Intravenous Lidocaine in Pain Management

Intravenous Lidocaine in Pain Management Dr. Dennis Reid, University of Ottawa S.A.C.A Meeting Kathmandu, February,2007 What Ottawans do in winter What Ottawans do in winter Intravenous Lidocaine in Pain Management Overview Pharmacology, systemic toxicity Proposed mechanisms of action Evidence in chronic pain management Evidence in postoperative pain management Effect on volatile anesthetic requirements Conclusions Pharmacology of Lidocaine Amino –amide Plasma half life 8 minutes Hepatic clearance. Metabolites - MEGX, half life 2 hours. - GX , half life 10 hours Pharmacology of Lidocaine Toxicity Lightheadedness -5 mcg/ml Unconsciousness -10 mcg/ml Seizures -(12-18)mcg/ml Respiratory and Cardiac Depression -(20-24)mcg/ml CD100 – HUMANS -(5-7)mg/kg CD 50 - HUMANS -(2-4)mg/kg Mechanism of action as systemic analgesic At peripheral A-delta and C fibre mechanical and chemical nociceptors Higher selectivity for injured nerve fibers. Antihyperalgesic and antihyperallodynic Action at dorsal horn Evidence of central action at postero-lateral thalamus Evidence for intravenous lidocaine in chronic pain management Use in chronic neuropathic pain. Intravenous lidocaine test Intravenous lidocaine in chronic pain management Analgesic response to intravenous lidocaine in the treatment of neuropathic pain. Ferrante et al. Anesth, Anal. 1996 Lidocaine 500mg i.v over 60 minutes V.A.S and venous lidocaine levels every 10 minutes E.D. – complete pain relief Analgesic response to intravenous lidocaine in the treatment of neuropathic pain Patient Demographics 13 patients studied 10 peripheral neuropathic pain 3 central neuropathic pain Analgesic response to intravenous lidocaine in the treatment of neuropathic pain Results: 10 patients complete relief,3 patients partial relief {55%; 40%; 62%;} Complete relief in 8/11 peripheral pain and 2/2 central pain Analgesic response to intravenous lidocaine in the treatment of neuropathic pain Results{continued}: Time to onset of complete analgesia 45+_8.6 minutes. ED20 330mg; ED50 372 mg;ED90 416 mg. Serum concentrations for complete analgesia 3.79+_1.00 mcg/ml Analgesic response to intravenous lidocaine in the treatment of neuropathic pain Results{continued}: Side effects-light headedness, dizziness, intoxication,nystagmus. No seizures or cardiotoxicity No evidence for prolonged analgesia at 1-2 weeks Analgesic response ,dramatic ,over a narrow dose and concentration range Long term administration of intravenous lidocaine for neuropathic cancer pain Jarvis et al Palliative Care Symposium, Abstract 1839, Venice 2006. 6 patients with refractory neuropathic pain,secondary to malignant disease All had VAS scores of 10/10 Long term administration of intravenous lidocaine for neuropathic cancer pain Lidocaine infusions at 65-110 mg/hour Plasma lidocaine levels of [1.48-4.94] mcg/ml. Four patients were discharged home. Reported side effects were tremors and brief hallucinations Average VAS 2/10 Intravenous lidocaine for chronic pain. An 18 month experience. Cahana et al, Harefuah, 1998; 134(9):692-4 106 patients with mainly neuropathic pain 212 treatment sessions Dosage-1mg/kg plus an infusion of 5mg/kg over 1 hour Significant pain relief with no significant side effects Duration of pain relief-few hours to 4 weeks Systemic administration of local anesthetics to relieve neuropathic pain Cochrane Database Systemic Review. October 19th,2005;(4) CD003345 Lidocaine and oral analogs were safe drugs in controlled clinical trials for neuropathic pain, were better than placebo and were as effective as other analgesics. Recommend studying specific disease states . Systemic administration of local anesthetics to relieve neuropathic pain.A systemic review and meta-analysis Tremont-Lukats et al, Anesth Analg Dec;101(6): 1736-1737 No major adverse events Superior to placebo in relieving neuropathic pain Intravenous lidocaine in chronic pain management Intravenous lidocaine test Galer et al J.Pain.Symptom.Manag,1996 Analgesia after i.v. lidocaine 2-5 mg./kg. predicted good response to oral mexilitene. Shetty,Reid Can J Anesth 1996.Analgesia after i.v.lidocaine 1.5mg./kg : - 50% chance of response to anticonvulsants - If no response to i.v. lidocaine then no response to anticonvulsants Intravenous lidocaine in Chronic Pain Management Conclusions: A potentially effective and inexpensive therapy for neuropathic and non-neuropathic pain of malignant and non-malignant origin. The length of action is variable. It may be of predictive value when prescribing oral sodium channel blockers and anticonvulsants. Evidence for Lidocaine as a systemic analgesic in perioperative pain management Major abdominal surgery Radical prostatectomy Perioperative Intravenous Lidocaine in Major Abdominal Surgery Koppert et al. Anesth. Analg 2004: 98:1050-5 ? Does Lidocaine decrease post-operative pain ? Does it decrease morphine consumption ? Side effects ? Other discernible benefits Perioperative Intravenous Lidocaine in Major Abdominal Surgery Study Design 40 patients (20 per group) Lidocaine -Bolus 1.5mg/kg -Infusion 1.5mg/kg/hr Incision – ½ hour after beginning of protocol Termination – 1 hour after skin closure Control group saline Perioperative Intravenous Lidocaine in Major Abdominal Surgery Anesthesia All staff blinded Fentanyl to 6mcg/kg PCA Morphine - Bolus 2mg - Lockout 10 minutes Perioperative Intravenous Lidocaine in Abdominal Surgery Results Plasma levels (1.9  0.7) mcg/ml No lidocaine related side effects Perioperative Intravenous Lidocaine in Abdominal Surgery Results Pain Scores Time to PCA same in both groups Pain scores 1-2/10 at rest in both groups Pain scores 5-6/10 on movement on day 1 in both groups. Pain scores 4-6/10 vs 3-4/10 on days 2&3 in favor of lidocaine group. * Perioperative Intravenous Lidocaine in Abdominal Surgery Results. Morphine requirements (103 72)mg vs (159 72)mg PCA requests 38 vs 68 * * PONV on Day 1 65% vs 85% Treatment of post-operative ileus by intravenous lidocaine infusion Rimback et al. Anesth. Analg. 1990; 70(4): 414-9 Study Design Open cholecystectomy 30 patients (15 per group) Lidocaine infusion 3mg/min vs Saline Infusion started 30 minutes preoperatively and continued for 24 hours Radioactive capsules swallowed evening before surgery Treatment of postoperative ileus by intravenous lidocaine infusion Results Radiopaque markers 60 hrs vs 75 hrs – appear 87 hrs vs 107 hrs – pass B.M. – 70 hrs vs 90 hrs Gas – 38 hrs vs 40 hrs. Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain and shortens hospital stay in patients undergoing radical retropubic prostatectomy Groudine et al. Anesth. Analg. 1998; 86(2): 235-239 Intravenous Lidocaine for Radical Prostatectomy Study Design 40 patients (20 per group) Anesthetic technique flexible but no lidocaine in control group. All patients to receive Ketorolac Pain scores, bowel function, LOS Intravenous Lidocaine for Radical Prostatectomy Lidocaine protocol Bolus 1.5mg/kg Infusion 3mg/min >70kg 2mg/min >70kg Recalculated 2.1mg/kg/hour Blood levels (1.3 –3.7)mcg/ml For 60 minutes postoperatively Intravenous Lidocaine for Radical Prostatectomy Management of Pain Ketorolac 30mg I.V. plus 15mg I.V. q6h PRN Morphine for breakthrough Pain Score Index – Average pain score for last 24 hours X number of days in hospital. Intravenous Lidocaine for Radical Prostatectomy Pain Scores 4.7  4.0/10 vs 13.3  7.7/10 in favor of lidocaine group. Factoring in LOS 1.175 v 2.62 Intravenous Lidocaine for Radical Prostatectomy Medication Use Morphine CONTROL GROUP PACU WARD Ketorolac (6.48 + (20.3  15.6)mg 5.97)mg (143  55.7)mg (7.7  15.0)mg LIDOCAINE GROUP PACU WARD (3.0  7.1)mg (5.67  8.1)mg (20.8  13.7)mg (111  77.3)mg Intravenous Lidocaine for Radical Prostatectomy Other Results First Bowel Movement (hrs) First Flatus (hrs) Hospital Stay (days) (73.9  16.3) v (61.8  13.25) (42.1  16) v (28.5  13.4) (5.1  2.18) v (4  6.9) Intravenous lidocaine infusion facilitates acute rehabilitation after laparoscopic colectomy Kaba et al, Anesthesiology 2007;106:11-18. 40 patients for laparoscopic colectomy. 20 patients received intravenous lidocaine bolus of 1.5mg/kg at induction then continuous intraoperative infusion of 2mg/kg/hour then 1.33mg/kg/hour for 24 hours post-operatively. The control group received an equal volume of saline Intravenous lidocaine infusion facilitates acute rehabilitation after laparoscopic colectomy Results: All in favour of lidocaine group Time to first flatus 17[11-24] vs28[25-63] hours. Time to first bowel movement 28[24-37] vs 51[41-70] hours . Time to hospital discharge 2[2-3] vs 3[3-4] days . Lidocaine plasma levels [1.6-4.6] mcg/ml Intravenous lidocaine infusion facilitates acute rehabilitation after laparoscopic colectomy Results :All in favour of lidocaine group. Abdominal discomfort 20/100 vs. 58/100 Post procedural fatigue 20/100 vs 40/100 . Decreased narcotic consumption in first 24 hours post-operatively [piritramide] 16mg vs 46mg . Decreased use of sevoflurane by 35%; end-tidal concentrations 1.5% vs 2.4%. Effect of Intravenous Lidocaine on Volatile Anesthetic Requirements Himes et al. Anesthesiology 1977: 47; 437-440 20 ASA I & II patients Constant infusion Lidocaine (3-6)mg/kg/hr 90-100% N2O – (60-90) seconds then 30/70 O2/N2O Further bolus (2-2.5)mg/kg - then surgery No patient movement above plasma level of 3.5 mcg/ml Conclusion,lidocaine decreases MAC by about 30%. Systemic Lidocaine as a Perioperative Analgesic Suggested method of administration Bolus 1.5mg/kg at induction Infusion (1.5 – 2 mg)/kg/hr May require up to a 30% reduction in volatile anesthetic administration Infuse mixed with narcotic Systemic Lidocaine as a Perioperative Analgesic Conclusions 30% reduction in narcotic and anesthetic requirements at plasma levels between (1.93.7)mcg/ml Has an analgesic effect through to the second and third post-operative day. Toxicity not an issue at doses presented Faster return of bowel function. Decreased hospital length of stay by 1 day in two studies Intravenous Lidocaine in Pain Management THANK YOU FOR YOUR KIND ATTENTION QUESTIONS OR COMMENTS ?