Clinical trial NCT04648540: Multimodal Opioid-free Anesthesia Versus Opioid-based Anesthesia for Patients Undergoing Cardiac Valve Surgeries: RCT
Official title: Multimodal Opioid-free Anesthesia Versus Opioid-based Anesthesia for Patients Undergoing Cardiac Valve Surgeries: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Anesthesia
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2020-12-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Extubation time (min)
timeFrame: 24 hours
Secondary outcomes:
measure: Heart rate (beats/min)
timeFrame: 24 hours
measure: Blood pressure (mm Hg)
timeFrame: 24 hours
measure: Postoperative rescue analgesia (number)
timeFrame: 24
measure: Postoperative morphine consumption (mg)
timeFrame: 24 hours
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Kasr Al Ainy School of Medicine Cairo University
Study officials:
affiliation: Cairo University
name: hossam El-Ashmawi, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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