Clinical Rheumatology (2019) 38:3015–3023 https://doi.org/10.1007/s10067-019-04651-w ORIGINAL ARTICLE Mortality of patients with rheumatoid arthritis requiring intensive care: a single-center retrospective study Yael Haviv-Yadid1 & Yulia Segal2 & Amir Dagan3,4,5 & Kassem Sharif6 & Nicola Luigi Bragazzi7 & Abdulla Watad6 & Howard Amital6,8,9 & Yehuda Shoenfeld8,9,10,11 & Ora Shovman6,8,9 Received: 20 February 2019 /Revised: 10 June 2019 /Accepted: 18 June 2019 /Published online: 26 June 2019 # International League of Associations for Rheumatology (ILAR) 2019 Abstract Background Patients with rheumatoid arthritis (RA) are at a high risk for life-threatening conditions requiring admission to the intensive care unit (ICU), but the data regarding the outcomes of these patients is limited. The present study investigated the clinical characteristics and outcomes of RA patients admitted to an ICU. Methods This retrospective cohort study included RA patients admitted to the general ICU of the Sheba Medical Center during 2002–2018. The main outcome was 30-day mortality. Using Student’s t test, χ2, and multivariable analyses, we compared the demographic, clinical, and laboratory parameters of the survivors and the non-survivors. Figures with p value < 0.05 were considered statistically significant. Results Forty-three RA patients were admitted to the ICU during the study period (mean age, 64.0 ± 13.1 years; 74.4% female). The leading causes of ICU admission were infection (72.1%), respiratory failure (72.1%), renal failure (60.5%), and septic shock (55.8%). The 30-day mortality rate was 34.9%, with infection (9/15, 60%) as the most frequent cause. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were 19.7 ± 12.5 and 7.0 ± 4.5, respec- tively. Multivariable analysis showed that heart failure (p = 0.023), liver failure (p = 0.012), SOFA score (p = 0.007), and vasopressor treatment in ICU (p = 0.039) were significantly associated with overall mortality. SOFA score was linked with overall mortality (area under the curve (AUC) = 0.781 ± 0.085, p = 0.003) and mortality from respiratory failure (AUC = 0.861 ± 0.075, p = 0.002), while APACHE II score was only correlated with mortality from infection (AUC = 0.735 ± 0.082, p = 0.032). Conclusions Our study demonstrated a relatively high mortality rate among RA patients who were admitted to the general ICU. RA patients with risk factors such as heart failure, liver failure, elevated SOFA score, and vasopressor treatment in ICU should be promptly identified and treated accordingly. Key Points • The 30-day mortality rate of patients with RA that were admitted to the general ICU of a tertiary hospital was 34.9%. • The most common causes of ICU admission among patients with RA were infections and respiratory failure. Infections were the most common cause of death among these patients. • Patients with RA that present to the ICU with heart failure, liver failure, elevated SOFA score, and/or require vasopressor treatment in ICU should be promptly identified and treated accordingly. * Ora Shovman 7 School of Public Health, Department of Health Sciences (DISSAL), [email protected] University of Genoa, Genoa, Italy 1 Intensive Care Unit, Sheba Medical Center, Ramat Gan, Israel 8 Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, 52621 Ramat Gan, Israel 2 Department of Internal Medicine ‘T’, Sheba Medical Center, Ramat Gan, Israel 9 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 3 Department of Internal Medicine ‘B’, Assuta Ashdod Medical Center, Ashdod, Israel 10 Past incumbent of the Laura Schwarz-Kipp Chair for Research of 4 Rheumatology Unit, Assuta Ashdod Medical Center, Ashdod, Israel Autoimmune Diseases, Tel Aviv University, Tel Aviv, Israel 5 Ben-Gurion University of the Negev, Beer Sheva, Israel 11 I.M. Sechenov First Moscow State Medical University of the 6 Department of Internal Medicine ‘B’, Sheba Medical Center, Ramat Ministry of Health of the Russian Federation (Sechenov University), Gan, Israel Moscow, Russia 3016 Clin Rheumatol (2019) 38:3015–3023 Keywords Acute physiology and chronic health evaluation (APACHE) II score . Intensive care unit . Rheumatoid arthritis mortality . Sequential organ failure assessment (SOFA) score Introduction Material and methods Patients with autoimmune rheumatic disorders (ARDs) are at Population high risk for complications requiring admission to the inten- sive care units (ICUs) [1, 2]. The prevalence of different This is a single-center observational retrospective study con- ARDs in ICUs has changed in the past decades, and systemic ducted in the general ICU of the Sheba Medical Center in lupus erythematosus (SLE) has surpassed rheumatoid arthritis Tel-Hashomer, a tertiary referral hospital in Israel. Using com- (RA) as the leading autoimmune disease necessitating admis- puterized ICU discharge summaries, we analyzed the medical sion to ICU [1]. However, RA remains the second most prev- records of 43 patients who have fulfilled the American College alent ARD in ICUs and represents a challenge for the physi- of Rheumatology (ACR) 1987 or ACR 2010 criteria for RA cians. The majority of previous studies on ARDs patients in and were admitted to the general ICU during 2002–2018. RA ICUs analyzed mixed cohorts of patients with different dis- patients who were admitted to the other ICUs of the hospital eases that have distinct courses, mortality rates, and mortality- such as the cardiac, neurological, or pediatric ICUs were not associated factors. This heterogeneity in cohorts may partially included. The study fulfilled the ethical guidelines of the most explain the significant variability in the reported mortality recent declaration of Helsinki (Edinburgh, 2000) and received rates that range from 17 to 55%, and the wide spectrum of approval (No. 3233-16-SMC) by the local ethical committee. variables that may be associated with increased mortality [1]. Data regarding patient demographics (age and gender) and To date, few retrospective studies have investigated the clinical and laboratory parameters were obtained retrospec- clinical aspects and the prognostic features of RA patients in tively from patient charts and laboratory records. Among ICU [3–6]. One of these studies is a large population-based those who were admitted twice to the ICU, only the first ad- study from Canada which demonstrated that RA patients had a mission was considered. In addition, data regarding the overall higher risk for ICU admission in comparison with the general mortality rate in the general ICU was extracted from the com- population (HR 1.65; 95% CI 1.50–1.83) [3]. According to puterized records of Sheba Medical Center in Tel-Hashomer. this study, during 2000–2010, the yearly ICU admission rate The severity of the disease was assessed within 24 hours of RA patients was 1%, with a 10-year cumulative rate of 8%, after ICU admission using the “Acute Physiology and a figure that was 60% higher compared with that in the general Chronic Health Evaluation II” (APACHE II) [11] and the population. The most frequent reasons for ICU admission “Sequential Organ Failure Assessment” (SOFA) [12]scores. were ischemic heart disease (IHD) followed by infections [3]. The APACHE II score is calculated based on the age of the In the last decades, several therapeutic advancements have patient and 12 routine physiological measurements, including been achieved in the management of RA, and this led to a alveolar-arterial oxygen difference (AaDO2) or partial pressure decreasing mortality rate for the last 50 years [7]. Despite this, of oxygen in arterial blood (PaO2), depending on the fraction of RA patients still have a higher mortality risk compared with the inspired oxygen (FiO2), rectal temperature, mean arterial that in the general population [7]. With regard to the ICU pressure, arterial pH, heart rate, respiratory rate, serum sodium mortality rate, the data is relatively limited. In the Canadian and potassium, creatinine, hematocrit, white blood cell count, study [3], the mortality rate found in the RA cohort was not and Glasgow coma scale [11]. A score of 25 represents a pre- different from that in the general population admitted to the dicted mortality of 50% in the general ICU. The SOFA score is ICU. Another work from Israel investigated the 30-day sur- calculated using objective measures of organ dysfunction or vival rate of patients hospitalized in the ICU following sepsis failure in major organ systems, including respiratory, renal, car- and found that the mortality rate within the RA subgroup was diovascular, neurologic, liver, and coagulation systems. The 51.2%, similar to non-RA patients [6]. Previous studies have SOFA score ranges from 0 to 24, and higher scores predict described the course and the outcome of dermatomyositis, worse outcomes and higher mortality rates [12]. scleroderma, and vasculitis patients admitted to the general Mortality was defined as death within 30 days of ICU ad- ICU of a tertiary hospital in Israel [8–10]. The objective of mission. Survival was defined as being successfully trans- the current study is to analyze the clinical characteristics of ferred from the ICU into another department and either sur- RA patients admitted to the ICU between 2002 and 2018, to viving until day 30 in the hospital or being released from the investigate their clinical course and outcome, and to identify hospital and then having another medical entry recorded into