BackgroundPredictive 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.MethodsForty-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.ResultsA 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.ConclusionsThis 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.

1. Current-clamp recordings were made in whole-cell patch-clamp configuration from ninetyone granule cells in parasagittal cerebellar slices obtained from 21-to 31-day-old rats.Recordings were performed at 30 'C. 2. Resting membrane potential was -58 + 6 mV (n = 43). The membrane voltage response to step current injection showed inward rectification consistent with increasing input resistance during membrane depolarization. Over -35 + 7 mV (n = 14) repetitive firing with little or no adaptation was activated. Spike frequency increased nearly linearly with injected current. 3. Unitary EPSPs obtained by stimulating the mossy fibre bundle had an amplitude of 11-4 + 2-1 mV (n = 22, holding potential = -75 mV). Synchronous activation of greater than one to two mossy fibres was needed to elicit action potentials. Antidromic stimulation elicited antidromic spikes and also EPSPs, presumably through a mossy fibre 'axon reflex'. 4. EPSPs were brought about by NMDA and non-NMDA receptor activation, accounting for about 70 and 30%, respectively, of peak amplitude at the holding potential of -70 mV. The EPSP decay conformed to passive membrane discharge after blocking the NMDA receptors. 5. No appreciable correlation was found between the time-to-peak and decay time constant of the EPSPs, consistent with the compact electrotonic structure of these neurons. 6. During membrane depolarization EPSP amplitude increased transiently, due to both a voltage-dependent increase of the NMDA component and inward rectification. In addition, EPSPs slowed down due to a slowdown of the NMDA component. 7. Temporal summation during high-frequency stimulation was sustained by NMDA receptors, whose contribution to depolarization tended to prevail over that of non-NMDA receptors during the trains. A block of the NMDA receptors resulted in reduced depolarization and output spike frequency. 8. This study, as well as extending previous knowledge to the intracellular level in vivo, provides evidence for a primary role of NMDA receptors in determining mossy fibre excitation of granule cells. It is suggested that the marked voltage dependence of the EPSP time course, which was mainly caused by voltage dependence in NMDA conductance, promotes the NMDA receptor-dependent enhancement of granule cell coding observed during repetitive mossy fibre activity.

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Although substantial knowledge has been accumulated on cerebellar granule cell voltage-dependent currents, their role in regulating electroresponsiveness has remained speculative. In this paper, we have used patch-clamp recording techniques in acute slice preparations to investigate the ionic basis of electroresponsiveness of rat cerebellar granule cells at a mature developmental stage. The granule cell generated a Na+-dependent spike discharge resistant to voltage and time inactivation, showing a linear frequency increase with injected currents. Action potentials arose when subthreshold depolarizing potentials, which were driven by a persistent Na+ current, reached a critical threshold. The stability and linearity of the repetitive discharge was based on a complex mechanism involving a N-type Ca2+ current blocked by omega-CTx GVIA, and a Ca2+-dependent K+ current blocked by charibdotoxin and low tetraethylammonium (TEA; <1 mM); a voltage-dependent Ca2+-independent K+ current blocked by high TEA (>1 mM); and an A current blocked by 2 mM 4-aminopyridine. Weakening TEA-sensitive K+ currents switched the granule cell into a bursting mode sustained by the persistent Na+ current. A dynamic model is proposed in which the Na+ current-dependent action potential causes secondary Ca2+ current activation and feedback voltage- and Ca2+-dependent afterhyperpolarization. The afterhyperpolarization reprimes the channels inactivated in the spike, preventing adaptation and bursting and controlling the duration of the interspike interval and firing frequency. This result reveals complex dynamics behind repetitive spike discharge and suggests that a persistent Na+ current plays an important role in action potential initiation and in the regulation of mossy fiber-granule cells transmission.

Considerable interest has recently focused on theweavermutation, which causes inward rectifier channel alterations leading to profound impairment of neuronal differentiation and to severe motor dysfunction in mice (Hess, 1996). The principal targets of mutation are cerebellar granule cells, most of which fail to differentiate and degenerate in a premigratory position (Rakic and Sidman, 1973a,b). Two hypotheses have been put forward to explain the pathogenetic role of mutant inward rectifier channels: namely that inward rectifier channel activity is either lacking (Surmeier et al., 1996) or altered (Kofuji et al., 1996; Silverman et al., 1996;Slesinger et al., 1996). We have examined this question by recording inward rectifier currents from cerebellar granule cellsin situat different developmental stages in wild-type and weaver mutant mice. In wild-type mice, the inward rectifier current changed from a G-protein-dependent activation to a constitutive activation as granule cells developed from premigratory to postmigratory stages. In weaver mutant mice, G-protein-dependent inward rectifier currents were absent in premigratory granule cells. A population of putative granule cells in the postmigratory position expressed a constitutive inward rectifier current with properties compatible with mutated GIRK2 channels expressed in heterologous systems. Because granule cells degenerate at the premigratory stage (Smeyne and Goldowitz, 1989), the loss of inward rectifier current and its regulation of membrane potential are likely to play a key role in the pathogenesis of weaver neuronal degeneration.