skip_previous play_arrow skip_next
00:00 00:00
playlist_play chevron_left


ICU Fellowship Snippet – Type 1 Respiratory failure in immunocompramised patient

Dr Swapnil Pawar July 5, 2024 31

share close

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.


  • 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


  • 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


  • 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.

Rate it
Previous post
ICU Fellowship PrepCast
  • 92


ICU Fellowship Snippet – Asthma Management

Dr Swapnil Pawar May 8, 2024

play_arrow ICU Fellowship Snippet – Asthma Management Dr Swapnil Pawar   As the duty locum intensivist you have been called to urgently review a patient on the medical ward of […]

Read more trending_flat