Opioid-free Anesthesia in Thyroidectomies

Recovery Parameters and Nociception Levels in Opioid-free Versus Opioid Based Anesthesia for Thyroidectomy

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 thyroidectomies. Recovery parameters and nociception levels throughout the operation will be evaluated

Study Overview

• Status: Recruiting
• Conditions: Analgesia; Pain, Acute; Pain, Post Operative; Ketamine; Dexmedetomidine; Pain, Chronic; Fentanyl; Pain, Neuropathic; Lidocaine; Analgesics; Pain, Nociceptive; Analgesics Non-narcotic
• Intervention / Treatment: Drug: dexmedetomidine-ketamine-lidocaine (DKL); Drug: remifentanil infusion

Detailed Description

In the usual anesthetic practice opioids are often administered in the perioperative period for intraoperative analgesia to control the nociceptive pathway of pain and post-surgical pain management. However, in recent years, opioid Free Anesthesia (OFA) has become increasingly popular, in which opioid administration is avoided intraoperatively and minimized or avoided in the postoperative period.

Opioid-free anesthesia (OFA) has been shown to decrease postoperative complications associated with opioids, include sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression.

Therefore, the investigators aim to perform this study to determine a goal-directed approach, which targets adequate antinociception (e.g., by measuring nociceptive/antinociceptive balance) that could reduce the negative effects of excessive drug infusion, prevent postoperative pain and improve patient outcomes.

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

Contacts and Locations

• Study Contact: Name: KASSIANI THEODORAKI, MD, PhD, DESA; Phone Number: +306974634162; Email: ktheodoraki@hotmail.com
• Study Contact Backup: Name: Rammi Devadze, MD; Phone Number: +306949535388; Email: gurdevadze@gmail.com

Study Locations

• Greece
  • Attiki
    • Athens, Attiki, Greece
      • Recruiting
      • General Hospital of Athens, "Georgios Gennimatas"
      • Contact: Rammi Devadze, MD; Phone Number: +306949535388; Email: gurdevadze@gmail.com
      • Contact: Antonia Dimakopoulou, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• adult patients
• American Society of Anesthesiologists (ASA) classification I-II
• elective thyroidectomy

Exclusion Criteria:

• body mass index (BMI) >35 kg/m2
• contraindications to local anesthetic 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: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: dexmedetomidine-ketamine-lidocaine (DKL) group; combination of dexmedetomidine-ketamine-lidocaine in one syringe	Drug: dexmedetomidine-ketamine-lidocaine (DKL); patients will be administered 0.25 mcg/kg Dexmedetomidine in 100 mL of normal saline within 10 minutes. Followingly, they will receive 1 mL/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.
Active Comparator: remifentanil (control) group; remifentanil infusion (TCI Minto protocol)	Drug: remifentanil infusion; remifentanil infusion under the Minto model (target controlled infusion-TCI aiming at 4ng/ml blood concentration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
change from baseline in Quality of Recovery (QoR)-40 score after surgery	The QoR-40 is used to measure functional recovery and has been validated in patients undergoing general surgical procedures. Five general quality-of-recovery dimensions are measured within the QoR-40: physical comfort (12 items), emotional state (9 items), physical independence (5 items), psychological support (7 items), and pain (7 items). Each item is graded on a five-point Likert scale, and the global scores range from 40 (extremely poor quality of recovery) to 200 (excellent quality of recovery)	24 hours postoperatively
Nociception Level	Nociception Level as measured via the NOL (Nociception Level) index, whose values vary from 0 to 100 (100 represents the maximum level of nociception and 0 represents total absence of nociception). The aim of the current study will be to record percentage of operative time during which NOL levels will be <25	intraoperatively

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
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
side effects intraoperatively	patients will be monitored for side-effects of the administered agents intraoperatively	intraoperatively
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
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
tramadol consumption in the first 48 hours	patients will be followed for cumulative tramadol consumption for 48 hours postoperatively	48 hours postoperatively
remifentanil requirement during anesthesia	rescue remifentanil required intraoperatively to maintain systolic arterial blood pressure and heart rate within the 20% of baseline value	intraoperatively
morphine consumption in Post-Anesthesia Care Unit (PACU	mg of morphine requested during patient PACU stay	immediately 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

• Ziemann-Gimmel P, Goldfarb AA, Koppman J, Marema RT. Opioid-free total intravenous anaesthesia reduces postoperative nausea and vomiting in bariatric surgery beyond triple prophylaxis. Br J Anaesth. 2014 May;112(5):906-11. doi: 10.1093/bja/aet551. Epub 2014 Feb 18.
• 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.
• Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. Br J Anaesth. 2014 Jun;112(6):991-1004. doi: 10.1093/bja/aeu137.
• Forget P. Opioid-free anaesthesia. Why and how? A contextual analysis. Anaesth Crit Care Pain Med. 2019 Apr;38(2):169-172. doi: 10.1016/j.accpm.2018.05.002. Epub 2018 Sep 13.
• Ledowski T. Objective monitoring of nociception: a review of current commercial solutions. Br J Anaesth. 2019 Aug;123(2):e312-e321. doi: 10.1016/j.bja.2019.03.024. Epub 2019 Apr 30.
• Martin JL, Koodie L, Krishnan AG, Charboneau R, Barke RA, Roy S. Chronic morphine administration delays wound healing by inhibiting immune cell recruitment to the wound site. Am J Pathol. 2010 Feb;176(2):786-99. doi: 10.2353/ajpath.2010.090457. Epub 2009 Dec 30.
• Song JY, Choi H, Chae M, Ko J, Moon YE. The effect of opioid-free anesthesia on the quality of recovery after gynecological laparoscopy: study protocol for a prospective randomized controlled trial. Trials. 2021 Mar 12;22(1):207. doi: 10.1186/s13063-021-05166-z.

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2022
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: February 8, 2022
• First Submitted That Met QC Criteria: February 8, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

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; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Ketamine; Remifentanil; Dexmedetomidine; Lidocaine
• Other Study ID Numbers: annie-rammi

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