Delirium is a frequent and serious neuropsychiatric complication in critically ill patients, particularly those requiring mechanical ventilation in the intensive care unit (ICU). Characterized by acute confusion, impaired attention, and fluctuating mental status, ICU delirium is associated with prolonged mechanical ventilation, increased ICU and hospital stays, higher healthcare costs, long-term cognitive dysfunction, and elevated mortality risk [1,2]. Its pathophysiology is multifactorial, involving neuroinflammation, neurotransmitter dysregulation, sleep disruption, and sedative-induced neurotoxicity [3].

Sedation plays a pivotal role in the management of mechanically ventilated ICU patients to ensure comfort, safety, and ventilator synchrony. However, the selection of sedative agents may significantly influence the development and severity of delirium. Propofol, a widely used GABAergic sedative-hypnotic, provides rapid onset and short duration of action, but its effects on delirium risk remain inconsistent [4]. On the other hand, dexmedetomidine, a highly selective α2-adrenergic receptor agonist, exerts sedative, anxiolytic, and analgesic effects without causing significant respiratory depression. Its unique mechanism—sparing GABA receptors and preserving non-REM sleep architecture—has been hypothesized to reduce the incidence of delirium [5,6].

Several studies, including large randomized trials and meta-analyses, have compared the efficacy of dexmedetomidine versus propofol in minimizing ICU delirium, yielding varying results. While some investigations demonstrate superior cognitive outcomes with dexmedetomidine [1–3], others highlight the need for further high-quality trials to confirm its comparative advantage in different ICU subpopulations [4–6].

This study aims to evaluate and compare the effects of dexmedetomidine versus propofol on the incidence of delirium in mechanically ventilated ICU patients and to assess secondary outcomes including duration of mechanical ventilation, ICU length of stay, mortality, and sedation-related adverse events.

Study Design

This study was designed as a prospective, randomized, controlled comparative trial to assess the effect of dexmedetomidine versus propofol on the incidence of delirium and other clinical outcomes in mechanically ventilated ICU patients.

Study Setting and Duration

The study was conducted in the Intensive Care Unit (ICU) of Government Medical College, Srikakulam, over a period of four months, from March 2024 to June 2024.

Study Population

Inclusion Criteria:

Patients aged 18 years and above

Requiring mechanical ventilation for more than 24 hours

Needing continuous sedation in the ICU

Exclusion Criteria:

Pre-existing cognitive impairment or diagnosed delirium

Neurological or psychiatric disorders

Severe hepatic or renal dysfunction

Use of antipsychotic or sedative medications prior to ICU admission

Sample Size and Randomization

A total of 100 patients meeting the inclusion criteria were recruited and randomly assigned to two groups (n = 50 each) using a computer-generated random number sequence:

Group D (Dexmedetomidine Group): Received intravenous dexmedetomidine infusion at 0.2–0.7 μg/kg/h

Group P (Propofol Group): Received intravenous propofol infusion at 1–3 mg/kg/h

Sedation was titrated to achieve a target Richmond Agitation-Sedation Scale (RASS) score between -2 and 0 in both groups.

Outcome Measures

Primary Outcome:

Incidence of delirium, measured using the Confusion Assessment Method for the ICU (CAM-ICU), assessed twice daily (morning and evening)

Secondary Outcomes:

Duration of mechanical ventilation

ICU length of stay

ICU mortality

Adverse events related to sedation, such as hypotension and bradycardia

Data Collection Tools and Procedure

All relevant clinical data were collected using a structured case record form. Sedation levels were monitored using RASS, while delirium assessment was performed by trained ICU staff using the validated CAM-ICU tool.

Statistical Analysis

Data were analyzed using IBM SPSS Statistics for Windows, Version 26.0 (IBM Corp., Armonk, NY, USA).Continuous variables were presented as mean ± standard deviation and compared using the independent sample t-testCategorical variables were expressed as frequencies and percentages and analyzed using the chi-square test or Fisher’s exact test, as appropriateA p-value < 0.05 was considered statistically significant.

Necessary permissions were obtained from the concerned authorities before starting the study.  The study followed the ethical principles of the Declaration of Helsinki and ensured confidentiality, voluntariness, and the right to withdraw at any time without prejudice to treatment.

A total of 100 mechanically ventilated ICU patients were enrolled and randomly assigned to receive either dexmedetomidine (n = 50) or propofol (n = 50) as their primary sedative agent. The baseline demographic and clinical characteristics were comparable between the two groups (data not shown).

The incidence of delirium, assessed using the Confusion Assessment Method for the ICU (CAM-ICU), was significantly lower in the dexmedetomidine group compared to the propofol group. Specifically, 11 patients (22%) in the dexmedetomidine group experienced delirium, versus 20 patients (40%) in the propofol group, yielding a statistically significant difference (p = 0.045), as presented in Table No. 1.

Table No:1. Comparison of Dexmedetomidine vs. Propofol on Clinical Outcomes (n = 100)

*Statistically significant at p < 0.05

Figure No.1: Comparison of Dexmedetomidine vs. Propofol on Clinical Outcomes

Furthermore, the duration of mechanical ventilation was significantly shorter in the dexmedetomidine group, with a mean duration of 4.2 ± 1.5 days, compared to 5.1 ± 1.8 days in the propofol group (p = 0.030). This finding suggests that dexmedetomidine may facilitate earlier weaning from ventilatory support.

Although the ICU length of stay was slightly lower in the dexmedetomidine group (7.6 ± 2.4 days) than in the propofol group (8.1 ± 2.6 days), the difference did not reach statistical significance (p = 0.210). Likewise, ICU mortality rates were comparable between the two groups, with 4 deaths (8%) in the dexmedetomidine group and 5 deaths (10%) in the propofol group (p = 0.729).

In terms of hemodynamic adverse events, the occurrence of hypotension episodes was lower in the dexmedetomidine group (12%) compared to the propofol group (18%), though the difference was not statistically significant (p = 0.402). Conversely, bradycardia was more frequently observed in the dexmedetomidine group (20%) compared to the propofol group (8%), approaching but not achieving statistical significance (p = 0.082).

Overall, these findings suggest that dexmedetomidine is associated with a lower incidence of ICU delirium and shorter mechanical ventilation duration, without significantly increasing ICU mortality or adverse events, compared to propofol (Table No. 1).

The present study demonstrates that dexmedetomidine is associated with a significantly lower incidence of delirium compared to propofol among mechanically ventilated ICU patients. Delirium was observed in 22% of patients in the dexmedetomidine group versus 40% in the propofol group (p = 0.045), indicating a substantial cognitive benefit. These findings are in agreement with a comprehensive meta-analysis by Lewis et al. [7], which concluded that dexmedetomidine significantly reduces the risk of delirium in mechanically ventilated adults compared to other sedatives.

The neuroprotective effects of dexmedetomidine may be attributed to its selective α2-adrenergic agonism, which promotes arousable sedation, better sleep architecture, and reduced neuroinflammation [8,9]. Wang et al. [8] further demonstrated its efficacy in septic patients, showing improved neurological outcomes and reduced sedation-related complications. Similarly, Ahmed and Murugan [9] highlighted dexmedetomidine’s favorable pharmacological profile for ICU sedation, especially where cognitive preservation is crucial.

The shorter mean duration of mechanical ventilation observed in this study (4.2 ± 1.5 days for dexmedetomidine vs. 5.1 ± 1.8 days for propofol, p = 0.030) is supported by the findings of Wanat et al. [10] and Dou et al. [11], both of whom reported faster ventilator weaning with dexmedetomidine due to enhanced patient-ventilator synchrony and lighter sedation levels. Dou et al. [11] also reported a reduced incidence of ventilator-associated pneumonia, further validating its clinical benefits.

Although ICU length of stay and mortality were not significantly different between groups in our study, prior investigations indicate that dexmedetomidine may enhance recovery and reduce ICU complications [12,13]. Busani et al. [12] highlighted its effectiveness in managing agitated delirium, while Dong et al. [13] confirmed its overall safety and efficacy in mechanically ventilated patients through a pooled analysis of randomized trials.

Regarding safety, this study found a higher, though statistically non-significant, incidence of bradycardia in the dexmedetomidine group (20% vs. 8%), a known side effect linked to its sympatholytic action. This is consistent with earlier observations across several trials and meta-analyses [7,13].

These findings emphasize the potential role of dexmedetomidine in sedation strategies that prioritize not only hemodynamic stability but also cognitive preservation. However, given the relatively small sample size and single-center setting, broader multicenter trials are warranted to validate these results and explore long-term cognitive and functional outcomes post-ICU discharge.

This study demonstrates that dexmedetomidine is more effective than propofol in reducing the incidence of ICU delirium among mechanically ventilated patients. In addition to significantly lowering delirium rates, dexmedetomidine was also associated with a shorter duration of mechanical ventilation, without increasing ICU mortality or length of stay. While bradycardia was more frequent with dexmedetomidine, it was not statistically significant and did not result in adverse clinical outcomes. These findings support the use of dexmedetomidine as a preferable sedative agent in critically ill patients where cognitive preservation is a priority. Further large-scale, multicenter trials are recommended to confirm these outcomes and guide evidence-based sedation practices.

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