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

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

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

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.

Pain, Postoperative, Pain, Acute, Pain, Chronic, Pain, Neuropathic, Pain, Nociceptive, Ketamine, Dexmedetomidine, Lidocaine, Central Nervous System Depressants, Analgesia, Analgesics, Analgesics Non-narcotic

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.

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%.

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

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 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 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 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 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"

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 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

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

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)

patients will be questioned regarding the time they first felt enteral sounds and the time they had their first flatus after surgery

satisfaction from postoperative analgesia on a six-point Likert scale with 1 marked as minimal satisfaction and 6 as maximal satisfaction

dose of required fentanyl intraoperatively to maintain systolic arterial blood pressure and heart rate within the 20% of baseline value

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

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

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

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