Critically ill patients exhibit reduced melatonin secretion, both in nocturnal peaks and basal daytime levels. Oral melatonin supplementation may be useful for known sedative and antioxidant properties. Its early enteral absorption and daily pharmacokinetics were determined in two cohorts of six high-risk patients in this prospective trial. During their third and fourth Intensive Care Unit (ICU) day, they underwent two different sets of repeated blood samples to detect serum melatonin levels through radio-immuno-assay. Cohort 1: samples taken at 20:00, 20:45, 21:30, 24:00, 03:00, 06:00, 14:00, 20:00 to describe the daily pharmacokinetics. Cohort 2: 20:00, 20:05, 20:10, 20:20, 20:30, 20:45 to study the early absorption. On ICU day 3, endogenous levels were measured, while the absorption of exogenous melatonin was determined on ICU day 4 after administration, at 20:00, of 3 mg melatonin. All basal levels were below the expected values. Following enteral administration, pharmacological levels were already reached in 5 min, with a serum peak after 16 min (half-absorption time: 3 min 17 s). The maximum serum level observed was 11040 pg/mL and the disappearance rate indicated a half-elimination time of 1 hr 34 min. Serum melatonin levels decreased significantly after midnight; pharmacological levels were maintained up to 10 hr following administration. No excessive sleepiness was reported in this patient group. Critically ill patients exhibited reduced melatonin secretion, as reported in the literature. Despite the critical illness, the oral bioavailability was satisfactory: serum levels after oral administration showed basically unchanged intestinal absorption, while disappearance rate was slower than reported elsewhere in healthy volunteers.

No abstract

No abstract

Objectives. Viral bronchiolitis represents one of the main cause of hospitalization for children in developed and incoming countries. Nasal High Flow (NHF) oxygen therapy improves oxygenation and reduces respiratory drive by enhancing carbon dioxide wash-out. However, little is known about physiological effects of noninvasive helmet-Continuous Positive Airway Pressure (h-CPAP) and NHF on respiratory Work Of Breathing (WOB) in bronchiolitis. Objective of the study is to measure Esophageal Pressure Time Product*minute (PTPes*min-1) as a surrogate for WOB in acute bronchiolitis during NH at different flow rates in comparison with conventional h-CPAP. Pressure Rate Product, physiological parameters and gas exchange were considered as secondary end-points. Methods. This is a physiological randomized crossover-study comparing four 20-minute trials: oxygen therapy delivered by non-fitting mask, NHF2l/Kg, NHF3l/Kg, h-CPAP 7cmH2O. Results. Were enrolled ten children with bronchiolitis needing noninvasive respiratory support. PTPes*min-1, Respiratory Rate and Pressure Rate Product decreased progressively from h-CPAP compared to NHF3l/kg, NHF2l/kg and oxygen mask (p<0.01 for all parameters). SpO2:FiO2 increased during h-CPAP versus NHF3l/kg, NHF2l/kg and oxygen mask (p<0.01). Transcutaneous carbon dioxide tension was affected by increasing flow rate showing a progressive reduction at NHF3l/kg, NHF2l/kg and during h-CPAP compared to oxygen mask (p<0.001). Conclusions. h-CPAP was associated with a reduction in WOB and with a better oxygenation compared to oxygen mask and NHF trials; 2) NHF trials improved oxygenation and reduced the carbon dioxide tension compared to oxygen mask 3) NHF3l/kg does not offer advantages compared to NHF 2 l/kg in improving oxygenation and carbon dioxide wash-out.

Objectives Acute viral bronchiolitis (AVB) is a major cause of hospitalization for children in developed and developing countries. Nasal high flow (NHF) therapy improves oxygenation and reduces respiratory drive by enhancing carbon dioxide wash-out. However, little is known about the physiological effects of non-invasive helmet continuous positive airway pressure (h-CPAP) and NHF on respiratory work of breathing (WOB) in pediatric patients with AVB. The present study measured esophageal pressure time product over 1 min (PTPes*min−1), as a close surrogate for WOB during standard oxygen therapy (SOT), NHF delivered at incremental flow rates, and h-CPAP in hospitalized patients with AVB. Methods This is a physiological randomized crossover study with four 20-min steps: SOT delivered by a Venturi mask; NHF2 set at 2L/kg*min−1PBW; NHF3 set at 3L/kg*min−1PBW; and h-CPAP with PEEP 7 cmH2O. PTPes *min−1, pressure rate product (PRP), respiratory and other physiological parameters were collected towards the end of each step. Results Ten hypoxemic children with AVB were enrolled. PTPes*min−1, respiratory rate (RR), PRP, and heart rate (HR) decreased progressively from h-CPAP to NHF3, NHF2, and SOT (p < 0.01). Transcutaneous carbon dioxide tension (tcCO2) was lower during h-CPAP, NHF3, and NHF2 than during SOT (p < 0.001). SpO2:FiO2 was higher during h-CPAP than with all other support (p < 0.01). Conclusions In pediatric patients with AVB, h-CPAP was associated with lower WOB, better oxygenation, and lower tcCO2 than with SOT and NHF trials. Trial registration Clinicaltrials.gov NCT03689686 Registered 1 August 2018.