Objective To investigate the effect of sequential sedation mode of dexmedetomidine on prognosis and delirium in mechanically ventilated patients with moderate and deep sedation requirements in the ICU.
Methods A prospective randomized controlled study was conducted after screening experiments to divide 74 mechanically ventilated patients with moderate and deep sedation requirements in the ICU of the Affiliated People's Hospital of Jiangsu University from January 2021 to December 2022 into a sequential sedation group (38 cases) and a conventional sedation group (36 cases). The duration of mechanical ventilation, length of ICU stay, total length of hospital stay, 28 d mortality, incidence of ventilator associated pneumonia (VAP) and adverse reactions (patients with unplanned extubation, re-intubation, and bradycardia), duration of sedation, dose of sedative drugs, and incidence of delirium were compared between these two groups. Serum concentrations of brain-derived neurotrophic factor (BDNF), neuron-specific enolase (NSE), and S100 calcium-binding protein B (S100B) were measured at ICU admission, on the day of diagnosis of delirium, and 48 h after diagnosis of delirium in both groups by enzyme-linked immunosorbent assay (ELLSA). A receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum concentrations of BDNF, NSE, and S100B on admission to the ICU for delirium occurrence.
Results The mechanical ventilation time [(6 ± 3) d vs. (8 ± 4) d, t = 2.555, P = 0.013], length of ICU stay [(12 ± 4) d vs. (17 ± 8) d, t = 3.371, P = 0.001], total length of stay [(23 ± 5) d vs. (31 ± 7) d, t = 5.680, P < 0.001], incidence of delirium [34.2% (13/38) vs. 58.3% (21/36), χ2 = 4.331, P = 0.037], dosage of sedative midazolam [(2.7 ± 1.7) mg/kg vs. (4.3 ± 2.3) mg/kg, t = 3.416, P = 0.001], and duration of sedation [(7.3 ± 2.4) d vs. (9.7 ± 3.1) d, t = 3.735, P < 0.001] in the sequential sedation group were lower than those in the conventional sedation group. There were no significant differences in the 28 d mortality, incidence of VAP, patients with accidental extubation, re-intubation and bradycardia, and dosage of analgesic fentanyl between these two groups (all P > 0.05). The concentrations of BDNF [(0.37 ± 0.12) vs. (0.56 ± 0.27), t = 2.385, P = 0.023], NSE [(0.078 ± 0.020) vs. (0.234 ± 0.079), t = 6.598, P < 0.001], and S100B [(0.28 ± 0.16) vs. (0.47 ± 0.24), t = 2.521, P = 0.017] were significantly lower in the sequential sedation group than in the conventional sedation group 48 h after diagnosis of delirium. ROC curve analysis showed that BDNF at ICU admission predicted the onset of delirium in mechanically ventilated patients with an area under the curve (AUC) of 0.744 [95% confidence interval (CI) (0.627, 0.861), P < 0.001], together with the AUC of 0.711 [95%CI (0.593, 0.830), P = 0.002] for NSE and 0.727 [95%CI (0.609, 0.845), P = 0.001] for S100B.
Conclusions Sequential sedation with dexmedetomidine can reduce the occurrence of delirium, and shorten the duration of mechanical ventilation and ICU stay without increasing the incidence of adverse reactions for mechanically ventilated patients in the ICU. Serum levels of BDNF, NSE, and S100B at ICU admission can predict the occurrence of delirium.