Therapeutic role of anakinra, an interleukin-1 receptor antagonist, in the management of secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction/macrophage activating syndrome in critically ill children*.

OBJECTIVES: Secondary hemophagocytic lymphohistiocytosis, macrophage activating syndrome, and sepsis share the same inflammatory phenotype leading often to multiple organ dysfunction syndrome needing intensive care. The goal of this article is to describe our experience with anakinra (Kineret), a recombinant interleukin-1 receptor antagonist, in decreasing the systemic inflammation. DESIGN: Retrospective case series. SETTING: The PICU at the Helen DeVos Children's Hospital (Grand Rapids, MI). PATIENTS: The records of eight critically ill children presumed to have secondary hemophagocytic lymphohistiocytosis at our institution between January 1, 2011, and July 31, 2012, were reviewed. INTERVENTIONS: All of the patients were treated with anakinra (Kineret) and in some cases systemic corticosteroids as first-line therapy for secondary hemophagocytic lymphohistiocytosis. MEASUREMENTS AND MAIN RESULTS: Patients had a median age of 14 years and a median Pediatric Risk of Mortality score of 11.5. Four were previously healthy and four had underlying diseases that could have made them susceptible to secondary hemophagocytic lymphohistiocytosis. Indications for PICU transfer were respiratory distress 50% (4 of 8), cardiovascular instability 37.5% (3 of 8), and chest pain (1 of 8). Five of the patients (62.5%) were mechanically ventilated and 62.5% (5 of 8) received vasoactive infusions. Inflammatory markers were assessed linearly at the start of therapy and 7 days later. Baseline C-reactive protein was 206 ± 50 mg/L (mean ± SEM) at the start of anakinra and decreased by 67.1% to 68 ± 36 mg/L (p = 0.03). Ferritin decreased by 63.8% to 3,210 ± 1,178 ng/mL (p = 0.30), and fibrinogen decreased by 42% to 158 ± 41 mg/dL (p = 0.03). Absolute neutrophil count (p = 0.38) and absolute lymphocyte count (p = 0.69) did not change significantly. No infections were attributed to anakinra therapy. One patient died long after treatment with anakinra while receiving pre-hematopoietic stem cell transplant chemotherapy. CONCLUSIONS: Anakinra could represent a promising therapeutic approach in these life-threatening disorders that are likely underdiagnosed and often difficult to treat.

Utilizing Closed Incisional Negative Pressure Therapy Reduces Peripheral Bypass Infection Rates Without Increasing Costs.

INTRODUCTION: We evaluated outcomes of closed incisional negative pressure therapy (ciNPT) on surgical site infection (SSI) rates in lower extremity bypass patients. We sought to determine whether or not the routine use of ciNPT is a cost-effective measure. METHODS: During a period from May 2018 to August 2018, our institution transitioned to the routine use of ciNPT for re-vascularization procedures. We retrospectively reviewed our outcomes before and after the initiation of ciNPT. Group A included patients from September 2017 to April 2018 without ciNPT and Group B included patients from September 2018 to April 2019 with ciNPT. Chi-squared analysis was performed and the p value was set at <0.05 to obtain statistical significance. Cost analysis was separately performed utilizing hospital metrics. RESULTS: There were a total of 102 patients in Group A and 113 patients in Group B. There was no difference in demographic information between the two groups. The overall SSI rate for Group A was 11.8% (12/102). Group B had an overall SSI rate of 3.5% (4/113; p=0.02). Deep infection rate for Group A was 7% (7/102) and for Group B was 1% (1/113; p=0.01). Cost analysis demonstrated a minimum of $62,000 in infection-related cost savings between both groups. CONCLUSIONS: ciNPT has had a profound effect on our practice and has resulted in a decrease in both deep and superficial infections. This has led to a significant cost-effective measure for our institution. We now routinely use ciNPT on all lower extremity bypass patients.

Red cell transfusions as an independent risk for mortality in critically ill children.

BACKGROUND: Severity of illness is an important consideration in making the decision to transfuse as it is the sicker patient that often needs a red cell transfusion. Red blood cell (RBC) transfusions could potentially have direct effects and interact with presenting illness by contributing to pathologies such as multi-organ dysfunction and acute lung injury thus exerting a considerable impact on overall morbidity and mortality. In this study, we examine if transfusion is an independent predictor of mortality, or if outcomes are merely a result of the initial severity as predicted by Pediatric Risk of Mortality (PRISM) III, Pediatric Index of Mortality (PIM2), and day 1 Pediatric Logistic Organ Dysfunction (PELOD) scores. METHODS: A single center retrospective study was conducted using data from a prospectively maintained transfusion database and center-specific data at our pediatric ICU between January 2009 and December 2012. Multivariate regression was used to control for the effects of clinical findings, therapy, and severity scores, with mortality as the dependent variable. Likelihood ratios and area under the curve were used to test the fidelity of severity scores by comparing transfused vs. non-transfused patients. RESULTS: There were 4975 admissions that met entry criteria. In multivariate analysis, PRISM III scores and serum hemoglobin were significant predictors of transfusion (p < 0.05). Transfused and non-transfused subjects were distinctly disparate, so multivariate regression was used to control for differences. Severity scores, age, volume transfused, and vasoactive agents were significantly associated with mortality whereas hemoglobin was not. A substantial number of transfusions (45 %) occurred in the first 24 h, and patients transfused later (24-48 h) were more likely to die compared to this earlier time point. Likelihood ratio testing revealed statistically significant differences in severity scoring systems to predict mortality in transfused vs. non-transfused patients. CONCLUSIONS: This study suggests that RBC transfusion is an important risk factor that is statistically independent of severity. The timing of transfusions that related strongest to mortality remained outside the purview of severity scoring, as these happened beyond the timing of data collection for most scoring systems.

Respiratory Impairment after Early Red Cell Transfusion in Pediatric Patients with ALI/ARDS.

Introduction. In the first 48 hours of ventilating patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), a multipronged approach including packed red blood cell (PRBC) transfusion is undertaken to maintain oxygen delivery. Hypothesis. We hypothesized children with ALI/ARDS transfused within 48 hours of initiating mechanical ventilation would have worse outcome. The course of 34 transfused patients was retrospectively compared to 45 nontransfused control patients admitted to the PICU at Helen DeVos Children's Hospital between January 1st 2008 and December 31st 2009. Results. Mean hemoglobin (Hb) prior to transfusion was 8.2 g/dl compared to 10.1 g/dl in control. P/F ratio decreased from 135.4 ± 7.5 to 116.5 ± 8.8 in transfused but increased from 148.0 ± 8.0 to 190.4 ± 17.8 (P < 0.001) in control. OI increased in the transfused from 11.7 ± 0.9 to 18.7 ± 1.6 but not in control. Ventilator days in the transfused were 15.6 ± 1.7 versus 9.5 ± 0.6 days in control (P < 0.001). There was a trend towards higher rates of MODS in transfused patients; 29.4% versus 17.7%, odds ratio 1.92, 95% CI; 0.6-5.6 Fisher exact P < 0.282. Conclusion. This study suggests that early transfusions of patients with ALI/ARDS were associated with increased ventilatory needs.