Lidocaine and Prevention of Chronic Pain

• ClinicalTrials.gov Identifier: NCT01619852
• Recruitment Status: Completed
• First Posted: June 14, 2012
• Results First Posted: November 27, 2019
• Last Update Posted: November 27, 2019
• Sponsor: Northwestern University
• Information provided by (Responsible Party): Gildasio De Oliveira, Northwestern University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Surgery
• Interventions: Drug: .9 normal saline placebo; Drug: Group L (lidocaine)
• Enrollment: 148

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Lidocaine (Group L)	.9% Normal Saline Placebo
Arm/Group Description	Lidocaine (Group L) will receive a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2mg/kg/hr infusion that will be started at the time of surgical induction and will be discontinued one hour after the end of the surgical procedure.	.9% normal saline administered as a bolus then as a maintenance infusion for the length of the surgical case. .9 normal saline placebo: Administration of .9 normal saline placebo as a bolus and as maintenance throughout the length of the surgical procedure.
Period Title: 24 Hour Assessment
Started	75	75
Completed	74	74
Not Completed	1	1
Reason Not Completed
Withdrawal by Subject	1	1
Period Title: 3 Month Follow up
Started	74	74
Completed	43	40
Not Completed	31	34
Reason Not Completed
Lost to Follow-up	31	34

Baseline Characteristics

Arm/Group Title		Group L	.9% Normal Saline Placebo	Total
Arm/Group Description		Group L will receive a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2mg/kg/hr infusion that will be started at the time of surgical induction and will be discontinued one hour after the end of the surgical procedure. Group L (lidocaine): Group L will receive a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2mg/kg/hr infusion that will be started at the time of surgical induction and will be discontinued one hour after the end of the surgical procedure.	.9% normal saline administered as a bolus then as a maintenance infusion for the length of the surgical case. .9 normal saline placebo: Administration of .9 normal saline placebo as a bolus and as maintenance throughout the length of the surgical procedure.	Total of all reporting groups
Overall Number of Baseline Participants		75	75	150
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	75 participants	75 participants	150 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	75 100.0%	75 100.0%	150 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	75 participants	75 participants	150 participants
	Female	75 100.0%	75 100.0%	150 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	75 participants	75 participants	150 participants
White		58	60	118
African American		12	10	22
Asian		2	3	5
Hispanic		2	2	4
Other		1	0	1
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	75 participants	75 participants	150 participants
		75	75	150
Body Mass Index (BMI) [1]; Mean (Full Range); Unit of measure: Kg/mg^2
	Number Analyzed	75 participants	75 participants	150 participants
		24; (21 to 29)	25; (22 to 30)	24.5; (21 to 30)
		[1] Measure Description: BMI =(weight in kilograms) / height in meters²

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Chronic Persistent Pain 3 Months After Surgery as Determined by Character Severity (Yes/no).
Description	The participants development of chronic persistent pain 3 months after surgery as determined by character severity (yes/no).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group L	.9% Normal Saline Placebo
Arm/Group Description:	Group L will receive a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2mg/kg/hr infusion that will be started at the time of surgical induction and will be discontinued one hour after the end of the surgical procedure. Group L (lidocaine): Group L will receive a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2mg/kg/hr infusion that will be started at the time of surgical induction and will be discontinued one hour after the end of the surgical procedure.	.9% normal saline administered as a bolus then as a maintenance infusion for the length of the surgical case. .9 normal saline placebo: Administration of .9 normal saline placebo as a bolus and as maintenance throughout the length of the surgical procedure.
Overall Number of Participants Analyzed	43	40
Measure Type: Number; Unit of Measure: participants
	2	6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group L, .9% Normal Saline Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.19
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

2. Secondary Outcome

Title	Quality of Recovery
Description	Quality of recovery (QoR-40 instrument) is a 40-item questionnaire that provides a global score and sub-scores across five dimensions: patient support, comfort, emotions, physical independence, and pain. Score range: 40 to 200. A score of 40 demonstrates poor recovery and a maximum score of 200 represents good recovery. The higher the score the better recovery after surgery.
Time Frame	24 hours post operative

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lidocaine (Group L)	.9% Normal Saline Placebo
Arm/Group Description:	Lidocaine (Group L) will receive a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2mg/kg/hr infusion that will be started at the time of surgical induction and will be discontinued one hour after the end of the surgical procedure. Lidocaine (Group L): will receive a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2mg/kg/hr infusion that will be started at the time of surgical induction and will be discontinued one hour after the end of the surgical procedure.	.9% normal saline administered as a bolus then as a maintenance infusion for the length of the surgical case. .9 normal saline placebo: Administration of .9 normal saline placebo as a bolus and as maintenance throughout the length of the surgical procedure.
Overall Number of Participants Analyzed	74	74
Median (Inter-Quartile Range); Unit of Measure: units on a scale
	158; (147 to 178)	169; (151 to 176)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lidocaine (Group L), .9% Normal Saline Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.64
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

3. Secondary Outcome

Title	Post-surgical Persistent Pain Using Validated Questionnaires (S-LANNS Questionnaire, McGill Questionnaire, Brief Pain Inventory) to Assess Pain Qualities in Accordance With IMMPACT Recommendations.
Description	The development of chronic pain 3 months after surgery determined by the Leads Assessment of Neuropathic Symptoms and Signs (LANSS) scale, a valid 7-item tool for identifying patients whose pain is dominated by neuropathic mechanisms. Each item is a binary response (yes or no) to the presence of symptoms (5 items) or clinical signs (2 items), range 0-24 points. A score ≥ 12, neuropathic mechanisms are likely to be contributing to the patient's pain. A score < 12 is unlikely to be contributing. McGill questionnaire (Sensory domain) - 11 descriptors rated on an intensity scale as 0=none, 1=mild, 2=moderate, 3=severe. The higher the score, greater the pain (range 0-33). McGill questionnaire (Motivational-affective) 4 affect descriptors rated on an intensity scale as 0=none, 1=mild, 2=moderate, 3=severe.The higher the score the greater the pain (range 0-12) Brief pain inventory - pain severity (0, no pain, 10 excruciating pain); Greater the score; greater the pain (range 0-10).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group L	.9% Normal Saline Placebo
Arm/Group Description:	Group L will receive a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2mg/kg/hr infusion that will be started at the time of surgical induction and will be discontinued one hour after the end of the surgical procedure. Group L (lidocaine): Group L will receive a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2mg/kg/hr infusion that will be started at the time of surgical induction and will be discontinued one hour after the end of the surgical procedure.	.9% normal saline administered as a bolus then as a maintenance infusion for the length of the surgical case. .9 normal saline placebo: Administration of .9 normal saline placebo as a bolus and as maintenance throughout the length of the surgical procedure.
Overall Number of Participants Analyzed	43	40
Median (Inter-Quartile Range); Unit of Measure: units on a scale
S-LANNS	3; (0 to 10)	3; (0 to 8)
McGill Questionaire-Sensory Discrimation	4; (1 to 7)	3; (1 to 7)
McGill Questionaire-Motivational-affective	0; (0 to 1)	0; (0 to 2)
Brief Pain Inventory	1; (0 to 3)	1; (0 to 3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group L, .9% Normal Saline Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.68
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group L, .9% Normal Saline Placebo
	Comments	McGill Questionnaire-Sensory-discriminative dimension
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.69
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group L, .9% Normal Saline Placebo
	Comments	McGill Questionnaire-affective dimension
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.75
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Group L, .9% Normal Saline Placebo
	Comments	Brief Pain Inventory
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.81
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

4. Secondary Outcome

Title	Opioid Consumption
Description	The amount of opioid analgesics consumed was converted to an equivalent dose of intravenous morphine.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group L	.9% Normal Saline Placebo
Arm/Group Description:	Group L will receive a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2mg/kg/hr infusion that will be started at the time of surgical induction and will be discontinued one hour after the end of the surgical procedure. Group L (lidocaine): Group L will receive a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2mg/kg/hr infusion that will be started at the time of surgical induction and will be discontinued one hour after the end of the surgical procedure.	.9% normal saline administered as a bolus then as a maintenance infusion for the length of the surgical case. .9 normal saline placebo: Administration of .9 normal saline placebo as a bolus and as maintenance throughout the length of the surgical procedure.
Overall Number of Participants Analyzed	74	74
Median (Inter-Quartile Range); Unit of Measure: equivalent dose of intravenous morphine
	34; (17 to 46)	39; (21 to 57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group L, .9% Normal Saline Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.19
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

5. Secondary Outcome

Title	Postoperative Pain
Description	Postoperative pain within the first 24 hours. Area under the numeric rating scale for pain versus time curve during the first 24 hours after surgery (score * hr). Numeric rating scale for pain on a scale of 0-10 (0 is no pain and 10 is high pain) versus time curve during the first 24 hours ( score * hr). The pain scores were collected upon arrival to recovery area, 30 minutes, 1 hour and every 6 hours up to 24 hours following the procedure. Minimum score is 60, Maximum score is 170. A higher value indicates more pain.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group L	.9% Normal Saline Placebo
Arm/Group Description:	Group L will receive a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2mg/kg/hr infusion that will be started at the time of surgical induction and will be discontinued one hour after the end of the surgical procedure. Group L (lidocaine): Group L will receive a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2mg/kg/hr infusion that will be started at the time of surgical induction and will be discontinued one hour after the end of the surgical procedure.	.9% normal saline administered as a bolus then as a maintenance infusion for the length of the surgical case. .9 normal saline placebo: Administration of .9 normal saline placebo as a bolus and as maintenance throughout the length of the surgical procedure.
Overall Number of Participants Analyzed	74	74
Median (Inter-Quartile Range); Unit of Measure: score on a scale
	116; (88 to 142)	119; (91 to 148)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group L, .9% Normal Saline Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.29
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Adverse Events

Time Frame	24 hours after surgery completion.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Group L	.9% Normal Saline Placebo
Arm/Group Description	Group L will receive a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2mg/kg/hr infusion that will be started at the time of surgical induction and will be discontinued one hour after the end of the surgical procedure. Group L (lidocaine): Group L will receive a 1.5 mg/kg bolus of intravenous lidocaine followed by a 2mg/kg/hr infusion that will be started at the time of surgical induction and will be discontinued one hour after the end of the surgical procedure.	.9% normal saline administered as a bolus then as a maintenance infusion for the length of the surgical case. .9 normal saline placebo: Administration of .9 normal saline placebo as a bolus and as maintenance throughout the length of the surgical procedure.
All-Cause Mortality
	Group L	.9% Normal Saline Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Group L	.9% Normal Saline Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/74 (0.00%)	0/74 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Group L	.9% Normal Saline Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/74 (0.00%)	0/74 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Gildasio De Oliveira, M.D.
• Organization: Northwestern University
• Phone: 312-695-4858
• EMail: gjr@northwestern.edu

Publications:

1) Eric J. Visser. Chronic post-surgical pain: Epidemiology and clinical implications for acute pain management. Acute Pain.2006:8; 73-81

Phillips CJ, Harper C. The economics associated with persistent pain. Curr Opin Support Palliat Care. 2011 Jun;5(2):127-30. doi: 10.1097/SPC.0b013e3283458fa9. Review.

Amr YM, Yousef AA. Evaluation of efficacy of the perioperative administration of Venlafaxine or gabapentin on acute and chronic postmastectomy pain. Clin J Pain. 2010 Jun;26(5):381-5. doi: 10.1097/AJP.0b013e3181cb406e.

Vigneault L, Turgeon AF, Côté D, Lauzier F, Zarychanski R, Moore L, McIntyre LA, Nicole PC, Fergusson DA. Perioperative intravenous lidocaine infusion for postoperative pain control: a meta-analysis of randomized controlled trials. Can J Anaesth. 2011 Jan;58(1):22-37. doi: 10.1007/s12630-010-9407-0. Review.

Attal N, Gaudé V, Brasseur L, Dupuy M, Guirimand F, Parker F, Bouhassira D. Intravenous lidocaine in central pain: a double-blind, placebo-controlled, psychophysical study. Neurology. 2000 Feb 8;54(3):564-74.

• Responsible Party: Gildasio De Oliveira, Northwestern University
• ClinicalTrials.gov Identifier: NCT01619852
• Other Study ID Numbers: STU00061676
• First Submitted: June 12, 2012
• First Posted: June 14, 2012
• Results First Submitted: January 25, 2016
• Results First Posted: November 27, 2019
• Last Update Posted: November 27, 2019