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Current Perspectives on Postoperative Cognitive Dysfunction in the Ageing Population.

Introduction

Postoperative cognitive dysfunction (POCD) is a prolonged impairment in cognitive function that lasts weeks to months following surgery (1). First documented in the late 1800s, it is still a poorly understood problem in the medical community (2). POCD is especially prevalent in the elderly (3, 4). As such, the fragility of cognition in the elderly is already carefully monitored to prevent the manifestation of delirium or the progression to dementia, both of which increase morbidity and are main contributors to major financial burden on our healthcare system (5-7). POCD has been associated with increased mortality, and it can develop as a result of delirium (8). It is therefore crucial to examine any factors that may contribute to the cognitive decline in preoperative patients. With a rapidly increasing need for surgical procedures and an increase in the number of elderly patients undergoing elective surgical procedures that necessitate the use of anaesthetic medications, the medical community is responsible for exploring the risk factors, strategies for prevention and treatment of POCD.

Epidemiology

The POCD incidence is estimated at 10%-54%. POCD occurs several weeks postoperatively and affects primarily the elderly (9). The ISPOCD1 study found an incidence of 25.8% one week and 9.9% three months postsurgery in patients >60 years who underwent major non-cardiac surgery (10). As the number of surgical procedures in the elderly population increases, so does the need to identify the POCD risk factors (11).

Preoperatively, some established POCD risk factors are similar to those of mild cognitive impairment (MCI), and they include diabetes, poor glycaemic control and low cognitive reserve (1214). Other MCI risk factors such as obesity, sleep fragmentation and APOE4 homozygosity have shown to have weaker risk associations with POCD (15-17). In addition, preoperative history of cognitive or functional impairment, major coronary bypass surgery, pulmonary disease, alcohol abuse, electrolyte abnormalities, psychoactive medication or preoperative delirium (POD) have all been shown to increase the POCD risk (18-20). Chief among these is an increased risk due to pre-existing MCI, which has a prevalence of 38%-56% in elderly patients. Intraoperatively, cerebral desaturation, a prolonged exposure and depth of anaesthesia have been associated with an increased POCD risk (21). Finally, postoperative patients are at higher risk of developing POCD if they experience POD, infection, respiratory complications, poorly controlled pain or low haematocrit.

The effect of the type of surgery has been debated in POCD. Some factors that implicate the type of surgery are the length of procedure, postoperative complications, stress response or hospitalisation length of stay (22). Previous studies have described a higher incidence of POCD in major cardiac surgeries, such as coronary artery bypass graft, even reporting an incidence of 30%-80% a few weeks post cardiac surgery and 10-%60% three to six months post non-cardiac surgery in the elderly (23). However, recently Evered et al. (24) denied the importance of the surgery type in POCD. Most literature emphasises the need for specific epidemiological research on POCD, and for that reason, a precise definition is required.

Clinical Presentation

The primary issue facing POCD is finalising a distinct definition. Until this task is complete, clinical identification of POCD will vary between medical professionals. Some general guidelines suggest considering POCD as form of mild cognitive impairment and looking for similar clinical signs to help with diagnosis. Using this concept, POCD can be considered a persistent cognitive dysfunction that gradually develops postoperatively after a period of at least 1 week (25). The ISPOCD1 study identifies POCD as the presence of postoperative deficits in at least one area of mental state, including concentration, attention, memory, executive function, visuospatial ability and psychomotor speed. To achieve a reliable diagnosis, appropriate pre- and postoperative cognitive testing must be performed. Several tests are available to assess the cognitive function and impairment such as the mini mental state exam, Montreal cognitive assessment, Cognistat exam and Postoperative Quality Recovery Scale, as well as several computerised examinations (26). At this point, clinical evidence that suggests a new cognitive decline in postoperative patients from a pre-established baseline can qualify as POCD at the treating physician's discretion.

Pathophysiology

Although the pathophysiology behind the development of POCD has been debated, causative mechanisms are thought to be the following: the mode of anaesthesia application, anaesthetic choice, hypoperfusion, hyperventilation and neuroinflammation (27). Multiple studies have proposed a possible correlation between the mode of anaesthesia and the subsequent likelihood of developing POCD (Table 1). Specifically, long-term outcomes in patients receiving general anaesthesia or regional anaesthesia have been compared. The study by Mason et al. (28) is based on the hypothesis that general anaesthesia affects gene transcription, receptor efficacy, synaptic vesicle cycling, intracellular calcium homeostasis and anticholinergic effects. However, results did not statistically prove that regional anaesthesia is less likely to cause POCD. Another study involving 483 elderly patients found that POCD was less likely in patients who received regional anaesthesia than in those who received general anaesthesia 1 week postoperatively but that it did not vary significantly 3 months following general or regional anaesthesia (29). While limiting the depth of anaesthesia has been shown to reduce the risk of POD, no such research has been successful with POCD.

Additional research has attempted to correlate the incidence of Alzheimer's disease and specific modes of anaesthesia. Inhaled anaesthetics have been demonstrated to increase the formation of B-amyloid plaques and neurofibrillary tangles in animal models and in vitro studies. Such pathologies are typically present in Alzheimer's disease (30, 31). However, a subsequent meta-analysis showed no correlation between previous exposure to inhaled anaesthetics and the development of Alzheimer's disease.

The incidence of POCD is not correlated with the use or avoidance of sedating agents such as propofol when a patient is receiving anaesthesia (Table 2). With this in mind, the use of dexmedetomidine instead of a propofol supplementary for a peripheral nerve block is significantly associated with a reduced incidence of POCD (32). Interestingly, patients who received dexmedetomidine in place of Propofol were found to have a significantly lower postoperative creatinine and a significantly higher postoperative GFR (33). Dexmedetomidine also yielded a significantly lower number of cases of postoperative hyperactive delirium and postoperative agitation.

Another hypothesis addressing the development of POCD involves intraoperative cerebrovascular autoregulation and hypoperfusion. In patients receiving general anaesthesia, the mean arterial pressure may stray outside the range in which cerebrovascular autoregulation can be maintained (Table 3). A study that involved patients undergoing surgery with a cardiopulmonary bypass found that the duration of the longest cerebrovascular autoregulation impairment was significantly associated with the occurrence of POCD (34). Currently, there is no consensus on an optimal mean arterial pressure during cardiopulmonary bypass. Using near-infrared spectroscopy to monitor cerebral oxygen saturation and the mean arterial pressure as a surrogate for cerebral blood flow, clinicians can monitor cerebral autoregulation in real time during surgery. Research has found a relationship between the mean arterial pressure falling below the lower limit of cerebral autoregulation and an increased incidence of major morbidity and operative mortality. Thus, the blood pressure management during cardiopulmonary bypass using physiologic end-points to monitor cerebral autoregulation may optimise organ perfusion and improve postoperative outcomes (35).

Cognitive dysfunction has been linked to hyperoxia caused by hyperventilation following surgical procedures involving cardiopulmonary bypass. High oxygen content has been shown to be toxic to many organ systems, including cardiovascular, nervous, respiratory and gastrointestinal. High levels of oxygen increase free-radical formation and oxidative stress. Such stress is particularly damaging to the brain, as neurons have a higher rate of oxygen consumption and lower antioxidant defences (36). In a randomised controlled trial, patients were divided into one group receiving supplemental oxygen at a Fi[O.sub.2] of 0.35 (normoxic) and another group receiving a Fi[O.sub.2] of 1.0 (hyperoxic). It is currently suggested that monitoring and maintaining normal levels of oxygen intraoperatively, and avoiding a hyperoxic state, will reduce the incidence and presentation of POCD (37). The role of hypertension and risk of POCD is also being investigated, as one study found that hypertension is not associated with the POCD development, while also admitting that many confounding variables have not been adjusted for (38).

Anaesthesia during surgery is thought to produce a neuroinflammatory state that leads to POCD. The role of inflammation leading to neuronal dysfunction has been assessed. Systemic inflammation from bacterial LPS produces both working memory deficits and acute brain injury by acting on hippocampal neurons, causing hyperexcitation and permanent loss of membrane potential (39). Specifically, preoperative elevations in Il-6 and Il-8 were associated with poorer cognitive function postoperatively (40). POCD patients also had an increased plasma TNF-a and a decreased IGF-1 when compared to healthy patients (41). Neuroinflammation and oxidative stress secondary to anaesthesia are also thought to be caused by interrupted plasticity of neurons and interference in glutamate signalling (Table 4). The need for neuroprotective agents is therefore justified. Although more research needs to be conducted before definitive results can be concluded, lidocaine, ketamine, Cox II inhibitors, minocycline, and dexmedetomidine currently show the most neuroprotective potential (42, 43). The use of remifentanil instead of fentanyl is correlated with lower levels of inflammation (specifically IL-6) on postoperative Day 7, but no correlation was found between the remifentanil use and a decreased incidence of POCD (44).

Differentiating postoperative delirium from postoperative cognitive dysfunction

Differentiating POCD from POD is an important step to guide future clinical research (Table 5). POD is a subset of delirium and is defined in DSM-5 as a disturbance in attention and awareness, an acute change from baseline, and a disturbance in cognition that cannot be explained by an existing cognitive or otherwise attributable disorder. Millions are spent annually to alleviate the burden of POD, and current studies focus on addressing the risk of stratification, geriatric consultation, multidisciplinary programmes, optimising depth of anaesthesia, opioid-sparing pain management and polypharmacy avoidance (45). POCD also poses a significant burden on healthcare worldwide, but statistical analysis is thus far most limited by the inability of many POCD patients to adhere to study guidelines (46).

Although POCD currently has no agreed-upon diagnostic criteria, it broadly includes a prolonged impairment in cognitive function after surgery with deficits in memory, intellectual ability and executive function. While POD may develop between 24 and 72 hours following surgery, POCD may occur anywhere between 1 week to 1 month afterwards. Inadequate sample sizes renders many POCD clinical studies statistically insignificant, indicating the need for a structured consensus on a POCD definition (47). Research also indicates that many patients with POD may go on to develop POCD (48).

Prevention and improving outcomes

Outlining parameters to clinically assess POCD is required first to identify factors and guide the prevention of its development. This includes the incorporation of pre- and postoperative neuropsychological tests for POCD diagnosis into presurgical routine (49). Rasmussen et al. (23) point out that special considerations must be made when using neuropsychological exams. The tests must possess a high sensitivity for POCD and a clear definition of what constitutes as postoperative change. O'Brien et al. (1) state that change within one standard deviation from baseline may be a good starting point for identifying POCD. Finally, we should remember the preoperative setting is one of efficiency, and thus preoperative cognitive testing should not delay the process to the point that physicians will not use them regularly.

Knowing patient baselines can prove important for not only diagnosis of POCD, but also prevention. Several preoperative measures can be taken to prevent POCD and hopefully improve patient outcomes. For example, O'Brien et al. (1) has identified that cognitive training in preoperative patients reduces POCD incidence. They also point out that patients should be carefully assessed for factors such as polypharmacy that may predispose them to delirium. Also, assessing the patient for weakness or frailty may alert the healthcare team to extra precautions to be taken. These kinds of interventions are especially important in patients with known risk factors for POCD as discussed above. Finally, Lu et al. (50) found that pretreatment with parecoxib sodium combined with dexmedetomidine followed by a continuous low dose infusion causes a decrease in the incidence of POCD in patients undergoing arthroscopy by over 10%. This combined therapy is theorised to improve the sleep quality as, well as provide the central nervous system protective, anti-inflammatory and improved analgesic effects. This intervention should be considered especially in high-risk patients, moving forward.

Intraoperatively, other aspects to consider to reduce the incidence are the extent and duration of anaesthesia. Two interventional approaches address this: minimise the length of exposure accompanied by careful monitoring while exposed. Chan et al. (51) have shown a decrease in POCD at 3 months with monitoring of the brain activity via bispectral index (BIS) and an appropriate adjustment of anaesthetics during the procedure. However, Radtke et al. (52) found that the BIS guided anaesthesia decreased the risk of POD, but not POCD. Chen et al. (53) also found that the use of inhaled versus total intravenous anaesthetics for cardiac surgery produced higher postoperative scores on the mini mental state exam. Apart from anaesthetics, it is appropriate to try and control other potential pathophysiological causes. Sun et al. (54), for example, conducted a study based on the hypothesis that intraoperative hypotension contributes to POCD. They found that controlling blood pressure intraoperatively with nicardipine and nitroglycerine or nicardipine with other antihypertensives, such as esmolol, reduced the incidence of POCD in patients with cardiac ablation.

Lastly, postoperative management is crucial to POCD prevention. Early identification and treatment of postoperative complications, such as delirium and infection, may decrease the POCD risk. Special attention should be paid to polypharmacy and pain relief in elderly postoperative patients, which can be difficult in and of itself, in case this triggers the progression to POCD or delirium.

Conclusion

With the rapid increase of the elderly population undergoing elective surgical procedures, understanding their vulnerabilities to POCD, and the morbidity and mortality it can cause, only increases in importance. POCD is a well-documented phenomenon that places patients in a daunting situation. The first step is undoubtedly settling upon a finite definition of POCD, independent of CI and POD. Despite that they share many of the same risk factors, establishing a POCD definition will allow for homogeneity among studies and create a clear path for POCD research. Current research presents several theories as to the pathogenesis of POCD, most prominent among them being increased inflammation, hypoperfusion and anaesthetic use during surgery. Prior to this, physicians can take precautions with patients to prevent POCD, such as pre- and postoperative cognitive testing, careful monitoring during anaesthesia, blood pressure control and early treatment of postoperative complications as they arise. The research and understanding of POCD could significantly change the perioperative, and especially the postoperative, experience for elderly patients from a time of fearful tension to the one of safety and heathy recovery.

Peer-review: Externally peer-reviewed.

Author Contributions: Concept--I.U., MJ., VO., O.V; Design--I.U., MJ., VO., O.V; Supervision--I.U., M.J., VO., O.V; Resources--I.U., MJ., VO., O.V; Materials--I.U., MJ., VO., O.V; Data Collection and/or Processing--I.U., M.J., VO., O.V, D.H., A.S.; Analysis and/or Interpretation--I.U., M.J., VO., O.V; Literature Search--I.U., M.J., VO., O.V, D.H., A.S.; Writing Manuscript--I.U., MJ., VO., O.V, D.H., A.S.; Critical Review--I.U., M.J., VO., O.V.

Conflict of Interest: The authors have no conflicts of interest to declare.

Financial Disclosure: The authors declared that this study has received no financial support.

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Ivan Urits (1) [iD], Vwaire Orhurhu (1) [iD], Mark Jones (1) [iD], Dylan Hoyt (2) [iD], Allison Seats (2) [iD], Omar Viswanath (3) [iD]

(1) Department of Anaesthesia, Critical Care, and Pain Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA

(2) Creighton University School of Medicine, - Phoenix Regional Campus, Phoenix, AZ, USA

(3) Valley Anesthesiology and Pain Consultants, University of Arizona College of Medicine-Phoenix, Department of Anaesthesia, Phoenix, AZ, Creighton University School of Medicine, Department of Anesthesia, Omaha, NE, USA

Received: 26.01.2019 Accepted: 06.03.2019

Available Online Date: 02.09.2019

Cite this article as: Urits I, Orhurhu V Jones M, Hoyt D, Seats A, Viswanath O. Current Perspectives on Postoperative Cognitive Dysfunction in the Ageing Population. Turk J Anaesthesiol Reanim 2019; 47(6): 439-47.

Doi: 10.5152/TJAR.2019.75299
Table 1. Comparing the outcomes of general to regional anaesthesia

                        Sample
                        Characteristics
Study                   (n, age)         Surgery Type

Mason et al. (28),      * Mean age >50   Orthopaedic, urological,
The impact of           * 21 studies     vascular, abdominal,
general and             reviewed         cardiovascular
regional anaesthesia
on the incidence
of postoperative
cognitive dysfunction
and postoperative
delirium: A
systematic review
with meta-analysis.
Rasmussen et al. (29),  * Age >60        Orthopaedic, gynaecologic,
Does anaesthesia        * 428 patients   vascular, urological,
cause postoperative                      gastrointestinal
cognitive dysfunction?
A randomised study
of regional versus
general anaesthesia
in 438 elderly
patients.
Seitz et al. (31)       * 15 case        Cardiovascular, neurological
Exposure to general     control studies
anaesthesia and         reviewed
risk of Alzheimer's     * Mean age
disease: a systematic   >/=50
review and
meta-analysis.

                        Comparing
                        Pre- and
                        Postoperative          Results and Conclusions
Study                   Cognition

Mason et al. (28),      Postoperative          Delirium is unlikely to
The impact of           cognition-multiple     be influenced by the
general and             cognitive function     route of anaesthesia.
regional anaesthesia    tests: all covered     Unable to draw
on the incidence        domains of cognition,  conclusions regarding
of postoperative        including memory,      POCD because no
cognitive dysfunction   executive function     accepted definition
and postoperative       and calculation        exists.
delirium: A             (mini mental state
systematic review       examination most
with meta-analysis.     common)
Rasmussen et al. (29),  Four                   POCD significantly
Does anaesthesia        neuropsychological     greater at 1 week in vs
cause postoperative     tests undertaken       patients receiving GA
cognitive dysfunction?  preoperatively and at  RA. GA POCD: 33/156
A randomised study      7 days and 3 months    (21.2% [15.0-28.4%]) vs
of regional versus      postoperatively.       RA POCD: 20/158
general anaesthesia     POCD was defined       (12.7% [7.9-18.9%])
in 438 elderly          as a combined Z        (p=0.04)
patients.               score >1.96 or a Z
                        score >1.96 in two
                        or more test
                        parameters.
Seitz et al. (31)       Excluded studies       No significant
Exposure to general     that examined          association between any
anaesthesia and         POCD, postoperative    exposure to GA and risk
risk of Alzheimer's     delirium, or           of AD (pooled OR: 1.05;
disease: a systematic   abnormalities on       95% CI: 0.93-1.19,
review and              neuropsychological     Z=0.80, p=0.43)
meta-analysis.          testing without a
                        diagnosis of
                        dementia (focused
                        only on the outcome
                        of development of AD)

GA: general anaesthesia; RA: regional anaesthesia; AD: Alzheimer's
disease

Table 2. Comparison of intraoperative sedation using dexmedetomidine to
propofol

Study                    Sample                        Surgery Type
                         (n, age)

Intraoperative           * 296 patients                Total hip
sedation with            * Age                         arthroplasty
dexmedetomidine          [greater than or equal to]65
is superior to           * Prospective,
propofol for             randomised
elderly patients         controlled study
undergoing hip
arthroplasty (32).
Intraoperative           * 855 patients                Orthopaedic
dexmedetomidine          * Age                         surgery
sedation reduces         [greater than or equal to]65
the postoperative        * Retrospective
agitated behaviour       cohort study
in elderly patients
undergoing
orthopaedic surgery
compared to the
Propofol sedation (33).

Study                    Comparing           Results and Conclusions
                         Pre- and
                         Postoperative
                         Cognition

Intraoperative           Preoperative and    Patients sedated with
sedation with            postoperative       dexmedetomidine had
dexmedetomidine          cognitive           lower incidences of
is superior to           dysfunction was     postoperative delirium
propofol for             assessed with a     and postoperative
elderly patients         mini mental state   cognitive dysfunction
undergoing hip           examination.        than patients sedated
arthroplasty (32).                           with Propofol.
Intraoperative           Richmond            Incidence of agitation
dexmedetomidine          Agitation-Sedation  was lower in the
sedation reduces         Scale               dexmedetomidine group
the postoperative                            compared with the
agitated behaviour                           propofol group (6 [2.3%]
in elderly patients                          vs. 17 [6.5%], p=0.027)
undergoing
orthopaedic surgery
compared to the
Propofol sedation (33).

Table 3. Exploring the role of haemodynamic status and cerebral oxygen
delivery on postoperative cognitive dysfunction

                       Sample
Study                  (n, age)                      Surgery Type

Svagzdiene et          * 59 patients                 Coronary artery
al. (34)               * Observational               bypass graft
Cerebrovascular        study                         surgery with CPB
autoregulation
impairment
during cardiac
surgery is related
to postoperative
cognitive
dysfunction.
Ono et al. (35)        * 450 patients                Coronary artery
Duration and           * Age                         bypass graft and
magnitude of           [greater than or equal to]65  /or valve surgery
blood pressure         * Clinical study              with CPB
below cerebral
autoregulation
threshold during
cardiopulmonary
bypass is associated
with major
morbidity and
operative mortality.
Feinkohl et al. (38)   * 24 studies                  All surgery
Hypertension and       reviewed, 4317
Risk of Postoperative  patients
Cognitive Dysfunction  * Mean age, 63
(POCD): A Systematic
Review and
Meta-Analysis.

                       Comparing
                       Pre- and
                       Postoperative         Results and Conclusions
Study                  Cognition

Svagzdiene et          Neuropsychological    Duration of the single
al. (34)               tests the day before  longest cerebrovascular
Cerebrovascular        and 10 days           autoregulation impairment
autoregulation         following surgery.    event was found reliably
impairment                                   associated with
during cardiac                               occurrence of POCD
surgery is related                           (p<0.05)
to postoperative
cognitive
dysfunction.
Ono et al. (35)        Major morbidity       Duration and magnitude of
Duration and           and operative         blood pressure below the
magnitude of           mortality using       limits of cerebrovascular
blood pressure         the Society of        autoregulation was
below cerebral         Thoracic Surgeons     associated with major
autoregulation         National Cardiac      morbidity or operative
threshold during       Surgery Database      mortality after
cardiopulmonary        definition            cardiovascular surgery
bypass is associated                         (odds ratio, 1.36; 95%
with major                                   confidence interval,
morbidity and                                1.08-1.71; P % .008)
operative mortality.
Feinkohl et al. (38)   Meta-analysis with    Hypertension was not
Hypertension and       variety of            significantly associated
Risk of Postoperative  postoperative         with POCD risk (RR 1.01;
Cognitive Dysfunction  cognitive             95% CI 0.93, 1.09;
(POCD): A Systematic   assessments           p=0.82).
Review and
Meta-Analysis.

GA: general anaesthesia; RA: regional anaesthesia; CPB: cardiopulmonary
bypass

Table 4. Exploring an inflammatory mechanism for the development of
postoperative cognitive dysfunction during general anaesthesia

Study                  Sample                         Comparing Pre- and
                       (n, age)                       Postoperative
                                                      Cognition

Skvarc et al. (42)     * Multi-study                  Meta-analysis
Postoperative          review                         with variety of
Cognitive                                             postoperative
Dysfunction: An                                       cognitive
exploration of                                        assessments
the inflammatory
hypothesis and
novel therapies.
Nemeth et al. (43)     * 42 patients                  Cognitive function
Influence of the       * Age                          and mood state
postoperative          [greater than or equal to]60   were
inflammatory                                          preoperatively and
response on                                           postoperatively (7
cognitive decline                                     days following),
in elderly                                            tested with a set
patients                                              of five
undergoing                                            neurocognitive
on-pump cardiac                                       tests and two mood
surgery: A                                            inventories.
controlled,
prospective
observational
study.
Kline et al. (40)      * 31 patients                  Digit Span
Perioperative          * Age                          Forward and
inflammatory           [greater than or equal to] 65  Digit Span
cytokines in           * Prospective                  Backward
plasma of the          non-interventional             cognition exams
elderly correlate      non-randomised study
in prospective
study with
postoperative
changes in
cognitive test
scores.
De Cosmoso et          * 622 patients                 Stroop Colour
al. (44) Effect of     * Age                          Word Interference
remifentanil and       [greater than or equal to]60   Test, Visual
fentanyl on            * Randomised                   Verbal Learning
postoperative          double-blind controlled        Test, MMSE, Test
cognitive function     study                          of Rey
and cytokines level
in elderly patients
undergoing major
abdominal surgery.
Jiang et al. (41)      * 44 patients                  Mini Mental Status
Circulating                                           Exam
TNF-[alpha] levels
increased and
correlated negatively
with IGF-I in
postoperative
cognitive
dysfunction.

Study                  Results and Conclusions

Skvarc et al. (42)     Neuroinflammation and to surgery and anaesthesia
Postoperative          is strongly implicated in POCD. Interruption of
Cognitive              synaptic plasticity and glutamate signalling are
Dysfunction: An        potential mechanisms.
exploration of
the inflammatory
hypothesis and
novel therapies.
Nemeth et al. (43)     The low inflammatory' and high inflammatory'
Influence of the       groups did not vary in the scores of
postoperative          neurocognitive tests and frequencies of POCD (7
inflammatory           vs 8 cases, respectively, p>0.05).
response on
cognitive decline
in elderly
patients
undergoing
on-pump cardiac
surgery: A
controlled,
prospective
observational
study.
Kline et al. (40)      Increase in inflammatory burden correlated with
Perioperative          a greater decline in cognitive performance (IL6,
inflammatory           IL8; r>-0.560; p[less than or equal to] 0.008)
cytokines in
plasma of the
elderly correlate
in prospective
study with
postoperative
changes in
cognitive test
scores.
De Cosmoso et          The use of remifentanil did not reduce the
al. (44) Effect of     incidence of POCD. IL-6 levels were lower the
remifentanil and       7th day after surgery for remifentanil group
fentanyl on            (p=0.04)
postoperative
cognitive function
and cytokines level
in elderly patients
undergoing major
abdominal surgery.
Jiang et al. (41)      POCD was associated with lower IGF-1 levels
Circulating            (114.37[+ or -]9.55 vs. 136.08[+ or -]10.61
TNF-[alpha] levels     [micro]g [L.sup.-1], p<0.0001) and higher
increased and          TNF-[alpha] levels (45.46[+ or -]4.49 vs
correlated negatively  39.27[+ or -]4.99 ng [L.sup.-1], p=0.0001).
with IGF-I in          Combined monitoring of TNF- [alpha] and IGF-1
postoperative          may give insight into POCD pathogenesis.
cognitive
dysfunction.

Table 5. Comparing postoperative delirium to postoperative cognitive
dysfunction

               POD                    POCD

Clinical       Neuropsychological     No agreed consensus, but common
Findings       syndrome               findings include prolonged
               characterised by       impairment of cognitive function
               disturbance in         after surgery with limitations
               attention and          in memory, attention,
               awareness, altered     intellectual ability and
               level of               executive function
               consciousness,
               acute change from
               baseline, disturbance
               in cognition, all not
               explained by
               pre-existing
               neurocognitive
               condition. There is
               evidence of an
               attributable cause.
Postoperative  24-72 hours            1 week-1 month
time to onset
Research       Clinical findings      Deterioration from preoperative
Diagnosis      and delirium           cognition tests to postoperative
               assessment methods:    cognition tests (MMSE, Richmond
               CAM-ICU test, MMSE     Agitation-Sedation Scale,
                                      t-MoCA, Digit Span Forward/Digit
                                      Span Backward, Stroop Colour
                                      Word
                                      Interference Test, Visual Verbal
                                      Learning Test)
Long-term      POCD                   Additional research required
complications

POD: postoperative delirium; POCD: postoperative cognitive dysfunction;
CAM-ICU: Confusion Assessment Method for the ICU; MMSE: Mini Mental
Status Exam; t-MoCA: Telephone Montreal Cognitive Assessment
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Title Annotation:Perioperative Care
Author:Urits, Ivan; Orhurhu, Vwaire; Jones, Mark; Hoyt, Dylan; Seats, Allison; Viswanath, Omar
Publication:Turkish Journal of Anaesthesiology and Reanimation
Date:Dec 1, 2019
Words:5920
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