An integrated array of microfluidic oxygenators as a neonatal lung assist device: in vitro characterization and in vivo demonstration.

A miniaturized oxygenator device that is perfused like an artificial placenta via the umbilical vessels may have significant potential to save the lives of newborns with respiratory insufficiency. Recently we presented the concept of an integrated modular lung assist device (LAD) that consists of stacked microfluidic single oxygenator units (SOUs) and demonstrated the technical details and operation of SOU prototypes. In this article, we present a LAD prototype that is designed to accommodate the different needs of term and preterm infants by permitting changing of the number of parallel-stacked microfluidic SOUs according to the actual body weight. The SOUs are made of polydimethylsiloxane, arranged in parallel, and connected though 3D-printed polymeric interconnects to form the LAD. The flow characteristics and the gas exchange properties were tested in vitro using human blood. We found that the pressure drop of the LAD increased linearly with flow rate. Gas exchange rates of 2.4-3.8 µL/min/cm(2) (0.3-0.5 mL/kg/min) and 6.4-10.1 µL/min/cm(2) (0.8-1.3 mL/kg/min) for O2 and CO2 , respectively, were achieved. We also investigated protein adsorption to provide preliminary information on the need for application of anticoagulant coating of LAD materials. Albumin adsorption, as measured by gold staining, showed that surface uptake was evenly distributed and occurred at the monolayer level (>0.2 µg/cm(2) ). Finally, we also tested the LAD under in vivo conditions using a newborn piglet model (body weight 1.65-2.0 kg). First, the effect of an arteriovenous bypass via a carotid artery-to-jugular vein shortcut on heart rate and blood pressure was investigated. Heart rate and mean arterial blood pressure remained stable for extracorporeal flow rates of up to 61 mL/kg/min (101 mL/min). Next, the LAD was connected to umbilical vessels (maximum flow rate of 24 mL/min [10.4 mL/kg/min]), and O2 gas exchange was measured under hypoxic conditions (Fi O2 = 0.15) and was found to be 3.0 µL/min/cm(2) . These results are encouraging and support the feasibility of an artificial placental design for an LAD.

Factors affecting pediatric isotonic fluid resuscitation efficiency: a randomized controlled trial evaluating the impact of syringe size.

BACKGROUND: Goal-directed therapy guidelines for pediatric septic shock resuscitation recommend fluid delivery at speeds in excess of that possible through use of regular fluid infusion pumps. In our experience, syringes are commonly used by health care providers (HCPs) to achieve rapid fluid resuscitation in a pediatric fluid resuscitation scenario. At present, it is unclear which syringe size health care providers should use when performing fluid resuscitation to achieve maximal fluid resuscitation efficiency. The objective of this study was therefore to determine if an optimal syringe size exists for conducting manual pediatric fluid resuscitation. METHODS: This 48-participant parallel group randomized controlled trial included 4 study arms (10, 20, 30, 60 mL syringe size groups). Eligible participants were HCPs from McMaster Children's Hospital, Hamilton, Canada blinded to the purpose of the trial. Consenting participants were randomized using a third party technique. Following a standardization procedure, participants administered 900 mL (60 mL/kg) of isotonic saline to a simulated 15 kg child using prefilled provided syringes of the allocated size in rapid sequence. Primary outcome was total time to administer the 900 mL and this data was collected through video review by two blinded outcome assessors. Sample size was predetermined based upon a primary outcome analysis using one-way ANOVA. RESULTS: 12 participants were randomized to each group (n=48) and all completed trial protocol to analysis. Analysis was conducted according to intention to treat principles. A significant difference in fluid resuscitation time (in seconds) was found between syringe size group means: 10 mL, 563s [95% CI 521; 606]; 20 mL, 506s [95% CI 64; 548]; 30 mL, 454s [95% CI 412; 596]; 60 mL, 455s [95% CI 413; 497] (p<0.001). CONCLUSIONS: The syringe size used when performing manual pediatric fluid resuscitation has a significant impact on fluid resuscitation speed, in a setting where fluid filled syringes are continuously available. Greatest efficiency was achieved with 30 or 60 mL syringes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01494116.

Lung assist device: development of microfluidic oxygenators for preterm infants with respiratory failure.

This paper reports the development of microfluidic oxygenator (MFO) units designed for a lung assist device (LAD) for newborn infants. This device will be connected to the umbilical vessels like the natural placenta and provide gas exchange. The extracorporeal blood flow is only driven by the pressure difference between the umbilical artery and vein without the use of external pumps. The LAD is designed for use in ambient air (~21% of 760 mmHg). The main focus of this paper is the presentation of the development of the MFO units testing various membrane materials with human blood to enhance gas exchange and in the design of fluidic inlets to lower the pressure drop across the oxygenator. Four different membranes, including thin film PDMS, porous PDMS, and two different pore size porous polycarbonate membranes are compared in this study. Among them, the microfluidic oxygenator with porous PDMS membrane has the highest gas exchange rate of 1.46 µL min(-1) cm(2) for oxygen and 5.27 µL min(-1) cm(2) for carbon dioxide and performs better than a commercial hollow fiber-based oxygenator by 367 and 233%, respectively. A new tapered inlet configuration was designed to reduce the pressure drop across the oxygenator and showed a further 57% improvement over the traditional perpendicular inlet configuration.

Translating resuscitation guidelines into practice: health care provider attitudes, preferences and beliefs regarding pediatric fluid resuscitation performance.

INTRODUCTION: Children who require fluid resuscitation for the treatment of shock present to tertiary and non-tertiary medical settings. While timely fluid therapy improves survival odds, guidelines are poorly translated into clinical practice. The objective of this study was to characterize the attitudes, preferences and beliefs of health care providers working in acute care settings regarding pediatric fluid resuscitation performance. METHODS: A single-centre survey study was conducted at McMaster Children's Hospital from January to May, 2012. The sampling frame (n = 115) included nursing staff, physician staff and subspecialty trainees working in Pediatric Emergency Medicine (PEM) or Pediatric Critical Care Medicine (PCCM). A self-administered questionnaire was developed and assessed for face validity prior to distribution. Eligible participants were invited at 0, 2, and 4 weeks to complete a web-based version of the survey. A follow-up survey administration phase was conducted to improve the response rate. RESULTS: Response rate was 72.2% (83/115), with 83% (68/82) self-identifying as nursing staff and 61% (50/82) as PCCM providers. Resuscitation experience, frequency of shock management, and years in specialty, were similar between PCCM and PEM responders. Physicians and nurses had differing opinions regarding the most effective method to achieve rapid fluid resuscitation in young children presenting in shock (p<0.001). Disagreement also existed regarding the age and size of patients in whom rapid infuser devices, such as the Level-1 Rapid Infuser, should be used (p<0.001). Providers endorsed a number of potential concerns related to the use of rapid infuser devices in children, and only 14% of physicians and 55% of nursing staff felt that they had received adequate training in the use of such devices (p = 0.005). CONCLUSIONS: There is a lack of consensus among health care providers regarding how pediatric fluid resuscitation guidelines should be operationalized, supporting a need for further work to define best practices.

Prospective evaluation of direct approach with a tablet device as a strategy to enhance survey study participant response rate.

BACKGROUND: Investigators conduct survey studies for a variety of reasons. Poor participant response rates are common, however, and may limit the generalizability and utility of results. The objective of this study was to determine whether direct approach with a tablet device enhances survey study participant response rate and to assess participants' experiences with this mode of survey administration. FINDINGS: An interventional study nested within a single center survey study was conducted at McMaster Children's Hospital. The primary outcome was the ability to achieve of a survey study response rate of 70% or greater. Eligible participants received 3 email invitations (Week 0, 2, 4) to complete a web-based (Survey Monkey) survey. The study protocol included plans for a two-week follow-up phase (Phase 2) where non-responders were approached by a research assistant and invited to complete an iPad-based version of the survey. The Phase 1 response rate was 48.7% (56/115). Phase 2 effectively recruited reluctant responders, increasing the overall response rate to 72.2% (83/115). On a 7-point Likert scale, reluctant responders highly rated their enjoyment (mean 6.0, sd 0.83 [95% CI: 5.7-6.3]) and ease of use (mean 6.7, sd 0.47 [95% CI: 6.5-6.9]) completing the survey using the iPad. Reasons endorsed for Phase 2 participation included: direct approach (81%), immediate survey access (62%), and the novelty of completing a tablet-based survey (54%). Most reluctant responders (89%) indicated that a tablet-based survey is their preferred method of survey completion. CONCLUSIONS: Use of a tablet-based version of the survey was effective in recruiting reluctant responders and this group reported positive experiences with this mode of survey administration.

Rapid, easy, and cheap randomization: prospective evaluation in a study cohort.

BACKGROUND: When planning a randomized controlled trial (RCT), investigators must select randomization and allocation procedures based upon a variety of factors. While third party randomization is cited as being among the most desirable randomization processes, many third party randomization procedures are neither feasible nor cost-effective for small RCTs, including pilot RCTs. In this study we present our experience with a third party randomization and allocation procedure that utilizes current technology to achieve randomization in a rapid, reliable, and cost-effective manner. METHODS: This method was developed by the investigators for use in a small 48-participant parallel group RCT with four study arms. As a nested study, the reliability of this randomization procedure was prospectively evaluated in this cohort. The primary outcome of this nested study was the proportion of subjects for whom allocation information was obtained by the Research Assistant within 15 min of the initial participant randomization request. A secondary outcome was the average time for communicating participant group assignment back to the Research Assistant. Descriptive information regarding any failed attempts at participant randomization as well as costs attributable to use of this method were also recorded. Statistical analyses included the calculation of simple proportions and descriptive statistics. RESULTS: Forty-eight participants were successfully randomized and group allocation instruction was received for 46 (96%) within 15 min of the Research Assistant placing the initial randomization request. Time elapsed in minutes until receipt of participant allocation instruction was Mean (SD) 3.1 +/- 3.6; Median (IQR) 2 (2,3); Range (1-20) for the entire cohort of 48. For the two participants for whom group allocation information was not received by the Research Assistant within the 15-min pass threshold, this information was obtained following a second request at 18 and 20 min, respectively. The method described here produced an email audit trail, which proved useful to the primary study. CONCLUSIONS: We report a method of third party randomization that uses current technology to operationalize randomization and allocation in a rapid, easy, and cost-effective manner. Other investigators may find this method useful, particularly for small RCTs, including pilot RCTs, on a tight budget.