Pre-operative determination of dementia status appears to be critical in risk stratification for post-operative delirium among hip fracture surgery patients for two major reasons. First, the incidence of post-operative delirium was substantially higher among those with pre-operative dementia than without (54% vs. 26%; p≤ 0.001; OR: 3.35 [2.19, 5.12]) and pre-operative dementia was the most predictive predisposing factor for delirium, as was reported previously (14
). Higher morbidity and mortality have been associated with patients with delirium superimposed on dementia than with delirium or dementia alone (15
). Therefore, the clinical staff should implement close and frequent post-operative monitoring of mental status among all dementia patients after hip fracture repair so that delirium can be diagnosed and intervened as early as possible.
Secondly, types and magnitude of predisposing factors for post-operative delirium differ based on the pre-operative dementia status. In fact, without stratification by pre-operative dementia status, we would not have identified the important predisposing factors such as low BMI in the No Dementia group and the lag time between ED to surgery in the Probable Dementia group.
In the No Dementia group age and higher number of medical comorbidities (or ASA PA rating of 4 or higher) were significant risk factors for incident delirium. In addition, we found that male gender was a significant predisposing factor for post operative delirium. Recently, a systematic review of preoperative risk factors for delirium after non-cardiac surgery concluded that there is insufficient evidence to support an association between male gender and delirium based on pooled analysis of ten non-cardiac elective surgery studies (10
). In their analysis, however, significant heterogeneity (p<0.03) across the study samples were observed. Based on a more homogenous group of elective orthopedic surgery patients, Williams-Russo P, et al and Fisher et al. (19
) reported male gender as a significant predisposing factor for delirium, but only among those without pre-operative dementia. It is also important to note that male gender has comparable point estimates in the No Dementia group (OR: 2.06 [1.16, 3.63] and in the Probable Dementia group (OR: 1.85 [0.85, 4.02]), and that the differences in statistical significance may be due to a smaller sample size and lower power to detect associations in the Probable Dementia group than in the No Dementia group. Further study is needed to examine the mechanisms underlying the longitudinal relationship between male gender and incident delirium after hip fracture repair.
Another predisposing factor specific to the No Dementia Group was lower BMI. This is consistent with a recent report of BMI less than 20 as an independent risk factor after hip fracture repair (22
). Interestingly, however, in our study, BMI was in fact somewhat higher in patients with delirium superimposed on dementia than patients with dementia alone. Our findings suggest that the relationship between BMI and post-operative delirium may vary based on pre-operative cognitive status.
Consistent with findings from the previous systematic reviews, no difference in delirium incidence was found between those who had general anesthesia versus spinal anesthesia, regardless of their pre-operative dementia status (23
). However, the duration of hip fracture repair surgery appeared to be strongly associated with postoperative delirium in patients without pre-operative dementia. One possible explanation is the colinearity between the perioperative blood loss and the duration of surgery in our study. However, no association was found between pre-operative hematocrit level and incidence of post-operative delirium in our study. Also, the negative results from the recently completed, randomized clinical trial of blood transfusion thresholds on delirium severity after a hip fracture repair (25
) suggest that blood loss is unlikely to explain the link between the duration of surgery and post-operative delirium in our study.
A more likely explanation between duration of surgery and postoperative delirium in the No Dementia Group is the anesthesia effect. We have recently reported that depth of sedation in general anesthesia is often similar to spinal anesthesia during hip fracture repair (26
) and that minimizing sedation during spinal anesthesia reduces incident delirium (27
). The current study suggests that duration of anesthesia, regardless of type of anesthesia, might be just as important as depth of anesthesia and prolonged exposure to anesthesia may predispose a non-demented hip fracture repair patient to postoperative delirium.
Interestingly, the duration of surgery was not a significant predisposing factor for delirium in the Probable Dementia group. In fact, the only predisposing factor associated with postoperative delirium among patients with pre-operative dementia was the lag time between the ER to OR. In the Probable Dementia group the ER to OR lag time for those who developed delirium was nearly 15 hours longer than those who didn’t (50.93 + 38.7 hours versus 35.69 + 31.8 hours; p = 0.033). Reasons for the prolonged delay to surgery could be due to lack of surgical clearance due to anti-coagulation status and medical stability or limited availability of OR staff._Our study confirms the recent finding by Juliebo et al (22
) on the association between presurgical delay and postoperative delirium, focusing on the relationship in patients with preoperative dementia. Delay to acute hip fracture surgery has been implicated in longer length of stay and increased morbidity and mortality after hip fracture repair surgery (28
). However, why the ER to OR lag time impacts the incidence of delirium only in the Probable Dementia Group is unclear and further study is needed.
These differences in magnitude and types of predisposing factors for post-operative delirium potentially suggest different underlying mechanism in development of post-operative delirium among the patients with pre-operative dementia and these without. Alternatively, in the setting of severe precipitating events (e.g. surgery), the highly vulnerable state of demented brain itself renders other putative risk factors insignificant. Despite the well-established primacy of dementia as a delirium risk factor, the unifying biological and/or psychological mechanism to link delirium and dementia remains elusive (30
). Previous studies have postulated that neuropathophysiological changes - reduced “brain reserve” - accompanying dementia process, such as decreased cerebral metabolism, cholinergic deficiency, and inflammation, leads to increased vulnerability for POD (31
). In parallel, others have suggested that cognitive decline and accompanying reduction of “cognitive reserve” – resiliency of mind to cope with brain insults – due to dementia lead to vulnerability for POD (33
). Elucidation of linking mechanism between delirium and dementia could lead to development of specific strategies for early detection, prevention, intervention strategies among surgical patients with pre-operative dementia.
There are several important limitations to our study. First, detailed pre-operative cognitive and functional data were not available to ascertain preoperative dementia status with greater certainty. In order to avoid interference of preoperative clinical care for acute hip fracture repair, we chose to avoid prolonged cognitive and functional evaluation and relied on the pre-operative MMSE score and the geriatrician’s diagnosis of dementia for our stratification. Invariably, some misclassifications must have occurred and may have influenced our analysis. Second major limitation is the lack of availability of other important putative risk factors for delirium. Visual impairment has been reported to be a risk factor for hospitalized elderly patients (9
) and was not assessed in our study. Also, other the total number of medications and the amount of opioid medications, our clinical database lacked detailed information on specific medications that our participants were taking prior to surgery. We have recently reported the lack of association between narcotics and post-operative delirium (34
). However, besides narcotics, previous studies have reported association between delirium and several other classes of medications such as benzodiazepines, anticholinergics, and antihistamines (35
). Our study is limited by the absence of data on these classes of medications. Furthermore, our clinical database was initiated in 1999, before several putative, intra-operative risk factors (e.g. hypotension, 02
saturation, etc.) became known. Therefore, intraoperative details in our study are limited to surgical indication, types, duration, and amount of perioperative blood transfusion. Preoperative depression is a putative risk factor for postoperative delirium (37
), and we relied on self-report only to ascertain history of depression. Third, the long period of recruitment is vulnerable to changes in clinical practice that could influence the incidence of postoperative delirium. During this period, our hip fracture service has instituted a multidisciplinary team approach that involves perioperative co-management of hip fracture patients by geriatricians and orthopedic surgeons in 2003 (38
). Over the years, due to these changes in clinical practice, the incidence of post-operative complications among our hip fracture repair patients has decreased. Therefore, our findings based on a multidisciplinary hip fracture service may have limited generalizability to other services that do not employ similar multidisciplinary team approach. Fourth, our daily late morning delirium assessment that began on postoperative day two may have under-detected mild, transient delirium that only occurred on post-operative day one and at other times of the day.
Overall, our findings underscore the importance of pre-operative dementia assessment for risk stratification. For hip fracture repair patients at high risk for postoperative delirium, several prevention strategies are already available. For example, Marcantonio et al (39
) have reported that proactive consultation by a geriatrician before, or within, 24 hours of operation may reduce the incidence and severity of delirium in patients undergoing surgery for hip fracture. Identification of high risk patients for post-operative delirium based on our findings could lead to more efficient referral to geriatricians or more targeted development of delirium prevention strategies in the future.