Opioid-free Anesthesia in Thyroidectomies

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Drug: dexmedetomidine-ketamine-lidocaine (DKL)
* Drug: remifentanil infusion


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: dexmedetomidine-ketamine-lidocaine (DKL) group<br>combination of dexmedetomidine-ketamine-lidocaine in one syringe | Drug: dexmedetomidine-ketamine-lidocaine (DKL)<br>* 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.<br>|
| Active Comparator: remifentanil (control) group<br>remifentanil infusion (TCI Minto protocol) | Drug: remifentanil infusion<br>* remifentanil infusion under the Minto model (target controlled infusion-TCI aiming at 4ng/ml blood concentration<br>|

What is the study measuring?
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Primary Outcome Measures

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