Postoperative delirium in elderly citizens and current practice.

Postoperative delirium (POD) represents an acute brain dysfunction in the postsurgical period. Perioperative physicians caring for the older adults are familiar with the care of dysfunction of organs such as lungs, heart, liver, or kidney in the perioperative setting, but they are less familiar with management of brain dysfunction. As early detection and prompt treatment of inciting factors are utmost important to prevent or minimize the deleterious outcomes of delirium. The purpose of this review is to prepare perioperative physicians with a set of current clinical practice recommendations to provide optimal perioperative care of older adults, with a special focus on specific perioperative interventions that have been shown to prevent POD. On literature search in EMBASE, CINAHL, and PUBMED between January 2000 and September 2015 using search words delirium, POD, acute postoperative confusion, and brain dysfunction resulted in 9710 articles. Among them, 73 articles were chosen for review, in addition, National Institute for Health and Clinical Excellence guidelines, American Geriatric Society guidelines, hospital elderly life program-confusion assessment method training manual, New York geriatric nursing protocols, World Health Organization's International Classification of Diseases, 10th Revision classification of mental disorders, Food and Drug Administration requests boxed warnings on older class of antipsychotic drugs 2008 and delirium in Miller's text book of anesthesia were reviewed and relevant information presented in this article.

Introduction

Postoperative delirium (POD) is an acute disorder of cognition and attention, exhibits fluctuating symptoms of inattention, cognitive dysfunction, associated with disorganized thinking, and altered level of consciousness.[1] Other features of this syndrome include disorientation, impaired memory, perceptual instability, altered psychomotor activity, and altered sleep-wake cycles.[2] POD is one of the most unexpected and perplexing complications encountered following surgery. POD is associated with longer duration of hospital stays, more frequent discharge to long-term care amenities leading to greater cost with additional complications of poor recovery and increased mortality.[3] Even though POD is reversible in character, because of its long lasting sequelae in the form of cognitive deficits remaining for up to months, it can become chronic particularly in the elderly citizens following surgery.[4] In older patients, delirium can be a key factor in initiating a cascade of events that may lead to a, loss of independence, decline of executive function, institutionalization, and ultimately, death.[5]

The capability to predict patients at high risk for POD has enabled the physicians to do proactive interventions to prevent or to reduce the rate and severity of POD. Thus, a cornerstone in the management of POD is the detection and treatment of any underlying inciting factor. Therefore to familiarize the clinician in the management of POD a targeted literature search was performed, in EMBASE, CINAHL, and PUBMED between January 2000 and September 2015 using the keywords “delirium,” “postoperative delirium” “acute postoperative confusion” and “brain dysfunction” resulted in 9710 articles, among them 73 articles were chosen for review. In addition National Institute for Health and Clinical Excellence guidelines, American Geriatric Society Guidelines, Hospital elderly life program-confusion assessment method (CAM) training manual, New York geriatric nursing protocols, World Health Organization's International Classification of Diseases, 10th Revision (WHO ICD-10) classification of mental disorders, Food and Drug Administration requests boxed warnings on older class of antipsychotic drugs 2008 and delirium in Miller's text book of anesthesia were reviewed.

Articles published in English language, describing precipitating, predisposing factors, pathophysiology, clinical features, diagnosis, preventive strategies, treatment regimens and outcomes of POD particularly in elderly, were analyzed and relevant information presented in this article. Excluded topics were delirium biomarkers, predictive models, prognostic methods, tools of assessment, alcohol or substance abuse, withdrawal, nonelderly populations (e.g., pediatric), dementia (e.g., Alzheimer disease), psychosis (e.g., schizophrenia), terminal illness (e.g., acute stroke), brain surgery, and traumatic brain injury.

The Epidemiology

The overall incidence of delirium is just 1%–2%, in the society, but in the hospital setting after admission this increases to 14%–24%.[5] The rate of delirium occurring during a hospital stay increase from 6% to 56%, and this number is still higher in those admitted in the Postanesthesia Care Unit, Intensive Care Unit (ICU) and palliative-care settings.[678] POD complicates in 15%–53% of surgical patients aged above 65 years,[9] and among these patients admitted to ICU the occurrence of POD can reach as high as 70%–87%.[10]

Development of POD depends on a compound interaction of multiple risk factors. A few of these risk factors are modifiable and are possible targets for delirium prevention. Health-care workers caring for elderly surgical patients should conduct a preoperative assessment for delirium risk factors, including age older than 65 years, dementia or chronic cognitive decline, poor vision, impaired hearing, severe illness, existence of infection, and any other risk factor as shown Table 1.[59111213] Patients with two or more risk factors should have greater risk for POD than patients with no or single risk factor. The risk for POD, in general, is greater in the emergency situation in comparison with the elective setting.

Table 1

Risk factors for development of postoperative delirium

Pathophysiology

Many possible pathophysiologic mechanisms were postulated for the development of delirium. The widely suggested mechanisms include alterations in one of several neurotransmitter systems,[14] inflammatory mediators, physiological stress,[9] metabolic disorders, and electrolyte disturbances. An extensive evidence supports an imbalance between dopaminergic and cholinergic neurotransmitters as a key factor in the genesis of delirium.[15] In fact, drugs with anticholinergic properties can incite delirium,[16] and therapy with cholinesterase inhibitors such as physostigmine can effectively reverse delirium in some occasions.[9] The antipsychotics, which block dopamine receptors are successful in the treatment of delirium.[15] Thus, a reduced cholinergic reserve and relative excess of dopaminergic transmission in certain regions of the brain were related to the development of delirium.[16] Pro-inflammatory mediators, such as interferon α or β, interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumor necrosis factor-alpha, may contribute to the genesis of delirium by increasing the blood brain barrier permeability, thereby altering neurotransmission.[17] In addition, biological stressor response from anesthesia and surgery is known to incite sympathetic over activity to liberate glucocorticoids which may play a key role in the genesis of delirium.[18]

Although the basic pathophysiologic mechanisms of delirium are not yet completely understand, in the geriatrics prototype, delirium characterizes an atypical presentation of disease,[19] in which acute disease is manifested through weakest link of the most susceptible organ system, in this case, it is brain, results in delirium. This hypothesis explains that the normal course of aging can be characterized as homeostenosis, the progressive shrinkage and constriction of homeostatic reserve in every organ system's ability to respond to stress.[1920] In addition, the aging brain is more prone to be affected by drugs and that cloud the sensorium of brain. The sum of all these effects leads some older adults to be teetering on the edge of neurodysfunction. If these elderly people are subjected to the stressor, is now beyond the reserve limits as a result of homeostenosis of aging. In this case, it is brain centered, decompensation occurs, because compensatory mechanisms are over whelmed, results in delirium.[19]

Clinical Features

All health-care workers need familiarity with the symptoms and signs of delirium. POD can develop from the 1st to 3rd postoperative day.[21] The clinical manifestations of delirium vary and can often be vague. On the basis of psychomotor behavior Robinson et al.,[22] using validated instruments measured and broadly classified delirium into three subtypes.

The hypoactive type, in which patients are withdrawn and quiet, unaware, with prominent lethargy or apathy, decreased alertness, staring, psychomotor slowing, slowed movements, sparse, or slow speech

The hyperactive type, featuring prominent agitation, hyperarousal, hypervigilance, irritability, restlessness, combativeness, fast or loud speech, singing, swearing, laughing, fast motor responses, hallucinations, impatience, anger, uncooperative, wandering, easy startling tangentiality, distractibility, nightmares, or persistent thoughts, often associated with life-endangering autonomic instability

The last mixed type in which patients frequently fall somewhere along a spectrum between the hyperactive and hypoactive extremes, sometimes swinging from one to the other type within minutes.[1923]

In most cases, the clinical features of delirium have a tendency to fluctuate both in severity and type, with a lucid interval in between them. It has been implicated that each subtype of delirium can result from a different pathological mechanism, and that each one might carry a varied prognosis.[2425]

Delirium Screening Tools

A range of bedside screening devices are available to help the clinician in the recognition of delirium. Many screening instruments have been narrated in the published articles,[2627] among them 11 tools were identified for the evaluation of delirium.[2728] The CAM[29] was reported as the best validated and most accurate of the tools reviewed. The CAM operates on the Diagnostic and Statistical Manual, 4th edition (DSM-IV) criteria, increased reliability is demonstrated when health-care professionals trained in the use of a screening tool evaluated the patients for delirium. CAM is used by many as a screening instrument (short form) and diagnostic tool (long form with algorithm).[26272829] The CAM is a bedside rating scale developed to assist clinicians not trained in psychiatry for rapid and accurate diagnosis of delirium in clinical settings, can be administered by any health-care worker and may also be administered by trained lay interviewers. The sensitivity of the CAM is 94%–100%, with specificity 90%–95% against the gold standard of psychiatric diagnosis.[19] Other validated instruments commonly used for screening delirium are delirium symptom interview and nursing delirium screening scale.[30] The CAM-ICU[31] and Intensive Care Delirium Screening Check List[32] has been adapted for measuring delirium of ventilated patients in the ICU. For elective surgery, patients should have their preanesthetic cognitive testing to record their baseline level.[3334]

Diagnosis of Delirium

Early diagnosis and treatment of POD are crucial components for precise surgical care of older adults. The most important step to establish the diagnosis of delirium is obtaining history from an observer (e.g., caregiver or family member), doing a brief cognitive assessment (e.g., level of arousal for verbal stimulus, low arousal states of acute onset, disorientation to time place and changes in language indicate cognitive deficit. Attention can easily be assessed by simple bedside tests such as digit span or telling the months of the year backwards) and review of medical records. For laboratory investigations, targeted testing is the best strategy. Table 2[1135] summarizes the recommended work-up and diagnostic assessments (e.g., laboratory testing or neuroimaging) on the basis of the patient's history and physical examination.[35]

Table 2

Approach to a patient for evaluation of delirium

A high degree of clinical suspicion is the mainstay to discern delirium in older patients after surgery.[36] The hallmark of delirium is acute fluctuating cognition from baseline, inattention is the cardinal feature of delirium, associated with either disorganized thinking or an altered level of consciousness are diagnostic of delirium. Use of a cognitive test is required for accurate diagnosis, a formal delirium diagnostic tool such as the DSM-V,[3738] the WHO ICD-10,[39] or CAM diagnostic algorithm[29] used by a competent health care professionals will make the diagnosis of delirium more accurately.

Prevention

Prevention is the most effective strategy to minimize the detrimental outcomes of delirium, and an estimated 30%–40% of cases of POD can be preventable by early treatment of predisposing factors.[5] Although the evidence is weaker for prevention of delirium, several moderate to high quality studies demonstrated benefit from non-pharmacologic measures [Box 1].[94041424344] Implementing and monitoring these interventions by an interdisciplinary team, may successfully reduce the rate of POD about 30%–40% in the postsurgical period.[4244]

Box 1

Non-pharmacologic strategies for prevention of delirium

Perioperative Preventive Measures

Although several intra-operative issues were studied for their effect on POD, however there is inadequate information on the topics studied earlier, which including regional anesthesia versus general anesthesia (GA), specific anesthesia agents, intra-operative blood transfusion, systemic arterial pressure monitoring and use of medications such as statins or dexamethasone. Previous studies have found deep sedation was associated with increased rates of POD and lighter planes of anesthesia will reduce POD in comparison with deeper sedation.[45] A Randomized use of Bispectral Index by anesthesia providers to guide anesthesia depth during GA have reduced the incidence of POD in older patients when compared with those who received regular care. Monitoring anesthetic depth during intravenous sedation or GA for older patients using processed electroencephalographic (EEG) monitors may reduce POD. The idea is that by EEG monitoring and providing a lighter depth of anesthesia by administering lower doses or fewer anesthetic agents will reduce POD in comparison with deeper sedation.[4647]

Inadequate postoperative analgesia contributes to development of POD. Postoperative pain control is paramount to curtail the frequency of delirium.[4849] A magnitude of evidence suggests that nonopioid analgesics diminish POD in comparison with opioid-only analgesic regimes.[5051] The use of regional anesthesia has been found to reduce POD in two studies.[5253] Current practice guidelines to improve the safety of medication use in older adults advocated avoidance of drugs prone to enhance the severity or risk of delirium [Table 3].[5455] Poly-pharmacy use of 5 or more medicines has been associated with an increased risk of delirium, likely due to the psychoactive properties of one or more of the medications in the patient's regimen.[56]

Table 3

Drugs prone to increase the risk of postoperative delirium

Prescribing antipsychotic medications to prevent POD has limited, conflicting, and contradictory support in the literature. Several studies found decreased incidence of delirium with prophylactic antipsychotics,[575859] and a few did not.[606162] Potential tribulations of this class of medication are considerable; therefore, antipsychotics are not recommended to thwart delirium.[63646566] Prophylactic administration of newly approved cholinesterase inhibitors are not effective in reducing POD,[676869] and may cause increased harm including mortality;[70] hence, no prophylaxis is currently recommended with these agents in the current practice guidelines.

Treatment of Delirium

Even though, the quality of evidence is low for recognizing and treating the underlying inciting factors of a patient's delirium, health-care professionals are strongly recommended to carry out a medical evaluation, make environmental and medication adjustments, and perform appropriate investigations to identify and treat underlying contributors for development of POD. Neuroimaging is generally limited to patients with recent head trauma or falls, focal neurologic signs, use of anticoagulation and fever of unknown explanation [Table 2].[1135] Thus, the treatment of POD consists of treating the underlying cause, correcting fluid, electrolyte imbalance, hypoxia, and removing catheters if present. The next step consists of initiating the nonpharmacological measures, which are similar to preventive measures [Box 1][94041424344] but also include regimens for de-escalation of agitation, education of nurses, physicians, and proactive geriatric consultation, the last step is treating the patients who are restless, aggressive, agitating and harm to self or others with antipsychotics [Table 4].[39557172]

Table 4

Most commonly used drugs in the treatment of delirium

Current practice guidelines recommended lowest effective dose and shortest duration of antipsychotics to treat patients who are severely violent or aggressive, and are threatening sizeable harm to others or self. In all patients, management with antipsychotics should be started only if behavioral procedures have failed or are not possible, and continuing use should be assessed daily with physical examination of patients. Antipsychotic or benzodiazepines [Table 4][39557172] are not prescribed for treatment of POD in older adults who are not agitated or distressed.[25] No current evidence supports the routine use of benzodiazepines in the delirium treatment. There is a significant evidence that benzodiazepines promote delirium.[73] Conversely, benzodiazepines remains the suggested therapy for treatment of alcohol and drug withdrawal induced delirium.[74]

Outcome

POD, which results from dissimilar multiple etiologies, can contribute to poor patient outcome, irrespective of the underlying cause. It has been reported that POD is associated with poor outcomes even after controlling basic patient personality and etiological factors,[75] and the more severe the occurrence of POD, the poorer will be the outcome.[76] Some patients (33%) never get back to their baseline state of cognitive function following an attack of delirium and show persistent functional and cognitive deficits. Patients with dementia who subsequently develop delirium, besides demonstrating worst outcomes, have higher rates (33%) of institutionalization, hospitalization and death than those who do not suffer from this condition.[77787980]

Conclusion

POD is a serious cause and complication of hospitalized elderly patients. Irrespective of the specific etiology, POD has the potential to distinctly affect the overall outcome and prognosis of severely ill patients, as well as significantly increasing health-care costs. Nonpharmacologic prevention strategies have shown to be effective at diminishing the incidence of delirium; as pharmacological prevention strategies have no trial-based support. Assessing and recognizing delirium risk preoperatively, implementing delirium prevention strategies, and applying standardized treatment protocols when it occurs are essential components of optimal perioperative care for elderly citizens.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.