Pharmacokinetics of cefazolin delivery via the cardiopulmonary bypass circuit priming solution in infants and children.

OBJECTIVES: Our aim was to describe the pharmacokinetics of cefazolin in paediatric patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) who received cefazolin for peri-operative surgical prophylaxis in addition to having cefazolin added to the CPB circuit priming solution. Secondary aims were to determine the pharmacodynamic exposure associated with the addition of cefazolin to the CPB priming solution and to assess whether a target cefazolin concentration range for the CPB priming solution could be identified. METHODS: A multicentre, prospective, open-label pharmacokinetic study was carried out in children from birth to 16 years of age undergoing cardiac surgery. RESULTS: Forty-one patients met the inclusion criteria and accounted for 492 samples for analysis. Cefazolin concentrations were best described by a one-compartment model with weight as a covariate on the volume of distribution (Vd) with allometric scaling. The mean ± standard deviation (SD) total body CL for the birth-6 month cohort was 0.009 ± 0.006 mL/min/kg with a mean ± SD Vd of 0.59 ± 0.26 L/kg, the mean ± SD total body CL for the 7 month-3 year cohort was 0.01 ± 0.005 mL/min/kg with a mean ± SD Vd of 0.79 ± 0.15 L/kg, and the mean ± SD total body CL for the 4-16 year cohort was 0.007 ± 0.004 mL/min/kg with a mean ± SD Vd of 3.4 ± 0.94 L/kg. The median cefazolin loss in the CPB circuit ranged from 78% to 95% and the median patient cefazolin concentration after CPB circuit detachment ranged from 92 to 197 mg/L. CONCLUSIONS: These data demonstrate that mixing cefazolin in the CPB circuit priming solution was effective in maintaining cefazolin serum concentrations during surgery. If this practice is utilized, re-dosing of cefazolin during the CPB run and upon CPB circuit detachment is most probably not needed. Larger pharmacokinetic studies are warranted.

Acquired acrodermatitis enteropathica due to zinc-depleted parenteral nutrition.

Well-known causes of zinc deficiency, also referred to as acrodermatitis enteropathica (AE), include defects in intestinal zinc transporters and inadequate intake, but a rare cause of acquired zinc deficiency discussed here is an iatrogenic nutritional deficiency caused by parenteral nutrition administered without trace elements. While zinc-depleted parenteral nutrition causing dermatosis of acquired zinc deficiency was first reported in the 1990s, it is now again relevant due to a national vitamin and trace element shortage. A high index of suspicion may be necessary to diagnose zinc deficiency, particularly because early clinical findings are nonspecific. We present this case of acquired zinc deficiency in a patient admitted to a pediatric intensive care unit for respiratory distress and atypical pneumonia, who subsequently developed a severe bullous eruption due to iatrogenic zinc deficiency but was treated effectively with enteral and parenteral zinc supplementation, allowing for rapid re-epithelialization of previously denuded skin.

Elevated Levels of Urinary Biomarkers TIMP-2 and IGFBP-7 Predict Acute Kidney Injury in Neonates after Congenital Heart Surgery.

Objectives This article investigated the utility of urine biomarkers tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) in identifying acute kidney injury (AKI) in neonates after congenital heart surgery (CHS). TIMP-2 and IGFBP-7 are cell cycle arrest proteins detected in urine during periods of kidney stress/injury. Methods We conducted a single-center, prospective study between September 2017 and May 2019 with neonates undergoing CHS requiring cardiopulmonary bypass (CPB). Urine samples were analyzed using NephroCheck prior to surgery and 6, 12, 24, and 96 hours post-CPB. All patients were evaluated using the Acute Kidney Injury Network (AKIN) criteria. Wilcoxon rank sum tests were used to compare the medians of the [TIMP-2*IGFBP-7] values in the AKIN negative and positive groups at each time point. Receiver operating characteristic curves were used to measure how well the [TIMP-2*IGFBP-7] values predict AKIN status. Results Thirty-six patients were included. No patients met the AKIN criteria for AKI preoperatively. Postoperatively, 19 patients (53%) met the AKIN criteria for AKI diagnosis: 13 (36%) stage 1, 5 (14%) stage 2, and 1 (3%) stage 3. None required renal replacement therapy. At the 24-hour time points, patients who met the AKIN criteria for AKI had a statistically significantly higher [TIMP-2*IGFBP7] values than the patients without AKI (1.1 vs. 0.27 [ng/mL] 2 /1,000) at 24 hours (adj- p = 0.0019). Conclusion AKI is a serious complication associated with adverse outcomes in patients undergoing cardiac surgery. [TIMP-2*IGFBP-7] urinary level 24 hours after CPB is a good predictor of AKI in this population.

Safety Checklist Implementation Did Not Reduce Central Venous Catheter Duration in Pediatric Cardiac ICU Patients.

The Center for Disease Control recommends prompt removal of nonessential central venous catheters (CVCs) to reduce the risk for central line-associated bloodstream infections. Safety checklists have been trialed to reduce nonessential CVC days, but pediatric studies are lacking. Our specific aim was to detect >10% reduction in mean CVC duration after implementation of a safety checklist addressing CVCs in our unit. METHODS: All patients admitted to the Congenital Cardiovascular Care Unit at New York University Langone Medical Center who had a CVC placed between January 1, 2012, and December 31, 2017, were included. We implemented a checklist addressing CVC use in our unit on June 7, 2013, and modified it on March 10, 2016. We analyzed quarterly mean CVC duration and postsurgical CVC duration over the study period using statistical process control charts. RESULTS: We placed 778 CVCs for 7,947 CVC days during the study period. We noted special cause variation from Q4 2013 to Q2 2014 and a centerline shift in mean CVC duration from 8.91 to 11.10 days in Q1 2015. In a subgroup analysis of the 657 lines placed in surgical patients, there was a centerline shift in mean CVC duration from 6.48 to 8.86 days in Q4 2013. CONCLUSIONS: Our study demonstrated an unexpected increase in mean CVC duration after the implementation of a safety checklist designed to decrease nonessential CVC days. Additional studies are needed to identify the ideal method to detect and remove nonessential CVCs and reduce the risk of preventable harm.

Early Mobilization in the Pediatric Intensive Care Unit: A Quality Improvement Initiative.

Mobilizing patients during an intensive care unit admission results in improved clinical and functional outcomes. The goal of this quality improvement project was to increase the percentage of patients in the pediatric intensive care unit (PICU) mobilized early from 62% to 80%. Early mobilization was within 18 hours of admission for nonmechanically ventilated (non-MV) patients and 48 hours for mechanically ventilated (MV) patients. METHODS: We collected data from September 15, 2015, to December 15, 2016, identified key drivers and barriers, and developed interventions. Interventions included the development of an algorithm to identify patients appropriate for mobilization, management of barriers to mobilization, and education on the benefits of early mobilization. The percentage of PICU patients mobilized early; the percentage of patients with physical therapy, occupational therapy (OT), speech-language pathology (SLP), and activity orders; identified barriers; PICU and hospital length of stay (LOS) and discharge disposition, were compared between the pre- and postintervention groups and the non-MV and MV subgroups. The MV subgroup was too small for statistical testing. RESULTS: All measures in the combined postintervention group improved and reached significance (<0.05), except for the percentage of SLP orders and discharged home. Percentage mobilized early increased 25%, activity orders 50%, physical therapist orders 14%, OT orders 11%, SLP orders 7%, and discharged home 6%. Hospital LOS decreased by 35%, and PICU LOS decreased by 34%. All measures in the postintervention, non-MV subgroup improved and reached significance (<0.05). CONCLUSIONS: This early mobilization program was associated with statistically significant improvements in the rate of early mobilization, activity and therapy orders, and hospital and PICU LOS.

Co-designed PICU Family Stress Screening and Response System to Improve Experience, Quality, and Safety.

OBJECTIVE: Evidence for successful and sustainable models that systematically identify and address family stress in the pediatric intensive care unit (PICU) remains scarce. Using an integrated improvement science and family engagement framework, we implemented a standardized family stress screening tool and response protocol to improve family experience and reduce family crises through the timely coordination of parent support interventions. METHODS: We conducted this improvement initiative in the 12-bed PICU of a children's hospital within a large, urban academic medical center. Our team, which included 2 family advisors, adapted a validated Distress Thermometer for use in pediatric intensive care. A co-designed family stress screening tool and response protocol were iteratively tested, refined, and implemented in 2015-2017. Process and outcome measures included screening and response reliability, parent satisfaction, and security calls for distressed families. RESULTS: Over the 18 months, the percentage of families screened for stress increased from 0% to 100%. Among families who rated stress levels ≥5, 100% received the recommended response protocol, including family support referrals made and completed within 24 hours of an elevated stress rating. From 2015 to 2017, PICU parent satisfaction scores regarding emotional support increased from a mean score of 81.7-87.0 (P < 0.01; 95% CI). The number of security calls for distressed families decreased by 50%. CONCLUSIONS: The successful implementation of a co-designed family stress screening tool and response protocol led to the timely coordination of parent support interventions, the improved family perception of emotional support, and reduced family crises in the PICU.

Community-Acquired MRSA Pericarditis and Mediastinitis in a Previously Healthy Infant.

Invasive community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections disproportionately affect children, but there are few pediatric reports of pericarditis and mediastinitis caused by CA-MRSA in previously healthy children. Here we report a severe case of CA-MRSA pericarditis with extension to the mediastinum and carotid sheath in a previously healthy 8-month-old infant who was successfully treated with surgical interventions and with a combination of daptomycin and vancomycin. The relatively indolent clinical course in this patient was notable given the significant extent of infection. This case highlights the potential virulence of CA-MRSA in previously healthy children and the importance of early diagnosis, prompt drainage, and appropriate antibiotic coverage.

Novel Use of an Ultrafiltration Device as an Alternative Method for Fluid Removal in Critically Ill Pediatric Patients with Cardiac Disease: A Case Series.

Fluid overload (FO) is a common complication for pediatric patients in the intensive care unit. When conventional therapy fails, hemodialysis or peritoneal dialysis is classically used for fluid removal. Unfortunately, these therapies are often associated with cardiovascular or respiratory instability. Ultrafiltration, using devices such as the Aquadex™ system (Baxter Healthcare, Deerfield, IL, USA), is an effective tool for fluid removal in adult patients with congestive heart failure. As compared to hemodialysis, ultrafiltration can be performed using smaller catheters, and the extracorporeal volume and minimal blood flow rates are lower. In addition, there is no associated abdominal distension as is seen in peritoneal dialysis. Consequently, ultrafiltration may be better tolerated in critically ill pediatric patients. We present three cases of challenging pediatric patients with FO in the setting of congenital heart disease in whom ultrafiltration using the Aquadex™ system was successfully utilized for fluid removal while cardiorespiratory stability was maintained.

Definitions and pathophysiology of sepsis.

Mortality rates for sepsis and septic shock have not improved in the past decade. The Surviving Sepsis Campaign (SSC) guidelines released in 2012 emphasize early recognition and treatment of sepsis, in an effort to reduce the burden of sepsis worldwide. This series of review articles will discuss the pathophysiology of sepsis; comorbidities, such as multiorgan dysfunction syndrome (MODS), acute respiratory distress syndrome (ARDS), and endocrine issues; and finally, management of sepsis and septic shock.