1. Effect estimates for orphan studies.
| Comparison | Outcome | n | Statistical method | Effect estimate CI 95%) | P value | Study |
| Dexmedetomidine vs. lorazepam | The event rate of ICU delirium | 103 | Risk ratio | 0.96 (0.76 to 1.16) | 0.65 | Pandharipande 2007 |
| Dexmedetomidine vs. lorazepam | In‐hospital mortality | 103 | Risk ratio | 1.59 (0.75 to 3.33) | 0.22 | Pandharipande 2007 |
| Dexmedetomidine vs. lorazepam | Number of delirium‐ and coma‐free days (within 12 days) | 103 | Mean difference | 2.67 (0.58 to 4.76) | 0.01 | Pandharipande 2007 |
| Dexmedetomidine vs. lorazepam | Length of stay in the ICU | 103 | Mean difference | ‐0.50 (‐3.89 to 2.89) | 0.77 | Pandharipande 2007 |
| Haloperidol vs. placebo | Ventilator‐free days | 1439 | Mean difference | ‐0.30 (‐0.93 to 0.33) | 0.35 | Van Den Boogard 2018 ‐ unpublished data |
| Dexmedetomidine vs. haloperidol | The event rate of ICU delirium | 60 | Risk ratio | 0.3 (0.09 to 0.98) | 0.047 | Abdelgalel 2016 |
| Dexmedetomidine vs. haloperidol | In‐hospital mortality | 60 | Risk ratio | 1.00 (0.15 to 6.64) | 1.0 | Abdelgalel 2016 |
| Dexmedetomidine vs. haloperidol | Length of stay in the ICU | 60 | Mean difference | ‐3.40 (‐3.79 to ‐3.01) | < 0.00001 | Abdelgalel 2016 |
| Dexmedetomidine vs. haloperidol | Adverse events | 60 | Risk ratio | 0.40 (0,08 to 1.90) | 0.25 | Abdelgalel 2016 |
| Dexmedetomidine vs. placebo (saline) | The event rate of ICU delirium | 60 | Risk ratio | 0.23 (0.07 to 0.73) | 0.01 | Abdelgalel 2016 |
| Dexmedetomidine vs. placebo (saline) | In‐hospital mortality | 60 | Risk ratio | 0.67 (0.12 to 3.71) | 0.64 | Abdelgalel 2016 |
| Dexmedetomidine vs. placebo (saline) | Length of stay in the ICU | 60 | Mean difference | ‐3.80 (‐4.25 to ‐3.35) | < 0.00001 | Abdelgalel 2016 |
| Dexmedetomidine vs. placebo (saline) | Adverse events | 60 | Risk ratio | 1.00 (0.15 to 6.64) | 1.0 | Abdelgalel 2016 |
| Early goal directed sedation vs. standard sedation | The event rate of ICU delirium | 37 | Risk ratio | 1.02 (0.44 to 2.34) | 0.97 | Shehabi 2013 |
| Early goal directed sedation vs. standard sedation | In‐hospital mortality | 37 | Risk ratio | 1.14 (0.22 to 6.05) | 0.88 | Shehabi 2013 |
| Early goal directed sedation vs. standard sedation | Ventilator‐free days | 37 | Mean difference | 1.20 (‐5.12 to 7.52) | 0.71 | Shehabi 2013 |
| Early goal directed sedation vs. standard sedation | Length of stay in the ICU | 37 | Mean difference | 0.30 (‐2.97 to 3.57) | 0.86 | Shehabi 2013 |
| Early goal directed sedation vs. standard sedation | Adverse events | 37 | Risk ratio | 3.86 (0.20 to 75.28) | 0.37 | Shehabi 2013 |
| No sedation vs. sedation with daily interruption | The event rate of ICU delirium | 113 | Risk ratio | 2.90 (0.98 to 8.57) | 0.05 | Strøm 2010 |
| No sedation vs. sedation with daily interruption | In‐hospital mortality | 113 | Risk ratio | 0.78 (0.50 to 1.22) | 0.28 | Strøm 2010 |
| No sedation vs. sedation with daily interruption | Ventilator‐free days | 113 | Mean difference | 4.20 (0.32 to 8.08) | 0.034 | Strøm 2010 |
| No sedation vs. sedation with daily interruption | Length of stay in the ICU | 113 | Mean difference | ‐5.20 (‐8.48 to ‐1.92) | 0.002 | Strøm 2010 |
| No sedation vs. sedation with daily interruption | Adverse events | 113 | Risk ratio | 1.23 (0.44 to 3.43) | 0.69 | Strøm 2010 |
| Sedation with daily interruption vs. sedation | Number of delirium‐ and coma‐free days | 60 | Mean difference | 1.00 (‐0.94 to 2.94) | 0.31 | Nassar 2014 |
| ICU‐delirium prevention protocol vs. non preventive nursing care | The event rate of ICU delirium | 123 | Risk ratio | 0.60 (0.32 to 1.11) | 0.10 | Moon 2015 |
| ICU‐delirium prevention protocol vs. non preventive nursing care | In‐hospital mortality | 123 | Risk ratio | 0.38 (0.13 to 1.13) | 0.08 | Moon 2015 |
| ICU‐delirium prevention protocol vs. non preventive nursing care | Length of stay in the ICU | 123 | Mean difference | 0.80 (‐3.01 to 4.61) | 0.68 | Moon 2015 |
| Physical and cognitive therapy vs. standard care | In‐hospital mortality | 65 | Risk ratio | 0.94 (0.40 to 2.20) | 0.88 | Brummel 2014b |
| Physical and cognitive therapy vs. standard care | Number of delirium‐ and coma‐free days (within 30 days) | 65 | Mean difference | ‐2.77 (‐10.09 to 4.55) | 0.46 | Brummel 2014b |
| Physical and cognitive therapy vs. standard care | Length of stay in the ICU | 65 | Mean difference | 1.23 (‐0.68 to 3.14) | 0.21 | Brummel 2014b |
| Physical and cognitive therapy vs. standard care | Cognitive impairment (MMSE score) | 30 | Mean difference | 0.97 (‐0.19 to 2.13) | 0.10 | Brummel 2014b |
| Physical and cognitive therapy vs. standard care | Cognitive impairment (DEX score) | 30 | Mean difference | ‐8.76 (‐19.06 to 1.54) | 0.1 | Brummel 2014b |
| Enviromental intervention vs standard care | In‐hospital mortality | 734 | Risk ratio | 0.93 (0.96 to 1.26) | 0.66 | Simons 2016 |
| Enviromental intervention vs standard care | Number of delirium‐ and coma‐free days (within 28 days) | 734 | Mean difference | 0.06 (‐1.18 to 1.30) | 0.92 | Simons 2016 |
| Enviromental intervention vs standard care | Length of stay in the ICU | 734 | Mean difference | ‐0.33 (‐1.03 to 0.37) | 0.36 | Simons 2016 |
CI: confidence interval; DEX: Dysexecutive questionnaire; ICU: intensive care unit; MMSE: Mini‐Mental State Examination,