Nitrous oxide added at the end of sevoflurane anaesthesia hastens emergence and eliminates prolonged time to extubation (SEVONATE study): A randomised controlled trial

Abstract

Nitrous oxide (N₂O) has both MAC (Minimum Anaesthetic Concentration) sparing and rapid pharmacokinetic washout properties. We hypothesised that adding N₂O at the end of surgery would hasten emergence from anaesthesia, decrease variability in emergence duration and reduce the number of prolonged emergences. Adult patients, American Society of Anesthesiologists Physical Status I–III, undergoing general anaesthesia for surgery with duration of over 120 min were randomised into two groups according to carrier gas: air/30% oxygen, and the same mixture until the last 30 min of surgery when 70% N₂O in 30% oxygen was used. Anaesthesia was maintained at ~1 MAC with sevoflurane in both groups. Early and late recovery, postoperative nausea and vomiting, and pain scores and analgesic use were assessed. Time to extubation time was deemed prolonged if it lasted more than 15 min. Fifty-one patients in N₂O/O₂ and 50 in air/O₂ were enrolled. N₂O administration lasted (mean ± standard deviation) 24.8 ± 9.4 min. Time to extubation was faster with N₂O/O₂ (5.5 ± 2.6 min) than with air/O₂ (9.1 ± 4.0 min), mean difference 3.6 min; 95% confidence interval 2.3 to 4.9, p < 0.001. Ability to open eyes, follow commands and being oriented were similarly significantly faster (mean differences 3.6, 3.4 and 3.7 min, respectively, p < 0.001 in all). None of the patients with N₂O/O₂, but 6% of patients with air/O₂, had prolonged time to extubation, p < 0.001. There were no differences between the groups in postoperative pain scores, or in early and late postoperative recovery. Patients administered N₂O/O₂ received significantly less analgesics: tramadol (medians 0 vs 100 mg, p = 0.037), paracetamol (33% vs 62%, p = 0.004) and ketoprofen (16% vs 32%, p = 0.054). Adding N₂O at the end of sevoflurane-based anaesthesia hastened extubation, eye opening, following commands and orientation, and eliminated prolonged time to extubation without increasing early or late complications.

Keywords

Sevoflurane nitrous oxide general anaesthesia emergence PONV postoperative pain

Introduction

Sevoflurane is the most common volatile anaesthetic used in the USA. Although desflurane has a favourable blood/gas coefficient, making it the fastest on/off volatile anaesthetic, cost and environmental concerns have significantly decreased its usage, and many centres have completely eliminated desflurane from the operating room. Quick recovery and operating room turnovers are particularly important in ambulatory anaesthesia, where any prolonged emergence outlier could disrupt daily workflow. Indeed, desflurane use has been associated with a 65% relative reduction in the incidence of prolonged time to extubation, defined as 15 min or longer, compared with sevoflurane (95% confidence interval (CI) 49% to 76%, P <0.0001).¹ Generally, there are small mean differences among volatile agents, but very large differences in the occurrence of outliers, variability and prolonged time to extubation.¹

We demonstrated in the ISONATE (ISOflurane N₂O At The End) study that when nitrous oxide (N₂O) was administered for 27 ± 10 min at the end of isoflurane anaesthesia, it significantly shortened emergence and time to extubation by 2.0 min (95% CI 0.6 to 3.4, P = 0.009) and the ability to open eyes, follow commands and being oriented were all faster with mean differences of 3.9 min (95% CI 1.6 to 6.1, P = 0.001), 3.4 min (95% CI 1.0 to 5.7, P = 0.006) and 3.8 min (95% CI 0.9 to 6.7, P = 0.010), respectively, without increasing incidence of postoperative nausea and vomiting (PONV).² However, N₂O at the end of sevoflurane anaesthesia has not been similarly studied.

In the SEVONATE (SEVOflurane N₂O At The End) study, we investigated the effects of adding N₂O at the end of sevoflurane anaesthesia (terminal N₂O technique) on early and late recovery. We hypothesised that adding N₂O for 30 min at the end of surgery would hasten emergence from anaesthesia, decrease variability in the emergence duration and reduce the incidence of prolonged emergence.

Methods

This manuscript adheres to the applicable CONSORT (Consolidated Standards of Reporting Trials) guidelines. After obtaining the Ethics Committee of Zadar Hospital approval (No. 01-5623-7/17 on 4 December 2017) the study was registered with ClinicalTrials.gov (Identifier: NCT03420586, principal investigators: Tatjana Šimurina and Boris Mraovic) on 5 February 2018.

Study population

We recruited 115 patients aged 18–80 years, American Society of Anesthesiologists physical status (ASA PS) I–III, undergoing general anaesthesia for elective laparotomies or laparoscopic surgery with expected duration of at least 120 min in this assessor-blinded prospective randomised controlled trial. All patients provided written consent and were recruited from 7 February 2018 to 16 July 2021. The study was carried out in accordance with the latest version of the Declaration of Helsinki.

Exclusion criteria and methods were similar to the ISONATE study.² In short, patients were excluded if they had potentially confounding factors that could cause prolonged recovery from anaesthesia and/or increased risk for PONV, inability to complete questionnaires owing to language barrier or mental incapacity. Patients were also excluded after signing the consent if they had significant intraoperative complications, difficult intubation, unexpected intraoperative drug allergy, severe intraoperative hypotension, severe perioperative hypoxia, excessive blood loss, or hypothermia.

Study procedures and measures

All patients fasted after midnight but were allowed to drink clear fluids up to 2 h before the anaesthesia. Premedication was midazolam 7.5 mg orally 1 h before the anaesthesia. Standard intraoperative monitoring included electrocardiography, non-invasive blood pressure, pulse oximetry, capnography, neuromuscular blockade monitoring by train-of-four (TOF) and bispectral index (BIS) monitoring. Anaesthesia was propofol 1.5–2 mg.kg⁻¹, fentanyl 1–2 μg.kg⁻¹ or sufentanil 0.1–0.2 μg.kg⁻¹, and rocuronium 0.6 mg.kg⁻¹ for induction and intubation. All patients received 250 ml of crystalloids prior to induction and then 10 ml.kg⁻¹.h⁻¹ during surgery. Forced-air warming blankets were used to maintain normothermia. Patients with an Apfel simplified PONV risk score of 3 or more received dexamethasone 0.1 mg.kg⁻¹ as antiemetic prophylaxis after induction of anaesthesia.

Patients were randomised by computer generated random numbers into two groups. The allocation number was concealed in an opaque envelope before the start of surgery and opened at 30 min before expected end of the surgery. Only the anaesthesiologist providing anaesthesia was aware of the trial treatment allocation. The Oxygen Group (GO₂) received 30% O₂ in air throughout the procedure. The N₂O Group (GN₂O) received the same carrier gas mixture until the last 30 min of the surgery, when 70% N₂O in 30% O₂ was administered. Anaesthesia was maintained with sevoflurane at the end-tidal concentration of ~1 MAC (minimum alveolar concentration) adjusted by age in 3 l.min⁻¹ fresh gas flow (FGF) in both groups until the end of skin closure. BIS values between 40 and 60 were targeted during the anaesthesia maintenance. In the GO₂, sevoflurane was discontinued at the end of skin closure. In the GN₂O, 70% N₂O was started 30 min before skin closure. The delivered sevoflurane concentration was adjusted to keep the total of end-tidal anaesthetic concentrations (sevoflurane and N₂O) at ~1 MAC). Supplemental bolus doses of 1 μg.kg⁻¹ fentanyl or 0.1 µg.kg⁻¹ sufentanil were given to keep heart rate and blood pressure within 20% of baseline values in both groups. Additional doses of rocuronium were given to maintain one to two twitches on TOF. The lungs were mechanically ventilated to keep normocapnia (end-tidal CO₂ partial pressure (EtCO₂) of 36–38 mmHg) using pressure-controlled mode of ventilation with tidal volumes of 6–8 ml.kg⁻¹ and positive end-expiratory pressure (PEEP) of 5 cm H₂O. A nasogastric tube was not placed. All laparoscopic surgeries were performed with CO₂ insufflation to an intra-abdominal pressure of 15 mmHg. At the end of the skin closure, the FGF was increased to 10 l.min⁻¹ of 100% O₂ and neuromuscular blockade was reversed with neostigmine 2.5 mg and atropine 1 mg in both groups.

Extubation criteria were standardised. Patients were extubated when TOF ⩾0.9 was achieved and EtCO₂ was ⩽45 mmHg, and they opened their eyes and followed verbal commands. Time to extubation, eye opening, following commands, answering simple questions and orientation to time and place were recorded. Timing commenced immediately upon the cessation of all study gases and the initiation of 100% oxygen at a flow rate of 10 l.min⁻¹. Simple verbal orders (open your eyes, squeeze my hand, open your mouth) and simple questions (do you feel any pain? Or do you feel nausea?) were repeated every 15 s. Post-anaesthetic Recovery Score (PRS), Ramsay Sedation Scale (RSS) and Simplified Postoperative Nausea and Vomiting Impact Scale Score (SPONV ISS) were used to assess postoperative recovery in the post-anaesthesia care unit (PACU) and on the surgical floor. Patients with PRS ⩽11 were transferred to the PACU until discharge criteria were met.^3–5 RSS was assessed on awakening immediately prior to leaving the operating room, and in the PACU or the step-down unit at 30 min, 1 h and 2 h post anaesthesia. A SPONV ISS total score ⩾5 was defined as clinically important PONV.⁵

For postoperative analgesia, paracetamol 1 g intravenously was used. Ketoprofen 100 mg intravenously was administered 30 min before the end of surgery to all subjects and also administered at 12 h postoperatively only if needed. For severe pain (Visual Analogue Scale (VAS) >40 mm) tramadol (1 mg.kg⁻¹ intravenously) was given and repeated every 4 h, if needed. A 100 mm VAS (0 = no pain, 100 = maximal pain) was used for pain assessment during the first 24 h after surgery. Postoperative pain at rest and movement-evoked pain were assessed at 1, 2, 6 and 24 h. Pain VAS score and total amount of postoperative opioids were recorded at 2 and 24 h postsurgery, as well as the incidence of postoperative nausea (PON), postoperative vomiting (POV), PONV, and the use of rescue antiemetic. Patients were considered to have PONV if they experienced at least one episode of nausea, vomiting or retching, or any combination of these. Rescue antiemetic (metoclopramide 10 mg intravenously) was given to patients who experienced two or more episodes of vomiting and/or retching within a period of 30 min, any nausea lasting more than 15 min or when requested by the patient. Quality of Recovery questionnaire (QoR-40) translated and validated for use in the Croatian surgical population was used for assessment of postoperative quality of recovery on the first, second and third postoperative days.⁶ The QoR-40 score ranges from 40 (extremely poor quality of recovery) to 200 (excellent quality of recovery). An anaesthesiologist blinded to the anaesthesia technique collected all postoperative study measurements including the assessment of postoperative pain. Administration of postoperative analgesics was done by clinical nurses blinded to the group allocation.

Statistical analysis

The primary endpoint was the time to extubation from initiation of 100% oxygen at a flow rate of 10 l.min⁻¹. The sample size was calculated using the extubation times from our ISONATE study.² We used the same extubation time for GN₂O (325 ± 175 s) as in the ISONATE study. However, we estimated a faster recovery in the GO₂ than in the ISONATE study of approximately 100 s with the same standard deviation (SD), because we expected sevoflurane recovery to be faster than isoflurane recovery.^2,8 Therefore, using 350 ± 225 s for the GO₂ and 325 ± 175 s for the GN₂O, we would need at least 50 patients per group to show a difference between groups with a power of 0.8 and alpha level of 0.05. Prolonged time to extubation was defined as longer than 15 min.¹ Data were presented as mean ± SD, median, range (minimal–maximal value, interquartile range), 95% CIs and n (%). χ², Fisher’s exact test, Mann–Whitney test and Repeated Measures Analysis of Variance were used to analyse the data. P <0.05 was considered significant. The P values for the secondary endpoints were not adjusted for multiple testing.

Results

Demographic and baseline characteristics

Of the 115 patients enrolled, 101 were randomised and completed the study. A flow chart of the study enrolment and reasons for the exclusion from the analysis are in Figure 1. There were no significant differences in characteristics between the GN₂O and the GO₂ regarding patients’ sex, age, body mass index, ASA PS, duration of anaesthesia and surgery or use of induction agents. Most of the patients were males (89%) because the most common type of surgery was laparoscopic prostatectomy (34 patients in each group) followed by open prostatectomy (Table 1). N₂O was delivered for 24.8 ± 9.4 min. The total amount of fentanyl was higher by 30 µg in the GO₂ (Table 1). Estimated surgical blood loss, need for red blood cell transfusion, crystalloid infusion volumes during surgery, and complications during anaesthesia induction or perioperative surgical complications were not significantly different between the groups.

Figure 1.

CONSORT (Consolidated Standards of Reporting Trials) flow diagram of subject enrolment.

Table 1.

Demographics and intraoperative data.

Patients	GN₂O (O₂/N₂O) (N = 51)	GO₂ (O₂/air) (N = 50)
Sex (male/female)	44/7	46/4
Age (years)	63.0 ± 9.9	62.2 ± 6.9
BMI (kg/m²)	27.3 ± 2.9	28.1 ± 3.6
ASA physical status
I	6 (11.8)	6 (12)
II	36 (70.6)	42 (84)
III	9 (17.6)	2 (4)
Apfel score
1	11 (21.6)	22 (44)
2	34 (66.6)	25 (50)
3	6 (11.8)	3 (6)
Type of surgery
Laparoscopic	36 (71)	38 (76)
Open	15 (29)	12 (24)
Surgery time (min)	137 ± 33	137 ± 38
Anaesthesia time (min)	158 ± 35	158 ± 39
Nitrous oxide administration (min)	24.8 ± 9.4	0
Fentanyl (µg)	267 ± 57	297 ± 56
Sufentanil (µg)	26.6 ± 5.7	20.0 ± 8.1
Propofol (mg)	115 ± 17	126 ± 32

Data presented as mean ± SD and n (%).

BMI: body mass index; ASA: American Society of Anesthesiologists.

Emergence differences

GN₂O patients recovered significantly faster than patients in the GO₂ (Table 2). They were extubated on average 3.6 min (95% CI 2.3 to 4.9, P <0.001), opened eyes 3.6 min (95% CI 2.3 to 4.9, P <0.001), followed commands 3.4 min (95% CI 2.1 to 4.7, P <0.001), answered simple questions 1.5 min (95% CI 0.1 to 2.9, P <0.042) faster, and were oriented 3.4 min (95% CI 1.8 to 5.4, P <0.001) earlier. Prolonged time to extubation was significantly less frequent in the GN₂O (P <0.001; Table 3). Extubation variability (SD) was also reduced by 35%, 2.6 min vs 4.0 min. Terminal N₂O practically eliminated extubations longer than 15 min (0% vs 6%, respectively) and increased the number of quick extubations (<5 min) by 3.7 times: 53% vs 14% of the patients, respectively (Table 3).

Table 2.

Early recovery data.

Emergence	GN₂O (O₂/N₂O) (N = 51)	GO₂ (O₂/air) (N = 50)	P
Open eyes (s)	223 (153–304)	420 (340–587)	<0.001*
Follow commands (s)	273 (204–357)	452 (390–630)	<0.001*
Tracheal extubation (s)	286 (235–355)	493 (375–703)	<0.001*
Orientation (s)	468 (360–629)	699 (514–896)	<0.001*
Complications on emergence, n (%)	9 (18)	11 (22)	0.625

Data presented as median (interquartile range) and n (%).

P <0.05.

Table 3.

Times to extubation.

Time frame	GN₂O (O₂/N₂O) (N = 51)	GO₂ (O₂/air) (N = 50)
>15 min	0 (0)	3 (6.0)
10–15 min	5 (9.8)	14 (28.0)
5–10 min	19 (37.2)	26 (52.0)
<5 min	27 (52.9)	7 (14.0)

Data presented as n (%).

χ² test, overall P <0.001.

There were no differences in complications with anaesthesia emergence between groups. In the GN₂O, bucking on the endotracheal tube prior to extubation occurred in five patients, restlessness in three, hypertension (HTN) requiring treatment in one and nausea in the operating room in one. In the GO₂, bucking the endotracheal tube occurred in six patients, restlessness in two, agitation in one and HTN in two.

Recovery differences

There were no significant differences in postoperative pain between the two groups at 1, 2, 6 and 24 h, with the exception of less dynamic pain in the GN₂O at 6 h (Table 4). All patients received ketoprofen at the end of surgery. The GN₂O received significantly less tramadol (medians 0 vs 100 mg, P = 0.037, respectively). Furthermore, about half of the patients in the GN₂O compared with the GO₂ received paracetamol (33% vs 62%, P = 0.004, respectively) and the second dose of ketoprofen (16% vs 32%, P = 0.054, respectively) postoperatively. Apfel risk score for PONV was significantly higher in patients in the GN₂O than in the GO₂; 1.9 ± 0.6 vs 1.6 ± 0.6, P = 0.049 (Table 1). The GN₂O had significantly earlier PON and received more metoclopramide (Table 5). But POV and SPONV ISS were not significantly different from the GO₂. Only one patient had clinically significant PONV with Impact Score >5 in the GO₂.

Table 4.

Postoperative pain data and analgesic consumption during first 24 h.

	GN₂O (O₂/N₂O) (N = 51)	GO₂ (O₂/air) (N = 50)	P
Pain at rest (VAS, 0–100 mm):
Pain at 1 h	21 (3–70)	22 (8–70)	0.382
Pain at 2 h	19 (3–68)	21 (5–59)	0.660
Pain at 6 h	19 (3–38)	19 (4–51)	0.125
Pain at 24 h	11 (0–40)	11 (4–60)	0.569
Dynamic pain (VAS, 0–100 mm):
Pain at 1 h	35.0 (3–80)	31.5 (11–81)	0.924
Pain at 2 h	30.0 (6–70)	31.0 (10–72)	0.552
Pain at 6 h	29.0 (0–65)	30.5 (6–85)	0.032*
Pain at 24 h	21.0 (4–50)	26.5 (3–87)	0.147
Tramadol (mg)	0 (0–100)	100 (0–250)	0.037*
Paracetamol 1 g IV, n (%)	17 (33)	31 (62)	0.004
Ketoprofen IV, second dose, n (%)	8 (16)	16 (32)	0.054

Data presented as median (min–max value).

P <0.05.

VAS: Visual Analogue Scale; IV: intravenous.

Table 5.

Postoperative nausea and vomiting data.

	GN₂O (O₂/N₂O) (N = 51)	GO₂ (O₂/air) (N = 50)	P
PONV 24 h	11 (21.5)	1 (2)	0.002
Early 0–2 h	9 (17.6)	0
Late 2–24 h	2 (3.9)	1 (2)
PONV Impact Scale score ⩾5	0	1 (2)	NS
PON	11 (21.5)	1 (2)	0.002
Early 0–2 h	9 (17.6)	1 (2)
Late 2–24 h	2 (3.9)	1 (2)
POV 24 h	4 (7.8)	1 (2)	0.176
Early 0–2 h	3 (5.8)	1 (2)
Late 2–24 h	1 (1.9)	1 (2)
PONV prophylaxis	8 (15.7)	7 (14)	0.812
Metoclopramide	7 (13.7)	1 (2)	0.029*
Early rescue 0–2 h	6 (11.8)	0
Late rescue 2–24 h	1 (1.9)	1(2)

Data presented as n (%).

P <0.05.

PONV: postoperative nausea and vomiting; PON: postoperative nausea; POV: postoperative vomiting.

There were no significant differences between the GN₂O and the GO₂ in any other recovery scores at any time point: PRS (14 (13 to 14) vs 14 (12 to 14), P = 0.794), RSS (2 ± 0 vs 2 ± 0, P = 0.989, respectively) and postoperative recovery QoR-40 score total or in any of its characteristics (physical comfort, emotional status, physical independence, psychological support or pain) on postoperative day 1 (171.0 ± 12.0 vs 171.5 ± 12.6, P = 0.521, respectively). No patients experienced adverse events during the trial other than those listed in Figure 1, or emergence complications.

Discussion

This study showed that adding 70% N₂O in the last 30 min of general anaesthesia maintained with sevoflurane hastened extubation and early recovery in patients undergoing laparoscopic or open surgery. Moreover, it significantly reduced the variability in extubation time and eliminated prolonged time to extubation. The overall use of postoperative pain medications was reduced, and the quality of late recovery was not influenced by adding N₂O.

Duration and variability of emergence from anaesthesia

Our findings have implications for operating room efficiency, where prolonged extubation contributes significantly to reduced workflows.⁷ While we tested the terminal N₂O technique in a population undergoing major abdominal surgery, our findings have the most significant implications for anaesthesia for high turnover surgical environments such as ambulatory surgery centres (ASCs), which have increased in number and workload in recent years with advancements in minimally invasive surgery volume, duration and complexity. Ambulatory anaesthesia has a crucial role in ASCs by improving patient care, enhancing patients’ satisfaction, and operational efficiency. Since many ASCs aim for turnover between cases of below 10 min, more predictable extubation time optimises workflows, decreases overall delays and reduces wait times for patients. The use of terminal N₂O in inhalational anaesthesia with sevoflurane significantly reduced extubation times in our study, and is possibly more efficient than desflurane. It hastened the time to extubation by 3.6 min, which is shorter than when desflurane was used instead of sevoflurane-maintained anaesthesia (by 2.7 min) as shown in a large meta-analysis comparing extubation times after volatile anesthetics.⁸ Furthermore, when desflurane was substituted in the last 30 min of sevoflurane-maintained anaesthesia, the extubation time was similarly shortened by 2.7 min in another study.⁹ Using N₂O at the end of sevoflurane anaesthesia instead of desflurane has advantages: N₂O is readily available since desflurane requires a sophisticated vaporiser and desflurane is significantly more expensive than N₂O, even if used for only a short duration. In addition, although N₂O has a slightly higher blood–gas partition coefficient than desflurane (0.47 vs 0.42, respectively) its effect is augmented by concentration, diffusion and the second gas effects on accompanying volatile agent concentrations during emergence from anesthesia.¹⁰ Indeed, in our study the starting (just before turning on 100% O₂) end-tidal concentrations on emergence were N₂O 60–67% and sevoflurane 0.2–0.3% versus desflurane 4.23% in the study by Kim et al.⁹ Also, a less well-known effect of N₂O is that it may decrease the solubility of volatile anaesthetics in blood, which could contribute to faster endotracheal extubation.¹¹ Variability of the end tidal volatile anaesthetic concentration on emergence makes extubation time more unpredictable. Terminal N₂O significantly decreases this variability. The lower the end-tidal sevoflurane concentration at the start of emergence, the less variability and faster extubation and recovery will be expected.^1,12

Postoperative pain

Early pain control and reduced use of opioids are important in ambulatory anaesthesia to facilitate patient discharge in a timely fashion. This study confirmed our previous findings from the ISONATE study that short exposure to N₂O has profound effects on postoperative pain.² A secondary analysis of the ENIGMA trial showed a shorter patient-controlled analgesia usage but no difference in pain scores.¹³ In our study, patients in both groups also had no clinically significant difference in pain scores at rest. As in the ENIGMA trial, in our study postoperative analgesic usage was significantly less both clinically and statistically in patients who received N₂O. The mean difference in postoperative tramadol dose was 30 mg between groups. Additionally, there were twice as many patients who received paracetamol and a second dose of ketoprofen in the GO₂ as compared with the GN₂O (62 vs 33%, 32% vs 16%, respectively). In a previous study in volunteers, the maximal analgesic effect of N₂O was observed between 20 and 30 min and disappeared slowly after 150 min.¹⁴ Therefore, 30 min of N₂O at the end of anaesthesia could be used not only to shorten anaesthesia emergence but also to improve early postoperative pain control and reduce usage of pain medications.

PONV

Another important factor in ambulatory anaesthesia is PONV. N₂O increases risk for PONV in dose–response fashion.¹⁵ However, short exposure to 70% N₂O is not long enough to trigger emetic mechanisms.¹⁶ In the ISONATE study there was no difference in PONV between groups but subjects in the oxygen group (no N₂O) received more rescue antiemetic and more patients were treated for PONV.² This is most likely due to receiving more opioids. In this SEVONATE study, after similar exposure (25 ± 9 min) PON was increased but POV was not. Only one patient in the GO₂ had severe PONV but none in the GN₂O. This could be explained by significantly higher preoperative Apfel scores in patients in the GN₂O in the SEVONATE study. Furthermore, N₂O administration hastened emergence without influence on emergence quality (retching, bucking, restlessness, or agitation). The quality of late recovery was the same regardless of N₂O administration.

Limitations

This study was conducted in a single centre with a limited number of patients and anaesthesia duration was close to 3 h. The procedures here were done as same day surgeries, and the results might not be applicable for ASCs with procedures with short duration. We chose these types of surgeries because of their longer duration. Complete double blinding of administering N₂O is difficult and it was not done. A larger study could answer whether the terminal N₂O technique eliminates prolonged time to extubation in longer and different type of surgeries, as well as its impact on workflows in ASCs.

Environmental concerns of terminal N₂O use

Sevoflurane is the most used volatile anaesthetic not only because of fast emergence but also because it has about four times less global warming potential (GWP) than isoflurane and 17 times less than desflurane. One-hundred-year GWP (per kg, in comparison with 1 kg CO₂, where GWP CO₂ = 1) for sevoflurane is 144, for isoflurane is 539 and for desflurane is 2540.¹⁷ N₂O has been removed from many practices owing to environmental pollution and greenhouse effects. N₂O has a 100-year GWP of 273. Owing to leaking pipelines, recommendations have been to abandon central N₂O pipelines and substitute them with portable tanks that remain closed between uses to reduce waste.¹⁷ Terminal N₂O at 0.6 MAC for 30 min at the end is GWP equivalent to combusting 10 l of petrol, the fuel consumption of an average car driven for 125 km.

However, using already available catalysts that can decompose N₂O to oxygen and nitrogen could create the most environmentally favourable inhaled anaesthetic.¹⁸ Sweden is the only country that has widely adopted them in hospitals. N₂O has the potential to be the cleanest anaesthesia gas with zero gas emission by combining N₂O portable tanks with catalytic converters.

It is estimated that over 60 million major surgeries are performed in the USA each year, 20 million in Europe, and over 300 million worldwide. At 1 MAC and 1 l.min⁻¹ FGF, sevoflurane produces approximately 1.4 kg of carbon dioxide equivalent (CO₂e). The terminal N₂O technique could decrease sevoflurane waste by decreasing 30 min of sevoflurane delivery. In a conservative estimate, if only 50% of major surgeries are performed with volatile anaesthetics, by decreasing volatile anaesthetic usage for just 0.5 MAC-h per surgery, it could reduce 15 million MAC-h of volatile anaesthetic in the USA and five million in Europe. At 1 MAC-h at 1 l.min⁻¹ FGF sevoflurane produces approximately 1.4 kg of CO₂e. Therefore, 20 million sevoflurane MAC-h would produce 28 million kg of CO₂e, which is approximately equivalent to the annual greenhouse gas emissions of about 6000 average gasoline passenger vehicles.¹⁷

Conclusion

Using the terminal N₂O technique (adding 70% N₂O in the last 30 min of sevoflurane-maintained anaesthesia) hastens anaesthesia emergence. It significantly reduces the variability in duration of extubation and potentially eliminates prolonged time to extubation (more than 15 min). It also was associated with decreased use of analgesics in the first 24 h and did not have an influence on the quality of early and late recovery compared with sevoflurane alone anaesthesia.

Footnotes

Acknowledgements

We would like to pay special thanks to David Gassmayr, medical student, and Maureen McCloskey, MSPT for assisting with the technical aspects of the scientific writing.

Author Contribution(s)

Boris Mraovic: Conceptualization; Formal analysis; Methodology; Validation; Writing – original draft; Writing – review & editing.

Tatjana Simurina: Conceptualization; Data curation; Investigation; Methodology; Project administration; Resources; Supervision; Validation; Writing - review & editing.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Boris Mraovic

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Nitrous oxide added at the end of sevoflurane anaesthesia hastens emergence and eliminates prolonged time to extubation (SEVONATE study): A randomised controlled trial

Abstract

Keywords

Introduction

Methods

Study population

Study procedures and measures

Statistical analysis

Results

Demographic and baseline characteristics

Emergence differences

Recovery differences

Discussion

Duration and variability of emergence from anaesthesia

Postoperative pain

PONV

Limitations

Environmental concerns of terminal N2O use

Conclusion

Footnotes

Acknowledgements

Author Contribution(s)

Declaration of conflicting interests

Funding

ORCID iD

References

Environmental concerns of terminal N₂O use