Strategies for minimizing the long-term effects of cognitive impairment have mostly focused on preventing it.
During the ICU stay, optimizing hemodynamic, glucose, and oxygenation levels may prevent future long-term complications.18
Also, the association between sedation, delirium, and consequent cognitive impairment (see above) has led many investigators to apply the “ABCDE” bundle of strategies.25,45,46 Specifically, ABCDE stands for awakening and breathing, choice of sedatives with fewer adverse effects, daily delirium monitoring, and early mobility exercise. These strategies have been shown in randomized controlled trials to prevent delirium; however, they have not been proved to prevent cognitive impairment.
Awakening and breathing
In the Awakening and Breathing Controlled Trial,47 patients in the intervention group (ie, those who had their sedatives interrupted every morning to see if they would awaken, and if so, if they could breathe on their own) were extubated 3 days sooner than those in the control group (who underwent daily trials of spontaneous breathing, if deemed safe). Also, ICU and hospital length of stay were shorter by 4 days. Best of all, over 1 year, the mortality rate was lower by 14 absolute percentage points.
Choice of sedatives
Often, mechanically ventilated patients are given benzodiazepines, opiates, and propofol (Diprivan).21 Dexmedetomidine (Precedex), a newer agent, is an alpha-2 agonist and may offer advantages over the others.
To date, three randomized controlled trials have assessed the effect of dexmedetomidine in terms of outcomes associated with delirium, and one trial evaluated its association with intellectual capacity in ICU patients.
The Maximizing Efficacy of Targeted Sedation and Reducing Neurological Dysfunction (MENDS) trial randomized patients on mechanical ventilation to receive either dexmedetomidine or lorazepam (Ativan).48 Dexmedetomidine-treated patients had 4 more days alive without delirium or coma (7 vs 3 days, P = .01).
Subsequently, the Safety and Efficacy of Dexmedetomidine Compared With Midazolam (SEDCOM) trial compared dexmedetomidine and midazolam (Versed) in mechanically ventilated patients. Those who received dexmedetomidine had a lower incidence of delirium (54% vs 76%, P < .001), and 2 fewer days on mechanical ventilation.49
Reade et al50 evaluated time to extubation in already delirious patients randomized to receive either dexmedetomidine or haloperidol (Haldol). Those receiving dexmedetomidine had a shorter time to extubation as well as a shorter ICU length of stay.
The Acute Neuroscience Intensive Care Sedation Trial51 evaluated intellectual capacity in neurological ICU patients sedated with either dexmedetomidine or propofol. This randomized, double-blind trial included 18 brain-injured and 12 non-brain-injured intubated patients. In a crossover protocol, each received the combination of fentanyl (Sublimaze) and propofol and the combination of fentanyl and dexmedetomidine.
Cognition was evaluated using the Adapted Cognitive Exam (ACE), which assesses intellectual capacity through orientation, language, registration, attention, calculation, and recall. This 10-minute examination does not require verbal communication, as it relies on the ability to respond to yes-or-no questions and perform simple motor tasks. The maximum possible score is 100 points.
Interestingly, while on propofol, the patients’ adjusted ACE scores went down by a mean of 12.4 points, whereas they went up by 6.8 points while on dexmedetomidine. Even though brain-injured patients required less sedation than non-brain-injured patients, the effect of dexmedetomidine and propofol did not change.51
In summary, these studies suggest that all sedatives are not the same in their short-term and intermediate-term outcomes.
In our practice, we use dexmedetomidine as our first-line sedation therapy. In patients with hemodynamic instability, we use benzodiazepines. We reserve propofol for very short periods of intubation or for hemodynamically stable patients who cannot be sedated with dexmedetomidine.
Daily delirium monitoring
As mentioned above, delirium affects many patients on mechanical ventilation, and it is highly underrecognized if valid tests are not used.52 Therefore, it is critically important to be familiar with the tests for assessing delirium. Of these, the Confusion Assessment Method for the ICU is probably the one with the best performance, with a sensitivity of 93% to 100% and a specificity of 98% to 100%.53,54
A landmark study paired the awakening and breathing strategy with early mobilization through physical and occupational therapy in the ICU.55 Patients in the intervention group had a higher rate of return to independent functional status upon hospital discharge and a shorter duration of mechanical ventilation and delirium.
In conclusion, even though direct prevention of cognitive dysfunction is a challenging task, the ABCDE approach targets individual risk factors for delirium, which is an important contributor to cognitive impairment. Whether the ABCDE bundle directly affects the development of cognitive impairment requires further investigation.