European Journal of Cardiovascular Medicine

Mechanical ventilation (MV) remains a critical intervention in intensive care units (ICU) worldwide, supporting patients with respiratory failure from diverse etiologies. While lifesaving, MV is associated with significant risks and complications, including ventilator-associated pneumonia, ventilator-induced lung injury, and prolonged ICU stay. One of the essential aspects of MV management is sedation, which aims to optimize patient comfort, facilitate synchrony with the ventilator, reduce oxygen consumption, and prevent agitation or accidental extubation. However, sedation practices vary considerably, influenced by patient factors, ICU protocols, and clinician preferences. Sedation in the ICU has evolved over decades from deep sedation to lighter sedation or even sedation interruption strategies. Over-sedation can lead to prolonged mechanical ventilation, increased ICU length of stay, and higher morbidity and mortality rates, whereas under-sedation can cause patient discomfort, agitation, and increased risk of self-extubation and hemodynamic instability[1,2]. Current guidelines emphasize the importance of individualized sedation, aiming for the minimum effective dose to achieve patient comfort while maintaining safety[3]. Commonly used sedatives include benzodiazepines (midazolam, lorazepam), propofol, dexmedetomidine, and opioids (fentanyl, morphine). Each drug has distinct pharmacokinetic and pharmacodynamic profiles influencing sedation depth, duration, and adverse effects. For example, benzodiazepines are associated with increased delirium and prolonged ventilation, while dexmedetomidine has been shown to reduce delirium and facilitate early extubation[4]. Propofol, favored for its rapid onset and offset, requires close monitoring due to risks of hypotension and propofol infusion syndrome.

The assessment of sedation depth is crucial for titrating sedative medications appropriately. Tools such as the Richmond Agitation-Sedation Scale (RASS) and the Sedation-Agitation Scale (SAS) are widely used to objectively measure sedation levels, helping to prevent both over- and under-sedation. Regular monitoring also aids in detecting ICU delirium, a common and serious complication linked to sedative use and poor outcomes[5].

Aim

To analyze the sedation practices and their clinical outcomes in mechanically ventilated patients admitted to the intensive care unit.

Objectives

1. To evaluate the types of sedative agents used and sedation depth in mechanically ventilated ICU patients.
2. To assess the duration of mechanical ventilation and ICU stay in relation to sedation practices.
3. To determine the association between sedation practices and patient outcomes, including incidence of delirium and ICU mortality.

Source of Data

Data were obtained from patients admitted to the intensive care unit, who required mechanical ventilation and sedation during the study period.

Study Design

This was a cross-sectional observational study designed to analyze sedation practices and associated clinical outcomes in mechanically ventilated ICU patients.

Study Location

The study was conducted in the multidisciplinary ICU of at tertiary care teaching hospital.

Study Duration

The study was carried out over a period of one year from January 2024 to December 2024.

Sample Size

A total of 120 mechanically ventilated patients receiving sedation during their ICU stay were included in the study.

Inclusion Criteria

·         Patients aged 18 years and above.

·         Patients requiring invasive mechanical ventilation for more than 24 hours.

·         Patients receiving sedative medications as part of their ICU care.

Exclusion Criteria

·         Patients with documented neurological diseases affecting consciousness level (e.g., stroke, traumatic brain injury).

·         Patients on palliative care or with Do Not Resuscitate (DNR) orders.

·         Patients with incomplete medical records or missing sedation data.

Procedure and Methodology

Patient demographic details, clinical diagnoses, sedation protocols, types and doses of sedative agents used, and sedation depth scores (using Richmond Agitation-Sedation Scale - RASS, ranging from +4 to -5) were collected from ICU charts and electronic medical records. Sedation was assessed regularly as per unit protocol. Data on duration of mechanical ventilation, ICU length of stay, incidence of ICU delirium (assessed using CAM-ICU), and ICU mortality were recorded.

Sedation depth was categorized as follows:

·         Deep sedation (RASS ≤ -3)

·         Moderate sedation (RASS -2 to -1)

·         Light sedation (RASS 0)

·         Agitation (RASS +1 to +4)

Sample Processing

Data were anonymized and entered into a secure database. Sedation parameters were tabulated along with patient outcome variables for analysis.

Statistical Methods

Data were analyzed using statistical software SPSS version 27.0. Descriptive statistics were calculated for patient demographics and sedation practices. Continuous variables were expressed as mean ± standard deviation or median with interquartile range as appropriate. Categorical variables were presented as frequencies and percentages.

Comparisons between groups - different sedation depth categories were made using the chi-square test for categorical variables and Student’s t-test or Mann-Whitney U test for continuous variables. Correlations between sedation practices and clinical outcomes were assessed using Pearson or Spearman correlation coefficients. A p-value <0.05 was considered statistically significant.

Data Collection

Data were collected prospectively by the principal investigator and ICU nursing staff using a structured proforma designed for the study. All relevant data were checked for completeness and accuracy. Ethical approval was obtained from the Institutional Ethics Committee prior to study initiation, and informed consent was waived due to observational nature of the study.

Table 1: Demographic and Clinical Characteristics of Mechanically Ventilated Patients (n=120)

The study population comprised 120 mechanically ventilated patients with a mean age of 56.3 years (SD ±16.2), ranging approximately between 53.4 and 59.2 years. Males constituted a majority with 71 patients (59.2%), while females accounted for 49 (40.8%), showing no significant gender difference (χ² = 0.24, p = 0.62). The primary diagnoses among these patients included sepsis in 43 (35.8%), respiratory failure in 37 (30.8%), neurological conditions in 22 (18.3%), and trauma in 18 (15.1%) patients; these differences across diagnostic categories were not statistically significant (χ² = 3.17, p = 0.21). The severity of illness as assessed by the APACHE II score averaged 18.7 (SD ±6.9) with a confidence interval from 17.2 to 20.2. Common comorbidities included hypertension in 52 patients (43.3%), diabetes mellitus in 38 (31.7%), and chronic kidney disease in 17 (14.2%), with no statistically significant differences observed among these comorbid conditions (χ² = 1.02, p = 0.31). This demographic and clinical profile reflects a typical ICU mechanically ventilated cohort with diverse underlying illnesses and comorbidities.

Table 2: Sedation Practices and Sedation Depth in Mechanically Ventilated ICU Patients (n=120)

*Significant at p < 0.05

Among the sedative agents used, midazolam was the most common, administered to 56 patients (46.7%), followed by propofol in 39 (32.5%) and dexmedetomidine in 25 (20.8%) patients. The distribution of sedative agents was statistically significant (χ² = 9.87, p = 0.007), indicating variability in sedation choice across patients. The average daily doses were 4.2 mg (±1.9) for midazolam, 180.4 mg (±56.3) for propofol, and 0.7 mcg/kg/hr (±0.2) for dexmedetomidine, each with narrow confidence intervals, demonstrating consistent dosing practices.

Sedation depth, assessed by the Richmond Agitation-Sedation Scale (RASS; range +4 to -5), revealed that 41 patients (34.2%) were deeply sedated (RASS ≤ -3), 52 (43.3%) had moderate sedation (RASS -2 to -1), and 27 (22.5%) were lightly sedated (RASS 0). The sedation depth categories showed significant differences (χ² = 12.54, p = 0.002), reflecting varying sedation targets possibly tailored to clinical status.

Table 3: Duration of Mechanical Ventilation and ICU Stay in Relation to Sedation Practices (n=120)

*Significant at p < 0.05

Duration of mechanical ventilation varied significantly between sedation groups. Patients receiving midazolam had the longest ventilation duration with a mean of 8.6 days (±3.4), significantly longer compared to the propofol group (6.9 days ±2.8) and dexmedetomidine group (5.5 days ±2.1), with a t-value of 2.97 and p = 0.004. Similarly, ICU length of stay was longest in the midazolam group at 12.3 days (±4.5), followed by propofol at 10.2 days (±3.9), and dexmedetomidine at 8.7 days (±3.1), with a significant difference (t = 3.35, p = 0.001). These findings suggest that sedation choice may influence duration of mechanical ventilation and ICU hospitalization, with dexmedetomidine associated with shorter ventilation times and ICU stays.

Table 4: Association Between Sedation Practices and Patient Outcomes (Delirium and ICU Mortality) (n=120)

*Significant at p < 0.05

Regarding patient outcomes, the incidence of ICU delirium was highest among those sedated with midazolam (21 patients, 37.5%), significantly greater than in the propofol (8 patients, 20.5%) and dexmedetomidine (3 patients, 12.0%) groups (χ² = 10.21, p = 0.006). Although ICU mortality was highest in the midazolam group (14 patients, 25.0%) compared to propofol (7 patients, 17.9%) and dexmedetomidine (2 patients, 8.0%), this difference was not statistically significant (χ² = 2.87, p = 0.24). The data indicate a clear association between sedation type and delirium risk, with midazolam linked to higher delirium incidence, while no significant differences were observed in mortality outcomes across sedative groups.

Demographic and Clinical Characteristics (Table 1): The mean age of mechanically ventilated patients in this study was 56.3 ± 16.2 years, with a male predominance (59.2%), which is consistent with previous ICU cohort studies where the mean age ranged from 50 to 65 years and males typically constituted 55-65% of patients Goligher EC et al.(2015)[6] & Faust AC et al.(2016)[7]. The distribution of primary diagnoses—sepsis (35.8%), respiratory failure (30.8%), neurological conditions (18.3%), and trauma (15.1%)—reflects the typical spectrum observed in critical care settings Shetty RM et al.(2018)[8] & Stephens RJ et al.(2017)[9]. The mean APACHE II score of 18.7 ± 6.9 aligns with moderate to severe illness severity described in comparable ventilated populations. Comorbidities such as hypertension (43.3%), diabetes mellitus (31.7%), and chronic kidney disease (14.2%) were prevalent, echoing findings from other studies indicating these as common risk factors influencing ICU outcomes Porhomayon J et al.(2016)[10].

Sedation Practices and Depth (Table 2): Midazolam was the most frequently used sedative agent (46.7%), followed by propofol (32.5%) and dexmedetomidine (20.8%). This distribution highlights the ongoing preference for benzodiazepines in many ICUs despite emerging evidence favoring alternatives Olsen HT et al.(2020)[11]. The significant difference in sedative agent use (p=0.007) suggests varied clinical protocols or patient-specific considerations. Previous randomized trials and observational studies have demonstrated that benzodiazepines are associated with higher delirium rates and prolonged ventilation compared to dexmedetomidine or propofol Qi Z et al.(2021)[12]. The sedation depth results, with 34.2% deeply sedated patients, emphasize that over-sedation remains common and is known to adversely impact outcomes.

Duration of Mechanical Ventilation and ICU Stay (Table 3): Patients sedated with midazolam had significantly longer mechanical ventilation durations (8.6 ± 3.4 days) and ICU stays (12.3 ± 4.5 days) compared to propofol and dexmedetomidine groups (p=0.004 and p=0.001, respectively). These findings are consistent with those of Shehabi Y et al.(2018)[13] and Burry L et al.(2014)[14],

who reported that dexmedetomidine use was associated with reduced ventilation duration and ICU length of stay versus benzodiazepines. The shorter ventilation and ICU stay with dexmedetomidine could relate to its favorable pharmacokinetics and reduced delirium incidence.

Association between Sedation Practices and Outcomes (Table 4): The incidence of ICU delirium was highest in the midazolam group (37.5%), significantly greater than in the propofol (20.5%) and dexmedetomidine (12.0%) groups (p=0.006). This aligns with literature showing benzodiazepines significantly increase delirium risk compared to non-benzodiazepine sedatives Tanaka LM et al.(2014)[4]. Although ICU mortality was highest in the midazolam group (25.0%), the difference was not statistically significant (p=0.24), reflecting that sedation choice impacts morbidity (delirium) more clearly than mortality, as also seen in prior meta-analyses Curley MA et al.(2015)[15]. The lower delirium and mortality rates in dexmedetomidine-treated patients further support its potential benefits in ICU sedation.

This cross-sectional analysis of sedation practices in mechanically ventilated ICU patients revealed a predominant use of midazolam, followed by propofol and dexmedetomidine. Sedation depth varied, with a considerable proportion of patients experiencing deep sedation, which correlated with prolonged mechanical ventilation and ICU length of stay. Dexmedetomidine use was associated with shorter ventilation duration, reduced ICU stay, and significantly lower incidence of delirium compared to benzodiazepines. Although mortality differences between sedation groups were not statistically significant, the findings underscore the importance of tailored sedation strategies to optimize patient outcomes. The study highlights the need for adherence to sedation protocols favoring agents that minimize delirium and facilitate early weaning from mechanical ventilation.

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