Summary of findings for the main comparison. Haloperidol compared to placebo for preventing intensive care unit delirium.
| Haloperidol compared to placebo for preventing intensive care unit delirium | ||||||
| Patient or population: critically ill patients 18 years or older demanding mechanical ventilation within the first 72 hours (Page 2013) or anticipated needing ICU admission at least two days (Van Den Boogard 2018). Setting: in a general mixed medical‐surgical ICU in the UK and in 21 (non specified) ICUs in the Netherlands. Intervention: haloperidol 2.0/2.5 mg/ every 8 hours Comparison: placebo (0.9 % saline) every 8 hours | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with placebo | Risk with haloperidol | |||||
| The event rate of intensive care delirium within 28 days. | Study population | RR 1.01 (0.87 to 1.17) | 1439 (1 RCT) | ⊕⊕⊕⊝
Moderate ,2 |
Only measured in one study Downgraded one level due to imprecision (wide 95% CI) |
|
| 330 per 1000 | 333 per 1000 (287 to 386) | |||||
| In‐hospital mortality within 28 days. | Study population | RR 0.98 (0.80 to 1.22) | 1580 (2 RCTs) | ⊕⊕⊕⊝
Moderate 3 |
Downgraded one level due to imprecision (less than 300 events and wide 95% CI). | |
| 180 per 1000 | 177 per 1000 (144 to 218) | |||||
| Number of delirium ‐ and coma‐free days (within 28 days) measured by CAM‐ICU or ICDSC | The range of mean number of delirium ‐ and coma‐free days was 15 to 24 days. | MD 0.60 lower (1.37 lower to 0.17 higher) | ‐ | 1580 (2 RCTs) | ⊕⊕⊕⊝
Moderate 2 |
Downgraded one level for indirectness (primary outcome was survival and not delirium) |
| Ventilator‐free days (within the first 28 days) | The mean ventilator‐free days (within the first 28 days) was 23.8 | MD 0.30 lower (0.93 lower to 0.33) | 1439 (1 RCT) | ⊕⊕⊕⊕ High | ||
| Length of ICU stay (days) | The range of mean length of ICU stay was 5 to 11 days. | MD 0.25 higher (0.28 lower to 0.77 higher) | ‐ | 1580 (2 RCTs) | ⊕⊕⊕⊕ High | |
| Cognitive impairment | not estimable | (studies) | ‐ | Not measured in any study | ||
| Adverse events | Serious adverse events were reported 3 incidents in the intervention group (fast atrial fibrillation with hypotension (n = 1), readmission to ICU with sepsis (n = 1), failed extubation (n = 1)) and 5 in placebo group (apnoea post treatment for agitation (n = 1), readmission to ICU with sepsis (n = 1), failed extubation (n = 3) in Page 2013. Five serious adverse events were reported, three patients died, one in each group. The events were judged to be unrelated to the study medication. Two patients in the 1 mg haloperidol group and 1 patient in the 2 mg haloperidol group developed momorphic ventricular tachycardia, 1 patient in the 2 mg haloperidol group developed refractory shock, 1 patient in the placebo group developed a suspected malignant neuroleptic syndrome event (Van Den Boogard 2018) |
‐ | 1580 (2 RCTs) | ⊕⊕⊕⊝ Moderate4 | Downgraded one level due imprecision (few events) | |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CAM‐ICU: confusion assessment method for the ICU; CI: Confidence interval; ICDSC: Intensive Care Delirium Screening Checklist; MD: mean difference; RR: Risk ratio | ||||||
| GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect | ||||||
1
2 Downgraded due to indirectness: Indirect outcome as the primary outcome of Van den Boogaard study was 28 days survival, not delirium. This focus might have played a part in the missing collection of data on delirium outcomes.
3. Downgraded due to impression (less than 300 events)
4 Downgrade one level due to few events