Ambulatory Infusions of Lidocaine and Ketamine for Management of Chronic Pain
Condition: Chronic Neuropathic Pain and Fibromyalgia
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes; Neuralgia; Chronic Pain
Study type: Interventional
Phase: Phase 4

Summary: 
      As lidocaine and ketamine provide analgesia by acting on different molecular pathways,
      administering them together may produce synergistic effects, which can allow for using a
      lower dose of each medication and thereby reducing the corresponding side effects. To the
      investigator's knowledge, despite the common practice of multimodal analgesia,
      lidocaine-ketamine infusions have never been studied prospectively in an out of hospital
      setting to treat neuropathic pain. The aim of the present study is to evaluate the
      effectiveness of the current routine practice of lidocaine-ketamine infusions conducted at
      Allevio Pain Management Clinic, a large outpatient community based chronic pain management
      facility. Lidocaine-ketamine infusions are prescribed to patients that have pain that is
      considered to be neuropathic for which standard anti-neuropathic medications have been
      ineffective or poorly tolerated by patients. A prospective longitudinal study.
    

Detailed description: 
      Study objectives

        1. To evaluate effectiveness of lidocaine-ketamine infusions in reducing neuropathic pain,
           as assessed using the Revised Pain Quality Assessment Scale (PQAS-R) and Short Form
           Brief Pain Inventory (BPI-SF).

        2. To evaluate the effects of lidocaine-ketamine infusions on the measures of Global
           Improvement and Satisfaction Score, Pain Self-Efficacy Questionnaire (PSEQ), Pain
           Catastrophic Scale (PCS), Beck Depression Inventory (BDI), and Patient self-reported
           perceived duration of effect (PSPDE).

        3. To assess, analyze, and report adverse events

      The study will be conducted per IMMPACT recommendations (17). Multi variable parameters will
      be captured: pain unpleasantness, physical function, emotional function, global improvement
      and satisfaction with treatment, adverse events and disposition. Additional instruments will
      be used in the triage process and follow-up (S-LANSS, PSEQ).

      Number of subjects: all eligible consecutive patients accepted for lidocaine-ketamine
      infusions over period of 6 months.

      Patients with multi focal and/or non-dermatomal pain with neuropathic component will be
      included.

      Dosing and infusion orders are completed by one of the physician-investigators prior to
      patient arrival based on body weight, and modified if required after individual evaluation.
      Based on published literature and clinical impression, higher doses seem to be more effective
      and result in longer pain relief. Therefore, subsequent infusion doses will be increased to
      the maximally tolerated doses (i.e. minimal side effects).

      Doses will be calculated using the following:

        -  Lidocaine - initial dose of 5.0 mg/kg +/- 1.0 mg/kg (based on actual weight, up to
           maximum dose 600 mg) over 45 minutes, followed by increases of 0.5 mg/kg each infusion
           based on tolerability of side effects, not to exceed 7 mg/kg or 600 mg.

        -  Ketamine - initial dose of 0.1 mg/kg (based on actual weight) over 45 minutes (rounded
           to nearest 5 mg, up to maximum 15 mg), increased by 0.1 mg/kg (rounded to nearest 5 mg)
           each infusion based on tolerability of side effects.

      Standard clinic procedure will be followed for completing the infusions and managing side
      effects. The infusion will be initiated at 360 ml/hour for planned completion in 45 minutes,
      rate adjusted if side effects develop. Total doses of medication are recorded in the medical
      record.

      Data collection and Management All study tools will be completed by patients online using, or
      in the clinic RedCap system. RedCap is a mature, secure web application for building and
      managing online surveys and databases (Vanderbilt University). The system is secured by SSL
      protocol and data is encrypted. Patients will be contacted via Email with a secure link to
      RedCap database, or if they would not be able to do it at home research, they can complete
      the questionnaires with research coordinator's assistant in secure computers at the clinic.
      Participant will receive reminders about upcoming visits and promoted to complete the
      follow-up forms. Allevio data protection is also SSL enabled and secured by SHA256, and they
      are issued by Rapid SSL and purchased through Ceerts4Less.
    

Intervention name(s): Lidocaine Hydrochloride 2% Intravenous Solution, DIN 02421992
Intervention type(s): Drug
Intervention description(s): An intravenous will be started. • Lidocaine - initial dose of 5.0 mg/kg +/- 1.0 mg/kg (based on actual weight, up to maximum dose 600 mg) over 45 minutes, followed by increases of 0.5 mg/kg each infusion based on tolerability of side effects, not to exceed 7 mg/kg or 600 mg.
• Ketamine - initial dose of 0.1 mg/kg (based on actual weight) over 45 minutes (rounded to nearest 5 mg, up to maximum 15 mg), increased by 0.1 mg/kg (rounded to nearest 5 mg) each infusion based on tolerability of side effects During the infusion patient will be monitored by another MD for BP, PR, PO2. Patients will not be allowed to drive for 24 hours.
Other intervention name(s): ketamine Hydrochloride, Serial# 5751304560, DIN 02246796
Intervention MeSH terms: Lidocaine; Ketamine
Intervention model: Single Group Assignment
Intervention model description: Patients are assessed for eligibility on their first visit (screening visit); additional visits may be required to address patient questions and collect baseline data. Qualified participants will be scheduled for their 5 infusions at 8 week intervals.
Dosing and infusion orders are completed by one of the physician-investigators prior to patient arrival based on body weight, and modified if required after individual evaluation. Based on published literature and clinical impression, higher doses seem to be more effective and result in longer pain relief. Therefore, subsequent infusion doses will be increased to the maximally tolerated doses (i.e. minimal side effects).
Participants will be asked to complete the follow-up questionnaires every four weeks starting from their first infusion up to 8 times. On their last study visit, 4 weeks following the last infusion, participants will have an exit interview in addition to completing study measures.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Neuropathic pain; Fibromyalgia; Lidocaine infusion; Ketamine infusion; Chronic pain