Pharmacological premedication (in particular benzodiazepines) is not always needed, and its routine use has been questioned.208 However, for highly anxious patients or patients with alcohol or benzodiazepine use disorders, careful use of premedication for prevention and treatment can be considered.107,216,217
Prevention of POD in patients with alcohol use disorders (e.g. measured by the Alcohol Use Disorders Identification Test ≥8 points) may include long-acting benzodiazepines, neuroleptics, α2-agonists and alcohol.218 In the subset of patients with alcohol withdrawal-induced delirium, benzodiazepines should be one of the first-line medications.105 As second-line medication, α2-agonists or neuroleptics can be used. For emergence delirium, benzodiazepines might be a precipitating factor,48,107,219 although this remains controversial.180
Data on melatonin for premedication on the evening before surgery are insufficient to draw final conclusions, and currently no clear recommendation can be given.220–223 Perioperative α2-agonists, for example dexmedetomidine or clonidine, might be considered to decrease the incidence of POD after cardiac or vascular surgery.224–228
There are conflicting results regarding the incidence and severity of POD through prophylactic administration of haloperidol35,229–231 or atypical neuroleptics.122,232–234 Although there is some evidence that preventive low-dose haloperidol35,229–231 or preventive low-dose atypical neuroleptics122,233,234 reduce the incidence of POD231 or reduce its severity and duration,229 these findings remain uncertain due to inconsistent results of aggregated evidence.232,235 Therefore, their routine use is currently not advisable.
It remains unclear whether different regimens of anaesthesia influence the development of POD. Cohort studies, retrospective or secondary analyses185,236,237 and RCTs88,126,238–242 have shown mixed results and do not imply a role in adults. However, an important factor in managing POD is adequate stress reduction with sufficient analgesia, an appropriate choice of analgesia and the use of intraoperative opioids.13,180 Currently, it remains unclear if intraoperative administration of short-acting analgesia impacts on POD. Some observational data are available suggesting that analgesia provided with continuous administration of remifentanil might reduce the incidence of POD compared with a bolus-driven regimen with fentanyl,207 but to draw convincing conclusions, evidence from RCTs is required.
To standardise the assessment and treatment of postoperative pain, we refer to the American Society of Anesthesiologists’ guideline on acute pain management in the perioperative setting.243 Although high preoperative129 and postoperative pain244 are risk factors for delirium, opioid analgesics may also be a risk factor in respect of side effects and organ dysfunction.115,180,197,245,246 Patient-controlled analgesia (PCA) could be one option if the patient is able to titrate the medication and find the right balance between analgesia and the minimum dose of opioids.247 POD does not limit PCA use.247 Regional anaesthesia and regional analgesia have not shown any benefit in respect of POD.248
A healing environment should be considered for the prevention of POD. Apart from the consensual statements on nonpharmacological treatment, this should be embedded in an environment for cognitive,249 functional, social and emotional enhancement.250 Further research is required to optimise the use of self-healing competencies of patients.
A ‘threshold theory of cognitive decline’ was postulated to explain a situation of diminished brain reserve capacity occurring in older age, the genesis of which coincides with the degenerative phenomena occurring with ageing.251 Due to this reduced brain capacity, older patients are on a ‘functional cliff’ for developing POD when undergoing a major physiological stress.
In Europe, the percentage of people aged at least 65 years currently ranges from 12% in ‘young’ countries such as Ireland to 21% in ‘old’ countries such as Germany and Italy.252 With the passage of time, this will have a major impact on the demand for healthcare services, especially surgery. There are higher rates per population of both inpatient and outpatient surgical and nonsurgical procedures among the elderly compared with other age groups.253 Patients older than 80 years are the most rapidly increasing group among surgical admissions.254 In Italy, 38% of patients who undergo surgery are at least 65 years old.255 In the USA, approximately half of operations are performed in patients aged at least 65 years.254,256 Thus, the demand for surgery by older and sicker patients is increasing,257 and POD is regarded as a major problem.
Ageing involves a continuum of changes in biological and functional parameters that increase vulnerability and reduce functional reserve.258 Ageing is often accompanied by chronic multiple diseases, disability and frailty.
Although chronological age plays a role in predisposing to POD, it probably acts as a surrogate variable for the accumulation of age-related risk factors that are differentially expressed among individuals; it is almost certainly the sum of these risk factors that is most important in determining the probability of POD.
Dementia is a main predisposing factor for POD. This condition is very rare among patients under 60 years of age and becomes increasingly frequent as age increases. Data provided by the WHO for Western Europe report a prevalence of 1.6% in patients aged 60 to 64 years and up to 43.1% in patients older than 90 years.259 Previous dementia,23,67,146 cognitive impairment11,12,15,18,34,71,90,93,108–110,113,115,116,125,169,260,261 and depression20,22,71,91,110,112,123,143 are associated with development of POD.
Other chronic diseases are often reported to be present in more than 50% of patients aged 65 to 70 years. In 30% of these patients, more than one single chronic disease is present. Cardiovascular14,16,17,24,28,77,95,103,125,127,148,260,262 and metabolic15,34,131,135,136 risk factors/diseases were found to be most frequently associated with POD.
Multimorbidity consists of a situation in which clinical patterns, evolution and treatment become more complicated than the simple sum of the different illnesses. Multimorbidity reduces the capability to cope with stress and increases global vulnerability – including the risk for POD.257,263 Functional status, also called the sixth vital sign, is defined as the sum of behaviours that are needed to maintain daily activities, including social and cognitive functions.264 Impaired functional status (i.e. reduced levels of independence, abilities and socialisation) is common among the elderly as a result of gait alteration, loss of coordination, reduced or abolished sphincter control, malnutrition, associated illnesses and/or cognitive deterioration. Impaired functional status is associated with surgical site infection, increased mortality and complication rate. In the preoperative setting, performance measures such as the timed ‘Up & Go’ Test265 and other forms of Comprehensive Geriatric Assessment266 have often been used. Impaired functional status has been reported as a predisposing factor for POD.23,34,89,169,267–271
The term ‘frailty’ indicates a situation of critically reduced functional reserves, involving multiple organ systems. It manifests with impaired capability to cope with intrinsic and environmental stressors and limited capability to maintain physiological and psychosocial homeostasis. Currently, 5.8 to 27.3% of the elderly (≥65 years of age) in the general European population are reported to be frail.272 However, studies examining older patients undergoing elective cardiac and noncardiac surgery quote prevalences of frailty between 41.8 and 50.3%273,274; this highlights the great vulnerability of this patient age group. Hypoalbuminaemia, hypocholesterolaemia and high levels of inflammation together with muscular atrophy are specific markers. Frailty has been found to be a predisposing factor for POD among elderly surgical patients.75,123,133,275
Other preoperative variables that can influence the level of stress include the admission setting (emergency vs. nonemergency and inpatient vs. outpatient) and the adoption of dedicated perioperative strategies (prehabilitation,290 fast-track vs. traditional strategy, admission to surgical wards vs. dedicated units). The consensus-based statements regarding risk factors of POD in elderly surgical patients are listed in Table 9.
Intraoperative neuromonitoring is important to avoid unnecessarily deep anaesthesia,203–206 often reaching burst suppression in elderly patients.294 In addition, inflammatory responses due to surgical trauma might be much more relevant for systemic organ dysfunction, including the brain, after surgery. Recently, it was shown that increased blood pressure fluctuation, not absolute or relative hypotension, was predictive of POD in elderly patients after noncardiac surgery.295 If acute fluid replacement is required, cardiac function,296 in particular atrial fibrillation,297–299 should be the focus in respect of perfusion of the brain and all other organs.
Postoperatively, geriatric patients require immediate treatment of POD in the recovery room and on the peripheral ward because of their more vulnerable brain. Additional complications such as respiratory depression and hypoxia (e.g. due to analgesic requirements) should be avoided, and treated if necessary, despite the fact that it remains unclear whether postoperative hypoxia is an independent predictor of POD.22,267
POD and cognitive decline are seen more often after surgery and lead to a higher level of care dependency.36,260 Therefore, monitoring with validated scales (see above) is recommended to detect POD as early as possible. Besides, previous studies evaluating spontaneous eye movements, particularly blinks that appear to be affected in delirious patients, hold promise for delirium detection.300 In addition, EEG (electroencephalography) monitoring, using the relative δ-power from an eyes-closed EEG recording with two electrodes in a frontal–parietal lead, can distinguish between postoperative cardiac surgery patients who developed POD (mean age 77 years) and those who did not (mean age 74 years).301
In patients with dementia, a variety of instruments is available for the measurement of pain, including the Faces Pain Scale and other instruments such as the Pain Assessment in Advanced Dementia Scale302 or the Non-Communicative Patient's Pain Assessment Instrument.303 An overview of validated instruments is given by Hadjistavropoulos et al. 304 Apart from pain, opioids are also associated with an increased risk of POD89,245,305,306 and require close monitoring of POD.180,197,246
In the elderly, nonpharmacological measures are reported to reduce the incidences of POD and falls.307–309 Further research should evaluate different multi-component programmes to select the most useful interventions. The consensus-based statement regarding prevention and treatment of POD in elderly surgical patients is listed in Table 10.
POD is an expensive complication and multi-component interventions can reduce acute and long-term nursing home costs.312–314 Sufficient evidence supports the idea that organisational measures such as dedicated pathways are preventive.312 However, dedicated geriatric units aimed to promote co-management and a team-based approach are only (and rarely) present in academic hospitals. In many other small or intermediate hospitals, they are not at hand. In these hospitals, anaesthesiologists and surgeons share the responsibility to establish adequate organisational solutions. Increasing evidence exists that outcomes in geriatric surgery are highly dependent on the level of care that elderly patients receive perioperatively.315 Both the American Geriatric Association Guidelines on POD316 and the American College of Surgeons/National Surgical Quality Improvement Program Guidelines317 emphasise the importance of dedicated pathways as a means to improve quality of care in geriatric surgery. The most important dedicated models of care are Geriatric Consultation Services,318–321 Acute Care for the Elderly Units322,323 and co-management based models (Orthogeriatric Units and/or Geriatric Consultation Services).324,325 These structures were conceived with the aim of reducing complication rates and mortality in geriatric surgery, especially after hip fracture. Team-based approaches, quality of care and, in some cases, hospital design are basic elements. The introduction of proactive multidisciplinary geriatric interventions in elderly patients with acute hip surgery has been followed by a significant reduction in the incidence of POD.242,326–332
Delirium after anaesthesia in children is reported often. The majority of reported paediatric cases focus on emergence delirium (paedED) in the recovery room with a wide range of incidence from 2 to 80%.50,181,333 PaedED is based on the theoretical framework of delirium defined by DSM.40 PaedED was defined as a disturbance in a child's awareness of and attention to his or her environment with disorientation and perceptual alterations including hypersensitivity to stimuli and hyperactive motor behaviour in the immediate postanaesthesia period.181,334 The term ‘emergence agitation’ should not be used interchangeably with paedED because agitation is excessive motor activity, is more common than paedED in the postoperative period and is associated with discomfort, pain or anxiety.335 The majority of children who develop paedED do so in the recovery room/PACU.50,181,334,335 Research on paedED in peripheral wards is warranted.
For paediatric patients, risk factors for development of paedED should be considered, monitoring for paedED should be established and preventive and treatment measures should be taken to decrease the incidence of paedED. The evidence-based and consensus-based statements are listed in Table 11.
In addition to the Task Force's recommendations, there are several relevant topics of interest with regard to paedED. These topics need to be discussed and several of them warrant further studies.
Children with low adaptability to new situations seem more prone to develop paedED.343 Other influences on emotional stress such as the temperament of the child or the anxiety of parents/guardians might have an influence on paedED.352,383–385 The risk of recurrence of paedED after repetitive procedures is unclear. Research should be undertaken to identify preoperative (psychological, social and medical) risk factors for paedED to help the anaesthesiologist adapt preoperative preparation, whether psychological or pharmacological, to the child's needs.
Continuous EEG monitoring might help to distinguish between patients who will or will not develop paedED. Increased frontal lobe cortical functional connectivity observed in paedED, immediately after the termination of sevoflurane anaesthesia, might have important implications for the development of methods to predict paedED.392
For short-term procedures, propofol is considered to be well tolerated in children. The best model to provide total intravenous anaesthesia in small children seems to be the model designed by Short for adults.393 One should always bear in mind the small risk of developing a propofol infusion syndrome (PRIS), the pathophysiology of which is complex and may involve mitochondria.394 The risk of PRIS seems to be reduced if propofol can be titrated to 4 mg kg−1 h−1 and is used for a short duration (<48 h)395 and if IV glucose is provided (6 mg kg−1 min−1) to avoid lipid catabolism.396
Common side effects of using a continuous infusion of propofol for 60 min in small children are reversible increases in plasma lipid, triglyceride and pancreatic enzymes concentrations.397 Propofol infusions appear to be well tolerated when limiting doses to 4 mg kg−1 h−1 for less than 24 h.398
Strategies to reduce the risk of paedED require a protocol to facilitate implementation. Figure 3 presents a condensed version of the statements. This figure can be used to integrate evidence-based recommendations into local standards to fulfil the requirements of the best practice care of the hospital.
POD is a frequent complication and requires preventive measures as well as immediate and adequate treatment. Although numerous studies have documented the clinical and economic consequences of POD, systematic interventions aimed to reduce its incidence and duration are rarely implemented. Currently, care is not sufficiently focussed on the patient's safety with the aim of reducing long-term harms such as cognitive dysfunction and posttraumatic stress disorder, which can impair quality of life. Despite the huge costs of POD and its preventability, it receives little attention in terms of resource allocation from hospital administrators and healthcare institutional governance representatives. To date, no nation-based strategies have been applied in Europe to minimise POD or monitor its incidence. However, process control has become a key issue for success in many healthcare organisations.
Given the enormous burden exerted by POD on patients, their families, healthcare organisations and public resources, anaesthesiologists operating in Europe should engage to make efforts in designing integrated actions aimed to reduce the incidence and duration of POD. These efforts will become effective when conceived through a team-based multi-component approach. Single items reported may not gain sufficient power alone to ensure effective results. A collaborative path with all the suggested measures to improve the ‘quality chain’ is highly warranted. The main steps include
Patient organisations, politicians and decision-makers for resource allocation and quality assurance, as well as healthcare institutional representatives, should consider reduction of POD as a main goal of their activity for the benefit of the community.
Assistance with the guidelines: none.
Financial support and sponsorship: this guideline was financed solely by the European Society of Anaesthesia (ESA) and by institutional resources of the members of the Task Force and the Advisory Board.
Conflicts of interest: CDS has received a grant from the ESA for expenses related to this guideline and has received a grant from Orion Pharma outside the submitted work but relevant to the guideline; consequently, she abstained from voting on statements related to products from this company. No other conflicts of interest. If any financial activity inside or outside the submitted work might have interfered with independent voting for a recommendation, the person in question did not participate in this specific voting.
Presentation: none.
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1 Antonio Cherubini represented the European Union Geriatric Medicine Society (EUGMS).
2 Claudia D. Spies was the elected chair of the Task Force.