Diaphragm ultrasound as a new index of discontinuation from mechanical ventilation.

BACKGROUND: Predictive indexes of weaning from mechanical ventilation are often inaccurate. Among the many indexes used in clinical practice, the rapid shallow breathing index is one of the most accurate. We evaluated a new weaning index consisting in the diaphragm thickening fraction (DTF) assessed by ultrasound. METHODS: Forty-six patients were prospectively enrolled. All patients were ventilated in pressure support through a tracheostomy tube. Patients underwent a spontaneous breathing trial (SBT) when they met all the following criteria: FiO2 < 0.5, PEEP ≤5 cmH2O, PaO2/FiO2 > 200, respiratory rate <30 breaths per minute, absence of fever, alert and cooperative, and hemodynamic stability without vaso-active therapy support. During the trial, the right hemi-diaphragm was visualized in the zone of apposition using a 10-MHz linear ultrasound probe. The patient was then instructed to perform breathing to total lung capacity (TLC) and then exhaling to residual volume (RV). Diaphragm thickness was recorded at TLC and RV, and the DTF was calculated as percentage from the following formula: Thickness at end inspiration - Thickness at end expiration / Thickness at end expiration. Also, the rapid shallow breathing index (RSBI) was calculated. Weaning failure was defined as the inability to maintain spontaneous breathing for at least 48 h, without any form of ventilatory support. RESULTS: A significant difference between diaphragm thickness at TLC and RV was observed both in patients who succeeded SBT and patients who failed. DTF was significantly different between patients who failed and patients who succeeded SBT. A cutoff value of a DTF >36% was associated with a successful SBT with a sensitivity of 0.82, a specificity of 0.88, a positive predictive value (PPV) of 0.92, and a negative predictive value (NPV) of 0.75. By comparison, RSBI <105 had a sensitivity of 0.93, a specificity of 0.88, a PPV of 0.93, and a NPV of 0.88 for determining SBT success. CONCLUSIONS: This study shows that in our cohort of patients, the assessment of DTF by diaphragm ultrasound may perform similarly to other weaning indexes. If validated by other studies, this method may be used in clinical practice.

Standard-length catheters vs long catheters in ultrasound-guided peripheral vein cannulation.

PURPOSE: Ultrasound (US) is a useful tool for peripheral vein cannulation in patients with difficult venous access. However, few data about the survival of US-guided peripheral catheters in acute care setting exist. Some studies showed that the survival rate of standard-length catheters (SC) is poor especially in obese patients. The use of longer than normal catheters could provide a solution to low survival rate. The aim of the present study was to compare US-guided peripheral SCs vs US-guided peripheral long catheters inserted with Seldinger technique (LC) in acute hospitalized patients with difficult venous access. METHODS: This was a prospective, randomized controlled trial. A total of 100 consecutively admitted subjects in an urban High Dependency Unit were randomized to obtain US-guided intravenous access using either SC or LC after 3 failed blind attempts. Primary outcome was catheter failure rate. RESULTS: Success rate was 86% in the SC groups and 84% in the LC group (P=.77). Time requested to positioning venous access resulted to be shorter for SC as opposed to LC (9.5 vs 16.8 minutes, respectively; P=.001). Catheter failure was observed in 45% of patients in the SC group and in 14% of patients in the LC group (relative risk, 3.2; P<.001). CONCLUSIONS: Both SC and LC US-guided cannulations have a high success rate in patients with difficult venous access. Notwithstanding a higher time to cannulation, LC US-guided procedure is associated with a lower risk of catheter failure compared with SC US-guided procedure.

The subtype-selective nicotinic acetylcholine receptor positive allosteric potentiator 2087101 differentially facilitates neurotransmission in the brain.

Positive allosteric modulators of centrally expressed nicotinic acetylcholine receptors have therapeutic potentials in areas of cognition, motor function and reward. Several chemical classes of allosteric modulators that are selective for alpha7 nicotinic receptors have been characterised, but potentiators for the most widely expressed alpha4beta2 nicotinic receptor subtype are few and less defined, owing probably to the difficulty to achieve selectivity over other heteromeric receptor subtypes. 2087101 (2-amino-5-keto)thiazole) is a potent potentiator of both alpha7 and alpha4beta2 receptors and it has selectivity against the alpha3beta4 subtype, which may be responsible for the undesirable peripheral side effects. To further characterise its ability to differentiate between native nicotinic receptors, we examined the effects of 2087101 on alpha7, alpha4beta2* and alpha3beta4* receptor-mediated responses in the rat brain in electrophysiological and neurochemical experiments. 2087101 significantly potentiated agonist-induced, alpha7 and non-alpha7 receptor-mediated, GABAergic postsynaptic currents in cultured hippocampal neurones, but not the nicotine-stimulated [(3)H]noradrenaline release from hippocampal slices, which was primarily mediated by alpha3beta4* receptors, confirming its selectivity for alpha7 and alpha4beta2* receptors in native systems. 2087101 also significantly enhanced nicotine-stimulated firing increase in dopamine neurones of the ventral tegmental area, an effect that was dihydro-beta-erythroidine-sensitive and thereby mediated by alpha4beta2* nicotinic receptors. 2087101 can therefore enhance native nicotinic activities mediated by alpha7 and alpha4beta2*, but not alpha3beta4* receptors, showing its unique ability to discriminate between native heteromeric nicotinic receptor subtypes and its therapeutic potential for treating brain disorders by concurrent modulation of both alpha7 and alpha4beta2* nicotinic receptors.

Noninvasive positive airway pressure and risk of myocardial infarction in acute cardiogenic pulmonary edema: continuous positive airway pressure vs noninvasive positive pressure ventilation.

BACKGROUND: The addition of both noninvasive continuous positive airway pressure (n-CPAP) or noninvasive intermittent positive pressure ventilation (n-IPPV) to medical treatment has been shown to improve the outcome of patients with acute cardiogenic pulmonary edema (ACPE). Previous studies indicated a potential risk of new-onset acute myocardial infarction (AMI) associated with the use of n-IPPV. Although further studies did not confirm this observation, a few recent metaanalyses could not eliminate all the doubts at this regards because of the paucity of data available and the presence of confounding factors. This study aims to assess whether the application of n-IPPV, as opposed to n-CPAP, increases the rate of AMI in ACPE patients. METHODS: Fifty-two patients with severe hypoxemia consequent to ACPE were randomized to receive n-CPAP (n = 27) or n-IPPV (n = 25) in addition to medical therapy. Patients with signs of acute coronary syndrome on hospital admission were excluded from the study. Cardiac markers, ECG, and clinical/physiologic parameters were assessed at study entry, after 30 and 60 min, and every 6 h for the first 2 days. RESULTS: No significant difference was observed in the rate of AMI (26.9% and 16% with n-CPAP and n-IPPV, respectively, p = 0.244). Rate of intubation (p = 0.481), death (p = 0.662), and hospital stay (p = 0.529) were not different between the two groups. Both techniques were effective in improving gas exchange and vital signs in patients with ACPE. CONCLUSIONS: The AMI rate was not different with n-CPAP and n-IPPV, which resulted to be equally effective in the treatment of ACPE. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00453947.

Nicotinic receptor modulation of neurotransmitter release in the cerebellum.

Nicotinic ACh receptors (nAChRs) are formed by pentameric combinations of alpha and beta subunits, differentially expressed throughout the central nervous system (CNS), where they have been shown to play a role in the modulation of neurotransmitter release. nAChRs are also important during neuronal differentiation, regulating gene expression and contributing to neuronal pathfinding. The cerebellum, which is involved in the maintenance of balance and orientation as well as refinement of motor action, in motor memory and in some aspects of cognition, undergoes a significant process of development and maturation of its neuronal networks during the first three postnatal weeks in the rat. Autoradiographic as well as in situ hybridization and immunocytochemical studies have shown that several nicotinic receptor binding sites and subunits are expressed in the rat cerebellum from embryonic stage through to adulthood, with the highest expression levels seen during the development of the cerebellar cortex. A diffuse cholinergic afferent projection to all lobules of the cerebellar cortex has been described, with the uvulanodulus, flocculus and lobules I and II of the anterior vermis regions receiving a particularly dense projection. Low levels of nAChR subunit transcripts and immunoreactivity, particularly during adulthood, and the scattered distribution of immunoreactivity between neurons in the cerebellar cortex, can explain the difficulty in assessing electrophysiologically the presence of functional nAChRs in the cerebellar cortex and some contradictory results reported in the early-published papers. In recent years, several groups have shown that also in the cerebellum different nAChR subtypes modulate release of glutamate and GABA at different synapses. The possible role of these mechanisms in synaptic consolidation during development, as well as on plasticity phenomena and network activity at mature synapses, are discussed.