Opioid-free Anesthesia With a Mixture of Dexmedetomidine-lidocaine-ketamine

The Effect of a Mixture of Dexmedetomidine-lidocaine-ketamine in One Syringe Versus Opioids on Recovery Profile and Postoperative Pain After Gynecological Laparoscopic Surgery

The aim of this study will be to investigate the effect of an opioid-free anesthesia regimen with a mixture of dexmedetomidine-lidocaine-ketamine in the same syringe versus fentanyl analgesia in elective laparoscopic gynecological surgery

Study Overview

• Status: Recruiting
• Conditions: Pain, Postoperative; Analgesia; Pain, Acute; Ketamine; Dexmedetomidine; Pain, Chronic; Pain, Neuropathic; Lidocaine; Central Nervous System Depressants; Analgesics; Pain, Nociceptive; Analgesics Non-narcotic
• Intervention / Treatment: Drug: fentanyl; Drug: ketamine-lidocaine-dexmedetomidine

Detailed Description

Inadequately treated postoperative pain after gynecological surgery may untowardly affect early recovery and also lead to the development of chronic pain. Laparoscopic surgery is associated with diminished postoperative pain but this does not mean that patients subjected to laparoscopic operations are not in need for analgesia intra- and postoperatively. Opioid-based analgesia is associated with side-effects, such as respiratory depression, postoperative nausea and vomiting and occasional induction of tolerance and hyperalgesia. Therefore, in recent years research has focused on the quest for non-opioid-based regimens for perioperative analgesia in the context of multimodal analgesic techniques. These techniques have been shown to possess significant advantages, such as allowing earlier mobilization after surgery, early resumption of enteral feeding and reduced hospital length of stay.

In this context, the intraoperative intravenous injection of lidocaine has been reported to improve postoperative pain control, reduce opioid consumption and improve the quality of postoperative functional recovery after general anesthesia. Intraoperative infusions of ketamine (an N-methyl-D-aspartate receptor inhibitor) have also been correlated with reduced pain scores and a decrease in analgesic requirements postoperatively. Lastly, dexmedetomidine is a highly selective alfa-2 adreno-ceptor agonist that provides sedation, analgesia, and sympatholysis. Its perioperative intravenous administration has been associated with a reduction in postoperative pain intensity, analgesic consumption and nausea.

There is insufficient data in literature investigating the effect of combinations of these agents intraoperatively. It would be of interest to demonstrate whether the administration of combinations can be used towards the achievement of a completely opioid-free anesthetic regimen. Additionally, it can be hypothesized that the combination of non-opioid drugs with different targets can lead to enhanced postoperative recovery, an improved opioid-sparing effect and a decrease in the development of chronic pain as compared to the administration of opioids.

Therefore, the aim of this study will be to investigate the effect of a combination of intravenous infusions of lidocaine-ketamine-dexmedetomidine versus fentanyl on recovery profile, quality of recovery and postoperative pain after elective laparoscopic gynecological surgery.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sofia Apostolidou, MD; Email: sofia.apos@hotmail.com

Study Locations

• Greece
  • Athens, Greece, 115 28
    • Recruiting
    • ARETAIEION University Hospital
    • Contact: Kassiani Theodoraki, PhD, DESA; Phone Number: #306974634162; Email: ktheodoraki@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• adult female patients
• American Society of Anesthesiologists (ASA) classification I-II
• elective laparoscopic gynecological surgery

Exclusion Criteria:

• body mass index (BMI) >35 kg/m2
• contraindications to local anesthetic administration or non-steroidal agents administration
• systematic use of analgesic agents preoperatively
• chronic pain syndromes preoperatively
• neurological or psychiatric disease on treatment
• pregnancy
• severe hepatic or renal disease
• history of cardiovascular diseases/ arrhythmias/ conduction abnormalities
• bradycardia(<55 beats/minute)
• drug or alcohol abuse
• language or communication barriers lack of informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ketamine-lidocaine-dexmedetomidine (KLD) group; combination of ketamine-lidocaine-dexmedetomidine in one syringe	Drug: ketamine-lidocaine-dexmedetomidine; In the KLD group, patients will be administered 0,25 mcg/kg Dexmedetomidine in 100 mL of normal saline within 10 minutes. Followingly, they will receive 1mL/10 kg of the solution containing ketamine, lidocaine and dexmedetomidine at predefined concentrations. As maintenance, they will be receiving 1mL/10kg/h of the aforementioned solution.; Other Names: KLD group
Active Comparator: fentanyl (control) group; syringe of fentanyl	Drug: fentanyl; In the fentanyl group, patients will be administered 2 mcg/kg fentanyl in 100 mL of normal saline within 10 minutes. Followingly, they will receive 1mL/10 kg of normal saline solution 0.9%. As maintenance, they will be receiving 1mL/10kg/h of normal saline solution 0.9%.; Other Names: Control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change from baseline in Quality of Recovery (QoR)-15 score after surgery	The QoR-15 is a quality of recovery scale that consists of 15 questions (items),including questions regarding pain (2 items), physical comfort (5 items), self-care ability (2 items), psychological support (2 items) and emotional state (4 items). Every item is scored on a scale of 10, with the lowest total score of 0 and the highest score of 150. The higher the score, the better the recovery quality of the patient	24 hours postoperatively
pain score on arrival to Post-Anesthesia Care Unit (PACU)	pain score by the use of Numeric Rating Scale (NRS) on arrival to PACU, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"	immediately postoperatively
pain score 3 hours postoperatively	pain score by the use of Numeric Rating Scale (NRS) 3 hours postoperatively, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"	3 hours postoperatively
pain score 6 hours postoperatively	pain score by the use of Numeric Rating Scale (NRS) 6 hours postoperatively, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"	6 hours postoperatively
pain score 24 hours postoperatively	pain score by the use of Numeric Rating Scale (NRS) 24 hours postoperatively, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"	24 hours postoperatively
pain score at discharge from Post-Anesthesia Care Unit (PACU)	pain score by the use of Numeric Rating Scale (NRS) at discharge from PACU, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"	at discharge from Post Anesthesia Care Unit (PACU), approximately 1 hour postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post Anesthesia Care Unit (PACU) duration of stay	duration of patient stay at PACU	immediately postoperatively
sedation on arrival to Post-Anesthesia Care Unit	sedation will be assessed with a 5-point sedation scale, where: 1, patient perfectly conscious; 2, patient feels a little drowsy; 3, patient seems to be sleeping but immediately reacts to verbal stimulation; 4, patient seems to be sleeping but slowly reacts to verbal stimulation and 5, patient seems to be sleeping and does not react to verbal stimulation but does react to a stimulus such as shaking or pain	immediately postoperatively
morphine consumption in Post-Anesthesia Care Unit (PACU)	mg of morphine requested during patient PACU stay	immediately postoperatively
sleep quality	subjective evaluation of sleep quality by patients, based on a sleep questionnaire (evaluation of sleep duration, number of nocturnal awakenings and marking of sleep quality)	24 hours postoperatively
first mobilization after surgery	patients will be questioned regarding the time at which they mobilized after surgery	24 hours postoperatively
satisfaction from postoperative analgesia	satisfaction from postoperative analgesia on a six-point Likert scale with 1 marked as minimal satisfaction and 6 as maximal satisfaction	24 hours postoperatively
fentanyl requirement during surgery	dose of required fentanyl intraoperatively to maintain systolic arterial blood pressure and heart rate within the 20% of baseline value	intraoperatively
side effects intraoperatively	patients will be monitored for side-effects of the administered agents intraoperatively	intraoperatively
incidence of chronic pain 1 month after surgery	occurrence of chronic pain at the site of the operation 1 month after surgery, with the use of the Numeric Rating Scale (NRS), at rest and during movement	1 month after surgery
incidence of chronic pain 3 months after surgery	occurrence of chronic pain at the site of the operation 3 months after surgery, with the use of the Numeric Rating Scale (NRS), at rest and during movement	3 months after surgery
sedation at discharge from Post-Anesthesia Care (PACU) Unit	sedation will be assessed with a 5-point sedation scale, where: 1, patient perfectly conscious; 2, patient feels a little drowsy; 3, patient seems to be sleeping but immediately reacts to verbal stimulation; 4, patient seems to be sleeping but slowly reacts to verbal stimulation and 5, patient seems to be sleeping and does not react to verbal stimulation but does react to a stimulus such as shaking or pain	at discharge from Post Anesthesia Care Unit (PACU), approximately 1 hour postoperatively
time to first request for analgesia	the time for the first patient request for analgesia will be noted	during stay in Post-Anesthesia Care Unit (PACU), approximately 1 hour postoperatively
gastrointestinal recovery after surgery	patients will be questioned regarding the time they first felt enteral sounds and the time they had their first flatus after surgery	24 hours postoperatively
first fluid intake	patients will be questioned regarding the time they had their first fluid intake	24 hours postoperatively
first solid intake	patients will be questioned regarding the time they had their first solid intake	24 hours postoperatively
hospitalization time	duration of hospital stay after surgery in hours	96 hours postoperatively
side effects postoperatively	patients will be monitored for side-effects of the administered agents postoperatively	48 hours postoperatively
sevoflurane consumption during general anesthesia	the sevoflurane vaporizer will be weighed before anesthetic induction and at the end of anesthesia and consequently sevoflurane consumption during anesthesia will be determined	change of sevoflurane vaporizer weight from before induction to end of anesthesia, an average period of 2-3 hours
tramadol consumption in the first 48 hours	patients will be followed for cumulative tramadol consumption for 48 hours postoperatively	48 hours postoperatively

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to emergence	time from sevoflurane discontinuation to first patient response (eye opening)	up to 2-3 hours after start of surgery
time to extubation	time from sevoflurane discontinuation to tracheal extubation	up to 2-3 hours after start of surgery

Collaborators and Investigators

• Sponsor: Aretaieion University Hospital

Publications and helpful links

General Publications

• De Oliveira GS Jr, Castro-Alves LJ, Khan JH, McCarthy RJ. Perioperative systemic magnesium to minimize postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology. 2013 Jul;119(1):178-90. doi: 10.1097/ALN.0b013e318297630d.
• Vigneault L, Turgeon AF, Cote D, Lauzier F, Zarychanski R, Moore L, McIntyre LA, Nicole PC, Fergusson DA. Perioperative intravenous lidocaine infusion for postoperative pain control: a meta-analysis of randomized controlled trials. Can J Anaesth. 2011 Jan;58(1):22-37. doi: 10.1007/s12630-010-9407-0.
• Lavand'homme P, Steyaert A. Opioid-free anesthesia opioid side effects: Tolerance and hyperalgesia. Best Pract Res Clin Anaesthesiol. 2017 Dec;31(4):487-498. doi: 10.1016/j.bpa.2017.05.003. Epub 2017 May 17.
• Frauenknecht J, Kirkham KR, Jacot-Guillarmod A, Albrecht E. Analgesic impact of intra-operative opioids vs. opioid-free anaesthesia: a systematic review and meta-analysis. Anaesthesia. 2019 May;74(5):651-662. doi: 10.1111/anae.14582. Epub 2019 Feb 25.
• Lavand'homme P, Estebe JP. Opioid-free anesthesia: a different regard to anesthesia practice. Curr Opin Anaesthesiol. 2018 Oct;31(5):556-561. doi: 10.1097/ACO.0000000000000632.
• Mulier J. Opioid free general anesthesia: A paradigm shift? Rev Esp Anestesiol Reanim. 2017 Oct;64(8):427-430. doi: 10.1016/j.redar.2017.03.004. Epub 2017 Apr 18. No abstract available. English, Spanish.
• Mauermann E, Ruppen W, Bandschapp O. Different protocols used today to achieve total opioid-free general anesthesia without locoregional blocks. Best Pract Res Clin Anaesthesiol. 2017 Dec;31(4):533-545. doi: 10.1016/j.bpa.2017.11.003. Epub 2017 Nov 24.
• Panchgar V, Shetti AN, Sunitha HB, Dhulkhed VK, Nadkarni AV. The Effectiveness of Intravenous Dexmedetomidine on Perioperative Hemodynamics, Analgesic Requirement, and Side Effects Profile in Patients Undergoing Laparoscopic Surgery Under General Anesthesia. Anesth Essays Res. 2017 Jan-Mar;11(1):72-77. doi: 10.4103/0259-1162.200232.
• Mulier JP. Is opioid-free general anesthesia for breast and gynecological surgery a viable option? Curr Opin Anaesthesiol. 2019 Jun;32(3):257-262. doi: 10.1097/ACO.0000000000000716.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): September 30, 2023

Study Registration Dates

• First Submitted: April 16, 2021
• First Submitted That Met QC Criteria: April 22, 2021
• First Posted (Actual): April 26, 2021

Study Record Updates

• Last Update Posted (Actual): October 24, 2022
• Last Update Submitted That Met QC Criteria: October 21, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Postoperative Complications; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Pain, Postoperative; Chronic Pain; Neuralgia; Acute Pain; Nociceptive Pain; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Membrane Transport Modulators; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Ketamine; Fentanyl; Dexmedetomidine; Lidocaine
• Other Study ID Numbers: 306/26-03-2021

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