By exploring a single centre’s experience of providing HFNCO to a population of ward-based haemato-oncology patients, we provide the first description of the treatment’s efficacy and safety in this setting. Approximately 67% of patients receiving HFNCO were admitted to ICU and of those, 40% required intubation and IMV. Device settings at initiation and duration of stay on the ward were predictors of ICU admission. Patients’ ICU and hospital mortality were 42% and 55% respectively and were associated with the underlying reason for initiating HFNCO. In approximately 22% of patients that were recognized as EoL, treatment was continued for more than 3 days. This is, to our knowledge, the first report in patients with HM receiving HFNCO outside of ICU.
We report that more than 60% of the patients who received HFNCO on the ward were subsequently admitted to ICU, a percentage that is higher than the average admission rate for HM patients requiring CCOS review in our institution (38%), probably because they represent a sicker sub-population.
Over the last decade, there has been a gradual increase in the proportion of HM patients that get admitted to ICU (7 to 75%).
3,24−26 A possible explanation for this is the shifting mentality in the critical care community away from the nihilistic perception that precluded consideration of these patients for advanced support.
27 When considering predictors of admission to critical care, previous publications have highlighted patient-related factors, such as the presence of GvHD.
25 In the present study, we identified a therapy-related factor, an initial FiO
2 lower than 0.4, to be associated with decreased ICU admission. The lower FiO
2 suggests that the patients who improved without going to ICU, probably had less severe ARF than those who needed admission. Unfortunately, the retrospective nature of the study meant that an accurate calculation of the pO
2/FiO
2 or the respiratory rate-oxygenation (ROX) index
28 was not possible. Nonetheless, the reported HFNCO failure rate in the present study (indicated by the need for ICU admission and escalation of respiratory support) was approximately 42%, which is consistent with other results.
17, 29One of the most challenging decisions in the management of patients with ARF is the decision to escalate respiratory support. Studies have shown that delayed intubation and IMV in patients receiving HFNCO is associated with increased ICU mortality.30 This issue becomes even more pertinent in the immunocompromised population, where delays in escalation can have even more detrimental effects.11 In the present study, the days that the patients received HFNCO on the ward had no impact on mortality, a finding that was also observed in a previous publication from the same institution.22 On the contrary, our results suggest that patients who stayed on the ward for more than 24 hours were less frequently admitted to ICU. This result needs to be interpreted with caution, as the design of the study precludes robust conclusions from being drawn regarding the role of HFNCO in averting ICU admissions. A possible explanation is that patients who didn’t deteriorate rapidly (within 24 hours) on HFNCO, were less critically ill, required less intensive organ support and had better survival. This is in accordance with previous publications highlighting the absence of improvement as an important factor of treatment failure and worse outcomes, both for HFNCO30 and NIV31,32
In recent years, both the ICU and hospital survival of patients with HM have improved significantly, as a result of combined technological and therapeutic advances in both medical fields.3,4 Our reported mortality in ICU (42%) and hospital (55%) are comparable to those mentioned elsewhere,4,33,34 as are the worse outcomes that follow IMV in this patient population. An interesting finding was that when HFNCO was initiated for hypoxia, ICU survival was 2.5 times more likely than when the indication was ‘softer’, i.e., for increased work of breathing or dyspnoea. This result can be explained by the fact that approximately 75% of the ARF was due to infection, even if the study wasn’t designed to specifically distinguish between infective aetiologies. A large, multicentre study has identified an undetermined cause of ARF as an independent factor for mortality,35 a finding that is repeatedly observed in the relevant literature.36 The poorer outcomes associated with an undetermined reason for ARF could be a result of delay that ensues from the failure to recognise and treat a pulmonary complication.
The use of HFNCO in immunocompromised patients was summarised in two recent systematic reviews, which both concluded that the treatment reduced the need for intubation but yielded conflicting results regarding the effect on mortality.18,19 Both those reviews only included patients that received HFNCO in ICU, which leaves the question about the efficacy of the therapy delivered on the ward, unanswered. This question becomes pertinent in countries with low ICU bed availability, such as the UK which has fewer (6.6) beds per 100,000 capita of population than other European countries.37 The introduction of CCOS aims, among other things, to avert inappropriate and ensure timely admissions to ICU, when required.38 Their positive impact on patients with HM has been highlighted in a few studies, without the focus ever being on the use of HFNCO. 22,24,26 The present study, supports the results of another, smaller one from the same institution22 and crystalises the need for trials that assess the efficacy of HFNCO in immunocompromised patients outside of ICU. In the meantime, it provided reassurance towards the safety of the intervention, as hospital, 90-day and 1-year survival was comparable between those patients that were admitted to ICU and those that remained on the ward.
The role of CCOS in EoL decision-making has been previously described previously in the HM population.22,39 However, the role of HFNCO in the last days of a patient’s life remains unknown, with concerns being raised around potential prolongation of the dying process without any meaningful benefit.40,41 Our findings show that approximately 20% of the patients that were recognised as EoL after review from CCOS, remained on HFNCO for more than 3 days after the TEP was set. As this study wasn’t designed to investigate the effect of HFNCO around EoL, it is difficult to ascertain the impact of this therapy on the dying process. However, the fact that no adverse events were reported suggests that the use of HFNCO doesn’t add significant discomfort around EoL and could potentially be used in this patient population as well. Interestingly, 17% of the patients that were identified as dying while receiving the treatment survived to hospital discharge.
The main limitations of the study are its retrospective nature, which precludes any inferred causality and the lack of control group, that would have allowed for direct comparisons. Despite this, our results are concordant with the published literature, which increases their validity and allows for strong associations to be drawn. Another limitation is that the observational nature of the study meant that the initiation of HFNCO and its escalation to other modes of respiratory support were dependent on the individual physician, as no protocol for administration of HFNCO exists in our institution. This is an inherent issue with retrospective, observational studies and only properly conducted randomised trials will adjust for potential confounders. Last, the use of HFNCO on the ward and the existence of an outreach team may not be commonplace in countries outside the UK. Nonetheless, the results of an Australian study has reported similar use of HFNCO outside the ICU,42 with support from an outreach service, increasing awareness about its safe use in this setting.