Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_827_Библиотеки_им_академика_М_И_Перельмана
.pdf
294 A.N. LacKamp and F.E. Sieber
https://t.me/med1917
The Interplay of the Aging Cardiovascular
System and the Effects of Anesthesia
Cardiovascular compensation occurs even in the healthy
aging patient, and the significance of age-related change varies greatly on an individual basis. Physiologic limitations,
however, may be unmasked by anesthesia.
The most frequent cardiovascular problem that occurs
with anesthesia in the elderly is hemodynamic instability,
which manifests itself primarily as hypotension. This effect
is mediated through interactions with myocardium, preload,
and afterload. Anesthesia causes sympatholysis which results
in decreased afterload because the primary resistance vessels
are sympathetic sensitive. However, the ability to augment
cardiac output to maintain blood pressure in the face of
decreased systemic vascular resistance is lessened. Anesthesia
decreases contractility and inhibits baroreceptor responses.
This makes the aging heart with diastolic dysfunction more
dependent on adequate preload to maintain cardiac output.
The margin of safety in administering an anesthetic decreases
as the aging heart with diastolic dysfunction becomes
increasingly preload dependant. Important clinical situations
in which hypotension frequently occurs in the elderly in the
setting of relative perioperative hypovolemia include causes
such as chronic hypertension, prolonged NPO status,
impaired renal salt conservation, and use of diuretics [5].
Most anesthetic drugs can be used safely without hemodynamic compromise in the elderly population if several
principles are kept in mind. Anesthetic dose requirements of
both intravenous induction agents and inhalational agents
decrease with age. In addition, slower titration of medication
as opposed to bolus administration may be warranted because
changes in body composition alter the pharmacokinetics of
intravenous agents. The loss of lean body mass, increase in
percent body fat, and 20–30% decrease in blood volume
observed with aging cause the initial drug bolus to be dispersed in a reduced volume of distribution. The so-called
greater “sensitivity” of aged patients to the bolus administration of certain drugs has been related to a reduction in either
the initial volume of distribution or the initial distribution
clearance. In elderly patients compared to younger ones, the
same bolus dose will generate a markedly higher plasma
concentration and thus a greater pharmacologic effect.
The elderly are at increased risk of fluid overload during
management of hypotension and correction of fluid deficits.
The balance of euvolemia is more delicate in the elderly than
in the younger patient, as the clinical range between hypovolemia and fluid overload is narrowed. Perioperative congestive heart failure in the elderly occurs in a bimodal type of
time frame. It may first appear in the immediate recovery
phase after anesthetic emergence. It is most likely to occur
when sympathetic tone reappears and may be the result of
pain or fluid shifts from the peripheral vasculature to the
heart. It may next appear on postoperative day 2–3, and likely
occurs with mobilization of extravascular fluid. Late postoperative congestive heart failure is exacerbated by underlying
renal dysfunction, and its prevention requires physician
attentiveness and diuresis.
Mode of ventilation during anesthesia can have significant cardiovascular effects in the elderly. Positive pressure
ventilation decreases venous return via an increase in
intrathoracic pressure. Similarly, hyperventilation can cause
hypotension via impairment of venous return. An additional
mechanism of hypotension is the decrease in sympathetic
tone associated with hypocapnea [
tilation is associated with less hypotension in the elderly
patient with diminished cardiovascular reserve, because
venous return is augmented during inspiration.
The prone position can be associated with a significant
reduction in the cardiac index secondary to vena caval compression [45]. Both the sitting position and reverse
Trendelenberg position decrease venous return and can
worsen hypotension in severely preload-dependant elderly
patients. Trendelenberg augments venous return. Lateral
position is generally not associated with significant hemodynamic effects. Although right lateral decubitus has improved
venous return over the supine and left lateral decubitus positions, the effect is probably minimal except in patients with
congestive heart failure [46].
Laparoscopic insufflation causes decreased venous return.
This, coupled with the depressant effect of anesthetic drugs,
can result in hypotension. It is typical for PaCO2 to slowly rise
after 30 min of laparoscopy. This results from the increased
CO2 load and the decreased ability to eliminate CO2 secondary
to pneumoperitoneum. The hypercapnea and its associated
increase in sympathetic tone [47] may cause hypertension and
ectopy. Correction of hypercapnea requires ventilatory changes
such as increased respiratory rate, tidal volume, and peak airway pressures, which may further impair venous return.
Elderly patients frequently take cardiovascular medications, which interact with anesthetics. For instance, bradycardias are apt to occur in anesthetized patients being treated
with b-blockers and calcium channel blockers. Bradycardia
may also be associated with anesthesia-specific medications
such as high-dose narcotics, acetylcholinesterase inhibitors
for reversal of neuromuscular junction blockade, and with a
rare acetylcholine-like effect of succinylcholine (a shortacting neuromuscular relaxant). Under rare instances, heart
block can occur; the risk increases with preexisting bundle
branch block. Preoperative use of ACE inhibitors [48] and
angiotensin receptor blockers [49] has been closely associated with increased risk of hypotension in anesthetized
patients. It is controversial, however, whether discontinuing
these medications preoperatively will decrease the incidence
of perioperative hypotension.
42–44]. Spontaneous ven-
29524 Physiologic Response to Anesthesia in the Elderly
https://t.me/med1917
Regional Anesthesia: Spinal and Epidural
Spinal and epidural anesthesia cause significant afterload
reduction due to blockade of sympathetic fibers. Because the
sympathetic fibers are small in diameter, they are highly susceptible to local anesthetic blockade. The sympathectomy
associated with regional anesthesia has greater effects in the
elderly because of limited ability to mount a compensatory
response and possibly greater propensity to obtain a higher
spinal anesthetic level [50]. With epidural anesthetics, the
decreased compliance of the epidural space in the elderly is
associated with achievement of a higher dermatome level
of anesthesia with the same dose of local anesthetic in
comparison to younger patients. A decrease in blood pressure
with neuraxial blockade is nearly universal and often heralds
the onset of motor and sensory blockade (Fig. 24.3). Preload
reduction contributes to hypotension as well as afterload
reduction. Tachycardia is the normal compensatory response
but may be impaired in the elderly. With a very high sensory
level (T1–T4), the cardioaccelerator fibers may be blocked,
thus precluding the tachycardia response and predisposing
the patient to severe hypotension and reduction in cardiac
output. When hypotension occurs after administration of
spinal anesthesia in the elderly, volume loading is generally
insufficient to correct the hypotension, and vasopressors are
generally required [51]. Furthermore, excessive volume loading can be associated with ventricular dysfunction [52].
It should be noted that the careless use of spinal anesthesia
in a hypovolemic patient with limited cardiac reserve will
likely result in cardiovascular collapse. These events are asso-
Fi g u r e 24.3 The effect of spinal anesthesia on mean arterial pressure is
shown in 15 elderly men with cardiac disease. The thoracic block level
is noted on the “during spinal” side of the graph. The four patients with
a baseline ejection fraction (EF) less than 50% were no more or less
likely to demonstrate significant decreases in mean arterial pressure
than those with normal baseline ejection fraction (used with permission
from Rooke et al. [122]).
ciated with profound bradycardia resulting from activation of
the Bezold–Jarisch reflex. When patients are hypovolemic
and spinal anesthesia is to be used, it may be best to use a
continuous catheter technique. This allows slow titration of
drug so that hemodynamic changes have a slower onset and
can be treated in a timely manner. Epidural anesthesia also
can be administered slowly via a catheter so that the hemodynamic response can be gradual and controlled. Even with
gradual administration, there is a risk of rapid hemodynamic
changes if the patient is not closely monitored.
Spinal and epidural anesthesia can be desirable modes of
anesthesia in the elderly in order to attenuate the stress response
to surgery, avoid central nervous system depressants, avoid
airway manipulation and its associated pulmonary complications, and to assist in postoperative pain management.
Pulmonary Implications of Anesthesia
in the Elderly
Pulmonary Effects of Anesthesia
During spontaneous ventilation, the inhalational agents
decrease tidal volume and minute ventilation [53–55].
This is associated with an increase in PaCO2 and respiratory rate (Fig. 24.4). In the absence of opioids or other
respiratory depressants, profound tachypnea can occur.
Despite the increase in respiratory rate, however, the net
effect on the alveoli is a decrease in ventilation. In the
anesthetized state, spontaneous ventilation in the supine
position results in decreased functional residual capacity
due to cephalad displacement of the diaphragm and inward
displacement of the ribcage [56]. The work of breathing
[57] is increased because the weight of the abdominal
contents must be displaced with inspiration. Decreased
functional residual capacity means less oxygen reserve
prior to any apneic interval.
Normal ventilatory drive depends on central and peripheral chemoreceptor response to hypercapnea, hydrogen ion
concentration, and pH. The response to hypercapnea is
independent and synergistic with the response to hypoxia.
The carbon dioxide response curve is shifted to the right
under anesthesia requiring higher CO2 [58] for a given
minute ventilation. Likewise, there is impaired response to
hypoxia with even minimal residual inhalational anesthetic
levels [59].
Ventilation–perfusion (V/Q) mismatching occurs during
anesthesia and is caused largely by atelectasis [60] and
impaired hypoxic pulmonary vasoconstriction. Atelectasis
commonly forms in dependent regions of the lung shortly
after induction of anesthesia and progresses as gas is absorbed
from poorly ventilated regions [61]. Positive end-expiratory
296 A.N. LacKamp and F.E. Sieber
https://t.me/med1917
Fi g u r e 24.4 Comparison of mean changes in resting PaCO2, tidal
volume, respiratory rate, and minute ventilation in patients anesthetized
with either halothane, isoflurane, enflurane, sevoflurane, desflurance, or
nitrous oxide. Anesthetic-induced tachypnea compensates in part for
the ventilatory depression caused by all volatile anesthetics (decrease in
minute ventilation and tidal volume and concomitant increase in PaCO
Desflurane results in the greatest increase in PaCO
with corresponding
2
2
pressure can reduce atelectasis formation, but large tidal volume recruitment maneuvers are generally necessary to
reverse shunt [62]. Hypoxic pulmonary vasoconstriction
reduces blood flow to underventilated regions, but this mechanism is partially inhibited by anesthetic agents [63].
Other anesthetic effects on the pulmonary system include
impairment of bronchial mucociliary clearance in intubated
patients [64, 65] and impairment of swallowing reflex from
pharyngeal dysfunction and risk of aspiration at subhypnotic
concentrations of anesthetic [66]. Decreased pharyngeal tone
results in upper airway obstruction. The incidence of apnea due
to upper airway obstruction is increased in obese individuals.
Inhalational anesthetics are potent bronchial dilators in the face
of bronchoconstriction [67], although bronchoconstriction can
be induced during anesthesia by the stimulus of tracheal intubation [68] and by the inhalational agent desflurane [69].
reductions in tidal volume and minute ventilation. Isoflurane, like all
other inhaled agents, increases respiratory rate, but does not result in
dose-dependent tachypnea. MAC is a means of defining dose of inhaled
volatile anesthetics, higher MAC values representing higher anesthetic
dose. One MAC equals the minimum alveolar concentration at which
50% of subjects age 40d would not move in response to a surgical stim-
).
ulus (used with permission from Barash et
al. [123]).
Pulmonary Changes with Aging That Effect
Anesthetic Physiology
The loss of muscle mass with aging does not spare the muscles
of respiration. Decreased muscle strength in the intercostals
and accessory muscles of respiration impairs the ability to perform maximal ventilatory maneuvers and impairs the ability to
mount a strong cough. Clearance of secretions is in part dependent on the patient having sufficient strength to perform the
maneuver. Elderly patients are less able to maintain adequate
tidal volume and generate sufficient inspiratory or expiratory
force. If the weakness is severe enough, it may interfere with
extubation and weaning efforts.
Less efficient gas exchange is inherent in the aging lung.
The incidence of overt chronic lung disease increases with
29724 Physiologic Response to Anesthesia in the Elderly
https://t.me/med1917
age, a problem compounded by smoking. Normal structural
changes account for some of the increased risk of respiratory
compromise in the elderly. There is a loss of elasticity of the
lung tissue, and the chest wall becomes less compliant. The
result is increased residual volume of the lung. Total lung
capacity remains unchanged or slightly decreases, but the
increase in residual volume causes a decrease in vital capacity [70]. The effect is increased work of breathing for given
level of gas exchange, and increased shunt and dead space.
Functional residual capacity also increases along with residual volume, yet the geriatric patient is more susceptible to
hypoxia stemming from the increased closing capacity of the
small airways. As the aging lung loses elasticity, the smallest
airways are no longer stented open by elastic tissue but
instead rely on some minimal amount of lung inflation, or
closing capacity, to maintain small airway patency. As lung
volumes decrease with active expiration, there comes a point
when the summation of intra-airway pressure and elastic
forces stenting open distal air passages become insufficient
to overcome the tendency of these distal airways to collapse.
There is a general trend toward increased closing capacity
with aging. By age 66, closing capacity exceeds FRC in the
sitting position [71]. When closing capacity exceeds FRC,
some portion of the lung will be ineffective in gas exchange
during part of the respiratory cycle. This mechanism leads to
increasing V/Q mismatch in the elderly and a gradual
decrease in blood oxygenation. On average, the PaO2
decreases 0.31 mmHg per year of age [70].
ventilation, depress hypoxic and hypercarbic respiratory drive,
and increase the work of breathing in the face of decreased
muscle mass. Many of the changes outlined act in concert with
a less effective cough and impaired airway protective mechanisms to increase the risk of aspiration and pneumonia.
The pulmonary implications of residual anesthetic effects
after emergence is a serious issue in the elderly. Of primary
importance are the effects of muscle relaxants. Age-related
pharmacokinetic and pharmacodynamic changes interact
with the decrease in muscle mass to potentiate the effects of
these drugs, thus increasing the risk of respiratory compromise in the early postoperative period [
tory depressant effects of sedative agents, narcotics, and
inhalational anesthetics are prolonged. As a special case, the
inhaled anesthetics are eliminated primarily by the lung.
Decreases in minute ventilation and cardiac output, as well
as V/Q mismatch, will prolong the elimination of inhaled
anesthetic agents [78, 79].
The insufflation pressure during laparoscopy displaces
the diaphragm cephalad; this reduces tidal volumes toward
that of the dead space volume. In this case, adequate ventilation is maintained either by increasing the airway pressure to
maintain adequate tidal volume or by decreasing insufflation
pressures. Under these conditions, atelectasis develops at an
accelerated rate. Low levels of PEEP may be used in this setting as long as intrathoracic pressures do not impair venous
return so as to cause hemodynamic compromise.
75–77]. The respira-
Other changes in the elderly that are of importance to
anesthetic physiology include a blunting of the response to
hypoxia and hypercarbia [72, 73]. In addition, aging leads to
dysphagia, decreased esophageal motility, and decreased
cough reflex.
The Interplay of the Aging Pulmonary System
and the Effects of Anesthesia
Pulmonary complications are a major cause of postoperative
morbidity in the elderly. Postoperative respiratory complications are associated with 40% of the perioperative deaths in
patients older than 65 years of age [74]. The aging of the pul-
monary system and anesthesia interact to increase the likelihood of these events. Increased A–a gradient is likely to occur
under anesthesia. Impaired oxygenation is secondary to the
anesthetic effects of decreased minute ventilation, increased
atelectasis, and the aging effect of increased closing capacity.
In addition, hypoxic pulmonary vasoconstriction is impeded by
the aging effect on pulmonary vascular rigidity and by anesthetic inhibition. Ventilatory failure may occur secondary to the
combined effects of anesthesia and aging to decrease minute
Regional Anesthesia and Pulmonary
Implications
With spinal or epidural blockade of sufficient dermatomal
height for abdominal procedures, the musculature of the thoracic cage will be anesthetized, eliminating the contribution
of the intercostal muscles to respiration. Spontaneous ventilation is still possible, however, because the diaphragm is the
major muscle of respiration. In these circumstances, loss of
accessory muscle function may be an issue in patients with
limited pulmonary reserve. Protective airway reflexes are
maintained although cough may be impaired.
Spinal and epidural anesthesia have been advocated as a
means of decreasing postoperative pulmonary complications,
although there is little data to support this contention. Epidural
anesthesia continued into the postoperative period may help in
promoting early mobilization, cough, and deep breathing by
relieving postoperative pain. In theory, spinal or epidural anesthesia helps to minimize the administration of central nervous
system depressants during the perioperative period, thereby
maintaining protective airway reflexes. It is common practice,
however, for sedation to be administered during spinal and
epidural anesthetics. Therefore, it is important to identify at
298 A.N. LacKamp and F.E. Sieber
https://t.me/med1917
risk patients, and verify recovery of protective reflexes in the
elderly after an anesthetic, including sedation for spinal.
Physiologic Response to Anesthesia
in the Aging Nervous System
Age-related decreases in central nervous system functional
reserve lead to alterations in pharmacodynamics, and
increased susceptibility to postoperative cognitive dysfunction and delirium.
Altered Pharmacodynamics
Brain sensitivity to most anesthetic agents increases with
age. This necessitates decreasing the drug dose in the elderly
(Fig. 24.5). Some components of the elderly drug response
can be explained by pharmacokinetic changes associated
with aging; these are specific to each drug. The underlying
mechanism to explain altered brain pharmacodynamics is
unclear at present. Altered brain pharmacodynamics may
Fi g u r e 24.5 Aging influences MAC in humans for desflurane,
isoflurane, halothane, and sevoflurane. MAC is at its peak in humans
less than 1 year of age, decreasing by approximately 40% in older
adults. MAC is a means of defining dose of inhaled volatile anesthetics,
higher MAC values representing higher anesthetic dose. One MAC
equals the minimum alveolar concentration at which 50% of subjects
aged 40 would not move in response to a surgical stimulus (used with
permission from Eger et al. [124]).
result from age-related changes in the receptors, signal
transduction, or homeostatic mechanisms. Within the central
nervous system, aging is associated with decreases in dopaminergic and cholinergic neurons and receptors as well as a
decrease in the number of synapses. There are also alterations in brain phospholipid chemistry associated with
changes in second messengers such as diacylglycerol [80].
A definitive association between these changes and agerelated brain pharmacodynamics has yet to be established.
Increased Susceptibility to Postoperative
Delirium and Cognitive Dysfunction
The incidence of postoperative delirium and postoperative
cognitive dysfunction may exceed 50% in certain surgical
populations [81]. The incidence of cognitive dysfunction in
elderly patients after major surgery seems to be highest after
cardiac surgery and hip fracture repair [82, 83]. Thus, postoperative delirium and postoperative cognitive dysfunction
are two of the most common postoperative complications in
the elderly, and their incidence may be higher than that of
myocardial infarction or respiratory failure [81, 84, 85].
A wide variety of drugs are associated with delirium,
many of which are used frequently in the perioperative
period. These include benzodiazepines, anticholinergics,
opioids, corticosteroids, anticonvulsants, antidopaminergic
antiemetics, and H2 antagonists [86]. Although a recent critical review of the literature concerning the relationship of
psychoactive medications and delirium found that the evidence for an association is weak, the authors attributed this
to methodological issues in the studies and concluded that a
relationship may indeed exist [87].
The hypothesis that postoperative delirium is the result of
age-associated central cholinergic deficiency has been the
driving force behind studies examining the role of intraoperative management as it relates to postoperative delirium.
Arguably, the most important decision concerning anesthetic
management is whether patients should have a regional or
general anesthetic. In theory, regional anesthetic techniques
should be associated with a reduced incidence of postoperative delirium because these techniques minimize exposure to
agents that influence central cholinergic activity and drugs
that are associated with delirium in medical patients, such as
opiates and benzodiazepines. Furthermore, regional anesthesia deeply suppresses the neuroendocrine stress response to
surgery [88–90]. Unfortunately, studies to date have not
demonstrated that regional anesthetic techniques reduce the
incidence of postoperative delirium [91].
Postoperative pain increases the risk of postoperative
delirium. Interestingly, maximum pain and pain with movement
are not predictive of delirium. Only high levels of rest pain
are associated with postoperative delirium [92]. As a class,
29924 Physiologic Response to Anesthesia in the Elderly
https://t.me/med1917
opiates are not associated with postoperative delirium, except
for meperidine [93]. This may be because of its atropine-like
structure and influence on brain cholinergic activity.
Postoperative use of benzodiazepines has also been associated with postoperative delirum [94].
It is important to recognize that postoperative delirium may
be the presenting symptom of a number of complications,
including sepsis, urinary tract infections, myocardial infarction, stroke, pneumonia, etc [95]. Thus, the first step in managing postoperative delirium is to identify and treat underlying
medical and/or surgical causes.
Many surgeons are aware of patients who complain after
surgery of difficulties performing cognitive tasks that they were
previously able to do without difficulty. Postoperative cognitive
dysfunction is the term used to describe this condition. It can
consist of a variety of cognitive deficits. Unlike patients with
postoperative delirium, however, those with postoperative
cognitive dysfunction are generally alert and oriented.
In vitro and animal studies suggest that inhalational and
intravenous anesthetic agents alter neuronal function after
exposure [96–98]. Neurons exposed to volatile anesthetics
in vitro have increased oligomerization and cytotoxicity of
b-amyloid, the protein associated with Alzheimer disease
[98]. In aged rats, exposure to anesthetic agents causes longterm declines in cognitive function [99–101]. The clinical
relevance of these findings is unclear because studies examining the influence of regional versus general anesthesia on
the incidence of postoperative cognitive dysfunction in
humans have not found a difference between the two techniques [91, 102]. One reason may be that patients who
received regional anesthesia in those studies also received
intravenous sedatives. Another may be that postoperative
management was not controlled. Stress plays a role in cognitive function [103]. Although regional anesthetic techniques
attenuate the surgical stress response [88, 104], if these techniques were not continued into the postoperative period, any
benefit may have been negated. Also, by not continuing
regional analgesic techniques into the postoperative period,
patients were exposed to higher doses of opiates, which may
have influenced their cognitive outcomes. Interestingly,
unlike the case with postoperative delirium, perioperative
use of benzodiazepines is not associated with postoperative
cognitive dysfunction [105, 106].
Though the exact mechanisms by which postoperative
delirium and postoperative cognitive dysfunction occur are
not well understood, the likely cause is an acute insult in a
vulnerable patient. The degree of surgical or physiological
insult required to precipitate postoperative delirium or postoperative cognitive dysfunction varies from patient to patient.
In patients with a high degree of preoperative cognitive
reserve, a substantial insult is required for postoperative
delirium and/or postoperative cognitive dysfunction to occur.
Conversely, in patients with a lower degree of cognitive
reserve, a relatively minor stress is all that is necessary for
postoperative delirium and/or postoperative cognitive
dysfunction to develop [107].
Renal Implications of Anesthesia
in the Elderly
Anesthesia decreases renal perfusion and glomerular filtration
rate. When a patient receives an anesthetic, glomerular filtration rate may be acutely decreased by hypotension, redistribution of blood flow away from body core, or a specific pressure
effect of laparoscopy. The potential for postoperative acute
renal injury is greater with preexisting renal disease.
Drug excretion and metabolism by the kidney is proportionately decreased with aging. Many anesthetic drugs
depend on renal elimination. Dose adjustment of most medications should be anticipated in the elderly. Of special note,
many of the commonly used opioids and muscle relaxants
have some component of renal elimination, and their effects
are prolonged in the elderly. Fortunately, there are alternate
drugs, with little or no dependence on renal elimination.
Inhaled anesthetics are eliminated primarily by the respiratory route. Serum enzymes degrade certain drugs such as
cisatracurium, remifentanil, and chloroprocaine. Due to the
blood stream degradation of cisatracurium, this agent may be
of special value in the elderly patient with renal impairment
who requires muscle relaxation.
Hepatic Implications of Anesthesia
in the Elderly
Hepatic functional reserve is fairly well maintained with healthy
aging. As a result, anesthetic drug binding to serum proteins
produced by the liver is not significantly affected. One potential
effect of anesthesia is decreased hepatic blood flow. Hepatic
blood flow parallels cardiac output and correlates with the rate
of elimination of drugs with high hepatic extraction ratio [108,
109]. Commonly administered anesthetic agents with high
hepatic extraction ratios include fentanyl, sufentanyl, lidocaine,
meperidine, ketamine, and propofol. Drugs with lower hepatic
extraction ratios are less impacted by hepatic blood flow.
Endocrine Implications of Anesthesia
in the Elderly
Hyperglycemia is a frequent issue during surgery in the
elderly patient. Inhalational anesthetics impair glucose tolerance. The mechanism is unclear but may be secondary to
direct inhibition of insulin secretion [110]. Thus, hyperglycemia
300 A.N. LacKamp and F.E. Sieber
https://t.me/med1917
occurs in the anesthetized state with or without surgery.
Insulin resistance and prevalence of diabetes is increased in
the elderly. This effect is compounded in the face of obesity.
Thermoregulation
Normal human thermoregulation allows only small fluctuations in core temperature within the narrow interthreshold
range of 0.2°C; this range can be extended to 2–4°C under
the effects of anesthesia [111]. Multiple inputs from the core
and periphery contribute to the detection of temperature variation. Peripheral sensation tends to contribute largely to
behavioral aversion to unpleasant environments, while core
sensing mechanisms have a relatively larger impact on autonomic responses [111]. The response to decreased temperature begins when the threshold of vasoconstriction is reached.
Beyond the vasoconstriction threshold lays the threshold for
the energy intensive shivering mechanism. Non-shivering
thermogenesis, although important in neonates, is negligible
in adults. The response to elevation in core temperature
begins when the threshold for sweating is reached. With
extremes of temperature elevation, active vasodilation can
also occur [111].
During anesthesia, hypothermia is a common challenge
as a consequence of several colluding factors. Preparations
for surgery entail exposing large surfaces of the patient’s
skin. Operating rooms are traditionally kept very cool.
Under anesthesia, vasodilation occurs as a direct anesthetic
effect. This results in an immediate decrease in core body
temperature from a redistribution of body heat from the
core to the periphery, and eventually results in greater dissipation of heat to the environment. By central mechanisms,
anesthesia decreases the threshold temperature for vasoconstriction and shivering, allowing drift of the core
temperature.
The elderly are predisposed to hypothermia [70, 112] as a
result of decreased muscle mass and neural and hormonal
mechanisms. Thyroid function and overall metabolic rate
decrease with aging. Decreased muscle mass leads to greater
heat loss and less heat generation. The neural thermoregulatory mechanisms [112] are altered with a lowered threshold
for vasoconstriction, decreased maximum vasoconstriction
response, decreased a-adrenergic response [113, 114], and
decreased thermal perception.
These changes with aging compound the tendency, present among all patients, to develop hypothermia during both
general and spinal anesthesia. The effects occur across a
wide spectrum of anesthetic techniques and agents [115].
Complications of hypothermia include possible coagulopathy [116, 117], increased risk of surgical wound infection
[118], and increased cardiac risk [119, 120] secondary to
hypermetabolism if shivering occurs after emergence from
anesthesia. See the physiology table at the beginning of this
chapter, which summarizes the interactions of anesthesia and
aging in the brain, kidney, liver, endocrine system, and with
thermoregulation.
Summary
Aging affects every body system, so the interplay between
anesthesia and aging is necessarily complex. Because of
decreases in hepatic and renal reserve, pharmacodynamic/
pharmacokinetic changes must be taken into account when
administering anesthetics. Other important considerations
include the cardiopulmonary and neurologic systems. Labile
hemodynamics and potential for diastolic heart failure are
the important cardiovascular issues as compared to younger
adults. The risks of postoperative ventilatory failure and
pneumonia are increased in the elderly. Postoperative cognitive dysfunction is a common entity after all types of major
surgery. At this time, it is difficult to define the optimal anesthetic for the elderly because both regional and general anesthesia affect many of these organ systems, and definitive data
concerning the advantage of one anesthetic technique over
another has yet to be established.
References
1. Kanaya N, Murray PA, Damron DS (1998) Propofol and ketamine
only inhibit intracellular Ca2+ transients and contraction in rat
ventricular myocytes at supraclinical concentrations.
Anesthesiology 88(3):781–791
2. Nishikawa K, Kanaya N, Kawamata M, Namiki A (2004) Left
ventricular mechanical performance in elderly patients after induction of anaesthesia. A comparison of inhalational induction with
sevoflurane and intravenous induction with fentanyl and propofol.
Anaesthesia 59(10):948–953
3. Kawakubo A, Fujigaki T, Uresino H, Zang S, Sumikawa K (1999)
Comparative effects of etomidate, ketamine, propofol, and fentanyl on myocardial contractility in dogs. J Anesth 13(2):77–82
4. Gelissen HP, Epema AH, Henning RH, Krijnen HJ, Hennis PJ, den
Hertog A (1996) Inotropic effects of propofol, thiopental, midazolam, etomidate, and ketamine on isolated human atrial muscle.
Anesthesiology 84(2):397–403
5. Priebe HJ (2000) The aged cardiovascular risk patient. Br J
Anaesth 85(5):763–778
6. Fragen RJ, Shanks CA, Molteni A, Avram MJ (1984) Effects of
etomidate on hormonal responses to surgical stress. Anesthesiology
61(6):652–656
7. Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D (1984)
Inhibition of adrenal steroidogenesis by the anesthetic etomidate.
N Engl J Med 310(22):1415–1421
8. Hanley PJ, ter Keurs HE, Cannell MB (2004) Excitationcontraction coupling in the heart and the negative inotropic action
of volatile anesthetics. Anesthesiology 101(4):999–1014
30124 Physiologic Response to Anesthesia in the Elderly
https://t.me/med1917
9. Weiskopf RB, Cahalan MK, Eger EI 2nd et al (1991) Cardiovascular
actions of desflurane in normocarbic volunteers. Anesth Analg
73(2):143–156
10. Stevens WC, Cromwell TH, Halsey MJ, Eger EI 2nd, Shakespeare
TF, Bahlman SH (1971) The cardiovascular effects of a new inhalation anesthetic, forane, in human volunteers at constant arterial
carbon dioxide tension. Anesthesiology 35(1):8–16
11. Pagel PS, Kampine JP, Schmeling WT, Warltier DC (1991)
Alteration of left ventricular diastolic function by desflurane, isoflurane, and halothane in the chronically instrumented dog with
autonomic nervous system blockade. Anesthesiology
74(6):1103–1114
12. Malan TP Jr, DiNardo JA, Isner RJ et al (1995) Cardiovascular
effects of sevoflurane compared with those of isoflurane in volunteers. Anesthesiology 83(5):918–928
13. Eger EI 2nd (1981) Isoflurane: a review. Anesthesiology
55(5):559–576
14. Bastard OG, Carter JG, Moyers JR, Bross BA (1984) Circulatory
effects of isoflurane in patients with ischemic heart disease: a comparison with halothane. Anesth Analg 63(7):635–639
15. Rouby JJ, Andreev A, Leger P et al (1991) Peripheral vascular
effects of thiopental and propofol in humans with artificial hearts.
Anesthesiology 75(1):32–42
16. Moore PG, Quail AW, Cottee DB, McIlveen SA, White SW (2000)
Effect of fentanyl on baroreflex control of circumflex coronary
conductance. Clin Exp Pharmacol Physiol 27(12):1028–1033
17. Nagasaki G, Tanaka M, Nishikawa T (2001) The recovery profile
of baroreflex control of heart rate after isoflurane or sevoflurane
anesthesia in humans. Anesth Analg 93(5):1127–1131
18. Knaggs AL, Delis KT, Mason P, Macleod K (2005) Perioperative
lower limb venous haemodynamics in patients under general
anaesthesia. Br J Anaesth 94(3):292–295
19. Nichols WW, O’Rourke MF, Avolio AP et al (1985) Effects of age
on ventricular-vascular coupling. Am J Cardiol 55(9):1179–1184
20. Levy D, Anderson KM, Savage DD, Kannel WB, Christiansen JC,
Castelli WP (1988) Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. The Framingham
heart study. Ann Intern Med 108(1):7–13
21. Schulman SP, Lakatta EG, Fleg JL, Lakatta L, Becker LC,
Gerstenblith G (1992) Age-related decline in left ventricular filling at rest and exercise. Am J Physiol 263(6 Pt 2):H1932–H1938
22. Groban L (2005) Diastolic dysfunction in the older heart. J
Cardiothorac Vasc Anesth 19(2):228–236
23. Rooke GA (2003) Cardiovascular aging and anesthetic implications. J Cardiothorac Vasc Anesth 17(4):512–523
24. O’Rourke MF (2007) Arterial aging: pathophysiological principles. Vasc Med 12(4):329–341
25. Plehn G, Vormbrock J, Perings C et al (2008) Loss of diastolic
time as a mechanism of exercise-induced diastolic dysfunction in
dilated cardiomyopathy. Am Heart J 155(6):1013–1019.
doi:10.1016/j.ahj.2008.01.027
26. Siri FM, Malhotra A, Factor SM, Sonnenblick EH, Fein FS (1997)
Prolonged ejection duration helps to maintain pump performance
of the renal-hypertensive-diabetic rat heart: correlations between
isolated papillary muscle function and ventricular performance in
situ. Cardiovasc Res 34(1):230–240
27. Takehana K, Sugiura T, Nagahama Y, Hatada K, Okugawa S,
Iwasaka T (2000) Cardiovascular response to combined staticdynamic exercise of patients with myocardial infarction. Coron
Artery Dis 11(1):35–40
28. Arshad W, Duncan AM, Francis DP, O’Sullivan CA, Gibson DG,
Henein MY (2004) Systole-diastole mismatch in hypertrophic cardiomyopathy is caused by stress induced left ventricular outflow
tract obstruction. Am Heart J 148(5):903–909
29. Juneja R (2006) Anaesthesia for the elderly cardiac patient. Ann
Card Anaesth 9(1):67–77
30. Hoffmann E, Sulke N, Edvardsson N et al (2006) New insights
into the initiation of atrial fibrillation: a detailed intraindividual
and interindividual analysis of the spontaneous onset of atrial
fibrillation using new diagnostic pacemaker features. Circulation
113(16):1933–1941
31. Fleg JL, Das DN, Wright J, Lakatta EG (1990) Age-associated
changes in the components of atrioventricular conduction in apparently healthy volunteers. J Gerontol 45(3):M95–M100
32. Erikssen J, Amlie JP, Thaulow E, Kjerkshus J (1982) PR interval
in middle-aged men with overt and latent coronary heart disease
compared to PR in angionegative and normal men of similar age.
Clin Cardiol 5(6):353–359
33. Fleg JL, O’Connor F, Gerstenblith G et al (1995) Impact of age on
the cardiovascular response to dynamic upright exercise in healthy
men and women. J Appl Physiol 78(3):890–900
34. Bullington J, Mouton Perry SM, Rigby J et al (1989) The effect of
advancing age on the sympathetic response to laryngoscopy and
tracheal intubation. Anesth Analg 68(5):603–608
35. Folkow B, Svanborg A (1993) Physiology of cardiovascular aging.
Physiol Rev 73(4):725–764
36. Poldermans D, Boersma E, Fioretti PM, van Urk H, Boomsma F,
Man in’t Veld AJ (1995) Cardiac chronotropic responsiveness to
b-adrenoceptor stimulation is not reduced in the elderly. J Am Coll
Cardiol 25(5):995–999
37. Hees PS, Fleg JL, Mirza ZA, Ahmed S, Siu CO, Shapiro EP (2006)
Effects of normal aging on left ventricular lusitropic, inotropic,
and chronotropic responses to dobutamine. J Am Coll Cardiol
47(7):1440–1447
38. Elliott HL, Sumner DJ, McLean K, Reid JL (1982) Effect of age
on the responsiveness of vascular alpha-adrenoceptors in man. J
Cardiovasc Pharmacol 4(3):388–392
39. Taylor JA, Hayano J, Seals DR (1995) Lesser vagal withdrawal
during isometric exercise with age. J Appl Physiol 79(3):805–811
40. Laitinen T, Niskanen L, Geelen G, Lansimies E, Hartikainen J
(2004) Age dependency of cardiovascular autonomic responses to
head-up tilt in healthy subjects. J Appl Physiol 96(6):2333–2340.
doi:10.1152/japplphysiol.00444.2003
41. Latson TW, Ashmore TH, Reinhart DJ, Klein KW, Giesecke AH
(1994) Autonomic reflex dysfunction in patients presenting for
elective surgery is associated with hypotension after anesthesia
induction. Anesthesiology 80(2):326–337
42. Theye RA, Milde JH, Michenfelder JD (1966) Effect of hypocapnia
on cardiac output during anesthesia. Anesthesiology 27(6):778–782
43. Markello R, Thweatt RC, Lauria JI, Baker JM, Schuder RJ (1969)
Effect of hyperventilation on cardiac output during ether anesthesia. Anesth Analg 48(1):99–105
44. Hewitt PB, Chamberlain JH, Seed RF (1973) The effect of carbon
dioxide on cardiac output in patients undergoing mechanical ventilation following open-heart surgery. Br J Anaesth 45(6):640–641
45. Sudheer PS, Logan SW, Ateleanu B, Hall JE (2006) Haemodynamic
effects of the prone position: a comparison of propofol total intravenous and inhalation anaesthesia. Anaesthesia 61(2):138–141
46. Tanabe K, Ishibashi Y, Ohta T et al (1993) Effect of left and right lateral decubitus positions on mitral flow pattern by Doppler echocardiography in congestive heart failure. Am J Cardiol 71(8):751–753
47. Norman J, Atkinson SA (1970) The effect of cardiac sympathetic
blockade on the relationship between cardiac output and carbon dioxide tension in the anaesthetized dog. Br J Anaesth 42(7):592–602
48. Licker M, Schweizer A, Hohn L, Farinelli C, Morel DR (2000)
Cardiovascular responses to anesthetic induction in patients chronically treated with angiotensin-converting enzyme inhibitors. Can
J Anaesth 47(5):433–440
49. Brabant SM, Bertrand M, Eyraud D, Darmon PL, Coriat P (1999)
The hemodynamic effects of anesthetic induction in vascular surgical patients chronically treated with angiotensin II receptor
antagonists. Anesth Analg 89(6):1388–1392
302 A.N. LacKamp and F.E. Sieber
https://t.me/med1917
50. Simon MJ, Veering BT, Stienstra R, van Kleef JW, Burm AG
(2002) The effects of age on neural blockade and hemodynamic
changes after epidural anesthesia with ropivacaine. Anesth Analg
94(5):1325–1330, table of contents
51. Critchley LA, Stuart JC, Short TG, Gin T (1994) Haemodynamic
effects of subarachnoid block in elderly patients. Br J Anaesth
73(4):464–470
52. Baron JF, Coriat P, Mundler O, Fauchet M, Bousseau D, Viars P
(1987) Left ventricular global and regional function during lumbar
epidural anesthesia in patients with and without angina pectoris.
influence of volume loading. Anesthesiology 66(5):621–627
53. Fourcade HE, Stevens WC, Larson CP Jr et al (1971) The ventilatory effects of forane, a new inhaled anesthetic. Anesthesiology
35(1):26–31
54. Doi M, Ikeda K (1987) Respiratory effects of sevoflurane. Anesth
Analg 66(3):241–244
55. Lockhart SH, Rampil IJ, Yasuda N, Eger EI 2nd, Weiskopf RB
(1991) Depression of ventilation by desflurane in humans.
Anesthesiology 74(3):484–488
56. Warner DO, Warner MA, Ritman EL (1995) Human chest wall
function while awake and during halothane anesthesia. I. quiet
breathing. Anesthesiology 82(1):6–19
57. Sprung J, Gajic O, Warner DO (2006) Review article: age related
alterations in respiratory function - anesthetic considerations:
[article de synthese: Les modifications de fonction respiratoire
liees a l’age – considerations anesthesiques]. Can J Anaesth
53(12):1244–1257
58. Regan MJ, Eger EI 2nd (1966) Ventilatory responses to hypercapnia and hypoxia at normothermia and moderate hypothermia during constant-depth halothane anesthesia. Anesthesiology 27(5):
624–633
59. van den Elsen M, Sarton E, Teppema L, Berkenbosch A, Dahan A
(1998) Influence of 0.1 minimum alveolar concentration of sevoflurane, desflurane and isoflurane on dynamic ventilatory response
to hypercapnia in humans. Br J Anaesth 80(2):174–182
60. Tokics L, Hedenstierna G, Svensson L et al (1996) V/Q distribution and correlation to atelectasis in anesthetized paralyzed
humans. J Appl Physiol 81(4):1822–1833
61. Gunnarsson L, Strandberg A, Brismar B, Tokics L, Lundquist H,
Hedenstierna G (1989) Atelectasis and gas exchange impairment
during enflurane/nitrous oxide anaesthesia. Acta Anaesthesiol
Scand 33(8):629–637
62. Tokics L, Hedenstierna G, Strandberg A, Brismar B, Lundquist H
(1987) Lung collapse and gas exchange during general anesthesia:
effects of spontaneous breathing, muscle paralysis, and positive
end-expiratory pressure. Anesthesiology 66(2):157–167
63. Pagel PS, Fu JL, Damask MC et al (1998) Desflurane and isoflurane produce similar alterations in systemic and pulmonary hemodynamics and arterial oxygenation in patients undergoing one-lung
ventilation during thoracotomy. Anesth Analg 87(4):800–807
64. Forbes AR, Gamsu G (1979) Mucociliary clearance in the canine
lung during and after general anesthesia. Anesthesiology
50(1):26–29
65. Keller C, Brimacombe J (1998) Bronchial mucus transport velocity in
paralyzed anesthetized patients: a comparison of the laryngeal mask
airway and cuffed tracheal tube. Anesth Analg 86(6):1280–1282
66. Sundman E, Witt H, Sandin R et al (2001) Pharyngeal function and
airway protection during subhypnotic concentrations of propofol,
isoflurane, and sevoflurane: volunteers examined by pharyngeal videoradiography and simultaneous manometry. Anesthesiology 95(5):
1125–1132
67. Rooke GA, Choi JH, Bishop MJ (1997) The effect of isoflurane,
halothane, sevoflurane, and thiopental/nitrous oxide on respiratory
system resistance after tracheal intubation. Anesthesiology
86(6):1294–1299
68. Hirshman CA, Bergman NA (1990) Factors influencing intrapulmonary airway calibre during anaesthesia. Br J Anaesth 65(1):
30–42
69. Goff MJ, Arain SR, Ficke DJ, Uhrich TD, Ebert TJ (2000) Absence
of bronchodilation during desflurane anesthesia: a comparison to
sevoflurane and thiopental. Anesthesiology 93(2):404–408
70. Tonner PH, Kampen J, Scholz J (2003) Pathophysiological changes
in the elderly. Best Pract Res Clin Anaesthesiol 17(2):163–177
71. Leblanc P, Ruff F, Milic-Emili J (1970) Effects of age and body position on “airway closure” in man. J Appl Physiol 28(4):448–451
72. Kronenberg RS, Drage CW (1973) Attenuation of the ventilatory
and heart rate responses to hypoxia and hypercapnia with aging in
normal men. J Clin Invest 52(8):1812–1819
73. Wahba WM (1983) Influence of aging on lung function-clinical
significance of changes from age twenty. Anesth Analg
62(8):764–776
74. Zaugg M, Lucchinetti E (2000) Respiratory function in the elderly.
Anesthesiol Clin North America 18(1):47–58, vi
75. Murphy GS, Szokol JW, Marymont JH, Greenberg SB, Avram MJ,
Vender JS (2008) Residual neuromuscular blockade and critical
respiratory events in the postanesthesia care unit. Anesth Analg
107(1):130–137
76. Rose DK, Cohen MM, Wigglesworth DF, DeBoer DP (1994)
Critical respiratory events in the postanesthesia care unit. patient,
surgical, and anesthetic factors. Anesthesiology 81(2):410–418
77. Murphy GS, Szokol JW, Franklin M, Marymont JH, Avram MJ,
Vender JS (2004) Postanesthesia care unit recovery times and neuromuscular blocking drugs: a prospective study of orthopedic surgical patients randomized to receive pancuronium or rocuronium.
Anesth Analg 98(1):193–200, table of contents
78. Sprung J, Whalen FX, Comfere T et al (2009) Alveolar recruitment and arterial desflurane concentration during bariatric surgery.
Anesth Analg 108(1):120–127
79. Lu CC, Tsai CS, Hu OY, Chen RM, Chen TL, Ho ST (2008)
Pharmacokinetics of isoflurane in human blood. Pharmacology
81(4):344–349
80. Turnheim K (2003) When drug therapy gets old: pharmacokinetics
and pharmacodynamics in the elderly. Exp Gerontol 38(8):843–853
81. Rasmussen LS, Moller JT (2000) Central nervous system dysfunction after anesthesia in the geriatric patient. Anesthesiol Clin North
America 18(1):59–70, vi
82. Olofsson B, Lundstrom M, Borssen B, Nyberg L, Gustafson Y
(2005) Delirium is associated with poor rehabilitation outcome in
elderly patients treated for femoral neck fractures. Scand J Caring
Sci 19(2):119–127
83. Newman MF, Kirchner JL, Phillips-Bute B et al (2001) Longitudinal
assessment of neurocognitive function after coronary-artery
bypass surgery. N Engl J Med 344(6):395–402
84. Lawrence VA, Hilsenbeck SG, Mulrow CD, Dhanda R, Sapp J,
Page CP (1995) Incidence and hospital stay for cardiac and pulmonary complications after abdominal surgery. J Gen Intern Med
10(12):671–678
85. Ashton CM, Petersen NJ, Wray NP et al (1993) The incidence of
perioperative myocardial infarction in men undergoing noncardiac
surgery. Ann Intern Med 118(7):504–510
86. Alagiakrishnan K, Wiens CA (2004) An approach to drug induced
delirium in the elderly. Postgrad Med J 80(945):388–393
87. Gaudreau JD, Gagnon P, Roy MA, Harel F, Tremblay A (2005)
Association between psychoactive medications and delirium in
hospitalized patients: a critical review. Psychosomatics 46(4):
302–316
88. Cosgrove DO, Jenkins JS (1974) The effects of epidural anaesthesia on the pituitary-adrenal response to surgery. Clin Sci Mol Med
46(3):403–407
89. Pflug AE, Halter JB (1981) Effect of spinal anesthesia on adrenergic tone and the neuroendocrine responses to surgical stress in
humans. Anesthesiology 55(2):120–126
30324 Physiologic Response to Anesthesia in the Elderly
https://t.me/med1917
90. Seitz W, Luebbe N, Bechstein W, Fritz K, Kirchner E (1986) A
comparison of two types of anaesthesia on the endocrine and
metabolic responses to anaesthesia and surgery. Eur J
Anaesthesiol 3(4):283–294
91. Williams-Russo P, Sharrock NE, Mattis S, Szatrowski TP, Charlson
ME (1995) Cognitive effects after epidural vs general anesthesia in
older adults. A randomized trial. JAMA 274(1):44–50
92. Lynch EP, Lazor MA, Gellis JE, Orav J, Goldman L, Marcantonio
ER (1998) The impact of postoperative pain on the development of
postoperative delirium. Anesth Analg 86(4):781–785
93. Fong HK, Sands LP, Leung JM (2006) The role of postoperative
analgesia in delirium and cognitive decline in elderly patients: a
systematic review. Anesth Analg 102(4):1255–1266
94. Marcantonio ER, Juarez G, Goldman L et al (1994) The relationship of postoperative delirium with psychoactive medications.
JAMA 272(19):1518–1522
95. Francis J, Martin D, Kapoor WN (1990) A prospective study of
delirium in hospitalized elderly. JAMA 263(8):1097–1101
96. Hanning CD, Blokland A, Johnson M, Perry EK (2003) Effects of
repeated anaesthesia on central cholinergic function in the rat cerebral cortex. Eur J Anaesthesiol 20(2):93–97
97. Jevtovic-Todorovic V, Todorovic SM, Mennerick S et al (1998)
Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nat Med 4(4):460–463
98. Eckenhoff RG, Johansson JS, Wei H et al (2004) Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology 101(3):703–709
99. Blokland A, Honig W, Jolles J (2001) Long-term consequences of
repeated pentobarbital anaesthesia on choice reaction time performance in ageing rats. Br J Anaesth 87(5):781–783
100. Culley DJ, Baxter M, Yukhananov R, Crosby G (2003) The memory effects of general anesthesia persist for weeks in young and
aged rats. Anesth Analg 96(4):1004–1009, table of contents
101. Culley DJ, Baxter MG, Yukhananov R, Crosby G (2004) Longterm impairment of acquisition of a spatial memory task following
isoflurane-nitrous oxide anesthesia in rats. Anesthesiology
100(2):309–314
102. Rasmussen LS, Johnson T, Kuipers HM et al (2003) Does anaesthesia cause postoperative cognitive dysfunction? A randomised
study of regional versus general anaesthesia in 438 elderly patients.
Acta Anaesthesiol Scand 47(3):260–266
103. Sapolsky RM (2000) Glucocorticoids and hippocampal atrophy in
neuropsychiatric disorders. Arch Gen Psychiatry 57(10):925–935
104. Gordon NH, Scott DB, Percy Robb IW (1973) Modification of
plasma corticosteroid concentrations during and after surgery by
epidural blockade. Br Med J 1(5853):581–583
105. Moller JT, Cluitmans P, Rasmussen LS et al (1998) Long-term
postoperative cognitive dysfunction in the elderly ISPOCD1 study.
ISPOCD investigators. International study of post-operative cognitive dysfunction. Lancet 351(9106):857–861
106. Rasmussen LS, Steentoft A, Rasmussen H, Kristensen PA, Moller
JT (1999) Benzodiazepines and postoperative cognitive dysfunction in the elderly. ISPOCD group. International study of postoperative cognitive dysfunction. Br J Anaesth 83(4):585–589
107. Inouye SK (2006) Delirium in older persons. N Engl J Med
354(11):1157–1165
108. Nies AS, Shand DG, Wilkinson GR (1976) Altered hepatic blood
flow and drug disposition. Clin Pharmacokinet 1(2):135–155
109. Wilkinson GR, Shand DG (1975) Commentary: a physiological
approach to hepatic drug clearance. Clin Pharmacol Ther 18(4):
377–390
110. Tanaka T, Nabatame H, Tanifuji Y (2005) Insulin secretion and
glucose utilization are impaired under general anesthesia with
sevoflurane as well as isoflurane in a concentration-independent
manner. J Anesth 19(4):277–281
111. Sessler DI (2005) Temperature monitoring. In: Miller RD (ed)
Miller’s anesthesia, 6th edn. Elsevier, Philadelphia, PA, p 1571
112. Frank SM, Raja SN, Bulcao C, Goldstein DS (2000) Age-related
thermoregulatory differences during core cooling in humans. Am
J Physiol Regul Integr Comp Physiol 279(1):R349–R354
113. Frank SM, Raja SN, Wu PK, el-Gamal N (1997) Alpha-adrenergic
mechanisms of thermoregulation in humans. Ann N Y Acad Sci
813:101–110
114. Thompson CS, Holowatz LA, Kenney WL (2005) Attenuated
noradrenergic sensitivity during local cooling in aged human skin.
J Physiol 564(Pt 1):313–319
115. Ozaki M, Sessler DI, Suzuki H, Ozaki K, Atarashi K, Negishi C
(1997) The threshold for thermoregulatory vasoconstriction during nitrous oxide/sevoflurane anesthesia is lower in elderly than in
young patients. Ann N Y Acad Sci 813:789–791
116. Schmied H, Kurz A, Sessler DI, Kozek S, Reiter A (1996) Mild
hypothermia increases blood loss and transfusion requirements
during total hip arthroplasty. Lancet 347(8997):289–292
117. Winkler M, Akca O, Birkenberg B et al (2000) Aggressive warming reduces blood loss during hip arthroplasty. Anesth Analg
91(4):978–984
118. Polk HC Jr, Simpson CJ, Simmons BP, Alexander JW (1983)
Guidelines for prevention of surgical wound infection. Arch Surg
118(10):1213–1217
119. Frank SM, Fleisher LA, Breslow MJ et al (1997) Perioperative
maintenance of normothermia reduces the incidence of morbid
cardiac events. A randomized clinical trial. JAMA 277(14):
1127–1134
120. Frank SM, Beattie C, Christopherson R et al (1993) Unintentional
hypothermia is associated with postoperative myocardial ischemia.
the perioperative ischemia randomized anesthesia trial study
group. Anesthesiology 78(3):468–476
121. Calahan MK (1996) Hemodynamic effects of inhaled anesthetics.
Review courses. International Anesthesia Research Society,
Cleveland, OH, pp 14–18
122. Rooke GA, Freund PR, Jacobson AF (1997) Hemodynamic
response and change in organ blood volume during spinal anesthesia in elderly men with cardiac disease. Anesth Analg 85(1):
99–105
123. Ebert TJ (2005) Inhalation anesthesia. In: Barash PG, Cullen BF,
Stoelting RK (eds) Clinical anesthesia, 5th edn. Lippincott
Williams & Wilkins, Philadelphia, PA, p 406
Соседние файлы в папке Библиотека им академика М.И. Перельмана