Background: Sedation strategy is linked to liberation from mechanical ventilation. Approaches include nurse-driven protocols, daily sedation interruption (DSI), spontaneous-awakening and breathing trial pairing (SAT+SBT), lighter or no-sedation targets, and agent selection (dexmedetomidine, remifentanil). Objective: To synthesize evidence on how sedative choice and dose-adjustment strategies influence spontaneous breathing trials (SBTs), time to extubation, and weaning outcomes in adult ICU patients on invasive ventilation. Methods: Following PRISMA principles, we analyzed eight user-provided original studies (randomized and randomized-protocol trials) addressing protocolized sedation, DSI, SAT+SBT, no sedation plans, and sedative class comparisons; and used eight review/guideline papers for context. Outcomes included duration of mechanical ventilation (MV), ICU/hospital length of stay (LOS), SBT/extubation success, adverse events, and mortality. Results: Nurse-implemented protocols and DSI were associated with shorter MV and LOS in several trials, and pairing SAT+SBT increased ventilator-free days and accelerated ICU/hospital discharge. A no-sedation strategy reduced MV time in a single-center RCT but did not reduce 90-day mortality versus light-sedation with DSI in a multicenter RCT. Compared with midazolam, dexmedetomidine generally reduced time to extubation and delirium but increased bradycardia; remifentanil-based analgosedation shortened MV and weaning time. Conclusions: Lighter/algorithmic strategies and carefully chosen agents (dexmedetomidine, remifentanil) tend to facilitate SBT performance and earlier extubation, whereas deep/continuous GABA-ergic sedation prolongs ventilation. Implementation fidelity and patient selection remain critical.