Analgesic Efficacy of Ropivacaine Alone or in Combination With Adjuvants on Post-operative Analgesia Following Video-Assisted Thoracoscopic Surgery.

NCT03809442 | Completed Phase 4 DMC

• 1 other identifier: 0743
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is to investigate the analgesic effects of the subcutaneous wound infiltration with tramadol, ketamine, dexamethasone, dexmedetomidine and midazolam as adjuvant to ropivacaine, compared to ropivacaine alone in patients undergoing Video-Assisted thoracoscopic Surgery (VATS) procedures.

Conditions

Postoperative Analgesia

Outcome Measures

Primary Outcomes (2)

• Time to the first postoperative analgesia requirement

  Time to the first analgesic requirement will be calculated as the time from the performance of local wound infiltration to the first analgesic dose administered. This time will be noted in minutes.

  Follow till 24 hours postoperatively

• Visual analogue scale (VAS)

  Assessement for Postoperative Pain. The requirement of postoperative analgesia of the patient will be evaluated by using Visual analogue scale (VAS). It scored from 0 to 10 (where 0 \[minimum score\] = no pain and 10 \[maximum score\] = worst pain). Aggregate score will be added. Score less than 4 will be consider adequate analgesia while score greater than 4 will be consider inadequate analgesia. This score is just a numerical number with no other value attached to it.

  Follow till 24 hours postoperatively

Secondary Outcomes (1)

• Sedation using Pasero Opioid-Induced Sedation Scale (POSS)

  Follow till 24 hours postoperatively

Study Arms (6)

Ropivacaine with Ketamine

EXPERIMENTAL

Ropivacaine is a propyl analog of bupivacaine with longer duration of action with much safer cardiotoxicity profile than bupivacaine. Ropivacaine has the same analgesic effects as bupivacaine and levobupivacaine, but it is associated with a low incidence of motor block. Thus, ropivacaine appears to be an important component for local anesthesia and postoperative analgesia. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that possesses both central and peripheral analgesic effects. Preincisional infiltration of ketamine prolongs the time to first analgesic requirement and also decreases the total amount of analgesics used postoperatively. Patients will receive subcutaneous wound infiltration with total volume of 24 mL of 0.25% ropivacaine + 1mg/kg ketamine (8 mL per incision) (ketamine group).

Drug: Ropivacaine + Ketamine

Ropivacaine with Tramadol

EXPERIMENTAL

Tramadol hydrochloride is a synthetic analog of codeine that acts on both opioid (weak mu receptor agonist) and nonopioid receptors (inhibits reuptake of nor-adrenaline and serotonin as well as release stored serotonin from nerve endings) which play a crucial role in pain inhibition pathway. It also blocks nerve conduction which imparts its local anesthetics like action on peripheral nerves. In one study it was found that the addition of tramadol or midazolam to caudal epidural ropivacaine prolongs the duration of analgesia without causing significant side effects. Patients will receive subcutaneous wound infiltration with total volume of 24 mL of 0.25% ropivacaine + 2mg/kg tramadol (8 mL per incision) (Tramadol group).

Drug: Ropivacaine + Tramadol

Ropivacaine with Midazolam

EXPERIMENTAL

The analgesic effect of extradurally administered midazolam is through γ-amino butyric acid (GABA)/benzodiazepine system of spinal cord. Patients will receive subcutaneous wound infiltration with total volume of 24 mL of 0.25% ropivacaine + 50 μg/kg midazolam (8 mL per incision) (Midazolam group).

Drug: Ropivacaine + Midazolam

Ropivacaine with Dexamethasone

EXPERIMENTAL

The glucocorticoid dexamethasone appears to be effective in a small number of preclinical and clinical studies and found that dexamethasone prolongs analgesia from interscalene blocks using ropivacaine or bupivacaine, with the effect being stronger with ropivacaine. Patients will receive subcutaneous wound infiltration with total volume of 24 mL of 0.25% ropivacaine+ 8mg dexamethasone (8 mL per incision) (Dexamethasone group).

Drug: Ropivacaine + Dexamethasone

Ropivacaine with Dexmedetomidine

EXPERIMENTAL

Dexmedetomidine is a new highly selective alpha2 (a2) agonist with known sedative, antihypertensive, anxiolytic, and analgesic properties. In one study, it was found that wound infiltration with combined ropivacaine and dexmedetomidine found to be significantly superior for postoperative analgesia compared with either combined ropivacaine and tramadol or ropivacaine alone for lumbar discectomies. Patients will receive subcutaneous wound infiltration with total volume of 24 mL of 0.25% Ropivacaine + 0.5μg/kgdexmedetomidine (8mL per incision) (Dexmedetomidine group).

Drug: Ropivacaine + Dexmedetomidine

Ropivacaine

PLACEBO COMPARATOR

Ropivacaine is a propyl analog of bupivacaine with longer duration of action with much safer cardiotoxicity profile than bupivacaine. Ropivacaine has the same analgesic effects as bupivacaine and levobupivacaine, but it is associated with a low incidence of motor block. Thus, ropivacaine appears to be an important component for local anesthesia and postoperative analgesia. Patients will receive subcutaneous wound infiltration with 24ml of 0.25% Ropivacaine in three divided doses (i.e. 8 mL per incision) (control group). Total dose of Ropivacaine will be 60 mg.

Drug: Ropivacaine

Interventions

Ropivacaine + Ketamine DRUG

Patients will receive subcutaneous wound infiltration with total volume of 24 mL of 0.25% ropivacaine + 1mg/kg ketamine (8 mL per incision) (ketamine group).

Ropivacaine with Ketamine

Ropivacaine + Tramadol DRUG

Patients will receive subcutaneous wound infiltration with total volume of 24 mL of 0.25% ropivacaine + 2mg/kg tramadol (8 mL per incision) (Tramadol group).

Ropivacaine with Tramadol

Ropivacaine + Midazolam DRUG

Patients will receive subcutaneous wound infiltration with total volume of 24 mL of 0.25% ropivacaine + 50 μg/kg midazolam (8 mL per incision) (Midazolam group).

Ropivacaine with Midazolam

Ropivacaine + Dexmedetomidine DRUG

Patients will receive subcutaneous wound infiltration with total volume of 24 mL of 0.25% Ropivacaine + 0.5μg/kg dexmedetomidine (8mL per incision) (Dexmedetomidine group).

Ropivacaine with Dexmedetomidine

Ropivacaine + Dexamethasone DRUG

Patients will receive subcutaneous wound infiltration with total volume of 24 mL of 0.25% ropivacaine+ 8mg dexamethasone (8 mL per incision) (Dexamethasone group).

Ropivacaine with Dexamethasone

Ropivacaine DRUG

Patients will receive subcutaneous wound infiltration with 24ml of 0.25% Ropivacaine in three divided doses (i.e. 8 mL per incision) (control group). Total dose of Ropivacaine will be 60 mg.

Ropivacaine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ASA I to III.
• Age \>18 years.
• Either sex.
• Elective Video assisted thoracotomy surgery (VATS) under general anaesthesia

You may not qualify if:

• ASA IV \& V.
• Coagulation disorders.
• Infection at the vicinity of the surgical wound.
• Raised intracranial pressure.
• History of hypersensitivity or known allergy to any study drug.
• History of opioid addiction.
• History of seizure disorder.
• Those who are not willing to participate in the study.
• Allergy to local anesthetics.
• Duration of surgery greater than 2 hours.

Sponsors & Collaborators

• Aga Khan University: lead

Study Sites (1)

Aga Khan University Hospital

Karachi, Sindh, 74800, Pakistan

Location

Related Publications (14)

• Sommer M, de Rijke JM, van Kleef M, Kessels AG, Peters ML, Geurts JW, Gramke HF, Marcus MA. The prevalence of postoperative pain in a sample of 1490 surgical inpatients. Eur J Anaesthesiol. 2008 Apr;25(4):267-74. doi: 10.1017/S0265021507003031. Epub 2007 Dec 6.

  PMID: 18053314 BACKGROUND

• Bernucci F, Carli F. Functional outcome after major orthopedic surgery: the role of regional anesthesia redefined. Curr Opin Anaesthesiol. 2012 Oct;25(5):621-8. doi: 10.1097/ACO.0b013e328357a3d5.

  PMID: 22914354 BACKGROUND

• Bafna U, Sharma G, Sapru S, et al. Comparison of clonidine anddexmedetomidine as an adjuvant to 0.5% ropivacaine in supraclavicularbrachial plexus block: a prospective, randomized,doubleblindand controlled study. J Recent Adv Pain. 2015;1:73-77.

  BACKGROUND

• Ng A, Swami A, Smith G, Davidson AC, Emembolu J. The analgesic effects of intraperitoneal and incisional bupivacaine with epinephrine after total abdominal hysterectomy. Anesth Analg. 2002 Jul;95(1):158-62, table of contents. doi: 10.1097/00000539-200207000-00028.

  PMID: 12088961 BACKGROUND

• Li M, Wan L, Mei W, Tian Y. Update on the clinical utility and practical use of ropivacaine in Chinese patients. Drug Des Devel Ther. 2014 Sep 9;8:1269-76. doi: 10.2147/DDDT.S57258. eCollection 2014.

  PMID: 25246768 BACKGROUND

• Pedersen JL, Galle TS, Kehlet H. Peripheral analgesic effects of ketamine in acute inflammatory pain. Anesthesiology. 1998 Jul;89(1):58-66. doi: 10.1097/00000542-199807000-00011.

  PMID: 9667294 BACKGROUND

• Tan PH, Cheng JT, Kuo CH, Tseng FJ, Chung HC, Wu JI, Hsiao HT, Yang LC. Preincisional subcutaneous infiltration of ketamine suppresses postoperative pain after circumcision surgery. Clin J Pain. 2007 Mar-Apr;23(3):214-8. doi: 10.1097/AJP.0b013e31802e3377.

  PMID: 17314579 BACKGROUND

• Lewis KS, Han NH. Tramadol: a new centrally acting analgesic. Am J Health Syst Pharm. 1997 Mar 15;54(6):643-52. doi: 10.1093/ajhp/54.6.643.

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• Desmeules JA, Piguet V, Collart L, Dayer P. Contribution of monoaminergic modulation to the analgesic effect of tramadol. Br J Clin Pharmacol. 1996 Jan;41(1):7-12. doi: 10.1111/j.1365-2125.1996.tb00152.x.

  PMID: 8824687 BACKGROUND

• Krishnadas A, Suvarna K, Hema VR, Taznim M. A comparison of ropivacaine, ropivacaine with tramadol and ropivacaine with midazolam for post-operative caudal epidural analgesia. Indian J Anaesth. 2016 Nov;60(11):827-832. doi: 10.4103/0019-5049.193672.

  PMID: 27942056 BACKGROUND

• Vieira PA, Pulai I, Tsao GC, Manikantan P, Keller B, Connelly NR. Dexamethasone with bupivacaine increases duration of analgesia in ultrasound-guided interscalene brachial plexus blockade. Eur J Anaesthesiol. 2010 Mar;27(3):285-8. doi: 10.1097/EJA.0b013e3283350c38.

  PMID: 20009936 BACKGROUND

• Cummings KC 3rd, Napierkowski DE, Parra-Sanchez I, Kurz A, Dalton JE, Brems JJ, Sessler DI. Effect of dexamethasone on the duration of interscalene nerve blocks with ropivacaine or bupivacaine. Br J Anaesth. 2011 Sep;107(3):446-53. doi: 10.1093/bja/aer159. Epub 2011 Jun 14.

  PMID: 21676892 BACKGROUND

• Reddy VS, Shaik NA, Donthu B, Reddy Sannala VK, Jangam V. Intravenous dexmedetomidine versus clonidine for prolongation of bupivacaine spinal anesthesia and analgesia: A randomized double-blind study. J Anaesthesiol Clin Pharmacol. 2013 Jul;29(3):342-7. doi: 10.4103/0970-9185.117101.

  PMID: 24106359 BACKGROUND

• Mitra S, Purohit S, Sharma M. Postoperative Analgesia After Wound Infiltration With Tramadol and Dexmedetomidine as an Adjuvant to Ropivacaine for Lumbar Discectomies: A Randomized-controlled Clinical Trial. J Neurosurg Anesthesiol. 2017 Oct;29(4):433-438. doi: 10.1097/ANA.0000000000000422.

  PMID: 28266950 BACKGROUND

MeSH Terms

Interventions

Ropivacaine; Ketamine; Tramadol; Midazolam; Dexmedetomidine; Dexamethasone

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Dimethylamines; Methylamines; Lipids; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized control trial

Study Record Dates

• First Submitted: January 17, 2019
• First Posted: January 18, 2019
• Study Start: June 25, 2019
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2023
• Last Updated: July 31, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)