Balance Tables

Expanded Preoperative Evaluation

Table 1. Benefits, harms, and strength of evidence (GRADE) for expanded versus standard preoperative evaluation.

			Preoperative Evaluation
Outcome	RCT	NRSI	Expanded	Standard	GRADE*	Effect	Estimate (95% CI)
			N (Total)	N (Total)
Delirium incidence	6		189 (662)	253 (703)	⨁⨁◯◯	RR	0.77 (0.60–0.99)
Neurocognitive disorder <30 days		1	13 (96)	16 (84)	⨁◯◯◯	RR	0.71 (0.36-1.39)
Neurocognitive disorder 30 days to 1 yr	none	none
Physical function	5		(563)	(576)	⨁◯◯◯	SMD	0.09 (-0.16 to 0.31)
Complications†	4	9			⨁◯◯◯		See Table 2
Patient satisfaction		1	32 (32)	29 (30)	⨁◯◯◯	RD/100	3.3 (-5.3 to 12.0)‡
Length of stay (days)	8		(968)	(1,001)	⨁◯◯◯	MD	0.0 (-1.7 to 1.7)
Discharge to institution	4		252 (419)	271 (424)	⨁⨁◯◯	RR	0.98 (0.76-1.27)
Mortality (in-hospital or 30-day)	4		19 (498)	19 (526)	⨁◯◯◯	RR	1.02 (0.30–3.53)
Mortality (1-year)	2		42 (215)	57 (226)	⨁◯◯◯	RR	0.78 (0.54–1.10)
RCT: randomized clinical trial; NRSI: nonrandomized studies of interventions (non-randomized trial, before-after and cohort studies); GRADE: Grades of Recommendation, Assessment, Development, and Evaluation; RR: risk ratio; SMD: standardized mean difference; RD: risk difference; MD: mean difference.
* Very low: ⨁◯◯◯; Low: ⨁⨁◯◯; Moderate: ⨁⨁⨁◯; High: ⨁⨁⨁⨁.
† Cardiovascular, pulmonary, and renal.
‡ High versus lower satisfaction.

Table 2. Included complications and strength of evidence (GRADE) for expanded versus standard preoperative evaluation.

			Preoperative Evaluation
Outcome	RCT	NRSI	Expanded	Standard	GRADE*	Effect	Estimate (95% CI)
			N (Total)	N (Total)
Myocardial infarction	1	4	9 (811)	12 (714)	⨁◯◯◯	RR	0.58 (0.22–1.53)
						RD/1000	-2.7 (-17.7 to 12.3)
Cardiac arrest	1	1	2 (268)	7 (234)	⨁◯◯◯	RR	0.28 (0.06–1.37)
						RD/1000	17.5 (-47.2 to 12.3)
Acute kidney injury	2	4	85 (808)	104 (805)	⨁◯◯◯	RR	0.83 (0.60–1.16)
						RD/1000	3.4 (-26.8 to 33.7)
Pneumonia	2	7	78 (1,261)	94 (1,198)	⨁◯◯◯	RR	0.82 (0.51–1.32)
						RD/1000	-2.8 (-20.4 to 14.8)
Respiratory failure		1	16 (183)	21 (143)	⨁◯◯◯	RD/1000	-5.9% (-13.0 to 1.2)
Pulmonary embolism		4	6 (468)	5 (354)	⨁◯◯◯	RR	0.90 (0.26–3.08)
						RD/1000	1.2 (-14.6 to 16.9)
RCT: randomized clinical trial; GRADE: Grades of Recommendation, Assessment, Development, and Evaluation; RR: risk ratio; RD: risk difference.
* Very low: ⨁◯◯◯; Low: ⨁⨁◯◯; Moderate: ⨁⨁⨁◯; High: ⨁⨁⨁⨁.

Neuraxial versus General Anesthesia

Table 3. Benefits, harms, and strength of evidence (GRADE) for regional versus general anesthesia.

Outcome	RCT	Neuraxial	General	GRADE*	Effect	Estimate (95% CI)
		N (Total)	N (Total)
Delirium	10	215 (1,840)	213 (1,908)	⨁⨁⨁◯	RR	1.06 (0.84–1.33)†,‡
Neurocognitive disorder <30 days	4	78 (336)	88 (355)	⨁⨁◯◯	RR	0.91 (0.56–1.48)
Neurocognitive disorder 30 days to 1 yr	1	23 (176)	25 (188)	⨁◯◯◯	RR	0.98 (0.58–1.67)
Physical function	3	(355)	(371)	⨁◯◯◯	SMD	0.01 (-0.39 to 0.42)§
Complications**	13			⨁⨁◯◯ ⨁◯◯◯		See Table 4
Patient satisfaction	10	913 (1,055)	839 (991)	⨁⨁◯◯	RR	1.02 (0.98–1.05)††
Length of stay (days)	13	(2,355)	(2,373)	⨁⨁◯◯	MD	-0.4 (-1.1 to 0.3)
Discharged to institution	1	576 (777)	586 (777)	⨁◯◯◯	RR	0.98 (0.93-1.04)
Mortality (in-hospital and 30-day)
All procedures	6	19 (1,789)	32 (1,859)	⨁⨁◯◯	RR	0.66 (0.28–1.50)
Hip fracture	4	19 (1,467)	28 (1,536)	—	RR	0.75 (0.34–1.64)
Other	2	19 (322)	31 (323)	—	RR	0.20 (0.02–1.71)‡‡
Mortality (90-day)	3	15 (427)	16 (499)	⨁◯◯◯	RR	1.12 (0.57–2.20)
RCT: randomized clinical trial; GRADE: Grades of Recommendation, Assessment, Development, and Evaluation; RR: risk ratio; SMD: standardized mean difference; MD: mean difference.
* Very low: ⨁◯◯◯; Low: ⨁⨁◯◯; Moderate: ⨁⨁⨁◯; High: ⨁⨁⨁⨁.
† Hip fracture trials (n = 6) RR 1.08 (95% CI, 0.87–1.35); other procedures (n = 4) RR 0.74 (95% CI, 0.35–1.57).
‡ RD per 100 for all surgeries 0.1 (-1.8 to 2.2); in hip fracture trials 1.3 (-1.3 to 3.9); others -2.2 (-9.2 to 4.8).
§ Using Neuman 2021 primary result of inability to walk 60 feet without human assistance in a sensitivity analysis including 1644 patients yield a pooled SMD -0.07 (95% CI, -0.25 to 0.12).
** Complications reported variously across the 13 trials.
†† Comparing higher/highest category or categories with lower ones.
‡‡ Common effects model (2 trials).

Table 4. Included complications and strength of evidence (GRADE) for regional versus general anesthesia.

Outcome	RCT	Neuraxial	General	GRADE*	Effect†	Estimate (95% CI)
		N (Total)	N (Total)
Myocardial infarction	5	12 (1,655)	12 (1,600)	⨁⨁◯◯	RR	0.86 (0.44–1.66)
					RD/1000	0.7 (-3.4 to 4.9)
Cardiac arrest	1	2 (783)	0 (793)	⨁◯◯◯	RD/1000	2.6 (-2.2 to 6.7)
Bradycardia	3	6 (67)	4 (67)	⨁◯◯◯	RR	1.33 (0.14–13.0)
	4	6 (107)	4 (107)		RD/1000	10.4 (-39.7 to 60.6)
Stroke	3	7 (1,365)	8 (1,370)	⨁◯◯◯	RR	0.83 (0.30–2.28)
					RD/1000	-1.6 (-6.8 to 3.5)
Acute Kidney Injury	4	33 (1,118)	58 (1,129)	⨁⨁◯◯	RR	0.59 (0.39–0.89)
					RD/1000	-21.7 (-38.1 to -5.3)
Pulmonary complications‡	1	5 (58)	9 (118)	⨁◯◯◯	RR	0.90 (0.29–2.81)
					RD/1000	-7.4 (-88.2 to 73.6)
Pneumonia	7	14 (1,714)	26 (1,659)	⨁⨁◯◯	RR	0.53 (0.31–0.92)
					RD/1000	-7.4 (-15.0 to 0.1)
Pulmonary congestion	1	9 (783)	8 (793)	⨁◯◯◯	RR	1.14 (0.44–2.94)
					RD/1000	1.4 (-8.8 to 11.6)
Pulmonary embolism	6	7 (1,455)	13 (1,406)	⨁◯◯◯	RR	0.56 (0.27–1.16)
					RD/1000	-4.9 (-11.4 to 1.7)
Reintubation	1	4 (783)	7 (793)	⨁◯◯◯	RR	0.37 (0.17–1.97)
					RD/1000	-3.7 (-11.9 to 4.5)
RCT: randomized clinical trial; GRADE: Grades of Recommendation, Assessment, Development, and Evaluation; AKI: acute kidney injury; RR: risk ratio; RD/1000: risk difference per 1000.
* Very low: ⨁◯◯◯; Low: ⨁⨁◯◯; Moderate: ⨁⨁⨁◯; High: ⨁⨁⨁⨁.
† Fixed/common effects models when 2 studies.
‡ Complications reported included pneumonia, respiratory failure, or unspecified.

TIVA versus Inhalation Anesthesia

Table 5. Benefits, harms, and strength of evidence (GRADE) for TIVA versus inhaled anesthesia.

Outcome	RCT	NRSI*	TIVA	Inhaled	GRADE†	Effect	Estimate (95% CI)
			N (Total)	N (Total)
Delirium	8		143 (1,001)	158 (995)	⨁⨁◯◯	RR	0.94 (0.62–1.43)
Neurocognitive disorder <30 days	5		125 (704)	175 (703)	⨁⨁⨁◯	RR	0.72 (0.54–0.96)
Neurocognitive disorder days to 1 yr	1		4 (96)	6 (97)	⨁◯◯◯	RR	0.67 (0.20–2.31)
Physical function	none	none
Complications	10	9			⨁⨁◯◯ ⨁◯◯◯		See Table 6
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)
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)
Mortality (1-year)	1	1	5 (64)	4 (70)	⨁◯◯◯	RR	1.47 (0.42–5.18)
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.

Table 6. Included complications and strength of evidence (GRADE) for TIVA versus inhaled anesthesia.

Outcome	RCT	NRSI	TIVA	Inhaled	GRADE*	Effect	Estimate (95% CI)
			N (Total)	N (Total)
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.

Delirium Prophylaxis

Table 7. Benefits, harms, and strength of evidence (GRADE) for dexmedetomidine versus placebo or no delirium prophylaxis.

Outcome	RCT	NRSI	Dexmedetomidine	Placebo*	GRADE†	Effect	Estimate      (95% CI)	I 2	(95% PI)
			N (Total)	N (Total)
Delirium	31		457 (4,035)	666 (3,739)	⨁⨁⨁◯	RR	0.58 (0.49–0.67)	46%	(0.30–1.10)
Neurocognitive disorder <30 days	9		68 (666)	83 (392)	⨁⨁⨁◯	RR	0.54 (0.39–0.73)	0%	(0.39–0.74)
Neurocognitive disorder 30 days to 1 yr	2		5 (50)	22 (50)	⨁◯◯◯	RR	0.24 (0.11–0.55)	0%	‡
Physical function	1		(30)	(31)	⨁◯◯◯	SMD	0.39 (-1.57 to 2.34)		‡
Bradycardia	17		236 (2,031)	129 (1,755)	⨁⨁⨁⨁	RR	1.52 (1.22–1.88)	0%	(0.97–2.37)
	18		236 (2,121)	129 (1,842)		RD/100	2.0 (-0.4 to 4.4)	57%	(-2.2 to 6.2)
Hypotension	20		611 (2,797)	409 (2,539)	⨁⨁⨁⨁	RR	1.38 (1.10–1.72)	52%	(0.65–2.91)
	22		611 (2,916)	409 (2,662)		RD/100	4.3 (0.5 to 8.0)	77%	(-10.5 to 19.0)
Other complications	27	3					see Table 8
Length of stay (days)	20		(3,051)	(3,075)	⨁⨁◯◯	MD	-0.8 (-1.3 to -0.2)§	95%	(-3.3 to 1.7)
Mortality, in-hospital and 30-day	11		17 (2,123)	31 (2,141)	⨁⨁◯◯	RR	0.64 (0.35–1.16)	0%	(0.31–1.32)
	12		17 (2,479)	31 (2,495)		RD/1000	-0.8 (-4.7 to 3.1)	17%	(-4.7 to 3.2)
RCT: randomized clinical trial; NRSI: nonrandomized studies of interventions; GRADE: Grades of Recommendation, Assessment, Development, and Evaluation; PI: prediction interval; RR: risk ratio; SMD: standardized mean difference; RD: risk difference; MD: mean difference.
* In some studies (randomized or not) the control incorporated neither placebo or prophylaxis.
† Very low: ⨁◯◯◯; Low: ⨁⨁◯◯; Moderate: ⨁⨁⨁◯; High: ⨁⨁⨁⨁.
‡ Insufficient data to estimate a valid prediction interval.
§ With Hartung-Knapp adjustment MD -0.8 (-1.5 to -0.08).

Table 8. Other complications and strength of evidence (GRADE) for dexmedetomidine versus placebo or no delirium prophylaxis.

Outcome	RCT	NRSI	Dexmedetomidine	Placebo*	GRADE†	Effect	Estimate (95% CI)	I 2	(95% PI)
			N (Total)	N (Total)
Myocardial infarction	2	1	7 (763)	8 (830)	⨁⨁◯◯	RR	0.98 (0.36–2.67)	0%	‡
	3	1	7 (1,107)	8 (1,161)		RD/1000	0.3 (-4.6 to 5.2)	0%	(-10.5 to 11.0)
Cardiac arrest	1		2 (222)	1 (283)	⨁◯◯◯	RR	0.85 (0.14–5.04)		‡
	1		2 (222)	1 (283)		RD/1000	-1.6 (-18.8 to 15.6)		‡
Stroke	5	1	12 (1,139)	16 (1,231)	⨁⨁◯◯	RR	0.84 (0.40–1.77)	0%	(0.30–2.41)
	6	1	12 (1,483)	16 (1,562)		RD/1000	-1.4 (-6.0 to 3.2)	0%	(-7.4 to 4.7)
Acute kidney injury	5	1	101 (1,034)	107 (1,092)	⨁⨁◯◯	RR	1.05 (0.69–1.59)	31%	(0.35–2.56)
	5	1	101 (1,034)	107 (1,092)		RD/1000	3.1 (-12.3 to 18.6)	38%	(-18.8 to 25.0)
Pneumonia	3		14 (315)	13 (329)	⨁◯◯◯	RR	1.09 ( 0.52–2.30)	0%	‡
	3		14 (315)	13 (329)		RD/1000	8.4 (-14.5 to 31.2)	0%	‡
Pulmonary congestion	1		1 (147)	0 (157)	⨁◯◯◯	RR	3.20 (0.13–78.02)
	1		1 (147)	0 (157)		RD/1000	6.8 (-11.6 to 25.2)
Pulmonary embolism	1		1 (147)	1 (157)	⨁◯◯◯	RR	1.07 (0.07–16.92)
	1		1 (147)	1 (157)		RD/1000	0.4 (-17.8 to 18.6)
Respiratory Depression/Failure	3		5 (230)	9 (242)	⨁◯◯◯	RR	0.65 (0.22–1.94)	0%	‡
	5		5 (621)	9 (416)		RD/1000	0.2 (-10.6 to 11.0)	0%	(-17.3 to 17.7)
RCT: randomized clinical trial; GRADE: Grades of Recommendation, Assessment, Development, and Evaluation; RR: risk ratio; RD: risk difference.
* In some studies (randomized or not) the control incorporated neither placebo or prophylaxis.
† Very low: ⨁◯◯◯; Low: ⨁⨁◯◯; Moderate: ⨁⨁⨁◯; High: ⨁⨁⨁⨁.
‡ Insufficient data to estimate a valid prediction interval.