Agitation, delirium, and sleep dysfunction in the intensive care unit (ICU) are common occurrences that result in negative patient outcomes. With the recent publication of the 2018 Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (PAD-IS), several areas are of particular interest due to emerging literature or conflicting results of research.
Objective
To highlight areas where emerging literature or variable study results exist and to provide the clinician with recommendations regarding patient management.
Methods
The 2018 PAD-IS guidelines were reviewed, and areas of emerging literature or lack of consensus of included investigations surrounding pharmacologic management of sedation, delirium, and sleep in the ICU were identified. A review and appraisal of the literature was conducted specifically to address the identified areas. Prospective, randomized trials were included in this narrative review.
Results
Four areas with emerging data or conflicting evidence were identified and included: use of propofol or dexmedetomidine for sedation, pharmacologic prevention of delirium, treatment of delirium, and pharmacologic strategies to improve sleep.
Conclusion
A comprehensive approach to the prevention and management of delirium, sedation, and sleep in the ICU is necessary to optimize patient outcomes.
DevlinJWSkrobikYGélinasC. 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(9):e825–e873.
2.
BrummelNEGirardTDElyEW. 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(3):370–379.
3.
FosterJKellyM. 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(5):231–238.
4.
MoonKJLeeSM. The effects of a tailored intensive care unit delirium prevention protocol: a randomized controlled trial. Int J Nurs Stud. 2015;52(9):1423–1432.
5.
RivosecchiRMKane-GillSLSvecS. The implementation of a nonpharmacologic protocol to prevent intensive care delirium. J Crit Care. 2016;31(1):206–211.
6.
LouzonPJenningsHAliM. Impact of pharmacist management of pain, agitation, and delirium in the intensive care unit through participation in multidisciplinary bundle rounds. Am J Health Syst Pharm. 2017;74(4):253–262.
7.
MarshallJFinnCATheodoreAC. Impact of a clinical pharmacist-enforced intensive care unit sedation protocol on duration of mechanical ventilation and hospital stay. Crit Care Med. 2008;36(2):427–433.
8.
Barnes-DalyMAPhillipsGElyEW. Improving hospital survival and reducing brain dysfunction at seven California community hospitals: implementing PAD guidelines via the ABCDEF bundle in 6064 patients. Crit Care Med. 2017;45(2):171–178.
9.
BalasMCBurkeWJGannonD. Implementing the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle into everyday care: opportunities, challenges, and lessons learned for implementing the ICU pain, agitation, and delirium guidelines. Crit Care Med. 2013;41(9 suppl 1):S117–127.
10.
HerrDLSum-PingSTEnglandM. ICU sedation after coronary artery bypass graft surgery: dexmedetomidine based versus propofol-based sedation regimens. J Cardiothorac Vasc Anesth. 2003;17(5):576–584.
11.
KaramanYAbudBTekgulZT. Effects of dexmedetomidine and propofol on sedation in patients after coronary artery bypass graft surgery in a fast-track recovery room setting. J Anesth. 2015;29(4):522–528.
12.
VennRMGroundsRM. Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions. Br J Anaesth. 2001;87(5):684–690.
13.
TeraoYIchinomiyaTHigashijimaU. Comparison between propofol and dexmedetomidine in postoperative sedation after extensive cervical spine surgery. J Anesth. 2012;26(2):179–186.
14.
SrivastavaVKAgrawalSKumarS. Comparison of dexmedetomidine, propofol and midazolam for short-term sedation in postoperatively mechanically ventilated neurosurgical patients. J Clin Diagn Res. 2014;8(9):GC04–07.
15.
ShahPNDongreVPatilV. Comparison of post-operative ICU sedation between dexmedetomidine and propofol in Indian population. Indian J Crit Care Med. 2014;18(5):291–296.
16.
ChenJZhouJChenZ. Efficacy and safety of dexmedetomidine versus propofol for the sedation of tube-retention after oral maxillofacial surgery. J Oral Maxillofac Surg. 2014;72(2):285.e1–7.
17.
MaldonadoJRWysongAvan der StarrePJ. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics. 2009;50(3):206–217.
18.
DjaianiGSilvertonNFedorkoL. Dexmedetomidine versus propofol sedation reduces delirium after cardiac surgery: a randomized controlled trial. Anesthesiology. 2016;124(2):362–368.
19.
JakobSMRuokonenEGroundsRM. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012;307(11):1151–1160.
20.
ContiGRanieriVMCostaR. Effects of dexmedetomidine and propofol on patient-ventilator interaction in difficult-to-wean, mechanically ventilated patients: a prospective, open-label, randomized, multicenter study. Crit Care. 2016;20(1):206.
21.
RoodPHuisman-de WaalGVermeulenH. Effect of organizational factors on the variation in incidence of delirium in intensive care unit patients: a systematic review and meta-regression analysis. Aust Crit Care. 2018;31(3):180–187.
22.
Klen KlouwenbergPMZaalIJSpitoniC. The attributable mortality of delirium in critically ill patients: prospective cohort study. BMJ. 2014;349:g6652.
23.
van den BoogaardMPetersSAvan der HoevenJG. The impact of delirium on the prediction of in-hospital mortality in intensive care patients. Crit Care. 2010;14(4):R146.
24.
GirardTDThompsonJLPandharipandePP. Clinical phenotypes of delirium during critical illness and severity of subsequent long-term cognitive impairment: a prospective cohort study. Lancet Respir Med. 2018;6(3):213–222.
25.
TurunenHJakobSMRuokonenE. Dexmedetomidine versus standard sedation with propofol or midazolam in intensive care: an economic evaluation. Crit Care. 2015;19:67.
26.
BiocJJMageeCCucchiJ. Cost effectiveness of a benzodiazepine vs a nonbenzodiazepine-based sedation regimen for mechanically ventilated, critically ill adults. J Crit Care. 2014;29(5):753–757.
27.
PatanwalaAEErstadBL. Comparison of dexmedetomidine versus propofol on hospital costs and length of stay. J Intensive Care Med. 2016;31(7):466–470.
28.
Precedex (dexmedetomidine) [package insert]. Lake Forest, IL: Hospira; 2016.
29.
Diprivan (propofol) [package insert]. Lake Zurich, IL: Fresenius Kabi; 2017.
30.
NelsonKMPatelGPHammonDA. Effects from continuous infusion of dexmedetomidine and propofol on hemodynamic stability in critically ill adult patients with septic shock [published online September 27, 2018]. J Intensive Care Med. 2018.
31.
MorelliASandilippoFArnemannP. The effect of propofol and dexmedetomidine sedation on norepinephrine requirements in septic shock patients: a crossover trial. Crit Care Med. 2019;47(2):e89–95.
BalasMCWeinhouseGLDenehyL. Interpreting and implementing the 2018 pain, agitation/sedation, delirium, immobility, and sleep disruption clinical practice guideline. Crit Care Med. 2018;46(9):1464–1470.
34.
ReadeMCEastwoodGMBellomoR. Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: a randomized clinical trial. JAMA. 2016;315(14):1460–1468.
35.
KrajčováAWaldaufPAndělM. Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports. Crit Care. 2015;19:398.
36.
PrakanrattanaUPrapaitrakoolS. Efficacy of risperidone for prevention of postoperative delirium in cardiac surgery. Anaesth Intensive Care. 2007;35(5):714–719.
37.
HudetzJAPattersonKMIqbalA. Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2009;23(5):651–657.
38.
HakimSMOthmanAINaoumDO. Early treatment with risperidone for subsyndromal delirium after on-pump cardiac surgery in the elderly: a randomized trial. Anesth. 2012;116(5):987–997.
39.
LiXYangJNieXL. Impact of dexmedetomidine on the incidence of delirium in elderly patients after cardiac surgery. A randomized controlled trial. PLoS One. 2017;12(2):e0170757.
40.
AzeemTMAYosifNEAlansaryAM. Dexmedetomidine vs morphine and midazolam in the prevention and treatment of delirium after adult cardiac surgery: a randomized, double blinded clinical trial. Saudi J Anaesth. 2018;12(2):190–197.
41.
WangWLiHLWangDX. Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial. Crit Care Med. 2012;40(3):731–739.
42.
SuXMengZTWuXH. Dexmedetomidine for prevention of delirium in elderly patients after non- cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet. 2016;388(10054):1893–1902.
43.
AvidanMSMaybrierHRAbdallahAB. 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.
44.
Al-QadheebNSSkrobikYSchumakerG. Preventing ICU subsyndromal delirium conversion to delirium with low-dose haloperidol: a double-blind, placebo-controlled pilot study. Crit Care Med. 2016;44(3):583–591.
45.
GirardTDPandharipandePPCarsonSS. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: The MIND randomized, placebo-controlled trial. Crit Care Med. 2010;38(2):428–437.
46.
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.
47.
AbdelgalelEF. Dexmedetomidine versus haloperidol for prevention of delirium during non-invasive mechanical ventilation. Egypt J Anaesth. 2016;32(4):472–481.
48.
AzumaKTakaesuYSoedaH. Ability of suvorexant to prevent delirium in patients in the intensive care unit: a randomized controlled trial. Acute Med Surg. 2018;5(4):362–368.
49.
Van den BoogaardMSlooterAJCBruggemannRJM. Effect of haloperidol on survival among critically ill adults with a high risk of delirium. JAMA. 2018;319(7):680–690.
50.
SkorbikYDupreyMSHillNS. Low-dose nocturnal dexmedetomidine prevents ICU delirium: a randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2018;197(9):1147–1156.
51.
KusumiIBokuSTakahashiY. Psychopharmacology of atypical antipsychotic drugs: From the receptor binding profile to neuroprotection and neurogenesis. Psychiatry Clin Neurosci. 2015;69(5):243–258.
52.
SkrobikYKBergeronNDumontM. Olanzapine vs haloperidol: treating delirium in a critical care setting. Intensive Care Med. 2004;30(3):444–449.
53.
DevlinJWRobertsRJFongJJ. 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(2):419–427.
54.
van EijkMMRoesKCHoningML. Effect of rivastigmine as an adjunct to usual care with haloperidol on duration of delirium and mortality in critically ill patients: a multicenter, double-blind, placebo-controlled randomized trial. Lancet. 2010;376(9755):1829–1837.
55.
BakriMHIsmailEAIbrahimA. Comparison of dexmedetomidine or ondansetron with haloperidol for treatment of postoperative delirium in trauma patients admitted to an intensive care unit: randomized controlled trial. Anaesthesia Pain and Intensive Care. 2015;19:118–123.
56.
NeedhamDMColantuoniEDinglasVD. Rosuvastatin versus placebo for delirium in the intensive care and subsequent cognitive impairment in patients with sepsis-associated acute respiratory distress syndrome: an ancillary study to a randomized controlled trial. Lancet Respir Med. 2016;4(3):203–212.
57.
PageVJCasarinAElyEW. Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MoDUS): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2017;5(9):727–737.
58.
GirardTDExlineMCCarsonSS. Haloperidol and ziprasidone for treatment of delirium in critical illness. N Engl J Med. 2018;379(26):2506–2516.
59.
ShiloLDaganYSmorjikY. Effect of melatonin on sleep quality of COPD intensive care patients: a pilot study. Chronobiol Int. 2000;17(1):71–76.
60.
IbrahimMGBellomoRHartGK. A double-blind placebo-controlled randomised pilot study of nocturnal melatonin in tracheostomised patients. Crit Care Resusc. 2006;8(3):187–191.
61.
BourneRSMillsGHMinelliC. Melatonin therapy to improve nocturnal sleep in critically ill patients: encouraging results from a small randomised controlled trial. Crit Care. 2008;12(2):R52.
62.
Treggiari-VenziMBorgeatAFuchs-BuderT. Overnight sedation with midazolam or propofol in the ICU: effects on sleep quality, anxiety and depression. Intensive Care Med. 1996;22(11):1186–1190.
63.
KondiliEAlexopoulouCXirouchakiN. Effects of propofol on sleep quality in mechanically ventilated critically ill patients: a physiological study. Intensive Care Med. 2012;38(10):1640–1646.
64.
EngelmannCWallenbornJOlthoffD. Propofol versus flunitrazepam for inducing and maintaining sleep in postoperative ICU patients. Indian J Crit Care Med. 2014;18(4):212–219.
65.
WuXHCuiFZhangC. Low-dose dexmedetomidine improves sleep quality pattern in elderly patients after noncardiac surgery in the intensive care unit. Anesthesiology. 2016;125(5):979–991.
66.
MistralettiGUmbrelloMSabbatiniG. Melatonin reduces the need for sedation in ICU patients: a randomized controlled trial. Minerva Anestesiol. 2015;81(12):1298–1310.
67.
HattaKKishiYWadaK. Preventive effects of ramelteon on delirium: a randomized, placebo-controlled trial. JAMA Psychiatry. 2014;71(4):397–403.
68.
HattaKKishiYWadaK. Ramelteon for delirium in hospitalized patients. JAMA. 2015;314(10):1071–1072.
69.
NishikimiMNumaguchiATakahashiK. Effect of administration of ramelteon, a melatonin receptor agonist, on the duration of stay in the ICU: a single-center randomized placebo-controlled trial. Crit Care Med. 2018;46(7):1099–1105.
70.
BourneRSMinelliCMillsGH. Clinical review: sleep measurement in critical care patients: research and clinical implications. Crit Care. 2007;11(4):226–242.
71.
PisaniMAFrieseRSGehlbackBK. Sleep in the intensive care unit. Am J Respir Crit Care Med. 2015;191(7):731–738.
72.
ErlandLASaxenaPK. Melatonin natural health products and supplements: presence of serotonin and significant variability of melatonin content. J Clin Sleep Med. 2017;13(2):275–281.
73.
PunBTBalasMCBarnes-DalyMA. Caring for critically ill patients with the ABCDEF bundle: results of the ICU liberation collaborative in over 15,000 adults. Crit Care Med. 2018;47(1):3–14.
74.
DemouleACarreiraSLavaultS. Impact of earplugs and eye mask on sleep in critically ill patients: a prospective randomized study. Crit Care. 2017;21(1):284.
75.
HuRFJiangXYHegadorenKM. Effects of earplugs and eye masks combined with relaxing music on sleep, melatonin and cortisol levels in ICU patients: a randomized controlled trial. Crit Care. 2015;19:115.
76.
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.
77.
PatelJBaldwinJBuntingP. 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.
