Cannabidiol Reduces Inflammatory Lung Damage After Meconium Aspiration in Newborn Piglets.

Aim: To assess the effects of cannabidiol (CBD) on lung damage in a piglet model of meconium aspiration syndrome (MAS). Materials and Methods: Meconium aspiration syndrome was modelled in newborn piglets via intratracheal instillation of 20% meconium in saline collected from healthy newborn humans. Piglets were treated i.v. with 5 mg/kg CBD (MAS + CBD) or Vehicle (MAS + VEH) 30 min after MAS induction and monitored for 6 h. Ventilated piglets without meconium instillation served as controls (CTL). Ventilatory and haemodynamic monitoring, histological and biochemical studies assessed the effects of treatment. Results: Post-insult administration of CBD reduced MAS-induced deterioration of gas exchange, improving respiratory acidosis (final pH 7.38 ± 0.02, 7.22 ± 0.03 and 7.33 ± 0.03 and final pCO2 39.8 ± 1.3, 60.4 ± 3.8 and 45.7 ± 3.1 mmHg for CTL, MAS + VEH and MAS + CBD, respectively, p < 0.05). These beneficial effects were obtained despite the less aggressive ventilatory settings required for CBD-treated animals (final minute volume 230 ± 30, 348 ± 33 and 253 ± 24 mL/kg/min and final Oxygenation Index 1.64 ± 0.04, 12.57 ± 3.10 and 7.42 ± 2.07 mmHg for CTL, MAS + VEH and MAS + CBD, respectively, p < 0.05). CBD's beneficial effects on gas exchange were associated with reduced histological lung damage, reduced leucocyte infiltration and oedema (histopathological score 1.6 ± 0.3, 8.6 ± 1.4 and 4.6 ± 0.7 points for CTL, MAS + VEH and MAS + CBD, respectively, p < 0.05), as well as reduced TNFα production (0.04 ± 0.01, 0.34 ± 0.06 and 0.12 ± 0.02 A.U. for CTL, MAS + VEH and MAS + CBD, respectively, p < 0.05). Moreover, CBD improved blood pressure stability (final mean blood pressure 74.5 ± 0.2, 62.2 ± 6.2, and 78.67 ± 4.1 mmHg for CTL, MAS + VEH and MAS + CBD, respectively, p < 0.05). Conclusion: Cannabidiol reduces histologic lung damage and inflammation in a piglet model of MAS. This translates into improved gas exchange and blood pressure stability.

Congenital Cutaneous Candidiasis With Systemic Dissemination in a Preterm Infant.

Congenital cutaneous candidiasis is an infrequent invasive fungal infection that usually appears in the first days of life. Extremely low birth weight infants are the most frequently affected. Classic presentation includes diffuse extensive erythematous rash with papules, plaques, pustules and vesicles, which later undergoes desquamation. Systemic dissemination is common in extremely low birth weight infants. Blood, urine and cerebrospinal fluid evaluation should be included in the initial assessment. Early and prolonged treatment has been associated with decreased mortality. We report the case of congenital cutaneous candidiasis in a preterm infant. Early skin lesion recognition allowed establishing adequate treatment in the first hours of life.

Neuroprotection by cannabidiol and hypothermia in a piglet model of newborn hypoxic-ischemic brain damage.

OBJECTIVE: Hypothermia, the gold standard after a hypoxic-ischemic insult, is not beneficial in all treated newborns. Cannabidiol is neuroprotective in animal models of newborn hypoxic-ischemic encephalopathy. This study compared the relative efficacies of cannabidiol and hypothermia in newborn hypoxic-ischemic piglets and assessed whether addition of cannabidiol augments hypothermic neuroprotection. METHODS: One day-old HI (carotid clamp and FiO2 10% for 20 min) piglets were randomized to vehicle or cannabidiol 1 mg/kg i.v. u.i.d. for three doses after being submitted to normothermia or 48 h-long hypothermia with a subsequent rewarming period of 6 h. Non-manipulated piglets (naïve) served as controls. Hemodynamic or respiratory parameters as well as brain activity (aEEG amplitude) were monitored throughout the experiment. Following termination, brains were obtained for histological (TUNEL staining, apoptosis; immunohistochemistry for Iba-1, microglia), biochemical (protein carbonylation, oxidative stress; and TNFα concentration, neuroinflammation) or proton magnetic resonance spectroscopy (Lac/NAA: metabolic derangement; Glu/NAA: excitotoxicity). RESULTS: HI led to sustained depressed brain activity and increased microglial activation, which was significantly improved by cannabidiol alone or with hypothermia but not by hypothermia alone. Hypoxic-ischemic-induced increases in Lac/NAA, Glu/NAA, TNFα or apoptosis were not reversed by either hypothermia or cannabidiol alone, but combination of the therapies did. No treatment modified the effects of HI on oxidative stress or astroglial activation. Cannabidiol treatment was well tolerated. CONCLUSIONS: cannabidiol administration after hypoxia-ischemia in piglets offers some neuroprotective effects but the combination of cannabidiol and hypothermia shows some additive effect leading to more complete neuroprotection than cannabidiol or hypothermia alone.

Infection in critically ill pediatric patients on continuous renal replacement therapy.

INTRODUCTION: Continuous renal replacement therapies (CRRT) are frequently used in critically ill children and may increase the risk of infection. However, the incidence, characteristics and prognosis of infection in critically ill children on CRRT have not been studied. METHODS: Data from a prospective, single-center register of critically ill children treated with CRRT was analyzed. RESULTS: 55 children (40% under 1 year of age) were treated with CRRT between June 2008 and January 2012; 43 patients (78.2%) presented 1 or more infections. The most common condition of patients requiring CRRT was heart disease (69%). Infection occurred a median of 11 days after the initiation of CRRT (IQ range: 4 to 21 days). A total of 21 patients (48.8 %) developed 1 infection, 7 (16.2%) developed 2 infections and 15 (34.9%) developed 3 or more infections. The most frequent infection was catheter-related bacteremia, with no differences in catheter location. CRRT duration longer than 4.5 days was the only risk factor for infection. Patients with infection had a longer length of stay (LOS) in the Pediatric Intensive Care Unit (PICU) than patients without it (37.8 vs. 17.6, p = 0.019), but there were no differences in mortality (30.2% vs. 33.3%; p = 0.84). CONCLUSIONS: Infection rate is high in critically ill children treated with CRRT. More than 4 days of CRRT increases the risk of infection. Infection in these patients entails a longer stay in the PICU but did not increase mortality.