**4.3 Delirium prevention and reduction of length of stay**

Postoperative delirium (POD) is one of the most severe complications after surgery, and it is a distressing syndrome both for old surgical patients and their families. It is a complex syndrome that affects 7–65% of patients after hip-fracture surgery [100, 101]. Its social consequences are likely to escalate with a growing old surgical population. The pathogenesis of POD is unclear and probably multifactorial. The most frequent causes are:


The most important predisposing risk factors are:


Pain is the most common complication after surgical procedures, and it is associated with increased risk of delirium [102]. Conversely, the use of opioids (particularly longeracting opioids) has also been associated with increased risk of POD [103]. Postoperative mean oxygen saturation at night may also have a role in the development of POD [104]. The mean score of the Mini-Mental State Examination (MMSE) decreased significantly only in patients who received general anesthesia. This suggests that the use of a multimodal opioid-sparing analgesia regime may reduce risk of POD and, therefore, may be considered as a choice especially in patients at high risk for POD. However, there is no consistent evidence about the effects of general anesthesia and regional anesthesia on the incidence of POD following total hip replacement. Even in elderly patients, there was no significant difference in the incidence of cognitive dysfunction 3 months after the use of either general or regional anesthesia [105]. In an RCT among 950 patients aged

65 years and older undergoing hip fracture surgery, regional anesthesia without sedation did not significantly reduce the incidence of POD compared with general anesthesia [91]. The incidence of POD overall was 5.6%. Regardless of the techniques used, patients with POD have been independently associated with adverse clinical and economic outcomes such as death, decreased functional outcome, and cognitive decline, as well as higher cost of care and longer hospitalization. Therefore, it is important to characterize perioperative risk factors related to the incidence of POD and to optimize the quality of care in patients with total hip replacement arthroplasty. Despite the knowledge gaps in delirium pathogenesis, POD may still be preventable with targeted pharmacologic and nonpharmacologic strategies. The first-line preventative interventions for POD are the nonpharmacological interventions. Reorientation is a strategy to help patients get familiarized with the environment and the people. This is done through minimizing staff change and patient transfer, consistent introduction of staff members, access to natural light and time-keeping devices, reminders about the previous events, and future planning. A clinical trial has shown that reorientation alone can reduce the incidence of overt delirium by 40% [106]. Other nonpharmacological interventions include cognitive exercises, vision, sleep and hearing optimization, mobilization, hydration, and nutrition. These interventions are often instituted as a multicomponent care package. The Hospital Elder Life Program (HELP) is a multidisciplinary program designed to prevent cognitive and functional decline in older hospitalized patients, and the focus is on delirium [107]. Nonpharmacologic interventions, such as delirium education programs for medical staff, have led to reductions in delirium duration, hospitalization, and mortality. Antipsychotic drugs are dopamine antagonists and also have varying degrees of affinity to muscarinic, serotonergic, and adrenergic receptors [108]. They are divided into first-generation and second-generation agents, with the first generation (haloperidol) associated with higher risks of psychomotor complications and the second generation associated with higher risks of cardiovascular and metabolic complications. Several studies and meta-analyses have reported that prophylactic administration of second-generation antipsychotics, such as olanzapine and risperidone, may reduce the incidence of postoperative delirium [109]. Because of the risk of complications, the clinical value of antipsychotic prophylaxis is not clear. Pharmacologic ketamine has been found to reduce postoperative inflammation and improve perioperative pain outcomes [110]. In addition, results from a small trial also demonstrated decreased occurrence of delirium and decreased incidence of delayed neurocognitive recovery in cardiac surgery patients who received intraoperative ketamine compared with placebo [110]. Conversely, the PODCAST (Prevention of Delirium and Complications Associated with Surgical Treatments) trial shows that intraoperative ketamine does not prevent delirium. On the contrary, ketamine may increase the risk of adverse perioperative psychoactive experiences [111]. Dexmedetomidine has also been tested in large RCTs in relation to POD and its use is associated with reduction in the composite outcome of delirium, agitation, and confusion [112]. Other drugs have shown some promise as prophylactic agents in noncardiac surgery. These include acetaminophen, ramelteon, gabapentin, statins, clonidine, and melatonin [113].
