American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jan 1998
Comparative StudySelective iNOS inhibition is superior to norepinephrine in the treatment of rat endotoxic shock.
S-methyl-isothiourea (SMT) is a potent inhibitor of NO synthase (NOS) with relative selectivity towards the inducible isoform (iNOS). We compared SMT and norepinephrine for the treatment of experimental endotoxic shock. Anesthetized rats challenged intravenously with lipopolysaccharide (LPS), 10 mg/kg, were treated after 1 h with a 4-h infusion of norepinephrine (titrated to maintain blood pressure within baseline values), SMT at low dose (0.1 mg x kg-1 x h-1), or at high dose (1 mg x kg-1 x h-1), or an equivalent volume of saline (2 ml x kg-1 x h-1). ⋯ Both doses reduced the signs of renal, but not liver, dysfunction. In additional studies, we obtained evidence that, in contrast with the high dose, SMT at low dose did not interfere with the function of constitutive NOS. These findings suggest a potential advantage of selective iNOS inhibition over standard adrenergic support in the therapy of septic shock.
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Am. J. Respir. Crit. Care Med. · Jan 1998
Randomized Controlled Trial Comparative Study Clinical Trial Controlled Clinical TrialEffects of flow triggering on breathing effort during partial ventilatory support.
The effects of flow triggering (FT) as compared with pressure triggering (PT) on breathing effort have been the focus of several studies, and discrepant results have been reported. In the initial part of our study, a lung model was used to quantify triggering effort (airway pressure-time product, PTPaw) for a range of sensitivity settings in nine new-generation ventilators. A ventilator providing both FT and PT was then used to compare these systems during pressure-support (PSV) and volume-targeted assist-control ventilation (ACV) in eight ventilator-dependent patients, using sensitivity settings (2 L/min for FT and -2 cm H2O for PT) that had proven significantly different in the initial bench study. ⋯ By contrast, no differences were found when FT was used during ACV. Although FT reduced triggering effort in both modes (p < 0.001), the effects observed during the post-trigger phase differed, and explained the discrepant results between the two modes. We conclude that FT more effectively reduces breathing effort when used in conjunction with a pressure-targeted mode than with a volume-targeted mode, especially when flow delivery is close to or below demand.
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Am. J. Respir. Crit. Care Med. · Jan 1998
Clinical Trial Controlled Clinical TrialContribution of the endotracheal tube and the upper airway to breathing workload.
The influence of the endotracheal tube (ETT) during a T-piece trial remains controversial. Our aim was to compare the work of breathing of 14 successfully extubated patients at the end of a 2-h trial (T) and after extubation (E) of the trachea, and to assess, using the acoustic reflection method, the resistance of the endotracheal tube and of the supraglottic airway as well as their related work. We found that the work of breathing of the patients was identical between T and E (1.72 +/- 0.59 versus 1.63 +/- 0.45 J/L; p = 0.50 and 23.5 +/- 10.6 versus 22.6 +/- 9.7 J/min; p = 0.70). ⋯ The work caused by the ETT amounted to 11.0 +/- 3.9% of the total work of breathing. The supraglottic airway resistance was in the normal range and was significantly smaller than the endotracheal tube resistance (0.79 +/- 0.4 versus 1.43 +/- 0.31 cm H2O x s/L; p = 0.008, flow = 0.25 L/s). We conclude that a 2-h trial of spontaneous breathing through an endotracheal tube well mimics the work of breathing performed after extubation, in patients who pass a weaning trial and do not require reintubation.
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Am. J. Respir. Crit. Care Med. · Jan 1998
Effects of ventilation strategies on the efficacy of exogenous surfactant therapy in a rabbit model of acute lung injury.
We evaluated the effects of various ventilation strategies on the efficacy of exogenous surfactant therapy in lung-injured adult rabbits. Lung injury was induced by repetitive whole-lung saline lavage followed by mechanical ventilation. Three hours after the final lavage, 100 mg lipid/kg bovine lipid extract surfactant was instilled. ⋯ Animals ventilated with the low-VT modes (Low VT [5 cm H2O] and Low VT [9 cm H2O]) had higher PaO2 values (430 +/- 7 mm Hg and 425 +/- 18 mm Hg versus 328 +/- 13 mm Hg) and higher percentages of surfactant in large aggregate forms (83 +/- 2% and 82 +/- 2% versus 67 +/- 4%) at 3 h after treatment than did the Normal VT (5 cm H2O) group (p < 0.05). Increasing the PEEP level was beneficial for a short period after surfactant administration to maintain oxygenation, but did not affect exogenous surfactant aggregate conversion. We speculate that ventilation strategies resulting in low exogenous surfactant aggregate conversion will result in superior physiologic responses to exogenous surfactant.