Two days after a total knee replacement, a patient with chronic obstructive pulmonary disease, coronary artery disease, hypertension and chronic kidney disease develops sudden shortness of breath—what are the likely differential diagnoses and how should I initially manage him?

Differential Diagnosis and Initial Management of Post-TKR Sudden Breathlessness

Pulmonary embolism is the most critical diagnosis to rule out immediately in this patient, given the high-risk orthopedic surgery, multiple comorbidities, and sudden onset of dyspnea 2 days post-operatively. 1

Primary Differential Diagnoses

1. Pulmonary Embolism (PE) - HIGHEST PRIORITY

• PE is the most likely cause of postoperative hypoxia after TKR, with research demonstrating frequent subclinical pulmonary embolism even in asymptomatic patients 1
• The 2-day post-operative timing is classic for venous thromboembolism manifestation 2
• Multiple risk factors present: major orthopedic surgery, CKD, CAD, HTN, and immobilization 2
• D-dimer levels correlate positively with decreased PaO2 after TKR 1

2. Acute Coronary Syndrome/Myocardial Infarction

• CAD history makes this a critical consideration 2
• In elderly patients with established ischemic heart disease, dyspnea frequently substitutes for typical anginal symptoms 3
• Paradoxical embolization through patent foramen ovale can cause simultaneous MI and PE 2

3. Acute Decompensated Heart Failure/Pulmonary Edema

• Orthopnea specifically indicates elevated pulmonary capillary pressure from left ventricular dysfunction 3
• The combination of CAD, HTN, and CKD represents a high-risk profile for heart failure 3
• Perioperative fluid shifts and surgical stress can precipitate cardiac decompensation 2

4. Atelectasis

• Most common cause of dyspnea after major surgery (42% in cardiac surgery patients) 4
• General anesthesia and postoperative pain limit respiratory effort 5
• However, typically presents with gradual onset rather than sudden breathlessness 4

5. Pneumonia

• Associated with longer ICU stay and higher mortality when present 4
• Consider if fever, productive cough, or infiltrates develop 4

6. Fat Embolism Syndrome

• Can occur 24-72 hours after long bone or joint surgery 1
• Presents with respiratory distress, confusion, and petechial rash

Immediate Management Algorithm

Step 1: Stabilization and Initial Assessment (First 15 minutes)

• Administer supplemental oxygen immediately, targeting SpO2 88-92% given COPD history 6
• Obtain vital signs including heart rate, blood pressure, respiratory rate, and oxygen saturation 6
• Perform focused physical examination for:
  • Signs of respiratory distress: tachypnea, accessory muscle use, cyanosis 6
  • Cardiac signs: elevated JVP, peripheral edema, S3 gallop, new murmurs 2, 3
  • Unilateral leg swelling suggesting DVT 2
  • Chest auscultation for rales (pulmonary edema) vs decreased breath sounds (atelectasis/effusion) 2

Step 2: Urgent Diagnostic Testing (Within 60 minutes)

• Arterial blood gas with documented FiO2 - essential to assess hypoxemia and acid-base status 6
• ECG - evaluate for acute MI, right heart strain pattern (S1Q3T3), or arrhythmias 6
• Chest radiograph - assess for pulmonary edema, infiltrates, atelectasis, or pneumothorax 6
• D-dimer level - if elevated with clinical suspicion, proceed to definitive imaging 2, 1
• Troponin - rule out acute MI given CAD history 2
• BNP or NT-proBNP - if heart failure suspected 2, 3

Step 3: Risk Stratification for PE

If any of the following present, proceed immediately to CT pulmonary angiography: 2

• Hypoxemia (PaO2 decreased >10% from baseline) 1
• Tachycardia or tachypnea
• Elevated D-dimer
• Unilateral leg swelling
• Pleuritic chest pain
• Hemodynamic instability

Step 4: Definitive Imaging Based on Leading Diagnosis

• CT pulmonary angiography (CTPA) - gold standard for PE diagnosis 2
• Echocardiography - if PE confirmed, assess for RV dysfunction (McConnell sign: RV free wall hypokinesis with apical sparing), elevated RV systolic pressure, and septal flattening 2
• Lower extremity compression ultrasound - identify DVT source 2
• Ventilation/perfusion scan - alternative if contrast contraindicated due to CKD 2

Step 5: Therapeutic Interventions

If PE Confirmed:

• Initiate anticoagulation immediately (do not delay for imaging if high clinical suspicion and no contraindications) 2
• Unfractionated heparin or LMWH (dose-adjust for CKD) 2
• Consider thrombolysis if massive PE with hemodynamic instability 2
• Admit to monitored setting 2

If Acute Heart Failure/Pulmonary Edema:

• Diuretic therapy (IV furosemide, adjust for CKD) 2
• Optimize preload and afterload reduction 2
• Treat underlying precipitant 2

If Acute MI:

• Urgent cardiology consultation for revascularization 2
• Dual antiplatelet therapy, anticoagulation, statin 2

If Atelectasis:

• Incentive spirometry and chest physiotherapy 5, 4
• Adequate analgesia to facilitate deep breathing 5
• Early mobilization 5

Critical Pitfalls to Avoid

• Do NOT assume atelectasis without ruling out PE - even asymptomatic TKR patients can have pulmonary embolism 1
• Do NOT over-oxygenate if COPD present - excessive oxygen (>35% or PaO2 >75 mmHg) causes CO2 retention and respiratory acidosis 6
• Do NOT delay anticoagulation if PE is highly suspected - waiting for imaging can be fatal 2
• Do NOT dismiss cardiac causes - absence of chest pain does not exclude MI in elderly patients with CAD 3
• Do NOT rely on D-dimer alone - positive correlation with hypoxia after TKR, but requires definitive imaging for diagnosis 1
• Monitor for hypophosphatemia - rare but can cause acute muscle weakness and respiratory failure post-operatively 7

Monitoring Requirements

• Continuous pulse oximetry 6
• Serial arterial blood gases if clinical deterioration 6
• Cardiac monitoring for arrhythmias 2
• Repeat imaging if no improvement with initial therapy 2