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HARRISON'S 22E - PART 8: CRITICAL CARE MEDICINE

Complete Study Guide

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SECTION 1: RESPIRATORY CRITICAL CARE

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CHAPTER 311 - APPROACH TO THE PATIENT WITH CRITICAL ILLNESS

The Core Philosophy of ICU Care

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SEVERITY-OF-ILLNESS SCORING SYSTEMS

• Define patient populations for clinical trials
• Guide resource allocation (nursing ratios, beds)
• Assess quality of ICU care over time
• Newer use: sepsis prognostication (qSOFA)

SOFA Score (Sequential Organ Failure Assessment)

• Rising SOFA score = rising mortality
• A rise of ≥2 points from baseline in the setting of suspected infection = SEPSIS (Sepsis-3 definition)

qSOFA (Quick SOFA)

1. Respiratory rate ≥ 22 breaths/min
2. Altered mental status
3. Systolic BP ≤ 100 mmHg

APACHE (Acute Physiology and Chronic Health Evaluation)

• Based on: age + chronic medical illness + physiologic derangements from normal
• Used predominantly for research and epidemiology

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ICU MONITORING AND MANAGEMENT TOOLS

Hemodynamic Monitoring

• Measures: CVP, PA pressure, PCWP (wedge), cardiac output, SvO2
• Allows calculation of systemic and pulmonary vascular resistance
• Use has declined due to lack of mortality benefit in most trials, but remains useful for:
  • Differentiating cardiogenic vs. non-cardiogenic pulmonary edema
  • Managing refractory shock
  • Evaluating pulmonary hypertension

Respiratory Monitoring

• Pulse oximetry: Non-invasive SpO2 monitoring (limitations in poor perfusion, dark skin pigmentation)
• End-tidal CO2 (ETCO2): Confirms ETT placement, trends in ventilation
• Arterial Blood Gas (ABG): Gold standard for oxygenation, ventilation, acid-base

Neurological Monitoring

• GCS, pupillary responses
• Continuous EEG in comatose patients (detect non-convulsive seizures)
• ICP monitoring in TBI, hepatic failure

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COMMON ICU INTERVENTIONS

Renal Replacement Therapy (RRT)

• Acidosis (refractory metabolic acidosis)
• Electrolytes (life-threatening hyperkalemia)
• Ingestion (dialyzable toxins)
• Overload (refractory fluid overload)
• Uremia (uremic pericarditis, encephalopathy, platelets dysfunction)

Nutrition in the ICU

• Early enteral nutrition preferred (within 24-48h) - preserves gut mucosal integrity
• Parenteral nutrition if enteral is contraindicated (>5-7 days)
• Target: ~25 kcal/kg/day; protein 1.2-2.0 g/kg/day
• Avoid overfeeding - causes hyperglycemia and immunosuppression

Glycemic Control

• Hyperglycemia worsens outcomes in ICU
• Target glucose: 140-180 mg/dL (NICE-SUGAR trial showed harm from tight control <110 mg/dL)
• Use insulin infusions

Stress Ulcer Prophylaxis

• Indications: mechanical ventilation >48h, coagulopathy, head injury, burns
• Agents: PPIs or H2 blockers

DVT/PE Prophylaxis

• All ICU patients unless contraindicated
• LMWH preferred; UFH acceptable; SCDs if anticoagulation contraindicated

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END-OF-LIFE ISSUES IN THE ICU

• Intensivists must counsel patients and families on prognosis honestly
• Withdrawing support (e.g., ventilator) is ethically equivalent to withholding it
• Palliative care should be integrated early, not just at "end"
• Document advance directives, goals-of-care discussions
• Address pain, dyspnea, and existential distress even during active treatment

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CHAPTER 312 - ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)

Definition - The Berlin Definition (2012)

1. Timing: Onset within 1 week of known clinical insult or new/worsening respiratory symptoms
2. Imaging: Bilateral opacities on CXR or CT not fully explained by effusions, collapse, or nodules
3. Origin: Not fully explained by cardiac failure or fluid overload (if no risk factor, need echo to rule out cardiogenic)
4. Oxygenation (on PEEP ≥5 cmH2O):
   • Mild: PaO2/FiO2 201-300 mmHg
   • Moderate: PaO2/FiO2 101-200 mmHg
   • Severe: PaO2/FiO2 ≤100 mmHg

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ARDS Imaging - Classic Features

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CAUSES OF ARDS

• Pneumonia (most common) - bacterial, viral, fungal
• Aspiration of gastric contents
• Pulmonary contusion
• Near-drowning
• Inhalation injury

• Sepsis (most common overall cause)
• Pancreatitis
• Non-pulmonary trauma with shock
• Massive transfusion / transfusion-related acute lung injury (TRALI)
• Burns
• Drug overdose (heroin, aspirin, cocaine)

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PATHOPHYSIOLOGY OF ARDS

Phase 1: Exudative Phase (0-7 days)

• Alveolar epithelial and endothelial injury
• Neutrophil activation and recruitment
• Disruption of the alveolar-capillary barrier
• Diffuse alveolar damage (DAD) - protein-rich fluid floods alveoli
• Hyaline membrane formation
• Surfactant dysfunction → alveolar collapse
• Result: severe hypoxemia (shunt physiology)

Phase 2: Proliferative Phase (7-21 days)

• Type II pneumocyte proliferation to repair alveolar epithelium
• Alveolar macrophage activation
• Fibroproliferation begins
• Some patients improve; others progress to fibrosis

Phase 3: Fibrotic Phase (>21 days)

• Architectural remodeling
• Dense fibrosis
• Bullae formation
• Loss of gas exchange surface area
• Associated with poor prognosis, prolonged ventilation

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MANAGEMENT OF ARDS

Lung-Protective Ventilation (ARDSNet Protocol) - THE MOST IMPORTANT TREATMENT

Additional Supportive Strategies

• Indicated in severe ARDS (PaO2/FiO2 <150 despite FiO2 ≥0.6 and PEEP ≥5)
• 16+ hours/day in prone position
• The PROSEVA trial showed 28-day mortality reduced from 32.8% to 16% with proning
• Mechanism: recruits dependent (posterior) atelectatic lung, improves V/Q matching, reduces VILI

• Cisatracurium infusion for 48h in moderate-severe ARDS
• ACURASYS trial showed benefit; ROSE trial questioned it
• Reduces patient-ventilator dyssynchrony and oxygen consumption
• Use only with adequate sedation

• After initial resuscitation, target neutral to negative fluid balance
• FACTT trial: conservative strategy improved oxygenation and shortened ventilator days without increasing renal failure

• Low-dose methylprednisolone (1 mg/kg/day) may be beneficial in early ARDS (<14 days)
• Reduces fibroproliferation
• Not beneficial if started >14 days

• VV-ECMO for severe refractory ARDS (PaO2/FiO2 <80 despite optimal management)
• CESAR trial and EOLIA trial data support use in specialized centers
• Provides "lung rest" while native lung recovers

• Inhaled NO (improves oxygenation but no mortality benefit)
• Surfactant (benefit only in neonates, not adults)
• High-frequency oscillatory ventilation (HFOV) - OSCILLATE trial showed harm
• Ketoconazole, lisofylline, salbutamol

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OUTCOMES OF ARDS

• Overall mortality: ~40% (severe ARDS up to 45%)
• Most deaths from underlying cause/MOF, not pure respiratory failure
• Survivors have:
  • Muscle weakness and wasting (ICU-acquired weakness)
  • Cognitive impairment and PTSD
  • Quality of life impairment for months-years
  • Pulmonary function usually recovers within 6-12 months

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CHAPTER 313 - MECHANICAL VENTILATOR SUPPORT

INDICATIONS FOR MECHANICAL VENTILATION

1. Respiratory failure - inability to maintain adequate oxygenation or ventilation
2. Airway protection - altered consciousness, inability to protect airway
3. Excessive work of breathing - impending respiratory fatigue
4. Hemodynamic support - reduces O2 consumption by respiratory muscles

• PaO2 <60 mmHg despite supplemental O2
• PaCO2 >50 mmHg with acidosis (pH <7.35) and rising
• RR >30-35 breaths/min with fatigue
• GCS ≤8

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TYPES OF MECHANICAL VENTILATION

Invasive Mechanical Ventilation (IMV)

• Set: tidal volume + flow rate
• Variable: peak pressure (depends on compliance/resistance)
• Guarantees minute ventilation regardless of lung mechanics
• Use: standard first-line in most ICU patients

• Set: inspiratory pressure above PEEP
• Variable: tidal volume (depends on lung compliance)
• Produces decelerating flow waveform (better gas distribution)
• Use: ARDS, when pressure control desired

• Patient-triggered; each breath augmented to set pressure
• Fully spontaneous - patient controls rate and timing
• Use: Weaning; assesses readiness for extubation

• Delivers mandatory breaths plus allows spontaneous breathing
• Largely fallen out of favor - may prolong weaning

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VENTILATOR SETTINGS

PEEP (Positive End-Expiratory Pressure)

• Purpose: Prevents alveolar collapse at end-expiration; recruits alveoli; improves oxygenation
• Intrinsic PEEP (auto-PEEP): Dangerous - air trapping in obstructive disease (asthma, COPD)
  • Detect by expiratory hold maneuver
  • Treat: reduce RR, reduce I:E ratio (longer expiration), bronchodilators
• Optimal PEEP: Balances recruitment vs. overdistension

Key Lung Mechanics Measurements

• Measured during inspiratory hold
• Reflects alveolar pressure (static compliance)
• Target: ≤30 cmH2O

• Reflects stress on lung parenchyma
• Target: ≤15 cmH2O
• Best predictor of ARDS outcomes

• Normal: 60-100 mL/cmH2O
• Low in ARDS, fibrosis (stiff lungs)
• Normal in airway obstruction

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NON-INVASIVE VENTILATION (NIV)

CPAP (Continuous Positive Airway Pressure)

• Single level of pressure throughout respiratory cycle
• Patient breathes spontaneously
• Use: OSA, cardiogenic pulmonary edema, hypoxemia

BiPAP/NPPV (Bilevel Positive Airway Pressure)

• IPAP (inspiratory) + EPAP (expiratory)
• Reduces work of breathing, improves gas exchange
• Best evidence in:
  • COPD exacerbation with hypercapnia (reduces intubation, mortality)
  • Cardiogenic pulmonary edema
  • Immunocompromised patients (avoids infectious complications of intubation)

• Inability to protect airway
• Hemodynamic instability
• Copious secretions
• Recent upper GI/esophageal surgery
• Uncooperative patient
• Facial trauma

High-Flow Nasal Cannula (HFNC)

• Delivers up to 60 L/min of humidified, heated O2
• Provides modest PEEP (~2-5 cmH2O)
• Reduces work of breathing
• FLORALI trial: noninferior to NIV for hypoxemic respiratory failure
• Does not delay intubation if patient failing

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WEANING FROM MECHANICAL VENTILATION

1. Underlying cause resolving
2. Adequate oxygenation: SpO2 ≥90% on FiO2 ≤0.4-0.5 and PEEP ≤5-8
3. Hemodynamically stable (no/minimal vasopressors)
4. Able to initiate breaths
5. Alert enough to follow commands

• Trial of T-piece, CPAP 5 cmH2O, or PSV 5-8 cmH2O
• Duration: 30-120 minutes
• Failure criteria: SpO2 <90%, RR >35, HR >140 or change >20%, agitation, diaphoresis, accessory muscle use

• <105 = likely to wean successfully

• 105 = likely to fail

• Assess: cough strength, secretion load, gag reflex
• Cuff leak test: predicts stridor post-extubation
• After extubation: HFNC reduces reintubation risk (OPTIVENT trial data)

• Consider if ventilation expected >14-21 days
• Benefits: patient comfort, oral care, secretion management, may facilitate weaning
• Timing: early (7-10 days) vs. late (>10 days) - no clear mortality difference

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SECTION 2: SHOCK AND CARDIAC ARREST

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CHAPTER 314 - APPROACH TO THE PATIENT WITH SHOCK

DEFINITION

• Without O2, cells switch from aerobic → anaerobic metabolism
• Pyruvate → lactate instead of entering mitochondria
• Far less ATP generated per glucose
• ATP failure → disrupts Na+/K+ ATPase → osmotic, ionic, pH disruption
• Calcium influx → activates phospholipases and proteases → cell death
• Intracellular contents leak → activate systemic inflammation → microvascular injury

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OXYGEN DELIVERY (DO2) - THE KEY EQUATION

• CO = cardiac output (HR × SV)
• CaO2 = arterial oxygen content = (Hgb × 1.34 × SaO2) + (0.003 × PaO2)

1. Heart rate
2. Stroke volume (preload, contractility, afterload)
3. Hemoglobin concentration
4. Oxygen saturation

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CLASSIFICATION OF SHOCK - THE FOUR TYPES

1. Distributive Shock

• Problem: Maldistribution of blood flow - vasodilation
• CO is normal or HIGH (hyperdynamic), SVR is LOW
• Despite adequate/increased cardiac output, cells are hypoperfused due to abnormal microvascular distribution
• Causes: Septic shock (most common), anaphylaxis, neurogenic shock (spinal injury), adrenal crisis

2. Cardiogenic Shock

• Problem: Pump failure - heart cannot generate adequate CO
• CO is LOW, SVR is HIGH (compensatory)
• PCWP (wedge) is HIGH
• Causes: MI, decompensated heart failure, myocarditis, arrhythmia, mechanical complications

3. Hypovolemic Shock

• Problem: Inadequate circulating volume
• CO is LOW (low preload), SVR is HIGH
• PCWP is LOW
• Causes:
  • Hemorrhagic: trauma, GI bleed, ruptured aneurysm
  • Non-hemorrhagic: severe dehydration, burns, third-spacing

4. Obstructive Shock

• Problem: Obstruction to blood flow
• CO is LOW despite normal/increased pump function
• Causes: Massive PE, tension pneumothorax, cardiac tamponade, severe aortic stenosis

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HEMODYNAMIC PROFILES OF SHOCK

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CLINICAL ASSESSMENT OF SHOCK

History and Physical

• Skin: Cold/clammy (cardiogenic/hypovolemic) vs. warm/flushed (distributive early)
• BP: SBP <90 or MAP <65 mmHg (but shock can exist with normal BP)
• HR: Tachycardia (may be absent with beta-blockers or in neurogenic shock)
• Urine output: <0.5 mL/kg/h = oliguria = end-organ hypoperfusion
• Mentation: Altered consciousness from cerebral hypoperfusion
• JVP: Elevated in cardiogenic/obstructive; flat in hypovolemic/distributive

Diagnostic Tests

• Lactate: Best marker of tissue hypoperfusion; >2 mmol/L elevated; >4 = severe; correlates with mortality
• ABG: Metabolic acidosis with elevated anion gap, low bicarb
• CBC, BMP, LFTs, coags: Multi-organ dysfunction assessment
• Troponin: Cardiogenic shock, but also elevated in septic shock
• Echo (bedside point-of-care):
  • Assesses LV/RV function
  • Pericardial effusion (tamponade)
  • IVC collapsibility (volume responsiveness)
  • Wall motion abnormalities
• CXR: Pulmonary edema (cardiogenic), air (pneumothorax), wide mediastinum

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TREATMENT PRINCIPLES

1. Airway and Breathing

• Supplemental O2 - target SpO2 ≥92%
• Early intubation if unable to maintain airway/oxygenation
• Note: intubation itself can worsen shock (vasodilation from sedatives, loss of sympathetic drive)

2. Fluid Resuscitation

• Crystalloids first: Balanced crystalloids (LR or PlasmaLyte) preferred over NS (reduces hyperchloremic acidosis)
• 30 mL/kg IV bolus initial resuscitation in sepsis
• Assess fluid responsiveness:
  • Passive leg raise (PLR): raises CO by ~10% = fluid responsive
  • Pulse pressure variation (PPV): >13% with mechanical ventilation = fluid responsive
  • IVC collapsibility on ultrasound

3. Vasopressors

• Alpha-1 agonist (vasoconstriction) + beta-1 (mild inotropy)
• Target MAP ≥65 mmHg

• Non-adrenergic vasoconstriction
• 0.03-0.04 units/min (avoid higher doses - mesenteric/cardiac ischemia)
• VASST trial: may reduce NE requirements; benefit in less severe sepsis

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CHAPTER 315 - SEPSIS AND SEPTIC SHOCK

DEFINITIONS - EVOLUTION OVER TIME

• Low specificity (any physiologic stress can cause SIRS)
• Does not capture the unique biology of organ dysfunction

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EPIDEMIOLOGY

• ~88% community-onset (within 48h of admission); ~12% hospital-onset
• Most common organisms: S. aureus, Streptococcus, E. coli, Klebsiella, Pseudomonas
• Most common sites: Urinary tract (49%) > Respiratory (33%) > Intraabdominal (14%) > Skin/soft tissue (10%)

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PATHOPHYSIOLOGY OF SEPSIS

Innate Immune Activation

• PAMPs (Pathogen-Associated Molecular Patterns): LPS from gram-negative bacteria, peptidoglycan, flagellin
• DAMPs (Damage-Associated Molecular Patterns): HMGB1, mitochondrial DNA from injured host cells
• Recognized by TLRs (Toll-Like Receptors) on macrophages, monocytes, neutrophils

Pro-Inflammatory Response

• TNF-α, IL-1β, IL-6, IL-8 release
• Neutrophil activation and endothelial adhesion
• Complement activation
• Coagulation cascade activation → DIC
• Endothelial dysfunction → capillary leak → edema

Anti-Inflammatory / Immunosuppressive Response (CARS)

• Concurrent with pro-inflammation
• Treg expansion, T-cell exhaustion/apoptosis
• Anti-inflammatory cytokines (IL-10, IL-4)
• Immunosuppression → susceptibility to secondary infections (especially nosocomial)
• Late-phase sepsis deaths from immunosuppression, not hyperinflammation

Microvascular Dysfunction

• Capillary leak → interstitial edema
• Maldistribution of blood flow (some beds vasoconstricted, others vasodilated)
• Endothelial activation → expression of adhesion molecules
• Mitochondrial dysfunction → impaired oxygen utilization

Coagulopathy in Sepsis

• Activation of extrinsic coagulation pathway
• Widespread fibrin deposition → microvascular thrombosis
• Consumption of clotting factors and platelets → DIC
• Ischemic injury to kidneys, liver, adrenals, brain

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CLINICAL FEATURES

• Fever, tachycardia, tachypnea
• Warm, flushed skin (vasodilation)
• Widened pulse pressure
• Bounding pulses
• CO elevated

• Hypotension, cool extremities
• Mottling, cyanosis
• Altered consciousness
• Oliguria
• Evidence of organ failure

• Lungs: ARDS, hypoxemia
• Kidneys: AKI (creatinine, oliguria)
• Liver: Elevated bilirubin, transaminases
• Coagulation: Thrombocytopenia, elevated PT/INR - DIC
• CNS: Encephalopathy (delirium, altered consciousness)
• Adrenals: Relative adrenal insufficiency

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MANAGEMENT - THE SEPSIS BUNDLE (Surviving Sepsis Campaign)

Hour-1 Bundle (Immediate Actions):

1. Measure lactate - repeat if initial >2 mmol/L
2. Blood cultures x2 sets before antibiotics (but do not delay antibiotics >45 min)
3. Broad-spectrum antibiotics - within 1 hour of recognition
4. IV crystalloid 30 mL/kg if MAP <65 or lactate ≥4 mmol/L
5. Vasopressors (norepinephrine) if MAP <65 despite fluids

Antibiotic Principles:

• Start broad, then de-escalate based on cultures
• Common choices: Pip-tazo ± vancomycin; carbapenems for resistant organisms
• Duration: typically 5-7 days; 7-10 for bacteremia
• Procalcitonin-guided de-escalation reduces antibiotic duration

Vasopressors:

• Norepinephrine: first-line
• Vasopressin 0.03 units/min: add when NE >0.25 mcg/kg/min
• Angiotensin II (Giapreza): FDA-approved add-on for refractory vasodilatory shock
• Hydrocortisone 200 mg/day: use if refractory to NE + vasopressin

Source Control:

• Remove infected foreign bodies (lines, catheters, implants)
• Drain abscesses (percutaneous or surgical)
• Resect infected/necrotic tissue (e.g., cholecystectomy, Fournier's)

Corticosteroids in Septic Shock:

• ADRENAL trial: Hydrocortisone accelerated resolution of shock, reduced vasopressor days, but no 90-day mortality benefit
• APROCCHSS trial: Hydrocortisone + fludrocortisone reduced 90-day mortality
• Current recommendation: use hydrocortisone 200 mg/day (continuous or divided) if septic shock refractory to vasopressors

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SURVIVING SEPSIS LONG-TERM

• Post-sepsis syndrome: cognitive impairment, PTSD, weakness, recurrent infections
• 1-year mortality after sepsis hospitalization remains ~50% (from comorbidities)
• Increased risk of subsequent infection and cardiovascular events

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CHAPTER 316 - CARDIOGENIC SHOCK AND PULMONARY ARTERY RUPTURE (PARMAR)

CARDIOGENIC SHOCK

• SBP <90 mmHg for ≥30 minutes (or requires vasopressors)
• CI (cardiac index) <2.2 L/min/m²
• PCWP (wedge pressure) >18 mmHg (congested)

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CLASSIFICATION - SCAI SHOCK STAGES

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CAUSES OF CARDIOGENIC SHOCK

1. Acute MI - most common (40% of cardiogenic shock)
   • LV failure from large infarct (usually anterior MI, >40% LV mass lost)
   • Mechanical complications:
     • Acute MR: papillary muscle rupture (postero-medial > anterolateral, 2-7 days post-MI)
     • VSD: septal rupture (anterior MI - apical; inferior MI - posterior, 2-7 days post-MI)
     • Free wall rupture: 1-5 days post-MI; typically fatal from tamponade
     • RV infarction: inferior MI with RV involvement
2. Decompensated chronic heart failure (HFrEF)
3. Myocarditis (fulminant)
4. Takotsubo (stress) cardiomyopathy
5. Arrhythmias (VT/VF, complete heart block, rapid AF)
6. End-stage valvular disease
7. Massive pulmonary embolism (right heart failure)

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PATHOPHYSIOLOGY - THE CARDIOGENIC SHOCK SPIRAL

• ↑ PCWP → pulmonary congestion → hypoxemia → ↓ O2 supply → more ischemia

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DIAGNOSIS

• ECG: ST elevation/depression, new LBBB, arrhythmias
• Echocardiography (KEY):
  • Wall motion abnormalities
  • LV/RV systolic function
  • Valvular pathology (MR, VSD)
  • Pericardial effusion
• Coronary angiography: essential if ischemic etiology suspected
• PA Catheter (Swan-Ganz): confirm low CO, high PCWP, high SVR
• Labs: Troponin, BNP/proBNP, lactate, LFTs

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MANAGEMENT

Revascularization (for AMI-CS)

• Emergent PCI: First-line for AMI-cardiogenic shock - SHOCK trial showed survival benefit
• Do NOT perform PCI of all non-culprit vessels acutely (CULPRIT-SHOCK trial)
• CABG for multi-vessel disease after stabilization (or if PCI not feasible)

Pharmacologic Support

• Dobutamine: Inotrope of choice (β1 agonist) - increases CO; may worsen hypotension
• Norepinephrine: Vasopressor to maintain MAP (preferred over dopamine per SOAP-II trial)
• Epinephrine: Combined inotrope/vasopressor
• Milrinone: PDE inhibitor; inotrope + vasodilator (use carefully; may worsen hypotension)
• Avoid: Negative inotropes, diuretics in underfilled patients, aggressive diuresis initially

Mechanical Circulatory Support (MCS)

• IABP-SHOCK II trial: IABP did NOT reduce 30-day mortality in AMI-CS - not routinely recommended anymore
• Impella increasingly used; RECOVER IV trial ongoing
• VA-ECMO: Reserved for most severe cases; concern for LV distension (may need concurrent Impella = "ECPella")

Surgical Options

• For mechanical complications: emergency surgery (MV repair, VSD repair, LV assist device)
• Cardiac transplantation: definitive therapy for refractory cardiogenic shock as bridge-to-transplant

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CHAPTER 317 - CARDIOVASCULAR COLLAPSE, CARDIAC ARREST, AND SUDDEN CARDIAC DEATH

DEFINITIONS

• ~450,000-500,000 deaths/year in the USA
• 80-85% caused by coronary artery disease
• Most frequently due to ventricular fibrillation (VF) or pulseless VT

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CAUSES OF CARDIAC ARREST - THE H's AND T's

• Hypoxia
• Hypovolemia
• Hydrogen ion (acidosis)
• Hypo/Hyperkalemia
• Hypothermia

• Tension pneumothorax
• Tamponade (cardiac)
• Toxins (drugs, poisons)
• Thrombosis - pulmonary (PE)
• Thrombosis - coronary (MI)

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CARDIAC ARREST RHYTHMS

1. Ventricular Fibrillation (VF): Chaotic electrical activity - no coordinated contraction; shockable; most common in out-of-hospital arrest; most favorable prognosis if defibrillated rapidly
2. Pulseless Ventricular Tachycardia (VT): Organized rapid ventricular activity but no effective output; shockable
3. Pulseless Electrical Activity (PEA): Organized electrical activity but no mechanical contraction; non-shockable; causes = H's and T's
4. Asystole: No electrical activity; non-shockable; worst prognosis

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BASIC LIFE SUPPORT (BLS) AND ADVANCED CARDIAC LIFE SUPPORT (ACLS)

High-Quality CPR - The Foundation

• Compression rate: 100-120/min
• Compression depth: ≥5 cm (2 inches) in adults, <6 cm
• Full chest recoil: Allow complete chest recoil between compressions
• Minimize interruptions: <10 seconds for any interruption
• Avoid excessive ventilation: 30:2 ratio until advanced airway; then continuous compressions with 1 breath/6 seconds
• Dispatcher-assisted CPR: Improves bystander CPR rates

ACLS - Shockable Rhythms (VF/Pulseless VT)

1. Recognition + Activation of EMS
2. Immediate high-quality CPR
3. Rapid defibrillation
4. Advanced resuscitation (ACLS)
5. Post-cardiac arrest care
6. Recovery

• Defibrillation: Biphasic 120-200J; monophasic 360J. Shock FIRST in witnessed arrest.
• CPR 2 minutes → rhythm check → shock if still shockable → CPR 2 minutes
• Epinephrine 1 mg IV/IO q3-5 min (given as soon as IV access obtained)
• Amiodarone 300 mg IV bolus after 3rd shock (can repeat 150 mg); or Lidocaine 1-1.5 mg/kg
• After every 2-min CPR cycle: check rhythm and pulse

ACLS - Non-Shockable Rhythms (PEA/Asystole)

• CPR 2 minutes → check rhythm
• Epinephrine 1 mg IV q3-5 min
• Treat reversible causes (H's and T's)
• No role for atropine, sodium bicarbonate routinely
• Vasopressin was removed from guidelines (not superior to epinephrine)

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POST-CARDIAC ARREST CARE

Targeted Temperature Management (TTM) / Therapeutic Hypothermia

• Indication: Comatose survivors of cardiac arrest (any rhythm)
• Target temperature: 32-36°C for 24 hours
• Mechanism: reduces cerebral metabolic demand, decreases excitotoxicity, free radical damage
• TTM2 trial (2021): 33°C vs. 37.5°C showed NO difference in mortality or neurological outcomes
• Current recommendation: prevent fever (>37.5°C) actively; mild hypothermia (33°C) still used at many centers
• Duration: 24h TTM → 24-48h gradual rewarming (avoid rapid rewarming)

Hemodynamic Optimization Post-Arrest

• Target MAP ≥65-70 mmHg
• Avoid hypotension: worsens neurological outcomes
• CULPRIT: Perform emergent coronary angiography if ST elevation or suspected ischemia
• Even without ST elevation: consider angiography within 24h if suspected cardiac etiology

Neuroprognostication

• Wait 72h after arrest (or after rewarming to normothermia) before prognostication
• Predictors of poor outcome (multimodal):
  • Absent pupillary light reflexes at 72h
  • Absent N20 peak on somatosensory evoked potentials (SSEP)
  • EEG: burst suppression or isoelectric
  • CT: diffuse cerebral edema (sulcal effacement, loss of gray-white differentiation)
  • NSE (neuron-specific enolase) >60 µg/L at 48-72h
  • No motor response (extension or absent) at 72h

Other Post-Arrest Management

• Treat underlying cause (PCI, PE thrombolysis, etc.)
• Avoid hypoxia (SpO2 94-98%) AND hyperoxia
• Avoid hypercapnia (target normocarbia)
• Glycemic control (140-180 mg/dL)
• Seizure treatment (can be subclinical post-arrest)
• ICD before discharge (survivors of VF/VT arrest without reversible cause)

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PREVENTION OF SUDDEN CARDIAC DEATH

• EF ≤35% with HF (NYHA II-III) despite optimal medical therapy ≥3 months
• Certain genetic arrhythmia syndromes: Long QT, Brugada, ARVD, HCM

• All survivors of VF/VT cardiac arrest without reversible cause
• Sustained VT with structural heart disease

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SECTION 3: NEUROLOGICAL CRITICAL CARE

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CHAPTER 318 - NERVOUS SYSTEM DISORDERS IN CRITICAL CARE

INTRODUCTION

1. Primary neurologic illness - stroke, TBI, SAH, encephalitis, status epilepticus
2. Secondary neurologic complications of systemic illness - septic encephalopathy, anoxic brain injury post-arrest, metabolic encephalopathy

• Ischemia (hypotension, vasospasm)
• Hemorrhage extension
• Cerebral edema and herniation
• Elevated ICP
• Seizures
• Fever/hyperglycemia (increase metabolic demand)
• Hypoxia

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PATHOPHYSIOLOGY

Brain Edema - Two Types

• Disruption of blood-brain barrier (BBB)
• Protein-rich fluid enters brain interstitium
• Seen in: tumors, abscesses, meningitis, severe hypertension, trauma
• Responds to corticosteroids (dexamethasone - reduces BBB permeability)

• Cellular swelling from ATP failure and membrane dysfunction
• Na+/K+ ATPase fails → Na and water enter cells
• Seen in: ischemic stroke, global hypoxia/ischemia
• Does NOT respond to corticosteroids
• Apparent diffusion coefficient (ADC) reduced on DWI-MRI

• Either type → ↑ ICP
• Focal processes → brain shifts, herniation
• Herniation = mechanical distortion and ischemia from impaired perfusion

Ischemic Cascade

1. Excitatory amino acid (glutamate) release
2. Ca²⁺ and Na⁺ influx (NMDA receptor activation)
3. Protease and lipase activation
4. Lipid peroxidation and free radical damage
5. Cell membrane rupture → necrotic death

• Target of stroke reperfusion therapy (thrombolysis, thrombectomy)
• Worsened by: hypotension, hypoxia, fever, hyperglycemia, seizures

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ELEVATED INTRACRANIAL PRESSURE (ICP)

• Target CPP: 50-70 mmHg in TBI
• If ICP ↑ → CPP ↓ → cerebral ischemia
• Compensated initially by cerebral autoregulation; fails at high ICP

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HERNIATION SYNDROMES

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APPROACH TO ELEVATED ICP

1. Head of bed at 30°
2. Avoid neck flexion (impairs venous drainage)
3. Adequate sedation/analgesia (cough/pain elevate ICP)
4. Treat fever (antipyretics, cooling)
5. Avoid hypercapnia (causes cerebrovascular dilation)
6. Maintain normoglycemia
7. Seizure prophylaxis (in appropriate patients)

1. Hyperosmolar therapy:
   • Mannitol 0.25-1.0 g/kg IV bolus (acts within 20 min; lasts 2-6h)
   • Hypertonic saline (3% or 23.4%) - preferred by many (maintains euvolemia; avoids Mannitol's diuresis)
   • Create osmotic gradient to draw water out of brain
   • Target serum Na 145-155 mEq/L with HTS; serum osmolality 310-320 with Mannitol
2. Hyperventilation (temporary): Reduce PaCO2 to 30-35 mmHg → vasoconstriction → ↓CBV → ↓ICP
   • Effect within minutes; NOT sustained (cerebrovascular adaptation within 6-12h)
   • Use only as bridge while definitive treatment arranged
3. CSF drainage via EVD (extraventricular drain)
4. Neuromuscular blockade (reduces patient effort/Valsalva)

1. Decompressive craniectomy: Remove bone flap to allow brain expansion
   • DECIMAL, HAMLET, DESTINY trials: reduces mortality in malignant MCA infarction
   • Trade-off: may survive with severe disability
2. Barbiturate coma (pentobarbital): Reduces CMR-O2; reduces ICP; monitor with EEG (burst-suppression target)
3. Therapeutic hypothermia: Reduces cerebral metabolic rate

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CRITICAL CARE DISORDERS OF THE CNS

Hypoxic-Ischemic Encephalopathy (HIE)

• Follows cardiac arrest, severe hypotension, respiratory failure
• Global cerebral ischemia → watershed and cortical necrosis
• Clinical spectrum: coma → seizures → vegetative state → brain death
• TTM used post-arrest (see Chapter 317)
• Neuroprognostication at 72h (multimodal)

Septic Encephalopathy

• Most common cause of altered consciousness in ICU
• Diffuse cerebral dysfunction from systemic sepsis (no direct CNS infection)
• Mechanisms: endotoxin crossing BBB, microabscesses, cerebral ischemia, toxic metabolites
• Usually reversible with treatment of underlying sepsis
• MRI: diffuse white matter changes, restricted diffusion in severe cases
• Treatment: treat sepsis; avoid benzodiazepines (worsen encephalopathy)

Metabolic Encephalopathies

• Hepatic encephalopathy: ammonia accumulation; asterixis; treat with lactulose, rifaximin; avoid sedatives
• Uremic encephalopathy: AKI/CKD; myoclonus; reverse with dialysis
• Hyponatremic encephalopathy: acute Na <120 mEq/L; cerebral edema; seizures; treat with HTS
• Hyperammonemia: ornithine transcarbamylase deficiency; dialysis + nitrogen scavengers
• Wernicke's encephalopathy: thiamine deficiency (alcoholics, malnutrition); THIAMINE BEFORE GLUCOSE; ataxia + confusion + ophthalmoplegia

Status Epilepticus (SE)

1. Benzodiazepines (lorazepam 0.1 mg/kg IV or diazepam 5-10 mg IV) - first-line; within 5 min
2. Fosphenytoin 20 mg PE/kg IV, or Levetiracetam 60 mg/kg IV, or Valproate 40 mg/kg IV - second-line; 20-40 min
3. Anesthetic agents: Midazolam, propofol, pentobarbital infusion - refractory SE; continuous EEG monitoring required
4. Non-convulsive SE (NCSE): EEG required to diagnose in comatose patients (no visible convulsions but ongoing ictal activity)

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CRITICAL CARE DISORDERS OF THE PERIPHERAL NERVOUS SYSTEM

ICU-Acquired Weakness (ICU-AW)

• Develops in >25-50% of mechanically ventilated patients
• Two main subtypes:
  • Critical Illness Polyneuropathy (CIP): axonal degeneration (sensorimotor neuropathy); failed weaning from vent
  • Critical Illness Myopathy (CIM): muscle atrophy and necrosis; thick filament loss (myosin)
• Risk factors: sepsis, MODS, prolonged bed rest, corticosteroids, NMBAs, glucose dysregulation
• Diagnosis: EMG/NCS, CK (elevated in myopathy), muscle biopsy
• Treatment: early mobilization and physical therapy (most important); treat underlying illness
• Prognosis: full recovery in months in many; some have permanent deficits

Neuromuscular Transmission Disorders in ICU

• Prolonged NMB effect: after cisatracurium/vecuronium; especially with renal/hepatic failure
• Myasthenia crisis: acute respiratory failure from myasthenia; treat with plasmapheresis or IVIG + immunosuppression + avoid precipitating drugs
• Lambert-Eaton: paraneoplastic; presynaptic ACh release failure

Guillain-Barré Syndrome (GBS) in ICU

• Ascending demyelinating polyneuropathy
• Respiratory failure requiring ventilation in ~30%
• Treatment: IVIG 2g/kg over 5 days or plasmapheresis (equal efficacy); NOT steroids
• Monitor FVC and NIF (negative inspiratory force):
  • Rule of 20-30: Intubate if FVC <20 mL/kg, NIF <-30 cmH2O, SpO2 <92%
• Autonomic instability: BP swings, arrhythmias - avoid anticholinergics

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BRAIN DEATH

• Hypothermia (temp <36°C)
• Drug intoxication/overdose
• Severe metabolic derangements
• Hypotension

1. Coma - no response to pain
2. Absent brainstem reflexes:
   • No pupillary light reflex (fixed, dilated)
   • No corneal reflex
   • No oculocephalic reflex (doll's eyes)
   • No oculovestibular reflex (caloric testing)
   • No gag/cough reflex
   • No facial motor response to painful stimuli
3. Apnea test: No breathing drive with PaCO2 >60 mmHg (rise ≥20 mmHg from baseline)

• EEG: isoelectric (electrocerebral silence)
• Cerebral blood flow study (radionuclide scan, CT angiography, TCD)
• SSEP: absent N20 bilaterally

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DELIRIUM IN THE ICU

• Prevalence: 60-80% of mechanically ventilated ICU patients
• Strong predictor of prolonged LOS, increased mortality, long-term cognitive impairment
• Risk factors: ABCDEF bundle violations, benzodiazepines, immobility, sleep deprivation, sensory deprivation

Types of Delirium:

• Hyperactive: Agitated, pulling at lines (15%)
• Hypoactive: Quiet, withdrawn (50%) - most missed
• Mixed: Both features (35%)

Assessment Tool - CAM-ICU (Confusion Assessment Method for ICU):

1. Acute change in mental status or fluctuating course
2. Inattention (attention screening test)
3. Altered level of consciousness (RASS not 0)
4. Disorganized thinking

The ABCDEF Bundle (Prevention and Management):

• Awaken (daily SAT - Spontaneous Awakening Trials)
• Breathing (daily SBT)
• Choice of analgesia/sedation (minimize benzos; prefer propofol or dexmedetomidine)
• Delirium assess and manage
• Early mobility and exercise
• Family engagement

• Haloperidol: Still commonly used but HOPE-ICU trial showed no mortality benefit; use for patient safety
• Quetiapine or olanzapine: alternatives
• Dexmedetomidine: Reduces delirium duration (alpha-2 agonist; allows rousable sedation)
• Avoid benzodiazepines (worsens delirium - use only for alcohol withdrawal/seizures)

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QUICK-REFERENCE SUMMARY TABLE

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