OBJECTIVES: Adequacy of 16-20mm extracardiac conduits for adolescent Fontan patients remains unknown. This study aims to evaluate conduit adequacy using the inferior vena cava (IVC)-conduit... Show moreOBJECTIVES: Adequacy of 16-20mm extracardiac conduits for adolescent Fontan patients remains unknown. This study aims to evaluate conduit adequacy using the inferior vena cava (IVC)-conduit velocity mismatch factor along the respiratory cycle.METHODS: Real-time 2D flow MRI was prospectively acquired in 50 extracardiac (16-20mm conduits) Fontan patients (mean age 16.9 +/- 4.5 years) at the subhepatic IVC, conduit and superior vena cava. Hepatic venous flow was determined by subtracting IVC flow from conduit flow. The cross-sectional area (CSA) was reported for each vessel. Mean flow and velocity was calculated during the average respiratory cycle, inspiration and expiration. The IVC-conduit velocity mismatch factor was determined as follows: V-conduit/V-IVC where V is the mean velocity.RESULTS: Median conduit CSA and IVC CSA were 221 mm(2) (Q1-Q3 201-255) and 244 mm(2) (Q1-Q3 203-265), respectively. From the IVC towards the conduit, flow rates increased significantly due to the entry of hepatic venous flow (IVC 1.9, Q1-Q3 1.5-2.2) versus conduit (3.3, Q1-Q3 2.5-4.0 1/min, P < 0.001). Consequently, mean velocity significantly increased (IVC 12 (Q1-Q3 11-14 cm/s) versus conduit 25 (Q1-Q3 17-31 cm/s), P < 0.001), resulting in a median IVC-conduit velocity mismatch of 1.8 (Q1-Q3 1.5-2.4), further augmenting during inspiration (median 2.3, Q1-Q3 1.8-3.0). IVC-conduit mismatch was inversely related to measured conduit size and positively correlated with conduit flow. The normalized IVC-conduit velocity mismatch factor during expiration and the entire respiratory cycle correlated with peak VO2 (r = -0.37, P = 0.014 and r = -0.31, P = 0.04, respectively).CONCLUSIONS: Important blood flow accelerations are observed from the IVC towards the conduit in adolescent Fontan patients, which is related to peak VO2. This study, therefore, raises concerns that implanted 16-20mm conduits have become undersized for older Fontan patients and future studies should clarify its effect on long-term outcome. Show less
Aim: To determine whether the use of a respiratory function monitor (RFM) during PPV of extremely preterm infants at birth, compared with no RFM, leads to an increase in percentage of inflations... Show moreAim: To determine whether the use of a respiratory function monitor (RFM) during PPV of extremely preterm infants at birth, compared with no RFM, leads to an increase in percentage of inflations with an expiratory tidal volume (Vte) within a predefined target range.Methods: Unmasked, randomised clinical trial conducted October 2013 - May 2019 in 7 neonatal intensive care units in 6 countries. Very preterm infants (24-27 weeks of gestation) receiving PPV at birth were randomised to have a RFM screen visible or not. The primary outcome was the median proportion of inflations during manual PPV (face mask or intubated) within the target range (Vte 4-8 mL/kg). There were 42 other prespecified monitor measurements and clinical outcomes.Results: Among 288 infants randomised (median (IQR) gestational age 26(+2) (25(+3)-27(+1)) weeks), a total number of 51,352 inflations were analysed. The median (IQR) percentage of inflations within the target range in the RFM visible group was 30.0 (18.0-42.2)% vs 30.2 (14.8-43.1)% in the RFM non-visible group (p = 0.721). There were no dierences in other respiratory function measurements, oxygen saturation, heart rate or FiO(2). There were no dierences in clinical outcomes, except for the incidence of intraventricular haemorrhage (all grades) and/or cystic periventricular leukomalacia (visible RFM: 26.7% vs non-visible RFM: 39.0%; RR 0.71 (0.68-0.97); p = 0.028).Conclusion: In very preterm infants receiving PPV at birth, the use of a RFM, compared to no RFM as guidance for tidal volume delivery, did not increase the percentage of inflations in a predefined target range. Show less
The opioid antagonist naloxone has a special place in pharmacology __ it has no intrinsic action of its own, but it is able to save lives in the case of life threatening side-effects caused by... Show moreThe opioid antagonist naloxone has a special place in pharmacology __ it has no intrinsic action of its own, but it is able to save lives in the case of life threatening side-effects caused by other drugs. Naloxone is an antagonist for all opioid receptors, but most specifically for the _-opioid receptor, which is the receptor through which opioids such as morphine and fentanyl exert their effects. Those effects include first and foremost analgesia, but also nausea and vomiting, sedation and life-threatening respiratory depression. It is in the case of the latter effect that naloxone can be life-saving, as it is able to reverse respiratory depression. Paradoxically, naloxone, as an antagonist, was a side product of the search for an opioid agonist, one without addictive properties. For many centuries, the addictive properties of opium (and later morphine) were the cause of severe medical and social problems. However, there was (and still is) no alternative to morphine when it comes to analgesia. The solution to this problem was expected to come in the form of a non-addictive opioid agonist and since the start of the twentieth century, scientists have been working to find such a compound. This search has been fruitless with regard to a non-addictive opioid agonist, but has produced several opioid antagonistic drugs. Minor alterations to a drug__s chemical structure can change an agonist into an antagonist. The first opioid antagonist, N-allylnorcodeine was discovered in 1915, by changing a methyl group in the codeine molecule to an allyl group.1 After this discovery, however, the research in non-addictive opioids lay dormant for a while and it would take until 1944 for a second member of the opioid antagonist class, N-allylnormorphine (or nalorphine), to be characterized. Nalorphine showed antagonism for morphine induced respiratory depression,2 but was later found to be a _-opioid receptor agonist as well, with severe dysphoric side-effects (due to its agonism of the opioid receptor).3 Further experimentation with nalorphine__s chemical structure finally yielded N-allylnoroxymorphone, or naloxone, in 1960.4 Show less
