Multimodal Opioid-free Anesthesia Versus Opioid-based Anesthesia for Patients Undergoing Cardiac Valve Surgeries: RCT
Condition: Anesthesia
Study type: Interventional
Phase: Early Phase 1

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.
    

Intervention name(s): Dexmedetomidine 0.5 mic/kg/h; Fentanyl 1 mic/kg/hr
Intervention type(s): Drug; Drug
Intervention description(s): 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; 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 intervention name(s): Lidocaine 0.5 mg/kg/h; Pregabalin 150 mg; Acetaminophen 1g; Ketorolac 30 mg; Celecoxib 200 mg; Morphine 0.1 mg/kg/hr
Intervention MeSH terms: Acetaminophen; Celecoxib; Ketorolac; Lidocaine; Pregabalin; Fentanyl; Dexmedetomidine; Morphine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment