Indications for Implantable drug-delivery systems:
Implantable infusion pumps are considered medically necessary when used to deliver drugs for the treatment of:
Primary liver cancer (intrahepatic artery injection of chemotherapeutic agents);
Metastatic colorectal cancer where metastases are limited to the liver (intrahepatic artery injection of chemotherapeutic agents);
Head/neck cancers (intra-arterial injection of chemotherapeutic agents);
Severe, refractory spasticity of cerebral or spinal cord origin in patients who are unresponsive to or cannot tolerate oral baclofen (Lioresal®) therapy (intrathecal injection of baclofen)
Permanently implanted intrathecal (intraspinal) infusion pumps for the administration of opioids or non-opioid analgesics, in the treatment of chronic intractable pain, are considered medically necessary when:
Used for the treatment of malignant (cancerous) pain and all of the following criteria are met:
Strong opioids or other analgesics in adequate doses, with fixed schedule (not PRN) dosing, have failed to relieve pain or intolerable side effects to systemic opioids or other analgesics have developed; and
Life expectancy is greater than 3 months (less invasive techniques such as external infusion pumps provide comparable pain relief in the short term and are consistent with standard of care); and
Tumor encroachment on the thecal sac has been ruled out by appropriate testing; and
No contraindications to implantation exist such as sepsis or coagulopathy; and
A temporary trial of spinal (epidural or intrathecal) opioids has been successful prior to permanent implantation as defined by a 50% reduction in pain. A temporary trial of intrathecal (intraspinal) infusion pumps is considered medically necessary only when criteria 1-4 above are met.Used for the treatment of non-malignant (non-cancerous) pain with a duration of greater than 6 months and all of the following criteria are met and documented by treating providers in the medical record:
Non-opioid oral medication regimens have been tried and have failed to relieve pain and improve function (Refer to the DWC “Guideline for the Use of Opioids to Treat Work-Related Injuries” for a description of functional improvement); and
At least 6 months of other conservative treatment modalities (injection, surgical, psychologic or physical) have been ineffective in relieving pain and improving function; and
Intractable pain secondary to a disease state with objective documentation of pathology in the medical record (per symptoms, physicial examination, and diagnostic testing); and
Further surgical intervention or other treatment is not indicated or likely to be effective; and
Independent psychological evaluation has been obtained and evaluation states that the pain is not primarily psychologic in origin, the patient has realistic expectations and that benefit would occur with implantation despite any psychiatric comorbidity; and
No contraindications to implantation exist such as sepsis, spinal infection, anticoagulation or coagulopathy; and
There has been documented improvement in pain and function in response to oral opioid medications, but intolerable adverse effects preclude their continued use; and
A temporary trial of spinal (epidural or intrathecal) opiates has been successful prior to permanent implantation as defined by at least a 50% to 70% reduction in pain and documentation in the medical record of functional improvement and associated reduction in oral pain medication use. A temporary trial of intrathecal (intraspinal) infusion pumps is considered medically necessary only when criteria 1-5 above are met.
For average hospital LOS if criteria are met, see Hospital length of stay (LOS).
If treatment is determined to be medically necessary, as with all other treatment modalities, the efficacy and continued need for this intervention and refills should be periodically reassessed and documented.
Medications for IDDS if determined to be medically necessary:
First stage: Morphine is generally the initial IDDS medication. The maximum recommended dose for this drug is 15 mg/day with a concentration of 20 mg/mL. An alternative non-FDA approved medication is hydromorphone. The maximum recommended dose for this medication is 4 mg/day with a concentration of 10 mg/mL. Other opioids (including Fentanyl and Sufentanil) have been used for intrathecal chronic non-malignant pain but are non-FDA approved and have little research associated with their use. (Waara-Wolleat, 2006) (Deer, 2007) The previous 2003 Polyanalgesic conference recommended a maximum dose of intrathecal morphine at 15 mg/day with a maximum concentration of 30 mg/mL. They also recommended a maximum dose of hydromorphone of 10 mg/day with a concentration of 30 mg/mL. (Hassenbusch, 2004) The newer maximum concentrations were recommended, in part, to prevent granulomas.
Second stage: If side effects occur, an upper limit of dosing is reached, or neuropathic pain is present, clonidine is next recommended as an addition to an opioid (maximum recommended dose of 1 mg/day and a concentration of 2 mg/mL). Bupivacaine has also been recommended as an alternative to clonidine (maximum dose of 30 mg/day and a concentration of 40 mg/mL). Clonidine, which is FDA approved for intrathecal delivery, is thought to provide analgesic effect via a non-opioid mechanism. It has been found to offer only short-term relief when used as a single agent. (Deer, 2007)
Third stage: The recommendation has been made to add both clonidine and bupivacaine. Baclofen has been used to treat intractable spasticity from brain injury, cerebral palsy, and spinal cord injury and has resulted in improvement in muscle tone and pain relief. (Guillaume, 2005) See also Ziconotide (Prialt®), which is recommended after documentation of a failure of a trial of intrathecal morphine or hydromorphone (Dilaudid).
Refills: IDDSs dispense drugs according to instructions programmed by the clinician to deliver a specific amount of drug per day or to deliver varying regimens based on flexible programming options, and the pump may need to be refilled at regular intervals. The time between refills will vary based on pump reservoir size, drug concentration, dose, and flow rate. A programming session, which may occur along with or independent of a refill session, allows the clinician to adjust the patient’s prescription as well as record or recall important information about the prescription. (Hassenbusch, 2004) According to the FDA, the manufacturer’s manuals should be consulted for specific instructions and precautions for initial filling, refilling and programming. (FDA, 2010) For most pumps, the maximum dose that can be delivered between refills is 1000mg. If refills are usually administered after 16 to 17 mL have been infused, and most pumps are 18-20mL, the minimum time between each visit is 42 days if the daily dose rate is 20 mg/day. Given that a refill visit presents a good opportunity for monitoring, this panel suggested that the concentration be adjusted to allow refill visits a minimum of every 4 to 6 weeks, and maximum of every 2–3 months. (Bennett, 2000)
Implantable spinal cord stimulators
See Spinal Cord Stimulators (SCS).
Indomethacin (Indocin®, Indocin SR®)
Not recommended. A large systematic review of available evidence on NSAIDs confirms that naproxen and low-dose ibuprofen are least likely to increase cardiovascular risk. Indomethacin is an older, rather toxic drug, and the evidence on cardiovascular risk should cast doubt on its continued clinical use. (McGettigan, 2011) See NSAIDs (non-steroidal anti-inflammatory drugs); NSAIDs, GI symptoms & cardiovascular risk; NSAIDs, hypertension and renal function; & NSAIDs, specific drug list & adverse effects for general guidelines, as well as specific Indomethacin (Indocin®, Indocin SR®) listing for more information and references. See also Tivorbex (indomethacin).
Injection with anaesthetics and/or steroids
See more specific modality. The following are choices: Epidural steroid injections (ESI’s); Facet-joint injections; Lumbar sympathetic block; Trigger point injections; Stellate ganglion block; Prolotherapy; Piriformis injections; in this chronic pain guideline.
Pain injections general: Consistent with the intent of relieving pain, improving function, decreasing medications, and encouraging return to work, repeat pain and other injections not otherwise specified, should at a very minimum relieve pain to the extent of 50% for a sustained period, and clearly result in documented reduction in pain medications, improved function, and/or return to work.
Recommend correcting deficits, as nonrestorative sleep is one of the strongest predictors for pain. Definition: Difficulty in sleep initiation or maintenance, and/or early awakening. Also characterized by impairment in daily function due to sleep insufficiency. These impairments include fatigue, irritability, decreased memory, decreased concentration, and malaise. Classifications: (1) Based on symptoms: Categories of symptoms include sleep onset, sleep maintenance, non-restorative sleep. These symptoms have been found to change over time. (2) Based on duration: (a) Acute insomnia (transient insomnia): Usually the result of specific environmental or social events. Generally treated by addressing the episode directly (death of a family member, working on a different shift, travel), or prophylactically. (b) Chronic insomnia: Generally defined as lasting more than one month. This condition may be correlated with other intrinsic sleep disorders, primary insomnia, or chronic medical conditions. Chronic insomnia is more likely to occur in the elderly, depressed patients, and medically ill populations. (3) Based on etiology: (a) Primary insomnia: No known physical or mental condition is noted as an etiology. This condition is generally consistent and responsive to treatment. (b) Secondary insomnia (comorbid insomnia): insomnia that is secondary to other medical and psychiatric illnesses, medications, or sleep disorders. Examples include chronic pain, gastroesophogeal reflux disease (GERD), heart failure, end-stage renal disease, diabetes, neurologic problems, psychiatric disorders, and certain medications. Diabetic patients appear to suffer insomnia due to alterations of circadian rhythm. They may also suffer from sleep disorders related to obesity. Psychiatric disorders associated with insomnia include depression, anxiety and alcoholism. (Reeder, 2007) (Benca, 2005) Poor or insufficient sleep is the strongest predictor for pain in adults over 50. Among factors associated with new-onset pain were: age (OR 0.97); baseline pain status (OR 1.1); anxiety (OR 1.5); physical health–related quality of life (OR 1.3); cognitive complaint (OR 1.3); & nonrestorative sleep (OR 1.9; 95% CI 1.2 - 2.8). This study points to the need to address underlying sleep problems to bring pain relief. (McBeth, 2014) See Insomnia treatment. See also Sleep studies.
Recommend that treatment be based on the etiology, with the medications recommended below. See Insomnia. Pharmacological agents should only be used after careful evaluation of potential causes of sleep disturbance. Failure of sleep disturbance to resolve in a 7 to 10 day period may indicate a psychiatric and/or medical illness. (Lexi-Comp, 2008) Primary insomnia is generally addressed pharmacologically. Secondary insomnia may be treated with pharmacological and/or psychological measures. The specific component of insomnia should be addressed: (a) Sleep onset; (b) Sleep maintenance; (c) Sleep quality; & (d) Next-day functioning.
Pharmacologic Treatment: There are four main categories of pharmacologic treatment: (1) Benzodiazepines; (2) Non-benzodiazepines; (3) Melatonin & melatonin receptor agonists; & (4) Over-the-counter medications. The majority of studies have only evaluated short-term treatment (i.e., ≤ 4 weeks) of insomnia; therefore more studies are necessary to evaluate the efficacy and safety of treatments for long-term treatment of insomnia. In 2007, the FDA requested that manufacturers of all sedative-hypnotic drugs strengthen product labeling regarding risks (i.e., severe allergic reactions and complex sleep-related behaviors, such as sleep driving). It is recommended that treatments for insomnia should reduce time to sleep onset, improve sleep maintenance, avoid residual effects and increase next-day functioning. (Morin, 2007) (Reeder, 2007) (1) Benzodiazepines: FDA-approved benzodiazepines for sleep maintenance insomnia include estazolam (ProSom®), flurazepam (Dalmane®), quazepam (Doral®), and temazepam (Restoril®). Triazolam (Halcion®) is FDA-approved for sleep-onset insomnia. These medications are only recommended for short-term use due to risk of tolerance, dependence, and adverse events (daytime drowsiness, anterograde amnesia, next-day sedation, impaired cognition, impaired psychomotor function, and rebound insomnia). These drugs have been associated with sleep-related activities such as sleep driving, cooking and eating food, and making phone calls (all while asleep). Particular concern is noted for patients at risk for abuse or addiction. Withdrawal occurs with abrupt discontinuation or large decreases in dose. Decrease slowly and monitor for withdrawal symptoms. Benzodiazepines are similar in efficacy to benzodiazepine-receptor agonists; however, the less desirable side-effect profile limits their use as a first-line agent, particularly for long-term use. (Holbrook, 2000) (Ramakrishnan, 2007) (Buscemi, 2007) (Morin, 2007) (Wafford, 2008) (Benca, 2005). (2) Non-Benzodiazepine sedative-hypnotics (Benzodiazepine-receptor agonists): First-line medications for insomnia. This class of medications includes zolpidem (Ambien® and Ambien® CR), zaleplon (Sonata®), and eszopicolone (Lunesta®). Benzodiazepine-receptor agonists work by selectively binding to type-1 benzodiazepine receptors in the CNS. All of the benzodiazepine-receptor agonists are schedule IV controlled substances, which means they have potential for abuse and dependency. Although direct comparisons between benzodiazepines and the non-benzodiazepine hypnotics have not been studied, it appears that the non-benzodiazepines have similar efficacy to the benzodiazepines with fewer side effects and short duration of action. (Ramakrishnan, 2007) (Halas, 2006) (Buscemi, 2007) (Morin, 2007) (Erman, 2005) Zolpidem [Ambien® (generic available), Ambien CR™] is indicated for the short-term treatment of insomnia with difficulty of sleep onset (7-10 days). Ambien CR is indicated for treatment of insomnia with difficulty of sleep onset and/or sleep maintenance. Longer-term studies have found Ambien CR to be effective for up to 24 weeks in adults. (Buscemi, 2005) (Ramakrishnan, 2007) (Morin, 2007). The extended-release dual-layer tablet (Ambien CR™) has a biphasic release system; an initial release of zolpidem reduces sleep latency and a delayed release facilitates sleep maintenance. Side effects: headache, daytime drowsiness, dizziness, blurred vision, confusion, abnormal thinking and bizarre behavior have occurred. Sleep driving and other activities for which the patient has no recollection may occur. The medication should be discontinued if the latter occurs. Abrupt discontinuation may lead to withdrawal. Dosing: Ambien 5 to 10 mg at bedtime (5 mg in women, the elderly and patients with hepatic dysfunction); Ambien CR 6.25 to 12.5 mg at bedtime (6.25 mg in women, the elderly and patients with hepatic dysfunction) (Morin, 2007). Adults who use zolpidem have a greater than 3-fold increased risk for early death, according to results of a large matched cohort survival analysis. (Kripke, 2012) Due to adverse effects, FDA now requires lower doses for zolpidem. The dose of zolpidem for women should be lowered from 10 mg to 5 mg for IR products (Ambien, Edluar, Zolpimist, and generic) and from 12.5 mg to 6.25 mg for ER products (Ambien CR). (FDA, 2013) See also Zolpidem. Zaleplon (Sonata®) reduces sleep latency. Side effects: headache, drowsiness, dizziness, fatigue, confusion, abnormal thinking. Sleep-related activities have also been noted such as driving, cooking, eating and making phone calls. Abrupt discontinuation may lead to withdrawal. Dosing: 10 mg at bedtime (5 mg in the elderly and patients with hepatic dysfunction). (Morin, 2007) Because of its short half-life (one hour), may be readministered upon nocturnal wakening provided it is administered at least 4 hours before wake time. (Ramakrishnan, 2007) This medication has a rapid onset of action. Short-term use (7-10 days) is indicated with a controlled trial showing effectiveness for up to 5 weeks. Eszopicolone (Lunesta™) has demonstrated reduced sleep latency and sleep maintenance. (Morin, 2007) The only benzodiazepine-receptor agonist FDA approved for use longer than 35 days. A randomized, double blind, controlled clinical trial with 830 primary insomnia patients reported significant improvement in the treatment group when compared to the control group for sleep latency, wake after sleep onset, and total sleep time over a 6-month period. (Walsh, 2007) Side effects: dry mouth, unpleasant taste, drowsiness, dizziness. Sleep-related activities such as driving, eating, cooking and phone calling have occurred. Withdrawal may occur with abrupt discontinuation. Dosing: 1-2 mg for difficulty falling asleep; 2-3 mg for sleep maintenance. The drug has a rapid onset of action. (Ramakrishnan, 2007) Sedating antidepressants (e.g., amitriptyline, trazodone, mirtazapine) have also been used to treat insomnia; however, there is less evidence to support their use for insomnia (Buscemi, 2007) (Morin, 2007), but they may be an option in patients with coexisting depression. (Morin, 2007) Trazodone is one of the most commonly prescribed agents for insomnia. Side effects of this drug include nausea, dry mouth, constipation, drowsiness, and headache. Improvements in sleep onset may be offset by negative next-day effects such as ease of awakening. Tolerance may develop and rebound insomnia has been found after discontinuation. (3) Melatonin-receptor agonist: Ramelteon (Rozerem™) is a selective melatonin agonist (MT1 and MT2) indicated for difficulty with sleep onset; is nonscheduled (has been shown to have no abuse potential). One systematic review concluded that there is evidence to support the short-term and long-term use of ramelteon to decrease sleep latency; however, total sleep time has not been improved. (Reynoldson, 2008) (Zammit, 2007) Ramelteon is not a controlled substance. Side effects: CNS depression, somnolence, dizziness, fatigue, abnormal thinking and bizarre behavior have occurred. Use with caution in patients with depression, hepatic impairment, and respiratory conditions such as COPD or sleep apnea. Dosing: 8mg within 30 minutes of bedtime; recommended for short-term (7 – 10 days) use only. (4)Over-the-counter medications:Sedating antihistamines have been suggested for sleep aids (for example, diphenhydramine). Tolerance seems to develop within a few days. Next-day sedation has been noted as well as impaired psychomotor and cognitive function. Side effects include urinary retention, burred vision, orthostatic hypotension, dizziness, palpitations, increased liver enzymes, drowsiness, dizziness, grogginess and tiredness.
Non-pharmacologic treatment: Empirically supported treatment includes stimulus control, progressive muscle relaxation, and paradoxical intention. Treatments that are thought to probably be efficacious include sleep restriction, biofeedback, and multifaceted cognitive behavioral therapy. Suggestions for improved sleep hygiene: (a) Wake at the same time everyday; (b) Maintain a consistent bedtime; (c) Exercise regularly (not within 2 to 4 hours of bedtime); (d) Perform relaxing activities before bedtime; (e) Keep your bedroom quiet and cool; (f) Do not watch the clock; (g) Avoid caffeine and nicotine for at least six hours before bed; (h) Only drink in moderation; & (i) Avoid napping. (Benca, 2005) In a head-to-head comparison of treatment approaches to determine separate and combined effects on insomnia, adding a prescription sleeping pill to cognitive behavioral therapy (CBT) appeared to be the optimal initial treatment approach in patients with persistent insomnia, but after 6 weeks, tapering the medication and continuing with CBT alone produced the best long-term outcome. These results suggest that there is a modest short-term added value to starting therapy with CBT plus a medication, especially with respect to total sleep gained, but that this added value does not persist. In terms of first-line therapy, for acute insomnia lasting less than 6 months, medication is probably the best treatment approach, but for chronic insomnia, a combined approach might give the best of both worlds; however, after a few weeks, the recommendation is to discontinue the medication and continue with CBT. Prescribing medication indefinitely will not work. The authors said that the conclusion that patients do better in the long-term if medication is stopped after 6 weeks and only CBT is continued during an additional 6-month period is an important new finding. (Morin, 2009)
Integrative manual therapy (IMT™)
See Chronic pain programs. Integrative Manual Therapy (IMT™) is a proprietary type of multidisciplinary chronic pain program with a unique set of techniques, approaches, and methodologies that address pain, dysfunction, disease and disability. The treatment approach is multidisciplinary and includes physical therapy, manual therapy, nutrition, and psychology, and involves specific proprietary training. (Giammatteo, 2013) There are no recommendations for this type of therapy as there are no published high-quality studies specific to IMT. See the Criteria for the general use of multidisciplinary pain management programs, under Chronic pain programs.
Interdisciplinary rehabilitation programs
See Chronic pain programs.
Interferential current stimulation (ICS)
Not recommended as an isolated intervention. There is no quality evidence of effectiveness except in conjunction with recommended treatments, including return to work, exercise, and medications, and limited evidence of improvement on those recommended treatments alone. The randomized trials that have evaluated the effectiveness of this treatment have included studies for back pain, jaw pain, soft tissue shoulder pain, cervical neck pain and knee pain. (Van der Heijden, 1999) (Werners, 1999) (Hurley, 2001) (Hou, 2002) (Jarit, 2003) (Hurley, 2004) (CTAF, 2005) (Burch, 2008, 2008) The findings from these trials were either negative or insufficient for recommendation due to poor study design and/or methodologic issues. In addition, although proposed for treatment in general for soft tissue injury or for enhancing wound or fracture healing, there is insufficient literature to support Interferential current stimulation for treatment of these conditions. There are no standardized protocols for the use of interferential therapy; and the therapy may vary according to the frequency of stimulation, the pulse duration, treatment time, and electrode-placement technique. Two recent randomized double-blind controlled trials suggested that ICS and horizontal therapy (HT) were effective in alleviating pain and disability in patients with chronic low back pain compared to placebo at 14 weeks, but not at 2 weeks. The placebo effect was remarkable at the beginning of the treatment but it tended to vanish within a couple of weeks. The studies suggested that their main limitation was the heterogeneity of the low back pain subjects, with the interventions performing much better for back pain due to previous multiple vertebral osteoporotic fractures, and further studies are necessary to determine effectiveness in low back pain from other causes. (Zambito, 2006) (Zambito, 2007) A recent industry-sponsored study concluded that interferential current therapy plus patterned muscle stimulation (using the RS-4i Stimulator) has the potential to be a more effective treatment modality than conventional low-current TENS for osteoarthritis of the knee. (Burch, 2008) This recent RCT found that either electroacupuncture or interferential electrotherapy, in combination with shoulder exercises, is equally effective in treating frozen shoulder patients. It should be noted that this study only showed the combined treatment effects with exercise as compared to no treatment, so the entire positive effect could have been due to the use of exercise alone. (Cheing, 2008) See also Sympathetic therapy. See also TENS, chronic pain.
How it works: Paired electrodes of two independent circuits carry differing medium-frequency alternating currents so that current flowing between each pair intersects at the underlying target. The frequency allows the Interferential wave to meet low impedance when crossing the skin. Treatments involve the use of two pairs of electrodes and most units allow variation in waveform, stimulus frequency and amplitude or intensity, and the currents rise and fall at different frequencies. It is theorized that the low frequency of the interferential current causes inhibition or habituation of the nervous system, which results in muscle relaxation, suppression of pain and acceleration of healing.
How it is different from TENS: It has been postulated that ICS allows for deeper penetration of tissue, whereas TENS is predominantly a cutaneous or superficial stimulus. Interferential current is proposed to produce less impedance in the tissue and the intensity provided is suggested to be perceived as more comfortable. Because there is minimal skin resistance with the interferential current therapy, a maximum amount of energy goes deeper into the tissue. It also crisscrosses, as opposed to the linear application of the TENS. This crisscrossing is postulated to be more effective because it serves to confuse the nerve endings, preventing the treated area from adjusting to the current. There are no published randomized trials comparing TENS to ICS.
Current recommendations: Health plans have taken a variety of positions with respect to ICS. See H-wave stimulation (HWT), and Interferential current stimulation. California Technology Assessment Forum concluded that the treatment does not meet their criteria for coverage. (CTAF, 2005) Aetna considers it experimental because its effectiveness has not been established. (Aetna, 2007) United Healthcare concluded that clinical evidence supports its use for treatment of pain or non-surgical soft tissue injuries. (United, 2007) Humana provides coverage for acute postoperative or post-traumatic pain, or chronic pain of at least three months duration that is not responsive to other methods of pain management. (Humana, 2008) There is considerable variance in the Blue Cross/Blue Shield coverage recommendations, and some BC/BS licensees reference ICS as investigational/not medically necessary (BlueCross BlueShield, 2006), but others do cover it. (BC/BS_TN, 2008) CMS does not directly address its use. In workers’ comp, Washington L&I covers these devices, but only from a single TENS supplier. (Washington, 2008) [Note: Coverage determinations by health insurance plans are not considered high-quality evidence in formulating ODG recommendations, but may be provided for reference when high-quality studies are not available.]