Incidence and risk factors of postoperative delirium in the elderly patients with hip fracture

Delirium, or acute cognitive function state, is a common postoperative complication that is manifested by a change of mindset and attention deficit over time [1]. Previous literature has described that the incidence of delirium in hospitalized patients vary from 11 to 42% according to population studied [2]. However, the incidence of delirium is 51% following orthopedic surgery for hip fractures. Moreover, in ICU, up to 81% of patients manifest delirium [3]. Postoperative delirium (POD) is associated with extended lengths of stay, higher patient care costs, increased morbidity, and functional and cognitive decline [4]. POD has been reported to be associated with a large number of risk factors: age, dementia, impaired left ventricular function, electrolyte disorder, alcoholism, smoking, high perioperative transfusion requirements, intraoperative pressure fluctuation, and use of benzodiazepine [5‐9]. POD occurs mostly in some types of surgery, such as hip surgery, major gastrointestinal surgery, and major cardiac surgery [10‐12]. The occurrence and development of delirium following the hip surgery in the elderly is not conducive to the early functional exercise and rehabilitation process [13, 14].The preoperative assessment of the risk factors for delirium is one of the ways to clarify the pathogenesis of POD and propose effective prevention measures. This study focused on elderly patients (aged 65 years or more) admitted to a hospital for conditions (including femoral neck fracture, intertrochanteric fracture) and general surgical procedures (hip arthroplasty, proximal femoral nail fixation). Univariate and multivariate logistic analysis was used to determine the incidence and risk factors of delirium and provide a reliable and accurate theoretical basis for the prevention and treatment of POD.

Delirium is an important postoperative complication which can cause delayed recovery, prolonged hospitalization, and the waste of medical resources [15]. The incidence of POD in our research was 19.29% compared with the incidence rate of 13 to 48% reported by other research [6, 16]. Inouye SK reported that the occurrence of delirium following hip surgery is 12–51% [3]. A variety of diagnostic criteria may be the cause of a significant difference in the incidence of POD. A review of 25 studies showed that 11 instruments have been used to identify the delirium and the CAM was the best choice [17]. Furthermore, small simple size, inclusion criteria, surgery procedures, and anesthesia may lead to variations in incidence rates and risk factors [18, 19]. In our study, delirium was identified by nerve physician according to the evaluation tool of CAM. These measures were designed to ensure the accuracy and integrity of the study.

Although a number of theories have been proposed in an attempt to explain the processes leading to the development of delirium, there is no effective way for the prevention or treatment of POD [20]. The comprehensive assessment of the risk factors for delirium can improves the preventive measures. Many factors were supposed to be associated with POD, such as anesthesia, intraoperative blood loss, blood transfusion, malnutrition, electrolyte disorder high perioperative transfusion requirements, intraoperative pressure fluctuation, and use of benzodiazepine [5, 21, 22]. The results of our research indicate that age (> 75 years old), diabetes, and ASA classification (> 2 level) were strongly independently associated with POD.

Advanced age was consistently considered to be an overlapping risk factor in a review of 80 primary data collection studies by Dyer et al. [23, 24]. Previous studies showed that the occurrence rate of POD increased by 2% when the age of the patient increased by 1 year [4, 25]. Wang et al. [5] believe that the incidence of postoperative delirium in patients aged 70~79 years and over 80 years was higher than that in patients under 70 years old, and the odds ratio (OR) values were 6.33 and 26.37 respectively. Consistent with previous reports, our study demonstrated that the elderly patients over the age of 75 years is the independent risk factors of POD. Older patients are thought to be more susceptible because of the association between aging and the impaired physiologic compensatory capability to adjust to the physical stress of surgery [26]. The changes in the content of central neurotransmitters such as acetylcholine, norepinephrine, epinephrine, and gamma aminobutyric acid are an important cause of delirium as the age increases [27, 28]. In addition, the sensitivity of various mechanisms of blood pressure regulation in the elderly is reduced, so hypotension is easily induced in the induction period. Prolonged hypotension leads to low cerebral perfusion, cerebral ischemia, hypoxia, impairment of brain function, metabolic disorder, disorder of orientation, hallucination, irritability, etc. Edlund et al. [29] found that hypotension within a period of time (systolic pressure of < 100 mmHg) was an independent risk factor for POD and combined epidural anesthesia could lead to a decrease of at least 30% of the blood pressure in the hip joint. The mean arterial pressure fluctuated 30% relative to baseline level when the duration of hypotension lasted for 1 min, which means that the risk of stroke increased by 1.3% [30]. However, Steve [26] believes that age was not an independent risk factor for POD. One reason that age was not significant in multivariate analysis could be that this study dichotomized the age group (i.e., >75 years), while our study use yearly increments in multivariate analysis.

Diabetes is thought to increase the risk of dementia and mild cognitive impairment, as well as an accelerated cognitive decline [31] The cause of susceptibility to delirium in diabetic patients is that there is a general change in the microvascular structure of the brain: the decrease in the number of capillaries, the thickening of the basement membrane, and the increase of the arteriovenous short circuit, which makes the brain tissue more vulnerable to hypoxic damage when the perfusion pressure drops or the blood flow is not smooth [32]. The evaluation of cerebral blood flow and radiation-activity ratio of brain tissue by SPECT indicated that the decrease of senile cerebral blood flow is aggravated by hyperglycemia [33, 34]. A meta-analysis of 14 studies demonstrates that diabetic patients are more prone to cognitive dysfunction [22]. Our research shows that diabetes is associated with an increased incidence of POD, which is consistent with a prospective observational study conducted by Sabol [35], while a single systematic review concluded that diabetes was unrelated to cognitive dysfunction. Reasons for disparity from our findings are that true effect sizes for the association of diabetes with cognitive dysfunction may have been underestimated. Patients with undiagnosed diabetes were included in the respective “no diabetes” groups while the patients with confirmed diabetes were included in our study [36].

The result of our research shows that ASA classification (> 2 level) was strongly independently associated with POD. Several studies have shown that the ASA status is associated with an impaired general physical status and multiple comorbidities [37, 38]. The comorbidities such as diabetes, hypertension, and preoperative cognitive impairment have been previously proved to be the risk factors of delirium in elderly patients [24, 25], and our results corroborated this finding. Multiple comorbidities probably increase baseline vulnerability in older adults, contributing to POD, if combined with other precipitating factors such as major hip surgery. However, Brouquet et al. [39] believe ASA classification (> 3 level) is more likely to lead to POD in elderly patients undergoing major abdominal surgery. The reason may be due to the difference of age criteria for inclusion in the population. All consecutive patients aged 75 years or more were included in Brouquet’s study, while we focused on elderly patients aged 65 years or more.

A practical important finding of our research is that patients in delirium group need more protein consumption during the perioperative period. It accords well with the researches indicating that postoperative delirium is associated with malnutrition and nutritional supplementation could reduce the occurrence of delirium and mortality in the duration of acute trauma and after 4 months [40‐42].

To sum up, we recommend that preoperatively comprehensive, accurate management of elderly patients with diabetes and comorbidity could reduce the happening of POD. Furthermore, malnutrition intervention including protein application is beneficial to recovery of patients in delirium group.

This study has some limitations. First, the selected two common types of hip surgery cannot represent the incidence of POD across all kinds of orthopedic surgery. Second, case collection does not follow the principle of randomization. Third, there are misdiagnoses for POD even when medical records were carefully checked.

The elderly patients over the age of 75 years with the history of diabetes or ASA classification > 2 level were at higher risk of POD. Delirium is an important postoperative complication, which had prolonged hospitalization and high perioperative albumin infusion.