Introduction

In the middle of the past century, Bedford in his retrospective study first described the adverse effect of anesthesia in elderly patients. Considering the extended lifespan and growing number of aged population, health professionals are now facing this problem in an extended way. Postoperative delirium (POD) is one of the common but sometimes unrecognized postoperative complications. Its incidence varies between 25% and 60% in elderly postsurgical patients. POD is a disturbance of consciousness with a reduced ability to focus, sustain, or shift attention; a change in cognition; or the development of a perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia. Delirium can occur soon after surgery, and it can last up to 7 days. It is associated with increased mortality and prolonged hospital stay, functional and cognitive decline, and poor long-term outcome.

Postoperative cognitive dysfunction is postoperative neurological complication associated with cognitive decline, memory impartment, and functional decline; it may last up to 3 months after the surgery. The main risk factors for development of POCD are advanced age, cognitive impartment, multimorbidity, and lower education level. Despite the fact that POCD is strongly associated with the surgery, no studies have been able to demonstrate the causal link with anesthesia. On the other hand, perioperative stress may reveal preexisting cognitive impairment that is often present in elderly patients.

Definitions, Epidemiology, and Pathophysiology

POCD and POD are common among the surgical population during the postoperative period. They are thought to be majorly underdiagnosed, and there is concern about the relative value of the testing instruments in use. In recent years, influential studies have reinforced the perception that up to 50% of elderly patients undergoing both cardiac and noncardiac surgery experience persistent POCD. POCD is a controversial diagnosis: it is not described in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and there is no International Classification of Disease Code for POCD. Conceptually, POCD is a subtle and frequently transient cognitive decline that is often only detectable with appropriate neuropsychological tests and a comparison with preoperative cognition. The spectrum of abilities referred to as cognition is diverse, including learning and memory, verbal abilities, perception, attention, executive functions, and abstract thinking. It is possible to have a decrement in one area without a deficit in another. Different studies have found that older patients undergoing major surgery experience POCD lasting for weeks to months, with 10% of those older than 60 having POCD at 3 months after operation. Incidences of POCD vary as well: 10.4% after major abdominal, noncardiac thoracic, or orthopedic surgery, and 12.7% after major noncardiac surgery. This early POCD has negative impact on patients and their families, could delay return to work, has been associated with increased mortality, and has been linked with premature departure from the workforce.

The American Psychiatric Association’s DSM-V provides five key components of delirium : there is a disturbance in attention and awareness; the disturbance is acute and develops over a short period of time while fluctuating during the course of the day; a disturbance in cognition occurs; these disturbances are not explained by another neurocognitive disorder and do not occur during a state of reduced level of arousal including coma; and there is evidence to suggest that the disturbance is caused by a medical condition, substance intoxication or withdrawal, or side effect of a medication. Typically, delirium is diagnosed by examining history, physical examination, and review of medical records. There are many subtypes of delirium: a hypoactive, a hyperactive, as well as a mixed form, in which traits from both hypoactive and hyperactive forms can be seen in the same patient in a single delirious episode. Hypoactive delirium is more often seen in elderly patients, whereas hyperactive delirium is more frequent in patients with alcohol-use disorder. The incidence of POD between studies is variable and depends on the type of surgery: 44% after major abdominal, thoracic, or vascular surgery; 13.2% after emergency and elective surgery; 41.7% after open heart surgery; and 11.8% after major noncardiac surgery.

The exact pathophysiology of POD and POCD is not fully understood and largely based on animal research. Several mechanisms have been proposed :

• 1.
  

  Neurotransmitter imbalance, with acetylcholine deficiency and dopamine excess;

  
  
• 2.
  

  Reduced cerebral blood flow and metabolism;

  
  
• 3.
  

  Dysregulation of stress response and the sleep–wake cycle;

  
  
• 4.
  

  Inflammation.

Some authors hypothesize a relative decrease in acetylcholine and a relative increase in dopamine norepinephrine, and glutamate, levels in the brain, and these changes disrupt the cortical neurotransmitter interactions, interfering with serotonergic and γ-aminobutyric acid activity. This imbalance results in decreases in the alertness and wakefulness of the patients. The importance of dopamine in the development of delirium, in particular, seems to be supported by the therapeutic effect of haloperidol, a powerful dopamine blocker. In addition to acetylcholine and dopamine, there is evidence that other neurotransmitters such as tryptophan can play a significant role in delirium. Tryptophan, a serotonin precursor, was reduced in a population of patients with delirium undergoing cardiac surgery. Importantly, it appears that abnormal tryptophan metabolism can modulate the type of delirium, i.e., hyperactive or hypoactive. Tryptophan, moreover, is tightly connected to melatonin, a hormone involved in the regulation of circadian rhythm that has also been linked to delirium. Studies conducted mainly in cardiac surgical patients indicate that sleep deprivation can either cause delirium, be a result of it, or may simply lower the clinical threshold for delirium. Decreased low wave sleep and decreased-stage rapid eye movement sleep have been hypothesized as contributing factors for the development of delirium.

An impaired cerebral perfusion caused by a decreased cardiac output, or loss of perfusion autoregulation, is another important aspect in the development of delirium. Intraoperative mean arterial pressure and partial pressure of carbon dioxide are among the physiologic variables related to the occurrence of POD because they induce a significant reduction of cerebral blood flow. Surgery is associated with activation of an inflammatory response syndrome and the release of cytokines that can impair brain function. Despite the protection of the blood–brain barrier, it is now recognized that the brain is in communication with the immune system, thereby allowing systemic, peripheral inflammatory reactions to influence brain function, making the brain susceptible to the consequences of systemic inflammation. One cited proposed mechanism is systemic cytokine release, in particular interleukin (IL)-6, IL-8, S100B, and C-reactive protein. Cytokine dysregulation can lead to neuronal injury through a variety of mechanisms, including:

• 1.
  

  altered neurotransmission

  
  
• 2.
  

  apoptosis

  
  
• 3.
  

  activation of microglia and astrocytes, which leads to the production of free radicals, complement factors, glutamate, and nitric oxide.

Risk Factors

Delirium after surgery is preventable in approximately 40% of cases and is often associated with a reduced cognitive reserve defined as incapacity of the brain to resist external factors. It is important to account for risk factors to prevent delirium and minimize the risk. Each type of risk factor can be modifiable or nonmodifiable.