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Delirium, what's in a name?

2017; Elsevier BV; Volume: 119; Issue: 2 Linguagem: Inglês

10.1093/bja/aex125

1471-6771

Arjen J. C. Slooter,

Anesthesia and Neurotoxicity Research

Delirium has been known since ancient times. Hippocrates [460–370 Before Common Era (BCE)] may have been the first to describe the syndrome that he called 'phrenitis', marked by confusion and restlessness that fluctuated unpredictably and that was associated with physical illness.1Morandi A Pandharipande P Trabucchi M et al.Understanding international differences in terminology for delirium and other types of acute brain dysfunction in critically ill patients.Intensive Care Med. 2008; 34: 1907-1915Crossref PubMed Scopus (120) Google Scholar Many other names have been used, including acute mental status change, confusional state, confusion, acute brain dysfunction, brain failure, encephalopathy, postoperative psychosis and acute organic syndrome.1Morandi A Pandharipande P Trabucchi M et al.Understanding international differences in terminology for delirium and other types of acute brain dysfunction in critically ill patients.Intensive Care Med. 2008; 34: 1907-1915Crossref PubMed Scopus (120) Google Scholar Of these, the term delirium (derived from the Latin word delirare, deviate from a straight track) has gained acceptance. Besides a more uniform terminology, an important recent achievement includes publication of criteria to define delirium. Although criticized,2European Delirium Association, American Delirium Society The DSM-5 criteria, level of arousal and delirium diagnosis: inclusiveness is safer.BMC Med. 2014; 12: 141Crossref PubMed Scopus (259) Google Scholar3Reade MC Aitken LM The problem of definitions in measuring and managing ICU cognitive function.Crit Care Resusc. 2012; 14: 236-243PubMed Google Scholar the criteria of the Diagnostic and Statistical Manual of Mental Disorders (5th edition, DSM-5) have become standard.4American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. 5th Edn. American Psychiatric Publishing, Arlington, VA2013Crossref Google Scholar According to these criteria, a patient can be considered delirious when all items listed in Table 1 are present at the same time.4American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. 5th Edn. American Psychiatric Publishing, Arlington, VA2013Crossref Google Scholar In essence, this means that a patient has acutely developed disturbed attention with other cognitive deficits, which is not solely due to underlying dementia and is caused by a physical condition.Table 1Criteria for delirium according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)4American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. 5th Edn. American Psychiatric Publishing, Arlington, VA2013Crossref Google Scholar A.A disturbance in attention (i.e. reduced ability to direct, focus, sustain and shift attention) and awareness (reduced orientation to the environment).B.The disturbance develops over a short period of time (usually hours to a few days), represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day.C.An additional disturbance in cognition (e.g. memory deficit, disorientation, language, visuospatial ability or perception).D.The disturbances in Criteria A and C are not better explained by another pre-existing, established or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal, such as coma.E.There is evidence from the history, physical examination or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal (i.e. due to a drug of abuse or to a medication), or exposure to a toxin, or is due to multiple aetiologies. Open table in a new tab Delirium defined according to these criteria is not innocent. Affecting 20–40% of non-critically ill hospitalized patients and up to 80% of critically ill Intensive Care Unit (ICU) patients, delirium is associated with worsened outcome.1Morandi A Pandharipande P Trabucchi M et al.Understanding international differences in terminology for delirium and other types of acute brain dysfunction in critically ill patients.Intensive Care Med. 2008; 34: 1907-1915Crossref PubMed Scopus (120) Google Scholar Delirium increases the risk of admission to a nursing home and mortality, and is independently related to long-term cognitive impairment and dementia.5Slooter AJ Van D Leur RR Zaal IJ Delirium in critically ill patients.Handb Clin Neurol. 2017; 141: 449-466Crossref PubMed Scopus (52) Google Scholar In addition, delirium can be disturbing for affected patients because of anxiety, hallucinations and delusions. There is a large societal impact because it increases ICU and hospital admission, and therefore medical costs.5Slooter AJ Van D Leur RR Zaal IJ Delirium in critically ill patients.Handb Clin Neurol. 2017; 141: 449-466Crossref PubMed Scopus (52) Google Scholar When a disorder is frequent, serious and has been known since ancient times, when increasing numbers of articles are published, and when international societies (European Delirium Association, American Delirium Society, Australasian Delirium Association) exist with annual meetings that are well attended, one would expect that fundamental issues have been resolved. The opposite appears to be true: in many ways, delirium is almost as mysterious as it was in the fourth century BCE, and research is still in its infancy. Although terminology has become more uniform, there is variability regarding which tests should be used to make the diagnosis of delirium.6Neufeld KJ Nelliot A Inouye SK et al.Delirium diagnosis methodology used in research: a survey-based study.Am J Geriatr Psychiatry. 2014; 22: 1513-1521Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar In addition, there is still confusing heterogeneity in the literature, in particular with regard to the use of the term encephalopathy. Different disciplines have a preference for different terms. Whereas geriatricians, psychiatrists, anaesthetists and intensivists seem to prefer the term delirium, neurologists appear to use the term encephalopathy more often to describe the same syndrome.7Sutter R Kaplan PW Valença M De Marchis GM EEG for diagnosis and prognosis of acute nonhypoxic encephalopathy: history and current evidence.J Clin Neurophysiol. 2015; 32: 456-464Crossref PubMed Scopus (19) Google Scholar This leads to parallel literatures and communication barriers between involved disciplines, limiting the advancement of research. Another reason for limited progress may be that the definition of delirium is quite broad. Although the DSM-5 definition of delirium is well established, the opinion of clinicians of what looks like delirium may be a separate issue. An example of a case that fulfils DSM-5 criteria for delirium while not being considered delirious by many clinicians is a patient with subarachnoid haemorrhage who develops attention deficits and a decreased level of consciousness due to delayed cerebral ischaemia. Another example is a neurologically intact patient who undergoes conscious sedation for a medical procedure such as endoscopy. In patients who are considered delirious, an important yet unresolved issue is whether they all suffer from the same condition. Delirium has a rather homogeneous presentation, suggesting a final common pathway. However, the substrate of this presumed pathway is unclear, and there is a lack of comparison studies on clinical features in delirium due to different aetiologies and different settings (e.g. ICU, nursing home). Studies on different delirium aetiologies are difficult to perform as it is usually impossible to assign one specific cause for delirium.8Ely EW Gautam S Margolin R et al.The impact of delirium in the intensive care unit on hospital length of stay.Intensive Care Med. 2001; 27: 1892-1900Crossref PubMed Scopus (794) Google Scholar Almost all delirious patients are subject to numerous risk factors,8Ely EW Gautam S Margolin R et al.The impact of delirium in the intensive care unit on hospital length of stay.Intensive Care Med. 2001; 27: 1892-1900Crossref PubMed Scopus (794) Google Scholar which can be disentangled into predisposing and precipitating risk factors. The severity of a precipitating risk factor can be mild (e.g. uncomplicated cystitis) in an individual with a strong predisposition to develop delirium (e.g. 90-yr-old with advanced dementia and pre-existing depression) whereas precipitating factors need to be severe (e.g. septic shock with multi-organ failure) for a young, previously healthy person to become delirious. Almost all articles on delirium describe the syndrome as an entity that can be dichotomized as either being present or absent. Publications on ICU delirium often consider a third category of mental status (i.e. a comatose or unarousable state).9Zaal IJ Tekatli H van der Kooi AW et al.Classification of daily mental status in critically ill patients for research purposes.J Crit Care. 2015; 30: 375-380Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar It should be noted that delirium involves a continuum of mental status changes. In case of progression of the underlying disorder (e.g. uraemia), the level of consciousness of a delirious patient can further decrease to coma. The level of consciousness in delirium could therefore reflect severity. The duration of delirium could also indicate delirium severity. Until now, it is unclear how the severity of delirium should be operationalized. Not all patients with an acute disorder of cognition fulfil DSM-5 criteria for delirium. One possibility for not fulfilling criteria is that the patient shows a very mild form of delirium. The term subsydromal delirium has been used to describe patients with some delirium features, but who do not fulfil all diagnostic criteria for delirium.10Ouimet S Riker R Bergeron N et al.Subsyndromal delirium in the ICU: evidence for a disease spectrum.Intensive Care Med. 2007; 33: 1007-1013Crossref PubMed Scopus (245) Google Scholar Another possibility for not fulfilling delirium criteria of an acute disorder of cognition is that it represents a separate entity, as could be the case in isolated postoperative hallucinations after cardiac surgery with possible opioid overdose.11Eriksson M Samuelsson E Gustafson Y Aberg T Engström KG Delirium after coronary bypass surgery evaluated by the organic brain syndrome protocol.Scand Cardiovasc J. 2002; 36: 250-255Crossref PubMed Scopus (71) Google Scholar With so many important unanswered questions, the contribution of Palanca and colleagues12Palanca BJA Wildes TS Ju YS Ching S Avidan MS Electroencephalography and delirium in the postoperative period.Br J Anaesth. 2017; 119: 294-307Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar to this issue of the British Journal of Anaesthesia is welcomed. They provide an overview of delirium and its associated EEG features.12Palanca BJA Wildes TS Ju YS Ching S Avidan MS Electroencephalography and delirium in the postoperative period.Br J Anaesth. 2017; 119: 294-307Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar Postoperative delirium is an important condition on its own given its frequency and association with poor outcome as described above. In addition, studies on postoperative delirium are important as these can provide important insights on delirium in other settings, assuming that postoperative delirium and other types of delirium are similar conditions. Compared with other types of delirium, such as delirium in nursing home residents, postoperative delirium might be less difficult to investigate. Patients themselves can provide informed consent for study participation before elective surgery while awake and non-delirious. Baseline cognitive and mental status can be assessed, which facilitates detection of changes from baseline. In addition, surgical patients can undergo neuro-imaging and EEG before surgery, enabling the study of factors that predispose to postoperative delirium. With delirium research in its infancy, contribution from neurosciences is urgently needed. Neurosciences have recently shown a spectacular development and tremendously improved our understanding of a variety of neurological and psychiatric diseases. Areas that have benefitted substantially include disorders of consciousness and cognitive disorders. As delirium can be regarded as a disorder of both consciousness and cognition, the current relative absence of neuroscientists in delirium research is striking. As an example, there is currently not more than one publication on functional connectivity during delirium using functional Magnetic Resonance Imaging.13Choi SH Lee H Chung TS et al.Neural network functional connectivity during and after an episode of delirium.Am J Psychiatry. 2012; 169: 498-507Crossref PubMed Scopus (132) Google Scholar Admittedly, it can be challenging to scan a patient with an acute disorder, usually of short duration, that interferes with cooperation. However, this seems not to be the only explanation for the relative paucity of neuroscientists in delirium research. The multifactorial and heterogeneous aetiology of delirium may not appeal to scientists who appreciate a reductionist approach. Delirium by definition complicates a variety of underlying diseases that are primarily treated by geriatricians, physicians, surgeons, anaesthetists and intensivists whereas psychiatrists and particularly neurologists are in many institutions less involved. The limited opportunities for funding of delirium research relative to other fields in neurology and psychiatry are not attractive either. In this context, research collaboration of anaesthetists and neuroscientists on EEG in postoperative delirium is applauded. EEG is a relatively old technique, first recorded in man in 1924 by the German psychiatrist Hans Berger. In the last two decades, there appears to be a renaissance of interest in EEG fuelled by rapid developments in network science. Network science has introduced exciting new opportunities for understanding the brain as a complex system of interacting units.14Stam CJ Modern network science of neurological disorders.Nat Rev Neurosci. 2014; 15: 683-695Crossref PubMed Scopus (779) Google Scholar EEG is easy to apply, associated with low risks and is relatively cheap, enabling studies in different settings (e.g. operation theatre, ICU, hospital ward, nursing home). It should however be noted that whereas EEG has excellent temporal resolution, spatial resolution is poor, hampering anatomical inferences. EEG has the potential to contribute substantially to various areas of delirium research. Firstly, it can provide valuable insights into the pathophysiology of delirium. Studies are needed in which different groups of delirium patients based on aetiology (e.g. postoperative, infection, metabolic) are compared with regard to various EEG characteristics, although it can be challenging to classify delirium into aetiological subgroups because of its multifactorial nature. Combining these findings with simulation of large populations of neurones, using neural mass models and neural network analysis, can fundamentally increase our understanding of EEG disturbances in delirium.15Ponten SC Tewarie P Slooter AJ Stam CJ van Dellen E Neural network modeling of EEG patterns in encephalopathy.J Clin Neurophysiol. 2013; 30: 545-552Crossref PubMed Scopus (13) Google Scholar Secondly, EEG can be applied in routine diagnosis and monitoring of delirium. Delirium is a clinical diagnosis and can be made by properly trained experts. Delirium is however often not recognized in daily clinical practice by non-delirium experts, such as ICU physicians.16Van Eijk MM van Marum RJ Klijn IA de Wit N Kesecioglu J Slooter AJ Comparison of delirium assessment tools in a mixed intensive care unit.Crit Care Med. 2009; 37: 1881-1885Crossref PubMed Scopus (246) Google Scholar To improve recognition, delirium screening tools have been developed. While these have adequate characteristics in a research setting where a limited number of research assistants administer a test,17Inouye SK van Dyck CH Alessi CA Balkin S Siegal AP Horwitz RI Clarifying confusion: the confusion assessment method. A new method for detection of delirium.Ann Intern Med. 1990; 13: 941-948Crossref Scopus (3775) Google Scholar18Ely EW Inouye SK Bernard GR et al.Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU).JAMA. 2001; 286: 2703-2710Crossref PubMed Scopus (2112) Google Scholar these instruments appear to be insensitive in routine, daily practice where numerous bedside nurses have to perform screening in addition to other tasks as part of day-to-day care.19Van Eijk MM van den Boogaard M van Marum RJ et al.Routine use of the confusion assessment method for the intensive care unit: a multicenter study.Am J Respir Crit Care Med. 2011; 184: 340-344Crossref PubMed Scopus (198) Google Scholar20Rice KL Bennett M Gomez M Theall KP Knight M Foreman MD Nurses' recognition of delirium in the hospitalized older adult.Clin Nurse Spec. 2011; 25: 299-311Crossref PubMed Scopus (94) Google Scholar There is therefore a need for an objective delirium detection tool. A conventional 30 minute recording with a 21-channel EEG can detect non-convulsive seizure activity that can present as delirium,21Epstein D Diu E Abeysekera T Kam D Chan Y Review of non-convulsive status epilepticus and an illustrative case history manifesting as delirium.Australas J Ageing. 2009; 28: 110-115Crossref PubMed Scopus (6) Google Scholar but it is not practical for routine purposes. However, a one minute, one channel quantitative EEG seems to be promising to detect delirium,22Van der Kooi AW Zaal IJ Klijn FA et al.Delirium detection using EEG: what and how to measure.Chest. 2015; 147: 94-101Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar and should be studied further. Thirdly, EEG can be used to assess prognosis in ICU patients with a decreased level of consciousness who fail to wake up,7Sutter R Kaplan PW Valença M De Marchis GM EEG for diagnosis and prognosis of acute nonhypoxic encephalopathy: history and current evidence.J Clin Neurophysiol. 2015; 32: 456-464Crossref PubMed Scopus (19) Google Scholar although it is currently unclear which EEG characteristic is optimal in predicting outcome. Today, about 2500 years after Hippocrates, we have the tools to explore this further. Not applicable.