Accuracy of delirium assessments in critically ill children: A prospective, observational study during routine care.

OBJECTIVES: The objectives of this study was to explore the accuracy of the Cornell Assessment for Pediatric Delirium (CAP-D), Pediatric Confusion Assessment Method for the Intensive Care Unit (pCAM-ICU), and Preschool Confusion Assessment Method for the Intensive Care Unit (psCAM-ICU) when implemented in routine care as delirium screening tools, and to assess patient characteristics and clinical variables that may affect their validity. DESIGN: This is a prospective observational study. SETTING: The study was conducted in a 36-bed, mixed paediatric intensive care unit (PICU) at an Australian tertiary hospital. PATIENTS: The study included critically ill children developmentally aged 6 months to 17 years, with a PICU length of stay >18 h. INTERVENTIONS: No interventions were provided in the study. MEASUREMENTS AND MAIN RESULTS: Patients were screened for delirium by their bedside nurse (CAP-D and pCAM-ICU/psCAM-ICU) once daily, for up to 5 d. Delirium status identified using screening instruments was compared with delirium diagnosis using the diagnostic criteria for delirium (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition). In this sample, the CAP-D retained its high sensitivity (91.3%) and good specificity (75.2%), whereas the psCAM-ICU and pCAM-ICU had moderate sensitivity (58.8% and 75.0%, respectively) and excellent specificity (89.8% and 84.9%, respectively). There was moderate agreement between the CAP-D and the psCAM-ICU (κ = 0.52, p < .001) and good agreement between the CAP-D and the pCAM-ICU (κ = 0.80, p < .01). CONCLUSIONS: Although the CAP-D, psCAM-ICU, and pCAM-ICU all appear promising in their validation studies, when implemented in routine care, their performance can be variable. The CAP-D performed well in routine clinical practice, but follow-up diagnosis is required to confirm delirium. The psCAM-ICU and pCAM-ICU both provide valuable, objective assessments of delirium in critically ill children; however, further evaluation of their implementation in routine clinical practice is needed.

Insertion, management, and complications associated with arterial catheters in paediatric intensive care: A clinical audit.

INTRODUCTION: Peripheral arterial catheters (PAC) are used for haemodynamic monitoring and blood sampling in paediatric critical care. Limited data are available regarding PAC insertion and management practices, and how they relate to device function and failure. This information is necessary to inform future interventional research. OBJECTIVES: The primary objective of this study was to describe PAC insertion and management practices, and associated complications. Secondary objectives were to determine patient and clinical characteristics associated with risk of PAC successful insertion and failure. METHODS: A prospective, observational study was conducted in the anaesthetic department and paediatric intensive care unit of a tertiary paediatric facility. Data were collected on PAC insertion, PAC management and PAC removal. Standard incidence and prevalence were calculated per 1,000 device days. Risk factors for multiple insertions and PAC failure were identified using Cox regression. RESULTS: A total of 100 catheters in 89 children were examined capturing 472 device days. PACs were primarily inserted for blood sampling (78%) in the radial artery (78%) using ultrasound guidance (67%), with 31% inserted on first attempt. Heparin saline solution was used in 82% of devices. Median catheter dwell was 50.6 hours (IQR 24.0 - 158.0), with PAC failure occurring in 19 devices (20%), at a rate of 40.2 per 1000 catheter days (95% CI 25.7 - 63.1). Arm board immobilisation (HR 2.9; 95% CI 1.02-8.02; p = 0.05), higher PIM3 score (HR 1.06; 95% CI 1.03-1.09; p < 0.01) was associated with an increased the risk of PAC failure, and non-2% chlorhexidine antisepsis was associated with a decrease in PAC failure (HR 0.32; 95% CI 0.11-0.96; p = 0.04), in univariate analysis. CONCLUSIONS: PAC insertion is challenging, and failure is common. Prospective clinical trial data is needed to identify high risk patient groups and to develop interventions which optimise practices, thereby reducing failure.

Adverse events and practice variability associated with paediatric endotracheal suction: An observational study.

OBJECTIVE: The objective of this study was to determine the incidence of endotracheal tube (ETT) suction-related adverse events (AEs) and to examine associations between AEs and patient and suction characteristics. Secondary objectives were to describe ETT suction practices in an Australian paediatric intensive care unit (PICU). METHODS: A prospective, observational study was undertaken in a mixed cardiac and general PICU. Children were eligible for inclusion if they were intubated and mechanically ventilated. Data on patient and suction variables (indication for ETT suction, number of suction episodes per mechanical ventilation episode, indication for normal saline instillation [NSI] and NSI dose) including potential predictive variables (age, Paediatric Index of Mortality 3 [PIM3], NSI, positive end-expiratory pressure, and hyperoxygenation) were collected. The main outcome variable was a composite measure of any AE. MAIN RESULTS: A total of 955 suction episodes were recorded in 100 children. AEs occurred in 211 (22%) ETT suctions. Suction-related AEs were not associated with age, diagnostic category, or index of mortality score. Desaturation was the most common AE (180 suctions; 19%), with 69% of desaturation events requiring clinician intervention. Univariate logistic regression showed the odds of desaturation decreased as the internal diameter of the ETT increased (odds ratio [OR]: 0.59; 95% confidence interval [CI]: 0.37-0.95; p = 0.028). Multivariable modelling revealed NSI was significantly associated with an increased risk of desaturation (adjusted OR [aOR]: 3.23; 95% CI: 1.99-5.40; p < 0.001) and the occurrence of an AE (aOR: 2.76; 95% CI: 1.74-4.37; p < 0.001). Presuction increases in fraction of inspired oxygen (FiO2) was significantly associated with an increased risk of experiencing an AE (aOR: 2.0; 95% CI: 1.27-3.15; p = 0.003). CONCLUSIONS: ETT suction-related AEs are common and associated with NSI and the requirement for pre-suction increases in FiO2. Clinical trial data are needed to identify high-risk patient groups and to develop interventions which optimise practice and reduce the occurrence of ETT suction-related AEs.

Innovation in Central Venous Access Device Security: A Pilot Randomized Controlled Trial in Pediatric Critical Care.

OBJECTIVES: Central venous access devices enable many treatments during critical illness; however, 25% of pediatric central venous access devices fail before completion of treatment due to infection, thrombosis, dislodgement, and occlusion. This is frequently attributed to inadequate securement and dressing of the device; however, high-quality research evaluating pediatric central venous access device securement innovation to prevent central venous access device failure is scarce. This study aimed to establish the feasibility of a definitive randomized control trial examining the effectiveness of current and new technologies to secure central venous access devices in pediatrics. DESIGN: Single-center, parallel group, superiority, pilot randomized control trial. SETTING: Anesthetic and intensive care departments of a tertiary pediatric hospital SUBJECTS:: One-hundred eighty pediatric patients with nontunneled central venous access device INTERVENTIONS:: Participants were randomized to receive central venous access device securement via standard care (bordered polyurethane dressing, with prolene sutures, chlorhexidine gluconate disc), tissue adhesive (Histoacryl, B Braun, Melsungen, Germany) in addition to standard care; or integrated dressing securement (SorbaView SHIELD [Centurion Medical Products, Franklin, MA], with prolene sutures and chlorhexidine gluconate disc). OUTCOMES: Primary: Feasibility (including effect size estimates, acceptability); central venous access device failure; central venous access device complications; secondary: individual central venous access device complications, skin damage, dressing performance, and product cost. MEASUREMENTS AND MAIN RESULTS: Feasibility criteria were achieved as recruitment occurred with acceptable eligibility, recruitment, missing data, and attrition rates, as well as good protocol adherence. Family members and staff-reported comparable levels of acceptability between study arms; however, tissue adhesive was reported as the most difficult to apply. Overall, 6% of central venous access devices failed, including 6% (3/54; incident rate, 13.2 per 1,000 catheter days) standard care, 2% (1/56; incident rate, 3.65 per 1,000 catheter days) integrated, and 8% (5/59; 25.0 per 1,000 catheter days) tissue adhesive. CONCLUSIONS: It is feasible to conduct an efficacy randomized control trial of the studied interventions. Further research is required to definitively identify clinical, cost-effective methods to prevent central venous access device failure by examining new dressing and securement technologies and techniques.

Assessment of the Access AMH assay as an automated, high-performance replacement for the AMH Generation II manual ELISA.

BACKGROUND: The manual Generation II (Gen II) ELISA method used to measure Anti-Müllerian Hormone (AMH) from Beckman Coulter has recently been superseded by a fully automated AMH immunoassay. The aim of this study was to evaluate the performance of the Access AMH assay and directly compare it to the modified Gen II ELISA method. A secondary aim was to verify that the fertile age-related AMH range previously established using the Gen II ELISA could be used to interpret results from the new automated Access assay. METHODS: The precision, stability, linearity, measurement range and detection limits were determined using recombinant AMH and patient serum samples. Different diluents and their effects on AMH concentration were compared. A correlation study was performed on patient samples to compare the Access AMH assay to the ELISA method on the Access2 and DxI800 analysers. The fertile AMH range was verified by comparing the 10th, 50th and 90th percentile values from both methods obtained from 489 natural conception pregnant women. RESULTS: The Access AMH assay showed good performance across the measuring range for both intra-assay (CV 1.41-3.30 %) and inter-assay (CV 3.04-5.76 %) precision and acceptable sample stability. Dilution of the high concentration samples with the recommended diluent resulted in a small but significant downward shift in values. The assay was linear over the range of values recommended by the manufacturer, allowing for accurate reporting within the reported range. The two assay types were highly correlated (R(2) = 0.9822 and 0.9832 for Access2 and DxI800, respectively), and the differences observed between the Access2 and DxI800 analysers were within clinically acceptable ranges, indicating that the methods are interchangeable. Furthermore, we demonstrated that results from the published reference range for the Gen II ELISA correlate with those from the automated Access AMH assay. CONCLUSION: Here, we verified the published performance of the Access AMH assay and showed excellent correlation with the Gen II ELISA method. Moreover, we validated this correlation by confirming that the results from a fertile AMH reference range established using the preceding Gen II ELISA are interchangeable with the new automated Access AMH assay.

Isolation and characterization of an IgNAR variable domain specific for the human mitochondrial translocase receptor Tom70.

The new antigen receptor (IgNAR) from sharks is a disulphide bonded dimer of two protein chains, each containing one variable and five constant domains, and functions as an antibody. In order to assess the antigen-binding capabilities of isolated IgNAR variable domains (VNAR), we have constructed an in vitro library incorporating synthetic CDR3 regions of 15-18 residues in length. Screening of this library against the 60 kDa cytosolic domain of the 70 kDa outer membrane translocase receptor from human mitochondria (Tom70) resulted in one dominant antigen-specific clone (VNAR 12F-11) after four rounds of in vitro selection. VNAR 12F-11 was expressed into the Escherichia coli periplasm and purified by anti-FLAG affinity chromatography at yields of 3 mg x L(-1). Purified protein eluted from gel filtration columns as a single monomeric protein and CD spectrum analysis indicated correct folding into the expected beta-sheet conformation. Specific binding to Tom70 was demonstrated by ELISA and BIAcore (Kd = 2.2 +/- 0.31 x 10(-9) m-1) indicating that these VNAR domains can be efficiently displayed as bacteriophage libraries, and selected against target antigens with an affinity and stability equivalent to that obtained for other single domain antibodies. As an initial step in producing 'intrabody' variants of 12F-11, the impact of modifying or removing the conserved immunoglobulin intradomain disulphide bond was assessed. High affinity binding was only retained in the wild-type protein, which combined with our inability to affinity mature 12F-11, suggests that this particular VNAR is critically dependent upon precise CDR loop conformations for its binding affinity.