The analgesic effect of intravenous lidocaine in the treatment of chronic
               pain: a literature review

Souza, Maiara Ferreira de; Kraychete, Durval Campos

doi:10.1016/j.rbr.2014.01.010

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Revista Brasileira de Reumatologia

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Review articles • Rev. Bras. Reumatol. 54 (5) • Sep-Oct 2014 • https://doi.org/10.1016/j.rbr.2014.01.010 copy

The analgesic effect of intravenous lidocaine in the treatment of chronic pain: a literature review

Authorship SCIMAGO INSTITUTIONS RANKINGS

Background:

Pain is a public health problem, greatly impairing quality of life. Almost 80% of patients with chronic pain reported that their pain interferes with activities of daily living, and two thirds reported that the pain causes negative impact on their personal relationships. The physical and functional disability, whether temporary or permanent, compromises the professional activity and causes work absenteeism, increasing costs of health systems.

Objectives:

The aim of this review is to analyze, based on the literature, the analgesic effect of lidocaine administered intravenously for the treatment of chronic pain and to evaluate the reduction of pain intensity in patients with chronic pain, focusing on musculoskeletal and neuropathic etiology.

Methodology:

The method used was a review the literature, consisting in searching the scientific literature on the efficacy of intravenous lidocaine infusion in the treatment of patients with chronic pain.

Content:

Of the 19 studies reviewed, 12 had results that confirm the analgesic effect of intravenous lidocaine in patients with chronic pain. Most authors used doses of 5 mg/kg infused for 30 minutes or more, producing significant analgesia with variable duration (minutes to weeks).

Conclusions:

Based on the literature review, it is not possible to uniformly specify the most effective and safe dose of lidocaine administered intravenously for the treatment of neuropathic or musculoskeletal pain. As for effectiveness, the intravenous infusion of lidocaine as an alternative for the treatment of chronic pain of various etiologies seems very promising, but further studies need to be conducted.

Lidocaine; Intravenous lidocaine; Chronic pain

Author(s)/year		Sample size (cases/controls)		Test type (crossover/parallel/open)		No. of infusions of lidocaine		Infusion for each dose		Infusion time	Significant relief compared to placebo
Wallace et al., 1996²⁹29 Wallace MS, Dyck JB, Rossi SS, Yaksh TL. Computer-controlled lidocaine infusion for the evaluation of neuropathic painafter peripheral nerve injury. Pain. 1996;66:69-77.		11 (11/11)		Crossover		1		****		****	Yes
Baranowski et al., 1999³⁹39 Baranowski AP, De Courcey J, Bonello E. A trial of intravenous lidocaine on the pain and allodynia of postherpetic neuralgia. J Pain Symptom Manage. 1999;17:429-33.		24 (24/24)		Crossover		2		1 and 5 mg/kg		2 h	No
Attal et al., 2000³³33 Attal N, Gaudé V, Brasseur L, Dupuy M, Guirimand F, Parker F, et al. Intravenous lidocaine in central pain: a double-blind, placebo-controlled, psychophysical study. Neurology.2000;54:564-74.		16(16/16)		Crossover		1		5 mg/kg		30 min	Yes
Finnerup et al., 2005⁴³43 Finnerup NB, Biering-Sørensen F, Johannesen IL, Terkelsen AJ, Juhl GI, Kristensen AD, et al. Intravenous lidocaine relieves spinal cord injury pain: a randomized controlled trial. Anesthesiology. 2005;102:1023-30.		24 (13/11)		Crossover		1		5 mg/kg		30 min	Yes
Lemming et al., 2005¹⁸18 Lemming D, Sörensen J, Graven-Nielsen T, Arendt-Nielsen L, Gerdle B. The responses to pharmacological challenges and experimental pain in patients with chronic whiplash-associated pain. Clin J Pain. 2005;21:412-21.		33 (missing data)		Crossover		1		5 mg/kg		30 min	Yes
Tremont-Lukats et al., 2006²⁸28 Tremont-Lukats IW, Hutson PR, Backonja MM. A randomized, double-masked, placebo-controlled pilot trial of extended IV lidocaine infusion for relief of ongoing neuropathic pain. Clin J Pain. 2006;22:266-71.		32 (7/9/8/8)		Parallel		1		1, 3 e 5 mg/kg		6 h	Yes (higher dose)
Attal et al., 2004²¹21 Attal N, Rouaud J, Brasseur L, Chauvin M, Bouhassira D. Systemic lidocaine in pain due to peripheral nerve injury and predictors of response. Neurology. 2004;62:218-25.		22 (22/22)		Crossover		1		5 mg/kg		30 min	Yes
Wallace et al., 2000³²32 Wallace MS, Ridgeway BM, Leung AY, Gerayli A, Yaksh TL. Concentration-effect relationship of intravenous lidocaine on the allodynia of complex regional pain syndrome types I and II. Anesthesiology. 2000;92:75-83.		16 (16/16)		Crossover		1		^** ****** Missing data.		^** ****** Missing data.	Yes
Gottrup et al., 2006²⁵25 Gottrup H, Bach FW, Juhl G, Jensen TS. Differential effect of ketamine and lidocaine on spontaneous and mechanical evoked pain in patients with nerve injury pain. Anesthesiology. 2006;104:527-36.		20 (10/10)		Crossover		1		5 mg/kg		30 min	No
Vlainich et al;, 2010¹⁷17 Vlainich R, Issy AM, Gerola LR, Sakata RK. Effect of intravenous lidocaine on manifestations of fibromyalgia. Pain Pract. 2010;10:301-5.		30 (15/15)		Parallel		4		3 mg/kg		60 min	No
Schafranski et al., 2009¹⁵15 Schafranski MD, Malucelli T, Machado F, Takeshi H, Kaiber F, Schmidt C, et al. Intravenous lidocaine for fibromyalgia syndrome: an open trial. Clin Rheumatol. 2009;28:853-5.^,^* * Uncontrolled studies.		23		Open		5		2-5 mg/kg		2 h	Yes
Kastrup et al., 1987²³23 Kastrup J, Petersen P, Dejgård A, Angelo HR, Hilsted J. Intravenous lidocaine infusion: a new treatment of chronic painful diabetic neuropathy? 1987.		15 (8/7)		Crossover		1		5 mg/kg		30 min	Yes
Kvarnström et. al., 2003/2004⁶6 Kvarnström A, Karlsten R, Quiding H, Gordh T. The analgesic effect of intravenous ketamine and lidocaine on pain after spinal cord injury. Acta Anaesthesiol Scand. 2004;48:498-506.^,²⁷27 Kvarnström A, Karlsten R, Quiding H, Emanuelsson BM, Gordh T. The effectiveness of intravenous ketamine and lidocaine on peripheral neuropathic pain. Acta Anaesthesiol Scand. 2003;47:868-77.		10 (10/10)		Crossover		1		2,5 mg/kg		40 min	No
Ferrante et al., 1996⁴⁰40 Ferrante FM, Paggioli J, Cherukuri S, Arthur GR. The analgesic response to intravenous lidocaine in the treatment of neuropathic pain. Anesth Analg. 1996;82:91-7.^,^* * Uncontrolled studies.		13		Open		1		500 mg		60 min	Yes
Gormsen et al., 2009²⁶26 Gormsen L, Finnerup NB, Almqvist PM, Jensen TS. The efficacy of the AMPA receptor antagonist NS1209 and lidocaine in nerve injury pain: a randomized, double-blind, placebo-controlled, three-way crossover study. Anesth Analg.2009;108:1311-9.		15 (15/13)		Crossover		1		5 mg/kg		4 h	No
Viola et al., 2006²⁴24 Viola V, Newnham HH, Simpson RW. Treatment of intractable painful diabetic neuropathy with intravenous lignocaine. 2006.		15 (15/15/15)		Crossover		2		5 e 7,5 mg/kg		4 h	Yes
Wu et al., 2002²²22 Wu CL, Tella P, Staats PS, Vaslav R, Kazim DA, Wesselmann U, et al. Analgesic effects of intravenous lidocaine and morphine on postamputation pain: a randomized doubleblind, active placebo-controlled, crossover trial. Anesthesiology. 2002;96:841-8.		32 (11/11/12)		Crossover		1		5 mg/kg		42 min	No
Author(s)/year	Reduction of pain (%)		No. of patients who reported relief in each group (cases/controls)		Duration of effect		Plasma concentration at which there was relief		Adverse effects			Jadad score
Wallace et al., 1996²⁹29 Wallace MS, Dyck JB, Rossi SS, Yaksh TL. Computer-controlled lidocaine infusion for the evaluation of neuropathic painafter peripheral nerve injury. Pain. 1996;66:69-77.	>50		^** ****** Missing data.		^** ****** Missing data.		1,5-2,5 μg/mL		Delirium, nausea			2
Baranowski et al., 1999³⁹39 Baranowski AP, De Courcey J, Bonello E. A trial of intravenous lidocaine on the pain and allodynia of postherpetic neuralgia. J Pain Symptom Manage. 1999;17:429-33.	~ 50 (1 mg/kg) and >30 (5 mg/kg)		^** ****** Missing data.		^** ****** Missing data.		1,7 μg/ml		Perioral paraesthesia (higher dose)			2
Attal et al., 2000³³33 Attal N, Gaudé V, Brasseur L, Dupuy M, Guirimand F, Parker F, et al. Intravenous lidocaine in central pain: a double-blind, placebo-controlled, psychophysical study. Neurology.2000;54:564-74.	~50		10/6		45 min		^** ****** Missing data.		^** ****** Missing data.			4
Finnerup et al., 2005⁴³43 Finnerup NB, Biering-Sørensen F, Johannesen IL, Terkelsen AJ, Juhl GI, Kristensen AD, et al. Intravenous lidocaine relieves spinal cord injury pain: a randomized controlled trial. Anesthesiology. 2005;102:1023-30.	>30		19/4		^** ****** Missing data.		1,5-4,1 μg/mL		Delirium, dizziness, drowsiness, dysarthria, blurred vision, tremors, dry mouth, headache.			5
Lemming et al., 2005¹⁸18 Lemming D, Sörensen J, Graven-Nielsen T, Arendt-Nielsen L, Gerdle B. The responses to pharmacological challenges and experimental pain in patients with chronic whiplash-associated pain. Clin J Pain. 2005;21:412-21.	^** ****** Missing data.		11/2		^** ****** Missing data.		^** ****** Missing data.		^** ****** Missing data.			5
Tremont-Lukats et al., 2006²⁸28 Tremont-Lukats IW, Hutson PR, Backonja MM. A randomized, double-masked, placebo-controlled pilot trial of extended IV lidocaine infusion for relief of ongoing neuropathic pain. Clin J Pain. 2006;22:266-71.	>30		****		6 h		^** ****** Missing data.		Delirium, nausea/vomiting, diplopia, headache, tinnitus, perioral paresthesia, metallic taste, tightness in throat.			5
Attal et al., 2004²¹21 Attal N, Rouaud J, Brasseur L, Chauvin M, Bouhassira D. Systemic lidocaine in pain due to peripheral nerve injury and predictors of response. Neurology. 2004;62:218-25.	>60		11/***		6 h		^** ****** Missing data.		Delirium, drowsiness, perioral numbness, truncated speech, dizziness, dysarthria.			5
Wallace et al., 2000³²32 Wallace MS, Ridgeway BM, Leung AY, Gerayli A, Yaksh TL. Concentration-effect relationship of intravenous lidocaine on the allodynia of complex regional pain syndrome types I and II. Anesthesiology. 2000;92:75-83.	≥ 25		^** ****** Missing data.		^** ****** Missing data.		3 μg/mL		Delirium			2
Gottrup et al., 2006²⁵25 Gottrup H, Bach FW, Juhl G, Jensen TS. Differential effect of ketamine and lidocaine on spontaneous and mechanical evoked pain in patients with nerve injury pain. Anesthesiology. 2006;104:527-36.	~10		4/0		^** ****** Missing data.		^** ****** Missing data.		Delirium, nausea, paresthesia, blurred vision, dizziness, dysarthria, headache, dry mouth.			4
Vlainich et al;, 2010¹⁷17 Vlainich R, Issy AM, Gerola LR, Sakata RK. Effect of intravenous lidocaine on manifestations of fibromyalgia. Pain Pract. 2010;10:301-5.	>45		^** ****** Missing data.		^** ****** Missing data.		^** ****** Missing data.		^** ****** Missing data.			4
Schafranski et al., 2009¹⁵15 Schafranski MD, Malucelli T, Machado F, Takeshi H, Kaiber F, Schmidt C, et al. Intravenous lidocaine for fibromyalgia syndrome: an open trial. Clin Rheumatol. 2009;28:853-5.^,^* * Uncontrolled studies.	>15and >10 (after 30 days)		^** ****** Missing data.		30 days		^** ****** Missing data.		No adverse effects			Not applicable
Kastrup et al., 1987²³23 Kastrup J, Petersen P, Dejgård A, Angelo HR, Hilsted J. Intravenous lidocaine infusion: a new treatment of chronic painful diabetic neuropathy? 1987.	>40 (1-3 days) and >15		9/4		3-21 days		^** ****** Missing data.		^** ****** Missing data.			2
Kvarnström et. al., 2003/2004⁶6 Kvarnström A, Karlsten R, Quiding H, Gordh T. The analgesic effect of intravenous ketamine and lidocaine on pain after spinal cord injury. Acta Anaesthesiol Scand. 2004;48:498-506.^,²⁷27 Kvarnström A, Karlsten R, Quiding H, Emanuelsson BM, Gordh T. The effectiveness of intravenous ketamine and lidocaine on peripheral neuropathic pain. Acta Anaesthesiol Scand. 2003;47:868-77.	~10 (>50 in 1 patient)		1/0		^** ****** Missing data.		^** ****** Missing data.		Drowsiness, perioral paresthesia.			4
Ferrante et al., 1996⁴⁰40 Ferrante FM, Paggioli J, Cherukuri S, Arthur GR. The analgesic response to intravenous lidocaine in the treatment of neuropathic pain. Anesth Analg. 1996;82:91-7.^,^* * Uncontrolled studies.	100 (100 patients), 62, 55 and 40 (the other)		13		^** ****** Missing data.		0,62 μg/mL		^** ****** Missing data.			Not applicable
Gormsen et al., 2009²⁶26 Gormsen L, Finnerup NB, Almqvist PM, Jensen TS. The efficacy of the AMPA receptor antagonist NS1209 and lidocaine in nerve injury pain: a randomized, double-blind, placebo-controlled, three-way crossover study. Anesth Analg.2009;108:1311-9.	~36		11/8		^** ****** Missing data.		^** ****** Missing data.		Drowsiness, perioral paresthesia, headache, dizziness, fatigue, discomfort, dry mouth, nausea, muscle spasms.			5
Viola et al., 2006²⁴24 Viola V, Newnham HH, Simpson RW. Treatment of intractable painful diabetic neuropathy with intravenous lignocaine. 2006.	^** ****** Missing data.		^** ****** Missing data.		28 days		^** ****** Missing data.		Delirium (higher dose)			3
Wu et al., 2002²²22 Wu CL, Tella P, Staats PS, Vaslav R, Kazim DA, Wesselmann U, et al. Analgesic effects of intravenous lidocaine and morphine on postamputation pain: a randomized doubleblind, active placebo-controlled, crossover trial. Anesthesiology. 2002;96:841-8.	~30		^** ****** Missing data.		^** ****** Missing data.		^** ****** Missing data.		^** ****** Missing data.			4

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[1] * Corresponding author. E-mail: maifsmr@hotmail.com (M.F. de Souza).