Nitrous Oxide Added at the End of Sevoflurane Anesthesia and Recovery

Study Overview
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Brief Summary
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Addition of nitrous oxide N2O towards the end of prolonged isoflurane anesthesia hastens patients recovery. The hypothesis is that the addition of N2O at the end of prolonged sevoflurane anaesthesia also hastens early recovery without increasing the frequencies and intensity of PONV and improves quality of recovery.

Detailed Description
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The investigators will include 100 adult patients, American Society of Anesthesiologists (ASA) physical status I-III, who will be scheduled for elective laparotomies or laparoscopic surgeries under sevoflurane anesthesia lasting 120 minutes or longer. After written informed consent participants will be randomized into two groups: GO2 - air in 30% oxygen and GN2O - the same mixture until the last 30 minutes of surgery when 70% N2O in 30% oxygen will be used. General anesthesia will be performed with propofol and fentanyl for anesthesia induction, rocuronium for muscle relaxation and volatile anesthetic sevoflurane for maintenance. The participants will be extubated in the operation room (OR) after they open their eyes and follow commands. Postanesthetic recovery score by Aldrete, Ramsay sedation scale (RSS), and Simplified postoperative nausea and vomiting impact scale score by Myles (PONV ISS) will be used to assess recovery in PACU and surgical ward. Modified Aldrete score assigns a score of 0, 1, or 2 to activity, respiration, circulation, consciousness, and color, giving a maximal score of 10 ( score of 9 indicates recovery sufficient for the patient to be transferred from the PACU). RSS [score 1-6] consists of six levels of sedation [Awake levels: 1, anxious and agitated or restless or both; 2, co-operative, orientated, and tranquil; 3,responds to commands only. Asleep levels are dependent on the response to a light glabellar tap or loud auditory stimulus: 4, a brisk response; 5, a sluggish response; 6, no response]. PONV ISS is the sum of the numerical responses to questions Q1 and Q2 ( Q1: The vomiting or dry-retching count? 0 - 2 or 3 (three or more times); Q2: Severity of nausea - interference with activities of daily living: score 0-3 [0 - not at all, 1-sometimes, 2- often or most of the time, 3 - all of the time] and score ≥5 defines clinically important PONV. Quality of Recovery questionnaire (QoR-40) on the first, second and third postoperative days will be used for assessment of postoperative quality of recovery.The QoR-40 consists of five clinically relevant dimensions: (i) physical comfort (12 items), (ii) emotional state (9 items), (iii) physical independence (5 items), (iv) psychological support (7 items), and (v) pain (7 items). Each item is rated on a five-point Likert scale. The QoR-40 score ranges from 40 (extremely poor quality of recovery) to 200 (excellent quality of recovery). A 100 mm visual analogue scale (VAS) [0= no pain, 10= maximal pain] and the use of postoperative analgesics (opioids/non-opioids: yes or no, quantity in milligrams) shall be used for pain assessment during the first 24 postoperative hours.The sample size for early recovery time (primary endpoint) is based on the results of our recent study. The sample size was calculated on the assumption that 15 (SD 7) min would be needed for early recovery for the GO2 patients and that the GN2O patients would require four minutes less time (11 [SD 5] min). We would need 38 participants in each group for the primary outcome to have a power of 0.8 and an alpha level of 0.05.

Official Title
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Effects of Nitrous Oxide Added at the End of Sevoflurane Anesthesia on Recovery and Postoperative Nausea and Vomiting - a Randomized Clinical Trial (SEVONATE)

Conditions
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Elective Surgical Procedures, Laparoscopy, Laparotomy, Anesthesia, General, Anesthesia Recovery Period

Intervention / Treatment
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* Drug: Nitrous Oxide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, American Society of Anesthesiologists Physical status ASA PS I-III, scheduled for laparotomic and laparoscopic surgery expected to last 2 hours or more who can understand and signed informed consent. Exclusion Criteria: Patients who will be discharged within 72 hours after surgery Patients on intensive care within few months before the study enrollment Diseases that impair gastric motility (diabetes mellitus, chronic cholecystitis, gastric and intestinal disease, neuromuscular disorders, neuropathies, liver dysfunction) Vestibular disease; history of migraine headaches, central nervous system injury Renal impairment Patients on antihistamines, antipsychotics, contraceptives, steroids within 72 hours before surgery Known hypersensitivity to drugs used in the study protocol Alcoholism, and/or opioid addiction Conditions that can influence the incidence of PONV, postoperative pain or morbidity (e.g., significant intraoperative surgery complications), intraoperative drug allergy, severe intraoperative hypotension, perioperative hypoxia, excessive blood loss, difficult intubation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nitrous oxide Group<br>The nitrous oxide group (GN2O) will receive air in 30% O2 during general anesthesia until the last 30 min of surgery, when 70% N2O in 30% O2 will be administered. | Drug: Nitrous Oxide<br>* The nitrous oxide group (GN2O) will receive 70% N2O in 30% O2 at the end of surgery.<br>|
| No Intervention: Oxygen Group<br>The Oxygen group will receive gas carrier mixture consisting of air in 30% O2 during general anesthesia. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early recovery (awakening) in the operation room (OR) | eye opening (in minutes), following verbal commands (in minutes), time to extubation (in minutes ), orientation to time and place (in minutes) | 15 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative nausea and vomiting | Simplified postoperative nausea and vomiting impact scale:the sum of the numerical responses to questions Q1 and Q2 ( Q1: The vomiting or dry-retching count? 0 -2 or 3 (three or more times); Q2: Severity of nausea - interference with activities of daily living: score 0-3 [0 - not at all, 1-sometimes, 2- often or most of the time, 3- all of the time] ) and score ≥5 defines clinically important PONV. | 24 hours | 
| Quality of recovery | Quality of Recovery 40 questionnaire on the first, second and third postoperative days: The QoR-40 consists of five clinically relevant dimensions: (i) physical comfort (12 items), (ii) emotional state (9 items), (iii) physical independence (5 items), (iv) psychological support (7 items), and (v) pain (7 items). Each item is rated on a five-point Likert scale. The QoR-40 score ranges from 40 (extremely poor quality of recovery) to 200 (excellent quality of recovery). | 72 hours | 
| Postoperative pain | Visual analogue scale VAS pain score [a 100 mm visual analogue scale (VAS) 0= no pain, 10= maximal pain] | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anesthetics, Inhalation, Anesthesia Recovery Period, Postoperative Nausea and Vomiting, Pain, Postoperative