The Impact of a Single Dexmedetomidine Bolus on Intraoperative Sevoflurane Consumption (DEXHALE)

Study Overview
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Brief Summary
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Sevoflurane is a volatile agent easy to control thanks to the Minimum Alveolar Concentration (MAC) allowing its titration for an optimal depth of anesthesia. Growing biomedical evidence also highlight its anti-inflammatory and antioxidant effects protecting against ischemia-reperfusion injury in cardiac surgery and, potentially, in organ transplant. The estimated annual contribution of inhalational anesthetic agents represents about 0.01% of global CO2 production. Alternatives such as total intravenous anesthesia (TIVA) avoid direct greenhouse emission, but their indirect carbon footprint remains a major problem. For all these reasons, this research aim to find a way to maintain the use of sevoflurane for its clinical benefits while reducing its consumption to limit the environmental consequences. The use of dexmedetomidine could help anesthesiologists to achieve this greener sevoflurane anesthesia. Dexmedetomidine is a potent, highly selective α-2 adrenergic receptor agonist described as a unique sedative with analgesic and sympatholytic properties. This new randomized controlled trial (RCT) will answer the question whether a single bolus of dexmedetomidine (0.6 mcg.kg-1 on 10 minutes during induction) compared to placebo has a clinically significant impact on sevoflurane consumption during laparoscopic elective surgery.

Detailed Description
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Inhaled gases have been used since the advent of anesthesia due to their analgesic and dissociative properties. However, these are now part of a growing environmental debate which leads us to reconsider their systematic use for general anesthesia. Sevoflurane is a volatile agent easy to monitor using the Minimal Alveolar Concentration (MAC) facilitating its titration for adequate anesthesia depth. Growing biomedical evidence also highlight its anti-inflammatory and antioxidant effects protecting against ischemia-reperfusion injury in cardiac surgery and, potentially, in organ transplant. The estimated annual contribution of inhalational anesthetic agents represents about 0.01% of global CO2 production. This data can be illustrated as a commercial airliner flying 418 times around the world. Desflurane is gradually abandoned as its greenhouse effect is 25 times more potent than sevoflurane for an equivalent MAC and fresh gas flow. As low-flow inhalational techniques and scavenging technologies become the standard of practice, anesthesiologists still cannot prevent the gas to be released in the atmosphere . Alternatives such as total intravenous anesthesia (TIVA) avoid direct greenhouse emission, but their indirect carbon footprint remains a major problem. Propofol has a high potential for bioaccumulation. It has high mobility in soil, resists degradation in aquatic environment and concentrates in adipose tissue of aquatic organism. To control its toxicity, destruction should be done by incineration over 1000°C. Unfortunately, studies prove that 32-49% of dispensed propofol is waisted and is mostly disposed unproperly. For all these reasons, this research aim to find a way to maintain the use of sevoflurane for its clinical benefits while reducing its consumption to limit the environmental consequences. The use of dexmedetomidine could help us achieve this greener sevoflurane anesthesia. Dexmedetomidine is a potent, highly selective α-2 adrenergic receptor agonist described as a unique sedative with analgesic and sympatholytic properties. Currently approved for sedation, this molecule shows many advantages compared to hypnotic drugs such as propofol. Although still under investigation, dexmedetomidine would possibly have a lower hazard environmental score. The use of dexmedetomidine also shows promising results regarding the reduction of emergence cough and agitation. Decrease in pain and post-operative nausea and vomiting (PONV) are other benefits of dexmedetomidine providing conditions to promote enhanced recovery after surgery (ERAS). Many investigations have studied impacts of dexmedetomidine as an adjuvant to general anesthesia for its opioid sparing capacity, and hemodynamics response during laparoscopic surgeries. Fewer research specifically wondered about sevoflurane dispense outcome. Moreover, they don't reflect the anesthesia practice of North America and their sample sizes are low. This new randomized controlled trial (RCT) will answer the question whether a single bolus of dexmedetomidine (0.6 mcg.kg-1 on 10 minutes during induction) compared to placebo has a clinically significant impact on sevoflurane consumption during laparoscopic elective surgery. Opioid requirement, need for vasopressors, post-operative events (PONV, shivering, critical respiratory event) and time for readiness for Post-Anesthesia Care Unit (PACU) will also be assessed.

Official Title
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A Randomized Clinical Study to Assess the Impact of a Single Dexmedetomidine Bolus During Induction of General Anesthesia on Intraoperative Sevoflurane Consumption in Elective Laparoscopic Surgery

Conditions
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Inhalation Anesthesia, Dexmedetomidine, Sevoflurane, Laparoscopy

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA 1-3 patients Undergoing laparoscopic surgery of duration time expected under 120 minutes using general anesthesia with sevoflurane Fully consented Age > 18yo No allergy to one of the medications used in this study. Exclusion Criteria: History of severe coronary artery disease; ventricular dysfunction, serious cardiac arrhythmia (including atrial fibrillation and high-grade atrioventricular block) Moderate to severe renal or hepatic dysfunction Allergy to any drug used in the study protocol Refusal of the patient for participation in the study History of severe PONV

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be 1:1 randomly assign to one of the two following groups: dexmedetomidine 0.6 mcg.kg-1 (group D) or a saline placebo of equivalent volume (group C) to be administered on 10 minutes during induction. The patient presenting all the inclusion criteria and no exclusion criteria for this study will be approached by the anesthesia research team. They will provide explanations on the study as well as a consent form to the patient for him to have time to read it before the surgery. The risk of serious and unexpected adverse reactions to dexmedetomidine will also be disclosed to the patient before his agreement to participate to the study. After his approval, the patient will sign the consent and will be randomized.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Normal saline in volume equivalent of dexmedetomidine dose according to patient weight ; Administered via infusion pump (Smith Medical Medfusion® 4000 Syringe Infusion Pump) so that the full dose is delivered over 10 minutes during induction of general anesthesia | Drug: Placebo<br>* Volume equivalent in infusion over 10 minutes<br>* Other names: NaCl 0.9%;|
| Active Comparator: Dexmedetomidine<br>Dexmedetomidine 0.6 mcg/kg (adjusted body weight) ; Administered via infusion pump (Smith Medical Medfusion® 4000 Syringe Infusion Pump) so that the full dose is delivered over 10 minutes during induction of general anesthesia | Drug: Dexmedetomidine<br>* 0.6 mcg/kg in infusion over 10 minutes<br>* Other names: DIN : 02339366;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sevoflurane consumption expressed in mL.kg-1.h-1 | To compare the total sevoflurane consumption when using a dexmedetomidine single bolus (group D) of 0.6 mcg.kg-1 on 10 minutes during induction versus placebo (group C). This will be expressed in mL.kg-1.h-1 of surgery. | From intubation to end of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total intra-operative remifentanil consumption (in mcg.kg-1) | To compare the total intra-operative remifentanil consumption during anesthesia based on the NoL index (Medasense Ltd., Ramat Gan, Israel) | From intubation to end of surgery | 
| Percentage of time during the intraoperative period for which the NOL index will be above the pain threshold of 25 (in % of surgical time) | To compare the percentage of time during the intraoperative period for which the NOL index will be above the pain threshold of 25 | From intubation to end of surgery | 
| Total amount of hydromorphone given IV in PACU (in mg) | To quantify the total amount of hydromorphone needed in PACU | From PACU admission to discharge | 
| Intra-operative and postanesthesia care unit (PACU) doses of vasopressors | To compare the intra- and post-operative requirements of phenylephrine, ephedrine, glycopyrrolate and atropine | From intubation to PACU discharge | 
| Mean end tidal sevoflurane (in %) and MAC needed to maintain the BIS index (Medtronic, Canada) between 40 and 60 | To compare the mean end tidal sevoflurane (EtSevo) and MAC needed to maintain the BIS index between 40 and 60 | From intubation to end of surgery | 
| Total intraoperative time from intubation until end of surgery with BIS index between 40 and 60 (in minutes) | To compare the % of total intraoperative time from intubation until end of surgery with BIS index between 40 and 60 | From intubation to end of surgery | 
| Time for extubation (in minutes) | To compare the time for extubation | From sevoflurane discontinuation to extubation | 
| Time for awakening (in minutes) | To compare the time for awakening | From sevoflurane discontinuation to when the patient is opening his eyes | 
| Postoperative outcomes such as postoperative nausea and vomiting (PONV), shivering and critical respiratory event (CRE) | To assess postoperative outcomes such as postoperative nausea and vomiting (PONV), shivering and critical respiratory event (CRE) A CRE will be defined as the occurrence of one of the following criteria: Upper airway obstruction requiring an intervention Moderate hypoxemia: SpO2 of 90-93% on 2 L.min-1 nasal cannula O2 Severe hypoxemia: SpO2 < 90% on 2 L.min-1 nasal cannula O2 Signs of respiratory distress or impeding ventilatory failure Patient requiring reintubation in the PACU Clinical evidence or suspicion of pulmonary aspiration after tracheal extubation | From PACU admission to discharge | 
| Total time spent in PACU (in minutes) | To compare total time for readiness for discharge from PACU between groups assessed by recovery scores (Aldrete's modified score and Maisonneuve-Rosemont PACU score) | From PACU admission to discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Environment, kgCO2eq