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Respiratory Failure in Patients with Haematological Malignancies

Created: 11/7/2008
Updated: 15/7/2008

Respiratory Failure in Patients with Haematological Malignancies

Christopher J Loew FRCA MRCP DICM
Advanced Trainee in Intensive Care Medicine & Anaesthesia
Oxford Radcliffe Hospitals NHS Trust

Focus on intensive chemotherapy treatments

Modern intensive chemotherapies, with or without bone marrow transplantation or peripheral stem cell therapy, have markedly improved overall survival rates of patients with haematological malignancies. However, intensive chemotherapy treatment is associated with severe complications that can lead to significant morbidity and increased mortality (Table 1).

Table 1. Complications associated with intensive chemotherapy

 Renal failure
 Hepatic dysfunction
 Graft versus host disease

A common problem in patients with haematological malignancies is either disease- or treatment-related immunosuppression, which renders them susceptible to bacterial, viral and fungal infection.

Focus on respiratory failure in patients with haematological malignancies
Due to a widespread perceived dismal prognosis, there is often reluctance among ICU practitioners to admit patients with haematological malignancies for invasive organ support if the reason for the referral is of a respiratory nature.

In immunocompromised patients, respiratory failure can be due to a variety of causes (Table 2).

Table 2. Causes of respiratory failure in immunocompromised patients

 - Infection
 - Haemorrhage
 - Leukaemic or lymphomatous pulmonary involvement
 - Alveolar proteinosis
 - Drug and transfusion reactions
 - Opportunistic infections
 - Neoplasms
 - Unrelated disease process (e.g. cardiogenic pulmonary oedema, asthma)

Initial treatment concentrates on the reversal of the underlying cause and includes conventional supportive therapy with oxygen, physiotherapy and broad-spectrum antimicrobial cover. Failing that, non-invasive or invasive ventilatory support may be indicated.

Focus on mortality in patients requiring invasive respiratory support

Overall ICU mortality of patients with haematological malignancies has been quoted by several studies to be in the order of 34-44%. Invasive mechanical ventilation for respiratory failure, however, is associated with a much higher mortality, and several studies have found it to be an independent predictor of death. Two recent retrospective studies by Pene et al. and Rabitsch et al. enrolled a total of 282 patients post-stem-cell transplant for haematological malignancies. Of 169 patients invasively ventilated, 22 survived to leave the ICU (87% mortality). Rabbat et al. reported the same mortality figure for 23 invasively ventilated patients with acute myeloid leukaemia. Kroschinsky et al. reported on 54 critically ill haematology patients following chemotherapy or stem-cell transplant requiring invasive ventilation. ICU and 1-year mortality were 74% and 82%, respectively. Taken together, the prognosis for patients with haematological malignancies and respiratory failure requiring invasive ventilation is poor.

Focus on mortality in patients requiring NIV

Non-invasive ventilation (NIV) in patients with haematological malignancies has been associated with lower mortality rates. In recent studies, overall hospital mortality in patients responding to NIV has been described as 36% by Rabitsch et al. and 55% in the study by Pene et al. Rabbat et al. report an ICU mortality of 33%. Rabitsch et al. reported that in the ‘NIV-responder group’ all patients improved within 4 hours. In 2001, Hilbert et al. described the beneficial effects of early NIV in patients with haematological malignancies and acute respiratory failure. In this study, 52 patients with PaO2/FIO2 ratios <27 kPa, a respiratory rate of >30, pyrexia and pulmonary infiltrates were randomised to receive either intermittent NIV or standard treatment with oxygen, but no ventilation. In the ‘NIV-group’ fewer patients required endotracheal intubation, had serious complications, or died in the ICU or in hospital.

Key Learning Points

In patients with haematological malignancies:

• Respiratory failure requiring mechanical ventilation is associated with a high mortality.
• It is difficult to predict confidently which patients will benefit from aggressive and prolonged ICU treatment or in whom such treatment is futile.
• Early initiation of NIV may prevent intubation and improve the likelihood of survival.
• In the absence of contraindications, the current literature would suggest that NIV appears to be the most sensible first step of respiratory support.

Key References

1. Hildebrand FL, Jr et al. Pulmonary complications of leukemia. Chest 1990; 98(5): 1233-9.
2. Ferra C et al. Outcome and prognostic factors in patients with hematologic malignancies admitted to the intensive care unit: a single-center experience. Int J Hematol 2007; 85(3): 195-202.
3. Kroschinsky F et al. Outcome and prognostic features of intensive care unit treatment in patients with hematological malignancies. Intensive Care Med 2002; 28(9): 1294-300.
4. Rabbat, A et al. Prognosis of patients with acute myeloid leukaemia admitted to intensive care. Br J Haematol 2005; 129(3): 350-7.
5. Ewig S et al. Pulmonary complications in patients with haematological malignancies treated at a respiratory ICU. Eur Respir J 1998; 12(1): 116-22.
6. Pene F et al. Outcome of critically ill allogeneic hematopoietic stem-cell transplantation recipients: a reappraisal of indications for organ failure supports. J Clin Oncol 2006; 24(4): 643-9.
7. Rabitsch W et al. Respiratory failure after stem cell transplantation: improved outcome with non-invasive ventilation. Leuk Lymphoma 2005; 46(8): 1151-7.
8. Hilbert G et al. Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med 2001; 344(7): 481-7.

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