One-Year Outcome of Critically Ill Patients With Systemic Rheumatic Disease
2020; Elsevier BV; Volume: 158; Issue: 3 Linguagem: Inglês
10.1016/j.chest.2020.03.050
ISSN1931-3543
AutoresRomaric Larcher, Marc Pineton de Chambrun, Fanny Garnier, Emma Rubenstein, Julie Carr, Jonathan Charbit, Kévin Chalard, Marc Mourad, Matthieu Amalric, Laura Platon, Vincent Brunot, Zahir Amoura, Samir Jaber, Boris Jung, Charles‐Édouard Luyt, Kada Klouche,
Tópico(s)Rheumatoid Arthritis Research and Therapies
ResumoBackgroundCritically ill patients with systemic rheumatic disease (SRD) have benefited from better provision of rheumatic and critical care in recent years. Recent comprehensive data regarding in-hospital mortality rates and, most importantly, long-term outcomes are scarce.Research QuestionThe aim of this study was to assess short and long-term outcome of patients with SRD who were admitted to the ICU.Study Design and MethodsAll records of patients with SRD who were admitted to ICU between 2006 and 2016 were reviewed. In-hospital and one-year mortality rates were assessed, and predictive factors of death were identified.ResultsA total of 525 patients with SRD were included. Causes of admission were most frequently shock (40.8%) and acute respiratory failure (31.8%). Main diagnoses were infection (39%) and SRD flare-up (35%). In-hospital and one-year mortality rates were 30.5% and 37.7%, respectively. Predictive factors that were associated with in-hospital and one-year mortalities were, respectively, age, prior corticosteroid therapy, simplified acute physiology score II ≥50, need for invasive mechanical ventilation, or need for renal replacement therapy. Knaus scale C or D and prior conventional disease modifying antirheumatic drug therapy was associated independently with death one-year after ICU admission.InterpretationCritically ill patients with SRD had a fair outcome after an ICU stay. Increased age, prior corticosteroid therapy, and severity of critical illness were associated significantly with short- and long-term mortality rates. The one-year mortality rate was also associated with prior health status and conventional disease modifying antirheumatic drug therapy. Critically ill patients with systemic rheumatic disease (SRD) have benefited from better provision of rheumatic and critical care in recent years. Recent comprehensive data regarding in-hospital mortality rates and, most importantly, long-term outcomes are scarce. The aim of this study was to assess short and long-term outcome of patients with SRD who were admitted to the ICU. All records of patients with SRD who were admitted to ICU between 2006 and 2016 were reviewed. In-hospital and one-year mortality rates were assessed, and predictive factors of death were identified. A total of 525 patients with SRD were included. Causes of admission were most frequently shock (40.8%) and acute respiratory failure (31.8%). Main diagnoses were infection (39%) and SRD flare-up (35%). In-hospital and one-year mortality rates were 30.5% and 37.7%, respectively. Predictive factors that were associated with in-hospital and one-year mortalities were, respectively, age, prior corticosteroid therapy, simplified acute physiology score II ≥50, need for invasive mechanical ventilation, or need for renal replacement therapy. Knaus scale C or D and prior conventional disease modifying antirheumatic drug therapy was associated independently with death one-year after ICU admission. Critically ill patients with SRD had a fair outcome after an ICU stay. Increased age, prior corticosteroid therapy, and severity of critical illness were associated significantly with short- and long-term mortality rates. The one-year mortality rate was also associated with prior health status and conventional disease modifying antirheumatic drug therapy. Systemic rheumatic diseases (SRD), also known as connective tissue diseases, include various disorders, namely rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary Sjögren's syndrome, myositis, and systemic vasculitides.1Goldblatt F. O'Neill S.G. Clinical aspects of autoimmune rheumatic diseases.Lancet. 2013; 382: 797-808Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar All these diseases share common features such as difficult diagnosis, low incidence rate, multiorgan involvement, natural history of flare-up, treatment-induced immunosuppression, infectious, and cardiovascular complications. They remain associated with substantial morbidity and mortality rates.2Janssen N.M. Karnad D.R. Guntupalli K.K. Rheumatologic diseases in the intensive care unit: epidemiology, clinical approach, management, and outcome.Crit Care Clin. 2002; 18: 729-748Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar Consequently, 10% to 25% of patients with SRD require a hospital admission during the course of their disease, and one-third of them will need ICU admission.2Janssen N.M. Karnad D.R. Guntupalli K.K. Rheumatologic diseases in the intensive care unit: epidemiology, clinical approach, management, and outcome.Crit Care Clin. 2002; 18: 729-748Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar Godeau et al,3Godeau B. Mortier E. Roy P.M. et al.Short and long term outcomes for patients with systemic rheumatic diseases admitted to intensive care units: a prognostic study of 181 patients.J Rheumatol. 1997; 24: 1317-1323PubMed Google Scholar who studied 181 patients with SRD who were admitted to the ICU before 1990, reported a high in-hospital mortality rate (42.5% ) and an estimated five-year survival of 69% for discharged patients. During these last 20 years, survival in patients with SRD has improved due to advances in rheumatic care.4Murphy G. Lisnevskaia L. Isenberg D. Systemic lupus erythematosus and other autoimmune rheumatic diseases: challenges to treatment.Lancet. 2013; 382: 809-818Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar At the same time, implementation of management bundles, especially for acute respiratory distress syndrome and septic shock, have also improved the outcome of ICU patients.5Singer M. Deutschman C.S. Seymour C.W. et al.The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).JAMA. 2016; 315: 801-810Crossref PubMed Scopus (8305) Google Scholar,6Ranieri V.M. Rubenfeld G.D. et al.ARDS Definition Task ForceAcute respiratory distress syndrome: the Berlin Definition.JAMA. 2012; 307: 2526-2533Crossref PubMed Scopus (5023) Google Scholar Nonetheless, to date, it remains unclear whether the outcome of patients with SRD who have been admitted to the ICU has really changed. Most of the recent studies included a limited number of subjects and/or only investigated in-ICU deaths.7Faguer S. Ciroldi M. Mariotte E. et al.Prognostic contributions of the underlying inflammatory disease and acute organ dysfunction in critically ill patients with systemic rheumatic diseases.Eur J Intern Med. 2013; 24: e40-e44Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar, 8Brünnler T. Susewind M. Hoffmann U. Rockmann F. Ehrenstein B. Fleck M. Outcomes and prognostic factors in patients with rheumatologic diseases admitted to the ICU.Intern Med. 2015; 54: 1981-1987Crossref PubMed Scopus (19) Google Scholar, 9Dumas G. Géri G. Montlahuc C. et al.Outcomes in critically ill patients with systemic rheumatic disease: a multicenter study.Chest. 2015; 148: 927-935Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, 10Heijnen T. Wilmer A. Blockmans D. Henckaerts L. Outcome of patients with systemic diseases admitted to the medical intensive care unit of a tertiary referral hospital: a single-centre retrospective study.Scand J Rheumatol. 2016; 45: 146-150Crossref PubMed Scopus (20) Google Scholar, 11Beil M. Sviri S. de la Guardia V. Stav I. Ben-Chetrit E. van Heerden P.V. Prognosis of patients with rheumatic diseases admitted to intensive care.Anaesth Intensive Care. 2017; 45: 67-72Crossref PubMed Google Scholar Obviously, recent comprehensive data regarding in-hospital deaths and, most importantly, long-term outcome of patients with SRD who were admitted to the ICU are scarce. The aim of this study was therefore to assess short- and long-term outcome of patients with SRD who were admitted to an ICU in the era of advanced critical and rheumatic care and to determine prognostic factors. This observational retrospective cohort study was carried out from January 1, 2006, to December 31, 2016, in six French university hospital ICUs. An investigator on each site retrieved eligible patients by (1) screening SRD in ICU databases using the International Classification of Diseases, Tenth Revision, codes of SRD (in French: PMSI, programme de medicalisation des systemes d'information) and (2) reviewing all ICU discharge summaries. Patients were followed for at least one year after ICU admission. The Institutional Review Board of Montpellier University Hospital approved the study (No. 2018_IRB-MTP_07-12). All consecutive patients with SRD who were admitted to ICUs during the study period were included. SRD was defined according to previously published classification criteria for each SRD.12Hochberg M.C. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus.Arthritis Rheum. 1997; 40: 1725Crossref PubMed Scopus (8071) Google Scholar, 13Miyakis S. Lockshin M.D. Atsumi T. et al.International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).J Thromb Haemost. 2006; 4: 295-306Crossref PubMed Scopus (4571) Google Scholar, 14van den Hoogen F. Khanna D. Fransen J. et al.2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative.Arthritis Rheum. 2013; 65: 2737-2747Crossref PubMed Scopus (1562) Google Scholar, 15Lundberg I.E. Tjärnlund A. Bottai M. et al.2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups.Ann Rheum Dis. 2017; 76: 1955-1964Crossref PubMed Scopus (268) Google Scholar, 16Shiboski C.H. Shiboski S.C. Seror R. et al.2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome: a consensus and data-driven methodology involving three international patient cohorts.Ann Rheum Dis. 2017; 76: 9-16Crossref PubMed Scopus (504) Google Scholar, 17Alarcón-Segovia D. Cardiel M.H. Comparison between 3 diagnostic criteria for mixed connective tissue disease: study of 593 patients.J Rheumatol. 1989; 16: 328-334PubMed Google Scholar, 18Aletaha D. Neogi T. Silman A.J. et al.2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.Arthritis Rheum. 2010; 62: 2569-2581Crossref PubMed Scopus (4467) Google Scholar, 19Hunder G.G. Arend W.P. Bloch D.A. et al.The American College of Rheumatology 1990 criteria for the classification of vasculitis.Arthritis Rheum. 1990; 33: 1065-1067Crossref PubMed Scopus (581) Google Scholar, 20Jennette J.C. Falk R.J. Bacon P.A. et al.2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides.Arthritis Rheum. 2013; 65: 1-11Crossref PubMed Scopus (3140) Google Scholar, 21Davatchi F. Assaad-Khalil S. et al.International Team for the Revision of the International Criteria for Behçet's Disease (ITR-ICBD)The International Criteria for Behçet's Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria.J Eur Acad Dermatol Venereol. 2014; 28: 338-347Crossref PubMed Scopus (605) Google Scholar, 22Sieper J. Rudwaleit M. Baraliakos X. et al.The Assessment of SpondyloArthritis International Society (ASAS) handbook: a guide to assess spondyloarthritis.Ann Rheum Dis. 2009; 68: ii1-ii44Crossref PubMed Scopus (908) Google Scholar, 23Fautrel B. Zing E. Golmard J.-L. et al.Proposal for a new set of classification criteria for adult-onset still disease.Medicine (Baltimore). 2002; 81: 194-200Crossref PubMed Scopus (283) Google Scholar, 24Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999.Am J Respir Crit Care Med. 1999; 160: 736-755Crossref PubMed Scopus (1948) Google Scholar, 25Michet C.J. Relapsing polychondritis: survival and predictive role of early disease manifestations.Ann Intern Med. 1986; 104: 74Crossref PubMed Scopus (486) Google Scholar, 26Sipe J.D. Benson M.D. Buxbaum J.N. et al.Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines.Amyloid. 2016; 23: 209-213Crossref PubMed Scopus (331) Google Scholar Patients with SRD who were admitted to the ICU after scheduled surgery or trauma were excluded. Suicide attempts unrelated to neurologic involvement of SRD were excluded. We also excluded patients with SRD who had been treated for cancer with chemotherapy within a month before ICU admission. When a patient was admitted twice or more, only the first ICU admission was considered (Fig 1). Demographic data and morbidities were collected retrospectively. Patients' prior health status was evaluated by the Knaus scale27Knaus W.A. Zimmerman J.E. Wagner D.P. Draper E.A. Lawrence D.E. APACHE-acute physiology and chronic health evaluation: a physiologically based classification system.Crit Care Med. 1981; 9: 591-597Crossref PubMed Scopus (1520) Google Scholar and Charlson Comorbidity Index.28Charlson M. Szatrowski T.P. Peterson J. Gold J. Validation of a combined comorbidity index.J Clin Epidemiol. 1994; 47: 1245-1251Abstract Full Text PDF PubMed Scopus (3849) Google Scholar Characteristics and main treatment of SRD that included immunosuppressive therapy and corticosteroid (prednisone-equivalent daily-dose) within one month prior to ICU admission were also collected. Time elapsed from hospital to ICU admission was recorded and considered early if <24 hours. The main reason for ICU admission was classified as acute respiratory failure,6Ranieri V.M. Rubenfeld G.D. et al.ARDS Definition Task ForceAcute respiratory distress syndrome: the Berlin Definition.JAMA. 2012; 307: 2526-2533Crossref PubMed Scopus (5023) Google Scholar septic shock and sepsis,5Singer M. Deutschman C.S. Seymour C.W. et al.The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).JAMA. 2016; 315: 801-810Crossref PubMed Scopus (8305) Google Scholar other shock, acute kidney injury,29Kellum J.A. Lameire N. Aspelin P. et al.Kidney disease: Improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury.Kidney Int Suppl. 2012; 2: 1-138Google Scholar or neurologic dysfunction.30Teasdale G. Jennett B. Assessment of coma and impaired consciousness: a practical scale.Lancet. 1974; 2: 81-84Abstract PubMed Scopus (8690) Google Scholar Severity of disease was assessed 24 hours after admission with the Simplified Acute Physiology Score II (SAPS II)31Gall J.-R.L. Lemeshow S. Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study.JAMA. 1993; 270: 2957-2963Crossref PubMed Scopus (5116) Google Scholar and Sequential Organ Failure Assessment (SOFA) score.32Vincent J.L. Moreno R. Takala J. et al.The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure: on behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine.Intensive Care Med. 1996; 22: 707-710Crossref PubMed Scopus (6146) Google Scholar Information on the treatment that was instituted during ICU stay was collected, as was occurrence of acute kidney injury,29Kellum J.A. Lameire N. Aspelin P. et al.Kidney disease: Improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury.Kidney Int Suppl. 2012; 2: 1-138Google Scholar severe acute respiratory distress syndrome,6Ranieri V.M. Rubenfeld G.D. et al.ARDS Definition Task ForceAcute respiratory distress syndrome: the Berlin Definition.JAMA. 2012; 307: 2526-2533Crossref PubMed Scopus (5023) Google Scholar multidrug resistant bacteria colonization, or infection during ICU stay. ICU diagnoses were classified into one of the following categories: infection, SRD flare-up, and other. All diagnoses (SRD, infection, and others) were confirmed retrospectively and blindly by two investigators (R. L. and M. P. de C.). Whenever a discrepancy between reviewers appeared, diagnosis was discussed with a third reviewer (K. K.) until a consensus was achieved. ICU and hospital length of stay and outcome that included ICU, in-hospital, and one-year deaths were collected. The survival state and date and cause of death, if applicable, were collected with the use of electronic medical records of each hospital or by phone call to the family doctor or the patient or his family. Death by limitation of care was informed. Predictive factors of hospital and one-year mortality rate were then identified. Categoric data are summarized as numbers and percentages; continuous data are given as mean with SD or median with interquartile range (IQR). Data of patients who died after one year after ICU admission and data of patients who are lost to follow up within one year after ICU admission are censored. Survival one year after ICU admission is presented with Kaplan-Meier curve. We performed a Cox regression model to identify variables that were associated with in-hospital death and one-year survival prognostic factors. For the multivariable analysis, we selected the variables according to their clinical relevance and statistical significance in univariate analysis (P < .2). Then a conditional stepwise regression was used to select the most informative variables to include in the multivariable analysis. The hypotheses of log-linearity and hazard proportionality were assessed respectively with the use of regression splines and Schoenfeld residues. In the case of non-log-linearity (SAPS II, SOFA score), continuous covariates were discretized to the third quartile to select the most critically ill patients. Results of the Cox regression analysis are presented as hazard ratios and 95% CI. All tests were two-tailed with a statistical significance level of 5%. The analyses are stratified by center and performed using R statistical software (version 3.3.5; Free Software Foundation). Five hundred twenty-five patients (316 women; 60.2%) with a mean age of 56.1 years were included in the study (Fig 1). Mean Charlson index was at 3.7, and most patients had a Knaus scale of A or B (64.8%). The patients' characteristics are displayed in Table 1 and e-Table 1.Table 1Characteristics of the Study Population, Reasons of ICU Admission, Clinical Variables at ICU Admission, and Organ SupportsVariablesPopulation (N = 525)Characteristics Age, mean (SD), y56.1 (18.6) Female, No. (%)316 (60.2) Charlson comorbidity index, mean (SD)3.7 (2.5) Knaus scale, No. (%)A or B340 (64.8)C or D185 (35.2)SRD features SRD type,aEach patient fulfilled SRD diseases classification criteria. No. (%)Vasculitidesb84 small vessels vasculitides (28 granulomatosis with polyangiitis, 11 eosinophilic granulomatosis with polyangiitis, 12 microscopic polyangiitis, 13 cryoglobulinemia, 9 Goodpasture diseases, 4 IgA vasculitides, 7 undifferentiated vasculitides), 6 medium vessels vasculitides (6 polyarteritis nodosa), 28 large vessels vasculitides (24 giant cell arteritis and 4 Takayasu arteritis) and 11 Behçet disease.129 (24.6)Systemic lupus erythematosus109 (20.8)Rheumatoid arthritis99 (18.9)Systemic sclerosis46 (8.8)Myositis27 (5.1)Primary Sjogren's syndrome13 (2.5)Mixed connective tissue disease8 (1.5)Primary antiphospholipid syndrome12 (2.3)AA-amyloidosis8 (1.5)Miscellaneousc31 sarcoidosis, 30 spondylarthritis, 10 still disease, 3 relapsing polychondritis.74 (14.1) SRD-related organ involvement, No. %Lung184 (35.0)Kidney149 (28.4)Heart99 (18.9)Nervous system69 (13.1) SRD diagnosed in ICU, No. (%)75 (14.3) SRD previously diagnosed, No. (%)450 (85.7) Time elapsed from SRD diagnosis to ICU admission, median [IQR], y7.2 [2.6-16.3] Rheumatic treatmentNone, No. (%)120/450 (26.7)Corticosteroids, No. (%)292/450 (64.9)Corticosteroid daily dose, median [IQR], mg10.0 [5.0-30.0] Immunosuppressive treatment, No. (%)170/450 (37.8)Conventional DMARDs134 (29.8)Biologic DMARDs51 (11.3)IV immunoglobulins11/450 (2.4)ICU admission Reasons for admissionShock, No. (%)214 (40.8)Septic97 (44.3)Cardiogenic77 (35.9)Hypovolemic/hemorrhagic33 (15.4)Other7 (3.3)Acute respiratory failure, No. (%)167 (31.8)Neurologic dysfunction, No. (%)60 (11.4)Acute kidney injury, No. (%)39 (7.4)Sepsis/systemic inflammatory response syndrome, No. (%)45 (8.6) Scores, mean (SD)Simplified Acute Physiology Score II45.5 (21.5)Sequential Organ Failure Assessment7.2 (4.7)Glasgow12 (4.5)ICU management, No. (%) Vasoactive drugs258 (49.1) High flow nasal oxygen therapy47 (8.9) Mechanical ventilation328 (61.3)Noninvasive100 (19.0)Invasive282 (53.7) Renal replacement therapy161 (30.6) Extracorporeal membrane oxygenation63 (12.0)Venoarterial39 (4.6)Venovenous24 (7.4)Severity scores were calculated during the first 24 hours of ICU stay. DMARDs = disease modifying antirheumatic drugs (conventional: azathioprine, methotrexate, mycophenolate, anticalcineurin, cyclophosphamide, leflunomide, and biological: anti-tumor necrosis factor, tocilizumab, abatacept, anakinra, rituximab); IQR = interquartile range; SRD = systemic rheumatic diseases.a Each patient fulfilled SRD diseases classification criteria.b 84 small vessels vasculitides (28 granulomatosis with polyangiitis, 11 eosinophilic granulomatosis with polyangiitis, 12 microscopic polyangiitis, 13 cryoglobulinemia, 9 Goodpasture diseases, 4 IgA vasculitides, 7 undifferentiated vasculitides), 6 medium vessels vasculitides (6 polyarteritis nodosa), 28 large vessels vasculitides (24 giant cell arteritis and 4 Takayasu arteritis) and 11 Behçet disease.c 31 sarcoidosis, 30 spondylarthritis, 10 still disease, 3 relapsing polychondritis. Open table in a new tab Severity scores were calculated during the first 24 hours of ICU stay. DMARDs = disease modifying antirheumatic drugs (conventional: azathioprine, methotrexate, mycophenolate, anticalcineurin, cyclophosphamide, leflunomide, and biological: anti-tumor necrosis factor, tocilizumab, abatacept, anakinra, rituximab); IQR = interquartile range; SRD = systemic rheumatic diseases. Diagnosis of SRD was made during ICU stay in 75 patients (14.3%). In the remaining 450 patients, the median time elapsed from diagnosis to ICU admission was 7.2 years (IQR, 2.6-16.3). SRD were mainly vasculitides (24.6%), systemic lupus erythematosus (20.8%), and rheumatoid arthritis (18.9%). Excluding joint and skin, SRD-related organ involvements were lung (35%), kidney (28.4%), and heart (18.9%). More than two-thirds of the patients (366; 69.7%) exhibited at least two organ involvements. A corticosteroid treatment with a median prednisone-equivalent daily dose of 10 mg (IQR, 5-30) was already instituted in 292 of the 450 patients (64.9%), and an immunosuppressive treatment (in association or not) was already instituted in 170 of them (37.8%). Immunosuppressive therapy included mostly conventional disease-modifying antirheumatic drugs (DMARDs) in 78.8% and biologic DMARDs in 30%. Reasons for ICU admission were shock (40.8%, mainly septic and cardiogenic) and acute respiratory failure (31.8%) (Table 1). Iatrogenic complications were involved in 14.9% of admissions (78 patients); 111 patients (21.1%) needed an early ICU admission. As shown in Table 1, high mean SAPS II and SOFA scores at ICU admission underlined the severity of the patient's illnesses. During the ICU stay, 47 patients (8.9%) required high flow nasal oxygen therapy, and 328 patients (61.3%) required mechanical ventilation. Severe acute respiratory distress syndrome was diagnosed in 71 patients (13.5%) of which 23 required venovenous extracorporeal membrane oxygenation (4.4%). Also, 258 patients (49.1%) received vasoactive drugs, and 39 patients required venoarterial extracorporeal membrane oxygenation support for severe cardiogenic shock (7.4%). Acute kidney injury occurred in 232 patients, of whom 161 (69.4%) underwent renal replacement therapy (Table 1). During the ICU stay, hospital-acquired infections occurred in 106 patients (20.1%), mostly ventilator-associated pneumonia. Seventy-one patients experienced a multidrug-resistant bacterial infection or carriage, and 42 patients had viral reactivation (e-Table 2). Diagnoses of the event that led to ICU admission are displayed in Table 2. They were represented mainly by infection and SRD flare-up.Table 2Diagnoses of the Acute Event That Led to ICU Admission and OutcomesVariablePopulation (N = 525), No. (%) Infection205 (39.0) Pneumonia105 (51.2) Bloodstream infection29 (14.1) Intraabdominal infection23 (11.2) Urinary tract infection11 (5.4) Other19 (9.3) Sepsis of unknown origin18 (8.8) Documented infections124 (60.5)Bacteria93 (75.0)Virus19 (15.3)Fungus12 (9.7)Flare-up184 (35.0) Lung involvement59 (32.1) Heart involvement49 (26.6) Kidney involvement30 (16.3) Nervous system involvement28 (15.2) Other involvement18 (9.8)Other diagnosis136 (26.0) Cardiovascular event60 (44.1) Hemorrhage33 (24.3) Other43 (31.6)Outcomes In-ICU death125 (23.8) In-hospital death160 (30.5) One-year death198 (37.7) Open table in a new tab A diagnosis of SRD flare-up was determined in 184 patients (35%) that led to severe organ dysfunction that affected mainly lung (32.1%; 59 patients), heart (26.6%; 49 patients), and kidney (16.3%; 30 patients). SRD flare-up was treated with corticosteroids pulses in more than one-half of these patients (50.5%) associated or not with plasma exchange (28.8%), cyclophosphamide (24.5%), IV immunoglobulin therapy (9.8%), and rituximab (6.5%). A severe infection was considered as a main diagnosis in 205 patients (39%) of whom more than one-half (105/205) experienced pneumonia. Infection was documented in almost two-thirds of them (124/205; 60.5%), mostly bacterial. It is noteworthy that 385 patients (73.3%) received antimicrobial treatment when only 205 of them had been diagnosed with infection. The study population was followed for a median period of 486 days (IQR, 35-1,354] after ICU admission. Among 525 patients, 125 died in ICU, with a mortality rate at 23.8%. Thirty-five patients died before hospital discharge, which brought in-hospital mortality rate to 30.5% (Table 2; Fig 1). At ICU and hospital discharge, the survival probability was estimated at 76% (95% CI, 72-80) and 70% (95% CI, 65-74), respectively. Median ICU and hospital length-of-stay were 5 (IQR, 2-13) and 27 (IQR, 14-49) days. Of note, a limitation of life support was decided in 23.8% of deceased patients (e-Table 3). Among the 365 patients who were discharged from the hospital, 38 died one-year after admission to ICU, which brings mortality rates to 37.7% (Table 2; Fig 1). The survival probability one-year after ICU admission was 61% (95% CI, 57-66) (Fig 2). By univariate analysis, in-hospital and one-year deaths were associated statistically with age, Knaus scale C or D, and prior corticosteroid treatment. SOFA score ≥10; a SAPS II ≥50; the need for vasoactive drugs, invasive mechanical ventilation, or renal replacement therapy; and diagnosis of infection were associated significantly with in-hospital and one-year mortality rates (Table 3). Moreover, a diagnosis of infection while in the ICU was associated with worse outcome as compared with SRD flare-up (e-Table 4).Table 3Factors Associated With In-hospital and One-Year DeathsPredictive Factors of DeathUnivariate Analysis With Strata (Center), Hazard Ratio [95% CI], P ValueMultivariable Analysis With Strata (Center), Hazard Ratio [95% CI], P ValueIn hospital Age1.02 [1.01-1.03], < .011.02 [1.01-1.03], < .01 Knaus scale C or D1.52 [1.11-2.09], < .011.28 [0.91-1.78], .15 Prior corticosteroids1.80 [1.29-2.53], < .011.93 [1.37-2.73], < .01 Sequential Organ Failure Assessment score ≥103.05 [2.21-4.21], < .01… Simplified Acute Physiology Score II ≥503.34 [2.39-4.66], < .012.03 [1.40-2.96], < .01 ICU diagnosis of severe acute event……Flare-up (Reference)……Infection1.54 [1.05-2.26], .03…Other diagnosis1.59 [1.03-2.44], .03… Vasoactive drugs2.38 [1.67-3.39], < .01… Invasive mechanical ventilation2.59 [1.75-3.81], < .011.76 [1.14-2.71], .01 Renal replacement therapy2.41 [1.74-3.33], < .011.75 [1.23-2.48], < .01One-year after ICU admission…… Age1.02 [1.01-1.03], < .011.02 [1.01-1.03], <.01 Knaus scale C or D1.75 [1.32-2.31], < .011.35 [1.01-1.82], .04 Prior corticosteroids1.64 [1.22-2.21], < .011.59 [1.16-2.16], .01 Prior conventional DMARDs1.33 [0.98-1.82], .071.50 [1.09-2.07], <.01 Prior biologic DMARDs0.96 [0.59-1.54], .86… Sequential Organ Failure Assessment score ≥103.41 [2.56-4.54], < .01… Simplified Acute Physiology Score II ≥503.42 [2.55-4.54], < .011.72 [1.24-2.39], < .01 Diagnosis in ICU……Flare-up (Reference)……Infection1.72 [1.22-2.43], < .01…Other diagnosis1.68 [1.14-2.47], < .01… Vasoactive drugs2.67 [1.99-3.59], < .01… Invasive mechanical ventilation2.95 [2.15-4.05], < .012.15 [1.52-3.04], < .01 Renal replacement therapy2.87 [2.16-3.82], < .012.18 [1.60-2.97], < .01See Table 1 legend for the expansion of abbreviation. Open table in a new tab See Table 1 legend for the expansion of abbreviation. Multivariable analysis showed that age and previous corticosteroid treatment were associated independently with in-hospital and one-year deaths. Moreover, a SAPS II ≥50, the need for renal replacement therapy, or invasive mechanical ventilation were also associated factors with in-hospital and one-year mortality rates. In addition, multivariable analysis showed that Knaus scale C or
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