiology. 2010; 113:1144. Prager J, Deer T, Levy R, et al. Best practices for intrathecal drug delivery for pain. Neuromodulation: Journal of the International Neuromodulation Society. 2014; 17(4): 354 372; discussion 372. 14

Turunen P, Carpelan-Holmström M, Kairaluoma P, et al. Epidural analgesia diminished pain but did not otherwise improve enhanced recovery after laparoscopic sigmoidectomy: a prospective randomized study. Surg Endosc. 2009; 23:31. Wegener JT, van Ooij B, van Dijk CN, et al. Value of single-injection or continuous sciatic nerve block in addition to a continuous femoral nerve block in patients undergoing total knee arthroplasty: a prospective, randomized, controlled trial. Reg Anesth Pain Med. 2011;36:481. 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 36563 Insertion of tunneled centrally inserted central venous access device with subcutaneous pump 36576 Repair of central venous access device, with subcutaneous port or pump, central or peripheral insertion site 36578 Replacement, catheter only, of central venous access device, with subcutaneous port or pump, central or peripheral insertion site 36583 Replacement, complete, of a tunneled centrally inserted central venous access device, with subcutaneous pump, through same venous access 36590 Removal of tunneled central venous access device, with subcutaneous port or pump, central or peripheral insertion 62350-62351 Implantation, revision or repositioning of tunneled intrathecal or epidural catheter, for long-hyphenterm medication administration via an external pump or implantable reservoir/infusion pump 62355 Removal of previously implanted intrathecal or epidural catheter 62360-62362 Implantation or replacement of device for intrathecal or epidural drug infusion 62365 Removal of subcutaneous reservoir or pump, previously implanted for intrathecal or epidural infusion 62367-62370 Electronic analysis of programmable, implanted pump for intrathecal or epidural drug infusion (includes evaluation of reservoir status, alarm status, drug prescription status) 15

CPT Code Description Comments 95990-95991 Refilling and maintenance of implantable pump or reservoir for drug delivery, spinal (intrathecal, epidural) or brain (intraventricular) 96365-96368 Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug) 96374-96376 Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); intravenous push 96522 Refilling and maintenance of implantable pump or reservoir for drug delivery, systemic (e.g., intravenous, intra-hyphenarterial) 96523 Irrigation of implanted venous access device for drug delivery systems 99601-99602 Home infusion/specialty drug administration ICD-10 Code Description Comments C18.0 - C21.8 Malignant neoplasm of colon, rectosigmoid junction, rectum, anus and anal canal C22.0 Liver cell carcinoma C78.7 Secondary malignant neoplasm of liver and intrahepatic bile duct G25.82 Stiff-hyphenman syndrome G35 Multiple sclerosis G80.0 - G80.9 Cerebral palsy G81.10 - G81.14 Spastic hemiplegia G82.20 - G82.22 Paraplegia G82.50 - G82.54 Quadriplegia G89.0 Central pain syndrome G89.21 - G89.29 Chronic pain, not elsewhere classified G89.3 Neoplasm related pain (acute) (chronic) G89.4 Chronic pain syndrome G95.11 - G95.19 Vascular myelopathies M62.40 - M62.49 M62.830 - M62.838 Spasm of muscle R25.0 - R25.9 Abnormal involuntary movements R26.0 - R26.1, R26.81 -R26.9 Abnormalities of gait and mobility S12.000+ - S12.001+ S12.100+ - S12.101+ S12.200+ - S12.201+ S12.300+ - S12.301+ S12.400+ - S12.401+ S12.500+ - S12.501+ S12.600+ - S12.601+ Fracture of vertebral column with spinal cord injury S14.101+ - S14.107+ S14.111+ - S14.117+ S14.121+ - S14.127+ S14.131+ - S14.137+ S14.151+ - S14.157+ S14.101+ - S14.139+ S14.151+ - S14.159+ Injury of nerves and spinal cord at neck level 16

HCPCS Level II Code A4220 A4221 A4223 A4224 A4225 A4300 A4301 A4305 A4306 C1772 C1891 C2626 C8957 E0782 E0783 E0785 E0786 J0475 J0476 J0735 J2270 J2278 J9000 - J9999 Q0081 Q0084 S0093 S5035 S5036 Description Refill kit for implantable infusion pump Supplies for maintenance of drug infusion catheter, per week (list drug separately) Infusion supplies not used with external infusion pump, per cassette or bag (list drugs separately) Supplies for maintenance of insulin infusion catheter, per week Supplies for external insulin infusion pump, syringe type cartridge, sterile, each Implantable access catheter, (e.g., venous, arterial, epidural subarachnoid, or peritoneal, etc) external access Implantable access total catheter, port/reservoir (e.g., venous, arterial, epidural, subarachnoid, peritoneal, etc.) Disposable drug delivery system, flow rate of 50 ml or greater per hour [not covered for intralesional administration of narcotic analgesics and anesthetics] Disposable drug delivery system, flow rate of less than 50 ml per hour [not covered for intralesional administration of narcotic analgesics and anesthetics] Infusion pump, programmable (implantable) Infusion pump, nonprogrammable, permanent (implantable) Infusion pump, nonprogrammable, temporary (implantable) Intravenous infusion for therapy/diagnosis; initiation of prolonged infusion (more than 8 hours), requiring use of portable or implantable pump Infusion pump, implantable, nonprogrammable (includes all components, e.g., pump, catheter, connectors, etc.) Infusion pump system, implantable, programmable (includes all components, e.g., pump, catheter, connectors, etc.) Implantable intraspinal (epidural/intrathecal) catheter used with implantable infusion pump, replacement Implantable programmable infusion pump, replacement (excludes implantable intraspinal catheter) Injection baclofen, 10 mg Injection, baclofen, 50 mcg for intrathecal trial Injection, clonidine HCl, 1 mg Injection, morphine sulfate, up to 10 mg Injection, ziconotide, 1 microgram Chemotherapy drugs Infusion therapy, using other than chemotherapeutic drugs, per visit Chemotherapy administration by infusion technique only, per visit Injection, morphine sulphate, 500 mg (loading dose for infusion pump) Home infusion therapy, routine service of infusion device (e.g., pump maintenance) Home infusion therapy, repair of infusion device (e.g., pump repair) Comments 17

HCPCS Level II Code S5497 S5502 S5517 S5518 S9325 S9326 S9327 S9328 S9329 S9330 S9331 S9363 Description Home infusion therapy, catheter care/maintenance, not otherwise classified; includes administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem Home infusion therapy, catheter care/maintenance, implanted access device, includes administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment, (drugs and nursing visits coded separately), per diem (use this code for interim maintenance of vascular access not currently in use) Home infusion therapy, all supplies necessary for restoration of catheter patency or declotting Home infusion therapy, all supplies necessary for catheter repair Home infusion therapy, pain management infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem (do not use this code with S9326, S9327 or S9328) Home infusion therapy, continuous (24 hours or more) pain management infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem Home infusion therapy, intermittent (less than 24 hours) pain management infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem Home infusion therapy, implanted pump pain management infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem Home infusion therapy, chemotherapy infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem (do not use this code with S9330 or S9331) Home infusion therapy, continuous (24 hours or more) chemotherapy infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem Home infusion therapy, intermittent (less than 24 hours) chemotherapy infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem Home infusion therapy, antispasmodic therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem Comments 18

Appendix A PerformRx Opiate Dependence Agents Prior Authorization Criteria Generic buprenorphine/naloxone tablets are the preferred formulary agent. All requests for brand or non-formulary products will require documentation of a medical reason (e.g., contraindication, hypersensitivity) why the generic form of the drug is not able to be used to treat the member s condition. Buprenorphine/naloxone tablets formulary Buprenorphine-non-formulary Suboxone-non-formulary Zubsolv-non-formulary Bunavail-non-formulary Any other newly marketed agent for opiate dependence non-formulary PA criteria for approval initial: Physician must be a participating provider or a participating provider with the behavioral health managed care organization (MCO) or be enrolled in the Medical Assistance program. Member is > or = 16 years old. Physician meets all qualifications to prescribe buprenorphine. Diagnosis is opioid dependence and/or opioid addiction (requests for pain will be denied). Provider attests that member has signed a consent form authorizing the provider to release member information in the member record for purposes of referral to substance use or behavioral health treatment. Provider attests that the risks of using buprenorphine/naloxone with alcohol or benzodiazepines have been explained to the member. Provider attests that the member has had a mental health screening and, if a co-occurring mental health disorder has been discovered, that the member has been referred for or is receiving treatment for that condition. If member has had more than one prior attempt to treat opioid addiction with buprenorphine in the last twelve months, provider acknowledges previous attempt, and completed an assessment indicating the need for buprenorphine treatment. If member is female of childbearing age (as indicated), provider attests that a pregnancy test was completed within 30 days of the request (if positive only buprenorphine generic will be approved). Provider attests to and has supplied information (date of evaluation, name of treatment program, referral date, name of counselor and frequency of counseling for approval) of an initial evaluation by a licensed drug and alcohol (D and A) provider to determine recommended level of care, and either a referral has been made, or member is actively 19