A 42-year-old male is admitted to your ICU day 4 post-induction chemotherapy for acute promyelocytic leukemia (AML-M3). The patient was initially treated with idarubicin and all-trans retinoic acid (ATRA). He has progressively become more dyspnoeic in the ward. A chest X-ray demonstrates a bilateral, diffuse pulmonary infiltrate.
Initial examination reveals:
40 breaths/min, SpO2 88% on 10 L/min O2 by face mask
Glasgow Coma Scale
14 (E4 M6 V4)
Full blood count is as follows on admission:
Adult Normal Range
135 – 180
White Cell Count
26.0 x 109/L* ( no differential)
4.0 – 11.0
22 x 109/L*
150 – 400
Comment: Blasts visible
International normalised ratio (INR)
- Give your differential diagnosis for his respiratory failure.
- What are the major issues in this patient and how would you manage them?
Differential for respiratory failure
*common CAP/HAP bacteria
*resistant organisms/less virulent bacteria (given immunosuppression, hospitalisation)
*PJP/toxoplasmosis (although probably not yet immunosuppressed for long
*Differentiation syndrome (previously called ATRA syndrome)
*Drug induced pneumonitis
Cardiogenic pulmonary oedema
Non-cardiogenic capillary leak syndrome
Major issues and management
During early phase there is usually DIC and high risk of haemorrhage (especially pulmonary heamorrhage and ICH). After ATRA or ATO there is risk of differentiation syndrome. Despite this the overall prognosis is better than all other types of AML with cure rates ~90%. Hence, it would generally be appropriate to offer routine ICU supportive care (including invasive ventilation).
Specific issues and management:
- Infection: seek and treat infection (usually a broad septum anti-pseudomonal B-lactam and vancomycin would be appropriate empiric antimicrobials). It is probably too early for fungal infection but there would usually be fungal prophylaxis (e.g. voriconazole or fluconazole) prescribed and viral prophylaxis prescribed (e.g. aciclovir). CMV status relevant. Septrin if PJP. Advice from haematology and ID should be sought. Cultures should be sent.
- Differentiation syndrome: Steroids (e.g. dexamethasone 10 mg bd) for differentiation syndrome 3. Coagulopathy: Factor replacement is more aggressive given risk of bleeding from DIC (aim fib >1.5, pats >30-50).
- Management of respiratory failure: Optimise oxygenation/ventilation (Invasive ventilation is not routinely avoided given overall good prognosis).
- Routine supportive care. Seek and treat shock (most likely septic, other types possible (haemorrhagic, hypovolaemic, cardiogenic, obstructive). Stress ulcer prophylaxis given high dose steroids and coagulopathy. Nutritional support – enteral feeding (oral if possible). No thrombophophylaxis required. Consultation with haematologist and ID specialist.
- Haematologic management: Routine cytotoxic precautions for staff if cytotoxic (e.g. idarubicin given). WCC maybe mainly blasts and patient maybe neutropenic. Should have routine neutropaemic precautions. Role of G-CSF controversial given potential to stimulate malignant clone. Usually continue ATRA but discontinue chemotherapy.
Many candidates listed coagulopathy and differentiation syndrome in their differential, but few discussed the management of these problems.
This question is identical to Question 4 from the second paper of 2015, including not only the history but also the wording of the questions. However, weirdly, the college model answer is different. Even more weirdly, it is a different answer which is not obviously better than the previous one. Confidently, the author presents the same identical discussion section for both of these SAQs, as it is unclear as to why they might need to be different.
- Airway: The need to avoid intubation
- Respiratory: Hypoxic respiratory failure
- Circulatory: Haemodynamic instability: likely, septic shock (HR 144, BP 95/50)
- Neuro: A decreased level of consciousness (GCS 14)
- Haematological: anaemia, thrombocytopenia, likely neutropenia, and coagulopathy.
- Infectious: High fever (38.9°C) and raised WCC (26)
- Definitive diagnosis: cause of respiratory failure is uncertain
- Social: prognosis and family understanding of the situation, medical consensus
- Airway plan:
- Avoid intubation- unless it is clear that the patient is failing. See the non-invasive ventilation chapter for the rationale behind this. In short, recommendations to avoid intubation in immunosuppressed patients are based on early studies (eg. Scales et al, 2008) which do not reflect the recent improvements in critical care for such patients. The college answer reflects this fact. This is very interesting, as in the 2015 version of the question the college model answer recommended to "attempt to avoid invasive respiratory support if possible". Generally, mortality rates for BMT patients in the ICU are improving (from 14% survival at 1 year to 32%, according to ), but mechanical ventilation is still one of the most important negative prognostic indicators (in the series by Al-Zubaidi from 2018, it was associated with a 90% mortality at 1 year, not much different to 92% in Scales et al ten years ago).
- Thus: keep patient fasted (nil by mouth) in the event intubation is required.
- Respiratory support plan:
- Commence CPAP NIV
- Aim for SpO2 >90%, PaO2 > 60mmHg
- Breaks every 2 hours for chest physiotherapy (on high flow nasal prongs)
- Ensure humidified circuit
- Ensure frequent cough; encourage expectoration of sputum
- Circulatory support plan:
- Assess for fluid responsiveness using dynamic parameters
- If fluid responsive, resuscitate with 20% albumin
- If fluid resuscitation is ineffective, maintain MAP >65 with noradrenaline
- Consider stress dose steroids (unless steroids are already being given)
- Neurological plan:
- Avoid sedating analgesics
- Change NIV mode to BiPAP if hypercapnea develops
- Transfuse to Hb >70 (TRISS)
- Correct platelets for CVC insertion
- Administer Vitamin K and FFP for correction of the INR
- Seek clarification re. WCC differential (All neutrophils? All blasts?)
- Fungal cover with voriconazole or caspofungin
- PJP cover with Bactrim
- Viral cover with aciclovir
- Atypical cover with azithromycin
- Gram negative and anaerobe cover with meropenem
- Gram-positive cover with vancomycin
- Definitive diagnosis:
- Blood and sputum cultures
- Atypical pneumonia serology
- Urinary legionella and pneumococcal antigens
- Sputum culture
- TTE to exclude the contribution of cardiac failure to shock and hypoxia
- Discussion with haematology team regarding the use of high dose steroids for ATRA syndrome (10mg bd of dexamethasone for 3 days, or addition of cytarabine to the chemotherapy cocktail to suppress the bone marrow).
- Schedule family discussion
- Confer with haematology regarding prognosis
Panoskaltsis-Mortari, Angela, et al. "An official American Thoracic Society research statement: noninfectious lung injury after hematopoietic stem cell transplantation: idiopathic pneumonia syndrome." American journal of respiratory and critical care medicine 183.9 (2011): 1262-1279.
Patatanian, E., and D. F. Thompson. "Retinoic acid syndrome: a review." Journal of clinical pharmacy and therapeutics 33.4 (2008): 331-338.
Lee, Hwa Young, Chin Kook Rhee, and Jong Wook Lee. "Feasibility of high-flow nasal cannula oxygen therapy for acute respiratory failure in patients with hematologic malignancies: A retrospective single-center study." Journal of critical care 30.4 (2015): 773-777.
Scales, Damon C., et al. "Intensive care outcomes in bone marrow transplant recipients: a population-based cohort analysis." Critical Care 12.3 (2008): R77.
Lueck, Catherina, et al. "Improved short-and long-term outcome of allogeneic stem cell recipients admitted to the intensive care unit: a retrospective longitudinal analysis of 942 patients." Intensive care medicine 44.9 (2018): 1483-1492.
Al-Zubaidi, Nassar, et al. "Predictors of outcome in patients with hematologic malignancies admitted to the intensive care unit." Hematology/oncology and stem cell therapy (2018).