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

Dexmedetomidine Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05615194
• Other study ID #: 2023-3190
• Status: Recruiting
• Phase: N/A
• Start date: December 5, 2022
• Est. completion date: September 2023

Study information

• Verified date: February 2023
• Source: Ciusss de L'Est de l'Île de Montréal
• Contact: Olivier Verdonck
• Phone: +15142523426
• Email: overdonck[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: September 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Dexmedetomidine
• Inhalation Anesthesia
• Laparoscopy
• Respiratory Aspiration
• Sevoflurane

Intervention

Drug:
• Dexmedetomidine
0.6 mcg/kg in infusion over 10 minutes
• Placebo
Volume equivalent in infusion over 10 minutes

Locations

Country	Name	City	State
Canada	Hôpital Maisonneuve-Rosemont, CIUSSS de l'Est de l'Ile de Montréal	Montréal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Ciusss de L'Est de l'Île de Montréal

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Time for extubation (in minutes)	To compare the time for extubation	From sevoflurane discontinuation to extubation
Secondary	Time for awakening (in minutes)	To compare the time for awakening	From sevoflurane discontinuation to when the patient is opening his eyes
Secondary	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
Secondary	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