Sedation in critically ill patients is an essential therapeutic strategy to reduce anxiety, ensure ventilator synchrony, and facilitate invasive procedures. Among the most commonly used sedatives in the intensive care unit (ICU) are propofol and dexmedetomidine, both of which are recommended by the Society of Critical Care Medicine (SCCM) guidelines for patients requiring mechanical ventilation.^[1] While the short-term efficacy and safety of these agents are well studied, evidence surrounding their long-term impact on cognitive function and cardiovascular outcomes remains limited, creating a significant gap in critical care practice. ^[2]

Propofol is a γ-aminobutyric acid (GABA) receptor agonist with rapid onset and offset, making it a preferred agent for short-term sedation. It is associated with predictable recovery profiles and reduced delirium compared to benzodiazepines. ^[3] However, propofol can cause dose-dependent hypotension, hypertriglyceridemia, and rarely, the potentially fatal propofol infusion syndrome. ^[4]

Dexmedetomidine, on the other hand, is a selective α2-adrenergic receptor agonist with sedative, anxiolytic, and analgesic-sparing properties. It promotes an arousable sedation that more closely resembles natural sleep. ^[5] Dexmedetomidine has been associated with a lower incidence of ICU delirium, reduced opioid requirements, and potential neuroprotective effects. ^[6] However, its use can be limited by bradycardia and hypotension, particularly in patients with pre-existing cardiovascular instability. ^[7]

The long-term cognitive outcomes of ICU sedation are of increasing concern. Survivors of critical illness often suffer from post-intensive care syndrome (PICS), characterised by persistent cognitive dysfunction, anxiety, depression, and post-traumatic stress disorder. ^[8] Studies have suggested that the choice of sedative may influence the trajectory of cognitive recovery. ^[9] Dexmedetomidine, by reducing delirium and preserving sleep architecture, may protect against long-term neurocognitive decline. ^[10] Propofol, while advantageous for short procedures, lacks strong evidence of long-term neurocognitive benefits. ^[11]

From a cardiovascular perspective, sedatives exert profound effects on haemodynamics. Propofol frequently induces hypotension due to systemic vasodilation, which can be detrimental in haemodynamically unstable patients. ^[12] Dexmedetomidine, through sympatholytic effects, can reduce tachyarrhythmias but may precipitate bradycardia and atrioventricular block. ^[13] Evaluating which sedative provides a more favourable long-term cardiovascular profile remains a key clinical question.

Therefore, this study was designed to directly compare dexmedetomidine versus propofol for ICU sedation, focusing specifically on long-term cognitive and cardiovascular outcomes in critically ill, mechanically ventilated patients. By integrating structured neurocognitive assessments and cardiovascular follow-up, this study aims to inform evidence-based sedation strategies that extend beyond ICU discharge.

This was a prospective, randomized controlled study conducted in a tertiary care ICU over 18 months. Ethical approval was obtained from the Institutional Review Board, and written informed consent was provided by patients’ legal surrogates.

Inclusion Criteria

• Adults aged 18–75 years.
• Patients requiring mechanical ventilation >48 hours.
• Expected ICU stay >72 hours.
• ASA physical status II–IV.
• Consent available from patient/legal representative.

Exclusion Criteria

• Known hypersensitivity to dexmedetomidine or propofol.
• Severe hepatic failure (Child–Pugh C) or renal failure requiring dialysis.
• Pre-existing severe cognitive impairment (MoCA <20).
• Advanced atrioventricular block without pacing.
• Pregnancy or lactation.
• Anticipated death within 24 hours.

Intervention

Patients were randomized (1:1) to receive either dexmedetomidine infusion (0.2–1.4 µg/kg/hr) or propofol infusion (5–50 µg/kg/min) titrated to maintain light sedation (Richmond Agitation-Sedation Scale, RASS –2 to 0). Rescue midazolam was permitted if target sedation was not achieved.

Monitoring

• Continuous haemodynamic monitoring (arterial line, ECG, SpO₂, capnography).
• Sedation depth monitored via RASS every 2 hours.
• Delirium assessed using the Confusion Assessment Method for ICU (CAM-ICU) daily.

Statistical Analysis

Data were analysed using SPSS v26. Continuous variables were compared with Student’s t-test/Mann–Whitney U, categorical with Chi-square/Fisher’s exact. Repeated measures ANOVA assessed longitudinal cognitive outcomes. Logistic regression identified predictors of poor cognitive recovery

Table 1. Baseline Characteristics of Study Participants

Table 2. ICU Sedation and Delirium Outcomes

In table 2, Both groups maintained similar sedation depth (RASS –1.4 vs –1.5). Delirium incidence was significantly lower with Dexmedetomidine (19%) than Propofol (34%, p=0.018).

Table 3. Long-Term Cognitive Outcomes (MoCA Scores)

In table 3, At 3 and 6 months, MoCA scores were higher in the Dexmedetomidine group (26.8 and 27.1) compared to Propofol (24.9 and 25.2), both highly significant (p<0.001). Cognitive decline was seen in only 12% with Dexmedetomidine versus 31% with Propofol (p=0.002).

Table 4. Cardiovascular Outcomes

In table 4, Dexmedetomidine had fewer hypotension (23% vs. 39%) and tachyarrhythmias (7% vs. 19%), both significant. However, it caused more bradycardia (21% vs. 9%, p=0.018).

Table 5. ICU and Hospital Outcomes

Table 6. Predictors of Poor Cognitive Recovery (Multivariate Logistic Regression)

In table 6, Delirium during ICU stay (OR 2.95, p=0.001). Prolonged mechanical ventilation >7 days (OR 2.41, p=0.011). Propofol sedation itself was an independent risk factor (OR 1.98, p=0.034). Age >65 and higher APACHE II scores were not statistically significant [[

This study demonstrates that dexmedetomidine provides superior long-term cognitive outcomes compared with propofol, consistent with previous trials such as the MENDS and SEDCOM studies,^[14] which reported reduced delirium incidence and improved neurological recovery with dexmedetomidine. The observed cognitive benefits likely stem from preserved sleep architecture, anti-inflammatory effects, and reduced delirium burden.^[15]

The long-term follow-up in this study strengthens the evidence by confirming sustained neurocognitive advantage at 3 and 6 months, aligning with meta-analyses showing dexmedetomidine reduces the risk of post-ICU cognitive impairment. ^[16]

Cardiovascular outcomes revealed distinct risk profiles. Dexmedetomidine reduced tachyarrhythmias, supporting its sympatholytic role, consistent with earlier findings in cardiac surgery populations. ^[17] However, the higher incidence of bradycardia aligns with prior reports. ^[18] Propofol’s association with hypotension corroborates existing literature, ^[21] reinforcing the need for careful haemodynamic monitoring during prolonged infusions.

Interestingly, no difference in 90-day mortality was observed, echoing findings from large RCTs such as SPICE III, ^[22] which reported no survival advantage of dexmedetomidine despite reduced delirium incidence. This suggests that while dexmedetomidine improves intermediate outcomes (delirium, cognition), mortality benefit remains unproven.

The predictors of poor cognitive recovery identified—delirium, prolonged mechanical ventilation, and propofol sedation—highlight modifiable ICU practices. Strategies that minimise delirium (early mobilisation, sleep hygiene, dexmedetomidine use) could significantly improve post-ICU quality of life. ^[23,24]

Limitations include single-centre design, exclusion of patients with pre-existing severe cognitive impairment, and reliance on MoCA as the sole cognitive assessment. Multicentre trials with broader neuropsychological batteries are warranted.

Dexmedetomidine offers significant long-term cognitive benefits and a more favourable cardiovascular risk profile compared to propofol for ICU sedation. While propofol remains useful in short-term sedation and haemodynamically stable patients, dexmedetomidine should be prioritised in critically ill patients requiring prolonged sedation, particularly where delirium prevention and neuroprotection are desired.

Dexmedetomidine should be considered the preferred sedative in patients at high risk of delirium or long-term cognitive decline. However, in patients with baseline bradyarrhythmia or haemodynamic instability, propofol may remain the safer choice.

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