Best Practice & Research Clinical Anaesthesiology

Vol. 17, No. 2, pp. 163 177, 2003

doi:10.1053/ybean.2003.289, www.elsevier.com/locate/jnlabr/ybean

1
Pathophysiological changes in the elderly
Peter H. Tonner

MD

Professor of Anaesthesiology

Joerg Kampen*

MD

Resident in Anaesthesiology

Jens Scholz

MD

Professor of Anaesthesiology
Department of Anaesthesiology and Intensive Care Medicine, University Hospital Kiel, Schwanenweg 21,
D-24105 Kiel, Germany

Demographic data indicate an increasing workload of geriatric anaesthesia due to advancing life
expectancy and reduced thresholds for high-invasive and high-risk surgery in the elderly.
Chronological and biological age may be inconsistent, and the existence of age-related changes
may vary between organ systems in the same individual. Age itself is not an illness, but is the most
important contributing factor for perioperative complications and adverse outcome when the
overall narrowed margins of organ function reserve are transgressed during the perioperative
period. Age-related changes in the cardiovascular, pulmonary, nervous, metabolic and locomotive
systems that are frequently present in the elderly are discussed with regard to their potential
relevance to anaesthesiology.
In conclusion, listing current diagnoses will not be sufficient in the assessment of the geriatric
patient because age-related changes do not necessarily manifest as pathological entities. Rather,
pre-operative examination should focus on determination of individual margins of organ function
reserve.
Key words: ageing; demographic changes; geriatric anaesthesia; organ function reserve.

DEMOGRAPHIC CHALLENGES OF THE 21ST CENTURY

Increasing life expectancy
In recent decades life expectancy in the USA and Europe has been prolonged in men
and women to approximately 74 years and 80 years, respectively. Many factors
contribute to this development, but medical progress seems to be the most effective
one.1 Demographical data indicate that the elderly are the most rapidly growing
segment of the population in industrialized countries.
* Corresponding author. Tel.: 49-431-597-2991; Fax: 49-431-597-3002.
E-mail address: kampen@anaesthesie.uni-kiel.de (J. Kampen).
1521-6896/03/$ - see front matter Q 2003 Elsevier Science Ltd. All rights reserved.

164 P. H. Tonner et al

Currently, in Europe, inhabitants aged 65 and older represent 15 19% of the

population. It is estimated for the year 2025 that this group will grow to over 20% of
the population in Europe, Canada and Japan.2 (see Figure 1.)
At present, more than 6% of the population in the USA are older than 75 years of
age.3 By the year 2030, 17% of the population in the USA will be over 65 years.4
The 2000 census in the USA led to the prediction that, in 2050, there will be 31 million
citizens older than 80 years of age.5
Increasing workload of geriatric anaesthesia
Surgical interventions will be required by more than half of the population older than 65
years at least once during the remainder of their lives.6 There is no doubt that the
anaesthesia community has to prepare to treat an increasing number of old patients.3
The increased workload in big teaching hospitals over the last 10 years was identified to
be due mainly to increased admission of geriatric patients of age 65 or older who
require surgery.7
A nationwide survey in France covering all anaesthetic procedures performed on 3
consecutive days highlighted the relevance that care for people in extremes of age
already has in the anaesthetic workload.8 One-third of all cases were performed in
patients older than 60 years and 3% of all anaesthetic procedures were performed
in patients older than 85 years. The total annual rate of anaesthesia per 100 population
of age 65 or older was 27.2% and 21.3% for women. Old age had an impact on prevalent
pathologies, reflected by the American Society of Anesthesiologists (ASA) physical
status, as 81% of procedures in ASA 3 5 were performed in patients aged 55 and older.
It may be assumed that age over 85 years led to restraint in performing surgery in
patients with ASA physical state 3 or higher from the fact that less than 10% of the
procedures were performed in ASA state 4 or 5, but more than 50% of procedures
were performed in ASA state 1 or 2. In this study, elderly patients and those with high
ASA states showed the highest increase in anaesthesiology activity throughout all
groups, when data for 1980 were compared with 1996 figures. Herniorrhaphy, cataract
surgery, transurethral extraction of the prostate, cholecystectomy and surgery for
reduction of the fractured hip were the most frequently performed surgical procedures
with need for anaesthesia in the geriatric patient.9
It has been demonstrated that elective surgery can be performed in patients aged
90 and older in ASA physical state 2 or 3 with relatively low mortality rates.10
Existing surgical thresholds for conducting high-risk surgerysuch as transplant
surgery, cardiovascular surgery and radical tumour removaltend to be further
withdrawn in the future, and providers of anaesthesia and critical care will be challenged
to develop methods of perioperative care and safety for the elderly receiving high-risk
surgical procedures.
Assessing the geriatric patient
Ageing is not an illness11 but an independent risk-factor of morbidity and mortality, and
it has been shown to be an independent predictor of perioperative outcome, too.12
It is broadly accepted in paediatric anaesthesia that children cannot be looked at as
small adults. Similarly, anaesthesia for the elderly has to take into account the specific
physiology of the aged that develops naturally during the course of life. Therefore, not all
physiological changes of ageing should be looked at as pathological entities because they
may be completely compensated for in normal life and their potentially pathological

1910

1999

2050

Age 95

Age 95

85

85

85

75

75

75

65

65

65

55

55

55

45

45

45

35

35

35

25

25

25

15

15

15

Men

Women
64.9 Mio Inhabitants

81,0 Mio

70,0 Mio

Figure 1. Demographic changes in Germany. The age pyramid of 1910 will nearly invert to the shape of a mushroom in 2050 (German Federal Bureau of Statistics 2000).

Pathophysiological changes in the elderly 165

Age 95

166 P. H. Tonner et al

character is revealed only in extreme conditions. For example, the disability of the elderly
to increase heart rate appropriately in order to maintain cardiac output may not have
relevance in normal life in that no excessive physical efforts are made, but it will be highly
relevant to induce circulatory breakdown in case of hypovolaemia due to blood loss or
due to vasodilatation in spinal anaesthesia.13,14 Discrepancies between chronological and
biological age are frequently found and may vary between organ systems of the same
individual. Thus, in assessing the impact of advanced age on perioperative mortality and
morbidity, all patients over 65 years should not be classified together as elderly.9,15 To
adjust anaesthesiological management for the elderly with regard to individual
pathophysiological changes related to ageing, it is necessary to examine patients with
regard to the specific organ systems that are of special relevance for the anaesthetist16,17
and may directly change the individual anaesthetic approach to care safely for the old.

THE CARDIOVASCULAR SYSTEM

Heart
Age-related cardiovascular morbidity and mortality has been determined to be the
main contributor in cases of overall adverse perioperative outcome.18
Cardiovascular reserve is strongly affected by ageing. Stress factorssuch as
increased flow demand by physical exercise, or post-operative demand due to acute
autonomic reflex control (e.g. change of posture) or severe disease with hyperdynamic
response (myocardial ischaemia, tachyarrhythmia, uncontrolled hypertension)may
induce a rapid decompensation of cardiac performance even in subjects who are not
apparently compromised by prevalent age-related changes.19 Steady increment of
blood pressure with age is associated with thickening of elastic fibres in large arterial
vessels that lose their compliance to blood pressure changes during the pulse wave
pattern.20 A left-ventricular hypertrophy frequently evolves during the course of life in
adults and may be related to a chronically elevated left-ventricular afterload due to the
increased peripheral vascular resistance. This concentric hypertrophy is a result of
the increased size of cardiac myocytes.21
It is suspected that interstitial fibrosis in the myocardium leads to loss of
contractility associated with an increased diastolic and systolic stiffness of the
ventricular wall. Stiffening of the myocardium affects diastolic relaxation as well as
systolic contraction of the aged heart. Late augmentation of aortic impedance due to
an early reflected pulse wavebecause of low vascular compliance and left-ventricular
hypertrophyleads to a prolonged systolic myocardial contraction. This may be an
adaptation to maintain left-ventricular pump function, but left-ventricular relaxation
time is delayed at the time of mitral valve opening. Therefore, the early diastolic
filling rate declines to half of its value by the age of 80 compared to the age of 20.20
Late diastolic filling is increased in a partly compensatory manner in order to maintain
end-diastolic volume and stroke volume.22 The age-related increase in left-atrial
volume and the enhanced contribution of atrial contraction to late diastolic filling
reflects the importance of atrial function in the aged heart.23,24 Therefore, with
advancing age, stable haemodynamic conditions depend on sinus rhythm, and atrial
fibrillation may strongly affect cardiac output.25
Ventricular eccentric hypertrophy and loss of wall tension may lead to valve closure
deficiency with consecutive loss of cardiac output due to systolic regurgitation of blood
through the mitral or aortic valve.

Pathophysiological changes in the elderly 167

Cardiac output is known to decrease in an almost linear manner after the third
decade of life with a rate of about 1% per year in healthy individuals without prevalent
cardiac disease. The cardiac index decreases at a rate of approximately 0.8% per year
due to the fact that body surface area becomes slightly smaller with age. Roughly, an
80-year-old man will have 50% of cardiac output compared to the one he used to have
at the age of 20.9
Vasculature
Ageing of the vascular system mainly appears as alteration of the endothelial and muscle
tissue of the vasculature, commonly summarized as arteriosclerotic damage.
Development of arteriosclerosis is a progressive process affected by many contributing
factors. Hypertension, hypercholesterolaemia and oxidative stress are detectable
parameters, whereas the impact of genetic disposition needs to be elucidated.
Arteriosclerosis is an irreversible process so that the feasibility of arteriosclerotic
pathologysuch as aneurysm, arterial occlusion and organ ischaemiais cumulative
with age.26
Carotid endarterectomy (for high-grade carotid artery stenosis) and abdominal
aortic aneurysm repair are the most frequently performed procedures of vascular
surgery beyond the age of 80 and have been shown to be safe and effective
procedures even in the very old.27 Cardiac surgery at the age of 80 or older has also
been shown to be beneficial for people in advanced age with respect to overall
survival and improvement in quality of life.28
Adrenergic sensitivity
Cardiac response is influenced not only by anatomical changes but also by changes in
sensitivity of the aged to adrenergic stimulation. Plasma catecholamine levels after
exposure to external stimuli have not been demonstrated to diminish with age.29
Whether the overall density of beta-adrenergic receptors decreases with age is still a
matter of debate, but the blunted beta-adrenoceptor responsiveness indicates
a decrease in affinity of the adrenergic transmitter towards these receptors.30
The mechanism for the decline in beta-adrenergic sensitivity has not yet been
determined exactly. Down-regulation and decreased agonist binding of adrenoceptors
might occur as an effect of the increased plasma levels of adrenalin (norepinephrine) in
the elderly.31,32 Additionally, other age-related contributing factors have been
discussed, such as alterations in adrenoceptor density33,34 and post receptor effects
induced by changes in signal transduction.35 Catecholamines will find a decreased
maximum responsiveness in increasing heart rate in the elderly.33,34,36,37 These changes
may be reflected by a 20% loss of heart rate response during dynamic exercise when a
75-year-old man is compared to a 25-year-old.
Parasympathetic system
Change in vagal tone seems to play another important role in the physiological changes
of advanced age, as in the elderly the inability to decrease cardiac vagal tone below
an already reduced baseline level has been suspected to be responsible for a
reduced tachycardic response to isometric exercise in a study using highfrequency heart rate variability.38 Respiratory sinus arrhythmia diminishes with

168 P. H. Tonner et al

advancing age, providing further evidence for attenuated parasympathetic influence

in the elderly.39,40
Influence of gender on beta-adrenergic response
An interesting issue of beta-adrenergic physiology in the aged concerns gender-related
differences in adaptation to endurance training. Beta-adrenergic-mediated cardiovascular response is known to be enhanced in young endurance athletes.41 Accordingly,
aerobic power (measured as maximal oxygen consumption), echocardiographically
registered left-ventricular function pattern, cardiac output and stroke volumeat rest
and in response to beta-adrenergic pharmaceutical stimulationhave been observed
to increase as a response to training in older men.42 In contrast, in women, the effect of
training showed a marked increase in maximum oxygen consumption, but no cardiac
adaptation in left-ventricular function, cardiac output or stroke volume. Increased
aerobic power in women was due to adaptations only in skeletal muscles.43 It has been
concluded that beta-adrenergic cardiac sensitivity does not change and that there is
no increase in left-ventricular function in response to endurance training in
post-menopausal women.
Nevertheless, vigorous aerobic exercise training is effective to elevate levels of
muscle sympathetic nerve activity and enhanced response to acute stress in healthy
older women and men.44

THE RESPIRATORY SYSTEM

Changes in volumes
Ageing is characterized by a loss of elastic recoil of the lungs and impaired thoracic
movement for inducing intrathoracic volume changes, resulting in a shift of the
pressure volume curve to the left.45 Static lung compliance increases with age, whereas
dynamic compliance becomes more frequency dependent. Airway conductance is not
altered by ageing.46
The total lung capacity is not subject to change during the course of life, but it is
important to note changes of functional volumes reflected by residual volume and vital
capacity: the residual volume of a 20-year-old will increase from 20% to almost 40% by
the age of 65, marking an increase in lung volumes that will not be ventilated during
normal breathing. Concomitantly, the vital capacity diminishes with age. Small airway
closure volume increases in the elderly. The amount of trapped air due to small
airway closure may exceed the functional residual volume at rest in the supine position
and even during tidal breathing.47 Thus, the increased anatomical and functional
dead-space ventilation fraction reduces the efficacy of carbon dioxide elimination.
Changes in flow rates
General loss of lung elasticity, calcification of costochondral cartilage, stiffening of the
costovertebral joints and progressive weakening of auxiliary musculature of ventilation
affect flow rates in the geriatric patient.48 The forced exhaled volume (FEV) in second 1
and the midmaximal expiratory flow rates decrease progressively with ageing. A 70%
ratio of FEV to total lung capacity is a normal finding at the age of 70, whereas in young
adults it is commonly found to be at least 80% or higher. Thus, the total work of

Pathophysiological changes in the elderly 169

breathing increases and ultimately limits the maximum breathing capacity at the age of
70 to one-half of that at the age of 30.
Oxygenation
The decreased efficacy of arterial oxygenation is reflected by an almost linear loss of
oxygen partial pressure in arterial blood after the age of 20. The alveolar partial pressure
of oxygen (PAO2) remains constant throughout life, but the mean arterial partial
pressure of oxygen (PaO2) is reduced by a rate of approximately 0.31 mmHg/year.
The inverse relationship between PaO2 and age is reflected by the formula
PaO2 102 2 (0.498 age).49 Reduced cardiac output contributes to this as well as
increasing airway closure volumeleading to a mismatch in the ventilation-to-perfusion
ratio. Another contributing factor is the overall reduced surface area for gas exchange,
as the parenchymal integrity of the lung is progressively deteriorated with ageing, when
alveolar membranes are disintegrated or thickened.50 As a result, the alveolar-to-arterial
gradient of oxygen partial pressure increases with ageing and the arterial oxygen content
and saturation of haemoglobin are reduced. There is no significant change in
arterial carbon dioxide tension.48 In spite of these numerous and variable changes,
the lung is capable of maintaining adequate gas exchange throughout our lifetime,
although ageing diminishes the functional reserve of the respiratory system during acute
exertion. The overall decreased sensitivity of respiratory centres to hypoxia and
hypercapnia leads to a diminished or delayed ventilatory response to heart failure,
infection or aggravated airway obstruction in the elderly.48

THE METABOLIC SYSTEM

Kidneys
The kidneys are characterized by a progressive reduction of renal mass with ageing due
to glomerulosclerosis, paralleled by thickening of the vascular intima, fibrosis of the
stoma and chronic infiltration by inflammatory cells. Glomerulosclerosis results in a
decline in renal plasma flow (RPF) and glomerular filtration rate (GFR).51 Because GFR
diminishes less than RPF, the filtration fraction increases to a state of hyperfiltration
that, to some extent, represents a mechanism for adaptation to the overall reduced
number of functioning glomeruli. Consequently, the intraglomerular pressure rises,
possibly accelerating glomerulosclerotic deterioration of the renal parenchyma.52
Additionally, the progressive decrease in cardiac output with advancing age affects RPF
and GFR. The fluid state is susceptible to overload, and substances and drugs that
depend on renal clearance may be subject to cumulation. Therefore, drug-induced
acute renal failure is frequently observed in the elderly after administration of nonsteroidal anti-inflammatory agents, antibiotics and diuretics.53 The plasma level of
creatinine often may not reflect renal dysfunction properly because the overall reduced
skeletal muscle mass of aged people produces less creatinine. Nevertheless, the
creatinine clearance can be used for estimation of glomerular filtration rate and is the
most important renal function to monitor.53 Concentration ability is another sensitive
marker for renal function. Even with lack of fluids the aged patient shows a reduced
capability to concentrate, and the ability to excrete an acid load diminishes.
Reduced sodium intake due to insufficient or imbalanced nutrition may induce low
sodium plasma levels, but impaired renal sodium conservation is the main reason for

170 P. H. Tonner et al

disturbed electrophysiological excitation and cardiac conduction.25 The age-associated

decline in renal function may be determined by impaired glucose tolerance due to
essential hypertension and diabetes mellitus, representing the two most important risk
factors for chronic renal failure in the elderly.54
Liver
Metabolism of drugs dependent on hepatic elimination will be affected by reduced
hepatic blood flow that parallels reduced cardiac output, although the size of the liver
allows a wide margin of functional reserve.55,56 There is a lack of correlation between
structural and functional data concerning the ageing liver57, as a decline in organ volume
does not necessarily reflect impaired metabolic function. Nevertheless, a reduced in
vivo and in vitro metabolic capacity resulting in a reduced hepatic drug clearance is a
common finding in the elderly.
Body composition and energy expenditure
Body composition changes with ageing. Abdominal fat mass and obesity is often
increased and may contribute to the increased prevalence of type-2-diabetes and
cardiovascular disease among the elderly.58 Patterns of energy expenditure may be
associated with ageing and it has been determined that resting metabolic rate declines
with age.59 63
Heat production per square metre of body surface area decreases steadily until the
start of puberty because of changes in the body surface-to-weight ratio taking place
during that time. Energy expenditure is documented to decrease gradually as
age increases, with a rate of decline of about 1 or 2% per decade from the age of 20
to 80.64 The metabolic rate of a newborn infant will be about 53 kcal/m2/height, with
age 20 less than 40 kcal/m2/height (about 38 in men and 35 in women) and by the age
of 70 it has declined to about 33 kcal/m2/height in men and 31 kcal/m2/height in women.
Levels of circulating adrenaline (norepinephrine) reflect an increased basal
sympathetic activity in the aged65 68 but the sympathetically induced metabolic
response is blunted with ageing. It has been hypothesized that the decline in dietinduced thermogenesis in old subjects may be related to the well documented
diminished sympathetic nervous system activity.67 Beta-adrenoceptors have been
identified to be involved in the sympathetically mediated thermogenesis that has been
found to diminish in old men and referred to a diminished beta-adrenergic sensitivity.69
This blunted thermogenic response may be an explanation for increased fat storage and
obesity in the elderly due to a resulting positive energy balance.
Metabolic response to trauma and surgery
The neural arc in the development of the metabolic response to surgery and trauma
was demonstrated by a classic experiment of Hume and Egdahl.70 Division of afferent
fibres from the site of an injury suppressed development of the adrenocortical
response. Several studies demonstrated the impact of peripheral blockage by epidural
anaesthesia71 and opioids.72
Age-related changes in the metabolic system seem to play an important role in the
altered neuroendocrine response of geriatric patients towards surgery and trauma.
On this issue the hypothalamic pituitary adrenal axis is of special interest. An early

Pathophysiological changes in the elderly 171

ebb phase immediately after traumatic injury, when there is increased fuel production
and enforced activity of the sympathoadrenergic and hypothalamic pituitary response,
is followed 24 48 hours later by a flow phase, characterized by fuel use, catabolism and
high metabolic rates.73 Increased plasma levels of cortisol have been reported 2 weeks
after trauma, but still the mediating stimulus is unclear as neither precursor peptides
nor adrenocorticotropic hormone were found with increased levels. The sensitivity
towards adrenocorticotropic hormone is unchanged in the aged, despite a defective
feedback inhibition generated previously.74
Glucose metabolism
Glucose metabolism is another important issue in the geriatric response to trauma.
Plasma glucose levels have been reported to be higher in patients than in a matched-pair
control group of volunteers without trauma.75 Basal secretion of insulin was similar
between patients and volunteers, but was significantly higher in the young when
different age groups were compared. Ageing was also associated with glucose
intolerance and a longer time-to-response to glucose administration. Therefore,
control of hyperglycaemia by administration of insulin would possibly be beneficial for
the geriatric trauma patient in order to blunt the catabolic effects of physiologically
increased stress hormones.

THE NERVOUS SYSTEM

Drug therapy
Ageing of the nervous system is characterized by a general loss of neuronal substance.
The most obvious sign is a reduced average brain weight in the elderly; brain weight was
reported to be 1375 g at age 20 and 1200 g at age 80.76 The number of peripheral
neurons also decreases, and muscles become innervated, overall, by fewer axons,
possibly leading to denervation atrophy. A particular neuromuscular junction is not
functionally changed with ageing. The plasma concentration of pancuronium required
to induce a certain degree of depression in neurophysiological monitoring was
determined to be the same in old and young subjects77, but with a trend towards
reduced clearance and prolonged elimination half-life in the elderly compared to the
young. Conduction velocity is slightly affected by ageing and tends to become slower.78
The overall loss of neuronal substance and decreased synaptic activity may be one
explanation for the higher susceptibility of the elderly to drugs that interact with
the peripheral or central nervous system. Epidural anaesthesia has been reported to be
achieved with dose requirements that decrease in an almost linear manner with age;
theoretically, a 137-year-old would not need any local anaesthetic at all.79 The minimal
alveolar concentration (MAC) for volatile anaesthetics also decreases steeply with
ageing.80 Neither local anaesthetics nor volatile anaesthetics seem to interact
with specific receptors. Thus, decreased cell density, lower cerebral oxygen
consumption and lower cerebral blood flow with an overall reduced turnover are
part of the explanation for lower dose requirements in elderly patients.
Several studies have demonstrated that elderly patients have an increased sensitivity
to opioid analgesics. It was determined by electroencephalography (EEG) that the most
important difference is an increase in pharmacodynamic sensitivity in the elderly subject
compared to the young.81 Changes in opioid disposition with ageing, such as decreased

172 P. H. Tonner et al

plasma clearance and decreased volumes of distribution, were found to play a minor
role.82
The dose requirements of remifentanil were found to be lower in the
elderly, possibly due to reduced esterase activity. An 80-year-old person requires
approximately one-half of the dose of a 20-year-old to reach the same EEG effect.83
Thus, compared to young subjects, elderly patients will need lower opioid
concentrations for an equal analgesic effect and lower loading doses for equal plasma
levels, and they will eliminate opioids more slowly than young subjects.
Cognitive dysfunction
Mental capabilities may be compromised in the elderly by age-related disease or
drug therapy. Almost any kind of medical treatmentbut especially invasive
proceduresmay lead to loss of cognitive function. There is an enhanced susceptibility
in old people to delirium as a reaction to physical illness of any kind or even to
therapeutic dosage of drugs.84,85 Delirium has to be distinguished from dementia and
Alzheimer disease because delirium usually does not extend for a period of 1 month.
The validity of written informed consent has been demonstrated to be adversely
affected by old age, but cognitive impairment reduced the recall of information only
during hospital stay.86
When a patient is known to have reduced mental capabilities of a certain degree,
general anaesthesia is often suspected to deteriorate this condition. The term early
post-operative cognitive dysfunction (POCD) summarizes a variety of non-specific
symptoms such as confusion and delirium, transient fluctuation of consciousness or
mood. POCD has been shown to be particularly more common in elderly patients after
orthopaedic surgery.87,88 POCD may last from several days to several weeks and it
contributes to increased perioperative morbidity and prolonged hospital stay.
The development of early POCD is affected by co-factors such as poor educational
and social background, repeated surgical procedures and complications, but age has
been shown to be the only major risk factor for late POCD in a long-term
post-operative study that included patients after major abdominal and orthopaedic
surgery.89 Hypoxaemia and hypotension did not play a role in causing POCD, and even
prevalent depression had no impact on post-operative cognitive impairment.
General anaesthesia itself was not determined to be a risk factor for an accelerated
age-related cognitive decline in a cross-sectional retrospective population study.90 Up to
now it is not clear whether the susceptibility to late POCD is associated with the
development of structural irreversible brain damage and how prevalent age-related
changes of the central nervous system might interact with other predisposing factors.91

THE LOCOMOTIVE SYSTEM

Shrinkage of body height with ageing occurs because of the tendency of the cervical and
thoracal spine towards hyperlordosis due to atrophy of the muscle groups of the back
that usually erect the spine. Additionally, there is a reduction in height of the
intervertebral discs due to changes in collagen content and architecture which add up
to a reduction in height of about 5 to 7 cm when comparing age 20 with age 70; this
occasionally increases the technical difficulties of spinal anaesthesia.92 Osteoporosis is
a common finding among older women, as bone composition and potassium content

Pathophysiological changes in the elderly 173

are affected by low levels of oestrogen. This contributes to structural weakness as well
as remodelling of the bone spongiosa due to inactivity.
Decline in strength, and atrophy, of skeletal muscles is associated with advancing age
in humans.93,94 These changes relate mainly to the loss of motor units (MU), as about
one-half the MU comprising the thenar muscle in healthy subjects have been counted in
subjects aged 60 80 years compared with subjects aged 20 40 years95; this has also
been demonstrated for other peripheral muscles.96 Muscular strength is reduced in an
age-related manner.97 The loss of nearly one-half of the MU is partially compensated by
collateral sprouting from surviving motor axons to re-innervate previously denervated
muscle fibres98,99, leading to the finding of an increased size of the MU action
potential.100 Thus, old subjects have larger MU twitch tensions in electromyographic
stimulation, slower MU twitch contraction speed and longer relaxation times.78
Therefore, the age-related loss of MU is accompanied by partial adaptation, and the
reduction in muscle strength and mass with ageing may be attributed mainly to inactivity,
although the question of whether these adaptations affect all MU to the same extent
regardless of their original physical type and originhas not yet been answered.

CONCLUSION
Old age can be characterized as a continuation of life with decreasing capacities for
adaptation.101 Changes in organ function may not be apparent in normal life, but may be
revealed by narrowed margins of reserve to unusual exertion during surgery and
anaesthesia. This is also true for the care-givers of anaesthesia themselves; although, in
general, physicians tend to deny issues involving their own ageing, 80% of
anaesthesiologists older than 50 were reported to have already planned their
retirement.102 This may be due to discernment that the margins of reserve required
to keep up an adequate level of vigilance, to perform complex tasks rapidly, to adapt to
changing conditions, to process and evaluate incoming information, to make complex
decisions under pressure of time and to perform effectively in a stressful environment103
will be affected by their own ageing. However, the anaesthesiologists performance in the
operating theatre relies on skills that are based primarily on experience and judgement,
which often allows older professionals to compensate for any cognitive deterioration
and gives them a definite advantage over their younger colleagues. Experience and
wisdom fail to compensate only in advanced stages of cognitive impairment, as seen in
Alzheimer disease.104
Research agenda
determine the impact of genetic disposition on the development of
arteriosclerotic damage
elucidate the mechanism for the decline in beta-adrenergic sensivity in the
elderly
elucidate the mechanism for the decreased sensitivity of respiratory centres to
hypoxia and hypercapnia in the elderly
examine the association of postoperative cognitive dysfunction with prevalent
age-related brain damage
determine the extent of motor unit adaptation (collateral sprouting of surviving
axons) with regard to physical type and origin

174 P. H. Tonner et al

Practice points
age is not an illness, but an independent risk factor of morbidity and mortality
age alone is not a contraindication for surgery or anaesthesia
assessment of individual margins of organ function reserve is of greater
importance than the listing of current diseases
REFERENCES
1. Schneider EL. Aging in the third Millennium. Science 1999; 283: 796797.
2. World Health Organization, The World Health Report : Life in the 21st Century a Vision for All. Geneva:
World Health Organization, 1998.
3. Rooke GA, Reves G & Rosow C. Anesthesiology and geriatric medicine. Anesthesiology 2002; 96: 24.
4. US Bureau of Census, Statistical Abstracts of the United States, 13th edn. Washington, DC: Department of
Commerce, 1993.
5. Day JC. Population Projection of the United States by Age, Sex, Race and Hispanic Origin, 1995 to 2050.
Current Population Report, Bureau of the Census, p. 25. Washington, DC: US Printing Office, 1996.
6. Veering BT. Management of anaesthesia in elderly patients. Current Opinion in Anaesthesiology 1999; 12:
333336.
7. Klopfenstein CE, Herrmann FR, Michel JP et al. The influence of an ageing surgical population on the
anaesthesia workload: a ten-year survey. Anaesthesia and Analgesia 1998; 86: 11651170.
* 8. Clergue F, Auroy Y, Pequinot F et al. French survey of anaesthesia in 1996. Anesthesiology 1999; 91:
15091520.
9. Musunuru VS. The geriatric patient. In Stoelting RK & Dierdorf SF (eds) Anaesthesia and Co-existing Disease.
New York: Churchill Livingstone, 1983.
10. Burns-Cox N, Campbell WB, Van Nimmen BAJ et al. Surgical care and outcome for patients in their
nineties. British Journal of Surgery 1997; 84: 496498.
11. International Classification of Diseases, 10th Revision. Geneva: World Health Organization, 1992.
12. Kazmers A, Perkins AJ & Jacobs LA. Outcomes after abdominal aortic aneurysm repair in those . than 80
years of age. Recent Veterans Affairs experience. Annals of Vascular Surgery 1998; 12: 106 112.
13. Rooke GA, Freund PR & Jacobson AF. Hemodynamic response and change in organ blood volume during
spinal anaesthesia in elderly men with cardiac disease. Anaesthesia and Analgesia 1997; 85: 99 105.
14. Lim HH, Ho KM, Choi WY et al. The use of intravenous atropine after a saline infusion in the prevention
of spinal anaesthesia-induced hypotension in the elderly. Anaesthesia and Analgesia 2000; 91: 12031206.
15. Polanczyk CA, Marcantonio E, Goldman E et al. Impact of age on perioperative complications and length
of stay in patients undergoing noncardiac surgery. Annals of Internal Medicine 2001; 134: 637643.
16. Thomas DR & Ritchie CS. Preoperative assessment of older adults. Journal of the American Geriatric Society
1995; 43: 811821.
17. Rady MY, Ryan T & Starr NJ. Perioperative determinants of morbidity and mortality in elderly patients
undergoing cardiac surgery. Critical Care Medicine 1998; 26: 225 235.
18. Mangano DT. Perioperative cardiac morbidity. Anesthesiology 1990; 72: 153184.
* 19. Priebe HJ. The aged cardiovascular risk patient. British Journal of Anaesthesia 2001; 86: 897898.
20. Lakatta EG. Changes in cardiovascular function with aging. European Heart Journal 1990;
11(supplement C): 2229.
21. Olivetti G, Melissari M, Capasso JM & Anversa P. Cardiomyopathy of the aging human heart. Myocyte loss
and reactive cellular hypertrophy. Circulation Research 1991; 68: 15601568.
22. Lakatta EG. Cardiovascular aging research: the next horizons. Journal of the American Geriatric Society 1999;
47: 613625.
23. Gardin JM, Arnold AM, Bild ED et al. Left ventricular diastolic filling in the elderly: the cardiovascular
health study. American Journal of Cardiology 1998; 82: 345351.
24. Klein AL, Leung DY, Murray RD et al. Effects of age and physiologic variables on right ventricular dynamics
in normal subjects. American Journal of Cardiology 1999; 84: 440 448.
25. Amar D, Hao Z, Leung DHY et al. Older age is the strongest predictor of postoperative atrial fibrillation.
Anesthesiology 2002; 96: 352356.
26. Alexander KP, Peterson ED & Durham MPH. Coronary artery bypass grafting in the elderly.
American Heart Journal 1997; 134: 856864.
27. Wong DT, Ballard JL & Killeen JD. Carotid endarterectomy and abdominal aortic aneurysm repair:
are these reasonable treatments for patients over age 80. American Journal of Surgery 1998; 64: 9981001.

Pathophysiological changes in the elderly 175

28. Kolh P, Kerzmann A, Lahaye L et al. Cardiac surgery in octogenariansperi-operative outcome and
long-term results. European Heart Journal 2001; 22: 1235 1243.
29. Kudoh A, Katagai H & Takazawa T. Endocrine response to surgical stress in three patients over 100 yr.
Canadian Journal of Anaesthesia 2001; 48: 340343.
30. White M, Roden R, Minobe W et al. Age-related changes in beta-adrenergic neuroeffector systems in the
human heart. Circulation 1994; 90: 12251238.
31. van Zwieten PA. Pharmacological backgrounds of hypertension in the elderly. Blood Pressure 1995; 4:
1520.
32. Montamat SC & Davies AO. Physiological response to isoproterenol and coupling of beta-adrenergic
receptors in young and elderly human subjects. Journal of Gerontology 1989; 44: M100M105.
33. Fitzgerald D, Doyle V, Kelly JG & OMalley KO. Cardiac sensitivity to isoprenaline, lymphocyte
beta-adrenoceptors and age. Clinical Science 1984; 66: 697699.
34. Heinsimer JA & Lefkowitz RJ. The impact of aging on adrenergic receptor function: clinical and
biochemical aspects. Journal of the American Geriatric Society 1986; 33: 184188.
35. Feldman RD, Tan CM & Chorazyczewski J. G-protein alterations in hypertension and aging. Hypertension
1995; 25: 725 732.
36. Colangelo PM, Blouin RA, Steinmetz JE et al. Age and beta-adrenergic receptor sensitivity to S(2) and R,S
( /2)-propranolol in humans. Clinical Pharmacological Therapy 1992; 51: 549 554.
37. Vestal RE, Wood AJJ & Shand DG. Reduced beta-adrenoceptor sensivity in the elderly.
Clinical Pharmacological Therapy 1979; 26: 181186.
* 38. Taylor JA, Hayano J & Seals DR. Lesser vagal withdrawal during isometric exercise with age. Journal of
Applied Physiology 1995; 79: 805811.
39. Ebert TJ, Morgan BJ, Barney JR et al. Effects of aging on baroreflex regulation of sympathetic activity in
humans. Journal of Applied Physiology 1992; 263: H798H803.
* 40. Kuo TBJ, Lin Yang CH, Li CL et al. Effect of aging on gender differences in neural control of heart rate.
Journal of Applied Physiology 1999; 277: H2233H2239.
41. Hopkins MG, Spina RJ & Ehsani AA. Enhanced beta-adrenergic-mediated cardiovascular response in
endurance athletes. Journal of Applied Physiology 1996; 80: 516 521.
42. Spina RJ, Ogawa T, Kohrt WM et al. Differences in cardiovascular adaptations to endurance exercise
training between older men and women. Journal of Applied Physiology 1993; 75: 849855.
43. Spina RJ, Rashid S, Davilla-Roman VG & Ehsani AA. Adaptations in beta-adrenergic cardiovascular
responses to training in older women. Journal of Applied Physiology 2000; 89: 23002305.
44. Ng AV, Callister R, Johnson DG & Seals DR. Endurance exercise training is associated with elevated basal
sympathetic nerve activity in healthy older humans. Journal of Applied Physiology 1994; 77: 13661374.
45. Yernault JC, DeTroyer A & Rodenstein D. Sex and age differences in intrathoracic airways mechanics in
normal man. Journal of Applied Physiology 1979; 46: 556 564.
46. Berry RB, Pai UP & Fairshter RD. Effect of age on changes in flow rates and airway conductance after a
deep breath. Journal of Applied Physiology 1990; 69: 635643.
47. Muravchick S. Anaesthesia for the elderly. In Miller RD (ed.) Anesthesia, 5th edn. Philadelphia:
Churchill Livingstone, 2000.
* 48. Janssens JP, Pache JC & Nicod LP. Physiological changes in respiratory function associated with ageing.
European Respiration Journal 1999; 13: 197205.
49. Wahba WM. Body build and preoperative arterial oxygen tensions. Canadian Anaesthesiological Society
Journal 1975; 22: 653658.
50. Auerbach O, Hammond EC & Garfinkel L. Thickening of walls of arterioles and small arteries in relation
to age and smoking habits. New England Journal of Medicine 1968; 278: 980984.
51. Fliser D, Zeier M, Nowack R & Ritz E. Renal functional reserve in healthy elderly people. Journal of the
American Society of Nephrology 1993; 3: 13711377.
52. Anderson S & Brenner BM. Effects of aging on the renal glomerulus. American Journal of Medicine 1986; 80:
435442.
53. Muhlberg W & Platt D. Age dependent changes of the kidneys: pharmacological implications.
Gerontology 1999; 45: 243253.
54. Ribstein J, DuCailar G & Mimran A. Glucose tolerance and age-associated decline in renal function of
hypertensive patients. Journal of Hypertension 2001; 19: 22572264.
55. Seaman DS. Adult living donor liver transplantation: current status. Journal of Clinical Gastroenterology
2001; 33: 97 106.
56. Ettore GM, Sommacale D, Farges O et al. Postoperative liver function after elective right hepatectomy in
elderly patients. British Journal of Surgery 2001; 88: 7376.
57. Zeeh J & Platt D. The aging liver: structural and functional changes and their consequences for drug
treatment in old age. Gerontology 2002; 48: 121127.

176 P. H. Tonner et al
58. Fielding RA. The role of progressive resistance training and nutrition in the preservation of lean body
mass in the elderly. Journal of the American College of Nutrition 1995; 14: 587594.
59. Fukugawa NK, Bandini LG & Young JB. Effect of age on body composition and resting metabolic rate.
Journal of Applied Physiology 1990; 22: E233E238.
* 60. Poehlmann ET, Goran MI, Gardner AW et al. Determinants of decline in resting metabolic rate in aging
females. Journal of Applied Physiology 1993; 27: E450 E455.
61. Poehlmann ET & Horton ES. Regulation of energy expenditure in aging humans. Annual Review of Nutrition
1990; 10: 255275.
62. Ravussin E & Bogardus C. Relationship of genetics, age and physical fitness to daily energy expenditure and
fuel utilization. American Journal of Clinical Nutrition 1989; 49: 968 975.
63. Roberts SB, Fuss P, Heyman MB & Young VR. Influence of age on energy requirements. American Journal of
Clinical Nutrition 1995; 62: 1053S1058S.
64. Wilmore DW. The Metabolic Management of the Critically Ill., pp 28. New York: Plenum, 1977.
* 65. Feldmann RD, Limbird LE, Nadeau J et al. Alterations in leukocyte beta-receptor affinity with ageing:
a potential explanation for altered beta-adrenergic sensitivity in the elderly. New England Journal of
Medicine 1984; 310: 815819.
66. Schwartz RS, Jaeger LF & Veith RC. The importance of body composition to the increase in plasma
norepinephrine appearance in elderly men. Journal of Gerontology 1987; 42: 546 551.
67. Schwartz RS, Jaeger LF & Veith RC. The thermic effect of feeding in older men: the importance of the
sympathetic nervous system. Metabolism 1990; 39: 733737.
68. Lonnkvist F, Nyberg H, Wahrenberg H & Arner P. Catecholamine-induced lipolysis in adipose tissue of the
elderly. Journal of Clinical Investigation 1990; 85: 16141621.
69. Kerckhoffs DAJM, Blaak EE, van Baak M & Saris WHM. Effect of ageing on beta-adrenergically mediated
thermogenesis in men. Journal of Applied Physiology 1998; 274: E1075E1079.
70. Hume RJ & Egdahl RH. The importance of the brain in the endocrine response to trauma. Annals of Surgery
1959; 150: 697.
71. Kehlet H, Brandt MR, Hansen AP & Alberti KG. Effect of epidural analgesia on metabolic profiles during
and after surgery. British Journal of Surgery 1979; 66: 534.
72. Walsh ES, Paterson JL, ORiordan JB et al. Effect of high dose fentanyl on the metabolic and endocrine
response to cardiac surgery. British Journal of Anaesthesiology 1981; 53: 1155.
73. Silverstein JH & McClesky CH. Geriatric trauma. Current Opinion in Anaesthesiology 1996; 9: 194 197.
74. Horan MA. Aging, injury and the hypothalamic-pituitary-adrenal-axis. Annals of the New York Academy of
Sciences 1994; 719: 285 290.
75. Watters JM, Moulton SB, Clancy SM et al. Aging exaggerates glucose intolerance following injury. Journal of
Trauma 1994; 37: 786791.
76. Brody H. The aging brain. Acta Neurologica Scandinavica 1992; 137(supplement): 40 44.
77. Rupp SM, Castagnoli KP, Fisher DM & Miller RD. Pancuronium and vecuronium pharmacokinetics and
pharmacodynamics in younger and elderly adults. Anesthesiology 1987; 67: 45 49.
78. Doherty TJ & Brown WF. Age-related changes in the twitch contractile properties of human thenar
motor units. Journal of Applied Physiology 1997; 82: 93 101.
79. Bromage PR. Ageing and epidural dose requirements. Segmental spread and predictability of epidural
analgesia in youth and extreme age. British Journal of Anaesthesia 1969; 41: 10161022.
80. Eger EL II. Age, minimum alveolar anesthetic concentration and minimum alveolar anesthetic
concentration-awake. Anaesthesia and Analgesia 2001; 93: 947 953.
81. Macintyre PE & Jarvis DA. Age is the best predictor of postoperative morphine requirements. Pain 1996;
64: 357364.
82. Scott JC & Stanski DR. Decreased fentanyl and alfentanil dose requirements with age: a simultaneous
pharmacokinetic and pharmacodynamic evaluation. Journal of Pharmacology and Experimental Therapy 1987;
240: 159 166.
83. Minto CF, Schnider TW, Egan TD et al. Influence of age and gender on the pharmakokinetics
pharmakodynamics of remifentanil, I: model development. Anesthesiology 1997; 86: 1023.
84. Schor JD, Levkoff SE, Lipsitz LA et al. Risk factors for delirium in hospitalized elderly. Journal of the American
Medical Association 1992; 267: 827 831.
85. Parikh SS & Chung F. Postoperative delirium in the elderly. Anaesthesia and Analgesia 1995; 80:
12231232.
86. Lavelle-Jones C, Byrne DJ, Rice P & Cuschieri A. Factors affecting quality of informed consent.
British Medical Journal 1993; 306: 885890.
87. Gustafson Y, Beggren D, Banstom B et al. Acute confusional states in elderly patients treated for femoral
neck fracture. Journal of the American Geriatric Society 1988; 36: 525530.
88. Williams-Russo P, Urquhart RN, Sharrock NE & Charison ME. Postoperative delirium: predictors and
prognosis in elderly orthopedic patients. Journal of the American Geriatric Society 1992; 40: 759767.

Pathophysiological changes in the elderly 177

* 89. Moller JT, Cluitmans P, Rasmussen LS et al. Long-term postoperative cognitive dysfunction in the elderly:
ISPOCD 1 Study. Lancet 1998; 351: 857 861.
90. Dijkstra JB, van Boxtel MPJ, Houx PJ & Jolles J. An operation under general anaesthesia is a risk factor for
age-related cognitive decline: results from a large cross-sectional population study. Journal of the American
Geriatric Society 1998; 46: 12581265.
91. Newman MF, Kirchner JL, Phillips-Bute B et al. Neurological Outcome Research Group of the Duke Heart
Center: longitudinal assessment of neurocognitive function after coronary artery bypass surgery:
perioperative decline predicts long-term (5-year) neurocognitive deterioration. New England Journal of
Medicine 2001; 344: 395 402.
92. Tessler MJ, Kardash K, Wahba RM et al. The performance of spinal anaesthesia is marginally more difficult
in the elderly. Regional Anaesthesia and Pain Medicine 1999; 24: 126130.
93. Doherty TJ, Vandervoort AA, Taylor AW & Brown WF. Effects of motor unit losses on strength in older
men and women. Journal of Applied Physiology 1993; 74: 868874.
94. Faulkner JA, Brooks SV & Zerba E. Skeletal muscle weakness and fatigue in old age: underlying
mechanisms. Annual Review of Geriatrics and Gerontology 1990; 10: 147166.
95. Doherty TJ & Brown WF. The estimated numbers and relative sizes of thenar motor units as selected by
multiple point stimulation in young and older adults. Muscle and Nerve 1993; 16: 355366.
96. Campbell MJ, McComas AJ & Petito F. Physiological changes in ageing muscles. Journal of Neurology,
Neurosurgery and Psychiatry 1974; 36: 174182.
97. Klein C, Cunningham DA, Paterson DH & Taylor AW. Fatigue and recovery contractile properties of
young and elderly men. European Journal of Applied Physiology and Occupational Physiology 1988; 57:
684690.
98. McComas AJ, Sica REP, Campbell MJ & Upton ARM. Functional compensation in partially denervated
muscles. Journal of Neurology, Neurosurgery and Psychiatry 1971; 34: 453460.
99. McComas AJ, Galea V & deBruin H. Motor unit populations in healthy and diseased muscles.
Physical Therapy 1993; 73: 868877.
100. Brown WF, Strong MJ & Snow RS. Methods for estimating numbers of motor units in biceps-brachialis
muscles and losses of motor units with aging. Muscle and Nerve 1988; 11: 423 432.
101. Stoelting RK & Dierdorf SF. Physiologic changes and disorders unique to aging. Anaesthesia and Co-existing
Disease, 3rd edn. New York: Churchill Livingstone, 1993.
102. Travis KW, Mihevc NT, Orkin FK & Zeitlin GL. Age and anesthetic practice: a regional perspective.
Journal of Clinical Anesthesiology 1999; 11: 175186.
103. Eyraud MY & Borowsky MS. Age and pilot performance. Aviation, Space and Environmental Medicine 1985;
56: 553558.
* 104. Katz JD. Issues of concern for the aging anesthesiologist. Anaesthesia and Analgesia 2001; 92: 14871492.