Clinical trial NCT04085588: Low Dose Ketamine Infusion for Postoperative Analgesia After Total Knee Arthroplasty
Official title: Low Dose Ketamine Infusion for Postoperative Analgesia After Total Knee Arthroplasty: Optimum Dose to Reduce Morphine Consumption
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Postoperative Pain
Keywords: Pain
analgesia
Postoperative
Ketamine
Morphine
Lead sponsor: Mustafa Kemal University
Sponsor class: OTHER
First posted: 2019-09-11
Enrollment: 75
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: unilateral total knee arthroplasty cases

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Optimal dose of Ketamine to reduce morphine consumption
timeFrame: 48 hours from the operation
Secondary outcomes:
measure: Early and late period pain
timeFrame: 3 months from the operation
measure: side effects,
timeFrame: 3 months
measure: length of hospital stay
timeFrame: 3 months
measure: patient satisfaction
timeFrame: 3 months
Other outcomes:
Locations:
city: Hatay
country: Turkey
facility: Mustafa Kemal University Medical School
Study officials:
affiliation: Mustafa Kemal University, Medical School, 31100 Hatay, Turkey
name: Selim Turhanoglu, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Pai A, Heining M. Ketamine. Continuing Education in Anaesthesia, Critical Care and Pain 2007; Volume 7,Number 2.