What's New in Pulmonology 2025: A Critical Care Perspective

Dr Neeraj Manikath , claude.ai

Abstract

The field of pulmonology has witnessed remarkable advances in 2025, with paradigm shifts in our understanding and management of acute and chronic respiratory diseases. This comprehensive review synthesizes recent developments relevant to critical care practitioners, including innovations in mechanical ventilation strategies, emerging therapies for acute respiratory distress syndrome (ARDS), novel approaches to refractory hypoxemia, advances in interstitial lung disease management, and the evolving landscape of severe asthma and COPD care. We highlight evidence-based updates alongside practical clinical pearls to enhance bedside decision-making for postgraduate trainees and intensivists.

INTRODUCTION

The respiratory system remains at the epicenter of critical illness, with acute respiratory failure accounting for a substantial proportion of intensive care unit (ICU) admissions worldwide. The landscape of pulmonology in critical care continues to evolve rapidly, driven by technological innovations, refined physiological understanding, and high-quality clinical trials. This review examines the most significant developments in 2025, focusing on practical applications for the busy intensivist.

MECHANICAL VENTILATION: REFINED STRATEGIES AND EMERGING CONCEPTS

Ultra-Protective Ventilation: Beyond the ARDSNet Protocol

While lung-protective ventilation with tidal volumes of 6 ml/kg predicted body weight (PBW) remains the cornerstone of ARDS management, recent evidence suggests that further reduction in driving pressure (ΔP) and mechanical power may improve outcomes in selected patients.

Pearl: Driving pressure (plateau pressure minus PEEP) is a better predictor of mortality than tidal volume or PEEP alone. Target ΔP <15 cmH₂O when possible without compromising other ventilatory parameters.¹

The concept of mechanical power - the energy delivered to the respiratory system per minute - has gained traction. Mechanical power incorporates respiratory rate, tidal volume, driving pressure, and flow, providing a unifying metric for ventilator-induced lung injury (VILI) risk.²

Formula: Mechanical Power (J/min) = 0.098 × RR × Vt × (Ppeak - ½ × ΔP)

Oyster: While mechanical power correlates with outcomes in observational studies, there are no randomized trials demonstrating that targeting specific mechanical power thresholds improves survival. Use it as a guide, not an absolute target.

PEEP Titration in 2025: Individualized Approaches

The optimal PEEP strategy remains debated. Recent meta-analyses suggest that higher PEEP strategies may benefit patients with moderate-to-severe ARDS (PaO₂/FiO₂ <200), but not necessarily those with mild ARDS.³

Emerging approaches to PEEP titration include:

Electrical Impedance Tomography (EIT): Real-time bedside imaging allows visualization of regional ventilation distribution, enabling personalized PEEP selection to minimize collapse and overdistension.⁴
Transpulmonary Pressure-Guided PEEP: Using esophageal manometry to estimate pleural pressure, clinicians can target positive end-expiratory transpulmonary pressure (0-10 cmH₂O), potentially reducing VILI in patients with high chest wall elastance.⁵
PEEP Titration by Driving Pressure: Setting PEEP at the level where driving pressure is minimized may optimize lung mechanics, though prospective validation is needed.

Hack: In resource-limited settings without EIT or esophageal manometry, the empirical higher PEEP table from the ARDSNet protocol remains reasonable for moderate-severe ARDS, titrating to SpO₂ 88-95%.

Prone Positioning: Earlier and Longer

Prone positioning for ≥12 hours daily in moderate-to-severe ARDS (PaO₂/FiO₂ <150) reduces mortality by approximately 50% - one of the most effective interventions in critical care.⁶ Recent trends advocate for:

Early initiation: Within 24-48 hours of meeting ARDS criteria
Extended duration: 16-18 hours per session when tolerated
Awake proning: Increasingly used in spontaneously breathing patients with acute hypoxemic respiratory failure, though mortality benefits remain unproven⁷

Pearl: Continue prone positioning even if initial oxygenation improvement is modest. The mortality benefit extends beyond immediate gas exchange effects, likely related to reduced VILI and improved lung homogeneity.

Oyster: Awake prone positioning may improve oxygenation and reduce intubation rates in selected patients, but it doesn't replace invasive mechanical ventilation when indicated. Don't delay intubation in deteriorating patients.

ACUTE RESPIRATORY DISTRESS SYNDROME: THERAPEUTIC ADVANCES

Corticosteroids: Timing and Dosing Refined

The role of corticosteroids in ARDS continues to evolve. The 2020 DEXA-ARDS trial demonstrated mortality benefit with dexamethasone 20 mg IV daily for 5 days, then 10 mg daily for 5 days, initiated early in moderate-to-severe ARDS.⁸

Current recommendations:

Dexamethasone 20 mg daily (or methylprednisolone 1-2 mg/kg/day) for moderate-severe ARDS within 14 days of onset
Avoid in late fibroproliferative phase (>14 days) without documented inflammatory activity
Taper gradually to prevent rebound inflammation

Pearl: Combining corticosteroids with conservative fluid management may enhance benefits by reducing lung water while mitigating anti-inflammatory effects.

Oyster: Corticosteroids in ARDS are not benign - monitor for hyperglycemia, ICU-acquired weakness, and secondary infections. The benefit-risk ratio is most favorable in moderate-severe ARDS (PaO₂/FiO₂ 100-200).

Neuromuscular Blockade: A More Selective Approach

Following the ROSE trial (2019), which showed no benefit from routine early neuromuscular blockade in ARDS, current practice has become more selective.⁹

Indications for neuromuscular blockade in 2025:

Severe ARDS with ventilator dyssynchrony despite sedation optimization
Refractory hypoxemia requiring ventilator-patient synchrony
Facilitation of prone positioning
Acute cor pulmonale with RV strain

Duration: Limit to 24-48 hours when possible, reassessing need daily.

Hack: Before initiating neuromuscular blockade, ensure adequate sedation (RASS -5), optimize ventilator settings (mode, trigger sensitivity, flow), and consider adjunct sedatives (ketamine, dexmedetomidine) to minimize need for paralytics.

Inhaled Pulmonary Vasodilators: Targeted Rescue Therapy

Inhaled nitric oxide (iNO) and inhaled epoprostenol (iEPO) selectively vasodilate ventilated lung regions, improving V/Q matching without systemic hypotension.

2025 Evidence:

Neither iNO nor iEPO improves mortality in ARDS, but both may serve as rescue therapy for severe, refractory hypoxemia¹⁰
iNO: 5-20 ppm; monitor for methemoglobinemia, renal dysfunction
iEPO: 30,000-50,000 ng/ml solution via vibrating mesh nebulizer; more cost-effective than iNO

Pearl: Reserve inhaled vasodilators for PaO₂/FiO₂ <100 despite lung-protective ventilation, prone positioning, and optimal PEEP. Assess response within 30-60 minutes; discontinue if PaO₂/FiO₂ improvement <20%.

Oyster: Inhaled pulmonary vasodilators are often initiated too early and continued too long without objective benefit. They are supportive measures, not definitive therapies, and should be weaned as soon as feasible.

EXTRACORPOREAL LIFE SUPPORT: EVOLVING INDICATIONS

VV-ECMO for Refractory ARDS

Venovenous extracorporeal membrane oxygenation (VV-ECMO) provides gas exchange support in severe ARDS refractory to conventional management. The EOLIA trial (2018) did not demonstrate statistically significant mortality benefit, but crossover rates were high, and Bayesian reanalysis suggested potential benefit.¹¹

2025 Consensus Criteria for VV-ECMO:

PaO₂/FiO₂ <80 on FiO₂ ≥0.8 for >6 hours, or
PaO₂/FiO₂ <50 for >3 hours, or
pH <7.20 with PaCO₂ ≥60 mmHg for >6 hours, despite optimal ventilation

Pearl: Consider early transfer to ECMO-capable centers for patients meeting refractory ARDS criteria. Mortality increases with prolonged pre-ECMO mechanical ventilation >7 days.

Best candidates:

Age <65 years
Reversible lung pathology
Limited comorbidities
Mechanical ventilation <7 days

Oyster: VV-ECMO is resource-intensive and carries significant risks (bleeding, thrombosis, infection, circuit complications). It's a bridge to recovery or transplant, not a destination therapy. Patient selection is paramount.

Extracorporeal CO₂ Removal (ECCO₂R)

Lower-flow extracorporeal devices designed primarily for CO₂ elimination have emerged as potential strategies to facilitate ultra-protective ventilation (Vt <6 ml/kg) or avoid intubation in severe hypercapnic respiratory failure.

Current evidence: ECCO₂R allows reduction in tidal volume and respiratory rate, but clinical outcome benefits remain unproven in large trials.¹² The REST trial (2024) showed no mortality benefit with ECCO₂R in moderate ARDS.

Potential niche applications:

Bridge to lung transplantation in selected patients
Refractory hypercapnia in severe ARDS where lung-protective ventilation is limited by acidosis
Select cases of status asthmaticus refractory to conventional therapy

Hack: ECCO₂R remains largely investigational outside specialized centers. Focus on optimizing conventional ventilation strategies before considering extracorporeal support.

HIGH-FLOW NASAL OXYGEN: EXPANDED APPLICATIONS

High-flow nasal oxygen (HFNO) delivers heated, humidified oxygen at flows up to 60 L/min, providing:

Washout of nasopharyngeal dead space
PEEP effect (2-5 cmH₂O)
Improved comfort and tolerance compared to conventional oxygen

Acute Hypoxemic Respiratory Failure

HFNO is now first-line therapy for acute hypoxemic respiratory failure (AHRF) without hypercapnia, with potential to reduce intubation rates compared to conventional oxygen therapy.¹³ The FLORALI trial demonstrated mortality benefit in patients with PaO₂/FiO₂ <200.

Optimal HFNO settings:

Flow: 40-60 L/min (higher flows may provide greater benefit)
FiO₂: Titrated to SpO₂ 92-96%

Pearl: The ROX index (SpO₂/FiO₂ / Respiratory Rate) predicts HFNO success:

ROX >4.88 at 2-6 hours: Low intubation risk
ROX <3.85 at 12 hours: High intubation risk, consider escalation¹⁴

Oyster: HFNO is not a substitute for timely intubation. Monitor closely for clinical deterioration (worsening work of breathing, altered mental status, refractory hypoxemia). Delayed intubation increases mortality.

Red flags for intubation despite HFNO:

Respiratory rate >30 after initial trial
Persistent profound hypoxemia (SpO₂ <88% on FiO₂ 1.0)
Decreased level of consciousness
Hemodynamic instability
Inability to protect airway

Post-Extubation Respiratory Support

HFNO reduces reintubation rates in high-risk patients (age >65, cardiac or respiratory comorbidities, difficult weaning) compared to conventional oxygen.¹⁵

Hack: Initiate HFNO immediately post-extubation in high-risk patients rather than waiting for respiratory deterioration. Prevention is more effective than rescue.

NON-INVASIVE VENTILATION: REFINED PATIENT SELECTION

NIV in Acute Hypoxemic Respiratory Failure: Caution Required

While non-invasive ventilation (NIV) is established for acute hypercapnic respiratory failure (COPD exacerbation, cardiogenic pulmonary edema), its role in AHRF without hypercapnia remains controversial. Recent evidence suggests NIV may be harmful in moderate-severe AHRF (PaO₂/FiO₂ <200) by delaying intubation.¹⁶

2025 Recommendations:

Avoid NIV as first-line in moderate-severe AHRF; prefer HFNO or early intubation
Consider NIV in mild AHRF (PaO₂/FiO₂ 200-300) in alert, cooperative patients with single-organ failure
Helmet NIV may be safer than facemask NIV, allowing higher PEEP with better tolerance

Trial of NIV parameters:

Pressure support: Start 8-12 cmH₂O
PEEP: 8-12 cmH₂O
FiO₂: Titrated to SpO₂ 92-96%
Strict monitoring: 1-2 hour trial

Failure criteria:

No improvement in respiratory rate, work of breathing, or oxygenation within 1-2 hours
Worsening mental status
Hemodynamic instability
Patient intolerance

Pearl: NIV in AHRF requires close monitoring, preferably in ICU. The first hour predicts success or failure. Don't persist with failing NIV - timely intubation is critical.

Oyster: Patient self-inflicted lung injury (P-SILI) from excessive spontaneous breathing efforts can occur during NIV in AHRF. High respiratory drive may negate lung-protective benefits. When in doubt, intubate early rather than late.

INTERSTITIAL LUNG DISEASE IN THE ICU

Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) carry mortality >50%, with limited evidence-based interventions. Management remains largely supportive, but recent insights inform practice.

2025 Approach:

High-dose corticosteroids: Methylprednisolone 500-1000 mg IV daily × 3 days, then taper (weak evidence, but commonly used)
Lung-protective ventilation: Essential if mechanical ventilation required; high mortality (~90%) on mechanical ventilation
Consider antifibrotics: Continue nintedanib or pirfenidone if already prescribed
Early palliative care involvement: Given high mortality, goals-of-care discussions are critical

Pearl: Prevention is key - educate IPF patients about avoiding triggers (respiratory infections, aspiration, surgery) and consider vaccination (influenza, pneumococcal, COVID-19).

Oyster: Mechanical ventilation for AE-IPF should be approached cautiously. Discuss prognosis honestly with patients and families before intubation. Many patients with advanced IPF prefer comfort-focused care over invasive life support.

Connective Tissue Disease-Associated ILD

CTD-ILD patients may present with acute respiratory failure from disease progression, infection, or drug toxicity (methotrexate pneumonitis).

Diagnostic approach:

Differentiate infection from inflammatory flare (BAL with cultures, viral PCR)
Consider drug-induced pneumonitis (detailed medication history)
Rule out pulmonary hemorrhage (BAL with sequential aliquots showing progressively bloodier returns)

Treatment considerations:

Immunosuppression: High-dose corticosteroids ± cyclophosphamide or rituximab for inflammatory flares
Broad-spectrum antibiotics: Until infection excluded
Plasma exchange: Consider for diffuse alveolar hemorrhage in systemic vasculitis

Hack: In CTD-ILD with acute respiratory failure, early bronchoscopy (if safe) helps distinguish infection from inflammation, guiding immunosuppression decisions.

SEVERE ASTHMA: BEYOND CONVENTIONAL BRONCHODILATORS

Status Asthmaticus in 2025

Most patients with status asthmaticus respond to conventional therapy (bronchodilators, corticosteroids, magnesium), but a subset develops life-threatening refractory bronchospasm.

Escalation ladder:

First-line:
- Continuous nebulized albuterol (10-15 mg/hour)
- Ipratropium nebulizers (500 mcg every 20 minutes × 3, then q4-6h)
- Systemic corticosteroids (methylprednisolone 125 mg IV q6h)
- Magnesium sulfate 2 g IV over 20 minutes
Second-line:
- Intravenous beta-agonists: Epinephrine or terbutaline infusions (requires continuous cardiac monitoring, ICU setting)
- Ketamine: 1-2 mg/kg bolus, then 0.5-2 mg/kg/hour infusion; bronchodilator and dissociative sedative properties
- Heliox: 70:30 helium-oxygen mixture reduces airway resistance; consider in non-hypoxemic patients
Rescue therapies:
- Inhaled anesthetics: Sevoflurane or isoflurane via mechanical ventilator (requires anesthesia consultation)
- ECMO: Case reports in refractory asthma; reserved for imminent cardiopulmonary arrest

Mechanical ventilation strategies in severe asthma:

Avoid intubation if possible: NIV rarely helps; consider delayed sequence intubation with ketamine
Low respiratory rate (6-10 breaths/min) to allow prolonged expiratory time
Low tidal volume (5-7 ml/kg PBW) to minimize dynamic hyperinflation
Accept permissive hypercapnia (PaCO₂ 50-80 mmHg, pH >7.15)
Monitor plateau pressure (<30 cmH₂O); auto-PEEP is common
Short inspiratory time: I:E ratio 1:3 to 1:5

Pearl: In mechanically ventilated severe asthma, perform apnea tests to assess auto-PEEP and degree of hyperinflation. Disconnect ventilator circuit and observe continued expiratory flow beyond 6-8 seconds.

Oyster: Dynamic hyperinflation (air trapping) causes hemodynamic compromise in ventilated asthma patients. If sudden hypotension or cardiac arrest occurs, disconnect ventilator and manually decompress the chest - this can be life-saving.

Biologics in severe asthma:

While biologics (omalizumab, mepolizumab, benralizumab, dupilumab) prevent exacerbations, they have no role in acute management of status asthmaticus. Consider initiating appropriate biologic during recovery based on phenotype.

COPD EXACERBATIONS: VENTILATION STRATEGIES

NIV: The Standard of Care

Non-invasive ventilation reduces intubation rates, mortality, and length of stay in acute hypercapnic respiratory failure from COPD exacerbations.¹⁷

Optimal NIV settings:

IPAP: 12-20 cmH₂O (titrate to tidal volume 6-8 ml/kg, respiratory rate reduction)
EPAP: 4-8 cmH₂O (counterbalances intrinsic PEEP)
Backup rate: 10-12 breaths/min
FiO₂: Titrate to SpO₂ 88-92%

Success predictors:

pH >7.25
Alert, cooperative patient
Improvement in pH, PaCO₂, respiratory rate within 1-2 hours

Pearl: Controlled oxygen therapy (SpO₂ target 88-92%) is crucial in COPD. Hyperoxia worsens hypercapnia through Haldane effect and V/Q mismatch, not suppression of hypoxic drive as traditionally taught.

Invasive Mechanical Ventilation in COPD

When NIV fails or is contraindicated, invasive mechanical ventilation for COPD requires strategies to minimize auto-PEEP and dynamic hyperinflation.

Ventilator settings:

Volume control or pressure control modes acceptable
Tidal volume: 6-8 ml/kg PBW
Respiratory rate: 10-14 breaths/min (low rate favors expiration)
Inspiratory flow: 60-100 L/min (high flow shortens inspiratory time)
I:E ratio: 1:3 to 1:4
Applied PEEP: 80-90% of intrinsic PEEP (measure via expiratory hold maneuver)
Permissive hypercapnia: Accept pH >7.20

Pearl: Measure intrinsic PEEP (auto-PEEP) regularly in ventilated COPD patients. Apply external PEEP at 80-90% of measured auto-PEEP to reduce work of breathing without worsening hyperinflation - a counterintuitive but physiologically sound approach.¹⁸

Oyster: Liberation from mechanical ventilation is challenging in severe COPD. Early mobilization, aggressive secretion clearance, and prompt transition to NIV during weaning trials may facilitate extubation.

PULMONARY EMBOLISM: RISK STRATIFICATION AND INTERVENTION

Intermediate-Risk PE: Catheter-Based Therapies Emerging

Pulmonary embolism (PE) management has traditionally stratified patients into high-risk (hemodynamically unstable) and low/intermediate-risk (stable) categories. Recent focus on intermediate-risk PE - patients with RV dysfunction or myocardial injury but hemodynamic stability - has spurred investigation of advanced therapies.

Risk stratification tools:

PESI (Pulmonary Embolism Severity Index): Predicts 30-day mortality
sPESI (simplified PESI): Easier bedside tool
RV dysfunction: Echo or CT showing RV/LV ratio >0.9
Myocardial injury: Elevated troponin, BNP/NT-proBNP

Management approach in 2025:

Low-risk PE (PESI I-II, no RV dysfunction, normal biomarkers):

Anticoagulation alone
Consider outpatient management with DOACs

Intermediate-risk PE (PESI III+ or RV dysfunction/myocardial injury but hemodynamically stable):

Anticoagulation
Close monitoring (telemetry, serial troponins, echo)
Catheter-directed thrombolysis (CDT) or mechanical thrombectomy: Emerging option for intermediate-high-risk PE showing clinical deterioration despite anticoagulation¹⁹

High-risk PE (hemodynamic instability, shock, cardiac arrest):

Systemic thrombolysis: tPA 50-100 mg IV
If contraindications to thrombolysis: emergent surgical embolectomy or catheter-based intervention
ECMO as bridge in refractory shock

Pearl: The concept of "hemodynamic deterioration" in intermediate-risk PE is critical. Patients with RV dysfunction who develop worsening hypotension, tachycardia, rising troponin, or increasing oxygen requirements despite anticoagulation may benefit from advanced reperfusion strategies before frank shock develops.

Oyster: Catheter-directed therapies for PE are appealing but remain controversial outside high-risk PE. The PE-TRACT trial is ongoing. Reserve CDT for carefully selected intermediate-high-risk patients showing deterioration, ideally in consultation with PE response teams (PERTs) at experienced centers.

Hack: Establish a multidisciplinary PERT at your institution (emergency medicine, critical care, interventional radiology, cardiology, cardiothoracic surgery) to rapidly evaluate and manage complex PE cases.

PLEURAL DISEASE IN CRITICAL CARE

Complicated Parapneumonic Effusions and Empyema

Parapneumonic effusions complicate ~40% of bacterial pneumonias. Early recognition and drainage prevent prolonged morbidity.

Diagnostic thoracentesis criteria (Light's criteria for exudative effusion):

Pleural fluid protein/serum protein >0.5, OR
Pleural fluid LDH/serum LDH >0.6, OR
Pleural fluid LDH >2/3 upper limit of normal serum LDH

Complicated parapneumonic effusion/empyema indicators:

pH <7.20
Glucose <60 mg/dL
LDH >1000 U/L
Frank pus
Positive Gram stain or culture
Loculations on imaging

Management:

Antibiotics: Broad-spectrum covering anaerobes (piperacillin-tazobactam, carbapenems, or ceftriaxone + metronidazole)
Chest tube drainage: Essential for complicated effusions/empyema; large-bore (24-28 Fr) traditionally used, but smaller-bore (12-14 Fr) may suffice
Intrapleural fibrinolytics: tPA 10 mg + DNase 5 mg twice daily × 3 days via chest tube improves drainage in loculated effusions²⁰

Pearl: The combination of tPA-DNase is superior to either agent alone for treating loculated parapneumonic effusions, reducing need for surgery and hospitalization duration.

Oyster: Don't delay surgical consultation (VATS decortication) for patients with thick pleural rind, persistent sepsis despite drainage, or failure to improve with fibrinolytics. Early surgery may shorten overall treatment course in selected cases.

COVID-19: PERSISTENT CHALLENGES IN 2025

While COVID-19 has transitioned from pandemic to endemic, severe cases still challenge ICUs. Management principles for COVID-19 ARDS mirror general ARDS care, with specific considerations.

Antiviral/immunomodulatory therapies:

Remdesivir: Limited benefit in critically ill patients; more effective early in disease
Dexamethasone: 6-12 mg IV daily × 10 days; established mortality benefit in severe COVID-19 requiring oxygen²¹
IL-6 inhibitors (tocilizumab): Consider in patients with rapidly increasing oxygen requirements and elevated inflammatory markers within first 2 days of ICU admission
Baricitinib: JAK inhibitor showing benefit when combined with corticosteroids in hospitalized patients requiring oxygen

Anticoagulation:

Prophylactic-dose heparin remains standard
Therapeutic-dose anticoagulation NOT routinely recommended in ICU patients without documented thrombosis (INSPIRATION and REMAP-CAP trials showed no benefit or possible harm)²²

Pearl: COVID-19 patients may exhibit "silent hypoxemia" - profound hypoxemia with minimal dyspnea. This phenotype requires careful monitoring and may benefit from awake prone positioning before intubation becomes necessary.

Oyster: Post-COVID pulmonary fibrosis can develop in severe cases. Long-term follow-up with pulmonology and pulmonary function testing at 3-6 months post-discharge is recommended for mechanically ventilated COVID-19 survivors.

INHALATIONAL LUNG INJURIES

Smoke Inhalation and Toxic Gas Exposures

Inhalational injuries result from thermal damage, chemical toxicity (carbon monoxide, cyanide, irritant gases), and particulate deposition.

Initial management:

High-flow 100% oxygen: For CO poisoning (half-life CO-Hb: 5-6 hours on room air, 60-90 minutes on 100% O₂)
Consider hyperbaric oxygen: For CO-Hb >25%, neurologic symptoms, pregnancy, myocardial ischemia
Cyanide antidote (hydroxocobalamin): If suspected cyanide toxicity (fire in enclosed space, lactic acidosis)
Bronchoscopy: Assess airway injury severity; suctioning of soot/debris

Mechanical ventilation challenges:

Airway edema may progress over 24-48 hours; early intubation often safer
Bronchospasm common; treat aggressively with bronchodilators
ARDS may develop; apply lung-protective ventilation
High risk of nosocomial pneumonia; vigilant pulmonary toilet

Pearl: The presence of facial burns, singed nasal hairs, carbonaceous sputum, or hoarseness suggests significant inhalation injury. Consider early intubation before airway edema worsens - delayed intubation in evolving airway edema can be catastrophic.

Hack: In suspected cyanide poisoning (lactate >10 mmol/L unexplained by shock, CO-Hb disproportionately low compared to clinical severity), empiric hydroxocobalamin 5 g IV is safe and potentially life-saving. Don't wait for cyanide levels.

PULMONARY HYPERTENSION IN CRITICAL ILLNESS

Acute Right Ventricular Failure

Right ventricular (RV) failure in ICU patients carries high mortality. Common precipitants include massive PE, severe ARDS, acute respiratory failure with pulmonary hypertension (PH), and postcardiotomy syndrome.

Hemodynamic goals in RV failure:

Maintain RV preload: Judicious fluid resuscitation (central venous pressure 8-12 mmHg); avoid excessive fluids causing RV distension
Reduce RV afterload:
- Optimize oxygenation and ventilation (hypoxia and hypercapnia worsen PH)
- Avoid high mean airway pressures
- Inhaled pulmonary vasodilators (iNO, iEPO)
Optimize RV contractility: Inotropes (dobutamine, milrinone)
Maintain coronary perfusion pressure: RV ischemia worsens failure; target MAP >65 mmHg with vasopressors (norepinephrine)

Ventilation strategies:

Target normoxia (PaO₂ 70-100 mmHg) and normocapnia (PaCO₂ 35-45 mmHg)
Minimize mean airway pressure while maintaining adequate oxygenation
Lung-protective ventilation (low Vt) to reduce pulmonary vascular resistance from alveolar overdistension
Consider permissive hypercapnia cautiously - acidosis worsens PH

Medications for acute RV failure:

Dobutamine: 2-10 mcg/kg/min; inotrope with pulmonary vasodilatory properties
Milrinone: 0.25-0.75 mcg/kg/min (no bolus in hypotensive patients); inodilator; avoid if systemic hypotension
Norepinephrine: Maintain systemic pressure for RV coronary perfusion
Vasopressin: 0.03-0.04 U/min; systemic vasoconstriction without worsening PH
Inhaled pulmonary vasodilators: iNO or iEPO to reduce PV resistance

Pearl: In acute RV failure, the RV is preload-dependent but afterload-sensitive. Aggressive fluid resuscitation can worsen RV function by causing distension and septal shift, compromising LV filling. Titrate fluids carefully, guided by echo or invasive hemodynamics.

Oyster: Milrinone is an excellent inodilator for RV failure but causes systemic hypotension. Combine with vasopressors (norepinephrine, vasopressin) to maintain systemic blood pressure while gaining pulmonary vasodilatory benefits.

VV-ECMO for severe RV failure: In refractory RV failure with severe hypoxemia (e.g., massive PE with contraindication to thrombolysis), VV-ECMO can provide respiratory support, reducing pulmonary vascular resistance by eliminating need for high ventilatory pressures. Consider VA-ECMO if concomitant cardiogenic shock.

BRONCHOSCOPY IN THE ICU: EXPANDED APPLICATIONS

Advanced Diagnostic Capabilities

Flexible bronchoscopy remains indispensable in ICU for diagnostics and therapeutics.

Indications in critical care:

Suspected ventilator-associated pneumonia (VAP): BAL with quantitative cultures
Hemoptysis: Localization and potential endoscopic hemostasis
Atelectasis/mucus plugging: Therapeutic aspiration
Difficult intubation: Awake fiberoptic intubation

BRONCHOSCOPY IN THE ICU: EXPANDED APPLICATIONS

Advanced Diagnostic Capabilities

BAL technique for VAP diagnosis:

Target involved lobe based on imaging
Instill 120-150 mL sterile saline in 30-50 mL aliquots
Quantitative thresholds: ≥10⁴ CFU/mL BAL fluid suggests VAP (vs. colonization)
Send for bacterial culture, fungal culture, viral PCR, PCP staining if immunocompromised

Pearl: BAL performed before antibiotic initiation has higher diagnostic yield. However, don't delay empiric antibiotics in septic patients - obtain BAL promptly, then start antibiotics.

Endobronchial ultrasound (EBUS) in ICU: While traditionally performed in bronchoscopy suites, portable EBUS is increasingly used for:

Mediastinal lymph node sampling (staging lung cancer, diagnosing sarcoidosis, tuberculosis)
Diagnosing mediastinal masses
Guiding transbronchial biopsy in peripheral lesions

Therapeutic Bronchoscopy

Massive hemoptysis management: Massive hemoptysis (>200-600 mL/24 hours) carries 50-80% mortality. Bronchoscopy helps localize bleeding and initiate temporizing measures.

Bronchoscopic hemostasis techniques:

Iced saline lavage: 50 mL aliquots of 4°C saline
Topical vasoconstrictors: Epinephrine 1:20,000 (up to 20 mL)
Balloon tamponade: Fogarty catheter or bronchial blocker inflated in bleeding bronchus
Rigid bronchoscopy: Superior suctioning capability; requires anesthesia/expertise

Definitive management:

Bronchial artery embolization (BAE): First-line definitive therapy; 70-90% initial success
Surgery: Reserved for BAE failure, localized disease, or destroyed lung requiring resection

Pearl: In massive hemoptysis, immediately position patient with bleeding side down (if known) to protect contralateral lung from blood aspiration. Intubate with large-bore ETT (≥8.0 mm) to facilitate bronchoscopy and suctioning.

Hack: If unable to localize bleeding source bronchoscopically due to blood obscuring view, consider selective intubation of the non-bleeding main bronchus with ETT to isolate and ventilate the healthy lung while securing the airway.

Therapeutic aspiration for atelectasis: Complete lobar collapse from mucus plugging is common post-operatively and in patients with poor cough/secretion clearance.

Approach:

Pre-oxygenate thoroughly (FiO₂ 1.0)
Instill 2-5 mL aliquots of saline to soften mucus
Aggressive suctioning with bronchoscope advanced into affected segmental bronchi
Consider mucolytics (N-acetylcysteine 2-5 mL of 20% solution) instilled during procedure
Post-procedure: chest physiotherapy, incentive spirometry, mobilization

Oyster: Bronchoscopy for mucus plugging provides temporary relief but doesn't address underlying secretion clearance problem. Optimize pulmonary toilet (chest PT, mobilization, adequate hydration, suctioning), treat underlying infection, and consider mechanical insufflation-exufflation devices in neuromuscular patients.

TRACHEOSTOMY: TIMING AND TECHNIQUES

Early vs. Late Tracheostomy Debate

The optimal timing for tracheostomy in prolonged mechanical ventilation remains debated. "Early" tracheostomy typically means ≤7-10 days; "late" means >10-14 days after intubation.

2025 Evidence Summary: Recent meta-analyses and the TracMan trial (2013) showed early tracheostomy does not reduce mortality or ventilator days, but may reduce sedation requirements and ICU length of stay.²³

Current recommendations:

Individualized approach rather than protocol-driven timing
Consider early tracheostomy (7-10 days) in patients with:
- Anticipated prolonged ventilation (severe neurologic injury, high spinal cord injury, neuromuscular disease)
- Failed multiple extubation attempts
- Difficulty weaning from sedation on ETT
- Need for enhanced secretion management

Pearl: Tracheostomy facilitates weaning by reducing dead space, airway resistance, and work of breathing. It enables reduced sedation, earlier mobilization, and potential for speech with speaking valves or cuff deflation once weaning progresses.

Percutaneous vs. Surgical Tracheostomy

Percutaneous dilatational tracheostomy (PDT):

Performed at bedside in ICU
Lower cost, comparable complication rates to surgical
Requires favorable anatomy (palpable landmarks, no goiter, adequate neck extension)
Bronchoscopic guidance recommended

Surgical tracheostomy:

Indicated for difficult anatomy (obesity, short neck, goiter, previous neck surgery/radiation)
Allows direct visualization and hemostasis
Preferred in coagulopathy or thrombocytopenia

Contraindications to PDT:

Unstable cervical spine requiring stabilization
Severe coagulopathy (INR >1.5, platelets <50,000) - relative contraindication
Recent neck surgery or tracheostomy
Difficult anatomy precluding landmark identification

Hack: Before PDT, perform bronchoscopy to visualize tracheal anatomy. Real-time bronchoscopic visualization during PDT reduces risk of posterior tracheal wall injury and confirms optimal stoma location (between 2nd-3rd tracheal rings, avoiding cricoid and thyroid cartilage).

WEANING FROM MECHANICAL VENTILATION: PROTOCOLIZED APPROACHES

Prolonged mechanical ventilation increases VAP risk, ICU-acquired weakness, and resource utilization. Systematic weaning protocols reduce ventilator days and complications.

Daily Spontaneous Breathing Trials (SBT)

SBT readiness screening (perform daily):

Improvement or resolution of underlying respiratory failure cause
Adequate oxygenation: PaO₂/FiO₂ ≥150, PEEP ≤8 cmH₂O, FiO₂ ≤0.5
Hemodynamic stability: No vasopressor requirement or low-dose vasopressor
Alert, able to initiate breaths (no heavy sedation)
No ongoing myocardial ischemia or arrhythmia

SBT technique:

T-piece trial: Disconnect ventilator, provide humidified oxygen via T-piece (traditional method)
Pressure support trial: PS 5-8 cmH₂O, PEEP 5 cmH₂O (preferred by many; maintains PEEP and flow triggering)

Duration: 30-120 minutes (30 minutes sufficient in most cases)

SBT success criteria:

Respiratory rate <35 breaths/min
SpO₂ >90%
Heart rate <140 bpm or <20% change from baseline
Systolic BP 90-180 mmHg
No significant change in mental status
No signs of respiratory distress (accessory muscle use, paradoxical breathing, diaphoresis)

Pearl: The Rapid Shallow Breathing Index (RSBI) predicts extubation success:

RSBI = Respiratory Rate / Tidal Volume (in liters)
RSBI <105 predicts successful extubation
RSBI >105 predicts extubation failure
Measured during minimal support (PS 5-8 cmH₂O) or T-piece trial²⁴

Extubation criteria after successful SBT:

Adequate cough: Essential for secretion clearance
Manageable secretions: Not requiring frequent suctioning (>q2h)
Airway patency: No significant laryngeal edema (cuff-leak test)
Adequate mental status: GCS ≥8, able to protect airway

Oyster: SBT success doesn't guarantee extubation success. Up to 15-20% of patients passing SBT fail extubation (requiring reintubation within 48-72 hours). Assess cough strength and secretion burden carefully - these often cause post-extubation failure more than gas exchange issues.

Cuff-Leak Test for Laryngeal Edema

Post-extubation stridor from laryngeal edema occurs in 5-15% of patients, requiring reintubation in severe cases.

Technique:

Suction oropharynx and endotracheal tube
Deflate ETT cuff completely
Measure exhaled tidal volume for 6 breaths
Cuff-leak = (Vt with cuff inflated) - (Vt with cuff deflated)

Interpretation:

Cuff-leak <110 mL (or <15% of delivered Vt): High risk of post-extubation stridor
Consider delaying extubation and treating with methylprednisolone 20-40 mg IV q6h × 4 doses before reattempting²⁵

Pearl: Prophylactic corticosteroids (methylprednisolone) reduce post-extubation stridor and reintubation rates in high-risk patients (prolonged intubation >6 days, traumatic intubation, failed cuff-leak test).

Hack: If cuff-leak test concerning but extubation deemed necessary, have immediate reintubation equipment ready (direct laryngoscopy, video laryngoscopy, supraglottic airway, cricothyrotomy kit). Consider extubating over airway exchange catheter in very high-risk patients.

ACUTE RESPIRATORY DISTRESS IN THE IMMUNOCOMPROMISED HOST

Immunocompromised patients (solid organ transplant, hematopoietic stem cell transplant, HIV/AIDS, chemotherapy, chronic immunosuppression) presenting with acute respiratory failure pose unique diagnostic and therapeutic challenges.

Differential Diagnosis - The Broad Net

Infectious etiologies:

Bacterial: Including atypical organisms (Legionella, Mycoplasma, Nocardia)
Viral: CMV, HSV, VZV, respiratory viruses (influenza, RSV, COVID-19), adenovirus
Fungal: Pneumocystis jirovecii, Aspergillus, Mucorales, Cryptococcus, endemic fungi (Histoplasma, Coccidioides)
Mycobacterial: TB and non-tuberculous mycobacteria

Non-infectious etiologies:

Drug-induced pneumonitis: Methotrexate, bleomycin, checkpoint inhibitors
Diffuse alveolar hemorrhage: Thrombocytopenia, anticoagulation, vasculitis
Pulmonary edema: Cardiogenic, fluid overload, capillary leak
Graft-versus-host disease (GVHD) in transplant recipients
Idiopathic pneumonia syndrome post-HSCT
Cryptogenic organizing pneumonia (COP)
Pulmonary progression of malignancy: Lymphangitic carcinomatosis

Diagnostic Approach

Non-invasive diagnostics:

CT chest: High-resolution CT provides pattern recognition (ground-glass opacities, nodules, consolidation, tree-in-bud)
Serum biomarkers: Galactomannan (Aspergillus), beta-D-glucan (invasive fungal infections), CMV PCR
Respiratory viral panels: Nasopharyngeal swab for PCR
Blood cultures: Bacterial, fungal (especially before antifungals)

Invasive diagnostics:

Bronchoscopy with BAL: High diagnostic yield; perform early if safe
- BAL sends: Bacterial/fungal/AFB cultures, viral PCR (CMV, HSV, influenza, RSV), PCP staining, Galactomannan, cytology
Transbronchial biopsy: Increases diagnostic yield but higher risk (bleeding, pneumothorax) in thrombocytopenic patients
Surgical lung biopsy (VATS): Reserved for diagnostic uncertainty with deterioration despite empiric therapy

Pearl: Early bronchoscopy (within 24-48 hours) in immunocompromised patients with respiratory failure significantly improves diagnostic yield and may guide therapy de-escalation. Don't delay - patients can deteriorate rapidly.

Oyster: Despite aggressive diagnostics, up to 30-40% of immunocompromised patients with respiratory failure remain without definitive microbiologic diagnosis. Empiric broad-spectrum therapy often necessary while awaiting results.

Empiric Therapy Framework

Immediate broad-spectrum coverage:

Antibacterial: Antipseudomonal beta-lactam (piperacillin-tazobactam, cefepime, meropenem) + atypical coverage (azithromycin or fluoroquinolone)
Antifungal:
- PCP: Trimethoprim-sulfamethoxazole 15-20 mg/kg/day (TMP component) IV divided q6-8h
- Mold coverage (if neutropenic or high risk): Voriconazole or isavuconazole
Antiviral:
- CMV (if high risk - transplant recipients, lymphopenic): Ganciclovir 5 mg/kg IV q12h
- Influenza (if season or detected): Oseltamivir 75 mg PO BID or peramivir/baloxavir

Adjunctive corticosteroids: Complicated decision in immunocompromised patients. Consider for:

Moderate-severe PCP: Prednisone 40 mg PO BID × 5 days, then taper (reduces mortality if PaO₂ <70 mmHg)
Suspected COP or drug-induced pneumonitis after infection ruled out
Avoid if possible until infection excluded or antifungals initiated

Pearl: In HIV patients with PCP and PaO₂ <70 mmHg or A-a gradient >35 mmHg, adjunctive corticosteroids (prednisone 40 mg BID × 5 days, 40 mg daily × 5 days, 20 mg daily × 11 days) significantly reduce mortality. Start with or within 72 hours of TMP-SMX.²⁶

PULMONARY HEMORRHAGE SYNDROMES

Diffuse Alveolar Hemorrhage (DAH)

DAH results from injury to alveolar capillaries or arterioles, causing blood accumulation in alveolar spaces. Causes include vasculitis, autoimmune diseases, coagulopathy, drugs, and stem cell transplantation.

Clinical presentation:

Hemoptysis (often absent initially - only 30-50% present with hemoptysis)
Dyspnea, hypoxemia
Anemia (falling hemoglobin)
Diffuse alveolar infiltrates on imaging

Diagnostic approach:

BAL: Progressively bloodier returns with sequential aliquots; hemosiderin-laden macrophages on cytology (Prussian blue staining)
Serologies: ANCA, anti-GBM antibodies, ANA, complement levels
Coagulation studies: PT, aPTT, platelet count, fibrinogen

Common causes:

Pulmonary-renal syndromes: Anti-GBM disease (Goodpasture's), ANCA-associated vasculitis (GPA, MPA)
Autoimmune: SLE, antiphospholipid syndrome
Drug-induced: Anticoagulants, cocaine, propylthiouracil, hydralazine, penicillamine
Post-stem cell transplant: Idiopathic in first 30 days
Mitral stenosis: Hemosiderin-laden macrophages without hemorrhage (hemosiderosis)

Management:

Supportive care:
- Mechanical ventilation with lung-protective strategies if respiratory failure
- Transfuse PRBCs to maintain Hgb >7 g/dL (higher targets if active bleeding)
- Correct coagulopathy: FFP, platelets, vitamin K, prothrombin complex concentrate as indicated
Immunosuppression (if autoimmune/vasculitis suspected):
- High-dose corticosteroids: Methylprednisolone 500-1000 mg IV daily × 3-5 days
- Cyclophosphamide: 2 mg/kg/day PO or 500-1000 mg/m² IV monthly
- Rituximab: 375 mg/m² weekly × 4 doses or 1000 mg × 2 (alternative to cyclophosphamide)
- Plasma exchange: For anti-GBM disease or severe ANCA vasculitis with pulmonary hemorrhage (1.5 plasma volume exchanges daily × 14-21 days or until anti-GBM antibodies clear)²⁷

Pearl: Anti-GBM disease (Goodpasture's syndrome) requires urgent plasma exchange combined with immunosuppression (corticosteroids + cyclophosphamide). Delay worsens renal outcomes irreversibly. If clinical suspicion high (pulmonary hemorrhage + acute kidney injury), initiate plasma exchange empirically while awaiting serology.

Oyster: Bronchoscopy in DAH carries bleeding risk but is usually safe and diagnostically critical. Avoid if severe coagulopathy (INR >3, platelets <20,000) that cannot be corrected. In these cases, empiric treatment based on clinical suspicion may be necessary.

VENTILATOR-ASSOCIATED PNEUMONIA (VAP): PREVENTION AND MANAGEMENT

VAP Prevention Bundles 2025

VAP remains a leading HAI in ICUs, prolonging mechanical ventilation and increasing mortality. Evidence-based prevention bundles reduce VAP incidence by 50-70%.

Core VAP prevention bundle elements:

Elevate head of bed 30-45 degrees (reduces aspiration)
Daily sedation vacation and SBT assessment (reduces ventilator days)
Oral care with chlorhexidine 0.12% q12h
Subglottic secretion drainage: ETT with suction port above cuff
Avoid gastric overdistension: Appropriate NGT placement, avoid large-volume feeds
DVT/stress ulcer prophylaxis: H2 blockers or PPIs (controversial for VAP risk but benefits outweigh risks)

Controversial/emerging strategies:

Selective digestive decontamination (SDD): Oral/gastric topical antibiotics; reduces VAP in some regions but antibiotic resistance concerns limit use
Closed inline suction: Reduces VAP vs. open suction in some studies
Silver-coated ETT: Reduces VAP but cost-effectiveness questioned

Pearl: Oral care with chlorhexidine is one of the most cost-effective VAP prevention strategies. Implement consistent every-12-hour oral care protocols with chlorhexidine gel/rinse for all intubated patients.

VAP Diagnosis and Treatment

Clinical criteria (suggestive, not definitive):

New or progressive infiltrate on chest X-ray
Plus ≥2 of: fever >38°C, leukocytosis or leukopenia, purulent secretions

Microbiologic diagnosis:

Quantitative BAL (≥10⁴ CFU/mL) or endotracheal aspirate (≥10⁶ CFU/mL) most specific
Send before antibiotic initiation when possible

Antimicrobial therapy:

Early-onset VAP (<5 days, no risk factors for MDR):

Ceftriaxone, levofloxacin, or ampicillin-sulbactam

Late-onset VAP (>5 days) or MDR risk factors:

Antipseudomonal beta-lactam: Piperacillin-tazobactam 4.5 g IV q6h, cefepime 2 g IV q8h, or meropenem 1 g IV q8h
Plus antipseudomonal fluoroquinolone (ciprofloxacin 400 mg IV q8h) or aminoglycoside (gentamicin/tobramycin 7 mg/kg IV daily)
Plus MRSA coverage: Vancomycin 15-20 mg/kg IV q8-12h (target trough 15-20) or linezolid 600 mg IV q12h

Duration: 7-8 days for most pathogens (adequate for non-fermenting GNRs like Pseudomonas); consider 14 days for Acinetobacter or cavitary pneumonia

Pearl: VAP is often overdiagnosed. The presence of purulent secretions alone doesn't confirm VAP - colonization is common in ventilated patients. Use quantitative cultures and clinical criteria together. De-escalate antibiotics based on culture results and clinical improvement.

Hack: Procalcitonin-guided antibiotic de-escalation reduces antibiotic duration in suspected VAP without increasing mortality. If procalcitonin levels declining and clinical improvement, consider stopping antibiotics at day 7 even for Pseudomonas VAP.²⁸

NUTRITION IN ACUTE RESPIRATORY FAILURE

Feeding Strategies in Mechanically Ventilated Patients

Optimal nutrition delivery in critically ill patients with respiratory failure remains nuanced, balancing adequate nutritional support with risks of overfeeding.

General principles:

Early enteral nutrition (within 24-48 hours) preferred over parenteral when gut functional
Trophic/hypocaloric feeding (10-20 kcal/kg/day) for first week in hemodynamically unstable patients may be equivalent to full feeding while reducing aspiration/diarrhea risk
Target: 25-30 kcal/kg/day (ideal body weight) after stabilization
Protein: 1.2-2.0 g/kg/day

Special considerations in ARDS:

Avoid overfeeding: Excessive carbohydrate increases CO₂ production, worsening ventilatory requirements
High-fat formulas: May reduce CO₂ production compared to high-carbohydrate formulas
Omega-3 fatty acids (EPA/DHA): Early meta-analyses suggested benefit in ARDS, but subsequent trials (OMEGA trial) showed no mortality benefit; not routinely recommended²⁹

Pearl: Calculate caloric needs using Penn State equation or indirect calorimetry when available. Avoid using standard 25 kcal/kg calculations in obese patients - use adjusted body weight: IBW + 0.4(actual weight - IBW).

Gastric vs. post-pyloric feeding:

Gastric feeding simpler, preferred initially
Post-pyloric (jejunal) feeding if high gastric residuals, aspiration risk, or feeding intolerance

Gastric residual volume (GRV) monitoring: Recent guidelines de-emphasize routine GRV checks; consider feeding intolerance based on clinical signs (vomiting, abdominal distension) rather than arbitrary GRV thresholds. If checking GRVs, thresholds of 500 mL (vs. older 200 mL cutoffs) are safe.³⁰

Oyster: Parenteral nutrition should be reserved for patients unable to tolerate enteral nutrition. Initiating PN too early (within first week) may increase complications without improving outcomes. Trial enteral nutrition adequately first.

INHALED THERAPIES: BEYOND OXYGEN

Helium-Oxygen Mixtures (Heliox)

Heliox (typically 70% helium, 30% oxygen) is less dense than air, reducing turbulent flow and airway resistance in obstructive airway diseases.

Indications:

Severe upper airway obstruction (post-extubation stridor, croup, angioedema)
Severe asthma exacerbation (adjunct to bronchodilators)
COPD exacerbation with severe dyspnea

Mechanism: Lower density reduces turbulent flow, decreasing work of breathing in flow-limited states.

Limitations:

Cannot be used if FiO₂ requirement >0.3-0.4 (need sufficient helium concentration for benefit)
Requires special flow meters (helium viscosity differs from oxygen)
Expensive, limited availability

Pearl: Heliox may "buy time" in severe upper airway obstruction (e.g., post-extubation stridor, epiglottitis) while definitive therapies (corticosteroids, epinephrine, reintubation) are prepared.

Inhaled Bronchodilators: Optimization

Beta-agonists:

Albuterol: Continuous nebulization (10-15 mg/hour) for status asthmaticus; intermittent (2.5-5 mg q20min × 3, then q1-4h) for moderate exacerbations
Levalbuterol: R-isomer of albuterol; may have fewer cardiac side effects but significantly more expensive; reserve for patients with intolerable tachycardia on albuterol

Anticholinergics:

Ipratropium: 500 mcg nebulized q20min × 3, then q4-6h; additive benefit to beta-agonists in asthma/COPD exacerbations
Tiotropium: Long-acting antimuscarinic; useful in COPD but not acute exacerbations

Delivery in ventilated patients:

Use metered-dose inhalers (MDI) with spacer rather than nebulizers when possible (more efficient delivery, less circuit contamination)
Pause ventilator or ensure adequate inspiratory time for aerosol deposition
Vibrating mesh nebulizers more efficient than jet nebulizers in ventilated patients

Hack: When administering MDI via ventilator circuit, insert spacer/chamber between ETT and circuit, actuate 4-8 puffs, wait 5 seconds, then allow patient to take next breath. This improves drug delivery to lower airways vs. deposition in ETT.

TRANSFUSION THRESHOLDS IN RESPIRATORY FAILURE

Red Blood Cell Transfusion

The optimal hemoglobin threshold for transfusion in critically ill patients with respiratory failure balances oxygen-carrying capacity with transfusion risks (TRALI, TACO, immunomodulation).

2025 Evidence:

Restrictive strategy (transfuse if Hgb <7 g/dL, target 7-9 g/dL) is safe in most hemodynamically stable ICU patients, including those with respiratory failure³¹
Liberal strategy (transfuse if Hgb <9-10 g/dL) may benefit patients with:
- Acute coronary syndrome
- Acute brain injury
- Active hemorrhage
- Severe hypoxemia despite maximal ventilatory support (controversial)

Pearl: In ARDS patients with severe hypoxemia (PaO₂/FiO₂ <100), some experts advocate higher Hgb targets (>9-10 g/dL) to optimize oxygen delivery, though no RCT confirms benefit. Individualize based on tissue perfusion markers (lactate, ScvO₂).

Transfusion-related complications relevant to pulmonary patients:

TRALI (Transfusion-Related Acute Lung Injury): Noncardiogenic pulmonary edema within 6 hours of transfusion; mimics ARDS; supportive management
TACO (Transfusion-Associated Circulatory Overload): Cardiogenic pulmonary edema; treat with diuretics
Differentiate TRALI (normal BNP, acute onset, fever) from TACO (elevated BNP, gradual onset, hypertension)

PROCEDURAL SEDATION FOR ICU PROCEDURES

Sedation for Awake Bronchoscopy, Tracheostomy, Chest Tube Insertion

Safe procedural sedation in critically ill patients requires balancing adequate sedation/analgesia with hemodynamic stability and respiratory drive preservation.

Agents for ICU procedural sedation:

Propofol:

Rapid onset/offset, titratable
Dose: 0.5-1 mg/kg bolus, then 25-75 mcg/kg/min infusion
Caution: Hypotension, respiratory depression; avoid in hemodynamically unstable patients

Ketamine:

Dissociative anesthetic, maintains respiratory drive and hemodynamics
Dose: 0.5-1 mg/kg IV bolus, may repeat 0.25-0.5 mg/kg q5-10min
Advantages: Bronchodilation (useful in asthma/COPD), analgesia, hemodynamic stability
Caution: Emergence phenomena (hallucinations), increased secretions (co-administer glycopyrrolate)

Dexmedetomidine:

Alpha-2 agonist, provides sedation without respiratory depression
Dose: 0.5-1 mcg/kg load over 10 minutes, then 0.2-0.7 mcg/kg/hour
Advantages: Cooperative sedation, maintains airway reflexes
Caution: Bradycardia, hypotension, slow onset

Fentanyl/Remifentanil:

Opioid analgesia for painful procedures
Fentanyl: 50-100 mcg IV boluses
Remifentanil: 0.05-0.2 mcg/kg/min infusion (ultra-short-acting, useful for brief procedures)

Pearl: Ketamine is the ideal agent for bronchoscopy in status asthmaticus - provides sedation, analgesia, and bronchodilation without respiratory depression. Dose: 1-2 mg/kg IV bolus, then 0.5-2 mg/kg/hour infusion.

Topical anesthesia for awake bronchoscopy:

Lidocaine: 4% nebulized (5 mL), plus spray-as-you-go technique during bronchoscopy (1-2% lidocaine via bronchoscope working channel)
Maximum lidocaine dose: 7 mg/kg (9 mg/kg with epinephrine); monitor for toxicity (perioral numbness, tinnitus, seizures)

POINT-OF-CARE ULTRASOUND (POCUS) IN PULMONARY CRITICAL CARE

Lung Ultrasound: The "New Chest X-Ray"

Lung ultrasound (LUS) has emerged as a rapid, radiation-free bedside tool for diagnosing and monitoring respiratory pathology, often superior to chest X-ray for pleural effusions, pneumothorax, and consolidation.

Basic LUS findings:

Finding	Pathology	Characteristics
A-lines	Normal lung or COPD	Horizontal reverberations parallel to pleura
B-lines	Interstitial syndrome	Vertical artifacts extending from pleura to screen edge; ≥3 in one intercostal space abnormal
Consolidation	Pneumonia, atelectasis	Hypoechoic area with loss of aeration; may have air bronchograms
Pleural effusion	Fluid	Anechoic space above diaphragm; respiratory variation
Abolished lung sliding	Pneumothorax	Absent pleural movement; "stratosphere sign" on M-mode

BLUE Protocol (Bedside Lung Ultrasound in Emergency): Systematic approach to diagnose acute respiratory failure cause:

Profile A (bilateral A-lines): COPD, asthma, pulmonary embolism
Profile B (bilateral diffuse B-lines): Cardiogenic pulmonary edema, ARDS
Profile A/B (asymmetric A/B-lines): Pneumonia
Profile C (consolidation): Pneumonia
Abolished lung sliding + A-lines + lung point: Pneumothorax³²

Pearl: Multiple B-lines (≥3 per intercostal space) in multiple zones indicate interstitial syndrome (pulmonary edema, ARDS, interstitial pneumonia). Bilateral symmetric B-lines suggest cardiogenic pulmonary edema; asymmetric suggests unilateral pneumonia or ARDS.

Ultrasound-guided thoracentesis:

Identifies effusion, loculations, optimal site
Reduces pneumothorax risk from

POINT-OF-CARE ULTRASOUND (POCUS) IN PULMONARY CRITICAL CARE (Continued)

Lung Ultrasound: The "New Chest X-Ray" (Continued)

Ultrasound-guided thoracentesis: (Continued)

Identifies effusion, loculations, optimal site
Reduces pneumothorax risk from 10-20% (blind) to <1% (ultrasound-guided)
Measure distance from skin to pleural fluid to ensure adequate depth for safe needle insertion
Mark site with patient in procedure position (gravity-dependent)

Pearl: Before thoracentesis, use ultrasound to measure the maximum safe depth of needle insertion by identifying the distance from skin to lung parenchyma at the planned insertion site. This prevents inadvertent lung puncture.

Cardiac Ultrasound in Respiratory Failure

Focused cardiac ultrasound helps differentiate cardiogenic from non-cardiogenic respiratory failure and identifies RV dysfunction.

Key cardiac views for pulmonologists:

Parasternal long axis:

LV systolic function (eyeball ejection fraction)
LV dilation (cardiomyopathy)
RV size relative to LV

Apical 4-chamber:

RV:LV ratio (normal <0.6; RV strain if >1.0)
Septal flattening/bowing (RV pressure overload)
Tricuspid regurgitation for RVSP estimation

Subcostal:

IVC size and collapsibility (volume status)
IVC >2 cm non-collapsible: elevated RAP, volume overload
IVC <1.5 cm collapsible >50%: low RAP, hypovolemia

Findings suggesting cardiogenic pulmonary edema:

Reduced LV systolic function
LV dilation
B-lines on lung ultrasound
Non-collapsible IVC

Findings suggesting acute cor pulmonale/RV failure:

RV dilation (RV:LV >1.0)
RV hypokinesis (McConnell sign: RV free wall hypokinesis with preserved apical motion in PE)
Septal flattening (D-shaped LV in short axis)
TR jet velocity >3 m/s (RVSP >50 mmHg)

Pearl: The combination of RV dilation + septal flattening + TR velocity provides non-invasive assessment of pulmonary hypertension severity and RV dysfunction. In ARDS patients, development of acute cor pulmonale is associated with higher mortality and suggests need to reduce ventilator pressures/consider rescue therapies.

Oyster: Focused cardiac ultrasound by non-cardiologists has limitations. Image quality varies with body habitus, lung hyperinflation (COPD), and operator experience. When clinical decisions hinge on cardiac function, obtain formal echocardiography by cardiology/trained sonographer.

AIRWAY MANAGEMENT PEARLS AND PITFALLS

Difficult Airway Prediction and Preparation

Failed intubation in ICU patients carries higher morbidity than in OR due to hemodynamic instability, hypoxemia, and full stomachs.

Difficult airway predictors (LEMON criteria):

Look externally: Facial trauma, obesity, beard, small mouth opening
Evaluate 3-3-2 rule:
- 3 fingers mouth opening (mandibular space)
- 3 fingers thyroid-to-floor-of-mouth (hyomental distance)
- 2 fingers thyroid notch-to-floor-of-mouth
Mallampati score: Grade III-IV (soft palate/uvula obscured)
Obstruction: Epiglottitis, angioedema, mass, abscess
Neck mobility: Cervical spine immobilization, arthritis, limited extension

Preparation for anticipated difficult airway:

Experienced operator immediately available
Two operators at bedside
Video laryngoscope prepared as first-line device (superior to direct laryngoscopy in difficult airways)
Backup airway devices ready: supraglottic airway (LMA, i-gel), bougie/stylet, fiberoptic bronchoscope
Surgical airway kit at bedside
Preoxygenation maximized: 3-5 minutes 100% FiO₂ via HFNO or NIV
Consider awake fiberoptic intubation in severe anticipated difficulty

Pearl: Apneic oxygenation via nasal cannula (15 L/min) or HFNO (60 L/min) during intubation prolongs safe apnea time by 2-3 minutes, reducing hypoxemia during attempts. Continue supplemental oxygen via nasal cannula throughout intubation procedure.

Rapid Sequence Intubation (RSI) Modifications for ICU

Standard RSI (induction agent + paralytic, no bag-mask ventilation) requires modification in critically ill patients.

Preoxygenation strategies:

Standard: 100% FiO₂ via non-rebreather × 3-5 minutes
Enhanced: NIV (CPAP 10 cmH₂O, FiO₂ 1.0) or HFNO (60 L/min, FiO₂ 1.0) for patients with baseline hypoxemia
Goal: EtO₂ >90% (if available) or SpO₂ 100% before induction

Induction agents - choose based on hemodynamics:

Ketamine (preferred in shock/asthma):

Dose: 1-2 mg/kg IV
Maintains hemodynamics, bronchodilation
Caution in suspected elevated ICP (controversial)

Etomidate:

Dose: 0.3 mg/kg IV
Hemodynamically neutral
Brief adrenal suppression (likely not clinically significant with single dose)

Propofol (avoid in shock):

Dose: 1-2 mg/kg IV
Causes hypotension; reduce dose (0.5-1 mg/kg) in hemodynamically unstable patients

Neuromuscular blocking agents:

Succinylcholine:

Dose: 1-1.5 mg/kg IV
Rapid onset (45 seconds), short duration (5-10 minutes)
Contraindications: Hyperkalemia risk (burns, crush injury, prolonged immobilization, neuromuscular disease), malignant hyperthermia history

Rocuronium:

Dose: 1-1.2 mg/kg IV (standard), 1.5-2 mg/kg IV (rapid onset dosing for RSI)
Onset 60 seconds at high dose; duration 45-60 minutes
Reversible with sugammadex if needed

Pearl: In hemodynamically unstable patients, push-dose vasopressors (phenylephrine 100-200 mcg IV or ephedrine 5-10 mg IV) prepared before intubation can rapidly treat post-induction hypotension.

Delayed Sequence Intubation (DSI): Administer dissociative dose ketamine (1 mg/kg IV) to facilitate preoxygenation in agitated, hypoxemic patients unable to tolerate NIV/HFNO, then proceed with RSI after adequate preoxygenation. This "bridges" from awake agitated state to controlled RSI.³³

Oyster: Post-intubation hypotension occurs in 25-40% of ICU intubations and increases mortality. Causes include sedation-induced vasodilation, positive pressure ventilation reducing venous return, loss of endogenous catecholamine surge in exhausted patients, and unrecognized hypovolemia. Have vasopressors drawn up before induction; consider fluid bolus in hypovolemic patients.

Cricothyrotomy - The Last Resort

When intubation and bag-mask/supraglottic ventilation fail ("can't intubate, can't oxygenate"), emergent surgical airway is life-saving.

Indications:

CICO situation
Massive facial trauma precluding oral/nasal intubation
Upper airway obstruction unreachable by laryngoscopy

Technique:

Identify cricothyroid membrane (between thyroid and cricoid cartilages)
Stabilize larynx with non-dominant hand
Vertical skin incision, then horizontal incision through cricothyroid membrane
Insert tracheal hook to elevate/stabilize, or use Bougie
Insert 6.0 cuffed tracheostomy or ETT
Confirm placement, secure tube

Hack: Bougie-assisted cricothyrotomy is faster and easier than traditional technique: After incising cricothyroid membrane, pass bougie caudally into trachea, railroad 6.0 ETT over bougie into trachea, remove bougie, inflate cuff, ventilate.

Commercial kits: Numerous available (e.g., Portex, Cook Melker); follow package instructions but surgical technique often faster in true emergencies.

NONINVASIVE RESPIRATORY SUPPORT: EMERGING TECHNOLOGIES

Nasal High-Flow Therapy in Acute Settings

Beyond traditional HFNO discussed earlier, newer applications and refinements have emerged.

HFNO in COVID-19 and post-COVID era: HFNO became widely adopted during COVID-19 pandemic due to reduced aerosol generation compared to NIV. Benefits extend beyond pandemic:

Lower aerosol dispersion than NIV (important for airborne infections: TB, measles, varicella)
Better patient tolerance for prolonged use
Facilitates early mobilization compared to mechanical ventilation

HFNO in chronic respiratory failure: Home HFNO emerging as option for chronic hypercapnic failure patients intolerant of home NIV, though evidence still developing.

Adaptive Support Ventilation (ASV) and Intelligent Ventilation Modes

Modern ventilators incorporate closed-loop modes that automatically adjust minute ventilation based on patient effort and compliance.

Adaptive Support Ventilation (ASV):

Clinician sets target minute ventilation (% of normal)
Ventilator selects optimal respiratory rate and tidal volume based on Otis equation (minimizes work of breathing)
Automatically adapts as patient effort increases (ventilator support decreases)

Potential benefits:

Reduced sedation requirements
Faster weaning
Lung-protective ventilation maintenance

Current status: Promising in observational studies; large RCTs comparing outcomes to conventional modes ongoing. Not yet standard of care but available on most modern ICU ventilators.

Pearl: Intelligent modes like ASV, NAVA (neurally adjusted ventilatory assist), and PAV (proportional assist ventilation) represent the future of mechanical ventilation - personalized, adaptive support matching individual patient physiology. Consider using in difficult-to-wean patients where conventional modes failing.

SPECIAL POPULATIONS

Pregnancy and Acute Respiratory Failure

Pregnant women with acute respiratory failure require special considerations due to physiologic changes and fetal safety.

Physiologic changes in pregnancy:

Increased minute ventilation (30-40%) → baseline mild respiratory alkalosis (PaCO₂ 28-32 mmHg)
Reduced FRC (20%) → faster desaturation
Increased oxygen consumption (20-30%)
Mild elevation in D-dimer (physiologic)

Common causes of respiratory failure in pregnancy:

Pulmonary edema (preeclampsia, peripartum cardiomyopathy, tocolytics)
Aspiration pneumonitis
Thromboembolism (5× increased risk)
Amniotic fluid embolism
Pneumonia (including COVID-19, influenza - more severe in pregnancy)

Management principles:

Oxygenation target: Maintain SpO₂ >95% (fetal oxygenation depends on maternal PaO₂)
Ventilation: Maintain PaCO₂ ~32-35 mmHg (physiologic for pregnancy); avoid hyperventilation or profound hypercapnia
Positioning:
- Left lateral decubitus (after ~20 weeks) to relieve aortocaval compression
- Prone positioning possible in early pregnancy if needed for severe ARDS (controversial in late pregnancy)
Delivery timing: Multidisciplinary decision (OB, ICU, neonatology); periviable/viable fetus may benefit from delivery if maternal condition deteriorating

Medications in pregnancy:

Most ICU medications acceptable (sedatives, paralytics, vasopressors, antibiotics)
Avoid: ACE inhibitors, some anticoagulants (fondaparinux), ribavirin
Preferred anticoagulation: LMWH or unfractionated heparin (no DOACs in pregnancy)

Pearl: Pregnant patients desaturate faster during intubation due to reduced FRC and increased oxygen consumption. Optimize preoxygenation with NIV or HFNO, consider ramping (head-up) position, and have experienced operator perform intubation.

Obesity and Respiratory Failure

Morbidly obese patients (BMI >40 kg/m²) present unique challenges in respiratory critical care.

Obesity-specific issues:

Obesity hypoventilation syndrome (OHS): Chronic hypercapnia (PaCO₂ >45 mmHg) due to obesity; often coexists with OSA
Difficult airway: Increased aspiration risk, difficult mask ventilation and intubation
Reduced chest wall compliance: Higher airway pressures required
Atelectasis: Baseline reduced FRC, dependent atelectasis
Increased VTE risk: 2-3× baseline risk

Ventilation strategies:

Calculate predicted body weight using height alone (ignore actual weight for Vt calculation)
- Male PBW = 50 + 2.3 × (height in inches - 60)
- Female PBW = 45.5 + 2.3 × (height in inches - 60)
Tidal volume: 6-8 mL/kg PBW (not actual body weight)
PEEP: Higher PEEP (10-15 cmH₂O) often needed to prevent atelectasis
Recruitment maneuvers: Consider in refractory hypoxemia
Positioning: Reverse Trendelenburg (head-up) improves FRC and oxygenation; prone positioning feasible and effective in morbidly obese ARDS patients

Extubation considerations:

High risk of post-extubation respiratory failure
Transition to NIV or HFNO immediately post-extubation
Consider prophylactic CPAP/BiPAP if history of OHS or OSA

Pearl: In morbidly obese patients, recruitment maneuvers followed by higher PEEP often dramatically improve oxygenation by opening atelectatic dependent lung regions. Try sustained inflation (CPAP 30-40 cmH₂O × 30-40 seconds) if oxygenation poor despite conventional settings (ensure hemodynamic stability first).

Hack: Position obese patients in reverse Trendelenburg 30-45 degrees routinely when mechanically ventilated - this improves chest wall compliance, FRC, and oxygenation by reducing abdominal pressure on diaphragm.

NOVEL THERAPIES ON THE HORIZON

Mesenchymal Stem Cell (MSC) Therapy for ARDS

MSCs have immunomodulatory and anti-inflammatory properties. Early-phase trials explored MSC therapy for ARDS with promising safety profiles.

Mechanism: MSCs secrete anti-inflammatory mediators, enhance alveolar fluid clearance, reduce neutrophil infiltration, and may promote lung repair.

Current status: Phase 2 trials (REALIST, MUST-ARDS) completed; MSC therapy appears safe but efficacy uncertain. Phase 3 trials ongoing.³⁴

Oyster: MSC therapy for ARDS remains experimental. Not ready for clinical use outside trials, but represents promising regenerative medicine approach for future.

Extracorporeal Carbon Dioxide Removal (ECCO₂R) Refinements

Lower-flow extracorporeal devices continue evolving, with smaller cannulas, simpler circuits, and reduced anticoagulation requirements.

Potential applications:

Ultra-protective ventilation (Vt <4 mL/kg PBW) in severe ARDS
Avoidance of intubation in severe COPD exacerbations with refractory hypercapnia on NIV
Bridge to lung transplantation

Current limitations: No mortality benefit demonstrated; bleeding complications; cost; technical complexity.

Pearl: ECCO₂R may have niche role in bridge to lung transplant patients with end-stage lung disease and refractory hypercapnic respiratory failure where conventional ventilation inadequate but full ECMO not yet needed.

Artificial Intelligence in Critical Care Pulmonology

AI and machine learning applications emerging in ICU respiratory care:

Current applications:

Automated weaning protocols: AI-driven SBT readiness assessment and weaning algorithms
Early ARDS prediction: Machine learning models predicting ARDS development hours before clinical diagnosis
Ventilator waveform analysis: Real-time detection of patient-ventilator asynchrony, auto-PEEP, dynamic hyperinflation
CXR interpretation: AI algorithms detecting pneumothorax, effusions, infiltrates with high sensitivity

Future directions:

Personalized ventilator settings based on individual lung mechanics and physiology
Predictive analytics for clinical deterioration and VAP risk
Integration of multimodal data (labs, vitals, imaging, ventilator parameters) for decision support

Oyster: AI tools are adjuncts, not replacements for clinical judgment. Always validate AI recommendations against bedside assessment and physiologic reasoning. Beware algorithmic bias and errors.

KEY CLINICAL PEARLS: RAPID REFERENCE

ARDS Management:

Driving pressure <15 cmH₂O more important than specific PEEP level
Prone positioning for ≥16 hours in moderate-severe ARDS (PaO₂/FiO₂ <150)
Dexamethasone 20 mg IV daily if moderate-severe ARDS within 14 days of onset
Conservative fluid management after shock resuscitation

Mechanical Ventilation:

Always use PBW for tidal volume calculation, not actual body weight
Measure auto-PEEP in obstructive lung disease; apply external PEEP at 80-90% of auto-PEEP
Permissive hypercapnia safe if pH >7.20-7.25 in most patients

Weaning:

Daily SBT readiness screening reduces ventilator days
RSBI <105 predicts successful extubation
Cuff-leak test identifies laryngeal edema risk; prophylactic steroids if high risk

NIV:

First-line for hypercapnic respiratory failure (COPD, cardiogenic pulmonary edema)
Avoid in moderate-severe hypoxemic respiratory failure - use HFNO instead
Trial for 1-2 hours maximum; don't delay intubation if failing

HFNO:

ROX index >4.88 at 2-6 hours predicts success
Reduces intubation rates in AHRF; superior post-extubation support in high-risk patients
Not a substitute for timely intubation when indicated

Airway Management:

Apneic oxygenation via nasal cannula 15 L/min during intubation attempts
Ketamine preferred induction agent in shock and severe asthma
Push-dose vasopressors prepared before intubation in hemodynamically unstable patients

Pulmonary Embolism:

Intermediate-risk PE with RV dysfunction: close monitoring, consider advanced therapy if deteriorating
Massive PE: systemic thrombolysis or catheter-based therapy
Maintain multidisciplinary PERT for complex cases

VAP Prevention:

HOB elevation 30-45 degrees, daily sedation vacation, oral care with chlorhexidine q12h
Quantitative BAL cultures to guide therapy and enable de-escalation

Special Populations:

Pregnant patients: target SpO₂ >95%, maintain PaCO₂ ~32-35 mmHg
Obese patients: use PBW for ventilation calculations, higher PEEP, reverse Trendelenburg positioning

CONCLUSION

Pulmonology in critical care continues advancing rapidly, with refined understanding of lung-protective ventilation, expanding roles for noninvasive support, targeted therapies for ARDS, and sophisticated diagnostic tools. Intensivists must stay current with evolving evidence while maintaining focus on fundamental principles: early recognition of respiratory failure, prompt appropriate intervention, meticulous supportive care, and prevention of complications.

The most impactful interventions often remain simple: lung-protective ventilation, prone positioning, conservative fluid management, VAP prevention bundles, and systematic weaning protocols. Emerging therapies like advanced ECMO techniques, targeted immunomodulation, and AI-assisted decision support hold promise but require rigorous validation.

Postgraduate trainees should master physiologic principles underlying respiratory failure, develop systematic diagnostic approaches, gain proficiency in bedside procedures and POCUS, and cultivate clinical judgment to integrate evidence with individual patient factors. The art and science of critical care pulmonology demand continuous learning, humility in the face of uncertainty, and commitment to improving outcomes for our sickest patients.

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Disclosure: The author has no conflicts of interest to declare.

Word Count: ~12,500 words

This comprehensive review synthesizes current evidence and practical guidance for managing critically ill patients with respiratory failure in 2025, providing postgraduate critical care trainees with both foundational knowledge and cutting-edge insights to optimize patient outcomes.

Tuesday, October 28, 2025