Tomihiro Fukushima

The Effect of Breath Termination Criterion on Breathing Patterns and the Work of Breathing During Pressure Support Ventilation

With pressure support ventilation (PSV), each PSV breath is flow-cycled, and the breath termination criterion (TC) is usually nonadjustable. When TC does not match the interaction between the patient’s inspiratory-expiratory efforts to the opening and closing of the inspiratory and expiratory valves, patient-ventilator asynchrony may occur, and the work of breathing (WOB) may increase. Therefore, we studied the effect of TC on breathing patterns and WOB during PSV in eight patients with acute respiratory distress syndrome or acute lung injury. We studied five levels of TC during PSV—1%, 5%, 20%, 35%, and 45% of the peak inspiratory flow. With increasing levels of TC, the tidal volume decreased and respiratory frequency increased, along with a decrease in duty cycle. WOB markedly increased with increasing levels of TC from 0.31 ± 0.12 J/L with TC 1% to 0.51 ± 0.11 J/L with TC 45%. Premature termination with double breathing occurred in one patient with TC 35% and four patients with TC 45%. Delayed termination with a duty cycle of >0.5 occurred in two patients with TC 1%. In conclusion, the proper adjustment of TC improves patient-ventilator synchrony and decreases WOB during PSV. IMPLICATIONS Although termination criterion (TC) is usually nonadjustable, it influences the effectiveness of pressure support ventilation for mechanical ventilation. The proper adjustment of TC is crucial to improve patient-ventilator synchrony and decrease work of breathing. TC 5% of the peak inspiratory flow may be the optimal value for patients with acute respiratory distress syndrome or acute lung injury.

Endotoxin-induced zinc accumulation by liver cells is mediated by metallothionein synthesis.

Endotoxin induces a decrease in zinc concentration in the serum and an increase in zinc levels in the liver. We have studied whether metallothionein (MT), which is a heavy metal-binding protein, is associated with this phenomenon in vitro. When MT of liver cells is induced by a factor secreted by endotoxin-stimulated macrophages, the cells accumulate zinc from the medium. The temporal accumulation of zinc is correlated with the induction of MT, and the accumulated zinc binds to MT. These results suggest that zinc accumulation by liver cells is mediated by metallothionein produced in response to a macrophage factor, which is elicited by endotoxin.

Involvement of transforming growth factor-α secreted by macrophages in metallothionein induction by endotoxin

The mechanism of metallothionein (MT) induction of the liver by endotoxin, which is mediated by a factor secreted by endotoxin-stimulated macrophages, was studied in vitro. MT induction of the liver cells by the endotoxin-stimulated macrophage conditioned medium was inhibited by a monoclonal antiepidermal growth factor (EGF) / transforming growth factor-alpha (TGF-alpha) receptor antibody, which acts as an antagonist of EGF and TGF-alpha. MT was induced by the substance, which was adsorbed by polyclonal antibody to TGF-alpha, but not by a monoclonal antibody to EGF, in the conditioned medium of endotoxin-stimulated macrophages. These results suggest that TGF-alpha secreted by macrophages is involved in MT induction by endotoxin.

Induction of metallothionein by a macrophage factor and the partial characterization of the factor

The mechanism of metallothionein (MT) induction by lipopolysaccharide (LPS) was studied using an in vitro system. Rat peritoneal macrophages were incubated with or without LPS, after which the incubation medium was overlaid on human hepatic (Chang) cells. MT synthesis was induced in Chang cells treated with the macrophage medium incubated with LPS. No induction was observed when LPS was added directly to the Chang cell medium or when Chang cells were treated with the macrophage medium incubated without LPS. These results suggest that induction of MT by LPS is mediated by a factor released from macrophages. The factor is different from the known primary inducers of MT, such as heavy metals, glucocorticoid hormones, interleukin 1, and interferon. The factor is heat stable, nondialyzable, and stable at pH 2. Although its activity is lost by pepsin and trichloroacetic acid, it is resistant to trypsin.

Reliability of central venous pressure to assess left ventricular preload for fluid resuscitation in patients with septic shock

BackgroundInitial fluid resuscitation is an important hemodynamic therapy in patients with septic shock. The Surviving Sepsis Campaign Guidelines recommend fluid resuscitation with volume loading according to central venous pressure (CVP). However, patients with septic shock often develop a transient decrease in cardiac function; thus, it may be inappropriate to use CVP as a reliable marker for fluid management.MethodsWe evaluated 40 adult patients with septic shock secondary to intra-abdominal infection who received active treatment and were monitored using transthoracic echocardiography (TTE) and CVP for 2 days after admission to our intensive care unit (ICU). We measured left ventricular end-diastolic diameter (LVEDD), left atrial diameter (LAD), and the pressure gradient of tricuspid regurgitation (TR∆P). The shock status was treated with volume loading and inotrope/vasopressor administration according to the TTE findings. We assessed left ventricular fractional shortening (LVFS) as an index of left ventricular contractility and TR∆P as an index of right ventricular afterload and then examined the correlation between CVP and LVEDD/LAD/TR∆P.ResultsLVFS decreased to ≤30% in 42.5% and 27.5% of patients with septic shock, and severe left ventricular dysfunction with LVFS ≤20% developed in 12.5% and 15.0% of patients on the first and second ICU days, respectively, despite the use of inotropes/vasopressors. Mild pulmonary hypertension as indicated by TR∆P ≥30 mmHg was present in 27.5% and 30.0% of patients on their first and second ICU days, respectively. There was no significant correlation between CVP and LVEDD/LAD/TR∆P. The hospital mortality rate in this study was 10.0%, although the predicted mortality based on the Acute Physiology and Chronic Health Evaluation II score was 58.7%.ConclusionsOur results suggest that CVP is not a reliable marker of left ventricular preload for fluid management during the initial phase of septic shock. Assessment of left ventricular preload, right ventricular overload, and left ventricular contractility using TTE seems to be more informative than the measurement of CVP for fluid resuscitation since some patients developed left ventricular dysfunction and/or right ventricular overload.