Nitrous Oxide Added at the End of Sevoflurane Anesthesia and Recovery

Anesthesia, General Clinical Trial

— SEVONATE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03420586
• Other study ID #: 01-5623-7/17
• Status: Completed
• Phase: N/A
• Start date: February 7, 2018
• Est. completion date: July 25, 2021

Study information

• Verified date: August 2020
• Source: General Hospital Zadar
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: July 25, 2021
• Est. primary completion date: July 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Anesthesia Recovery Period
• Anesthesia, General
• Elective Surgical Procedures
• Laparoscopy
• Laparotomy
• Postoperative Nausea and Vomiting

Intervention

Drug:
• Nitrous Oxide
The nitrous oxide group (GN2O) will receive 70% N2O in 30% O2 at the end of surgery.

Locations

Country	Name	City	State
Croatia	General Hospital Zadar	Zadar

Sponsors (1)

Lead Sponsor	Collaborator
General Hospital Zadar

Country where clinical trial is conducted

Croatia, 

References & Publications (7)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. Erratum in: Anesthesiology. 2014 Dec;121(6):1359. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Postoperative sedation	Ramsay Sedation Scale [score 1-6] consists of six levels of sedation [Awake levels: 1, patient anxious and agitated or restless or both; 2, patient co-operative, orientated, and tranquil; 3, patient responds to commands only. Asleep levels are dependent on the patient's response to a light glabellar tap or loud auditory stimulus: 4, a brisk response; 5, a sluggish response; and 6, no response].	2 hours
Other	Postoperative nausea and vomiting	The use of rescue antiemetics (yes/no and quantity in milligrams)	24 hours
Other	Postoperative pain	The use of analgesics (opioids/nonopioids:yes/no and quantity in milligrams)	24 hours
Other	Readiness for Discharge from the Postanesthesia Care Unit (PACU)	Modified Aldrete score: Activity - able to move voluntarily or on command: 2 - four extremities ; 1- two extremities ; 0- extremities 0; Respiration: 2 - able to deep breathe and cough freely , 1 - dyspnea, shallow or limited breathing , 0 - apneic. Circulation - blood pressure , BP of preanesthetic level: 2 - BP ± 20 mm; 1 - BP ± 20-50 mm; 0 - BP ± 50 mm. Consciousness: 2 fully awake;1 arousable on calling; 0 not responding.O2 saturation : 2 - able to maintain O2 saturation >92% on room air; 1- needs O2 inhalation to maintain O2 saturation >90%; 0 - O2 saturation <90% even with O2 supplementation. A score 9 and more = Ready for Discharge from the Postanesthesia Care Unit	2 hours
Primary	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	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
Secondary	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
Secondary	Postoperative pain	Visual analogue scale VAS pain score [a 100 mm visual analogue scale (VAS) 0= no pain, 10= maximal pain]	24 hours