| Article Access Statistics|
| Viewed||7454 |
| Printed||115 |
| Emailed||1 |
| PDF Downloaded||398 |
| Comments ||[Add] |
Click on image for details.
|Year : 2016
: 19 | Issue : 2 | Page
|Current approach to diagnosis and treatment of delirium after cardiac surgery
Adam S Evans1, Menachem M Weiner2, Rakesh C Arora3, Insung Chung2, Ranjit Deshpande4, Robin Varghese5, John Augoustides6, Harish Ramakrishna7
1 Department of Anesthesiology, Cleveland Clinic Florida, Weston, Florida, USA
2 Department of Anesthesiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
3 Department of Surgery, University of Mannitoba, Canada
4 Department of Anesthesiology, Yale University, New Haven, CT, USA
5 Department of Cardiothoracic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
6 Department of Anesthesiology, University of Pennsylvania, PA, USA
7 Department of Anesthesiology, Mayo Clinic, Jacksonville, Florida, United States
Click here for correspondence address and
|Date of Submission||26-Jan-2016|
|Date of Acceptance||09-Mar-2016|
|Date of Web Publication||1-Apr-2016|
| Abstract|| |
Delirium after cardiac surgery remains a common occurrence that results in significant short- and long-term morbidity and mortality. It continues to be underdiagnosed given its complex presentation and multifactorial etiology; however, its prevalence is increasing given the aging cardiac surgical population. This review highlights the perioperative risk factors, tools to assist in diagnosing delirium, and current pharmacological and nonpharmacological therapy options.
Keywords: Cardiac surgery; Delirium; Postoperative critical care
|How to cite this article:|
Evans AS, Weiner MM, Arora RC, Chung I, Deshpande R, Varghese R, Augoustides J, Ramakrishna H. Current approach to diagnosis and treatment of delirium after cardiac surgery. Ann Card Anaesth 2016;19:328-37
|How to cite this URL:|
Evans AS, Weiner MM, Arora RC, Chung I, Deshpande R, Varghese R, Augoustides J, Ramakrishna H. Current approach to diagnosis and treatment of delirium after cardiac surgery. Ann Card Anaesth [serial online] 2016 [cited 2019 Aug 19];19:328-37. Available from: http://www.annals.in/text.asp?2016/19/2/328/179634
| Introduction|| |
Delirium is a condition characterized by an acute cognitive decline, a fluctuating mental status, disturbance of consciousness, inattention, or disorganized thinking.  It is a well-recognized adverse prognostic marker in Intensive Care Unit (ICU) patients and is associated with increased morbidity, mortality, and the development of long-term neurocognitive deficits. , The incidence has been reported to occur between 16% and 73% ,,,, of patients after cardiac surgery; yet, cardiac surgeons, anesthesiologists, intensivists, and nurses may fail to recognize delirium in up to 84% of patients. , In this article, we review delirium after cardiac surgery including its perioperative risk factors, tools to assist in diagnosing delirium, and current pharmacological and nonpharmacological therapy options. With a focus on early detection and treatment of delirium, it is hoped that the ensuing complications can be prevented.
| What is Delirium?|| |
The current criteria for the diagnosis of delirium are based on the Diagnostic and Statistical Manual of Mental Disorders-4 th Edition (DSM-IV), Text Revision from the American Psychiatric Association.  Key diagnostic features of delirium include abnormalities of attention, particularly problems sustaining and shifting attention. In some instances, disturbances such as illusions, delusions, and hallucinations may be seen. Delirium can be categorized as either hyperactive, hypoactive, or mixed. In hyperactive delirium, patients are agitated and restless. Hypoactive delirium is characterized by lethargy, flat affect, and decreased responsiveness. Hyperactive delirium confers a favorable prognosis compared to hypoactive delirium and is often easier to identify. 
Subsyndromal delirium occurs when a patient exhibits one or more symptoms of delirium without fulfilling DSM criteria.  It is important to distinguish delirium from agitation, a state of extreme mental and physical activity associated with nonpurposeful movement.  Delirium is also separate from psychosis, an altered thinking process without a distinguishable physiologic abnormality. 
| Risk factors for delirium in the cardiac surgical intensive care unit|| |
The etiology of postoperative delirium is multifactorial resulting from a combination of patient risk factors at admission and perioperative insults.  [Table 1] summarizes preoperative, intraoperative, and postoperative risk factors.
Several studies have looked at severity of illness and incidence of postoperative delirium. Six of seven studies examined by Smith et al. showed a positive correlation after surgery.  Older age is also considered an independent risk factor for delirium  as the incidence of postoperative delirium is diminished in cases of congenital heart operations.  The presence of previous brain injury or abnormal neurological findings before surgery was also found to correlate with delirium after surgery. Alzheimer's disease, Parkinson's disease, prior stroke, and transient ischemic attacks (TIAs) may also increase the risk of delirium postoperatively.  Use of psychoactive drugs preoperatively has also been demonstrated to increase the incidence of delirium. 
Studies have examined whether length of cardiopulmonary bypass (CPB) contributes to delirium after cardiac surgery and yielded conflicting results. Smith et al. reviewed 12 studies pertaining to this question and found six studies where it contributed to postoperative delirium; five found no effect and one study found a negative correlation.  The duration of bypass is often dependent on the complexity of the procedure with longer bypass times required for more technically challenging procedures. Kimball and Blachy each independently found that as the complexity of the surgical procedure increased, the risk for postoperative delirium also increased. , It is believed that this may be due to the increased release of microemboli in complex procedures such as mitral and aortic valve replacement. For coronary artery bypass surgery (CABG), no linkage has been demonstrated between microemboli and delirium. 
Type of surgery is also known to influence the incidence of delirium. Valve surgery is associated with a 70% increase in delirium relative to CABG.  Delirium rates up to 90% have been reported in operations that required replacement of both the mitral and aortic valves. , While several studies have suggested that avoiding CPB altogether decreases the incidence of psychiatric and neurological complications postoperatively, , no difference has been found between on-pump and off-pump CABG. , For procedures requiring complex aortic reconstruction or deep hypothermic circulatory arrest, the incidence of delirium has been described in a range of 5-30%.  Delirium after heart transplantation has been reported to occur between 2% and 9% of cases.  There are no reported studies on the incidence of delirium following cases ventricular assist device placement.
Use of high-dose steroids to prevent the systematic inflammatory response during bypass has also been shown in two recent major trials not to have any impact on the incidence or duration of delirium after cardiac surgery.  The Intraoperative High-Dose Dexamethasone for Cardiac Surgery trial published in 2012 randomly assigned 4494 patients across 8 cardiac surgical centers to receive a single intraoperative dose of 1 mg/kg dexamethasone and found no statistically significant difference in the incidence of delirium.  The methylprednisolone in patients undergoing CPB trial (SIRS) was published in 2015. In eighty hospital or cardiac surgery centers in 18 countries, a dose of 250 mg of methylprednisolone administered at anesthetic induction and again at initiation of CPB compared to placebo did not yield any difference or reduction in the incidence of delirium. 
Neuromonitors commonly used during cardiac surgery such as cerebral oximetry and/or processed electroencephalogram (EEG) monitors (i.e., bispectral index [BIS]) have also proven helpful in predicting postoperative delirium. A total of four studies analyzing cerebral oximetry and its impact on postoperative delirium have been published.  However, only one used an objective assessment to monitor delirium in the postoperative period.  The authors reported a delirium rate of 27% in that study and found that patients with lower preoperative cerebral saturation or a cerebral saturation of <50% intraoperatively were associated with delirium. Another study demonstrated that intraoperative excursions of mean arterial blood pressure above the upper cerebral autoregulation limit during CPB are associated with risk for delirium.  With respect to the BIS monitor, a longer duration of intraoperative EEG burst suppression along with BIS value <20 has been shown to correlate with increased odds of developing delirium. ,
Temperature management during CPB has also been extensively researched in the past 20 years with widely disparate outcomes. , Unfortunately, the confounding variables of type of cardioplegia (i.e., dextrose-rich), glucose management, and postoperative hyperthermia management make these studies inconclusive when looking for causal relationships to postoperative cognitive events.
The hematocrit level during CPB has also been shown to affect postoperative morbidity. Karkouti et al. studied 9080 patients and observed a 10% increased stroke rate for each percentage decrease from a hematocrit of 21%. Other studies have shown that hematocrits under 22-23% on bypass were independent risk factors for neurologic injury. 
Arenson et al. recently completed a retrospective review of >1000 patients who underwent cardiac surgery at a single hospital in Manitoba. Postoperative risk factors associated with in-hospital delirium after cardiac surgery included postoperative stroke or TIA, mechanical ventilation longer than 24 h, the requirement for any transfusion in the postoperative period, and postoperative acute kidney injury. 
Postoperative medications can also contribute to delirium in the cardiac surgical ICU. Age-related changes in absorption, distribution, and renal excretion all affect drug metabolism and pharmacokinetics.  A recent prospective study that followed 418 cognitively intact elderly patients taking benzodiazepines admitted to the hospital found that these drugs accounted for 29% of the delirium that occurred. Patients were especially at risk if the benzodiazepines were withdrawn while the patient was in the hospital. 
Low cardiac output has also been examined as a potential cause of psychiatric abnormalities. It has been shown that patients who demonstrate a low cardiac output during the first several postoperative days experienced hallucinations. , Interestingly, these symptoms present when a rapid rise in cardiac output occurs. One study showed that the use of an intra-aortic balloon pump (IABP) correlated with an increased risk of delirium. This most likely was related to the increased use of neuroleptics and narcotics to sedate patients with an IABP. 
| Strategies to identify delirium|| |
Detection of delirium has substantially improved with the development of scoring methods designed specifically for ICU patients.  The American College of Critical Care Medicine guidelines  as well as the Society of Critical Care Medicine guidelines  recommend routine monitoring for delirium in adult ICU patients stating that early detection and treatment improve outcomes. Valid scoring methods especially designed for ICU patients allow delirium to be detected in both intubated and nonintubated patients even by ICU personnel that have no formal psychiatric training.  There are currently a number of assessment instruments for use in ICU patients [Table 2]. However, a recent survey found that only 33% of practitioners use a specific standardized tool for assessing delirium.  The use of a standardized method is recommended that the sensitivity of "clinical impression" for detection of delirium is only 29%. 
|Table 2: Delirium scoring methods validated in Intensive Care Unit patients |
Click here to view
Among the various scoring methods developed for use in ICU patients, the confusion assessment method for the ICU (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) were found to be the most valid when compared to the gold standard (DSM-IV criteria) [Table 3] and were also found in 2 meta-analyses to be the most sensitive and specific tools for detecting and monitoring delirium in adult ICU patients. , In addition, predictive validation of the presence of delirium using these tools was associated with clinical outcomes such as increased ICU and hospital length of stay  and mortality. 
|Table 3: Validation and reliability studies of confusion assessment method for the Intensive Care Unit and Intensive Care Delirium Screening Checklist |
Click here to view
The CAM-ICU delirium scoring instrument  was adapted from the original CAM  delirium scoring method to allow for testing of nonverbal mechanically ventilated patients. In 2 meta-analyses, the pooled sensitivity of CAM-ICU was found to be 75.5-80%, and specificity was 95.8-95.9% for detection of delirium. , No formal psychiatric training is necessary for its use. It uses nonverbal tasks such as picture recognition, vigilance tasks, simple commands, and simple yes/no logic questions to allow for assessment of the four main components of delirium.  It should be conducted once or twice daily, and patients are scored as either positive or negative for delirium. No assessment of severity of delirium is possible. In addition, it cannot be used in patients who are heavily sedated. Thus, before screening for delirium, a patient's level of consciousness and sedation should be assessed using a sedation scale such as the Richmond agitation sedation scale. 
As opposed to CAM-ICU, ICDSC is an assessment using data collected over time (e.g., a nursing shift) to capture the fluctuation of symptoms required for the diagnosis of delirium.  It consists of an 8-item screening checklist based on the DSM-IV criteria and other components found in delirium.  An ICDSC score of 4 points or higher exhibited a sensitivity of 99% and specificity of 64% for ICU delirium.  In 2 meta-analyses, the pooled sensitivity was found to be 74-80.1% and specificity was 74.6-81.9%. , ICDSC also can provide an indication of the severity of delirium based on the score.
| Management strategies for prevention of postoperative delirium|| |
In this section, we highlight the current data on pharmacologic and nonpharmacologic strategies to prevent delirium in cardiac surgical patients.
Conventional sedatives used in the care of patients after cardiac surgery include propofol, midazolam, and morphine. Benzodiazepines have been demonstrated to increase delirium in the cardiac surgical ICU  and should be used with caution. Opioids have not been shown to influence the incidence of delirium in the cardiac surgical population.  Dexmedetomidine, a centrally acting α-2-adrenergic agonist, has gained attention given its ability to provide adequate postoperative sedation and analgesia and demonstrated a lower incidence of delirium after cardiac surgery.  In 2009, Maldonado et al. randomized patients to receive dexmedetomidine (loading dose = 0.4 μg/kg, infusion rate = 0.2-0.7 μg/kg/h), propofol (25-50 μg/kg/min), or midazolam (0.5-2 mg/h) for postoperative sedation and found that the rate of delirium was significantly lower in patients receiving dexmedetomidine compared to propofol or to midazolam (3% delirium in dexmedetomidine group vs. 50% in propofol group and 50% in midazolam group). These results were corroborated in 2015 when Djaiani et al. published the results of a prospective, randomized trial in elderly patients (>60 years old) undergoing cardiac surgery demonstrating a shorter duration of delirium and longer onset till delirium occurrence in patients receiving dexmedetomidine compared to propofol for postoperative sedation.  Patients can be safely extubated while receiving dexmedetomidine allowing them to remain sedated and spontaneously breathing while receiving analgesia. The benefits of dexmedetomidine on reducing the incidence of delirium have also been upheld when compared to other commonly used analgesics and sedatives in the ICU such as morphine or remifentanil. , Ketamine, when administered at a dose of 0.5 mg/kg at the time of induction intraoperatively, has also been shown to decrease delirium related to its ability to serve as an analgesic adjunct to opioids. ,
Data for the use of antipsychotic drugs in mitigating postoperative delirium in cardiac surgical patients are limited. The most commonly used antipsychotic drugs for treating delirium include haloperidol, olanzapine, and risperidone. However, risperidone is the only agent that has been studied in the context of delirium after cardiac surgery.  Risperidone acts by antagonizing dopamine D2 and serotonin 5-HT2 receptors and has a half-life that can be up to 20-h long in poor metabolizers with few adverse side effects. , In a randomized, double-blinded, placebo-controlled study, a single dose of 1 mg sublingually upon regaining consciousness from cardiac surgery demonstrated a reduced incidence of delirium (11.1% vs. 31.7%). 
Delirium has also been postulated to occur from a deficiency in the neurotransmitter acetylcholine in the brain.  Use of rivastigmine, a cholinesterase inhibitor that is known to inhibit the breakdown of acetylcholine in the neural synapse, is evaluated in a recent randomized, double-blind, prospective interventional study. A 1.5 mg dose of rivastigmine administered the evening before the surgery and every 6 h for 6 days after the surgery was unable to demonstrate a significantly lower rate of delirium.  Statins are often recommended preoperatively in cardiac surgical patients given their beneficial effects on outcomes. However, the results of several studies have yielded conflicting results with their ability to reduce delirium and are thus not solely recommended for this purpose. ,,
Recently published clinical practice guidelines are now recommending that nonpharmacologic therapies be considered as "first line" interventions for both prevention and in the management of postoperative delirium.  Healthcare teams should implement strategies for the primary prevention of postoperative delirium that involve a multicomponent intervention using an interdisciplinary team. This has reached utmost importance with the inclusion of delirium in the evidence-based ABCDE bundle approach involving awake and breathing coordination (ABC) of mechanically ventilated patients, delirium monitoring, and early mobility, designed to improve functional outcomes in critically ill patients. 
In the cardiac surgery patients, utilization of the appropriate history and physical screening and initial diagnostic tests in the preoperative planning phase can prospectively identify patients at high risk for delirium. ,,,,, Identification of cognitive, substance and alcohol abuse, mood disorders, and frailty in addition to the previously discussed risk factors can be identified in elective patients.  This information can be then communicated to the intraoperative and postoperative healthcare teams to assist with targeted surveillance and subsequent management of the patient. Furthermore, this information can allow patients and their families to be better informed of potential delirium risk in the postoperative period. 
In the ICU and step-down ward, healthcare teams can implement nonpharmacologic interventions to assist in the prevention of delirium or potentially mitigate delirium if it does occur. Postoperative strategies include the promotion of reorientation (i.e. provide orientation on a regular basis), sleep protocols, early mobility, avoiding restraints, visual and hearing impairment aids, adequate nutrition and hydration, pain management, appropriate medication usage, and adequate oxygenation. ,,,,,
Use of sleep protocols
Patients in ICU environment frequently experience markedly disrupted sleep, placing them at increased risk for delirium. ,, The use of relatively simple nonpharmacologic sleep protocols is recommended to improve delirium in the ICU. , This includes sleep aids such as earplugs, sleep masks, stress balls (to reduce anxiety/agitation), modification of medications and procedures to allow an uninterrupted period of sleep at night, and implementation of noise reduction strategies. ,, Recently Kamdar et al. have described the effectiveness of a multi-faceted sleep-promoting intervention protocol that included the use of daily reminder checklists for the healthcare team.  This protocol includes day/night environmental intervention (e.g., minimizing caffeine, avoiding excessive napping, and dimming lights) and use of nonpharmacologic sleep aids (e.g., ear plugs, sleep mask, and soothing music). Using a step-wise implementation process, the authors demonstrated significant improvements in daily noise ratings and daily delirium/coma-free status (odds ratio: 1.64, P = 0.03). The authors have provided further description of their practical multistep process to facilitate other teams with the implementation of a similar process at their center. 
There is increasing consensus that the traditional paradigm of prolonged bed-rest in the ICU contributes to acquired neuromuscular weakness, prolonged hospital length of stay and is associated with increased rates of delirium. , In 2009, Schweickert et al.  reported a single-center, randomized control trial of 104 mechanically ventilated patients randomized to either early exercise and mobilization during periods of daily interruption of sedation or to daily interruption of sedation with current standard therapy as ordered by the primary care team. Early mobilization interventions were initiated with passive and active range of motion activity in the supine position and progressed to sit-to-stand transfers, pre-gait exercises and ultimately walking depending on the patient's stability. The authors found that the daily interruption of sedation combined with physical and occupational therapy, from the onset of their critical illness in ICU, resulted in an improved return to baseline functional status (59% vs. 35%, P = 0.02) and a significant reduction in ICU length of stay (2 vs. 4 median days, P = 0.02) and hospital delirium (28% vs. 41% of total hospital days, P = 0.01). The creation of an ICU "Mobility Team" using a protocol that facilitates early physical therapy has been demonstrated to be feasible, safe, and associated with reduced costs. 
The delirium toolbox
Rudolph et al. have recently described a quality improvement project that was conducted at VA Boston Healthcare System facilities.  The authors describe the creation of a "Delirium Toolbox" that includes items to correct sensory input (reading glasses, magnifying glasses, and hearing amplifier), stimulate cognition (jigsaw puzzles, crossword/word search activity, books, playing cards, modeling clay, and stress balls), and promote sleep (earplugs, eye masks, and headphones). These items were chosen because of their correlation with modifiable delirium risk factors. , Using a propensity-matched analysis of 566 patients, the authors demonstrated the use of their "toolbox" was associated with lower hospital lengths of stay, restraint use, and variable direct costs. This study, however, was performed in a nonsurgical acute care ward and hence further analysis was required to determine the effectiveness in a postcardiac surgery in-patient ward.
Evidence of effective nonpharmacologic interventions
Previous reports and recently published clinical practice guidelines have stated that adherence to a nonpharmacologic multicomponent intervention strategy resulted in a "dose-response" such as reduction of rates of delirium.  However, the strong recommendations contained in these guidelines are largely informed by moderate levels of evidence from both surgical and nonsurgical patient populations. Interestingly, Al-Qadheeb et al. recently reviewed 17 trials enrolling 2849 patients that evaluated either a pharmacologic intervention (n = 13), a multimodal intervention (n = 2) or a nonpharmacologic intervention (n = 2). The authors found that while there was an overall reduction in delirium duration in the intervention groups (−0.64 days, P = 0.01), they were unable to demonstrate a reduction in mortality. Therefore, while it is unlikely that nonpharmacologic intervention is harmful, there is still an urgent need for further study of effectiveness in postoperative delirium in the cardiac surgery patient. 
| Conclusion|| |
Delirium remains a frequent manifestation in the cardiac surgical population and contributes to increased morbidity, mortality, and resource utilization. While many studies have identified risk factors and strategies to identify delirium, the ideal treatment strategy has yet to be determined. Future studies are needed in the cardiac surgical population to define better the optimal approach to managing delirium after cardiac surgery.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Naik RD, Ely EW, Elavarasi A. Sedoanalgesia and delirium. In: Mehta Y, Sharma J, Guta MK, editors. Text Book of Critical Care. New Delhi: Jaypee; 2016. p. 116-30.
Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and consequences of ICU delirium. Intensive Care Med 2007;33:66-73.
Augoustides JG, Floyd TF, McGarvey ML, Ochroch EA, Pochettino A, Fulford S, et al.
Major clinical outcomes in adults undergoing thoracic aortic surgery requiring deep hypothermic circulatory arrest: Quantification of organ-based perioperative outcome and detection of opportunities for perioperative intervention. J Cardiothorac Vasc Anesth 2005;19:446-52.
Smith LW, Dimsdale JE. Postcardiotomy delirium: Conclusions after 25 years? Am J Psychiatry 1989;146:452-8.
Santos FS, Velasco IT, Fráguas R Jr. Risk factors for delirium in the elderly after coronary artery bypass graft surgery. Int Psychogeriatr 2004;16:175-93.
Prakanrattana U, Prapaitrakool S. Efficacy of risperidone for prevention of postoperative delirium in cardiac surgery. Anaesth Intensive Care 2007;35:714-9.
Hudetz JA, Patterson KM, Iqbal Z, Gandhi SD, Byrne AJ, Hudetz AG, et al.
Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2009;23:651-7.
Afonso A, Scurlock C, Reich D, Raikhelkar J, Hossain S, Bodian C, et al.
Predictive model for postoperative delirium in cardiac surgical patients. Semin Cardiothorac Vasc Anesth 2010;14:212-7.
Eden BM, Foreman MD. Problems associated with underrecognition of delirium in critical care: A case study. Heart Lung 1996;25:388-400.
Morency CR, Levkoff SE, Dick KL. Research considerations. Delirium in hospitalized elders. J Gerontol Nurs 1994;20:24-30.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR. Washington, DC: American Psychiatric Association; 2000.
Cole M, McCusker J, Dendukuri N, Han L. The prognostic significance of subsyndromal delirium in elderly medical inpatients. J Am Geriatr Soc 2003;51:754-60.
Cry J. Sedation of the critically ill patient. Crit Care Nurs Curr 1994;12:1-4.
Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA 1996;275:852-7.
van der Mast RC, van den Broek WW, Fekkes D, Pepplinkhuizen L, Habbema JD. Incidence of and preoperative predictors for delirium after cardiac surgery. J Psychosom Res 1999;46:479-83.
van der Mast RC, Roest FH. Delirium after cardiac surgery: A critical review. J Psychosom Res 1996;41:13-30.
Rossi MS. The octogenarian cardiac surgery patient. J Cardiovasc Nurs 1995;9:75-95.
Kimball CP. The experience of open heart surgery 3. Toward a definition and understanding of postcardiotomy delirium. Arch Gen Psychiatry 1972;27:57-63.
Blachy PH, Starr A. Post-cardiotomy delirum. Am J Psychiatry 1964;121:371-5.
Rudolph JL, Babikian VL, Treanor P, Pochay VE, Wigginton JB, Crittenden MD, et al.
Microemboli are not associated with delirium after coronary artery bypass graft surgery. Perfusion 2009;24:409-15.
Lin Y, Chen J, Wang Z. Meta-analysis of factors which influence delirium following cardiac surgery. J Card Surg 2012;27:481-92.
Nussmeier NA, Arlund C, Slogoff S. Neuropsychiatric complications after cardiopulmonary bypass: Cerebral protection by a barbiturate. Anesthesiology 1986;64:165-70.
Lee WH Jr., Brady MP, Rowe JM, Miller WC Jr. Effects of extracorporeal circulation upon behavior, personality, and brain function. II. Hemodynamic, metabolic, and psychometric correlations. Ann Surg 1971;173:1013-23.
Weiss SM. Psychological adjustment following open-heart surgery. J Nerv Ment Dis 1966;143:363-8.
Tse L, Schwarz SK, Bowering JB, Moore RL, Barr AM. Incidence of and risk factors for delirium after cardiac surgery at a quaternary care center: A retrospective cohort study. J Cardiothorac Vasc Anesth 2015;29:1472-9.
Miyazaki S, Yoshitani K, Miura N, Irie T, Inatomi Y, Ohnishi Y, et al.
Risk factors of stroke and delirium after off-pump coronary artery bypass surgery. Interact Cardiovasc Thorac Surg 2011;12:379-83.
Alejaldre A, Delgado-Mederos R, Santos MÁ, Martí-Fàbregas J. Cerebrovascular complications after heart transplantation. Curr Cardiol Rev 2010;6:214-7.
Sauër AM, Slooter AJ, Veldhuijzen DS, van Eijk MM, Devlin JW, van Dijk D. Intraoperative dexamethasone and delirium after cardiac surgery: A randomized clinical trial. Anesth Analg 2014;119:1046-52.
Dieleman JM, Nierich AP, Rosseel PM, van der Maaten JM, Hofland J, Diephuis JC, et al.
Intraoperative high-dose dexamethasone for cardiac surgery: A randomized controlled trial. JAMA 2012;308:1761-7.
Whitlock RP, Devereaux PJ, Teoh KH, Lamy A, Vincent J, Pogue J, et al.
Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): A randomised, double-blind, placebo-controlled trial. Lancet 2015;386:1243-53.
Zheng F, Sheinberg R, Yee MS, Ono M, Zheng Y, Hogue CW. Cerebral near-infrared spectroscopy monitoring and neurologic outcomes in adult cardiac surgery patients: A systematic review. Anesth Analg 2013;116:663-76.
Schoen J, Meyerrose J, Paarmann H, Heringlake M, Hueppe M, Berger KU. Preoperative regional cerebral oxygen saturation is a predictor of postoperative delirium in on-pump cardiac surgery patients: A prospective observational trial. Crit Care 2011;15:R218.
Hori D, Brown C, Ono M, Rappold T, Sieber F, Gottschalk A, et al.
Arterial pressure above the upper cerebral autoregulation limit during cardiopulmonary bypass is associated with postoperative delirium. Br J Anaesth 2014;113:1009-17.
Fritz BA, Kalarickal PL, Maybrier HR, Muench MR, Dearth D, Chen Y, et al.
Intraoperative electroencephalogram suppression predicts postoperative delirium. Anesth Analg 2016;122:234-42.
Soehle M, Dittmann A, Ellerkmann RK, Baumgarten G, Putensen C, Guenther U. Intraoperative burst suppression is associated with postoperative delirium following cardiac surgery: A prospective, observational study. BMC Anesthesiol 2015;15:61.
Fakin R, Zimpfer D, Sodeck GH, Rajek A, Mora B, Dumfarth J, et al.
Influence of temperature management on neurocognitive function in biological aortic valve replacement. A prospective randomized trial. J Cardiovasc Surg (Torino) 2012;53:107-12.
Grimm M, Czerny M, Baumer H, Kilo J, Madl C, Kramer L, et al.
Normothermic cardiopulmonary bypass is beneficial for cognitive brain function after coronary artery bypass grafting - A prospective randomized trial. Eur J Cardiothorac Surg 2000;18:270-5.
Karkouti K, Djaiani G, Borger MA, Beattie WS, Fedorko L, Wijeysundera D, et al.
Low hematocrit during cardiopulmonary bypass is associated with increased risk of perioperative stroke in cardiac surgery. Ann Thorac Surg 2005;80:1381-7.
Arenson BG, MacDonald LA, Grocott HP, Hiebert BM, Arora RC. Effect of intensive care unit environment on in-hospital delirium after cardiac surgery. J Thorac Cardiovasc Surg 2013;146:172-8.
Summers WK. Psychiatric sequelae to cardiotomy. J Cardiovasc Surg (Torino) 1979;20:471-6.
Koolhoven I, Tjon-A-Tsien MR, van der Mast RC. Early diagnosis of delirium after cardiac surgery. Am J Psychiatry 1996;182:448-51.
Sanders KM, Cassem EH. Psychiatric complication in the critically ill cardiac patient. Psychiatr Crit Care 1993;20:180-7.
Devlin JW, Fong JJ, Schumaker G, O'Connor H, Ruthazer R, Garpestad E. Use of a validated delirium assessment tool improves the ability of physicians to identify delirium in medical intensive care unit patients. Crit Care Med 2007;35:2721-4.
Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, 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.
Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, et al.
Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 2002;30:119-41.
Spronk PE, Riekerk B, Hofhuis J, Rommes JH. Occurrence of delirium is severely underestimated in the ICU during daily care. Intensive Care Med 2009;35:1276-80.
Patel RP, Gambrell M, Speroff T, Scott TA, Pun BT, Okahashi J, et al.
Delirium and sedation in the intensive care unit: Survey of behaviors and attitudes of 1384 healthcare professionals. Crit Care Med 2009;37:825-32.
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;37:1881-5.
Ely EW, Margolin R, Francis J, May L, Truman B, Dittus R, et al.
Evaluation of delirium in critically ill patients: Validation of the confusion assessment method for the intensive care unit (CAM-ICU). Crit Care Med 2001;29:1370-9.
Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, et al.
Delirium in mechanically ventilated patients: Validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001;286:2703-10.
Lin SM, Liu CY, Wang CH, Lin HC, Huang CD, Huang PY, et al.
The impact of delirium on the survival of mechanically ventilated patients. Crit Care Med 2004;32:2254-9.
McNicoll L, Pisani MA, Ely EW, Gifford D, Inouye SK. Detection of delirium in the intensive care unit: Comparison of confusion assessment method for the intensive care unit with confusion assessment method ratings. J Am Geriatr Soc 2005;53:495-500.
Pun BT, Gordon SM, Peterson JF, Shintani AK, Jackson JC, Foss J, 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;33:1199-205.
van Eijk MM, van den Boogaard M, van Marum RJ, Benner P, Eikelenboom P, Honing ML, et al.
Routine use of the confusion assessment method for the intensive care unit: A multicenter study. Am J Respir Crit Care Med 2011;184:340-4.
Luetz A, Heymann A, Radtke FM, Chenitir C, Neuhaus U, Nachtigall I, et al.
Different assessment tools for intensive care unit delirium: Which score to use? Crit Care Med 2010;38:409-18.
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;27:859-64.
George C, Nair JS, Ebenezer JA, Gangadharan A, Christudas A, Gnanaseelan LK, et al.
Validation of the intensive care delirium screening checklist in nonintubated intensive care unit patients in a resource-poor medical intensive care setting in South India. J Crit Care 2011;26:138-43.
Neto AS, Nassar AP Jr., Cardoso SO, Manetta JA, Pereira VG, Espósito DC, et al.
Delirium screening in critically ill patients: A systematic review and meta-analysis. Crit Care Med 2012;40:1946-51.
Gusmao-Flores D, Salluh JI, Chalhub RÁ, 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:R115.
Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T, et al.
The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med 2001;27:1892-900.
Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr., et al.
Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291:1753-62.
Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: The confusion assessment method. A new method for detection of delirium. Ann Intern Med 1990;113:941-8.
Bruno JJ, Warren ML. Intensive care unit delirium. Crit Care Nurs Clin North Am 2010;22:161-78.
Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, et al.
The Richmond agitation-sedation scale: Validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002;166:1338-44.
Plaschke K, von Haken R, Scholz M, Engelhardt R, Brobeil A, Martin E, et al.
Comparison of the confusion assessment method for the intensive care unit (CAM-ICU) with the intensive care delirium screening checklist (ICDSC) for delirium in critical care patients gives high agreement rate(s). Intensive Care Med 2008;34:431-6.
McPherson JA, Wagner CE, Boehm LM, Hall JD, Johnson DC, Miller LR, et al.
Delirium in the cardiovascular ICU: Exploring modifiable risk factors. Crit Care Med 2013;41:405-13.
Tse L, Schwarz SK, Bowering JB, Moore RL, Burns KD, Richford CM, et al.
Pharmacological risk factors for delirium after cardiac surgery: A review. Curr Neuropharmacol 2012;10:181-96.
Maldonado JR, Wysong A, van der Starre PJ, Block T, Miller C, Reitz BA. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics 2009;50:206-17.
Djaiani G, Silverton N, Fedorko L, Carroll J, Styra R, Rao V, et al.
Dexmedetomidine versus propofol sedation reduces delirium after cardiac surgery: A randomized controlled trial. Anesthesiology 2016;124:362-8.
Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M, 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;111:1075-84.
Park JB, Bang SH, Chee HK, Kim JS, Lee SA, Shin JK. Efficacy and safety of dexmedetomidine for postoperative delirium in adult cardiac surgery on cardiopulmonary bypass. Korean J Thorac Cardiovasc Surg 2014;47:249-54.
Lahtinen P, Kokki H, Hakala T, Hynynen M. S(+)-ketamine as an analgesic adjunct reduces opioid consumption after cardiac surgery. Anesth Analg 2004;99:1295-301.
Huang ML, Van Peer A, Woestenborghs R, De Coster R, Heykants J, Jansen AA, et al.
Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy subjects. Clin Pharmacol Ther 1993;54:257-68.
Gamberini M, Bolliger D, Lurati Buse GA, Burkhart CS, Grapow M, Gagneux A, et al.
Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery - A randomized controlled trial. Crit Care Med 2009;37:1762-8.
Kulik A, Ruel M. Statins and coronary artery bypass graft surgery: Preoperative and postoperative efficacy and safety. Expert Opin Drug Saf 2009;8:559-71.
Mariscalco G, Cottini M, Zanobini M, Salis S, Dominici C, Banach M, et al.
Preoperative statin therapy is not associated with a decrease in the incidence of delirium after cardiac operations. Ann Thorac Surg 2012;93:1439-47.
Katznelson R, Djaiani GN, Borger MA, Friedman Z, Abbey SE, Fedorko L, et al.
Preoperative use of statins is associated with reduced early delirium rates after cardiac surgery. Anesthesiology 2009;110:67-73.
American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults. American Geriatrics Society abstracted clinical practice guideline for postoperative delirium in older adults. J Am Geriatr Soc 2015;63:142-50.
Morandi A, Brummel NE, Ely EW. Sedation, delirium and mechanical ventilation: The 'ABCDE' approach. Curr Opin Crit Care 2011;17:43-9.
Rudolph JL, Jones RN, Levkoff SE, Rockett C, Inouye SK, Sellke FW, et al.
Derivation and validation of a preoperative prediction rule for delirium after cardiac surgery. Circulation 2009;119:229-36.
Burkhart CS, Dell-Kuster S, Gamberini M, Moeckli A, Grapow M, Filipovic M, et al.
Modifiable and nonmodifiable risk factors for postoperative delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2010;24:555-9.
Koster S, Hensens AG, Schuurmans MJ, van der Palen J. Prediction of delirium after cardiac surgery and the use of a risk checklist. Eur J Cardiovasc Nurs 2013;12:284-92.
Gottesman RF, Grega MA, Bailey MM, Pham LD, Zeger SL, Baumgartner WA, et al.
Delirium after coronary artery bypass graft surgery and late mortality. Ann Neurol 2010;67:338-44.
Guenther U, Theuerkauf N, Frommann I, Brimmers K, Malik R, Stori S, et al.
Predisposing and precipitating factors of delirium after cardiac surgery: A prospective observational cohort study. Ann Surg 2013;257:1160-7.
Beggs T, Sepehri A, Szwajcer A, Tangri N, Arora RC. Frailty and perioperative outcomes: A narrative review. Can J Anaesth 2015;62:143-57.
Inouye SK, Bogardus ST Jr., Charpentier PA, Leo-Summers L, Acampora D, Holford TR, et al.
A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med 1999;340:669-76.
Lord RK, Mayhew CR, Korupolu R, Mantheiy EC, Friedman MA, Palmer JB, et al.
ICU early physical rehabilitation programs: Financial modeling of cost savings. Crit Care Med 2013;41:717-24.
Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook CL, et al.
Early physical and occupational therapy in mechanically ventilated, critically ill patients: A randomised controlled trial. Lancet 2009;373:1874-82.
Kamdar BB, Niessen T, Colantuoni E, King LM, Neufeld KJ, Bienvenu OJ, et al.
Delirium transitions in the medical ICU: Exploring the role of sleep quality and other factors. Crit Care Med 2015;43:135-41.
Rudolph JL, Archambault E, Kelly B; VA Boston Delirium Task Force. A delirium risk modification program is associated with hospital outcomes. J Am Med Dir Assoc 2014;15:957.e7-11.
Inouye SK, Bogardus ST Jr., Williams CS, Leo-Summers L, Agostini JV. The role of adherence on the effectiveness of nonpharmacologic interventions: Evidence from the delirium prevention trial. Arch Intern Med 2003;163:958-64.
Hardin KA. Sleep in the ICU: Potential mechanisms and clinical implications. Chest 2009;136:284-94.
Kamdar BB, Needham DM, Collop NA. Sleep deprivation in critical illness: Its role in physical and psychological recovery. J Intensive Care Med 2012;27:97-111.
Xie H, Kang J, Mills GH. Clinical review: The impact of noise on patients' sleep and the effectiveness of noise reduction strategies in intensive care units. Crit Care 2009;13:208.
Kamdar BB, King LM, Collop NA, Sakamuri S, Colantuoni E, Neufeld KJ, et al.
The effect of a quality improvement intervention on perceived sleep quality and cognition in a medical ICU. Crit Care Med 2013;41:800-9.
Needham DM. Mobilizing patients in the intensive care unit: Improving neuromuscular weakness and physical function. JAMA 2008;300:1685-90.
Morris PE, Goad A, Thompson C, Taylor K, Harry B, Passmore L, et al.
Early intensive care unit mobility therapy in the treatment of acute respiratory failure. Crit Care Med 2008;36:2238-43.
Reston JT, Schoelles KM. In-facility delirium prevention programs as a patient safety strategy: A systematic review. Ann Intern Med 2013;158 (5 Pt 2):375-80.
Al-Qadheeb NS, Balk EM, Fraser GL, Skrobik Y, Riker RR, Kress JP, et al.
Randomized ICU trials do not demonstrate an association between interventions that reduce delirium duration and short-term mortality: A systematic review and meta-analysis. Crit Care Med 2014;42:1442-54.
Adam S Evans
Cleveland Clinic Florida, Cleveland Clinic Florida 2950 Weston Boulevard Weston, FL 33331
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3]