Objective: Hyperferritinemia is frequently seen in critically ill patients. A rather rare though life-threatening condition related to severely elevated ferritin is hemophagocytic lymphohistiocytosis. We analyze ferritin levels to differentiate hemophagocytic lymphohistiocytosis from other causes of hyperferritinemia in a mixed cohort of critically ill patients. Design: Retrospective observational study. Setting: Adult surgical, anesthesiologic, and medical ICUs of a university hospital. Patients: Critical care patients (≥ 18 yr old) admitted to any of the adult ICUs at Charité – Universitätsmedizin Berlin between January 2006 and August 2018 with at least one ferritin value and hyperferritinemia (≥ 500 µg/L). Interventions: None. Measurements and Main Results: Patients were categorized into hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other diagnoses. These were further categorized into 17 subgroups. Hemophagocytic lymphohistiocytosis diagnosis was based on Hemophagocytic Lymphohistiocytosis-2004 criteria and the HScore. Of 2,623 patients with hyperferritinemia, 40 were considered to have hemophagocytic lymphohistiocytosis (1.52%). Maximum ferritin levels were highest in hemophagocytic lymphohistiocytosis patients compared with all other disease groups (each p < 0.001). Sepsis and septic shock patients had higher maximum ferritin levels than patients with other diagnoses (each p < 0.001). A maximum ferritin value of 9,083 µg/L was at 92.5% sensitivity and 91.9% specificity for hemophagocytic lymphohistiocytosis (area under the curve, 0.963; 95% CI, 0.949–0.978). Of all subgroups with other diagnoses, maximum ferritin levels were highest in patients with varicella-zoster virus, hepatitis, or malaria (median, 1,935, 1,928, and 1,587 µg/L, respectively). Maximum ferritin levels were associated with increased in-hospital mortality (odds ratio, 1.518 per log µg/L [95% CI, 1.384–1.665 per log µg/L]; p < 0.001). Conclusions: This is the largest study of patients with ferritin available in a mixed ICU cohort. Ferritin levels in patients with hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other conditions were distinctly different, with the highest ferritin levels observed in hemophagocytic lymphohistiocytosis patients. Maximum ferritin of 9,083 µg/L showed high sensitivity and specificity and, therefore, may contribute to improved diagnosis of hemophagocytic lymphohistiocytosis in ICU. The inclusion of ferritin into the sepsis laboratory panel is warranted.

BackgroundNucleated red blood cells (NRBCs) in critically ill patients are associated with increased mortality and poor outcome. The aim of the present study was to evaluate the predictive value of NRBCs in patients with acute respiratory distress syndrome (ARDS).MethodsThis observational study was conducted at an ARDS referral center and included patients from 2007 to 2014. Daily NRBC counts were assessed and the predictive validity of NRBCs on mortality was statistically evaluated. A cutoff for prediction of mortality based on NRBCs was evaluated using ROC analysis and specified according to Youden’s method. Multivariate nonparametric analysis for longitudinal data was applied to prove for differences between groups over the whole time course. Independent predictors of mortality were identified with multiple logistic and Cox’ regression analyses. Kaplan–Meier estimations visualized the survival; the corresponding curves were tested for differences with the log-rank test.ResultsA total of 404 critically ill ARDS patients were analyzed. NRBCs were found in 75.5% of the patients, which was associated with longer length of ICU stay [22 (11; 39) vs. 14 (7; 26) days; p < 0.05] and higher mortality rates (50.8 vs. 27.3%; p < 0.001). Logistic regression analysis with mortality as response showed NRBC positivity per se to be an independent risk factor for mortality in ARDS with a doubled risk for ICU death (OR 2.03; 95% CI 1.16–3.55; p < 0.05). Also, NRBC value at ICU admission was found to be an independent risk factor for mortality (OR 3.25; 95% CI 1.09–9.73, p = 0.035). A cutoff level of 220 NRBC/µl was associated with a more than tripled risk of ICU death (OR 3.2; 95% CI 1.93–5.35; p < 0.0001). ARDS patients below this threshold level had a significant survival advantage (median survival 85 days vs. 29 days; log rank p < 0.001). Presence of a severe ARDS was identified as independent risk factor for the occurrence of NRBCs > 220/µl (OR 1.81; 95% CI 1.1–2.97; p < 0.05).ConclusionsNRBCs may predict mortality in ARDS with high prognostic power. The presence of NRBCs in the blood might be regarded as a marker of disease severity indicating a higher risk of ICU death.

Background: Hemophagocytic lymphohistiocytosis (HLH), an uncontrolled overactivation of the immune system, is well characterized in pediatric patients, yet, much less is known about this life-threatening condition in adult patients. As HLH is often complicated by organ failure, patients will require admission to the intensive care unit for organ support therapy. However, recognition of HLH patients in the intensive care unit (ICU) is challenged by the clinical overlap with sepsis. Here, we analyze HLH patients to better understand its clinical presentation, diagnosis, and treatment. Methods: For the purpose of this retrospective observational study, we searched for suspected and diagnosed adult HLH of all patients admitted to at least one adult surgical, anesthesiological or medical ICU between January 2006 and August 2018 at the university hospital Charité — Universitätsmedizin Berlin. All cases were reviewed by two HLH experts, who confirmed or declined the diagnosis. Results: Of 6,340 ICU patients with ferritin measurement, 40 suffered from HLH (0.63%). Of these, in-hospital mortality was 60.0% over all cases, which was highest in malignancy-associated HLH (71.4%). Infections were identified as most common triggers (42.5%). A variety of 19 different treatment strategies were applied. Non-survivors showed higher ferritin at diagnosis compared with survivors ( P = 0.021), which was also seen in multivariable analyses. A minimum ferritin of 4083 μg/L after diagnosis was most predictive for 30-day mortality (AUC 0.888, 95% CI 0.771–1.000; sensitivity 93.8%, specificity 78.9%). Conclusions: Mortality in adult HLH patients in the ICU is high, particularly in malignancy-associated HLH. Infections are the most frequent HLH triggers in critically ill patients. At present, there is no standardized treatment for HLH in adult patients available. Assessment of ferritin is valuable for diagnosis, prognosis, and treatment monitoring. Trial registration: The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.