Adjunctive Options for Severe PCP. Dr Erica Shaddock Division of Pulmonology and Critical Care Charlotte Maxeke Johannesburg Academic Hospital

Transcription

1 Adjunctive Options for Severe PCP Dr Erica Shaddock Division of Pulmonology and Critical Care Charlotte Maxeke Johannesburg Academic Hospital

2 Is this topic still relevant?

3 Is this topic still relevant? Use of HAART Massive South Africa Department of Health ARV roll out Decreased mother to child transmission Co-trimoxazole prophylaxis

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5 Is this topic still relevant? PCP continues to be a common opportunistic infection in the HIV-infected population. Several studies have shown that between ¼ and 1/3 of all ICU admissions of HIV infected patients are due to PCP. Rapidly growing community of therapeutically immunosuppressed individuals at risk for PCP: - transplant patients - oncology and haematology patients - rheumatology patients

6 Before 1989 reports indicated that hospital survival rates were 20%. - many centres stopped considering these patients as good ICU candidates. Early 1990s showed hospital survival rates were higher, ranging from 40% to 54%. - due to use of adjunctive corticosteroids in severe PCP.

7 Later reports in 1990s suggested survival of patients with PCP and respiratory failure had not improved and was 25% -reflecting a poor outcome in patients who had failed adjuvant corticosteroids and who were admitted to the ICU >5 days after anti-pneumocystis treatment.

8 The changing face of PCP in ICU Before mid 1996 mortality 71% Post 1996 mortality 34% (p=0.008) Overall mortality 53% Miller, Thorax 2006

9 ICU mortality 29% If MV OR 14.8 risk of death 95% CI , p<0.001 Number of cases of PCP admitted to LA County-University of Southern California hospital Radhi BMC Infectious diseases 2008

10 Retrospective review HIV +ve and HIV ve patients 63.6% mortality Mean duration of MV was 14.9 days Boonsarngsuk, Int J of Infect Dis 2009

11 Outcomes of PCP with respiratory failure in HIV-negative patients In the first 7 days after ARF, the mortality rate was significantly higher in the HIV group (mortality 14.3% vs. 0%; p = 0.025) However, the in-hospital mortality rate was higher in the non-hiv group, although without statistical significance (66.7% vs. 57.1%; p = 0.606). Boonsarngsuk, Int J of Infect Dis 2009

12 Which patients are we talking about? FiO2 100%

13 Pneumocystis jirovecii

14 Thin section showing the presence of a large number of trophozoites (T) in the apical portion of a pneumocyte (P).

15 Why are these patients so hypoxic?

16 Massive V/Q mismatch Patients fit ARDS criteria

17 Factors associated with a poor outcome Age Poor oxygenation at admission (PaO2, or A-a O2 gradient) LDH low Hb low albumin Presence of bacterial and CMV co-pathogens Delay of >5 days in admission to ICU after starting specific anti-pneumocystis treatment, High APACHE II score Development of pneumothorax during ventilation.

18 Factors associated with a poor outcome Age Poor oxygenation at admission (PaO2, or A-a O2 gradient) LDH low Hb low albumin Presence of bacterial and CMV co-pathogens Delay of >5 days in admission to ICU after starting specific anti-pneumocystis treatment, High APACHE II score Development of pneumothorax during ventilation.

19 What can we do to improve outcomes? Correct diagnosis Correct treatment for 21 days - High dose trimethoprim sulfamethoxazole (TMP-SMX) OR - Primaquine mg/day PO daily PLUS Clindamycin 600 mg IV tds or qid or mg PO four times daily

20 Newer alternative treatments Caspofungin - Inhibits beta-d-glucan synthesis - No effect on the dominant trophic form - Add to TMP-SMX as part of initial therapy may provide synergism - Case reports shown its effectiveness as a salvage therapy and in patients who cannot tolerate first line treatment options.

21 Adjunctive corticosteroids Risk of respiratory failure in corticosteroid group in standard group (p=0.004) Risk of death in corticosteroid group standard treatment group (p=0.009) Rx : Prednisone 40mg bd X 5 days then 40mg dly X 5 days then 20mg dly X 11 days Bozzette NEJM 1990

22 Mode of Ventilation ARDSnet ventilation strategies Recruitable?? APRV assist pressure release ventilation High flow oxygen NIV

23 NIV in PCP Single centred study, 24 pts NIV, 24 pts Invasive ventilation NIV avoided intubation in 67% of pts Improved survival 100% vs 38% (p<0.001) NIV pnemothoraces 8.3% vs 37.5%, p=0.039 NIV group had mortality at discharge, at 2 months but disappeared by 6 months complications in NIV Confalonieri, Intensive Care Med 2002

24 Initiation of ARVs in ICU Retrospective cohort study at single centre Fifty-eight HIV-infected adults with PCP admitted to an ICU from % of patients were either receiving HAART or were started on therapy while hospitalized. Mortality in HAART group 25%, mortality in those not receiving therapy was 63% (p=0.03). Morris, AIDS 2003

25 Conclusions: Use of HAART is an independent predictor of decreased mortality in severe PCP and may represent a potential therapy to improve outcome. Morris, AIDS 2003

26 Problems with ARVs in ICU Consent Drug drug interactions Poor gut absorption Immune reconstitution syndrome Side effects

27 12 post mortem lung biopsies 1 July 2008 to 28 February men and 9 women. mean age was 34.7 years (range 24-46) mean CD4 count was 20.8 (range 1-68) cells/μl All specimens demonstrated typical PcP histopathology 9 had significant interstitial fibrosis. 3 had co-infection with CMV Shaddock et al S Afr J HIV Med 2012

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29 ECMO in Severe PCP ECMO is considered in patients with lifethreatening but potentially reversible respiratory failure. Since H1N1 epidemic and HAART availability ECMO has become an option in severe PCP patients.

30 ECMO in Severe PCP

31 Hyperoxia and PCP New and old evidence about the toxicity of too much oxygen, especially in ARDS literature Often PCP patients deteriorate after a few days of appropriate therapy

32 Hyperoxia and PCP Survival after sublethal hyperoxia. Beck, Infection and Immunity Oct. 2003

33 Immunoassay for apoptosis Scoring of immunohistochemical staining for caspase-3 Beck, Infection and Immunity Oct. 2003

34 Where to now?...

35 What if you still aren t getting it right? Dont strive for super normal PaO2 Palliation Sedation Counselling