Opioid-free Anesthesia in Thyroidectomies

• ClinicalTrials.gov Identifier: NCT05243940
• Recruitment Status: Recruiting
• First Posted: February 17, 2022
• Last Update Posted: April 20, 2022
• Sponsor: Aretaieion University Hospital
• Information provided by (Responsible Party): Dr Kassiani Theodoraki, Aretaieion University Hospital

Tracking Information

• First Submitted Date: February 8, 2022
• First Posted Date: February 17, 2022
• Last Update Posted Date: April 20, 2022
• Actual Study Start Date: March 7, 2022
• Estimated Primary Completion Date: February 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 8, 2022)

• change from baseline in Quality of Recovery (QoR)-40 score after surgery [ Time Frame: 24 hours postoperatively ]
  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)
• pain score on arrival to Post-Anesthesia Care Unit (PACU) [ Time Frame: immediately postoperatively ]
  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"
• pain score at discharge from Post-Anesthesia Care Unit (PACU) [ Time Frame: at discharge from Post Anesthesia Care Unit (PACU), approximately 1 hour postoperatively ]
  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"
• pain score 3 hours postoperatively [ Time Frame: 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"
• pain score 6 hours postoperatively [ Time Frame: 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"
• pain score 24 hours postoperatively [ Time Frame: 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"
• Nociception Level [ Time Frame: intraoperatively ]
  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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 8, 2022)

• remifentanil requirement during anesthesia [ Time Frame: intraoperatively ]
  rescue remifentanil required intraoperatively to maintain systolic arterial blood pressure and heart rate within the 20% of baseline value
• Post Anesthesia Care Unit (PACU) duration of stay [ Time Frame: immediately postoperatively ]
  duration of patient stay at PACU
• sedation on arrival to Post-Anesthesia Care Unit [ Time Frame: immediately postoperatively ]
  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
• sedation at discharge from Post-Anesthesia Care (PACU) Unit [ Time Frame: at discharge from Post Anesthesia Care Unit (PACU), approximately 1 hour postoperatively ]
  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
• time to first request for analgesia [ Time Frame: during stay in Post-Anesthesia Care Unit (PACU), approximately 1 hour postoperatively ]
  the time for the first patient request for analgesia will be noted
• morphine consumption in Post-Anesthesia Care Unit (PACU [ Time Frame: immediately postoperatively ]
  mg of morphine requested during patient PACU stay
• tramadol consumption in the first 48 hours [ Time Frame: 48 hours postoperatively ]
  patients will be followed for cumulative tramadol consumption for 48 hours postoperatively
• sleep quality [ Time Frame: 24 hours postoperatively ]
  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)
• first mobilization after surgery [ Time Frame: 24 hours postoperatively ]
  patients will be questioned regarding the time at which they mobilized after surgery
• satisfaction from postoperative analgesia [ Time Frame: 24 hours postoperatively ]
  satisfaction from postoperative analgesia on a six-point Likert scale with 1 marked as minimal satisfaction and 6 as maximal satisfaction
• first fluid intake [ Time Frame: 24 hours postoperatively ]
  patients will be questioned regarding the time they had their first fluid intake
• first solid intake [ Time Frame: 24 hours postoperatively ]
  patients will be questioned regarding the time they had their first solid intake
• hospitalization time [ Time Frame: 96 hours postoperatively ]
  duration of hospital stay after surgery in hours
• side effects intraoperatively [ Time Frame: intraoperatively ]
  patients will be monitored for side-effects of the administered agents intraoperatively
• side effects postoperatively [ Time Frame: 48 hours postoperatively ]
  patients will be monitored for side-effects of the administered agents postoperatively

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: February 8, 2022)

• time to emergence [ Time Frame: up to 2-3 hours after start of surgery] ]
  time from sevoflurane discontinuation to first patient response (eye opening)
• time to extubation [ Time Frame: up to 2-3 hours after start of surgery] ]
  time from sevoflurane discontinuation to tracheal extubation

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Opioid-free Anesthesia in Thyroidectomies
• Official Title: Recovery Parameters and Nociception Levels in Opioid-free Versus Opioid Based Anesthesia for Thyroidectomy
• Brief 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 thyroidectomies. Recovery parameters and nociception levels throughout the operation will be evaluated

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
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Prevention

Condition

• Pain, Post Operative
• Pain, Acute
• Pain, Chronic
• Pain, Neuropathic
• Pain, Nociceptive
• Ketamine
• Dexmedetomidine
• Lidocaine
• Fentanyl
• Analgesia
• Analgesics
• Analgesics Non-narcotic

Intervention

• 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.

• Drug: remifentanil infusion
  remifentanil infusion under the Minto model (target controlled infusion-TCI aiming at 4ng/ml blood concentration

Study Arms

• Active Comparator: dexmedetomidine-ketamine-lidocaine (DKL) group
  combination of dexmedetomidine-ketamine-lidocaine in one syringe
  Intervention: Drug: dexmedetomidine-ketamine-lidocaine (DKL)
• Active Comparator: remifentanil (control) group
  remifentanil infusion (TCI Minto protocol)
  Intervention: Drug: remifentanil infusion

Publications *

• 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. Review.
• 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. Review.
• 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.
• 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.
• 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.
• 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. Review.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 8, 2022): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 1, 2024
• Estimated Primary Completion Date: February 1, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 25 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: KASSIANI THEODORAKI, MD, PhD, DESA; +306974634162; ktheodoraki@hotmail.com

Contact: Rammi Devadze, MD; +306949535388; gurdevadze@gmail.com

• Listed Location Countries: Greece

Administrative Information

• NCT Number: NCT05243940
• Other Study ID Numbers: annie-rammi
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Dr Kassiani Theodoraki, Aretaieion University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Aretaieion University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: KASSIANI THEODORAKI, MD, PhD, DESA; Aretaieion University Hospital, National and Kapodistrian University of Athens, Greece

• PRS Account: Aretaieion University Hospital
• Verification Date: April 2022