Even if Viagra is not needed, it is possible that the doctor will be able to determine the etiology of erectile dysfunction and prescribe appropriate treatmen https://vgraustralia.net it doesn't pay to forget about sexual activeness even at the first sings of malfunction.
Should general anaesthesia be avoided in the elderly?
Anaesthesia 2014, 69 (Suppl. 1), 35–44
Should general anaesthesia be avoided in the elderly?
C. Strøm,1 L. S. Rasmussen2 and F. E. Sieber3
1 Research Assistant, 2 Professor, Department of Anaesthesia, Centre of Head and Orthopaedics, Rigshospitalet, Copen-hagen University Hospital, Copenhagen, Denmark3 Professor of Anaesthesiology, Department of Anaesthesiology/Critical Care Medicine, The Johns Hopkins MedicalInstitutions, Baltimore, Maryland, USA
SummarySurgery and anaesthesia exert comparatively greater adverse effects on the elderly than on the younger brain, mani-fest by the higher prevalence of postoperative delirium and cognitive dysfunction. Postoperative delirium and cogni-tive dysfunction delay rehabilitation, and are associated with increases in morbidity and mortality among elderlysurgical patients. We review the aetiology of postoperative delirium and cognitive dysfunction in the elderly with aparticular focus on anaesthesia and sedation, discuss methods of diagnosing and monitoring postoperative cognitivedecline, and describe the treatment strategies by which such decline may be prevented.
.
Correspondence to: C. StrømEmail:
[email protected]: 5 October 2013
clinical management insights by discussing some of
Don't have a general anaesthetic once you're 50 –
the more controversial methods for monitoring the
it'll wipe out a quarter of your brain.
brain during anaesthesia, and outline how postopera-
— Barbara Cartland, novelist (died aged 98)
tive cognitive changes might be assessed and pre-vented.
Concern has been growing over the last decade regard-ing whether anaesthesia can be harmful to the elderly
Pathophysiology of age-related
brain, because elderly surgical patients frequently expe-
neuropsychiatric decline
rience a postoperative deterioration in cognitive func-
A number of anatomical and physiological changes
tion, and such a decline may herald an increase in
manifest themselves as the human brain ages, and
both morbidity and mortality.
these may render the ageing brain more vulnerable to
In this review, we will outline some of the perti-
both reductions in cognitive reserve and the effects of
nent changes in human brain structure and function
surgery and anaesthesia (Table 1).
related to ageing, in order to understand the possiblemechanisms behind cognitive and behavioural changes
seen after surgery and anaesthesia. We will review
At approximately 45–50 years of age, a progressive
some of the pre-clinical evidence that has given rise to
decline in brain weight begins, reaching a nadir after
the hypothesis that progressive neurodegeneration may
the age of 86 years [1]. Grey matter volume increases
be exacerbated by anaesthesia. Finally, we will provide
in childhood, but then begins to decrease slowly.
2013 The Association of Anaesthetists of Great Britain and Ireland
Anaesthesia 2014, 69 (Suppl. 1), 35–44
Strøm et al. Use of general anaesthesia in the elderly
Table 1 Predisposing factors and possible mechanisms
evidence supports the hypothesis that age-associated
for the development of postoperative delirium/cogni-
injury to the blood–brain barrier plays a role in the
tive deterioration in elderly patients.
pathogenesis of white matter disease [3]. Blood–brainbarrier changes may also alter the response to ischae-mia, as well as drug entry to the central nervous
Predisposing factors
Structural changes
system (CNS) [3].
decreased whole-brain volume blood–brain barrier damage reduction of neurogenesis
hippocampal changes
In humans, neural stem cells are constitutively active in
amyloid or tau accumulation
the hippocampal dentate gyrus and subventricular
Brain inflammationCerebrovascular disease
regions of the lateral ventricles, and proliferate into pro-
Disturbances in levels of
genitors that differentiate into neurons in all age groups
Pre-operative cognitive impairment
[4]. Neurogenesis in the dentate gyrus may cause a
Reduction in cognitive reserve
unique form of neural plasticity that is involved in cog-
nitive and emotional functions. A gradual reduction in
increased frailty
neurogenesis occurs with ageing, limiting the ability to
increased incidence of pre-existing
learn and contributing to cognitive decline [4].
increased incidence of
Systemic vascular disease
Lower educational level
Communication between the peripheral immune sys-tem and cytokine-mediated signals within the CNS
Potential mechanisms
Neurohumoral inflammatory surgical stress response
form a co-ordinated response to stress. Signals initiated
in the peripheral immune system may result in CNS
Direct anaesthetic agent toxicityIschaemia (hypoperfusion, hypoxaemia)
inflammatory responses that can manifest as changes
in behaviour or cognition. Immunity in the CNS is
Hospital environment
mediated by microglia, astrocytes and CNS-associatedmacrophages. Microglia respond to, and propagate,inflammatory signals from the peripheral immune sys-
White matter volume increases until the age of approxi-
tem. During the peri-operative period, for example,
mately 45 years, reflecting increases in connectivity
microglia might release cytokines or perform macro-
between brain regions, and thereafter starts to decrease.
phage-like activities. Exaggerated or prolonged produc-
Decreases in whole-brain volume cannot be accounted
tion of cytokines can occur in response to peripheral
for solely by ageing-associated losses in either white or
immune system stimuli as a result of impaired anti-
grey matter, and seem to be multi-factorial in aetiology.
inflammatory feedback in the aged brain [5]. An
For example, co-morbidities associated with ageing,
increasing body of evidence suggests that increases in
such as diabetes and hypertension, can adversely affect
brain inflammation with ageing and systemic disease
changes in white matter tracts [2].
(e.g. metabolic syndrome) are associated with cognitivechanges [6].
Blood–brain barrierWith ageing, the blood–brain barrier decreases in
microvascular density and capillary lumen size, and
Cognition changes with age in two main ways. First,
the number of mitochondria per endothelial cell is
measures that reflect acquired knowledge, such as
reduced, changes that affect blood–brain barrier
vocabulary, improve up to 60 years of age, after
permeability [3]. Risk factors for acceleration of these
which they decline. Secondly, there is a nearly linear
changes include hypertension, hyperlipidaemia, diabe-
decline from early adulthood in cross-sectional and
tes mellitus and adverse drug reactions. Accumulating
longitudinal measures of processing speed, including
2013 The Association of Anaesthetists of Great Britain and Ireland
Strøm et al. Use of general anaesthesia in the elderly
Anaesthesia 2014, 69 (Suppl. 1), 35–44
reasoning, memory and spatial cognitive abilities [7].
Anaesthesia and the elderly brain
Memory decline occurs in more than 40% of people
Anaesthetic agents work on a relatively small number
aged over 60 and can dramatically affect the perfor-
of CNS targets, and most of these are postsynaptic
mance of daily living activities, but is not a universal
ligand-gated ion channels. Some drugs act at excit-
finding [8].
atory receptors, whereas others potentiate inhibitorysynaptic receptors, such as gamma-aminobutyric acid
Cognitive reserve
(GABA) receptors [12]. Intravenous anaesthetics may
Cognitive reserve describes the inconsistency between
have effects on GABA (propofol, etomidate), alpha-2
anatomic and functional age-related decline, and can
be classified as passive or active. Passive reserve relates
acetylcholine, adenosine and dopamine (opioids)
to brain size or neuronal count, and is measured, for
receptors [13]. Inhalational anaesthetic agents affect
example, by brain volume, synaptic count or dendritic
multiple ion channel receptors, including GABA, gly-
branching. Active reserve relates more to functional
cine, acetylcholine [14], glutamate, and serotonin
cognitive integrity, and is preserved better in people
[15]. The variety and complexity of anaesthetic
with higher socioeconomic status and educational
agent/ion channel interactions underlie the postopera-
attainment, although no ‘best measure' of active
tive cognitive problems experienced by the elderly.
reserve exists. Higher educational attainment, for
Interactions between anaesthetic agents and the CNS
example, modifies the association between post-mortem
cholinergic system may be of particular importance
Alzheimer's disease pathology and pre-mortem cogni-
[16], due to the close relationship between acetylcholine
tive function: for the same degree of brain pathology,
and cognition. Age-related decline in prefrontal cholin-
cognitive function is better with each year of education
ergic neurons may render the elderly more susceptible
[9]. Epidemiological evidence suggests that a patient's
than younger patients to anaesthesia-mediated depres-
cognitive reserve determines their cognition, rather than
sion of CNS cholinergic neurotransmission [17, 18].
their underlying neuropathology [9].
Although both biochemical and anatomical
Monitoring the elderly brain during
changes have been described in the ageing brain, the
general anaesthesia
exact mechanisms that cause changes in functional
Monitoring brain oxygenation/perfusion and depth of
reserve are unclear. Decreases in functional reserve
anaesthesia have been advocated for reducing postop-
are manifest as decreases in activities of daily living,
erative cognitive decline in the elderly. Studies have
increased sensitivity to anaesthetic agents, and
found an association between cerebral oxygen desatu-
increased risk for both postoperative delirium
ration detected by intra-operative near-infrared spec-
(POD) and postoperative cognitive dysfunction
troscopy (NIRS) and poorer cognitive outcomes [19],
but are limited by non-uniform definitions of desatura-tion and cognitive decline, as well as inadequate sam-
Cerebrovascular disease
ple size. Randomised controlled trials designed to
Risk factors, including hypertension, diabetes mellitus
assess the postoperative cognitive effects of minimising
and elevated plasma homocysteine and apolipoprotein
intra-operative cerebral oxygen desaturation have been
E, are associated with age-related large vessel arterio-
inconclusive [19]. The relevance of diminished age-
sclerotic and small vessel angiopathic cerebrovascular
related autoregulation of cerebral blood flow in the
disease, resulting in infarction and haemorrhage [10].
elderly as a contributory factor to cerebral oxygen de-
Subclinical vascular disease, manifest as white matter
saturation is also unclear [20].
hyperintensities on magnetic resonance images, is asso-
Commercially available means of monitoring
ciated with changes in cognition, including attention,
anaesthetic depth include electroencephalogram (EEG,
psychomotor speed and executive function [11],
processed or raw) and auditory evoked potentials. The
although the volume of these that is necessary to cause
most common EEG device in clinical use is the bispec-
cognitive changes is unknown.
tral index (BIS) monitor. The association between
2013 The Association of Anaesthetists of Great Britain and Ireland
Anaesthesia 2014, 69 (Suppl. 1), 35–44
Strøm et al. Use of general anaesthesia in the elderly
depth of anaesthesia and postoperative cognition
remains uncertain, with some studies concluding that
Postoperative delirium
‘lighter' levels of general anaesthesia guided by either
Postoperative delirium is an acute organic brain syn-
the BIS monitor or auditory evoked potentials improve
drome that usually develops within the first few days
postoperative cognitive outcomes [21, 22], whereas
after an operation. Postoperative delirium exhibits a
others have reported no association or the opposite
fluctuating course and is often accompanied by abnor-
[23, 24]. Studies utilising both BIS and NIRS suggest
mal circadian rhythm. The core symptom is inatten-
that reducing both cerebral oxygen desaturation and
tion, but other cognitive changes are also common,
the duration and depth of anaesthesia may be of bene-
including memory deficit and disorientation. Changes
fit in reducing POCD [25].
in psychomotor behaviour define whether delirium isclassified hypoactive, hyperactive or mixed variation
The elderly patient and sedation
[30]. The hypoactive form is associated with relatively
The sedation of elderly patients is a commonly
higher mortality, but is underdiagnosed because
employed, but under-researched, adjunct to regional
patients are quiet and relatively motionless, or misdi-
anaesthesia, often for orthopaedic procedures. Dosage
agnosed as symptomatic manifestations of dementia
and method of administration are invariably extrapo-
and/or depression [31]. Following a lucid interval,
lated from clinical trials involving younger patients,
POD symptoms tend to appear 24–72 h after surgery,
and fail to take into account the altered pharmaco-
and are distinct from cognitive ‘emergence phenom-
kinetics and pharmacodynamics of elderly patients,
ena' that occur during the transition from anaesthesia
resulting in relative overdosage and peri-operative cog-
to wakefulness [32]. ‘Subsyndromal delirium' has been
nitive alteration [26]. Patient-controlled sedation may
suggested as a diagnosis for elderly patients who dis-
avoid over-sedation, and has been used safely during
play one or more symptoms of, but do not meet
cataract surgery with a high level of patient satisfaction
defined diagnostic criteria for, delirium [33].
[27], although use of this technique requires validation
Approximately 10% of elderly surgical patients
in other elderly populations, and may be limited to
develop POD, rising to 30–65% after certain types of
patients without pre-morbid cognitive dysfunction.
surgery, such as hip fracture, cardiac and emergency
Evidence suggests that depth of sedation monitor-
surgery [34, 35]. Patient-specific factors including
ing is important for elderly surgical patients. In a
advanced age, cognitive impairment, lower educational
randomised double-blind study of 114 patients aged
level and pre-existing medical conditions predispose to
65 years or over administered spinal anaesthesia for
POD, as do potentially reversible risk factors such as
hip fracture repair, patients who received deep seda-
pre-morbid CNS co-medication, infection, malnutri-
tion (BIS 50) had a significantly higher prevalence of
tion, electrolyte imbalance, dehydration, environmental
POD than those patients who received light sedation
disturbances and substance withdrawal (alcohol, medi-
(BIS 80) (40% vs 19%, p = 0.02) [28]. The type of
cation). Severe pain and inadequate analgesia increase
sedation monitor used appears less important than the
the risk of POD in cognitively intact patients [36].
fact that the depth of sedation should always be moni-
The pathogenesis of POD is still to be elucidated,
tored; indeed, BIS monitoring correlates poorly with
but is generally thought to be multifactorial. Normal
clinical sedation scale scores [29].
brain function relies on numerous well-functioninghormonal and neuromodulatory systems. Disturbances
POD and POCD – an update on
in CNS acetylcholine, dopamine and melatonin levels
classification, assessment and
have been associated with POD [37]. It has been pro-
posed that the high prevalence of POD after major
The most common types of deterioration in cognitive
surgery is related to the inflammatory component of the
function are POD and POCD. Both are associated with
stress response to surgery. However, although a variety
significant morbidity and mortality, reinforcing the
of inflammatory biomarkers have been investigated,
importance of their peri-operative assessment.
postoperative elevations of only a few cytokines have
2013 The Association of Anaesthetists of Great Britain and Ireland
Strøm et al. Use of general anaesthesia in the elderly
Anaesthesia 2014, 69 (Suppl. 1), 35–44
been linked (weakly) to POD [38, 39]. It is of interest
bypass circuits [46], or intra-operative hypoxaemia or
that microglial cytokine responses to peripheral
hypotension [47].
immune system stimuli in vitro differ depending on
Similar to POD, several hypotheses regarding the
whether cultures are exposed to isoflurane, sevoflurane
aetiology of POCD have been suggested, including sur-
or propofol [40].
gical stress-associated systemic or localised inflamma-
Prolonged duration and increased severity of POD
tory reactions, alterations in hormonal homeostasis,
increase postoperative mortality [41]. Postoperative
and direct anaesthetic agent toxicity [48, 49]. Patterns
delirium is independently associated with prolonged
of diurnal salivary cortisol excretion, for example, are
hospital stay, short- and long-term risk of death and
significantly related to the development of POCD [48].
higher rates of institutionalisation after discharge, lead-
Intriguingly, serum levels of S-100B protein, a biomar-
ing to a cumulative increase in healthcare expenses [41].
ker of cerebral damage, are significantly elevated inabdominal and vascular surgery patients who develop
Postoperative cognitive dysfunction
POCD, when compared with those patients who do
Postoperative cognitive dysfunction is a syndrome of
not develop POCD [50] and after hip fracture in
prolonged impairment of cognitive function after sur-
patients who develop POD [51]. Experimental studies
gery, with limitations in memory, intellectual ability
in rats have shown that inhaled anaesthetics (in the
and executive function that usually last for weeks or
absence of surgical stress) have sustained effects on
months, but is distinct from delirium and dementia. It
memory formation, and are capable of inducing neuro-
is a subtle condition; some patients only have minor
degenerative changes on a cellular level [52]. Hippo-
symptoms, such as mild memory loss, whereas others
campal damage correlates with cognitive impairment
are severely affected with pronounced inability to con-
in rats [53], and reduction in hippocampal volume in
centrate, process information or execute formerly
humans measured by MRI may be valuable in predict-
uncomplicated tasks. Subjective symptoms or behavio-
ing POCD [54, 55]. Despite intensive investigation, the
ural changes observed before and after surgery may
pathogenesis of POCD remains poorly elucidated. It is
arouse suspicion, but formal neuropsychological testing
still to be established to what extent postoperative
is necessary to diagnose POCD. Mild cases can easily
decline in cognitive function is attributable specifically
be overlooked or dismissed as just normal signs of
to either surgical or anaesthetic management, as dis-
ageing, and often the patients or their relatives are the
tinct from patient-related risk factors such as extensive
only ones to notice that deterioration has occurred.
co-morbid cerebrovascular and systemic vascular dis-
To date, no formal diagnostic criteria have been
ease, or undiagnosed mild cognitive dysfunction, which
established for POCD, which makes it difficult to
may be of greater aetiological importance (Table 2)
evaluate in daily clinical practice. Nevertheless, recog-
nition is essential, as POCD has been associated with
Recent research interest has focused on whether
increased mortality, risk of prematurely leaving the
POCD and POD are prodromal forms of Alzheimer's
work market and dependence on socio-economic
disease. The cerebral accumulation of b-amyloid
support [42, 43].
and tau proteins are pathognomonic features of
The incidence of POCD varies according to the
Alzheimer's disease, and anaesthetic agents appear to
definitions used in various studies [44]. Higher inci-
enhance this process, as well as potentiating the cyto-
dences are demonstrated in populations of elderly
toxicity of b-amyloid proteins, and tau phosphoryla-
patients undergoing major surgery. For example, fol-
tion and aggregation [58, 59], although evidence
lowing coronary artery bypass grafting, the quoted
remains inconclusive. Surgery may have an indepen-
prevalence of POCD varies between 10 and 80% early
dent effect on these processes [60], and one study sug-
after the procedure and is thought to be associated
gested that elevation of b-amyloid concentrations
with emboli, atherosclerosis and intra-operative ischae-
might simply reflect synaptic activity [61]. The apoli-
mia [45]. Postoperative cognitive dysfunction does not
poprotein E genotype is strongly associated with Alz-
appear to be related to the use of cardiopulmonary
heimer's disease and vascular dementia, but has not
2013 The Association of Anaesthetists of Great Britain and Ireland
Anaesthesia 2014, 69 (Suppl. 1), 35–44
Strøm et al. Use of general anaesthesia in the elderly
been shown to be associated with POCD [62–64].
Other diagnostic tools have been developed and
Although it is methodologically difficult to establish
validated to diagnose POD. The confusion assessment
any correlation between POD and POCD, a recent
method (CAM) is easy to perform and sensitive, spe-
prospective study suggested that POD and POCD
cific and reliable across populations [68], but is unable
might represent a trajectory of postoperative cognitive
to stratify delirium according to severity; delirium is
impairment [65], perhaps as a progression of unrec-
diagnosed by patient inattention of acute onset and
ognised pre-operative mild cognitive impairment [66].
fluctuating course, accompanied by either/or alteredconsciousness and disorganised thinking (Table 3).
Subsequently, a CAM-ICU non-verbal screening tool
Postoperative delirium
was developed to diagnose delirium in intubated and
Diagnostic criteria are defined in the International Sta-
critically ill patients [68].
tistical Classification of Diseases and Related Health
Other scoring systems stratify POD severity, but
Problems, 10th Revision (ICD-10) and the Diagnostic
are less sensitive in diagnosing delirium, and should
and Statistical Manual of Mental Disorders, 4th edition
only be employed once a diagnosis of POD is estab-
(DSM-IV) (Table 3), the former including more specific
lished. Repeated testing is important as POD exhibits a
criteria than the latter, and proving more useful in estab-lishing the diagnosis of POD (after cardiac surgery) [67].
Table 3 The confusion assessment method (CAM)diagnostic algorithm adapted from Inouye et al. [89].
Table 2 Diagnostic criteria for postoperative delirium(POD).
Acute onset and fluctuating courseThis feature is usually obtained from a family
member or nurse and is shown by positive
A. Disturbance of consciousness (i.e. reduced clarity of
responses to the following questions: isthere evidence of acute change in mental
awareness of the environment) with reduced ability
status from the patient's baseline? Did the
to focus, sustain or shift attention
B. A change in cognition (e.g. memory deficit,
(abnormal) behaviour fluctuate during the
disorientation, language disturbance)
day, that is, tend to come and go, orincrease and decrease in severity?
C. Development of a perceptual disturbance that is
not better accounted for by a pre-existing,
established, or evolving dementia
This feature is shown by a positive response
D. Disturbance develops over a short period of time
to the following question: did the patient
(usually hours to days) and tends to fluctuate
have difficulty focusing attention, for
during the course of the day
example, being easily distractible, or
evidence from the history, physical
having difficulty keeping track of what
examination or laboratory findings that the
disturbance is caused by the direct physiological
Disorganised thinking
consequences of a general medical condition
This feature is shown by a positive response
to the following question: was the
patient's thinking disorganised or
An aetiologically non-specific organic cerebral syndromecharacterised by concurrent disturbances of
incoherent, such as rambling or irrelevantconversation, unclear or illogical flow of
consciousness and attention, perception, thinking,
ideas, or unpredictable switching from
memory, psychomotor behaviour, emotion and the sleep– wake schedule. The duration is variable and the
subject to subject?
degree of severity ranges from mild to very severe
Altered level of consciousnessThis feature is shown by any answer other
than ‘alert' to the following question:
overall, how would you rate this patient's
confusional state (non-alcoholic)
level of consciousness? (alert [normal]),
infective psychosis
vigilant (hyperalert), lethargic [drowsy,
organic reaction
easily aroused], stupor [difficult to rouse]
psycho-organic syndrome
or coma [unrousable])
The diagnosis of delirium by CAM requires the presence
delirium tremens, alcohol-induced or unspecified
of features 1 and 2 and either 3 or 4
2013 The Association of Anaesthetists of Great Britain and Ireland
Strøm et al. Use of general anaesthesia in the elderly
Anaesthesia 2014, 69 (Suppl. 1), 35–44
fluctuating time course, which is often overlooked in
systematic review suggested avoidance of opioids,
studies of POD [69]. Developing composite risk scores
may enhance the prediction of delirium.
H1-receptor antagonists in patients at risk of POD[74].
Postoperative cognitive dysfunction
The multifactorial aetiology of POD appears ame-
There are no generally agreed criteria for the assess-
nable to improvement by using multi-domain inter-
ment of POCD, and the diagnosis is not yet described
ventions, including BIS-guided depth of anaesthesia
in either ICD-10 or DSM-IV. There are considerable
monitoring combined with cerebral oxygen saturation
inconsistencies between the multiple studies that have
monitoring [25], and proactive, multidisciplinary
investigated POCD, which makes it difficult to formu-
assessment, goal-directed optimisation of oxygen deliv-
late diagnostic criteria. No single test can adequately
ery, blood volume and serum electrolytes, and non-
measure cognitive function with acceptable sensitivity.
pharmacological support, including early mobilisation
Instead, a battery of neuropsychological tests is
and sleep facilitation [75, 76]. Hypothetically, long-
required to assess individual cognitive domains, such as
term cognitive outcomes might be improved by pre-
verbal skills and memory. When testing a new diagnos-
operative diet, exercise and drug modification of
tic screening tool, baseline tests must have been
underlying, undiagnosed systemic and cerebrovascular
obtained pre-operatively and specific definitions of
disease [57].
what constitutes a decline in cognitive function must
Pharmacological intervention is rarely of benefit in
be pre-defined [70], but there is no agreed definition of
treating POD/POCD. Haloperidol can be used in cases
what constitutes a significant decline, even though most
of severe agitation, and may decrease the incidence of
studies are powered to detect a cognitive decline of one
delirium [77] and reduce the severity and duration of
standard deviation from pre-operative levels.
POD [77–79], but evidence is inconclusive. Pharmaco-
In addition, the constituent tests of the battery
logical modification of circadian disturbance using
administered vary between studies, and the intervals
diazepam, flunitrazepam and pethidine reduced POD
between testing are inconsistent [71]. Timing is crucial,
in a small randomised controlled trial (RCT) of 40
as factors such as postoperative pain, opioid use and
elderly patients after laparotomy [80], but this contra-
sleep disturbances all influence cognitive deterioration
dicts more recent evidence proscribing benzodiazepine
early after surgery. Furthermore, composite cognitive
administration [74]. Peri-operative dexmedetomidine
testing is associated with low sensitivity and specificity,
infusion may be useful in reducing the prevalence of
and floor/ceiling effects (the test is too easy or too dif-
POD if patients require intensive care postoperatively
ficult, reducing discrimination between individuals
[81]. A recent meta-analysis of 38 RCTs comparing
scoring near the highest/lowest possible values), and
prevention strategies for POD concluded that trials
may not always reflect specific patient symptoms.
showed great inconsistencies in definition, incidence,
Finally, many studies fail to use an appropriate control
severity and duration of POD, but supported the effec-
group, invalidating inter-individual and intra-individ-
tiveness of dexmedetomidine sedation (compared with
ual comparisons over time.
propofol or benzodiazepine sedation), multicomponentinterventions and antipsychotics in preventing POD,
Prevention of POD and POCD
without finding any benefit relating to type of anaes-
Treatment of POD is directed towards the correction
thesia (general/spinal) or analgesia (nerve block) or
of contributing factors after diagnosis, but prevention
use of anticholinesterase inhibitors (donepezil/rivastig-
can reduce prevalence and improve outcome, and the
mine) [82]. Other studies have found the risk of both
same probably applies for POCD. Postoperative delir-
POD and POCD to be similar after both regional and
ium may be predictable pre-operatively and therefore
general anaesthesia [83, 84], but may be confounded
preventable to a degree [72], but attempts to create
by concomitant use of sedation with regional anaesthe-
universal risk scales have failed, due to wide variation
sia. It is not yet clear whether the choice of general
in surgical, patient and anaesthetic factors [73]. A
anaesthesia agent is important, but recent studies
2013 The Association of Anaesthetists of Great Britain and Ireland
Anaesthesia 2014, 69 (Suppl. 1), 35–44
Strøm et al. Use of general anaesthesia in the elderly
suggest that volatile anaesthetic agents (isoflurane,
6. Ownby RL. Neuroinflammation and cognitive aging. Current
Psychiatry Reports 2010; 12: 39–45.
flurane) are associated with a lower prevalence of
7. Salthouse TA. Neuroanatomical substrates of age-related cog-
POD than propofol [85, 86].
nitive decline. Psychological Bulletin 2011; 137: 753–84.
Is anaesthesia harmful for elderly patients? It is
8. Small S. Age-related memory decline: current concepts and
future directions. Archives of Neurology 2001; 58: 360–4.
difficult to attribute cognitive changes to anaesthetic
9. Stern Y. Cognitive reserve. Neuropsychologia 2009; 47: 2015–
drugs per se. Even though some experimental research
indicates such a correlation, evidence is con
10. Grindberg LT, Thal DR. Vascular pathology in the aged human
brain. Neuropathology 2010; 119: 277–90.
and may not be significant in clinical practice. Surgi-
11. Warsch JR, Wright CB. The aging mind: vascular health in nor-
cal trauma or underlying pathology may be of greater
mal cognitive aging. Journal of the American Geriatrics Soci-ety 2010; 58: S319–24.
importance, although their causal contributions to the
12. Franks NP, Lieb WR. Molecular and cellular mechanisms of
pathogenesis of postoperative cognitive decline are yet
general anaesthesia. Nature 1994; 367: 607–14.
to be determined. Neurophysiological and anatomical
13. Brown EN, Purdon PL, Van Dort CJ. General anaesthesia and
altered states of arousal: a systems neuroscience analysis.
changes are relevant to the understanding of post-
Annual Review of Neuroscience 2011; 34: 601–28.
anaesthetic cognitive dysfunction in the ageing brain,
14. Rossman AC. The physiology of the nicotinic acetylcholine
receptor and its importance in the administration of anaes-
but numerous other factors are involved, including
thesia. American Association of Nurse Anesthetists Journal
surgical stress, inflammation, pain, co-morbidities and
2011; 79: 433–40.
the phenotypic trajectory of a patient's cognitive
15. Campagna JA, Miller KW, Forman SA. Mechanisms of actions
of inhaled anesthetics. New England Journal of Medicine
decline with age. Further studies of postoperative cog-
2003; 348: 2110–24.
nitive decline need to employ assessment methods
16. Pratico C, Quattrone D, Lucanto T, et al. Drugs of anaesthesia
acting on central cholinergic system may cause post-operative
that are reliable and reasonably applicable in daily
cognitive dysfunction and delirium. Medical Hypotheses 2005;
clinical practice, and these require further develop-
65: 972–82.
ment alongside well-designed clinical trials that aim
17. Fodale V, Quattrone D, Trecroci C, Caminiti V, Santamaria LB.
Alzheimer's disease and anaesthesia: implications for the cen-
to investigate (multimodal) interventions that reduce
tral cholinergic system. British Journal of Anaesthesia 2006;
the prevalence of this most distressing of postopera-
97: 445–52.
18. Jansson A, Olin K, Yoshitake T, et al. Effects of isoflurane on
tive complications.
prefrontal acetylcholine release and hypothalamic response inyoung adult and aged rats. Experimental Neurology 2004;
Competing interests
190: 535–43.
19. Zheng F, Sheinberg R, Yee MS, Ono M, Zheng Y, Hogue CW.
Supported by R01 AG033615 (FES), Tryg Foundation
Cerebral near-infrared spectroscopy monitoring and neurologic
(LSR). No other external funding or competing inter-
outcomes in adult cardiac surgery patients: a systematicreview. Anesthesia and Analgesia 2013; 116: 663–76.
ests declared.
20. Burkhart CS, Rossi A, Dell-Kuster S, et al. Effect of age on in-
traoperative cerebrovascular autoregulation and near-infrared
spectroscopy-derived cerebral oxygenation. British Journal ofAnaesthesia 2011; 107: 742–8.
1. Hedman AM, van Haren NE, Schnack HG, Kahn RS, Hulshoff
21. Chan MT, Cheng BC, Lee TM, Gin T; CODA Trial Group. BIS-
Pol HE. Human brain changes across the life span: a review of
guided anaesthesia decreases postoperative delirium and
56 longitudinal magnetic resonance imaging studies. Human
cognitive decline. Journal of Neurosurgical Anesthesiology
Brain Mapping 2012; 33: 1987–2002.
2013; 25: 33–42.
2. Aine CJ, Sanfratello L, Adair JC, Knoefel JE, Caprihan A, Ste-
22. Jildenstal PK, Hallen JL, Rawal N, Gupta A, Berggren L. Effect
phen JM. Development and decline of memory functions in
of auditory evoked potential-guided anaesthesia on consump-
normal, pathological and healthy successful aging. Brain
tion of anaesthetics and early postoperative cognitive dys-
Topography 2011; 24: 323–39.
function: a randomised controlled trial. European Journal of
3. Zeevi N, Pachter J, McCullough LD, Wolfson L, Kuchel GA. The
Anaesthesiology 2011; 28: 213–9.
blood-brain barrier: geriatric relevance of a critical brain-body
23. Steinmetz J, Funder KS, Dahl BT, Rasmussen LS. Depth of
interface. Journal of the American Geriatrics Society 2010; 58:
anaesthesia and post-operative cognitive dysfunction. Acta
Anaesthesiologica Scandinavica 2010; 54: 162–8.
4. Couillard-Despres S, Iglseder B, Aigner L. Neurogenesis, cellu-
24. Farag E, Chelune GJ, Schubert A, Mascha EJ. Is depth of anaes-
lar plasticity and cognition: the impact of stem cells in the
thesia, as assessed by the bispectral index, related to postop-
adult and aging brain – a mini-review. Gerontology 2011; 57:
erative cognitive dysfunction and recovery? Anesthesia and
Analgesia 2006; 103: 633–40.
5. Corona AW, Fenn AM, Godbout JP. Cognitive and behavioral
25. Ballard C, Jones E, Gauge N, et al. Optimised anaesthesia to
consequences of impaired immunoregulation in aging. Journal
reduce post operative cognitive decline (POCD) in older
of Neuroimmune Pharmacology 2012; 7: 7–23.
2013 The Association of Anaesthetists of Great Britain and Ireland
Strøm et al. Use of general anaesthesia in the elderly
Anaesthesia 2014, 69 (Suppl. 1), 35–44
patients undergoing elective surgery, a randomised controlled
44. Krenk L, Rasmussen LS. Postoperative delirium and postopera-
trial. PLoS One 2012; 7: e37410.
tive cognitive dysfunction in the elderly – what are the differ-
26. White SM. Including the very elderly in clinical trials. Anaes-
ences? Minerva Anestesiologica 2011; 77: 742–9.
thesia 2010; 65: 778–80.
45. Rudolph JL, Schreiber KA, Culley DJ, et al. Measurement of
27. Yun MJ, Oh AY, Kim KO, et al. Patient-controlled sedation vs.
post-operative cognitive dysfunction after cardiac surgery: a
anaesthetic nurse-controlled sedation for cataract surgery in
systematic review. Acta Anaesthesiologica Scandinavica;
elderly patients. International Journal of Clinical Practice
2010; 54: 663–77.
2008; 62: 776–80.
46. Van Dijk D, Spoor M. Cognitive and cardiac outcomes 5 years
28. Sieber FE, Zakriya KJ, Gottschalk A, et al. Sedation depth dur-
after off-pump vs. on-pump coronary artery bypass graft sur-
ing spinal anaesthesia and the development of postoperative
gery. Journal of the American Medical Association 2007; 297:
delirium in elderly patients undergoing hip fracture repair.
Mayo Clinic Proceedings 2010; 85: 18–26.
47. Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term postop-
29. Weaver CS, Hauter WH, Duncan CE, Brizendine EJ, Cordell WH.
erative cognitive dysfunction in the elderly ISPOCD1 study. IS-
An assessment of the association of bispectral index with 2
POCD investigators. International Study of Post-Operative
clinical sedation scales for monitoring depth of procedural
Cognitive Dysfunction. Lancet 1998; 351: 857–61.
sedation. American Journal of Emergency Medicine 2007; 25:
48. Rasmussen LS, O'Brien JT, Silverstein JH, et al. Is peri-opera-
tive cortisol secretion related to post-operative cognitive dys-
30. Young J, Inouye SK. Delirium in older people. British Medical
function? Acta Anaesthesiologica Scandinavica 2005; 49:
Journal 2007; 33: 842–6.
31. Yang FM, Marcantonio ER, Inouye SK, et al. Phenomeno-
49. Hudson AE, Hemmings HC. Are anaesthetics toxic to the
logical subtypes of delirium in older persons: patterns,
brain? British Journal of Anaesthesia 2011; 107: 30–7.
prevalence, and prognosis. Psychosomatics 2009; 50: 248–
50. Linstedt U, Meyer O, Kropp P, Berkau A, Tapp E, Zenz M.
Serum concentration of S-100 protein in assessment of cogni-
32. Radtke FM, Franck M, Hagemann L, Seeling M, Wernecke KD,
tive dysfunction after general anesthesia in different types of
Spies CD. Risk factors for inadequate emergence after anes-
surgery. Acta Anaesthesiologica Scandinavica 2002; 46: 384–
thesia: emergence delirium and hypoactive emergence.
Minerva Anestesiologica 2010; 76: 394–403.
51. Van Munster BC, Korse CM, de Rooij SE, et al. Markers of
33. Meagher D, Adamis D, Trzepacz P, et al. Features of subsyn-
cerebral damage during delirium in elderly patients with hip
dromal and persistent delirium. British Journal of Psychiatry
fracture. BMC Neurology 2009; 9: 21.
2012; 200: 37–44.
52. Jevtovic-Todorovic V, Beals J, Benshoff N, Olney JW. Prolonged
34. Rudolph JL, Marcantonio ER. Postoperative delirium: acute
exposure to inhalational anesthetic nitrous oxide kills neurons
change with long-term implications. Anesthesia and Analge-
in adult rat brain. Neuroscience 2003; 122: 609–16.
sia 2011; 112: 1202–11.
53. Lin D, Zuo Z. Isoflurane induces hippocampal cell injury and
35. Ansaloni L, Catena F, Chattat R, et al. Risk factors and inci-
cognitive impairments in adult rats. Neuropharmacology
dence of postoperative delirium in elderly patients after elec-
2011; 61: 1354–9.
tive and emergency surgery. British Journal of Surgery 2010;
54. Kline RP, Pirraglia E, Cheng H, et al. Surgery and brain atrophy
97: 273–80.
in cognitively normal elderly subjects and subjects diagnosed
36. Inouye SK, Charpentier PA. Precipitating factors for delirium in
with mild cognitive impairment. Anesthesiology 2012; 116:
hospitalized elderly persons: predictive model and interrela-
tionship with baseline vulnerability. Journal of the American
55. Chen MH, Liao Y, Rong PF, et al. Hippocampal volume reduc-
Medical Association 1996; 275: 852–7.
tion in elderly patients at risk for postoperative cognitive dys-
37. Tune L. Serum anticholinergic activity levels and delirium in
function. Journal of Anesthesia 2013; 27: 487–92.
the elderly. Seminars in Clinical Neuropsychiatry 2000; 110:
56. Evered LA, Silbert BS, Scott DA, et al. Preexisting cognitive
impairment and mild cognitive impairment in subjects pre-
38. Rudolph JL, Ramlawi B, Kuchel GA, et al. Chemokines are
senting for total hip replacement. Anesthesiology 2011; 114:
associated with delirium after cardiac surgery. Journal of Ger-
ontology 2008; 63A: 184–9.
57. Selnes OA, Gottesman RF, Grega MA, Baumgartner WA, Zeger
39. MacLullich AM, Edelshain BT, Hall RJ, et al. Cerebrospinal fluid
SL, McKhann GM. Cognitive and neurologic outcomes after
interleukin-8 levels are higher in people with hip fracture
coronary-artery bypass surgery. New England Journal of Medi-
with perioperative delirium than in controls. Journal of the
cine 2012; 366: 250–7.
American Geriatrics Society 2011; 59: 1151–3.
58. Xie Z, Dong Y, Maeda U, et al. The common inhalation anes-
40. Ye X, Lian Q, Eckenhoff MF, Eckenhoff RG, Pan JZ. Differential
thetic isoflurane induces apoptosis and increases amyloid
general anesthetic effects on microglial cytokine expression.
[beta] protein levels. Anesthesiology 2006; 104: 988–94.
PLoS One 2013; 8: e52887.
59. Fodale V, Santamaria LB, Schifilliti D, Mandal PK. Anesthetics
41. Marcantonio ER, Goldman L, Mangione CM, et al. A clinical
and postoperative cognitive dysfunction: a pathological mech-
prediction rule for delirium after elective noncardiac surgery.
anism mimicking Alzheimer's disease. Anaesthesia 2010; 65:
Journal of the American Medical Association 1994; 271:
60. Wan Y, Xu J, Meng F, et al. Cognitive decline following major
42. Monk TG, Weldon BC, Garvan CW, et al. Predictors of cognitive
surgery is associated with gliosis, [beta]-amyloid accumula-
dysfunction after major noncardiac surgery. Anesthesiology
tion, and [tau] phosphorylation in old mice. Critical Care Med-
2008; 108: 18–30.
icine 2010; 38: 2190–8.
43. Steinmetz J, Christensen KB, Lund T, Lohse N, Rasmussen LS.
61. Cirrito JR, Kang JE, Lee J, et al. Endocytosis is required for syn-
Long-term consequences of postoperative cognitive dysfunc-
aptic activity-dependent release of amyloid-beta in vivo. Neu-
tion. Anesthesiology 2009; 110: 548–55.
ron 2008; 58: 42–51.
2013 The Association of Anaesthetists of Great Britain and Ireland
Anaesthesia 2014, 69 (Suppl. 1), 35–44
Strøm et al. Use of general anaesthesia in the elderly
62. Abildstrom H, Christiansen M, Siersma VD, Rasmussen LS.
76. Krenk L, Rasmussen LS, Hansen TB, Bogø S, Søballe K, Kehlet
Apolipoprotein E genotype and cognitive dysfunction after
H. Delirium after fast-track hip and knee arthroplasty. British
noncardiac surgery. Anesthesiology 2004; 101: 855–61.
Journal of Anaesthesia 2012; 108: 607–11.
63. McDonagh DL, Mathew JP, White WD, et al. Cognitive function
77. Kalisvaart KJ, de Jonghe JF, Bogaards MJ, et al. Haloperidol
after major noncardiac surgery, apolipoprotein E4 genotype,
prophylaxis for elderly hip-surgery patients at risk for delir-
and biomarkers of brain injury. Anesthesiology 2010; 112:
ium: a randomized placebo-controlled study. Journal of the
American Geriatrics Society 2005; 53: 1658–66.
64. Bryson GL, Wyand A, Wozny D, Rees L, Taljaard M, Nathan H.
78. Schrader SL, Wellik KE, Demaerschalk BM, Caselli RJ, Woodruff
A prospective cohort study evaluating associations among
BK, Wingerchuk DM. Adjunctive haloperiodol prophylaxis
delirium, postoperative cognitive dysfunction, and Apolipopro-
reduces postoperative delirium severity and duration in at-risk
tein E genotype following open aortic repair. Canadian Journal
elderly patients. Neurologist 2008; 14: 134–7.
of Anesthesia 2011; 58: 246–55.
79. Wang W, Li HL, Wang DX, et al. Haloperidol prophylaxis
65. Saczynski JS, Marcantonio ER, Quach L, et al. Cognitive trajec-
decreases delirium incidence in elderly patients after non-car-
tories after postoperative delirium. New England Journal of
diac surgery: a randomized controlled trial. Critical Care Medi-
Medicine 2012; 367: 30–9.
cine 2012; 40: 731–9.
66. Crosby G, Culley DJ, Hyman BT. Preoperative cognitive assess-
80. Aizawa K, Kanai T, Saikawa Y, et al. A novel approach to the
ment of the elderly surgical patient: a call for action. Anes-
prevention of postoperative delirium in the elderly after gas-
thesiology 2011; 114: 1265–8.
trointestinal surgery. Surgery Today 2002; 32: 310–4.
67. Kazmierski J, Kowman M, Banach M, et al. The use of DSM-IV
81. Ji F, Li Z, Nguyen H, et al. Perioperative dexmedetomidine
and ICD-10 criteria and diagnostic scales for delirium among
improves outcomes of cardiac surgery. Circulation 2013; 127:
cardiac surgery patients: results from the IPDACS Study. The
Journal of Neuropsychiatry and Clinical Neurosciences 2010;
82. Zhang H, Lu Y, Liu M, et al. Strategies for prevention of post-
22: 426–32.
operative delirium: a systematic review and meta-analysis of
68. Luetz A, Heymann A, Radtke FM, et al. Different assessment
randomized trials. Critical Care 2013; 18: R47.
tools for intensive care unit delirium: which score to use? Crit-
83. Wu CL, Hsu W, Richman JM, Raja SN. Postoperative cognitive
ical Care Medicine 2010; 38: 409–18.
function as an outcome of regional anesthesia and analgesia.
69. Neufeld KJ, Leoutsakos JS, Sieber FE, et al. Evaluation of
Regional Anesthesia and Pain Medicine 2004; 29: 257–68.
two delirium screening tools for detecting post-operative
84. Rasmussen LS, Johnson T, Kuipers HM, et al. Does anesthesia
delirium in the elderly. British Journal of Anaesthesia 2013;
cause postoperative cognitive dysfunction? A randomised study
111: 612–8.
of regional versus general anesthesia in 438 elderly patients.
70. Silverstein JH, Timberger M, Reich DL, Uysal S. Central nervous
Acta Anaesthesiologica Scandinavica 2003; 47: 260–6.
system dysfunction after noncardiac surgery and anesthesia
85. Royse CF, Andrews DT, Newman SN, et al. The influence of
in the elderly. Anesthesiology 2007; 106: 622–8.
propofol or desflurane on postoperative cognitive dysfunction
71. Funder KS, Steinmetz J, Rasmussen LS. Methodological
in patients undergoing coronary artery bypass surgery. Anaes-
issues of postoperative cognitive dysfunction research. Semi-
thesia 2011; 66: 455–64.
nars in Cardiothoracic and Vascular Anesthesia 2010; 14:
86. Schoen J, Husemann L, Tiemeyer C, et al. Cognitive function
after sevoflurane- vs propofol-based anesthesia for on-pump
72. Rudolph JL, Jones RN, Levkoff SE, et al. Derivation and valida-
cardiac surgery: a randomized controlled trial. British Journal
tion of a preoperative prediction rule for delirium after cardiac
of Anaesthesia 2011; 106: 840–50.
surgery. Circulation 2009; 119: 229–36.
87. American Psychiatric Association (ed.). Diagnostic and Statisti-
73. Steiner LA. Postoperative delirium. Part 2: detection, preven-
cal Manual of Mental Disorders, 4th edn. Text Revised (DSM-
tion and treatment. European of Journal Anaesthesiology
IV). Washington, DC: American Psychiatric Association, 2000.
2011; 28: 723–32.
88. World Health Organisation. International Statistical Classifica-
74. Clegg A, Young JB. Which medications to avoid in people at
tion of Diseases and Related Health Problems 10th Revision
risk of delirium: a systematic review. Age and Ageing 2011;
2010/en (accessed 30/09/2013).
75. Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing
89. Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confusion:
delirium after hip fracture: a randomized trial. Journal of the
the confusion assessment method. A new method for detec-
American Geriatrics Society 2001; 49: 516–22.
tion of delirium. Annals of Internal Medicine 1990; 113: 941–8.
2013 The Association of Anaesthetists of Great Britain and Ireland
Source: http://congresoscare.co/cali/concursos/documentos-adicionales-juicio-del-siglo.html?download=108:should-general-anaesthesia-be-avoided-in-the-elderly_&start=100
New Reasons to SYSCO Produce. Providing Quality Brands You Can Count On As the leading supplier of fresh produce This team is dedicated to one mission: • Verification of product integrity and in North America, SYSCO takes food delivering SYSCO brand products that supplier compliance via routine quality, safety and security very seriously. meet the highest standards in terms of
Csir-Forestry research institute of Ghana R SCIENTIFIC AND INDUSTRIAL R Annual Report 2011 R SCIENTIFIC AND INDUSTRIAL RE CSIR-FORESTRY RESEARCH INSTITUTE OF GHANA Annual Report 2011 CSIR-FORESTRY RESEARCH INSTITUTE OF GHANA © Copyright CSIR-FORIG 2012 For more information please contact:The DirectorCSIR-Forestry Research Institute of GhanaU.P.O Box 63Kumasi, Ghana.