Improving Outcomes for Bronchiolitis Patients After Implementing a High-Flow Nasal Cannula Holiday and Standardizing Discharge Criteria in a PICU.

OBJECTIVES: To decrease length of high-flow nasal cannula (HFNC), PICU, and hospital length of stay (LOS). DESIGN: Quality improvement project. SETTING: A quaternary academic PICU. PATIENTS: Patients with bronchiolitis less than 24 months old. INTERVENTIONS: After initial implementation of a respiratory therapist (RT)-driven HFNC protocol (Plan-Do-Study-Act [PDSA] 1) in October 2017, additional interventions included adjusting HFNC wean rate (PDSA 2) in July 2020, a HFNC holiday (PDSA 3), and standardized discharge criteria (PDSA 4) in October 2021. MEASUREMENTS AND MAIN RESULTS: Duration of HFNC was used as the primary outcome measure. PICU LOS and hospital LOS were used as secondary outcome measures. Noninvasive ventilation use, invasive mechanical ventilation use, and 7-day PICU and hospital readmission rates were used as balancing measures. A total of 1,310 patients were included in this study. Patients in PDSA 2, PDSA 3 and 4 groups were older compared with pre-intervention and PDSA 1 (median of 9 and 10 mo compared with 8 mo; p = 0.01). HFNC duration decreased from 2.5 to 1.8 days after PDSA 1, then to 1.3 days after PDSA 2. PICU LOS decreased from 2.6 to 2.1 days after PDSA 1, 1.8 days after PDSA 2, and 1.5 days after PDSA 3 and 4. Hospital LOS decreased from 5.7 to 4.5 days after PDSA 1, 3.1 days after PDSA 2, and 2.7 days after PDSA 3 and 4. The use of noninvasive ventilation and invasive mechanical ventilation decreased throughout the study from 23.2% in the pre-intervention group, to 6.9% at the end of the project. The 7-day PICU and hospital readmission rates did not increase after implementation. The percentage of patients discharged from the PICU increased from 6.2% to 21.5%. CONCLUSIONS: Modifications to an existing RT-driven HFNC protocol and standardization of discharge criteria led to an improvement in outcomes for patients admitted to the PICU with bronchiolitis without an increase in adverse events.

The Heparin-Antithrombin Product: A Novel Value for Pediatric Extracorporeal Anticoagulation.

Hematologic complications are a source of morbidity and mortality for patients receiving extracorporeal membrane oxygenation (ECMO) support. There is no consensus strategy for monitoring anticoagulation for children supported with ECMO. This study evaluated a novel measurement of anticoagulation for children on ECMO. This was a single-center observational study of children supported with ECMO from 2015 to 2020. Each patient's current unfractionated heparin dose was multiplied by the current antithrombin III (AT) level to obtain a novel anticoagulation value, the heparin-antithrombin product (HAP). This value was compared with the heparin dose, AT, and activated clotting time (ACT) to predict anti-Xa value using linear correlation and decision tree methods. Data were obtained from 128 patients supported with ECMO. The HAP value was more highly correlated with anti-Xa level than heparin dose, AT level, and ACT. This correlation was highest in the neonatal population (r = .7). The variable importance metrics from the regression tree and random forest models both identified the HAP value as the most influential predictor variable for anti-Xa value. The HAP value is more highly correlated with the anti-Xa level than heparin dose, AT level, or ACT. Further research is needed to evaluate the effectiveness of the HAP value as a measurement of anticoagulation for children on ECMO.

Practice variation in the immediate postoperative care of pediatric liver transplant patients: Framework for a national consensus.

Advancements in critical care management have led to improvement in pediatric LT outcomes. However, there are no specific guidelines for many aspects of immediate post-LT care. This survey examines practice variations in the immediate postoperative care of pediatric LT patients at a large number of active US centers. This study is a cross-sectional survey of medical directors at PALISI-affiliated PICU in the United States. Centers performing pediatric LT were analyzed. Study measures included PICU practices regarding staffing, composition of the multidisciplinary team, early post-LT graft and patient monitoring, and anticoagulation. Of the thirty-five responding centers, twenty-five had a LT program which accounted for one-half of all US pediatric LTs. For analysis, centers were categorized by volume: high (7), medium (11), and low (7). The majority of PICU teams included an intensivist (80%) and hepatologist (84%). High-volume centers were less likely to have 24-hour in-house attending coverage (29%, compared to 64% (medium) and 100% (low)). High-volume centers were most likely to have pre-printed orders, but least likely to have written PICU management protocols. Most centers utilize routine daily liver ultrasound. Routine prophylactic anticoagulation, and the agent of choice, was variable. There is marked inconsistency in post-LT practice across PALISI centers in regards to team composition and immediate post-LT management. A national US consensus for post-LT PICU practices would facilitate outcomes research and would establish a platform for multicenter studies.

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.

Venoarterial Extracorporeal Membrane Oxygenation Versus Conventional Therapy in Severe Pediatric Septic Shock.

OBJECTIVES: The role of venoarterial extracorporeal membrane oxygenation in the treatment of severe pediatric septic shock continues to be intensely debated. Our objective was to determine whether the use of venoarterial extracorporeal membrane oxygenation in severe septic shock was associated with altered patient mortality, morbidity, and/or length of ICU and hospital stay when compared with conventional therapy. DESIGN: International multicenter, retrospective cohort study using prospectively collected data of children admitted to intensive care with a diagnosis of severe septic shock between the years 2006 and 2014. SETTING: Tertiary PICUs in Australia, New Zealand, Netherlands, United Kingdom, and United States. PATIENTS: Children greater than 30 days old and less than 18 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 2,452 children with a diagnosis of sepsis or septic shock, 164 patients met the inclusion criteria for severe septic shock. With conventional therapy (n = 120), survival to hospital discharge was 40%. With venoarterial extracorporeal membrane oxygenation (n = 44), survival was 50% (p = 0.25; CI, -0.3 to 0.1). In children who suffered an in-hospital cardiac arrest, survival to hospital discharge was 18% with conventional therapy and 42% with venoarterial extracorporeal membrane oxygenation (Δ = 24%; p = 0.02; CI, 2.5-42%). Survival was significantly higher in patients who received high extracorporeal membrane oxygenation flows of greater than 150 mL/kg/min compared with children who received standard extracorporeal membrane oxygenation flows or no extracorporeal membrane oxygenation (82%, 43%, and 48%; p = 0.03; CI, 0.1-0.7 and p < 0.01; CI, 0.2-0.7, respectively). Lengths of ICU and hospital stay were significantly longer for children who had venoarterial extracorporeal membrane oxygenation. CONCLUSIONS: The use of venoarterial extracorporeal membrane oxygenation in severe pediatric sepsis is not by itself associated with improved survival. However, venoarterial extracorporeal membrane oxygenation significantly reduces mortality after cardiac arrest due to septic shock. Venoarterial extracorporeal membrane oxygenation flows greater than 150 mL/kg/min are associated with almost twice the survival rate of conventional therapy or standard-flow extracorporeal membrane oxygenation.

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.

Solid Organ Transplantation for Children With Neurodevelopmental Disabilities-Ethical Considerations and a Call for Clarity.

Pediatric transplant centers are faced with the difficult task of maximizing the benefit of organs donated for transplantation while also ensuring that all patients undergoing transplant evaluation are fairly considered for this life-saving therapy. Children with neurodevelopmental disabilities are a complex patient population that on occasion may face the need for a solid organ transplant. Several concerns exist regarding transplantation in this population, yet standard transplant inclusion and exclusion criteria do not exist. Here we explore important factors regarding organ transplantation for children with neurodevelopmental disorders, including patient outcomes, quality of life considerations, and the fundamental ethical principles underlying this complex medical decision-making.

2009 pandemic influenza A (H1N1) in critically ill children in Cincinnati, Ohio.

OBJECTIVE: To compare the clinical features, management, and outcome of critically ill children with H1N1 to children with seasonal influenza from the previous three influenza seasons. DESIGN: The overall number of hospitalizations and the proportion cared for in the pediatric intensive care unit during the H1N1 epidemic period and the three previous influenza seasons (2007-2009) were determined. Medical records of patients admitted to the pediatric intensive care unit with H1N1 and seasonal influenza infection were reviewed. SETTING: Cincinnati Children's Hospital Medical Center, a large, 523-bed hospital located in Cincinnati. PATIENTS: Hospitalized children with laboratory-confirmed seasonal or H1N1 infection. MEASUREMENTS: Study variables included demographic data (age, gender), clinical factors (weight, Pediatric Risk of Mortality III scores, presenting signs and symptoms, comorbid conditions), management (length of mechanical ventilation, other treatments, including high-frequency oscillatory ventilatory support, inhaled nitric oxide, or extracorporeal membrane oxygenation), and outcome (overall and pediatric intensive care unit length of stay and mortality). MAIN RESULTS: Overall, 312 children were hospitalized with H1N1 and 222 with seasonal influenza from the three previous seasons. Children with H1N1 infection were significantly less likely to require pediatric intensive care unit care compared to children with seasonal influenza infection (14% vs. 24%, p = .02). Compared to children with seasonal influenza, children in the pediatric intensive care unit with H1N1 were older (median age in months 107 vs. 68, p = .05) and significantly more likely to have comorbid conditions (64% vs. 40%, p = .03), especially respiratory conditions. While there were no significant differences in severity of illness by Pediatric Risk of Mortality III scores or pediatric intensive care unit length of stay, children with H1N1 were significantly less likely to have acute respiratory failure (p = .04) or die compared to children with seasonal influenza infection (p = .03). CONCLUSIONS: In contrast to other studies, we found that critically ill children with H1N1 had a significantly lower morbidity and mortality compared to children with seasonal influenza.

The association of postoperative dexmedetomidine with pain, opiate utilization, and hospital length of stay in children post-Chiari malformation decompression.

OBJECTIVE: The aim of this study was to determine the association of postoperative dexmedetomidine with markers of pain in children undergoing Chiari malformation decompression. The authors hypothesized that patients receiving dexmedetomidine postoperatively would have decreased cumulative opiate use. They further hypothesized that there would be no difference in median pain scores, outcomes, or medication adverse events. METHODS: An IRB-approved retrospective cohort study of patients undergoing Chiari malformation decompression from December 1, 2015, to December 31, 2018, was performed. Patients aged 0-21 years who underwent intradural Chiari malformation decompression at a single institution were included. Data for those who used dexmedetomidine postoperatively were compared with those who did not use dexmedetomidine. The primary outcome was cumulative opiate use throughout hospitalization. Secondary outcomes included pain scores, ancillary medication use, adverse events, hospital and ICU length of stay, readmission rates, and hospital cost. RESULTS: The authors reviewed the records of 172 patients who underwent Chiari malformation decompression. Of those patients, 86 received dexmedetomidine postoperatively and 86 did not. Demographics were not different between the groups. Patients who received dexmedetomidine postoperatively received more doses of dexamethasone and were also more frequently exposed to dexmedetomidine intraoperatively (p = 0.028). Patients who received dexmedetomidine postoperatively used fewer morphine equivalents during their admission (1.02 mg/kg vs 1.43 mg/kg, p = 0.003). The patients who received dexmedetomidine postoperatively also had lower median pain scores on postoperative day 0 (0 vs 2, p < 0.001), lower median pain scores throughout the entire admission (1 vs 2, p < 0.001), and lower maximum pain scores recorded (6 vs 8, p = 0.005). Adjusting for steroid dose number and intraoperative dexmedetomidine exposure, postoperative dexmedetomidine remained associated with lower opiate dosing, lower pain scores on postoperative day 0, lower scores throughout hospital stay, and lower maximum pain scores. Patients who received dexmedetomidine had shorter hospital lengths of stay by 19 hours (p < 0.001). There were no statistically significant differences in medication adverse events or hospital costs between the two groups. CONCLUSIONS: Postoperative dexmedetomidine use was associated with decreased opiate use, lower pain scores, and shorter hospital length of stay in this cohort. Dexmedetomidine may be considered as a safe adjuvant medication that may have opiate-sparing effects for this patient population.

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.

Finding new therapies for sepsis: the need for patient stratification and the use of genetic biomarkers.

Reversing the immunoparalysis associated with septic shock remains a priority for improving the outcome of patients suffering from sepsis. The efficacy of future therapies may be better studied under an effective system of patient stratification. Gene expression biomarkers offer a mechanism by which patients may be appropriately stratified in such clinical trials.

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.

Conditional deletion of cardiomyocyte peroxisome proliferator-activated receptor γ enhances myocardial ischemia-reperfusion injury in mice.

The nuclear transcription factor peroxisome proliferator-activated receptor γ (PPARγ) is a key regulator of the inflammatory response to an array of biologic insults. We have previously demonstrated that PPARγ ligands reduce myocardial ischemia-reperfusion injury in rodents. In the current study, we directly determined the role of cardiomyocyte PPARγ in ischemia-reperfusion injury, using a model of conditional cardiomyocyte-specific deletion of PPARγ in vivo. In mice, α-myosin heavy chain-restricted Cre-mediated PPARγ deficiency was induced by tamoxifen treatment (30 mg/kg intraperitoneally) for 4 days (PPARγ mice), whereas controls included mice treated with the oil diluent vehicle (PPARγ mice). Western blot and histochemical analyses confirmed that expression of PPARγ protein was abolished in cardiomyocytes of mice treated with tamoxifen, but not with vehicle. After tamoxifen or vehicle treatment, animals were subjected to 30-min ligation of the left anterior descending coronary artery followed by 2-h reperfusion. In PPARγ mice, myocardial ischemia and reperfusion induced extensive myocardial damage, which was associated with elevated tissue activity of myeloperoxidase, indicating infiltration of neutrophils, and elevated plasma levels of troponin I when compared with PPARγ mice. Upon echocardiographic analysis, PPARγ mice also demonstrated ventricular dilatation and systolic dysfunction. Plasma levels of the proinflammatory cytokines interleukin 1ß and interleukin 6 were higher in PPARγ mice when compared with PPARγ mice. These pathological events in PPARγ mice were associated with enhanced nuclear factor κB DNA binding in the infarcted hearts. Thus, our data suggest that cardiomyocyte PPARγ is a crucial protective receptor and may prevent reperfusion injury by modulating mechanisms of inflammation.

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.