Nurse-Driven Sedation Protocols and Their Impact on Mechanical Ventilation Duration

Introduction

Sedation is frequently necessary to ensure comfort, safety, and ventilator synchrony among mechanically ventilated intensive care unit patients, yet prolonged or excessive sedation, particularly sedation managed without a structured target or systematic daily reassessment, has been consistently associated with longer duration of mechanical ventilation, increased incidence of delirium, and prolonged intensive care unit stay (Kress et al., 2000; Barr et al., 2013). Landmark trials evaluating daily sedation interruption and paired spontaneous awakening and breathing trial protocols have demonstrated that systematically reducing sedative accumulation, without compromising patient comfort or safety, can meaningfully shorten the duration of mechanical ventilation (Kress et al., 2000; Girard et al., 2008).

Nurses, given their continuous bedside presence and primary responsibility for titrating sedative infusions in most intensive care unit settings, are positioned to serve as the primary drivers of protocolized, target-based sedation management, an approach evaluated in an early and influential trial demonstrating that a nursing-implemented sedation protocol could significantly reduce ventilation duration relative to unstructured, physician-directed sedation orders (Brook et al., 1999). The subsequent development and validation of standardized sedation assessment instruments, including the Richmond Agitation-Sedation Scale, provided nurses with a reliable, reproducible tool for titrating sedation to a specific, physician-prescribed target rather than relying on subjective, unstructured assessment (Sessler et al., 2002; Ely et al., 2003).

Despite this foundational evidence, and subsequent updates to national clinical practice guidelines explicitly recommending protocolized, nurse-driven, target-based sedation management combined with daily spontaneous awakening trials (Devlin et al., 2018), sedation practice in many intensive care units continues to vary considerably, and continued trial evidence evaluating specific protocol implementations within contemporary practice settings remains valuable given ongoing variation in local implementation fidelity and combination with other elements of the broader ABCDE bundle (Balas et al., 2014). The purpose of this randomized controlled trial was to evaluate the effect of a nurse-driven sedation protocol, incorporating a validated sedation scale target and daily paired spontaneous awakening and breathing trials, on duration of mechanical ventilation among adult intensive care unit patients, relative to usual, physician-directed sedation management.

Methods

Design. This study used an individually randomized, parallel-group, single-blind (outcome assessor blinded) controlled trial design with outcomes assessed through the index hospitalization and 28-day mortality follow-up.

Setting and participants. Participants were recruited from two intensive care units within a single academic health system between March 2025 and February 2026. Adults aged 18 years or older requiring mechanical ventilation expected to exceed 24 hours were eligible. Patients with a primary neurological injury precluding sedation scale assessment, those receiving neuromuscular blockade at enrollment, and those with a pre-existing do-not-resuscitate order limiting the appropriateness of a spontaneous breathing trial protocol were excluded. Of 342 patients screened, 286 met eligibility criteria and were enrolled after surrogate or patient informed consent was obtained.

Randomization and blinding. Eligible participants were randomized 1:1 to the nurse-driven sedation protocol or usual care using a computer-generated randomization sequence with permuted blocks, stratified by admitting unit and admission diagnosis category (medical versus surgical). Given the nature of the intervention, bedside nurses and treating physicians could not be blinded; research staff assessing delirium and abstracting length-of-stay outcomes were blinded to group assignment.

Intervention. Participants randomized to the protocol condition were managed using a structured, nurse-driven sedation algorithm. The treating physician prescribed a target Richmond Agitation-Sedation Scale (RASS) score (Sessler et al., 2002), and bedside nurses titrated sedative infusions at least hourly to maintain the patient within the prescribed RASS range, following a standardized dose-adjustment algorithm. Each morning, in the absence of a contraindication such as active seizure, escalating vasopressor requirement, or active myocardial ischemia, the bedside nurse initiated a spontaneous awakening trial by discontinuing sedative infusion, paired with the respiratory therapist’s simultaneous spontaneous breathing trial, consistent with the paired awakening-and-breathing approach validated in prior trial evidence (Girard et al., 2008).

Usual care. Participants randomized to usual care received sedation management directed by ongoing physician orders without a standardized nurse-driven titration algorithm, structured daily spontaneous awakening trial protocol, or mandated pairing with spontaneous breathing trial timing, consistent with sedation practice at the study sites prior to the trial.

Outcome measures. The primary outcome was duration of mechanical ventilation, in days, from intubation to successful extubation without need for reintubation within 48 hours. Secondary outcomes included intensive care unit length of stay, hospital length of stay, cumulative sedative exposure expressed as midazolam-equivalent dose, delirium incidence assessed using the Confusion Assessment Method for the ICU (CAM-ICU) (Ely et al., 2001), self-extubation, and 28-day all-cause mortality.

Statistical analysis. Duration of mechanical ventilation and length-of-stay outcomes, given their expected right-skewed distribution, were summarized using median and interquartile range and compared using the Mann-Whitney U test. Delirium incidence was analyzed using logistic regression adjusted for admission diagnosis category and baseline severity of illness (APACHE II score), yielding an adjusted odds ratio. Self-extubation and mortality were compared using the chi-square test. A two-sided p value of less than .05 was considered statistically significant.

Results

A total of 286 patients were randomized, 143 to the nurse-driven sedation protocol and 143 to usual care. As shown in Table 1, the two groups were closely balanced across demographic, severity-of-illness, and admission-category characteristics at baseline. All randomized patients were included in the intention-to-treat analysis.

Median duration of mechanical ventilation was significantly shorter in the protocol group than the usual care group (4.5 days, IQR 2.8–7.1, vs. 7.6 days, IQR 4.6–11.9; Mann-Whitney U test, p < .001), as shown in Figure 1.

Secondary outcomes showed a consistent pattern favoring the protocol group, summarized in Figure 2. Intensive care unit length of stay was significantly shorter in the protocol group (median 6.1 vs. 9.4 days, p < .001), as was cumulative sedative exposure, expressed as midazolam-equivalent dose (mean 118 vs. 210 mg over the ventilation period, p < .001). Delirium incidence, assessed via CAM-ICU, was significantly lower in the protocol group (38.5% vs. 54.5%, adjusted OR 0.53, 95% CI 0.34–0.83, p = .006).

Self-extubation rate did not differ significantly between groups (4.9% vs. 3.5%, chi-square test, p = .55), nor did 28-day all-cause mortality (14.7% vs. 16.8%, p = .62), as shown in Figure 3, indicating that the protocol’s efficiency gains were not achieved at the cost of increased premature extubation or mortality risk.

Discussion

This randomized controlled trial found that a nurse-driven sedation protocol, combining algorithm-based titration to a target Richmond Agitation-Sedation Scale score with daily paired spontaneous awakening and breathing trials, significantly reduced duration of mechanical ventilation, intensive care unit length of stay, cumulative sedative exposure, and delirium incidence, without a corresponding increase in self-extubation or mortality. These findings are consistent with, and extend into a contemporary practice setting, the foundational trial evidence establishing both nursing-implemented sedation protocols (Brook et al., 1999) and paired spontaneous awakening and breathing trials (Girard et al., 2008) as effective strategies for reducing mechanical ventilation duration.

The magnitude of ventilation duration reduction observed in this trial, a 41% relative reduction in median duration, is comparable to effects reported in the original nursing-implemented sedation protocol trial and the subsequent Awakening and Breathing Controlled trial (Brook et al., 1999; Girard et al., 2008), suggesting that the core mechanism identified in these foundational studies, systematic prevention of sedative accumulation through structured, nurse-driven titration and daily awakening, remains similarly effective when implemented within current intensive care unit practice, more than two decades after the original protocol trials.

The significant reduction in delirium incidence observed in the protocol group is consistent with the broader literature linking cumulative sedative exposure, particularly benzodiazepine exposure, to increased delirium risk in mechanically ventilated patients, and reinforces current clinical practice guideline recommendations explicitly linking protocolized, lighter sedation targets to reduced delirium burden as part of the broader ABCDE bundle approach to critical care (Devlin et al., 2018; Balas et al., 2014).

The absence of a significant difference in self-extubation rate between groups is a reassuring safety finding, addressing a plausible concern that lighter, more frequently interrupted sedation might increase the risk of premature, unplanned extubation; this finding is consistent with prior sedation protocol and daily interruption trials, which have similarly found no significant increase in self-extubation despite systematically reduced sedative exposure (Kress et al., 2000; Mehta et al., 2012).

Several limitations should be considered. The inability to blind bedside nurses and treating physicians to group assignment, an inherent limitation of behavioral and protocol-based intervention trials of this kind, leaves open the possibility that some portion of the observed effect reflects heightened general attentiveness to sedation and weaning readiness among protocol-group nurses, rather than the specific structured algorithm and paired trial timing alone; however, the magnitude and specificity of the observed effects, including the significant reduction in the biologically plausible delirium outcome, make a pure attention effect an unlikely full explanation. This trial was conducted within two intensive care units at a single academic health system, and generalizability to intensive care units with different nurse staffing ratios, baseline sedation practice, or patient case-mix should be considered carefully. The trial excluded patients with primary neurological injury precluding sedation scale assessment, and findings may not generalize directly to this specific, clinically important subpopulation.

Future research should evaluate this protocol’s effectiveness specifically within neurocritical care populations, where sedation scale-based titration requires modification, and should examine the protocol’s integration with other components of the broader ABCDE bundle, including early mobility, to determine whether combined implementation produces effects beyond the sedation-focused component alone. Taken together, the findings of this trial reaffirm nurse-driven, protocolized, target-based sedation management, paired with daily spontaneous awakening and breathing trials, as an effective and safe strategy for reducing mechanical ventilation duration, intensive care unit length of stay, and delirium among mechanically ventilated intensive care unit patients.

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