18.1 Geriatric Physiology, Pharmacodynamics & Postoperative Delirium/POCD
Key Takeaways
- Cardiovascular aging is characterized by arterial stiffening, left ventricular diastolic dysfunction (impaired relaxation), increased reliance on sinus rhythm and atrial kick (up to 20-30% of LV end-diastolic volume), and blunted beta-adrenergic receptor responsiveness.
- Respiratory changes include loss of pulmonary elastic recoil, increased lung compliance, and stiffening of the chest wall; Closing Capacity (CC) increases progressively, exceeding FRC in the supine position at ~44 years and in the upright position at ~66 years, leading to ventilation-perfusion mismatch and age-related decline in PaO₂ (PaO₂ ≈ 100 - [0.3 × Age]).
- Central nervous system changes feature brain atrophy, loss of neurotransmitter synthesis, and a 6-7% decrease in volatile anesthetic Minimum Alveolar Concentration (MAC) per decade after age 40 (approximating a ~30% reduction by age 80).
- Renal GFR and blood flow decline by approximately 1 mL/min/year after age 40; serum creatinine remains deceptively normal due to concurrent loss of skeletal muscle mass, necessitating calculated creatinine clearance for drug dosing.
- Postoperative Delirium (POD) is an acute, fluctuating disturbance of attention and cognition presenting in the early postoperative period (evaluated via CAM-ICU), whereas Postoperative Cognitive Dysfunction (POCD) is a subtle, persistent decline in memory and executive function detected by formal neuropsychometric testing weeks to months later; Beers Criteria mandates avoiding high-risk medications including benzodiazepines, diphenhydramine, meperidine, and tertiary amine anticholinergics.
Last updated: August 2026
18.1 Geriatric Physiology, Pharmacodynamics & Postoperative Delirium/POCD
The geriatric surgical demographic is expanding rapidly, presenting anesthesia providers with unique physiological, pharmacological, and cognitive vulnerabilities. Aging is characterized by a progressive reduction in physiological functional reserve across all organ systems, altered body composition, diminished homeostatic adaptability, and heightened susceptibility to perioperative neurocognitive disorders.
1. Cardiovascular Aging Physiology & Hemodynamics
Cardiovascular alterations in the elderly are driven primarily by structural remodeling of large elastic arteries and the left ventricle, combined with autonomic dysregulation.
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| GERIATRIC CARDIOVASCULAR ALTERATIONS |
+-----------------------+--------------------------------------+------------------------------------------+
| Physiological Entity | Structural / Functional Alteration | Clinical Anesthetic Implication |
+-----------------------+--------------------------------------+------------------------------------------+
| **Vascular Tree** | • Loss of elastin & increased col- | • Elevated systolic BP, widened pulse |
| | lagen in arterial media | pressure, increased SVR |
| | • Decreased arterial compliance | • Elevated afterload → concentric LVH |
| | • Increased Pulse Wave Velocity | • Exaggerated hypotension upon induction |
+-----------------------+--------------------------------------+------------------------------------------+
| **Left Ventricle** | • Concentric hypertrophy & fibrosis | • Impaired active myocardial relaxation |
| | • **Diastolic Dysfunction (impaired | • Critical dependence on **atrial kick** |
| | early passive diastolic filling)** | • Tachycardia & Afib cause flash edema |
+-----------------------+--------------------------------------+------------------------------------------+
| **Autonomic System** | • Decreased β-adrenergic receptor | • Blunted max heart rate response to |
| | density & uncoupling of Gs-proteins| hypovolemia, stress, or atropine |
| | • Down-regulated baroreceptor reflex | • Severe postural / induction hypotension|
| | • Elevated circulating catecholamines| • Decreased inotropic response to β-agon |
+-----------------------+--------------------------------------+------------------------------------------+
| **Conduction System** | • Fibrofatty infiltration of SA/AV | • High incidence of sick sinus syndrome, |
| | nodes and bundle branches | bundle branch blocks, and 1st/2nd AVB |
+-----------------------+--------------------------------------+------------------------------------------+
Diastolic Dysfunction & The Critical "Atrial Kick"
In the young compliant heart, approximately $70 - 80%$ of left ventricular filling occurs during early rapid passive diastole (the $E$ wave on Doppler echocardiography), with the remaining $20 - 30%$ contributed by atrial contraction (the $A$ wave). In the stiff, non-compliant geriatric ventricle:
- Early passive filling is significantly impaired ($E/A \text{ ratio } < 1.0$).
- The atrial contraction ("atrial kick") contributes up to $30 - 40%$ of total left ventricular end-diastolic volume (LVEDV).
- Clinical Hazard: Sudden loss of sinus rhythm (e.g., new-onset atrial fibrillation or junctional rhythm) or severe tachycardia ($>100 \text{ bpm}$, which severely truncates diastolic filling time) precipitously drops stroke volume, triggering profound systemic hypotension and acute pulmonary edema.
Blunted Beta-Adrenergic Responsiveness
While baseline circulating plasma norepinephrine levels are elevated in older adults due to enhanced sympathetic tone, post-receptor intracellular signaling is blunted:
- Beta-1 and Beta-2 receptor density and affinity decrease, coupled with impaired adenylyl cyclase activation.
- The maximum heart rate declines predictably with age, estimated by:
- Sympathetic baroreceptor buffering is sluggish. Induction agents that cause peripheral vasodilation (e.g., propofol) produce precipitous drops in Mean Arterial Pressure (MAP) without compensatory reflex tachycardia.
- Direct-acting alpha-1 agonists (e.g., phenylephrine) or combined inotropes/vasopressors (e.g., norepinephrine, ephedrine) may be required in titrated doses to maintain coronary and cerebral perfusion.
2. Respiratory Aging Physiology & Gas Exchange
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| GERIATRIC PULMONARY MECHANICS |
+-------------------------------------------------------------------------+
| • Loss of Lung Elastic Recoil (Lung Compliance INCREASES) |
| • Calcification of Costochondral Cartilage (Chest Wall Compliance ↓) |
| • Flattening & Atrophy of Diaphragmatic Muscle Fibers |
| • Progressive Increase in Residual Volume (RV) & Closing Capacity (CC) |
| • Functional Residual Capacity (FRC) Remains Relatively Constant/Slight ↑|
| • Vital Capacity (VC) and FEV₁ DECREASE Progressively |
+-------------------------------------------------------------------------+
[CLOSING CAPACITY VS. FRC ACROSS THE LIFESPAN]
Volume (L)
^
| / Closing Capacity (CC)
| /
| -----------+----------------- FRC (Upright)
| / | (CC > FRC Upright at ~66 yrs)
| -----------+-------------+----------------- FRC (Supine)
| / | (CC > FRC Supine at ~44 yrs)
| / |
| / |
+--------------------+----------------------------------> Age (Years)
44 yrs 66 yrs
Closing Volume (CV) & Closing Capacity (CC)
- Closing Capacity ($CC = CV + RV$): The lung volume at which dependent terminal bronchioles begin to collapse during expiration.
- Age-Related Intersection Points:
- In the supine position, $CC$ exceeds resting $FRC$ at approximately $44 \text{ years}$ of age.
- In the upright (standing) position, $CC$ exceeds resting $FRC$ at approximately $66 \text{ years}$ of age.
- When $CC > FRC$, dependent airway closure occurs during normal tidal respiration, causing microatelectasis, intrapulmonary right-to-left shunting, and ventilation-perfusion ($V/Q$) mismatching.
Formula for Age-Related Decline in Arterial Oxygen Tension
Arterial oxygen tension ($PaO_2$) declines progressively with age during room air breathing due to increasing $V/Q$ inequality:
Example: An 80-year-old patient on room air has a predicted normal $PaO_2 \approx 100 - (0.3 \times 80) = 76 \text{ mmHg}$ (compared to $\approx 95 \text{ mmHg}$ in a 20-year-old).
Ventilatory Drive Reflexes
- Central hypercapnic ventilatory response and peripheral hypoxic ventilatory response are blunted by up to $50%$ in elderly patients.
- Geriatric patients exhibit heightened vulnerability to airway obstruction, hypercarbic respiratory failure, and severe hypoxemia under residual sedation, opioids, or volatile anesthetics.
3. Central & Peripheral Nervous System Aging
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| GERIATRIC NEUROLOGICAL ALTERATIONS |
+-----------------------+--------------------------------------+------------------------------------------+
| Neurological Domain | Structural / Biomolecular Change | Clinical Impact |
+-----------------------+--------------------------------------+------------------------------------------+
| **Brain Morphology** | • Loss of 10-20% cortical neurons | • Increased sensitivity to CNS depress- |
| | • Decreased brain mass & white matter| ants (propofol, midazolam, opioids) |
| | • Widened sulci & enlarged ventricles| • Increased free volume in dura/cranium |
+-----------------------+--------------------------------------+------------------------------------------+
| **Neurochemistry** | • Decreased acetylcholine synthesis | • Elevated baseline risk of delirium |
| | • Decreased dopamine & serotonin | • Enhanced vulnerability to anticholinerg|
| | • Decreased GABA-A receptor density | • Exaggerated sedative response |
+-----------------------+--------------------------------------+------------------------------------------+
| **Inhalational MAC** | • Decreased synaptic density and | • **MAC declines 6% to 7% per decade** |
| | neuronal metabolic activity | **after age 40** (~30% drop by age 80) |
+-----------------------+--------------------------------------+------------------------------------------+
| **Neuraxial Anatomy** | • Calcified interspinous ligaments | • Difficult epidural/spinal placement |
| | • Stenosis of intervertebral foramina| • Local anesthetic spreads higher; dose |
| | • Decreased CSF volume and pressure | requirements **reduced by 20-40%** |
+-----------------------+--------------------------------------+------------------------------------------+
NCE Clinical Rule — MAC Reduction Calculation: For every decade beyond 40 years of age, volatile anesthetic MAC decreases by $6.7%$ ($0.67%$ per year).
- Baseline Sevoflurane MAC at 40 years $= 2.0%$
- At 80 years (4 decades older): Reduction $= 4 \times 6.7% = 26.8%$
- Adjusted Sevoflurane MAC at 80 years $\approx 2.0% \times (1 - 0.268) \approx 1.46%$
4. Renal, Hepatic & Body Composition Pharmacokinetics
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| GERIATRIC PHARMACOKINETIC SHIFTS |
+-------------------------------------------------------------------------+
| 1. Total Body Water (TBW) DECREASES (↓ 20-30%) |
| → Smaller volume of distribution (Vd) for hydrophilic drugs |
| → Higher initial peak plasma concentration (e.g., muscle relaxants) |
| |
| 2. Total Body Fat INCREASES (↑ 30-50%) |
| → Larger volume of distribution (Vd) for lipophilic drugs |
| → Prolonged elimination half-life (t1/2β) (e.g., diazepam, fentanyl) |
| |
| 3. Serum Albumin DECREASES (↓ 15-20%) |
| → Higher free (unbound, active) fraction of acidic drugs (propofol, |
| warfarin, phenytoin, diazepam) |
| |
| 4. Alpha-1-Acid Glycoprotein (AAG) INCREASES (or remains stable) |
| → Increased binding / lower free fraction of basic drugs (lidocaine, |
| bupivacaine, ropivacaine) |
+-------------------------------------------------------------------------+
Renal Elimination & The Serum Creatinine Pitfall
- Renal Cortical Atrophy: Glomerular filtration rate (GFR) and renal blood flow decline at a rate of approximately $1 \text{ mL/min/year}$ after age 40 (or $\approx 8 - 10%$ per decade).
- The Serum Creatinine Trap: Because aging is accompanied by progressive skeletal muscle sarcopenia (decreased creatinine production), serum creatinine often remains completely normal ($0.8 - 1.1 \text{ mg/dL}$) despite a $50%$ reduction in true GFR.
- Creatinine Clearance Calculation (Cockcroft-Gault Equation):
- Hydrophilic drugs eliminated via renal excretion (e.g., pancuronium, rocuronium metabolites, vecuronium, neostigmine, sugammadex, antibiotics) exhibit delayed clearance and prolonged duration of action.
Hepatic Clearance & Biotransformation
- Total hepatic blood flow decreases by $30 - 40%$ with age due to decreased cardiac output and parenchymal atrophy.
- Phase I Metabolism (CYP450 Oxidation, Reduction, Hydrolysis): Significantly impaired in elderly patients, prolonging the clearance of midazolam, lidocaine, alfentanil, and diazepam.
- Phase II Metabolism (Conjugation: Glucuronidation, Sulfation, Acetylation): Relatively preserved in the elderly. Drugs metabolized primarily via Phase II conjugation (e.g., lorazepam, oxazepam, temazepam) do not accumulate active Phase I intermediates.
- Pseudocholinesterase (Butyrylcholinesterase): Activity decreases by $\approx 25%$ in elderly males, potentially prolonging succinylcholine and mivacurium duration slightly.
5. Postoperative Delirium (POD) vs. Postoperative Cognitive Dysfunction (POCD)
Perioperative neurocognitive disorders represent significant complications associated with increased morbidity, prolonged hospital stay, loss of functional independence, and elevated 1-year mortality.
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| POSTOPERATIVE DELIRIUM (POD) VS. COGNITIVE DYSFUNCTION (POCD) |
+-----------------------+--------------------------------------+------------------------------------------+
| Characteristic | Postoperative Delirium (POD) | Postoperative Cognitive Dysfunction (POCD|
+-----------------------+--------------------------------------+------------------------------------------+
| **Clinical Definition**| Acute, fluctuating disturbance of | Subtle, persistent neurocognitive decline|
| | attention, awareness, and cognition | in memory, executive function, attention |
+-----------------------+--------------------------------------+------------------------------------------+
| **Onset Timing** | **Acute (Postoperative Days 1 - 3)** | **Delayed / Insidious (Weeks to Months)**|
| | Often peaks at night ("sundowning") | Evident after discharge |
+-----------------------+--------------------------------------+------------------------------------------+
| **Duration** | Hours to days (transient & reversible| Months to permanent |
| | in most cases) | |
+-----------------------+--------------------------------------+------------------------------------------+
| **Diagnostic Tool** | **CAM-ICU** (Confusion Assessment | Formal, battery-style **Neuropsychometric|
| | Method for the ICU) or 3D-CAM | Testing** (preop vs postop z-scores) |
+-----------------------+--------------------------------------+------------------------------------------+
| **Clinical Subtypes** | • Hyperactive (agitation, combative) | Subtle deficits in processing speed, |
| | • **Hypoactive (lethargic, flat - | multitasking, recall, spatial awareness |
| | MOST COMMON & OFTEN MISSED)** | |
| | • Mixed (fluctuates between both) | |
+-----------------------+--------------------------------------+------------------------------------------+
| **Major Risk Factors**| Baseline dementia, age >70, severe | Advanced age, low baseline education, |
| | pain, infection, sleep deprivation, | major cardiac surgery / CPB, cerebral |
| | anticholinergic/sedative exposure | microemboli, prolonged inflammation |
+-----------------------+--------------------------------------+------------------------------------------+
[CAM-ICU DIAGNOSTIC ALGORITHM FOR DELIRIUM]
Feature 1: Acute Onset or Fluctuating Course
+
Feature 2: Inattention
|
+-------------------+-------------------+
| |
v v
Feature 3: Disorganized Feature 4: Altered Level of
Thinking Consciousness
| |
+-------------------+-------------------+
|
v
**DIAGNOSIS: POSITIVE DELIRIUM**
(Requires: Feature 1 + Feature 2 AND [Feature 3 OR 4])
6. The Beers Criteria & Perioperative Neurotoxicity
The American Geriatrics Society (AGS) Beers Criteria identifies medications with unfavorable risk-to-benefit profiles in older adults due to high anticholinergic burden, CNS depression, or toxic metabolite accumulation.
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| PERIOPERATIVE BEERS CRITERIA HIGH-RISK DRUGS |
+-----------------------+--------------------------------------+------------------------------------------+
| Medication / Class | Adverse Mechanism in Geriatrics | Anesthetic Alternative |
+-----------------------+--------------------------------------+------------------------------------------+
| **Benzodiazepines** | • Profound sedation, ataxia, memory | • Multimodal opioid-sparing analgesia, |
| (Midazolam, Diazepam) | impairment, 3-fold POD risk spike | reassurance, low-dose dexmedetomidine |
+-----------------------+--------------------------------------+------------------------------------------+
| **Tertiary Anticholin-| • Crosses blood-brain barrier (BBB), | • **Glycopyrrolate** (quaternary amine, |
| ergics** (Scopol- | precipitates central anticholiner- | does not cross BBB, peripheral only) |
| amine, Atropine) | gic syndrome and severe delirium | |
+-----------------------+--------------------------------------+------------------------------------------+
| **Diphenhydramine** | • Potent central muscarinic M₁ block | • 5-HT₃ antagonists (ondansetron), |
| (H₁ Antihistamine) | causes acute confusion and delirium| dexamethasone for antiemesis/pruritus |
+-----------------------+--------------------------------------+------------------------------------------+
| **Meperidine** | • Active metabolite **normeperidine**| • Fentanyl, hydromorphone (low-dose), |
| (Demerol) | causes CNS excitation, seizures | or IV acetaminophen; avoid meperidine |
+-----------------------+--------------------------------------+------------------------------------------+
| **Promethazine** | • Dopaminergic & anticholinergic blk | • Ondansetron, low-dose droperidol |
+-----------------------+--------------------------------------+------------------------------------------+
| **Ketorolac / NSAIDs**| • Acute renal failure, peptic ulcer, | • IV Acetaminophen, local infiltration, |
| | and platelet dysfunction | selective regional nerve blocks |
+-----------------------+--------------------------------------+------------------------------------------+
NCE Exam Trap — Reversal in the Geriatric Patient: When reversing non-depolarizing neuromuscular blockade in an 82-year-old with Neostigmine, pair it with Glycopyrrolate rather than Atropine. Glycopyrrolate is a quaternary ammonium compound that carries a permanent positive charge and cannot penetrate the blood-brain barrier, avoiding central anticholinergic syndrome and postoperative delirium. Furthermore, Sugammadex provides rapid, complete reversal without autonomic or cholinergic side effects, minimizing residual curarization in the elderly.
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