Preventive strategies and potential therapeutic interventions for delirium in sepsis

References

• Vincent JL, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006;34:344–353.
   PubMed Web of Science ®Google Scholar
• Martin GS, Mannino DM, Eaton S, et al. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348:1546–1554.
   PubMed Web of Science ®Google Scholar
• Warren BL, Eid A, Singer P, et al.; KyberSept Trial Study Group. Caring for the critically ill patient: high-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA. 2001;286:1869–1878.
   PubMed Web of Science ®Google Scholar
• Ranieri VM, Thompson BT, Barie PS, et al.; PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012;366:2055–2064.
   PubMed Web of Science ®Google Scholar
• Russell JA, Walley KR, Singer J, et al.; VASST Investigators. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358:877–887.
   PubMed Web of Science ®Google Scholar
• Annane D, Cariou A, Maxime V, et al.; COIITSS Study Investigators. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA. 2010;303:341–348.
   PubMed Web of Science ®Google Scholar
• Stevenson EK, Rubenstein AR, Radin GT, et al. Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis. Crit Care Med. 2014;42:625–631.
   PubMed Web of Science ®Google Scholar
• Levy MM, Dellinger RP, Townsend SR, et al.; Surviving Sepsis Campaign. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med. 2010;38:367–374.
   PubMed Web of Science ®Google Scholar
• Miller RR 3rd, Dong L, Nelson NC, et al. Multicenter implementation of a severe sepsis and septic shock treatment bundle. Am J Respir Crit Care Med. 2013;188:77–82.
   PubMed Web of Science ®Google Scholar
• Kumar A, Haery C, Paladugu B, et al. The duration of hypotension before the initiation of antibiotic treatment is a critical determinant of survival in a murine model of Escherichia coli septic shock: association with serum lactate and inflammatory cytokine levels. J Infect Dis. 2006;193:251–258.
   PubMed Web of Science ®Google Scholar
• Pronovost PJ, Angus DC, Dorman T, et al. Physician staffing patterns and clinical outcomes in critically ill patients: a systematic review. JAMA. 2002;288:2151–2162.
   PubMed Web of Science ®Google Scholar
• The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301–1308.
   PubMed Web of Science ®Google Scholar
• Shehabi Y, Chan L, Kadiman S, et al. Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study. Intensive Care Med. 2013;39:910–918.
   PubMed Web of Science ®Google Scholar
• Napolitano LM, Kurek S, Luchette FA, et al. Clinical practice guideline: red blood cell transfusion in adult trauma and critical care. Crit Care Med. 2009;37:3124–3157.
   PubMed Web of Science ®Google Scholar
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington (VA): American Psychiatric Association; 2013.
   Google Scholar
• Gofton TE, Young GB. Sepsis-associated encephalopathy. Nat Rev Neurol. 2012;8:557–566.
   PubMed Web of Science ®Google Scholar
• 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;291:1753–1762.
   PubMed Web of Science ®Google Scholar
• Garrouste Orgeas M, Timsit JF, Soufir L, et al. Impact of adverse events on outcomes in intensive care unit patients. Crit Care Med. 2008;36:2041–2047.
   PubMed Web of Science ®Google Scholar
• Thomason JW, Shintani A, Peterson JF, et al. 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–R381.
   PubMed Web of Science ®Google Scholar
• Miller RR, Shintani A, Girard TD, et al. Delirium predicts extubation failure. Proc Am Thorac Soc. 2006;3:A42.
   Google Scholar
• Lin SM, Liu CY, Wang CH, et al. The impact of delirium on the survival of mechanically ventilated patients. Crit Care Med. 2004;32:2254–2259.
   PubMed Web of Science ®Google Scholar
• Bone RC, Sprung CL, Sibbald WJ, et al. Definitions of sepsis and multiple organ failure. Crit Care Med. 1992;20:724–726.
   PubMed Web of Science ®Google Scholar
• van der Kooi AW, Zaal IJ, Klijn FA, et al. Delirium detection using EEG: what and how to measure. Chest. 2015;147:94–101.
   PubMed Web of Science ®Google Scholar
• Zauner C, Gendo A, Kramer L, et al. Impaired subcortical and cortical sensory evoked potential pathways in septic patients. Crit Care Med. 2002;30:1136–1139.
   PubMed Web of Science ®Google Scholar
• Pisani MA, Kong SYJ, Kasl SV, et al. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med. 2009;180:1092–1097.
   PubMed Web of Science ®Google Scholar
• Almeida ICT, Soares M, Bozza FA, et al. The impact of acute brain dysfunction in the outcomes of mechanically ventilated cancer patients. Plos One. 2014;9:e85332.
   Google Scholar
• Zhang LN, Wang XT, Ai YH, et al. Epidemiological features and risk factors of sepsis-associated encephalopathy in intensive care unit patients: 2008–2011. Chin Med J. 2012;125:828–831.
   PubMed Web of Science ®Google Scholar
• Kim S-Y, Kim S-W, Kim J-M, et al. Differential associations between delirium and mortality according to delirium subtype and age: a prospective cohort study. Psychosom Med. 2015;77:903–910.
   PubMed Web of Science ®Google Scholar
• Patel SB, Poston JT, Pohlman A, et al. Rapidly- reversible, sedation-related delirium versus persistent delirium in the intensive care unit. Am J Resp Crit Care Med. 2014;189:658–665.
   PubMed Web of Science ®Google Scholar
• 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;54:479–484.
   PubMed Web of Science ®Google Scholar
• Robinson TN, Raeburn CD, Tran ZV, et al. Motor subtypes of postoperative delirium in older adults. Arch Surg. 2011;146:295–300.
   PubMedGoogle Scholar
• 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;104:21–26.
   PubMed Web of Science ®Google Scholar
• Pisani MA, Murphy TE, Araujo KL, et al. Benzodiazepine and opioid use and the duration of intensive care unit delirium in an older population. Crit Care Med. 2009;37:177–183.
   PubMed Web of Science ®Google Scholar
• Patel SB, Kress JP. Sedation and analgesia in the mechanically ventilated patient. Am J Respir Crit Care Med. 2012;185:486–497.
   PubMed Web of Science ®Google Scholar
• Brummel NE, Ely EW. Sedation level and the prevalence of delirium. Intensive Care Med. 2014;40:136.
   PubMed Web of Science ®Google Scholar
• van Munster BC, Aronica E, Zwinderman AH, et al. Neuroinflammation in delirium: a post-mortem case-control study. Rejuvenation Res. 2011;14:615–622.
   PubMed Web of Science ®Google Scholar
• Zhao Y-J, Yi W-J, Wan X-J, et al. Blockade of ICAM-1 improves the outcome of polymicrobial sepsis via modulating neutrophil migration and reversing immunosuppression. Mediators Inflamm. 2014;2014:1–10.
   Google Scholar
• Taccone FS, Castanares-Zapatero D, Peres-Bota D, et al. Cerebral autoregulation is influenced by carbon dioxide levels in patients with septic shock. Neurocrit Care. 2010;12:35–42.
   PubMed Web of Science ®Google Scholar
• Xu W, Cao M, Zheng H, et al. Upregulation of SYF2 is associated with neuronal apoptosis caused by reactive astrogliosis to neuroinflammation. J Neurosci Res. 2014;92:318–328.
   PubMed Web of Science ®Google Scholar
• Semmler A, Frisch C, Debeir T, et al. Long-term cognitive impairment, neuronal loss and reduced cortical cholinergic innervation after recovery from sepsis in a rodent model. Exp Neurol. 2007;204:733–740.
   PubMed Web of Science ®Google Scholar
• Weberpals M, Hermes M, Hermann S, et al. NOS2 gene deficiency protects from sepsis-induced long-term cognitive deficits. J Neurosci. 2009;29:14177–14184.
   PubMed Web of Science ®Google Scholar
• Van Gool WA, Van De Beek D, Eikelenboom P. Systemic infection and delirium: when cytokines and acetylcholine collide. Lancet. 2010;375:773–775.
   PubMed Web of Science ®Google Scholar
• Kadoi Y, Saito S. An alteration in the gamma-aminobutyric acid receptor system in experimentally induced septic shock in rats. Crit Care Med. 1996;24:298–305.
   PubMed Web of Science ®Google Scholar
• Field RH, Gossen A, Cunningham C. Prior pathology in the basal forebrain cholinergic system predisposes to inflammation-induced working memory deficits: reconciling inflammatory and cholinergic hypotheses of delirium. J Neurosci. 2012;32:6288–6294.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Luetz A, Heymann A, Radtke FM, et al. Different assessment tools for intensive care unit delirium: which score to use? Crit Care Med. 2010;38:409–418.
   PubMed Web of Science ®Google Scholar
• Han JH, Wilson A, Graves AJ, et al. Validation of the confusion assessment method for the intensive care unit in older emergency department patients. Acad Emerg Med. 2014;21:180–187.
   PubMed Web of Science ®Google Scholar
• ICUDELIRIUM.ORG [Internet]. [ cited 2016 May 6]. Available from: www.icudelirium.org
   Google Scholar
• Mistraletti G, Pelosi P, Mantovani ES, et al. Delirium: clinical approach and prevention. Best Prac Res Clin Anaesthesiol. 2012;26:311–326.
   PubMedGoogle Scholar
• 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.
   PubMedGoogle Scholar
• Wassenaar A, van den Boogaard M, van Achterberg T, et al. Multinational development and validation of an early prediction model for delirium in ICU patients. Intensive Care Med. 2015;41:1048–1056.
   PubMed Web of Science ®Google Scholar
• Hosokawa K, Gaspard N, Su F, et al. Clinical neurophysiological assessment of sepsis-associated brain dysfunction: a systematic review. Crit Care. 2014;18:674.
   PubMed Web of Science ®Google Scholar
• Sharshar T, Carlier R, Bernard F, et al. Brain lesions in septic shock: a magnetic resonance imaging study. Intensive Care Med. 2007;33:798–806.
   PubMed Web of Science ®Google Scholar
• Jackson JC, Mitchell N, Hopkins RO. Cognitive functioning, mental health, and quality of life in ICU survivors: an overview. Anesthesiol. 2011;29:751–764.
   Google Scholar
• Jackson JC, Pandharipande PP, Girard TD, et al. 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;2:369–379.
   PubMed Web of Science ®Google Scholar
• Pandharipande PP, Girard TD, Jackson JC, et al.; for the BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369:1306–1316.
   PubMed Web of Science ®Google Scholar
• Iwashyna TJ, Ely EW, Smith DM, et al. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304:1787–1794.
   PubMed Web of Science ®Google Scholar
• Lazosky A, Young GB, Zirul S, et al. Quality of life after septic illness. J Crit Care. 2010;25:406–412.
   PubMed Web of Science ®Google Scholar
• Hopkins RO, Jackson JC. Long-term neurocognitive function after critical illness. Chest. 2006;130:869–878.
   PubMed Web of Science ®Google Scholar
• Sharshar T, Bastuji-Garin S, Stevens RD, et al. Presence and severity of intensive care unit acquired paresis at time of awakening are associated with increased intensive care unit and hospital mortality. Crit Care Med. 2009;37:3047–3053.
   PubMed Web of Science ®Google Scholar
• Kuo H-K, Sorond F, Iloputaife I, et al. Effect of blood pressure on cognitive functions in elderly persons. J Gerontol. 2004;59:1191–1194.
   Google Scholar
• Holmes C, Cunningham C, Zotova E, et al. Systemic inflammation and disease progression in Alzheimer disease. Neurology. 2009;73:768–774.
   PubMed Web of Science ®Google Scholar
• Semmler A, Widmann CN, Okulla T, et al. Persistent cognitive impairment, hippocampal atrophy and EEG changes in sepsis survivors. J Neurol Neurosurg Psychiatry. 2013;84:62–70.
   PubMed Web of Science ®Google Scholar
• Toga AW, Thompson PM. Mapping brain asymmetry. Nat Rev Neurosci. 2003;4:37–48.
   PubMed Web of Science ®Google Scholar
• Lyketsos CG, Toone L, Tschanz J, et al. Population-based study of medical comorbidity in early dementia and “cognitive impairment no dementia”: association with functional and cognitive impairment - the Cache County Study. Am J Geriatr Psychiatry. 2005;13:656–664.
   PubMed Web of Science ®Google Scholar
• Salluh JI, Wang H, Schneider EB, et al. Outcome of delirium in critically ill patients: systematic review and meta-analysis. BMJ. 2015;350:h2538.
   PubMed Web of Science ®Google Scholar
• van den Boogaard M, Peters SA, 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:R146.
   Google Scholar
• Salluh JI, Soares M, Teles JM, et al. Delirium epidemiology in critical care (DECCA): an international study. Crit Care. 2010;14:R210.
   PubMed Web of Science ®Google Scholar
• Kishi Y, Iwasaki Y, Takezawa K, et al. Delirium in critical care unit patients admitted through an emergency room. Gen Hosp Psychiatry. 1995;17:371–379.
   PubMed Web of Science ®Google Scholar
• Thomason JWW, Shintani A, Peterson JF, et al. Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients. Crit Care. 2005;9:R375–81.
   PubMed Web of Science ®Google Scholar
• Zhang Z, Pan L, Ni H. Impact of delirium on clinical outcome in critically ill patients: a meta-analysis. Gen Hosp Psychiatry. 2013;35:105–111.
   PubMed Web of Science ®Google Scholar
• Klein Klouwenberg PM, Zaal IJ, Spitoni C, et al. The attributable mortality of delirium in critically ill patients: prospective cohort study. BMJ. 2014;349:g6652.
   Google Scholar
• Martinez FT, Tobar C, Beddings CI, et al. Preventing delirium in an acute hospital using a non-pharmacological intervention. Age Ageing. 2012;41:629–634.
   PubMed Web of Science ®Google Scholar
• Marcantonio ER, Flacker JM, Wright RJ, et al. Reducing delirium after hip fracture: a randomized trial. J Am Geriatr Soc. 2001;49:516–522.
   PubMed Web of Science ®Google Scholar
• Kalisvaart KJ, De Jonghe JFM, Bogaards MJ, et al. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc;. 2005;53:1658–1666.
   PubMed Web of Science ®Google Scholar
• Larsen KA, Kelly SE, Stern TA, et al. Administration of olanzapine to prevent postoperative delirium in elderly joint-replacement patients: a randomized, controlled trial. Psychosomatics. 2010;51:409–418.
   PubMed Web of Science ®Google Scholar
• Prakanrattana U, Prapaitrakool S. Efficacy of risperidone for prevention of postoperative delirium in cardiac surgery. Anaesth Intensive Care. 2007;35:714–719.
   PubMed Web of Science ®Google Scholar
• Abraha I, Trotta F, Rimland JM, et al. Efficacy of non-pharmacological interventions to prevent and treat delirium in older patients: a systematic overview. The SENATOR project ONTOP series. Plos One. 2015;10:e0123090.
   PubMed Web of Science ®Google Scholar
• Serafim RB, Bozza FA, Soares M, et al. Pharmacologic prevention and treatment of delirium in intensive care patients: a systematic review. J Crit Care. 2015;30:799–807.
   PubMed Web of Science ®Google Scholar
• Hshieh TT, Yue J, Oh E, et al. Effectiveness of multicomponent nonpharmacological delirium interventions: a meta-analysis. JAMA Inter Med. 2015;175:512–520.
   PubMed Web of Science ®Google Scholar
• Martinez F, Tobar C, Hill N. Preventing delirium: should non-pharmacological, multicomponent interventions be used? A systematic review and meta-analysis of the literature. Age Ageing. 2015;44:196–204.
   PubMed Web of Science ®Google Scholar
• Eastwood GM, Peck L, Bellomo R, et al. A questionnaire survey of critical care nurses’ attitudes to delirium assessment before and after introduction of the CAM-ICU. Aust Crit Care. 2012;25:162–169.
   PubMed Web of Science ®Google Scholar
• Bryczkowski SB, Lopreiato MC, Yonclas PP, et al. Delirium prevention program in the surgical intensive care unit improved the outcomes of older adults. J Surg Res. 2014;190:280–288.
   PubMed Web of Science ®Google Scholar
• van den Boogaard M, Pickkers P, van der Hoeven H, et al. Implementation of a delirium assessment tool in the ICU can influence haloperidol use. Crit Care. 2009;13:R131.
   Google Scholar
• Hager DN, Dinglas VD, Subhas S, et al. Reducing deep sedation and delirium in acute lung injury patients: a quality improvement project. Crit Care Med. 2013;41:1435–1442.
   PubMed Web of Science ®Google Scholar
• Skrobik Y, Ahern S, Leblanc M, et al. Protocolized intensive care unit management of analgesia, sedation, and delirium improves analgesia and subsyndromal delirium rates. Anesth Analg. 2010;111:451–463.
   PubMed Web of Science ®Google Scholar
• 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;42:1024–1036.
   PubMed Web of Science ®Google Scholar
• Reade MC, Eastwood GM, Peck L, et al. Routine use of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) by bedside nurses may underdiagnose delirium. Crit Care Resusc. 2011;13:217–224.
   PubMed Web of Science ®Google Scholar
• 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;41:800–809.
   PubMed Web of Science ®Google Scholar
• Dale CR, Kannas DA, Fan VS, et al. Improved analgesia, sedation, and delirium protocol associated with decreased duration of delirium and mechanical ventilation. Ann Am Thorac Soc. 2014;11:367–374.
   PubMedGoogle Scholar
• Robinson BR, Mueller EW, Henson K, et al. An analgesia-delirium-sedation protocol for critically ill trauma patients reduces ventilator days and hospital length of stay. J Trauma. 2008;65:517–526.
   PubMedGoogle Scholar
• Mansouri P, Javadpour S, Zand F, et al. Implementation of a protocol for integrated management of pain, agitation, and delirium can improve clinical outcomes in the intensive care unit: a randomized clinical trial. J Crit Care. 2013;28:918–922.
   PubMed Web of Science ®Google Scholar
• Kratz T, Heinrich M, Schlaub E, et al. Preventing postoperative delirium. Dtsch Arztebl Int. 2015;24:289–296.
   Google Scholar
• Zaubler TS, Murphy K, Rizzuto L, et al. Quality improvement and cost savings with multicomponent delirium interventions: replication of the hospital elder life program in a community hospital. Psychosomatics. 2013;54:219–226.
   PubMed Web of Science ®Google Scholar
• Trogrlić Z, Van Derjagt M, Bakker J, et al. A systematic review of implementation strategies for assessment, prevention, and management of ICU delirium and their effect on clinical outcomes. Crit Care. 2015;19:157.
   PubMed Web of Science ®Google Scholar
• Morandi A, Brummel NE, Ely EW. Sedation, delirium and mechanical ventilation: the ‘ABCDE’ approach. Current Opinion in Critical Care. 2011;17:43–49.
   PubMed Web of Science ®Google Scholar
• 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;371:126–134.
   PubMed Web of Science ®Google Scholar
• Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301:489–499.
   PubMed Web of Science ®Google Scholar
• 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;298:2644–2653.
   PubMed Web of Science ®Google Scholar
• Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012;307:1151–1160.
   PubMed Web of Science ®Google Scholar
• Vasilevskis EE, Pandharipande PP, Girard TD, et al. A screening, prevention, and restoration model for saving the injured brain in intensive care unit survivors. Crit Care Med. 2010;38:S683–691.
   Google Scholar
• Page VJ, Casarin A. Missing link or not, mobilise against delirium. Crit Care. 2014;18:105.
   PubMed Web of Science ®Google Scholar
• Morris PE, Griffin L, Thompson C, et al. Receiving early mobility during an intensive care unit admission is a predictor of improved outcomes in acute respiratory failure. Am J Med Sci. 2011;341:373–377.
   PubMed Web of Science ®Google Scholar
• 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;373:1874–1882.
   PubMed Web of Science ®Google Scholar
• Wang W, Li H-L, Wang D-X, et al. Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial. Crit Care Med. 2012;40:731–739.
   PubMed Web of Science ®Google Scholar
• Pisani MA, Friese RS, Gehlbach BK, et al. Sleep in the intensive care unit. Am J Respir Crit Care Med. 2015;191:731–738.
   PubMed Web of Science ®Google Scholar
• Hakim SM, Othman AI, Naoum DO. Early treatment with risperidone for subsyndromal delirium after on-pump cardiac surgery in the elderly: a randomized trial. Anesthesiology. 2012;116:987–997.
   PubMed Web of Science ®Google Scholar
• Weinhouse GL. Delirium and sleep disturbances in the intensive care unit: can we do better? Curr Opin Anaesthesiol. 2014;27:403–408.
   PubMed Web of Science ®Google Scholar
• Van Rompaey B, Elseviers MM, Van Drom W, et al. The effect of earplugs during the night on the onset of delirium and sleep perception: a randomized controlled trial in intensive care patients. Crit Care. 2012;16:R73.
   Google Scholar
• American Geriatrics Society Expert Panel on Postoperative Delirium in Older. American geriatrics society abstracted clinical practice guideline for postoperative delirium in older adults. J Am Geriatr Soc. 2015;63:142–150.
   PubMed Web of Science ®Google Scholar
• Balas M, Buckingham R, Braley T, et al. Extending the ABCDE bundle to the post-intensive care unit setting. J Gerontol Nurse. 2013;39:39–51.
   PubMed Web of Science ®Google Scholar
• Pandharipande P, Banerjee A, McGrane S, et al. Liberation and animation for ventilated ICU patients: the ABCDE bundle for the back-end of critical care. Crit Care. 2010;14:157.
   PubMed Web of Science ®Google Scholar
• Vochteloo AJ, Moerman S, van der Burg BL, et al. Delirium risk screening and haloperidol prophylaxis program in hip fracture patients is a helpful tool in identifying high-risk patients, but does not reduce the incidence of delirium. BMC Geriatr. 2011;11:39.
   PubMed Web of Science ®Google Scholar
• van den Boogaard M, Schoonhoven L, van Achterberg T, et al. Haloperidol prophylaxis in critically ill patients with a high risk for delirium. Crit Care. 2013;17:R9.
   Google Scholar
• Fukata S, Kawabata Y, Fujisiro K, et al. Haloperidol prophylaxis does not prevent postoperative delirium in elderly patients: a randomized, open-label prospective trial. Surg Today. 2014;44:2305–2313.
   PubMed Web of Science ®Google Scholar
• 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;38:428–437.
   PubMed Web of Science ®Google Scholar
• Gilmore ML, Wolfe DJ. Antipsychotic prophylaxis in surgical patients modestly decreases delirium incidence – but not duration – in high-incidence samples: a meta-analysis. Gen Hosp Psychiatry. 2013;35:370–375.
   PubMed Web of Science ®Google Scholar
• Fok MC, Sepehry AA, Frisch L, et al. Do antipsychotics prevent postoperative delirium? A systematic review and meta-analysis. Int J Geriatr Psychiatry. 2015;30:333–344.
   PubMed Web of Science ®Google Scholar
• Gamberini M, Bolliger D, Lurati Buse GA, et al. Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery – a randomized controlled trial. Crit Care Med. 2009;37:1762–1768.
   PubMed Web of Science ®Google Scholar
• Marcantonio ER, Palihnich K, Appleton P, et al. Pilot randomized trial of donepezil hydrochloride for delirium after hip fracture. J Am Geriatr Soc. 2011;59:S282–288.
   PubMed Web of Science ®Google Scholar
• Al-Aama T, Brymer C, Gutmanis I, et al. Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial. Int J Geriatr Psychiatry. 2011;26:687–694.
   PubMed Web of Science ®Google Scholar
• Hatta K, Kishi Y, Wada K, et al. Preventive effects of ramelteon on delirium: a randomized placebo-controlled trial. J Am Med Assoc Psychiatry. 2014;71:397–403.
   Google Scholar
• Shehabi Y, Grant P, Wolfenden H, et al. Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study). Anesthesiology. 2009;111:1075–1084.
   PubMed Web of Science ®Google Scholar
• Lonergan E, Luxenberg J, Areosa Sastre A, et al. Benzodiazepines for delirium. Cochrane Database Syst Rev. 2009;1:CD006379.
   Google Scholar
• Katznelson R, Djaiani GN, Borger MA, et al. Preoperative use of statins is associated with reduced early delirium rates after cardiac surgery. Anesthesiology. 2009;110:67–73.
   PubMed Web of Science ®Google Scholar
• Mariscalco G, Cottini M, Zanobini M, et al. Preoperative statin therapy is not associated with a decrease in the incidence of delirium after cardiac operations. Ann Thorac Surg. 2012;93:1439–1447.
   PubMed Web of Science ®Google Scholar
• 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;189:666–673.
   PubMed Web of Science ®Google Scholar
• Dieleman JM, Nierich AP, Rosseel PM, et al. Intraoperative high-dose dexamethasone for cardiac surgery: a randomized controlled trial. J Am Med Assoc. 2012;308:1761–1767.
   PubMed Web of Science ®Google Scholar
• Leung JM, Sands LP, Rico M, et al. Pilot clinical trial of gabapentin to decrease postoperative delirium in older patients. Neurology. 2006;67:1251–1253.
   PubMed Web of Science ®Google Scholar
• Maldonado JR, Wysong A, van der Starre PJA, et al. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics. 2009;50:206–217.
   PubMed Web of Science ®Google Scholar
• Dasta JF, Kane-Gill SL, Pencina M, et al. A cost-minimization analysis of dexmedetomidine compared with midazolam for long-term sedation in the intensive care unit. Crit Care Med. 2010;38:497–503.
   PubMed Web of Science ®Google Scholar
• Bellelli G, Morandi A, Zanetti E, et al. Recognition and management of delirium among doctors, nurses, physiotherapists, and psychologists: an Italian survey. Int Psychogeriatr. 2014;26:2093–2102.
   PubMed Web of Science ®Google Scholar
• Patel J, Baldwin J, Bunting P, et al. The effect of a multicomponent multidisciplinary bundle of interventions on sleep and delirium in medical and surgical intensive care patients. Anaesthesia. 2014;69:540–549.
   PubMed Web of Science ®Google Scholar
• 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;27:231–238.
   PubMed Web of Science ®Google Scholar
• Murray MJ, Cowen J, DeBlock H, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002;30:119–141.
   PubMed Web of Science ®Google Scholar
• Grover S, Kumar V, Chakrabarti S. Comparative efficacy study of haloperidol, olanzapine and risperidone in delirium. J Psychosom Res. 2011;71:277–281.
   PubMed Web of Science ®Google Scholar
• Mu JL, Lee A, Joynt GM. Pharmacologic agents for the prevention and treatment of delirium in patients undergoing cardiac surgery: systematic review and metaanalysis. Crit Care Med. 2015;43:194–204.
   PubMed Web of Science ®Google Scholar
• Devlin JW, Skrobik Y. Antipsychotics for the prevention and treatment of delirium in the intensive care unit: what is their role? Harv Rev Psychiatry. 2011;19:59–67.
   PubMed Web of Science ®Google Scholar
• Kusumi I, Boku S, Takahashi Y. Psychopharmacology of atypical antipsychotic drugs: from the receptor binding profile to neuroprotection and neurogenesis. Psychiatry Clin Neurosci. 2015;69:243–258.
   PubMed Web of Science ®Google Scholar
• Etezadi F, Najafi A, Yarandi KK, et al. ICU sedation with haloperidol-propofol infusion versus midazolam-propofol infusion after coronary artery bypass graft surgery: a prospective, double-blind randomized study. Ann Card Anaesth. 2012;15:185–189.
   PubMedGoogle Scholar
• Van Eijk MMJ, Roes KCB, Honing MLH, 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 randomised trial. Lancet. 2010;376:1829–1837.
   PubMed Web of Science ®Google Scholar
• Milbrandt EB, Kersten A, Kong L, et al. Haloperidol use is associated with lower hospital mortality in mechanically ventilated patients. Crit Care Med. 2005;33:226–229.
   PubMed Web of Science ®Google Scholar
• Moots R, Al-Saff Ar Z, Hutchinson D, et al. Old drug, new tricks: haloperidol inhibits secretion of proinflammatory cytokines. Ann Rheum Dis. 1999;58:585–587.
   PubMed Web of Science ®Google Scholar
• Seeger TF, Seymour PA, Schmidt AW, et al. Ziprasidone (CP-88,059): a new antipsychotic with combined dopamine and serotonin receptor antagonist activity. J Pharmacol Exp Ther. 1995;275:101–113.
   PubMed Web of Science ®Google Scholar
• Meyer-Massetti C, Cheng CM, Sharpe BA, et al. The FDA extended warning for intravenous haloperidol and torsades de pointes: how should institutions respond? J Hosp Med. 2010;5:E8–16.
   PubMedGoogle Scholar
• Ray WA, Chung CP, Murray KT, et al. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med. 2009;360:225–235.
   PubMed Web of Science ®Google Scholar
• Leung JYT, Barr AM, Procyshyn RM, et al. Cardiovascular side-effects of antipsychotic drugs: the role of the autonomic nervous system. Pharmacol Ther. 2012;135:113–122.
   PubMed Web of Science ®Google Scholar
• Adnet P, Lestavel P, Krivosic-Horber R. Neuroleptic malignant syndrome. Br J Anaesth. 2000;85:129–135.
   PubMed Web of Science ®Google Scholar
• Peluso MJ, Lewis SW, Barnes TRE, et al. Extrapyramidal motor side-effects of first- and second-generation antipsychotic drugs. Br J Psychiatry. 2012;200:387–392.
   PubMed Web of Science ®Google Scholar
• Pertovaara A. Antinociception induced by alpha-2-adrenoceptor agonists, with special emphasis on medetomidine studies. Progr Neurobiol. 1993;40:691–709.
   PubMed Web of Science ®Google Scholar
• Charney DS, Heninger R, Redmond DE Jr. Yohimbine induced anxiety and increased noradrenergic function in humans: effects of diazepam and clonidine. Life Sci. 1983;33:19–29.
   PubMed Web of Science ®Google Scholar
• Sved AF, Felsten G. Stimulation of the locus coeruleus decreases arterial pressure. Brain Res. 1987;414:119–132.
   PubMed Web of Science ®Google Scholar
• van Oostrom H, Stienen PJ, Doornenbal A, et al. The alpha(2)-adrenoceptor agonist dexmedetomidine suppresses memory formation only at doses attenuating the perception of sensory input. Eur J Pharmacol. 2010;629:58–62.
   PubMed Web of Science ®Google Scholar
• Mervaala E, Alhainen K, Helkala E-L, et al. Electrophysiological and neuropsychological effects of a central alpha2-antagonist atipamezole in healthy volunteers. Behav Brain Res. 1993;55:85–91.
   PubMed Web of Science ®Google Scholar
• Savola JM, Virtanen R. Central alpha 2-adrenoceptors are highly stereoselective for dexmedetomidine, the dextro enantiomer of medetomidine. Eur J Pharmacol. 1991;195:193–199.
   PubMed Web of Science ®Google Scholar
• Sirviö J, Harju M, Riekkinen P Jr, et al. Comparative effects of alpha-2 receptor agents and THA on the performance of adult and aged rats in the delayed non-matching to position task. Psychopharmacology. 1992;109:127–133.
   PubMed Web of Science ®Google Scholar
• Riekkinen P Jr, Lammintausta R, Ekonsalo T, et al. The effects of α2-adrenoceptor stimulation on neocortical EEG activity in control and 6-hydroxydopamine dorsal noradrenergic bundle-lesioned rats. Eur J Pharmacol. 1993;238:263–272.
   PubMed Web of Science ®Google Scholar
• Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia. 1999;54:146–165.
   PubMed Web of Science ®Google Scholar
• Smith H, Elliott J. Alpha(2) receptors and agonists in pain management. Curr Opin Anaesthesiol. 2001;14:513–518.
   PubMedGoogle Scholar
• Cividjian A, Toader E, Wesseling KH, et al. Effect of clonidine on cardiac baroreflex delay in humans and rats. Am J Physiol Regul Int Comp Physiol. 2011;300:R949–957.
   Google Scholar
• Kim MH, Hahn TH. The effect of clonidine pretreatment on the perioperative proinflammatory cytokines, cortisol, and ACTH responses in patients undergoing total abdominal hysterectomy. Anesth Analg. 2000;90:1441–1444.
   PubMed Web of Science ®Google Scholar
• Pichot C, Ghignone M, Quintin L. Dexmedetomidine and clonidine: from second- to first-line sedative agents in the critical care setting? J Intensive Care Med. 2012;27:219–237.
   PubMedGoogle Scholar
• Rubino AS, Onorati F, Caroleo S, et al. Impact of clonidine administration on delirium and related respiratory weaning after surgical correction of acute type-A aortic dissection: results of a pilot study. Interact CardiovascThorac Surg. 2010;10:58–62.
   PubMed Web of Science ®Google Scholar
• Devlin JW, Skrobik Y, Riker RR, et al. Impact of quetiapine on resolution of individual delirium symptoms in critically ill patients with delirium: a post-hoc analysis of a double-blind, randomized, placebo-controlled study. Crit Care. 2011;15:R215.
   PubMedGoogle Scholar
• Reade MC, O’Sullivan K, Bates S, et al. Dexmedetomidine vs. haloperidol in delirious, agitated, intubated patients: a randomised open-label trial. Crit Care. 2009;13:R75.
   PubMed Web of Science ®Google Scholar
• Bohner H, Schneider F. Delirium in older persons. N Engl J Med. 2006;354:2509–2511.
   PubMed Web of Science ®Google Scholar
• Paris A, Tonner PH. Dexmedetomidine in anaesthesia. Curr Opin Anaesthesiol. 2005;18:412–418.
   PubMed Web of Science ®Google Scholar
• Giovannoni MP, Ghelardini C, Vergelli C, et al. Alpha2-agonists as analgesic agents. Med Res Rev. 2009;29:339–368.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Walker SM, Howard RF, Keay KA, et al. Developmental age influences the effect of epidural dexmedetomidine on inflammatory hyperalgesia in rat pups. Anesthesiology. 2005;102:1226–1234.
   PubMed Web of Science ®Google Scholar
• Venn RM, Hell J, Grounds RM. Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care. Crit Care. 2000;4:302–308.
   PubMed Web of Science ®Google Scholar
• Wijeysundera DN, Bender JS, Beattie WS. Alpha-2 adrenergic agonists for the prevention of cardiac complications among patients undergoing surgery. Cochrane Database Syst Rev. 2009;7:CD004126.
   Google Scholar
• Ickeringill M, Shehabi Y, Adamson H, et al. Dexmedetomidine infusion without loading dose in surgical patients requiring mechanical ventilation: haemodynamic effects and efficacy. Anaesth Intens Care. 2004;32:741–745.
   PubMed Web of Science ®Google Scholar
• Laudenbach V, Mantz J, Lagercrantz H, et al. Effects of α2-adrenoceptor agonists on perinatal excitotoxic brain injury: comparison of clonidine and dexmedetomidine. Anesthesiology. 2002;96:134–141.
   PubMed Web of Science ®Google Scholar
• Ma D, Hossain M, Rajakumaraswamy N, et al. Dexmedetomidine produces its neuroprotective effect via the α2A-adrenoceptor subtype. Eur J Pharmacol. 2004;502:87–97.
   PubMed Web of Science ®Google Scholar
• Cai Y, Xu H, Yan J, et al. Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury. Mol Med Rep. 2014;9:1542–1550.
   PubMed Web of Science ®Google Scholar
• Verkhratsky A, Rodríguez JJ, Parpura V. Neurotransmitters and integration in neuronal-astroglial networks. Neurochem Res. 2012;37:2326–2338.
   PubMed Web of Science ®Google Scholar
• Bu D-X, Griffin G, Lichtman AH. Mechanisms for the anti-inflammatory effects of statins. Curr Opin Lipidol. 2011;22:165–170.
   PubMed Web of Science ®Google Scholar
• Terblanche M, Almog Y, Rosenson RS, et al. Statins and sepsis: multiple modifications at multiple levels. Lancet Infect Dis. 2007;7:358–368.
   PubMed Web of Science ®Google Scholar
• Craig TR, Duffy MJ, Shyamsundar M, et al. A randomized clinical trial of hydroxymethylglutaryl-coenzyme a reductase inhibition for acute lung injury (the HARP Study). Am J Respir Crit Care Med. 2011;183:620–626.
   PubMed Web of Science ®Google Scholar
• Morandi A, Hughes CG, Girard TD, et al. Statins and brain dysfunction: a hypothesis to reduce the burden of cognitive impairment in patients who are critically ill. Chest. 2011;140:580–585.
   PubMed Web of Science ®Google Scholar
• Ifergan I, Wosik K, Cayrol R, et al. Statins reduce human blood-brain barrier permeability and restrict leukocyte migration: relevance to multiple sclerosis. Ann Neurol. 2006;60:45–55.
   PubMed Web of Science ®Google Scholar
• Sher Y, Miller AC, Lolak S, et al. Adjunctive valproic acid in management-refractory hyperactive delirium: a case series and rationale. J Neuropsychiatry Clin Neurosci. 2015;27:365–370.
   PubMed Web of Science ®Google Scholar
• Horiguchi J, Yamashita H, Yanai I, et al. Effectiveness of valproate on delirium and/or aggressive behavior in demented patients: a practical pilot study. Int J Psychiatry Clin Pract. 1998;2:35–39.
   PubMedGoogle Scholar
• Dellinger RP, Levy MM, Rhodes A, et al.; the Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580–637.
   PubMed Web of Science ®Google Scholar
• 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;42:369–377.
   PubMed Web of Science ®Google Scholar
• van den Boogaard M, Schoonhoven L, Evers AWM, et al. Delirium in critically ill patients: impact on long-term health-related quality of life and cognitive functioning. Crit Care Med. 2012;40:112–118.
   PubMed Web of Science ®Google Scholar
• Wilcox ME, Brummel NE, Archer K, et al. Cognitive dysfunction in ICU patients: risk factors, predictors, and rehabilitation interventions. Crit Care Med. 2013;41:S81–S98.
   PubMed Web of Science ®Google Scholar
• Morandi A, Hughes CG, Thompson JL, et al. Statins and delirium during critical illness: a multicenter, prospective cohort study. Crit Care Med. 2014;42:1899–1909.
   PubMed Web of Science ®Google Scholar