01Approach to the Critical Patient/attcp56

Immediate stabilization

›Airway and oxygenation priorities

›SpO2 target >= 92% on supplemental oxygen

›High-flow nasal cannula (HFNC) at 40-60 L/min, FiO2 0.5-1.0 as first-line non-invasive support

›Non-invasive positive pressure ventilation if HFNC fails or is unavailable

›Rapid sequence intubation for GCS < 8, refractory hypoxemia, or respiratory arrest

›Refractory hypoxemia trigger

›SpO2 < 88% despite FiO2 >= 0.6 on HFNC

›PaO2/FiO2 <= 150 mmHg = moderate-to-severe ARDS threshold

›PaO2/FiO2 <= 100 mmHg = severe ARDS, mortality 45-60%

›Intubation preparation if proceeding

›Pre-oxygenate 5 minutes with HFNC or non-rebreather 15 L/min

›Ketamine 1-2 mg/kg IV preferred induction agent (preserves respiratory drive until apnea)

›Succinylcholine 1.5 mg/kg or rocuronium 1.2 mg/kg for paralysis

›Hemodynamic stabilization

›MAP target >= 65 mmHg

›If hypotensive, 500 mL isotonic crystalloid bolus, reassess

›Norepinephrine 0.01-0.5 mcg/kg/min for vasopressor-dependent shock

›Arterial line for continuous blood pressure monitoring in mechanically ventilated patients

›Septic shock management

›Broad-spectrum antibiotics within 1 hour of sepsis recognition (Class I recommendation)

›Lactate >= 2 mmol/L defines occult shock requiring resuscitation

›Avoid excessive fluid once shock resolves; target net neutral-to-negative balance

›Fluid management caution

›NCPE is a permeability problem, not hydrostatic; avoid diuretics unless true volume overload

›Conservative fluid strategy after initial resuscitation reduces ventilator days

Monitoring and targets

›Monitoring bundle

02History/hx74

Symptom onset and characterization

›Core symptom complex

›Acute dyspnea

›Onset within hours to days of identifiable insult

›Progression to inability to speak in full sentences

›Cough

›Frothy sputum, may be pink-tinged

›Productive versus dry cough

›Tachypnea

›Respiratory rate > 30/min is alarm feature

›Accessory muscle use indicating respiratory fatigue

›Distinguishing features from cardiogenic edema

›Absence of orthopnea

›Orthopnea favors cardiogenic etiology

›PND absent in most NCPE

›Absence of peripheral edema

›Bilateral pitting edema favors cardiogenic cause

›Prior weight gain indicates chronic heart failure

›No response to upright positioning

›Cardiogenic edema typically improves with head elevation

›NCPE hypoxemia refractory regardless of position

Etiology search

›Precipitant identification

›Pneumonia or sepsis

›Fever, productive cough, recent upper respiratory illness

›Pneumonia is most common ARDS precipitant

›Aspiration event

›Witnessed vomiting and aspiration

03Physical Exam/exam68

Vital signs and general appearance

›Vital sign pattern

›Respiratory rate

›Tachypnea > 30/min typical; > 30 is severity marker

›Rapid rise indicates respiratory muscle fatigue and impending failure

›Heart rate

›Tachycardia from hypoxemia, pain, or sepsis

›Bradycardia may indicate severe hypoxemia or neurogenic cause

›Blood pressure

›Hypotension: SBP < 90 mmHg — sepsis, neurogenic, or severe ARDS

›Hypertension: may be seen in neurogenic pulmonary edema

›Temperature

›Fever supports infectious precipitant

›Hypothermia may indicate severe sepsis

›SpO2

›SpO2 < 90% on room air requires immediate supplemental oxygen

›Degree of hypoxemia correlates with ARDS severity

›General appearance

›Work of breathing

›Accessory muscle use (sternocleidomastoid, scalene)

›Intercostal and supraclavicular retractions

›Inability to speak full sentences

›Cyanosis

›Central cyanosis indicates severe hypoxemia

›Peripheral cyanosis may indicate low cardiac output

›Skin findings

›Mottling suggests sepsis or low flow state

›Track marks suggest intravenous drug use

04Differential Diagnosis/ddx52

Life-threatening mimics

›Cardiogenic pulmonary edema

›ICD-10: I50.1 (left ventricular failure)

›S3 gallop, JVD, peripheral edema, elevated BNP, cardiomegaly

›Responds to diuretics; edema fluid-to-plasma protein ratio < 0.65

›Pulmonary embolism

›ICD-10: I26.99

›Acute hypoxemia, pleuritic pain, tachycardia, RV strain on ECG

›D-dimer, CTA chest required

›Diffuse alveolar hemorrhage

›ICD-10: J98.01

›Hemoptysis, falling hemoglobin, progressively bloody BAL returns

›Bilateral infiltrates with anemia disproportionate to bleeding

›Tension pneumothorax

›ICD-10: J93.0

›Absent breath sounds unilateral, tracheal deviation, hypotension

›Immediate needle decompression required

Non-cardiogenic pulmonary edema subtypes

›ARDS (most common and severe NCPE manifestation)

›ICD-10: J80

›Bilateral infiltrates, PaO2/FiO2 < 300 mmHg, non-cardiogenic origin

›Berlin criteria classify mild, moderate, and severe

›TRALI vs. TACO

›TRALI: ICD-10 J70.11; non-cardiogenic; within 6 hours of transfusion; normal BNP

›TACO: ICD-10 E87.70; cardiogenic; elevated BNP; signs of volume overload

›Distinguishing clinically important as treatment differs

›Neurogenic pulmonary edema

›ICD-10: J81.0

05Laboratory Tests/lt61

Blood gas and oxygenation

›Arterial blood gas

›PaO2/FiO2 ratio — cornerstone of ARDS diagnosis and severity

›200-300 mmHg = mild ARDS

›100-200 mmHg = moderate ARDS

›< 100 mmHg = severe ARDS; mortality 45-60%

›A-a gradient

›Elevated in NCPE due to V/Q mismatch and shunt

›Age-corrected normal = (age/4) + 4 mmHg

›Acid-base status

›Hypercapnia indicates hypoventilation or fatigue

›Metabolic acidosis may indicate sepsis or salicylate toxicity

›Venous blood gas

›Adequate initial screen before ABG in stable patients

›pH and PaCO2 correlate reasonably with ABG values

›Not sufficient for PaO2/FiO2 calculation

Biomarkers differentiating etiology

›BNP/NT-proBNP

›BNP < 100 pg/mL makes cardiogenic edema unlikely

›Moderate discriminatory ability; AUC 0.67-0.87

›BNP may be elevated in ARDS/sepsis (false positive for cardiogenic)

›NT-proBNP < 300 pg/mL makes cardiogenic edema unlikely

›Use age-adjusted thresholds if available

›Elevated values require echocardiography for confirmation

›Troponin

›Elevated in ACS, myocarditis, or demand ischemia from severe hypoxemia

›High-sensitivity troponin for ACS exclusion

›Right heart strain pattern in severe ARDS

06Diagnostic Tests/dt82

Scoring Systems

›Berlin Definition of ARDS (2012)

›Timing: acute onset within 1 week of known clinical insult or new/worsening symptoms

›Bilateral opacities on chest imaging not explained by effusions, collapse, or nodules

›Respiratory failure not explained by cardiac failure or fluid overload (requires objective assessment)

›Severity stratification

›Mild: PaO2/FiO2 200-300 mmHg with PEEP/CPAP >= 5 cm H2O

›Moderate: PaO2/FiO2 100-200 mmHg with PEEP >= 5 cm H2O

›Severe: PaO2/FiO2 < 100 mmHg with PEEP >= 5 cm H2O

›Lung Injury Prediction Score (LIPS)

›Predicts risk of ARDS in at-risk patients before onset

›Shock (+2), aspiration (+2), sepsis (+1), pneumonia (+1.5), high-risk surgery (+1)

›Score > 4 indicates high risk for ARDS development

›Useful for early recognition and preventive ventilation strategies

›Murray Lung Injury Score

›Components: PaO2/FiO2, PEEP, lung compliance, quadrants on CXR

›Score 1-2.5 = moderate lung injury

›Score > 2.5 = severe lung injury; ECMO consideration

›Used for ECMO candidacy assessment in refractory ARDS

›Sequential Organ Failure Assessment (SOFA)

›Respiratory component: PaO2/FiO2 ratio

›Score 1-4 based on oxygenation worsening

›Overall SOFA score guides ICU severity and prognosis

›Serial SOFA better predictor of mortality than single value

MRI

›Chest MRI in NCPE

›Limited role in acute NCPE due to acquisition time and instability

›Not standard first-line imaging in acute setting

›Reserved for subacute diagnostic uncertainty or ILD characterization

›Distinguishing features

›Ground-glass opacities in dependent regions in ARDS

›Fibrotic reticulation in established or resolving ARDS

›May differentiate organizing pneumonia from ARDS in recovery phase

›Brain MRI for neurogenic pulmonary edema evaluation

›Indicated when SAH, TBI, or stroke is suspected precipitant

›MRI brain with DWI for ischemic stroke

›MRI brain with FLAIR for SAH detection (high sensitivity within first 48 hours)

›CT brain initially; MRI if CT negative and clinical suspicion remains

CT

›CT chest without contrast

›Bilateral ground-glass opacities

›Diffuse, often gravity-dependent distribution in ARDS

›Heterogeneous in ARDS vs. uniform in cardiogenic edema

›ARDS patterns

›Exudative phase: bilateral airspace consolidation with air bronchograms

›Proliferative phase: ground glass with traction bronchiectasis

›Fibrotic phase: reticulation, honeycombing in survivors

›Differentiating features from cardiogenic edema

›Cardiomegaly absent in NCPE

›Bilateral pleural effusions less prominent in NCPE

›Peribronchial cuffing and Kerley B lines favor cardiogenic

›CT pulmonary angiography

›Indicated to exclude pulmonary embolism as cause of acute hypoxemia

›Sensitivity 83-100%, specificity 89-97% for PE

›Consider when pre-test probability is intermediate or high

›Wells score to stratify PE probability before ordering

›CT head

›Indicated in suspected neurogenic pulmonary edema

›Subarachnoid hemorrhage: hyperdense cisterns on non-contrast CT

›TBI: hemorrhagic contusions, subdural or epidural hematoma

›If CT head negative and SAH suspected, LP for xanthochromia

Ultrasound

›Lung ultrasound (LUS)

›B-line pattern

›>= 3 B-lines per intercostal space in >= 2 bilateral zones = B-pattern (pulmonary edema)

›Critical care ultrasound differentiates ARDS from cardiogenic edema with high accuracy

›Sensitivity for pulmonary edema approximately 85%, specificity 93%

›BLUE protocol application

›Bilateral anterior B-lines with preserved lung sliding: pulmonary edema (cardiogenic or non-cardiogenic)

›Asymmetric distribution or consolidation: pneumonia pattern

›Anterior consolidation with air bronchograms: ARDS-associated consolidation

›A-profile vs. B-profile distinction

›A-profile (A-lines, no B-lines): lung aeration preserved; pneumothorax or PE more likely

›B-profile bilateral: alveolar-interstitial syndrome consistent with pulmonary edema

›Point-of-care cardiac ultrasound

›Left ventricular function assessment

›Reduced LVEF suggests cardiogenic cause

›Preserved LVEF and bilateral B-lines supports NCPE

›RV dilation in severe ARDS or pulmonary embolism

›IVC collapsibility index

›Collapsible IVC (> 50%) suggests low venous pressure consistent with NCPE

›Dilated non-collapsible IVC favors cardiogenic or TACO etiology

›Cardiopulmonary POCUS

›Combined lung and cardiac ultrasound improves diagnostic accuracy for undifferentiated dyspnea

›Reduces time to diagnosis and can guide fluid management

›ACEP supports POCUS for acute respiratory failure evaluation (Level B recommendation)

07Disposition/dispo38

ICU admission

›ICU admission criteria

›Moderate-to-severe ARDS

›PaO2/FiO2 < 200 mmHg

›Requiring mechanical ventilation or HFNC > 40 L/min

›Hemodynamic instability

›Vasopressor-dependent shock

›MAP < 65 mmHg despite initial resuscitation

›Multi-organ dysfunction

›AKI, hepatic dysfunction, altered mental status concurrent with respiratory failure

›SOFA score >= 2 indicates organ dysfunction

Intermediate care or step-down

›Step-down or monitored bed criteria

›Mild ARDS or mild-moderate NCPE on HFNC

›PaO2/FiO2 200-300 mmHg with stable hemodynamics

›No vasopressors required

›Responds to treatment of underlying cause

›Improving trajectory

›Declining oxygen requirements over first 6-12 hours

›Tolerating oral medications and fluids

Transfer indications

›Transfer to higher level of care

›Severe refractory ARDS

›PaO2/FiO2 < 80 mmHg despite optimal ventilation

›Transfer to VV-ECMO capable center

›Neurosurgical emergencies

›SAH or TBI requiring neurosurgical intervention

›If neurosurgery not available at current facility

08Treatment/t139

Respiratory support — non-invasive

›Oxygen therapy titration

›Conventional nasal cannula or face mask

›Initial approach for mild hypoxemia

›SpO2 target 92-96%

›Upgrade if SpO2 < 90% or work of breathing increases

›High-flow nasal cannula (HFNC)

›Flow: start at 40 L/min, titrate up to 60 L/min

›FiO2: start at 0.5-0.6, titrate to SpO2 target

›ROX index >= 4.88 at 2 hours predicts HFNC success

›ROX = (SpO2/FiO2) / respiratory rate

›ROX < 3.85 at 12 hours predicts HFNC failure; intubate

›Non-invasive positive pressure ventilation (NIV/NIPPV)

›CPAP or BiPAP as alternative if HFNC unavailable

›IPAP 10-20 cm H2O, EPAP 5-10 cm H2O

›Avoid NIV with high aspiration risk or poor mask tolerance

Mechanical ventilation — lung-protective strategy

›Lung-protective ventilation (ARDSNet protocol)

›Tidal volume

›6 mL/kg predicted body weight — Class I recommendation (ARDSNet ARMA trial)

›Reduce to 4 mL/kg if plateau pressure exceeds target

›Predicted body weight: male = 50 + 0.91 x (height in cm - 152.4); female = 45.5 + 0.91 x (height in cm - 152.4)

›Plateau pressure

›Target <= 30 cm H2O

›Reduce tidal volume if exceeded

›Driving pressure

›Target < 15 cm H2O

›Driving pressure = plateau pressure - PEEP

›PEEP

›Minimum 5 cm H2O for all mechanically ventilated ARDS patients

›Higher PEEP table for moderate-to-severe ARDS (PEEP 8-18 cm H2O based on FiO2 requirements)

›Respiratory rate

›12-35 breaths/min, titrate to maintain pH 7.30-7.45

›Permissive hypercapnia acceptable with pH >= 7.25

Mechanical ventilation — adjunctive strategies

›Prone positioning

›Indication: PaO2/FiO2 < 150 mmHg despite optimal supine ventilation

›Strong recommendation, Class I

›Duration: >= 12-17 hours/day until PaO2/FiO2 improves

›Mechanism: recruits dorsal lung units, reduces V/Q mismatch

›Prone positioning logistics

›Dedicated proning team (4-5 providers minimum)

›Continuous hemodynamic monitoring throughout

›Contraindications: unstabilized spine injury, open abdomen, facial trauma

›Corticosteroids

›Indication: moderate-to-severe ARDS within 14 days of onset

›Conditional recommendation based on RCT evidence

›Do not start after day 14 — may worsen outcomes

›Dexamethasone protocol (DEXA-ARDS trial)

›20 mg IV once daily for 5 days

›Then 10 mg IV once daily for 5 days

›Number needed to treat approximately 11 to prevent one death

›Methylprednisolone alternative

›1 mg/kg IV daily, taper over 14 days

›Use in early ARDS if dexamethasone unavailable

›Neuromuscular blockade

›Indication: early severe ARDS with refractory hypoxemia or ventilator dyssynchrony

›Goal duration < 48 hours

›Cisatracurium 37.5 mg/hour infusion preferred (renal/hepatic independent metabolism)

›Requires continuous sedation during NMB

›VV-ECMO

›Indication: PaO2/FiO2 < 80 mmHg despite optimal ventilator settings and prone positioning

›Strong recommendation at ECMO-capable centers

›CESAR trial and EOLIA trial support benefit in severe refractory ARDS

›Transfer if not available at current institution

›Conservative fluid strategy

›Target after initial shock resuscitation

›Net neutral-to-negative fluid balance once vasopressors weaned

›FACTT trial: conservative fluid strategy reduces ventilator days (7 vs. 15 days) without increasing mortality

›Furosemide IV if needed to achieve negative balance

Etiology-specific treatments

›Infectious etiology

›Empiric antibiotics for sepsis-associated ARDS

›Within 1 hour of recognition (Class I recommendation)

›Community-acquired: beta-lactam + macrolide or fluoroquinolone

›Hospital-acquired/VAP: piperacillin-tazobactam or cefepime + vancomycin

›Adjust based on culture results and de-escalate early

›Antifungal if Candida or Aspergillus risk (immunocompromised)

›Micafungin 100 mg IV daily for invasive candidiasis

›Voriconazole 4 mg/kg IV every 12 hours for invasive aspergillosis

›Opioid-induced NCPE

›Naloxone 0.4-2 mg IV/IM/IN every 2-3 minutes to effect

›Use cautiously — rapid reversal may precipitate negative-pressure pulmonary edema

›Preferred: titrate with 0.04 mg IV increments to adequate respiratory drive

›Naloxone infusion for long-acting opioids: 2/3 of reversal dose per hour

›Supportive respiratory care

›HFNC or NIV while awaiting naloxone effect

›Intubation if naloxone insufficient or contraindicated

›Salicylate toxicity

›Urinary alkalinization

›Sodium bicarbonate IV infusion: 3 ampules (150 mEq) in 1 L D5W at 150-250 mL/hour

›Target urine pH 7.5-8.0 to promote salicylate ionization and urinary excretion

›Correct hypokalemia first (alkalinization ineffective with hypokalemia)

›Hemodialysis indications

›Salicylate level > 7.2 mmol/L (100 mg/dL) regardless of symptoms

›Salicylate level > 4.3 mmol/L (60 mg/dL) with severe symptoms (NCPE, AMS, renal failure)

›Preferred over urinary alkalinization alone for severe toxicity

›HAPE treatment

›Immediate descent

›Definitive treatment; most effective single intervention

›Supplemental oxygen at 4-6 L/min while arranging descent

›Nifedipine (if descent delayed)

›30 mg sustained-release tablet immediately, then 30 mg SR every 12 hours

›Reduces pulmonary artery pressure

›Portable hyperbaric chamber (Gamow bag) if descent impossible

›Simulates descent of 300-4000 m depending on inflation

›Bridge to definitive descent

›Phosphodiesterase-5 inhibitors alternative

›Tadalafil 10 mg twice daily as prophylaxis for high-risk individuals

›Sildenafil 50 mg every 8 hours for treatment if nifedipine unavailable

›Neurogenic pulmonary edema

›Treat underlying neurologic cause

›SAH: neurosurgical consultation, nimodipine for vasospasm prevention

›TBI: ICP monitoring and management

›Seizure: benzodiazepine then antiepileptic therapy

›Supportive respiratory management

›Usually self-limiting within 24-48 hours if neurologic cause controlled

›HFNC or mechanical ventilation as needed

›Alpha-2 agonists (dobutamine, levosimendan) may help if catecholamine-mediated

›TRALI management

›Discontinue transfusion immediately

›Return blood product to blood bank for investigation

›Report to hemovigilance system

›Supportive respiratory care

›HFNC or mechanical ventilation

›No proven benefit from corticosteroids in TRALI

›Avoid diuretics (not volume-overloaded)

›Drug-induced NCPE (chemotherapy)

›Discontinue offending agent immediately

›Corticosteroids IV for differentiation syndrome (ATRA-associated)

›Dexamethasone 10 mg IV every 12 hours until symptom resolution

›Supportive oxygenation as for ARDS

Prophylaxis

›Preventive measures in ICU

›Stress ulcer prophylaxis

›Proton pump inhibitor (pantoprazole 40 mg IV daily) or H2 blocker

›For mechanically ventilated or coagulopathic patients

›DVT prophylaxis

›Enoxaparin 40 mg SC daily (dose-adjust for renal function)

›Sequential compression devices if anticoagulation contraindicated

›Early enteral nutrition

›Initiate within 24-48 hours of ICU admission

›Trophic feeds initially (10-20 mL/hour) then advance as tolerated

›Avoid parenteral nutrition unless enteral not possible for > 7 days

09Special Populations/sp78

Pregnancy

›Physiologic considerations

›Respiratory changes in pregnancy

›Increased tidal volume (~40%) and minute ventilation

›Reduced functional residual capacity (~20%), worsening atelectasis tendency

›Hypocapnia normal (PaCO2 28-32 mmHg); PaCO2 > 40 mmHg concerning for respiratory failure

›Common precipitants unique to pregnancy

›Amniotic fluid embolism: sudden cardiovascular collapse + DIC

›Pre-eclampsia/eclampsia: neurogenic edema, fluid shifts

›Peripartum cardiomyopathy: mixed cardiogenic/non-cardiogenic picture

›Tocolytic therapy: ritodrine and terbutaline can cause NCPE

›Management adaptations

›Left lateral decubitus positioning to relieve aortocaval compression

›Particularly important during prone positioning or supine ventilation

›Manual uterine displacement if lateral tilt insufficient

›Medication safety

›Corticosteroids: dexamethasone and betamethasone safe; also promote fetal lung maturity

›Avoid ACE inhibitors and ARBs

›Sedation: propofol limited to < 48 hours (propofol infusion syndrome risk)

›Fetal monitoring

›Continuous fetal heart rate monitoring if > 24 weeks gestation

›Maternal hemodynamic optimization takes priority over delivery

›Multidisciplinary team

›Maternal-fetal medicine, critical care, neonatology, obstetric anesthesia

Geriatric

›Physiologic vulnerability

›Reduced respiratory reserve

›Decreased FVC, FEV1, and FRC with aging

›Reduced cough reflex and mucociliary clearance

›Higher aspiration risk from dysphagia and reduced gag reflex

›Altered pharmacodynamics

›Reduced renal clearance; creatinine-adjusted dosing for antibiotics

›Increased sedation sensitivity; use lowest effective doses

›Prolonged neuromuscular blockade clearance

›Clinical presentation differences

›Atypical presentation

›Delirium or functional decline may precede respiratory symptoms

›Absence of fever in 30-50% of bacteremic elderly patients

›Tachypnea may be only early clue

›Higher baseline comorbidity

›Polypharmacy increases drug-induced NCPE risk

›Chronic heart failure complicates cardiogenic vs. non-cardiogenic distinction

›Management considerations

›Lower thresholds for ICU admission and early intubation

›Frailty index as adjunct to physiologic severity

›Goals-of-care discussion early given higher ARDS mortality in elderly

›ARDS mortality in elderly

›Age > 65 years: in-hospital mortality approximately 50-60%

›Post-ICU cognitive impairment particularly prevalent

›Fluid management

›Higher risk of volume overload with aggressive resuscitation

›Earlier consideration of conservative fluid strategy

Pediatrics

›Pediatric ARDS (PARDS) definition

›Berlin Definition does not apply directly to children

›PARDS defined by Pediatric Acute Lung Injury Consensus Conference (PALICC) 2015 criteria

›Age: > 1 week of age and less than 18 years

›Oxygenation thresholds

›Mild PARDS: oxygenation index 4-8 or OSI (SpO2-based) 5-7.5

›Moderate PARDS: OI 8-16 or OSI 7.5-12.3

›Severe PARDS: OI >= 16 or OSI >= 12.3

›Etiology differences in children

›Viral pneumonia most common precipitant (RSV, influenza, adenovirus)

›Respiratory syncytial virus in infants

›Bacterial sepsis and aspiration also common

›TRALI less common but may occur with blood product administration

›Neonates and infants at higher risk from immature immune system

›Treatment adaptations

›Lung-protective ventilation

›Tidal volume 4-8 mL/kg predicted body weight

›Plateau pressure < 28 cm H2O; driving pressure < 15 cm H2O

›PEEP titrated to oxygenation and lung compliance

›Prone positioning

›Supported in moderate-severe PARDS

›Sessions of >= 8-12 hours; may be better tolerated than adults

›Corticosteroids in PARDS

›Less evidence than in adults; use case-by-case

›Early methylprednisolone may help if inflammatory cause documented

›Weight-based fluid management

›Initial sepsis resuscitation: 10-20 mL/kg isotonic saline bolus, reassess

›Avoid > 60 mL/kg in first hour; reassess for pulmonary edema after each bolus

10Background/b96

Epidemiology

›Incidence and prevalence of ARDS

›ARDS incidence

›Approximately 200,000 cases per year in the United States

›Incidence 78.9 per 100,000 person-years in general population

›Rising incidence with aging populations and increased critical care utilization

›Mortality rates

›Overall ARDS mortality: 30-45% depending on severity and underlying cause

›Mild ARDS: approximately 27% mortality

›Moderate ARDS: approximately 32% mortality

›Severe ARDS (PaO2/FiO2 < 100 mmHg): 45-60% mortality

›Primary cause of death is multi-organ dysfunction syndrome (MODS), not refractory hypoxemia

›NCPE subtypes epidemiology

›TRALI incidence

›1 in 5,000-12,000 transfused components

›Leading cause of transfusion-related mortality

›Incidence declined with leukocyte-reduced products and male donor plasma

›HAPE incidence

›0.1-4% of individuals ascending above 4000 m

›Rate approaches 50-60% in susceptible individuals on re-exposure

›Neurogenic pulmonary edema

›20-30% of patients with severe SAH develop NPE

›TBI-associated NPE in up to 20% of severe cases

›Opioid-induced NCPE

›Incidence not well defined; rising with opioid epidemic

›Heroin is most common causative opioid

›Long-term outcomes

›ARDS survivors

›11% late mortality at 1 year; 20-34% at 5 years

›Hospital readmission in up to 40% of survivors within 1 year

›Fibrotic CT changes in 43-70% of survivors

›44% of previously employed survivors jobless at 1 year

Pathophysiology

›Alveolar-capillary barrier disruption

›Core mechanism of NCPE

›Injury to type 1 and type 2 alveolar epithelium and vascular endothelium

›Increased alveolar-capillary permeability (permeability edema, not hydrostatic)

›Protein-rich exudate floods alveolar space; impairs surfactant function

›Inflammatory cascade

›Neutrophil infiltration and activation: release of proteases, reactive oxygen species

›Macrophage activation: TNF-alpha, IL-1, IL-6, IL-8 cytokine storm

›Platelet-endothelial interactions: microthrombi in pulmonary vasculature

›Surfactant dysfunction

›Protein-rich edema fluid inactivates surfactant

›Decreased compliance, atelectasis, increased shunt fraction

›ARDS phases

›Exudative phase (days 1-7)

›Diffuse alveolar damage with hyaline membrane formation

›Neutrophil-rich exudate, hemorrhage, cellular debris

›Hypoxemia from shunt (collapsed, fluid-filled alveoli)

›Proliferative phase (days 7-21)

›Type 2 pneumocyte proliferation covering denuded basement membrane

›Fibroblast infiltration beginning

›Improving oxygenation in survivors

›Fibrotic phase (weeks to months)

›Obliterative fibrosis in some patients

›Residual CT changes in majority of survivors

›Subtype-specific mechanisms

›Neurogenic pulmonary edema

›Sudden catecholamine surge from acute brain injury

›Massive sympathetic discharge increases pulmonary venous pressure transiently (blast theory)

›Direct catecholamine toxicity to pulmonary endothelium (permeability theory)

›HAPE

›Hypobaric hypoxia causes uneven hypoxic vasoconstriction

›Stress failure of alveolar capillaries from elevated local pressures

›Impaired alveolar fluid clearance at altitude

›TRALI

›Two-hit model: primed neutrophils + donor antibody activation (HLA class I/II or HNA antibodies)

›Neutrophil-mediated endothelial injury and increased permeability

Therapeutic Considerations

›Mechanistic basis for lung-protective ventilation

›VILI (ventilator-induced lung injury)

›Volutrauma: overdistension of baby lung from normal tidal volumes

›Atelectrauma: cyclic collapse/reopening of unstable lung units

›Biotrauma: mechanical stretch triggers local and systemic cytokine release

›ARDSNet protocol rationale

›Low tidal volume reduces VILI and biotrauma

›Survival benefit: 31% vs. 40% mortality (6 mL/kg vs. 12 mL/kg)

›Most well-validated intervention in ARDS treatment

›Prone positioning rationale

›Recruits posterior (dorsal) lung units

›Reduces dependent atelectasis from abdominal pressure

›Homogenizes ventilation-perfusion matching

›PROSEVA trial: 28-day mortality 16% prone vs. 33% supine (PaO2/FiO2 < 150 mmHg)

›Corticosteroid evidence

›DEXA-ARDS trial (2020)

›Dexamethasone reduced 60-day mortality: 21% vs. 36% (NNT 11)

›Benefit limited to PaO2/FiO2 < 200 mmHg within 14 days of onset

›Mechanism: anti-inflammatory, reduces cytokine-mediated endothelial injury

›Treatment after day 14 increases mortality

›Mechanistic hypothesis: promotes fibrosis if given during proliferative phase

›VV-ECMO evidence

›CESAR trial (2009)

›Transfer to ECMO center improved survival without severe disability: 63% vs. 47%

›Confounded by better overall care at ECMO centers

›EOLIA trial (2018)

›No statistically significant mortality benefit in primary endpoint

›Crossover rescue ECMO reduced 60-day mortality in severe ARDS

›Current practice: VV-ECMO at ECMO-capable centers for PaO2/FiO2 < 80 mmHg refractory cases

11Patient Discharge Instructions/pdi39

copy discharge instructions

›Discharge instructions for non-cardiogenic pulmonary edema

›What happened

›You were treated for a serious lung condition called non-cardiogenic pulmonary edema

›This occurs when fluid leaks into the lungs due to injury or illness, not a heart problem

›Your oxygen levels were low and your lungs needed support to recover

›Medications

›Take all prescribed medications exactly as directed

›Do not stop any antibiotics or steroids early even if feeling better

›Ask your pharmacist or doctor before starting any new medications including over-the-counter drugs

›Activity

›Rest and limit strenuous activity for at least 2 weeks after discharge

›Shortness of breath with exertion is expected; increase activity gradually

›Pulmonary rehabilitation referral provided or to be arranged at follow-up

›Breathing

›Use supplemental oxygen at home as prescribed; do not adjust flow rate without medical guidance

›Practice incentive spirometry 10 times per hour while awake to prevent lung collapse

›Sleep with head of bed elevated 30-45 degrees if breathing is uncomfortable lying flat

›Follow-up appointments

›Primary care physician within 1-2 weeks of discharge

›Pulmonology or ICU recovery clinic at 1-3 months post-discharge

›Lung function tests (spirometry, DLCO) at 3-6 months

›Return to emergency department immediately if

›Worsening or sudden shortness of breath

›Oxygen level (SpO2) < 92% on home pulse oximeter

›Chest pain or pressure

›Coughing up blood

›New confusion, difficulty thinking clearly, or unusual behavior

12References/r36

Guidelines and key sources

›Gorman EA, O'Kane CM, McAuley DF. Acute Respiratory Distress Syndrome in Adults: Diagnosis, Outcomes, Long-Term Sequelae, and Management. Lancet. 2022

›PMID 36070788

›Comprehensive review of ARDS epidemiology, management, and long-term outcomes

›Qadir N, Sahetya S, Munshi L, et al. An Update on Management of Adult Patients With Acute Respiratory Distress Syndrome: An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2024

›PMID: PMC10870893

›Current ATS clinical practice guideline for ARDS management

›Bos LDJ, Ware LB. Acute Respiratory Distress Syndrome: Causes, Pathophysiology, and Phenotypes. Lancet. 2022

›PMID 36070787

›Pathophysiology and phenotypic classification of ARDS

›Ware LB, Matthay MA. Acute Pulmonary Edema. N Engl J Med. 2005

›DOI: 10.1056/NEJMcp052699

›Stepwise approach differentiating cardiogenic from non-cardiogenic pulmonary edema

›Fan E, Brodie D, Slutsky AS. Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment. JAMA. 2018

›DOI: 10.1001/jama.2017.21907

›Landmark JAMA review of diagnosis and treatment evidence

›Meyer NJ, Gattinoni L, Calfee CS. Acute Respiratory Distress Syndrome. Lancet. 2021

›PMID 34217425

›Pathophysiology and advances in phenotype-directed therapy

›Busl KM, Bleck TP. Neurogenic Pulmonary Edema. Crit Care Med. 2015

›PMID 26066018

›Neurogenic pulmonary edema pathogenesis and management

›Bartsch P, Swenson ER. Acute High-Altitude Illnesses. N Engl J Med. 2013

›DOI: 10.1056/NEJMcp1214870

›HAPE pathophysiology, prevention, and treatment

›Long B, Lentz S, Gottlieb M. Emergency Medicine Updates: Acute Respiratory Distress Syndrome. Am J Emerg Med. 2025

›PMID 40616875

›Emergency medicine perspective and updates on ARDS management

Evidence & Review