A total of 2243 records were initially identified through multiple search engines. Subsequently, 1504 where left as for abstract review by eliminating 736 duplications. Only 45 of those abstracts underwent full-text assessment, with 10 ultimately being chosen for inclusion in this review, which also involved a meta-analysis. All 10 selected articles utilized the RASS scale for sedative titration and 9 out 10 studies incorporated benzodiazepines into their pharmacological regimens.

Among the reported studies, only 2 did not provide information on the reasons for patient intubation, and none reported occurrences of ventilator-associated pneumonia. Additionally, all excluded patients had experienced resuscitation from cardiorespiratory arrest, displayed neurological deficits, needed muscle blockers, were in an imminent death situation, or were anticipated to spend less than 24 h in the ICU. The screening process is visually represented in Fig. 1, detailed characteristics of the studies can be found in Table 1 and Additional file 1: Table S1.

The majority of the studies were conducted in the USA, and they encompassed various types of sedative drugs. Among these studies, five specifically assessed sedation algorithms as a form of protocolized sedation. In contrast, four studies implemented daily sedation interruption, and another utilized both daily sedation interruption and a sedation algorithm as part of their approaches to protocolized sedation.

Of the 10 included studies, none had a high risk of bias for any component, only one had some concerns of bias in the component in the randomization process, and 7 studies had some concerns of bias in the missing data by nonreporting component. In the other components, all studies presented a low risk of bias. The complete evaluation with the RoB2 tool can be found in Table 2.

In terms of mortality, a statistically significant reduction was observed with protocolized sedation compared to usual ICU management, as indicated by an RR of 0.80 [95% CI 0.68–0.93, I2 = 0%; p < 0.01]. Both sedation protocols involving daily interruption (RR = 0.79, 95% CI 0.63–0.99, I2 = 0%, p = 0.04) and algorithm-based sedation (RR = 0.82, 95% CI 0.66–1.03, I2 = 0%, p = 0.09) contributed to decreased mortality. Conversely, in the context of self-extubation events, protocolized sedation did not show a significant decrease compared to usual ICU management, with an RR of 1.20 [95% CI 0.49–2.94, I2 = 35%; p = 0.69].

Regarding ventilation-related outcome, analysis of nine studies revealed that protocolized sedation led to a reduction in ventilation days by 1.12 days [95% CI − 2.11 to − 0.14, I2 = 89%; p = 0.03]. Notably, daily interruption demonstrated a more pronounced effect, showing a decrease of 2.50 days [95% CI − 3.19 to − 1.81, I2 = 0%; p < 0.01], while algorithm-based sedation was not statistically significant, resulting in 1.15 fewer days [95% CI − 2.48 to − 0.18, I2 = 87%; p = 0.9]. Furthermore, for the duration of ICU stay, protocolized sedation, both by daily interruption and algorithm, exhibited a reduction of 2.24 days [95% CI − 3.59 to − 0.89, I2 = 81%; p < 0.01], with subgroup analysis reducing heterogeneity to I2 = 0%. The results are visually represented in Figs. 2, 3, 4, and 5.

Mortality forest plot by protocolized sedation methodology

Self-extubation forest plot by protocolized sedation methodology

Days in ventilation forest plot by protocolized sedation methodology

Days in ICU forest plot by protocolized sedation methodology

No publication bias was identified, as evidenced by the absence of asymmetry in funnel plots for all evaluated outcomes, as illustrated in Fig. 6A–D. This indicates that the findings presented in this review are unlikely to be distorted by selective reporting, enhancing the robustness and reliability of the reported results.

Funnel plot. A Ventilation days. B Days on ICU. C Self-extubation. D Mortality

Given the considerable prevalence of bias related to lost data, a sensitivity analysis was conducted with a subset of 3 studies. The results for self-extubating events (RR = 1.19, 95% CI 0.08–17.22) and reduced days of ventilation (RR = 2.95, 95% CI − 5.39 to − 0.51) and ICU stay (RR = 4.82, 95% CI − 9.36 to − 0.28) maintained a consistent direction of effect, although with variations in magnitude compared to the overall results. Mortality, however, exhibited a nonsignificant RR of 0.70 (95% CI 0.48–1.02). A secondary sensitivity analysis, excluding the only study with concerns regarding the randomization process, indicated a shift in the ventilation day differences (RR = − 0.78, 95% CI − 1.74 to 0.18), with no statistically significant variations identified.

Based on the comprehensive assessment of the identified risks, predominantly low in various components with some concerns related to missing data, coupled with remarkable consistency in the results and the potential explanation of heterogeneity by the type of protocolized sedation, moderate evidence was established for the effectiveness of protocolized sedation in reducing mortality, ventilation days, and ICU stay. In contrast, due to significant inconsistency in the outcomes and the inability to elucidate heterogeneity through subgroup analysis, protocolized sedation was determined to have very low evidence concerning the occurrence of self-extubating events. A detailed summary of these findings is presented in Table 3.