Interventions for preventing delirium in hospitalised non‐ICU patients

Najma Siddiqi; Jennifer K Harrison; Andrew Clegg; Elizabeth A Teale; John Young; James Taylor; Samantha A Simpkins

doi:10.1002/14651858.CD005563.pub3

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Figure 1

Study flow diagram

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Figure 2

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

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Figure 3

Forest plot of comparison: 1 Multi‐component delirium prevention intervention (MCI) versus usual care, outcome: 1.1 Incident delirium.

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Figure 4

Forest plot of comparison: 2 Prophylactic cholinesterase inhibitor versus placebo, outcome: 2.1 Incident delirium.

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Figure 5

Figure 5Forest plot of comparison: 3 Prophylactic antipsychotic versus control, outcome: 3.1 Incidence of delirium.

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Figure 6

Forest plot of comparison: 4 Prophylactic melatonin versus placebo, outcome: 4.1 Incident delirium.

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Figure 7

Forest plot of comparison: 11 Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia, outcome: 11.1 Incident delirium.

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Analysis 1.1

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 1 Incident delirium.

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Analysis 1.2

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 2 Incidence of delirium in patients with dementia.

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Analysis 1.3

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 3 Duration of delirium.

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Analysis 1.4

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 4 Severity of delirium.

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Analysis 1.5

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 5 Length of admission.

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Analysis 1.6

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 6 Cognition.

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Analysis 1.7

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 7 Improvement in Activities of Daily Living.

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Analysis 1.8

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 8 Return to independent living.

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Analysis 1.9

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 9 Depression.

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Analysis 1.10

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 10 Withdrawal from protocol.

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Analysis 1.11

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 11 Falls.

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Analysis 1.12

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 12 Pressure ulcers.

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Analysis 1.13

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 13 Inpatient mortality.

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Analysis 1.14

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 14 12 month mortality.

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Analysis 1.15

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 15 Cardiovascular complication.

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Analysis 1.16

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 16 Urinary tract infection.

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Analysis 1.17

Comparison 1 Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 17 Mental health worsened.

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Analysis 2.1

Comparison 2 Prophylactic cholinesterase inhibitor versus placebo, Outcome 1 Incident delirium.

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Analysis 2.2

Comparison 2 Prophylactic cholinesterase inhibitor versus placebo, Outcome 2 Duration of delirium.

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Analysis 2.3

Comparison 2 Prophylactic cholinesterase inhibitor versus placebo, Outcome 3 Severity of delirium.

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Analysis 2.4

Comparison 2 Prophylactic cholinesterase inhibitor versus placebo, Outcome 4 Length of admission.

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Analysis 2.5

Comparison 2 Prophylactic cholinesterase inhibitor versus placebo, Outcome 5 Cognition.

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Analysis 2.6

Comparison 2 Prophylactic cholinesterase inhibitor versus placebo, Outcome 6 Withdrawal from protocol.

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Analysis 2.7

Comparison 2 Prophylactic cholinesterase inhibitor versus placebo, Outcome 7 Adverse events (continuous).

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Analysis 2.8

Comparison 2 Prophylactic cholinesterase inhibitor versus placebo, Outcome 8 Adverse events (binary).

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Analysis 3.1

Comparison 3 Prophylactic antipsychotic versus control, Outcome 1 Incident delirium.

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Analysis 3.2

Comparison 3 Prophylactic antipsychotic versus control, Outcome 2 Duration of delirium.

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Analysis 3.3

Comparison 3 Prophylactic antipsychotic versus control, Outcome 3 Severity of delirium.

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Analysis 3.4

Comparison 3 Prophylactic antipsychotic versus control, Outcome 4 Length of admission.

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Analysis 3.5

Comparison 3 Prophylactic antipsychotic versus control, Outcome 5 Cognition.

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Analysis 3.6

Comparison 3 Prophylactic antipsychotic versus control, Outcome 6 Withdrawal from protocol.

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Analysis 3.7

Comparison 3 Prophylactic antipsychotic versus control, Outcome 7 Adverse events.

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Analysis 3.8

Comparison 3 Prophylactic antipsychotic versus control, Outcome 8 Pneumonia.

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Analysis 3.9

Comparison 3 Prophylactic antipsychotic versus control, Outcome 9 Urinary tract infection.

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Analysis 3.10

Comparison 3 Prophylactic antipsychotic versus control, Outcome 10 Congestive heart failure.

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Analysis 4.1

Comparison 4 Prophylactic melatonin versus placebo, Outcome 1 Incident delirium.

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Analysis 4.2

Comparison 4 Prophylactic melatonin versus placebo, Outcome 2 Duration of delirium.

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Analysis 4.3

Comparison 4 Prophylactic melatonin versus placebo, Outcome 3 Severity of delirium (binary severe vs. not severe).

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Analysis 4.4

Comparison 4 Prophylactic melatonin versus placebo, Outcome 4 Severity of delirium (DRS‐R‐98).

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Analysis 4.5

Comparison 4 Prophylactic melatonin versus placebo, Outcome 5 Length of admission.

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Analysis 4.6

Comparison 4 Prophylactic melatonin versus placebo, Outcome 6 Cognitive impairment.

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Analysis 4.7

Comparison 4 Prophylactic melatonin versus placebo, Outcome 7 Activities of daily living.

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Analysis 4.8

Comparison 4 Prophylactic melatonin versus placebo, Outcome 8 Use of psychotropic medication (binary).

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Analysis 4.9

Comparison 4 Prophylactic melatonin versus placebo, Outcome 9 Antipsychotic medication use (cumulative).

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Analysis 4.10

Comparison 4 Prophylactic melatonin versus placebo, Outcome 10 Benzodiazepine use (cumulative).

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Analysis 4.11

Comparison 4 Prophylactic melatonin versus placebo, Outcome 11 Withdrawal from study.

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Analysis 4.12

Comparison 4 Prophylactic melatonin versus placebo, Outcome 12 In‐hospital mortality.

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Analysis 4.13

Comparison 4 Prophylactic melatonin versus placebo, Outcome 13 Mortality by 3 months.

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Analysis 4.14

Comparison 4 Prophylactic melatonin versus placebo, Outcome 14 Adverse events.

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Analysis 5.1

Comparison 5 Prophylactic citicoline versus placebo, Outcome 1 Incident delirium.

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Analysis 5.2

Comparison 5 Prophylactic citicoline versus placebo, Outcome 2 Cognitive status.

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Analysis 6.1

Comparison 6 Oral premedication with diazepam and diphenhydramine, Outcome 1 Incident delirium.

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Analysis 7.1

Comparison 7 Intravenous methylprednisolone versus placebo, Outcome 1 Incident delirium.

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Analysis 7.2

Comparison 7 Intravenous methylprednisolone versus placebo, Outcome 2 Length of admission.

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Analysis 7.3

Comparison 7 Intravenous methylprednisolone versus placebo, Outcome 3 Mortality at 30 days.

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Analysis 7.4

Comparison 7 Intravenous methylprednisolone versus placebo, Outcome 4 Myocardial injury.

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Analysis 7.5

Comparison 7 Intravenous methylprednisolone versus placebo, Outcome 5 Respiratory failure.

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Analysis 7.6

Comparison 7 Intravenous methylprednisolone versus placebo, Outcome 6 Infection.

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Analysis 8.1

Comparison 8 Gabapentinoids versus placebo, Outcome 1 Incident delirium.

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Analysis 8.2

Comparison 8 Gabapentinoids versus placebo, Outcome 2 Length of admission.

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Analysis 8.3

Comparison 8 Gabapentinoids versus placebo, Outcome 3 Cognition.

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Analysis 8.4

Comparison 8 Gabapentinoids versus placebo, Outcome 4 Psychotropic Medication Use.

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Analysis 8.5

Comparison 8 Gabapentinoids versus placebo, Outcome 5 Withdrawal from protocol.

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Analysis 9.1

Comparison 9 Ketamine versus placebo, Outcome 1 Incident delirium.

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Analysis 9.2

Comparison 9 Ketamine versus placebo, Outcome 2 Withdrawal from protocol.

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Analysis 10.1

Comparison 10 Intravenous parecoxib sodium analgesia versus Morphine and Saline, Outcome 1 Incident delirium.

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Analysis 10.2

Comparison 10 Intravenous parecoxib sodium analgesia versus Morphine and Saline, Outcome 2 Length of admission.

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Analysis 10.3

Comparison 10 Intravenous parecoxib sodium analgesia versus Morphine and Saline, Outcome 3 Postoperative cognitive dysfunction at 3 days.

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Analysis 10.4

Comparison 10 Intravenous parecoxib sodium analgesia versus Morphine and Saline, Outcome 4 Postoperative cognitive dysfunction at 1 week.

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Analysis 10.5

Comparison 10 Intravenous parecoxib sodium analgesia versus Morphine and Saline, Outcome 5 Postoperative cognitive dysfunction at 3 months.

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Analysis 10.6

Comparison 10 Intravenous parecoxib sodium analgesia versus Morphine and Saline, Outcome 6 Postoperative cognitive dysfunction at 6 months.

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Analysis 11.1

Comparison 11 Intrathecal morphine and PCA morphine versus PCA morphine, Outcome 1 Incident delirium.

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Analysis 11.2

Comparison 11 Intrathecal morphine and PCA morphine versus PCA morphine, Outcome 2 Length of admission.

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Analysis 11.3

Comparison 11 Intrathecal morphine and PCA morphine versus PCA morphine, Outcome 3 Cognition ‐ days for MMSE to return to preoperative level.

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Analysis 11.4

Comparison 11 Intrathecal morphine and PCA morphine versus PCA morphine, Outcome 4 Withdrawal from protocol.

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Analysis 11.5

Comparison 11 Intrathecal morphine and PCA morphine versus PCA morphine, Outcome 5 Mortality.

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Analysis 12.1

Comparison 12 Fascia iliaca compartment block (FICB) versus placebo, Outcome 1 Incident delirium.

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Analysis 12.2

Comparison 12 Fascia iliaca compartment block (FICB) versus placebo, Outcome 2 Severity of delirium.

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Analysis 12.3

Comparison 12 Fascia iliaca compartment block (FICB) versus placebo, Outcome 3 Duration of delirium.

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Analysis 12.4

Comparison 12 Fascia iliaca compartment block (FICB) versus placebo, Outcome 4 Mortality.

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Analysis 13.1

Comparison 13 Light versus deep propofol sedation, Outcome 1 Incident delirium.

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Analysis 13.2

Comparison 13 Light versus deep propofol sedation, Outcome 2 Duration of delirium.

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Analysis 13.3

Comparison 13 Light versus deep propofol sedation, Outcome 3 Length of admission.

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Analysis 13.4

Comparison 13 Light versus deep propofol sedation, Outcome 4 Cognition on day 2.

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Analysis 13.5

Comparison 13 Light versus deep propofol sedation, Outcome 5 In‐hospital mortality.

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Analysis 13.6

Comparison 13 Light versus deep propofol sedation, Outcome 6 Postoperative complications (>=1).

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Analysis 14.1

Comparison 14 Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia/clinical judgement, Outcome 1 Incident delirium.

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Analysis 14.2

Comparison 14 Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia/clinical judgement, Outcome 2 Length of admission.

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Analysis 14.3

Comparison 14 Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia/clinical judgement, Outcome 3 Cognition at 7 days.

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Analysis 14.4

Comparison 14 Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia/clinical judgement, Outcome 4 Cognition at 3 months.

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Analysis 14.5

Comparison 14 Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia/clinical judgement, Outcome 5 SF‐36 mental summary score.

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Analysis 14.6

Comparison 14 Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia/clinical judgement, Outcome 6 Mortality at 7 days.

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Analysis 14.7

Comparison 14 Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia/clinical judgement, Outcome 7 Mortality at 3 months.

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Analysis 14.8

Comparison 14 Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia/clinical judgement, Outcome 8 Cardiac complications.

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Analysis 14.9

Comparison 14 Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia/clinical judgement, Outcome 9 Respiratory complications.

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Analysis 14.10

Comparison 14 Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia/clinical judgement, Outcome 10 Infective complications.

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Analysis 15.1

Comparison 15 Sevoflurane versus propofol anaesthesia, Outcome 1 Incident delirium.

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Analysis 15.2

Comparison 15 Sevoflurane versus propofol anaesthesia, Outcome 2 Mortality at 12 months.

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Analysis 16.1

Comparison 16 Xenon versus sevoflurane anaesthesia, Outcome 1 Incident delirium.

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Analysis 16.2

Comparison 16 Xenon versus sevoflurane anaesthesia, Outcome 2 Length of admission.

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Analysis 16.3

Comparison 16 Xenon versus sevoflurane anaesthesia, Outcome 3 In‐hospital mortality.

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Analysis 16.4

Comparison 16 Xenon versus sevoflurane anaesthesia, Outcome 4 Adverse events.

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Analysis 16.5

Comparison 16 Xenon versus sevoflurane anaesthesia, Outcome 5 Sepsis.

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Analysis 17.1

Comparison 17 Epidural anaesthesia versus general anaesthesia, Outcome 1 Incident delirium.

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Analysis 17.2

Comparison 17 Epidural anaesthesia versus general anaesthesia, Outcome 2 Length of admission > 10 days.

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Analysis 17.3

Comparison 17 Epidural anaesthesia versus general anaesthesia, Outcome 3 Cognitive decline.

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Analysis 17.4

Comparison 17 Epidural anaesthesia versus general anaesthesia, Outcome 4 Urinary tract infection.

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Analysis 17.5

Comparison 17 Epidural anaesthesia versus general anaesthesia, Outcome 5 Psychological morbidity.

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Analysis 17.6

Comparison 17 Epidural anaesthesia versus general anaesthesia, Outcome 6 Postoperative complications.

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Analysis 17.7

Comparison 17 Epidural anaesthesia versus general anaesthesia, Outcome 7 Pressure ulcer.

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Analysis 18.1

Comparison 18 Liberal versus restrictive blood transfusion thresholds, Outcome 1 Incident delirium.

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Analysis 18.2

Comparison 18 Liberal versus restrictive blood transfusion thresholds, Outcome 2 Delirium severity.

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Analysis 18.3

Comparison 18 Liberal versus restrictive blood transfusion thresholds, Outcome 3 Length of admission.

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Analysis 18.4

Comparison 18 Liberal versus restrictive blood transfusion thresholds, Outcome 4 Psychoactive medication use.

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Analysis 18.5

Comparison 18 Liberal versus restrictive blood transfusion thresholds, Outcome 5 Infection.

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Analysis 18.6

Comparison 18 Liberal versus restrictive blood transfusion thresholds, Outcome 6 Congestive heart failure.

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Analysis 19.1

Comparison 19 Fast‐track surgery versus usual care, Outcome 1 Incident delirium.

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Analysis 19.2

Comparison 19 Fast‐track surgery versus usual care, Outcome 2 Length of admission.

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Analysis 19.3

Comparison 19 Fast‐track surgery versus usual care, Outcome 3 Urinary tract infection.

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Analysis 19.4

Comparison 19 Fast‐track surgery versus usual care, Outcome 4 Heart failure.

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Analysis 20.1

Comparison 20 Postoperative delirium‐free protocol (DFP) versus usual care, Outcome 1 Incident delirium.

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Analysis 20.2

Comparison 20 Postoperative delirium‐free protocol (DFP) versus usual care, Outcome 2 Length of admission.

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Analysis 20.3

Comparison 20 Postoperative delirium‐free protocol (DFP) versus usual care, Outcome 3 Behavioural disturbance.

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Analysis 21.1

Comparison 21 Computerised clinical decision support system (CCDS) versus usual care, Outcome 1 Incident delirium.

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Analysis 21.2

Comparison 21 Computerised clinical decision support system (CCDS) versus usual care, Outcome 2 Length of admission.

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Analysis 21.3

Comparison 21 Computerised clinical decision support system (CCDS) versus usual care, Outcome 3 Mortality within 30 days of discharge.

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Analysis 21.4

Comparison 21 Computerised clinical decision support system (CCDS) versus usual care, Outcome 4 Falls.

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Analysis 21.5

Comparison 21 Computerised clinical decision support system (CCDS) versus usual care, Outcome 5 Pressure ulcers.

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Analysis 22.1

Comparison 22 Geriatric unit care versus orthopaedic unit care, Outcome 1 Incident delirium.

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Analysis 22.2

Comparison 22 Geriatric unit care versus orthopaedic unit care, Outcome 2 Duration of delirium.

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Analysis 22.3

Comparison 22 Geriatric unit care versus orthopaedic unit care, Outcome 3 Severity of delirium.

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Analysis 22.4

Comparison 22 Geriatric unit care versus orthopaedic unit care, Outcome 4 Length of admission.

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Analysis 22.5

Comparison 22 Geriatric unit care versus orthopaedic unit care, Outcome 5 Cognitive function (composite score) at 4 months.

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Analysis 22.6

Comparison 22 Geriatric unit care versus orthopaedic unit care, Outcome 6 Incident dementia at 12 months.

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Analysis 22.7

Comparison 22 Geriatric unit care versus orthopaedic unit care, Outcome 7 ADL function at 4 months.

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Analysis 22.8

Comparison 22 Geriatric unit care versus orthopaedic unit care, Outcome 8 Institutionalisation at 4 months.

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Analysis 22.9

Comparison 22 Geriatric unit care versus orthopaedic unit care, Outcome 9 Institutionalisation at 12 months.

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Analysis 22.10

Comparison 22 Geriatric unit care versus orthopaedic unit care, Outcome 10 Inpatient mortality.

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Analysis 22.11

Comparison 22 Geriatric unit care versus orthopaedic unit care, Outcome 11 Falls.

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Analysis 22.12

Comparison 22 Geriatric unit care versus orthopaedic unit care, Outcome 12 Pressure ulcers.

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Analysis 22.13

Comparison 22 Geriatric unit care versus orthopaedic unit care, Outcome 13 Other medical adverse events.

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Analysis 22.14

Comparison 22 Geriatric unit care versus orthopaedic unit care, Outcome 14 Postoperative complications.

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Summary of findings for the main comparison. A multi‐component delirium prevention intervention compared to usual care for hospitalised non‐ICU patients

Multi‐component delirium prevention intervention compared to usual care for hospitalised non‐ICU patients
Intervention: A multi‐component delirium prevention intervention versus usual care
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
		A multi‐component delirium prevention intervention
Incidence of delirium validated instruments¹	209 per 1000²	144 per 1000 (123 to 172)	RR 0.69 (0.59 to 0.81)	1950 (7 studies³)	⊕⊕⊕⊝ moderate^4,5,6
Duration of delirium (days)	The mean duration of delirium in the control groups ranged from 2.1 to 10.2 days	The mean duration of delirium in the intervention groups was 1.16 days shorter (2.96 shorter to 0.64 longer)		244 (4 studies)	⊕⊝⊝⊝ very low^4,6,7,8,9
Severity of delirium DRS‐R‐98 and CAM‐S¹⁰		The standardised mean severity of delirium in the intervention groups was 1.04 standard deviations lower (1.65 to 0.43 lower)¹¹		67 (2 studies)	⊕⊕⊝⊝ low^4,12
Length of admission Days	The mean length of admission in the control groups ranged from 5 to 38 days	The mean length of admission in the intervention groups was 0.01 days longer (0.48 days shorter to 0.51 days longer)		1920 (6 studies)	⊕⊕⊕⊝ moderate^4,6,7
Return to independent living	682 per 1000²	648 per 1000 (580 to 723)	RR 0.95 (0.85 to 1.06)	1116 (4 studies)	⊕⊕⊕⊝ moderate^4,6,13
Inpatient mortality	81 per 1000²	73 per 1000 (45 to 116)	RR 0.90 (0.56 to 1.43)	859 (3 studies)	⊕⊝⊝⊝ very low^6,14,15
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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). CI: Confidence interval; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Three validated methods for delirium detection used ‐ the CAM, OBS and DRS ² The assumed risk is the risk in the control group ³ Four studies in medical in patients, three studies in surgical patients ⁴ High risk of performance bias due to the lack of blinding of participants and personal in all studies (due to the nature of the intervention). ⁵ Outcomes assessors unblinded 2 studies (one of which carries the largest weighting (58%) due to high event rate). Risk of bias otherwise low across studies ⁶ Higher baseline prevalence of dementia in the control groups of two studies compared to the intervention groups causing risk of bias ⁷Outcomes assessors unblinded in two studies ⁸ Minimal important difference (MID) of 1 day assumed. 95% confidence limits around the pooled estimate of mean difference includes both 'no difference', and the MID. ⁹ Downgraded because inconsistent results ¹⁰ Delirium Rating Scale‐Revised‐98 (0 to 46) and Confusion Assessment Method‐Severity (0 to 10) ¹¹This is a difference in standard deviations. A standard deviation of > 0.8 represents a large effect. ¹² Imprecise results ‐ small pooled sample size ¹³ Outcomes assessors unblinded in one study ¹⁴There is some inconsistency of results ¹⁵Imprecise results ‐ pooled estimate includes both no effect, appreciable benefit and appreciable harm

Summary of findings for the main comparison. A multi‐component delirium prevention intervention compared to usual care for hospitalised non‐ICU patients

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Summary of findings 2. Prophylactic cholinesterase inhibitor versus placebo for preventing delirium in hospitalised non‐ICU patients

Prophylactic cholinesterase inhibitor versus placebo for preventing delirium in hospitalised non‐ICU patients
Intervention: Prophylactic cholinesterase inhibitor versus placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Prophylactic cholinesterase inhibitors
Incidence of delirium DSM‐IV criteria, DSI, CAM,	218 per 1000¹	148 per 1000 (37 to 572)	RR 0.68 (0.17 to 2.62)	113 (2 studies)	⊕⊝⊝⊝ very low^2,3,4
Duration of delirium ‐ not measured	N/A	N/A		N/A	N/A
Severity of delirium MDAS	The mean severity of delirium in the control groups was 1.3 points	The mean severity of delirium in the intervention groups was 0.30 points lower (4.17 lower to 3.57 higher)		16 (1 study)	⊕⊕⊝⊝ low⁵
Length of admission Days	The mean length of admission ranged across control groups from 4‐12.1 days	The mean length of admission in the intervention groups was 0.34 days shorter (1.54 shorter to 0.86 longer)		128 (3 studies)	⊕⊕⊝⊝ low^6,7
Return to independent living ‐ not measured	N/A	N/A		N/A	N/A
Inpatient mortality ‐ not measured	N/A	N/A		N/A	N/A
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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). CI: Confidence interval; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ The assumed risk is the risk in the control group ² Both studies are at high risk of attrition bias and have incomplete outcome data. ³ Downgraded because inconsistent results ⁴ Estimate of effect includes 'no benefit' and both appreciable benefit and appreciable harm. ⁵ Estimate of effect includes both 'no effect' and minimally important difference, downgraded two levels due to serious imprecision ⁶ Risk of bias unclear in all domains in one study (abstract only available). Remaining two studies have incomplete outcome reporting and are at risk of attrition bias ⁷ Downgraded due to imprecision in result

Summary of findings 2. Prophylactic cholinesterase inhibitor versus placebo for preventing delirium in hospitalised non‐ICU patients

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Summary of findings 3. Prophylactic antipsychotic medications for preventing delirium in hospitalised non‐ICU patients

Prophylactic antipsychotic medications for preventing delirium in hospitalised non‐ICU patients
Intervention: Prophylactic antipsychotic medications versus placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Prophylactic antipsychotic medications
Incidence of delirium CAM/NEECHAM Follow‐up range: 0‐8 postoperative days	300 per 1000¹	165 per 1000 (69 to 390)	RR 0.55 (0.23 to 1.3)	916 (3 studies)	⊕⊝⊝⊝ very low^2,3,4
Duration of delirium Days Follow‐up: 3‐8 postoperative days	The mean duration of delirium in the control groups ranged from 2.2 to 5.4 days	The mean duration of delirium in the intervention groups was 2.74 days shorter (9.59 shorter to 4.11 longer)		178 (2 studies)	⊕⊝⊝⊝ very low^2,5
Severity of delirium DRS. Scale from: 0 to 46. Follow‐up: 3‐8 postoperative days	The mean severity of delirium in the control groups ranged from 14.4 to 16.4 points	The mean severity of delirium in the intervention groups was 1.02 points lower (6.8 lower to 4.76 higher)		178 (2 studies)	⊕⊝⊝⊝ very low^2,5
Length of admission Days	The mean length of admission in the control group was 17.1 days	The mean length of admission in the intervention groups was 5.5 days shorter (12.17 shorter to 1.17 longer)		68 (1 study)	⊕⊕⊝⊝ low⁵
Return to independent living ‐ not measured	N/A	N/A	N/A		N/A
Inpatient mortality ‐ not measured	N/A	N/A	N/A		N/A
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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). CI: Confidence interval; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ The assumed risk is the risk in the control group ²Downgraded because inconsistent results ³ Downgraded because of imprecision in results ⁴ Downgraded due to risk of bias ⁵ Downgraded two levels because very imprecise results

Summary of findings 3. Prophylactic antipsychotic medications for preventing delirium in hospitalised non‐ICU patients

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Summary of findings 4. Prophylactic melatonin for preventing delirium in hospitalised non‐ICU patients

Prophylactic melatonin for preventing delirium in hospitalised non‐ICU patients
Intervention: Prophylactic melatonin versus placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Prophylactic melatonin
Incidence of delirium CAM/DSM IV/DRS‐R‐9s Follow‐up: every 24 to 48 hours until discharge or 8 days	242 per 1000¹	128 per 1000 (22 to 788)	RR 0.53 (0.09 to 3.25)	529 (3 studies)	⊕⊝⊝⊝ very low^2,3,4
Duration of delirium Days Follow‐up: every 24 to 48 hours until discharge	The mean duration of delirium in the control group was 2 days	The mean duration of delirium in the intervention groups was 0 days longer (0.57 shorter to 0.57 longer)		104 (1 study)	⊕⊕⊕⊝ moderate³
Severity of delirium (binary severe vs. not severe) Number of patients requiring greater than 3mg of haloperidol Follow‐up: daily until discharge	531 per 1000	457 per 1000 (308 to 674)	RR 0.86 (0.58 to 1.27)	104 (1 study)	⊕⊕⊕⊝ moderate³
Severity of delirium DRS‐R‐98 score	The mean severity of delirium in the control group was 6.3 points	The mean severity of delirium in the intervention group was 4.1 points lower (19.47 points lower to 11.27 points higher)		6 (1 study)	⊕⊕⊝⊝ low⁵
Length of admission Days	The mean length of admission in the control groups ranged from 11 to 18.5 days	The mean length of admission in the intervention groups was 0.09 days longer (1.2 shorter to 1.39 longer)		500 (2 studies)	⊕⊕⊕⊝ moderate³
Return to independent living ‐ not measured	N/A	N/A	N/A		N/A
In‐hospital mortality Mortality Follow‐up: every 24 to 48 hours until discharge or 8 days	47 per 1000¹	39 per 1000 (17 to 88)	RR 0.84 (0.37 to 1.88)	543 (3 studies)	⊕⊕⊝⊝ low⁶
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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). CI: Confidence interval; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ The assumed risk is the risk in the control group ² Downgraded because inconsistent results ³ Downgraded because imprecise results ⁴ Downgraded due to risk of bias ⁵ Downgraded because imprecise results and very small number of events

Summary of findings 4. Prophylactic melatonin for preventing delirium in hospitalised non‐ICU patients

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Summary of findings 5. Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia/clinical judgement for preventing delirium in hospitalised non‐ICU patients

Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia/clinical judgement for preventing delirium in hospitalised non‐ICU patients
Intervention: Bispectral index (BIS)‐guided anaesthesia
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	BIS‐blinded/clinical judgement	BIS‐guided
Incidence of delirium CAM, DSM‐IV Follow‐up: daily after surgery until discharge; twice daily from postoperative day 1 to 7	226 per 1000¹	160 per 1000 (135 to 192)	RR 0.71 (0.60 to 0.85)	2057 (2 studies)	⊕⊕⊕⊝ moderate²
Duration of delirium ‐ not measured	N/A	N/A	N/A		N/A
Severity of delirium ‐ not measured	N/A	N/A	N/A		N/A
Length of admission Days	The mean length of admission in the control groups ranged from 7 to 15.7 days	The mean length of admission in the intervention group was 0.94 days shorter (0.43 days shorter to 1.45 days shorter)	‐	2057 (2 studies)	⊕⊕⊕⊝ moderate²
Return to independent living ‐ not measured	N/A	N/A	N/A		N/A
In‐hospital mortality ‐ not measured	N/A	N/A	N/A		N/A
*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). CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: 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 quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹ The assumed risk is the risk in the control group (BIS‐blinded/clinical judgement) ² Downgraded due to risk of bias

Summary of findings 5. Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia/clinical judgement for preventing delirium in hospitalised non‐ICU patients

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Table 1. Individual components of multi‐component interventions

Study

Intervention Components

Individualised care

Checklists/

protocols

Education/

training¹

Re‐orientation

Attention to sensory deprivation

Familiar objects

Cognitive stimulation

Nutrition/

hydration

Identification of infection

Mobilisation

Sleep hygiene

MDTcare²

CGA³

Oxygenation

Electrolytes

Pain control

Medication review

Mood⁴

Bowel/

bladder care

Postoperative complications

Abizanda 2011

✔

Bonaventura 2007

✔

Jeffs 2013

✔

Martinez 2012

✔

Hempenius 2013

✔

Lundstrom 2006

✔

Marcantonio 2001

✔

¹Education/training: structured education/training of staff or carers; ²MDT Multidisciplinary Team; ³CGA Comprehensive Geriatric Assessment; ⁴Mood: assessment for depression/anxiety

Table 1. Individual components of multi‐component interventions

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Comparison 1. Multi‐component delirium prevention intervention (MCI) versus usual care

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	7	1950	Risk Ratio (M‐H, Random, 95% CI)	0.69 [0.59, 0.81]

1.1 Medical patients	4	1365	Risk Ratio (M‐H, Random, 95% CI)	0.63 [0.43, 0.92]
1.2 Surgical patients	3	585	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.59, 0.85]
2 Incidence of delirium in patients with dementia Show forest plot	1	50	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.59, 1.36]

2.1 Surgical patients	1	50	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.59, 1.36]
3 Duration of delirium Show forest plot	4	244	Mean Difference (IV, Random, 95% CI)	‐1.16 [‐2.96, 0.64]

3.1 Medical patients	2	63	Mean Difference (IV, Random, 95% CI)	‐0.65 [‐2.43, 1.13]
3.2 Surgical patients	2	181	Mean Difference (IV, Random, 95% CI)	‐2.40 [‐7.27, 2.46]
4 Severity of delirium Show forest plot	2	67	Std. Mean Difference (IV, Random, 95% CI)	‐1.04 [‐1.65, ‐0.43]

4.1 Medical patients	1	36	Std. Mean Difference (IV, Random, 95% CI)	‐0.77 [‐1.46, ‐0.08]
4.2 Surgical patients	1	31	Std. Mean Difference (IV, Random, 95% CI)	‐1.39 [‐2.20, ‐0.58]
5 Length of admission Show forest plot	6	1920	Mean Difference (IV, Random, 95% CI)	0.01 [‐0.48, 0.51]

5.1 Medical patients	3	1335	Mean Difference (IV, Random, 95% CI)	0.04 [‐0.44, 0.52]
5.2 Surgical patients	3	585	Mean Difference (IV, Random, 95% CI)	‐1.24 [‐4.74, 2.25]
6 Cognition Show forest plot	1	60	Mean Difference (IV, Random, 95% CI)	9.10 [7.20, 11.00]

6.1 Medical patients	1	60	Mean Difference (IV, Random, 95% CI)	9.10 [7.20, 11.00]
7 Improvement in Activities of Daily Living Show forest plot	1	341	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.91, 1.47]

7.1 Medical patients	1	341	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.91, 1.47]
8 Return to independent living Show forest plot	4	1116	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.85, 1.06]

8.1 Medical patients	1	648	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.88, 1.06]
8.2 Surgical patients	3	468	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.75, 1.19]
9 Depression Show forest plot	1	149	Mean Difference (IV, Random, 95% CI)	0.70 [‐0.44, 1.84]

9.1 Surgical patients	1	149	Mean Difference (IV, Random, 95% CI)	0.70 [‐0.44, 1.84]
10 Withdrawal from protocol Show forest plot	1	126	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

10.1 Surgical patients	1	126	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
11 Falls Show forest plot	3	746	Risk Ratio (M‐H, Random, 95% CI)	0.57 [0.16, 2.01]

11.1 Medical patients	1	287	Risk Ratio (M‐H, Random, 95% CI)	0.11 [0.01, 2.03]
11.2 Surgical patients	2	459	Risk Ratio (M‐H, Random, 95% CI)	0.78 [0.18, 3.46]
12 Pressure ulcers Show forest plot	2	457	Risk Ratio (M‐H, Random, 95% CI)	0.48 [0.26, 0.89]

12.1 Surgical patients	2	457	Risk Ratio (M‐H, Random, 95% CI)	0.48 [0.26, 0.89]
13 Inpatient mortality Show forest plot	3	859	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.56, 1.43]

13.1 Medical patients	1	400	Risk Ratio (M‐H, Fixed, 95% CI)	0.64 [0.34, 1.18]
13.2 Surgical patients	2	459	Risk Ratio (M‐H, Fixed, 95% CI)	1.45 [0.69, 3.05]
14 12 month mortality Show forest plot	1	199	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.46, 1.56]

14.1 Surgical patients	1	199	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.46, 1.56]
15 Cardiovascular complication Show forest plot	1	260	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.78, 1.65]

16 Urinary tract infection Show forest plot	1	260	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.45, 3.20]

17 Mental health worsened Show forest plot	1	246	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.64, 1.20]

Comparison 1. Multi‐component delirium prevention intervention (MCI) versus usual care

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Comparison 2. Prophylactic cholinesterase inhibitor versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	2	113	Risk Ratio (M‐H, Random, 95% CI)	0.68 [0.17, 2.62]

1.1 Donepezil	2	113	Risk Ratio (M‐H, Random, 95% CI)	0.68 [0.17, 2.62]
2 Duration of delirium Show forest plot	1	15	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]

2.1 Donepezil	1	15	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
3 Severity of delirium Show forest plot	1	16	Mean Difference (IV, Random, 95% CI)	‐0.30 [‐4.17, 3.57]

3.1 Donepezil	1	16	Mean Difference (IV, Random, 95% CI)	‐0.30 [‐4.17, 3.57]
4 Length of admission Show forest plot	3	128	Mean Difference (IV, Random, 95% CI)	‐0.34 [‐1.54, 0.86]

4.1 Donepezil	3	128	Mean Difference (IV, Random, 95% CI)	‐0.34 [‐1.54, 0.86]
5 Cognition Show forest plot	1	15	Mean Difference (IV, Random, 95% CI)	‐1.40 [‐4.45, 1.65]

5.1 Donepezil	1	15	Mean Difference (IV, Random, 95% CI)	‐1.40 [‐4.45, 1.65]
6 Withdrawal from protocol Show forest plot	2	96	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.49, 1.87]

6.1 Donepezil	2	96	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.49, 1.87]
7 Adverse events (continuous) Show forest plot	1	33	Mean Difference (IV, Random, 95% CI)	0.13 [‐0.26, 0.52]

7.1 Donepezil	1	33	Mean Difference (IV, Random, 95% CI)	0.13 [‐0.26, 0.52]
8 Adverse events (binary) Show forest plot	1	16	Risk Ratio (M‐H, Random, 95% CI)	6.25 [0.35, 112.52]

Comparison 2. Prophylactic cholinesterase inhibitor versus placebo

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Comparison 3. Prophylactic antipsychotic versus control

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	3	916	Risk Ratio (M‐H, Random, 95% CI)	0.73 [0.33, 1.59]

1.1 Haloperidol	2	516	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.69, 1.60]
1.2 Olanzapine	1	400	Risk Ratio (M‐H, Random, 95% CI)	0.36 [0.24, 0.52]
2 Duration of delirium Show forest plot	2	178	Mean Difference (IV, Random, 95% CI)	‐2.74 [‐9.59, 4.11]

2.1 Haloperidol	1	68	Mean Difference (IV, Random, 95% CI)	‐6.4 [‐9.38, ‐3.42]
2.2 Olanzapine	1	110	Mean Difference (IV, Random, 95% CI)	0.60 [0.10, 1.10]
3 Severity of delirium Show forest plot	2	178	Mean Difference (IV, Random, 95% CI)	‐1.02 [‐6.80, 4.76]

3.1 Haloperidol	1	68	Mean Difference (IV, Random, 95% CI)	‐2.00 [‐5.86, ‐2.14]
3.2 Olanzapine	1	110	Mean Difference (IV, Random, 95% CI)	1.90 [0.41, 3.39]
4 Length of admission Show forest plot	1	68	Mean Difference (IV, Random, 95% CI)	‐5.5 [‐12.17, 1.17]

4.1 Haloperidol	1	68	Mean Difference (IV, Random, 95% CI)	‐5.5 [‐12.17, 1.17]
5 Cognition Show forest plot	1	110	Mean Difference (IV, Random, 95% CI)	‐4.90 [‐7.42, ‐2.38]

6 Withdrawal from protocol Show forest plot	2	925	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.68, 1.24]

6.1 Haloperidol	1	430	Risk Ratio (M‐H, Random, 95% CI)	0.73 [0.43, 1.26]
6.2 Olanzapine	1	495	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.71, 1.46]
7 Adverse events Show forest plot	1	430	Risk Ratio (M‐H, Random, 95% CI)	0.39 [0.10, 1.43]

7.1 Haloperidol	1	430	Risk Ratio (M‐H, Random, 95% CI)	0.39 [0.10, 1.43]
8 Pneumonia Show forest plot	1	400	Risk Ratio (M‐H, Random, 95% CI)	7.28 [0.38, 140.11]

9 Urinary tract infection Show forest plot	1	400	Risk Ratio (M‐H, Random, 95% CI)	0.26 [0.03, 2.31]

10 Congestive heart failure Show forest plot	1	400	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.07, 16.52]

Comparison 3. Prophylactic antipsychotic versus control

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Comparison 4. Prophylactic melatonin versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	3	529	Risk Ratio (M‐H, Random, 95% CI)	0.41 [0.09, 1.89]

2 Duration of delirium Show forest plot	1	104	Mean Difference (IV, Random, 95% CI)	0.0 [‐0.57, 0.57]

3 Severity of delirium (binary severe vs. not severe) Show forest plot	1	104	Risk Ratio (M‐H, Random, 95% CI)	0.86 [0.58, 1.27]

4 Severity of delirium (DRS‐R‐98) Show forest plot	1	6	Mean Difference (IV, Random, 95% CI)	‐4.10 [‐19.47, 11.27]

5 Length of admission Show forest plot	2	500	Mean Difference (IV, Random, 95% CI)	0.09 [‐1.20, 1.39]

6 Cognitive impairment Show forest plot	1	378	Risk Ratio (M‐H, Random, 95% CI)	0.86 [0.70, 1.04]

7 Activities of daily living Show forest plot	1	369	Mean Difference (IV, Random, 95% CI)	0.0 [‐1.20, 1.20]

8 Use of psychotropic medication (binary) Show forest plot	1	122	Risk Ratio (M‐H, Random, 95% CI)	0.87 [0.64, 1.18]

9 Antipsychotic medication use (cumulative) Show forest plot	1	378	Mean Difference (IV, Random, 95% CI)	‐1.0 [‐1.79, ‐0.21]

10 Benzodiazepine use (cumulative) Show forest plot	1	378	Mean Difference (IV, Random, 95% CI)	‐11.60 [‐24.34, 1.14]

11 Withdrawal from study Show forest plot	2	165	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.15, 6.87]

12 In‐hospital mortality Show forest plot	3	543	Risk Ratio (M‐H, Random, 95% CI)	0.84 [0.37, 1.88]

13 Mortality by 3 months Show forest plot	1	378	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.67, 1.45]

14 Adverse events Show forest plot	1	43	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Comparison 4. Prophylactic melatonin versus placebo

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Comparison 5. Prophylactic citicoline versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Incident delirium day 1 post surgery	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.68 [0.22, 2.06]
2 Cognitive status Show forest plot	1	81	Mean Difference (IV, Random, 95% CI)	‐1.47 [‐3.85, 0.91]

Comparison 5. Prophylactic citicoline versus placebo

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Comparison 6. Oral premedication with diazepam and diphenhydramine

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1	49	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Comparison 6. Oral premedication with diazepam and diphenhydramine

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Comparison 7. Intravenous methylprednisolone versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1	7507	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.87, 1.19]

2 Length of admission Show forest plot	1	7507	Mean Difference (IV, Random, 95% CI)	0.0 [‐0.20, 0.20]

3 Mortality at 30 days Show forest plot	1	7507	Risk Ratio (M‐H, Random, 95% CI)	0.87 [0.70, 1.07]

4 Myocardial injury Show forest plot	1	7507	Risk Ratio (M‐H, Random, 95% CI)	1.22 [1.07, 1.38]

5 Respiratory failure Show forest plot	1	7507	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.80, 1.05]

6 Infection Show forest plot	1	7507	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.84, 1.06]

Comparison 7. Intravenous methylprednisolone versus placebo

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Comparison 8. Gabapentinoids versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1	21	Risk Ratio (M‐H, Random, 95% CI)	0.12 [0.01, 1.90]

2 Length of admission Show forest plot	1	60	Mean Difference (IV, Random, 95% CI)	‐0.60 [‐2.12, 0.92]

3 Cognition Show forest plot	1	60	Mean Difference (IV, Random, 95% CI)	1.0 [‐2.76, 4.76]

4 Psychotropic Medication Use Show forest plot	1	60	Risk Ratio (M‐H, Random, 95% CI)	0.53 [0.21, 1.38]

5 Withdrawal from protocol Show forest plot	1	70	Risk Ratio (M‐H, Random, 95% CI)	9.00 [0.50, 161.13]

Comparison 8. Gabapentinoids versus placebo

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Comparison 9. Ketamine versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1	24	Risk Ratio (M‐H, Random, 95% CI)	2.0 [0.21, 19.23]

2 Withdrawal from protocol Show forest plot	1	26	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.07, 14.34]

Comparison 9. Ketamine versus placebo

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Comparison 10. Intravenous parecoxib sodium analgesia versus Morphine and Saline

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.5 [0.26, 0.98]

2 Length of admission Show forest plot	1	80	Mean Difference (IV, Random, 95% CI)	‐0.90 [‐1.58, ‐0.22]

3 Postoperative cognitive dysfunction at 3 days Show forest plot	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.47 [0.21, 1.02]

4 Postoperative cognitive dysfunction at 1 week Show forest plot	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.38 [0.15, 0.98]

5 Postoperative cognitive dysfunction at 3 months Show forest plot	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.30 [0.09, 1.01]

6 Postoperative cognitive dysfunction at 6 months Show forest plot	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.14 [0.02, 1.11]

Comparison 10. Intravenous parecoxib sodium analgesia versus Morphine and Saline

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Comparison 11. Intrathecal morphine and PCA morphine versus PCA morphine

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1	52	Risk Ratio (M‐H, Random, 95% CI)	0.9 [0.44, 1.85]

2 Length of admission Show forest plot	1	52	Mean Difference (IV, Random, 95% CI)	‐0.5 [‐1.51, 0.51]

3 Cognition ‐ days for MMSE to return to preoperative level Show forest plot	1	52	Mean Difference (IV, Random, 95% CI)	0.20 [‐1.03, 1.43]

4 Withdrawal from protocol Show forest plot	1	59	Risk Ratio (M‐H, Random, 95% CI)	0.78 [0.19, 3.17]

5 Mortality Show forest plot	1	59	Risk Ratio (M‐H, Random, 95% CI)	0.34 [0.01, 8.13]

Comparison 11. Intrathecal morphine and PCA morphine versus PCA morphine

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Comparison 12. Fascia iliaca compartment block (FICB) versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1	207	Risk Ratio (M‐H, Random, 95% CI)	0.45 [0.24, 0.87]

2 Severity of delirium Show forest plot	1	36	Mean Difference (IV, Random, 95% CI)	‐4.30 [‐6.81, ‐1.79]

3 Duration of delirium Show forest plot	1	36	Mean Difference (IV, Random, 95% CI)	‐5.7 [‐9.50, ‐1.90]

4 Mortality Show forest plot	1	219	Risk Ratio (M‐H, Random, 95% CI)	0.51 [0.05, 5.58]

Comparison 12. Fascia iliaca compartment block (FICB) versus placebo

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Comparison 13. Light versus deep propofol sedation

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1	114	Risk Ratio (M‐H, Random, 95% CI)	0.48 [0.26, 0.89]

2 Duration of delirium Show forest plot	1	34	Mean Difference (IV, Random, 95% CI)	‐0.60 [‐3.30, 2.10]

3 Length of admission Show forest plot	1	114	Mean Difference (IV, Random, 95% CI)	0.20 [‐0.80, 1.20]

4 Cognition on day 2 Show forest plot	1	114	Mean Difference (IV, Random, 95% CI)	3.10 [0.30, 5.90]

5 In‐hospital mortality Show forest plot	1	114	Risk Ratio (M‐H, Random, 95% CI)	0.5 [0.05, 5.36]

6 Postoperative complications (>=1) Show forest plot	1	114	Risk Ratio (M‐H, Random, 95% CI)	0.87 [0.60, 1.26]

Comparison 13. Light versus deep propofol sedation

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Comparison 14. Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia/clinical judgement

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	2	2057	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.60, 0.85]

2 Length of admission Show forest plot	2	2057	Mean Difference (IV, Random, 95% CI)	‐0.94 [‐1.45, ‐0.43]

3 Cognition at 7 days Show forest plot	2	1938	Risk Ratio (M‐H, Random, 95% CI)	0.87 [0.71, 1.05]

4 Cognition at 3 months Show forest plot	2	1990	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.53, 0.97]

5 SF‐36 mental summary score Show forest plot	1	902	Mean Difference (IV, Random, 95% CI)	‐1.90 [‐3.40, ‐0.40]

6 Mortality at 7 days Show forest plot	1	921	Risk Ratio (M‐H, Random, 95% CI)	1.49 [0.42, 5.25]

7 Mortality at 3 months Show forest plot	2	1938	Risk Ratio (M‐H, Random, 95% CI)	1.10 [0.77, 1.59]

8 Cardiac complications Show forest plot	1	902	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.52, 1.39]

9 Respiratory complications Show forest plot	1	902	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.59, 1.07]

10 Infective complications Show forest plot	1	902	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.55, 0.95]

Comparison 14. Bispectral index (BIS)‐guided anaesthesia versus BIS‐blinded anaesthesia/clinical judgement

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Comparison 15. Sevoflurane versus propofol anaesthesia

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1	385	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.47, 1.34]

2 Mortality at 12 months Show forest plot	1	385	Risk Ratio (M‐H, Random, 95% CI)	1.19 [0.70, 2.02]

Comparison 15. Sevoflurane versus propofol anaesthesia

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Comparison 16. Xenon versus sevoflurane anaesthesia

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1	30	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.20, 2.79]

2 Length of admission Show forest plot	1	30	Mean Difference (IV, Random, 95% CI)	4.0 [‐1.72, 9.72]

3 In‐hospital mortality Show forest plot	1	30	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

4 Adverse events Show forest plot	1	30	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.34, 1.64]

5 Sepsis Show forest plot	1	30	Risk Ratio (M‐H, Random, 95% CI)	1.5 [0.29, 7.73]

Comparison 16. Xenon versus sevoflurane anaesthesia

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Comparison 17. Epidural anaesthesia versus general anaesthesia

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	2	104	Risk Ratio (M‐H, Random, 95% CI)	1.19 [0.69, 2.03]

2 Length of admission > 10 days Show forest plot	1	47	Risk Ratio (M‐H, Random, 95% CI)	0.59 [0.28, 1.24]

3 Cognitive decline Show forest plot	1	47	Risk Ratio (M‐H, Random, 95% CI)	0.15 [0.02, 1.06]

4 Urinary tract infection Show forest plot	1	57	Risk Ratio (M‐H, Random, 95% CI)	1.33 [0.57, 3.09]

5 Psychological morbidity Show forest plot	1	57	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.23, 4.71]

5.1 Depression	1	57	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.23, 4.71]
6 Postoperative complications Show forest plot	1	47	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.35, 2.39]

7 Pressure ulcer Show forest plot	1	57	Risk Ratio (M‐H, Random, 95% CI)	0.62 [0.16, 2.36]

Comparison 17. Epidural anaesthesia versus general anaesthesia

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Comparison 18. Liberal versus restrictive blood transfusion thresholds

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1	108	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.45, 1.27]

2 Delirium severity Show forest plot	1	38	Mean Difference (IV, Random, 95% CI)	‐0.10 [‐2.99, 2.79]

3 Length of admission Show forest plot	1	138	Mean Difference (IV, Random, 95% CI)	‐0.10 [‐1.36, 1.16]

4 Psychoactive medication use Show forest plot	1	138	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.87, 1.12]

5 Infection Show forest plot	1	138	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.23, 5.22]

6 Congestive heart failure Show forest plot	1	138	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.05, 5.88]

Comparison 18. Liberal versus restrictive blood transfusion thresholds

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Comparison 19. Fast‐track surgery versus usual care

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1	233	Risk Ratio (M‐H, Random, 95% CI)	0.26 [0.09, 0.77]

2 Length of admission Show forest plot	1	233	Mean Difference (IV, Random, 95% CI)	‐4.20 [‐4.60, ‐3.80]

3 Urinary tract infection Show forest plot	1	233	Risk Ratio (M‐H, Random, 95% CI)	0.38 [0.14, 1.04]

4 Heart failure Show forest plot	1	233	Risk Ratio (M‐H, Random, 95% CI)	0.31 [0.10, 0.91]

Comparison 19. Fast‐track surgery versus usual care

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Comparison 20. Postoperative delirium‐free protocol (DFP) versus usual care

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1	40	Risk Ratio (M‐H, Random, 95% CI)	0.14 [0.02, 1.06]

2 Length of admission Show forest plot	1	40	Mean Difference (IV, Fixed, 95% CI)	‐4.30 [‐12.51, 3.91]

3 Behavioural disturbance Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.03, 1.56]

Comparison 20. Postoperative delirium‐free protocol (DFP) versus usual care

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Comparison 21. Computerised clinical decision support system (CCDS) versus usual care

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1	424	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.82, 1.43]

2 Length of admission Show forest plot	1	424	Mean Difference (IV, Random, 95% CI)	0.90 [‐0.35, 2.15]

3 Mortality within 30 days of discharge Show forest plot	1	424	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.49, 2.23]

4 Falls Show forest plot	1	424	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.39, 2.19]

5 Pressure ulcers Show forest plot	1	424	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.64, 1.84]

Comparison 21. Computerised clinical decision support system (CCDS) versus usual care

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Comparison 22. Geriatric unit care versus orthopaedic unit care

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incident delirium Show forest plot	1	329	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.79, 1.22]

2 Duration of delirium Show forest plot	1	163	Mean Difference (IV, Random, 95% CI)	‐1.0 [‐2.04, 0.04]

3 Severity of delirium Show forest plot	1	163	Mean Difference (IV, Random, 95% CI)	1.5 [1.00, 4.00]

4 Length of admission Show forest plot	1	329	Mean Difference (IV, Random, 95% CI)	3.0 [1.94, 4.06]

5 Cognitive function (composite score) at 4 months Show forest plot	1	228	Mean Difference (IV, Random, 95% CI)	1.80 [‐5.92, 9.52]

6 Incident dementia at 12 months Show forest plot	1	193	Risk Ratio (M‐H, Random, 95% CI)	2.26 [0.60, 8.49]

7 ADL function at 4 months Show forest plot	1	239	Mean Difference (IV, Random, 95% CI)	1.0 [‐0.70, 2.70]

8 Institutionalisation at 4 months Show forest plot	1	242	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.58, 1.91]

9 Institutionalisation at 12 months Show forest plot	1	193	Risk Ratio (M‐H, Random, 95% CI)	0.86 [0.47, 1.59]

10 Inpatient mortality Show forest plot	1	329	Risk Ratio (M‐H, Random, 95% CI)	0.56 [0.21, 1.47]

11 Falls Show forest plot	1	329	Risk Ratio (M‐H, Random, 95% CI)	1.30 [0.61, 2.77]

12 Pressure ulcers Show forest plot	1	329	Risk Ratio (M‐H, Random, 95% CI)	0.38 [0.10, 1.41]

13 Other medical adverse events Show forest plot	1	329	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.76, 1.23]

14 Postoperative complications Show forest plot	1	329	Risk Ratio (M‐H, Random, 95% CI)	0.68 [0.20, 2.36]

Comparison 22. Geriatric unit care versus orthopaedic unit care

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