Lidocaine and Prevention of Chronic Pain

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01619852
• Collaborator: (none)
• Enrollment: 148
• Location: 1
• Arms: 2
• Duration (Months): 31
• Patients Per Site Per Month: 4.8

Study Details

Study Description

Brief Summary

The study seeks to investigate a safe and inexpensive strategy to reduce persistent post-surgical pain that can affect up to 60% of patients undergoing surgical procedures.

Hypotheses: Perioperative systemic lidocaine reduces the persistence of chronic pain in patients undergoing surgical procedures.

Condition or Disease	Intervention/Treatment	Phase
Surgery	Drug: .9 normal saline placebo; Drug: Group L (lidocaine)	N/A

Detailed Description

After approval from Northwestern University's IRB, female subjects undergoing urologic, gynecologic or breast surgery will be included in the study. Informed consent will be obtained from all participants. Subject will be randomized using a computer generated table of random numbers into two groups: 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 P will receive the same amount of saline in the same fashion. This dose regimen of systemic lidocaine chosen in the current study has been consistently associated with a reduction of acute postoperative pain.4 There will be no visual characteristic differences between any of the infusions studied and they will all be labeled as a study drug. Patients will receive a standard anesthetic regimen consisting of propofol, fentanyl, succinylcholine, and sevoflurane. Patients will receive ondansetron 4mg and dexamethasone 4 mg to prevent postoperative nausea and vomiting. They will also receive 10 mcg/kg of hydromorphone at the end of surgery to prevent postoperative pain. In the PACU, patients will receive additional doses of hydromorphone to keep pain <4/10 (on a scale where 0 means no pain and 10 is the worst pain possible). On PACU discharge, patients will receive a patient-controlled IV hydromorphone analgesia pump set at 0.2mg IV bolus, no basal infusion and a lockout time of 15 minutes. The intraoperative and postoperative data (pain scores, opioid consumption, side effects) will be collected by a research assistant blinded to the group allocation). Other data collection variables include : Preoperative (Age, BMI, ethnicity, comorbidities, preoperative medication(s), psychiatric disease, pain in the operative area, pain at other locations), Intraoperative (description of surgical procedure, surgical duration, surgical procedure on nerve areas, preservation of the nerves in the operative area nerve, indication for the surgical procedure, intraoperative opioids dose, and Postoperative pain instruments (evaluation of early pain, twenty four hour opioid consumption, drugs and other treatments used in the postoperative period.

QOR 40 questionnaire will be completed by the participant at 24 hours after surgery if they have not been discharged from the hospital. If they have been discharged, the research assistant will contact the participant by telephone to complete the questionnaire.

Patients will be evaluated for the presence and severity of chronic pain as well as the quality of life impact of pain at baseline, three and six months after surgery using a validated instrument in accordance with the IMMPACT recommendations to assess chronic pain and its impact on the patient's quality of life (Brief pain Inventory).8 To characterize the chronic pain, both the short form McGill pain questionnaire and the Modified LANNS scale will be also administered at three and six months.9,10 If there is no response to the 3 month questionnaire, the subject will be contacted by telephone to complete the questionnaire.

Subjects who are experiencing suicidal ideation will be referred to Northwestern Memorial Hospital Emergency Department. The primary care surgeon will also be notified by the principal investigator. Mood will be assessed using the Beck Depression Inventory.14

Study Design

• Study Type: Interventional
• Actual Enrollment: 148 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: The Effect of Lidocaine to Prevent the Development of Chronic Post-Surgical Pain
• Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group L 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.	Drug: 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.
Placebo Comparator: .9% normal saline placebo .9% normal saline administered as a bolus then as a maintenance infusion for the length of the surgical case.	Drug: .9 normal saline placebo; Administration of .9 normal saline placebo as a bolus and as maintenance throughout the length of the surgical procedure.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Chronic Persistent Pain 3 Months After Surgery as Determined by Character Severity (Yes/no). [3 months]

   The participants development of chronic persistent pain 3 months after surgery as determined by character severity (yes/no).

Secondary Outcome Measures

1. Quality of Recovery [24 hours post operative]

   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.

2. Post-surgical Persistent Pain Using Validated Questionnaires (S-LANNS Questionnaire, McGill Questionnaire, Brief Pain Inventory) to Assess Pain Qualities in Accordance With IMMPACT Recommendations. [3 months]

   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).

3. Opioid Consumption [24 hours]

   The amount of opioid analgesics consumed was converted to an equivalent dose of intravenous morphine.

4. Postoperative Pain [24 hours]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18-64,

• Females undergoing gynecological, urological or breast surgery

Exclusion Criteria:

• pregnant,

• history of chronic use of opioids,

• allergy to local anesthetics,

• history of cardiac arrhythmias Drop out: patient or surgeon request

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Prentice Womens' Hospital	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University

Investigators

• Principal Investigator: Gildasio De Oliveira, M.D., Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

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

• Responsible Party: Gildasio De Oliveira, Principal Investigator, Northwestern University
• ClinicalTrials.gov Identifier: NCT01619852
• Other Study ID Numbers: STU00061676
• First Posted: Jun 14, 2012
• Last Update Posted: Nov 27, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Gildasio De Oliveira, Principal Investigator, Northwestern University: Surgery; Breast; Pain; Chronic Pain; Lidocaine; Anesthesia; Gynecologic; Urologic
• Additional relevant MeSH terms: Chronic Pain; Lidocaine

Study Results

Participant Flow

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
Period Title: 24 Hour Assessment
STARTED	74	74
COMPLETED	43	40
NOT COMPLETED	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 Participants	75	75	150
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	75 100%	75 100%	150 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	75 100%	75 100%	150 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
White	58 77.3%	60 80%	118 78.7%
African American	12 16%	10 13.3%	22 14.7%
Asian	2 2.7%	3 4%	5 3.3%
Hispanic	2 2.7%	2 2.7%	4 2.7%
Other	1 1.3%	0 0%	1 0.7%
Region of Enrollment (participants) [Number]
United States	75 100%	75 100%	150 100%
Body Mass Index (BMI) (kg/mg^2) [Mean (Full Range) ]
Mean (Full Range) [kg/mg^2]	24	25	24.5

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.
Measure Participants	43	40
Number [participants]	2 2.7%	6 8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group L, .9% Normal Saline Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	.19
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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.
Measure Participants	74	74
Median (Inter-Quartile Range) [units on a scale]	158	169

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group L, .9% Normal Saline Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.64
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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.
Measure Participants	43	40
S-LANNS	3	3
McGill Questionaire-Sensory Discrimation	4	3
McGill Questionaire-Motivational-affective	0	0
Brief Pain Inventory	1	1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group L, .9% Normal Saline Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.68
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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
Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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
Statistical Test of Hypothesis	p-Value	0.75
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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
Statistical Test of Hypothesis	p-Value	0.81
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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.
Measure Participants	74	74
Median (Inter-Quartile Range) [equivalent dose of intravenous morphine]	34	39

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group L, .9% Normal Saline Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	.19
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

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.
Measure Participants	74	74
Median (Inter-Quartile Range) [score on a scale]	116	119

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group L, .9% Normal Saline Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	.29
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	24 hours after surgery completion.
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Group L		.9% Normal Saline Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/74 (0%)		0/74 (0%)
Other (Not Including Serious) Adverse Events
	Group L		.9% Normal Saline Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/74 (0%)		0/74 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.