Safety of a 2-Day Antibiotic Regimen After Delayed Chest Closure Post Pediatric Cardiac Surgery.

BACKGROUND: There is no consensus for the length of prophylactic antibiotics after delayed chest closure (DCC) postcardiac surgery in pediatrics. In September 2014, our institution's pediatric cardiac intensive care unit changed the policy on length of prophylactic antibiotics after DCC from 5 days (control) to 2 days (study group). The objective of the study was to determine whether a 2-day course of antibiotics is as effective as a 5-day course in preventing blood stream and sternal wound infections in pediatric DCC. METHODS: Retrospective and prospective study. Primary end points included incidence of sternal wound infections and positive sternal imaging for infection. Surrogate markers of infection were collected at 4 time points. RESULTS: During the study period, 139 patients had DCC postcardiac surgery of which 110 patients were included for analysis, 54 patients in the control and 56 in the study group. There was no difference in total number of positive wound cultures/chest computed tomography (CT) findings (4/54 [7.5%] control vs 5/56 [8.9%] study group, P = .3), positive blood cultures (P = .586), median postsurgical length of stay (P = .4), or readmissions within 30 days postsurgery (P = .6). All secondary end points were similar in both groups except peak heart rate between weeks 2 and 4 (P = .041). CONCLUSION: Two days of prophylactic antibiotics is not inferior to 5 days of prophylactic antibiotics after DCC following pediatric cardiac surgery.

Procalcitonin Levels in Critically Ill Children With Status Asthmaticus.

BACKGROUND: Children with status asthmaticus (SA) often present with fever and are evaluated with chest radiographs (CXRs). In the absence of a confirmatory test for bacterial infection, antibiotics are started whenever there are radiological infiltrates or if there is a suspicion of pneumonia. We undertook this study to determine if serum procalcitonin (PCT) levels at admission are altered in critically ill children with SA. We also sought to determine if serum PCT levels are elevated in children with radiological infiltrates or in children who were treated with antibiotics. METHODS: This is a prospective single-center observational study evaluating serum PCT levels in critically ill children with SA. Study subjects included children 1 to 21 years old, admitted to a pediatric intensive care unit (PICU) with SA between March 2012 and April 2013. For the purposes of this study, patients whose CXRs were read by the radiologist as probable bacterial pneumonia was defined as having "radiological bacterial pneumonia," whereas patients who received antibiotics by the treating physician were defined as having "clinician-diagnosed pneumonia." RESULTS: Sixty-one patients with a median age of 7.3 years (interquartile range, 4-10 years) were included in the study. Fifty-one percent were male. Average Pediatric Risk of Mortality III score was 2.7 (SD, 2.9). Three patients (5%) were determined to have radiological bacterial pneumonia, whereas 52 (85%) did not. Six patients (10%) were indeterminate. The mean PCT level for all patients was 0.65 (SD, 1.54) ng/mL, whereas the median PCT level was 0.3 ng/mL. There was no significant difference in the mean PCT levels between the patients with and without clinician-diagnosed pneumonia (0.33 [SD, 0.36] vs 0.69 [SD, 1.67], P = 0.44). Using a PCT cutoff level of 0.5 ng/mL, a significant association was found with the presence of fever (P = 0.004), but no significant association was found with the presence of CXR infiltrates, radiological bacterial pneumonia, hospital length of stay, PICU length of stay, Pediatric Risk of Mortality III scores, or receipt of antibiotics. CONCLUSIONS: Serum PCT level was not elevated to greater than 0.5 ng/mL in 75% of this cohort of critically ill children with SA admitted to PICU. Presence of CXR infiltrates was not associated with higher PCT levels. Large clinical trials are needed to study the diagnostic and predictive role of PCT in this patient population.

A case of sinus pause induced by swallowing in the setting of olanzapine and guanfacine overdose.

Olanzapine, a second-generation antipsychotic, is used in both adult and pediatric populations for schizophrenia, bipolar disorder, and depression and has been associated with autonomic dysregulation in the setting of overdose. Guanfacine is a sympatholytic drug used in the treatment of attention deficit hyperactivity disorder and has also been associated with autonomic dysfunction. We present a unique case of a 17-year-old male who overdosed on 340 mg of olanzapine and 189 mg of extended-release guanfacine with a previously unreported adverse event. Specifically, five days after ingestion, he developed a 5-8 s sinus pause every time he forcefully swallowed any beverage, suggestive of a vagal hypersensitivity reaction. The report will review the autonomic dysfunction of olanzapine and guanfacine and management of asymptomatic sinus pause in the critical care setting.

Thenar Muscle Oxygen Saturation Levels: A Surrogate for Central Venous Oxygen Saturation?

PURPOSE: Shock is associated with increased tissue oxygen extraction. Near-infrared spectroscopy-derived thenar muscle tissue oxygenation (StO2) levels can provide an estimate of the oxygen supply-demand balance at the tissue level. We hypothesized that thenar StO2 levels would correlate with central venous oxygen saturation (ScvO2) levels, the gold standard for global tissue oxygen extraction in the body. METHODS: We prospectively enrolled 60 pediatric subjects admitted to pediatric intensive care unit or who underwent cardiac catheterization from September 2015 to March 2018. Thenar StO2 levels were measured using the InSpectra StO2 probe. Concurrent measurements of ScvO2 and peripheral tissue oxygenation (StO2) were achieved through simultaneous testing. For ScvO2, a central line placed in the superior vena cava was utilized for serum specimen collection, while the InSpectra probe recorded StO2 measurements from the thenar eminence of the patient's right hand. RESULTS: Sixty observations of thenar StO2 and ScvO2 levels were derived from 60 subjects. Mean thenar StO2 levels were 74.72 ± 11.18% and displayed significant correlation with paired ScvO2 measurements ( m = 72.17 ± 9.77%; ρ = 0.317, P = .018). Correlation was much more significant in subjects who were not on mechanical ventilatory support as opposed to those who were on it ( ρSORA = 0.496, PSORA = .003, vs ρVENT = 0.161, PVENT = .433). A thenar StO2 of 73% had a sensitivity of 80% and a specificity of 77.8% in predicting an ScvO2 of less than 65%. CONCLUSION: This is the first study to report correlation of thenar StO2 and ScvO2 levels in children. Our study results show a significant correlation between these levels. Thenar StO2 measurements may have a role in the bedside management of critically ill children in whom ScvO2 monitoring is not available.

Severe Direct Hyperbilirubinemia as a Consequence of Right Heart Failure in Congenital Heart Disease.

Adult literature documents increased cholestasis in right heart failure yet is poorly documented in the pediatric population. We describe three infants with congenital heart disease who developed significantly elevated direct bilirubin levels of 43, 23, and 12 mg/dL, respectively, in the absence of hepatic dysfunction. The common hemodynamic pathophysiology in these infants is right heart dysfunction with moderate to severe tricuspid regurgitation in the setting of low perfusion state. Right heart dysfunction in infants can result in severe conjugated bilirubin, likely as a consequence of venous congestion and can be used as an indirect marker of right heart dynamics.

End-organ recovery post-ventricular assist device can prognosticate survival.

BACKGROUND: This study examines our institutional ventricular assist devices (VADs) experience over two decades to understand trends towards predictors of mortality. METHODS: Retrospective study of patients aged 0-21years supported with a VAD from January 1996 to May 2015. Patient data was examined pre and post-VAD implant among survivors and non-survivors. RESULTS: Thirty-six patients identified (8 supported by Thoratec® VAD and 28 supported by EXCOR Berlin Heart®). Patient's diagnosis included dilated cardiomyopathy (DCM) (n=19,53%), congenital heart disease (CHD) (n=12,33%), and other (n=5,14%). Median age and body surface area (BSA) were 1.0years[0-7years] and 0.41[0.24-0.92], respectively. Survival to discharge was 75% with no deaths with DCM. The survival rate for patients with CHD was 42%. Univariate analysis showed diagnosis of CHD, smaller BSA and respiratory failure post-implant (Intermacs criteria) as risk factors for mortality. Median duration of VAD support was lower in non-survivors, 14 vs 63days (p=0.03). Renal function at time of transplant or death was normal/pRIFLE Risk category in 20(74%) of survivors and 2(22%) of non-survivors (p=0.06). Post-implant, peak total bilirubin in the first week trended lower in survivors (p=0.06). CONCLUSIONS: Persistent end-organ impairment in the first 2weeks after VAD placement could be a useful prognostic marker for survival to transplant.

Autophagy and mitochondrial biogenesis impairment contribute to age-dependent liver injury in experimental sepsis: dysregulation of AMP-activated protein kinase pathway.

Age is an independent risk factor of multiple organ failure in patients with sepsis. However, the age-related mechanisms of injury are not known. AMPK is a crucial regulator of energy homeostasis, which controls mitochondrial biogenesis by activation of peroxisome proliferator-activated receptor-γ coactivator-α (PGC-1α) and disposal of defective organelles by autophagy. We investigated whether AMPK dysregulation might contribute to age-dependent liver injury in young (2-3 mo) and mature male mice (11-13 mo) subjected to sepsis. Liver damage was higher in mature mice than in young mice and was associated with impairment of hepatocyte mitochondrial function, structure, and biogenesis and reduced autophagy. At molecular analysis, there was a time-dependent nuclear translocation of the active phosphorylated catalytic subunits AMPKα1/α2 and PGC-1α in young, but not in mature, mice after sepsis. Treatment with the AMPK activator 5-amino-4-imidazolecarboxamide riboside-1-ß-d-ribofuranoside (AICAR) improved liver mitochondrial structure in both age groups compared with vehicle. In loss-of-function studies, young knockout mice with systemic deficiency of AMPKα1 exhibited greater liver injury than did wild-type mice after sepsis. Our study suggests that AMPK is important for liver metabolic recovery during sepsis. Although its function may diminish with age, pharmacological activation of AMPK may be of therapeutic benefit.-Inata, Y., Kikuchi, S., Samraj, R. S., Hake, P. W., O'Connor, M., Ledford, J. R., O'Connor, J., Lahni, P., Wolfe, V., Piraino, G., Zingarelli, B. Autophagy and mitochondrial biogenesis impairment contribute to age-dependent liver injury in experimental sepsis: dysregulation of AMP-activated protein kinase pathway.

The Impact of Antithrombin III Use in Achieving Anticoagulant Goals in Pediatric Patients.

OBJECTIVES: To determine the percentage of patients with >10% reduction in heparin infusion rate within 48 hours of antithrombin III (ATIII) administration. Secondary objectives include the achievement of therapeutic anticoagulation and determining the days of subtherapeutic infusion prior to supplementation. METHODS: Retrospective chart review of 12 patients younger than 18 years of age who received ATIII concentrate supplementation while on continuous heparin infusion. Specific indications for heparin infusion therapy included extracorporeal membrane oxygenation (ECMO), treatment of thrombus, and post implantation of ventricular assist device(s). RESULTS: From time of heparin initiation to ATIII supplementation, patients spent a mean 4.9 ± 2.6 days of subtherapeutic infusion and required uptitration from a mean of 15.3 ± 4.4 units/kg/hr to a mean rate of 40.7 ± 9.5 units/kg/hr. 58.3% of the patients (n = 7) had a ≥10% reduction from the baseline heparin infusion rate within 48 hours of ATIII administration. Those patients considered responders (≥10% reduction from baseline rate) had a slightly higher mean baseline antithrombin level (76.3% ± 22.0% vs. 58.6% ± 2.7% in non-responders, p = 0.1) and were administered comparable doses of ATIII. ATIII supplementation did appear to increase the time of therapeutic anticoagulation within the 48 hours. CONCLUSIONS: Administration of ATIII is associated with >10% decrease in heparin requirements in more than half of the patients identified. In those patients deemed non-responders, there was a trend towards lower baseline antithrombin serum levels. Further studies are warranted to determine if the lack of response in some patients is due to inadequate dosing of ATIII or any patient-related factors.

The Impact of Catheter-Associated Urinary Tract Infection (CA-UTI) in Critically Ill Children in the Pediatric Intensive Care Unit.

Objective Catheter-associated urinary tract infections (CA-UTIs) comprise a significant proportion of hospital-acquired infections. However, the impact of CA-UTIs on important outcome measures, such as length of stay (LOS) and hospital charges, has not been examined in the pediatric intensive care unit (PICU) setting. Design Single-center, retrospective, case-matched, cohort study and financial analysis. Setting PICU in a tertiary-care children's medical center. Patients A total of 41 critically ill children with CA-UTIs and 73 critically ill children without CA-UTI, matched for age, gender, severity of illness, and primary admission diagnosis. Interventions None. Measurements and Main Results We compared the length of hospital stay (LOS in PICU and in hospital), mortality, and hospital costs in critically ill children with CA-UTIs and their matched controls. Critically ill children experiencing CA-UTI had significantly longer PICU LOS, hospital LOS, duration of mechanical ventilation, and mortality compared with matched controls without CA-UTI. The longer LOS resulted in higher PICU and hospital charges in this group. Conclusion Critically ill children with CA-UTI experience worse outcomes in the PICU compared with those without CA-UTI. Further studies on the impact of CA-UTI in the PICU are warranted.

Pediatric Longitudinal Clivus Fracture: Survival With Minimal Morbidity.

Longitudinal clivus fractures are rare in children, with only 5 cases published in the English literature to date. Clivus fractures, particularly longitudinal type, are associated with high mortality and morbidity. We report a case of longitudinal clivus fracture in a teenager with survival and complete neurological recovery. Our case is the first pediatric case of longitudinal clivus fracture caused by frontal impact and the first described pediatric case associated with transient diabetes insipidus (DI).

Near infrared spectroscopy (NIRS) derived tissue oxygenation in critical illness.

PURPOSE: Near infrared spectroscopy (NIRS) is an emerging technology that can measure tissue oxygen saturation levels (StO2) and has many potential clinical applications. NIRS devices have been studied in various disease states in the pediatric as well as adult populations. A review of this technology, with its potential applications and a review of current evidence is presented. PRINCIPAL FINDINGS: NIRS-derived regional tissue oxygen saturation (StO2) is superior to pulse oximetry as it measures tissue oxygen saturation and reflects imbalance between oxygen supply and local demand. Becoming more widely available, it still does not have a firmly established role due to its technical limitations and to the lack of large multi-centric randomized controlled studies necessary to confirm its utility, cost-benefit effectiveness and role in improving patient outcomes. CONCLUSION: Widespread availability, ease of use, non-invasive nature and continuous data display makes it an attractive option for bedside clinical monitoring.

Role of biomarkers in sepsis care.

Sepsis is one of the leading causes of mortality and morbidity, even with the current availability of extended-spectrum antibiotics and advanced medical care. Biomarkers offer a tool in facilitating early diagnosis, in identifying patient populations at high risk of complications, and in monitoring progression of the disease, which are critical assessments for appropriate therapy and improvement in patient outcomes. Several biomarkers are already available for clinical use in sepsis; however, their effectiveness in many instances is limited by the lack of specificity and sensitivity to characterize the presence of an infection and the complexity of the inflammatory and immune processes and to stratify patients into homogenous groups for specific treatments. Current advances in molecular techniques have provided new tools facilitating the discovery of novel biomarkers, which can vary from metabolites and chemical products present in body fluids to genes and proteins in circulating blood cells. The purpose of this review was to examine the current status of sepsis biomarkers, with special emphasis on emerging markers, which are undergoing validation and may transition into clinical practice for their informative value in diagnosis, prognosis, or response to therapy. We will also discuss the new concept of combination biomarkers and biomarker risk models, their existing challenges, and their potential use in the daily management of patients with sepsis.