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

Pain, Postoperative Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04858711
• Other study ID #: 306/26-03-2021
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2021
• Est. completion date: September 30, 2023

Study information

• Verified date: October 2022
• Source: Aretaieion University Hospital
• Contact: Kassiani Theodoraki, PhD, DESA
• Phone: +306974634162
• Email: ktheodoraki[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 30, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 25 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Pain
• Analgesia
• Analgesics
• Central Nervous System Depressants
• Chronic Pain
• Dexmedetomidine
• Ketamine
• Lidocaine
• Neuralgia
• Nociceptive Pain
• Pain, Acute
• Pain, Chronic
• Pain, Neuropathic
• Pain, Postoperative

Intervention

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.
• 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%.

Locations

Country	Name	City	State
Greece	Aretaieion University Hospital	Athens

Sponsors (1)

Lead Sponsor	Collaborator
Aretaieion University Hospital

Country where clinical trial is conducted

Greece, 

References & Publications (9)

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. English, Spanish. — View Citation

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. Review. — View Citation

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. — View Citation

Vigneault L, Turgeon AF, Côté 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	time to emergence	time from sevoflurane discontinuation to first patient response (eye opening)	up to 2-3 hours after start of surgery
Other	time to extubation	time from sevoflurane discontinuation to tracheal extubation	up to 2-3 hours after start of surgery
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Secondary	Post Anesthesia Care Unit (PACU) duration of stay	duration of patient stay at PACU	immediately postoperatively
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	morphine consumption in Post-Anesthesia Care Unit (PACU)	mg of morphine requested during patient PACU stay	immediately postoperatively
Secondary	tramadol consumption in the first 48 hours	patients will be followed for cumulative tramadol consumption for 48 hours postoperatively	48 hours postoperatively
Secondary	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
Secondary	first mobilization after surgery	patients will be questioned regarding the time at which they mobilized after surgery	24 hours postoperatively
Secondary	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
Secondary	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
Secondary	first fluid intake	patients will be questioned regarding the time they had their first fluid intake	24 hours postoperatively
Secondary	first solid intake	patients will be questioned regarding the time they had their first solid intake	24 hours postoperatively
Secondary	hospitalization time	duration of hospital stay after surgery in hours	96 hours postoperatively
Secondary	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
Secondary	side effects intraoperatively	patients will be monitored for side-effects of the administered agents intraoperatively	intraoperatively
Secondary	side effects postoperatively	patients will be monitored for side-effects of the administered agents postoperatively	48 hours postoperatively
Secondary	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
Secondary	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