Low Dose Ketamine Infusion for Postoperative Analgesia After Total Knee Arthroplasty

Low Dose Ketamine Infusion for Postoperative Analgesia After Total Knee Arthroplasty: Optimum Dose to Reduce Morphine Consumption

This study evaluates continous infusion of low-dose ketamine during intraoperative and postoperative periods at three different doses to provide postoperative analgesia in total knee arthroplasty cases. Patients enrolled randomly into one of 2, 4, 6 μg / kg / min perioperative ketamine groups. All groups were given spinal anesthesia and intravenous patient controlled anesthesia. Ketamine was started when sensorial block reached T10 dermatome level before the skin incision. By the end of the operation, in all groups, ketamine infusions were reduced by half doses. Intravenous patient-controlled analgesia device was set to 2 mg bolus morphine with no basal infusion for 48 hours during the postoperative period.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain

Detailed Description

Multimodal analgesia, which involves the administration of two or more analgesic agents targeting different levels of pain pathways, is used to improve pain control while also to reduce opioid use and related side effects. Pain can be treated at various neurophysiological levels, including peripheral, spinal and cortical targets. One of the agents used in the multimodal analgesia technique is ketamine.

Ketamine acts on the central nervous system (CNS) and has local anesthetic effect. Ketamine is an N-methyl D-Aspartate (NMDA) receptor antagonist, which appears to be the main mechanism of anesthetic and analgesic action at CNS and spinal cord receptors. Other mechanisms of action of ketamine include the interaction with opioid receptors, particularly mu and kappa receptors. Another effect is that it has local anesthetic effect in high doses. Studies have shown that ketamine is an effective agent in the treatment of postoperative pain. Continuous infusion of low-dose ketamine after total knee arthroplasty significantly reduced morphine consumption, and provided early rehabilitation without increasing side effects. However, when these studies are considered, there is no information about the optimal dose of ketamine that reduces opioid consumption at the highest level.

In our study, continuous infusion of low-dose ketamine at different doses was planned to provide postoperative analgesia. Therefore, our first aim in this study was to find out the optimal dose that reduced morphine consumption for postoperative analgesia after TKA with continuous ketamine infusion at different doses. The secondary objectives are to evaluate early and late period pain, side effects, length of hospital stay, patient satisfaction, and recovery.

• Study Type: Observational
• Enrollment (Actual): 75

Contacts and Locations

Study Locations

• Turkey
  • Hatay, Turkey, 31100
    • Mustafa Kemal University Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

unilateral total knee arthroplasty cases

Description

Inclusion Criteria:

• ASA I-Ⅲ female patients scheduled for unilateral total knee arthroplasty

Exclusion Criteria:

• Patients younger than 18 years of age
• ASA Ⅳ and above patients
• Having previous knee surgery on the same side
• Patients with allergies to drugs to be used in the study
• Contraindication for spinal anesthesia
• Body mass index 40 kg / m2 and above patients
• Opioid tolerance
• Patients with neurological or psychiatric disorders
• Patients who do not have the ability to use patient controlled analgesia device

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Group 1; All patients were revived spinal anesthesia with 3 mL marcaine 0.5% and after surgery a 2 mg bolus morphine PCA pump was connected to them. Before the skin incision, when sensorial block reached T10 dermatome level 2 μg / kg / min ketamine was started in Group 1. By the end of the operation ketamine infusion was reduced to 1 μg / kg / min.
Group 2; All patients were revived spinal anesthesia with 3 mL marcaine 0.5% and after surgery a 2 mg bolus morphine PCA pump was connected to them. Before the skin incision, when sensorial block reached T10 dermatome level 4 μg / kg / min ketamine was started . By the end of the operation ketamine infusion was reduced to 2 μg / kg /min and continued.
Group 3; All patients were revived spinal anesthesia with 3 mL marcaine 0.5% and after surgery a 2 mg bolus morphine PCA pump was connected to them. Before the skin incision, when sensorial block reached T10 dermatome level 6 μg / kg / min ketamine was started . By the end of the operation ketamine infusion was reduced to 3 μg / kg /min and continued.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optimal dose of Ketamine to reduce morphine consumption	Ketamine infusions 2μg 4μg and 6μg / kg / min will be started preoperatively in group 1, 2 and 3 respectively when sensory block level reaches T10 after spinal anesthesia, and they will be reduced by half by the end of the operation. Ketamine infusion will be continued for 48 hours postoperatively.	48 hours from the operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early and late period pain	The pain status of the patients at rest and in motion with 100 mm visual pain scale (VAS) (0= no pain and 100 = intolerable pain) will be evaluated and recorded preoperative and postoperative at 2nd, 6th, 12th, 24th and 48th hours.and after 3 months	3 months from the operation
side effects,	Nausea, vomiting, itching, respiratory depression, hallucination and diplopia	3 months
length of hospital stay	Hospital stay (as day) required for active knee flexion to 90 degrees (measured with goniometer) will be recorded.	3 months
patient satisfaction	5 point likert scale	3 months

Collaborators and Investigators

• Sponsor: Mustafa Kemal University
• Investigators: Study Director: Selim Turhanoglu, M.D., Mustafa Kemal University, Medical School, 31100 Hatay, Turkey

Publications and helpful links

General Publications

• Memtsoudis SG, Poeran J, Zubizarreta N, Cozowicz C, Morwald EE, Mariano ER, Mazumdar M. Association of Multimodal Pain Management Strategies with Perioperative Outcomes and Resource Utilization: A Population-based Study. Anesthesiology. 2018 May;128(5):891-902. doi: 10.1097/ALN.0000000000002132.
• Schmid RL, Sandler AN, Katz J. Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes. Pain. 1999 Aug;82(2):111-125. doi: 10.1016/S0304-3959(99)00044-5.
• Adam F, Chauvin M, Du Manoir B, Langlois M, Sessler DI, Fletcher D. Small-dose ketamine infusion improves postoperative analgesia and rehabilitation after total knee arthroplasty. Anesth Analg. 2005 Feb;100(2):475-480. doi: 10.1213/01.ANE.0000142117.82241.DC.
• Aveline C, Gautier JF, Vautier P, Cognet F, Hetet HL, Attali JY, Leconte V, Leborgne P, Bonnet F. Postoperative analgesia and early rehabilitation after total knee replacement: a comparison of continuous low-dose intravenous ketamine versus nefopam. Eur J Pain. 2009 Jul;13(6):613-9. doi: 10.1016/j.ejpain.2008.08.003. Epub 2008 Sep 14.
• Pai A, Heining M. Ketamine. Continuing Education in Anaesthesia, Critical Care and Pain 2007; Volume 7,Number 2.

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2019
• Primary Completion (Actual): September 2, 2021
• Study Completion (Actual): September 2, 2021

Study Registration Dates

• First Submitted: September 5, 2019
• First Submitted That Met QC Criteria: September 10, 2019
• First Posted (Actual): September 11, 2019

Study Record Updates

• Last Update Posted (Actual): September 14, 2021
• Last Update Submitted That Met QC Criteria: September 13, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Pain; Ketamine; Morphine; analgesia; Postoperative
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative
• Other Study ID Numbers: 15.04.2019-07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Sharing data have not been discussed among the investigators yet.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No