Low Doses of Ketamine and Postoperative Quality of Recovery

• ClinicalTrials.gov Identifier: NCT02571153
• Recruitment Status: Completed
• First Posted: October 8, 2015
• Results First Posted: March 6, 2017
• Last Update Posted: March 6, 2017
• Sponsor: Pontificia Universidade Catolica de Sao Paulo
• Information provided by (Responsible Party): Eduardo Toshiyuki Moro, Pontificia Universidade Catolica de Sao Paulo

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Conditions: Postoperative Pain; Postoperative Nausea and Vomiting
• Interventions: Drug: Ketamine 0.4 mg/kg; Drug: Normal saline; Drug: Ketamine 0.2 mg/kg
• Enrollment: 135

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Saline Group	Ketamine 0.2	Ketamine 0.4
Arm/Group Description	Normal saline 0.9% (5 mL) Normal saline: Intravenous normal saline 0.9% 5 mL	ketamine 0.2 mg/kg (5 mL) Ketamine 0.2 mg/kg: Intravenous ketamine 0.2 mg/kg after induction of anesthesia	ketamine 0.4 mg/kg (5 mL) Ketamine 0.4 mg/kg: Intravenous ketamine 0.4 mg/kg after induction of anesthesia
Period Title: Overall Study
Started	45	45	45
Completed	39	37	43
Not Completed	6	8	2

Baseline Characteristics

Arm/Group Title		Saline Group	Ketamine 0.2	Ketamine 0.4	Total
Arm/Group Description		Normal saline 0.9% (5 mL) Normal saline: Intravenous normal saline 0.9% 5 mL	ketamine 0.2 mg/kg (5 mL) Ketamine 0.2 mg/kg: Intravenous ketamine 0.2 mg/kg after induction of anesthesia	ketamine 0.4 mg/kg (5 mL) Ketamine 0.4 mg/kg: Intravenous ketamine 0.4 mg/kg after induction of anesthesia	Total of all reporting groups
Overall Number of Baseline Participants		39	37	43	119
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	39 participants	37 participants	43 participants	119 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	39 100.0%	37 100.0%	43 100.0%	119 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Median (Standard Deviation); Unit of measure: Years
	Number Analyzed	39 participants	37 participants	43 participants	119 participants
		41.8 (11.3)	47.2 (13.3)	44.1 (11.4)	44.3 (12.1)
Gender; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	39 participants	37 participants	43 participants	119 participants
	Female	31 79.5%	34 91.9%	37 86.0%	102 85.7%
	Male	8 20.5%	3 8.1%	6 14.0%	17 14.3%

Outcome Measures

1. Primary Outcome

Title	Quality of Postoperative Recovery Assessed by QoR-40 Questionnaire 24 Hours After Surgery
Description	Quality of postoperative functional recovery assessed by the questionnaire QoR40 The quality of postoperative functional recovery was assessed by the QoR-40 questionnaire, which assesses five dimensions of recovery (physical comfort - 12 items; emotional state - 7 items; physical independence - 5 items; physiological support - 7 items; and pain - 7 items). Each item was rated on a five-point Likert scale: none of the time, some of the time, usually, most of the time, and all the time. The total score on the QoR-40 ranges from 40 (poorest quality of recovery) to 200 (best quality of recovery). The QoR-40 was administered by a blind investigator 24 hours after surgery.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Total of 152 patients were first assessed for eligibility in this study; however, 17 were excluded because they refused participation, or met any of the exclusion criteria. Thus, 135 participants were randomly allocated to the study groups. Later, 6 participants in group S, 8 in group K2, and 2 in group K4 were excluded due to protocol deviations.

Arm/Group Title	Saline Group	Ketamine 0.2	Ketamine 0.4
Arm/Group Description:	Normal saline 0.9% (5 mL) Normal saline: Intravenous normal saline 0.9% 5 mL	ketamine 0.2 mg/kg (5 mL) Ketamine 0.2 mg/kg: Intravenous ketamine 0.2 mg/kg after induction of anesthesia	ketamine 0.4 mg/kg (5 mL) Ketamine 0.4 mg/kg: Intravenous ketamine 0.4 mg/kg after induction of anesthesia
Overall Number of Participants Analyzed	39	37	43
Mean (80% Confidence Interval); Unit of Measure: units on a scale
	187.8; (177.4 to 198.2)	189.6; (177.6 to 201.6)	186.8; (175.5 to 198.1)

2. Secondary Outcome

Title	Length of PACU Stay
Description	Length of stay at postanesthesia recovery room
Time Frame	During the stay at postanesthesia recovery room (about 90 to 120 minutes)

Outcome Measure Data

Analysis Population Description

Patients aged 18 to 65 years old, with an ASA physical status I or II, who would be scheduled to undergo laparoscopic cholecystectomy.

Arm/Group Title	Saline Group	Ketamine 0.2	Ketamine 0.4
Arm/Group Description:	Normal saline 0.9% (5 mL) Normal saline: Intravenous normal saline 0.9% 5 mL	ketamine 0.2 mg/kg (5 mL) Ketamine 0.2 mg/kg: Intravenous ketamine 0.2 mg/kg after induction of anesthesia	ketamine 0.4 mg/kg (5 mL) Ketamine 0.4 mg/kg: Intravenous ketamine 0.4 mg/kg after induction of anesthesia
Overall Number of Participants Analyzed	39	37	43
Mean (80% Confidence Interval); Unit of Measure: minutes
	82.9; (59.2 to 106.6)	84.5; (68 to 101)	86; (52.1 to 119.9)

3. Secondary Outcome

Title	Occurrence of Postoperative, Nausea and Vomiting
Description	Percentage of participants with postoperative nausea and vomiting at the PACU and during the hospital ward stay
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Patients aged 18 to 65 years old, with an ASA physical status I or II, who would be scheduled to undergo laparoscopic cholecystectomy.

Arm/Group Title	Saline Group	Ketamine 0.2	Ketamine 0.4
Arm/Group Description:	Normal saline 0.9% (5 mL) Normal saline: Intravenous normal saline 0.9% 5 mL	ketamine 0.2 mg/kg (5 mL) Ketamine 0.2 mg/kg: Intravenous ketamine 0.2 mg/kg after induction of anesthesia	ketamine 0.4 mg/kg (5 mL) Ketamine 0.4 mg/kg: Intravenous ketamine 0.4 mg/kg after induction of anesthesia
Overall Number of Participants Analyzed	39	37	43
Measure Type: Number; Unit of Measure: percentage of participants
	30.8	29.7	39.5

4. Secondary Outcome

Title	Occurrence of Pain at PACU Using a 0-10 Numeric Pain Rating Scale
Description	Occurrence of pain at the PACU. Average Pain will be calculated. The pain score will be evaluated using a 0-10 numeric pain rating scale, where zero mean no pain and 10 the worst imaginable pain.
Time Frame	90 minutes postanesthesia at recovery room

Outcome Measure Data

Analysis Population Description

Patients aged 18 to 65 years old, with an ASA physical status I or II, who would be scheduled to undergo laparoscopic cholecystectomy.

Arm/Group Title	Saline Group	Ketamine 0.2	Ketamine 0.4
Arm/Group Description:	Normal saline 0.9% (5 mL) Normal saline: Intravenous normal saline 0.9% 5 mL	ketamine 0.2 mg/kg (5 mL) Ketamine 0.2 mg/kg: Intravenous ketamine 0.2 mg/kg after induction of anesthesia	ketamine 0.4 mg/kg (5 mL) Ketamine 0.4 mg/kg: Intravenous ketamine 0.4 mg/kg after induction of anesthesia
Overall Number of Participants Analyzed	39	37	43
Mean (80% Confidence Interval); Unit of Measure: units on a scale
	3.8; (0.2 to 7.4)	2.6; (0 to 5.8)	2.8; (0 to 5.8)

5. Secondary Outcome

Title	Morphine Consumption (mg) at PACU
Description	Morphine consumption (mg) at PACU (about 90 to 120 minutes)
Time Frame	During the stay at postanesthesia recovery room (about 90 to 120 minutes)

Outcome Measure Data

Analysis Population Description

Patients aged 18 to 65 years old, with an ASA physical status I or II, who would be scheduled to undergo laparoscopic cholecystectomy.

Arm/Group Title	Saline Group	Ketamine 0.2	Ketamine 0.4
Arm/Group Description:	Normal saline 0.9% (5 mL) Normal saline: Intravenous normal saline 0.9% 5 mL	ketamine 0.2 mg/kg (5 mL) Ketamine 0.2 mg/kg: Intravenous ketamine 0.2 mg/kg after induction of anesthesia	ketamine 0.4 mg/kg (5 mL) Ketamine 0.4 mg/kg: Intravenous ketamine 0.4 mg/kg after induction of anesthesia
Overall Number of Participants Analyzed	39	37	43
Mean (80% Confidence Interval); Unit of Measure: mg
	1.6; (0 to 3.7)	0.9; (0 to 2.4)	1.1; (0 to 2.7)

6. Secondary Outcome

Title	The Severity of Postoperative Pain
Description	The severity of postoperative pain was rated the higher score of pain (NRS) during the hospital ward stay. Pain was evaluated using a 0-10 numeric pain rating scale (NRS), where zero meant no pain and 10 the worst imaginable pain.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Patients aged 18 to 65 years old, with an ASA physical status I or II, who would be scheduled to undergo laparoscopic cholecystectomy.

Arm/Group Title	Saline Group	Ketamine 0.2	Ketamine 0.4
Arm/Group Description:	Normal saline 0.9% (5 mL) Normal saline: Intravenous normal saline 0.9% 5 mL	ketamine 0.2 mg/kg (5 mL) Ketamine 0.2 mg/kg: Intravenous ketamine 0.2 mg/kg after induction of anesthesia	ketamine 0.4 mg/kg (5 mL) Ketamine 0.4 mg/kg: Intravenous ketamine 0.4 mg/kg after induction of anesthesia
Overall Number of Participants Analyzed	39	37	43
Mean (80% Confidence Interval); Unit of Measure: units on a scale
	3.2; (0.4 to 6)	2.8; (0 to 5.5)	3.6; (0.5 to 6.5)

7. Secondary Outcome

Title	Percentage of Participants With Tramadol Consumption
Description	Percentage of Participants with Tramadol during the ward stay
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Patients aged 18 to 65 years old, with an ASA physical status I or II, who would be scheduled to undergo laparoscopic cholecystectomy.

Arm/Group Title	Saline Group	Ketamine 0.2	Ketamine 0.4
Arm/Group Description:	Normal saline 0.9% (5 mL) Normal saline: Intravenous normal saline 0.9% 5 mL	ketamine 0.2 mg/kg (5 mL) Ketamine 0.2 mg/kg: Intravenous ketamine 0.2 mg/kg after induction of anesthesia	ketamine 0.4 mg/kg (5 mL) Ketamine 0.4 mg/kg: Intravenous ketamine 0.4 mg/kg after induction of anesthesia
Overall Number of Participants Analyzed	39	37	43
Measure Type: Number; Unit of Measure: percentage of participants
	5.1	10.8	13.9

Adverse Events

Time Frame	24 hours
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Saline Group	Ketamine 0.2	Ketamine 0.4
Arm/Group Description	Normal saline 0.9% (5 mL) Normal saline: Intravenous normal saline 0.9% 5 mL	ketamine 0.2 mg/kg (5 mL) Ketamine 0.2 mg/kg: Intravenous ketamine 0.2 mg/kg after induction of anesthesia	ketamine 0.4 mg/kg (5 mL) Ketamine 0.4 mg/kg: Intravenous ketamine 0.4 mg/kg after induction of anesthesia
All-Cause Mortality
	Saline Group	Ketamine 0.2	Ketamine 0.4
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	Saline Group	Ketamine 0.2	Ketamine 0.4
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/39 (0.00%)	0/37 (0.00%)	0/43 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Saline Group	Ketamine 0.2	Ketamine 0.4
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/39 (0.00%)	0/37 (0.00%)	0/43 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.

Results Point of Contact

• Name/Title: Eduardo Toshiyuki Moro
• Organization: Pontificia UCSP
• EMail: eduardo_moro@terra.com.br

Publications:

Xie H, Wang X, Liu G, Wang G. Analgesic effects and pharmacokinetics of a low dose of ketamine preoperatively administered epidurally or intravenously. Clin J Pain. 2003 Sep-Oct;19(5):317-22.

Myles PS, Weitkamp B, Jones K, Melick J, Hensen S. Validity and reliability of a postoperative quality of recovery score: the QoR-40. Br J Anaesth. 2000 Jan;84(1):11-5.

Wu L, Huang X, Sun L. The efficacy of N-methyl-D-aspartate receptor antagonists on improving the postoperative pain intensity and satisfaction after remifentanil-based anesthesia in adults: a meta-analysis. J Clin Anesth. 2015 Jun;27(4):311-24. doi: 10.1016/j.jclinane.2015.03.020. Epub 2015 Mar 29.

Pfenninger EG, Durieux ME, Himmelseher S. Cognitive impairment after small-dose ketamine isomers in comparison to equianalgesic racemic ketamine in human volunteers. Anesthesiology. 2002 Feb;96(2):357-66.

Kissin I, Bright CA, Bradley EL Jr. The effect of ketamine on opioid-induced acute tolerance: can it explain reduction of opioid consumption with ketamine-opioid analgesic combinations? Anesth Analg. 2000 Dec;91(6):1483-8.

• Responsible Party: Eduardo Toshiyuki Moro, Pontificia Universidade Catolica de Sao Paulo
• ClinicalTrials.gov Identifier: NCT02571153
• Other Study ID Numbers: PUCSP 057539/2015
• First Submitted: October 2, 2015
• First Posted: October 8, 2015
• Results First Submitted: September 28, 2016
• Results First Posted: March 6, 2017
• Last Update Posted: March 6, 2017