Acute Respiratory Distress Syndrome in Immunocompromised Patients

Transcription

1 Acute Respiratory Distress Syndrome in Immunocompromised Patients Laveena Munshi, MD, MSc Critical Care Canada Forum November 2018 Interdepartmental Division of Critical Care Medicine Mount Sinai Hospital/University Health Network University of Toronto Toronto, Canada

2 Disclosures: No Relevant Financial Disclosures

3 Acute Respiratory Failure is the Leading Cause of Critical Illness in Immunocompromised Patients Wide spectrum of conditions that can render a patient immunocompromised ICU Mortality Across Immunocompromised Patients Over Time Number of living IC patients increasing Increasingly they are presenting to ICU Historic skepticism surrounding utility of ICU should be changing given marked improvement in ICU survival Mokart et al ICM 2014

4 While Mortality is Improving, It Remains High in ARDS Improved ICU Outcomes Attributable to: Advancements in cancer, rheumatologic disease, transplant and ICU care Infection control and infection Immunocompromised disease practices Status? Better patient selection Underlying Mortality remains HIGH Disease? ICU Management? IC ARDS Mortality 52% General ICU ARDS Mortality 36% Cortegiani et al ICM 2014

5 OBJECTIVES: 1. Classification of Immunocompromised Patients 2. Etiologies of AHRF and ARDS 3. Challenges Surrounding Diagnostic Work Up 4. Management and Prognosis

6 No Consensus Exists Surrounding Categorization of Immunosuppressed Conditions Neutropenia Oncology/ Leukemia HM Chemotherapy HSCT Intrinsic/ Genetic Mechanisms of Immunodeficiency Impaired B-cell mediated immunity (humoral immunity) Asplenia HIV Ig Deficiency Multiple Myeloma Transplant Cancer and Cancer treatment remains the leading cause of immunosuppression in critically ill patients Impaired T cellmediated immunity (cell mediated) Corticosteroids (transplant/autoimmune) HIV Induced Infectious Intrinsic Complications Acquired Treatment GNB Associated Corticosteroids MSSA Fungal Chemotherapy Infections Encapsulated Genetic Disorders Bacterial Immunoglobulin Organisms Deficiency Intracellular(Mycobacteri HIV a, Leukemia/Lymphoma/ Legionella, Nocardia) Fungal Multiple infections/pjp Myeloma Cytomegalovirus Asplenia

7 Unique Features of Immunocompromised Patients A large proportion tends to be young with few comorbidities Critical illness may develop as a consequence of definitive treatment of underlying disease (curative intent) Unusual disease processes can complication their treatment concurrent infections/non infections AHRF Etiology of AHRF/ARDS not always easily identified

8 ETIOLOGY of ARDS: What about the neutrophil?? Is it possible to develop ARDS in the setting of neutropenia? Neutrophil activation one of the hallmarks of ARDS Alveolar Macrophages Baude et al Lancet 1985 Tafoya et al Can Ther Advisor 2017

9 Etiologies Disease Induced vs. Treatment Induced Acute Hypoxemic Respiratory Failure ARDS

10 Causes of AHRF in Immunocompromised Patients Immunosuppressi on Infectious Complications Bacterial Pneumonia Opportunistic/Fungal Reactivation Latent Infections Viral Infections Neutrophil Recovery Disease Treatment Direct Lung Toxicity CRS Cumulative Dosing DAH Idiosyncrati c Reaction Cardiogenic IPS Undetermined ARDS

11 EMERGING THERAPIES THAT CAN INDUCED ARDS Immune-Check Point Inhibitors Chimeric Antigen Receptor T Cell Therapy What they do Reprogram T cells to recognize cancer cells Target monoclonal Ab directed against regulatory immune check point molecules that inhibit T cell activity Remarkable results in eliminating or sustaining cancer control (melanoma/lung) Pulmonary pneumonitis <10% Neurotoxicity Efficacy T cells collected and engineered to recognize proteins on cancer cells, reinfused into patient 50-90% rates of complete remission reported in B cell ALL and Adult LBCL Toxicities on target off tumor Treatment Severe Cytokine Release Syndrome /ARDS Neurotoxicity

12 AHRF/ARDS Following Hematopoeitic Stem Cell Transplantation INFECTIOUS (HIGHER RISK FOR FUNGAL)

13 Undetermined ARDS Represents 15-20% of Immunocompromised Patients with ARDS? Undetermined Infectious/Disease or Treatment Associated Condition Atypical Presentations Atypical Infectious Organisms Concurrent Infectious Processes Concurrent Infectious/Non Infectious?? Familiarity with Unique Non- Poor Infectious Etiologies Outcomes for Condition is Necessary? Separate Entity of Lung Injury with Targeted Treatment

14 Risk of death higher when cause of respiratory failure unknown; however diagnostic approach has remained controversial Fiberoptic Bronchoscopy and Bronchoalveolar Non Invasive Strategies CT Thorax Blood cultures, Lavage sputum samples No difference in rates of diagnosis or adverse events in diagnostic strategy with FOB and without FOB Non Invasive Strategies Induced Sputum?Lung Nasopharyngeal Aspirates Biopsy PCR viral blood tests Circulating Aspergillus galactomannan Serologic tests for Mycoplasma etc Urine antigen for Legionella Echocardiography Fiberoptic bronchoscopy Diagnosis in fewer than 50% Risk in hypoxemic patient Risks Associated with Biopsy in IC and thrombocytopenic pts Azoulay, E et al. Am J Resp Crit Care Med 2010

15 Management Do we manage immunocompromised patients differently? Should we manage immunocompromised patients differently?

16 Differences in Acute Respiratory Distress Syndrome Management in Immunocompromised Patients Antonelli & Hilbert 2000/2001 High Flow Nasal Cannula NIV compared to COT in 2015 IC was INVICTUS found Frat to decrease et Study al patients need for IMV/Mort Azoulay FLORALI Early AHRF Study et al Increased patients enthusiasm No HFNC differences vs. COT in for vs IMV NIV HIGH or Early Mortality AHRF Study in IC ECLS Lemiale et al?? NIV vs. COT in IC patients Non Invasive Ventilation Noninvasive Ventilation HFNC lower death at ! Patients High rate of use of HFNC (pulmonary days compared edema/small/high to mortality) in control COT/NIV HFNC vs. COT in group IC patients Post Hoc-IC Early AHRF patients HFNC >NIV but not COT?Injurious No differences Tidal in Volumes IMV or Mortality Adapted from Ferguson, N et al Intensive Care Med 2012

17 Management ARDS Across NIV Patients, NIV Failure in 48% 80% 70% NIV Immunocompromised 21% 60% > NIV General ICU Pop 16% 50% 40% ARDS 30% 20% 10% 0% Mild ARDS Moderate ARDS Severe ARDS IMV NIV NIV failure

18 Historically NIV failure was associated with an increased mortality Rathi et al, JCC 2017

19 Factors Associated with NIV Failure and Mortality Risk Factors for Non-Invasive Oxygen Therapy Failure Demographic and Clinical Characteristics Hematologic malignancy, Allogeneic hematopoietic stem cell transplantation Pulmonary infection Prolonged duration of hospitalization prior to admission to ICU Critical Illness-Associated Features Greater severity of illness Worsened severity of ARDS Lack of physiologic response to non-invasive ventilatory therapies Vasopressors/Renal failure Tidal volume greater than 9 ml/kg 1 hour after initiation of NIV Bellani et al, Am J Resp Crit Care Med 2017 Risk Factors for Mortality after NIV PaO 2 /FiO 2 <150 ; Tidal Volume??

20 CO T Non-Invasive Oxygen Strategies in Acute Respiratory Failure for Immunocompromised Patients Severity of Acute Respiratory Failure PaO Dyspnea, Hypoxia, PaO 2 /FiO /FiO 2 PaO 2 /FiO Early Acute Respiratory Failure HFN XC HFN C? > NIV Time limited trial of NIV in select patients Frequent Re-assessment for Improved FiO2 Improved P/F Ratio Improved RR OR if PaO 2 /FiO 2 <200 and/or TV >9ml/kg at 1 hour consider intubation (Frat 2018) HFN C Acute Respiratory Distress Syndrome Mild ARDS Moderate ARDS IMV PaO 2 /FiO Severe ARDS Higher severity of illness, shock, vasopressors, renal failure, high tidal volumes on NIV, or PF <150 NIV Consider HFNC or NIV with a frequent Re-evaluation Adjuvant Strategies NMBA PRONE INO ECMO used at Same Frequency in Lung Safe in IC = non IC

21 Outcomes and complications of IC patients treated with ECMO for severe ARDS patients/8 years 42% weaned off of ECMO, 34% ICU survival, 30% 6-month survival HM significantly poorer outcomes vs. Transplant/Corticosteroids ECMO-related major bleeding/infections/vap were frequent Shorter time between ARDS and diagnosis of IC condition, plts, age, driving pressure pre-ecmo associated with 6 mo survival Realistic Oncologic/Therapeutic Prognosis, Early in IC state, Adequate Functional Status are imperative for ECMO consideration in this population

22 Immunocompromised Status (difficult to treat organisms, unclear etiologies) Should we manage them differently? We don t know. Underlying disease may lead to a lower threshold to limit care in ICU ICU Management? More susceptible to VALI? More susceptible to develop sarcopenia? Should we be more aggressive with investigations? Should we have a lower threshold to treat CMV? Is there a differential impact of NIV? Or need to prevent IMV?

23 Prognosis has improved markedly Historically mortality was high and associated with increased resource use Historic reluctance to admit pts to ICU is no longer justified Certain subgroups continue to do poorly

24 Demographics Age Mokart 2015, Nates 2017, Halpern 2017 Comorbidity Status Factors no longer associated with Number of comorbidities Azoulay 2013, Halpern 2017 Disease Allogeneic Hemapoietic Stem Cell Transplant Azoulay 2013, Mokart 2015 mortality >1 st line chemotherapy/lack of complete or partial remission Legrand 2012, Azoulay 2012 Lack of neutropenia recovery Darmon 2002, Bouchman 1999 ECOG 4 Soares 2010, Azoulay 2013, Wheatley GVHD/steroid refractory Groeger 1998, Groeger 1999, 1. Neutropenia Pene 2006, Afessa 2010, Burghi 2011, Benoit 2014, 2. Autologous bone Agarwal 2015 marrow transplant Lack of lifespan-extending treatment options, or less than 6 months of life expectancy Benoit 2015 Critical Illness 3. Type of hematologic malignancy Prolonged in hospital before ICU presentation/admission Azoulay 2013, Nates 2017 Cause of Critical Illness Acute Respiratory Failure/ Pene 2006, Azoulay 2013, Need for Invasive 4. Mechanical Stage Ventilation of disease Townsend 2013, Mokart 2014, Mokart 2015, Buckstein 2016, Nates 2017, Halpern 2017 Sepsis 5. Second line therapies Halpern 2017 Admission after cardiac arrest Azoulay 2013 Invasive Fungal Infections Azoulay 2013, Agarwal 2015 Halpern Blood transfusion requirements Neutropenic Enterocolitis Mokart 2015 Non-infectious cause of admission Legrand 2012 Organ infiltration by malignancy Azoulay Multidrug Management and organ resistant function bacteria Delay in Antibiotics >1 hour Mokart 2014 Delay in catheter removal in sepsis of unknown origin Legrand 2012 Continuous Renal Replacement Therapy Mokart 2015 Number of organs failed/apache III score >80 Nates 2017, Boyaci 2014, Azoulay 2013, Gill 2010 Neumann 2008, Soubani Age/Comorbid Conditions Poor Functional Status/Frailty Treatment Refractory-GVHD Non-Solid Tumor Azoulay, E et al Blood Reviews 2015 Severe ARDS?NIV Failure Organs Failed Invasive Fungal Infections

25 Future Considerations 1. Immunocompromised patients are heterogeneous group 2. Role of biomarkers in delineating categories and response to therapies 3. Improve diagnostic techniques 4. Evaluate differential response to AHRF/ARDS management 5. Better identify who benefits from NIV 6. Understand the impact of critical illness on ongoing care (oncology) and long term outcomes

26 Conclusions Infectious etiologies dominant causes of AHRF but need to be familiar with noninfectious causes of AHRF/ARDS unique to the population particularly in newer therapeutic era for cancer Diagnosis continues to remain a challenge with a large proportion of persistent undetermined ARDS NIV used in a higher proportion of pts than general IC while 60% success, failure may be associated with increased mortality and more data needed on who may benefit Prognosis has markedly improved more research is needed to understand if we can decreased the mortality gap through how we are managing IC patients and whether it should be different than general ICU population

27 Thank you

28 Non-Invasive Oxygen Selection Across Immunocompromised Patients with AHRF is Variable