annie-sophia: Lidocaine and Magnesium and Ketamine in Gynecological Surgery

Sponsor

Aretaieion University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04622904

Collaborator

(none)

Enrollment

Location

Arms

35.5

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Pain, Postoperative Pain, Acute Pain, Chronic Pain, Neuropathic Lidocaine Ketamine Magnesium Central Nervous System Depressants Analgesics Neurotransmitter Agents Analgesics, Non-narcotic	Drug: lidocaine-magnesium infusion Drug: lidocaine-ketamine infusion Drug: lidocaine infusion	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Nov 14, 2020

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: lidocaine-magnesium group combination of lidocaine and magnesium infusions	Drug: lidocaine-magnesium infusion 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 50 mL syringe and administered at a rate of 20 mL/h
Active Comparator: lidocaine-ketamine group combination of lidocaine and ketamine infusions	Drug: lidocaine-ketamine infusion 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 50 mL syringe and administered at a rate of 20 mL/h
Active Comparator: lidocaine group lidocaine infusion alone	Drug: lidocaine infusion 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

Arm

Intervention/Treatment

Active Comparator: lidocaine-magnesium group

combination of lidocaine and magnesium infusions

Drug: lidocaine-magnesium infusion

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 50 mL syringe and administered at a rate of 20 mL/h

Active Comparator: lidocaine-ketamine group

combination of lidocaine and ketamine infusions

Drug: lidocaine-ketamine infusion

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 50 mL syringe and administered at a rate of 20 mL/h

Active Comparator: lidocaine group

lidocaine infusion alone

Drug: lidocaine infusion

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

Outcome Measures

Primary Outcome Measures

change from baseline in Quality of Recovery (QoR)-15 score after surgery [24 hours postoperatively]
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 on arrival to Post-Anesthesia Care Unit (PACU) [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) [at discharge from PACU, approximately 1 h 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 [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 [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 [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"
pain score 48 hours postoperatively [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"

Secondary Outcome Measures

Post Anesthesia Care Unit (PACU) duration of stay [immediately postoperatively]
duration of patient stay at PACU
sedation on arrival to Post-Anesthesia Care Unit [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 [at discharge from 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
sevoflurane consumption during general anesthesia [change of sevoflurane vaporizer weight from before induction to end of anesthesia, an average period of 2 hours]
the sevoflurane vaporizer will be weighed before anesthetic induction and at the end of anesthesia and consequently sevoflurane consumption during anesthesia will be determined
time to first request for analgesia [during stay in Post-Anesthesia Care Unit, approximately 1 hour postoperatively]
the time for the first patient request for analgesia will be noted
morphine consumption in Post-Anesthesia Care Unit (PACU) [immediately postoperatively]
mg of morphine requested during patient PACU stay
morphine consumption in the first 48 hours [48 hours postoperatively]
patients will be followed for cumulative morphine consumption through patient-controlled analgesia device for 48 hours postoperatively
sleep quality [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 [24 hours postoperatively]
patients will be questioned regarding the time at which they mobilized after surgery
gastrointestinal recovery after surgery [48 hours postoperatively]
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 [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 [48 hours postoperatively]
patients will be questioned regarding the time they had their first fluid intake
first solid intake [48 hours postoperatively]
patients will be questioned regarding the time they had their first solid intake
hospitalization time [96 hours postoperatively]
duration of hospital stay after surgery in days
fentanyl requirement during surgery [intraoperatively]
dose of required fentanyl intraoperatively to maintain systolic arterial blood pressure and heart rate within the 20% of baseline value
side effects intraoperatively [intraoperatively]
patients will be monitored for side-effects of the administered agents intraoperatively
side effects postoperatively [72 hours postoperatively]
patients will be monitored for side-effects of the administered agents postoperatively
incidence of chronic pain 1 month after surgery [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
incidence of chronic pain 3 months after surgery [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

Other Outcome Measures

time to emergence [end of operation, approximately 2 hours after start of surgery]
time from sevoflurane discontinuation to first patient response (eye opening)
time to extubation [end of operation, approximately 2 hours after start of surgery]
time from sevoflurane discontinuation to tracheal extubation

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 75 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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