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Semin Respir Crit Care Med 2021; 42(01): 112-126
DOI: 10.1055/s-0040-1710572
Review Article

Prevention and Management of Delirium in the Intensive Care Unit

Matthew F. Mart   ∗
1   Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
2   Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, Tennessee
,
Shawniqua Williams Roberson   ∗
2   Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, Tennessee
3   Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee
4   Department of Bioengineering, Vanderbilt University, Nashville, Tennessee
,
Barbara Salas
5   The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
,
Pratik P. Pandharipande
2   Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, Tennessee
6   Division of Critical Care Medicine, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee
,
E. Wesley Ely
1   Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
2   Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Nashville, Tennessee
7   Vanderbilt Center for Health Services Research, Vanderbilt University Medical Center, Nashville, Tennessee
8   VA Tennessee Valley Healthcare System Geriatric Research Education and Clinical Center (GRECC), Nashville, Tennessee
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Abstract

Delirium is a debilitating form of brain dysfunction frequently encountered in the intensive care unit (ICU). It is associated with increased morbidity and mortality, longer lengths of stay, higher hospital costs, and cognitive impairment that persists long after hospital discharge. Predisposing factors include smoking, hypertension, cardiac disease, sepsis, and premorbid dementia. Precipitating factors include respiratory failure and shock, metabolic disturbances, prolonged mechanical ventilation, pain, immobility, and sedatives and adverse environmental conditions impairing vision, hearing, and sleep. Historically, antipsychotic medications were the mainstay of delirium treatment in the critically ill. Based on more recent literature, the current Society of Critical Care Medicine (SCCM) guidelines suggest against routine use of antipsychotics for delirium in critically ill adults. Other pharmacologic interventions (e.g., dexmedetomidine) are under investigation and their impact is not yet clear. Nonpharmacologic interventions thus remain the cornerstone of delirium management. This approach is summarized in the ABCDEF bundle (Assess, prevent, and manage pain; Both SAT and SBT; Choice of analgesia and sedation; Delirium: assess, prevent, and manage; Early mobility and exercise; Family engagement and empowerment). The implementation of this bundle reduces the odds of developing delirium and the chances of needing mechanical ventilation, yet there are challenges to its implementation. There is an urgent need for ongoing studies to more effectively mitigate risk factors and to better understand the pathobiology underlying ICU delirium so as to identify additional potential treatments. Further refinements of therapeutic options, from drugs to rehabilitation, are current areas ripe for study to improve the short- and long-term outcomes of critically ill patients with delirium.

Keywords

delirium - ABCDEF bundle - cognitive impairment - critical illness - intensive care - early mobility - antipsychotics - dementia

∗ These authors acted as co-first authors.




Publication History

Article published online:
03 August 2020

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
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  • References

  • 1 Celsus AC, Spencer WG. On Medicine [electronic resource]/with an English Translation by W.G. Spencer. Cambridge, MA: Harvard University Press; 2014
    Search in Google Scholar
  • 2 Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y. Delirium in an intensive care unit: a study of risk factors. Intensive Care Med 2001; 27 (08) 1297-1304
    CrossrefPubMedSearch in Google Scholar
  • 3 Ely 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 (21) 2703-2710
    CrossrefPubMedSearch in Google Scholar
  • 4 Pandharipande PP, Girard TD, Jackson JC. et al; BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med 2013; 369 (14) 1306-1316
    CrossrefPubMedSearch in Google Scholar
  • 5 Pisani MA, Murphy TE, Van Ness PH, Araujo KL, Inouye SK. Characteristics associated with delirium in older patients in a medical intensive care unit. Arch Intern Med 2007; 167 (15) 1629-1634
    CrossrefPubMedSearch in Google Scholar
  • 6 Pisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, Van Ness PH. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med 2009; 180 (11) 1092-1097
    Search in Google Scholar
  • 7 Ely EW, Shintani A, Truman B. et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004; 291 (14) 1753-1762
    Search in Google Scholar
  • 8 Lin SM, Liu CY, Wang CH. et al. The impact of delirium on the survival of mechanically ventilated patients. Crit Care Med 2004; 32 (11) 2254-2259
    CrossrefPubMedSearch in Google Scholar
  • 9 Girard TD, Jackson JC, Pandharipande PP. et al. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med 2010; 38 (07) 1513-1520
    CrossrefPubMedSearch in Google Scholar
  • 10 Wolters AE, van Dijk D, Pasma W. et al. Long-term outcome of delirium during intensive care unit stay in survivors of critical illness: a prospective cohort study. Crit Care 2014; 18 (03) R125
    CrossrefPubMedSearch in Google Scholar
  • 11 Sakusic A, O'Horo JC, Dziadzko M. et al. Potentially modifiable risk factors for long-term cognitive impairment after critical illness: a systematic review. Mayo Clin Proc 2018; 93 (01) 68-82
    CrossrefPubMedSearch in Google Scholar
  • 12 Ely 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 (12) 1892-1900
    CrossrefPubMedSearch in Google Scholar
  • 13 Thomason JW, Shintani A, Peterson JF, Pun BT, Jackson JC, Ely EW. Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients. Crit Care 2005; 9 (04) R375-R381
    Search in Google Scholar
  • 14 Milbrandt EB, Deppen S, Harrison PL. et al. Costs associated with delirium in mechanically ventilated patients. Crit Care Med 2004; 32 (04) 955-962
    Search in Google Scholar
  • 15 Leslie DL, Marcantonio ER, Zhang Y, Leo-Summers L, Inouye SK. One-year health care costs associated with delirium in the elderly population. Arch Intern Med 2008; 168 (01) 27-32
    CrossrefPubMedSearch in Google Scholar
  • 16 van Gool WA, van de Beek D, Eikelenboom P. Systemic infection and delirium: when cytokines and acetylcholine collide. Lancet 2010; 375 (9716): 773-775
    CrossrefPubMedSearch in Google Scholar
  • 17 Inouye SK, Ferrucci L. Elucidating the pathophysiology of delirium and the interrelationship of delirium and dementia. J Gerontol A Biol Sci Med Sci 2006; 61 (12) 1277-1280
    CrossrefPubMedSearch in Google Scholar
  • 18 Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet 2014; 383 (9920): 911-922
    CrossrefPubMedSearch in Google Scholar
  • 19 Marcantonio ER. In the clinic. Delirium. Ann Intern Med 2011; 154 (11) ITC6-ITC1 , ITC6–ITC2, ITC6–ITC3, ITC6–ITC4, ITC6–ITC5, ITC6–ITC6, ITC6–ITC7, ITC6–ITC8, ITC6–ITC9, ITC6–ITC10, ITC6–ITC11, ITC6–ITC12, ITC6–ITC13, ITC6–ITC14, ITC6–ITC15, quiz ITC6–ITC16
    CrossrefPubMedSearch in Google Scholar
  • 20 Girard TD, Exline MC, Carson SS. et al; MIND-USA Investigators. Haloperidol and ziprasidone for treatment of delirium in critical illness. N Engl J Med 2018; 379 (26) 2506-2516
    CrossrefPubMedSearch in Google Scholar
  • 21 Page VJ, Ely EW, Gates S. et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2013; 1 (07) 515-523
    CrossrefPubMedSearch in Google Scholar
  • 22 Pun BT, Balas MC, Barnes-Daly MA. et al. Caring for critically ill patients with the ABCDEF bundle: results of the ICU liberation collaborative in over 15,000 adults. Crit Care Med 2019; 47 (01) 3-14
    CrossrefPubMedSearch in Google Scholar
  • 23 Barnes-Daly MA, Phillips G, Ely EW. Improving hospital survival and reducing brain dysfunction at seven california community hospitals: implementing PAD guidelines via the ABCDEF bundle in 6,064 patients. Crit Care Med 2017; 45 (02) 171-178
    CrossrefPubMedSearch in Google Scholar
  • 24 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. Washington, DC: American Psychiatric Association; 2013
    CrossrefSearch in Google Scholar
  • 25 Abengaña J, Chong MS, Tay L. Delirium superimposed on dementia: phenomenological differences between patients with and without behavioral and psychological symptoms of dementia in a specialized delirium unit. Int Psychogeriatr 2017; 29 (03) 485-495
    CrossrefPubMedSearch in Google Scholar
  • 26 Patel MB, Bednarik J, Lee P. et al. Delirium monitoring in neurocritically ill patients: a systematic review. Crit Care Med 2018; 46 (11) 1832-1841
    CrossrefPubMedSearch in Google Scholar
  • 27 Vasilevskis EE, Han JH, Hughes CG, Ely EW. Epidemiology and risk factors for delirium across hospital settings. Best Pract Res Clin Anaesthesiol 2012; 26 (03) 277-287
    CrossrefPubMedSearch in Google Scholar
  • 28 Girard TD, Kress JP, Fuchs BD. et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet 2008; 371 (9607): 126-134
    CrossrefPubMedSearch in Google Scholar
  • 29 Pandharipande P, Cotton BA, Shintani A. et al. Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients. J Trauma 2008; 65 (01) 34-41
    CrossrefPubMedSearch in Google Scholar
  • 30 Peterson JF, Pun BT, Dittus RS. et al. Delirium and its motoric subtypes: a study of 614 critically ill patients. J Am Geriatr Soc 2006; 54 (03) 479-484
    CrossrefPubMedSearch in Google Scholar
  • 31 Siddiqi N, House AO, Holmes JD. Occurrence and outcome of delirium in medical in-patients: a systematic literature review. Age Ageing 2006; 35 (04) 350-364
    CrossrefPubMedSearch in Google Scholar
  • 32 Witlox J, Eurelings LS, de Jonghe JF, Kalisvaart KJ, Eikelenboom P, van Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA 2010; 304 (04) 443-451
    CrossrefPubMedSearch in Google Scholar
  • 33 van den Boogaard M, Peters SAE, van der Hoeven JG. et al. The impact of delirium on the prediction of in-hospital mortality in intensive care patients. Crit Care 2010; 14 (04) R146
    CrossrefPubMedSearch in Google Scholar
  • 34 Zhang Z, Pan L, Ni H. Impact of delirium on clinical outcome in critically ill patients: a meta-analysis. Gen Hosp Psychiatry 2013; 35 (02) 105-111
    CrossrefPubMedSearch in Google Scholar
  • 35 Leslie DL, Zhang Y, Holford TR, Bogardus ST, Leo-Summers LS, Inouye SK. Premature death associated with delirium at 1-year follow-up. Arch Intern Med 2005; 165 (14) 1657-1662
    CrossrefPubMedSearch in Google Scholar
  • 36 Stagno D, Gibson C, Breitbart W. The delirium subtypes: a review of prevalence, phenomenology, pathophysiology, and treatment response. Palliat Support Care 2004; 2 (02) 171-179
    CrossrefPubMedSearch in Google Scholar
  • 37 Meagher D. Motor subtypes of delirium: past, present and future. Int Rev Psychiatry 2009; 21 (01) 59-73
    CrossrefPubMedSearch in Google Scholar
  • 38 Salluh JI, Wang H, Schneider EB. et al. Outcome of delirium in critically ill patients: systematic review and meta-analysis. BMJ 2015; 350: h2538
    CrossrefPubMedSearch in Google Scholar
  • 39 Dessap AM, Roche-Campo F, Launay J-M. et al. Delirium and circadian rhythm of melatonin during weaning from mechanical ventilation: an ancillary study of a weaning trial. Chest 2015; 148 (05) 1231-1241
    CrossrefPubMedSearch in Google Scholar
  • 40 Dittrich T, Tschudin-Sutter S, Widmer AF, Rüegg S, Marsch S, Sutter R. Risk factors for new-onset delirium in patients with bloodstream infections: independent and quantitative effect of catheters and drainages-a four-year cohort study. Ann Intensive Care 2016; 6 (01) 104
    CrossrefPubMedSearch in Google Scholar
  • 41 Brummel NE, Jackson JC, Pandharipande PP. et al. Delirium in the ICU and subsequent long-term disability among survivors of mechanical ventilation. Crit Care Med 2014; 42 (02) 369-377
    CrossrefPubMedSearch in Google Scholar
  • 42 McCusker J, Cole M, Dendukuri N, Han L, Belzile E. The course of delirium in older medical inpatients: a prospective study. J Gen Intern Med 2003; 18 (09) 696-704
    CrossrefPubMedSearch in Google Scholar
  • 43 Sakuramoto H, Subrina J, Unoki T, Mizutani T, Komatsu H. Severity of delirium in the ICU is associated with short term cognitive impairment. A prospective cohort study. Intensive Crit Care Nurs 2015; 31 (04) 250-257
    CrossrefPubMedSearch in Google Scholar
  • 44 van den Boogaard M, Schoonhoven L, Evers AW, van der Hoeven JG, van Achterberg T, Pickkers P. Delirium in critically ill patients: impact on long-term health-related quality of life and cognitive functioning. Crit Care Med 2012; 40 (01) 112-118
    CrossrefPubMedSearch in Google Scholar
  • 45 Davis DH, Muniz Terrera G, Keage H. et al. Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study. Brain 2012; 135 (Pt 9): 2809-2816
    CrossrefPubMedSearch in Google Scholar
  • 46 Gross AL, Jones RN, Habtemariam DA. et al. Delirium and long-term cognitive trajectory among persons with dementia. Arch Intern Med 2012; 172 (17) 1324-1331
    CrossrefPubMedSearch in Google Scholar
  • 47 Gunther ML, Morandi A, Krauskopf E. et al; VISIONS Investigation, VISualizing Icu SurvivOrs Neuroradiological Sequelae. The association between brain volumes, delirium duration, and cognitive outcomes in intensive care unit survivors: the VISIONS cohort magnetic resonance imaging study. Crit Care Med 2012; 40 (07) 2022-2032
    CrossrefPubMedSearch in Google Scholar
  • 48 Morandi A, Gunther ML, Vasilevskis EE. et al. Neuroimaging in delirious intensive care unit patients: a preliminary case series report. Psychiatry (Edgmont Pa) 2010; 7 (09) 28-33
    PubMedSearch in Google Scholar
  • 49 Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev Neurol 2009; 5 (04) 210-220
    CrossrefPubMedSearch in Google Scholar
  • 50 Fong TG, Jones RN, Shi P. et al. Delirium accelerates cognitive decline in Alzheimer disease. Neurology 2009; 72 (18) 1570-1575
    CrossrefPubMedSearch in Google Scholar
  • 51 Norman B, Jackson J, Graves J. et al. Employment changes after critical illness. Am J Respir Crit Care Med 2014; 44 (11) 2003-2009
    PubMedSearch in Google Scholar
  • 52 Jones C, Griffiths RD, Humphris G, Skirrow PM. Memory, delusions, and the development of acute posttraumatic stress disorder-related symptoms after intensive care. Crit Care Med 2001; 29 (03) 573-580
    CrossrefPubMedSearch in Google Scholar
  • 53 Jackson JC, Pandharipande PP, Girard TD. et al; Bringing to light the Risk Factors And Incidence of Neuropsychological dysfunction in ICU survivors (BRAIN-ICU) study investigators. Depression, post-traumatic stress disorder, and functional disability in survivors of critical illness in the BRAIN-ICU study: a longitudinal cohort study. Lancet Respir Med 2014; 2 (05) 369-379
    CrossrefPubMedSearch in Google Scholar
  • 54 Patel MB, Jackson JC, Morandi A. et al. Incidence and risk factors for intensive care unit-related post-traumatic stress disorder in veterans and civilians. Am J Respir Crit Care Med 2016; 193 (12) 1373-1381
    CrossrefPubMedSearch in Google Scholar
  • 55 Page VJ, Ely EW. Delirium in Critical Care. 2nd ed. Cambridge: Cambridge University Press; 2015
    CrossrefSearch in Google Scholar
  • 56 Barr J, Fraser GL, Puntillo K. et al; American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013; 41 (01) 263-306
    Search in Google Scholar
  • 57 Spronk PE, Riekerk B, Hofhuis J, Rommes JH. Occurrence of delirium is severely underestimated in the ICU during daily care. Intensive Care Med 2009; 35 (07) 1276-1280
    CrossrefPubMedSearch in Google Scholar
  • 58 Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA 1996; 275 (11) 852-857
    CrossrefPubMedSearch in Google Scholar
  • 59 Zaal IJ, Devlin JW, Peelen LM, Slooter AJ. A systematic review of risk factors for delirium in the ICU. Crit Care Med 2015; 43 (01) 40-47
    CrossrefPubMedSearch in Google Scholar
  • 60 Van Rompaey B, Elseviers MM, Schuurmans MJ, Shortridge-Baggett LM, Truijen S, Bossaert L. Risk factors for delirium in intensive care patients: a prospective cohort study. Crit Care 2009; 13 (03) R77
    CrossrefPubMedSearch in Google Scholar
  • 61 Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and consequences of ICU delirium. Intensive Care Med 2007; 33 (01) 66-73
    CrossrefPubMedSearch in Google Scholar
  • 62 Santos FS, Velasco IT, Fráguas Jr R. Risk factors for delirium in the elderly after coronary artery bypass graft surgery. Int Psychogeriatr 2004; 16 (02) 175-193
    CrossrefPubMedSearch in Google Scholar
  • 63 Van Rompaey B, Schuurmans MJ, Shortridge-Baggett LM, Truijen S, Bossaert L. Risk factors for intensive care delirium: a systematic review. Intensive Crit Care Nurs 2008; 24 (02) 98-107
    CrossrefPubMedSearch in Google Scholar
  • 64 Abelha FJ, Fernandes V, Botelho M. et al. Apolipoprotein E e4 does not increase the risk of early post-operative delirium after major surgery. J Anesth 2012; 26: 412-421
    CrossrefPubMedSearch in Google Scholar
  • 65 Jung P, Pereira MA, Hiebert B. et al. The impact of frailty on postoperative delirium in cardiac surgery patients. J Thorac Cardiovasc Surg 2015; 149 (03) 869-75.e1 , 2
    CrossrefPubMedSearch in Google Scholar
  • 66 Leung JM, Tsai TL, Sands LP. Brief report: preoperative frailty in older surgical patients is associated with early postoperative delirium. Anesth Analg 2011; 112 (05) 1199-1201
    CrossrefPubMedSearch in Google Scholar
  • 67 Jones RN, Fong TG, Metzger E. et al. Aging, brain disease, and reserve: implications for delirium. Am J Geriatr Psychiatry 2010; 18 (02) 117-127
    CrossrefPubMedSearch in Google Scholar
  • 68 Quinlan N, Marcantonio ER, Inouye SK, Gill TM, Kamholz B, Rudolph JL. Vulnerability: the crossroads of frailty and delirium. J Am Geriatr Soc 2011; 59 (Suppl. 02) S262-S268
    CrossrefPubMedSearch in Google Scholar
  • 69 Pisani MA, Murphy TE, Araujo KL, Slattum P, Van Ness PH, Inouye SK. Benzodiazepine and opioid use and the duration of intensive care unit delirium in an older population. Crit Care Med 2009; 37 (01) 177-183
    CrossrefPubMedSearch in Google Scholar
  • 70 Pandharipande P, Shintani A, Peterson J. et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology 2006; 104 (01) 21-26
    CrossrefPubMedSearch in Google Scholar
  • 71 McPherson JA, Wagner CE, Boehm LM. et al. Delirium in the cardiovascular ICU: exploring modifiable risk factors. Crit Care Med 2013; 41 (02) 405-413
    CrossrefPubMedSearch in Google Scholar
  • 72 Pandharipande PP, Pun BT, Herr DL. et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA 2007; 298 (22) 2644-2653
    CrossrefPubMedSearch in Google Scholar
  • 73 Riker RR, Shehabi Y, Bokesch PM. et al; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 2009; 301 (05) 489-499
    Search in Google Scholar
  • 74 Kamdar BB, Niessen T, Colantuoni E. et al. Delirium transitions in the medical ICU: exploring the role of sleep quality and other factors. Crit Care Med 2015; 43 (01) 135-141
    CrossrefPubMedSearch in Google Scholar
  • 75 van den Boogaard M, Pickkers P, Slooter AJ. et al. Development and validation of PRE-DELIRIC (PREdiction of DELIRium in ICU patients) delirium prediction model for intensive care patients: observational multicentre study. BMJ 2012; 344: e420
    CrossrefPubMedSearch in Google Scholar
  • 76 Seymour CW, Pandharipande PP, Koestner T. et al. Diurnal sedative changes during intensive care: impact on liberation from mechanical ventilation and delirium. Crit Care Med 2012; 40 (10) 2788-2796
    CrossrefPubMedSearch in Google Scholar
  • 77 Burry LD, Williamson DR, Mehta S. et al. Delirium and exposure to psychoactive medications in critically ill adults: a multi-centre observational study. J Crit Care 2017; 42: 268-274
    CrossrefPubMedSearch in Google Scholar
  • 78 Schreiber MP, Colantuoni E, Bienvenu OJ. et al. Corticosteroids and transition to delirium in patients with acute lung injury. Crit Care Med 2014; 42 (06) 1480-1486
    CrossrefPubMedSearch in Google Scholar
  • 79 Gunther ML, Morandi A, Ely EW. Pathophysiology of delirium in the intensive care unit. Crit Care Clin 2008; 24 (01) 45-65 , viii
    CrossrefPubMedSearch in Google Scholar
  • 80 Figueroa-Ramos MI, Arroyo-Novoa CM, Lee KA, Padilla G, Puntillo KA. Sleep and delirium in ICU patients: a review of mechanisms and manifestations. Intensive Care Med 2009; 35 (05) 781-795
    CrossrefPubMedSearch in Google Scholar
  • 81 Angles EM, Robinson TN, Biffl WL. et al. Risk factors for delirium after major trauma. Am J Surg 2008; 196 (06) 864-869 , discussion 869–870
    CrossrefPubMedSearch in Google Scholar
  • 82 Serafim RB, Dutra MF, Saddy F. et al. Delirium in postoperative nonventilated intensive care patients: risk factors and outcomes. Ann Intensive Care 2012; 2 (01) 51
    CrossrefPubMedSearch in Google Scholar
  • 83 Veiga D, Luis C, Parente D. et al. Postoperative delirium in intensive care patients: risk factors and outcome. Rev Bras Anestesiol 2012; 62 (04) 469-483
    CrossrefPubMedSearch in Google Scholar
  • 84 Guillamondegui OD, Richards JE, Ely EW. et al. Does hypoxia affect intensive care unit delirium or long-term cognitive impairment after multiple trauma without intracranial hemorrhage?. J Trauma 2011; 70 (04) 910-915
    CrossrefPubMedSearch in Google Scholar
  • 85 Agarwal V, O'Neill PJ, Cotton BA. et al. Prevalence and risk factors for development of delirium in burn intensive care unit patients. J Burn Care Res 2010; 31 (05) 706-715
    CrossrefPubMedSearch in Google Scholar
  • 86 Pandharipande PP, Morandi A, Adams JR. et al. Plasma tryptophan and tyrosine levels are independent risk factors for delirium in critically ill patients. Intensive Care Med 2009; 35 (11) 1886-1892
    CrossrefPubMedSearch in Google Scholar
  • 87 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 (04) 809-817
    CrossrefPubMedSearch in Google Scholar
  • 88 Needham DM, Korupolu R, Zanni JM. et al. Early physical medicine and rehabilitation for patients with acute respiratory failure: a quality improvement project. Arch Phys Med Rehabil 2010; 91 (04) 536-542
    CrossrefPubMedSearch in Google Scholar
  • 89 Hopkins RO, Suchyta MR, Farrer TJ, Needham D. Improving post-intensive care unit neuropsychiatric outcomes: understanding cognitive effects of physical activity. Am J Respir Crit Care Med 2012; 186 (12) 1220-1228
    CrossrefPubMedSearch in Google Scholar
  • 90 Vasilevskis EE, Ely EW, Speroff T, Pun BT, Boehm L, Dittus RS. Reducing iatrogenic risks: ICU-acquired delirium and weakness--crossing the quality chasm. Chest 2010; 138 (05) 1224-1233
    CrossrefPubMedSearch in Google Scholar
  • 91 Zeevi N, Pachter J, McCullough LD, Wolfson L, Kuchel GA. The blood-brain barrier: geriatric relevance of a critical brain-body interface. J Am Geriatr Soc 2010; 58 (09) 1749-1757
    CrossrefPubMedSearch in Google Scholar
  • 92 de Rooij SE, van Munster BC, Korevaar JC, Levi M. Cytokines and acute phase response in delirium. J Psychosom Res 2007; 62 (05) 521-525
    CrossrefPubMedSearch in Google Scholar
  • 93 Turon M, Fernández-Gonzalo S, de Haro C, Magrans R, López-Aguilar J, Blanch L. Mechanisms involved in brain dysfunction in mechanically ventilated critically ill patients: implications and therapeutics. Ann Transl Med 2018; 6 (02) 30
    CrossrefPubMedSearch in Google Scholar
  • 94 Sasannejad C, Ely EW, Lahiri S. Long-term cognitive impairment after acute respiratory distress syndrome: a review of clinical impact and pathophysiological mechanisms. Crit Care 2019; 23 (01) 352
    CrossrefPubMedSearch in Google Scholar
  • 95 Mikkelsen ME, Christie JD, Lanken PN. et al. The adult respiratory distress syndrome cognitive outcomes study: long-term neuropsychological function in survivors of acute lung injury. Am J Respir Crit Care Med 2012; 185 (12) 1307-1315
    CrossrefPubMedSearch in Google Scholar
  • 96 Macheda T, Roberts K, Lyons DN. et al. Chronic intermittent hypoxia induces robust astrogliosis in an alzheimer's disease-relevant mouse model. Neuroscience 2019; 398: 55-63
    CrossrefPubMedSearch in Google Scholar
  • 97 Snyder B, Shell B, Cunningham JT, Cunningham RL. Chronic intermittent hypoxia induces oxidative stress and inflammation in brain regions associated with early-stage neurodegeneration. Physiol Rep 2017; 5 (09) 5
    CrossrefPubMedSearch in Google Scholar
  • 98 Adams Wilson JR, Morandi A, Girard TD. et al. The association of the kynurenine pathway of tryptophan metabolism with acute brain dysfunction during critical illness*. Crit Care Med 2012; 40 (03) 835-841
    CrossrefPubMedSearch in Google Scholar
  • 99 Macdonald A, Adamis D, Treloar A, Martin F. C-reactive protein levels predict the incidence of delirium and recovery from it. Age Ageing 2007; 36 (02) 222-225
    CrossrefPubMedSearch in Google Scholar
  • 100 Vasunilashorn SM, Dillon ST, Inouye SK. et al. High C-reactive protein predicts delirium incidence, duration, and feature severity after major noncardiac surgery. J Am Geriatr Soc 2017; 65 (08) e109-e116
    CrossrefPubMedSearch in Google Scholar
  • 101 McGrane S, Girard TD, Thompson JL. et al. Procalcitonin and C-reactive protein levels at admission as predictors of duration of acute brain dysfunction in critically ill patients. Crit Care 2011; 15 (02) R78
    CrossrefPubMedSearch in Google Scholar
  • 102 Ali S, Patel M, Jabeen S. et al. Insight into delirium. Innov Clin Neurosci 2011; 8 (10) 25-34
    PubMedSearch in Google Scholar
  • 103 Rotondi AJ, Chelluri L, Sirio C. et al. Patients' recollections of stressful experiences while receiving prolonged mechanical ventilation in an intensive care unit. Crit Care Med 2002; 30 (04) 746-752
    CrossrefPubMedSearch in Google Scholar
  • 104 Hardin KA, Seyal M, Stewart T, Bonekat HW. Sleep in critically ill chemically paralyzed patients requiring mechanical ventilation. Chest 2006; 129 (06) 1468-1477
    CrossrefPubMedSearch in Google Scholar
  • 105 Weinhouse GL, Schwab RJ, Watson PL. et al. Bench-to-bedside review: delirium in ICU patients - importance of sleep deprivation. Crit Care 2009; 13 (06) 234
    CrossrefPubMedSearch in Google Scholar
  • 106 Kamdar BB, King LM, Collop NA. et al. The effect of a quality improvement intervention on perceived sleep quality and cognition in a medical ICU. Crit Care Med 2013; 41 (03) 800-809
    CrossrefPubMedSearch in Google Scholar
  • 107 Boyko Y, Ording H, Jennum P. Sleep disturbances in critically ill patients in ICU: how much do we know?. Acta Anaesthesiol Scand 2012; 56 (08) 950-958
    CrossrefPubMedSearch in Google Scholar
  • 108 Beadles CF. The treatment of acute maniacal delirium: means directed to relieve the acute symptoms and the subsequent treatment. Hospital (Lond 1886) 1893; 15 (375) 137-138
    PubMedSearch in Google Scholar
  • 109 Doty EJ. The incidence and treatment of delirious reactions in later life. Geriatrics 1946; 1: 21-26
    PubMedSearch in Google Scholar
  • 110 Greene LT. Physostigmine treatment of anticholinergic-drug depression in postoperative patients. Anesth Analg 1971; 50 (02) 222-226
    CrossrefPubMedSearch in Google Scholar
  • 111 Blachly PH, Starr A. Treatment of delirium with phenothiazine drugs following open heart surgery. Dis Nerv Syst 1966; 27 (02) 107-110
    PubMedSearch in Google Scholar
  • 112 Roberts AH. The value of E.C.T. in delirium. Br J Psychiatry 1963; 109: 653-655
    CrossrefPubMedSearch in Google Scholar
  • 113 Cassem N. Intravenous use of haloperidol for acute delirium in intensive care settings. In: Continuing Medical education syllabus and scientific proceedings in summary form from the 131st Annual Meeting of the American Psychiatric Association. Washington, DC: No. 394; 1978: 204-205
    Search in Google Scholar
  • 114 Jacobi J, Fraser GL, Coursin DB. et al; Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists (ASHP), American College of Chest Physicians. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 2002; 30 (01) 119-141
    CrossrefPubMedSearch in Google Scholar
  • 115 Wang PS, Schneeweiss S, Avorn J. et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med 2005; 353 (22) 2335-2341
    CrossrefPubMedSearch in Google Scholar
  • 116 Rea RS, Battistone S, Fong JJ, Devlin JW. Atypical antipsychotics versus haloperidol for treatment of delirium in acutely ill patients. Pharmacotherapy 2007; 27 (04) 588-594
    CrossrefPubMedSearch in Google Scholar
  • 117 Schrijver EJM, de Vries OJ, van de Ven PM. et al. Haloperidol versus placebo for delirium prevention in acutely hospitalised older at risk patients: a multi-centre double-blind randomised controlled clinical trial. Age Ageing 2018; 47 (01) 48-55
    CrossrefPubMedSearch in Google Scholar
  • 118 Agar MR, Lawlor PG, Quinn S. et al. Efficacy of oral risperidone, haloperidol, or placebo for symptoms of delirium among patients in palliative care: a randomized clinical trial. JAMA Intern Med 2017; 177 (01) 34-42
    CrossrefPubMedSearch in Google Scholar
  • 119 Nikooie R, Neufeld KJ, Oh ES. et al. Antipsychotics for treating delirium in hospitalized adults: a systematic review. Ann Intern Med 2019; 171 (07) 485-495
    CrossrefPubMedSearch in Google Scholar
  • 120 Oh ES, Needham DM, Nikooie R. et al. Antipsychotics for preventing delirium in hospitalized adults: a systematic review. Ann Intern Med 2019; 171 (07) 474-484
    CrossrefPubMedSearch in Google Scholar
  • 121 Devlin JW, Skrobik Y, Gélinas C. et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med 2018; 46 (09) e825-e873
    CrossrefPubMedSearch in Google Scholar
  • 122 Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology 2003; 98 (02) 428-436
    CrossrefPubMedSearch in Google Scholar
  • 123 Shehabi Y, Howe BD, Bellomo R. et al; ANZICS Clinical Trials Group and the SPICE III Investigators. Early sedation with dexmedetomidine in critically ill patients. N Engl J Med 2019; 380 (26) 2506-2517
    CrossrefPubMedSearch in Google Scholar
  • 124 The MENDS II Study. Accessed December 4, 2013 at: http://clinicaltrials.gov/ct2/show/NCT01739933
  • 125 Shelton KT, Qu J, Bilotta F. et al. Minimizing ICU Neurological Dysfunction with Dexmedetomidine-induced Sleep (MINDDS): protocol for a randomised, double-blind, parallel-arm, placebo-controlled trial. BMJ Open 2018; 8 (04) e020316
    CrossrefPubMedSearch in Google Scholar
  • 126 Burry L, Hutton B, Williamson DR. et al. Pharmacological interventions for the treatment of delirium in critically ill adults. Cochrane Database Syst Rev 2019; 9: CD011749
    Search in Google Scholar
  • 127 Morandi A, Hughes CG, Girard TD, McAuley DF, Ely EW, Pandharipande PP. Statins and brain dysfunction: a hypothesis to reduce the burden of cognitive impairment in patients who are critically ill. Chest 2011; 140 (03) 580-585
    CrossrefPubMedSearch in Google Scholar
  • 128 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 (01) 67-73
    CrossrefPubMedSearch in Google Scholar
  • 129 Morandi A, Hughes CG, Thompson JL. et al. Statins and delirium during critical illness: a multicenter, prospective cohort study. Crit Care Med 2014; 42 (08) 1899-1909
    CrossrefPubMedSearch in Google Scholar
  • 130 Page VJ, Davis D, Zhao XB. et al. Statin use and risk of delirium in the critically ill. Am J Respir Crit Care Med 2014; 189 (06) 666-673
    CrossrefPubMedSearch in Google Scholar
  • 131 Needham DM, Colantuoni E, Dinglas VD. et al. Rosuvastatin versus placebo for delirium in intensive care and subsequent cognitive impairment in patients with sepsis-associated acute respiratory distress syndrome: an ancillary study to a randomised controlled trial. Lancet Respir Med 2016; 4 (03) 203-212
    CrossrefPubMedSearch in Google Scholar
  • 132 Dale O, Somogyi AA, Li Y, Sullivan T, Shavit Y. Does intraoperative ketamine attenuate inflammatory reactivity following surgery? A systematic review and meta-analysis. Anesth Analg 2012; 115 (04) 934-943
    CrossrefPubMedSearch in Google Scholar
  • 133 Elia N, Tramèr MR. Ketamine and postoperative pain--a quantitative systematic review of randomised trials. Pain 2005; 113 (1-2): 61-70
    CrossrefPubMedSearch in Google Scholar
  • 134 Hudetz JA, Iqbal Z, Gandhi SD. et al. Ketamine attenuates post-operative cognitive dysfunction after cardiac surgery. Acta Anaesthesiol Scand 2009; 53 (07) 864-872
    CrossrefPubMedSearch in Google Scholar
  • 135 Avidan MS, Maybrier HR, Abdallah AB. et al; PODCAST Research Group. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet 2017; 390 (10091): 267-275
    CrossrefPubMedSearch in Google Scholar
  • 136 Balas MC, Vasilevskis EE, Olsen KM. et al. Effectiveness and safety of the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle. Crit Care Med 2014; 42 (05) 1024-1036
    CrossrefPubMedSearch in Google Scholar
  • 137 Lee HW, Park Y, Jang EJ, Lee YJ. Intensive care unit length of stay is reduced by protocolized family support intervention: a systematic review and meta-analysis. Intensive Care Med 2019; 45 (08) 1072-1081
    CrossrefPubMedSearch in Google Scholar
  • 138 Kanji S, MacPhee H, Singh A. et al. Validation of the critical care pain observation tool in critically ill patients with delirium: a prospective cohort study. Crit Care Med 2016; 44 (05) 943-947
    CrossrefPubMedSearch in Google Scholar
  • 139 Ely EW, Baker AM, Dunagan DP. et al. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996; 335 (25) 1864-1869
    CrossrefPubMedSearch in Google Scholar
  • 140 Gusmao-Flores D, Salluh JI, Chalhub RA, Quarantini LC. The Confusion Assessment Method for the intensive care unit (CAM-ICU) and intensive care delirium screening checklist (ICDSC) for the diagnosis of delirium: a systematic review and meta-analysis of clinical studies. Crit Care 2012; 16 (04) R115
    CrossrefPubMedSearch in Google Scholar
  • 141 Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive care delirium screening checklist: evaluation of a new screening tool. Intensive Care Med 2001; 27 (05) 859-864
    CrossrefPubMedSearch in Google Scholar
  • 142 Patel SB, Poston JT, Pohlman A, Hall JB, Kress JP. Rapidly reversible, sedation-related delirium versus persistent delirium in the intensive care unit. Am J Respir Crit Care Med 2014; 189 (06) 658-665
    CrossrefPubMedSearch in Google Scholar
  • 143 Schweickert WD, Pohlman MC, Pohlman AS. et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 2009; 373 (9678): 1874-1882
    CrossrefPubMedSearch in Google Scholar
  • 144 Brummel NE, Girard TD, Ely EW. et al. Feasibility and safety of early combined cognitive and physical therapy for critically ill medical and surgical patients: the Activity and Cognitive Therapy in ICU (ACT-ICU) trial. Intensive Care Med 2014; 40 (03) 370-379
    CrossrefPubMedSearch in Google Scholar
  • 145 Hung L, Au-Yeung A, Helmer C. et al. Feasibility and acceptability of an iPad intervention to support dementia care in the hospital setting. Contemp Nurse 2018; 54 (4-5): 350-361
    CrossrefPubMedSearch in Google Scholar
  • 146 Foster AM, Armstrong J, Buckley A. et al. Encouraging family engagement in the rehabilitation process: a rehabilitation provider's development of support strategies for family members of people with traumatic brain injury. Disabil Rehabil 2012; 34 (22) 1855-1862
    CrossrefPubMedSearch in Google Scholar
  • 147 Wilson JE, Collar EM, Kiehl AL. et al. Computerized cognitive rehabilitation in intensive care unit survivors: returning to everyday tasks using rehabilitation networks-computerized cognitive rehabilitation pilot investigation. Ann Am Thorac Soc 2018; 15 (07) 887-891
    CrossrefPubMedSearch in Google Scholar
  • 148 Johnson K, Fleury J, McClain D. Music intervention to prevent delirium among older patients admitted to a trauma intensive care unit and a trauma orthopaedic unit. Intensive Crit Care Nurs 2018; 47: 7-14
    CrossrefPubMedSearch in Google Scholar
  • 149 Salas B. Crossing the River Styx: the power of music, spirituality and religion at the end of life. Music Med 2019; 11(4): 226-235
    CrossrefPubMedSearch in Google Scholar
  • 150 Khan SH, Wang S, Harrawood A. et al. Decreasing delirium through music (DDM) in critically ill, mechanically ventilated patients in the intensive care unit: study protocol for a pilot randomized controlled trial. Trials 2017; 18 (01) 574
    CrossrefPubMedSearch in Google Scholar
  • 151 Pun BT, Gordon SM, Peterson JF. et al. Large-scale implementation of sedation and delirium monitoring in the intensive care unit: a report from two medical centers. Crit Care Med 2005; 33 (06) 1199-1205
    CrossrefPubMedSearch in Google Scholar
  • 152 Ely EW, Stephens RK, Jackson JC. et al. Current opinions regarding the importance, diagnosis, and management of delirium in the intensive care unit: a survey of 912 healthcare professionals. Crit Care Med 2004; 32 (01) 106-112
    CrossrefPubMedSearch in Google Scholar
  • 153 Soja SL, Pandharipande PP, Fleming SB. et al. Implementation, reliability testing, and compliance monitoring of the Confusion Assessment Method for the intensive care unit in trauma patients. Intensive Care Med 2008; 34 (07) 1263-1268
    CrossrefPubMedSearch in Google Scholar
  • 154 Devlin JW, Fong JJ, Howard EP. et al. Assessment of delirium in the intensive care unit: nursing practices and perceptions. Am J Crit Care 2008; 17 (06) 555-565 , quiz 566
    CrossrefPubMedSearch in Google Scholar
  • 155 Patel RP, Gambrell M, Speroff T. et al. Delirium and sedation in the intensive care unit: survey of behaviors and attitudes of 1384 healthcare professionals. Crit Care Med 2009; 37 (03) 825-832
    CrossrefPubMedSearch in Google Scholar
  • 156 Riekerk B, Pen EJ, Hofhuis JG, Rommes JH, Schultz MJ, Spronk PE. Limitations and practicalities of CAM-ICU implementation, a delirium scoring system, in a Dutch intensive care unit. Intensive Crit Care Nurs 2009; 25 (05) 242-249
    CrossrefPubMedSearch in Google Scholar
  • 157 Scott P, McIlveney F, Mallice M. Implementation of a validated delirium assessment tool in critically ill adults. Intensive Crit Care Nurs 2013; 29 (02) 96-102
    CrossrefPubMedSearch in Google Scholar
  • 158 Andrews L, Silva SG, Kaplan S, Zimbro K. Delirium monitoring and patient outcomes in a general intensive care unit. American journal of critical care: an official publication. Am J Crit Care 2015; 24: 48-56
    CrossrefPubMedSearch in Google Scholar
  • 159 Ely EW. Confusion Assessment Method for the ICU (CAM-ICU): The Complete Training Manual. Vanderbilt University Medical Center: Vanderbilt University; 2014
    Search in Google Scholar
  • 160 Elliott SR. ICU delirium: a survey into nursing and medical staff knowledge of current practices and perceived barriers towards ICU delirium in the intensive care unit. Intensive Crit Care Nurs 2014; 30 (06) 333-338
    CrossrefPubMedSearch in Google Scholar
  • 161 van 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 (06) 1881-1885
    CrossrefPubMedSearch in Google Scholar
  • 162 Pun BT, Devlin JW. Delirium monitoring in the ICU: strategies for initiating and sustaining screening efforts. Semin Respir Crit Care Med 2013; 34 (02) 179-188
    Thieme ConnectPubMedSearch in Google Scholar
  • 163 Guenther U, Weykam J, Andorfer U. et al. Implications of objective vs subjective delirium assessment in surgical intensive care patients. Am J Crit Care 2012; 21 (01) e12-e20
    CrossrefPubMedSearch in Google Scholar
  • 164 Trogrlić Z, Ista E, Ponssen HH. et al. Attitudes, knowledge and practices concerning delirium: a survey among intensive care unit professionals. Nurs Crit Care 2017; 22 (03) 133-140
    CrossrefPubMedSearch in Google Scholar
  • 165 van den Boogaard M, Pickkers P, van der Hoeven H, Roodbol G, van Achterberg T, Schoonhoven L. Implementation of a delirium assessment tool in the ICU can influence haloperidol use. Crit Care 2009; 13 (04) R131
    CrossrefPubMedSearch in Google Scholar
  • 166 Oxenbøll-Collet M, Egerod I, Christensen V, Jensen J, Thomsen T. Nurses' and physicians' perceptions of Confusion Assessment Method for the intensive care unit for delirium detection: focus group study. Nurs Crit Care 2018; 23 (01) 16-22
    CrossrefPubMedSearch in Google Scholar
  • 167 Mitasova A, Kostalova M, Bednarik J. et al. Poststroke delirium incidence and outcomes: validation of the Confusion Assessment Method for the intensive care unit (CAM-ICU). Crit Care Med 2012; 40 (02) 484-490
    CrossrefPubMedSearch in Google Scholar
  • 168 Frenette AJ, Bebawi ER, Deslauriers LC. et al. Validation and comparison of CAM-ICU and ICDSC in mild and moderate traumatic brain injury patients. Intensive Care Med 2016; 42 (01) 122-123
    CrossrefPubMedSearch in Google Scholar
  • 169 Costa DK, White MR, Ginier E. et al. Identifying barriers to delivering the awakening and breathing coordination, delirium, and early exercise/mobility bundle to minimize adverse outcomes for mechanically ventilated patients: a systematic review. Chest 2017; 152 (02) 304-311
    CrossrefPubMedSearch in Google Scholar
  • 170 Boehm LM, Dietrich MS, Vasilevskis EE. et al. Perceptions of workload burden and adherence to ABCDE bundle among intensive care providers. American journal of critical care: an official publication. American Association of Critical-Care Nurses 2017; 26: e38-e47
    CrossrefPubMedSearch in Google Scholar
  • 171 Balas MC, Pun BT, Pasero C. et al. Common challenges to effective ABCDEF bundle implementation: the ICU liberation campaign experience. Crit Care Nurse 2019; 39 (01) 46-60
    CrossrefPubMedSearch in Google Scholar
  • 172 Carrothers KM, Barr J, Spurlock B, Ridgely MS, Damberg CL, Ely EW. Contextual issues influencing implementation and outcomes associated with an integrated approach to managing pain, agitation, and delirium in adult ICUs. Crit Care Med 2013; 41 (09) (Suppl. 01) S128-S135
    CrossrefPubMedSearch in Google Scholar
  • 173 Swan JT, Fitousis K, Hall JB, Todd SR, Turner KL. Antipsychotic use and diagnosis of delirium in the intensive care unit. Crit Care 2012; 16 (03) R84
    CrossrefPubMedSearch in Google Scholar
  • 174 Herzig SJ, Rothberg MB, Guess JR, Gurwitz JH, Marcantonio ER. Antipsychotic medication utilization in nonpsychiatric hospitalizations. J Hosp Med 2016; 11 (08) 543-549
    CrossrefPubMedSearch in Google Scholar