A 42-year-old male is admitted to your intensive care 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:
Full blood count is as follows on admission:
Parameter |
Patient value |
Normal Adult Range |
|
Haemoglobin |
88 g/L* |
135 – 180 |
|
White Cell Count |
26 x 109/L* ( no differential) |
4.0 – 11.0 |
|
Platelets |
22 x 109/L* |
150 – 400 |
|
Comment: Blasts visible |
|||
International normalised ratio (INR) |
3.2 |
a) Give your differential diagnosis for his respiratory failure. (40% marks)
b) What are the major issues in this patient and how would you manage them? (60% marks)
a)
Sepsis in a patient with immune compromise secondary to leukaemia. Nosocomial pneumonia
– Bacterial –Gm negative –E.coli, Pseudomonas, Klebsiella
– Gm positive: Strep, Staph epi
– Fungal: Aspergillus, Candida, Cryptococcus
– Atypical: Legionella, mycoplasma
– Viral: CMV, HSV, RSV, Influenza, H1N1, VZV
– PCP: Toxoplasmosis
– TB (depending on background)
Non- infective
- Idiopathic pneumonia syndrome
- Cardiac failure (cardiotoxicity due to induction chemo)
- Diffuse alveolar haemorrhage
- Non cardiogenic capillary leak syndrome
- Chemo induced ALI / pneumonitis
- Retinoic Acid Syndrome
b)
Major issues are:
1. Hypoxic respiratory failure
Probable nosocomial pneumonia now requiring respiratory support and is likely to be progressive
Problem with invasive respiratory support carrying very high mortality and complications including barotrauma, further nosocomial infections
Management - Non-invasive respiratory support commencing with CPAP progressing to BiPAP using the lowest FiO2 to maintain PaO2 above 60 mmHg. Attempt to avoid invasive respiratory support if possible.
2. Possible Sepsis
May rapidly progress to septic shock in this patient Possible unusual infective agent
Early commencement of Broad cover (Cefepime / Ceftazadime / Tazocin and Vancomycin + Voriconazole / caspofungin / liposomal amphotericin + acyclovir + Bactrim.) Discussion with ID and haematology specialists for prior antimicrobial therapy, CMV status, previous aspergillus infection etc
Removal of indwelling intravenous catheters that are in anyway suspicious for infection
Central access (with platelet cover), consideration of inotropes after transfusion of blood products and IV fluids preferentially using Albumin containing solutions.
Steroids.
3. Prognosis from acute promyelocytic leukemia (AML-M3).
Management is to liaise early with treating haematologist to ascertain likely outcome from primary disease and also discuss with family and patient the significant risk of deterioration and mortality.
4. Other
Treatment of coagulopathy- Vit K, Platelets, FFP
Difficulties in making definitive diagnosis
Possible atypical infection with low yield probable from cultures Significant other non-infective differential diagnosis.
Management includes having a high degree of suspicion for resistant or unusual organism and managing with broad cover.
Additional Examiners’ Comments:
Candidates were expected to give some indication of treatment strategies e.g. antibiotics, reversal of coagulopathy rather than just writing D/W ID, haematology etc.
a)
A long list of differenials for a diffuse pulmoanry infiltrate is given in the chapter on the causes of ARDS. After this question came out, the list was amended to include ATRA syndrome, which is a freakishly rare thng and unlikely to ever be seen by anyobne outside of a major bone marrow transplant centre. The list mainly comes from an excellent article from Silvia Blanco and Antoni Torres (antimicrobe.org).
Vascular:
Infectious
Neoplastic
Idiopathic
|
Drug-induced
Autoimmune
Traumatic
|
ATRA syndrome (or "retinoic acid syndrome", or "differentiation syndrome") listed in the differentials above is a complication of therapy with all-trans-retinoic acid. A good references for those interested is a 2008 paper by Patatanian and Thompson. The authors describe this complication of ATRA therapy as "unpredictable but frequent" and offer little in the way of aetiological information.
Idiopathic pneumonia syndrome (also mentioned in the college list of differentials) is a (probably autoimmune) complication of bone marrow transplant, which is well covered in this 2011 article by Panoskaltsis et al. Characteristic features consist of pneumonia-like infiltrates and a demonstrated absence of respiratory tract infection.
b)
"What are the major issues in this patient and how would you manage them?" This part of the question requires a structured answer. There are many ways to structure an answer like this. The suggested answer below is organised by important systems.
Issues:
Plans:
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.