Akunne Ndika

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.

The safety of propofol sedation for elective nonintubated esophagogastroduodenoscopy in pediatric patients.

Objectives: To evaluate the safety of deep sedation provided by pediatric intensivists for elective nonintubated esophagogastroduodenoscopy. Design: Retrospective observational study. Setting: The sedation program at the Helen DeVos Children’s Hospital. Patients: A 4-year retrospective analysis was done on all outpatient elective pediatric esophagogastroduodenoscopy procedures performed in an intensivist run sedation program. Safety was examined by reviewing the occurrence of minor and major adverse effects during esophagogastroduodenoscopy sedation. Interventions were studied and reported. Interventions: None. Measurements and Main results: During the study period, 12,447 sedations were performed by the pediatric sedation program for various procedures. Two thousand one hundred forty-seven patients received 2,325 sedations (18.6%) for esophagogastroduodenoscopies performed for various indications. During the same time period, 53 (one for every 40 esophagogastroduodenoscopy sedations) were screened, found unsuitable for nonintubated sedation, and referred for general anesthesia. There were 2,254 sedations with propofol, 65 methohexital, five ketamine, and one fentanyl/midazolam sedation. Propofol sedation proved safe with a 2.1% prevalence of minor adverse events and no major events. Methohexital, on the other hand, had higher rate (p < 0.001) of minor events and one patient developed an anaphylactic reaction to its use. Regression analysis showed that other sedative agents were 8.6 times more likely to be associated with complications than propofol (odds ratio, 8.6; 95% CI, 4.1–18.2; p < 0.001). Conclusions: This study demonstrates that deep sedation for elective esophagogastroduodenoscopies can be provided safely in the appropriately screened patient by nonanesthesiologist physicians in a sedation program. These data suggest that propofol is a safe and effective agent for esophagogastroduodenoscopy sedation.

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 Childrens 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.

Intravenous Ferumoxytol in Pediatric Patients With Iron Deficiency Anemia

Background: Iron deficiency anemia (IDA) is common in children. Limited data exist on the efficacy and safety of ferumoxytol in children. Objective: To assess the efficacy of 10 mg/kg dose given over 15-60 minutes in correcting IDA and report any adverse drug reactions (ADRs). Methods: We conducted a retrospective review of all patients who received ferumoxytol infusions for the management of IDA by the Pediatric Blood Management Program between October 2010 and March 2015. Results: A total of 110 infusions were given to 54 patients. Compared with baseline preinfusion hemoglobin (Hb; 9.2 ± 1.9 g/dL), a significant rise was seen at 1 week and 4 weeks postinfusion (11.5 ± 1.5 and 11.8 ± 1.7 g/dL, respectively, P < 0.001). Also, a significant rise in serum ferritin at 1 week and 4 weeks postinfusion was seen (51 ± 71 vs 192 ± 148 and 89 ± 135 ng/mL, P < 0.001 and <0.035, respectively). Patients who concomitantly received erythropoietin had a significantly larger Hb rise from baseline than those who did not at 4 weeks (2.7 ± 2.2 vs 1.6 ± 1.1 g/dL, P < 0.017). ADRs included pruritus (n = 1), urticaria (n = 1), and multisymptom episodes (n = 3) that included shortness of breath, chest tightness, back pain, and epigastric cramping that responded to therapy with IV diphenhydramine and methylprednisolone. Conclusion: Ferumoxytol was effective in treating IDA in our small study. Slow infusion rate and close monitoring allowed early detection of the infrequent ADRs.