Open abdomen during extracorporeal membrane oxygenation is a safe and effective treatment for abdominal compartment syndrome.

BACKGROUND/PURPOSE: Decompressive laparotomy and open abdomen for abdominal compartment syndrome have been historically avoided during Extracorporeal Membrane Oxygenation (ECMO) due to seemingly elevated risks of bleeding and infection. Our goal was to evaluate a cohort of pediatric respiratory ECMO patients who underwent decompressive laparotomy with open abdomen at a single institution and to compare these patients to ECMO patients without open abdomen. METHODS: We reviewed all pediatric respiratory ECMO (30 days-18 years) patients treated with decompressive laparotomy with open abdomen at Riley Hospital for Children (1/2000-12/2019) and compared these patients to concurrent respiratory ECMO patients with closed abdomen. We excluded patients with surgical cardiac disease. We assessed demographics, ECMO data, and outcomes and defined significance as p = 0.05. RESULTS: 6 of 81 ECMO patients were treated with decompressive laparotomy and open abdomen. Open and closed abdomen groups had similar age (p = 0.223) and weight (0.286) at cannulation, but the open abdomen group had a higher reliance on vasoactive medications (Vasoactive Inotropic Score, p = 0.040). Open abdomen group survival was similar to closed abdomen patients (66.7%, vs 62.7%, p = 1). Open abdomen patients had lower incidence of ECMO complications (33.3% vs 83.6%, p = 0.014), but the groups had similar bleeding complications (p = 0.412) and PRBC transfusion volume (p = 0.941). CONCLUSION/IMPACT: Pediatric ECMO patients with open abdomen after decompressive laparotomy had similar survival, blood products administered, and complications as those with a closed abdomen. An open abdomen is not a contra-indication to ECMO support in pediatric respiratory patients and should be considered in select patients.

Outcomes of pediatric oncology and hematopoietic cell transplant patients receiving extracorporeal membrane oxygenation.

BACKGROUND/OBJECTIVES: There is controversy regarding the utilization of extracorporeal membrane oxygenation in pediatric patients with an underlying oncologic diagnosis or who have undergone hematopoietic cell transplant. We hypothesized that these patients have higher mortality, more bleeding complications, more blood product utilization, and a higher rate of new infections than the general pediatric intensive care unit population supported with extracorporeal membrane oxygenation. DESIGN/METHODS: This is a retrospective chart review at a single center quaternary care pediatric hospital including all pediatric intensive care unit extracorporeal membrane oxygenation patients from 2011 to 2016. Patients were categorized as either oncology/hematopoietic cell transplant or general pediatric intensive care unit. Patients from the cardiovascular intensive care unit or the neonatal intensive care unit were excluded. RESULTS: A total of 38 patients met inclusion criteria of which 7 were oncology/hematopoietic cell transplant patients. The oncology/hematopoietic cell transplant group had lower platelets at the start of extracorporeal membrane oxygenation (p = 0.02) but other pre-extracorporeal membrane oxygenation characteristics were similar. Extracorporeal membrane oxygenation survival was lower in the oncology/hematopoietic cell transplant group (29% vs 77%, p = 0.02). The incidence of bleeding complications and new infections did not differ. The oncology/hematopoietic cell transplant group received more platelets (median of 15.9 mL/kg/day (interquartile range 8.4, 36.6) vs 7.9 mL/kg/day (3.3, 21.9), p = 0.04) and fresh frozen plasma (14.0 mL/kg/day (3, 15.7) vs 1.8 mL/kg/day (0.5, 5.9), p = 0.04). CONCLUSION: Oncology and hematopoietic cell transplant patients had a higher mortality and received more blood products while on extracorporeal membrane oxygenation than the general pediatric intensive care unit patients despite similar pre-extracorporeal membrane oxygenation characteristics. Physicians should use caution when deciding whether or not to utilize extracorporeal membrane oxygenation in this population.

Association of BMI With Propofol Dosing and Adverse Events in Children With Cancer Undergoing Procedural Sedation.

OBJECTIVES: Obesity increases the risk of complications during pediatric procedural sedation. The risk of being underweight has not been evaluated in this arena. We therefore investigated the association of BMI with sedation dosing and adverse events in children across a range of BMIs. METHODS: A total of 1976 patients ages 2 to 21 years old with oncologic diagnoses underwent lumbar punctures and/or bone marrow aspirations. All children received a standard adjunctive dose of ketamine before sedation with propofol. Weight categories were stratified by BMI percentile: underweight <5%, normal weight 5% to 85%, overweight >85%, and obese >95%. Dosing and adverse events (hypoxia, apnea, bradycardia, or hypotension) were reviewed. RESULTS: There were no differences in propofol dosing for procedural sedation between patients who were normal weight and underweight. However, children who were overweight and those who were obese used less propofol compared with children who were normal weight (P < .01). Children who were underweight had a higher proportion of adverse events overall relative to those children of normal weight (P < .001). In contrast, there was not an increase in adverse events for patients who were overweight and obese. CONCLUSIONS: Children who are overweight and children with obesity who require deep sedation can undergo successful sedation with lower propofol dosing relative to children of a normal weight. This dosing strategy may help to mitigate the risks associated with sedating patients who are obese. Notably, children who were underweight had an increased rate of complications despite receiving an equal amount of sedation compared with patients who were normal weight. This should alert the clinicians to the risks associated with sedating children who are underweight.

Low serum albumin levels prior to pediatric allogeneic HCT are associated with increased need for critical care interventions and increased 6-month mortality.

Poor nutritional status in HCT patients is a negative prognostic factor. There are no pediatric studies evaluating albumin levels prior to HCT and need for critical care interventions. We hypothesized that pediatric patients with low albumin levels, routinely measured 30 days (±10 days) prior to allogeneic HCT, have a higher risk of critical care interventions in the post-transplant period. We performed a 5-year retrospective study of pediatric patients who underwent allogeneic HCT for any indication. Patients were categorized based on albumin level. Hypoalbuminemia was defined as <3.1 g/dL. A total of 73 patients were included, with a median age of 7.4 years (IQR 3.3, 13.2). Patients with hypoalbuminemia had higher needs for critical care interventions including non-invasive ventilation (44% vs 8%, P=.01), mechanical ventilation (67% vs 17%, P<.01), and vasoactive therapy (56% vs 16%, P=.01). Patients with hypoalbuminemia also had a higher 6-month mortality (56% vs 17%, P=.02). Our data demonstrate that children undergoing allogeneic HCT with hypoalbuminemia in the pretransplant period are more likely to require critical care interventions and have higher 6-month mortality. These findings identify an at-risk population in which nutritional improvements may be instituted prior to HCT in hopes of improving outcomes.

Appendicitis in childhood hematologic malignancies: analysis and comparison with typhilitis.

BACKGROUND/PURPOSE: Recognition of appendicitis in the child with hematologic malignancy may be difficult particularly in the setting of neutropenia and multiple medications causing an altered inflammatory response. Typhilitis may produce a similar constellation of clinical findings causing further diagnostic confusion. This review compares the relative frequency of these two conditions in children with hematologic malignancy with a focus on the clinical presentation, distinguishing features, surgical management, and outcome for patients with appendicitis. METHODS: This institutional review board-approved retrospective study evaluated 464 pediatric patients treated for hematologic malignancy at our institution from 1997 to 2003. From this cohort, we identified all children with a diagnosis of appendicitis or typhilitis. Data include demographics, clinical presentation, laboratory studies, and computed tomography (CT) scan findings. Groups were compared using the Fisher exact test. Significance was defined as P < .05. RESULTS: Eight (1.7%) of 464 children were diagnosed with typhilitis and 7 (1.5%) with appendicitis. There were no demographic differences between patients with appendicitis and typhilitis. Distinguishing clinical features in children with typhilitis included presence of fever and diarrhea. Clinical presentation in children with appendicitis was atypical in 5 of 7 cases yielding an incorrect preoperative diagnosis in all 5. Radiographic evaluation by CT scan accurately defined typhilitis, but not appendicitis. An operation was performed on all 7 children with appendicitis with no operative morbidity or mortality. CONCLUSIONS: Appendicitis and typhilitis occur with similar frequency in children with leukemia and lymphoma. Typhilitis is accurately diagnosed with clinical findings of fever, diarrhea, abdominal pain, and typical CT scan findings. Appendicitis tends to present with atypical findings, but can be successfully managed with standard surgical care.

Acquisition of apoptotic resistance in arsenic-induced malignant transformation: role of the JNK signal transduction pathway.

This study examined the role of signal transduction and apoptosis in malignant transformation induced by arsenic. Prior study showed that chronic arsenite exposure (500 nM, > or =18 weeks) induced malignant transformation in rat liver TRL 1215 cells. In the present work, these transformed cells were compared with passage-matched control cells. In addition, TRL 1215 cells were treated subchronically (up to 6 weeks) with arsenic (termed pre-transformed cells) to define events occurring prior to arsenic-induced transformation. Flow cytometry using annexin/FITC revealed that arsenic-induced apoptosis in transformed cells was markedly suppressed in comparison to control or pre-transformed cells. Ro318220, a strong activator of JNK, enhanced arsenite-induced apoptosis in transformed cells. Densitometric analysis of western blots revealed that the ratios of both Bcl-x(L)/Bax and Bcl-2/Bax were significantly increased (>2.5-fold) in arsenic-transformed cells. Transformed, pre-transformed and control cells were treated with arsenic and levels of phosphorylated extracellular signal-regulated kinases, ERK1/2, JNK1/2 and p38 were determined by western blot analysis. The three mitogen-activated protein kinases (MAPKs) were phosphorylated in a dose-dependent fashion in all cell types. However, the levels of phosphorylated JNK1/2 were markedly decreased in the arsenic-transformed cells, whereas in pre-transformed cells the levels of phosphorylated MAPKs remained the same as in control cells. JNK kinase activity was suppressed in transformed cells whereas Ro318220 enhanced this activity. Thus, during arsenic-induced malignant transformation resistance to apoptosis develops, possibly due to perturbation of the JNK pathway.