This study demonstrates an improved survival for HIV infected patients with PCP who require admission to the ICU. Although overall mortality was 53%, mortality rates at this treatment centre have fallen since mid 1996. Independent predictors of mortality in this study were the year of diagnosis of PCP, the age of the patient, and the need for mechanical ventilation and/or development of pneumothorax. In multivariate analysis these factors remained significant. Overall survival from PCP has improved during the last two decades.38,39
Morris et al28
suggested that improved survival among HIV infected patients with severe PCP who were admitted to the ICU was related to the patient's receipt of HAART which became available in the UK in mid 1996. In our institution, mortality from severe PCP requiring admission to the ICU fell from 71% before mid 1996 to 34% subsequently, despite the fact that no patient received HAART before or during admission to the ICU. These survival figures are similar to those reported by Morris et al
In our study the observed improved survival cannot be ascribed to HAART.
Over the last decade there have been several changes in the ICU management of patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) which have positively impacted on survival.40,41
In particular, the use of lower tidal volumes and higher levels of positive end expiratory pressure for mechanical ventilation are associated with better outcomes.40,41
With these interventions survival from ARDS has improved from 41–52% before 1991 to 60–75% in 1993 and subsequently.40,41
This centre's strategy for management of mechanically ventilated patients with ALI/ARDS changed soon after publication of data from Hickling et al
which showed a reduced mortality rate if low tidal volume ventilation with permissive hypercapnia was used.42
Thus, by early 1996 our centre allowed mechanically ventilated patients with ALI/ARDS to tolerate greater levels of hypoxaemia and permissive hypercapnia. Additionally, mechanically ventilated patients were less frequently paralysed and less intravenous fluid was administered to critically ill patients than previously. This suggests that the observed improvement in survival from severe PCP reflects improvements in ICU management of severe respiratory failure rather than changes in the specific management of PCP.
The introduction and uptake of HAART in mid 1996 was associated with a marked reduction in AIDS events and mortality.43
This was accompanied by a changed perception among clinicians caring for patients with HIV infection such that they were more likely to refer to the ICU patients with severe PCP, as shown by the results from the last quarter of this study where a greater proportion of patients with PCP were admitted to the ICU. Throughout the study period there were no changes in clinical practice, as bronchoscopy with BAL was used as the exclusive diagnostic modality and no transbronchial biopsies (with the attendant risk of pneumothorax) nor open lung biopsies were performed. First line treatment was co‐trimoxazole, regardless of disease severity, and adjuvant corticosteroids had been introduced in late 1989 for those with Pao2
<9.3 kPa. However, among those surviving severe PCP there was a trend (which did not reach statistical significance) for the duration of ICU stay to be longer after mid 1996, perhaps reflecting treatment optimism among clinicians.
This study has two weaknesses. Firstly, only patients with microscopically confirmed PCP were included in the analysis. Those with a presumptive diagnosis and those who were treated empirically were excluded.33
Many of these latter patients were too sick to undergo bronchoscopy and may or may not have had PCP. No necropsy was performed in these patients, so uncertainty remains regarding their diagnosis. Secondly, the study population was small and is not based on a power calculation, yet is comparable in size to most of the studies of PCP in the ICU between 1981 and 2003 which have previously identified factors with prognostic significance.3,4,7,9,12,14,15,16,17,18,19,20,21,22,23,24,25,26,27
Nevertheless, interpretation of associations which are not statistically significant requires caution.
The suggestion that the observed improved prognosis in this study results from patients being more likely to be younger in recent years, to present with milder disease, and with a previous diagnosis of HIV is not supported by the study findings. No differences were seen over time in the age of patients, prior knowledge of their HIV serostatus, CD4 count and haemoglobin (both surrogates of advanced HIV infection), or median Pao2
at presentation. Throughout the study most of the patients presented with late stage HIV infection and PCP as their AIDS defining events. These data contrast with previous reports which have found that these prognostic factors are associated with death from PCP.3,4,7,9,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27
Two previous studies showed that the patient's prior receipt of PCP prophylaxis was associated with a poor outcome from severe PCP44,45
which was ascribed to acquired co‐trimoxazole resistance.45
By contrast, we were unable to demonstrate an association between patient's prior receipt of sulpha prophylaxis and death, although only nine patients (15%) had received co‐trimoxazole before presentation with PCP.
We identified no difference in outcome from severe PCP, regardless of the duration of specific treatment before admission to the ICU, as reported previously.44
These data contrast with other reports which hypothesised that, if a patient deteriorated within 5 days of starting anti‐Pneumocystis
treatment deterioration was occurring before adjuvant corticosteroids had become effective whereas, if deterioration occurred
5 days after starting treatment, patients in whom adjunctive corticosteroids had not worked and who were deteriorating despite maximal treatment had been selected.5,25
Our data suggest that referral to the ICU for management of severe PCP is appropriate even in patients deteriorating after >5 days of maximal treatment. In contrast to the study by El Sadr and Simberkoff7
which found better ICU outcomes for patients with PCP who deteriorated immediately after bronchoscopy and BAL, in the present study 16 patients (18%) admitted to the ICU within 24 hours of BAL had similar outcomes and showed no differences in Pao2
compared with the group as a whole.
The data from this study show improved survival from severe PCP in recent years in the context of the advent of HAART, and support early referral to the ICU of patients with severe PCP for management of respiratory failure. We failed to identify specific factors associated with a poor outcome such as patients failing first line treatment or a prolonged interval between hospitalisation and ICU admission which would preclude referral to the ICU for management. The observed improvements in outcome from the ICU for patients with severe PCP occurred in the absence of intervention with HAART, and probably reflect general improvements in ICU management of respiratory failure and ARDS rather than improvements in the management of PCP per se.