Opioid-free Anesthesia in Laparoscopic Cholecystectomies

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 laparoscopic cholecystectomies

Detailed Description
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Inadequately treated postoperative pain after laparoscopic cholecystectomy 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. Pneumoperitoneum can lead to postoperative discomfort and occasionally intense postoperative shoulder pain. 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 and postoperative pain after elective laparoscopic cholecystectomy.

Official Title
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Opioid-free Anesthesia With a Mixture of Dexmedetomidine-lidocaine-ketamine in Laparoscopic Cholecystectomies

Conditions
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Pain, Postoperative, Pain, Acute, Pain, Chronic, Cholecystectomy, Ketamine, Dexmedetomidine, Lidocaine, Central Nervous System Depressants, Analgesia, Analgesics, Analgesic Non-narcotic

Intervention / Treatment
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* Drug: ketamine-lidocaine-dexmedetomidine
* Drug: fentanyl


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 laparoscopic cholecystectomy 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

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ketamine-lidocaine-dexmedetomidine (KLD) group<br>combination of ketamine-lidocaine-dexmedetomidine in one syringe | Drug: ketamine-lidocaine-dexmedetomidine<br>* 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.<br>* Other names: KLD group;|
| Active Comparator: fentanyl (control) group<br>syringe of fentanyl | Drug: fentanyl<br>* 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%.<br>* Other names: Control group;|

What is the study measuring?
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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 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 | 

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 | 
| 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 | 
| 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 1-2 hours | 
| 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 24 hours | patients will be followed for cumulative tramadol consumption for 24 hours postoperatively | 24 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 | 
| 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 | 
| 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 | 
| 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 | 
| side effects postoperatively | patients will be monitored for side-effects of the administered agents postoperatively | 48 hours postoperatively | 
| 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 |