. 2021 Feb 23;325(8):732–741. doi: 10.1001/jama.2021.0658

Table 2. Outcomes in a Study of the Effect of Baclofen on Agitation Events Among Patients With Alcohol Use Receiving Mechanical Ventilation.

Outcome	Baclofen (n = 159)	Placebo (n = 155)	Absolute difference (95% CI), %	Odds ratio (95% CI)^a	P value
Primary outcome
Patients with ≥1 agitation-related event over the treatment period, No. (%)^b	31/157 (19.7)	46 (29.7)	–9.93 (–19.45 to –0.42)	0.58 (0.34 to 0.98)^c	.04
Secondary outcomes by day 28^d
Patients with ≥1 agitation-related event, No. (%)	44/158 (27.8)	54 (34.8)	–6.99 (–17.24 to 3.30)	0.72 (0.45 to 1.17)^c	.19
Total agitation-related events	70	111		Rate ratio, 0.63 (0.46 to 0.85)^e	.003
No. of rapid hypnotic or neuroleptic injections for agitation, mean (SD)	3.2 (5.5)	2.9 (5.1)	0.22 (–1.27 to 0.84)^f		.69
Sedative dose in the ICU, median (IQR), mg/d
Propofol	1172.50 (510.0 to 2292.9)	1544.44 (918.3 to 2510.0)	–304.00 (–640.00 to 33.33)^j^,^g		.08
Ketamine	165.00 (106.6 to 200.0)	150.00 (107.1 to 200.0)	2.67 (–62.5 to 70.71)^j^,^g		.94
Midazolam	82.52 (36.7 to 156.8)	81.08 (36.5 to 168.3)	2.23 (–17.00 to 20.50)^j^,^g		.82
Levomepromazine	31.98 (19.8 to 53.4)	45.15 (39.7 to 51.8)	–10.98 (–38.00 to 18.88)^j^,^g		.52
Haloperidol	2.00 (1.5 to 7.0)	2.75 (1.1 to 5.5)	0.32 (–2.00 to 3.00)^j^,^g		.73
Clonidine	0.69 (0.3 to 1.5)	0.60 (0.3 to 0.8)	0.12 (–0.42 to 1.14)^j^,^g		.47
Dexmedetomidine	0.51 (0.2 to 0.7)	0.60 (0.3 to 1.6)	–0.12 (–1.09 to 0.43)^j^,^g		.53
Sevoflurane inhalation time, h	14.13 (11.5 to 16.8)	17.67 (17.0 to 21.0)	–4.58 (–9.92 to 0.75)^j^,^g		.22
Daily dose of analgesics in the ICU, median (IQR), mg/d
Sufentanil	0.20 (0.1 to 0.4)	0.23 (0.1 to 0.4)	–0.01 (–0.07 to 0.04)^j^,^g		.63
Fentanyl	1.54 (0.7 to 2.7)	2.55 (1.3 to 3.2)	–0.89 (–1.66 to –0.01)^j^,^g		.06
Morphine	16.67 (9.0 to 54.3)	19.25 (9.0 to 36.7)	1.50 (–4.17 to 9.08)^j^,^g		.63
Remifentanil	4.80 (3.0 to 5.9)	3.93 (2.7 to 18.0)	–0.93 (–13.20 to 3.99)^j^,^g		.92
Reintubation within 48 h of extubation, No. (%)	11/155 (7.1)	14/152 (9.0)	–2.11 (–8.24 to 4.00)	0.76 (0.33 to 1.75)^c	.52
Tracheotomy, No. (%)	7/158 (4.4)	6 (3.9)	0.55 (–3.86 to 4.98)	1.16 (0.38 to 3.55)^c	.80
ICU-acquired infection, No. (%)^h	36/156 (23.1)	32 (20.6)	2.43 (–6.75 to 11.61)	1.14 (0.66 to 1.96)^c	.63
Ventilator-free days, median (IQR)ⁱ	14.0 (0.0 to 20.0)	19.0 (0.0 to 24.0)	–2.00 (–4.00 to 0.00)^j		.01^k
Length of mechanical ventilation, median (IQR), d	9.0 (5.5 to 16.0)	8.0 (4.0 to 13.0)	2.00 (0.00 to 3.00)^j	HR, 0.76 (0.60 to 0.97)^l	.02
Length of ICU stay, median (IQR), d	14.0 (8.0 to 23.0)	11.0 (7.0 to 18.0)	2.00 (0.00 to 4.00)^j	HR, 0.70 (0.54 to 0.90)^l	.01
Length of hospital stay, median (IQR), d	22.0 (13.0 to 41.0)	20.0 (14.0 to 38.0)	0.00 (–4.00 to 3.00)^j	HR, 0.81 (0.62 to 1.07)^l	.14
Agitation-related event or mortality, No. (%)	66/154 (42.9)	71/155 (45.8)	–5.12 (–16.34 to 6.10)	0.82 (0.52 to 1.30)^c	.39
Death, No. (%)^m	39/154 (25.3)	32/148 (20.6)	3.70 (–5.84 to 13.25)	1.24 (0.72 to 2.13)^c	.44

Abbreviations: ICU, intensive care unit; IQR, interquartile range.

^{^a}

Unless otherwise noted. For all odds ratios and hazard ratios (HRs), the placebo group is used as the reference group.

^{^b}

Analysis included all randomized patients. Missing data (1 patient withdrew consent and 1 did not receive the treatment because the enteral route was unavailable) were handled by multiple imputation methods (eTable 2 in Supplement 2). Agitation-related events included pulling out lines, catheters, or drains; falling out of bed; leaving against the physician’s advice or without being seen; immobilization device removal; self-aggression; and aggression toward medical staff (eTable 5 in Supplement 2). An odds ratio less than 1 indicates that the risk of agitation was lower in the baclofen group than the placebo group. One patient was admitted to the ICU twice and included in the primary outcome analysis as 2 of the 155 placebo treatment periods.

^{^c}

Center-adjusted after logistic regression model (center as random effect).

^{^d}

For secondary outcomes, 95% CIs were not adjusted for multiplicity and therefore should not be used to infer definitive treatment effects. Other secondary outcomes are shown in eTable 4 in Supplement 2.

^{^e}

Center-adjusted after Poisson regression (center as random effect).

^{^f}

Center-adjusted mean difference after mixed linear regression analysis (center as random effect).

^{^g}

Groups were compared with a Wilcoxon test. This includes continuous and discontinuous infusion of sedatives or analgesics until day 28. The daily dose corresponds to the ratio of the total dose of each medication and the length of stay in the ICU in days. The repartition of sedatives and analgesics by day 28 is available in eTable 6 in Supplement 2.

^{^h}

Includes pneumonia, catheter infection, urinary infection, or bacteremia (eTable 4 in Supplement 2).

^ⁱ

Calculated as the number of days between day 1 and 28 the patient was alive and not intubated. For patients who died between day 1 and 28, the ventilator-free days was null.

^{^j}

Differences in medians were estimated with the Hodges-Lehmann method.

^{^k}

For ventilator-free days, groups were compared using a Wilcoxon test.

^{^l}

Center-adjusted HR after subdistribution hazard regression analysis (Fine-Gray regression) considering death as a competing event of extubation (for length of mechanical ventilation) or discharge from the ICU (for length of ICU stay) or from the hospital (for length of hospital stay). The proportionality of the hazard assumption was checked using the scaled Schoenfeld residuals. An HR less than 1 meant that at all times the probability of extubation, discharge from the ICU, or discharge from the hospital was lower in the baclofen group. Data are censored on day 60 for ICU stay and on day 90 for hospital stay. P values for these parameters correspond to the analysis of the HR.

^{^m}

See eTable 4 in Supplement 2 for death at other time points.