ICU Fellowship Snippet – Type 1 Respiratory failure in immunocompramised patient

Written by Dr Madhuri Anupindi

42M admitted to ICU day 4 post induction chemotherapy for APML. The patient was initially treated with idarubicin and all-trans retinoic acid (ATRA). He has become progressively more dyspnoeac in the ward. CXR demonstrates a bilateral, diffuse pulmonary infiltrate. Initial exam reveals RR 40, sats 88% on 10L via face mask, GCS 14 (E4V4M6), temp 38.9, Hr 144, BP 95/50. Full blood count on admission shows Hb 88 WCC 26 and platelets 22 with blasts visible. INR 3.2. Suggest a differential diagnosis.

There are multiple potential causes for this gentleman’s respiratory failure, both infective (of which there are many possibilities given his immunosuppressed state), and non-infective causes.

Infective:

• Bacterial:
  • Pneumonia (CAP/HAP), pseudomonas
  • Sepsis from another source with ARDS
  • MROs
  • Atypical, mycobacterium
• Viral
  • CMV
  • Influenza, respiratory viruses
  • HSV
  • EBV
• Fungal
  • Candidemia (most likely in this time frame compared to the other fungi)
  • PJP
  • Aspergillosis
  • Cryptococcus
• Parasitic
  • Toxoplasmosis
  • Strongyloides

Non-infective

• Drug related
  • Differentiation syndrome (ATRA)
  • Chemotherapy pneumonitis
  • Transfusion related acute lung injury
• Cardiac
  • Cardiac failure (may have cardiomyopathy secondary to chemo)
• Vascular
  • Diffuse alveolar haemorrhage
  • Pulmonary haemorrhage
• Autoimmune
  • TTP
• Neoplasm
  • Secondary to the lymphoma
• Aspiration

Outline the management priorities for this patient

Assessment and specific management of underlying cause of deterioration: empirically treat for infection

• Requires history, exam and investigations to identify cause/s of deterioration à particularly important to assess for infection in this immunosuppressed patient
• Septic screen
• Broad spectrum antibiotics: Tazocin + vancomycin and gentamicin (adjust depending on allergies, MROs, risk of fungal infection, presence of devices etc) and patient should be on fungal and viral prophylaxis
• TTE to evaluate cardiac function
• Steroids if thought to be differentiation syndrome

Management of respiratory failure

• Commence NIV with breaks onto HFNP aiming for sats > 92%, low threshold for intubation if no improvement
• Humidified circuit

Assessment and management of shock

• Full cardiorespiratory monitoring, insertion of arterial and central line à CVC with platelet cover, may need to be femoral if patient cannot lie flat due to respiratory deterioration
• Trial small bolus 250mls 5% albumin depending on history/exam findings and see if fluid responsive
• Noradrenaline aiming for MAP > 65
• Likely septic shock but shock may be multi-factorial or due to other causes such as haemorrhage in context of coagulopathy requiring transfusion, or cardiogenic in context of chemotherapy requiring inotropes
• Stress dose steroids if high vasopressor requirements and not on steroids already

Management of coagulopathy

• AMPL characterised by high risk of haemorrhage due to DIC and/or fibrinolysis: blood transfusion aiming Hb > 70, platelets > 30-50, fibrinogen > 1.5
• Vitamin K and FFP to correct INR aiming INR < 1.5
• Evaluate for bleeding especially intra-cranial and pulmonary: CTB if GCS worsens or does not improve
• Liaise with haematology regarding ongoing therapy and prognosis

Supportive management

• Cytotoxic precautions for all staff
• Positive pressure room if patient neutropenic
• Keep NBM initially in first few hours while assessing whether patient may need intubation à ideally enteral nutrition following
• PPI
• Family updates about critical nature

What is differentiation syndrome?

Differentiation syndrome is a life-threatening complication of treatment of APML with arsenic trioxide and/or all-trans retinoic acid. It is a systemic inflammatory response syndrome thought to be caused by the release of cytokines from differentiating blast cells and pro-inflammatory cytokines.

What are the clinical features of differentiation syndrome and what is the specific management?

Historical features:

• Occurs most frequently in the first 7-10 days of treatment but can occur at any time during therapy
• Risk factors: leucocytosis, creatinine > 125umol/L, male, BMI > 30g/m², microgranular FAB subtype
• Symptoms: dyspnoea, myalgia, headache

Examination features:

• Fever, hypoxia, hypotension, weight gain
• Peripheral oedema, pleural effusion, pericardial effusion

Investigative features

• FBC: leukocytosis
• CXR: pulmonary infiltrates
• UEC, LFT: renal and/or hepatic failure

Management:

• Patients may be on prophylactic corticosteroids with aim to reduce risk of differentiation syndrome (although not strong evidence for same)
• Change prophylactic steroids to high dose IV: generally dexamethasone 10mg IV BD
• Early recognition and treatment is key: high index of suspicion required and treatment instituted while assessment is ongoing
• Liaise with haematology regarding ATRA dosing: if signs are severe the dose is usually decreased or discontinued until patient improves

This patient has a raised INR and thrombocytopenia. List other potential causes for these abnormalities in the critically ill?

• Disseminated intra-vascular coagulopathy
• Acute liver failure
• Massive haemorrhage or dilutional coagulopathy
• Sepsis associated coagulopathy
• Snake bite
• HITTS after Warfarin or Argatroban is given
• Haemophagocytosis lymphohistiocytosis
• Paracetamol overdose

What are the investigative findings of acute DIC? 

• Prolonged PT and aPTT
• Low Fibrinogen
• Raised D dimer
• Thrombocytopenia

** International Society for Thrombosis and Haemostasis DIC score (ISTH criteria) uses these four parameters to give patients with a clinical disorder known to cause DIC a score from 0 – 8. A score of ≥ 5 is consistent with DIC.