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Lidocaine and Ketamine in Abdominal Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00721110
Recruitment Status : Terminated (Futility)
First Posted : July 23, 2008
Results First Posted : July 26, 2017
Last Update Posted : July 26, 2017
Sponsor:
Information provided by (Responsible Party):
The Cleveland Clinic

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Abdominal Hysterectomy (& Wertheim)
Interventions Drug: Lidocaine
Drug: Placebo
Drug: Ketamine
Drug: Ketamine + Lidocaine
Enrollment 64
Recruitment Details  
Pre-assignment Details This is a factorial study design with 64 patients randomized to 2 treatments each: lidocaine or placebo and ketamine or placebo. Each treatment was analyzed separately (i.e., lidocaine versus placebo and ketamine versus placebo separately). Though there are 4 distinct groups, the same 64 patients are in both lidocaine and ketamine analyses.
Arm/Group Title Lidocaine/Ketamine Lidocaine Ketamine Placebo
Hide Arm/Group Description

Intravenous Lidocaine + Ketamine Group

Lidocaine was given as a bolus (1.5 mg/kg), followed by an infusion of 2 mg/kg/h for the first 2 hours, and then 1.2 mg/kg/h for 24 postoperative hours.

Ketamine was given as a bolus (0.35 mg/kg), followed by ketamine infusion of 0.2 mg/kg/h for the first 2 hours, and then 0.12 mg/kg/h for 24 postoperative hours.

Medication doses were based on actual patient body weight to a maximum of 150% of ideal body weight based on the formula: 49 kg + 0.6 kg for each centimeter of height exceeding 152 centimeters

Intravenous lidocaine Group - Lidocaine was given as a bolus (1.5 mg/kg), followed by an infusion of 2 mg/kg/h for the first 2 hours, and then 1.2 mg/kg/h for 24 postoperative hours.

Intravenous Ketamine Group - Ketamine is administered intravenously throughout surgery and during the 24 hours following surgery

Ketamine: Upon induction of anesthesia, a bolus of ketamine (0.25mg/kg) will be given followed by an infusion of ketamine (0.25mg/kg/hour) up to 25 mg/hour. The ketamine infusion will be reduced to 0.12 mg/kg/hour up to a maximum of 12 mg/hour at skin closure and discontinued 24 hours postoperatively.

A placebo is administered intravenously throughout surgery and during the 24 hours after surgery.

A placebo infusion will be substituted for the ketamine or lidocaine not given

Period Title: Overall Study
Started 16 16 16 16
Completed 15 16 15 16
Not Completed 1 0 1 0
Reason Not Completed
Ultram use             1             0             0             0
vertical incision             0             0             1             0
Arm/Group Title Lidocaine/Ketamine Lidocaine Ketamine Placebo Total
Hide Arm/Group Description

Intravenous Lidocaine and Ketamine Group -

Lidocaine was given as a bolus (1.5 mg/kg), followed by an infusion of 2 mg/kg/h for the first 2 hours, and then 1.2 mg/kg/h for 24 postoperative hours. Ketamine was given as a bolus (0.35 mg/kg), followed by ketamine infusion of 0.2 mg/kg/h for the first 2 hours, and then 0.12 mg/kg/h for 24 postoperative hours. Medication doses were based on actual patient body weight to a maximum of 150% of ideal body weight based on the formula: 49 kg + 0.6 kg for each centimeter of height exceeding 152 centimeters.

Intravenous lidocaine Group - A lidocaine is administered intravenously through out surgery and 24 hours after surgery.

Lidocaine was given as a bolus (1.5 mg/kg), followed by an infusion of 2 mg/kg/h for the first 2 hours, and then 1.2 mg/kg/h for 24 postoperative hours.

Intravenous Ketamine Group - Ketamine is administered intravenously throughout surgery and during the 24 hours following surgery

Ketamine: Upon induction of anesthesia, a bolus of ketamine (0.25mg/kg) will be given followed by an infusion of ketamine (0.25mg/kg/hour) up to 25 mg/hour. The ketamine infusion will be reduced to 0.12 mg/kg/hour up to a maximum of 12 mg/hour at skin closure and discontinued 24 hours postoperatively.

A placebo is administered intravenously throughout surgery and during the 24 hours after surgery.

A placebo infusion will be substituted for the ketamine or Lidocaine not given

Total of all reporting groups
Overall Number of Baseline Participants 15 16 15 16 62
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 16 participants 15 participants 16 participants 62 participants
46  (7) 46  (7) 46  (9) 47  (8) 46  (8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 16 participants 15 participants 16 participants 62 participants
Female
15
 100.0%
16
 100.0%
15
 100.0%
16
 100.0%
62
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
American Society of Anesthesiologists Physical Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 16 participants 15 participants 16 participants 62 participants
A normal healthy patient 0 0 2 0 2
A patient with mild systemic disease 14 13 10 15 52
A patient with severe systemic disease 1 3 3 1 8
[1]
Measure Description:

American Society of Anesthesiologists Physical Status applied to each patient ranging from I to VI. The scale is defined as follows:

I: A normal healthy patient II: A patient with mild systemic disease III: A patient with severe systemic disease IV: A patient with severe systemic disease that is a constant threat to life V: A moribund patient who is not expected to survive without the operation VI: A declared brain-dead patient whose organs are being removed for donor purposes

Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg per meters squared
Number Analyzed 15 participants 16 participants 15 participants 16 participants 62 participants
28  (6) 29  (6) 29  (10) 28  (6) 29  (7)
Preoperative 6-MWD  
Mean (Standard Deviation)
Unit of measure:  m
Number Analyzed 15 participants 16 participants 15 participants 16 participants 62 participants
318  (47) 320  (44) 304  (41) 338  (52) 320  (47)
1.Primary Outcome
Title The Effects of Lidocaine and Ketamine on Functional Recovery Assessed by 6 Minute Walk Test on Postoperative Day Two
Hide Description The effects of lidocaine and ketamine on functional recovery assessed by 6 minute walk test on postoperative day two after hysterectomy. This outcome measures return to ambulation after surgery.
Time Frame postoperative day 2
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Lidocaine Nonlidocaine Ketamine Nonketamine
Hide Arm/Group Description:

Intravenous Lidocaine Group - Lidocaine is administered intravenously throughout surgery and during the 24 hours following surgery

Lidocaine: Upon general anesthesia induction, lidocaine (1.5 mg/kg) will be given. Lidocaine infusion of 2 mg/kg/hour, to a maximum of 200 mg/hour during The lidocaine infusion will be reduced to 1.3 mg/kg/hour, to a maximum of 133 mg/hour, at skin closure and discontinued 24 hours postoperatively.

Intravenous Nonlidocaine Group - A lidocaine placebo is administered intravenously through out surgery and 24 hours after surgery.

Placebo boluses and infusions will be substituted for the lidocaine

Intravenous Ketamine Group - Ketamine is administered intravenously throughout surgery and during the 24 hours following surgery

Ketamine: Upon induction of anesthesia, a bolus of ketamine (0.25mg/kg) will be given followed by an infusion of ketamine (0.25mg/kg/hour) up to 25 mg/hour. The ketamine infusion will be reduced to 0.12 mg/kg/hour up to a maximum of 12 mg/hour at skin closure and discontinued 24 hours postoperatively.

A ketamine placebo is administered intravenously throughout surgery and during the 24 hours after surgery.

A placebo infusion will be substituted for the ketamine not given

Overall Number of Participants Analyzed 31 31 30 32
Mean (Standard Deviation)
Unit of Measure: meters
202  (66) 202  (73) 193  (77) 210  (61)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lidocaine, Nonlidocaine
Comments The effect of lidocaine on 6-minute walk distance on the 2nd postoperative morning was assessed using analysis of covariance. We expected the control group's mean 6-minute walk distance to be 300 meters with a standard deviation (SD) of about 20% of the mean for each group. Assuming a correlation of 0.5 between baseline and 2nd postoperative day, a maximum 128 total patients (32 for each group) was needed to have 80% power at the 0.025 significance level to detect effects of 36 meters or more.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.96
Comments Significant if P < 0.003 for efficacy and P > 0.5311 for futility; 97.5% confidence intervals adjusted for group sequential design to maintain the overall alpha of 0.025 for each primary intervention.
Method ANCOVA
Comments Adjusted for baseline 6-minute walk distance
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.93
Confidence Interval (2-Sided) 97.5%
-52 to 54
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ketamine, Nonketamine
Comments The effect of ketamine on 6-minute walk distance on the 2nd postoperative morning was assessed using analysis of covariance. We expected the control group's mean 6-minute walk distance to be 300 meters with a standard deviation (SD) of about 20% of the mean for each group. Assuming a correlation of 0.5 between baseline and 2nd postoperative day, a maximum 128 total patients (32 for each group) was needed to have 80% power at the 0.025 significance level to detect effects of 36 meters or more.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.54
Comments 97.5% confidence interval adjusted for group sequential design (using confidence coefficient of 2.97) to maintain theoverall α of 0.025 for each primary intervention and 0.05 for the trial.
Method ANCOVA
Comments Adjusted for baseline 6-minute walk distance
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -11
Confidence Interval (2-Sided) 97.5%
-65 to 44
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Verbal Response Pain Scores (VRS) at PACU Admission and Discharge as Well as Mornings and Afternoons of Postoperative Days 1 and 2
Hide Description Verbal response pain scores (VRS) at PACU admission and discharge as well as mornings and afternoons of postoperative days 1 and 2. VRS scale ranges from 0 to 10, with 0 denoting no pain and 10 denoting worst possible pain.
Time Frame PACU admission and discharge, postoperative mornings and afternoons on days 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Lidocaine Nonlidocaine Ketamine Nonketamine
Hide Arm/Group Description:

Intravenous Lidocaine Group - Lidocaine is administered intravenously throughout surgery and during the 24 hours following surgery

Lidocaine: Upon general anesthesia induction, lidocaine (1.5 mg/kg) will be given. Lidocaine infusion of 2 mg/kg/hour, to a maximum of 200 mg/hour during The lidocaine infusion will be reduced to 1.3 mg/kg/hour, to a maximum of 133 mg/hour, at skin closure and discontinued 24 hours postoperatively.

Intravenous Nonlidocaine Group - A lidocaine placebo is administered intravenously through out surgery and 24 hours after surgery.

Placebo boluses and infusions will be substituted for the lidocaine

Intravenous Ketamine Group - Ketamine is administered intravenously throughout surgery and during the 24 hours following surgery

Ketamine: Upon induction of anesthesia, a bolus of ketamine (0.25mg/kg) will be given followed by an infusion of ketamine (0.25mg/kg/hour) up to 25 mg/hour. The ketamine infusion will be reduced to 0.12 mg/kg/hour up to a maximum of 12 mg/hour at skin closure and discontinued 24 hours postoperatively.

A ketamine placebo is administered intravenously throughout surgery and during the 24 hours after surgery.

A placebo infusion will be substituted for the ketamine not given

Overall Number of Participants Analyzed 31 31 30 32
Mean (Standard Deviation)
Unit of Measure: units on a scale
PACU admit 6.2  (3.3) 7.1  (2.5) 6.4  (3.4) 6.9  (2.5)
PACU discharge 4.0  (2.3) 4.9  (1.9) 4.6  (2.4) 4.3  (1.9)
POD 1 4.0  (1.8) 3.3  (2.2) 3.7  (2.2) 3.6  (1.7)
POD 2 3.1  (1.7) 2.9  (1.9) 3.1  (2.1) 2.8  (1.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lidocaine, Nonlidocaine
Comments Groups compared on VRS scores at PACU admit using a t test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.20
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.0
Confidence Interval (2-Sided) 97.5%
-3.3 to 1.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ketamine, Nonketamine
Comments Ketamine compared to placebo at PACU admit using a t test
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.54
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 97.5%
-2.8 to 1.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lidocaine, Nonlidocaine
Comments Lidocaine versus nonlidocaine on pain severity at postoperative care unit discharge was assessed using a t test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.9
Confidence Interval (2-Sided) 97.5%
-2.5 to 0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ketamine, Nonketamine
Comments Ketamine versus nonketamine on postoperative care unit discharge pain severity was assessed using a t test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.56
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 97.5%
-1.4 to 2.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lidocaine, Nonlidocaine
Comments Lidocaine versus nonlidocaine on postoperative day 1 pain severity assessed using a t test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.20
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.6
Confidence Interval (2-Sided) 97.5%
-0.9 to 2.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ketamine, Nonketamine
Comments Ketamine versus nonketamine on postoperative day 1 pain severity was assessed using a t test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.79
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 97.5%
-1.4 to 1.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lidocaine, Nonlidocaine
Comments Lidocaine versus nonlidocaine on postoperative day 2 pain severity was assessed using a t test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.55
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 97.5%
-1.1 to 1.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Ketamine, Nonketamine
Comments Ketamine versus nonketamine on postoperative day 2 pain severity was assessed using a t test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 97.5%
-1.1 to 1.8
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Total Opioid Consumption at PACU Admission and Discharge as Well as Mornings of Postoperative Days 1 and 2
Hide Description [Not Specified]
Time Frame intraoperative through postoperative day 2
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Lidocaine Nonlidocaine Ketamine Nonketamine
Hide Arm/Group Description:

Intravenous Lidocaine Group - Lidocaine is administered intravenously throughout surgery and during the 24 hours following surgery

Lidocaine: Upon general anesthesia induction, lidocaine (1.5 mg/kg) will be given. Lidocaine infusion of 2 mg/kg/hour, to a maximum of 200 mg/hour during The lidocaine infusion will be reduced to 1.3 mg/kg/hour, to a maximum of 133 mg/hour, at skin closure and discontinued 24 hours postoperatively.

Intravenous Nonlidocaine Group - A lidocaine placebo is administered intravenously through out surgery and 24 hours after surgery.

Placebo boluses and infusions will be substituted for the lidocaine

Intravenous Ketamine Group - Ketamine is administered intravenously throughout surgery and during the 24 hours following surgery

Ketamine: Upon induction of anesthesia, a bolus of ketamine (0.25mg/kg) will be given followed by an infusion of ketamine (0.25mg/kg/hour) up to 25 mg/hour. The ketamine infusion will be reduced to 0.12 mg/kg/hour up to a maximum of 12 mg/hour at skin closure and discontinued 24 hours postoperatively.

A ketamine placebo is administered intravenously throughout surgery and during the 24 hours after surgery.

A placebo infusion will be substituted for the ketamine not given

Overall Number of Participants Analyzed 31 31 30 32
Median (Inter-Quartile Range)
Unit of Measure: milligram morphine sulfate equivalents
intraoperative
20
(15 to 30)
20
(19 to 30)
20
(15 to 26)
23
(20 to 30)
postoperative care unit
20
(7 to 27)
23
(18 to 27)
20
(7 to 27)
23
(19 to 27)
postoperative day 1
23
(15 to 48)
22
(13 to 50)
21
(12 to 48)
23
(17 to 47)
postoperative day 2
10
(3 to 18)
6
(2 to 15)
9
(3 to 20)
8
(3 to 14)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lidocaine, Nonlidocaine
Comments Lidocaine versus nonlidocaine on intraoperative opioid consumption was assessed using the Wilcoxon rank sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.63
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0
Confidence Interval (2-Sided) 97.5%
-7 to 7
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ketamine, Nonketamine
Comments Ketamine versus nonketamine on intraoperative opioid consumption was assessed using a Wilcoxon rank sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.27
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -2
Confidence Interval (2-Sided) 97.5%
-10 to 5
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lidocaine, Nonlidocaine
Comments Lidocaine versus nonlidocaine on postoperative care unit opioid consumption was assessed using a Wilcoxon rank sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -3
Confidence Interval (2-Sided) 97.5%
-15 to 5
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ketamine, Nonketamine
Comments Ketamine versus nonketamine on postoperative care unit opioid consumption was assessed using a Wilcoxon rank sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -4
Confidence Interval (2-Sided) 97.5%
-15 to 4
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lidocaine, Nonlidocaine
Comments Lidocaine versus nonlidocaine on postoperative day 1 opioid consumption was assessed using a Wilcoxon rank sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.76
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 2.5
Confidence Interval (2-Sided) 97.5%
-13 to 21
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ketamine, Nonketamine
Comments Ketamine versus nonketamine on postoperative day 1 opioid consumption was assessed using a Wilcoxon rank sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.66
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -3
Confidence Interval (2-Sided) 97.5%
-19 to 14
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lidocaine, Nonlidocaine
Comments Lidocaine versus nonlidocaine on postoperative day 2 opioid consumption was assessed using a Wilcoxon rank sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 2.5
Confidence Interval (2-Sided) 97.5%
-5 to 10
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Ketamine, Nonketamine
Comments Ketamine versus nonketamine on postoperative day 2 opioid consumption was assessed using a Wilcoxon rank sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.79
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0
Confidence Interval (2-Sided) 97.5%
-5 to 8
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Presence of Nausea and Vomiting After Two Hours in the PACU and the First Postoperative Day
Hide Description [Not Specified]
Time Frame 2 hours after surgery, on postoperative day 1
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Lidocaine Nonlidocaine Ketamine Nonketamine
Hide Arm/Group Description:

Intravenous Lidocaine Group - Lidocaine is administered intravenously throughout surgery and during the 24 hours following surgery

Lidocaine: Upon general anesthesia induction, lidocaine (1.5 mg/kg) will be given. Lidocaine infusion of 2 mg/kg/hour, to a maximum of 200 mg/hour during The lidocaine infusion will be reduced to 1.3 mg/kg/hour, to a maximum of 133 mg/hour, at skin closure and discontinued 24 hours postoperatively.

Intravenous Nonlidocaine Group - A lidocaine placebo is administered intravenously through out surgery and 24 hours after surgery.

Placebo boluses and infusions will be substituted for the lidocaine

Intravenous Ketamine Group - Ketamine is administered intravenously throughout surgery and during the 24 hours following surgery

Ketamine: Upon induction of anesthesia, a bolus of ketamine (0.25mg/kg) will be given followed by an infusion of ketamine (0.25mg/kg/hour) up to 25 mg/hour. The ketamine infusion will be reduced to 0.12 mg/kg/hour up to a maximum of 12 mg/hour at skin closure and discontinued 24 hours postoperatively.

A ketamine placebo is administered intravenously throughout surgery and during the 24 hours after surgery.

A placebo infusion will be substituted for the ketamine not given

Overall Number of Participants Analyzed 31 31 30 32
Measure Type: Number
Unit of Measure: percentage of participants
Nausea, PACU 32 26 30 28
Nausea, POD 1 55 48 53 50
Vomiting, PACU 6 19 10 16
Vomiting, POD 1 23 16 23 16
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lidocaine, Nonlidocaine
Comments Lidocaine versus nonlidocaine on PACU (postoperative care unit) nausea assessed using Pearson chi square test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.58
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.06
Confidence Interval (2-Sided) 97.5%
-0.28 to 0.41
Estimation Comments numerator: lidocaine; denominator: control
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ketamine, Nonketamine
Comments Ketamine versus nonketamine on PACU (postoperative care unit) nausea assessed using Pearson chi square test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.87
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.02
Confidence Interval (2-Sided) 97.5%
-0.32 to 0.36
Estimation Comments Numinator: ketamine; denominator: nonketamine
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lidocaine, Nonlidocaine
Comments Lidocaine versus nonlidocaine on POD 1 (first postoperative day) nausea assessed using Pearson chi square test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.61
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.06
Confidence Interval (2-Sided) 97.5%
-0.31 to 0.44
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ketamine, Nonketamine
Comments Ketamine versus nonketamine on POD 1(first postoperative day) nausea assessed using Pearson chi square test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.79
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.03
Confidence Interval (2-Sided) 97.5%
-0.34 to 0.41
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lidocaine, Nonlidocaine
Comments Lidocaine versus nonlidocaine on PACU (postoperative care unit) vomiting assessed using Pearson chi square test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.26
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value -0.13
Confidence Interval (2-Sided) 97.5%
-0.38 to 0.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ketamine, Nonketamine
Comments Ketamine versus nonketamine on PACU (postoperative care unit) vomiting assessed using a Pearson chi square test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.71
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value -0.06
Confidence Interval (2-Sided) 97.5%
-0.31 to 0.19
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lidocaine, Nonlidocaine
Comments Lidocaine versus nonlidocaine on postoperative day 1 vomiting assessed using a Pearson chi square test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.52
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.06
Confidence Interval (2-Sided) 97.5%
-0.23 to 0.36
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Ketamine, Nonketamine
Comments Ketamine versus nonketamine on postoperative day 1 vomiting assessed using Pearson chi square test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.44
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.07
Confidence Interval (2-Sided) 97.5%
-0.22 to 0.38
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Verbal Response Fatigue Score on Postoperative Day 1
Hide Description Verbal response fatigue score on postoperative day 1. Verbal response fatigue score measured on a scale ranging from 0 to 10, where 0 is no fatigue and 10 is the worst possible fatigue.
Time Frame postoperative day 1
Hide Outcome Measure Data
Hide Analysis Population Description
11 patients had missing POD 1 fatigue scores (e.g., 11 for lidocaine vs. nonlidocaine and 11 for ketamine vs. nonketamine).
Arm/Group Title Lidocaine Nonlidocaine Ketamine Nonketamine
Hide Arm/Group Description:

Intravenous Lidocaine Group - Lidocaine is administered intravenously throughout surgery and during the 24 hours following surgery

Lidocaine: Upon general anesthesia induction, lidocaine (1.5 mg/kg) will be given. Lidocaine infusion of 2 mg/kg/hour, to a maximum of 200 mg/hour during The lidocaine infusion will be reduced to 1.3 mg/kg/hour, to a maximum of 133 mg/hour, at skin closure and discontinued 24 hours postoperatively.

Intravenous Nonlidocaine Group - A lidocaine placebo is administered intravenously through out surgery and 24 hours after surgery.

Placebo boluses and infusions will be substituted for the lidocaine

Intravenous Ketamine Group - Ketamine is administered intravenously throughout surgery and during the 24 hours following surgery

Ketamine: Upon induction of anesthesia, a bolus of ketamine (0.25mg/kg) will be given followed by an infusion of ketamine (0.25mg/kg/hour) up to 25 mg/hour. The ketamine infusion will be reduced to 0.12 mg/kg/hour up to a maximum of 12 mg/hour at skin closure and discontinued 24 hours postoperatively.

A ketamine placebo is administered intravenously throughout surgery and during the 24 hours after surgery.

A placebo infusion will be substituted for the ketamine not given

Overall Number of Participants Analyzed 26 25 24 27
Mean (Standard Deviation)
Unit of Measure: units on a scale
7.2  (2.5) 7.2  (2.4) 7.4  (2.6) 7.0  (2.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lidocaine, Nonlidocaine
Comments Lidocaine was compared to nonlidocaine on mean VRS fatigue score using a t test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.96
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.03
Confidence Interval (2-Sided) 97.5%
-2.14 to 2.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ketamine, Nonketamine
Comments Ketamine was compared to nonketamine on mean VRS fatigue score using a t test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.59
Comments 97.5% confidence intervals (CIs) adjusted for group sequential design (using confidence coefficient of 2.97) to maintain the overall α of 0.025 for each intervention and 0.05 for the trial.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 97.5%
-1.80 to 2.57
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Lidocaine Placebo Ketamine Ketamine + Lidocaine
Hide Arm/Group Description

Intravenous Lidocaine Group - Lidocaine is administered intravenously throughout surgery and during the 24 hours following surgery

Lidocaine: Upon general anesthesia induction, lidocaine (1.5 mg/kg) will be given. Lidocaine infusion of 2 mg/kg/hour, to a maximum of 200 mg/hour during The lidocaine infusion will be reduced to 1.3 mg/kg/hour, to a maximum of 133 mg/hour, at skin closure and discontinued 24 hours postoperatively.

placebo is administered intravenously through out surgery and 24 hours after surgery.

Intravenous Ketamine Group - Ketamine is administered intravenously throughout surgery and during the 24 hours following surgery

Ketamine: Upon induction of anesthesia, a bolus of ketamine (0.25mg/kg) will be given followed by an infusion of ketamine (0.25mg/kg/hour) up to 25 mg/hour. The ketamine infusion will be reduced to 0.12 mg/kg/hour up to a maximum of 12 mg/hour at skin closure and discontinued 24 hours postoperatively.

both ketamine and Lidocaine administered intravenously throughout surgery and during the 24 hours after surgery.
All-Cause Mortality
Lidocaine Placebo Ketamine Ketamine + Lidocaine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   16/16 (100.00%)   16/16 (100.00%)   15/15 (100.00%)   15/15 (100.00%) 
Hide Serious Adverse Events
Lidocaine Placebo Ketamine Ketamine + Lidocaine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)   0/16 (0.00%)   0/15 (0.00%)   0/15 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Lidocaine Placebo Ketamine Ketamine + Lidocaine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)   0/16 (0.00%)   0/15 (0.00%)   0/15 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Daniel Sessler, MD
Organization: Cleveland Clinic
Phone: 216-444-4200
EMail: sesslerd@ccf.org
Layout table for additonal information
Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT00721110    
Other Study ID Numbers: 08-454
First Submitted: July 21, 2008
First Posted: July 23, 2008
Results First Submitted: June 20, 2016
Results First Posted: July 26, 2017
Last Update Posted: July 26, 2017