Effect of Remimazolam on Postoperative Delirium in Older Adult Patients Undergoing Orthopedic Surgery: A Prospective Randomized Controlled Clinical Trial

Figures & data

Figure 1 CONSORT 2010 flow diagram. Adapted from Schulz K F, Altman D G, Moher D. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials BMJ. 2010;340: c332. Open Access.⁴⁴

Table 1 Demographic and Baseline Variables

	R Group N=147	P Group N=153	P
Age, yr,	68 (65–71)	68 (65–71)	0.81
Male, n (%)	61 (41.5)	56 (36.6)	0.38
Weight, kg,	67 (58–74)	65 (60–72)	0.80
BMI (kg m^−2)	25.0 (3.3)	25.3 (3.6)	0.38
Level of education, n (%)			0.89
≤primary school	79 (53.7)	84 (54.9)
Junior high school	38 (25.9)	36 (23.5)
≥senior high school	30 (20.4)	33 (21.6)
MMSE	25 (21–27)	25 (21–27)	0.56
ASA classification, n (%)			0.34
I	4 (2.7)	8 (5.2)
II	112 (76.2)	120 (78.4)
III	31 (21.1)	25 (16.3)
Preoperative comorbidities, n (%)
Hypertension	68 (46.3)	66 (43.1)	0.59
Diabetes	20 (13.6)	25 (16.3)	0.51
Coronary artery disease	23 (15.6)	13 (8.5)	0.06
Cerebrovascular disease	27 (18.4)	22 (14.4)	0.35
Chronic pain	96 (65.3)	97 (63.4)	0.73
Preoperative opioid user within 1 month, n (%)	0(0.0)	1(0.6)	1.00
Preoperative BDZ user within 1 month, n (%)	3(2.0)	3(2.0)	1.00
Smoker, n (%)	25 (17.1)	22 (14.4)	0.52
Drinker, n (%)	20 (13.7)	25 (16.4)	0.51
aCCI	3 (2–3)	3 (2–3)	0.22

Notes: Data are expressed as mean (standard deviation), n (%), or median (interquartile range).

Abbreviations: R, Remimazolam; P, Propofol; BMI, Body Mass Index; MMSE, Mini-Mental State Examination; ASA, American Society of Anesthesiologists; BDZ, Benzodiazepines; aCCI, age-adjusted Charlson Comorbidity Index.

Table 2 Intra- and Postoperative Characteristics

	R Group N=147	P Group N=153	P
Type of surgery, n (%)			0.58
Spine	99 (67.3)	103 (67.3)
Knee	31 (21.1)	32 (20.9)
Hip	14 (9.5)	11 (7.2)
Others	3 (2.0)	7 (4.6)
Length of surgery (min)	138 (105–183)	130 (98–175)	0.20
Length of anesthesia (min)	177 (143–223)	165 (131–211)	0.11
R/P infusion usage (mg/kg/h)	0.36 (0.29–0.48)	3.40(2.60–4.13)
Total R/P usage (mg)	67.0(56.0–83.3)	435.0(360.0–580.0)
Vasoactive drugs dose (μg)^a	17 (8–40)	26 (15–50)	< 0.01
Total fluid infusion (mL)	1900 (1500–2400)	1800 (1500–2200)	0.78
Blood loss (mL)	200 (100–350)	150 (100–300)	0.14
Urine output (mL)	400 (250–700)	500 (300–750)	0.24
Perioperative blood transfusion, n (%)	22 (15.0)	24 (15.7)	0.86
NRS
Postoperative day 1	3 (2–4)	3 (2–3)	0.40
Postoperative day 2	2 (2–3)	2 (2–3)	0.34
Postoperative day 3	2 (2–3)	2 (2–3)	0.86
Length of stay(days)^b, days	10 (7–13)	9 (7–12)	0.20

Notes: Data are expressed as mean (standard deviation), n (%), or median (interquartile range). ^aNorepinephrine equivalent dose. ^bWas defined as the number of days admitted to the hospital following surgery.

Abbreviations: R, Remimazolam; P, Propofol; NRS, Numeric Rating Scale.

Table 3 Primary and Secondary Outcome

	R Group N=147	P Group N=153	RR, Difference (95% CI)	RD, Difference (95% CI)	P
Postoperative delirium incidence, n (%)	23 (15.6)	19 (12.4)	1.26 (0.72 to 2.21)	3.2% (−4.7% to 11.2%)	0.42
Onset time of delirium, d, median (IQR)^a	1 (1 to 2)	1 (1 to 1)	0 (0 to 0)	0 (0 to 0)	0.13
Duration of delirium, d, median (IQR)^a	2 (1 to 2)	2 (1 to 2)	0 (0 to 0)	0 (0 to 0)	0.77
Subtype of delirium, n (%)^a					0.56
Hyperactive	11 (47.8)	6 (31.6)	16.3% (−16.0% to 44.0%)	16.3% (−16.0% to 44.0%)
Hypoactive	8 (34.8)	9 (47.4)	−12.6% (−38.9% to 16.0%)	−12.6% (−38.9% to 16.0%)
Mixed	4 (17.4)	4 (21.1)	−3.7% (−28.3% to 19.7%)	−3.7% (−28.3% to 19.7%)
Emergence agitation, n (%)	16 (10.9)	10 (6.6)	1.35 (0.82 to 2.22)	4.4% (−2.2% to 11.1%)	0.19
Extubation time, min, median (IQR)	21 (15 to 28)	16 (12 to 22)	4 (2 to 6)	4 (2 to 6)	< 0.001
Length of PACU stay, min, median (IQR)	60 (50 to 75)	53 (44 to 67)	7 (4 to11)	7 (4 to 11)	< 0.001

Note: ^awas calculated only for patients who experienced delirium.

Abbreviations: R, Remimazolam; P, Propofol; RR, risk ratio; RD, risk difference; IQR, interquartile range; PACU, Post-anesthesia Care Unit.

Table 4 Perioperative Adverse Events. n (%)

	R Group N=147	P Group N=153	RR (95% CI)	RD (95% CI)	P
Intraoperative awareness	0 (0%)	0 (0%)	–	–	>0.99
Post-induction hypotension	25 (17.1)	65 (43.0)	0.58 (0.47 to 0.71)	−25.5% (−35% to −15.3%)	<0.001
PACU hypoxia	24 (16.4)	16 (10.7)	1.31 (0.88 to 1.95)	5.9% (−2.0% to 13.7%)	0.15
Postoperative nausea, vomiting	37 (27.2)	31 (21.1)	1.18 (0.89 to 1.58)	5.0% (−4.6% to14.3%)	0.23
Non-planned transfer to ICU	1 (0.8)	4 (3.5)	0.26 (0.03 to 2.27)	−1.9% (−5.9% to1.5%)	0.37

Abbreviations: R, Remimazolam; P, Propofol; RR, risk ratio; RD, Risk difference; PACU, Post-anesthesia Care Unit; ICU, Intensive Care Unit.

Schulz KF, Altman DG, Moher D. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c332. doi:10.1136/bmj.c332

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