Abstract: We included four studies with a total of 3323 participants (864 adults and 2459 paediatrics) in this update. Three studies were single-centre, patient-level RCTs and one study was a multicentre cluster-RCT. The settings were in metropolitan centres and included general, mixed medical-surgical, medical only and a range of paediatric units. All four included studies compared the use of protocol-directed sedation, specifically protocols delivered by nurses, with usual care. We rated the risk of selection bias due to random sequence generation low for two studies and unclear for two studies. The risk of bias was highly variable across the domains and studies, with the risk of selection and performance bias generally rated high and the risk of detection and attrition bias generally rated low. When comparing protocol-directed sedation with usual care, there was no clear evidence of difference in duration of mechanical ventilation in hours for the entire duration of the first ICU stay for each patient (MD -28.15 hours, 95% CI -69.15 to 12.84; I2 = 85%; 4 studies; adjusted sample 2210 participants; low-quality evidence). There was no clear evidence of difference in ICU mortality (RR 0.77, 95% CI 0.39 to 1.50; I2 = 67%; 2 studies; 513 participants; low-quality evidence), or hospital mortality (RR 0.90, 95% CI 0.72 to 1.13; I2 = 10%; 3 studies; adjusted sample 2088 participants; low-quality evidence). There was no clear evidence of difference in ICU length of stay (MD -1.70 days, 95% CI-3.71 to 0.31; I2 = 82%; 4 studies; adjusted sample of 2123 participants; low-quality of evidence), however there was evidence of a significant reduction in hospital length of stay (MD -3.09 days, 95% CI -5.08 to -1.10; I2 = 2%; 3 studies; adjusted sample of 1922 participants; moderate-quality evidence). There was no clear evidence of difference in the incidence of self-extubation (RR 0.88, 95% CI 0.55 to 1.42; I2 = 0%; 2 studies; adjusted sample of 1687 participants; high-quality evidence), or incidence of tracheostomy (RR 0.67, 95% CI 0.35 to 1.30; I2 = 66%; 3 studies; adjusted sample of 2008 participants; low-quality evidence). Only one study examined incidence of reintubation, therefore we could not pool data; there was no clear evidence of difference (RR 0.65, 95% CI 0.35 to 1.24; 1 study; 321 participants; low-quality evidence). There is currently limited evidence from RCTs evaluating the effectiveness of protocol-directed sedation on patient outcomes. The four included RCTs reported conflicting results and heterogeneity limited the interpretation of results for the primary outcomes of duration of mechanical ventilation and mortality. Further studies, taking into account differing contextual characteristics, are necessary to inform future practice. Methodological strategies to reduce the risk of bias need to be considered in future studies.

Plain-language summary: We searched scientific databases for studies that examined protocol-directed sedation in adult and paediatric intensive care patients. We identified four studies with 3308 participants (864 adults and 2459 paediatrics) to include in this review. All of these included studies compared the use of protocol-directed sedation delivered by nurses to usual care (that is, non-protocol-directed sedation). There was no difference in the length of time mechanical ventilation was needed or in ICU or hospital deaths between people who received protocol-directed sedation and those people managed with usual care. There was a significant reduction in the number of days people treated with protocol-directed sedation spent in hospital, when compared to those managed with usual care. There was no difference between the two groups in the number of people who accidentally removed their breathing tube or required their tube to be reinserted after accidentally removing it. In conclusion, the benefits of protocol-directed sedation delivered by nurses compared to usual care are currently unclear in relation to the important outcomes of length of time mechanical ventilation was needed or number of deaths. The evidence available to answer our review question is low to moderate. This is mainly due to the often conflicting results that were reported from the four eligible studies. Further studies need to be conducted to determine the effectiveness of this intervention.