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Postoperative cerebral dysfunction in the elderly: Diagnosis and prophylaxis
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Postoperative cerebral dysfunction in the elderly: Diagnosis and prophylaxis D. Benhamou a,∗, A. Brouquet b a
Département d’Anesthésie-Réanimation, Groupe Hospitalier et faculté de Médecine Paris Sud, Hôpital Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre, France b Service de Chirurgie Digestive et Oncologique, Groupe Hospitalier et faculté de Médecine Paris Sud, Hôpital Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre, France
KEYWORDS Neuro-inflammation; Delirium; Cognitive disorders; Post-operative complications; Enhanced recovery
Summary Post-operative cerebral dysfunction includes delirium, usually occurring early and reversible, and post-operative cognitive disorders, usually occurring later and prolonged. This is a frequent complication in patients older than 75 years old. The two neurological pictures are often inter-related. The pathophysiology of both entities is similar and related to post-operative neuro-inflammation; therefore onset may occur independently of any surgical complication. Post-operative cerebral dysfunction is a serious organic complication. Reduction of inflammation represents the most logical preventive measure but currently there are no studies that show this to be effective. Prevention therefore means combining several minor measures, elements that fit well into programs of enhanced post-operative recovery after surgery. Diminished preoperative cognitive status being a major risk factor, pre-operative rehabilitation combining nutritional, physical and cognitive support can be helpful. © 2016 Published by Elsevier Masson SAS.
Introductory clinical case An 82 year old female was admitted to the postanesthesia care unit (PACU) after undergoing emergency surgery during the proceeding night for intestinal obstruction secondary to colonic cancer. Patient history included arterial hypertension, chronic atrial fibrillation and moderate renal insufficiency. Prior to surgery, she was physically active and autonomous. A few days before admission, she complained of abdominal pain and, the day before, vomiting. At admission, the diagnosis of mechanical bowel obstruction was made and a nasogastric tube was inserted. Crystalloids were given to compensate for vomiting and gastric aspiration losses, avoiding pre-operative hypovolemia. Left colectomy with a double barrel colostomy was performed 8 h after admission. Esophageal Doppler was used to monitor vascular filling; small doses of nor-epinephrine were administered to maintain mean systolic blood pressure at 75 mmHg. The patient was extubated at the end of the operation and sent to the PACU around 4 AM. Arterial blood lactate was 3.2 mmol/L upon leaving the operation room and therefore she was transferred
∗
Corresponding author. Tel.: +33 1 45 21 34 47; fax: +33 1 45 21 28 75. E-mail address: [email protected] (D. Benhamou).
http://dx.doi.org/10.1016/j.jviscsurg.2016.09.015 1878-7886/© 2016 Published by Elsevier Masson SAS.
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to intensive care for more prolonged surveillance, because of concern that organ failure, and particularly renal failure, might develop. Post-operatively volume restoration led to improvement of serum lactate within 12 h and progressive weaning from nor-epinephrine infusion. Renal function was satisfactory with urine flow of 1 ml/kg/h. Her abdomen was soft, she complained of no pain, and output from gastric suction was low. The patient was scheduled to be transferred back to the ward on post-operative day 2. However, she was apathetic and hypo-active. Her vigilance dropped from time to time, alternating with phases of agitation and anxiety treated with small fractionated doses of haloperidol. Postoperative delirium was the diagnosis: possible promoting factors found in workup included advanced age, use of opioids for pain control, and moderate renal failure. Two days later, her neurological condition improved without any short-term neuro-psychopathological sequelae.
What are post-operative delirium and cognitive disorders: how do they fit into the notion of post-operative cerebral dysfunction? Delirium is a neurological disorder that is characterized by the sudden onset of altered consciousness, reduced capacity to maintain one’s attention, and a disorganized thought process [1]. Disorientation, episodic memory disorders, delusions and/or hallucinations lead to an abnormal perception of the environment. Other cognitive disorders are possible, such as sleep-wake cycle or mood disorders. Even though cognitive disorders can be associated with postoperative delirium, delirium is above all characterized by impaired awareness [2]. Clinically the patient is most often hypoactive but with periods of agitation; the diagnosis is then easy. More rarely, the patient is just hypoactive and the medical or paramedical personnel may not realize this, considering that the patient is simply calm and does not require any specific care. Notwithstanding, the severity and prognosis of the hypoactive form of delirium are similar to the typical form. Consciousness fluctuates throughout the day and this variation has enormous diagnostic value. This fluctuation means that the immediate entourage may not realize what is happening in up to 70% of cases if an evaluation program is not set up with mental status assessments at regular intervals [3]. Delirium is the most frequent post-operative complication in the elderly, involving between 10 and 50% of patients undergoing non-cardiac surgery [1]. Diagnosis is clinical; however, several surveillance scores are available. Among these, the most classical is the CAM (Confusion Assessment Method) [4] and its variation for intensive care (CAM-ICU) [5]. While the CAM has been translated into several languages, there is not yet a validated French version although a research project on this topic is currently underway in Nimes [6]. Several aspects of delirium help to distinguish it from post-operative cognitive dysfunction (POCD) [7]. Unlike the late onset of POCD (weeks or sometimes months), delirium usually occurs during the initial post-operative period, after a free interval of only a few hours or days from the operation. The duration of delirium is generally short (1—3 days) whereas POCD can last for several months, sometimes even longer. POCD may become more or less permanent but most
follow-up studies do not extend beyond 6—12 months, making it difficult to determine whether this outcome really occurs [8,9]. While the rate of POCD can sometimes attain 50—60% during the first post-operative weeks, about 10% of elderly patients still have this disorder at 6 months post-operative [8]. It is therefore impossible to determine whether these disorders disappear progressively and slowly over several months or whether some patients continue to have some degree of cerebral dysfunction for several years, without complete recovery, occasionally, progressing to dementia [10]. Clinically speaking, delirium is above all a vigilance disorder associated with a loss of attention [2] while POCD is characterized by cerebral cortex function disorders (ideation). Therefore this is a cognitive deterioration temporally related to surgery. The clinical diagnosis is more difficult and relies on several investigations centered on patient attention, perception, verbal capacity, learning and capacity of synthesis. In fact, the analysis is slightly more complex because it must take into account the initial cognitive status, which varies from one individual to another and the fact that cognitive status spontaneously deteriorates with age. The main risk factors are age, the degree of invasiveness of surgery (degree of tissue aggression and inflammation) and several studies have also suggested a deleterious effect of anesthesia agents [1]. As mentioned before, cognitive dysfunction can be associated with delirium. The relationship between the two is not well established but several recent sources suggest that delirium is a risk factor for onset of POCD [11]. POCD can occur without initial delirium or conversely delirium can be present in the immediate post-operative period without POCD at a later date. Likewise, in the early post-operative period, delirium can occur alone or be associated with cognitive disorders, or even, evolve to a cognitive disorder the next day, just as a cognitive disorder can occur without delirium and evolve into delirium the next day [11]. A relationship between these two entities has been suggested because of the common pathophysiology (neuroinflammation) that we will deal with later. Saczynski et al. [9] found a strong link between the degree of pre-operative and post-operative confusion (CAM) and cognition impairment (MMSE, mini-mental state examination) (up until one year after cardiac surgery in a series of 225 patients). The rate of post-operative delirium was 46%. Patients with delirium were older, more often female, with a lower educational level, non-white, and with more co-morbidity (especially antecedent cerebral vascular events or transient ischemia) and lastly, a weaker pre-operative cognitive status. Patients who eventually developed POCD had a greater degree of cognitive alteration on post-operative day 2 and this difference persisted 6—12 months. It is possible that the initial concomitant association of cognitive dysfunction with delirium is a marker of subsequent onset of POCD.
Risk factors, mechanisms and clinical consequences of delirium and POCD The risk factors of these two clinical entities are quite close and are presented in Fig. 1 and Table 1. The principal mechanism behind these two neurological syndromes is neuro-inflammation [12,13]. When the surgical procedure is major and involves substantial tissular aggression, the resulting inflammatory response produces
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No difference between general anesthesia and locoregional anesthedia
Neurodegenerative effects of anesthtic agents well shown in the animal model Anesthesia ?
Pre-operative aggravating factors • age • pre-existing disease + • low educational level • cognitive dysfunction
POCD
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Post-operative aggravating factors • inflammatory response • post-operative pain • spleeping disorder • opioids
Figure 1.
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Effective operations • iminimally invasive surgery • morphine-sparing post-operating pain management • early discharge • pharmacologically assisted sleep • reduction of noise at night
Risk factors for post-operative cognitive disorders (POCD).
important quantities of pro-inflammatory molecules, cytokines, that overflow into the vascular system, resulting in ‘‘cytokinemia’’. These substances, necessary in the fight against the inflammation at the operative site, may also cause undesirable effects when they penetrate into organs that are not inflamed. This is what happens in the brain and when these plasmatic cytokines arrive in excess quantities in the brain after crossing the blood—brain barrier, they activate the microglia (macrophages of the brain). These, in turn, release other pro-inflammatory molecules causing neuronal damage that can lead to an apoptotic phenomenon responsible for the death of certain neurons and clinical cerebral dysfunction. The critical zone where neuro-inflammation seems to act predominantly is the hippocampus [12]. The short-term clinical manifestation is essentially delirium associated with a decrease in vigilance, whereas, later, cognitive disorders predominate. At least two mechanisms can explain the higher frequency of these disorders in the elderly, and are the very reasons why these effects are more pronounced in this sub-group compared to the younger population. The brain of the elderly is more permeable to cytokines, facilitating their penetration and access to neurons and to the microglia [13]. Indeed, experimental studies have shown that the microglia of the normal elderly person are already in a Table 1
Hospital-related factors • noise and monitoring • sleep deprivation • hospital stay
basal pro-inflammatory state, called ‘‘microglial priming’’, which can release excessive amounts of cytokines and contribute to prolongation of the neuro-inflammatory process [14]. Other pathological situations are also associated with the risk of delirium. In one observational study, Flink et al. [15] studied 106 patients without any pre-operative cognitive abnormality (MMSE ≥ 24) or psychiatric disorder who had undergone total knee replacement. Post-operative evaluation was performed by a nurse on post-operative days 2 and 3. While the overall rate of post-operative delirium was 27%, it was 53% among those patients who had an obstructive sleep apnea syndrome (OSAS). This increased incidence is not surprising since it is known that patients with OSAS already have a substantial basal inflammatory state [16] responsible for other complications such pro-thrombotic events due to hypercoagulability [17]. Cytokinemia can also involve other organs such as the lungs (cause of post-operative respiratory disorders), the kidney (leading to renal failure), or even the heart (hypercoagulability and myocardial ischemia). The intensity of cytokinemia is proportional to the magnitude of the operation. This multiple organ dysfunction (including the brain) can explain the severity of the clinical picture and explain why delirium can be associated with a substantial increased risk
Risk factors for post-operative delirium [1,7,12].
Age (>75 years) Pre-existing cognitive disorders Major disease (ASA class, type of surgical operation) Renal failure Vision (glasses) or auditive disturbances Alcoholism and alcoholic weaning
Restricted movements
Infection Electrolyte disorders Pre-operative opioids Transfusion and blood loss Blood pressure fluctuations Drugs Opioids Anti-cholinergics Benzodiazepins Bladder catheter
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of mortality, as shown in a recent meta-analysis (hazard ratio: 1.95; 95% confidence interval 1.51—2.52) [18], even in the absence of other, essentially surgical, complications. This reaction can be likened to an excessive and inappropriate reaction in response to local aggression [12]. A pro-inflammatory phenomena cascade can also be encountered in septic shock but there, the concentration of plasmatic cytokines is much higher, explaining multiple organ involvement and the higher mortality [12]. It is easy to understand that if a post-operative infectious complication occurs, this will lead to additional cytokine release and aggravate the cerebral dysfunction.
Can the onset of delirium be avoided or treated? Since the principal mechanisms are inflammation and operative aggression, this is where preventive measures should be directed. Laparoscopic surgery is associated with less plasmatic cytokine release [19] and therefore the risk of delirium should be lower. However, to date, only a few retrospective studies have evaluated this aspect and have not been able to show any clear relationship or beneficial effect of the laparoscopic approach on the incidence of delirium [20—22]. A phase III prospective randomized study (CELL study: Colectomy for cancer in the Elderly through Laparoscopy or Laparotomy [PHRC-K 2013]) will soon start in France to evaluate the value of the laparoscopic approach to reduce the risk of post-operative complications, including delirium after surgery for colonic cancer in patients older than 75. Other strategies could also be effective to reduce the rate of delirium although clinical effectiveness remains to be shown. Pre-operative carbohydrate loading could lead to increased peri-operative insulin, an enzyme well known for its anti-inflammatory properties that could limit the post-operative release of cytokines [23]. However, this effect does not seem to correspond to any clinical benefit [24]. The favorable effect of laparoscopy or carbohydrate loading on cytokinemia, even in the absence of demonstrable clinical effects, suggests that a single action might not be effective and underscores the value of complementary combined programs that could provide a sufficient preventive effect. An enhanced recovery program after surgery seems to be an efficient means to decrease the risk of delirium. A recent preliminary study on 247 elderly patients undergoing colonic surgery with a post-operative enhanced recovery program and short hospital stay (median 3 days) was associated with a 2.8% post-operative delirium rate [25]. Although this rate cannot be compared to that observed when patients undergo traditional operation and hospitalization schemes, the rate seems quite low relative to those usually reported for traditional care. Likewise, Krenk et al. [26] studied a series of patients (mean age 69) undergoing hip or knee replacements without pre-operative cognitive disorders (MMSE > 23). Hospital stay was organized according to ‘‘fast track’’ principles, including pre-operative information to the patient, loco-regional anesthesia (90% of cases), early physical therapy and multimodal post-operative analgesia. Mean hospital stay was three days. No patients were diagnosed with post-operative delirium as assessed by the experienced and cognizant nursing staff during the first 12 post-operative days. Although it would not be possible to say with certainty which of the elements of the enhanced
recovery program is most effective against the onset of postoperative delirium, it is most likely that there are several combined factors that intervene to obtain the ideal clinical effect. All these different actions are included in post-operative recovery programs, but some recent experimental data suggest that it is possible to prepare the brain mentally before the operation, so-called prehabilitation. This idea has been suggested by several clinical studies that have shown that increased physical and cognitive activity slows down the degradation of cognitive status induced by aging [27]. Experimental studies have shown that physical exercise is associated with reduced inflammation of the microglia [28]. In a very recent study, elderly rats submitted to physical and mental training before an abdominal surgical procedure had less loss of cognitive function than rats that did not have this preparation [29]. The microglia of the hippocampus in the elderly and in trained animals produce fewer cytokines than the controls. Human studies are now necessary to determine if these experimental data are applicable to man. Obviously, this prehabilitation strategy is only applicable to elective surgery. In emergency surgery, however, some actions are possible. Notably it is important to shorten the post-operative period of care in order to retard the onset of local inflammation secondary to tissue trauma. This argues, again, in favor of enhanced recovery programs in emergency surgery. This notion is also included in the concept of acute care surgery that aims to reduce the delay between the emergency insult and surgical management [30]. Programs composed of several prevention factors for delirium have been shown to be effective after femoral neck fractures [31]. Some additional non-pharmacological measures are useful in the prevention of post-operative cerebral dysfunction. Showing oneself interested and talking to patients, promoting exchanges between the players of the caretaker team, limiting sleep deprivation, giving glasses and hearing devices back to the patients as soon as possible, placing a big visible clock in patients’ rooms so that they can keep in contact with the world outside the hospital and maintain their cognitive capacities. Aside from non-pharmacological strategies, several drugs have been tested with the goal of reducing the inflammatory state. In one study Dieleman et al. [32] tested the hypothesis that administration of dexamethasone (1 mg/kg) could reduce the rate of post-operative morbidity and mortality after heart surgery. However, these authors were unable to show any reduction in severity, even at high doses (evaluated by a composite endpoint which included death, onset of myocardial infraction, renal failure, pneumonia or cerebrovascular event). Conversely, patients receiving steroids had significantly higher glycemia values. In the end, the rate of cognitive dysfunction was not altered by steroid therapy [33]. Risperidone (Risperdal® ) seems to be a promising drug. This molecule is a 5 HT2 serotoninergic and D2 dopaminergic antagonist that possesses little undesirable effects on histaminergic and alphadrenergic receptors. Hakim et al. [34] compared the effects of risperidone (0.5 mg/12 h) to those of placebo in 101 cardiac surgery patients who did not have any pre-operative cognitive (MMSE > 24) or psychic disorder. The post-operative delirium rate in the risperidone group (13.7%) was statistically significantly lower than in the placebo group (34%). The rate of extra-pyramidal manifestations was not found to be statistically significantly increased in the risperidone group (3.9% vs. 2% (placebo)). On the other
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Post-operative cerebral dysfunction in the elderly hand, pharmacological treatment is not advised for patients with hypoactive delirium, and who do not present periods of agitation [35]. Several recent studies have suggested that intraoperative surveillance of the depth of anesthesia [36,37] or associated with cerebral oxygen supply monitoring [38] could play an effective role in the prevention of cerebral dysfunction. Effective morphine-sparing pain management and use of loco-regional analgesia also represent a recognized means to prevent delirium [39]. During pre-operative evaluation, simple tests can be used to detect cognitive dysfunction pre-operatively [40] which could potentiate the occurrence of post-operative cognitive disorders, as the association can favor progression to dementia.
Conclusion Post-operative cerebral dysfunction includes early delirium and cognitive disorders that usually appear later and tend to be prolonged. However, these two neurologic pictures are often intricated, a phenomenon logically supported by a common physiopathologic cause; i.e. post-operative neuro-inflammation. Post-operative cerebral dysfunction is a severe organic complication just as much as cardiac, pulmonary or renal complications. Reducing the inflammatory reaction is the most logical preventive measure but for the time being, there are no data that show any benefit for specific measures. Prevention therefore should involve combining several individual elements that integrate into post-operative enhanced recovery programs. Since preoperative cognitive status is a major risk factor, nutritional, physical and cognitive prehabilitation can be associated as an adjunctive measure.
Disclosure of interest The authors declare that they have no competing interest.
References [1] Inouye SK, Westendorp RGJ, Saczynski JS. Delirium in elderly people. Lancet 2014;383:911—22. [2] European Delirium Association; American Delirium Society. The DSM-5 criteria, level of arousal and delirium diagnosis: inclusiveness is safer. BMC Med 2014;12(October):141. [3] Inouye SK, Foreman MD, Mion LC, Katz KH, Cooney Jr LM. Nurses’ recognition of delirium and its symptoms: comparison of nurse and researcher ratings. Arch Intern Med 2001;161:2467—73. [4] Wong CL, Holroyd-Leduc J, Simel DL, Straus SE. Does this patient have delirium? Value of bedside instruments. JAMA 2010;304:779—86. [5] Ely EW, Inouye SK, Bernard GR, 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. [6] Validation of a French Version of the Confusion Assessment Method (CAM). https://clinicaltrials.gov/ct2/show/ NCT01775982. [7] Nadelson MR, Sanders RD, Avidan MS. Perioperative cognitive trajectory in adults. Br J Anaesth 2014;112(3):440—51. [8] Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet 1998;351:857—61.
5 [9] Saczynski JS, Marcantonio ER, Quach L, et al. Cognitive trajectories after postoperative delirium. N Engl J Med 2012;367:30—9. [10] Fong TG, Davis D, Growdon ME, Albuquerque A, Inouye SK. The interface between delirium and dementia in elderly adults. Lancet Neurol 2015;14(8):823—32. [11] Youngblom E, DePalma G, Sands L, Leung J. The temporal relationship between early postoperative delirium and postoperative cognitive dysfunction in older patients: a prospective cohort study. Can J Anesth 2014;61(12):1084—92. [12] Wan Y, Xu J, Ma D, Zeng Y, Cibelli M, Maze M. Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated inflammation in the hippocampus. Anesthesiology 2007;106:436—43. [13] Brouquet A, Cudennec T, Benoist S, et al. Impaired mobility, ASA status and administration of tramadol are risk factors for postoperative delirium in patients aged 75 years or more after major abdominal surgery. Ann Surg 2010;251(4):759—65. [14] Dilger RN, Johnson RW. Aging, microglial cell priming, and the discordant central inflammatory response to signals from the peripheral immune system. J Leukoc Biol 2008;84:932—9. [15] Flink BJ, Rivelli SK, Cox EA, et al. Obstructive sleep apnea and incidence of postoperative delirium after elective knee replacement in the nondemented elderly. Anesthesiology 2012;116(4):788—96. [16] Wang J, Yu W, Gao M, et al. Impact of obstructive sleep apnea syndrome on endothelial function, arterial stiffening, and serum inflammatory markers: an updated meta-analysis and metaregression of 18 studies. J Am Heart Assoc 2015;4(11). [17] Toraldo DM, De Benedetto M, Scoditti E, De Nuccio F. Obstructive sleep apnea syndrome: coagulation anomalies and treatment with continuous positive airway pressure. Sleep Breath 2015;(July). [18] Witlox J, Eurelings LS, de Jonghe JF, et al. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA 2010;304:443—51. [19] Watt DG, McSorley ST, Horgan PG, McMillan DC. Enhanced recovery after surgery: which components, if any, impact on the systemic inflammatory response following colorectal surgery? A systematic review. Medicine (Baltimore) 2015;94(36):e1286. [20] Tan CB, Ng J, Jeganathan R, et al. Cognitive changes after surgery in the elderly: does minimally invasive surgery influence the incidence of postoperative cognitive changes compared to open colon surgery? Dement Geriatr Cogn Disord 2015;39(3—4):125—31. [21] Shin YH, Kim DK, Jeong HJ. Impact of surgical approach on postoperative delirium in elderly patients undergoing gastrectomy: laparoscopic versus open approaches. Korean J Anesthesiol 2015;68(4):379—85. [22] Scholz AF, Oldroyd C, McCarthy K, Quinn TJ, Hewitt J. Systematic review and meta-analysis of risk factors for postoperative delirium among older patients undergoing gastrointestinal surgery. Br J Surg 2016;103(2):e21—8. [23] Viganò J, Cereda E, Caccialanza R, et al. Effects of preoperative oral carbohydrate supplementation on postoperative metabolic stress response of patients undergoing elective abdominal surgery. World J Surg 2012;36(8):1738—43. [24] Mathur S, Plank LD, McCall JL, et al. Randomized controlled trial of preoperative oral carbohydrate treatment in major abdominal surgery. Br J Surg 2010;97:485—94. [25] Kurbegovic S, Andersen J, Krenk L, Kehlet H. Delirium in fast-track colonic surgery. Langenbecks Arch Surg 2015;400(4):513—6. [26] Krenk L, Rasmussen LS, Hansen TB, Bogø S, Søballe K, Kehlet H. Delirium after fast-track hip and knee arthroplasty. Br J Anaesth 2012;108(4):607—11. [27] Blondell SJ, Hammersley-Mather R, Veerman JL. Does physical activity prevent cognitive decline and dementia? A systematic review and meta-analysis of longitudinal studies. BMC Public Health 2014;14:510.
Please cite this article in press as: Benhamou D, Brouquet A. Postoperative cerebral dysfunction in the elderly: Diagnosis and prophylaxis. Journal of Visceral Surgery (2016), http://dx.doi.org/10.1016/j.jviscsurg.2016.09.015
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[28] Kohman RA, Bhattacharya TK, Wojcik E, Rhodes JS. Exercise reduces activation of microglia isolated from hippocampus and brain of aged mice. J Neuroinflammation 2013;10:114. [29] Kawano T, Eguchi S, Iwata H, Tamura T, Kumagai N, Yokoyama M. Impact of preoperative environmental enrichment on prevention of development of cognitive impairment following abdominal surgery in a rat model. Anesthesiology 2015;123(1):160—70. [30] Lim DW, Ozegovic D, Khadaroo RG, Widder S. Impact of an acute care surgery model with a dedicated daytime operating room on outcomes and timeliness of care in patients with biliary tract disease. World J Surg 2013;37(10):2266—72. [31] Björkelund KB, Hommel A, Thorngren KG, Gustafson L, Larsson S, Lundberg D. Reducing delirium in elderly patients with hip fracture: a multi-factorial intervention study. Acta Anaesthesiol Scand 2010;54(6):678—88. [32] Dieleman JM, Nierich AP, Rosseel PM, et al. Dexamethasone for Cardiac Surgery (DECS) Study Group. Intraoperative high-dose dexamethasone for cardiac surgery: a randomized controlled trial. JAMA 2012;308(17):1761—7. [33] Ottens TH, Dieleman JM, Sauër AM, et al. DExamethasone for Cardiac Surgery (DECS) Study Group. Effects of dexamethasone on cognitive decline after cardiac surgery: a randomized clinical trial. Anesthesiology 2014;121(3):492—500. [34] Hakim SM, Othman AI, Naoum DO. Early treatment with risperidone for subsyndromal delirium after on-pump cardiac
[35]
[36]
[37]
[38]
[39]
[40]
surgery in the elderly: a randomized trial. Anesthesiology 2012;116(5):987—97. American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults. Postoperative delirium in older adults: best practice statement from the American Geriatrics Society. J Am Coll Surg 2015;220:136—48, e1. Chan MT, Cheng BC, Lee TM, Gin T. BIS-guided anesthesia decreases postoperative delirium and cognitive decline. J Neurosurg Anesthesiol 2013;25:33—42. Radtke FM, Franck M, Lendner J, Kruger S, Wernecke KD, Spies CD. Monitoring depth of anaesthesia in a randomized trial decreases the rate of postoperative delirium but not postoperative cognitive dysfunction. Br J Anaesth 2013;110(Suppl. 1):i98—105. Ballard C, Jones E, Gauge N, et al. Optimised anaesthesia to reduce post operative cognitive decline (POCD) in older patients undergoing elective surgery, a randomised controlled trial. PLoS ONE 2012;7:e37410. Vaurio LE, Sands LP, Wang Y, Mullen EA, Leung JM. Postoperative delirium: the importance of pain and pain management. Anesth Analg 2006;102:1267—73. Mézière A, Paillaud E, Belmin J, et al. Delirium in older people after proximal femoral fracture repair: role of a preoperative screening cognitive test. Ann Fr Anesth Reanim 2013;32(9):e91—6.
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Postoperative cerebral dysfunction in the elderly: Diagnosis and prophylaxis D. Benhamou a,∗, A. Brouquet b a
Département d’Anesthésie-Réanimation, Groupe Hospitalier et faculté de Médecine Paris Sud, Hôpital Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre, France b Service de Chirurgie Digestive et Oncologique, Groupe Hospitalier et faculté de Médecine Paris Sud, Hôpital Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre, France
KEYWORDS Neuro-inflammation; Delirium; Cognitive disorders; Post-operative complications; Enhanced recovery
Summary Post-operative cerebral dysfunction includes delirium, usually occurring early and reversible, and post-operative cognitive disorders, usually occurring later and prolonged. This is a frequent complication in patients older than 75 years old. The two neurological pictures are often inter-related. The pathophysiology of both entities is similar and related to post-operative neuro-inflammation; therefore onset may occur independently of any surgical complication. Post-operative cerebral dysfunction is a serious organic complication. Reduction of inflammation represents the most logical preventive measure but currently there are no studies that show this to be effective. Prevention therefore means combining several minor measures, elements that fit well into programs of enhanced post-operative recovery after surgery. Diminished preoperative cognitive status being a major risk factor, pre-operative rehabilitation combining nutritional, physical and cognitive support can be helpful. © 2016 Published by Elsevier Masson SAS.
Introductory clinical case An 82 year old female was admitted to the postanesthesia care unit (PACU) after undergoing emergency surgery during the proceeding night for intestinal obstruction secondary to colonic cancer. Patient history included arterial hypertension, chronic atrial fibrillation and moderate renal insufficiency. Prior to surgery, she was physically active and autonomous. A few days before admission, she complained of abdominal pain and, the day before, vomiting. At admission, the diagnosis of mechanical bowel obstruction was made and a nasogastric tube was inserted. Crystalloids were given to compensate for vomiting and gastric aspiration losses, avoiding pre-operative hypovolemia. Left colectomy with a double barrel colostomy was performed 8 h after admission. Esophageal Doppler was used to monitor vascular filling; small doses of nor-epinephrine were administered to maintain mean systolic blood pressure at 75 mmHg. The patient was extubated at the end of the operation and sent to the PACU around 4 AM. Arterial blood lactate was 3.2 mmol/L upon leaving the operation room and therefore she was transferred
∗
Corresponding author. Tel.: +33 1 45 21 34 47; fax: +33 1 45 21 28 75. E-mail address: [email protected] (D. Benhamou).
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to intensive care for more prolonged surveillance, because of concern that organ failure, and particularly renal failure, might develop. Post-operatively volume restoration led to improvement of serum lactate within 12 h and progressive weaning from nor-epinephrine infusion. Renal function was satisfactory with urine flow of 1 ml/kg/h. Her abdomen was soft, she complained of no pain, and output from gastric suction was low. The patient was scheduled to be transferred back to the ward on post-operative day 2. However, she was apathetic and hypo-active. Her vigilance dropped from time to time, alternating with phases of agitation and anxiety treated with small fractionated doses of haloperidol. Postoperative delirium was the diagnosis: possible promoting factors found in workup included advanced age, use of opioids for pain control, and moderate renal failure. Two days later, her neurological condition improved without any short-term neuro-psychopathological sequelae.
What are post-operative delirium and cognitive disorders: how do they fit into the notion of post-operative cerebral dysfunction? Delirium is a neurological disorder that is characterized by the sudden onset of altered consciousness, reduced capacity to maintain one’s attention, and a disorganized thought process [1]. Disorientation, episodic memory disorders, delusions and/or hallucinations lead to an abnormal perception of the environment. Other cognitive disorders are possible, such as sleep-wake cycle or mood disorders. Even though cognitive disorders can be associated with postoperative delirium, delirium is above all characterized by impaired awareness [2]. Clinically the patient is most often hypoactive but with periods of agitation; the diagnosis is then easy. More rarely, the patient is just hypoactive and the medical or paramedical personnel may not realize this, considering that the patient is simply calm and does not require any specific care. Notwithstanding, the severity and prognosis of the hypoactive form of delirium are similar to the typical form. Consciousness fluctuates throughout the day and this variation has enormous diagnostic value. This fluctuation means that the immediate entourage may not realize what is happening in up to 70% of cases if an evaluation program is not set up with mental status assessments at regular intervals [3]. Delirium is the most frequent post-operative complication in the elderly, involving between 10 and 50% of patients undergoing non-cardiac surgery [1]. Diagnosis is clinical; however, several surveillance scores are available. Among these, the most classical is the CAM (Confusion Assessment Method) [4] and its variation for intensive care (CAM-ICU) [5]. While the CAM has been translated into several languages, there is not yet a validated French version although a research project on this topic is currently underway in Nimes [6]. Several aspects of delirium help to distinguish it from post-operative cognitive dysfunction (POCD) [7]. Unlike the late onset of POCD (weeks or sometimes months), delirium usually occurs during the initial post-operative period, after a free interval of only a few hours or days from the operation. The duration of delirium is generally short (1—3 days) whereas POCD can last for several months, sometimes even longer. POCD may become more or less permanent but most
follow-up studies do not extend beyond 6—12 months, making it difficult to determine whether this outcome really occurs [8,9]. While the rate of POCD can sometimes attain 50—60% during the first post-operative weeks, about 10% of elderly patients still have this disorder at 6 months post-operative [8]. It is therefore impossible to determine whether these disorders disappear progressively and slowly over several months or whether some patients continue to have some degree of cerebral dysfunction for several years, without complete recovery, occasionally, progressing to dementia [10]. Clinically speaking, delirium is above all a vigilance disorder associated with a loss of attention [2] while POCD is characterized by cerebral cortex function disorders (ideation). Therefore this is a cognitive deterioration temporally related to surgery. The clinical diagnosis is more difficult and relies on several investigations centered on patient attention, perception, verbal capacity, learning and capacity of synthesis. In fact, the analysis is slightly more complex because it must take into account the initial cognitive status, which varies from one individual to another and the fact that cognitive status spontaneously deteriorates with age. The main risk factors are age, the degree of invasiveness of surgery (degree of tissue aggression and inflammation) and several studies have also suggested a deleterious effect of anesthesia agents [1]. As mentioned before, cognitive dysfunction can be associated with delirium. The relationship between the two is not well established but several recent sources suggest that delirium is a risk factor for onset of POCD [11]. POCD can occur without initial delirium or conversely delirium can be present in the immediate post-operative period without POCD at a later date. Likewise, in the early post-operative period, delirium can occur alone or be associated with cognitive disorders, or even, evolve to a cognitive disorder the next day, just as a cognitive disorder can occur without delirium and evolve into delirium the next day [11]. A relationship between these two entities has been suggested because of the common pathophysiology (neuroinflammation) that we will deal with later. Saczynski et al. [9] found a strong link between the degree of pre-operative and post-operative confusion (CAM) and cognition impairment (MMSE, mini-mental state examination) (up until one year after cardiac surgery in a series of 225 patients). The rate of post-operative delirium was 46%. Patients with delirium were older, more often female, with a lower educational level, non-white, and with more co-morbidity (especially antecedent cerebral vascular events or transient ischemia) and lastly, a weaker pre-operative cognitive status. Patients who eventually developed POCD had a greater degree of cognitive alteration on post-operative day 2 and this difference persisted 6—12 months. It is possible that the initial concomitant association of cognitive dysfunction with delirium is a marker of subsequent onset of POCD.
Risk factors, mechanisms and clinical consequences of delirium and POCD The risk factors of these two clinical entities are quite close and are presented in Fig. 1 and Table 1. The principal mechanism behind these two neurological syndromes is neuro-inflammation [12,13]. When the surgical procedure is major and involves substantial tissular aggression, the resulting inflammatory response produces
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No difference between general anesthesia and locoregional anesthedia
Neurodegenerative effects of anesthtic agents well shown in the animal model Anesthesia ?
Pre-operative aggravating factors • age • pre-existing disease + • low educational level • cognitive dysfunction
POCD
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Post-operative aggravating factors • inflammatory response • post-operative pain • spleeping disorder • opioids
Figure 1.
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Effective operations • iminimally invasive surgery • morphine-sparing post-operating pain management • early discharge • pharmacologically assisted sleep • reduction of noise at night
Risk factors for post-operative cognitive disorders (POCD).
important quantities of pro-inflammatory molecules, cytokines, that overflow into the vascular system, resulting in ‘‘cytokinemia’’. These substances, necessary in the fight against the inflammation at the operative site, may also cause undesirable effects when they penetrate into organs that are not inflamed. This is what happens in the brain and when these plasmatic cytokines arrive in excess quantities in the brain after crossing the blood—brain barrier, they activate the microglia (macrophages of the brain). These, in turn, release other pro-inflammatory molecules causing neuronal damage that can lead to an apoptotic phenomenon responsible for the death of certain neurons and clinical cerebral dysfunction. The critical zone where neuro-inflammation seems to act predominantly is the hippocampus [12]. The short-term clinical manifestation is essentially delirium associated with a decrease in vigilance, whereas, later, cognitive disorders predominate. At least two mechanisms can explain the higher frequency of these disorders in the elderly, and are the very reasons why these effects are more pronounced in this sub-group compared to the younger population. The brain of the elderly is more permeable to cytokines, facilitating their penetration and access to neurons and to the microglia [13]. Indeed, experimental studies have shown that the microglia of the normal elderly person are already in a Table 1
Hospital-related factors • noise and monitoring • sleep deprivation • hospital stay
basal pro-inflammatory state, called ‘‘microglial priming’’, which can release excessive amounts of cytokines and contribute to prolongation of the neuro-inflammatory process [14]. Other pathological situations are also associated with the risk of delirium. In one observational study, Flink et al. [15] studied 106 patients without any pre-operative cognitive abnormality (MMSE ≥ 24) or psychiatric disorder who had undergone total knee replacement. Post-operative evaluation was performed by a nurse on post-operative days 2 and 3. While the overall rate of post-operative delirium was 27%, it was 53% among those patients who had an obstructive sleep apnea syndrome (OSAS). This increased incidence is not surprising since it is known that patients with OSAS already have a substantial basal inflammatory state [16] responsible for other complications such pro-thrombotic events due to hypercoagulability [17]. Cytokinemia can also involve other organs such as the lungs (cause of post-operative respiratory disorders), the kidney (leading to renal failure), or even the heart (hypercoagulability and myocardial ischemia). The intensity of cytokinemia is proportional to the magnitude of the operation. This multiple organ dysfunction (including the brain) can explain the severity of the clinical picture and explain why delirium can be associated with a substantial increased risk
Risk factors for post-operative delirium [1,7,12].
Age (>75 years) Pre-existing cognitive disorders Major disease (ASA class, type of surgical operation) Renal failure Vision (glasses) or auditive disturbances Alcoholism and alcoholic weaning
Restricted movements
Infection Electrolyte disorders Pre-operative opioids Transfusion and blood loss Blood pressure fluctuations Drugs Opioids Anti-cholinergics Benzodiazepins Bladder catheter
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of mortality, as shown in a recent meta-analysis (hazard ratio: 1.95; 95% confidence interval 1.51—2.52) [18], even in the absence of other, essentially surgical, complications. This reaction can be likened to an excessive and inappropriate reaction in response to local aggression [12]. A pro-inflammatory phenomena cascade can also be encountered in septic shock but there, the concentration of plasmatic cytokines is much higher, explaining multiple organ involvement and the higher mortality [12]. It is easy to understand that if a post-operative infectious complication occurs, this will lead to additional cytokine release and aggravate the cerebral dysfunction.
Can the onset of delirium be avoided or treated? Since the principal mechanisms are inflammation and operative aggression, this is where preventive measures should be directed. Laparoscopic surgery is associated with less plasmatic cytokine release [19] and therefore the risk of delirium should be lower. However, to date, only a few retrospective studies have evaluated this aspect and have not been able to show any clear relationship or beneficial effect of the laparoscopic approach on the incidence of delirium [20—22]. A phase III prospective randomized study (CELL study: Colectomy for cancer in the Elderly through Laparoscopy or Laparotomy [PHRC-K 2013]) will soon start in France to evaluate the value of the laparoscopic approach to reduce the risk of post-operative complications, including delirium after surgery for colonic cancer in patients older than 75. Other strategies could also be effective to reduce the rate of delirium although clinical effectiveness remains to be shown. Pre-operative carbohydrate loading could lead to increased peri-operative insulin, an enzyme well known for its anti-inflammatory properties that could limit the post-operative release of cytokines [23]. However, this effect does not seem to correspond to any clinical benefit [24]. The favorable effect of laparoscopy or carbohydrate loading on cytokinemia, even in the absence of demonstrable clinical effects, suggests that a single action might not be effective and underscores the value of complementary combined programs that could provide a sufficient preventive effect. An enhanced recovery program after surgery seems to be an efficient means to decrease the risk of delirium. A recent preliminary study on 247 elderly patients undergoing colonic surgery with a post-operative enhanced recovery program and short hospital stay (median 3 days) was associated with a 2.8% post-operative delirium rate [25]. Although this rate cannot be compared to that observed when patients undergo traditional operation and hospitalization schemes, the rate seems quite low relative to those usually reported for traditional care. Likewise, Krenk et al. [26] studied a series of patients (mean age 69) undergoing hip or knee replacements without pre-operative cognitive disorders (MMSE > 23). Hospital stay was organized according to ‘‘fast track’’ principles, including pre-operative information to the patient, loco-regional anesthesia (90% of cases), early physical therapy and multimodal post-operative analgesia. Mean hospital stay was three days. No patients were diagnosed with post-operative delirium as assessed by the experienced and cognizant nursing staff during the first 12 post-operative days. Although it would not be possible to say with certainty which of the elements of the enhanced
recovery program is most effective against the onset of postoperative delirium, it is most likely that there are several combined factors that intervene to obtain the ideal clinical effect. All these different actions are included in post-operative recovery programs, but some recent experimental data suggest that it is possible to prepare the brain mentally before the operation, so-called prehabilitation. This idea has been suggested by several clinical studies that have shown that increased physical and cognitive activity slows down the degradation of cognitive status induced by aging [27]. Experimental studies have shown that physical exercise is associated with reduced inflammation of the microglia [28]. In a very recent study, elderly rats submitted to physical and mental training before an abdominal surgical procedure had less loss of cognitive function than rats that did not have this preparation [29]. The microglia of the hippocampus in the elderly and in trained animals produce fewer cytokines than the controls. Human studies are now necessary to determine if these experimental data are applicable to man. Obviously, this prehabilitation strategy is only applicable to elective surgery. In emergency surgery, however, some actions are possible. Notably it is important to shorten the post-operative period of care in order to retard the onset of local inflammation secondary to tissue trauma. This argues, again, in favor of enhanced recovery programs in emergency surgery. This notion is also included in the concept of acute care surgery that aims to reduce the delay between the emergency insult and surgical management [30]. Programs composed of several prevention factors for delirium have been shown to be effective after femoral neck fractures [31]. Some additional non-pharmacological measures are useful in the prevention of post-operative cerebral dysfunction. Showing oneself interested and talking to patients, promoting exchanges between the players of the caretaker team, limiting sleep deprivation, giving glasses and hearing devices back to the patients as soon as possible, placing a big visible clock in patients’ rooms so that they can keep in contact with the world outside the hospital and maintain their cognitive capacities. Aside from non-pharmacological strategies, several drugs have been tested with the goal of reducing the inflammatory state. In one study Dieleman et al. [32] tested the hypothesis that administration of dexamethasone (1 mg/kg) could reduce the rate of post-operative morbidity and mortality after heart surgery. However, these authors were unable to show any reduction in severity, even at high doses (evaluated by a composite endpoint which included death, onset of myocardial infraction, renal failure, pneumonia or cerebrovascular event). Conversely, patients receiving steroids had significantly higher glycemia values. In the end, the rate of cognitive dysfunction was not altered by steroid therapy [33]. Risperidone (Risperdal® ) seems to be a promising drug. This molecule is a 5 HT2 serotoninergic and D2 dopaminergic antagonist that possesses little undesirable effects on histaminergic and alphadrenergic receptors. Hakim et al. [34] compared the effects of risperidone (0.5 mg/12 h) to those of placebo in 101 cardiac surgery patients who did not have any pre-operative cognitive (MMSE > 24) or psychic disorder. The post-operative delirium rate in the risperidone group (13.7%) was statistically significantly lower than in the placebo group (34%). The rate of extra-pyramidal manifestations was not found to be statistically significantly increased in the risperidone group (3.9% vs. 2% (placebo)). On the other
Please cite this article in press as: Benhamou D, Brouquet A. Postoperative cerebral dysfunction in the elderly: Diagnosis and prophylaxis. Journal of Visceral Surgery (2016), http://dx.doi.org/10.1016/j.jviscsurg.2016.09.015
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Post-operative cerebral dysfunction in the elderly hand, pharmacological treatment is not advised for patients with hypoactive delirium, and who do not present periods of agitation [35]. Several recent studies have suggested that intraoperative surveillance of the depth of anesthesia [36,37] or associated with cerebral oxygen supply monitoring [38] could play an effective role in the prevention of cerebral dysfunction. Effective morphine-sparing pain management and use of loco-regional analgesia also represent a recognized means to prevent delirium [39]. During pre-operative evaluation, simple tests can be used to detect cognitive dysfunction pre-operatively [40] which could potentiate the occurrence of post-operative cognitive disorders, as the association can favor progression to dementia.
Conclusion Post-operative cerebral dysfunction includes early delirium and cognitive disorders that usually appear later and tend to be prolonged. However, these two neurologic pictures are often intricated, a phenomenon logically supported by a common physiopathologic cause; i.e. post-operative neuro-inflammation. Post-operative cerebral dysfunction is a severe organic complication just as much as cardiac, pulmonary or renal complications. Reducing the inflammatory reaction is the most logical preventive measure but for the time being, there are no data that show any benefit for specific measures. Prevention therefore should involve combining several individual elements that integrate into post-operative enhanced recovery programs. Since preoperative cognitive status is a major risk factor, nutritional, physical and cognitive prehabilitation can be associated as an adjunctive measure.
Disclosure of interest The authors declare that they have no competing interest.
References [1] Inouye SK, Westendorp RGJ, Saczynski JS. Delirium in elderly people. Lancet 2014;383:911—22. [2] European Delirium Association; American Delirium Society. The DSM-5 criteria, level of arousal and delirium diagnosis: inclusiveness is safer. BMC Med 2014;12(October):141. [3] Inouye SK, Foreman MD, Mion LC, Katz KH, Cooney Jr LM. Nurses’ recognition of delirium and its symptoms: comparison of nurse and researcher ratings. Arch Intern Med 2001;161:2467—73. [4] Wong CL, Holroyd-Leduc J, Simel DL, Straus SE. Does this patient have delirium? Value of bedside instruments. JAMA 2010;304:779—86. [5] Ely EW, Inouye SK, Bernard GR, 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. [6] Validation of a French Version of the Confusion Assessment Method (CAM). https://clinicaltrials.gov/ct2/show/ NCT01775982. [7] Nadelson MR, Sanders RD, Avidan MS. Perioperative cognitive trajectory in adults. Br J Anaesth 2014;112(3):440—51. [8] Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet 1998;351:857—61.
5 [9] Saczynski JS, Marcantonio ER, Quach L, et al. Cognitive trajectories after postoperative delirium. N Engl J Med 2012;367:30—9. [10] Fong TG, Davis D, Growdon ME, Albuquerque A, Inouye SK. The interface between delirium and dementia in elderly adults. Lancet Neurol 2015;14(8):823—32. [11] Youngblom E, DePalma G, Sands L, Leung J. The temporal relationship between early postoperative delirium and postoperative cognitive dysfunction in older patients: a prospective cohort study. Can J Anesth 2014;61(12):1084—92. [12] Wan Y, Xu J, Ma D, Zeng Y, Cibelli M, Maze M. Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated inflammation in the hippocampus. Anesthesiology 2007;106:436—43. [13] Brouquet A, Cudennec T, Benoist S, et al. Impaired mobility, ASA status and administration of tramadol are risk factors for postoperative delirium in patients aged 75 years or more after major abdominal surgery. Ann Surg 2010;251(4):759—65. [14] Dilger RN, Johnson RW. Aging, microglial cell priming, and the discordant central inflammatory response to signals from the peripheral immune system. J Leukoc Biol 2008;84:932—9. [15] Flink BJ, Rivelli SK, Cox EA, et al. Obstructive sleep apnea and incidence of postoperative delirium after elective knee replacement in the nondemented elderly. Anesthesiology 2012;116(4):788—96. [16] Wang J, Yu W, Gao M, et al. Impact of obstructive sleep apnea syndrome on endothelial function, arterial stiffening, and serum inflammatory markers: an updated meta-analysis and metaregression of 18 studies. J Am Heart Assoc 2015;4(11). [17] Toraldo DM, De Benedetto M, Scoditti E, De Nuccio F. Obstructive sleep apnea syndrome: coagulation anomalies and treatment with continuous positive airway pressure. Sleep Breath 2015;(July). [18] Witlox J, Eurelings LS, de Jonghe JF, et al. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA 2010;304:443—51. [19] Watt DG, McSorley ST, Horgan PG, McMillan DC. Enhanced recovery after surgery: which components, if any, impact on the systemic inflammatory response following colorectal surgery? A systematic review. Medicine (Baltimore) 2015;94(36):e1286. [20] Tan CB, Ng J, Jeganathan R, et al. Cognitive changes after surgery in the elderly: does minimally invasive surgery influence the incidence of postoperative cognitive changes compared to open colon surgery? Dement Geriatr Cogn Disord 2015;39(3—4):125—31. [21] Shin YH, Kim DK, Jeong HJ. Impact of surgical approach on postoperative delirium in elderly patients undergoing gastrectomy: laparoscopic versus open approaches. Korean J Anesthesiol 2015;68(4):379—85. [22] Scholz AF, Oldroyd C, McCarthy K, Quinn TJ, Hewitt J. Systematic review and meta-analysis of risk factors for postoperative delirium among older patients undergoing gastrointestinal surgery. Br J Surg 2016;103(2):e21—8. [23] Viganò J, Cereda E, Caccialanza R, et al. Effects of preoperative oral carbohydrate supplementation on postoperative metabolic stress response of patients undergoing elective abdominal surgery. World J Surg 2012;36(8):1738—43. [24] Mathur S, Plank LD, McCall JL, et al. Randomized controlled trial of preoperative oral carbohydrate treatment in major abdominal surgery. Br J Surg 2010;97:485—94. [25] Kurbegovic S, Andersen J, Krenk L, Kehlet H. Delirium in fast-track colonic surgery. Langenbecks Arch Surg 2015;400(4):513—6. [26] Krenk L, Rasmussen LS, Hansen TB, Bogø S, Søballe K, Kehlet H. Delirium after fast-track hip and knee arthroplasty. Br J Anaesth 2012;108(4):607—11. [27] Blondell SJ, Hammersley-Mather R, Veerman JL. Does physical activity prevent cognitive decline and dementia? A systematic review and meta-analysis of longitudinal studies. BMC Public Health 2014;14:510.
Please cite this article in press as: Benhamou D, Brouquet A. Postoperative cerebral dysfunction in the elderly: Diagnosis and prophylaxis. Journal of Visceral Surgery (2016), http://dx.doi.org/10.1016/j.jviscsurg.2016.09.015
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ARTICLE IN PRESS
6
D. Benhamou, A. Brouquet
[28] Kohman RA, Bhattacharya TK, Wojcik E, Rhodes JS. Exercise reduces activation of microglia isolated from hippocampus and brain of aged mice. J Neuroinflammation 2013;10:114. [29] Kawano T, Eguchi S, Iwata H, Tamura T, Kumagai N, Yokoyama M. Impact of preoperative environmental enrichment on prevention of development of cognitive impairment following abdominal surgery in a rat model. Anesthesiology 2015;123(1):160—70. [30] Lim DW, Ozegovic D, Khadaroo RG, Widder S. Impact of an acute care surgery model with a dedicated daytime operating room on outcomes and timeliness of care in patients with biliary tract disease. World J Surg 2013;37(10):2266—72. [31] Björkelund KB, Hommel A, Thorngren KG, Gustafson L, Larsson S, Lundberg D. Reducing delirium in elderly patients with hip fracture: a multi-factorial intervention study. Acta Anaesthesiol Scand 2010;54(6):678—88. [32] Dieleman JM, Nierich AP, Rosseel PM, et al. Dexamethasone for Cardiac Surgery (DECS) Study Group. Intraoperative high-dose dexamethasone for cardiac surgery: a randomized controlled trial. JAMA 2012;308(17):1761—7. [33] Ottens TH, Dieleman JM, Sauër AM, et al. DExamethasone for Cardiac Surgery (DECS) Study Group. Effects of dexamethasone on cognitive decline after cardiac surgery: a randomized clinical trial. Anesthesiology 2014;121(3):492—500. [34] Hakim SM, Othman AI, Naoum DO. Early treatment with risperidone for subsyndromal delirium after on-pump cardiac
[35]
[36]
[37]
[38]
[39]
[40]
surgery in the elderly: a randomized trial. Anesthesiology 2012;116(5):987—97. American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults. Postoperative delirium in older adults: best practice statement from the American Geriatrics Society. J Am Coll Surg 2015;220:136—48, e1. Chan MT, Cheng BC, Lee TM, Gin T. BIS-guided anesthesia decreases postoperative delirium and cognitive decline. J Neurosurg Anesthesiol 2013;25:33—42. Radtke FM, Franck M, Lendner J, Kruger S, Wernecke KD, Spies CD. Monitoring depth of anaesthesia in a randomized trial decreases the rate of postoperative delirium but not postoperative cognitive dysfunction. Br J Anaesth 2013;110(Suppl. 1):i98—105. Ballard C, Jones E, Gauge N, et al. Optimised anaesthesia to reduce post operative cognitive decline (POCD) in older patients undergoing elective surgery, a randomised controlled trial. PLoS ONE 2012;7:e37410. Vaurio LE, Sands LP, Wang Y, Mullen EA, Leung JM. Postoperative delirium: the importance of pain and pain management. Anesth Analg 2006;102:1267—73. Mézière A, Paillaud E, Belmin J, et al. Delirium in older people after proximal femoral fracture repair: role of a preoperative screening cognitive test. Ann Fr Anesth Reanim 2013;32(9):e91—6.
Please cite this article in press as: Benhamou D, Brouquet A. Postoperative cerebral dysfunction in the elderly: Diagnosis and prophylaxis. Journal of Visceral Surgery (2016), http://dx.doi.org/10.1016/j.jviscsurg.2016.09.015