Halothane inhibits endothelium-dependent relaxation elicited by acetylcholine in human isolated pulmonary arteries.

This study examined whether a clinically relevant concentration of the volatile anaesthetic halothane modifies the endothelium-dependent relaxation produced by acetylcholine (3 nM-10 microM), histamine (1 pM-0.1 microM) and anti-human immunoglobulin E (1:1000) in human isolated pulmonary arteries submaximally precontracted with noradrenaline. An inhibitor of nitric oxide formation, N(G)-nitro-L-arginine (100 microM), attenuated acetylcholine-induced relaxation but failed to inhibit histamine- and anti-human immunoglobulin E-induced relaxation. Indomethacin (2.8 microM, a cyclooxygenase inhibitor) preferentially reduced the relaxation to histamine and anti-human IgE. Halothane (2%) significantly attenuated the relaxation to acetylcholine but had no significant effect on the relaxation elicited by histamine and anti-human IgE. Halothane (2%) enhanced the basal release of prostaglandin I2 by human pulmonary arteries (control 0.31 +/- 0.04 ng mg(-1); treated tissues 0.50 +/- 0.06 ng mg(-1); n = 5; P < 0.05). Halothane (2%) did not alter the responsiveness and sensitivity of preparations to relaxants acting through activation of adenylyl cyclase (forskolin) or guanylyl cyclase (sodium nitroprusside) or by the opening of K(ATP) channels (cromakalim). In conclusion, halothane inhibits the endothelium-dependent relaxation of human pulmonary arteries to acetylcholine by interfering with the nitric oxide pathway at a site before activation of soluble guanylyl cyclase in vascular smooth muscle.

[Ventilatory management of the severely brain-injured patient]. / Manejo ventilatorio del paciente con traumatismo craneoencefálico grave.

Mechanical ventilation is necessary for treating patients with severe brain injury because it guarantees the airway (through endotracheal intubation), permits sedation (and even curarization), and prevents hypoxemia and/or hypercapnia. Hyperventilation continues to be a focus of debate in the current literature. Nevertheless, the weight of scientific evidence to date suggests that it should not be applied prophylactically during the first 24 hours and that patients should not be hyperventilated for prolonged periods in the absence of intracranial hypertension. Acute lung injury and respiratory distress are among the most frequent and serious complications related to severe brain injury that benefit from the use of positive end-expiratory pressure (PEEP) and ventilation to protect the lung. Gas insufflation through the trachea is a promising therapeutic option for correcting hypercapnia secondary to ventilation for lung protection in such patients. Finally, multimodal monitoring (intracranial pressure, central venous pressure, oxygen saturation detected in the jugular bulb, cerebral oxygen pressure) is recommended for adjusting PEEP and controlling hyperventilation.

[Comparison of patient-ventilator synchronization during pressure support ventilation versus amplified spontaneous pattern in postoperative patients]. / Comparación de la sincronización paciente-ventilador durante la ventilación con presión de soporte y con patrón espontáneo amplificado en pacientes postoperados.

INTRODUCTION: Patient-ventilator desynchronization can develop during weaning from proportional-assist ventilation. Poor adaptation between ventilator assistance and the patient's ventilatory demand is termed asynchrony. OBJECTIVES: Comparative analysis of types and incidence of asynchrony in patients receiving pressure support (PS) ventilation or amplified spontaneous pattern (ASP) ventilation, to determine whether the presence of asynchrony is related to a patient's level of dyspnea or anxiety. PATIENTS AND METHODS: Eighteen patients were studied prospectively after undergoing coronary revascularization. Baseline anxiety was assessed before surgery. A pleural catheter was inserted during surgery. After surgery patients were randomly assigned to ventilation with PS mode or ASP. Flow curves, flow volume, airway pressure and pleural pressure were recorded by a BioCore CP100 monitor once the patient's work of breathing held steady between 0.3 and 0.5 J/l. The curves were recorded for 10 m on a computer for later analysis. After each recording dyspnea and anxiety were assessed. Fifty consecutive cycles per patient were analyzed, signalling in each case the start of inspiration and expiration. RESULTS: Nine hundred ventilatory cycles were analyzed to identify five types of patient-ventilator asynchrony: 1) self-cycled (SC: inspiratory assistance from the ventilator without demand by patient); 2) no effort detected (NED: patient inspiratory effort but no flow response from the ventilator); 3) interrupted support (IS: interruption of ventilatory support during patient inspiration); 4) prolonged mechanical inspiration (PMI: maintenance of ventilatory support during patient expiration), and 5) double-breath, single cycle (DBSC: sequence of inspiration-expiration-inspiration of the patient within a single assisted inspiration). Asynchronic cycles were found in all PS-ventilated patients (84 of 450; 18.7%): 9.1% SC, 4% NED, 2.2% IS, 1.5% PMI and 1.8% DBSC. Asynchronic cycles were seen in only two ASP patients (16 of 450; 3.5%); both cases were NED asynchrony. Levels of anxiety and dyspnea were slightly higher with the PS mode than with ASP but the differences were not significant (p = 0.05). CONCLUSIONS: The incidence of asynchrony during assisted ventilation is very high with the PS mode and is substantially less with ASP. Asynchrony is difficult to detect clinically and is revealed only by advanced cycle-to-cycle monitoring.

[Evaluation of amplified spontaneous pattern ventilation in postoperative patients. Comparison with pressure support]. / Evaluación de la ventilación con patrón espontáneo amplificado en pacientes postoperados. Comparación con la presión de soporte.

HYPOTHESIS: Amplified spontaneous pattern (ASP) ventilation is a new method for giving partial support by reproducing, in an amplified manner, the patients' own spontaneous flow wave form, thereby optimizing patient adaptation to support. OBJECTIVES: To study clinical use of ASP ventilation for the first time in terms of flow wave form, patient synchronization, ventilation pattern, work of breathing (WOB), and inspiratory effort by transpulmonary pressure (TPP) and to compare ASP and pressure support ventilation applied in a similar clinical setting. PATIENTS AND METHOD: We studied 20 patients after heart surgery during weaning from controlled ventilation. Each patient was ventilated during 4 phases of 15 min each with two similar levels of support using ASP and PS applied successively and randomly. Maximum support (ASPmax and PSmax) was that which was set to give the same respiratory frequency (F) and tidal volume (VT) as that recorded during the earlier period of controlled ventilation. Half support (PEA1/2 and PS1/2) was set for half the aforementioned levels. At the end of each phase we obtained gas measurements and flow (V) curves and VT and pressure in airways and esophagus (Pes) to measure F, VT, the ratio of inspiratory to total time (TI/TTOT and TPP, as well as the VT/Pes loop with a mechanical ventilation monitor. The WOB was determined by measuring area under the curve (Campbell's method). RESULTS: We observed no significant differences between the two modes, with similar levels of support, with regard to ventilation (PaCO2) or ventilatory pattern (F, VT, TI/TTOT). De-adaptation occurred, however, eight times with PS (25%) but never with ASP. WOB and TPP decreased with PS when level of support increased, whereas with ASP these variables were constant regardless of level of amplification within the normal range. CONCLUSIONS: Adaptation to support is better with ASP than with PS during postoperative weaning and causes no significant respiratory work overload.