We found that delirium after cardiac surgery was associated with a postoperative cognitive trajectory characterized by an initial decline in performance on the MMSE and a prolonged period of impairment. After adjustment for baseline differences, the mean MMSE score did not differ significantly between the patients with and those without delirium 6 months and 1 year after surgery. However, patients with postoperative delirium were significantly less likely to have returned to their preoperative level of performance at 6 months than were patients without delirium. These findings suggest that delirium, which was once thought of as a short-term, transient cognitive disorder, may have longer-term observed effects on cognitive function in patients who have undergone cardiac surgery. This study establishes an association between delirium after cardiac surgery and cognitive dysfunction by means of preoperative and serial objective assessments of cognitive function and state-of-the-art assessments of delirium, both of which were not, to our knowledge, used in previous studies.33–38
With the aging of the patient population undergoing cardiac surgery and increases in survival after surgery, clinicians and patients are increasingly concerned with factors associated with quality of life, including cognitive status, as major outcomes of surgery.11,15
Although a high proportion of patients undergoing cardiac surgery have cognitive impairment immediately after the surgery, impairment diminishes in the weeks and months after discharge.6,39,40
Whether postoperative delirium is associated with prolonged cognitive dysfunction has been unclear.
The few studies that have addressed the effect of delirium on the course of cognitive function after cardiac surgery differed with respect to the timing and frequency of follow-up assessments. One study assessed cognitive function in 112 patients (delirium developed in 21%) 1 to 1.5 years after cardiac surgery and showed that memory and concentration problems were more prevalent among patients with postoperative delirium than among those without delirium; however, preoperative cognitive function was not assessed.38
Hudetz et al. assessed cognitive function in 28 patients (delirium developed in 32%) 1 week after surgery and found that patients with delirium were more than 10 times as likely as patients without delirium to have impaired memory and executive function.37
We assessed cognitive function pre-operatively and an average of five times during the year after surgery, allowing us to accurately model the course of cognitive function and to compare the rate of recovery among patients with and those without postoperative delirium.
In our cohort, postoperative delirium was common, affecting 46% of patients. The rate of delirium is dependent on the methods used for its ascertainment, and our study used a rigorous assessment27
with diagnosis by means of the CAM, the most widely adopted, validated approach in the literature.21,25
Most of the extensive literature examining neurocognitive function after cardiac surgery has not integrated these methods of assessing delirium and therefore has not been able to address our specific study question.29,39,41,42
Our findings are of clinical significance, since the risk of delirium among patients undergoing cardiac surgery can be predicted preoperatively, and delirium is potentially preventable.19,43–45
Multifactorial proactive interventions such as the Hospital Elder Life Program43
have not been well tested in patients undergoing cardiac surgery. However, findings such as ours argue for further development and testing of such interventions. In patients with postoperative delirium, cognitive screening at hospital discharge may identify high-risk patients who require close monitoring after discharge or tailored transitional care in order to enhance functional and clinical outcomes.
Although patients without delirium did not, on average, have significant gains in cognitive function beyond day 30, patients with postoperative delirium continued to have improvement throughout the 6-month postoperative period. Given that delirium is associated with poor functional recovery after cardiac surgery15
and that cognitive impairment is associated with poor functional recovery after hospital discharge (for any condition),46
our finding that cognitive function improves more slowly in patients with delirium than in those without delirium has implications for the duration of postoperative care and rehabilitation services after cardiac surgery. Since patients with postoperative delirium continue to have improvements in cognitive function up to 6 months after surgery, rehabilitation services, such as physical and occupational therapy, may need to be extended for these patients.
Several additional factors that we were unable to examine may have contributed to our findings. The lower level of cognitive function at baseline in the group with postoperative delirium, as compared with the group without delirium, may have been related to a greater burden of preexisting disease that was not fully addressed in our multivariate models. Postoperative cognitive decline in patients with delirium may be the continuation of a trajectory of decline that began before surgery.47
Since we did not perform multiple preoperative assessments over time and did not include a nonsurgical comparison group, our study cannot address this question. Nonetheless, our findings suggest that the development of postoperative delirium should be added to the list of risk factors for prolonged impairment after cardiac surgery, which includes the development of atrial fibrillation,48
a history of depression,49
a lower level of education,7
and preexisting cerebrovascular disease.7,50
As opposed to many of the other identified risk factors, delirium is preventable and treatable.43–45
In a sensitivity analysis, we controlled for baseline differences in cognitive function by matching patients with and those without postoperative delirium on preoperative MMSE scores, and the results did not change. We used sophisticated analytic methods that allowed the use of all available data and descriptions of nonlinear trajectories of cognitive function after surgery. However, several limitations should be noted. Our sample consisted of patients who were predominantly white and well educated and who were enrolled in a single geographic region, potentially limiting the generalizability of the findings. However, this study was conducted at multiple sites that included urban, rural, and socioeconomically diverse populations. In addition, the MMSE may lack the sensitivity to identify mild cognitive impairment; thus, it is possible that more sensitive measures would have shown a slower return to the preoperative level of function in the group of patients without postoperative delirium. We do not have data on cognitive function beyond 1 year after surgery and were unable to control for apolipoprotein E status, although on the basis of the current literature, its association with delirium remains unclear.51,52
Finally, as noted above, our study lacked a nonsurgical comparison group.
In conclusion, this prospective study of patients undergoing cardiac surgery showed that postoperative development of delirium was a risk factor for a decline in cognitive function and a prolonged period of impairment after surgery. Identifying patients at high risk for delirium19
and promoting the development of interventions to prevent delirium in patients undergoing cardiac surgery may reduce the rate of long-term cognitive impairment in this population. Patients in whom delirium develops after cardiac surgery may require further interventions and customized rehabilitation programs to optimize recovery.