Efficacy of Adrenaline in Periarticular Analgesic Injection on Postoperative Pain Control After Total Knee Arthroplasty

Efficacy of Adrenaline in Periarticular Analgesic Injection on Postoperative Pain Control After Total Knee Arthroplasty: A Randomized Controlled Trial

Multimodal anesthetic drug injection has been used extensively and the results of many studies suggest that postoperative pain can relief and improve the postoperative satisfaction of patients. Adrenaline is a combination of multimodal anesthetic cocktail to relieve pain. It is believed that Adrenaline causes vasoconstriction, reduces absorption of anesthetic drug into the system circulation. Currently, a comparative study on the effect of pain reduction of Adrenaline injection in the anesthetic cocktail is relatively low. There are different doses in each institution. In addition, the use of new anesthetic is Levobupivacaine that has more vasoconstrictive effect compare with traditional Bupivacaine. It also reduces the side effects of systemic and cardiotoxic effect. Therefore, the investigators think that It may not be necessary to mix Adrenaline in the multimodal anesthetic drug. Levobupivacaine already to avoid the potential side effects of Adrenaline.

Study Overview

• Status: Unknown
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: 0.6 mg 1:1000 epinephrine (0.6 ml)

Detailed Description

The patients will be divided into two groups. In group 1, the multimodal anesthetic cocktail consisted of 100 mg Levobupivacaine (0.5%, 20 mL) and 30 mg ketorolac (1 ml). In group 2, the multimodal anesthetic cocktail consisted of 100 mg Levobupivacaine (0.5%, 20 mL), 30 mg ketorolac (1 ml) and 0.6 mg 1:1000 epinephrine (0.6 ml). Both groups were mixed with a 0.9% normal saline solution to a total volume of 100 ml. The outcome research assistant who collects data was blinded to the treatment groups. Patients will be treated with the routine standard regimen for total knee arthroplasty. Surgeons will use same surgical techniques through a standard medial parapatellar approach. In addition, standardized posterior-stabilized TKA (Zimmer Nexgen LPS flex) was used in all patients. After bone cutting before inserting the actual implant, the assistant scrub nurse in the operating room will open the envelope that the patient was classified in group 1 or group 2 and perform mixing according to the prescribed medication. The doctor who undergoes surgery was blinded. The anesthetic cocktail was divided into 4 parts 25 ml each and it was injected into 4 areas. First 25 ml cocktail was injected into the posterior capsule (P), posteromedial (PM) and posterolateral capsule (PL). The second part was injected into the medial gutter (M). The third part was injected into the lateral gutter and the forth part was injected into quadriceps muscle, retinacula tissues, pes anserinus, suprapatellar and infrapatellar fat pads (A). During the first 48 hours, all patients received intravenous morphine prn for pain, as well as dynastat, Tylenol with codeine, as required, for control of pain. After 48 hours, the pain was controlled by oral intravenous morphine and medication as requires until the patient was discharged from the hospital.

The primary outcome measure was the severity of postoperative pain during the first 48 hours after surgery. The pain was assessed by a Visual Analogue Scale (VAS) ranging from 0 (no pain) to 10 (extreme pain) every 6 hours postoperatively. Secondary outcome measures compared the consumption of intravenous morphine, which was measured every six hours in 48 hours after surgery. Additionally, blood loss in the drain at 24, 48 hours was recorded. Any complications following surgery were recorded.

• Study Type: Interventional
• Enrollment (Anticipated): 82
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chaturong Pornrattanamaneewong, MD; Phone Number: 6681-7553977; Email: toonchaturong@gmail.com
• Study Contact Backup: Name: Suphawat Tantithawornwat, MD; Phone Number: 6686-9088084; Email: dr.suphawat@gmail.com

Study Locations

• Thailand
  • Bangkok, Thailand, 10700
    • Recruiting
    • Chaturong Pornrattanamaneewong
    • Contact: Rapeepat Narkbunnam, MD; Phone Number: 6681-9351669; Email: mai_parma@hotmail.com
    • Contact: Keerati Chareancholvanivh, MD; Phone Number: 6681-8188568; Email: keesi93@gmail.com
    • Sub-Investigator: Suphawat Tantithawornwat, MD
    • Sub-Investigator: Chaturong Pornrattanamaneewong, MD
    • Principal Investigator: Keerati Chareancholvanich, MD
    • Sub-Investigator: Rapeepat Narkbunnam, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with primary knee osteoarthritis
• Aged between 40 and 80 years
• Must be able to understand and willing to follow instructions

Exclusion Criteria:

• Patients unable to undergo anesthesia during surgery by spinal block or adductor block
• Patients with the history of levobupivacaine, etoricoxib drug allergy
• Patients with the history of allergic or nausea vomiting severely when receiving morphine
• Patients with kidney disease who have a creatinine clearance of less than 50 ml/min, cirrhosis, cardiovascular disease, stroke, poorly controlled hypertension
• Patients with the history of venous thrombosis
• Patients with complications during surgery such as torn ligaments
• Patients who refuse to participate in the research.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MAC with adrenaline; the multimodal anesthetic cocktail (MAC) consisted of 100 mg Levobupivacaine (0.5%, 20 mL) 30 mg ketorolac (1 ml) and 0.6 mg 1:1000 epinephrine (0.6 ml). They were mixed with a 0.9% normal saline solution to a total volume of 100 ml.	Drug: 0.6 mg 1:1000 epinephrine (0.6 ml); In group 1, the multimodal anesthetic cocktail consisted of 100 mg Levobupivacaine (0.5%, 20 mL) 30 mg ketorolac (1 ml) and 0.6 mg 1:1000 epinephrine (0.6 ml). In group 2, the multimodal anesthetic cocktail consisted of 100 mg Levobupivacaine (0.5%, 20 mL) and 30 mg ketorolac (1 ml). Both groups were mixed with a 0.9% normal saline solution to a total volume of 100 ml.; Other Names: 100 mg Levobupivacaine (0.5%, 20 mL); 30 mg ketorolac (1 ml)
NO_INTERVENTION: MAC without adrenaline; the multimodal anesthetic cocktail (MAC) consisted of 100 mg Levobupivacaine (0.5%, 20 mL) and 30 mg ketorolac (1 ml). They were mixed with a 0.9% normal saline solution to a total volume of 100 ml.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the severity of postoperative pain	The pain was assessed by a Visual Analogue Scale (VAS) ranging from 0 (no pain) to 10 (extreme pain) every 6 hours postoperatively.	The first 48 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the consumption of intravenous morphine	the consumption of intravenous morphine, which was measured every six hours	The first 48 hours after surgery
blood loss in the drain	blood loss in the radivac drain	at 24, 48 hours after surgery

Collaborators and Investigators

• Sponsor: Mahidol University
• Investigators: Study Chair: Keerati Chareancholvanich, MD, Mahidol University

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 26, 2018
• Primary Completion (ANTICIPATED): October 31, 2018
• Study Completion (ANTICIPATED): October 31, 2018

Study Registration Dates

• First Submitted: May 25, 2018
• First Submitted That Met QC Criteria: June 6, 2018
• First Posted (ACTUAL): June 7, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 12, 2018
• Last Update Submitted That Met QC Criteria: June 8, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: blood loss; total knee arthroplasty; Levobupivacaine; morphine consumption; adrenaline; multimodal anesthetic cocktail
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Adrenergic alpha-Agonists; Adrenergic Agonists; Anesthetics, Local; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Ketorolac; Levobupivacaine; Epinephrine
• Other Study ID Numbers: 696/2560

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No