Clinical trial NCT03420586: Nitrous Oxide Added at the End of Sevoflurane Anesthesia and Recovery
Official title: Effects of Nitrous Oxide Added at the End of Sevoflurane Anesthesia on Recovery and Postoperative Nausea and Vomiting - a Randomized Clinical Trial (SEVONATE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Elective Surgical Procedures
Laparoscopy
Laparotomy
Anesthesia, General
Anesthesia Recovery Period
Keywords: Anesthetics, Inhalation
Anesthesia Recovery Period
Postoperative Nausea and Vomiting
Pain, Postoperative
Lead sponsor: General Hospital Zadar
Sponsor class: OTHER
First posted: 2018-02-05
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Intervention Model: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Early recovery (awakening) in the operation room (OR)
timeFrame: 15 minutes
Secondary outcomes:
measure: Postoperative nausea and vomiting
timeFrame: 24 hours
measure: Quality of recovery
timeFrame: 72 hours
measure: Postoperative pain
timeFrame: 24 hours
Other outcomes:
measure: Postoperative sedation
timeFrame: 2 hours
measure: Postoperative nausea and vomiting
timeFrame: 24 hours
measure: Postoperative pain
timeFrame: 24 hours
measure: Readiness for Discharge from the Postanesthesia Care Unit (PACU)
timeFrame: 2 hours
Locations:
city: Zadar
country: Croatia
facility: General Hospital Zadar
Study officials:
affiliation: GH Zadar, Dpt. of Anesthesiology and Intensive Care Medicine
name: Tatjana Simurina, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Anesthesiology & Parioperative Medicine School of Medicine, University of Missouri, Columbia, US
name: Boris Mraovic, Prof, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mraovic B, Simurina T, Gan TJ. Nitrous oxide added at the end of isoflurane anesthesia hastens early recovery without increasing the risk for postoperative nausea and vomiting: a randomized clinical trial. Can J Anaesth. 2018 Feb;65(2):162-169. doi: 10.1007/s12630-017-1013-y. Epub 2017 Nov 17.
citation: Peyton PJ, Wu CY. Nitrous oxide-related postoperative nausea and vomiting depends on duration of exposure. Anesthesiology. 2014 May;120(5):1137-45. doi: 10.1097/ALN.0000000000000122.
citation: Myles PS, Weitkamp B, Jones K, Melick J, Hensen S. Validity and reliability of a postoperative quality of recovery score: the QoR-40. Br J Anaesth. 2000 Jan;84(1):11-5. doi: 10.1093/oxfordjournals.bja.a013366.
citation: Myles PS, Hunt JO, Nightingale CE, Fletcher H, Beh T, Tanil D, Nagy A, Rubinstein A, Ponsford JL. Development and psychometric testing of a quality of recovery score after general anesthesia and surgery in adults. Anesth Analg. 1999 Jan;88(1):83-90. doi: 10.1097/00000539-199901000-00016.
citation: Myles PS, Wengritzky R. Simplified postoperative nausea and vomiting impact scale for audit and post-discharge review. Br J Anaesth. 2012 Mar;108(3):423-9. doi: 10.1093/bja/aer505. Epub 2012 Jan 29.
citation: Agoliati A, Dexter F, Lok J, Masursky D, Sarwar MF, Stuart SB, Bayman EO, Epstein RH. Meta-analysis of average and variability of time to extubation comparing isoflurane with desflurane or isoflurane with sevoflurane. Anesth Analg. 2010 May 1;110(5):1433-9. doi: 10.1213/ANE.0b013e3181d58052.
citation: Jones PM, Bainbridge D, Chu MWA, Fernandes PS, Fox SA, Iglesias I, Kiaii B, Lavi R, Murkin JM. Comparison of isoflurane and sevoflurane in cardiac surgery: a randomized non-inferiority comparative effectiveness trial. Can J Anaesth. 2016 Oct;63(10):1128-1139. doi: 10.1007/s12630-016-0706-y. Epub 2016 Jul 27.