Elective Surgical ProceduresSEVONATENCT03420586
Nitrous Oxide Added at the End of Sevoflurane Anesthesia and Recovery
A study testing Nitrous Oxide in people with Elective Surgical Procedures and Laparoscopy, run by General Hospital Zadar at 1 site in Croatia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Elective Surgical Procedures, Laparoscopy, Laparotomy
- What is being tested?
- Nitrous Oxide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteCroatia
- Study dates
- 7 Feb 2018to 25 Jul 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the 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.
- Conditions
- Elective Surgical Procedures, Laparoscopy, Laparotomy, Anesthesia, General, Anesthesia Recovery Period
- Being tested
- Nitrous Oxide
- Keywords
- Anesthetics, Inhalation, Anesthesia Recovery Period, Postoperative Nausea and Vomiting, Pain, Postoperative
- Medical subject headings
- Respiratory Aspiration, Postoperative Nausea and Vomiting, Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitrous OxideDrug
The nitrous oxide group (GN2O) will receive 70% N2O in 30% O2 at the end of surgery.
| Study group | Role | What they receive |
|---|---|---|
| Nitrous oxide Group | Active comparator | 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. Receives: Drug: Nitrous Oxide |
| Oxygen Group | No intervention | The Oxygen group will receive gas carrier mixture consisting of air in 30% O2 during general anesthesia. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 15 minutes
Secondary outcomes (3)
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.
Measured: 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).
Measured: 72 hours
Postoperative pain
Visual analogue scale VAS pain score [a 100 mm visual analogue scale (VAS) 0= no pain, 10= maximal pain]
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2018
- Study start7 Feb 2018
- Primary completion10 Jul 2021
- Study completion25 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Elective Surgical ProceduresStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Intervention Model: Parallel Assignment
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- General Hospital Zadar
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tatjana Simurina, MD, PhD, Principal investigator, GH Zadar, Dpt. of Anesthesiology and Intensive Care MedicineBoris Mraovic, Prof, MD, Principal investigator, Anesthesiology & Parioperative Medicine School of Medicine, University of Missouri, Columbia, US
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03420586
- Sponsor's protocol ID
- 01-5623-7/17
- Acronym
- SEVONATE
- Status last verified
- Aug 2020
- First submitted
- 19 Jan 2018
- Last updated
- 9 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 29150782Peyton 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.
PubMed 24401771Myles 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.
PubMed 10740540Myles 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.
PubMed 9895071Myles 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.
PubMed 22290456Agoliati 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.
PubMed 20418303Jones 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.
PubMed 27465213
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03420586
- Acronym / sponsor ID
- SEVONATE / 01-5623-7/17
- Conditions
- Elective Surgical Procedures, Laparoscopy, Laparotomy, Anesthesia, General, Anesthesia Recovery Period
- Keywords
- Anesthetics, Inhalation, Anesthesia Recovery Period, Postoperative Nausea and Vomiting, Pain, Postoperative
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- General Hospital ZadarUniversity, hospital or other
- Study start
- 7 Feb 2018 (actual)
- Primary completion
- 10 Jul 2021 (actual)
- Study completion
- 25 Jul 2021 (actual)
- First posted
- 5 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Intervention Model: Parallel Assignment
| Arm | Type | Receives |
|---|---|---|
| Nitrous oxide Group | Active comparator | Drug: Nitrous OxideThe 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. |
| Oxygen Group | No intervention | –The Oxygen group will receive gas carrier mixture consisting of air in 30% O2 during general anesthesia. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitrous OxideThe nitrous oxide group (GN2O) will receive 70% N2O in 30% O2 at the end of surgery. | Drug | Nitrous oxide Group |
Primary outcome
Early recovery (awakening) in the operation room (OR)
Time frame: 15 minutes
eye opening (in minutes), following verbal commands (in minutes), time to extubation (in minutes ), orientation to time and place (in minutes)
3 secondary outcomes
Postoperative nausea and vomiting
Time frame: 24 hours
Quality of recovery
Time frame: 72 hours
Postoperative pain
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2022.
- Background: PubMed 29150782Mraovic 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.
- Background: PubMed 24401771Peyton 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.
- Background: PubMed 10740540Myles 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.
- Background: PubMed 9895071Myles 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.
- Background: PubMed 22290456Myles 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.
- Background: PubMed 20418303Agoliati 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.
- Background: PubMed 27465213Jones 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tatjana Simurina, MD, PhD principal investigator
GH Zadar, Dpt. of Anesthesiology and Intensive Care Medicine
Boris Mraovic, Prof, MD principal investigator
Anesthesiology & Parioperative Medicine School of Medicine, University of Missouri, Columbia, US
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nitrous Oxide in people with Elective Surgical Procedures and Laparoscopy, run by General Hospital Zadar at 1 site in Croatia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Croatia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Early recovery (awakening) in the operation room (OR) (time frame: 15 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03420586, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2022.