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

NCT ID: NCT04648540

Last Updated: 2023-08-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-01
• Study Completion Date: 2022-10-01

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

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.

Conditions

Anesthesia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Dexmedetomidine 0.5 mic/kg/h

Intervention Type: DRUG

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

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

Group Type: ACTIVE_COMPARATOR

Fentanyl 1 mic/kg/hr

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Lidocaine 0.5 mg/kg/h; Pregabalin 150 mg; Acetaminophen 1g; Ketorolac 30 mg; Celecoxib 200 mg; Morphine 0.1 mg/kg/hr

Eligibility Criteria

Inclusion Criteria

1. Patients undergoing cardiac valve surgeries ( replacement or repair ) .

2. Age (18-80) years

3. 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Cairo University

OTHER

Sponsor Role: lead

Responsible Party

Hossam El-Ashmawi

Professor of anesthiology and pain management

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

hossam El-Ashmawi, Professor

Role: PRINCIPAL_INVESTIGATOR

Cairo University

Locations

Kasr Al Ainy School of Medicine Cairo University

Cairo, , Egypt

Countries

Egypt

References

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Other Identifiers

MD-242-2019

Identifier Type: -

Identifier Source: org_study_id