Infants with moderate-to-severe CHD frequently undergo cardiopulmonary bypass surgery in childhood. Morbidity and mortality are highest in those who develop post-operative low cardiac output syndrome. Vasoactive and inotropic medications are mainstays of treatment for these children, despite limited evidence supporting their use.

To help inform clinical practice, as well as the conduct of future trials, we performed a systematic review of existing literature on inotropes and vasoactives in children after cardiac surgery using the PubMed and EMBASE databases. We included studies from 2000 to 2020, and the patient population was defined as birth – 18 years of age. Two reviewers independently reviewed studies to determine final eligibility.

The final analysis included 37 papers. Collectively, selected studies reported on 12 different vasoactive and inotropic medications in 2856 children. Overall evidence supporting the use of these drugs in children after cardiopulmonary bypass was limited. The majority of studies were small with 30/37 (81%) enrolling less than 100 patients, 29/37 (78%) were not randomised, and safety and efficacy endpoints differed widely, limiting the ability to combine data for meta-analyses.

Vasoactive and inotropic support remain critical parts of post-operative care for children after cardiopulmonary bypass surgery. There is a paucity of data for the selection and dosing of vasoactives and inotropes for these patients. Despite the knowledge gaps that remain, numerous recent innovations create opportunities to rethink the conduct of clinical trials in this high-risk population.

Modafinil was tested for efficacy in facilitating abstinence in cocaine-dependent patients, compared to placebo.

This is a double-blind placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. 210 treatment-seekers with DSM-IV diagnosis of cocaine dependence consented and enrolled. 72 participants were randomized to placebo, 69 to modafinil 200mg, and 69 to modafinil 400mg, taken once daily on awakening. Participants attended the clinic three times per week for assessments and urine drug screens, and had one hour of individual psychotherapy once per week. The primary outcome was the increase in weekly percentage of non-use days. Secondary outcomes included: decrease in the weekly median log of urine benzoylecgonine, subgroup analyses of balancing factors and co-morbid conditions, self-report of alcohol use, addiction severity, craving, and risk behaviors for HIV.

125 participants completed 12 weeks of treatment (60%). The GEE regression analysis showed that for the total sample, the difference between modafinil groups and placebo in the weekly percentage of cocaine non-use days over the 12-week treatment period was not statistically significant (p=0.95). A post-hoc analysis showed a significant effect for modafinil, only in the subgroup of cocaine patients without alcohol dependence. Modafinil 200mg also showed significant effects of an increase in the total number of consecutive non-use days for cocaine (p=0.02), and a reduction in craving (p=0.04).

These data suggest that modafinil, in combination with individual behavioral therapy, was effective for increasing cocaine non-use days in participants without co-morbid alcohol dependence, and in reducing craving.

The air gap technique (AGT) is an approach to radiation dose optimisation during fluoroscopy where an “air gap” is used in place of an anti-scatter grid to reduce scatter irradiation. The AGT is effective in adults but remains largely untested in children. Effects are expected to vary depending on patient size and the amount of scatter irradiation produced.

Fluoroscopy and cineangiography were performed using a Phillips Allura Fluoroscope on tissue simulation anthropomorphic phantoms representing a neonate, 5-year-old, and teenager. Monte Carlo simulations were then used to estimate effective radiation dose first using a standard recommended imaging approach and then repeated using the AGT. Objective image quality assessments were performed using an image quality phantom.

Effective radiation doses for the neonate and 5-year-old phantom increased consistently (2–92%) when the AGT was used compared to the standard recommended imaging approaches in which the anti-scatter grid is removed at baseline. In the teenage phantom, the AGT reduced effective doses by 5–59%, with greater dose reductions for imaging across the greater thoracic dimension of lateral projection. The AGT increased geometric magnification but with no detectable change in image blur or contrast differentiation.

The AGT is an effective approach for dose reduction in larger patients, particularly for lateral imaging. Compared to the current dose optimisation guidelines, the technique may be harmful in smaller children where scatter irradiation is minimal.