Expert Consensus on Acute Respiratory Failure in Critically Ill Oncology Patients (2023 Version)

1. Preface

2. Definition and Etiological Classification of ARF in Critically Ill Oncology Patients

2.1 Definition

• Hypoxemic ARF: Partial pressure of arterial oxygen (PaO₂) < 60 mmHg with fractional inspired oxygen (FiO₂) ≥ 0.5, or oxygenation index (PaO₂/FiO₂) < 300 mmHg;
• Hypercapnic ARF: Partial pressure of arterial carbon dioxide (PaCO₂) > 50 mmHg accompanied by respiratory acidosis (pH < 7.35), regardless of PaO₂ levels.

2.2 Etiological Classification

3. Clinical Evaluation of ARF in Critically Ill Oncology Patients

3.1 Rapid Initial Assessment (Within 1 Hour of Admission)

• Airway (A): Evaluate for obstruction (e.g., SVCS, mediastinal mass) via clinical signs (stridor, hoarseness) or imaging (chest CT). Secure the airway promptly if obstruction is suspected (e.g., endotracheal intubation).
• Breathing (B): Monitor respiratory rate (RR > 25 breaths/min indicates respiratory distress), SpO₂ (target ≥ 92% with FiO₂ < 0.6), and chest auscultation (rales, wheezes, or decreased breath sounds). Perform arterial blood gas (ABG) analysis to confirm hypoxemia/hypercapnia and acid-base status.
• Circulation (C): Assess blood pressure, heart rate, and signs of shock (e.g., cool extremities, delayed capillary refill). Rule out cardiogenic or septic shock as triggers for ARF.
• Disability (D): Evaluate consciousness (Glasgow Coma Scale, GCS) to identify central nervous system (CNS) involvement (e.g., brain metastases, hypercapnic encephalopathy).
• Exposure (E): Review the patient’s cancer history (type, stage, treatment course) and recent events (e.g., chemotherapy cycles, radiation fields, HSCT status) to narrow etiological possibilities.

3.2 Etiological Evaluation

3.2.1 Laboratory Tests

• Infection screening: Complete blood count (CBC, focus on neutropenia: absolute neutrophil count < 1.0×10⁹/L), C-reactive protein (CRP), procalcitonin (PCT), blood culture (2 sets from peripheral veins), and respiratory pathogen testing (e.g., PCR for influenza, COVID-19, Pneumocystis jirovecii).
• Organ function: Liver function (ALT, AST, bilirubin), renal function (creatinine, urea), and lactate (to assess tissue perfusion).
• Tumor markers: For patients with progressive cancer, monitor tumor markers (e.g., CEA, CA125) to evaluate tumor progression.

3.2.2 Imaging Studies

• Chest radiography (CXR): First-line imaging to detect pleural effusion, pulmonary infiltrates, or mediastinal widening. Limitations include low sensitivity for early interstitial lung disease (ILD) or small pulmonary emboli.
• Chest computed tomography (CT): Recommended for patients with unclear etiology (e.g., negative CXR but persistent hypoxemia) or suspected cancer-related causes (e.g., SVCS, pulmonary metastases). Contrast-enhanced CT is required to rule out PE.
• Ultrasound: Bedside lung ultrasound (BLUS) helps identify pleural effusion, consolidation, or B-lines (indicative of pulmonary edema/ILD) without radiation exposure, suitable for critically ill patients unable to undergo CT.

3.2.3 Specialized Tests

• Bronchoscopy: Indicated for patients with suspected infectious pneumonia (to collect bronchoalveolar lavage fluid, BALF, for pathogen detection) or endobronchial tumor obstruction. Avoid in patients with severe coagulopathy (platelet < 50×10⁹/L) unless life-saving.
• Pleural fluid analysis: Perform thoracentesis for patients with moderate-to-large pleural effusion. Analyze fluid for cell count, protein, lactate dehydrogenase (LDH), and cytology (to rule out malignant effusion).
• Cardiac evaluation: Echocardiography to assess left ventricular function (e.g., chemotherapy-induced cardiomyopathy) or right ventricular strain (e.g., PE). Brain natriuretic peptide (BNP) > 100 pg/mL suggests cardiogenic ARF.

3.3 Risk Stratification

4. Treatment Strategies for ARF in Critically Ill Oncology Patients

4.1 General Principles

• Etiology-directed treatment: Prioritize targeted interventions (e.g., antibiotics for infection, glucocorticoids for ICI-pneumonitis, thoracentesis for malignant effusion).
• Lung-protective ventilation: For ARDS, apply low tidal volume (6–8 mL/kg predicted body weight) and moderate PEEP (5–15 cmH₂O) to reduce ventilator-induced lung injury (VILI).
• Supportive care: Maintain adequate tissue perfusion (avoid hypotension: mean arterial pressure ≥ 65 mmHg), correct electrolyte disturbances, and provide nutritional support (enteral nutrition preferred if gastrointestinal function is intact).

4.2 Etiology-Specific Treatment

4.2.1 Infectious ARF

• Empirical antibiotic therapy: Initiate within 1 hour of suspected infection. For neutropenic patients, use broad-spectrum antibiotics (e.g., piperacillin-tazobactam + amikacin) to cover gram-negative (e.g., Pseudomonas aeruginosa) and gram-positive pathogens (e.g., Staphylococcus aureus). Adjust based on culture results.
• Anti-fungal therapy: Add empirically if neutropenia persists > 7 days or if fungal infection is suspected (e.g., Aspergillus, via galactomannan test or CT findings of halo signs).
• Pneumocystis jirovecii pneumonia (PJP): For immunocompromised patients (e.g., lymphoma, HSCT), initiate trimethoprim-sulfamethoxazole (TMP-SMX) if PJP is suspected, even with negative initial testing.

4.2.2 Cancer Treatment-Related ARF

• ICI-pneumonitis: Grade 2–4 pneumonitis (per CTCAE v5.0) requires immediate discontinuation of ICIs and high-dose glucocorticoids (methylprednisolone 1–2 mg/kg/day). For refractory cases (no response after 48–72 hours), add infliximab or mycophenolate mofetil.
• Radiation pneumonitis: Acute radiation pneumonitis (grade ≥ 2) is treated with glucocorticoids (prednisone 0.5–1 mg/kg/day) for 2–4 weeks, followed by gradual tapering over 4–8 weeks to avoid relapse.
• Chemotherapy-induced lung injury: Discontinue the offending agent (e.g., bleomycin) and administer glucocorticoids. For bleomycin-induced fibrosis, add pirfenidone or nintedanib if progressive.

4.2.3 Cancer Direct-Related ARF

• Malignant pleural effusion: Perform therapeutic thoracentesis (remove ≤ 1500 mL at one time) to relieve dyspnea. For recurrent effusions, consider indwelling pleural catheter (IPC) or chemical pleurodesis (e.g., talc).
• SVCS: For life-threatening obstruction (e.g., severe dyspnea), initiate emergency radiation therapy (3–5 fractions) or chemotherapy (for chemotherapy-sensitive tumors, e.g., small cell lung cancer). Use glucocorticoids (dexamethasone 4–8 mg/day) to reduce edema.
• Pulmonary embolism: Anticoagulate with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH). For high-risk PE (e.g., hypotension), consider systemic thrombolysis (alteplase) if no contraindications (e.g., active bleeding, recent surgery).

4.3 Respiratory Support Modalities

4.3.1 Non-Invasive Respiratory Support (NIRS)

• High-flow nasal oxygen (HFNO): Recommended for mild-to-moderate hypoxemic ARF (PaO₂/FiO₂ 150–300 mmHg) or post-extubation support. Set flow rate 30–60 L/min and FiO₂ to maintain SpO₂ ≥ 92%. Avoid in patients with hypercapnic ARF or high aspiration risk.
• Non-invasive ventilation (NIV): Indicated for hypercapnic ARF (e.g., COPD exacerbation) or cardiogenic pulmonary edema. Use pressure support ventilation (PSV) mode with PEEP 5–8 cmH₂O and PS 10–15 cmH₂O. Discontinue and switch to invasive ventilation if no improvement within 2–4 hours.

4.3.2 Invasive Mechanical Ventilation (IMV)

• Initiation criteria: Severe hypoxemia (PaO₂/FiO₂ < 150 mmHg despite NIRS), respiratory arrest, airway obstruction, or severe consciousness disturbance (GCS < 8).
• Ventilation settings:
  • Mode: Assist-control ventilation (ACV) or synchronized intermittent mandatory ventilation (SIMV) with PSV.
  • Tidal volume: 6–8 mL/kg predicted body weight (to limit plateau pressure < 30 cmH₂O).
  • PEEP: Titrate using FiO₂-PEEP tables (e.g., FiO₂ 0.6 → PEEP 8 cmH₂O) to maintain PaO₂/FiO₂ > 200 mmHg.
• Sedation: Use light sedation (Richmond Agitation-Sedation Scale, RASS -1 to 0) to facilitate spontaneous breathing and reduce VILI. Avoid deep sedation unless required for patient-ventilator asynchrony.

4.3.3 Advanced Respiratory Support

• Extracorporeal membrane oxygenation (ECMO): Consider for refractory ARF (PaO₂/FiO₂ < 100 mmHg despite optimal IMV) in high-potential patients (e.g., young age, reversible etiology, no progressive cancer). Veno-venous (VV)-ECMO is preferred for isolated respiratory failure.
• Extracorporeal carbon dioxide removal (ECCO₂R): Indicated for hypercapnic ARF unresponsive to NIV/IMV (e.g., severe COPD with hypercapnia) to allow lower ventilation settings and reduce VILI.

4.4 Supportive Care and Comorbidity Management

• Hematological support: For neutropenic patients, administer granulocyte colony-stimulating factor (G-CSF) 5 μg/kg/day until ANC > 1.0×10⁹/L. Transfuse packed red blood cells (PRBC) to maintain Hb ≥ 80 g/L and platelets to maintain PLT ≥ 50×10⁹/L (≥ 100×10⁹/L for invasive procedures).
• Renal protection: Avoid nephrotoxic drugs (e.g., aminoglycosides). Initiate continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) with fluid overload or severe electrolyte disturbances (e.g., hyperkalemia).
• Nutritional support: Start enteral nutrition within 48 hours of ICU admission if gastrointestinal function is intact. For patients with severe ARF, use high-fat, low-carbohydrate formulas to reduce CO₂ production.

5. Prognosis Assessment and End-of-Life Care

5.1 Prognosis Assessment

• Favorable indicators: Resolution of neutropenia, improvement in PaO₂/FiO₂ > 200 mmHg within 72 hours, and successful weaning from IMV.
• Poor indicators: Persistent multi-organ failure, refractory ARF (PaO₂/FiO₂ < 100 mmHg for > 7 days), and progressive cancer with no effective treatment options.

5.2 End-of-Life Care

• Goals of care: Shift from curative to palliative care, focusing on symptom relief (e.g., opioids for dyspnea, sedatives for anxiety).
• Withdrawal of support: Discontinue IMV/ECMO only after explicit consent from the family and interdisciplinary team (oncologist, intensivist, palliative care specialist). Provide continuous comfort care during withdrawal.

6. Implementation Recommendations

• Multidisciplinary team (MDT) collaboration: Establish an MDT team including oncologists, intensivists, respiratory physicians, and radiologists to develop individualized treatment plans.
• Training and education: Provide training on ARF evaluation and management for oncology and ICU staff, especially on the recognition of treatment-related lung injury (e.g., ICI-pneumonitis).
• Data registration: Establish a national registry for ARF in critically ill oncology patients to collect real-world data and optimize future guidelines.

References

1. Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-2533.
2. Churpek MM, Yuen TC, Winslow C, et al. Predicting in-hospital mortality for critically ill cancer patients. Am J Respir Crit Care Med. 2014;190(10):1149-1155.
3. Naidoo J, Chong SU, Chauhan S, et al. Management of immune checkpoint inhibitor-induced pneumonitis: a systematic review. J Thorac Oncol. 2020;15(1):37-55.
4. Chinese Anti-Cancer Association. Guidelines for the diagnosis and treatment of severe infections in cancer patients (2021 version). Chin J Cancer. 2021;40(5):217-230. (In Chinese)
5. Zhang L, Wang Y, Li J, et al. Clinical characteristics and outcomes of acute respiratory failure in critically ill oncology patients in China: a multicenter retrospective study. Crit Care. 2022;26(1):189.