Postoperative delirium and cognitive dysfunction
S.Deiner 1and J.H.Silverstein 123*
1
Department of Anesthesiology,2Department of Surgery and 3Department of Geriatrics and Adult Development,Box 1010,Mount Sinai School of Medicine,New York,NY 10029-6574,USA
*Corresponding author.E-mail:jeff.
Postoperative delirium and cognitive dysfunction (POCD)are topics of special importance in the geriatric surgical population.They are parate entities,who relationship has yet to be fully elucidated.Although not limited to geriatric patients,the incidence and impact of both are more profound in geriatric patients.Delirium has been shown to be associated with longer and more costly hospital cour and higher likelihood of death within 6months or postopera-tive institutionalization.POCD has been associated with incread mortality,risk of leaving the labour market prematurely,and dependency on social transfer payments.Here,we review their definitions and aetiology,and discuss treatment and prevention in elderly patients under-going major non-cardia
c surgery.Good basic care demands identification of at-risk patients,awareness of common perioperative aggravating factors,simple prevention interventions,rec-ognition of the dia states,and basic treatments for patients with vere hyperactive manifestations.
Br J Anaesth 2009;103(Suppl.1):i41–i46
Keywords :age factors;anaesthesia,geriatric;brain;complications
Definitions
Delirium is well defined and is described in the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV–TR;/).The key characteristics are a change in mental status characterized by a reduced awareness of the environment and a disturbance in atten-tion.This may be accompanied by other,more florid,per-ceptual symptoms (hallucinations)or cognitive symptoms including disorientation or temporary memory dysfunction.The patient may express hypoactive,hyperactive,or mixed psychomotor behaviours.Several tests have been developed and validated for u in diagnosis and grading of delirium.The include the Confusion Asssment Method (CAM),the Delirium Rating Scale Revid-9诱惑的英文
8,and the Delirium Symptom Interview.921A recent study from Japan found that the NEECHAM Confusion Scale and the Estimation of Physiologi
c Ability and Surgical Stress (E-PASS)are uful in diagnosis as well.17Severity may vary,can be graded,and may have prognostic value.52By definition,although the disorder develops acutely,the condition will wax and wane during the cour of a day.The symptoms are not exclusive to delirium.Patients who have baline dementia,psychosis,or anxiety/depressive disorder may prent diagnostic challenges.
There are many subtypes of delirium,including tho attributable to an underlying medical condition (delirium due to a general medical condition ),medications
(substance-induced delirium,substance intoxication delir-ium ),or withdrawal from medications (substance withdrawal delirium ).Sometimes delirium may be multifactorial (delir-ium due to multiple aetiologies )or of unclear aetiology (delirium not otherwi specified—NOS ).Emergence agita-tion or delirium might be thought of as a subt of substance-induced delirium.It has predominance in paedia-tric patients,has been correlated with general anaesthesia,and provided the patient is guarded from harming them-lves,usually resolves without quelae.24Emergence delirium in the paediatric population has been demonstrated to be associated with preoperative anxiety and responds to behavioural preparation and preoperative dation.25For the purpo of this review,we are interested in delirium that occurs after a relatively normal emergence and that occurs at some int
erval after surgery and anaesthesia.This entity,which is more cloly associated with older age,is referred to as postoperative (interval)delirium.
Postoperative delirium (POD)is not temporally related to emergence from anaesthesia.By definition,patients with POD do not have an identifiable aetiology,although there can be other contributing factors.The patients often emerge smoothly,and may be lucid in the post-anaesthesia care unit.However,after this initial lucid interval,the patients develop the classic fluctuating mental status,most commonly between postoperative days 1and 3.Some postoperative patients may reside in the ICU;
#The Author [2009].Published by Oxford University Press on behalf of the British Journal of Anaesthesia.All rights rerved.British Journal of Anaesthesia 103(BJA/PGA Supplement):i41–i46(2009)
doi:10.1093/bja/aep291
however,the term ICU delirium(previously known as ICU psychosis)may include both medical and surgical patients.POD can differ from delirium in medical patients becau the admission characteristics of the two groups can be different.By definition,patients hospitalized for medical indications are either acutely ill or have exacer-bations of chronic dias.Most surgical operations are elective and patients have been managed to ensure optimal physical status before entering the hospital.Surgery and the associated anaesthetics and analgesics are generally abnt in medical patients,but can contribute to POD.An important reason to distinguish POD from delirium en in medical patients is the report by Brauer and colleagues,8 suggesting that patients with POD are more likely to result in initial complete recovery than other forms of delirium. However,POD is far from benign.In veral recent2 yr-plus cohort studies of elderly patients,hip fracture patients who develop POD are more likely to die,be diag-nod with dementia or mild cognitive impairment(MCI), and require institutionalization.626
In contrast,postoperative cognitive dysfunction(POCD) is more difficult to define.Broadly,POCD refers to deterioration in cognition temporally associated with surgery.While the diagnosis of delirium requires a detec-tion of symptoms,the diagnosis of POCD requires pre-operative neuropsyc92年属啥的
hological
testing(baline)and a determination that defines how much of a decline is called cognitive dysfunction.The spectrum of abilities referred to as cognition is diver,including learning and memory, verbal abilities,perception,attention,executive functions, and abstract thinking.It is possible to have a decrement in one area without a deficit in another.Self-reporting of cog-nitive symptoms has been shown to correlate poorly with objective testing,so valid pre-and postoperative testing is esntial to the diagnosis of POCD.23Many elderly patients have pre-existing MCI that has gone undiagnod. Unfortunately,there has not been a s画板图片
tandard methodology ud in the multiple studies within the POCD literature.36 Selection of neuropsychological test instruments and the amount of change considered to be significant,timing of testing,and inclusion and exclusion criteria have all varied.38Furthermore,the batteries ud,while relevant, have hadfloor effects and we have not incorporated batteries that are somewhat different from tho ud by dementia rearchers.Hence,it is difficult to define the prence and therefore incidence of POCD or to clearly understand the relationship between POCD and other dementing illness. Some commonly ud testing instruments include the Logical Memory Test,the CERAD word list memory,the Boston Naming test,Category Fluency test,Digit Span Test, Trail making test,and Digit symbol substitution test. Interestingly,POCD test batteries tend to be a compilation of tests which have shown differences among subjects in previous studies of POCD.The domains that were most n-sitive include verbal learning and working memory,episodic memory,processing speed,and t shifting.
The method of scoring the testing batteries and deter-mining how much dysfunction is clinically significant remains an open subject.One method is the percentage change method,that is,postoperative score2preoperative score/preoperative score.Averaging across groups is dis-couraged,becau while some patients will decline,others improve over time and this difference can be masked. Another method defines a number of standard deviations outside of which a score will be called a decline. However,this method isflawed for patients with low ba-line scores(floor effect).By necessity,the absolute magni-tude of the change required for significance will vary between studies,since the norm is determined from the preoperative baline test scores.Finally,some studies have ud per cent 20%)to define decline. The limitation of this method is that the baline low scoring patients require a smaller change in their raw score to meet POCD criterion.
The timing of testing is important as well.It is possible that patients who undergo baline testing on the morning of their procedure might not score and also patients tested days before,condary,preprocedural anxiety.After oper-ation,patients who are testing shortly after surgery can test wor than tho who are tested weeks to months later possibly due to pain,residual drugs,and health status. However,long-term follow-up and testing is confounded by attri
tion,that is,patients who experience the greatest decline are the least likely to follow-up with their post-operative cognitive testing and drop out of the study.This may be a significant cau for underestimating the true incidence of POCD.Additionally,there can be significant variability between testing ssions due to learning and examiner bias.29Although variability in neuropsychologi-cal test data contributes to a low consistency between post-operative test ssions,the differences detected suggest that this does not fully explain the detection of cognitive dysfunction after major surgery.39It is clear that deterio-ration is not random variation between testing ssions. The current literature is also diver with respect to inclusion and exclusion criteria of patients with MCI.MCI is described as the prodromal state,a heterogeneous group of conditions including Alzheimer’s dementia,cerebral vascular dia,and other dementia.Most of the major studies have excluded this group due to limitations of the test battery.This is true even though this group may be the most significant risk for POCD by virtue of having less cognitive rerve.45By not differentiating this patient population,it is possible that the incidence of cognitive decline has been‘washed out’by the larger sample. Pathophysiology and aetiology
Delirium as a behavioural manifestation of cortical dys-function is associated with characteristic signs.The EEG may show diffu slowing of background activity.A wide
Deiner and Silverstein
variety of disturbances in neurotransmitter systems has been described.Serum anticholingeric activity has been associated with delirium and may be especially important, and also other mediators such as melatonin,norepi-nephrine,and lymphokines.1948Delirium has been hypothesized to occur as a result of the inflammatory respon associated with the stress of surgery. Interestingly,elevated preoperative inflammatory markers including C-reactive protein,interleukin6,and insulin growth factor1(IGF-1)have not been found to be associ-ated with the development of POD.2742However,post-operative chemokines have been found to be more elevated in patients who became delirious than in matched controls.This difference was non-significant by postopera-tive day4,and other inflammatory cytokines were not found to be different in the two groups at any time point. This would point to a mechanism for delirium which might include initial leucocyte migration into the central nervous system(CNS)and potentially a breakdown of the blood–brain barrier.42
Although the mechanism of delirium has not been eluci-dated,there has been significant description of associated patient risk factors.Some of the may be considered pre-existing,that is,existing vulnerabilities,and others precipi-tating,that is,noxious injuries.Age.70,pre-existing cognitive impairment,preoperative u of narcotics or benzodiazepines,previous history of POD,and lf-repor
ted health impairment from alcohol are all cloly associated with the development of POD.28Other predis-posing risk factors include vision impairment,vere illness,cognitive impairment,and rum urea nitrogen: creatinine ratio of18or greater.19Vascular risk factors have also been strongly associated with development of delirium(tobacco u and vascular surgery),although it is unclear whether the incread risk is due to atherosclerotic burden or the surgical procedure itlf.40Decread cer-ebral perfusion as a risk factor for POD is supported by a recent study which associated low preoperative regional oxygen saturation as measured by a cerebral oximeter.35 Low preoperative executive scores and depressive symp-toms,as measured by the veral different instruments, have been found to identify patients at risk of POD.1546 POD is also associated with pre-existing attentional defi-cits in non-demented patients.30Precipitating factors include:the u of physical restraints,malnutrition,more than three medications added24–48h before the ont of delirium,the u of a urinary bladder catheter,and iatro-genic events,including electrolyte andfluid abnormal-ities.19Specific perioperative risk factors include greater intraoperative blood loss,more postoperative transfusions, and postoperative haematocrit of,30%.32Severe acute pain regardless of the method of analgesia(opioid type, method,and do)is associated with POD.13Although it is tempting to speculate the mechanism from the obr-vations,association may not infer causality.Certain types of injury,particularly hip fractures,and rious illness requi平行线的传递性
ring intensive care are also associated with a high incidence of delirium.
Aetiology of postoperative cognitive decline is also unclear.Several mechanisms have been postulated.The include perioperative hypoxaemia and ischaemia. However,the variables as measured by pul oximetry and arterial pressure were not found to be significant by the ISPOCD group.34This surprising result may become somewhat more comprehensible in future studies involving cerebral oximetry.Although there have been laboratory studies which su为什么遗精
ggest that general anaesthetic agents have toxic effects on the CNS,this effect is less evident in clinical studies.Interestingly,choice of anaesthesia (general vs regional)has not been found to be signifi-cant.10115051However,major surgery does appear to be a principle culprit,whereas general anaesthesia and ambulat-ory surgery are not.34Incread inflammatory activity may play a role in early POCD.Elevated C-reactive protein is associated with impaired mental status in elderly hip frac-ture patients.5
Similar to POD literature,more has been described regarding risk factors and associations for POCD than the mechanism itlf.Advancing age has been found as a risk factor for POCD,although minor declines have been described in younger patients as well.22Preoperative cog-nitive and physical impairment and cognitive impairment during hospitalization correlate with poorer postoperative outcomes at2and12months.16However,the epsilon-4 allele of the ApoE gene,which is strongly assoc
iated with the development of Alzheimer’s dia,is not associated with the development of POCD.1POD has also been associated with early postoperative dysfunction(at7days); however,the association with long-term cognitive function is less clear.4149There may indeed be an association between POD and POCD,but the relationship has yet to be elucidated.The ISPOCD1study did notfind that the patients who developed delirium were the same patients who developed POCD.Most studies have focud on either POD or POCD;in the future,studies designed to evaluate this patient population for both and examine their association may enhance our understanding of this issue. Perioperative patient risk factors and perioperative triggers associated with POD and POCD are summarized in Tables1and2,respectively.
Incidence
The incidence of POD between studies ranges from5%to 15%.4Within certain high-risk groups such as hip fracture patients,the range is16–62%with an average of35%.7 POCD is more complicated to describe,as the true inci-dence can be masked by attrition of the worst cas. Additionally,POCD can improve with time,so incidence must be described at a particular interval after surgery. Currently,it ems the incidence of initial deterioration i伊索寓言的读后感
n
POD and cognitive dysfunction
older patients is high (25%at 2–10days)with gradual resolution (10%at 3months,5%at 6months,and 1%at 1yr).2At 1yr,the cognitive decline is indistinguishable from matched controls.However,no study has accounted for the aforementioned attrition.
Treatment and prevention
POD is preventable in some patients,and delirium preven-tion/intervention programmes have met with some success.A proactive geriatric consult alone has been shown to sig-nificantly decrea the incidence of POD.31Successful intervention programmes include the Hospital Elder Life Program.This programme focud on protocol-driven management of six risk factors for delirium:visual and hearing impairment,cognitive impairment,sleep depri-vation,immobility,and dehydration.The study patients had significant reduction in the number and duration of episodes of delirium.20Specific interventions include prom-inent prentation of orienting information,for example,date,time,name of hospital personnel,cognitive stimu-lation activities,exerci,feeding and fluid assistance,and non-pharmacological sleep aids (laxing music and massage).Attempts at pharmacological prophylaxis have met with mix教师个人学习计划
ed results.Although we have excluded cardiac surgery patients from our discussion,it is interest-ing to note that a single do of ketamine (0.5mg kg 21)given upon induction was associated with lower rum levels of C-reactive protein and lower i
ncidence of delir-ium in this population.Authors postulate that ketamine’s
neuroprotective effects including prevention of excitotoxic injury and apoptosis and its suppression of CNS inflamma-tory respon might be responsible.18It should be noted that a single do of ketamine has been reported to have a profound,2week impact on patients with refractory depression.37Another study of cardiac surgery patients tar-geted the reduced cholinergic transmission associated with delirium with rivastigmine,a cholinestera inhibitor.This study did not find that prophylaxis was associated with a decread incidence of delirium,although the study found an overall lower rate of delirium than expected and was therefore underpowered for their primary outcome.A study of haloperidol prophylaxis in combination with non-pharmacological delirium prevention strategies had similar methodological difficulties,and showed no difference in the incidence of delirium.However,patients who received delirium prophylaxis with haloperidol did have a signifi-cant reduction in delirium verity and duration with an associated decrea in hospital length of stay.43
Treatment of POD has remained constant—identifi-cation of underlying medical issues,optimization of environment and pain control,and pharmacological treat-ment for refractory cas.It is important to stress that pharmacological treatment is not first line.However,it may be necessary when agitation
puts the patient and care-givers at risk of harm or prevents normal postoperative care.The drug of choice remains haloperidol.It is an anti-psychotic D2dopamine receptor antagonist and is admi-nistered at a do of 0.5–1mg i.v.every 10–15min until the behaviour is controlled.I.M.dosing is possible as well,but much less desirable.The dosage is 2–10mg and interval for titration is 60–90min.Careful titration is important to avoid overdation and prolonged effects c-ondary to its long (up to 72h)half-life.Newer antipsycho-tics have 歇后语大全搞笑
been shown to be effective in acute agitation when administered injections,but have not been tested in medical and surgical patients.3Physical restraints are undesirable except in the most vere cas and then only as a temporary measure while pharmacological and other interventions have failed.Treatment of POD is sum-marized in Table 3.
Prevention and treatment of postoperative cognitive decline is still undefined.It is unclear whether delirium prevention strategies affect long-term cognitive outcomes.
Future directions
High-quality perioperative care for elderly patients is a social and financial necessity.One of the fastest growing
Table 2Delirium:perioperative triggers
Acute pain
U of physical restraints Malnutrition
Addition of three or more medications in 24–48h U of a urinary bladder catheter Anaemia
Electrolyte and fluid a一年级读书笔记
bnormalities
Greater surgical blood loss,greater intraoperative transfusion
Table 1Preoperative risk factors Delirium
Cognitive decline
Dementia Older age
Depression Preoperative cognitive impairment Age .70
Preoperative physical impairment Preoperative u of narcotics or benzodiazepines
Cognitive impairment during hospitalization Self-reported u of alcohol Delirium
Previous history of delirium Vision impairment Severe illness
BUN/creatinine ratio .18Tobacco u Vascular surgery Depressive symptoms Attentional deficits
Table 3Treatment of POD
Avoidance of known perioperative triggers Delirium intervention programmes
Haloperidol for refractory hyperactive symptoms
Deiner and Silverstein
gments of the population is individuals over65.12 Delirium is immediately costly,by increasing hospital length of stay and more insidiously by its association with mortality and cognitive decline.14POCD can remove indi-viduals prematurely from the workforce or require pre-viously independent individuals to ek help with activities of daily living or assisted care facilities.47 Identification of at-risk individuals is possible,given the available literature.The creation of‘centres of excellence’where process measures are implemented and risk-adjusted outcomes explored might all
ow us to identify strategies to optimize care.33There is already evidence that this is poss-ible and helpful.20However,there are not enough geriatri-cians to relegate the perioperative care of the elderly to specialists.Caring for perioperative geriatric patients by necessity must be a multidisciplinary effort.33
The Cochrane review on delirium prevention in hospi-talized elderly patients found that there is a paucity of high-quality rearch on delirium prevention.Reasons include the difficulties with detection and conducting rearch in the frail and debilitated patients,and the con-founding factors of medical problems,pre-existing cogni-tive deficits,and attrition which we have mentioned previously.44An ideal study would focus on long-and short-term outcomes including mortality and physical and cognitive/psychological morbidity.
POCD,while established as a diagnostic entity,requires more rearch to understand its aetiology.This may facili-tate future studies regarding treatment and prevention.At a minimum,larger studies using a standard definition and meticulous follow-up may enhance our understanding of this perioperative phenomenon.An agreement of what tests and degree of change defines a clinically significant cognitive deficit would facilitate comparison across studies examining either its incidence or the efficacy of an inter-vention.With respect to mechanistic understanding of POCD,new modalitie
s such as cerebral oximetry and detection of rum markers of inflammation show promi.
Conclusion
As members of society and practitioners of perioperative medicine,we are invested in the future of excellence in geriatric care.In the clinical arena,more awareness and deliberate care plans are necessary to implement tho interventions which are already known to decrea or ame-liorate the incidence of POD.Education of care teams regarding the strategies for prevention is of the utmost importance.Geriatrician involvement where possible is helpful,but the esnce of good basic care is identification of the at-risk individual,awareness of common periopera-tive aggravating factors,simple prevention interventions, recognition of the dia state when it occurs,and basic treatments for patients with vere hyperactive manifes-tations.Ongoing studies of clinical cohorts with and without MCI before operation may help us understand the risks of cognitive dysfunction after non-cardiac surgery. Future rearch may help us understand underlying bio-chemical or physical insults which may lead us to better directed prophylactic treatment.
Funding
J.H.S.is supported by grants AG029656and AG030141 from the US National Institutes of Health.
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POD and cognitive dysfunction
