International Journal of Anesthesiology & Research (IJAR)  /  IJAR-2332-2780-01-301

Emergence Delirium: Revisiting a Clinical Enigma

Nicoleta Stoicea MD PhD1*, Wiebke Ackermann MD1, Thomas Ellis MD3, Kenneth Moran MD1, Eduardo Reyes MD1, Quinones Alexander BS4 , Sergio Bergese MD1,2

1* Department of Anesthesiology, Wexner Medical Center, Ohio State University, Columbus, OH.
2 Department of Neurological Surgery, Wexner Medical Center, Ohio State University, Columbus, OH.
3 Department of Orthopaedics, Wexner Medical Center, Ohio State University, Columbus, OH.
4 Ohio State University, College of Medicine.

*Corresponding Author

Nicoleta Stoicea,
Department of Anesthesiology,
Wexner Medical Center,
Ohio State University,
Columbus, OH.
Tel: (614)-293-0775;
Fax: (614)-366-1943

Article Type: Research Article
Received: November 04, 2013; Accepted: November 27, 2013; Published: November 29, 2013

Citation: Stoicea N et al (2013) Emergence Delirium: Revisiting A Clinical Enigma. Int J Anesth Res. 1(3), 15-17. doi:

Copyright: Stoicea N© 2013. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.


Delirium seems to result from the interaction between pre-operative patient vulnerabilities and exposure to precipitating factors. Post-operative delirium (POD) is often observed in elderly patients undergoing orthopedic surgery, particularly hip fracture repair and may persist for several days postoperatively. Emergence delirium (ED) is known as an acute agitation and confusion occurring during or immediately following emergence from general anesthesia, in the OR orpost anesthesia care unit. Stress and inflammation are important triggers in the development of delirium.

3.Post-Operative Delirium Risk Factors
4.Emergence Delirium Risk Factors
5. Disclosure
6. References


Emergence Delirium; Delirium; Cognitive Impairment; Acute Confusional State; Orthopaedic Surgey.


The term delirium was used for the first time by Celsius to describe a cognitive deficit associated with fever or head trauma. Hippocrates in 500 BC introduced the term of phrenitis to describe the acute onset of mental abnormalities accompanied by a change in behavior, disturbances of sleep and cognitive deficit in patients experiencing fever [1].

At the end of the nineteenth century and the beginning of the twentieth century the general agreement was that the outcome of delirium was either death or full recovery [2].

During the twentieth century EEG recording performed in patients diagnosed with delirium found a reduction of cerebral metabolic rate, indicated by an increase in slow wave activity [3].

Delirium is defined by the DSM-V as a disturbance in attention and awareness according to several criteria [4]:
A. “Disturbance in level of awareness and reduced ability to direct, focus, sustain, and shift attention (this represents a minor change from: Disturbance of consciousness (i.e., reduced clarity of awareness of the environment) with reduced ability to focus,sustain or shift attention).
B. A change in cognition (such as deficits in orientation, executive ability, language, visuoperception, learning and memory).

  • Cannot be assessed in face of severely reduced level of awareness
  • Should not be better accounted for by a preexisting neurocognitive disorder (A minor change from a change in cognition or the development of a perceptual disturbance that is not better accounted for by a preexisting, established or evolving dementia.)
C. There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by the direct physiologic consequences of a general medical condition (no change from DSM IV).
D. The disturbance develops over a short period of time (usually hours to a few days) and tends to fluctuate in severity during the course of a day (no change from DSM IV).”

The post-operative timing of the onset of delirium is used as the primary clinical differentiator in determining whether a patient is suffering from post-operative delirium or emergence delirium [5]. Since ED is associated with emergence from anesthesia, it typically occurs in the OR and PACU. In contrast, POD can persist for several days after surgery.

Post-Operative Delirium Risk Factors

Delirium seems to result from the interaction between pre-operative patient vulnerabilities and exposure to precipitating factors [6].

POD is frequently observed in elderly patients undergoing orthopedic surgery, particularly hip fracture repair. It most often occurs between postoperative days 1-3 and usually resolves within hours to days [5, 7]. Incidence rates fluctuate from 6% in total knee arthroplasty (TKA) to 16% in total hip arthroplasty (THA) [8]. POD appears more frequently following orthopedic surgery for traumatic injuries than after elective surgeries [9,10].

A growing interest in studying pathophysiology of postoperative delirium identified multiple risk factors in elderly patients undergoing orthopedic surgery. A higher incidence of POD was associated with poor post-operative pain control [8, 11]. Other proposed risk factors include age, the male gender, number of comorbidities, lower body mass index (BMI) following unintentional weight loss, impaired hearing and vision, pre-operative cognitive decline, depression, alcohol use and pre-operative benzodiazepine administration [12-13]. Dementia free elderly patients who suffered from pre-existing chronic obstructive sleep apnea exhibited an increased POD incidence following a TKA procedure [14].

In patients with pre-existing dementia, a longer emergency department (you already use ED to mean emergence delirium) waiting time and ICU length of stay were also associated with an increased incidence of POD [15]. The sleep–wake cycle is frequently disrupted in delirium. The pineal hormone melatonin is essential in the regulation of the sleep–wake cycle. Studies using polysomnography have demonstrated extensive sleep impairment in ICU patients, with mostly stage 1 and 2 sleep and little to no stage 3, 4 or rapid eye movement (REM) sleep, decreased REM periods and sleep fragmentation [16]. A lower delirium rate was reported in patients receiving melatonin 5mg two times before intervention compared with controls [17].

Emergence Delirium Risk Factors

Emergence delirium (ED) is known as an acute agitation and confusion occurring during or immediately following emergence from general anesthesia, in the OR or post anesthesia care unit (PACU) [15]. Most research on ED involves the pediatric population. However, ED is also seen in adults and is associated with breast, abdominal and musculoskeletal surgery [18, 19]. Emergence delirium was studied as a phenomenon occurring after cessation of general anesthesia and was referred to as a general excitation. Silverstein considers postoperative delirium as “a specific subset of the panorama of deliria, consistent with the classical definition of delirium.” Emergence delirium should be considered as an independent, separate syndrome due, in part, to its extremely limited duration. A research study involving veterans has identified anxiety, PTSD and depression as risk factors for emergence delirium [20]. Inhalational anesthesia compared to total intravenous anesthesia (TIVA) has also been associated with an increased incidence of ED [21]. Similarly, pre-operative benzodiazepines, chronic illness and long-term anti-depressant use have all been identified as risk factors for agitation in the PACU [18].

There is evidence that regional anesthesia used in conjunction with general anesthesia is associated with a reduction in acute post-operative confusion in both children and adults immediately following orthopedic surgery [22, 23]. In elderly orthopedic surgery patients, a retrospective study identified a reduction in ED incidence when elderly patients were treated with morphine instead of meperidine immediately following hip fracture repair surgeries [11, 24]. However, there seems to be a paucity of work examining links between orthopedic surgery and ED in adults. The relationship between certain drugs and the incidence of ED or POD is difficult to assess considering the lack of an animal model and the multiple medication use in anesthesia protocol. Sieber considered depth of anesthesia as a primary variable when assessing the incidence of postoperative delirium in patient undergoing hip fracture repair [25].

Stress and inflammation are important triggers in the development of delirium [26]. There is evidence of an increase in cortisol level in patients over 60 years of age undergoing hip arthroplasty who experienced delirium [27]. This same study also found that the magnitude of this process was related to an increase in IL-6 and IL-8 compared to pre-operative baseline [27]. Also, C-reactive protein (a part of the acute phase inflammatory response) has been associated with dementia in the elderly [28]. Specifically, Beloosesky et al found evidence of increased C-reactive protein (CRP) and inflammatory cytokine (IL-6, TNF-α, IL-1RA, IL-10, IL-8) production in elderly patients undergoing hip fracture repair surgery who developed an impaired mental status and complications (including POD) post-operatively [29]. A study done by Liu et al. using a much larger sample size (330 compared to the 94 used by Beloosesky et al) found evidence of a link between elevated serum interleukin- 6 and POD in elderly patients undergoing noncardiac surgery, 119 of whom were undergoing bone and joint surgery [30]. Patients experiencing POD had a mean post-operative IL-6 serum level of 31.7 pg/ml compared to 23.7 in non-delirious patients (p = 0.001) [30]. However, more research is necessary to elucidate the exact mechanism of this proposed etiology in elderly patients experiencing POD.

ED seems to be more associated with arousal and excitation. There is a link between inhalational anesthesia and pre-operative benzodiazepine use in adults experiencing ED [18, 31]. Qualitative research by military nursing staff has anecdotally identified a relationship between traumatic brain injury (TBI), post-traumatic stress disorder (PTSD) and hyperactive anesthesia emergence (ED) [32]. This relationship was backed up in research study, confirming an association between pre-operative anxiety, PTSD and ED in military personnel [20]. Pre-operative benzodiazepine administration is associated with ED in the general adult population [31]. Perhaps the association of benzodiazepine use with ED is incidental, and ED has a stronger relationship to anxiety than to anxiolytics.

Increased incidence of ED was also associated with inhalational anesthetic use than when compared to TIVA [21, 33]. Experimental evidence from mice suggests that this is due to the excitatory response elicited by these drugs [33]. In this experiment, sevoflurane (an inhalational anesthetic associated with ED) was shown to excite the locus coeruleus neurons (an area involved in adrenergic excitation) in the brains of rats, suggesting that the excitatory properties of some anesthetic drugs are involved in the etiology of ED [33].

Since ED and POD seem to be studied in different populations - ED mostly in pediatric population and POD in elderly patients - a presumed common etiology would require further research to link the two phenomena. An accurate differentiation of delirium from other contributing factors requires a complex analysis of symptoms involved in acute emergence-associated disturbed behavior. Delirium syndromes such as ED and POD present as a heterogeneous mix of symptoms, risk factors and etiologies. Its relationship to central neurotransmitter imbalance has prompted several hypotheses regarding its’ association with genetic risk, the cholinergic system and inflammatory reaction associated with biomarkers release.

Geriatric population represents more than 15% of U.S population and advanced age requires emergency and elective orthopaedic surgery in order to maintain independence. The long term effects of surgery and anesthesia on patients’ cognition still remain unclear requiring further investigation.


The authors did not receive any funding and have no conflicts of interests related to this publication.


  1. Dimitrios Adamis et al., A brief review of the history of delirium as a mental disorder. History of Psychiatry, 18(4): 459–469 Copyright © 2007 SAGE Publications (Los Angeles, London, New Delhi, and Singapore).
  2. Berrios, G. E. (1981) Delirium and confusion in the 19th century: a conceptual history. British Journal of Psychiatry, 139, 439–49.
  3. Engel, G. L. and Romano J. (1959) Delirium, a syndrome of cerebral insufficiency. Journal of Chronic Diseases, 9, 260–7730.
  4. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. 2013, American Psychiatric Association: Arlington, VA.
  5. Silverstein, J.H., et al., Central nervous system dysfunction after noncardiac surgery and anesthesia in the elderly. Anesthesiology, 2007. 106(3):p.622- 8.
  6. Inouye SK & Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. Jama 1996 Mar 20; 275(11): 852–857.
  7. Silverstein, J.H. and S.G. Deiner, Perioperative delirium and its relationship to dementia. Prog Neuropsychopharmacol Biol Psychiatry, 2013.43: p. 108-15.
  8. Lynch, E.P., et al., The impact of postoperative pain on the development of postoperative delirium. Anesth Analg, 1998. 86(4): p. 781-5.
  9. Galanakis, P., et al., Acute confusional state in the elderly following hip surgery: incidence, risk factors and complications. Int J Geriatr Psychiatry, 2001. 16(4): p. 349-55.
  10. Kalisvaart, K.J., 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(5): p. 817-22.
  11. Morrison, R.S., 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(1): p. 76-81.
  12. Juliebo, V., et al., Risk factors for preoperative and postoperative delirium in elderly patients with hip fracture.J Am Geriatr Soc, 2009. 57(8): p. 1354-61.
  13. Nandi, S., et al., Pharmacologic Risk Factors for Post-Operative Delirium in Total Joint Arthroplasty Patients: A Case-Control Study. J Arthroplasty, 2013.
  14. Flink, B.J., et al., Obstructive sleep apnea and incidence of postoperative delirium after elective knee replacement in the nondemented elderly. Anesthesiology, 2012. 116(4): p. 788-96.
  15. Lee, H.B., et al., Predisposing factors for postoperative delirium after hip fracture repair in individuals with and without dementia. J Am Geriatr Soc, 2011. 59(12): p. 2306-13.
  16. Weinhouse GL, Schwab RJ, Watson PL et al. Bench-to-bedside review: delirium in ICU patients – importance of sleep deprivation. Crit Care 2009; 13(6): 234.
  17. Sultan SS. Assessment of role of perioperative melatonin in prevention and treatment of postoperative delirium after hip arthroplasty under spinal anesthesia in the elderly. Saudi J Anaesth 2010; 4:169–173.
  18. Lepouse, C., et al., Emergence delirium in adults in the post-anaesthesia care unit. Br J Anaesth, 2006. 96(6): p. 747-53.
  19. Radtke, F.M., et al., Risk factors for inadequate emergence after anesthesia: emergence delirium and hypoactive emergence. Minerva Anestesiol, 2010. 76(6): p. 394-403.
  20. McGuire, J.M., The incidence of and risk factors for emergence delirium in U.S. military combat veterans. J Perianesth Nurs, 2012. 27(4): p. 236-45.
  21. Yu, D., et al., Emergence agitation in adults: risk factors in 2,000 patients. Can J Anaesth, 2010. 57(9): p. 843-8.
  22. Kim, H.S., et al., Fascia iliaca compartment block reduces emergence agitation by providing effective analgesic properties in children. J Clin Anesth, 2011. 23(2): p. 119-23.
  23. Parker, M.J., H.H. Handoll, and R. Griffiths, Anaesthesia for hip fracture surgery in adults. Cochrane Database Syst Rev, 2004(4): p. Cd000521.
  24. Adunsky, A., et al., Meperidine analgesia and delirium in aged hip fracture patients. Arch Gerontol Geriatr, 2002. 35(3): p. 253-9. .
  25. Sieber FE, Zakriya KJ, Gottschalk A, Blute MR, Lee HB, Rosenberg PB, et al. Sedation depth during spinal anesthesia and the development of postoperative delirium in elderly patients undergoing hip fracture repair. MayoClin Proc 2010;85:18–26.
  26. Hshieh, T.T., et al., Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence.. J Gerontol A Biol Sci Med Sci, 2008. 63(7): p.764-72.
  27. Cerejeira, J., 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(3): p. 185-94.
  28. Macdonald, A., et al., C-reactive protein levels predict the incidence of delirium and recovery from it. Age Ageing, 2007. 36(2): p. 222-5.
  29. Beloosesky, Y., et al., Cytokines and C-reactive protein production in hipfracture- operated elderly patients. J Gerontol A Biol Sci Med Sci, 2007. 62(4): p. 420-6.
  30. Liu, P., 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 (Engl), 2013. 126(19): p. 3621-7.
  31. Radtke, F.M., et al., Risk factors for inadequate emergence after anesthesia: emergence delirium and hypoactive emergence. Minerva Anestesiologica, 2010. 76(6): p. 394-404.
  32. Wilson, J.T. and M.E. Pokorny, Experiences of military CRNAs with service personnel who are emerging from general anesthesia. Aana j, 2012. 80(4): p. 260-5.
  33. Yasui, Y., E. Masaki, and F. Kato, Sevoflurane directly excites locus coeruleus neurons of rats. Anesthesiology, 2007. 107(6): p. 992-1002

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