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Objectives: Ventilator-associated pneumonia diagnosis remains a debatable topic. New definitions of ventilator-associated conditions involving worsening oxygenation have been recently proposed to make surveillance of events possibly linked to ventilator-associated pneumonia as objective as possible. The objective of the study was to confirm the effect of subglottic secretion suctioning on ventilator-associated pneumonia prevalence and to assess its concomitant impact on ventilator-associated conditions and antibiotic use., Design: Randomized controlled clinical trial conducted in five ICUs of the same hospital., Patients: Three hundred fifty-two adult patients intubated with a tracheal tube allowing subglottic secretion suctioning were randomly assigned to undergo suctioning (n = 170, group 1) or not (n = 182, group 2)., Main Results: During ventilation, microbiologically confirmed ventilator-associated pneumonia occurred in 15 patients (8.8%) of group 1 and 32 patients (17.6%) of group 2 (p = 0.018). In terms of ventilatory days, ventilator-associated pneumonia rates were 9.6 of 1,000 ventilatory days and 19.8 of 1,000 ventilatory days, respectively (p = 0.0076). Ventilator-associated condition prevalence was 21.8% in group 1 and 22.5% in group 2 (p = 0.84). Among the 47 patients with ventilator-associated pneumonia, 25 (58.2%) experienced a ventilator-associated condition. Neither length of ICU stay nor mortality differed between groups; only ventilator-associated condition was associated with increased mortality. The total number of antibiotic days was 1,696 in group 1, representing 61.6% of the 2,754 ICU days, and 1,965 in group 2, representing 68.5% of the 2,868 ICU days (p < 0.0001)., Conclusions: Subglottic secretion suctioning resulted in a significant reduction of ventilator-associated pneumonia prevalence associated with a significant decrease in antibiotic use. By contrast, ventilator-associated condition occurrence did not differ between groups and appeared more related to other medical features than ventilator-associated pneumonia.

Objective: It was investigated whether pharmacologically induced changes in right ventricular contractility can be detected by a so-called "single-beat" method that does not require preload reduction., Design: Prospective animal research., Setting: Laboratory at a large university medical center., Subjects: Eight anesthetized pigs., Interventions: End-systolic elastance values obtained by a recently proposed single-beat method (Eessb) were compared with those obtained using the reference multiple-beat method (Eesmb)., Measurements and Main Results: Administration of dobutamine increased Eesmb from 1.6 +/- 0.3 to 3.8 +/- 0.5 mm Hg/mL (p =.001), whereas there was only a trend toward an increase in Eessb from 1.5 +/- 0.2 to 1.7 +/- 0.4 mm Hg/mL. Esmolol decreased Eesmb from 1.7 +/- 0.3 to 1.1 +/- 0.2 mm Hg/mL (p =.006), whereas there was only a trend for a decrease in Eessb from 1.5 +/- 0.2 to 1.3 +/- 0.1., Conclusions: The present method using single-beat estimation to assess right ventricular contractility does not work as expected, since it failed to detect either increases or decreases in right ventricular contractility induced by pharmacologic interventions.

Objective: To evaluate the effects of inhaled nitric oxide (NO) on pulmonary circulation in a porcine endotoxin shock model., Design: Prospective, randomized trial., Setting: Laboratory at a large university medical center., Subjects: Twelve pathogen-free pigs weighing 15 to 31 kg., Interventions: After surgical preparation, all pigs received a 0.5 mg/kg endotoxin infusion over 30 mins. One hour after the start of endotoxin, NO inhalation (40 ppm) was initiated in six pigs, whereas the six remaining pigs served to control the progression of shock in this model. Consecutive changes in systemic and pulmonary hemodynamics, including characteristic resistance, vascular compliance, peripheral vascular resistance, and inductance, were continuously assessed during the experimental protocol using a four-element Windkessel model of the pulmonary circulation., Measurements and Main Results: Endotoxin insult resulted in a biphasic pulmonary artery pressure increase from 14 +/- 2 to 32 +/- 4 mm Hg. Inhaled NO reversed the resistance to blood flow in small pulmonary arteries from 596 +/- 69 to 424 +/- 36 dyne-sec/ cm5. In contrast, the vascular capacitance of the entire pulmonary circuit, which decreased from 2.4 +/- 0.2 to 0.8 +/- 0.1 mL/mm Hg throughout endotoxin challenge, remained insensitive to NO administration., Conclusion: In endotoxin-induced pulmonary hypertension, inhaled NO may function as a modulator of distal pulmonary arterial tone but fails to act as a regulator of larger capacitance pulmonary vessels.

Objective: To identify possible alterations in the skeletal muscle high-energy phosphate metabolism at the early phase of endotoxic shock in rats., Design: A prospective, randomized study of skeletal muscle energetics in endotoxemic and in control rats, by in vivo 31P nuclear magnetic resonance (NMR) spectroscopy at rest, under regional ischemia, and during reperfusion., Setting: Biochemical NMR laboratory equipped for surgery and hemodynamic monitoring., Subjects: Wistar rats were randomized to different groups. Eight rats were injected with Escherichia coli endotoxin (15 mg/kg, survival time 19 +/- 4 hrs) intraperitoneally. Seven other rats served as controls. The additional nine rats were studied for the saturation recovery pulse sequence., Interventions: In the treatment group, endotoxin was injected 8 hrs before NMR spectroscopy. The right hind limbs were studied under anaesthesia using a surface coil NMR probe. Their high-energy phosphate contents and intracellular pH were determined by 31P NMR spectroscopy. After baseline measurements, an ischemia-reperfusion challenge was imposed on the muscle by transient clamping of the abdominal aorta. Contralateral femoral artery pressure was constantly monitored., Measurements and Main Results: During the baseline period, the endotoxin-treated muscles did not show any difference in the distribution of the high-energy phosphate compounds or in intracellular pH, as compared with the controls. Ischemia resulted in a significantly faster decline of the inorganic phosphate/creatine phosphate ratio in the endotoxin-treated rats (1.35 +/- 0.17 vs. 0.51 +/- 0.06 at the end of the 38-min ischemic period). Skeletal muscle acidosis developed earlier and was deeper in the endotoxemic animals (pH: 6.94 +/- 0.02 vs. 7.02 +/- 0.03 at the end of ischemia). During reperfusion, the calculated time constants of recovery of inorganic phosphate to phosphocreatine ratios were identical between groups., Conclusions: Resting nonischemic muscles of endotoxin-treated rats show no evidence of alterations in high-energy phosphate metabolism. However, under ischemic conditions, high-energy phosphate metabolism deteriorates faster in the skeletal muscles of treated animals. These data support the hypothesis of a greater mismatch during perfusion at very low pressure between residual oxygen availability and oxygen needs in the endotoxin-treated muscle cell.

Background and Methods: We aimed to characterize the effects of an endotoxin insult (Escherichia coli 0127:B8) on the relationships between pulmonary vascular pressure and flow in intact dogs. To achieve this goal, multipoint plots of total pressure gradient, arterial pressure gradient, and venous pressure gradient vs. flow were generated by graded inflation of a right atrial balloon, which was used to vary flow. The partitioning of the total pressure decrease across the pulmonary vasculature (total pressure gradient = pulmonary arterial pressure-pulmonary artery occlusion pressure [PAOP]) into gradients across pulmonary arterial (arterial pressure gradient = pulmonary arterial pressure--effective capillary pressure) and pulmonary venous (venous pressure gradient = effective capillary pressure--PAOP) regions was assessed by a waveform mathematical analysis of the pulmonary arterial pressure profile during arterial occlusion, with computation of both PAOP and effective pulmonary capillary pressures. Slopes and extrapolated pressure intercepts from linear regression fits to the pulmonary vascular pressure/flow plots were determined in seven dogs after a 2-hr endotoxic infusion interval and were compared with the corresponding values that characterized a similar group of sham-operated dogs., Results: Under normal conditions, the extrapolated pressure intercept for pulmonary arterial pressure gradient was virtually 0 mm Hg; for total pulmonary arterial pressure gradient and pulmonary venous pressure gradient, the mean extrapolated pressure intercepts were substantially positive: 2.4 +/- 0.2 and 2.1 +/- 0.3 mm Hg, respectively. Endotoxin infusion at 0.25 micrograms/kg/min significantly increased the pressure intercepts from 2.4 to 8.7 and from 2.1 to 8.3 mm Hg of total pressure gradient and venous pressure gradient vs. flow, respectively. This infusion produced a minor, nonsignificant change in the intercept of arterial pressure gradient vs. flow, whereas it increased its slope significantly (p less than .05) from 0.036 to 0.081 mm Hg/mL/min/kg., Conclusions: These data suggest that endotoxin's effects on vascular resistance are exerted at two different loci such that these effects are additive. These endotoxin-induced effects consisted of increased vascular resistance of the arterial segment and appearance of a Starling resistor at the venous side of the pulmonary circulation, which acted as the relevant back-pressure to flow.

Background and Methods: We studied the effect of volume resuscitation on lung fluid balance and systemic oxygen extraction during septic shock in eight anesthetized dogs. Sepsis was induced using a 2-hr continuous infusion of Escherichia coli endotoxin at 0.25 micrograms/min.kg. Relationships between oxygen uptake (VO2) and oxygen supply (DO2) were performed acutely during stepwise controlled decrements in cardiac output by progressive inflation of an intracardiac balloon. At each stage, DO2 and corresponding VO2 were measured independently and the individual critical DO2 level was referred to as the point below which the relationship held. The slope of such a constructed relationship was defined as the maximal oxygen extraction ratio. Lung fluid balance was assessed by measurements of extravascular lung water. All values were studied at baseline, after endotoxin insult, and after reversing hypotension by a 10% dextran infusion., Results: Endotoxin infusion led to a shock state that associated hypotension (from 135 to 63 mm Hg) with increases in blood lactate (from 0.53 to 3.9 mmol/L). The mean critical DO2 and maximal oxygen extraction ratio were significantly altered from 7.9 to 17.8 mL/min.kg and from 0.81 to 0.38, respectively. After reversing hypotension by 28 mL/kg colloid infusion, the critical DO2 (11.4 mL/min.kg) and maximal oxygen extraction ratio (0.48) were significantly improved. However, restoration of normal values required a state of fluid overload by further dextran infusion (8 mL/kg). At the end of the fluid challenge, extravascular lung water significantly increased from 6.4 to 17.4 mL/kg., Conclusions: These data suggest that volume loading may reverse endotoxin-induced peripheral perfusion abnormalities. However, substantial pulmonary edema may occur, possibly jeopardizing the beneficial effects of fluid expansion.

In 26 consecutive septic shock patients, we analyzed the clinical, hemodynamic, and metabolic data before and during volume infusion to test their circulatory reserve in response to fluid repletion. These patients were investigated to identify early variables that could predict outcome. There were 15 survivors (group A) and 11 nonsurvivors (group B). As a mean, group A patients were hemodynamically evaluated 2.3 h after onset of the sepsis syndrome, whereas group B patients underwent cardiac catheterization after a 12-h interval. At the initial evaluation, both groups demonstrated similarly decreased mean arterial pressure, mean heart rate, and mean cardiac filling pressure. Only group A patients evidenced elevated cardiac index (CI) (greater than 4 L/min.m2) associated with low systemic vascular resistance index (less than 7400 dyne.sec/cm5.m2), which is generally recognized as hyperdynamic cardiac state. However, none of the initial cardiovascular variables could serve as a predictor for survival. Fluid challenge increased left ventricular preload from 6 to 12.4 and from 7.8 to 12.7 mm Hg in group A and group B, respectively. The increases were associated with significant increases in CI from 4.4 to 6.9 and from 3 to 3.8 L/min.m2. However, at the end of fluid challenge, only group A patients exhibited normal cardiac response, as evidenced by the change in left ventricular stroke work index (LVSWI) for a given increase in the pulmonary capillary wedge pressure (WP) that was referred to as left cardiac preload.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of the present study was to determine possible effects of Escherichia coli endotoxin on peripheral vascular compliance and relate them to concomitant central hemodynamic disturbances. Endotoxin was infused at 0.25 micrograms/kg.min during 2 h in six anesthetized dogs, while six additional animals served as controls. Vascular compliance of the systemic circulation was calculated in intact animals from the changes in CVP after known changes in systemic blood volume. In control dogs, vascular compliance averaged 2.3 ml/mm Hg.kg body weight. During slow endotoxin infusion, cardiovascular effects were measurable only after a certain period of time had elapsed from the start of endotoxin insult and consisted of hypotension associated with systemic vasodilation. Systemic BP decreased gradually from 124 to 68 mm Hg while vascular compliance was finally increased by 100%, when compared to control values. This latter rise was responsible for a reduction in the cardiac preloads. Pulmonary wedge pressure and CVP were decreased from 7.1 to 3.4 and from 4.5 to 2.6 mm Hg, respectively. However, parallel to the decrease in left ventricular preload, endotoxin induced a progressive decrease in left ventricular afterload. Because of the balance in ventricular loading, cardiac output remained almost unchanged. After volume loading (dextran 30 ml/kg), cardiac output was remarkably increased from 3.28 to 6.24 L/min.m2 while peripheral vasodilation was not affected by this maneuver. It is concluded that low dose endotoxin infusion induces in dogs a hemodynamic pattern similar to human sepsis. The left ventricular loading changes are related to an enhanced systemic vascular compliance from 2.3 to 4.5 ml/mm Hg.kg. High flow shock state is encountered provided peripheral blood pooling is compensated by adequate volume replacement.

We tested the early effects of endotoxin on both the permeability of capillary membranes and microvascular pressure. One group of dogs (n = 8) were fluid loaded (30 ml/kg dextran-40) after having been subjected to a 2-h Escherichia coli endotoxin infusion (0.25 micrograms/kg X min). A second control group of animals (n = 6) was submitted to a similar (25 ml/kg) volume loading over an equivalent 30-min period. We estimated extravascular lung water (EVLW), calculated the effective pulmonary capillary pressure, and determined the alveolar-capillary filtration coefficient (Kf) after volume loading. Only the septic animals consistently showed elevated EVLW values consistent with pulmonary edema. The results showed, however, that the Kf calculated for the dogs that received endotoxin was no different from that of control group (Kf = 0.005 ml/kg X min X mm Hg). Instead, endotoxin constricted the pulmonary veins which led to a considerable rise in microvascular hydrostatic pressure above the level at which the lungs could not resist edema formation. We conclude that acute pulmonary edema that follows endotoxin insult and subsequent therapeutic volume replacement is due to an increased filtration force instead of an alteration in the microvascular permeability.

The effects of endotoxin on pulmonary hemodynamics were studied in seven intact dogs. The distribution of pulmonary vascular resistance was estimated by the effective pulmonary capillary pressure, which was derived from the pressure transient recorded while the pulmonary artery catheter was rapidly wedged. After the injection of endotoxin, cardiac output and aortic pressure consistently fell. Pulmonary artery occlusion (wedge) pressure also decreased, but not significantly. Although pulmonary artery pressure did not necessarily rise, total pulmonary vascular resistance increased in every dog. The absolute increase in pulmonary artery resistance was greater (142 mm Hg/L X min/kg); than in venous resistance (111 mm Hg/L X min/kg); however, the relative increase in venous resistance was higher (410% for venous resistance vs. 220% for pulmonary artery resistance). As a result of venoconstriction, there was a consistent increase in effective pulmonary capillary pressure (from 2.5 to 6.3 mm Hg). Our data indicate that the pulmonary vascular response to endotoxin injection is characterized by constriction of both pulmonary arteries and pulmonary veins. The capillary wedge pressure did not reflect the pulmonary microvascular pressure, since it varied in the opposite direction to the effective capillary pressure.