Multimodal Opioid-free Anesthesia Versus Opioid-based Anesthesia for Patients Undergoing Cardiac Valve Surgeries: RCT

Sponsor

Cairo University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04648540

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Several studies demonstrated the effectiveness of OFA in patients undergoing non-cardiac surgery. Preoperative use of Cox inhibitors, GABA analogues and acetaminophen have been shown to decrease use of opioids postoperatively . Intraoperative use of agents that lead to opioid sparing effects via sodium channel blockade, blockade of G protein-coupled receptors, NMDA blockade, central alpha-2 agonists and anti-inflammatory effects can make opioid-free anesthesia (OFA) possible. On the other hand, there have been no studies demonstrating the effectiveness of an OFA technique in patients undergoing cardiac surgery except for two case reports who successfully implemented the OFA regimen in two patients undergoing valve replacement surgeries. The investigators therefore propose this prospective randomized controlled trial to investigate whether a multimodal opioid-free anesthesia regimen will be suitable as an alternative to conventional opioid-based regimen in patients undergoing valve surgery

Condition or Disease	Intervention/Treatment	Phase
Anesthesia	Drug: Dexmedetomidine 0.5 mic/kg/h Drug: Fentanyl 1 mic/kg/hr	Early Phase 1

Detailed Description

High-dose opioid anesthesia during cardiac surgery has been the mainstay of cardiac anesthesia for decades due to its ability to preserve hemodynamic stability and attenuate hormonal and metabolic response to surgical stress (1) . However, large doses of long-acting opioids required patients to be ventilated post-operatively for 12-24 h. Modifications in these practices have been dictated by the increasing cost, complications of prolonged mechanical ventilation, and the changes in demographics of patients presenting for cardiac surgery (2) . Moreover, the intraoperative use of large bolus doses or continuous infusions of potent opioids may be associated with postoperative hyperalgesia and tolerance (3). When it comes to ambulatory surgery, opioid related side effects, such as postoperative nausea and vomiting (PONV), prolonged sedation, ileus and urinary retention may delay recovery and discharge or cause unanticipated hospital readmission (4) . Such complications might, at least in part, also apply to cardiac anesthesia.

Recent evidence suggests that increased total dose of opioids during cardiac surgery may lead to increased in-hospital, as well as long-term post-operative pain medication requirements for up to one year (5). Moreover, according to Hirji et al study , ongoing opioid use three months after CABG was present in 21.7% of opioid-exposed patients versus 3.2% of opioid-naive patients (6). In addition, Opioids have many known side effects such as somnolence, brainstem and respiratory depression , and chronic opioid dependence (7-9), and there is a national trend to decrease opioid use during non-cardiac surgery to promote faster recovery and decrease narcotic use post-operatively (1) .

Several studies demonstrated the effectiveness of Opioid-free Anesthesia (OFA) in patients undergoing non-cardiac surgery(4,10,11). Preoperative use of COX inhibitors, GABA analogues and acetaminophen have been shown to decrease use of opioids postoperatively(10). Intraoperative use of agents that lead to opioid sparing effects via sodium channel blockade, blockade of G protein-coupled receptors, NMDA blockade, central alpha-2 agonists and anti-inflammatory effects can make opioid-free anesthesia (OFA) possible (12,13). On the other hand, there have been no studies demonstrating the effectiveness of an OFA technique in patients undergoing cardiac surgery except for two case reports who successfully implemented the OFA regimen in two patients undergoing valve replacement surgeries (14,15). The investigators therefore propose this prospective randomized controlled trial to investigate whether a multimodal opioid-free anesthesia regimen will be suitable as an alternative to conventional opioid-based regimen in patients undergoing valve surgery.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

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

Primary Purpose:

Treatment

Official Title:

Multimodal Opioid-free Anesthesia Versus Opioid-based Anesthesia for Patients Undergoing Cardiac Valve Surgeries: A Randomized Controlled Trial

Actual Study Start Date :

Dec 1, 2020

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Opioid-Free Anesthesia (OFA) The following drugs will be administered 10 minutes before induction of anesthesia in group I (OFA): Pregabalin 150 mg orally with a small sip of water Acetaminophen 1 gm and Ketorolac 30 mg in 100 mL i.v. over 10 minutes Dexmedetomidine loading dose of 0.5 mic/kg i.v. over 10 minutes Lidocaine loading dose of 1.5 mg/kg i.v. over 10 minutes For simplicity, the weight-based doses of dexmedetomidine and lidocaine will be prepared in a 20 mL syringe the following drugs will be administered as a continuous infusion: Dexmedetomidine 0.5 mic/kg/h Lidocaine 0.5 mg/kg/h Patients in both groups will be extubated when they meet our institutional criteria for extubation. Postoperative analgesia will be started as follows: Group I (OFA): Acetaminophen 1 gm/6h ketorolac 30 mg/8h Pregabalin 150 mg once at night Celecoxib 200 mg/24 hours	Drug: Dexmedetomidine 0.5 mic/kg/h In Group I (OFA) the following drugs will be administered preoperatively: Acetaminophen 1 gm and Ketorolac 30 mg in 100 mL i.v. over 10 minutes Dexmedetomidine loading dose of 0.5 mic/kg i.v. over 10 minutes Lidocaine loading dose of 1.5 mg/kg i.v. over 10 minutes The following drugs will be administered as a continuous infusion throughout the operation: Dexmedetomidine 0.5 mic/kg/h Lidocaine 0.5 mg/kg/h The following drugs will be administered postoperatively: Acetaminophen 1 gm/6h ketorolac 30 mg/8h Pregabalin 150 mg once at night Celecoxib 200 mg/24 hours Other Names: Lidocaine 0.5 mg/kg/h Pregabalin 150 mg Acetaminophen 1g Ketorolac 30 mg Celecoxib 200 mg
Active Comparator: Opioid Anesthesia (OA) Before induction In Group II (OA) patients will receive placebo pills and normal saline in equivalent volumes . Maintenance In Group II (OA) patients will receive a continuous infusion of Fentanyl (1 mic/kg/h) Patients in both groups will be extubated when they meet our institutional criteria for extubation. Postoperative analgesia will be started as follows: • Morphine 0.1 mg /kg PRN every 8 hours	Drug: Fentanyl 1 mic/kg/hr In Group II (OA) patients will receive a continuous infusion of Fentanyl (1 mic/kg/h) Morphine 0.1 mg/kg PRN will be administered every 8 hours for postoperative analgesia Other Names: Morphine 0.1 mg/kg/hr

Arm

Intervention/Treatment

Experimental: Opioid-Free Anesthesia (OFA)

The following drugs will be administered 10 minutes before induction of anesthesia in group I (OFA): Pregabalin 150 mg orally with a small sip of water Acetaminophen 1 gm and Ketorolac 30 mg in 100 mL i.v. over 10 minutes Dexmedetomidine loading dose of 0.5 mic/kg i.v. over 10 minutes Lidocaine loading dose of 1.5 mg/kg i.v. over 10 minutes For simplicity, the weight-based doses of dexmedetomidine and lidocaine will be prepared in a 20 mL syringe the following drugs will be administered as a continuous infusion: Dexmedetomidine 0.5 mic/kg/h Lidocaine 0.5 mg/kg/h Patients in both groups will be extubated when they meet our institutional criteria for extubation. Postoperative analgesia will be started as follows: Group I (OFA): Acetaminophen 1 gm/6h ketorolac 30 mg/8h Pregabalin 150 mg once at night Celecoxib 200 mg/24 hours

Drug: Dexmedetomidine 0.5 mic/kg/h

In Group I (OFA) the following drugs will be administered preoperatively: Acetaminophen 1 gm and Ketorolac 30 mg in 100 mL i.v. over 10 minutes Dexmedetomidine loading dose of 0.5 mic/kg i.v. over 10 minutes Lidocaine loading dose of 1.5 mg/kg i.v. over 10 minutes The following drugs will be administered as a continuous infusion throughout the operation: Dexmedetomidine 0.5 mic/kg/h Lidocaine 0.5 mg/kg/h The following drugs will be administered postoperatively: Acetaminophen 1 gm/6h ketorolac 30 mg/8h Pregabalin 150 mg once at night Celecoxib 200 mg/24 hours

Other Names:

Lidocaine 0.5 mg/kg/h

Pregabalin 150 mg

Acetaminophen 1g

Ketorolac 30 mg

Celecoxib 200 mg

Active Comparator: Opioid Anesthesia (OA)

Before induction In Group II (OA) patients will receive placebo pills and normal saline in equivalent volumes . Maintenance In Group II (OA) patients will receive a continuous infusion of Fentanyl (1 mic/kg/h) Patients in both groups will be extubated when they meet our institutional criteria for extubation. Postoperative analgesia will be started as follows: • Morphine 0.1 mg /kg PRN every 8 hours

Drug: Fentanyl 1 mic/kg/hr

In Group II (OA) patients will receive a continuous infusion of Fentanyl (1 mic/kg/h) Morphine 0.1 mg/kg PRN will be administered every 8 hours for postoperative analgesia

Other Names:

Morphine 0.1 mg/kg/hr

Outcome Measures

Primary Outcome Measures

Extubation time (min) [24 hours]
Extubation time, defined as the time from discontinuation of inhalation agents to extubation

Secondary Outcome Measures

Heart rate (beats/min) [24 hours]
HR o Arterial blood pressure (systolic, diastolic, and mean)
Blood pressure (mm Hg) [24 hours]
Systolic, diastolic, and mean blood pressure
Postoperative rescue analgesia (number) [24]
The number of patients requiring rescue analgesia with Morphine
Postoperative morphine consumption (mg) [24 hours]
The total dose of morphine administered

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Patients undergoing cardiac valve surgeries ( replacement or repair ) .
Age (18-80) years
Both sexes

Exclusion Criteria:

Patient refusal
Known allergy to any of the medications used in the study
Combined valve and CABG surgeries
Redo surgery
Infective endocarditis
Patients in heart failure or heart block or with significant systolic dysfunction (EF < 40%) or diastolic dysfunction more than grade II
Pregnant females
Patients being treated for chronic pain or with recent use (< two weeks) of opioids, gabapentin, or pregabalin.
Substance abuse
Patients with renal impairment (creatinine > 2 mg/dL) or hepatic impairment (ALT > 2 folds, INR > 1.5 and/or serum albumin < 2.5 g/dl)