Evaluating the use of dexmedetomidine for the reduction of delirium: An integrative review
Introduction
Delirium, a common problem for hospitalized older adults particularly after surgery or with acute illness, is defined as an acute change in cognition and attention not described by a pre-existing condition, established or evolving dementia.1 Delirium contributes to distress in patients, caregivers and families, and more seriously is associated with increased mortality,2, 3, 4 long-term cognitive deficits, and a greater likelihood for requiring post-hospitalization residential care.5, 6, 7, 8, 9, 10 Older adult patients (ages ≥ 65) are more vulnerable to developing delirium as a result of surgery and acute illness than are younger patients, and aging itself is a risk factor for developing delirium. By 2060, it is estimated that the number of older adults in the United States will rise to 98.2 million, comprising nearly 25% of the population. Consequently, healthcare providers in acute care settings will be expected to care for higher numbers of older adults with delirium in future decades.
To date, no single pharmacological intervention has been shown to be effective in treating delirium.5 Multiple variables contribute to the development of delirium, including underlying health conditions, but the pathophysiology of delirium remains poorly understood. Current interventions for the prevention of delirium involve the recognition and amelioration of modifiable risk factors. These risk factors include pain, immobility, sleep disturbances, and exposure to medications that have the potential for psychoactive and depressant effects on the central nervous system such as opioids and benzodiazepines.11 A number of pharmacological strategies to both prevent and treat delirium have been, and continue to be, highly tested including, antipsychotic medications,12 acetylcholinesterase inhibitors,13 melatonin,14 benzodiazepines,15, 16 corticosteroids, statins and gabapentin.13 Thus far, no single strategy has amassed enough evidence to support its role in delirium prevention or treatment.
Studies purport that dexmedetomidine (Precedex©) may reduce or prevent delirium.5,17, 18, 19, 20, 21, 22, 23, 24 Dexmedetomidine, approved by the FDA in 1999 for short-term sedation (not to exceed 24 h), is the most specific alpha-2 receptor agonist currently used in clinical care.25 Dexmedetomidine, like clonidine, exerts its anti-nociceptive effects in two ways. Primarily, it acts at alpha-2 receptors in the descending inhibitory nociceptive pathway in the spinal cord.26, 27 Dexmedetomidine helps down-regulate nociceptive information transmission by disinhibiting inhibitory interneurons, which in turn block early nociceptive information transmission into the spinal cord by dorsal root ganglion neurons.26 Dexmedetomidine also exerts a key anti-nociceptive effect by decreasing arousal.
Traditionally, dexmedetomidine is administered as an anesthetic adjunct in non-intubated patients prior to and/or during surgical and other procedures. Additionally, it is indicated for sedation of intubated and mechanically ventilated patients in critical care settings. Patients who are sedated with dexmedetomidine are arousable and responsive in a manner that is similar to that seen in people who are sleeping.28, 29 The neurophysiological and behavioral characteristics of the sedative state induced by dexmedetomidine closely resemble non-rapid eye movement sleep.28, 30,31
It is hypothesized that dexmedetomidine may reduce delirium by addressing its underlying cause or ameliorating pain.5,17, 18, 19, 20, 21 Maldonado and colleagues5 attribute an intrinsic “delirium-saving” property of all alpha-2 adrenoceptor agonists, which typically have minimal effects on cognitive impairment. They postulate that dexmedetomidine may lessen the occurrence and severity of delirium because it decreases the need for gamma-Aminobutyric acid (GABA)ergic agents, benzodiazepines and opioids typically required for sedation and analgesia.11, 32 In addition, dexmedetomidine has limited effects on the cholinergic system, which is involved in cognitive function and in the subsequent development of delirium.33 It has also been proposed that dexmedetomidine may reduce delirium by ameliorating pain, an independent risk factor for the development of delirium.34, 35, 36, 37 As such, an integrative review to examine whether use of dexmedetomidine was associated with a reduction in delirium as compared to other analgesic and sedation strategies was conducted.
Section snippets
Methods
Our literature search, article selection, and evaluation were guided by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) for quality of reporting for systematic and meta-analyses.38 A literature search was conducted with National Library of Medicine Medical Subject Headings (MeSH) terms dexmedetomidine and delirium. The search was further refined by keywords (elderly, intensive care, critical care and clinical trial) entered into the electronic search. Studies
Results
Across studies, there was relative consistency in how delirium was identified. Twelve of the studies relied on the CAM-ICU for evaluation of delirium; one study utilized a trained neuropsychiatrist,19 and three studies defined the development of delirium as “the presence of illusions, confusion, cerebral excitement having a comparatively short course.”41, 45,49 The studies retained for this review were delineated into three patient subgroups; those: (1) on mechanical ventilation; (2) having had
Overview of findings
Across studies, there was significant variability in the timing of administration of dexmedetomidine including preoperative, intraoperative and postoperative, and sample populations (e.g., mechanically ventilated patients not following a surgical procedure, cardiac surgery patients, or other surgical patients). Within the cardiac surgery sample, there was evidence favoring the use of dexmedetomidine to reduce the incidence of delirium, while the mechanically ventilated and non-cardiac surgery
Conclusions
At present, dexmedetomidine administration does not reduce the incidence and/or duration of delirium uniformly across all patient populations included in this review. However, there is good evidence to support the administration of dexmedetomidine during and following cardiac surgical procedures. This finding is in good agreement with the results of three recent meta-analysis in ICU patients.58, 59, 60 In future work, non-pharmacologic interventions, pain management, and quality of sleep should
Funding
This work was supported by The Rita & Alex Hillman Foundation, Hillman Scholars Program in Nursing Innovation (KJP).
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2021, Journal of Dental SciencesCitation Excerpt :Sedation with DEX has a minimal effect on respiratory rate and percutaneous arterial oxygen saturation (SpO2) and is associated with fast recovery from sedation with physical stimulation if needed.8–10 It might be an appropriate sedative for elderly patients with dementia since animal studies have shown that it has cerebral protective effects, such as maintenance of cerebral blood flow during hypoxia and focal cerebral ischemia.8–10 A factor that may trigger POD and POCD is inflammation from surgery that spreads to the central nervous system.5–7
Related factors and treatment of postoperative delirium in old adult patients: An integrative review
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