Mechanisms to expedite pediatric clinical trial site activation: The DOSE trial experience.

BACKGROUND: Timely trial start-up is a key determinant of trial success; however, delays during start-up are common and costly. Moreover, data on start-up metrics in pediatric clinical trials are sparse. To expedite trial start-up, the Trial Innovation Network piloted three novel mechanisms in the trial titled Dexmedetomidine Opioid Sparing Effect in Mechanically Ventilated Children (DOSE), a multi-site, randomized, double-blind, placebo-controlled trial in the pediatric intensive care setting. METHODS: The three novel start-up mechanisms included: 1) competitive activation; 2) use of trial start-up experts, called site navigators; and 3) supplemental funds earned for achieving pre-determined milestones. After sites were activated, they received a web-based survey to report perceptions of the DOSE start-up process. In addition to perceptions, metrics analyzed included milestones met, time to start-up, and subsequent enrollment of subjects. RESULTS: Twenty sites were selected for participation, with 19 sites being fully activated. Across activated sites, the median (quartile 1, quartile 3) time from receipt of regulatory documents to site activation was 82 days (68, 113). Sites reported that of the three novel mechanisms, the most motivating factor for expeditious activation was additional funding available for achieving start-up milestones, followed by site navigator assistance and then competitive site activation. CONCLUSION: Study start-up is a critical time for the success of clinical trials, and innovative methods to minimize delays during start-up are needed. Milestone-based funds and site navigators were preferred mechanisms by sites participating in the DOSE study and may have contributed to the expeditious start-up timeline achieved. CLINICALTRIALS: gov #: NCT03938857.

Nonadherence to appropriate tidal volume and PEEP in children with pARDS at a single center.

BACKGROUND: Low tidal volume and adequate positive end-expiratory pressure (PEEP) are evidence-based approaches for pediatric acute respiratory distress syndrome (pARDS), however, data are limited regarding their use since pARDS guidelines were revised in 2015. OBJECTIVE: To identify prevalence of, and factors associated with, nonadherence to appropriate tidal volume and PEEP in children with pARDS. METHODS: Retrospective cohort study of children 1 month to <18 years with pARDS who received invasive mechanical ventilation from 2016 to 2018 in a single pediatric intensive care unit (PICU). RESULTS: At 24 h after meeting pARDS criteria, 48/86 (56%) patients received tidal volume ≤8 ml/kg of ideal body weight and 45/86 (52%) received appropriate PEEP, with 22/86 (26%) receiving both. Among patients ≥2 years of age, a lower proportion of patients with overweight/obesity (9/25, 36%) had appropriate tidal volume versus those in the normal or underweight category (16/22, 73%, p = 0.02). When FIO2 was ≥50%, PEEP was appropriate in 19/60 (32%) cases versus 26/26 (100%) with FIO2 < 50% (p < 0.0001). pARDS was documented in the progress note in 7/86 (8%) patients at 24 h. Severity of pARDS, documentation in the progress note, and other clinical factors were not significantly associated with use of appropriate tidal volume and PEEP, however pARDS was documented more commonly in patients with severe pARDS. CONCLUSIONS: In a single PICU in the United States, children with pARDS did not receive appropriate tidal volume for ideal body weight nor PEEP. Targets for improving tidal volume and PEEP adherence may include overweight patients and those receiving FIO2 ≥ 50%, respectively.

Eutectic Mixture of Lidocaine and Prilocaine Decreases Movement and Propofol Requirements for Pediatric Lumbar Puncture During Deep Sedation: A Randomized, Placebo-Controlled, Double Blind Trial.

Deep sedation/general anesthesia is commonly used in pediatric oncology patients undergoing lumbar puncture (LP). Propofol is often used for sedation, with or without a narcotic. We hypothesized that eutectic mixture of lidocaine and prilocaine (EMLA) would allow for lower cumulative doses of propofol and less movement. We performed a prospective, randomized, double blind, placebo-controlled trial in children undergoing sedation for LP. Standard initial weight-based doses of propofol and fentanyl were administered, with either EMLA cream or a placebo cream applied topically. The primary outcome was the total dose of propofol administered to each patient. We also tracked patient movement and complications. Twenty-seven patients underwent 152 LPs. Patients randomized to EMLA cream (n=75) were significantly more likely to receive a lower dose of propofol (2.94 mg/kg, SE=0.25, vs. 3.22 mg/kg, SE=0.19; P=0.036) and to not require additional propofol doses (probability 0.49, SE=0.08 vs. 0.69, SE=0.06; P=0.001) compared with patients randomized to placebo cream (n=77). In addition, patients with EMLA cream were significantly less likely to demonstrate minor or major movement. EMLA cream results in less movement and less propofol administration in pediatric oncology patients undergoing sedation for LP.

A Framework for Pediatric Intensivists Providing Compassionate Extubation at Home.

For families facing end-of-life decisions for their critically ill children, compassionate extubation at home is a valuable service that pediatric intensivists can provide. Compassionate extubation at home is resource intensive and can be logistically challenging. Discouragingly, guidance on compassionate extubation at home in the literature is limited. We developed an evidence- and experience-based framework for compassionate extubation at home addressing common planning challenges and resource management. Our objective is to share this framework and an accompanying checklist, so that pediatric intensivists in other institutions can adapt these tools for their use, reducing barriers to providing compassionate extubation at home for critically ill children at the end of life.

Setting positive end-expiratory pressure during jet ventilation to replicate the mean airway pressure of oscillatory ventilation.

BACKGROUND: High-frequency ventilation can be delivered with either oscillatory ventilation (HFOV) or jet ventilation (HFJV). Traditional clinician biases may limit the range of function of these important ventilation modes. We hypothesized that (1) the jet ventilator can be an accurate monitor of mean airway pressure (P (aw)) during HFOV, and (2) a mathematical relationship can be used to determine the positive end-expiratory pressure (PEEP) setting required for HFJV to reproduce the P (aw) of HFOV. METHODS: In phase 1 of our experiment, we used a differential pressure pneumotachometer and a jet adapter in-line between an oscillator circuit and a pediatric lung model to measure P (aw), PEEP, and peak inspiratory pressure (PIP). Thirty-six HFOV setting combinations were studied, in random order. We analyzed the correlation between the pneumotachometer and HFJV measurements. In phase 2 we used the jet as the monitoring device during each of the same 36 combinations of HFOV settings, and recorded P (aw), PIP, and DeltaP. Then, for each combination of settings, the jet ventilator was placed in-line with a conventional ventilator and was set at the same rate and PIP as was monitored during HFOV. To determine the appropriate PEEP setting, we calculated the P (aw) contributed by the PIP, respiratory rate, and inspiratory time set for HFJV, and subtracted this from the goal P (aw). This value was the PEEP predicted for HFJV to match the HFOV P (aw). RESULTS: The correlation coefficient between the pneumotachometer and HFJV measurements was r = 0.99 (mean difference 0.62 +/- 0.30 cm H(2)O, p < 0.001). The predicted and actual PEEP required were highly correlated (r = 0.99, p < 0.001). The mean difference in these values is not statistically significantly different from zero (mean difference 0.25 +/- 1.02 cm H(2)O, p > 0.15). CONCLUSIONS: HFJV is an accurate monitor during HFOV. These measurements can be used to calculate the predicted PEEP necessary to match P (aw) on the 2 ventilators. Replicating the P (aw) with adequate PEEP on HFJV may help simplify transitioning between ventilators when clinically indicated.