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14
ability of the kidney to control electrolyte homeostasis, especially under stress,
makes uid and electrolyte balance challenging [10].
C. Tommasino and A. Corcione
2.9 Gastrointestinal System
Geriatric individuals may have prolonged gastric emptying, which predisposes to
higher risk for aspiration during anesthetic induction or in the postoperative period.
2.10 Pharmacokinetic andPharmacodynamic Differences
intheElderly
Aging inuences the pharmacologic responses to drugs, because of alterations in
the absorption, distribution, metabolism, and excretion. Anesthetic agents, to
some extent, are bound to plasma proteins; since in the elderly protein binding is
less efcient, this will result in an exaggerated pharmacologic effect. Body composition changes with age, and there will be a progressive decrease in lean body
mass, an increase in body fat (greater volume of distribution of lipophilic drugs),
and a decrease in total body water (smaller central compartment and increased
serum concentrations of hydrophilic drugs). As discussed previously, drug metabolism and clearance are reduced because of the effects of aging on the liver and
kidney. All these factors will affect the drugs’ pharmacokinetic and pharmacodynamic, and the anesthetic drug dosage needs to be adjusted accordingly [11]
(Table2.3).
2.11 Anesthetic Requirement
2.11.1 Inhaled Anesthetics
Older patients will generally require lower absolute doses of inhalational anesthetics to obtain equivalent anesthetic effects. The minimum alveolar concentration
(MAC) decreases 6.7% per decade for most volatile agents [12] (Table2.3), likely
because of neurophysiological changes in the brain (ion channels, synaptic activity,
or receptor sensitivity modications). In the clinical setting, however, anesthesiologists tend to deliver higher age-adjusted doses of volatile anesthetics during maintenance of anesthesia in elderly patients, 3.8% less volatile anesthetics per decade
rather than the recommended 6.7% [13], and this should not be the case since
emerging, although controversial, evidence suggests that increased depth of anesthesia may be associated with postoperative cognitive dysfunction, delirium, and
increased mortality [14]. The best strategy is to titrate volatile anesthetics with the
assistance of depth of anesthesia monitoring [15].
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Table 2.3 Suggested dose adjustments in geriatric patients for drugs frequently used in
anesthesia
Drug
Propofol •
Midazolam 0.2–0.3mg/kg •
Sevourane MAC closest to age 40=2.1% MAC is reduced by 6.7% per decade of
Desurane MAC closest to age 45=6.0% MAC is reduced by 6.7% per decade of
Morphine • 0.1–0.2mg/kg intraoperatively
Fentanyl 1–2mcg/kg for short-term analgesia 50% reduction in dose
Remifentanil •
MAC minimum alveolar concentration, MAC values for geriatric patients from [
Adult dose
Bolus 2-2.5 mg/kg
Infusion 100-250 mcg/kg/min
•
• 1–2mg boluses tritrated to effect
for acute postoperative analgesia
Bolus 0.5–1mcg/kg
• Infusion 0.03–0.1mcg/kg/min
Geriatric dose
•
1.2-1.7 mg/kg or 20% reduction in
bolus dose
30% reduction in infusion
•
0.05–0.15mg/kg in premedicated
patients
• 20% reduction in patients aged >55
years
• 75% reduction in patients aged >
90years
increasing age
• 60 years≅1.6%
• 70 years≅1.5%
• 80 years≅1.4%
90 years≅1.3%
•
increasing age
• 60 years≅5.8%
• 70 years≅5.5%
• 80 years≅5.1%
• 90 years≅4.8%
•
50% reduction in dose
• No change
• 50% reduction in bolus dose
• 33% reduction in infusion dose
12]
15
2.11.2 Intravenous Anesthetic Agents
Thiopental is not used in modern anesthesia and has been replaced by propofol, a
rapid, short-acting alkylphenol. The brain becomes more sensitive to the effects of
propofol with age [16], and for patients older than 60 years, the elimination clearance decreased linearly. Therefore, propofol dosing needs to be reduced (Table2.3),
mostly when administered with any other induction agent, narcotics or benzodiazepines, as anesthetic depth is synergistically increased. Induction dose with 1.0–1.5
mg/kg in the elderly produces a rapid onset of anesthesia (<1 min), lasting 5–10
min; the dose must be reduced to 0.5–1.0 mg/kg with opioids or when midazolam is
given. The induction dose should be further reduced for patients over the age of
70–80 [17]. Propofol is a good choice because of rapid recovery time and few side
effects. For example, patients older than 80 years exhibit less postanesthetic cognitive impairment as compared to other hypnotic agents.
16
C. Tommasino and A. Corcione
Aging may inuence sedation and cardiorespiratory functions in response to
midazolam, a short-acting benzodiazepine, widely used as an anxiolytic, sedative,
and anesthetic adjuvant. These effects are related to increased brain sensitivity and
decreased drug clearance. A dosage of 0.02 mg/kg for preoperative sedation is
effective in reducing anxiety, without compromising cardiorespiratory function
[18]. Sedation with midazolam is safe and well tolerated in the elderly, provided
that the dosage is reduced according to patient age (Table2.3). Induction of general
anesthesia with midazolam is feasible, and the dose should be 0.1–0.15 mg/kg, with
further reduction to <0.1 mg/kg if synergistic drugs, such as opioids, are used.
2.11.3 Opioid Analgesics
Opioids suppress pain by their action in the brain, spinal cord, and peripheral nervous system and provide the analgesic component of anesthesia, especially during
total intravenous anesthesia (TIVA). With age, the brain becomes more sensitive to
opioids and older patients are more sensitive to the respiratory depressant effects of
opioids.
Morphine is metabolized (>90%) mainly in the liver, with most of the conversion
to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G, analgesic
effects). Patients with renal insufciency may have impaired elimination of morphine glucuronides, and this may account for some of the enhanced analgesia from
a given dose of morphine in the older patient [19].
Sufentanil, alfentanil, and fentanyl are approximately twice as potent in older
patients, and the dose requirements decrease by 50% over the age range 20–89 years
[20] (Table2.3). These ndings are related to brain increased sensitivity to opioids
with age, rather than alterations in pharmacokinetics [20].
Remifentanil, a relatively new synthetic opioid, is quickly hydrolyzed by nonspecic plasma and tissue esterases to essentially inactive compounds, which are excreted
by the kidneys. Remifentanil has a context-sensitive half-time that is very short, is not
inuenced by hepatic or renal failure, and is also independent on the duration of infusion. In the older adults, remifentanil is approximately twice as potent. Minto etal.,
comparing 20- vs. 80-year-old patients, demonstrated an age- dependent reduction of
both central compartment volume and clearance, and a much smaller remifentanil
dose infusion is required in the elderly [21]. With the Minto model for target-controlled infusion of remifentanil, elderly patients receive less drug for a similar target
concentration than younger patients of similar height and weight [22].
Although recommendations currently exist for intravenous dosing, recent studies
have found that elderly patients are routinely given intravenous anesthetic drugs
greater-than-recommended doses for their age, and this is associated with clinically
signicant hypotensive episodes (MAP < 60mm Hg or reduction by >40% from
baseline) [17, 23].
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2.11.4 Neuromuscular Blocking Agents
Muscle relaxation is one of the components of balanced anesthesia. Aging can
have signicant effects on the pharmacokinetics of neuromuscular-blocking
drugs, when the drug depends on liver or renal metabolism [24]. Intermediateacting relaxants, vecuronium and rocuronium, which depend on end-organ elimination, may have a signicantly prolonged duration of action in elderly patients,
and appropriate changes must be made to drug dosage and dose intervals.
Atracurium and cisatracurium, eliminated primarily by temperature-dependent,
spontaneous Hoffman degradation, do not have prolonged duration. Recovery
time is almost identical to young subjects, with no difference in dosage requirements in the elderly. Mivacurium action is prolonged, due to the decreased plasma
acetylcholinesterase that accompanies aging. Short- to intermediate-acting muscle relaxants should be used in all elderly patients when extubation is planned at
the end of the surgery. Pharmacological reversal of neuromuscular blockade must
be a standard procedure in the geriatric population, since postoperative residual
curarization may increase postoperative pulmonary complications, such as pneumonia and atelectasis [25].
2.11.5 Local Anesthetics
In the elderly, the response to local anesthetics is more intense [26]. With aging,
there is a decline in the number of neurons within the spinal cord and slowing of
conduction velocity in the peripheral nerves. A progressive sclerotic closure of the
intervertebral foramina occurs with aging, and the epidural compliance increases,
and a lower dose of epidural local anesthetic is required to block the same number
of segments. After epidural administration, there is an increased spread of the local
anesthetic, intensity of the motor blockade is enhanced, and the level of the block
may be higher [27]. Both bupivacaine and ropivacaine enhance the intensity of
motor blockade, and bupivacaine provides a fast onset time.
When local anesthetics are administered in the subarachnoidal space (spinal
anesthesia), the spread of analgesia varies with the baricity of the solution. With
hyperbaric bupivacaine, sensory analgesia develops more rapidly in patients older
than 80 years, and the maximum level of analgesia is also higher (at least by one
dermatome) [28]. Hemodynamic changes (bradycardia, hypotension) after neuraxial anesthesia are more frequent with advancing age [29], requiring continuous and
careful hemodynamic monitoring.
The effects of local anesthetic agents, administered for obtaining peripheral
nerve blocks, have longer duration in the elderly population. Ropivacaine (0.75%)
induces sensory and motor blocks that last longer, likely as a consequence of alterations of nerve physiology and sensitivity to local anesthetics [30].
18
C. Tommasino and A. Corcione
2.12 Preoperative Assessment
The preoperative assessment of the elderly patient must embrace not only physical
status and comorbidities but also domains, such as cognition, functionality, frailty,
polypharmacy, nutrition, and social support [31]. The patient should be evaluated
several days before the surgery, possibly after medical information has been obtained
from the surgeon or primary care physician. The assessment includes history, physical examination, and review of the medical chart. Due to the high frequency of postoperative neurologic, pulmonary, and cardiac complications in the elderly, the
anesthesiologist should pay special attention to these specic organ systems.
With the aim of improving the quality of care, recent guidelines recommend
precise preoperative assessments for every geriatric patient [32, 33]. The punctual
assessment emphasized in the guidelines is intended to be as a multidisciplinary
approach from the full team involved in the care of the patient: the physician (internist, geriatrician), the surgeon, and the anesthesiologist.
2.12.1 Performing Complete History andPhysical Examination
Clinical history and physical examination allow the assessment of the physical status, the comorbidities, and the functional reserve of the patient. During the visit, the
anesthesiologist should recognize the alterations that may require preoperative correction (dehydration, hypovolemia, anemia, electrolyte disturbances, arrhythmias).
2.12.2 Conducting Cognitive Assessment, Including thePatient’s
Ability toUnderstand thePurpose ofthePlanned Surgical
Procedure
Assessment and documentation of the baseline cognitive status will facilitate recognition of postoperative cognitive dysfunctions. Simple-to-administer and reproducible tests can be useful, such as the Mini-Cog, a composite of three-item recall and
clock drawing [34], or the Mini-Mental Status Examination, with scores from 0 to 30
(a score less than 17 indicates dementia) [35]. The patients must understand the anesthesia plan and give his/her consent to treatment. When the patient loses decisionmaking capacity, because of cognitive dysfunction, it will be necessary for a legal
representative to grant informed consent, according to the laws of the country [36].
2.12.3 Screening forDepression
Depression has been associated with higher pain perception and increased postoperative analgesic use. To evaluate depression, the anesthesiologist may use very
simple tools, such as the Patient Health Questionnaire-2 [37], or ask for advice from
a psychiatrist.
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2.12.4 Determining Risk Factors forPostoperative Delirium
Delirium is an acute decline in cognitive function with reduced awareness and disturbance of attention that tends to uctuate throughout the day. The main predisposing risk factors for delirium are cognitive impairment (Mini-Mental State
Examination score < 24) [35], dementia (main predisposing factor), depression,
multimorbidity, reduced functional status (i.e., reduced levels of independence,
abilities, and socialization) and/or frailty, malnutrition (low serum albumin), dehydration (blood urea nitrogen-to-creatinine ratio < 18), alcohol abuse, sensory
impairment (hearing and visual), drug interactions (anticholinergics, benzodiazepines), pain, hypoxia, and metabolic disturbances [38].
2.12.5 Screening forSubstance Abuse/Dependence, Including
Alcohol
Alcohol abuse and dependence are associated with increased rates of postoperative
mortality and complications, including pneumonia, sepsis, wound infection, and
prolonged hospitalization [39]. Prophylaxis for withdrawal syndromes should be
considered, and in the case of alcohol abuse, patients should receive, in the perioperative period, daily multivitamins (with folic acid) and high-dose oral or parenteral
thiamine (100 mg).
2.12.6 Performing Cardiac Evaluation
Older patients are more vulnerable to perioperative cardiac adverse events [40].
Therefore, it is critical to evaluate the cardiac functional reserve of the patient and
plan the appropriate perioperative screening (Fig.2.2) and management. Functional
capacity can be measured in metabolic equivalents (METs) and can be used as a
predictor of future cardiac events. One MET equals the basal metabolic rate (oxygen consumption at rest = 3.5 mL O
objective assessment of functional capacity. Without testing, functional capacity
can be estimated from the ability to perform daily living activities. Walking on level
ground (about 6 km/h) or climbing two ights of stairs demands 4 METs, while
strenuous sports, such as swimming, >10 METs. Generally, <4 METs indicates
poor functional capacity, associated with increased incidence of postoperative cardiac events and worse short- and long-term outcome in patients undergoing noncardiac surgery. Cardiac risk estimation is based on patient characteristics and type of
surgery (nature and duration of the surgical procedure), and laboratory measurements and noninvasive/invasive testing are required accordingly, following evidence-based algorithms (Fig.2.2) [41].
/kg bw/min), and exercise testing provides an
2
20
C. Tommasino and A. Corcione
Step 1
Step 2
Step 3
Step 4
Step 5
Step 6
Step 7
Urgent surgery
No
Active/Unstable cardiac
condition
No
Surgical risk
Intermediate
High
Functional capacity
<= 4
METs
Surgical risk
High
Cardiac risk factors
>= 3
Non invasive stress
test
Yes No further cardiac testing
Yes
Low
> 4
METs
Inter-
mediate
<= 2
No/Mild/
Moderate Ischmeia
Cardiologist
ECG
+ Risk factors, medical tx
+ Non invasive stress test
+ Echocardiography,
biomarkers
Procede to surgery
Extensive Stress
Induced Ischemia
Individualized
management
Fig. 2.2 Algorithm for patients undergoing noncardiac surgical procedure
2.12.7 Assessing Risk Factors forPostoperative Pulmonary
Complications
Postoperative pulmonary complications have an incidence of 40% in the
elderly and contribute to overall morbidity and mortality. Many independent
variables are associated with respiratory failure, as the American Society of
Anesthesiologists (ASA status) classication, emergency and/or complex surgery, preoperative sepsis, and elevated creatinine. Older age, male patients,
smokers, and patients with a history of congestive heart failure or COPD, or
both, are also predisposed [42].
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2.12.8 Documenting Functional Status andFall History
Reduced levels of independence, abilities, and socialization are common among the
elderly, as a result of gait alteration, loss of coordination, reduced or nullied
sphincter control, malnutrition, associated illnesses, and/or cognitive deterioration.
Impaired functional status is associated with surgical site infection, increased mortality, and complication rate [43]. Functional status can be measured by activities of
daily living (ADL, physical day-to-day self-care) and instrumental ADL (IADL,
complex task activity) [44]. Patients who are not able to complete the Timed Up and
Go test in less than 20 s are regarded as being at risk of falls [45].
2.12.9 Calculate Frailty Score at Baseline
Frailty, a condition of critically reduced functional reserves, involving multiple
organ systems, is an age-associated decline in ve domains: shrinking (weight loss),
weakness (decreased grip strength), exhaustion, low physical activity, and slowed
walking speed (measured by the speed at which the patient walks a xed distance).
These domains can be easily assessed using the frailty index [46]. Hypoalbuminemia,
hypocholesterolemia, and high levels of inammation, together with muscular atrophy, are specic markers. Frailty (6.9% in older patients) independently predicts
postoperative complications, length of stay, and discharge to a skilled or assisted
living facility [46].
2.12.10 Assessing Nutritional Status andConsidering
Implementation ofPreoperative Interventions
forHigh-Risk Patients
Suitable tools for evaluating the nutritional status are the body mass index and
weight loss within the last 6 months. Among acutely hospitalized older patients, the
prevalence of malnutrition is 52%, and the most widely used test to assess nutritional status and diagnose malnutrition is the Mini-Nutritional Assessment, which
can be performed at the bedside using a questionnaire, with scores ranging from 0
to 30 (<17 indicates malnutrition) [47]. Malnutrition may be secondary to somatic,
psychic, or social problems, is associated with a worse prognosis, and is an independent risk factor for morbidity and mortality. Reversing established preoperative
nutritional decit, especially in short periods of time, is challenging. In high-risk
patients, improvement in the nutritional status can be achieved over time by adequate diet, hand feeding, additional sip feeding, or enteral nutrition [48]. A multimodal rehabilitation program, consisting of exercise training and nutritional and
psychological support, seems to improve the ability to undergo the stress of surgery
and provides faster recovery [49]. Every effort should be made to prevent the development of malnutrition during hospitalization.
22
C. Tommasino and A. Corcione
2.12.11 Taking aComplete Medication History, Making Needed
Perioperative Adjustments, andMonitoring
forPolypharmacy
Older patients take multiple medications, which can be appropriate, but increase the
risk of adverse drug reactions (ADRs), impaired physical and cognitive function,
and hospital admission. To minimize the risk for ADRs, the anesthesiologist needs
to identify potential interactions between medications and anesthetic drugs and
medications that should be discontinued or avoided before surgery, according to the
Beers criteria, which must be used as a guide of good practice [50]. Polypharmacy
is dened as taking more than ve regular prescribed medicines. Deprescribing
(reducing specic classes of medicines) may decrease ADRs and improve quality of
life. This process, however, should be the aim of the full team taking care of the
patient, because it can be a difcult task for the anesthesiologist when the preoperative visit is very close to the surgery or in case of emergency.
2.13 Perioperative Anesthetic Procedure
2.13.1 Preoperative Testing
Screening in the elderly patient should always include hemoglobin, renal function
tests (blood urea nitrogen, creatinine), and albumin evaluation. Further diagnostic
tests may be required on an individual basis, according to preoperative clinical
assessment and surgical plan, to conrm the presence or absence of diseases (e.g.,
Fig.2.2).
2.13.2 Preoperative Fasting
Clear uids (water, tea, black coffee, fruit juices without pulp) can be given up to 2
h before anesthesia (general anesthesia, regional anesthesia, or sedation/analgesia),
and the minimum fasting period for a light solid meal should be 6 h [51]. A
carbohydrate- rich beverage before elective surgery improves subjective well-being,
reduces thirst and hunger, and reduces postoperative insulin resistance. Recent evidence suggests that the carbohydrate-rich beverage attenuates fasting-induced stress
in the elderly, without known risks of pulmonary aspiration [52].
2.13.3 Choice ofAnesthetic Technique
Scientic evidence is insufcient to recommend the “most appropriate” anesthetic
approach for elderly patients. General and regional anesthetic techniques have
advantages and disadvantages, and the baseline functional status of the patient (as
well as the type of surgery) needs to be considered when selecting anesthetic drugs
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Table 2.4 Geriatric physiology and anesthetic implication
System
Cardiovascular Decresed sympathetic tone Labile blood pressure
Pulmonary Increased pulmonary arterial
Nervous system Decreased neurotransmitters Increased risk of postoperative
Endocrine system Impaired glucose tolerance Increased intraoperative
Hepatic/renal system Altered drug metabolism Decreased drug clearance
Thermoregulation Decreased muscle mass and
Geriatric physiology
Decreased venous compliance and
preload
Impaired baroreceptor response
Cardiac diastolic dysfunction
pressure
Decreased responce to hypoxia and
hypercarbia
Decreased muscle mass and lung
elasticity
Decreased cough reex and
esophageal motility
vascular reactivity
Anesthetic implications
Sensitivity to hypotension and
volume overload
Cardiac function decline with
inadequate cardiac lling
Raised PAO
Sensitivity to hypoxia and
hypercarbia
Increased dead space ventilation
and work of breathing
Sensitivity to residual anesthetic
effects
Aspiration risk
cognitive dysfunction
hyperglycemia
Increased risk of hypothermia
-PaO2 gradient
2
23
and technique (Tables 2.3 and 2.4). Intensity of monitoring, during and following
anesthesia, is determined on an individual basis, considering the patient’s physical
status and the surgical procedure. Monitoring depth of anesthesia (with processed
EEG signal, e.g., Bispectral Index monitoring) may be a useful guide for effective
titration of hypnotic drugs administration and avoids deep level of anesthesia, detrimental for elderly patients [15, 53].
Anesthesia-related complications are rare, and postoperative complications in
the elderly are mostly related to the entire perioperative procedure [54]. General
and locoregional techniques are both appropriate for older patients [55]. Neuraxial
anesthesia, however, is increasingly viewed as a reasonable alternative to general
anesthesia, and some surgical procedures, especially hip fracture surgery, seem to
benet from locoregional approaches [56]. Various benecial effects from neuraxial blocks (epidural, spinal, or combined spinal-epidural techniques) have been
reported, such as reduced 30-day mortality, decreased risk of pneumonia, opiatesparing effects, and postoperative inhibition of brinolysis [57]. General anesthesia has a lower incidence of systemic hypotension and cerebrovascular accidents
compared to neuraxial anesthesia [56], and the occurrence of hypotension is a
strong and highly signicant predictor for worse outcome in the elderly [53, 58].
Future studies will indicate whether the anesthesia choice will affect outcome in
elderly patients. The recently started REGAIN trial is a multicenter randomized
trial that will compare several outcomes, including recovery of functional independence, in patients undergoing spinal or general anesthesia for hip fracture surgery
in the USA and Canada [59].
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