Introduction
The number of adults age 65 and older within the United States will increase to 71 million by 2030, representing 16% of the total population. Approximately 50% of older adults will have surgery after the age of 65, which represents about one-third of all inpatient surgeries performed by general surgeons.1 Older adults are more likely to have poor surgical outcomes compared to their younger counterpart in part due to physiological deterioration associated with aging such as frailty and multiple medical conditions. Emergent surgeries also present a special challenge for surgeons, as postoperative mortality increases with age.2
One of the most common postoperative complications is delirium, ranging from 5% to 50% after an operation.3 Clinical features of delirium include disturbance in attention and awareness that develops over a short period of time that is a change from their baseline.4 The course fluctuates throughout the day, and is accompanied by disturbance in cognition.5 Delirium is a complication which costs upward of $150 billion annually, and is associated with poor functional recovery and institutionalization.3 It is also thought to be associated with incident dementia and cognitive decline as well as high mortality rate, with 1 year mortality as high as 40%.6, 7 Thus development of postoperative delirium is associated with serious ramifications.
Key points:
Postoperative delirium is common, associated with poor outcomes and incomplete functional recovery along with increased rates of mortality.
Postoperative delirium may be associated with incident dementia and cognitive decline.
Delirium is estimated to cost $150 billion a year within the United States.
Incidence
The incidence of postoperative delirium varies considerably depending on multiple factors including age, type of surgery being performed, whether the surgery was emergent or if intensive care unit (ICU) stay is required. According to estimates, the incidence of perioperative delirium is as high as 60% in adults 65 and older, especially after hip surgery, and recognized as the most common postoperative complication in this age group.3, 8 For patients in the surgical ICU, the incidence can be even higher and be associated with more complications and a prolonged postoperative course.
Even though delirium is common, it is often an underdiagnosed and an improperly treated complication in older adults following surgery. However, delirium is thought to be preventable in up to 40% of cases, a fact that makes it a prime candidate for prevention interventions targeted to improve surgical outcomes.
Pathophysiology
The pathophysiology of delirium is not fully understood but it is likely to be multifactorial (Figure 2.1). One prominent theory of delirium pathogenesis is diminished activity in the central cholinergic system. A key premise for this idea is that attention and consciousness is partially controlled by acetylcholine; a premise that has been supported by functional neuroimaging showing abnormalities in the areas of the cholinergic pathway in patients with delirium.9 Thus, when there are pathological or pharmacological alterations leading to cholinergic deficiency, this can lead to inattention and fluctuations in consciousness, two diagnostic features of delirium.
Another important theory of delirium pathogenesis is overactivity in the dopaminergic system. Dopamine in particular has many roles within the brain including memory, pleasure, movement, attention, sleep, mood, cognition, and behavior. Therefore, it is not surprising that dopamine could also be involved in the pathophysiology of delirium. This is also the reason why dopaminergic anti-parkinsonian drugs are associated with delirium, and why dopamine antagonists have been studied for treatment of delirium.
However, the imbalances between and within the cholinergic and dopaminergic systems alone do not fully explain the pathophysiology of delirium, as treatment with cholinesterase inhibitor or dopaminergic antagonist does not always lead to resolution of delirium. There are other neurotransmitters including serotonin, γ-aminobutyric acid (GABA), and norepinephrine (NE) which are thought to be involved in the pathogenesis of delirium, as abnormalities in these neurotransmitters can lead to thalamic dysfunction causing sensory overload and hyperarousal.10
Other theories of delirium pathophysiology include inflammation, stress, neuronal injury, and melatonin deficiency.10 Inflammation from trauma, infection, or surgery may cause alterations in cytokine levels that can lead to dysfunctions in neurotransmitter levels producing neural miscommunication which in turn can cause the development of delirium.11 It is also becoming evident that the integrity of the blood-brain barrier (BBB) also may play a major role in the pathophysiology of delirium.12 Moreover, it is thought that the integrity of this critical barrier becomes compromised as individuals age. Thus, as surgery-induced cytokines rise systemically, they can rapidly cross the BBB, which can lead to damage directly to the BBB causing further permeability, endothelial dysfunction, destruction of tight junctions, and activation of central innate immunity (neuroinflammation).13, 14 In addition, it is theorized that acute stress may lead to an increase in cortisol levels which in turn contributes to the development of delirium. Another pathway might be that neuronal injuries caused by mitochondrial dysfunction and metabolic derangements are somehow involved in the development of delirium. Finally, melatonin may play an important role in the development of delirium since it is involved in regulation of the sleep-wake system, which is often dysfunctional in delirious patients.
Key points:
Pathophysiology of delirium is multifactorial.
Pathophysiology may involve alterations in the neurotransmitter systems including acetylcholine, dopamine, serotonin, glutamate, γ-aminobutyric acid, norepinephrine, as well as stress, inflammation, neuronal injury, BBB damage, and melatonin deficiency.
Etiology
Predisposing Factors and Precipitating Factors
Postoperative delirium has a multifactorial etiology with multiple potential predisposing and precipitating factors that contribute to its development (Table 2.1).2, 8, 15 Early identification of patients at risk for postoperative delirium is important for prevention and optimization of care. Although some of the predisposing factors may not be modifiable preoperatively (e.g., age), identification of these risk factors can aid in preoperative risk stratification for potential delirium prevention methods. Age and underlying cognitive impairment are the strongest preexisting risk factors that can contribute to the development of delirium.2 Another strong preoperative risk factor found in elderly patients after hip fractures is the presence of multiple comorbidities.16 Frailty is also a significant risk factor and is thought to be caused by a dysregulation and decline of physiological reserve.
A. Predisposing Factors
| Risk factors |
| Demographics |
| Older age |
| Sex (male) |
| Preexisting conditions |
| Cognitive impairment/dementia |
| Poor overall health (multiple chronic conditions), Charlson Comorbidity Index (CCI) ≥ 3, American Society of Anesthesiologists (ASA) physical status score > 2 |
| Low body mass index (BMI), low albumin |
| Renal failure, abnormal electrolytes, abnormal glucose, dehydration |
| Frailty |
| Depression |
| Constipation, urinary retention |
| Prior delirium |
| Bone metastases/CNS tumor/CNS radiation/intrathecal chemotherapy |
| Heart failure |
| Obstructive sleep apnea (preoperative apnea-hypopnea index of 19 or higher ) |
| Social factors |
| Substance abuse (alcohol) |
| Smoking |
| Sensory deprivation, such as preexisting hearing and visual impairment |
| Baseline function |
| Baseline immobility/functional impairment/diminished activities of daily living; timed up and go test (TUG) ≥ 15 s, increased gait speed |
| Medications |
| Polypharmacy or “high-risk” medication use (anticholingerics, opiates, H1 blockers, steroids, chemotherapy, psychotropic drug use, etc.) |
| Risk factors |
| Acute medical condition/acute infection (APACHEa II score >15) |
| Abnormal levels of leukocytes |
| Anemia |
| Blood transfusion |
| Prolonged hospitalization, sleep deprivation |
| Hypoxia or hypercapnia |
| Uncontrolled pain, constipation |
| Restraints/indwelling devices |
| Hypotension |
| Emergent surgery, orthopedic, cardiac, or vascular surgery |
| Renal failure, urinary retention, abnormal electrolytes, abnormal glucose, dehydration |
| Polypharmacy or “high-risk” medication use (anticholinergics, opiates, H1 blockers, steroids, chemotherapy, psychotropic drug use, etc.) |
| Intermediate- to high-risk surgical procedures |
| Fever |
| Sepsis |
| Hepatic dysfunction |
| Metabolic acidosis |
| Respiratory failure |
a Acute Physiologic Assessment and Chronic Health Evaluation.
Many of the precipitating factors are iatrogenic in nature and thus possibly preventable. Certain drugs, for example, are associated with delirium in the elderly. Opioid and anticholinergic drugs are some of the more common medications used in the perioperative period, and that are thought to contribute to the development of delirium. On the other hand, undertreated pain can also lead to increased incidence of delirium. One study showed that severe pain was associated with ninefold greater risk of delirium.17 Thus it is critically important to both adequately control pain while limiting opiate use if possible.
Patients with multiple preexisting and precipitating factors will of course be especially vulnerable to the development of delirium, and there are many existing postoperative delirium prediction models to estimate a patient’s delirium risk index to aid in risk stratification.18–21 Studies have shown that just performing a simple Mini-Cog can predict the likelihood of postoperative delirium.21 Since the etiology of delirium is often multifactorial, its amelioration requires a more comprehensive approach to care. Therefore, a multidisciplinary care team consisting of anesthesiologists, geriatricians, surgeons, physical and occupational therapists, nurses, and pharmacists is often required to reduce the risk or duration of postoperative delirium.
Intraoperative Factors
There are multiple intraoperative factors that can contribute to the development of postoperative delirium. Intraoperative risk factors include duration of surgery, types and amounts of anesthesia used, blood pressure control, blood loss, and intraoperative blood transfusions.22 In patients 80 years or older, a 30 min increment in operative duration is associated with increase in odds of mortality by 17%.2 The risk of delirium also varies with the type of surgery, with vascular, cardiac, and orthopedic surgeries being associated with the highest rates of postoperative delirium.23 Emergent operations are also associated with higher risk than elective surgery.
Whether or not anesthetic technique is a precipitating factor for postoperative delirium remains unclear. Recently, a randomized clinical trial examining the depth of propofol sedation demonstrated that limiting the level of sedation provided no significant benefit in reducing incident delirium. However, in a subgroup analysis stratified by the Charlson Comorbidity Index (CCI), heavier sedation was associated with double the risk of delirium in those with CCI = 0.24 Some investigators also advocate use of processed electroencephalography (EEG) such as Bispectral Index (BIS) to monitor anesthetic depth during intravenous sedation or general anesthesia in older surgical patients as a means of reducing postoperative delirium. Since uncontrolled pain is associated with higher rates of delirium, studies have shown that the use of epidural analgesia may be helpful in reducing intraoperative and postoperative pain and thus delirium.25, 26 However, the use of intraoperative dexmedetomidine has not been shown to prevent postoperative delirium in older adults undergoing major elective noncardiac surgery.27 It is also important to avoid anticholinergic medications perioperatively, such as meperidine or atropine, which can provoke delirium.
Large blood loss procedures and their accompanying fluid shifts and high levels of transfusion have been associated with an elevated risk of delirium.28 It is unclear if either the surgical stress, blood transfusion and its associated inflammatory response, or all of these is the important precipitating factor. The role of blood pressure management in triggering delirium is unclear. However, recent studies suggest that extremes of both high and low blood pressure values are associated with increased odds of developing delirium.
Related posts:
Chapter 1 – Emergence Delirium
Chapter 4 – Postoperative Cognitive Improvement
Chapter 5 – Persistent Perioperative Neurocognitive Disorder
Chapter 12 – Biomarkers of Postoperative Cognitive Dysfunction: Finding the Signal amid the Noise
Chapter 11 – Cognitive Testing for Perioperative Neurocognitive Disorder
Chapter 14 – Preoperative Testing to Identify Vulnerable Subgroups
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