Anesthesia, Nociceptive Pain, Opioid Use, Perioperative/Postoperative Complications
Conditions
Brief summary
Background: Analgesia remains to this day a challenge for anesthesiologists. Dexmedetomidine, a potent central alpha-2 agonist, has been shown to have analgesic and opioid sparing effects. The classic analgesic strategy focuses on opioid administration guided by estimated time of elimination and hemodynamic response (increase in blood pressure and heart rate). This technique is not sensitive and forces the anesthesiologist to be one step behind nociception, the patient's unconscious response to pain. PMD-200 (Medasense, Israel) displays the Nociceptive level (NOL)-Index as marker of nociception. The NOL-Index ranges from 0 (no nociception) to 100 (intense nociception) and the recommended analgesic range during surgery is from 10 to 25 (Medasense recommendations). The goal of this study is to compare two analgesia strategies guided by the NOL Index (range 10-25) using either remifentanil TCI (target controlled infusion) alone or remifentanil TCI associated with a continuous dexmedetomidine infusion. Methods: A total of 100 patients will be included and informed consent will be acquired. This bi-center study will take place at Erasme University Hospital (primary center) and Saint-Pierre University Hospital. Patients will be randomized into either two groups: remifentanil and placebo versus remifentanil and dexmedetomidine. Both groups will be monitored using the PMD-200 that will guide the analgesic therapy strategy. Investigators and patients will be blinded to dexmedetomidine and placebo administration. The primary outcome will be intraoperative remifentanil consumption. Secondary outcomes will include postoperative opioid administration, opioid associated complications, hemodynamics, and hospital length of stay.
Interventions
DRUGDexmedetomidine
Patients in the dexmedetomidine-remifentanil group will receive an infusion of 0.6 mcg/kg in half an hour followed by an infusion of 0.6 mcg/kg/hour.
DRUGsodium chloride
Patients in the remifentanil group will receive an infusion of 0.9% sodium chloride instead of dexmedetomidine (identical infusion rate)
DRUGRemifentanil
Both groups will have remifentanil analgesia guided by the Nol-Index
Sponsors
Saint-Pierre University Hospital
Erasme University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
\- American Society of Anesthesiologists (ASA) grades 1-2 undergoing scheduled stomatological, cervical, and thyroid surgery anticipated to last at least two hours
Exclusion criteria
* ASA score \>2 * Preoperative organ dysfunction * Patients with non-regular cardiac rhythm * Implanted pacemakers * Emergent surgery * Pregnancy or lactation * Allergy or intolerance to any of the study drugs * Participation in another interventional study * Patient refusal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Remifentanil consumption measured as the amount (µg) of remifentanil administered during the anesthestic | 6 hours | Intraoperative remifentanil consumption |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Use of vasoactive drugs | 6 hours | Use and amount of vasoactive drugs used (ephedrine/phenylephrine/noradrenaline) |
| Use of hypotensive drugs | 6 hours | Use and amount of hypotensive drugs used (nicardipine/esmolol) |
| Net fluid balance | 6 hours | Sum of in (infused fluids) and out (net blood loss, diuresis, other losses) |
| Time to extubation | 6 hours | Time from end of surgery to extubation of patient |
| Number of patients with intraoperative hypotension | 6 hours | Intraoperative MAP (mean arterial pressure) \<65 mmHg\* * Patients that have chronic hypertension or that are 65 years of age or older will have a MAP threshold of 75mmHg (and not 65mmHg). |
| Number of patients with intraoperative hypertension | 6 hours | Intraoperative MAP≥100 or surgical need to decrease blood pressure |
| Number of patients with hemodynamic instability | 6 hours | MAP\<65 mmHg\*, HR\<45, MAP≥100, HR\>90 \* Patients that have chronic hypertension or that are 65 years of age or older will have a MAP threshold of 75mmHg for hypotension (and not 65mmHg). |
| Propofol Consumption measured as the amount of propofol (mg) administered during the anesthestic | 6 hours | Intraoperative propofol consumption |
| Intraoperative blood pressure | 6 hours | Measurement during key intraoperative periods (before induction, after induction, after intubation, before incision, after incision, every 15 minutes after incision, after end of surgery, and after reversal of anesthesia) |
| Intraoperative Nol-Index | 6 hours | Measurement during key intraoperative periods (before induction, after induction, after intubation, before incision, after incision, every 15 minutes after incision, after end of surgery, and after reversal of anesthesia) |
| Intraoperative remifentanil target cite concentration | 6 hours | Measurement during key intraoperative periods (before induction, after induction, after intubation, before incision, after incision, every 15 minutes after incision, after end of surgery, and after reversal of anesthesia) |
| Postoperative morphine consumption | 24 hours | mg of morphine administered postoperatively |
| Number of patients with postoperative opioid-related side effect (composite and individual complications) | 72 hours | Post-operative nausea or vomiting within the first 24 h, postoperative hypoxemia (need within 24h postop to have supplemental oxygen (to maintain sat \>94%), and pruritus. |
| PACU length of stay (LOS) | 48 hours | hours spent at PACU |
| Hospital LOS | 28 days | days spents hospitalized |
| Intraoperative heart rate | 6 hours | Measurement during key intraoperative periods (before induction, after induction, after intubation, before incision, after incision, every 15 minutes after incision, after end of surgery, and after reversal of anesthesia) |
Countries
Belgium
Outcome results
None listed