TIVA versus Inhaled (volatile) Anesthesia

Key Question

Among older patients undergoing surgery with general anesthesia, does the use of intravenous agents for maintenance of anesthesia improve postoperative outcomes compared with inhaled agents?

Balance Tables

Benefits, harms, and strength of evidence (GRADE) for TIVA versus inhalation anesthesia.

Outcome	RCT	NRSI^*	TIVA	Inhaled	GRADE^†	Effect	Estimate (95% CI)
Outcome	RCT	NRSI^*	N (Total)	N (Total)	GRADE^†	Effect	Estimate (95% CI)
Delirium	8		143 (1,001)	158 (995)	⨁⨁◯◯	RR	0.94 (0.62–1.43)
		5	10,297 (142,850)	32,955 (427,929)	⨁◯◯◯	OR	1.01 (0.39–2.63)
Neurocognitive disorder <30 days	5		125 (704)	175 (703)	⨁⨁⨁◯	RR	0.72 (0.54–0.96)
		1	24 (160)	24 (119)	⨁◯◯◯	RR	0.74 (0.44–1.24)
Neurocognitive disorder days to 1 yr	1		4 (96)	6 (97)	⨁◯◯◯	RR	0.67 (0.20–2.31)
		3	40 (252)	32 (207)	⨁◯◯◯	RR	1.09 (0.72–1.66)
Physical function	none	none
Complications	10	9			⨁⨁◯◯ ⨁◯◯◯		see below
Patient satisfaction	3		90 (109)	82 (141)	⨁⨁◯◯	RR	1.39 (1.19–1.63)^‡
Length of stay (days)	6		(1,343)	(1,341)	⨁◯◯◯	MD	0.0 (-1.5 to 1.4)
		4	(147,809)	(432,893)	⨁◯◯◯	MD	-0.6 (-2.4 to 1.5)
Discharged to institution		1	8 (9)	26 (20)	⨁◯◯◯	RR	1.46 (0.69–3.41)
Mortality (in-hospital and 30-day)	4		11 (377)	8 (375)	⨁◯◯◯	RR	1.17 (0.47–2.89)
	5		11 (566)	8 (565)		RD/1000	4.1 (-7.7 to 16.0)
		7	1,876 (149,333)	5,175 (434,640)	⨁◯◯◯	OR	0.93 (0.47–1.85)
						RD/1000	-0.32 (-2.20 to 1.55)
Mortality (1-year)	1	1	5 (64)	4 (70)	⨁◯◯◯	RR	1.47 (0.42–5.18)
						RD/1000	24.2 (-46.5 to 95.0)
RCT: randomized clinical trial; NRSI: nonrandomized studies of interventions; GRADE: Grades of Recommendation, Assessment, Development, and Evaluation; RR: risk ratio; MD: mean difference; RD: risk difference.
^* Results from nonrandomized designed shown only when evidence not available from randomized trials.
^† Very low: ⨁◯◯◯; Low: ⨁⨁◯◯; Moderate: ⨁⨁⨁◯; High: ⨁⨁⨁⨁.
^‡ Comparing higher/highest category or categories with lower ones.

Included complications and strength of evidence (GRADE) for TIVA versus inhalation anesthesia.

Outcome	RCT	NRSI	TIVA	Inhaled	GRADE^*	Effect	Estimate (95% CI)
Outcome	RCT	NRSI	N (Total)	N (Total)	GRADE^*	Effect	Estimate (95% CI)
Myocardial infarction	1	5	4,027 (157,987)	8,898 (443,067)	⨁⨁◯◯	OR	0.90 (0.85–0.96)
	2	5	4,027 (158,031)	8,898 (443,111)		RD/1000	-1.9 (3.0 to -0.7)^†
Cardiac arrest	1	1	5 (1,972)	1 (1,799)	⨁◯◯◯	RR	3.47 (0.57–21.2)^‡
						RD/1000	1.7 (-0.7 to 4.1)^‡
Bradycardia	4	1	20 (416)	16 (416)	⨁◯◯◯	RR	1.57 (0.42–5.81)
						RD/1000	13.4 (-43.1 to 69.9)
Hypotension	2	2	226 (919)	237 (884)	⨁◯◯◯	RR	0.99 (0.91–1.07
						RD/1000	-24.6 (-58.6 to 9.4)
Stroke	1	1	37 (9,320)	42 (9,319)	⨁◯◯◯	OR	1.14 (0.73–1.78)
						RD/1000	0.5 (-2.4 to 1.3)^†
Acute kidney injury	1	5	823 (144,819)	2,283 (430,321)	⨁⨁◯◯	OR	0.99 (0.88–1.11)
						RD/1000	-0.2 (-4.4 to 4.1)^†
Pneumonia	3	2	293 (9,264)	335 (9,270)	⨁⨁◯◯	OR	0.80 (0.39–1.64)
						RD/1000	-3.6 (-8.3 to 1.2)^†
Pulmonary edema		2	0 (143,939)	3 (428,897)	⨁◯◯◯	—	—^§
Pulmonary embolism	2	3	212 (153,413)	465 (438,369)	⨁◯◯◯	OR	1.32 (1.13–1.53)
						RD/1000	0.2 (-2.0 to 2.4)^†
Respiratory failure	2	2	670 (151,981)	1,718 (437,111)	⨁◯◯◯	OR	0.87 (0.79–0.95)
						RD/1000	0.0 (-2.0 to 2.0)^†
RCT: randomized clinical trial; NRSI: nonrandomized studies of interventions; GRADE: Grades of Recommendation, Assessment, Development, and Evaluation; RR: risk ratio; OR: odds ratio; RD: risk difference.
^* Very low: ⨁◯◯◯; Low: ⨁⨁◯◯; Moderate: ⨁⨁⨁◯; High: ⨁⨁⨁⨁.
^† Approximate owing to pruning in studies using propensity matching.
^‡ Common effects model.
^§ No events in 1 study; 3 in the other.

Outcomes Reported

Table 2. Publications reporting dichotomous or count outcomes (not necessarily unique studies)..

Outcome	RCT, N = 34	NR Trial, N = 1	Prosp Coh, N = 3	Retro Coh, N = 13
ADL	—	—	—	—
Complications	10 (29%)	1 (100%)	—	11 (85%)
DNCR/POCD	9 (26%)	1 (100%)	2 (67%)	1 (7.7%)
Delirium	8 (24%)	—	1 (33%)	4 (31%)
Delirium duration	—	—	—	—
Discharge location	—	—	—	1 (7.7%)
Mortality	5 (15%)	—	—	7 (54%)
Opioid use	2 (5.9%)	—	—	—
Pain	1 (2.9%)	—	—	—
QoR	—	—	—	—
Readmission	1 (2.9%)	—	—	—
Satisfaction	3 (8.8%)	—	—	—
ADL: activities of daily living; NCR: neurocognitive recovery; POCD: postoperative neurocognitive disorder; QoR: quality of recovery; RCT: randomized clinical trial; NR Trial: non-randomized trial; Prosp Coh: prospective cohort; Retro Coh: retrospective cohort.

Table 3. Publications reporting continuous outcomes (not necessarily unique studies).

Outcome	RCT, N = 34	NR Trial, N = 1	Prosp Coh, N = 3	Retro Coh, N = 13
Delirium duration	1 (2.9%)	—	—	—
Length of stay	6 (18%)	—	—	4 (31%)
Opioid use	3 (8.8%)	—	—	—
RCT: randomized clinical trial; NR Trial: non-randomized trial; Prosp Coh: prospective cohort; Retro Coh: retrospective cohort.

Table 4. Publications reporting likert or ordinal outcomes (not necessarily unique studies).

Outcome	RCT, N = 34	NR Trial, N = 1	Prosp Coh, N = 3	Retro Coh, N = 13
ADL	—	—	—	—
DNCR/POCD	16 (47%)	1 (100%)	—	—
Delirium	3 (8.8%)	—	—	—
Complications	—	—	—	—
Pain	4 (12%)	—	—	—
Quality of life	—	—	—	—
QoR	1 (2.9%)	—	—	—
Satisfaction	—	—	—	—
ADL: activities of daily living; NCR: neurocognitive recovery; POCD: postoperative neurocognitive disorder; QoR: quality of recovery; RCT: randomized clinical trial; NR Trial: non-randomized trial; Prosp Coh: prospective cohort; Retro Coh: retrospective cohort.

Included Studies

See Appendix for detailed summary study and patient characteristics including primary outcomes.

Table 5. Number of studies by design.

Design	Studies
Randomized Clinical Trial	34
Nonrandomized Trial	1
Prospective Cohort	3
Retrospective Cohort	13
Total	51

Design, centers, country, and surgery

Table 6. Study design, enrollment, centers, country, and surgery (see References for citations).

ID	Study	Centers	Enrolled	Country^a	Surgery
Randomized Clinical Trial
20083	Kalimeris 2013	1	50	Greece	Cardiac
18510	Kang 2023	1	102	South Korea	Cardiac
13719	Ozer 2017	1	88	Turkey	Cardiac
4033	Qiao 2015	1	90	China^a	ENT
16931	Qiao 2023	1	69	China^a	ENT
15440	Fazel 2017	1	60	Iran^a	GI/Abdominal
11652	Forsmo 2016	1	653	Norway	GI/Abdominal
16559	Geng 2017	1	150	China^a	GI/Abdominal
16572	Ishii 2016	1	59	Japan	GI/Abdominal
17	Li 2021a	4	544	China^a	GI/Abdominal
385	Nishikawa 2004	1	50	Japan	GI/Abdominal
331	Nishikawa 2007a	1	30	Japan	GI/Abdominal
16622	Tang 2014	1	220	China^a	GI/Abdominal
18152	Yang 2022	1	80	China^a	GI/Abdominal
9011	Ding 2021	1	180	China^a	GI/Abdominal\|Ortho\|ENT
2794	Rohan 2005	1	45	Ireland	Gyn\|Urol
5915	Jellish 2003	1	60	USA	Headneck
16557	Epple 2001	1	124	Germany	Ophtho
16587	Luntz 2004	1	96	Germany	Ophtho
18987	Mei 2020b	1	240	China^a	Ortho
285	Tanaka 2017	1	100	USA	Ortho
18378	Farrer 2023	2	200	USA	Ortho\|Spine
16726	Liang 2022	1	224	China^a	Spine
16556	Egawa 2016	1	148	Japan	Thoracic
150	Qin 2019	1	104	China^a	Thoracic
20412	Tian 2021	1	62	China^a	Thoracic
10	Zhang 2018a	1	392	China^a	Thoracic
376	Zangrillo 2011	1	153	Italy	Thoracic\|Vasc
16547	Celik 2011	1	100	Turkey	Urol
534	Cai 2012	1	2,216	China^a	Various^b
17101	Cao 2023	14	1,228	China^a	Various^b
6506	Dai 2021	1	164	China^a	Various^b
18867	Villalobos 2023	1	140	USA	Various^b
447	Lindholm 2013	1	231	Norway	Vasc
Nonrandomized Trial
13116	Zhou 2021	1	265	China^a	Thoracic
Prospective Cohort
17080	Deiner 2014	1	76	USA	General\|Spine\|Thoracic\|Urol
155	Deiner 2015	1	105	USA	General\|Thoracic\|Urol
22	Konishi 2018	1	300	Japan	Ortho
Retrospective Cohort
332	Goins 2018	1	116	USA	Cardiac
234	Jakobsen 2007	3	10,535	Denmark	Cardiac
20764	Kadoi 2007	1	109	Japan	Cardiac
17551	Hasselager 2022		22,179	Denmark	GI/Abdominal
15331	Koo 2016	1	1,934	South Africa	GI/Abdominal
14821	Shimizu 2010	1	265	Japan	GI/Abdominal
18477	Huang 2023b	1	46	Taiwan	Ortho
383	Kishimoto 2018	^c	21,899	Japan	Ortho
18986	Chang 2024	1	281	South Korea	Spine
132	Oh 2019	1	3,084	South Korea	Thoracic
6964	Cho 2021	1	3,045	South Korea	Various^b
1134	Park 2020	1	1,254	South Korea	Various^b
16890	Yoshimura 2022	1,730	738,600	Japan	Various^b
GI: gastrointestinal; Ortho: orthopedic; Ent: ear, nose, and throat; Neuro: neurological; Oralmax: oral maxillofacial; Vasc: vascular.
^a Non very-high Human Development Index country.
^b Described as various or more than 4 different types of surgery.
^c National national administrative claims database.

Country Summary

Table 7. Summary of studies by country where conducted.

	N = 51^a
Country
China	16 (31%)
Japan	9 (18%)
USA	7 (14%)
South Korea	5 (9.8%)
Denmark	2 (3.9%)
Germany	2 (3.9%)
Norway	2 (3.9%)
Turkey	2 (3.9%)
Greece	1 (2.0%)
Iran	1 (2.0%)
Ireland	1 (2.0%)
Italy	1 (2.0%)
South Africa	1 (2.0%)
Taiwan	1 (2.0%)
^a n (%)

Comparators

Randomized

Table 8. Selected characteristics of randomized clinical trials.

Study	N	Arm	ASA	Age^b	MMSE^b	Inhaled			TIVA
Study	N	Arm	PS^a	Age^b	MMSE^b	Des	Iso	Sev	Fen	Pro	Rem	Suf	Oth
Gastrointestinal/Abdominal
Nishikawa 2004	25	Inhaled	12	71.0 (7.0)				✓
	25	TIVA		71.0 (8.0)						●
Nishikawa 2007a	15	Inhaled	12	70.9 (6.5)				✓
	15	TIVA		71.2 (5.3)									●^c
Tang 2014	99	Inhaled		70.0 (4.3)	25.0 (1.7)			✓	○
	101	TIVA		69.6 (4.8)	24.6 (1.7)					●
Forsmo 2016	153	Inhaled	123	66.0 [19-93]			✓^d	✓^d	○	○
	154	TIVA		65.0 [23-89]						●	●
Ishii 2016	30	Inhaled		76.5 (4.5)				✓
	29	TIVA		77.3 (4.6)						●
Fazel 2017	30	Inhaled		71.0 (2.6)	27.3 (1.9)			✓
	30	TIVA		73.0 (3.2)	27.2 (2.4)					●
Geng 2017	50	Inhaled	23		28.9 (1.4)			✓
	50	Inhaled			29.4 (1.9)		✓
	50	TIVA			29.2 (1.5)					●
Li 2021a	272	Inhaled		65.0 {62-69}	29 {28-30}			✓			○
	272	TIVA		64.0 {62-68}	29 {28-30}					●	●
Yang 2022	40	Inhaled	12	71.8 (2.1)	29.7 (0.4)			✓
	40	TIVA		72.0 (3.1)	29.6 (0.4)					●
Various
Ding 2021	90	Inhaled	12	71.3 (5.6)	27.0 (2.7)			✓
	90	TIVA		70.2 (4.3)	26.0 (2.5)					●
Rohan 2005	15	Inhaled		73.8 [67-86]	28.0 [25-30]			✓	○
	15	TIVA		72.9 [65-83]	27.0 [25-30]				●	●
Farrer 2023	99	Inhaled		73.6 (5.4)			✓
	100	TIVA		72.9 (5.4)					●	●
Zangrillo 2011	44	Inhaled	1234	65.0 (11.8)				✓	○
	44	TIVA		64.0 (12.2)						●
Cai 2012	1,000	Inhaled		69.3 (5.1)	27.4 (1.1)		✓		○	○
	1,000	TIVA		71.2 (3.8)	27.2 (1.1)				●	●
Dai 2021	81	Inhaled	234	72.0 (7.0)				✓
	83	TIVA		73.0 (8.0)						●	●
Cao 2023	597	Inhaled	123	71.0 [65-88]	28 {26-30}			✓
	598	TIVA		72.0 [65-88]	28 {26-30}					●
Villalobos 2023	54	Inhaled	1234	67.5 {64-71}	29 {27-29}		✓
	53	TIVA		69.0 {64-73}	29 {28-29}					●
Thoracic
Egawa 2016	72	Inhaled	123	72.0 {63-72}	30 {28-30}			✓
	72	TIVA		69.0 {63-73}	30 {29-30}					●
Zhang 2018a	190	Inhaled	123	72.4 (5.6)	28.3 (1.7)			✓
	189	TIVA		72.8 (5.5)	28.2 (1.7)					●
Qin 2019	52	Inhaled		67.6 (2.5)	28.6 (1.0)			✓
	52	TIVA		67.6 (2.5)	28.8 (1.0)					●
Tian 2021	31	Inhaled	12	65.5 (16.2)	28.9 (1.5)			✓
	31	TIVA		68.3 (13.5)	28.3 (1.4)					●
Ophthalmologic
Epple 2001	62	Inhaled	123	76.0 (6.0)			✓		○
	62	TIVA		77.0 (6.0)						●	●
Luntz 2004	32	Inhaled	123	77.0 (7.0)				✓^e
	32	Inhaled		76.0 (6.0)				✓		○
	32	TIVA		74.0 (7.0)						●
Otolaryngological
Qiao 2015	30	Inhaled		68.0 (3.0)	27.8 (1.8)			✓
	30	TIVA		68.0 (2.0)	28.6 (1.1)					●
Qiao 2023	31	Inhaled	12	66.7 (7.2)	27 {26-29}	✓					○
	32	TIVA		63.9 (5.3)	28 {26-28}					●	●
Orthopedic
Tanaka 2017	45	Inhaled	123	69.8 (4.3)		✓			○	○
	45	TIVA		70.6 (5.0)						●
Mei 2020b	103	Inhaled	123	71.5 (6.8)	26.3 (2.0)			✓
	106	TIVA		70.9 (6.7)	26.2 (1.8)					●
Cardiac
Kalimeris 2013	21	Inhaled		69.0 (7.0)	27.5 (2.0)			✓
	23	TIVA		67.0 (9.0)	27.0 (3.0)					●
Ozer 2017	40	Inhaled		69.0 (3.0)	28.7 (1.3)		✓		○
	40	TIVA		66.0 (4.0)	28.8 (1.3)					●	●
Kang 2023	48	Inhaled	34	64.5 (9.4)				✓
	47	TIVA		66.0 (7.3)						●		●
Urologic
Celik 2011	50	Inhaled	123	69.8 (3.9)				✓			○
	50	TIVA		69.2 (4.8)						●	●
Head & Neck
Jellish 2003	29	Inhaled	3	69.2 (1.7)			✓		○	○
	30	TIVA		72.1 (1.5)						●	●
Vascular
Lindholm 2013	97	Inhaled	234	69.0 (9.0)				✓	○
	96	TIVA		67.0 (9.0)						●	●
Spine
Liang 2022	70	Inhaled	23	70.1 (3.5)				✓
	70	TIVA		69.5 (3.3)						●
TIVA: total intravenous anesthesia; NR: not reported; ASA PS: ASA Physical Status; MMSE: Mini-Mental State Exam; Des: desflurane; Iso: isoflurane; Sev: sevoflurane; Fen: fentanyl; Pro: propofol; Rem: remifentanil; Suf: sufentanil; Oth: other.
^a Not reported if none specified.
^b Mean Med (SD)[Range]{IQR}.
^c Thimylal.
^d Induction with sevoflurane; either inhalant used.
^e Induction with sevoflurane.

Nonrandomized

Table 9. Selected characteristics of nonrandomized studies.

Study	N	Comparator	ASA	Age^a	MMSE^a	Inhaled			TIVA
Study	N	Comparator	PS	Age^a	MMSE^a	Des	Iso	Sev	Fen	Pro	Rem	Suf
Cardiac - Retrospective Cohort
Jakobsen 2007	5,325	Inhaled		64.9				✓
	5,210	TIVA		64.7						●		●
Kadoi 2007	58	Inhaled		63.0 (10.0)				✓
	48	TIVA		66.0 (11.0)						●
Goins 2018	32	Inhaled		78.3 (9.0)		✓^b	✓	^b			○
	84	TIVA		79.6 (8.7)						●	●
Various - Retrospective Cohort
Park 2020	386	Inhaled	1234	65.5 (14.8)		^c	^c	^c
	100	TIVA		65.6 (14.9)						●	●
Cho 2021^d	1,202	Inhaled	34	62.7 (13.7)		✓^b		✓^b
	1,374	TIVA		65.6 (12.8)						●	●
Yoshimura 2022	427,695	Inhaled		76.3		✓^e	✓^e	✓^e
	142,565	TIVA		76.6						●
GI/Abdominal - Retrospective Cohort
Shimizu 2010	84	Inhaled	123	67.9 (13.6)				✓
	84	TIVA		68.1 (14.0)						●
Koo 2016	390	Inhaled	1234	61.7 (13.4)		✓^b		✓^b
	390	TIVA		61.5 (12.4)						●	●
Hasselager 2022	8,722	Inhaled	1234	71.0 {63-78}				✓
	8,722	TIVA		71.0 {64-77}						●
General\|Spine\|Thoracic\|Urol - Prospective Cohort
Deiner 2014	36	Inhaled	1234	76.3 (5.8)	27 {26-30}			✓
	40	TIVA		73.5 (5.0)	29 {28-30}					●
General\|Thoracic\|Urol - Prospective Cohort
Deiner 2015	34	Inhaled		73.8				✓
	43	TIVA		73.8						●
Ortho - Prospective Cohort
Konishi 2018	121	Inhaled		69.9 (6.3)	28.1 (1.2)			✓
	171	TIVA		70.1 (6.7)	28.2 (1.3)					●
Ortho - Retrospective Cohort
Kishimoto 2018	5,140	Inhaled		74.4 (7.4)				✓
	5,140	TIVA		74.5 (7.2)						●
Huang 2023b	26	Inhaled	4	85.6 (7.8)		✓		✓
	20	TIVA		83.8 (9.1)						●
Thoracic - Retrospective Cohort
Oh 2019	1,477	Inhaled	123	65.0 (10.4)				✓		○	○
	1,395	TIVA		65.0 (10.0)						●	●
Spine - Retrospective Cohort
Chang 2024	140	Inhaled	123	72.9 (4.7)				✓
	141	TIVA		72.4 (4.5)						●
Thoracic - Nonrandomized Trial
Zhou 2021	116	Inhaled	12	63.4 (17.1)	25.9 (1.2)			✓
	149	TIVA		67.2 (15.1)	26.1 (1.4)					●
TIVA: total intravenous anesthesia; NR: not reported; ASA PS: ASA Physical Status; MMSE: Mini-Mental State Exam; Des: desflurane; Iso: isoflurane; Sev: sevoflurane; Fen: fentanyl; Pro: propofol; Rem: remifentanil; Suf: sufentanil.
^a Mean Med (SD)[Range]{IQR}.
^b Either of the two inhalent agents used.
^c Agent used not specified.
^d End-stage renal disease patients.
^e Any agent used.

Delirium Incidence

Table 10. Delirium incidence and days of ascertainment during hospitalization.

Study	N	Arm	Scale	Day(s)^a	Incidence Proportion		RR OR (95% CI)
Study	N	Arm	Scale	Day(s)^a	N (%)	0 – 100%	RR OR (95% CI)
GI/Abd – Randomized Clinical Trial
Nishikawa 2004	25	Inhaled	DRS	3	0 (0)
	25	TIVA			4 (16.0)
Nishikawa 2007a	15	Inhaled	DRS	3	2 (13.3)		—
	15	TIVA			3 (20.0)		1.50 (0.29-7.73)
Ishii 2016	30	Inhaled	CAM	Stay	8 (26.7)		—
	29	TIVA			2 (6.9)		0.26 (0.06-1.12)
Ortho – Randomized Clinical Trial
Tanaka 2017	45	Inhaled	CAM	2	0 (0)
	45	TIVA			1 (2.2)
Mei 2020b	103	Inhaled	CAM	3	24 (23.3)		—
	106	TIVA			35 (33.0)		1.42 (0.91-2.21)
Various – Randomized Clinical Trial
Dai 2021	81	Inhaled	NS	Stay	36 (44.4)		—
	83	TIVA			35 (42.2)		0.95 (0.67-1.35)
Cao 2023	597	Inhaled	CAM	7	74 (12.4)		—
	598	TIVA			50 (8.4)		0.67 (0.48-0.95)
Farrer 2023	99	Inhaled	CAM	3	14 (14.1)		—
	100	TIVA			13 (13.0)		0.92 (0.46-1.85)
Cardiac – Retrospective Cohort
Goins 2018	32	Inhaled	CAM	2	11 (34.4)		—
	84	TIVA			12 (14.3)		0.22 (0.06-0.79)^b
Various – Prospective Cohort
Deiner 2014	36	Inhaled	CAM	3	8 (22.2)		—
	40	TIVA			6 (15.0)		0.62 (0.19-1.99)^c
Various – Retrospective Cohort
Yoshimura 2022	427,695	Inhaled	ICD-10^d	Stay	32,912 (7.7)		—
	142,565	TIVA			10,269 (7.2)		0.93 (0.91-0.95)^e
Ortho – Retrospective Cohort
Huang 2023b	26	Inhaled	NS	Stay	2 (7.7)		—
	20	TIVA			3 (15.0)		2.12 (0.32-14.07)^c
Spine – Retrospective Cohort
Chang 2024	140	Inhaled	KNDSS	Stay	22 (15.7)		—
	141	TIVA			7 (5.0)		4.12 (1.55-10.95)
RR: risk ratio; OR: odds ratio; DRS: Delirium Rating Scale; CAM: Confusion Assessment Method; KNDSS: Korean Nursing Delirium Screening Scale; NS: not specified.
^a Day(s) over which incidence proportion assessed. Stay indicates duration of hospitalization.
^b Adjusted from multivariable model.
^c Calculated crude odds ratio.
^d Or new antipsychotic prescription.
^e Propensity score matched.

Pooled

Randomized

Figure 1. Delirium incidence (randomized clinical trials).

RR: risk ratio; D1: bias arising from the randomization process; D2: bias due to deviations from intended interventions; D3: bias due to missing outcome data; D4: bias in measurement of the outcome; D5: bias in selection of the reported result: All: overall risk of bias.
Risk of bias ratings: low +, some concerns ?, high – .
Continuity correction of 0.5 added to studies with no events in one arm.

Meta-analysis methods detail.

- Mantel-Haenszel method (common effect model)
- Inverse variance method (random effects model)
- Restricted maximum-likelihood estimator for τ²
- Q-Profile method for confidence interval of τ² and τ
- Hartung-Knapp adjustment for random effects model (df = 7)
- Hartung-Knapp prediction interval (df = 6)
- Continuity correction of 0.5 in studies with zero cell frequencies

Figure 2. Delirium incidence in randomized clinical trials — risk difference per 100. .

Figure 3. Delirium incidence (small study effects).

Figure 4. Control arm/baseline risk (inhaled anesthesia) and risk ratios.

No suggestion for dependence of risk ratio on baseline risk.

Figure 5. Delirium incidence summary risk of bias in randomized clinical trials (weighted).

Nonrandomized

Figure 6. Delirium incidence (nonrandomized designs).

D1: Bias due to confounding; D2: Bias in selection of participants into the study; D3: Bias in classification of interventions; D4: Bias due to deviations from intended interventions; D5: Bias due to missing data; D6: Bias in measurement of outcomes; D7: Bias in selection of reported results; All: overall risk of bias (ratings: low ++, moderate +, serious -, critical - - ; NI: no information; NA: not applicable).
Note: adjusted odds ratios pooled from Yoshimura 2022 (propensity matching); Goins 2018 and Chang 2022 (multivariable adjustment).

Meta-analysis methods detail.

- Inverse variance method
- Restricted maximum-likelihood estimator for τ²
- Q-Profile method for confidence interval of τ² and τ

Neurocognitive Disorder
<30 days

Table 11. Neurocognitive disorder <30 days incidence and ascertainment (randomized and nonrandomized designs). Table includes only studies conducting cognitive testing at day 3 or later.

Study	N	Comparator	Preop	Instrument				Day^c	Neurocognitive Disorder <30 days
Study	N	Comparator	MMSE^a	MMSE	MoCA	Multiple^b	NS	Day^c	N (%)	0 — 100%	RR (95% CI)
Randomized Clinical Trial — Gastrointestinal/Abdominal
Tang 2014	99	Inhaled	25.0 (1.7)	✓^d				7	33 (33.3)		—
	101	TIVA	24.6 (1.7)						30 (29.7)		0.89 (0.59-1.34)
Geng 2017	50	Inhaled	28.9 (1.4)			✓^e,f		3	10 (20.0)		—
	50	Inhaled	29.4 (1.9)						15 (30.0)		1.50 (0.75-3.01)
	50	TIVA	29.2 (1.5)						2 (4.0)		0.20 (0.05-0.87)
Li 2021a	272	Inhaled	29 {28-30}	✓^d				7	51 (18.8)		—
	272	TIVA	29 {28-30}						41 (15.1)		0.80 (0.55-1.17)
Randomized Clinical Trial — Thoracic
Egawa 2016	72	Inhaled	30 {28-30}	✓^f				5	24 (33.3)		—
	72	TIVA	30 {29-30}						16 (22.2)		0.67 (0.39-1.15)
Zhang 2018a	190	Inhaled	28.3 (1.7)	✓^d				7	44 (23.2)		—
	189	TIVA	28.2 (1.7)						28 (14.8)		0.64 (0.42-0.98)
Randomized Clinical Trial — Spine
Liang 2022	70	Inhaled			✓^g			7	23 (32.9)		—
	70	TIVA							10 (14.3)		0.43 (0.22-0.84)
Prospective Cohort — Orthopedic
Konishi 2018	119	Inhaled	28.1 (1.2)	✓^d				7	24 (20.2)		—
	160	TIVA	28.2 (1.3)						24 (15.0)		0.74 (0.44-1.24)
MMSE: Mini-Mental State Exam; MoCA: MoCA: Montreal Cognitive Assessment; NS: not specfied; RR: risk ratio; CI: confidence interval.
^a Mean Med (SD)[Range]{IQR}.
^b Failed 2 or more tests.
^c Day of assessment.
^d Z ≥1.96.
^e Digit Span Test; Digit Symbol Test; Grooved Pegboard Test; Mini-Mental State Examination; Rey Auditory Verbal Learning; Trail Marking Test A.
^f Difference from baseline >20%.
^g Difference from baseline ≥1 SD.

Pooled

Figure 7. Neurocognitive disorder <30 days assessed at postoperative day 5 or later (randomized clinical trials).

RR: risk ratio; D1: bias arising from the randomization process; D2: bias due to deviations from intended interventions; D3: bias due to missing outcome data; D4: bias in measurement of the outcome; D5: bias in selection of the reported result: All: overall risk of bias.
Risk of bias ratings: low +, some concerns ?, high – .
Four trials conducted in China and one each in Norway (Lindholm 2013) and Japan (Egawa 2016).
Including Geng 2017 assessments at day 3 — RR 0.66 (95% CI, 0.54–0.81; prediction interval, 0.54–0.91)

Meta-analysis methods detail

- Mantel-Haenszel method (common effect model)
- Inverse variance method (random effects model)
- Restricted maximum-likelihood estimator for τ²
- Q-Profile method for confidence interval of τ² and τ
- Hartung-Knapp adjustment for random effects model (df = 4)
- Prediction interval based on t-distribution (df = 3)

Figure 8. Neurocognitive disorder <30 days assessed at postoperative day 5 or later (randomized clinical trials; risk difference per 100).

Figure 9. Neurocognitive disorder <30 days assessed at postoperative day 5 or later (small study effects).

Too few studies to test for the presence of small study effects.

Figure 10. Neurocognitive disorder <30 days summary risk of bias from randomized clinical trials (weighted).

Neurocognitive Disorder
30 days to 1 year

Table 12. Neurocognitive disorder ≥30 days (cognitive dysfunction after 30 days) and ascertainment.

Study	N	Comparator	Preop	Instrument				Day^b	Neurocognitive Disorder ≥30 days
Study	N	Comparator	MMSE^a	MMSE	MoCA	Other	NS	Day^b	N (%)	0 — 100%	RR (95% CI)
Randomized Clinical Trial
Lindholm 2013	97	Inhaled					✓	30	6 (6.2)		—
	96	TIVA							4 (4.2)		0.67 (0.20-2.31)
Prospective Cohort
Deiner 2015	34	Inhaled				✓^c		90	9 (26.5)		—
	43	TIVA							12 (27.9)		1.05 (0.50-2.21)
Konishi 2018	115	Inhaled	28.1 (1.2)	✓^d				90	10 (8.7)		—
	161	TIVA	28.2 (1.3)						17 (10.6)		1.21 (0.58-2.55)
Retrospective Cohort
Kadoi 2007	58	Inhaled				✓^e,f		180	13 (22.4)		—
	48	TIVA							11 (22.9)		1.02 (0.50-2.07)
Mini-Mental State Exam; MoCA: Montreal Cognitive Assessment; NS: not stated; RR: risk ratio.
Pooled RR 1.10 (95% CI, 0.72–1.68)
^a Mean Med (SD)[Range]{IQR}.
^b Day of assessment.
^c Uniform Data Set of the Alzheimer’s Disease Centers.
^d Z ≥1.96.
^e Digit Span Test; Grooved Pegboard Test; Mini-Mental State Examination; Rey Auditory Verbal Learning; Trail Marking Test A; Trail Making Test B.
^f Failed 2 or more tests.

Pooled

Figure 11. Neurocognitive disorder ≥30 days (nonrandomized designs).

Meta-analysis methods detail.

Physical Function

No studies

Complications

Table 13. Complications — cardiac, pulmonary, and renal (randomized and nonrandomized designs).

Study	N	Arm	Age^a	Surgery	N (%)	RD OR (95% CI)^b
Myocardial Infarction – Randomized Clinical Trial
Zangrillo 2011	44	Inhaled	65.0 (11.8)	Various	0 (0)	—
	44	TIVA	64.0 (12.2)		0 (0)	0.00% (-4.33, 4.33)
Lindholm 2013	97	Inhaled	69.0 (9.0)	Vascular	5 (5.2)	—
	96	TIVA	67.0 (9.0)		3 (3.1)	-2.03% (-7.64, 3.58)
Myocardial Infarction – Retrospective Cohort
Jakobsen 2007	5,325	Inhaled	64.9	Cardiac	2,076 (39.0)	—
	5,210	TIVA	64.7		1,891 (36.3)	-2.69% (-4.54, -0.84)
Cho 2021	1,202	Inhaled	62.7 (13.7)	Various	15 (1.2)	—
	1,374	TIVA	65.6 (12.8)		6 (0.4)	-0.81% (-1.53, -0.09)
Hasselager 2022	8,722	Inhaled	71.0 {63-78}	GI/Abd	82 (0.9)	—
	8,722	TIVA	71.0 {64-77}		88 (1.0)	0.93 (0.69—1.26)
Yoshimura 2022	427,695	Inhaled	76.3	Various	6,717 (1.6)	—
	142,565	TIVA	76.6		2,039 (1.4)	0.91 (0.86—0.96)
Huang 2023b	26	Inhaled	85.6 (7.8)	Ortho	3 (11.5)	—
	20	TIVA	83.8 (9.1)		0 (0)	-11.54% (-25.79, 2.71)
Cardiac Arrest – Randomized Clinical Trial
Cao 2023	597	Inhaled	71.0 [65-88]	Various	1 (0.2)	—
	598	TIVA	72.0 [65-88]		3 (0.5)	0.33% (-0.32, 0.99)
Cardiac Arrest – Retrospective Cohort
Cho 2021	1,202	Inhaled	62.7 (13.7)	Various	0 (0)	—
	1,374	TIVA	65.6 (12.8)		2 (0.1)	0.15% (-0.11, 0.40)
Bradycardia – Randomized Clinical Trial
Luntz 2004^c	32	Inhaled	77.0 (7.0)	Ophtho	1 (3.1)	—
	32	Inhaled	76.0 (6.0)		4 (12.5)	—
	32	TIVA	74.0 (7.0)		8 (25.0)	17.19% (0.81, 33.57)^d
Nishikawa 2007a^e	15	Inhaled	70.9 (6.5)	GI/Abd	2 (13.3)	—
	15	TIVA	71.2 (5.3)		0 (0)	-13.33% (-33.06, 6.40)
Zhang 2018a^f	190	Inhaled	72.4 (5.6)	Thoracic	8 (4.2)	—
	189	TIVA	72.8 (5.5)		6 (3.2)	-1.04% (-4.83, 2.76)
Tian 2021^c	31	Inhaled	65.5 (16.2)	Thoracic	0 (0)	—
	31	TIVA	68.3 (13.5)		1 (3.2)	3.23% (-5.27, 11.72)
Bradycardia – Nonrandomized Trial
Zhou 2021^c	116	Inhaled	63.4 (17.1)	Thoracic	1 (0.9)	—
	149	TIVA	67.2 (15.1)		5 (3.4)	2.49% (-0.85, 5.84)
Hypotension – Randomized Clinical Trial
Tian 2021^c	31	Inhaled	65.5 (16.2)	Thoracic	3 (9.7)	—
	31	TIVA	68.3 (13.5)		1 (3.2)	-6.45% (-18.58, 5.67)
Cao 2023^g	597	Inhaled	71.0 [65-88]	Various	101 (16.9)	—
	598	TIVA	72.0 [65-88]		97 (16.2)	-0.70% (-4.91, 3.52)
Hypotension – Nonrandomized Trial
Zhou 2021^c	116	Inhaled	63.4 (17.1)	Thoracic	11 (9.5)	—
	149	TIVA	67.2 (15.1)		5 (3.4)	-6.13% (-12.19, -0.06)
Hypotension – Retrospective Cohort
Chang 2024	140	Inhaled	72.9 (4.7)	Spine	122 (87.1)	—
	141	TIVA	72.4 (4.5)		123 (87.2)	0.09% (-7.72, 7.91)
Other Cardiac – Randomized Clinical Trial
Zangrillo 2011^h	44	Inhaled	65.0 (11.8)	Various	1 (2.3)	—
	44	TIVA	64.0 (12.2)		1 (2.3)	0.00% (-6.23, 6.23)
Dai 2021ⁱ	81	Inhaled	72.0 (7.0)	Various	2 (2.5)	—
	83	TIVA	73.0 (8.0)		2 (2.4)	-0.06% (-4.78, 4.66)
Cao 2023^j	597	Inhaled	71.0 [65-88]	Various	9 (1.5)	—
	598	TIVA	72.0 [65-88]		13 (2.2)	0.67% (-0.86, 2.19)
Stroke – Randomized Clinical Trial
Cao 2023	597	Inhaled	71.0 [65-88]	Various	3 (0.5)	—
	598	TIVA	72.0 [65-88]		3 (0.5)	-0.00% (-0.80, 0.80)
Stroke – Retrospective Cohort
Hasselager 2022	8,722	Inhaled	71.0 {63-78}	GI/Abd	39 (0.4)	—
	8,722	TIVA	71.0 {64-77}		34 (0.4)	1.15 (0.72—1.83)
Acute Kidney Injury – Randomized Clinical Trial
Cao 2023	597	Inhaled	71.0 [65-88]	Various	36 (6.0)	—
	598	TIVA	72.0 [65-88]		38 (6.4)	0.32% (-2.41, 3.06)
Acute Kidney Injury – Retrospective Cohort
Oh 2019	1,477	Inhaled	65.0 (10.4)	Thoracic	71 (4.8)	—
	1,395	TIVA	65.0 (10.0)		69 (4.9)	0.96 (0.53—1.71)
Park 2020	386	Inhaled	65.5 (14.8)	Various	47 (12.2)	—
	100	TIVA	65.6 (14.9)		7 (7.0)	0.44 (0.18—0.95)
Yoshimura 2022	427,695	Inhaled	76.3	Various	2,123 (0.5)	—
	142,565	TIVA	76.6		706 (0.5)	1.00 (0.91—1.09)
Huang 2023b	26	Inhaled	85.6 (7.8)	Ortho	4 (15.4)	—
	20	TIVA	83.8 (9.1)		1 (5.0)	-10.38% (-27.22, 6.45)
Chang 2024	140	Inhaled	72.9 (4.7)	Spine	2 (1.4)	—
	141	TIVA	72.4 (4.5)		2 (1.4)	-0.01% (-2.78, 2.76)
Pneumonia – Randomized Clinical Trial
Lindholm 2013	97	Inhaled	69.0 (9.0)	Vascular	13 (13.4)	—
	96	TIVA	67.0 (9.0)		9 (9.4)	-4.03% (-12.97, 4.91)
Forsmo 2016	153	Inhaled	66.0 [19-93]	GI/Abd	8 (5.2)	—
	154	TIVA	65.0 [23-89]		7 (4.5)	-0.68% (-5.51, 4.14)
Li 2021a	272	Inhaled	65.0 {62-69}	GI/Abd	1 (0.4)	—
	272	TIVA	64.0 {62-68}		0 (0)	-0.37% (-1.38, 0.65)
Pneumonia – Retrospective Cohort
Hasselager 2022	8,722	Inhaled	71.0 {63-78}	GI/Abd	303 (3.5)	—
	8,722	TIVA	71.0 {64-77}		275 (3.2)	1.11 (0.94—1.31)
Huang 2023b	26	Inhaled	85.6 (7.8)	Ortho	10 (38.5)	—
	20	TIVA	83.8 (9.1)		2 (10.0)	-28.46% (-51.32, -5.60)
Pneumothorax – Randomized Clinical Trial
Cao 2023	597	Inhaled	71.0 [65-88]	Various	3 (0.5)	—
	598	TIVA	72.0 [65-88]		6 (1.0)	0.50% (-0.48, 1.48)
Pulmonary Embolism – Randomized Clinical Trial
Forsmo 2016	153	Inhaled	66.0 [19-93]	GI/Abd	0 (0)	—
	154	TIVA	65.0 [23-89]		2 (1.3)	1.30% (-0.88, 3.48)
Cao 2023	597	Inhaled	71.0 [65-88]	Various	1 (0.2)	—
	598	TIVA	72.0 [65-88]		1 (0.2)	-0.00% (-0.46, 0.46)
Pulmonary Embolism – Retrospective Cohort
Cho 2021	1,202	Inhaled	62.7 (13.7)	Various	0 (0)	—
	1,374	TIVA	65.6 (12.8)		2 (0.1)	0.15% (-0.11, 0.40)
Hasselager 2022	8,722	Inhaled	71.0 {63-78}	GI/Abd	32 (0.4)	—
	8,722	TIVA	71.0 {64-77}		22 (0.3)	1.46 (0.85—2.54)
Yoshimura 2022	427,695	Inhaled	76.3	Various	432 (0.1)	—
	142,565	TIVA	76.6		185 (0.1)	1.29 (1.06—1.53)
Pulmonary Edema – Retrospective Cohort
Cho 2021	1,202	Inhaled	62.7 (13.7)	Various	3 (0.2)	—
	1,374	TIVA	65.6 (12.8)		0 (0)	-0.25% (-0.57, 0.07)
Yoshimura 2022	427,695	Inhaled	76.3	Various	0 (0)	—
	142,565	TIVA	76.6		0 (0)	—
Respiratory Failure – Randomized Clinical Trial
Lindholm 2013	97	Inhaled	69.0 (9.0)	Vascular	9 (9.3)	—
	96	TIVA	67.0 (9.0)		6 (6.2)	-3.03% (-10.56, 4.51)
Cao 2023	597	Inhaled	71.0 [65-88]	Various	6 (1.0)	—
	598	TIVA	72.0 [65-88]		8 (1.3)	0.33% (-0.89, 1.55)
Respiratory Failure – Retrospective Cohort
Hasselager 2022	8,722	Inhaled	71.0 {63-78}	GI/Abd	216 (2.5)	—
	8,722	TIVA	71.0 {64-77}		236 (2.7)	0.91 (0.76—1.10)
Yoshimura 2022	427,695	Inhaled	76.3	Various	1,487 (0.3)	—
	142,565	TIVA	76.6		420 (0.3)	0.85 (0.76—0.94)
RD: risk difference; OR: odds ratio; Ophtho: ophthalmologic; GI: gastointestinal; GI: gastrointestinal; Abd: abdominal.
^a Mean Med (SD)[Range]{IQR}.
^b Odds ratios for propensity-matched studies (risk differences accounting for matching were not reported).
^c Definition not reported.
^d Compared with combined inhalation arms (differed only in induction agents).
^e <50 bpm.
^f <50 bpm or ↓30% and require chronotropic agent.
^g Systolic blood pressure <90 mm Hg or a decrease of >30% from baseline.
^h Atrial fibrillation.
ⁱ Cardiac dysfunction.
^j Arrhythmia.

Pooled

Note: given the limited number of randomized studies and absence of convincing evidence for any complication, randomized and nonrandomized designs were poole without detriment to any strength of evidence rating. When odds ratios were pooled (to include adjusted results from nonrandomized designs), approximate risk differences were calculated based on the event rate across inhaled anesthetic arms and risk ratio derived from the odds ratio.

Myocardial Infarction

Figure 12. Odds ratio for myocardial infarction (randomized and nonrandomized studies).

Cardiac Arrest

Figure 13. Risk ratio for cardiac arrest (randomized and nonrandomized studies).

Bradycardia

Figure 14. Risk ratio for bradycardia (randomized and nonrandomized studies).

Insufficient data to estimate a valid prediction interval.

Hypotension

Figure 15. Risk ratio for hypotension (randomized and nonrandomized studies).

Stroke

Figure 16. Odds ratio for stroke (randomized and nonrandomized studies).

Acute Kidney Injury

Figure 17. Odds ratio for acute kidney injury complications (randomized and nonrandomized studies).

Pneumonia

Figure 18. Risk ratio for pneumonia (randomized clinical trials).

Pulmonary Embolism

Figure 19. Odds ratio for pulmonary embolism (randomized and nonrandomized studies).

Respiratory Failure

Figure 20. Odds ratio for respiratory failure (randomized and nonrandomized studies).

Patient Satisfaction

Table 14. Patient reported satisfaction.

Study	N	Anesth	Surgery	ASA	Age^a	N (%)	0 – 100%	RD (95% CI)
Study	N	Anesth	Surgery	PS	Age^a	N (%)	0 – 100%	RD (95% CI)
Epple 2001	62	Inhaled	Ophthalmologic	123	76.0 (6.0)	41 (66.1)^b		—
	62	TIVA			77.0 (6.0)	58 (93.5)^b		27.4% (14.1, 40.7)
Luntz 2004	64	Inhaled^c	Ophthalmologic	123	77.0 (7.0)	15 (46.9)^d		—
	32	TIVA			74.0 (7.0)	23 (71.9)^d		17.2% (-2.6, 37.0)
Nishikawa 2007a	15	Inhaled	GI/Abdominal	12	70.9 (6.5)	6 (40.0)^e		—
	15	TIVA			71.2 (5.3)	9 (60.0)^e		20.0% (-15.1, 55.1)
TIVA: total intravenous anesthesia; ASA PS: ASA Physical Status; RD: risk difference.
^a Mean (SD).
^b Completely satisfied.
^c Inhaled arms combined.
^d Highly satisfied.
^e Very satisfied.

Pooled

Figure 21. Risk ratio for patient satisfaction (randomized clinical trials).

Length of Stay

Table 15. Length of stay according to procedure classification and comparator.

Study	N	Anesth	PS^a	Age^b	LOS^b	Country
Randomized Clinical Trial - Cardiac
Kang 2023	48	Inhaled	34	64.5 (9.4)	13.8 (4.6)	South Korea
	47	TIVA	34	66.0 (7.3)	12.6 (3.3)
Randomized Clinical Trial - Thoracic
Zhang 2018a	190	Inhaled	123	72.4 (5.6)	8.0 {6-11}	China
	189	TIVA	123	72.8 (5.5)	9.0 {6-13}
Randomized Clinical Trial - Gastrointestinal/Abdominal
Forsmo 2016	153	Inhaled	123	66.0 [19-93]	8.0 [2-48]	Norway
	154	TIVA	123	65.0 [23-89]	5.0 [2-50]
Li 2021a	272	Inhaled	NR	65.0 {62-69}	14.0 {11-16}	China
	272	TIVA	NR	64.0 {62-68}	15.0 {12-17}
Randomized Clinical Trial - Various
Dai 2021	81	Inhaled	234	72.0 (7.0)	8.0 (9.9)	China
	83	TIVA	234	73.0 (8.0)	9.0 (10.8)
Cao 2023	597	Inhaled	123	71.0 [65-88]	10.0 {7-14}	China
	598	TIVA	123	72.0 [65-88]	10.0 {7-14}
Retrospective Cohort - Cardiac
Goins 2018	32	Inhaled	NR	78.3 (9.0)	5.9 (3.3)	USA
	84	TIVA	NR	79.6 (8.7)	3.8 (3.3)
Retrospective Cohort - Orthopedic
Kishimoto 2018	5,140	Inhaled	NR	74.4 (7.4)	31.4 (14.4)	Japan
	5,140	TIVA	NR	74.5 (7.2)	32.5 (18.4)
Huang 2023b	26	Inhaled	4	85.6 (7.8)	14.5 (17.8)	Taiwan
	20	TIVA	4	83.8 (9.1)	8.8 (3.8)
Retrospective Cohort - Various
Yoshimura 2022	427,695	Inhaled	NR	76.3	21.0 (21.0)	Japan
	142,565	TIVA	NR	76.6	21.0 (21.8)
NR: not reported
^a ASA Physical Status.
^b Mean Med (SD)[Range]{IQR}.

Pooled

Figure 22. Mean difference in length of stay (randomized clinical trials).

Meta-analysis methods detail.

- Inverse variance method
- Restricted maximum-likelihood estimator for τ²
- Q-Profile method for confidence interval of τ² and τ
- Hartung-Knapp adjustment for random effects model (df = 5)
- Prediction interval based on t-distribution (df = 4)

Figure 23. Mean difference in length of stay (nonrandomized designs).

Meta-analysis methods detail.

- Inverse variance method
- Restricted maximum-likelihood estimator for τ²
- Q-Profile method for confidence interval of τ² and τ
- Prediction interval based on t-distribution (df = 2)

Discharge Location

Table 16. Discharge location in nonrandomized study.

Study	N	Arm	Age^a	Country	Discharge to Institution		RR (95% CI)
Study	N	Arm	Age^a	Country	N (%)	0 — 100%	RR (95% CI)
Retrospective Cohort — Orthopedic
Huang 2023b	26	Inhaled	85.6 (7.8)	Taiwan	8 (30.8)
	20	TIVA	83.8 (9.1)		9 (45.0)		1.46 (0.69-3.11)
Gen: general; Neur: neuraxial; RR: risk ratio.
^a Mean Med (SD)[Range]{IQR}.

Mortality

Table 17. Reported in-hospital, 30-day, and 1-year mortality in randomized clinical trials.

Study	N	Arm	Surgery	ASA	Age^a	Mortality		RD (95% CI)
Study	N	Arm	Surgery	PS	Age^a	N (%)	0 - 100%	RD (95% CI)
Hospital
Dai 2021	81	Inhaled	Various	234	72.0 (7.0)	2 (2.5)		—
	83	TIVA			73.0 (8.0)	1 (1.2)		-1.3% (-5.4, 2.9)
30-day
Zangrillo 2011	44	Inhaled	Various	1234	65.0 (11.8)	0 (0)		—
	44	TIVA			64.0 (12.2)	1 (2.3)		2.3% (-3.8, 8.3)
Lindholm 2013	97	Inhaled	Vasc	234	69.0 (9.0)	4 (4.1)		—
	96	TIVA			67.0 (9.0)	4 (4.2)		0.0% (-5.6, 5.7)
Forsmo 2016	153	Inhaled	GI/Abd	123	66.0 [19-93]	0 (0)		—
	154	TIVA			65.0 [23-89]	3 (1.9)		1.9% (-0.6, 4.5)
Zhang 2018a	190	Inhaled	Thoracic	123	72.4 (5.6)	0 (0)		—
	189	TIVA			72.8 (5.5)	0 (0)		0.0% (-1.0, 1.0)
Dai 2021	81	Inhaled	Various	234	72.0 (7.0)	4 (4.9)		—
	83	TIVA			73.0 (8.0)	3 (3.6)		-1.3% (-7.5, 4.9)
1-year
Zangrillo 2011	44	Inhaled	Various	1234	65.0 (11.8)	1 (2.3)		—
	44	TIVA			64.0 (12.2)	2 (4.5)		2.3% (-5.3, 9.8)
ASA PS: American Society of Anesthesiologists Physical Status; Vasc: vascular; GI/Abd: gastrointestinal/abdominal; RD: risk difference; NR: not reported.
^a Mean Med (SD)[Range]{IQR}.

Table 18. Reported in-hospital and 30-day mortality in nonrandomized designs (all retrospective cohort studies).

Study	N	Arm	Surgery	ASA	Age^a	Mortality		RD OR (95% CI)^b
Study	N	Arm	Surgery	PS	Age^a	N (%)	0 - 100%	RD OR (95% CI)^b
Hospital
Jakobsen 2007	5,325	Inhaled	Cardiac	NR	64.9	116 (2.2)		—
	5,210	TIVA			64.7	172 (3.3)		1.1% (0.5, 1.7)
Park 2020	386	Inhaled	Various	1234	65.5 (14.8)	52 (13.5)		—
	100	TIVA			65.6 (14.9)	22 (22.0)		1.78 (1.08—2.92)
Yoshimura 2022	427,695	Inhaled	Various	NR	76.3	4,936 (1.2)		—
	142,565	TIVA			76.6	1,665 (1.2)		1.01 (0.96—1.07)
30-day
Jakobsen 2007	5,325	Inhaled	Cardiac	NR	64.9	151 (2.8)		0.7% (0.1, 1.3)
	5,210	TIVA			64.7	172 (3.3)		1.1% (0.5, 1.7)
Goins 2018	32	Inhaled	Cardiac	NR	78.3 (9.0)	2 (6.2)		—
	84	TIVA			79.6 (8.7)	0 (0)		-6.2% (-15.4, 2.9)
Park 2020	386	Inhaled	Various	1234	65.5 (14.8)	35 (9.1)		—
	100	TIVA			65.6 (14.9)	17 (17.0)		2.6 (1.14—5.93)
Cho 2021	1,202	Inhaled	Various	34	62.7 (13.7)	51 (4.2)		—
	1,374	TIVA			65.6 (12.8)	22 (1.6)		-2.6% (-4.0, -1.3)
Hasselager 2022	8,722	Inhaled	GI/Abd	1234	71.0 {63-78}	278 (3.2)		—
	8,722	TIVA			71.0 {64-77}	280 (3.2)		0.99 (0.84—1.18)
Huang 2023b	26	Inhaled	Ortho	4	85.6 (7.8)	1 (3.8)		—
	20	TIVA			83.8 (9.1)	1 (5.0)		1.2% (-10.9, 13.2)
1-year
Huang 2023b	26	Inhaled	Ortho	4	85.6 (7.8)	3 (11.5)		7.7% (-6.6, 22.0)
	20	TIVA			83.8 (9.1)	3 (15.0)		11.2% (-6.2, 28.5)
ASA PS: American Society of Anesthesiologists Physical Status; RD: risk difference; GI: gastrointestinal; Abd: abdominal (includes hepatic); Various: more that one procedure category.
^a Mean Med (SD)[Range]{IQR}.
^b Odds ratios for studies reporting adjusted results (e.g., propensity matched).

Pooled

Figure 24. Risk ratio for hospital or 30-day mortality (randomized clinical trials).

Figure 25. Risk ratio for hospital or 30-day mortality (nonrandomized designs).

Figure 26. Risk ratio for 1-year mortality (randomized and nonrandomized).

Risk of Bias

Randomized

Figure 27. Summary risk of bias assessment for randomized clinical trials.

Figure 28. Risk of bias assessments for randomized clinical trials.

Nonrandomized

Figure 29. Summary risk of bias assessment for nonrandomized studies.

Figure 30. Risk of bias assessments for nonrandomized studies.

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Key Question

Balance Tables

Outcomes Reported

Included Studies

Design, centers, country, and surgery

Country Summary

Comparators

Randomized

Nonrandomized

Delirium Incidence

Pooled

Randomized

Nonrandomized

Neurocognitive Disorder <30 days

Pooled

Neurocognitive Disorder 30 days to 1 year

Pooled

Physical Function

Complications

Pooled

Myocardial Infarction

Cardiac Arrest

Bradycardia

Hypotension

Stroke

Acute Kidney Injury

Pneumonia

Pulmonary Embolism

Respiratory Failure

Patient Satisfaction

Pooled

Length of Stay

Pooled

Discharge Location

Mortality

Pooled

Risk of Bias

Randomized

Nonrandomized

References

Neurocognitive Disorder
<30 days

Neurocognitive Disorder
30 days to 1 year