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Table 2 Comparison of delirium- and coma-free days and predefined secondary outcomes between the haloperidol and placebo group

From: Efficacy of haloperidol to decrease the burden of delirium in adult critically ill patients: the EuRIDICE randomized clinical trial

Outcome

Haloperidol (n = 65)

Placebo (n = 67)

Adjusted difference (95%CI)

Adjusted relative risk (95% CI)a

p value

Primary outcome: delirium- and coma-free days

No. of DCFDs, median (IQR)b

9 (3–12)

9 (2–11)

 

0.98 (0.73–1.31)

0.871

Predefined secondary outcomes: clinical outcomes

Daily RASS score, median (IQR)

− 0.5 (− 0.9 to − 0.1)

− 0.3 (− 0.6 to − 0.1)

− 9.9% (− 55.1% to 80.6%)c

 

0.777

Maximum mobility level, median (IQR)d

4 (1.5–5)

3 (1.8–5)

− 0.03 (− 0.8 to 0.74)

 

0.938

Sleep quality as assessed by nurse, mean (SD)d

4.2 (1.3)

4.4 (1.2)

− 0.26 (− 0.7 to 0.18)

 

0.251

Sleep quality according to patient (RCSQ), mean (SD)d

4.1 (1.4)

4.4 (1.5)

− 0.27 (− 0.92 to 0.38)

 

0.416

Mechanical ventilation, n (%)

50 (77)

51 (76)

 

OR: 1.17 (0.51–2.71)

0.707

No. of days, median (IQR)

2 (1–7.5)

2 (1–7)

 

1.17 (0.77–1.78)

0.465

Time to first resolution of delirium in days, median (IQR)

2 (1–3)

2 (1–4)

− 16.6% (− 35.5% to 7.7%)c

 

0.168

Median time to ICU discharge alive, days (95% CI)d,e

18.1 (9.8–26.4)

15.5 (12.3–18.7)

 

HR: 0.69 (0.47–1.02)

0.061

28-day mortality, n (%)d

10 (16)

13 (21)

 

0.79 (0.31–2.01)

0.622

Predefined secondary outcomes: medication-related outcomes

Daily study drug corrected for body weight (mg/kg), median (IQR)

0.08 (0.05–0.11)

0.10 (0.08–0.13)

− 0.01 (− 0.03 to 0.00)

 

0.101

Use of “escape medication”, n (%)

64 (99)

64 (96)

 

OR: 3.59 (0.43–75.62)

0.283

Open-label haloperidol, n (%)

4 (6)

9 (13)

 

OR: 0.43 (0.12–1.56)

0.201

Open-label haloperidol, mean 24 h dose in mg, mean (SD)c

3.6 (3.2)

2.6 (1.1)

1.32 (− 0.9 to 3.54)

 

0.295

Atypical antipsychotic, n (%)f

23 (35)

32 (48)

 

OR: 0.63 (0.29–1.32)

0.223

Clonidine, n (%)

26 (40)

34 (51)

 

OR: 0.61 (0.28–1.30)

0.198

Dexmedetomidine, n (%)

13 (20)

16 (24)

 

OR: 0.87 (0.31–2.46)

0.787

Benzodiazepine, n (%)

37 (57)

49 (73)

 

OR: 0.41 (0.18–0.89)

0.028

Propofol, n (%)

39 (60)

38 (57)

 

OR: 1.43 (0.67–3.07)

0.357

Opioid, n (%)

57 (88)

60 (90)

 

OR: 0.94 (0.31–2.88)

0.919

Other sedatives, n (%)

3 (5)

6 (9)

 

OR: 0.42 (0.08–1.79)

0.256

Predefined secondary outcomes: safety outcomes

Self-extubation or removal of invasive devices, ever, n (%)

6 (9.2)

10 (14.9%)

 

OR: 0.70 (0.22–2.18)

0.539

QTc prolongation, n (%)

3 (5)

6 (9)

 

OR: 0.62 (0.12–2.71)

0.535

Muscle rigidity and associated movement disorders, n (%)

3 (5)

1 (2)

 

OR: 4.52 (0.53–97.33)

0.211

Ventricular arrhythmia, n (%)

4 (6)

1 (2)

 

OR: 5.21 (0.71–105.98)

0.153

Systolic blood pressure change after first study drug dose, median (IQR)

− 5 (− 21 to 9.25)

2 (− 4.5 to 10)

− 12.41 (− 19.63 to 5.18)

 

0.001

Diastolic blood pressure change after first study drug dose, median (IQR)

− 3 (− 9 to 1)

2 (− 2 to 6.5)

− 7.96 (− 11.78 to − 4.20)

 

 < .001

  1. CI confidence interval, DCFD delirium- and coma-free day, IQR interquartile range, OR odds ratio, RR relative risk
  2. aRR unless mentioned otherwise. The placebo group was used as a reference. The RR may be interpreted as follows: the number of DCFDs in the haloperidol group is 0.98 times the number in the placebo group
  3. bThe mean number of DCFDs in the haloperidol group was 7.4 (SD 4.7) and in the placebo group 7.2 (SD 4.8). In order to increase comparability and to assess the impact of assumptions related to the definition of DCFD, post hoc analyses were performed (Additional file 1: Online Supplement 4)
  4. cAfter log transformation due to non-normality and/or heteroscedasticity, and needs to be interpreted as adjusted percent change for the haloperidol vs. placebo group. For example, compared to placebo, haloperidol decreases the median time to first resolution of delirium in days by 16.6 percent (adjusted percent change for haloperidol vs. placebo is − 16.6%, not significant) if all other variables are kept constant
  5. dData were missing for some patients: maximum mobility 1 (0.8%), mean sleep quality as assessed by nurse 5 (3.9%), mean sleep quality according to patient 50 (37.9%), systolic blood pressure change after first study drug administration 15 (11.4%), diastolic blood pressure change after first study drug administration 15 (11.4%), time to ICU discharge 3 (2.3%), 28-day mortality 10 (7.6%). No missing data were present for the other outcomes, study drug or covariates (mSOFA and hospital)
  6. eUnadjusted differences were estimated with the Kaplan–Meier method
  7. fOlanzapine or quetiapine
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Critical Care

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