Skip to main content
SpringerLink
Log in

Treatment Strategies for Delirium

  • Chapter
  • First Online:
Delirium

  • 1251 Accesses

Abstract

Despite rapidly expanding experience in the prevention and treatment of delirium in various care environments, no pharmacologic agent is approved for the prevention or treatment of delirium. Non-pharmacologic approaches, which address many of the risk factors for delirium, have shown reductions in delirium incidence in general medical wards. In critically ill populations, protocols combining aggressive physical and occupational therapy, daily awakening, and reduced sedation exposure reduced duration of delirium. Studies employing pharmacologic agents such as antipsychotics, statins, acetylcholinesterase inhibitors, and alpha-2 agonists have not generated acceptable data supporting a recommendation for the prevention or treatment of delirium in all patient populations. The current state of literature is highlighted by many gaps in the knowledge of delirium prevention and treatment strategies. Future research will clarify whether pharmacologic interventions can be added to non-pharmacologic interventions and whether these interventions impact short-term and/or long-term outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 119.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Colombo R, Corona A, Praga F, et al. A reorientation strategy for reducing delirium in the critically ill. Results of an interventional study. Minerva Anestesiol. 2012;78:1026–33.

    CAS  PubMed  Google Scholar 

  2. Foster J, Kelly M. A pilot study to test the feasibility of a nonpharmacologic intervention for the prevention of delirium in the medical intensive care unit. Clin Nurse Spec. 2013;27:231–8.

    Article  PubMed  Google Scholar 

  3. Moon KJ, Lee SM. The effects of a tailored intensive care unit delirium prevention protocol: a randomized controlled trial. Int J Nurs Stud. 2015;52:1423.

    Article  PubMed  Google Scholar 

  4. Hanison J, Conway D. A multifaceted approach to prevention of delirium on intensive care. BMJ Qual Improv Rep 2015;(1)4. https://doi.org/10.1136/bmjquality.u209656.w4000.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Rivosecchi RM, Kane-Gill SL, Svec S, Campbell S, Smithburger PL. The implementation of a nonpharmacologic protocol to prevent intensive care delirium. J Crit Care. 2016;31:206–11.

    Article  PubMed  Google Scholar 

  6. Inouye SK, Bogardus STJ, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999;340:669–76.

    Article  CAS  PubMed  Google Scholar 

  7. Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet (London, England). 2009;373:1874–82.

    Article  Google Scholar 

  8. 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;371:126–34.

    Article  PubMed  Google Scholar 

  9. Kress JP, Pohlman AS, O’Connor M, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342:1471–7.

    Article  CAS  PubMed  Google Scholar 

  10. 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;373:1874–82.

    Article  PubMed  Google Scholar 

  11. 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;335:1864–9.

    Article  CAS  PubMed  Google Scholar 

  12. 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;42:1024–36.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 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;45:171–8.

    Article  PubMed  Google Scholar 

  14. 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;47:3–14.

    Article  PubMed  PubMed Central  Google Scholar 

  15. 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.

    Article  PubMed  Google Scholar 

  16. Adults AGSEPoPDiO. American Geriatrics Society abstracted clinical practice guideline for postoperative delirium in older adults. J Am Geriatr Soc. 2015;63:142–50.

    Article  Google Scholar 

  17. Maldonado JR. Pathoetiological model of delirium: a comprehensive understanding of the neurobiology of delirium and an evidence-based approach to prevention and treatment. Crit Care Clin. 2008;24:789–856.

    Article  CAS  PubMed  Google Scholar 

  18. Maldonado JR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Am J Geriatr Psychiatry. 2013;21:1190–222.

    Article  PubMed  Google Scholar 

  19. Hshieh TT, Fong TG, Marcantonio ER, Inouye SK. Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence. J Gerontol Ser A Biol Med Sci. 2008;63:764–72.

    Article  Google Scholar 

  20. Tune LE, Egeli S. Acetylcholine and delirium. Dement Geriatr Cogn Disord. 1999;10:342–4.

    Article  CAS  PubMed  Google Scholar 

  21. Flacker JM, Cummings V, Mach JR, Bettin k KDK, Wei J. The association of serum anticholinergic activity with delirium in elderly medical patients. Am J Geriatr Psychiatry. 1998;6:31–41.

    Article  CAS  PubMed  Google Scholar 

  22. Itil T, Fink M. Anticholinergic drug-induced delirium: experimental modification, quantitative EEG and behavioral correlations. J Nerv Ment Dis. 1966;143:492–507.

    Article  CAS  PubMed  Google Scholar 

  23. Holinger PC, Klawans HL. Reversal of tricyclic-overdosage-induced central anticholinergic syndrome by physostigmine. Am J Psychiatry. 1976;133:1018–23.

    Article  CAS  PubMed  Google Scholar 

  24. Trzepacz PT. Is there a final common neural pathway in delirium? Focus on acetylcholine and dopamine. Semin Clin Neuropsychiatry. 2000;5:132–48.

    CAS  PubMed  Google Scholar 

  25. van der Mast RC. Pathophysiology of delirium. J Geriatr Psychiatry Neurol. 1998;11:138–45.

    Article  PubMed  Google Scholar 

  26. Graham DG. Catecholamine toxicity: a proposal for the molecular pathogenesis of manganese neurotoxicity and Parkinson’s disease. Neurotoxicology. 1984;5:83–95.

    CAS  PubMed  Google Scholar 

  27. Devlin JW, Skrobik Y, Gelinas 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:e825–73.

    Article  PubMed  Google Scholar 

  28. Girard TD, Pandharipande PP, Carson SS, et al. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med. 2010;38:428–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Girard TD, Exline MC, Carson SS, et al. Haloperidol and ziprasidone for treatment of delirium in critical illness. N Engl J Med. 2018;379:2506–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. 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;177:34–42.

    Article  PubMed  Google Scholar 

  31. 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;1:515–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Khan BA, Perkins AJ, Campbell NL, et al. Pharmacological management of deliruim (PMD) in the intensive care unit: a randomized pragmatic clinical trial. J Am Geriatr Soc. 2019;

    Google Scholar 

  33. Campbell NL, Perkins AJ, Khan BA, et al. Deprescribing in the pharmacologic management of delirium (de-PMD): a randomized trial in the intensive care unit. J Am Geriatr Soc. 2019;67:695–702.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Devlin JW, Roberts RJ, Fong JJ, et al. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med. 2010;38:419–27.

    Article  CAS  PubMed  Google Scholar 

  35. Devlin JW, Michaud CJ, Bullard HM, Harris SA, Thomas WL. Quetiapine for intensive care unit delirium: the evidence remains weak. Pharmacotherapy. 2016;36:e12–3.

    Article  PubMed  Google Scholar 

  36. Tahir TA, Eeles E, Karapareddy V, et al. A randomized controlled trial of quetiapine versus placebo in the treatment of delirium. J Psychosom Res. 2010;69:485–90.

    Article  PubMed  Google Scholar 

  37. Jasiak KD, Middleton EA, Camamo JM, Erstad BL, Snyder LS, Huckleberry YC. Evaluation of discontinuation of atypical antipsychotics prescribed for ICU delirium. J Pharm Pract. 2013;26:253–6.

    Article  PubMed  Google Scholar 

  38. Marshall J, Herzig SJ, Howell MD, et al. Antipsychotic utilization in the intensive care unit and in transitions of care. J Crit Care. 2016;33:119–24.

    Article  PubMed  Google Scholar 

  39. Tomichek JE, Stollings JL, Pandharipande PP, Chandrasekhar R, Ely EW, Girard TD. Antipsychotic prescribing patterns during and after critical illness: a prospective cohort study. Crit Care. 2016;20:378.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Kram BL, Kram SJ, Brooks KR. Implications of atypical antipsychotic prescribing in the intensive care unit. J Crit Care. 2015;30:814–8.

    Article  PubMed  Google Scholar 

  41. Marcantonio ER, Palihnich K, Appleton P, Davis RB. Pilot randomized trial of donepezil hydrochloride for delirium after hip fracture. J Am Geriatr Soc. 2011;59:S282–8.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Overshott R, Vernon M, Morris J, Burns A. Rivastigmine in the treatment of delirium in older people: a pilot study. Int Psychogeriatr. 2010;22:812–8.

    Article  PubMed  Google Scholar 

  43. Liptzin B, Laki A, Garb JL, Fingeroth R, Kushell R. Donepezil in the prevention and treatment of post-surgical deliruim. Am J Geriatr Psychiatry. 2005;13:1100–6.

    Article  PubMed  Google Scholar 

  44. van Eijk MM, Roes KC, Honing ML, et al. Effect of rivastigmine as an adjunct to usual care with haloperidol on duration of delirium and mortality in critically ill patients: a multicentre, double-blind, placebo-controlled randomized trial. Lancet. 2010;376:1829–37.

    Article  PubMed  CAS  Google Scholar 

  45. Bu DX, Griffin G, Lichtman H. Mechanisms for the anti-inflammatory effects of statins. Curr Opin Lipidol. 2011;22:165–70.

    Article  CAS  PubMed  Google Scholar 

  46. Niessner A, Steiner S, Speidl WS, et al. Simvastatin suppresses endotoxin-induced upregulation of toll-like receptors 4 and 2 in vivo. Atherosclerosis. 2006;189:408–13.

    Article  CAS  PubMed  Google Scholar 

  47. Wang H, Lynch JR, Song P, et al. Simvastatin and atorvastatin improve behavioral outcome, reduce hippocampal degeneration, and improve cerebral blood flow after experimental traumatic brain injury. Exp Neurol. 2007;206:59–69.

    Article  CAS  PubMed  Google Scholar 

  48. Morandi A, Hughes CG, Thompson JL, et al. Statins and delirium during critical illness: a multicenter, prospective cohort study. Crit Care Med. 2014;42:1899–909.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Page VJ, Davis DH, Zhao XB, et al. Statin use and risk of delirium in the critically ill. Am J Respir Crit Care Med. 2014;189:666–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Page VJ, Casarin A, Ely EW, et al. Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MoDUS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2017;5:727–37.

    Article  CAS  PubMed  Google Scholar 

  51. 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;4:203–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Reade MC, Eastwood GM, Bellomo R, et al. Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: a randomized clinical trial. J Am Med Assoc. 2016;315:1460–8.

    Article  CAS  Google Scholar 

  53. Pandharipande P, Shintani A, Peterson J, et al. Lorazepam is an independent risk factor for transition to delirium in intensive care unit patients. Anesthesiology. 2006;104:21–6.

    Article  CAS  PubMed  Google Scholar 

  54. 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;298:2644–53.

    Article  CAS  PubMed  Google Scholar 

  55. Pandharipande PP, Sanders RD, Girard TD, et al. Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial. Crit Care. 2010;14:R38.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafayette, IN, USA

    Noll L. Campbell

  2. Center for Health Innovation and Implementation Science, Regenstrief Institute, Indianapolis, IN, USA

    Noll L. Campbell & Babar A. Khan

  3. Indiana University Center for Aging Research, Regenstrief Institute, Indianapolis, IN, USA

    Noll L. Campbell & Babar A. Khan

  4. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Babar A. Khan

Authors
  1. Noll L. Campbell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Babar A. Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Noll L. Campbell .

Editor information

Editors and Affiliations

  1. Critical Illness, Brain Dysfunction, and Survivorship Center and the Division of Anesthesiology Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Christopher G. Hughes

  2. Critical Illness, Brain Dysfunction, and Survivorship Center and the Division of Anesthesiology Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Pratik P. Pandharipande

  3. Critical Illness, Brain Dysfunction, and Survivorship (CIBS), Center Department of Medicine, Pulmonary and Critical Care Vanderbilt University School of Medicine and the Tennessee Valley Veteran’s Affairs, Geriatric Research Education Clinical Center (GRECC), Nashville, TN, USA

    E. Wesley Ely

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Campbell, N.L., Khan, B.A. (2020). Treatment Strategies for Delirium. In: Hughes, C., Pandharipande, P., Ely, E. (eds) Delirium. Springer, Cham. https://doi.org/10.1007/978-3-030-25751-4_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-25751-4_14

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-25750-7

  • Online ISBN: 978-3-030-25751-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation