Lidocaine and Magnesium and Ketamine in Gynecological Surgery

Study Overview
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Brief Summary
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The aim of this study will be to investigate the effect of a combination of intravenous infusions of lidocaine and magnesium versus a combination of intravenous infusions of lidocaine and ketamine versus an intravenous infusion of lidocaine alone on recovery profile, quality of recovery and postoperative pain after elective gynecological surgery

Detailed Description
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Inadequately treated postoperative pain after gynecological surgery may untowardly affect early recovery and also lead to the development of chronic 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, magnesium (acting through modification of the action of N-methyl-D-aspartate receptors) is another agent, which, as an adjuvant to general anesthesia may improve postoperative recovery and pain control through inhibition of cardiovascular response, reduction in general anesthetic needs, enhanced analgesia and anti-inflammatory response. 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 of infusions 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 a sole agent alone. Therefore, the aim of this study will be to investigate the effect of a combination of intravenous infusions of lidocaine and magnesium versus a combination of intravenous infusions of lidocaine and ketamine versus an intravenous infusion of lidocaine alone on recovery profile, quality of recovery and postoperative pain after elective gynecological surgery.

Official Title
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The Effect of Intravenous Infusions of Lidocaine and Magnesium Versus Lidocaine and Ketamine Versus Lidocaine Alone on Recovery Profile and Postoperative Pain After Elective Gynecological Surgery

Conditions
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Pain, Postoperative, Pain, Acute, Pain, Chronic, Pain, Neuropathic, Lidocaine, Ketamine, Magnesium, Central Nervous System Depressants, Analgesics, Neurotransmitter Agents, Analgesics, Non-narcotic

Intervention / Treatment
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* Drug: lidocaine-magnesium infusion
* Drug: lidocaine-ketamine infusion
* Drug: lidocaine infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult female patients American Society of Anesthesiologists (ASA) classification I-II elective open 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 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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Female

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: lidocaine-magnesium group<br>combination of lidocaine and magnesium infusions | Drug: lidocaine-magnesium infusion<br>* A bolus dose of lidocaine of 1.5 mg/kg will be administered within 10 minutes preoperatively diluted in 100 mL of saline. Then, 3 mg/kg/h of lidocaine will be administered intraoperatively. A bolus dose of ketamine of 0.35 mg/kg will be administered within 10 minutes preoperatively diluted in 100 mL of saline. Followingly, 0.2 mg/kg/h of ketamine will be administered intraoperatively diluted in a 60 mL syringe and administered at a rate of 20 mL/h<br>|
| Active Comparator: lidocaine-ketamine group<br>combination of lidocaine and ketamine infusions | Drug: lidocaine-ketamine infusion<br>* A bolus dose of lidocaine of 1.5 mg/kg will be administered within 10 minutes preoperatively diluted in 100 mL of saline. Then, 3 mg/kg/h of lidocaine will be administered intraoperatively. A bolus dose of magnesium of 50 mg/kg will be administered within 10 minutes preoperatively diluted in 100 mL of saline. Followingly, 10 mg/kg/h of magnesium will be administered intraoperatively diluted in a 60 mL syringe and administered at a rate of 20 mL/h<br>|
| Active Comparator: lidocaine group<br>lidocaine infusion alone | Drug: lidocaine infusion<br>* A bolus dose of lidocaine of 1.5 mg/kg will be administered within 10 minutes preoperatively diluted in 100 mL of saline. Then, 3 mg/kg/h of lidocaine will be administered intraoperatively. A bolus dose of normal saline 100 mL will be administered preoperatively within 10 minutes. Followingly, normal saline will be administered intraoperatively at a rate of 20 mL/h<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)-15 score after surgery | 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 | 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 PACU, approximately 1 h 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 48 hours postoperatively | pain score by the use of Numeric Rating Scale (NRS) 48 hours postoperatively, ranging from 0 to 10, where 0 means no pain and 10 means worst pain imaginable | 48 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 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 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, approximately 1 hour postoperatively | 
| morphine consumption in Post-Anesthesia Care Unit (PACU) | mg of morphine requested during patient PACU stay | immediately postoperatively | 
| morphine consumption in the first 48 hours | patients will be followed for cumulative morphine consumption through patient-controlled analgesia device 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 | 
| 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 | 48 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 | 48 hours postoperatively | 
| first solid intake | patients will be questioned regarding the time they had their first solid intake | 48 hours postoperatively | 
| hospitalization time | duration of hospital stay after surgery in days | 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 | 72 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 |