Effective Date: 01/01/2012 Revision Date: Code(s): J2001 Injection, lidocaine HCl for intravenous infusion, 10 mg

Transcription

1 ARBenefits Approval: 09/28/2011 Effective Date: 01/01/2012 Revision Date: Code(s): J2001 Injection, lidocaine HCl for intravenous infusion, 10 mg Medical Policy Title: Intravenous Lidocaine or Ketamine for the Outpatient Management of Chronic Pain Document: ARB0216 Public Statement: Administered by: Intravenous (IV) infusion of anesthetics such as ketamine or lidocaine has been reported for the treatment of chronic pain from fibromyalgia and neuropathic pain disorders including phantom limb pain, post-herpetic neuralgia, complex regional pain syndromes, diabetic neuropathy, and pain related to stroke or spinal cord injuries. The use of intravenous anesthetics in the outpatient setting for chronic pain lacks scientific evidence of effectiveness, and is considered by ARBenefits to be investigational. Medical Policy Statement: Intravenous lidocaine or ketamine for the outpatient management of chronic pain is considered investigational and is not covered. This includes both use as therapy and test infusion to assess patient responsiveness. Background: IV infusion of anesthetic agents has been given in the inpatient or outpatient setting as part of a pain management program. The infusion of a sub-anesthetic dose may be preceded by a bolus infusion to achieve desired blood levels sooner. Lidocaine, which prevents neural depolarization through effects on voltage-dependent sodium channels, is also used systemically for the treatment of arrhythmias. Adverse effects for lidocaine are common and can be mild to moderate, including general fatigue, somnolence, dizziness, headache, periorbital and extremity numbness and tingling, nausea, vomiting, tremors, and changes in blood pressure and pulse. Severe adverse effects can be arrhythmias, seizures, loss of consciousness, confusion, or even death. Lidocaine Page 1 of 6

2 should only be given IV to patients with normal conduction on electrocardiography and normal serum electrolyte concentrations to minimize the risk of cardiac arrhythmias. Ketamine is an antagonist of the N-methyl-d-aspartate (NMDA) receptor and a dissociative anesthetic. It is the sole anesthetic agent approved for diagnostic and surgical procedures that do not require skeletal muscle relaxation. Respiratory depression may occur with overdosage or too rapid a rate of administration of ketamine; it should be used by or under the direction of physicians experienced in administering general anesthetics. Ketamine is a schedule III controlled substance. Psychological manifestations vary in severity from pleasant dream-like states to hallucinations and delirium, and can be accompanied by confusion, excitement, aggression, or irrational behavior. The occurrence of side effects with IV anesthetics may be reduced by the careful titration of sub-anesthetic doses. However, the potential benefits of pain control must be carefully weighed against the potential for serious, harmful side effects. Test infusion of ketamine or lidocaine has also been used in treatment planning to assess patient responsiveness to lidocaine to determine whether medications such as oral mexiletine or oral ketamine may be effective. This policy does not address lidocaine or ketamine administered by continuous subcutaneous infusion for chronic pain. Nor does it address the use of IV lidocaine or ketamine in the inpatient setting. IV lidocaine is FDA approved systemically for the treatment of antianythmias and locally as an anesthetic. IV lidocaine for the treatment of chronic pain is an off-label usage. Ketamine hydrochloride injection is FDA approved for diagnostic and surgical procedures that do not require skeletal muscle relaxation, for the induction of anesthesia prior to the administration of other general anesthetic agents, and to supplement low-potency agents, such as nitrous oxide. IV ketamine for the treatment of chronic pain is an off-label use. The available evidence in peer-reviewed publications on the use of IV lidocaine for chronic pain is lacking. Information on patient selection criteria, treatment protocols, long tern benefits and comparisons to standard pain management therapy or alternatives is not available. In general, reported regimens for IV lidocaine have been single-episode lidocaine infusions of one to two hours duration. Outcomes assessed have included reductions in pain using VAS scales and verbal reports; durations of pain relief; and the absence of adverse side effects. In the literature available, duration of pain relief has only been measured over a short period of time (from one hour to five days). Therefore, IV lidocaine does not appear to be intended to provide long term pain relief, but only short term relief. What role short term relief for chronic pain serves in the overall management of the patient is not clear. There are no studies to compare IV lidocaine to standard treatment for pain management (i.e., oral medications, physical therapy, behavioral and cognitive therapy, etc,) or other alternatives (e.g., spinal cord stimulation, electrical stimulation devices, etc.). Additionally, the available literature focuses on IV lidocaine therapy for patients with a variety of chronic pain etiologies but there are no studies defining appropriate patient selection criteria. Page 2 of 6

3 In a randomized, double-blind, placebo-controlled, cross-over designed trial, Kvamstrom and colleagues evaluated the effects of lidocaine in twelve patients with long-term peripheral neuropathic pain of traumatic origin. The authors reported no significant differences in pain reduction over placebo on a visual analogue scale (VAS). Wu, et al, evaluated the effects of IV lidocaine on 31 patients with postamputation pain in a randomized, double-blind, active placebo-controlled, crossover trial. Wu and colleagues found stump pain was significantly reduced with IV lidocaine, yet phantom pain was not relieved and the stump pain relief was short-lived. In a double-blind, placebo-controlled, crossover study of 16 patients either poststroke or spinal cord injury, Attal and colleagues reported IV lidocaine significantly reduced pain over placebo. However, the duration of this significance lasted only 45 minutes. Wallace, et al, reported on a randomized, double-blind, placebo-controlled study of sixteen patients with complex regional pain syndrome types I and II. While IV lidocaine significantly reduced the pain response to cool stimuli, mechanical pain relief was not significant. In a study of 24 patients with postherpefc neuralgia, Baranowski et al, reported IV lidocaine provided significant pain reduction over placebo. However, the pain was not eliminated. Medrik- Goldberg and colleagues evaluated 30 patients with sciatica in a randomized, doubleblind, three-arm crossover trial. The authors found lidocaine significantly reduced spontaneous pain as reported by VAS and pain evoked by straight leg raises. The pain reduction continued during saline infusion for one-hour post the two-hour lidocaine infusion. However, the evaluation did not extend beyond the 3 hour treatment period. Finally, in a randomized, double-blind, crossover study of eighteen patients with fibromyalgia, Sorensen and colleagues found mixed responses with IV lidocaine with ketamine, morphine or both suggesting that pain processing mechanisms must differ in fibromyalgia. However, no patients responded to IV lidocaine alone. The above studies and a review of the evidence demonstrate a need for a further studies that are randomized, controlled and double-blinded, to determine the incremental effects of lidocaine over active placebo and as compared to other standard treatments for chronic pain, such as the use of antidepressants for fibromyalgia. A placebo response due to the significant side effects with IV lidocaine warrants the use of active placebos to increase the probability of determining the true analgesic effect of Lidocaine in clinical trials. Additionally, further studies are needed to determine appropriate patient selection criteria, predictive values, effective dosage ranges, frequencies and duration of treatment. Additional Information The American Academy of Neurology guideline for the treatment of migraine headache indicates: "Evidence is insufficient at this time to establish a defined role for intranasal lidocaine or lidocaine intravenous in the management of acute migraine headache." In 1994, the ANCPR noted in its guideline on the Management of Cancer Pain that "Systemically administered local anesthetic (intravenous lidocaine, oral mexiletine, and tocainide) and antiarrhythmic agents have been used clinically to treat neuropathic pain, although this is not currently an FDA-approved indication for these drugs." No other professional society guidelines mentioning the use of IV lidocaine for chronic pain could be found. Page 3 of 6

4 A Cochrane review examined controlled clinical trials on lidocaine and its oral analogs (i.e., mexiletine, tocainide, and flecainide) for neuropathic pain treatment and found these drugs safely provided more pain relief than placebo and with similar effectiveness as other analgesics (Challapalli et al, 2005). The Cochrane review noted further investigation is needed to determine the clinical meaning of statistically significant pain relief and to test for less toxic analogs. A meta-analysis by the authors of the Cochrane review described above estimated an 11-point improvement in pain scales with IV lidocaine or oral analogues compared with placebo (Tremonts-Lukats et al, 2005). Although side effects were reportedly not significantly different from other active controls (amitriptyline, carbamazine, gabapentin, morphine), the severity and nature of the adverse events could not be assessed. As indicated in an accompanying editorial, the limitations of the contributing studies preclude drawing useful conclusions about the adverse effect profiles of these drugs (Rathmell et al, 2005). In addition, Tremont-Lukats and colleagues noted that 1) lidocaine s short serum half-life (120 min) precludes the use of this drug for chronic use, and 2) all of the trials measured pain relief within 24 hours because in most patients the effect disappears a few hours after treatment. In 2006, Tremont-Lukats and colleagues reported results of a randomized, double-blinded, placebo-controlled pilot trial in 32 subjects with ongoing neuropathic pain (Tremonts-Lukats et al, 2006). Infusion of 5 mg/kg/h, but not 1 or 3 mg/kg/h, over a period of 6 hours was observed to decrease pain by about 30%. This effect lasted for the next 4 hours of observation. Side effects were frequent; in 2 subjects, infusion was terminated early due to bothersome side effects. Given the high frequency of side effects and the short duration of action, the health benefits of IV lidocaine have remained unclear. In a retrospective analysis, 104 patients with suspected neuropathic pain who had undergone diagnostic IV lidocaine were found from screening 635 sequential charts; of these, 5 patients had requested discontinuation mid-infusion, resulting in a cohort of 99 patients with baseline and post-treatment numerical pain ratings (Carroll et al, 2007). Forty-two of the patients met the criteria of 30% or greater pain reduction; some of this subset was subsequently treated with mexiletine. Another study compared the efficacy of placebo, ketamine, calcitonin, and combined calcitonin and ketamine to relieve phantom limb pain (Eichenberger et al, 2008). One-hour infusion of ketamine or ketamine plus calcitonin resulted in >40% improvement in pain immediately after treatment. The mean and maximum pain scores remained significantly better than placebo for 48 hours after treatment. As concluded here, additional study is needed to determine the safety and efficacy of N-methyl-D-aspartate (NMDA)-antagonists for the treatment of chronic neuropathic pain. Intravenous administration of anesthetics has not been shown to improve the net health outcome. Therefore, there is no change in the policy statement. Page 4 of 6

5 References: Attal N, Gaude V, et al.(2000) Intravenous lidocaine in central pain: a double-blind, placebo-controlled, psychophysical study. Neurology 2000; 54: Baranowski AP, DeCourcey J, Bonello E.(1999) A trial of intraveous lidocaine on the pain and allodynia of postherpatic neuralgia. J Pain Symptom Manage 1999; 17: Bell R, Eccleston C, Kalso E.(2003) Ketamine as an adjuvant to opiods for cancer pain. Cochrane Database Syst Rev 2003;(1):CD Carroll I, Gaeta R, Mackey S.(2007) Multivariate analysis of chronic pain patients undergoing lidocaine infusions: increasing pain severity and advancing age predict likelihood of clinically meaningful analgesia. Clin J Pain 20-07; 23(8): Challapalli V, Tremont-Lukats IW, McNicol ED et al.(2005) Systemic administration of local anesthetic agents to relieve neuropathic pain. Cochrane Database Syst Rev 2005; (4):CD Correll GE, Maleki J, Gracely EJ et al.(2004) Subanesthetic ketamine infusion therapy: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome. Pain Med 2004; 5(3): Eichenberger U, Neff F, Sveticic G et al.(2008) Chronic phantom limb pain: the effects of calcitonin, ketamine, and their combination on pain and sensory thresholds. Anesth Analg 2008; 106(4): Finnerup NB, Biering-Sorenson F, Johannesen Il et al.(2005) Intravenous lidocaine relieves spinal cord injury pain: a randomized controlled trial. Anesthesiology 2005; 102(5): Hocking G, Cousins MJ.(2003) Ketamine in chronic pain management: an evidencebased review. Anesth Analg 2003; 97(6): Kvarnstrom A, Karlsten R, et al.(2001) The effectiveness of intravenous ketamine and lidocaine on peripheral neuropathic pain. Acta Anaesthesiol Scand 2001; 47: Kvarnstrom A, Karlsten R, Quiding H et al.(2004) The analgesic effect of intravenous ketamine infusions for neuropathic pain. Acta Anaesthesiol Scand 2004; 48(4): Lossignol DA, Obiols-Portis M, Body JJ.(2005) Successful use of ketamine for intractable cancer pain. Support Care Cancer 2005; 13(3): Medrik-Goldberg T, Lifschitz D, et al.(1999) Intravenous lidocaine, amantadine, and placebo in the treatment of sciatica: a double-blind, randomized, controlled study. Reg Anesth Pain Med 1999; 24: Page 5 of 6

6 Rathmell JP, Ballantyne JC.(2005) Local anesthetics for the treatment of neuropathic pain: on the limits of meta-analysis. Anesth Analg 2005; 101(6): Silberstein SD for US Headache Consortium.(2000) Practice Parameter: Evidencebased guidelines for migraine headache (An evidence-based review). Neurology 2000; 55: Sorenson J, Bengtsson A, et al.(1997) Fibromyalgia - are there different mechanisms in the processing of pain? A double blind crossover comparison of analgesic drugs. J Rheumatol 1997; 24: Tremont-Lukats IW, Hutson PR, Backonja MM.(2006) A randomized, double-masked, placebo-controlled pilot trial of extended IV lidocaine infusion for relief of ongoing neuropathic pain. Clin J Pain 2006; 22(3): Tremont-Lukats, IW, Challapalli V, McNicol ED et al.(2005) Systemic administration of local anesthetics to relieve neuropathic pain: a systmeatic review and meta-analysis. Anesth Analg 2005; 101(6): Wallace MS, Ridgeway BM, et al.(2000) Concentration-effect relationship of intravenous lidocaine on the allodynia of complex regional pain syndrome types I and II. Anesthesiology 2000; 92: Webster LR, Walker MJ.(2006) Safety and efficacy of prolonged outpatient ketamine infusions for neuropathic pain. Am J Ther 2006; 13(4): Wu CL, Tella P, et al.(2002) Analgesic effects of intravenous lidocaine and morphine on postamputation pain: a randomized double-blind, active placebo-controlled, crossover trial. Anesthesiology 2002; 96: Application to Products This policy applies to ARBenefits. Consult ARBenefits Summary Plan Description (SPD) for additional information. Last modified by: Date: Page 6 of 6