Aortic stenosis with severe left ventricular dysfunction and low transvalvular pressure gradients: risk stratification by low-dose dobutamine echocardiography.

OBJECTIVES: We sought to assess risk stratification by using dobutamine stress echocardiography (DSE) in patients with aortic stenosis (AS) and severe left ventricular (LV) dysfunction. BACKGROUND: Few data are available on risk stratification for valve replacement in patients with AS, LV dysfunction and low transvalvular gradients. METHODS: Low-dose DSE was performed in 45 patients (16 women and 29 men; median [quartile range] age in years: 75 [69 to 79]; left ventricular ejection fraction: 0.29 [0.23 to 0.32]; aortic valve area [cm2]: 0.7 [0.5 to 0.8]; mean transaortic gradient [mm Hg]: 26 [21 to 33]). Patients were classified into two groups: group I (n = 32, LV contractile reserve on DSE) and group II (n = 13, no contractile reserve). Valve replacement was performed in 24 and 6 patients in groups I and II, respectively. RESULTS: Perioperative mortality was 8% in group I and 50% in group II (p = 0.014). Survival at five years after the operation was 88% in group I. Compared with medical therapy, valve surgery was associated with better long-term survival in group I (hazard ratio for death [HR-D] 0.13, 95% confidence interval [CI] 0.002 to 0.49) and reduced survival in group II (HR-D 19.6, 95% CI 2.7 to 142). The effect of valve surgery on survival remained significant in both groups after adjustment for age, diabetes, respiratory disease and hypertension. Medical therapy had the same effect in both groups. CONCLUSIONS: In patients with AS, LV dysfunction and low transvalvular gradients, contractile reserve on DSE is associated with a low operative risk and good long-term prognosis after valve surgery. In contrast, operative mortality remains high in the absence of contractile reserve.

Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study.

CONTEXT: Tumor necrosis factor alpha (TNF-alpha) is believed to be a cytokine central to pathogenesis of septic shock. TNF2, a polymorphism within the TNF-alpha gene promoter, has been associated with enhanced TNF-alpha production and negative outcome in some severe infections. OBJECTIVES: To investigate the frequency of the TNF2 allele in patients with septic shock and to determine whether the allele is associated with the occurrence and outcome of septic shock. DESIGN: Multicenter case-control study conducted from March 1996 to June 1997. SETTING: Seven medical intensive care units in university hospitals. SUBJECTS: Eighty-nine patients with septic shock and 87 healthy unrelated blood donors. MAIN OUTCOME MEASURES: Frequency of the TNF2 allele among patients with septic shock and among those who died and the level of corresponding TNF-alpha concentrations. RESULTS: Mortality among patients with septic shock was 54%, consistent with the predicted mortality from the Simplified Acute Physiologic Score (SAPS II) value. The polymorphism frequencies of the controls and the patients with septic shock differed only at the TNF2 allele (39% vs 18% in the septic shock and control groups, respectively, P =.002). Among the septic shock patients, TNF2 polymorphism frequency was significantly greater among those who had died (52% vs 24% in the survival group, P =.008). Concentrations of TNF-alpha were higher in 68% and 52% with the TNF2 and TNF1 polymorphisms, respectively, but their median values (48 pg/mL vs 29 pg/mL) were not statistically different (P = .31). After controlling for age and the probability of death, derived by the SAPS II score, multiple logistic regression analysis showed that, for the same rank of SAPS II value, patients with the TNF2 allele had a 3.7-fold risk of death (95% confidence interval, 1.37-10.24). CONCLUSION: The TNF2 allele is strongly associated with susceptibility to septic shock and death due to septic shock.

Should mechanical ventilation be optimized to blood gases, lung mechanics, or thoracic CT scan?

This study was aimed at providing data for optimization of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). The effects of ventilation with positive end-expiratory pressure (PEEP) titrated to blood gases were studied by thoracic computed tomographic (CT) scans and lung mechanics measurements in eight patients. CT density histograms at end-expiration were used to investigate the effects of PEEP on three differently aerated zones. Static pressure-volume (P-V) curves were used to determine the deflection point above which baro-volotrauma (a combination of barotrauma and volotrauma) may occur. Peak pressures, plateau pressures, and lung volumes measured by Respitrace were compared with the deflection point. CT scan showed that PEEP increased "normally aerated" areas, decreased "nonaerated" areas, and did not change "poorly aerated" zones. No correlations were found between CT scan and either PaO2 or mechanical data. Pressure at the deflection point was lower than the usually recommended 35 to 40 cm H2O for peak pressure in four patients (range, 28 to 32 cm H2O). With regard to plateau pressures, only one patient was ventilated above the deflection point. However, monitoring of volumes showed that these four patients had an end-inspiratory volume above this point. We conclude that mechanical ventilation may be initially adjusted on the basis of blood gas values and then optimized on the basis of lung mechanics to limit the risk of baro-volotrauma.

Is tracheal gas insufflation an alternative to extrapulmonary gas exchangers in severe ARDS?

Tracheal gas insufflation (TGI) of pure oxygen combined with mechanical ventilation decreases dead space and increases CO2 clearance. In the present study, TGI was used in six patients with ARDS who met extracorporeal membrane oxygenation criteria and who were severely hypoxemic and hypercapnic despite optimal pressure-controlled ventilation. This open clinical study aimed to investigate the effects of 4 L/min continuous flow of oxygen given via an intratracheal catheter. PaCO2 decreased from 108 +/- 32 to 84 +/- 26 mm Hg (p < 0.05), and no significant change in PaO2 (68 +/- 18 vs 96 +/- 43, p = 0.06). There was no change in airway pressures and hemodynamic variables. A slight increase in end-expiratory and end-inspiratory volumes with TGI possibly occurred, as seen on tracings from respiratory inductive plethysmography (Respitrace). We conclude that TGI improves tolerance of limited pressure ventilation by removing CO2, but it may induce changes in lung volumes that are not detected by ventilator measurements.

Extracorporeal carbon dioxide removal technique improves oxygenation without causing overinflation.

Extracorporeal CO2 removal combined with low frequency positive pressure ventilation (ECCO2R-LFPPV) improves gas exchange and decreases peak pressures, respiratory rates, and tidal volumes in animals and in humans. Recent evidence suggests that pulmonary barotrauma results from lung overinflation rather than from high pressures. This study was to test the hypothesis whether ECCO2R-LFPPV could improve gas exchange without causing lung overinflation, despite the use of higher levels of PEEP, when compared with conventional mechanical ventilation. Eleven patients with severe adult respiratory distress syndrome (ARDS) who failed to respond to different modes of mechanical ventilation were treated with ECCO2R-LFPPV. Risk of pulmonary barotrauma was evaluated by static pressure-volume (P-V) curves and dynamic changes in volumes monitored by respiratory inductive plethysmography (Respitrace). ECCO2R-LFPPV PaO2/FIO2 increased from 79 +/- 21 to 207 +/- 108 (p = 0.003). Risk of barotrauma, as shown by the shape of the P-V curve, was present in all patients receiving mechanical ventilation even though most of them were treated with permissive hypoventilation. By contrast, no evidence of persistent lung overinflation could be detected by either static P-V curves or dynamic measurements in nine of 11 patients who were treated by ECCO2R-LFPPV. The two remaining patients had severe airway obstruction because of bleeding, and they remained ventilated with persistent risk of barotrauma. We conclude that ECCO2R-LFPPV improves gas exchange without causing lung overinflation in a majority of patients with ARDS.