Delirium is a multifactorial entity, and its understanding continues to evolve. Delirium has been associated with increased morbidity, mortality, length of stay, and cost for hospitalized patients, especially for patients in the intensive care unit (ICU). Recent literature on delirium focuses on specific pharmacologic risk factors and pharmacologic interventions to minimize course and severity of delirium. While medication management clearly plays a role in delirium management, there are a variety of nonpharmacologic interventions, pharmacologic minimization strategies, and protocols that have been recently described. A PubMed search was performed to review the evidence for nonpharmacologic management, pharmacologic minimization strategies, and prevention of delirium for patients in the ICU. Recent approaches were condensed into 10 actionable steps to manage delirium and minimize medications for ICU patients and are presented in this review.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.
2.
MaldonadoJR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Am J Geriatr Psychiatry. 2013;21(12):1190–222. doi:10.1016/j.jagp.2013.09.005
3.
KalabalikJBrunettiLEl-SrougyR. Intensive care unit delirium: a review of the literature. J Pharm Pract. 2014;27(2):195–207. doi:10.1177/0897190013513804
4.
ThomasonJWShintaniAPetersonJFJacksonJCElyEW. Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients. Crit Care. 2005;9:R375. doi:10.1186/cc3729.
5.
PisaniMAKongSYKaslSVMurphyTEAraujoKLVan NessPH. 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. doi:10.1164/rccm.200904-0537OC.
6.
BurkhartCSDell-KusterSGamberiniM. Modifiable and nonmodifiable risk factors for postoperative delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2010;24(4):555–559. doi:10.1053/j.jvca.2010.01.003.
7.
DuceppeMAElliottAParaM. Modifiable risk factors for delirium in critically ill trauma patients: a multicenter prospective study. Crit Care. 2015;19(suppl 1):P478. doi:10.1186/cc14558.
8.
McPhersonJAWagnerCEBoehmLM. Delirium in the cardiovascular ICU: exploring modifiable risk factors. Crit Care Med. 2013;41(2):405–413. doi:10.1097/CCM.0b013e31826ab49b.
9.
NeufeldKJYueJInouyeSKNeedhamDM. Antipsychotic medication for prevention and treatment of delirium in hospitalized adults: a systematic review and meta-analysis. J Am Geriatr Soc. 2016;64(4):705–714. doi:10.1111/jgs.14076.
10.
BathulaMGonzalesJP. The pharmacologic treatment of intensive care unit delirium: a systematic review. Ann Pharmacother. 2013;47(9):1168–1174. doi:10.1177/1060028013500466.
11.
van den BoogaardMSlooterAJCBrüggemannRJM; REDUCE Study Investigators. Effect of haloperidol on survival among critically ill adults with a high risk of delirium: the REDUCE randomized clinical trial. JAMA. 2018;319(7):680–690. doi:10.1001/jama.2018.0160.
12.
PageVJElyEWGatesS. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (HOPE-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515–523. doi:10.1016/S2213-2600(13)70166-8.
13.
ErstadBLPuntilloKGilbertHC. Pain management principles in the critically ill. Chest. 2009;135(4):1075–1086. doi:10.1378/chest.08-2264.
14.
PuntilloKAMaxATimsitJF. Determinants of procedural pain intensity in the intensive care unit. The Europain(R) study. Am J Respir Crit Care Med. 2014;189(1):39–47. doi:10.1164/rccm.201306-1174OC.
15.
TanakaLMSAzevedoLCParkM. ERICC study investigators. Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study. Crit Care. 2014;18(4):R156. doi:10.1186/cc13995.
16.
CleggAYoungJB. Which medications to avoid in people at risk of delirium: a systematic review. Age Ageing. 2011;40(1):23–29. doi:10.1093/ageing/afq140.
17.
Van RompaeyBElseviersMMSchuurmansMJShortridge-BaggettLMTruijenSBossaertL. Risk factors for delirium in intensive care patients: a prospective cohort study. Crit Care. 2009;13(3):R77. doi:10.1186/cc7892.
18.
ColomboRCoronaAPragaF. A reorientation strategy for reducing delirium in the critically ill. Results of an interventional study. Minerva Anestesiol. 2012;78(9):1026–1033.
19.
EngelHNeedhamDMMorrisPEGropperMA. ICU early mobilization: from recommendation to implementation at three medical centers. Crit Care Med. 2013;41(9 suppl 1):S69–S80. doi:10.1097/CCM.0b013e3182a240d5.
20.
DavidsonJEAslaksonRALongAC. Guidelines for family-centered care in the neonatal, pediatric, and adult ICU. Crit Care Med. 2017;45(1):103–128. doi:10.1097/CCM.0000000000002169.
21.
Pain terms: a list with definitions and notes on usage. Recommended by the IASP Subcommittee on Taxonomy. Pain. 1979;6(3):249
22.
PayenJFChanquesGMantzJ. Current practices in sedation and analgesia for mechanically ventilated critically ill patients: a prospective multicenter patient-based study. Anesthesiology. 2007;106(4):687–695. doi:10.1097/01.anes.0000264747.09017.da.
23.
MorrisonRSMagazinerJGilbertM. Relationship between pain and opioid analgesics on the development of delirium following hip fracture. J Gerontol A Biol Sci Med Sci. 2003;58(1):76–81.
24.
BaumbachPGötzTGüntherAWeissTMeissnerW. Prevalence and characteristics of chronic intensive care-related pain: the role of severe sepsis and septic shock. Crit Care Med. 2016;44(6):1129–1137. doi:10.1097/CCM.0000000000001635.
25.
BarrJFraserGLPuntilloK. 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(1):263–306. doi:10.1097/CCM.0b013e3182783b72.
26.
Barnes-DalyMAPhillipsGElyEW. 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(2):171–178. doi:10.1097/CCM.0000000000002149.
27.
DuboisMJBergeronNDumontM. Delirium in an intensive care unit: a study of risk factors. Intensive Care Med. 2001;27(8):1297–1304.
28.
ChouRGordonDBde Leon-CasasolaOA. Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016;17(2):131–157. doi:10.1016/j.jpain.2015.12.008.
29.
DaleCRKannasDAFanVS. Improved analgesia, sedation, and delirium protocol associated with decreased duration of delirium and mechanical ventilation. Ann Am Thorac Soc. 2014;11(3):367–374. doi:10.1513/AnnalsATS.201306-210OC.
30.
ShehabiYBellomoRReadeMC; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials Group. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012;186(8):724–731. Epub 2012 Aug 2. doi:10.1164/rccm.201203-0522OC.
31.
LaerknerEStroemTToftP. No-sedation during mechanical ventilation: impact on patient’s consciousness, nursing workload and costs. Nurs Crit Care. 2016;21(1):28–35. doi:10.1111/nicc.12161.
32.
SchwieckertWDPohlmanMCPohlmanAS. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomized controlled trial. Lancet. 2009;373(9678):1874–1882. doi:10.1016/S0140-6736(09)60658-9.
33.
MinhasMAVelasquezAGKaulASalinasPDCeliLA. Effect of protocolized sedation on clinical outcomes in mechanically ventilated intensive care unit patients: a systematic review and meta-analysis of randomized controlled trials. Mayo Clin Proc. 2015;90(5):613–623. doi:10.1016/j.mayocp.2015.02.016.
34.
MillerMAGovindanSWatsonSRHyzyRCIwashynaTJ. ABCDE, but in that order? A cross-sectional survey of Michigan intensive care unit sedation, delirium, and early mobility practices. Ann Am Thorac Soc. 2015;12(7):1066–1071. doi:10.1513/AnnalsATS.201501-066OC.
35.
ChanquesGConseilMRogerC; SOS-Ventilation Study Investigators. Immediate interruption of sedation compared with usual sedation care in critically ill postoperative patients (SOS-Ventilation): a randomised, parallel-group clinical trial. Lancet Respir Med. 2017;5(10):795–805. doi:10.1016/S2213-2600(17)30304-1.
36.
StrømT. Sedation in the ICU. Dan Med J. 2012;59(5):B4458.
37.
ToftPOlsenHTJørgensenHK. Non-sedation versus sedation with a daily wake-up trial in critically ill patients receiving mechanical ventilation (NONSEDA Trial): study protocol for a randomised controlled trial. Trials. 2014;15:499. doi:10.1186/1745-6215-15-499.
38.
BalzerFWeißBKumpfO. Early deep sedation is associated with decreased in-hospital and two-year follow-up survival. Crit Care. 2015;19:197. doi:10.1186/s13054-015-0929-2.
39.
PandharipandePShintaniAPetersonJ. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology; 2006;104(1):21–26.
40.
RikerRRShehabiYBokeschPM; 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(5):489–499. Epub 2009 Feb 2. doi:10.1001/jama.2009.56.
41.
PandharipandePPPunBTHerrDL; 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. doi:10.1001/jama.298.22.2644.
42.
GirardTDKressJPFuchsBD; 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. doi:10.1016/S0140-6736(08)60105-1.
43.
GillKVVoilsSAChenaultGABrophyGM. Perceived versus actual sedation practices in adult intensive care unit patients receiving mechanical ventilation. Ann Pharmacother. 2012;46(10):1331–1339. doi:10.1345/aph.1R037.
44.
BlackwoodBBurnsKECardwellCRO’HalloranP. Protocolized versus non-protocolized weaning for reducing the duration of mechanical ventilation in critically ill adult patients. Cochrane Database Syst Rev. 2014;(11):Cd006904. doi:10.1002/14651858.CD006904.pub3.
45.
ShehabiYChanLKadimanS. Sedation Practice in Intensive Care Evaluation (SPICE) Study Group investigators. Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study. Inten Care Med. 2013;39(5):910–918. doi:10.1007/s00134-013-2830-2.
46.
KlompasMAndersonDTrickW. CDC Prevention Epicenters. The preventability of ventilator-associated events: the CDC Prevention Epicenters Wake Up and Breathe Collaborative. Am J Respir Crit Care Med. 2015;191(3):292–301. doi:10.1164/rccm.201407-1394OC.
47.
ChenYYChiMMChenYCChanYJChouSSWangFD. Using a criteria-based reminder to reduce use of indwelling urinary catheters and decrease urinary tract infections. Am J Crit Care. 2013;22(2):105–114. doi:10.4037/ajcc2013464.
48.
HalmMA. Daily goals worksheets and other checklists: are our critical care units safer?Am J Crit Care. 2008;17(6):577–580.
49.
da SilvaPSFonsecaMC. Unplanned endotracheal extubations in the intensive care unit: systematic review, critical appraisal, and evidence-based recommendations. Anesth Analg. 2012;114(5):1003–1014. doi:10.1213/ANE.0b013e31824b0296.
50.
Van RompaeyBSchuurmansMJShortridge-BaggettLMTruijenSBossaertL. Risk factors for intensive care delirium: a systematic review. Intensive Crit Care Nurs. 2008;24(2):98–107. doi:10.1016/j.iccn.2007.08.005.
51.
RoseLBurryLMallickR. Prevalence, risk factors, and outcomes associated with physical restraint use in mechanically ventilated adults. J Crit Care. 2016;31(1):31–35. doi:10.1016/j.jcrc.2015.09.011.
52.
KirkAPMcGlinseyABeckettARuddPArbourR. Restraint reduction, restraint elimination, and best practice: role of the clinical nurse specialist in patient safety. Clin Nurse Spec. 2015;29(6):321–328. doi:10.1097/NUR.0000000000000163.
53.
RivosecchiRKane-GillSLSvecSCampbellSSmithburgerPL. The implementation of a nonpharmacologic protocol to prevent intensive care delirium. J Crit Care. 2016;31(1):206–211. doi:10.1016/j.jcrc.2015.09.031.
54.
ÁlvarezEAGarridoMATobarEA. Occupational therapy for delirium management in elderly patients without mechanical ventilation in an intensive care unit: a pilot randomized control trial. J Crit Care. 2017;37:85–90. doi:10.1016/j.jcrc.2016.09.002.
55.
WatsonPLCerianaPFanfullaF. Delirium: is sleep important?Best Pract Res Clin Anaesthesiol. 2012;26(3):355–366. doi:10.1016/j.bpa.2012.08.005.
56.
KamdarBBNeedhamDMCollopNA. Sleep deprivation in critical illness: its role in physical and psychological recovery. J Intensive Care Med. 2012;27(2):97–111. doi:10.1177/0885066610394322.
57.
FitzgeraldJO’ReganNAdamisD. Sleep-wake cycle disturbances in elderly acute general medical inpatients: longitudinal relationship to delirium and dementia. Alzheimers Dement (Amst). 2017;7:61–68. doi:10.1016/j.dadm.2016.12.013.
58.
KamdarBBKingLMCollopNA. The effect of a quality improvement intervention on perceived sleep quality and cognition in a medical ICU. Crit Care Med. 2013;41(3):800–809. doi:10.1097/CCM.0b013e3182746442.
59.
PatelJBaldwinJBuntingPLahaS. The effect of a multicomponent multidisciplinary bundle of interventions on sleep and delirium in medical and surgical intensive care patients. Anaesthesia. 2014;69(6):540–549. doi:10.1111/anae.12638.
60.
HuRFJiangXYChenJ. Non-pharmalogical interventions for sleep promotion in the intensive care unit. Cochrane Database Syst Rev. 2015;(10):CD008808. doi:10.1002/14651858.CD008808.pub2.
61.
MartinezFEAnsteyMFordA. Prophylactic melatonin for delirium in intensive care (Pro-MEDIC): study protocol for a randomised controlled trial. Trials. 2017;18(1):4. doi:10.1186/s13063-016-1751-0.
62.
KressJPHallJB. ICU-Acquired weakness and recovery from critical illness. N Engl J Med. 2014;370(17):1626–1635. doi:10.1056/NEJMc1406274.
