In this randomized clinical trial in 737 cardiac surgical patients, we did not find a difference in the incidence and duration of delirium over the first 4 postoperative days between patients who received a high dose of intraoperative dexamethasone and those who received placebo, despite controlling for other factors that could have affected delirium incidence. Sensitivity analyses in which deceased patients were assigned to have delirium did not change our findings.
Previous reports on the incidence of delirium in cardiac surgery vary widely ranging from 3% to 50%.2–4,7,16,21,22 The incidence found in this study corresponds closely to a similar, large trial that reported an incidence of 11.9% in 1528 cardiac patients.22 The incidence of postoperative delirium in our Utrecht cohort (14.5%) was higher than in the overall DECS study population (10.4%).20 This most likely resulted from different methods to detect delirium between the 2 cohorts. In Utrecht, delirium was evaluated in detail on a daily basis by trained research personnel. By contrast, patients at the other centers were not screened for delirium using a formalized procedure. Instead, delirium was deemed to have occurred based on a retrospective review of the patient’s record and documentation of antipsychotics use in discharge letters. The results of our study support earlier observations that failure to use a validated delirium screening will miss delirium that is present.21,22
Compared with other assessment methods for delirium in the ICU, the CAM-ICU shows good validity and sensitivity in a research setting35 and is proven to be superior to diagnosis by critical care physicians alone.21 However, it might not capture the fluctuating nature of the disease. To overcome this, we also based our definition of delirium on inspection of the medical records and prescription of antipsychotics.
The anti-inflammatory effects of dexamethasone may lead to a number of potential beneficial effects in patients undergoing cardiac surgery, including potential decrease of cerebral edema and neuroinflammation, improved pulmonary gas exchange, and the reduced need for postoperative inotropic support.17 We hypothesized that dexamethasone would reduce the occurrence of delirium, either directly through its anti-inflammatory effect or indirectly through faster postsurgical recovery that would reduce the risk for delirium. Although there is some evidence that inflammation is an important mechanism for postoperative cognitive dysfunction,10 the results of our investigation suggest that other, not yet identified, factors might play a greater role in the development of delirium in this population, also explaining why (pre) treatment with other drugs with anti-inflammatory properties such as statins36 and haloperidol37,38 does not seem to decrease the incidence of postoperative delirium.
Our study has several strengths including its large sample size compared with that of other studies investigating delirium, the detailed method that was used to identify delirium, and the use of multivariate models to adjust for possible confounding. The potential limitations are, first, that the assessment for delirium was limited to the first 4 postoperative days. While it is possible that patients may have developed delirium after 4 days, previous studies suggest that the vast majority of delirium in this population is clinically apparent over the first 3 postoperative days. The number of patients with later-onset delirium, who may have been missed in the current study, is therefore likely very small.9,39–41 Second, we may also have missed delirium in patients who were transferred before the fourth postoperative day. It is, however, unlikely that this would have influenced our findings, because the number of patients who were transferred before the fourth day was low and similar between the 2 study groups. Third, we did not collect data on some potential risk factors for delirium, including preoperative cognitive status, education level, sensory impairment, and history of psychiatric disease. Although these factors may be relatively rare in a population undergoing elective cardiac surgery, we cannot exclude that there may have been a disbalance between the 2 study groups, despite the randomized, controlled design of the trial. Finally, to obtain full workday and weekend coverage on delirium assessments, 7 individual observers were involved in this study who were thoroughly trained by 2 staff members (AJCS, MMJvE). Despite this extensive training, interindividual differences in assessment may have occurred.
In conclusion, the administration of a single intraoperative injection of high-dose dexamethasone did not influence the incidence or duration of delirium in the first 4 days after cardiac surgery.
We would like to acknowledge Linda M. Peelen, PhD, biostatistician at the Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands for her support in this revision.
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