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Post-Operative Hypotension: Notes & Stepwise Pharmacological Management

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1. Definition

• MAP < 65 mmHg (most commonly used threshold)
• SBP < 90 mmHg, OR
• A drop of >20-30% below the patient's individual baseline BP

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2. Pathophysiology - Why Does It Happen?

Vasodilation is the most common cause of POH after noncardiac surgery - Douglas et al., Br J Anaesth 2023 (PMID: 37778937)

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3. Clinical Recognition

• Low MAP/SBP on monitoring
• Tachycardia (compensatory) - but may be absent with beta-blockers or in vagally mediated states
• Oliguria / decreased urine output
• Altered consciousness, agitation
• Pale, cold, clammy skin (low CO states) vs. warm vasodilated peripheries (distributive)
• Narrow pulse pressure = low stroke volume / low CO
• Low diastolic pressure = vasodilation

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4. Causes to Actively Exclude (AABC Rule of Thumb)

• A - Arrhythmia / Anesthetic residual (volatile, neuraxial)
• A - Anaphylaxis / Adrenal crisis (pheochromocytoma post-resection, Addison's)
• B - Bleeding / Blood loss (surgical site, internal hemorrhage)
• C - Cardiac (STEMI, tamponade, tension pneumothorax, PE)
• C - Compression / obstruction

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5. Stepwise Pharmacological Management

Step 1 - Immediately Identify the Cause

• Get a quick history: surgical procedure, estimated blood loss, anesthetic used, pre-op meds (ACE inhibitors, beta-blockers, diuretics)
• Check: SBP trends, HR, urine output, SpO2, ECG
• Assess fluid responsiveness (passive leg raise, stroke volume variation if invasive monitoring available)

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Step 2 - Position + Oxygen

• Trendelenburg or passive leg raise (auto-transfusion effect, assess fluid responsiveness)
• 100% supplemental oxygen
• Call for help / escalate if needed

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Step 3 - Fluid Resuscitation (if hypovolemia is likely)

Do NOT fluid overload - assess response after each bolus (MAP, HR, UO). If no response after 1-2 boluses, move to vasopressors.

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Step 4 - Vasopressors (First-Line)

A. Phenylephrine

• Mechanism: Pure alpha-1 agonist -> increases SVR
• Dose: 50-200 mcg IV bolus; infusion 0.5-3 mcg/kg/min
• Indication: Anesthesia-induced vasodilation, spinal/epidural hypotension
• Cautions: Reduces cardiac output via reflex bradycardia; avoid in septic shock; avoid if CO is already low
• Note: Most commonly used vasopressor in the US for perioperative hypotension - Miller's Anesthesia, 10e

B. Ephedrine

• Mechanism: Mixed alpha + beta agonist (direct + indirect); increases both SVR and CO
• Dose: 5-10 mg IV bolus, repeat every 3-5 min (max ~50 mg)
• Indication: Hypotension + bradycardia (e.g., spinal anesthesia), preferred when cardiac stimulation is wanted
• Cautions: Tachyphylaxis with repeated dosing; avoid in tachycardia
• Note: Preferred over phenylephrine in patients on amitriptyline or where indirect-acting agents are inappropriate - Morgan & Mikhail, Clinical Anesthesiology, 7e

C. Norepinephrine (Noradrenaline)

• Mechanism: Potent alpha-1 + weak beta-1 agonist -> increases SVR while largely maintaining CO
• Dose: 0.01-0.5 mcg/kg/min IV infusion (start low, titrate)
• Indication: Most common vasopressor globally for POH; preferred when phenylephrine has failed or CO must be maintained; first-line in septic shock
• Cautions: Peripheral vasoconstriction; requires central line for prolonged use (peripheral short-term administration is acceptable in emergencies)
• Note: Norepinephrine was the most common vasopressor used for postoperative hypotension in the 2023 systematic review [PMID: 37778937]

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Step 5 - Second-Line Vasopressors

D. Vasopressin

• Mechanism: V1 receptor agonist -> vasoconstriction without catecholamine stimulation
• Dose: 0.03-0.04 units/min fixed-rate infusion (not titrated like catecholamines)
• Indication: Adjunct when norepinephrine is insufficient; catecholamine-refractory vasodilatory shock; may be particularly useful in adrenal insufficiency or post-cardiopulmonary bypass
• Cautions: Mesenteric and coronary vasoconstriction at high doses; reduces cardiac output

E. Epinephrine (Adrenaline)

• Mechanism: Alpha + beta-1 + beta-2 -> increases HR, CO, SVR
• Dose: 0.01-0.5 mcg/kg/min infusion; 0.1-1 mg bolus in cardiac arrest / anaphylaxis
• Indication: Cardiogenic shock with hypotension, anaphylaxis (IM 0.3-0.5 mg = drug of choice), severe refractory shock
• Cautions: Increases myocardial oxygen demand; arrhythmogenic; causes hyperglycemia

F. Dopamine

• Mechanism: Dose-dependent: low dose (1-5 mcg/kg/min) = dopaminergic; moderate (5-10) = beta-1; high (>10) = alpha-1
• Dose: 5-20 mcg/kg/min
• Indication: Less commonly used now; consider in POH with bradycardia and impaired cardiac function
• Cautions: More arrhythmogenic than norepinephrine; no longer preferred first-line

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Step 6 - Specific Scenarios

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Step 7 - Adjuncts for Refractory Hypotension

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6. Vasopressor Comparison Summary

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7. Monitoring Targets

• MAP > 65 mmHg (or within 10% of individual baseline)
• UO > 0.5 mL/kg/hr
• SpO2 > 95%, lactate trending down
• HR within normal range (avoid excessive tachycardia from aggressive beta stimulation)
• Avoid phenylephrine in low-output states - it may worsen splanchnic perfusion

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8. Special Notes

1. Chronic antihypertensive medications (ACE inhibitors, ARBs, diuretics) taken on the morning of surgery are a major risk factor for POH - delay restarting these postoperatively until clearly necessary. - APSF perioperative hypotension guidance
2. Even transient POH (MAP <65 for as little as 11-20 minutes) is associated with AKI, myocardial injury, and stroke. - Miller's Anesthesia, 10e
3. Neuraxial anesthesia (spinal/epidural) causes sympatholysis -> vasodilation + bradycardia. Treat with phenylephrine (if HR normal/high) or ephedrine (if bradycardia present).
4. Post-pheochromocytoma resection: Up to 20-70% of patients require postoperative vasopressor therapy. Ensure adequate volume loading pre-vein ligation to reduce post-resection hypotension severity. - Miller's Anesthesia, 10e
5. Fluids and vasopressors are complementary, not competing. Fluid responsiveness testing (passive leg raise, SV variation) guides rational use.

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Quick Reference - Stepwise Algorithm

Recognize POH (MAP <65 or SBP <90)
       ↓
ABCDE assessment + 12-lead ECG
       ↓
Identify cause: Hemorrhage? Vasodilation? Pump failure? Obstruction?
       ↓
  ┌─────────────────────────────────────────────┐
  │  Fluid responsive? → IV bolus 250-500 mL   │
  │  (Repeat x1-2, reassess)                   │
  └─────────────────────────────────────────────┘
       ↓ (No response / contraindicated)
  ┌─────────────────────────────────────────────┐
  │  VASODILATION → Phenylephrine or NE         │
  │  BRADYCARDIA + vasodilation → Ephedrine     │
  │  ANAPHYLAXIS → Epinephrine IM 0.5 mg        │
  │  CARDIOGENIC → NE + Dobutamine              │
  │  ADRENAL → Hydrocortisone 100 mg IV         │
  └─────────────────────────────────────────────┘
       ↓ (Refractory)
  ┌─────────────────────────────────────────────┐
  │  Add Vasopressin 0.03 units/min             │
  │  Consider Angiotensin II / Methylene Blue   │
  └─────────────────────────────────────────────┘
       ↓
  Target MAP >65, UO >0.5 mL/kg/hr, Lactate ↓

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• Douglas et al., Vasopressors to treat postoperative hypotension, Br J Anaesth 2023 (PMID: 37778937) - systematic review; norepinephrine most common vasopressor used; vasodilation most common mechanism
• Miller's Anesthesia, 10e - perioperative blood pressure management, pheo resection
• Morgan & Mikhail's Clinical Anesthesiology, 7e - agent selection in neuraxial/valvular anesthesia
• APSF perioperative hypotension guidance

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Post-Operative Nausea & Vomiting (PONV): Comprehensive Notes

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1. Definition

• Incidence: 20-30% in general surgical patients; up to 70-80% in high-risk populations
• One of the most common and distressing post-operative complications
• Leads to: dehydration, wound dehiscence, aspiration, delayed discharge, unplanned hospital admission

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2. Pathophysiology - The Vomiting Reflex

"The CTZ contains opioid, serotonin (5HT3), histamine, dopamine (D2), and muscarinic acetylcholine receptors. The CTZ, vagal nerve, and vestibular organs all send neural projections to the vomiting center in the medulla." - Barash, Cullen & Stoelting's Clinical Anesthesia, 9e

• Volatile anesthetic agents (most important intraoperative cause)
• Opioids (act directly on CTZ and increase vestibular sensitivity)
• Type/duration/site of surgery (gynecological, laparoscopic, ENT, strabismus)
• Patient-specific factors

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3. Risk Stratification - Apfel Score (Adults)

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4. Non-Pharmacological Risk Reduction (Baseline Mitigation)

• Use propofol TIVA instead of volatile anesthetics (reduces PONV by ~25%)
• Prefer regional/neuraxial anesthesia over general anesthesia
• Minimize intraoperative and postoperative opioids (use NSAIDs, acetaminophen, regional blocks)
• Adequate IV hydration intraoperatively
• Avoid nitrous oxide
• Use dexmedetomidine as opioid-sparing adjunct
• Minimize neostigmine (anticholinesterase use) - stimulates muscarinic receptors in GI tract
• Acupressure at P6 (Neiguan) point has modest evidence

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5. Treatment Guidelines - Stepwise Approach

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Step 1: Assess Risk (Apfel Score)

Step 2: Risk Mitigation (Non-pharmacological)

Step 3: Prophylaxis Based on Risk Tier

Guideline: "Patients with 1-2 risk factors should receive 2 agents; patients with >2 risk factors should receive 3-4 agents." - APSF/ASER 2025

Step 4: Rescue Treatment (if prophylaxis fails or none given)

• Use an antiemetic from a different pharmacological class than what was used for prophylaxis
• Do NOT re-dose the same class within 6 hours (no additional benefit vs. placebo)
• Exception: if >6 hours have passed, a 5-HT3 antagonist or butyrophenone may be re-dosed if no alternatives available

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6. Pharmacological Drugs - Mechanism, Dose, Side Effects

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CLASS 1: 5-HT3 RECEPTOR ANTAGONISTS (Serotonin Antagonists)

A. Ondansetron (Zofran) - First-Line

• Selectively blocks 5-HT3 (serotonin type 3) receptors in the CTZ (area postrema) and on vagal afferents in the GI tract
• Prevents serotonin (released from enterochromaffin cells of GI mucosa after surgical stress) from triggering the vomiting reflex via vagal and CTZ pathways
• Does NOT block dopamine or muscarinic receptors

• Headache (most common, ~9%)
• QTc prolongation (dose-dependent; ECG monitoring if high-risk)
• Constipation
• Dizziness, flushing
• Rare: anaphylaxis
• Serotonin syndrome risk if combined with other serotonergic drugs (rare)

• Most commonly used antiemetic globally for PONV
• Palonosetron (0.075 mg IV) is a newer 2nd-generation agent with longer half-life (~40h vs 3-4h for ondansetron)
• Granisetron 1 mg IV and tropisetron 5 mg IV are alternatives

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CLASS 2: CORTICOSTEROIDS

B. Dexamethasone

• Exact antiemetic mechanism is not fully established
• Proposed: reduces prostaglandin synthesis and release of serotonin from the gut; inhibits neuronal activation in the nucleus tractus solitarius; possible anti-inflammatory effect on the vomiting center
• Also provides adjunct analgesia (opioid-sparing) and mood-elevating effect

• Hyperglycemia (especially in diabetics; monitor blood glucose)
• Perineal burning/itching with rapid IV injection (use slow infusion)
• Risk of wound infection with repeated high doses (single-dose prophylaxis considered safe)
• Adrenal suppression (single dose - minimal risk)
• Insomnia (when given early)
• Immunosuppression concerns with repeated dosing

• Highly cost-effective; widely available
• Timing at induction is important (effect onset is delayed ~60 min)
• Combination with ondansetron is synergistic and superior to either alone (evidence A1)
• Fourth Consensus Guidelines, ASER 2025

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CLASS 3: DOPAMINE (D2) ANTAGONISTS / BUTYROPHENONES

C. Droperidol (Inapsine)

• D2 receptor antagonist in the CTZ (area postrema)
• Blocks dopaminergic transmission at the CTZ, preventing dopamine-mediated emetic signaling
• Also has mild alpha-1 adrenergic blocking activity

• QTc prolongation - FDA issued Black Box Warning in 2001 (risk of sudden cardiac death at doses >25 mg, NOT at antiemetic doses of 0.625 mg)
• Sedation
• Extrapyramidal symptoms (EPS): akathisia, dystonia (rare at antiemetic doses)
• Dysphoria
• Hypotension

• Multiple studies confirm antiemetic doses (0.625 mg) are safe and cause only transient QTc change comparable to ondansetron
• Comparable efficacy to ondansetron 4-8 mg at rescue doses of 1-1.25 mg
• Available and inexpensive

D. Haloperidol (Haldol)

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CLASS 4: NEUROKININ-1 (NK-1) RECEPTOR ANTAGONISTS

E. Aprepitant (Emend) / Fosaprepitant

• Selectively blocks Neurokinin-1 (NK-1) receptors in the brain (cerebral cortex and brainstem)
• Substance P (released during surgery/stress) acts on NK-1 receptors to trigger nausea and vomiting
• Blocking NK-1 receptors interrupts this pathway at a different site from 5-HT3 or D2 receptors - hence excellent in combination therapy and for refractory PONV
• Half-life: ~40 hours (much longer than 5-HT3 agents)

• Fatigue/asthenia
• Hiccups
• Constipation
• Drug interactions - aprepitant is a moderate CYP3A4 inhibitor; reduces efficacy of warfarin, oral contraceptives; levels altered by CYP3A4 inducers/inhibitors
• Headache

• Aprepitant 40 mg + dexamethasone is superior to ondansetron + dexamethasone for preventing vomiting especially in high-risk patients (neurosurgery)
• Amisulpride 5 mg IV (Barhemsys) - newest agent approved 2020; also a D2/D3 antagonist with NK-1 activity, given at induction; minimal QT effect

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CLASS 5: ANTICHOLINERGICS (MUSCARINIC ANTAGONISTS)

F. Transdermal Scopolamine (Hyoscine Patch)

• Muscarinic (M1) receptor antagonist at the vestibular nuclei and vomiting center
• Blocks cholinergic input from the vestibular apparatus to the vomiting center
• Particularly effective for motion-related and vestibular-mediated PONV
• Acts on M1 receptors in the CTZ and brainstem

• Dry mouth (very common)
• Blurred vision, mydriasis (do NOT use in narrow-angle glaucoma)
• Sedation, confusion, dizziness
• Urinary retention
• Tachycardia
• Skin irritation at patch site
• Risk of anticholinergic syndrome in elderly

• Primarily for high-risk patients; excellent as an add-on agent (different MOA from 5-HT3/NK-1)
• Remove before MRI
• Wash hands after application to avoid inadvertent eye contact

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CLASS 6: PHENOTHIAZINES / D2 ANTAGONISTS

G. Promethazine (Phenergan)

• Blocks D2 receptors in the CTZ
• Also blocks H1 histamine receptors and muscarinic receptors (anticholinergic effect)
• This dual D2/H1 blockade makes it effective for opioid-induced PONV and vestibular PONV

• Sedation (significant)
• Extrapyramidal symptoms (EPS) - akathisia, dystonia, tardive dyskinesia with prolonged use
• Anticholinergic effects (dry mouth, blurred vision, urinary retention)
• Tissue necrosis with inadvertent intra-arterial injection (IV only, never intra-arterial)
• QTc prolongation
• Respiratory depression (use caution with opioids)

• Lower dose (6.25 mg IV) is as effective as higher doses with fewer side effects per guidelines
• Useful as rescue agent when 5-HT3 antagonists fail

H. Prochlorperazine (Compazine)

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CLASS 7: PROKINETIC / D2 ANTAGONIST

I. Metoclopramide (Maxolon, Reglan)

• D2 receptor antagonist in the CTZ - antiemetic effect
• Also acts peripherally: enhances gastric emptying by increasing lower esophageal sphincter tone and accelerating gastric motility (prokinetic)
• Weak 5-HT3 antagonism at higher doses
• Weak 5-HT4 agonist - accelerates GI motility

• Extrapyramidal symptoms (EPS) - akathisia (restlessness), acute dystonia, tardive dyskinesia (with prolonged use)
• Sedation
• QTc prolongation
• FDA Black Box Warning: risk of tardive dyskinesia with prolonged use
• Diarrhea
• Headache

• As monotherapy, 10 mg metoclopramide has modest efficacy (evidence A1)
• Significantly inferior to ondansetron and droperidol as rescue therapy
• Not recommended for PONV prophylaxis as a standalone agent per 2025 guidelines
• Higher doses (25-50 mg) improve efficacy but increase EPS risk
• Avoid in patients with Parkinson's disease

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CLASS 8: ANTIHISTAMINES

J. Dimenhydrinate (Dramamine) / Diphenhydramine

• H1 histamine receptor antagonist in the vestibular nuclei and vomiting center
• Also has anticholinergic (muscarinic) activity
• Particularly effective for vestibular-mediated and motion sickness-associated PONV

• Dimenhydrinate: 25-50 mg IV or 0.5 mg/kg in children
• Diphenhydramine: 25-50 mg IV

• Sedation (prominent)
• Dry mouth (anticholinergic)
• Urinary retention
• Blurred vision
• Confusion (especially in elderly)

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CLASS 9: MISCELLANEOUS / ADJUNCTS

K. Dexmedetomidine (alpha-2 agonist)

L. Olanzapine (Zyprexa) - Atypical Antipsychotic

M. Propofol (sub-anesthetic dose)

N. Ephedrine

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7. Drug Combination Strategies (ASER 2025 Guidelines)

Triple therapy (ondansetron + dexamethasone + droperidol 0.625 mg) vs. placebo significantly reduces PONV 0-6 hours postoperatively.

Aprepitant 40 mg as 4th agent (added to ondansetron + dexamethasone + TIVA) further reduces PONV in highest-risk patients.

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8. Rescue Treatment Algorithm (When Prophylaxis Fails)

PONV occurs in PACU
       ↓
Did patient receive prophylaxis?
  ├─ NO → Give 5-HT3 antagonist (ondansetron 4 mg IV) as first-line
  └─ YES → Give drug from a DIFFERENT class
           (If got ondansetron → give droperidol or dexamethasone or promethazine)
       ↓
< 6 hours since prophylaxis dose?
  └─ YES → DO NOT re-dose same class (ineffective, same as placebo)
  └─ NO (>6h) → May re-dose 5-HT3 antagonist or butyrophenone if no alternatives
       ↓
Still refractory?
  → Propofol 20-40 mg IV (in monitored setting)
  → Olanzapine 10 mg PO (if available)
  → Consider NK-1 antagonist (aprepitant/fosaprepitant)

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9. Quick Reference - All Drugs Summary Table

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10. Special Populations

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• Barash, Cullen & Stoelting's Clinical Anesthesia, 9e - pathophysiology, CTZ, opioid-induced PONV
• Barash Clinical Anesthesia, 9e (Pediatric PONV section)
• Fourth Consensus Guidelines for the Management of PONV, ASER 2025 - drug doses, combination therapy, rescue treatment
• APSF PONV Guidelines Podcast - algorithm summary
• SAMBA Consensus Guidelines (archived, ASHP)

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Post-Operative Delirium & Emergence Agitation: Comprehensive Notes

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PART 1: POST-OPERATIVE DELIRIUM (POD)

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1. Definition

• Reduced awareness and attention
• Disorganized thinking
• Fluctuating course (often worse at night)
• Onset: hours to 5 days after surgery (most often starts in the PACU or POD 1-3)

• Incidence: 4-53% (varies widely by patient population and surgery type)
• Most common in elderly hip fracture patients; also common after cardiac, thoracic, and major abdominal surgery
• Associated with: longer hospital stay, increased mortality, functional decline, institutionalization, accelerated cognitive decline

"POD is defined as an acute and fluctuating alteration of mental state of reduced awareness and disturbance of attention. POD often starts in the recovery room and can occur up to 5 days after surgery." - Miller's Anesthesia, 10e

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2. Subtypes of Delirium

"The hypoactive subtype may easily go unnoticed, be therefore untreated, and potentially linked to a worse outcome." - Miller's Anesthesia, 10e

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3. Pathophysiology

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4. Risk Factors

Predisposing (Patient) Factors:

• Age >65 years (most important)
• Pre-existing cognitive impairment (dementia, MCI)
• Severe illness / high comorbidity burden (ASA 3-4)
• Sensory impairment (hearing loss, visual impairment)
• History of prior delirium
• Frailty, malnutrition
• Alcohol use disorder (especially withdrawal risk)
• Baseline functional impairment
• Presence of infection / fever

Precipitating (Perioperative) Factors:

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5. Diagnosis & Screening Tools

Gold Standard: Confusion Assessment Method (CAM)

1. Acute onset and fluctuating course
2. Inattention (difficulty focusing)
3. Disorganized thinking
4. Altered level of consciousness

Other Tools:

"The Confusion Assessment Method is the gold standard for delirium diagnosis. Other instruments exist that are easier to administer like the 3-Minute Diagnostic Confusion Assessment Method (3D-CAM)." - Barash Clinical Anesthesia, 9e

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6. Prevention Strategies

A. Non-Pharmacological (MOST EFFECTIVE - Evidence Grade A)

B. Pharmacological Prevention

"Dexmedetomidine sedation decreases delirium risk in mechanically ventilated ICU patients and cardiac surgery patients." - Barash Clinical Anesthesia, 9e

• Benzodiazepines (except for EtOH/benzo withdrawal)
• Anticholinergics (atropine, scopolamine, diphenhydramine, promethazine)
• Meperidine - clear delirium risk factor; avoid entirely
• Ketamine (mixed evidence; can cause psychoactive effects)

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7. Treatment of Established POD

Step 1: Immediate Assessment - Identify Reversible Causes (THINK DELIRIUM mnemonic)

Step 2: Non-Pharmacological Management (FIRST-LINE always)

Step 3: Pharmacological Treatment

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Pharmacological Drugs for POD Treatment

A. Haloperidol (Haldol) - Traditional First-Line

• Potent D2 (dopamine receptor 2) antagonist in the mesolimbic and mesocortical pathways
• Reduces excess dopaminergic activity thought to underlie hallucinations, agitation, and disorganized thinking
• Increases central acetylcholine levels indirectly
• Has anti-hallucinatory, anti-delusional, and anti-agitation effects

• Extrapyramidal symptoms (EPS): Akathisia, dystonia, Parkinsonism (especially in elderly)
• QTc prolongation - risk of Torsades de Pointes; monitor ECG
• Tardive dyskinesia (prolonged use)
• Hypotension (IV administration)
• Neuroleptic Malignant Syndrome (NMS) - rare but life-threatening
• Do NOT use in Parkinson's disease or Lewy Body Dementia (severe worsening of rigidity)
• Sedation
• Lowered seizure threshold

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B. Quetiapine (Seroquel) - Atypical Antipsychotic

• D2 and D1 antagonist (weaker D2 than haloperidol - fewer EPS)
• 5-HT2A, 5-HT2C antagonist - contributes to sedation and anxiolysis
• H1 antihistamine effect - promotes sleep
• Alpha-1 adrenergic blockade
• Broad receptor binding makes it effective for mixed and hypoactive delirium

• Sedation (beneficial in agitated patients)
• Orthostatic hypotension
• Mild QTc prolongation
• Hyperglycemia (chronic use)
• EPS rare at low doses
• Avoid in Lewy Body Dementia (caution)

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C. Risperidone (Risperdal) - Atypical Antipsychotic

• D2 + 5-HT2A receptor antagonist
• Less sedating than quetiapine
• Alpha-2 adrenergic blocking effects

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D. Dexmedetomidine (Precedex) - PREFERRED in ICU/Post-Op Agitated Delirium

• Highly selective Alpha-2 adrenergic receptor agonist (alpha-2:alpha-1 selectivity ratio = 1600:1)
• Acts on locus coeruleus (LC) in the brainstem - reduces norepinephrine release and sympathetic outflow
• Produces arousable sedation mimicking natural sleep (NREM Stage 2) without respiratory depression
• Opioid-sparing and analgesic properties via alpha-2 receptors in spinal cord
• Anti-inflammatory effects: reduces microglial activation, decreases pro-inflammatory cytokines
• Reduces requirement for benzodiazepines (which worsen delirium)
• Dexmedetomidine given postoperatively is more effective than intraoperatively for POD prevention (neuroinflammatory processes continue postoperatively)

• Bradycardia (dose-dependent; most common)
• Hypotension (especially with loading dose)
• Dry mouth
• Rebound hypertension with abrupt discontinuation
• Nausea

---

E. Lorazepam / Benzodiazepines - RESTRICTED USE ONLY

• ONLY indicated for delirium due to alcohol or benzodiazepine withdrawal (CIWA protocol)
• NOT for general delirium management - worsens and prolongs delirium
• Acceptable for procedural sedation if brief

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F. Olanzapine (Zyprexa) - Adjunct

---

G. Melatonin / Ramelteon - Circadian Adjunct

• Melatonin: 0.5-3 mg PO at bedtime
• Ramelteon: 8 mg PO at bedtime (prescription)

---

8. Drugs to AVOID in Delirium

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PART 2: EMERGENCE AGITATION (EA) / EMERGENCE DELIRIUM

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9. Definition

• Distinct from POD: EA occurs immediately on emergence (within 0-30 minutes), while POD occurs hours to days later
• Duration: usually 5-15 minutes, resolves as full consciousness returns
• Incidence: up to 21% in adults; 10-67% in children (especially with sevoflurane)

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10. Pathophysiology of Emergence Agitation

• Confusion, fear, and disorientation without full cortical awareness
• Pain or discomfort without the ability to communicate effectively
• Possibly: residual anesthetic in limbic circuits causing dysphoria/excitation before cortex clears

• Rapid wash-out (fast wake-up) before limbic/cortical reintegration is complete
• Possible GABA-A and glycine receptor dysregulation during offset

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11. Risk Factors for Emergence Agitation

"Risk factors for ED may include volatile anesthetic exposure (particularly sevoflurane), certain types of surgery including ophthalmology and otorhinolaryngology procedures, patient age around 3 to 7 years old, patient anxiety." - Barash Clinical Anesthesia, 9e

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12. Assessment Tools for EA

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13. Management - Stepwise Approach

Step 1: SAFETY FIRST

• Protect patient from self-injury (fall from bed, dislodging lines, wound disruption)
• Protect staff
• Protect airway - ensure adequate oxygenation and ventilation
• Do NOT physically restrain (worsens agitation)
• Call for help; two-person management

Step 2: Identify and Treat Reversible Causes (FAST check)

• Pain - inadequate analgesia is the most common cause; treat with IV opioid bolus
• Hypoxia/hypercapnia - check SpO2, ETCO2; give oxygen
• Full bladder - check and catheterize if needed
• Residual neuromuscular blockade - check train-of-four; reverse if needed
• Hypothermia - warm the patient
• Hypoglycemia - check BGL
• Anticholinergic syndrome - from atropine, scopolamine
• ETT discomfort - consider extubation if ready

Step 3: Calm the Environment

• Reduce noise, dim lights
• Speak calmly, reorient the patient: "You're safe, the surgery is over, you're in the recovery room"
• Parent presence for children
• Remove restraints if possible

Step 4: Pharmacological Treatment (if steps 1-3 insufficient)

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14. Pharmacological Treatment of Emergence Agitation

A. Adequate Analgesia First

• Mechanism: Mu-opioid receptor agonist - potent analgesia; reduces pain-driven agitation
• Dose: 0.5-1 mcg/kg IV bolus; titrate to effect
• Side Effects: Respiratory depression, nausea, chest wall rigidity (high doses)
• Note: Fentanyl 2.5 mcg/kg intraoperatively significantly reduces EA after adenotonsillectomy

• Longer-acting alternatives for sustained pain control; no superiority over fentanyl for delirium

---

B. Dexmedetomidine - FIRST-LINE pharmacological treatment (EA and POD)

• 0.5-1 mcg/kg IV over 10 minutes (slow infusion)
• Can repeat carefully if needed

---

C. Propofol - Rapid Rescue

• 0.5 mg/kg IV bolus (adults)
• Can use 0.5-1 mg/kg; titrate carefully

---

D. Ketamine - Low-Dose Adjunct

---

E. Midazolam - Cautious Use in Adults; Limited Pediatric Role

• Benzodiazepines as premedication do NOT reduce EA in pediatric patients
• May help in adult EA when pain is excluded and sedation is required; however, avoid in elderly
• Indicated for alcohol/benzo withdrawal-associated agitation

---

F. Physostigmine - Specific Use: Anticholinergic Syndrome

---

G. Clonidine - Alpha-2 Agonist (older alternative to dexmedetomidine)

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15. Prevention of Emergence Agitation - Drug Summary

---

16. Key Comparison: POD vs EA

---

17. Quick Drug Reference

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• Miller's Anesthesia, 10e - POD definition, risk factors, prophylaxis/management
• Barash, Cullen & Stoelting's Clinical Anesthesia, 9e - CAM, diagnosis, EA in pediatrics, dexmedetomidine
• ESAIC 2024 Guideline on POD (PMID: 37599617) - Evidence-based consensus guideline; multicomponent prevention; neuroinflammation pathogenesis
• Liu et al., Haloperidol meta-analysis BMC Anesthesiology 2024 - perioperative haloperidol reduces POD in elderly
• Deblois et al., J Patient Saf 2025 (PMID: 39907462) - systematic review of POD prevention and treatment in elderly