Acute respiratory failure (ARF) is a frequent disorder in cancer patients, commonly caused by several conditions including local effect of tumour, pulmonary infiltrates, pneumonia, acute respiratory distress syndrome and congestive heart failure. Supplemental oxygen and treatment of the underlying disorder is the mainstay of treatment for ARF, but severe cases require ventilatory support. Indeed, the need of this treatment modality is one of most frequent reasons for admission in the intensive care unit (ICU) for critically ill cancer patients.1–3

Mechanical ventilation (MV) is a primary method of organic function support in critically ill cancer patients treated in ICU, usually indicating a severe ARF (SARF). However, despite significant advances in ventilatory support and cancer management, MV remains associated with a high ICU, hospital and long-term mortality rate.4,5 In addition, the need of MV because of postoperative respiratory failure in operated cancer patients has been reported as high as 37%,6 which is associated with unfavourable outcomes as well.6,7

Although some previous studies have reported an association between SARF and VM with mortality in critically ill cancer patients, this relation is not clear because of methodological designs, participants’ characteristics and limitations of the studies. Conversely, the risk factors for SARF have not been consistently investigated in this type of patients. The study was aimed: 1) to identify the risk factors for severe acute respiratory failure requiring invasive mechanical ventilation (SARF-MV); and 2) to determine the effects of SARF-MV on clinical outcomes in cancer patients admitted in an oncological ICU.

This retrospective analysis showed that patients with cancer admitted to the ICU had a SARF-MV rate of 15.8%. The need of MV was higher in others studies, accounting for 35–50% of critically ill cancer patients.4,11,12 These differences with our results appear to derive from differences in the composition of the studied participants. In our study, most patients were admitted to the ICU for elective postoperative care. However, SARF-MV rate in medical patients was comparable to those reported in the international cohorts.13,14

We found that brain tumour, stage IV of cancer, sepsis at ICU admission and APACHE II score≥20 points were independently associated with SARF-MV. There are not studies in the literature evaluating risk factors for SARF-MV in critically ill cancer patients, so that this is the first study conducted under that purpose.

We observed an advanced cancer (tumour stage III or IV) rate of 63.3% for SARF-MV patients. Other authors found similar results. From 53 terminal cancer patients, Singh et al. found a MV rate of 77%.15 In patients with advanced solid cancer admitted to ICU, Xia and Wang observed that 57.4% of them required invasive MV.16 Thus, advanced oncological disease may be related with SARF-MV. This association is explained by several factors such as primary or metastatic pulmonary infiltrates, infectious complication secondary to immunosuppression, organ dysfunction, respiratory muscle weakness due to malnutrition, and drug-induced lung toxicity,4,17–19 all of which can predispose to SARF-MV.

Tumour site such as brain or lung can be a factor related with the need of MV in critically ill cancer patients, which is mainly explained by the local effect of the tumour. Patients with primary lung cancer or secondary pulmonary infiltrates are at high risk of MV as reported in previous studies.3,4 Pulmonary infiltrates predispose to infection, atelectasis, hemoptysis, pulmonary oedema, and pleural effusion,4,5 with gas exchange disturbances and a high respiratory muscles work increasing the risk of SARF-MV. On the other hand, we identified that brain tumour was associated with SARF-MV. The most frequent intracranial brain tumours are brain metastases, and all types of cancer can develop this complication. Primary o secondary brain tumours cause brain oedema, intracranial hypertension, alteration in consciousness level, and need of MV.20 In addition, some intervention such as neurosurgery or chemotherapy also would explain the higher rates of MV. Yutaka et al. observed that neurosurgery for brain tumour was associated with the need of MV.21 Flexman et al. reported similar results.22 Chemotherapy may have detrimental effects on central nervous system. Central nervous system neurotoxicity resulting from chemotherapy manifests as a wide range of clinical syndromes including acute, subacute, and chronic encephalopathies, posterior reversible encephalopathy, acute cerebellar dysfunction, chronic cognitive impairment, myelopathy, meningitis, and neurovascular syndromes.23 So that, MV would be required as supportive therapy for these clinical entities, which vary by causative agent, degree of severity, evolution, and timing of occurrence.

Sepsis affects the respiratory muscle because of muscular autophagy, dysfunction, decreased synthesis, and degradation of contractile proteins.24,25 More than fifteen years ago, Soares et al. identified that 63% of cancer patients requiring mechanical ventilatory support for more than 24h had sepsis.26 Recently, Yoo et al. also observed an infectious aetiology rate of 64% for cancer patients with diffuse pulmonary infiltrates causing acute respiratory failure admitted in ICU.4 We identified that sepsis was an independent factor associated with increased risk of SARF-MV, which suggests that sepsis acts as early prognostic factor in cancer patients admitted in ICU as observed in critically ill non-cancer patients.27

The APACHE II score was associated with SARF-MV. This model was developed for mortality prediction,28 but higher values indicate a greater severity of illness. Hence, the underlying pathophysiological disturbances may be associated with pulmonary damage and need of MV in critically ill cancer patients.

According to methodological design and included patients in previous studies, the ICU mortality rate and the hospital mortality rate in cancer patients range between 30% and 77%,1,15 and 30% and 56%,3,29 respectively. Over time, however, mortality rates have decreased.30

In ventilated cancer patients, some studies have shown an ICU mortality rate and a hospital mortality rate greater than 50%,11,26 and 65%,11,26,31 respectively. We observed a similar mortality rate for SARF-MV patients. SARF-MV is known as a risk factor for mortality in non-cancer patients32; however, their effect on outcomes has not been completely established for critically ill cancer subpopulation before.

MV is a temporary life-support method; however, despite the benefits of this therapy, many patients die after the initiation of mechanical ventilation, even though their arterial blood gases may have normalized. Mortality associated with SARF-MV can be associated with multiple factors including complications of ventilation such as barotrauma, oxygen toxicity, haemodynamic compromise, and ventilator-induced lung injury,33–35 as well as infectious complication such as ventilator-associated pneumonia.36 In cancer patients the local and systemic effects of tumour may play an additional role.

The length of hospital stay was similar between those patients with SARF-VM and those patients without SARF-VM. This is because higher hospital mortality rate among those subjects with SARF-VM, which in fact, died earlier. So that, the median length of hospital stay for ventilated patients was close to the median length of hospital stay for non-ventilated patients.

The present study has several shortcomings. First, our study was conducted at a single institution confined to oncological patients with a specialized ICU for critically ill cancer patients. Additionally, most patients were admitted to the ICU for postoperative care. Therefore, results of this study can only be applicable to other centres in which experienced intensivists are available for oncological and surgical critical care. Secondly, although data were extracted from a prospective database, given its retrospective nature, selection bias may have influenced our findings.

Results of this study demonstrated a significant association between some clinical factors with SARF-MV in cancer patients including primary tumour location, clinical stage of cancer, sepsis and APACHE II score. Our finding also highlights the powerful effect of SARF-MV on outcomes. However, this observation needs to be further evaluated by a multicentre, prospective study.

FDMB contributed in the Concepts, Design, Definition of intellectual content, Literature search, Clinical studies, Experimental studies, Data acquisition, Data analysis, Statistical analysis, Manuscript preparation, Manuscript editing, Manuscript review.

AGN contributed in the Design, Definition of intellectual content, Clinical studies, Data acquisition, Manuscript editing, Manuscript review.

MB contributed in the Literature search, Data analysis, Manuscript preparation, Manuscript editing, Manuscript review.

NAD contributed in the Literature search, Data analysis, Manuscript preparation, Manuscript editing, Manuscript review.

There are no conflicts of interest.