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European Society of Anaesthesiology evidence-based and consensus-based guideline on postoperative delirium

Aldecoa, César; Bettelli, Gabriella; Bilotta, Federico; Sanders, Robert D.; Audisio, Riccardo; Borozdina, Anastasia; Cherubini, Antonio; Jones, Christina; Kehlet, Henrik; MacLullich, Alasdair; Radtke, Finn; Riese, Florian; Slooter, Arjen J.C.; Veyckemans, Francis; Kramer, Sylvia; Neuner, Bruno; Weiss, Bjoern; Spies, Claudia D.

European Journal of Anaesthesiology: April 2017 - Volume 34 - Issue 4 - p 192–214
doi: 10.1097/EJA.0000000000000594
Guidelines

The purpose of this guideline is to present evidence-based and consensus-based recommendations for the prevention and treatment of postoperative delirium. The cornerstones of the guideline are the preoperative identification and handling of patients at risk, adequate intraoperative care, postoperative detection of delirium and management of delirious patients. The scope of this guideline is not to cover ICU delirium. Considering that many medical disciplines are involved in the treatment of surgical patients, a team-based approach should be implemented into daily practice. This guideline is aimed to promote knowledge and education in the preoperative, intraoperative and postoperative setting not only among anaesthesiologists but also among all other healthcare professionals involved in the care of surgical patients.

From the Department of Anesthesiology and Intensive Care Medicine, Charité Campus Virchow-Klinikum and Charité Campus Mitte, Charité – Universitätsmedizin Berlin, Berlin, Germany (FR, SK, BN, BW, CDS); Department of Anesthesiology, Facultad de Medicina de Valladolid, Hospital Universitario Rio Hortega, Valladolid, Spain (CA); Department of Geriatric Surgery; Department of Anaesthesia, Analgesia and Intensive Care, Italian National Research Centres on Aging/IRCCS, Ancona (GB); Department of Anesthesiology, Critical Care and Pain Medicine, ‘Sapienza’ University of Rome, Rome, Italy (FB); Department of Anaesthesiology, University of Wisconsin, Madison, Wisconsin, USA (RDS); Department of Surgery, St. Helens Hospital, Merseyside; University of Liverpool, Liverpool, United Kingdom (RA); Petrovsky National Research Center of Surgery, Moscow, Russia (AB); Geriatria ed Accettazione Geriatrica d’Urgenza, IRCCS-INRCA, Ancona, Italy (AC); Whiston Hospital, Prescot, Merseyside, United Kingdom (CJ); Section of Surgical Pathophysiology and The Lundbeck Centre for Fast-track Hip and Knee Arthroplasty, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (HK); Edinburgh Delirium Research Group, Geriatric Medicine Unit, University of Edinburgh, Edinburgh, United Kingdom (AM); Department of Anaesthesia, Anæstesiologisk Afdeling, Næstved, Denmark (FR); Psychiatric University Hospital, Zurich, Switzerland (FR); Department Intensive Care Medicine and Brain Centre Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands (AJCS); Service d’Anesthésiologie, Cliniques universitaires St Luc, Brussels, Belgium (FV)

Correspondence to Prof Claudia D. Spies, Department of Anaesthesiology and Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Charité Campus Virchow-Klinikum and Charité Campus Mitte, D-10117 Berlin, Germany Tel: +49 30 450 531012/+49 30 450 531052; fax: +49 30 450 531911; e-mail: claudia.spies@charite.de

Published online 9 February 2017

This article is accompanied by the following Invited Commentary:

Steiner LA. Postoperative delirium guidelines. The greater the obstacle, the more glory in overcoming it. Eur J Anaesthesiol 2017; 34:189–191.

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Introduction

The European Society of Anaesthesiology (ESA) is committed to develop evidence-based clinical guidelines of high quality. The ESA Guidelines Committee selected the ‘Reduction of Postoperative Delirium’ as a topic of interest and dedicated a Task Force – established in March 2013 – to cover this matter. The ESA Guidelines Committee chose the members of the Task Force (CDS, CA, GB, FB and RDS) based on their clinical and methodological expertise. The Task Force elected its chairperson, by common consent, at their first telephone conference on 15 March 2013, and the ESA formally confirmed this election during the first constitutional meeting at the European Anaesthesiology Congress in Barcelona on 2 June 2013. Following the first Task Force meeting, members of the Advisory Board were chosen by the Guidelines Committee and the Task Force based on their clinical and methodological expertise in regard to the key questions as agreed by the Task Force in Barcelona in June 2013 (Table 1). The Task Force received its entire financial support from the ESA, without any involvement from the healthcare industry. Sub-committees were established to address the questions of interest.

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Evidence-based and consensus-based methods

The guideline was designed following the ‘Appraisal of Guidelines for Research and Evaluation (AGREE II)’.1–3 During its meetings, the Task Force agreed on several key questions (Table 1). To answer these questions and to develop evidence-based recommendations, search strategies included PubMed, Cochrane, Scopus, ISI Web of knowledge and Embase up to March 2015. Afterwards, only selected new published articles in respect of current clinical practice were considered. Search terms were (delirium OR confusion OR confusion* OR disorientation OR bewilderment) AND (postoperative OR postoperative period OR postoperative period* OR post surgical OR postsurgical OR anesthesia recovery period OR anesthesia recovery period* OR postanesthesia). The searches were performed between January 2014 and March 2015. These searches led to 9425 hits. After automated and manual removal of duplicates, 5779 hits were screened for relevance. Relevant articles included existing systematic and narrative reviews, editorials, meta-analyses, randomised controlled trials (RCTs), cohort studies, case–control studies and cross-sectional studies. Case (series) reports were not included but screened for relevant references. We additionally used the ‘Cited by xx PubMed Central articles’ function in PubMed to identify potentially overlooked but relevant articles. We also screened the reference lists of relevant articles for further publications and included references suggested by the members of the Task Force and the advisory board. Overall, 405 articles were included in the guideline (Fig. 1). Relevant articles were graded according to their level of evidence (LoE) using the Critical Appraisal Worksheets from the Centre for Evidence-Based Medicine of the University of Oxford.4 The grade of recommendation (GoR) was obtained on the basis of the LoE of the literature (Table 2) and the consensus expert opinions by the majority (≥75%) of the Task Force and the advisory board. Experts had to disclose a conflict of interest before participating in the consensus-based voting on any recommendation. Experts were excluded from voting if a conflict of interest relating to any recommendation was possible. For all statements, the strength of the recommendation is prefaced by the GRADE phrase ‘we recommend’ for strong recommendations (GoR A) or by the GRADE phrase ‘we suggest’ for conditional recommendations (GoR B).

The final draft of the guideline was peer-reviewed by the relevant sub-committees of the ESA's Scientific Committee. The reviewed draft was made available between 8 October 2015 and 7 November 2015 on the ESA website for critical appraisal by ESA members. The final manuscript of the guideline was approved by the Guidelines Committee and Board of the ESA before publication. The guidelines expire after 5 years unless updated earlier.

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Background

Postoperative delirium (POD) is an adverse postoperative complication that can occur in patients of any age, from children to the elderly. Its incidence varies in the various age groups and is substantially influenced by patient-related risk factors that are variably distributed and differentially accumulate in the different age groups. Elderly patients are generally thought to be at higher risk because predisposing risk factors such as cognitive impairment, comorbidity, sensorial deficits, malnutrition, polymedication, impaired functional status and frailty (a condition that can only be observed among aged patients) accumulate and overlap with ageing.

Moreover, POD (refer to the specific definition in the ‘Paediatric patients’ section) is a common complication in children of pre-school age (5 to 7 years): whether this is due to age-related psychological issues or to additional inflammatory effects on the brain cannot currently be determined. There is a limited number of studies on cognitive outcomes in children.7 For the USA, the Food and Drug Administration (FDA) recently recommended cautious indications for anaesthesia and surgery in children aged less than 3 years.8 In Europe, the ESA launched an initiative, the EUROpean Safe Tots Anaesthesia Research (Eurostar) Initiative Task Force to promote translational research on anaesthesia neurotoxicity and long-term outcomes after paediatric anaesthesia and surgery.9

In addition, POD is more common in all age groups if precipitating risk factors such as major surgery10–13 or emergency surgery14–19 are present. The incidence increases with a high burden of comorbidities presenting as multiorgan dysfunction before surgery, for example low haemoglobin concentration,20–23 low ejection fraction,16 carotid artery stenosis,24 or high serum creatinine concentration.25–28 POD is associated with several negative clinical consequences, including major postoperative complications, cognitive decline, distress, longer hospitalisation with increased costs and higher mortality.17,20,29–36 Therefore, prevention of POD should be the aim in all patients; if it cannot be prevented, it is essential to intervene immediately.29,37–39

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Definition

Delirium is defined by either the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)40 or by the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD 10, Table 3).41 Delirium is an acute and fluctuating alteration of mental state of reduced awareness and disturbance of attention. POD often starts in the recovery room and occurs up to 5 days after surgery.42–44 One investigation43 found that many patients with POD on the peripheral ward already had POD in the recovery room.

Very early onset of POD in the immediate postanaesthesia period before or on arrival at the recovery room is referred to as ‘emergence delirium’.45–49 In children, paediatric emergence delirium (paedED) may present with purposeless agitation with kicking, absence of eye contact with caregivers or parents (with eyes staring or averting), inconsolability and absence of awareness of the surroundings.50

Delirium can present as hypoactive (decreased alertness, motor activity and anhedonia), as hyperactive (agitated and combative) or as mixed forms.51,52 Increased age seems to be a predisposing factor for the hypoactive form.51,53 The prognosis may be worse with hypoactive delirium, possibly due to relative under-detection by staff and consequently delayed treatment.51

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Relevance

More than 230 million surgical procedures are performed each year worldwide, of which more than 80 million are in Europe.54–56 In Europe, the in-hospital mortality rate up to a maximum of 60 days is 3% after elective surgery and nearly 10% after emergency surgery.55 In addition to mortality, postoperative cognitive impairments such as POD and postoperative cognitive dysfunction (POCD) impose a huge burden on individuals and society.39

The incidence of POD is dependent on perioperative and intraoperative risk factors.57 Therefore, the incidence of POD varies within a broad range.58,59 For example, a meta-analysis of 26 studies of POD reported an incidence of 4.0 to 53.3% in hip fracture patients and 3.6 to 28.3% in elective patients.60

POD, and delirium in general, is often regarded as a temporary attenuation of brain function, usually followed by a full remission. However, strong evidence exists that POD is linked with longer term cognitive and noncognitive morbidity as well as reduced quality of life. It is also associated with increased mortality in the short term and long term. The impact of POD on mortality has been found across different surgical disciplines, in elective and emergency surgery.17,20,23,24,29,31–33,36,61–71 Only a few studies, some of them after adjustment for preoperative cognitive status, found no72–77 or only borderline78 association between POD and mortality.

There is evidence that POD is associated with deteriorating cognition in both the short term (months) and long term (≥1 year) after its occurrence.39,79–81 Often referred to as postoperative cognitive dysfunction (POCD), altered cognition has been found shortly after POD in the ICU setting.82–84 Some investigators have found POD to be associated with POCD up to 12 months postsurgery30,78,85,86 and even associated with dementia up to 5 years after POD.68 In addition, POD has been associated with posttraumatic stress disorder 3 months after surgery.87

POD increases total hospital length of stay (LOS).13,15,20,23,31,34,84,88–96 POD on day 1 after surgery is most predictive of hospital LOS.13 In addition, even POD in the recovery room has been associated with increased total hospital LOS.13 After discharge, patients with POD have an increased level of care dependency20,23,30,32,34–36,61,89,92 or limitations in basic activities of daily living up to 12 months.31

Because patients can present with both delirium and cognitive impairment before surgery, preoperative evaluation of patients for the presence of delirium and cognitive impairment should be considered. Of note, studies that evaluated delirium on admission, that is before surgery, reported prevalence rates between 4.4 and 35.6%.92,97–104 Cognitive impairment at any time during surgical stay, including preoperative delirium, was a risk factor in hip fracture patients for poor functional outcome 12 months later.104 Any cognitive impairment before hospital admission was an independent risk factor for worse longer term cognitive impairment.104,105

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Risk factors

A widely accepted model of delirium differentiates predisposing factors (that are related to the patient) and precipitating factors (that trigger the onset of delirium).106 The risk of developing delirium can be seen as the product of predisposing and precipitating factors. Risk assessment is considered as the responsibility of different disciplines and should be implemented in the perioperative clinical pathway.

The evidence-based and consensus statements and their GoR for preoperative, intraoperative and postoperative risk factors for POD are listed in Table 4. As many studies identified advanced age as a risk factor for POD both in univariate and in multivariate analysis, we show the evidence in two columns (all adults vs. elderly ≥65 years of age) according to the inclusion criteria of the cited studies. In the medical literature, elderly patients are often defined as aged at least 65 years.105 However, chronological age may be an insufficient proxy to capture the complex underlying pathological mechanism leading to increased vulnerability to POD.

In addition to the above statements, emergency surgery14–19,155 and postoperative complications156 increase the risk of higher rates and prolonged duration of POD as well as long-term cognitive impairment.157 Protocols are required to identify these risk factors and to implement risk reduction strategies (e.g. fast track).105,158,159

Hypothermia on admission to the recovery room has also been reported to be a risk factor for hypoactive emergence.49 In addition, preoperative fasting glucose concentrations are associated with more delirium after cardiac surgery.128,160 Despite existing evidence on biomarkers for the detection and monitoring of POD from both the ICU setting93,161,162 and the non-ICU setting,14,116,163–169 their use in clinical routine cannot currently be recommended; further research is required.

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Monitoring of postoperative delirium

Early diagnosis of POD is critical to trigger focussed and effective treatment.29,37–39,79,80 Patients should not leave the recovery room without being screened for POD. Current reference standards for diagnosing delirium, including POD, are the DSM-540 or the ICD 1041 (Table 3). Extensive training is required to use these reference standards.105 In addition, the new definition of DSM-5 compared with DSM IV-TR decreases the sensitivity to diagnose delirium because the disturbances do not occur in the context of a severely reduced level of arousal.170,171 However, the DSM-5 guidance notes clarify this, stating that patients with a severely reduced level of arousal (of acute onset) above the level of coma should be considered as having ‘severe inattention’ and hence as having delirium.40,172 As this is relevant in the postoperative and ICU setting, it is important that both a sedation/agitation tool such as the Richmond Agitation-Sedation Scale173 (RASS; Table 5) and a delirium screening tool are used.

A delirium screening system suitable for use in the recovery room should be easily applicable and fast to perform.44 A high sensitivity (to detect POD as early as possible) may be achieved with two scores – the Nursing Delirium Screening Scale174 (Nu-DESC) and the Confusion Assessment Method (CAM).44,176 However, in a recent study, the sensitivities of both of these tests were lower than expected,177 and it is to be noted that the CAM has a low sensitivity when not used by staff specially trained in its use. In the latter study reporting lower sensitivities despite a high methodological standard, the measurements were performed in a prolonged time frame of 60 min, that is too slow to assess the sudden changes in the recovery room seen in this patient population.177 The study reporting a higher sensitivity was embedded in an accreditation process in which all team members – nurses and physicians – were educated before implementing quality indicators for delirium, pain and postoperative nausea and vomiting assessment in the recovery room.44 More research is needed regarding the optimal tools for detection of delirium in the recovery room.

If POD is detected, patients should not be discharged from the recovery room to the ward without having started aetiology-based and symptom-based treatment.179 This is because the longer the duration of delirium and the later the treatment is started, the more cognitive decline may be expected.39,79 On the postoperative ward, POD should be monitored at least once per shift due to the fluctuating course of POD.175 The evidence-based and consensus-based statements regarding POD monitoring are listed in Table 6.

POD screening is recommended by using standardised rating scales validated for the postoperative setting. The scales usually take less than 1 min to complete. Only those scores that are validated for the recovery room or the peripheral ward with an adequate sensitivity are listed below. Scores validated only for the ICU or other settings are not listed.

For emergence delirium immediately after surgery, agitation scales such as the RASS173 were used in all studies,47–49,180 whereas the Pediatric Anesthesia Emergence Delirium (PAED) scale (Table 7) was used in children.181

In the recovery room setting, the following delirium scores have undergone validation against the criteria according to the DSM:

1. Nu-DESC44,174,177 reported sensitivity between 32 and 95% and reported specificity up to 87%.44 If sensitivity in the different recovery room setting is in the lower range, it may be advisable to use a threshold of at least 1 point to increase sensitivity to 80%.177

2. CAM43,44,105,176 or the CAM-ICU.178 In a post-anaesthesia care unit (PACU), sensitivity has been reported between 28 and 43%, with a specificity of 98%.45,177

In special patient populations, other scores have been used, and diagnostic validity has been assessed. Although, these scores might be applicable and have been validated regarding standards (not necessarily DSM), they have either been assessed in special patient populations or in settings different from the postoperative setting. Some of these scores, such as the Delirium Rating Scale-98182 or the Memorial Delirium Assessment Scale,183 might be useful to evaluate postoperative patients, but they might take longer to perform in a busy recovery room setting. Several scores can be used as alternatives: the Bedside Confusion Scale,184 Clinical Assessment of Confusion,139 Confusion Rating Scale,186 the Delirium-O-Meter,187 Delirium Observation Screening,188 the delirium symptom interview (DSI),189 the Neelon and Champagne Confusion Scale190 or the 4 ‘A's Test.191

In general, the team (including nurses and physicians) should be involved in the choice of which score to use. For routine implementation, it is mandatory to train the team on the basic features of delirium as well as the features of any tools that will be used. This is not only because scores such as CAM require training, whereas the NuDesc does not, but also because the team needs to have a common understanding of delirium and to be able to communicate consistently on the results of tools used.105,192

In addition, it is important to note that not all scores are available in different languages. Therefore, national societies might consider validating the scores in the language in which it is to be applied.

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Prevention and treatment

Prevention and treatment options are available to reduce the incidence and duration of POD. If POD occurs, immediate treatment of both causative factors and symptoms has a major impact in reducing its duration29,37–39 (Fig. 2). The evidence-based and consensus-based statements regarding prevention and treatment are listed in Table 8.

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.

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Special patient groups

Geriatric 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.

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Risk factors and preoperative evaluation

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

Hearing loss was found to be a predisposing factor for POD in three studies276–278 and mentioned in three reviews58,270,279; the last two of these reviews and one additional study on internal medicine patients120 additionally mention visual impairment as a risk factor for POD.

Malnutrition affects 2 to 16% of community-dwelling elderly280 and is frequently undiagnosed in those living at home. Between 20 and 65% of these patients suffer from nutritional deficits.281,282 The main nutritional deficits concern proteins, minerals and vitamins. The most widely used test to diagnose malnutrition is the Mini-Nutritional Assessment283 that can be performed at the bedside using a questionnaire. Malnutrition including low serum albumin concentration and/or homeostatic alterations and dehydration have been found to be associated with POD.112,117,122,132,148,267,284,285

Preoperative alcohol use disorders are seen in many elderly patients.286 Many reports indicate that the number of older persons abusing alcohol is increasing in Europe.287–289 Due to age-related changes, they present increased sensitivity and reduced tolerance to alcohol. POD has been reported as increased in elderly patients with a history of alcohol use disorders.20,34,71,116,138,141,142

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.

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Intraoperative and postoperative management

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.

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Organisational issues

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

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Paediatric patients

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.

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Predisposing factors

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.

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Premedication

Premedication with midazolam reduces paedED after sevoflurane anaesthesia.361,362,364–366 However, different durations of procedures and different methods used to assess paedED make it difficult to provide a conclusion regarding the influence of midazolam on paedED.363,367 Melatonin might be superior to midazolam to decrease the risk of paedED but it does not reduce anxiety.386,387 Availability of melatonin differs widely among European countries. It is either an ‘over the counter’ drug or has to be prescribed.

Premedication with or intraoperative use of α2-agonists (dexmedetomidine372–374 or clonidine50) decreases the incidence of paedED.50,359,375–378 In a recent double-blind RCT, preoperative intranasal dexmedetomidine was more effective than clonidine in decreasing the incidence and severity of emergence agitation and also decreased fentanyl consumption after surgery.379 More recently, in small series, premedication with gabapentin,388 premedication with ketamine,389 intraoperative dexamethasone390 or magnesium391 were also found to decrease paedED.

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Neuromonitoring

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

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Anaesthesia

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

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Postoperative pain

Acute perioperative pain in infants and children is still often undertreated.399,400 Three of the most commonly performed surgical procedures in children (tonsillectomy, appendicectomy and orchidopexy) are more painful than usually expected. Up to 44% of children still suffer from severe pain until day 3, and up to 30% until day 7 after surgery.401 Several analgesic techniques, such as regional anaesthesia (caudal block354,381 and fascia iliaca compartment block349,402) or pharmacological interventions (fentanyl350,382 or nalbuphine351,403,404) are available and seem to reduce the incidence of paedED.

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Implementation

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.

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Conclusion

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

1. preoperative evaluation of POD risk and identification of patients at risk

2. communication about this risk to patients, their family and care team members

3. best possible preoperative conditions to be achieved

4. perioperative avoidance of use of anticholinergic agents and benzodiazepines except when needed. Benzodiazepines can be considered in cases of alcohol withdrawal

5. attempts to reduce surgical stress, together with organ-protective intraoperative management, including neuromonitoring to avoid excessively deep anaesthesia(a)effective multimodal opioid-sparing analgesia(b)implementation of enhanced recovery programmes

6. cognitive monitoring to be aimed at recognition of preoperative cognitive decline and to detect POD as early as possible, including in the recovery room

7. effective treatment of POD by protocols

8. follow-up of POD patients all along their hospital stay

9. patient information on adequate medical support, to ensure continuity of care after discharge.

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.

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Acknowledgements relating to this article

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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References

1. AGREE CollaborationDevelopment and validation of an international appraisal instrument for assessing the quality of clinical practice guidelines: the AGREE project. Qual Saf Healthcare 2003; 12:18–23.
2. Brouwers MC, Kho ME, Browman GP, et al. Development of the AGREE II, Part 1: Performance, usefulness and areas for improvement. CMAJ 2010; 182:1045–1052.
3. Brouwers MC, Kho ME, Browman GP, et al. Development of the AGREE II, Part 2: Assessment of validity of items and tools to support application. CMAJ 2010; 182:E472–E478.
4. University of Oxford, CEBM Centre for Evidence-Based MedicineCritical appraisal tools. 2015; http://http://www.cebm.net/critical-appraisal/http://www.cebm.net/critical-appraisal/ [Accessed 24 July 2015].
5. Atkins D, Best D, Briss PA, et al. Grading quality of evidence and strength of recommendations. BMJ 2004; 328:1490.
6. Council of Europe Publishing, Council of Europe CoMRecommendation Rec(2001)13 of the Committee of Ministers to member states on developing a methodology for drawing up guidelines on best medical practices. 2001; https://wcd.coe.int/ViewDoc.jsp?id=228755&Site=COEhttps://wcd.coe.int/ViewDoc.jsp?id=228755&Site=COE. [Accessed 27 July 2015].
7. Flick RP, Katusic SK, Colligan RC, et al. Cognitive and behavioral outcomes after early exposure to anesthesia and surgery. Pediatrics 2011; 128:e1053–e1061.
8. Rappaport BA, Suresh S, Hertz S, et al. Anesthetic neurotoxicity – clinical implications of animal models. N Engl J Med 2015; 372:796–797.
9. European Society of AnaesthesiologyEUROpean safe tots anaesthesia research initiative task force. 2015; https://http://www.esahq.org/research/research-groups/eurostar/https://www.esahq.org/research/research-groups/eurostar/. [Accessed 10 December 2015].
10. Do T-D, Lemogne C, Journois D, et al. Low social support is associated with an increased risk of postoperative delirium. J Clin Anesth 2012; 24:126–132.
11. Hempenius L, Slaets JPJ, van Asselt DZB, et al. Interventions to prevent postoperative delirium in elderly cancer patients should be targeted at those undergoing nonsuperficial surgery with special attention to the cognitive impaired patients. Eur J Surg Oncol 2015; 41:28–33.
12. Leung JM, Sands LP, Lim E, et al. Does preoperative risk for delirium moderate the effects of postoperative pain and opiate use on postoperative delirium? Am J Geriatr Psychiatry 2013; 21:946–956.
13. Radtke FM, Franck M, MacGuill M, et al. Duration of fluid fasting and choice of analgesic are modifiable factors for early postoperative delirium. Eur J Anaesthesiol 2010; 27:411–416.
14. Abelha FJ, Fernandes V, Botelho M, et al. Apolipoprotein E e4 allele does not increase the risk of early postoperative delirium after major surgery. J Anesth 2012; [Epub ahead of print].
15. Ansaloni L, Catena F, Chattat R, et al. Risk factors and incidence of postoperative delirium in elderly patients after elective and emergency surgery. Br J Surg 2010; 97:273–280.
16. Bucerius J, Gummert JF, Borger MA, et al. Predictors of delirium after cardiac surgery delirium: effect of beating-heart (off-pump) surgery. J Thorac Cardiovasc Surg 2004; 127:57–64.
17. Gottesman RF, Grega MA, Bailey MM, et al. Delirium after coronary artery bypass graft surgery and late mortality. Ann Neurol 2010; 67:338–344.
18. Kalisvaart KJ, Vreeswijk R, de Jonghe JFM, et al. Risk factors and prediction of postoperative delirium in elderly hip-surgery patients: implementation and validation of a medical risk factor model. J Am Geriatr Soc 2006; 54:817–822.
19. Koebrugge B, van Wensen RJ, Bosscha K, et al. Delirium after emergency/elective open and endovascular aortoiliac surgery at a surgical ward with a high-standard delirium care protocol. Vascular 2010; 18:279–287.
20. Fineberg SJ, Nandyala SV, Marquez-Lara A, et al. Incidence and risk factors for postoperative delirium after lumbar spine surgery. Spine (Phila Pa 1976) 2013; 38:1790–1796.
21. Joosten E, Lemiengre J, Nelis T, et al. Is anaemia a risk factor for delirium in an acute geriatric population? Gerontology 2006; 52:382–385.
22. Kazmierski J, Kowman M, Banach M, et al. Incidence and predictors of delirium after cardiac surgery: results from The IPDACS Study. J Psychosom Res 2010; 69:179–185.
23. Robinson TN, Raeburn CD, Tran ZV, et al. Postoperative delirium in the elderly: risk factors and outcomes. Ann Surg 2009; 249:173–178.
24. Norkiene I, Ringaitiene D, Misiuriene I, et al. Incidence and precipitating factors of delirium after coronary artery bypass grafting. Scand Cardiovasc J 2007; 41:180–185.
25. Bakker RC, Osse RJ, Tulen JHM, et al. Preoperative and operative predictors of delirium after cardiac surgery in elderly patients. Eur J Cardiothorac Surg 2012; 41:544–549.
26. Hatano Y, Narumoto J, Shibata K, et al. White-matter hyperintensities predict delirium after cardiac surgery. Am J Geriatr Psychiatry 2013; 21:938–945.
27. Miyazaki S, Yoshitani K, Miura N, et al. Risk factors of stroke and delirium after off-pump coronary artery bypass surgery. Interact Cardiovasc Thorac Surg 2011; 12:379–383.
28. Tan MC, Felde A, Kuskowski M, et al. Incidence and predictors of postcardiotomy delirium. Am J Geriatr Psychiatry 2008; 16:575–583.
29. Bellelli G, Mazzola P, Morandi A, et al. Duration of postoperative delirium is an independent predictor of 6-month mortality in older adults after hip fracture. J Am Geriatr Soc 2014; 62:1335–1340.
30. Bickel H, Gradinger R, Kochs E, et al. High risk of cognitive and functional decline after postoperative delirium. A three-year prospective study. Dement Geriatr Cogn Disord 2008; 26:26–31.
31. Edelstein DM, Aharonoff GB, Karp A, et al. Effect of postoperative delirium on outcome after hip fracture. Clin Orthop Relat Res 2004; 422:195–200.
32. Francis J, Martin D, Kapoor WN. A prospective study of delirium in hospitalized elderly. JAMA 1990; 263:1097–1101.
33. Krzych LJ, Wybraniec MT, Krupka-Matuszczyk I, et al. Detailed insight into the impact of postoperative neuropsychiatric complications on mortality in a cohort of cardiac surgery subjects: a 23,000-patient-year analysis. J Cardiothorac Vasc Anesth 2014; 28:448–457.
34. Marcantonio ER, Goldman L, Mangione CM, et al. A clinical prediction rule for delirium after elective noncardiac surgery. JAMA 1994; 271:134–139.
35. Vochteloo AJ, Moerman S, van der Burg BL, et al. Delirium risk screening and haloperidol prophylaxis program in hip fracture patients is a helpful tool in identifying high-risk patients, but does not reduce the incidence of delirium. BMC Geriatr 2011; 11:39.
36. Witlox J, Eurelings LSM, de Jonghe JFM, et al. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA 2010; 304:443–451.
37. Heymann A, Radtke F, Schiemann A, et al. Delayed treatment of delirium increases mortality rate in intensive care unit patients. J Int Med Res 2010; 38:1584–1595.
38. Pisani MA, Kong SY, Kasl SV, et al. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med 2009; 180:1092–1097.
39. Saczynski JS, Marcantonio ER, Quach L, et al. Cognitive trajectories after postoperative delirium. N Engl J Med 2012; 367:30–39.
40. American Psychiatric AssociationDiagnostic and statistical manual of mental disorders (Dsm-5®). 5th ed.Washigton, DC:Amer Psychiatric Pub Inc; 2013.
41. World Health Organization. International Statistical Classification of Diseases and Related Health Problems 10th Revision. http://apps.who.int/classifications/icd10/browse/2016/en, 2015. [Accessed 9 December 2015].
42. Olin K, Eriksdotter-Jonhagen M, Jansson A, et al. Postoperative delirium in elderly patients after major abdominal surgery. Br J Surg 2005; 92:1559–1564.
43. Sharma PT, Sieber FE, Zakriya KJ, et al. Recovery room delirium predicts postoperative delirium after hip-fracture repair. Anesth Analg 2005; 101:1215–1220.
44. Radtke FM, Franck M, Schneider M, et al. Comparison of three scores to screen for delirium in the recovery room. Br J Anaesth 2008; 101:338–343.
45. Bastron RD, Moyers J. Emergence delirium. JAMA 1967; 200:883.
46. Hudek K. Emergence delirium: a nursing perspective. AORN J 2009; 89:509–516.
47. Lepouse C, Lautner CA, Liu L, et al. Emergence delirium in adults in the postanaesthesia care unit. Br J Anaesth 2006; 96:747–753.
48. Radtke FM, Franck M, Hagemann L, et al. Risk factors for inadequate emergence after anesthesia: emergence delirium and hypoactive emergence. Minerva Anestesiol 2010; 76:394–403.
49. Xara D, Silva A, Mendonca J, et al. Inadequate emergence after anesthesia: emergence delirium and hypoactive emergence in the Postanesthesia Care Unit. J Clin Anesth 2013; 25:439–446.
50. Dahmani S, Delivet H, Hilly J. Emergence delirium in children: an update. Curr Opin Anaesthesiol 2014; 27:309–315.
51. Robinson TN, Raeburn CD, Tran ZV, et al. Motor subtypes of postoperative delirium in older adults. Arch Surg 2011; 146:295–300.
52. Meagher DJ, O’Hanlon D, O’Mahony E, et al. Relationship between symptoms and motoric subtype of delirium. J Neuropsychiatry Clin Neurosci 2000; 12:51–56.
53. Meagher D, Moran M, Raju B, et al. A new data-based motor subtype schema for delirium. J Neuropsychiatry Clin Neurosci 2008; 20:185–193.
54. European Union, EurostatYour key to European statistics. 2015; http://ec.europa.eu/eurostat/data/databasehttp://ec.europa.eu/eurostat/data/database [Accessed 15 March 2015].
55. Pearse RM, Moreno RP, Bauer P, et al. Mortality after surgery in Europe: a 7 day cohort study. Lancet 2012; 380:1059–1065.
56. Weiser TG, Regenbogen SE, Thompson KD, et al. An estimation of the global volume of surgery: a modelling strategy based on available data. Lancet 2008; 372:139–144.
57. Smulter N, Lingehall HC, Gustafson Y, et al. Delirium after cardiac surgery: incidence and risk factors. Interact Cardiovasc Thorac Surg 2013; 17:790–796.
58. Dasgupta M, Dumbrell AC. Preoperative risk assessment for delirium after noncardiac surgery: a systematic review. J Am Geriatr Soc 2006; 54:1578–1589.
59. Dyer CB, Ashton CM, Teasdale TA. Postoperative delirium. A review of 80 primary data-collection studies. Arch Intern Med 1995; 155:461–465.
60. Bruce AJ, Ritchie CW, Blizard R, et al. The incidence of delirium associated with orthopedic surgery: a meta-analytic review. Int Psychogeriatr 2007; 19:197–214.
61. Abelha FJ, Luís C, Veiga D, et al. Outcome and quality of life in patients with postoperative delirium during an ICU stay following major surgery. Crit Care 2013; 17:R257.
62. Borhani Haghighi A, Malekhoseini SA, Bahramali E, et al. Neurological complications of first 100 orthotopic liver transplantation patients in southern Iran. Transplant Proc 2005; 37:3197–3199.
63. Bussiere M, Hopman W, Day A, et al. Indicators of functional status for primary malignant brain tumour patients. Can J Neurol Sci 2005; 32:50–56.
64. Dubljanin-Raspopovic E, Markovic Denic L, Marinkovic J, et al. Use of early indicators in rehabilitation process to predict one-year mortality in elderly hip fracture patients. Hip Int 2012; 22:661–667.
65. Heijmeriks JA, Dassen W, Prenger K, et al. The incidence and consequences of mental disturbances in elderly patients post cardiac surgery – a comparison with younger patients. Clin Cardiol 2000; 23:540–546.
66. Koster S, Hensens AG, Schuurmans MJ, et al. Consequences of delirium after cardiac operations. Ann Thorac Surg 2012; 93:705–711.
67. Lee KH, Ha YC, Lee YK, et al. Frequency, risk factors, and prognosis of prolonged delirium in elderly patients after hip fracture surgery. Clin Orthop Relat Res 2011; 469:2612–2620.
68. Lundström M, Edlund A, Bucht G, et al. Dementia after delirium in patients with femoral neck fractures. J Am Geriatr Soc 2003; 51:1002–1006.
69. Mangoni AA, van Munster BC, Woodman RJ, et al. Measures of anticholinergic drug exposure, serum anticholinergic activity, and all-cause postdischarge mortality in older hospitalized patients with hip fractures. Am J Geriatr Psychiatry 2013; 21:785–793.
70. Mazzola P, Bellelli G, Broggini V, et al. Postoperative delirium and prefracture disability predict 6-month mortality among the oldest old hip fracture patients. Aging Clin Exp Res 2015; 27:53–60.
71. Pompei P, Foreman M, Rudberg MA, et al. Delirium in hospitalized older persons: outcomes and predictors. J Am Geriatr Soc 1994; 42:809–815.
72. Berry SD, Samelson EJ, Bordes M, et al. Survival of aged nursing home residents with hip fracture. J Gerontol A Biol Sci Med Sci 2009; 64:771–777.
73. Juliebo V, Krogseth M, Skovlund E, et al. Delirium is not associated with mortality in elderly hip fracture patients. Dement Geriatr Cogn Disord 2010; 30:112–120.
74. Kat MG, de Jonghe JF, Vreeswijk R, et al. Mortality associated with delirium after hip-surgery: a 2-year follow-up study. Age Ageing 2011; 40:312–318.
75. Kim S, Han H-S, Jung H, et al. Multidimensional frailty score for the prediction of postoperative mortality risk. JAMA Surg 2014; 149:633–640.
76. Large MC, Reichard C, Williams JTB, et al. Incidence, risk factors, and complications of postoperative delirium in elderly patients undergoing radical cystectomy. Urology 2013; 81:123–128.
77. Sasajima Y, Sasajima T, Azuma N, et al. Factors related to postoperative delirium in patients with lower limb ischaemia: a prospective cohort study. Eur J Vasc Endovasc Surg 2012; 44:411–415.
78. Kat MG, Vreeswijk R, de Jonghe JFM, et al. Long-term cognitive outcome of delirium in elderly hip surgery patients. A prospective matched controlled study over two and a half years. Dement Geriatr Cogn Disord 2008; 26:1–8.
79. Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med 2013; 369:1306–1316.
80. Neufeld KJ, Leoutsakos JM, Oh E, et al. Long-term outcomes of older adults with and without delirium immediately after recovery from general anesthesia for surgery. Am J Geriatr Psychiatry 2015; 23:1067–1074.
81. Monk TG, Weldon BC, Garvan CW, et al. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology 2008; 108:18–30.
82. Bryson GL, Wyand A, Wozny D, et al. A prospective cohort study evaluating associations among delirium, postoperative cognitive dysfunction, and apolipoprotein E genotype following open aortic repair. Can J Anaesth 2011; 58:246–255.
83. Hudetz JA, Patterson KM, Byrne AJ, et al. Postoperative delirium is associated with postoperative cognitive dysfunction at one week after cardiac surgery with cardiopulmonary bypass. Psychol Rep 2009; 105:921–932.
84. Norkiene I, Samalavicius R, Misiuriene I, et al. Incidence and risk factors for early postoperative cognitive decline after coronary artery bypass grafting. Medicina (Kaunas) 2010; 46:460–464.
85. Brown LJ, Ferner HS, Robertson J, et al. Differential effects of delirium on fluid and crystallized cognitive abilities. Arch Gerontol Geriatr 2011; 52:153–158.
86. Wacker P, Nunes PV, Cabrita H, et al. Postoperative delirium is associated with poor cognitive outcome and dementia. Dement Geriatr Cogn Disord 2006; 21:221–227.
87. Drews T, Franck M, Radtke FM, et al. Postoperative delirium is an independent risk factor for posttraumatic stress disorder in the elderly patient: a prospective observational study. Eur J Anaesthesiol 2015; 32:147–151.
88. Berggren D, Gustafson Y, Eriksson B, et al. Postoperative confusion after anesthesia in elderly patients with femoral neck fractures. Anesth Analg 1987; 66:497–504.
89. Brouquet A, Cudennec T, Benoist S, et al. Impaired mobility, ASA status and administration of tramadol are risk factors for postoperative delirium in patients aged 75 years or more after major abdominal surgery. Ann Surg 2010; 251:759–765.
90. Furlaneto ME, Garcez-Leme LE. Delirium in elderly individuals with hip fracture: causes, incidence, prevalence, and risk factors. Clinics (Sao Paulo) 2006; 61:35–40.
91. Greene NH, Attix DK, Weldon BC, et al. Measures of executive function and depression identify patients at risk for postoperative delirium. Anesthesiology 2009; 110:788–795.
92. Gustafson Y, Berggren D, Brannstrom B, et al. Acute confusional states in elderly patients treated for femoral neck fracture. J Am Geriatr Soc 1988; 36:525–530.
93. Liu P, Li Y, Wang X, et al. High serum interleukin-6 level is associated with increased risk of delirium in elderly patients after noncardiac surgery: a prospective cohort study. Chin Med J 2013; 126:3621–3627.
94. Markar SR, Smith IA, Karthikesalingam A, et al. The clinical and economic costs of delirium after surgical resection for esophageal malignancy. Ann Surg 2013; 258:77–81.
95. Santos FS, Velasco IT, Fráguas R. Risk factors for delirium in the elderly after coronary artery bypass graft surgery. Int Psychogeriatr 2004; 16:175–193.
96. Street JT, Noonan VK, Cheung A, et al. Incidence of acute care adverse events and long-term health-related quality of life in patients with TSCI. Spine J 2015; 15:923–932.
97. Brauer C, Morrison RS, Silberzweig SB, et al. The cause of delirium in patients with hip fracture. Arch Intern Med 2000; 160:1856–1860.
98. Edlund A, Lundstrom M, Lundstrom G, et al. Clinical profile of delirium in patients treated for femoral neck fractures. Dement Geriatr Cogn Disord 1999; 10:325–329.
99. Edlund A, Lundstrom M, Brannstrom B, et al. Delirium before and after operation for femoral neck fracture. J Am Geriatr Soc 2001; 49:1335–1340.
100. Formiga F, Lopez-Soto A, Sacanella E, et al. Mortality and morbidity in nonagenarian patients following hip fracture surgery. Gerontology 2003; 49:41–45.
101. Johansson IS, Hamrin EK, Larsson G. Psychometric testing of the NEECHAM Confusion Scale among patients with hip fracture. Res Nurs Health 2002; 25:203–211.
102. Kagansky N, Rimon E, Naor S, et al. Low incidence of delirium in very old patients after surgery for hip fractures. Am J Geriatr Psychiatry 2004; 12:306–314.
103. Morrison RS, Magaziner J, Gilbert M, et al. Relationship between pain and opioid analgesics on the development of delirium following hip fracture. J Gerontol A Biol Sci Med Sci 2003; 58:76–81.
104. Gruber-Baldini AL, Zimmerman S, Morrison RS, et al. Cognitive impairment in hip fracture patients: timing of detection and longitudinal follow-up. J Am Geriatr Soc 2003; 51:1227–1236.
105. American Geriatrics Society Expert Panel on Postoperative Delirium in Older AdultsPostoperative delirium in older adults: best practice statement from the American Geriatrics Society. J Am Coll Surg 2015; 220:136–148.
106. Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA 1996; 275:852–857.
107. Kim SD, Park SJ, Lee DH, et al. Risk factors of morbidity and mortality following hip fracture surgery. Korean J Anesthesiol 2013; 64:505–510.
108. Bickel H, Gradinger R, Kochs E, et al. Incidence and risk factors of delirium after hip surgery. Psychiatr Prax 2004; 31:360–365.
109. Dai YT, Lou MF, Yip PK, et al. Risk factors and incidence of postoperative delirium in elderly Chinese patients. Gerontology 2000; 46:28–35.
110. Galanakis P, Bickel H, Gradinger R, et al. Acute confusional state in the elderly following hip surgery: incidence, risk factors and complications. Int J Geriatr Psychiatry 2001; 16:349–355.
111. Gani H, Domi R, Kodra N, et al. The incidence of postoperative delirium in elderly patients after urologic surgery. Med Arch 2013; 67:45–47.
112. Harasawa N, Mizuno T. A novel scale predicting postoperative delirium (POD) in patients undergoing cerebrovascular surgery. Arch Gerontol Geriatr 2014; 59:264–271.
113. Litaker D, Locala J, Franco K, et al. Preoperative risk factors for postoperative delirium. Gen Hosp Psychiatry 2001; 23:84–89.
114. McAlpine JN, Hodgson EJ, Abramowitz S, et al. The incidence and risk factors associated with postoperative delirium in geriatric patients undergoing surgery for suspected gynecologic malignancies. Gynecol Oncol 2008; 109:296–302.
115. Schor JD, Levkoff SE, Lipsitz LA, et al. Risk factors for delirium in hospitalized elderly. JAMA 1992; 267:827–831.
116. Shah S, Weed HG, He X, et al. Alcohol-related predictors of delirium after major head and neck cancer surgery. Arch Otolaryngol Head Neck Surg 2012; 138:266–271.
117. Tei M, Ikeda M, Haraguchi N, et al. Risk factors for postoperative delirium in elderly patients with colorectal cancer. Surg Endosc 2010; 24:2135–2139.
118. Yoshimura Y, Kubo S, Shirata K, et al. Risk factors for postoperative delirium after liver resection for hepatocellular carcinoma. World J Surg 2004; 28:982–986.
119. Chen YL, Lin HC, Lin KH, et al. Low hemoglobin level is associated with the development of delirium after hepatectomy for hepatocellular carcinoma patients. PLoS One 2015; 10:e0119199.
120. Edlund A, Lundström M, Karlsson S, et al. Delirium in older patients admitted to general internal medicine. J Geriatr Psychiatry Neurol 2006; 19:83–90.
121. Bucerius J, Gummert JF, Walther T, et al. Diabetes in patients undergoing coronary artery bypass grafting. Impact on perioperative outcome. Z Kardiol 2005; 94:575–582.
122. Larsen KA, Kelly SE, Stern TA, et al. Administration of olanzapine to prevent postoperative delirium in elderly joint-replacement patients: a randomized, controlled trial. Psychosomatics 2010; 51:409–418.
123. Leung JM, Tsai TL, Sands LP. Brief report: preoperative frailty in older surgical patients is associated with early postoperative delirium. Anesth Analg 2011; 112:1199–1201.
124. Nötzold A, Michel K, Khattab AA, et al. Diabetes mellitus increases adverse neurocognitive outcome after coronary artery bypass grafting surgery. Thorac Cardiovasc Surg 2006; 54:307–312.
125. Otomo S, Maekawa K, Goto T, et al. Preexisting cerebral infarcts as a risk factor for delirium after coronary artery bypass graft surgery. Interact Cardiovasc Thorac Surg 2013; 17:799–804.
126. Papaioannou A, Fraidakis O, Michaloudis D, et al. The impact of the type of anaesthesia on cognitive status and delirium during the first postoperative days in elderly patients. Eur J Anaesthesiol 2005; 22:492–499.
127. Rudolph JL, Jones RN, Rasmussen LS, et al. Independent vascular and cognitive risk factors for postoperative delirium. Am J Med 2007; 120:807–813.
128. Krzych LJ, Wybraniec MT, Krupka-Matuszczyk I, et al. Complex assessment of the incidence and risk factors of delirium in a large cohort of cardiac surgery patients: a single-center 6-year experience. Biomed Res Int 2013; 2013:835850.
129. Vaurio LE, Sands LP, Wang Y, et al. Postoperative delirium: the importance of pain and pain management. Anesth Analg 2006; 102:1267–1273.
130. Kosar CM, Tabloski PA, Travison TG, et al. Effect of preoperative pain and depressive symptoms on the development of postoperative delirium. Lancet Psychiatry 2014; 1:431–436.
131. Bucerius J, Gummert JF, Walther T, et al. Impact of diabetes mellitus on cardiac surgery outcome. Thorac Cardiovasc Surg 2003; 51:11–16.
132. Rudolph JL, Jones RN, Levkoff SE, et al. Derivation and validation of a preoperative prediction rule for delirium after cardiac surgery. Circulation 2009; 119:229–236.
133. Kelly AM, Batke JNN, Dea N, et al. Prospective analysis of adverse events in surgical treatment of degenerative spondylolisthesis. Spine J 2014; 14:2905–2910.
134. Koebrugge B, Koek HL, van Wensen RJA, et al. Delirium after abdominal surgery at a surgical ward with a high standard of delirium care: incidence, risk factors and outcomes. Dig Surg 2009; 26:63–68.
135. Weed HG, Lutman CV, Young DC, et al. Preoperative identification of patients at risk for delirium after major head and neck cancer surgery. Laryngoscope 1995; 105:1066–1068.
136. Yildizeli B, Ozyurtkan MO, Batirel HF, et al. Factors associated with postoperative delirium after thoracic surgery. Ann Thorac Surg 2005; 79:1004–1009.
137. Tune LE, Damlouji NF, Holland A, et al. Association of postoperative delirium with raised serum levels of anticholinergic drugs. Lancet 1981; 2:651–653.
138. Minden SL, Carbone LA, Barsky A, et al. Predictors and outcomes of delirium. Gen Hosp Psychiatry 2005; 27:209–214.
139. Vermeersch PEH. The clinical assessment of confusion-A. Appl Nurs Res 1990; 3:128–133.
140. Tune L, Carr S, Cooper T, et al. Association of anticholinergic activity of prescribed medications with postoperative delirium. J Neuropsychiatry Clin Neurosci 1993; 5:208–210.
141. Kudoh A, Takase H, Matsuno S, et al. A history of aggression is a risk factor for postoperative confusion in elderly male drinkers. J Anesth 2007; 21:13–18.
142. Williams-Russo P, Urquhart BL, Sharrock NE, et al. Postoperative delirium: predictors and prognosis in elderly orthopedic patients. J Am Geriatr Soc 1992; 40:759–767.
143. Katznelson R, Djaiani GN, Borger MA, et al. Preoperative use of statins is associated with reduced early delirium rates after cardiac surgery. Anesthesiology 2009; 110:67–73.
144. Marcantonio ER, Goldman L, Orav EJ, et al. The association of intraoperative factors with the development of postoperative delirium. Am J Med 1998; 105:380–384.
145. Gao R, Yang ZZ, Li M, et al. Probable risk factors for postoperative delirium in patients undergoing spinal surgery. Eur Spine J 2008; 17:1531–1537.
146. Chrispal A, Mathews KP, Surekha V. The clinical profile and association of delirium in geriatric patients with hip fractures in a tertiary care hospital in India. J Assoc Physicians India 2010; 58:15–19.
147. Hamann J, Bickel H, Schwaibold H, et al. Postoperative acute confusional state in typical urologic population: incidence, risk factors, and strategies for prevention. Urology 2005; 65:449–453.
148. Sasajima Y, Sasajima T, Uchida H, et al. Postoperative delirium in patients with chronic lower limb ischaemia: what are the specific markers? Eur J Vasc Endovasc Surg 2000; 20:132–137.
149. Afonso A, Scurlock C, Reich D, et al. Predictive model for postoperative delirium in cardiac surgical patients. Semin Cardiothorac Vasc Anesth 2010; 14:212–217.
150. Nie H, Zhao B, Zhang Y-Q, et al. Pain and cognitive dysfunction are the risk factors of delirium in elderly hip fracture Chinese patients. Arch Gerontol Geriatr 2012; 54:e172–e174.
151. DeCrane SK, Stark LD, Johnston B, et al. Pain, opioids, and confusion after arthroplasty in older adults. Orthop Nurs 2014; 33:226–232.
152. Lynch EP, Lazor MA, Gellis JE, et al. The impact of postoperative pain on the development of postoperative delirium. Anesth Analg 1998; 86:781–785.
153. Mouzopoulos G, Vasiliadis G, Lasanianos N, et al. Fascia iliaca block prophylaxis for hip fracture patients at risk for delirium: a randomized placebo-controlled study. J Orthop Traumatol 2009; 10:127–133.
154. Kinjo S, Lim E, Sands LP, Bozic KJ, Leung JM. Does using a femoral nerve block for total knee replacement decrease postoperative delirium? BMC Anesthesiol 2012; 12:4.
155. Krahenbuhl ES, Immer FF, Stalder M, et al. Temporary neurological dysfunction after surgery of the thoracic aorta: a predictor of poor outcome and impaired quality of life. Eur J Cardiothorac Surg 2008; 33:1025–1029.
156. Martin BJ, Buth KJ, Arora RC, Baskett RJ. Delirium as a predictor of sepsis in postcoronary artery bypass grafting patients: a retrospective cohort study. Crit Care 2010; 14:R171.
157. Nadelson MR, Sanders RD, Avidan MS. Perioperative cognitive trajectory in adults. Br J Anaesth 2014; 112:440–451.
158. Jia Y, Jin G, Guo S, et al. Fast-track surgery decreases the incidence of postoperative delirium and other complications in elderly patients with colorectal carcinoma. Langenbecks Arch Surg 2014; 399:77–84.
159. Krenk L, Rasmussen LS, Hansen TB, et al. Delirium after fast-track hip and knee arthroplasty. Br J Anaesth 2012; 108:607–611.
160. Krzych LJ, Wybraniec MT, Krupka-Matuszczyk I, et al. Delirium Screening in Cardiac Surgery (DESCARD): a useful tool for nonpsychiatrists. Can J Cardiol 2014; 30:932–939.
161. Burkhart CS, Dell-Kuster S, Gamberini M, et al. Modifiable and nonmodifiable risk factors for postoperative delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2010; 24:555–559.
162. Robinson TN, Raeburn CD, Angles EM, et al. Low tryptophan levels are associated with postoperative delirium in the elderly. Am J Surg 2008; 196:670–674.
163. Cerejeira J, Batista P, Nogueira V, et al. The stress response to surgery and postoperative delirium: evidence of hypothalamic-pituitary-adrenal axis hyperresponsiveness and decreased suppression of the GH/IGF-1 axis. J Geriatr Psychiatry Neurol 2013; 26:185–194.
164. Chen XW, Shi JW, Yang PS, et al. Preoperative plasma leptin levels predict delirium in elderly patients after hip fracture surgery. Peptides 2014; 57:31–35.
165. Root JC, Pryor KO, Downey R, et al. Association of preoperative brain pathology with postoperative delirium in a cohort of nonsmall cell lung cancer patients undergoing surgical resection. Psychooncology 2013; 22:2087–2094.
166. van Munster BC, Korevaar JC, Zwinderman AH, et al. Time-course of cytokines during delirium in elderly patients with hip fractures. J Am Geriatr Soc 2008; 56:1704–1709.
167. Watne LO, Hall RJ, Molden E, et al. Anticholinergic activity in cerebrospinal fluid and serum in individuals with hip fracture with and without delirium. J Am Geriatr Soc 2014; 62:94–102.
168. Westhoff D, Witlox J, Koenderman L, et al. Preoperative cerebrospinal fluid cytokine levels and the risk of postoperative delirium in elderly hip fracture patients. J Neuroinflammation 2013; 10:122.
169. Witlox J, Kalisvaart KJ, de Jonghe JFM, et al. Cerebrospinal fluid ß-amyloid and tau are not associated with risk of delirium: a prospective cohort study in older adults with hip fracture. J Am Geriatr Soc 2011; 59:1260–1267.
170. Blazer DG, van Nieuwenhuizen AO. Evidence for the diagnostic criteria of delirium: an update. Curr Opin Psychiatry 2012; 25:239–243.
171. Neufeld KJ. Delirium classification by the diagnostic and statistical manual – a moving target. Int Psychogeriatr 2015; 27:881–882.
172. European Delirium Association, American Delirium SocietyThe DSM-5 criteria, level of arousal and delirium diagnosis: inclusiveness is safer. BMC Med 2014; 12:141.
173. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002; 166:1338–1344.
174. Gaudreau JD, Gagnon P, Harel F, et al. Fast, systematic, and continuous delirium assessment in hospitalized patients: the Nursing Delirium Screening Scale. J Pain Symptom Manage 2005; 29:368–375.
175. Radtke FM, Franck M, Schust S, et al. A comparison of three scores to screen for delirium on the surgical ward. World J Surg 2010; 34:487–494.
176. Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confusion: the Confusion Assessment Method. A new method for detection of delirium. Ann Intern Med 1990; 113:941e948.
177. Neufeld KJ, Leoutsakos JS, Sieber FE, et al. Evaluation of two delirium screening tools for detecting postoperative delirium in the elderly. Br J Anaesth 2013; 111:612–618.
178. Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med 2001; 29:1370–1379.
179. Neufeld KJ, Leoutsakos JM, Sieber FE, et al. Outcomes of early delirium diagnosis after general anesthesia in the elderly. Anesth Analg 2013; 117:471–478.
180. Card E, Pandharipande P, Tomes C, et al. Emergence from general anaesthesia and evolution of delirium signs in the postanaesthesia care unit. Br J Anaesth 2015; 115:411–417.
181. Sikich N, Lerman J. Development and psychometric evaluation of the pediatric anesthesia emergence delirium scale. Anesthesiology 2004; 100:1138–1145.
182. Trzepacz PT, Mittal D, Torres R, et al. Validation of the Delirium Rating Scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium. J Neuropsychiatry Clin Neurosci 2001; 13:229–242.
183. Breitbart W, Rosenfeld B, Roth A, et al. The memorial delirium assessment scale. J Pain Symptom Manage 1997; 13:128–137.
184. Stillman MJ, Rybicki LA. The Bedside Confusion Scale: development of a portable bedside test for confusion and its application to the palliative medicine population. J Palliat Med 2000; 3:449–456.
185. Slor CJ, de Jonghe JF, Vreeswijk R, et al. Anesthesia and postoperative delirium in older adults undergoing hip surgery. J Am Geriatr Soc 2011; 59:1313–1319.
186. Williams MA. Delirium/acute confusional states: evaluation devices in nursing. Int Psychogeriatr 1991; 3:301–308.
187. de Jonghe JF, Kalisvaart KJ, Timmers JF, et al. Delirium-O-Meter: a nurses’ rating scale for monitoring delirium severity in geriatric patients. Int J Geriatr Psychiatry 2005; 20:1158–1166.
188. Schuurmans MJ, Shortridge-Baggett LM, Duursma SA. The Delirium Observation Screening Scale: a screening instrument for delirium. Res Theory Nurs Pract 2003; 17:31–50.
189. Albert MS, Levkoff SE, Reilly C, et al. The delirium symptom interview: an interview for the detection of delirium symptoms in hospitalized patients. J Geriatr Psychiatry Neurol 1992; 5:14–21.
190. Neelon VJ, Champagne MT, Carlson JR, et al. The NEECHAM Confusion Scale: construction, validation, and clinical testing. Nurs Res 1996; 45:324–330.
191. Bellelli G, Morandi A, Davis DH, et al. Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people. Age Ageing 2014; 43:496–502.
192. Trogrlic Z, van der Jagt M, Bakker J, et al. A systematic review of implementation strategies for assessment, prevention, and management of ICU delirium and their effect on clinical outcomes. Crit Care 2015; 19:157.
193. Pedersen SJ, Borgbjerg FM, Schousboe B, et al. A comprehensive hip fracture program reduces complication rates and mortality. J Am Geriatr Soc 2008; 56:1831–1838.
194. Larsson G, Holgers K-M. Fast-track care for patients with suspected hip fracture. Injury 2011; 42:1257–1261.
195. Milstein A, Pollack A, Kleinman G, et al. Confusion/delirium following cataract surgery: an incidence study of 1-year duration. Int Psychogeriatr 2002; 14:301–306.
196. Nandi S, Harvey WF, Saillant J, et al. Pharmacologic risk factors for postoperative delirium in total joint arthroplasty patients: a case–control study. J Arthroplasty 2014; 29:268–271.
197. Davies EA, O’Mahony MS. Adverse drug reactions in special populations – the elderly. Br J Clin Pharmacol 2015; 80:796–807.
198. Panitchote A, Tangvoraphonkchai K, Suebsoh N, et al. Under-recognition of delirium in older adults by nurses in the intensive care unit setting. Aging Clin Exp Res 2015; 27:735–740.
199. Radtke FM, Franck M, Lendner J, et al. Monitoring depth of anaesthesia in a randomized trial decreases the rate of postoperative delirium but not postoperative cognitive dysfunction. Br J Anaesth 2013; 110 (Suppl. 1):i98–i105.
200. Chan MTV, Cheng BCP, Lee TMC, et al. CODA Trial GroupBIS-guided anesthesia decreases postoperative delirium and cognitive decline. J Neurosurg Anesthesiol 2013; 25:33–42.
201. Whitlock EL, Torres BA, Lin N, et al. Postoperative delirium in a substudy of cardiothoracic surgical patients in the BAG-RECALL clinical trial. Anesth Analg 2014; 118:809–817.
202. Sieber FE, Zakriya KJ, Gottschalk A, et al. Sedation depth during spinal anesthesia and the development of postoperative delirium in elderly patients undergoing hip fracture repair. Mayo Clin Proc 2010; 85:18–26.
203. Heo DY, Hwang BM. Intravenous patient-controlled analgesia has a positive effect on the prognosis of delirium in patients undergoing orthopedic surgery. Korean J Pain 2014; 27:271–277.
204. Taipale PG, Ratner PA, Galdas PM, et al. The association between nurse-administered midazolam following cardiac surgery and incident delirium: an observational study. Int J Nurs Stud 2012; 49:1064–1073.
205. Kurbegovic S, Andersen J, Krenk L, et al. Delirium in fast-track colonic surgery. Langenbecks Arch Surg 2015; 400:513–516.
206. Zywiel MG, Prabhu A, Perruccio AV, et al. The influence of anesthesia and pain management on cognitive dysfunction after joint arthroplasty: a systematic review. Clin Orthop Relat Res 2014; 472:1453–1466.
207. Radtke FM, Franck M, Lorenz M, et al. Remifentanil reduces the incidence of postoperative delirium. J Int Med Res 2010; 38:1225–1232.
208. Lassen K, Soop M, Nygren J, et al. Consensus review of optimal perioperative care in colorectal surgery: Enhanced Recovery After Surgery (ERAS) Group recommendations. Arch Surg 2009; 144:961–969.
209. Montes DM. Postoperative delirium in head and neck cancer patients: a survey of oncologic oral and maxillofacial surgeon practices. J Oral Maxillofac Surg 2014; 72:2591–2600.
210. Khan BA, Zawahiri M, Campbell NL, et al. Delirium in hospitalized patients: implications of current evidence on clinical practice and future avenues for research – a systematic evidence review. J Hosp Med 2012; 7:580–589.
211. Yoon HJ, Park KM, Choi WJ, et al. Efficacy and safety of haloperidol versus atypical antipsychotic medications in the treatment of delirium. BMC Psychiatry 2013; 13:240.
212. Hatta K, Kishi Y, Wada K, et al. Antipsychotics for delirium in the general hospital setting in consecutive 2453 inpatients: a prospective observational study. Int J Geriatr Psychiatry 2014; 29:253–262.
213. Lonergan E, Britton AM, Luxenberg J, et al. Antipsychotics for delirium. Cochrane Database Syst Rev 2007; 2:CD005594.
214. Pisani MA, Araujo KL, Murphy TE. Association of cumulative dose of haloperidol with next-day delirium in older medical ICU patients. Crit Care Med 2015; 43:996–1002.
215. Maust DT, Kim HM, Seyfried LS, et al. Antipsychotics, other psychotropics, and the risk of death in patients with dementia: number needed to harm. JAMA Psychiatry 2015; 72:438–445.
216. Spies CD, Dubisz N, Neumann T, et al. Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial. Crit Care Med 1996; 24:414–422.
217. Spies CD, Otter HE, Huske B, et al. Alcohol withdrawal severity is decreased by symptom-orientated adjusted bolus therapy in the ICU. Intensive Care Med 2003; 29:2230–2238.
218. Spies CD, Dubisz N, Funk W, et al. Prophylaxis of alcohol withdrawal syndrome in alcohol-dependent patients admitted to the intensive care unit after tumour resection. Br J Anaesth 1995; 75:734–739.
219. Rasmussen LS, Steentoft A, Rasmussen H, et al. Benzodiazepines and postoperative cognitive dysfunction in the elderly. ISPOCD Group. International Study of Postoperative Cognitive Dysfunction. Br J Anaesth 1999; 83:585–589.
220. Bourne RS, Mills GH. Melatonin: possible implications for the postoperative and critically ill patient. Intensive Care Med 2006; 32:371–379.
221. Cavaliere F, D’Ambrosio F, Volpe C, et al. Postoperative delirium. Curr Drug Targets 2005; 6:807–814.
222. Gosch M, Nicholas JA. Pharmacologic prevention of postoperative delirium. Z Gerontol Geriatr 2014; 47:105–109.
223. Hanania M, Kitain E. Melatonin for treatment and prevention of postoperative delirium. Anesth Analg 2002; 94:338–339.
224. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013; 41:263–306.
225. Ji F, Li Z, Young N, et al. Perioperative dexmedetomidine improves mortality in patients undergoing coronary artery bypass surgery. J Cardiothorac Vasc Anesth 2014; 28:267–273.
226. Park JB, Bang SH, Chee HK, et al. Efficacy and safety of dexmedetomidine for postoperative delirium in adult cardiac surgery on cardiopulmonary bypass. Korean J Thorac Cardiovasc Surg 2014; 47:249–254.
227. Rubino AS, Onorati F, Caroleo S, et al. Impact of clonidine administration on delirium and related respiratory weaning after surgical correction of acute type-A aortic dissection: results of a pilot study. Interact Cardiovasc Thorac Surg 2010; 10:58–62.
228. Young J, Murthy L, Westby M, et al. Diagnosis, prevention, and management of delirium: summary of NICE guidance. BMJ 2010; 341:c3704.
229. Kalisvaart KJ, de Jonghe JF, Bogaards MJ, et al. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc 2005; 53:1658–1666.
230. Kaneko T, Cai J, Ishikura T, et al. Prophylactic consecutive administration of haloperidol can reduce the occurrence of postoperative delirium in gastrointestinal surgery. Yonago Acta Medica 1999; 42:179–184.
231. Wang W, Li HL, Wang DX, et al. Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial. Crit Care Med 2012; 40:731–739.
232. Teslyar P, Stock VM, Wilk CM, et al. Prophylaxis with antipsychotic medication reduces the risk of postoperative delirium in elderly patients: a meta-analysis. Psychosomatics 2013; 54:124–131.
233. Hakim SM, Othman AI, Naoum DO. Early treatment with risperidone for subsyndromal delirium after on-pump cardiac surgery in the elderly: a randomized trial. Anesthesiology 2012; 116:987–997.
234. Prakanrattana U, Prapaitrakool S. Efficacy of risperidone for prevention of postoperative delirium in cardiac surgery. Anaesth Intensive Care 2007; 35:714–719.
235. Hirota T, Kishi T. Prophylactic antipsychotic use for postoperative delirium: a systematic review and meta-analysis. J Clin Psychiatry 2013; 74:e1136–e1144.
236. Ellard L, Katznelson R, Wasowicz M, et al. Type of anesthesia and postoperative delirium after vascular surgery. J Cardiothorac Vasc Anesth 2014; 28:458–461.
237. Liu JL, Wang XL, Gong MW, et al. Comparative outcomes of peripheral nerve blocks versus general anesthesia for hip fractures in geriatric Chinese patients. Patient Prefer Adherence 2014; 8:651–659.
238. Bryson GL, Wyand A. Evidence-based clinical update: general anesthesia and the risk of delirium and postoperative cognitive dysfunction. Can J Anaesth 2006; 53:669–677.
239. Luger TJ, Kammerlander C, Gosch M, et al. Neuroaxial versus general anaesthesia in geriatric patients for hip fracture surgery: does it matter? Osteoporos Int 2010; 21:S555–S572.
240. Luger TJ, Kammerlander C, Luger MF, et al. Mode of anesthesia, mortality and outcome in geriatric patients. Z Gerontol Geriatr 2014; 47:110–124.
241. Mason SE, Noel-Storr A, Ritchie CW. The impact of general and regional anesthesia on the incidence of postoperative cognitive dysfunction and postoperative delirium: a systematic review with meta-analysis. J Alzheimers Dis 2010; 22:67–79.
242. Moyce Z, Rodseth RN, Biccard BM. The efficacy of peri-operative interventions to decrease postoperative delirium in noncardiac surgery: a systematic review and meta-analysis. Anaesthesia 2014; 69:259–269.
243. American Society of Anesthesiologists Task Force on Acute Pain ManagementPractice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology 2012; 116:248–273.
244. Leung JM, Sands LP, Paul S, et al. Does postoperative delirium limit the use of patient-controlled analgesia in older surgical patients? Anesthesiology 2009; 111:625–631.
245. Laurila JV, Laakkonen ML, Tilvis RS, et al. Predisposing and precipitating factors for delirium in a frail geriatric population. J Psychosom Res 2008; 65:249–254.
246. Clegg A, Young JB. Which medications to avoid in people at risk of delirium: a systematic review. Age Ageing 2011; 40:23–29.
247. Mercadante S. Intravenous patient-controlled analgesia and management of pain in postsurgical elderly with cancer. Surg Oncol 2010; 19:173–177.
248. Zhang H, Lu Y, Liu M, et al. Strategies for prevention of postoperative delirium: a systematic review and meta-analysis of randomized trials. Crit Care 2013; 17:R47.
249. Zucchella C, Capone A, Codella V, et al. Cognitive rehabilitation for early postsurgery inpatients affected by primary brain tumor: a randomized, controlled trial. J Neurooncol 2013; 114:93–100.
250. Hiltunen EF, Winder PA, Rait MA, et al. Implementation of efficacy enhancement nursing interventions with cardiac elders. Rehabil Nurs 2005; 30:221–229.
251. Robinson TN, Wallace JI, Wu DS, et al. Accumulated frailty characteristics predict postoperative discharge institutionalization in the geriatric patient. J Am Coll Surg 2011; 213:37–42.
252. European Commission Directorate-General for Economic and Financial Affairs, Unit Communication and Interinstitutional RelationsThe 2015 ageing report. Underlying assumptions and projection methodologies. European Economy Series. 2014; http://ec.europa.eu/economy_finance/publications/european_economy/2014/pdf/ee8_en.pdfhttp://ec.europa.eu/economy_finance/publications/european_economy/2014/pdf/ee8_en.pdf. [Accessed 22 June 2016], 21, Table I.1.13.
253. Chow WB, Rosenthal RA, Merkow RP, et al. Optimal preoperative assessment of the geriatric surgical patient: a best practices guideline from the American College of Surgeons National Surgical Quality Improvement Program and the American Geriatrics Society. J Am Coll Surg 2012; 215:453–466.
254. Reiss R, Deutsch A, Nudelman I. Surgical problems in octogenarians: epidemiological analysis of 1,083 consecutive admissions. World J Surg 1992; 16:1017–1020.
255. Ministero della Salute. Direzione Generale della Comunicazione e dei rapporti europei e internazionaliRapporto annual sull’attività di ricovero ospedaliero. 2011; http://www.salute.gov.it/imgs/C_17_pubblicazioni_1690_allegato.pdfwww.salute.gov.it/imgs/C_17_pubblicazioni_1690_allegato.pdf. [Accessed 20 July 2015].
256. Etzioni DA, Liu JH, Maggard MA, et al. The aging population and its impact on the surgery workforce. Ann Surg 2003; 238:170–177.
257. Bettelli G. Preoperative evaluation in geriatric surgery: comorbidity, functional status and pharmacological history. Minerva Anestesiol 2011; 77:637–646.
258. Nobili A, Garattini MPM. Multiple disease and polypharmacy in the elderly. J Comorbid 2011; 1:28–44.
259. World Health Department (WHO) Department of Mental Health and Substance AbuseDementia: a public health priority. Geneva:WHO; 2012.
260. Visser L, Prent A, van der Laan MJ, et al. Predicting postoperative delirium after vascular surgical procedures. J Vasc Surg 2015; 62:183–189.
261. Freter SH, Dunbar MJ, MacLeod H, et al. Predicting postoperative delirium in elective orthopaedic patients: the Delirium Elderly At-Risk (DEAR) instrument. Age Ageing 2005; 34:169–171.
262. Kazmierski J, Banys A, Latek J, et al. Mild cognitive impairment with associated inflammatory and cortisol alterations as independent risk factor for postoperative delirium. Dement Geriatr Cogn Disord 2014; 38:65–78.
263. Gallardo-Prieto LM, Nellen-Hummel H, Hamui-Sutton A, et al. Perioperative evaluation in elderly patients. Cir Cir 2006; 74:59–68.
264. Inouye SK, Peduzzi PN, Robison JT, et al. Importance of functional measures in predicting mortality among older hospitalized patients. JAMA 1998; 279:1187–1193.
265. Podsiadlo D, Richardson S. The timed ‘Up & Go’: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc 1991; 39:142–148.
266. Rubenstein LZ, Wieland D. Comprehensive geriatric assessment. Annu Rev Gerontol Geriatr 1989; 9:145–192.
267. Ganai S, Lee KF, Merrill A, et al. Adverse outcomes of geriatric patients undergoing abdominal surgery who are at high risk for delirium. Arch Surg 2007; 142:1072–1078.
268. Jankowski CJ, Trenerry MR, Cook DJ, et al. Cognitive and functional predictors and sequelae of postoperative delirium in elderly patients undergoing elective joint arthroplasty. Anesth Analg 2011; 112:1186–1193.
269. Shim JJ, Leung JM. An update on delirium in the postoperative setting: prevention, diagnosis and management. Best Pract Res Clin Anaesthesiol 2012; 26:327–343.
270. Steiner LA. Postoperative delirium. Part 1: Pathophysiology and risk factors. Eur J Anaesthesiol 2011; 28:628–636.
271. Tognoni P, Simonato A, Robutti N, et al. Preoperative risk factors for postoperative delirium (POD) after urological surgery in the elderly. Arch Gerontol Geriatr 2011; 52:e166–e169.
272. Santos-Eggimann B, Cuenoud P, Spagnoli J, et al. Prevalence of frailty in middle-aged and older community-dwelling Europeans living in 10 countries. J Gerontol A Biol Sci Med Sci 2009; 64:675–681.
273. Makary MA, Segev DL, Pronovost PJ, et al. Frailty as a predictor of surgical outcomes in older patients. J Am Coll Surg 2010; 210:901–908.
274. Sundermann S, Dademasch A, Praetorius J, et al. Comprehensive assessment of frailty for elderly high-risk patients undergoing cardiac surgery. Eur J Cardiothorac Surg 2011; 39:33–37.
275. Pol RA, van Leeuwen BL, Visser L, et al. Standardised frailty indicator as predictor for postoperative delirium after vascular surgery: a prospective cohort study. Eur J Vasc Endovasc Surg 2011; 42:824–830.
276. Böhner H, Schneider F, Stierstorfer A, et al. Delirium after vascular surgery interventions. Intermediate-term results of a prospective study. Chirurg 2000; 71:215–221.
277. Duppils GS, Wikblad K. Acute confusional states in patients undergoing hip surgery. A prospective observation study. Gerontology 2000; 46:36–43.
278. Ushida T, Yokoyama T, Kishida Y, et al. Incidence and risk factors of postoperative delirium in cervical spine surgery. Spine (Phila Pa 1976) 2009; 34:2500–2504.
279. Dovjak P, Iglseder B, Mikosch P, et al. Treatment and prevention of postoperative complications in hip fracture patients: infections and delirium. Wien Med Wochenschr 2013; 163:448–454.
280. Whitehead C, Finucane P. Malnutrition in elderly people. Aust N Z J Med 1997; 27:68–74.
281. Elmstahl S, Persson M, Andren M, et al. Malnutrition in geriatric patients: a neglected problem? J Adv Nurs 1997; 26:851–855.
282. Sullivan D, Lipschitz D. Evaluating and treating nutritional problems in older patients. Clin Geriatr Med 1997; 13:753–768.
283. Guigoz Y, Vellas B, Garry PJ. Assessing the nutritional status of the elderly: The Mini Nutritional Assessment as part of the geriatric evaluation. Nutr Rev 1996; 54:S59–S65.
284. Ringaitienė D, Gineitytė D, Vicka V, et al. Impact of malnutrition on postoperative delirium development after on pump coronary artery bypass grafting. J Cardiothorac Surg 2015; 10:74.
285. Chu CS, Liang CK, Chou MY, et al. Short-Form Mini Nutritional Assessment as a useful method of predicting the development of postoperative delirium in elderly patients undergoing orthopedic surgery. Gen Hosp Psychiatry 2016; 38:15–20.
286. Kip MJ, Neumann T, Jugel C, et al. New strategies to detect alcohol use disorders in the preoperative assessment clinic of a German university hospital. Anesthesiology 2008; 109:171–179.
287. Gfroerer J, Penne M, Pemberton M, et al. Substance abuse treatment need among older adults in 2020: the impact of the aging baby-boom cohort. Drug Alcohol Depend 2003; 69:127–135.
288. O’Connell H, Chin AV, Cunningham C, et al. Alcohol use disorders in elderly people – redefining an age old problem in old age. BMJ 2003; 327:664–667.
289. Wang YP, Andrade LH. Epidemiology of alcohol and drug use in the elderly. Curr Opin Psychiatry 2013; 26:343–348.
290. Jack S, West M, Grocott MP. Perioperative exercise training in elderly subjects. Best Pract Res Clin Anaesthesiol 2011; 25:461–472.
291. Juliebø V, Bjøro K, Krogseth M, et al. Risk factors for preoperative and postoperative delirium in elderly patients with hip fracture. J Am Geriatr Soc 2009; 57:1354–1361.
292. Oresanya LB, Lyons WL, Finlayson E. Preoperative assessment of the older patient: a narrative review. JAMA 2014; 311:2110–2120.
293. Robinson TN, Wu DS, Pointer LF, et al. Preoperative cognitive dysfunction is related to adverse postoperative outcomes in the elderly. J Am Coll Surg 2012; 215:12–17.
294. Soehle M, Dittmann A, Ellerkmann RK, et al. Intraoperative burst suppression is associated with postoperative delirium following cardiac surgery: a prospective, observational study. BMC Anesthesiol 2015; 15:61.
295. Hirsch J, DePalma G, Tsai TT, et al. Impact of intraoperative hypotension and blood pressure fluctuations on early postoperative delirium after noncardiac surgery. Br J Anaesth 2015; 115:418–426.
296. Schoen J, Meyerrose J, Paarmann H, et al. Preoperative regional cerebral oxygen saturation is a predictor of postoperative delirium in on-pump cardiac surgery patients: a prospective observational trial. Crit Care 2011; 15:R218.
297. Lin Y, Chen J, Wang Z. Meta-analysis of factors which influence delirium following cardiac surgery. J Card Surg 2012; 27:481–492.
298. van Diepen S, Bakal JA, McAlister FA, et al. Mortality and readmission of patients with heart failure, atrial fibrillation, or coronary artery disease undergoing noncardiac surgery: an analysis of 38 047 patients. Circulation 2011; 124:289–296.
299. Zhang WY, Wu WL, Gu JJ, et al. Risk factors for postoperative delirium in patients after coronary artery bypass grafting: a prospective cohort study. J Crit Care 2015; 30:606–612.
300. van der Kooi AW, Rots ML, Huiskamp G, et al. Delirium detection based on monitoring of blinks and eye movements. Am J Geriatr Psychiatry 2014; 22:1575–1582.
301. van der Kooi AW, Zaal IJ, Klijn FA, et al. Delirium detection using EEG: what and how to measure. Chest 2015; 147:94–101.
302. Warden V, Hurley AC, Volicer L. Development and psychometric evaluation of the Pain Assessment in Advanced Dementia (PAINAD) scale. J Am Med Dir Assoc 2003; 4:9–15.
303. Horgas AL, Nichols AL, Schapson CA, et al. Assessing pain in persons with dementia: relationships among the Noncommunicative Patient's Pain Assessment Instrument, self-report, and behavioral observations. Pain Manag Nurs 2007; 8:77–85.
304. Hadjistavropoulos T, Herr K, Prkachin KM, et al. Pain assessment in elderly adults with dementia. Lancet Neurol 2014; 13:1216–1227.
305. Adunsky A, Levy R, Heim M, et al. Meperidine analgesia and delirium in aged hip fracture patients. Arch Gerontol Geriatr 2002; 35:253–259.
306. Marcantonio ER, Juarez G, Goldman L, et al. The relationship of postoperative delirium with psychoactive medications. JAMA 1994; 272:1518–1522.
307. Abraha I, Trotta F, Rimland JM, et al. Efficacy of nonpharmacological interventions to prevent and treat delirium in older patients: a systematic overview. The SENATOR project ONTOP series. PLoS One 2015; 10:e0123090.
308. Hshieh TT, Yue J, Oh E, et al. Effectiveness of multicomponent nonpharmacological delirium interventions: a meta-analysis. JAMA Intern Med 2015; 175:512–520.
309. Martinez F, Tobar C, Hill N. Preventing delirium: should nonpharmacological, multicomponent interventions be used? A systematic review and meta-analysis of the literature. Age Ageing 2015; 44:196–204.
310. Björkelund KB, Hommel A, Thorngren K-G, et al. Reducing delirium in elderly patients with hip fracture: a multifactorial intervention study. Acta Anaesthesiol Scand 2010; 54:678–688.
311. Harari D, Hopper A, Dhesi J, et al. Proactive care of older people undergoing surgery (‘POPS’): designing, embedding, evaluating and funding a comprehensive geriatric assessment service for older elective surgical patients. Age Ageing 2007; 36:190–196.
312. Leslie DL, Zhang Y, Bogardus ST, et al. Consequences of preventing delirium in hospitalized older adults on nursing home costs. J Am Geriatr Soc 2005; 53:405–409.
313. Rizzo JA, Bogardus ST Jr, Leo-Summers L, et al. Multicomponent targeted intervention to prevent delirium in hospitalized older patients: what is the economic value? Med Care 2001; 39:740–752.
314. Rubin FH, Williams JT, Lescisin DA, et al. Replicating the Hospital Elder Life Program in a community hospital and demonstrating effectiveness using quality improvement methodology. J Am Geriatr Soc 2006; 54:969–974.
315. Dodds C, Foo I, Jones K, et al. Peri-operative care of elderly patients – an urgent need for change: a consensus statement to provide guidance for specialist and nonspecialist anaesthetists. Perioper Med (Lond) 2013; 2:6.
316. American Geriatrics Society Expert Panel on Postoperative Delirium in Older AdultsAmerican geriatrics society abstracted clinical practice guideline for postoperative delirium in older adults. J Am Geriatr Soc 2015; 63:142–150.
317. Anaya DA, Johanning J, Spector SA, et al. Summary of the panel session at the 38th Annual Surgical Symposium of the Association of VA Surgeons: what is the big deal about frailty? JAMA Surg 2014; 149:1191–1197.
318. Cameron ID, Kurrle S. Geriatric consultation services-are wards more effective than teams? BMC Med 2013; 11:49.
319. Grigoryan KV, Javedan H, Rudolph JL. Orthogeriatric care models and outcomes in hip fracture patients: a systematic review and meta-analysis. J Orthop Trauma 2014; 28:e49–e55.
320. Inouye SK, Bogardus ST Jr, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med 1999; 340:669–676.
321. Zenilman ME. Geriatric consultation services for surgical patients. JAMA Surg 2014; 149:90.
322. Ahmed NN, Pearce SE. Acute care for the elderly: a literature review. Popul Health Manag 2010; 13:219–225.
323. Palmer RM, Landefeld CS, Kresevic D, et al. A medical unit for the acute care of the elderly. J Am Geriatr Soc 1994; 42:545–552.
324. Friedman SM, Mendelson DA, Kates SL, et al. Geriatric co-management of proximal femur fractures: total quality management and protocol-driven care result in better outcomes for a frail patient population. J Am Geriatr Soc 2008; 56:1349–1356.
325. Liem IS, Kammerlander C, Suhm N, et al. Identifying a standard set of outcome parameters for the evaluation of orthogeriatric co-management for hip fractures. Injury 2013; 44:1403–1412.
326. Deschodt M, Braes T, Flamaing J, et al. Preventing delirium in older adults with recent hip fracture through multidisciplinary geriatric consultation. J Am Geriatr Soc 2012; 60:733–739.
327. Friedman SM, Mendelson DA, Bingham KW, et al. Impact of a comanaged Geriatric Fracture Center on short-term hip fracture outcomes. Arch Intern Med 2009; 169:1712–1717.
328. Gustafson Y, Brannstrom B, Berggren D, et al. A geriatric-anesthesiologic program to reduce acute confusional states in elderly patients treated for femoral neck fractures. J Am Geriatr Soc 1991; 39:655–662.
329. Lundstrom M, Olofsson B, Stenvall M, et al. Postoperative delirium in old patients with femoral neck fracture: a randomized intervention study. Aging Clin Exp Res 2007; 19:178–186.
330. Marcantonio ER, Flacker JM, Wright RJ, et al. Reducing delirium after hip fracture: a randomized trial. J Am Geriatr Soc 2001; 49:516–522.
331. Stenvall M, Berggren M, Lundstrom M, et al. A multidisciplinary intervention program improved the outcome after hip fracture for people with dementia – subgroup analyses of a randomized controlled trial. Arch Gerontol Geriatr 2012; 54:e284–e289.
332. Chaput AJ, Bryson GL. Postoperative delirium: risk factors and management: continuing professional development. Can J Anaesth 2012; 59:304–320.
333. Dahmani S, Stany I, Brasher C, et al. Pharmacological prevention of sevoflurane- and desflurane-related emergence agitation in children: a meta-analysis of published studies. Br J Anaesth 2010; 104:216–223.
334. Costi D, Cyna AM, Ahmed S, et al. Effects of sevoflurane versus other general anaesthesia on emergence agitation in children. Cochrane Database Syst Rev 2014; 9:CD007084.
335. Wong DD, Bailey CR. Emergence delirium in children. Anaesthesia 2015; 70:383–387.
336. Eckenhoff JE, Kneale DH, Dripps RD. The incidence and etiology of postanesthetic excitement. A clinical survey. Anesthesiology 1961; 22:667–673.
337. Aono J, Ueda W, Mamiya K, et al. Greater incidence of delirium during recovery from sevoflurane anesthesia in preschool boys. Anesthesiology 1997; 87:1298–1300.
338. Breschan C, Platzer M, Jost R, et al. Midazolam does not reduce emergence delirium after sevoflurane anesthesia in children. Paediatr Anaesth 2007; 17:347–352.
339. Cole JW, Murray DJ, McAllister JD, et al. Emergence behaviour in children: defining the incidence of excitement and agitation following anaesthesia. Paediatr Anaesth 2002; 12:442–447.
340. Daoud A, Duff JP, Joffe AR. Diagnostic accuracy of delirium diagnosis in pediatric intensive care: a systematic review. Crit Care 2014; 18:489.
341. Nakayama S, Furukawa H, Yanai H. Propofol reduces the incidence of emergence agitation in preschool-aged children as well as in school-aged children: a comparison with sevoflurane. J Anesth 2007; 21:19–23.
342. Przybylo HJ, Martini DR, Mazurek AJ, et al. Assessing behaviour in children emerging from anaesthesia: can we apply psychiatric diagnostic techniques? Paediatr Anaesth 2003; 13:609–616.
343. Voepel-Lewis T, Malviya S, Tait AR. A prospective cohort study of emergence agitation in the pediatric postanesthesia care unit. Anesth Analg 2003; 96:1625–1630.
344. Beringer RM, Segar P, Pearson A, et al. Observational study of perioperative behavior changes in children having teeth extracted under general anesthesia. Paediatr Anaesth 2014; 24:499–504.
345. Cravero J, Surgenor S, Whalen K. Emergence agitation in paediatric patients after sevoflurane anaesthesia and no surgery: a comparison with halothane. Paediatr Anaesth 2000; 10:419–424.
346. Faulk DJ, Twite MD, Zuk J, et al. Hypnotic depth and the incidence of emergence agitation and negative postoperative behavioral changes. Paediatr Anaesth 2010; 20:72–81.
347. Smessaert A, Schehr CA, Artusio JF Jr. Observations in the immediate postanaesthesia period. II. Mode of recovery. Br J Anaesth 1960; 32:181–185.
348. Araki H, Fujiwara Y, Shimada Y. Effect of flumazenil on recovery from sevoflurane anesthesia in children premedicated with oral midazolam before undergoing herniorrhaphy with or without caudal analgesia. J Anesth 2005; 19:204–207.
349. Davis PJ, Greenberg JA, Gendelman M, et al. Recovery characteristics of sevoflurane and halothane in preschool-aged children undergoing bilateral myringotomy and pressure equalization tube insertion. Anesth Analg 1999; 88:34–38.
350. Galinkin JL, Fazi LM, Cuy RM, et al. Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia. Anesthesiology 2000; 93:1378–1383.
351. Bringuier S, Dadure C, Raux O, et al. The perioperative validity of the visual analog anxiety scale in children: a discriminant and useful instrument in routine clinical practice to optimize postoperative pain management. Anesth Analg 2009; 109:737–744.
352. Kain ZN, Caldwell-Andrews AA, Mayes LC, et al. Family-centered preparation for surgery improves perioperative outcomes in children: a randomized controlled trial. Anesthesiology 2007; 106:65–74.
353. Kain ZN, Caldwell-Andrews AA, Maranets I, et al. Preoperative anxiety and emergence delirium and postoperative maladaptive behaviors. Anesth Analg 2004; 99:1648–1654.
354. Weldon BC, Bell M, Craddock T. The effect of caudal analgesia on emergence agitation in children after sevoflurane versus halothane anesthesia. Anesth Analg 2004; 98:321–326.
355. Bajwa SA, Costi D, Cyna AM. A comparison of emergence delirium scales following general anesthesia in children. Paediatr Anaesth 2010; 20:704–711.
356. Johansson M, Kokinsky E. The COMFORT behavioural scale and the modified FLACC scale in paediatric intensive care. Nurs Crit Care 2009; 14:122–130.
357. Janssen NJ, Tan EY, Staal M, et al. On the utility of diagnostic instruments for pediatric delirium in critical illness: an evaluation of the Pediatric Anesthesia Emergence Delirium Scale, the Delirium Rating Scale 88, and the Delirium Rating Scale-Revised R-98. Intensive Care Med 2011; 37:1331–1337.
358. Somaini M, Sahillioglu E, Marzorati C, et al. Emergence delirium, pain or both? A challenge for clinicians. Paediatr Anaesth 2015; 25:524–529.
359. Dahmani S, Brasher C, Stany I, et al. Premedication with clonidine is superior to benzodiazepines. A meta analysis of published studies. Acta Anaesthesiol Scand 2010; 54:397–402.
360. Martin SR, Chorney JM, Tan ET, et al. Changing healthcare providers’ behavior during pediatric inductions with an empirically based intervention. Anesthesiology 2011; 115:18–27.
361. Arai YC, Fukunaga K, Hirota S. Comparison of a combination of midazolam and diazepam and midazolam alone as oral premedication on preanesthetic and emergence condition in children. Acta Anaesthesiol Scand 2005; 49:698–701.
362. Chen J, Li W, Hu X, et al. Emergence agitation after cataract surgery in children: a comparison of midazolam, propofol and ketamine. Paediatr Anaesth 2010; 20:873–879.
363. Cohen IT, Drewsen S, Hannallah RS. Propofol or midazolam do not reduce the incidence of emergence agitation associated with desflurane anaesthesia in children undergoing adenotonsillectomy. Paediatr Anaesth 2002; 12:604–609.
364. Ko YP, Huang CJ, Hung YC, et al. Premedication with low-dose oral midazolam reduces the incidence and severity of emergence agitation in pediatric patients following sevoflurane anesthesia. Acta Anaesthesiol Sin 2001; 39:169–177.
365. Lapin SL, Auden SM, Goldsmith LJ, et al. Effects of sevoflurane anaesthesia on recovery in children: a comparison with halothane. Paediatr Anaesth 1999; 9:299–304.
366. Veyckemans F. Excitation phenomena during sevoflurane anaesthesia in children. Curr Opin Anaesthesiol 2001; 14:339–343.
367. Viitanen H, Annila P, Viitanen M, et al. Premedication with midazolam delays recovery after ambulatory sevoflurane anesthesia in children. Anesth Analg 1999; 89:75–79.
368. Chandler JR, Myers D, Mehta D, et al. Emergence delirium in children: a randomized trial to compare total intravenous anesthesia with propofol and remifentanil to inhalational sevoflurane anesthesia. Paediatr Anaesth 2013; 23:309–315.
369. Kuratani N, Oi Y. Greater incidence of emergence agitation in children after sevoflurane anesthesia as compared with halothane: a meta-analysis of randomized controlled trials. Anesthesiology 2008; 109:225–232.
370. Singh R, Kharbanda M, Sood N, et al. Comparative evaluation of incidence of emergence agitation and postoperative recovery profile in paediatric patients after isoflurane, sevoflurane and desflurane anaesthesia. Indian J Anaesth 2012; 56:156–161.
371. Welborn LG, Hannallah RS, Norden JM, et al. Comparison of emergence and recovery characteristics of sevoflurane, desflurane, and halothane in pediatric ambulatory patients. Anesth Analg 1996; 83:917–920.
372. Ali MA, Abdellatif AA. Prevention of sevoflurane related emergence agitation in children undergoing adenotonsillectomy: a comparison of dexmedetomidine and propofol. Saudi J Anaesth 2013; 7:296–300.
373. Pasin L, Febres D, Testa V, et al. Dexmedetomidine vs midazolam as preanesthetic medication in children: a meta-analysis of randomized controlled trials. Paediatr Anaesth 2015; 25:468–476.
374. Sun L, Guo R, Sun L. Dexmedetomidine for preventing sevoflurane-related emergence agitation in children: a meta-analysis of randomized controlled trials. Acta Anaesthesiol Scand 2014; 58:642–650.
375. Almenrader N, Passariello M, Coccetti B, et al. Premedication in children: a comparison of oral midazolam and oral clonidine. Paediatr Anaesth 2007; 17:1143–1149.
376. Bock M, Kunz P, Schreckenberger R, et al. Comparison of caudal and intravenous clonidine in the prevention of agitation after sevoflurane in children. Br J Anaesth 2002; 88:790–796.
377. Kulka PJ, Bressem M, Tryba M. Clonidine prevents sevoflurane-induced agitation in children. Anesth Analg 2001; 93:335–338.
378. Pickard A, Davies P, Birnie K, et al. Systematic review and meta-analysis of the effect of intraoperative α2-adrenergic agonists on postoperative behaviour in children. Br J Anaesth 2014; 112:982–990.
379. Mukherjee A, Das A, Basunia SR, et al. Emergence agitation prevention in paediatric ambulatory surgery: a comparison between intranasal dexmedetomidine and clonidine. J Res Pharm Pract 2015; 4:24–30.
380. Aouad MT, Yazbeck-Karam VG, Nasr VG, et al. A single dose of propofol at the end of surgery for the prevention of emergence agitation in children undergoing strabismus surgery during sevoflurane anesthesia. Anesthesiology 2007; 107:733–738.
381. Aouad MT, Kanazi GE, Siddik-Sayyid SM, et al. Preoperative caudal block prevents emergence agitation in children following sevoflurane anesthesia. Acta Anaesthesiol Scand 2005; 49:300–304.
382. Kim MS, Moon BE, Kim H, et al. Comparison of propofol and fentanyl administered at the end of anaesthesia for prevention of emergence agitation after sevoflurane anaesthesia in children. Br J Anaesth 2013; 110:274–280.
383. Kain ZN. Premedication and parental presence revisited. Curr Opin Anaesthesiol 2001; 14:331–337.
384. Kain ZN, MacLaren J, McClain BC, et al. Effects of age and emotionality on the effectiveness of midazolam administered preoperatively to children. Anesthesiology 2007; 107:545–552.
385. Yip P, Middleton P, Cyna AM, et al. Nonpharmacological interventions for assisting the induction of anaesthesia in children. Cochrane Database Syst Rev 2009; 3:CD006447.
386. Kain ZN, MacLaren JE, Herrmann L, et al. Preoperative melatonin and its effects on induction and emergence in children undergoing anesthesia and surgery. Anesthesiology 2009; 111:44–49.
387. Ozcengiz D, Gunes Y, Ozmete O. Oral melatonin, dexmedetomidine, and midazolam for prevention of postoperative agitation in children. J Anesth 2011; 25:184–188.
388. Salman AE, Camkiran A, Oguz S, et al. Gabapentin premedication for postoperative analgesia and emergence agitation after sevoflurane anesthesia in pediatric patients. Agri 2013; 25:163–168.
389. Kararmaz A, Kaya S, Turhanoglu S, et al. Oral ketamine premedication can prevent emergence agitation in children after desflurane anaesthesia. Paediatr Anaesth 2004; 14:477–482.
390. Sajedi P, Baghery K, Hagibabie E, et al. Prophylactic use of oral acetaminophen or iv dexamethasone and combination of them on prevention emergence agitation in pediatric after adenotonsillectomy. Int J Prev Med 2014; 5:721–727.
391. Abdulatif M, Ahmed A, Mukhtar A, et al. The effect of magnesium sulphate infusion on the incidence and severity of emergence agitation in children undergoing adenotonsillectomy using sevoflurane anaesthesia. Anaesthesia 2013; 68:1045–1052.
392. Martin JC, Liley DT, Harvey AS, et al. Alterations in the functional connectivity of frontal lobe networks preceding emergence delirium in children. Anesthesiology 2014; 121:740–752.
393. Sepulveda P, Cortinez LI, Saez C, et al. Performance evaluation of paediatric propofol pharmacokinetic models in healthy young children. Br J Anaesth 2011; 107:593–600.
394. Vanlander AV, Okun JG, de Jaeger A, et al. Possible pathogenic mechanism of propofol infusion syndrome involves coenzyme q. Anesthesiology 2015; 122:343–352.
395. Bray RJ. Propofol infusion syndrome in children. Paediatr Anaesth 1998; 8:491–499.
396. Kam PC, Cardone D. Propofol infusion syndrome. Anaesthesia 2007; 62:690–701.
397. Chauhan M, Garg A, Bharadwaj A. Effect of short-term propofol administration on pancreatic enzymes and lipid biochemistry in children between 1 month and 36 months. Paediatr Anaesth 2013; 23:355–359.
398. Koriyama H, Duff JP, Guerra GG, et al. Is propofol a friend or a foe of the pediatric intensivist? Description of propofol use in a PICU. Pediatr Crit Care Med 2014; 15:e66–e71.
399. Gerbershagen HJ, Aduckathil S, van Wijck AJ, et al. Pain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures. Anesthesiology 2013; 118:934–944.
400. Schultz-Machata AM, Weiss M, Becke K. What's new in pediatric acute pain therapy? Curr Opin Anaesthesiol 2014; 27:316–322.
401. Stanko D, Bergesio R, Davies K, et al. Postoperative pain, nausea and vomiting following adeno-tonsillectomy – a long-term follow-up. Paediatr Anaesth 2013; 23:690–696.
402. Kim HS, Kim CS, Kim SD, et al. Fascia iliaca compartment block reduces emergence agitation by providing effective analgesic properties in children. J Clin Anesth 2011; 23:119–123.
403. Dalens BJ, Pinard AM, Letourneau DR, et al. Prevention of emergence agitation after sevoflurane anesthesia for pediatric cerebral magnetic resonance imaging by small doses of ketamine or nalbuphine administered just before discontinuing anesthesia. Anesth Analg 2006; 102:1056–1061.
404. Schnabel A, Reichl SU, Zahn PK, et al. Nalbuphine for postoperative pain treatment in children. Cochrane Database Syst Rev 2014; 7:CD009583.

1 Antonio Cherubini represented the European Union Geriatric Medicine Society (EUGMS).

2 Claudia D. Spies was the elected chair of the Task Force.

© 2017 European Society of Anaesthesiology