Mean arterial plasma concentrations of dexmedetomidine in infants and toddlers approached 100 pg ml, the low end reported for sedative efficacy, within 20 min of an atomised intranasal administration of 1 μg kg. Doubling the dose to 2 μg kg reached this plasma concentration within 10 min and achieved almost twice the peak concentration. Peak plasma concentrations with both doses were reached within 47 min of intranasal administration, with an overall bioavailability of 84%.

Over a 3-year period, medical staff at this institution have routinely used this risk stratification, which identifies groups of patients at high and low risk of mortality, re-bleeding and need for urgent treatment intervention following acute upper-gastrointestinal haemorrhage. Use of this risk stratification should allow targeting of more intensive treatment where it might be of most benefit. Those patients at lowest risk from outpatient management are also identified.

clinicaltrials.gov NCT02938065 clinicaltrials.gov/ct2/show/NCT02938065.

Increasingly end-organ injury is being demonstrated late after institution of the Fontan circulation, particularly liver fibrosis and cirrhosis. The exact mechanisms for these late phenomena remain largely elusive. Hypothesizing that exercise induces precipitous systemic venous hypertension and insufficient cardiac output for the exercise demand, i.e. a possible mechanism for end-organ injury, we sought to demonstrate the dynamic exercise responses in systemic venous (SVP) and concurrent end organ perfusion. Ten stable Fontan patients and 9 control subjects underwent incremental cycle ergometry based cardiopulmonary exercise testing. SVP was monitored in the right upper limb and regional tissue oxygen saturation was monitored in the brain and kidney using Near Infrared Spectroscopy. SVP rose profoundly in concert with workload in the Fontan group, described by the regression equation 15.97+0.073 Watts per mm Hg. In contrast SVP did not change in healthy controls. Regional renal (p<0.01) and cerebral tissue saturations (p<0.001) were significantly lower and fell more rapidly in Fontan patients. We conclude that in a stable group of adult patients with Fontan circulation high intensity exercise was associated with systemic venous hypertension and reduced systemic oxygen delivery. This physiologic substrate has the potential to contribute to endorgan injury.