Barry Wiggs

Bicarbonate Does Not Improve Hemodynamics in Critically III Patients Who Have Lactic Acidosis: A Prospective, Controlled Clinical Study

Abstract Study Objective:To determine whether correction of acidemia using bicarbonate improves hemodynamics in patients who have lactic acidosis. Design:Prospective, randomized, blinded, crossover...STUDY OBJECTIVE To determine whether correction of acidemia using bicarbonate improves hemodynamics in patients who have lactic acidosis. DESIGN Prospective, randomized, blinded, crossover study. Each patient sequentially received sodium bicarbonate and equimolar sodium chloride. The order of the infusions was randomized. SETTING Intensive care unit of a tertiary care hospital. PATIENTS Fourteen patients who had metabolic acidosis (bicarbonate less than 17 mmol/L and base excess less than -10) and increased arterial lactate (mean, 7.8 mmol/L). All had pulmonary artery catheters and 13 were receiving catecholamines. MEASUREMENTS AND MAIN RESULTS Sodium bicarbonate (2 mmol/kg body weight over 15 minutes) increased arterial pH (7.22 to 7.36, P less than 0.001), serum bicarbonate (12 to 18 mmol/L, P less than 0.001), and partial pressure of CO2 in arterial blood (PaCO2) (35 to 40 mm Hg, P less than 0.001) and decreased plasma ionized calcium (0.95 to 0.87 mmol/L, P less than 0.001). Sodium bicarbonate and sodium chloride both transiently increased pulmonary capillary wedge pressure (15 to 17 mm Hg, and 14 to 17 mm Hg, P less than 0.001) and cardiac output (18% and 16%, P less than 0.01). The mean arterial pressure was unchanged. Hemodynamic responses to sodium bicarbonate and sodium chloride were the same. These data have more than 90% power of detecting a 0.5 L/min (7%) change in mean cardiac output after administration of sodium bicarbonate compared with that after sodium chloride. Even the 7 most acidemic patients (mean pH, 7.13; range, 6.90 to 7.20) had no significant hemodynamic changes after either infusion. CONCLUSIONS Correction of acidemia using sodium bicarbonate does not improve hemodynamics in critically ill patients who have metabolic acidosis and increased blood lactate or the cardiovascular response to infused catecholamines in these patients. Sodium bicarbonate decreases plasma ionized calcium and increases PaCO2.

The effect of cigarette smoking on neutrophil kinetics in human lungs.

Neutrophils may play a part in the pathogenesis of the centrilobular emphysema associated with cigarette smoking. The capillary bed of the lungs concentrates neutrophils approximately 100-fold with respect to erythrocytes, producing a large pool of marginated cells. We examined the effect of cigarette smoking on the kinetics of this pool of cells, using 99mTc-labeled erythrocytes to measure regional blood velocity and 111In-labeled neutrophils to measure the removal of neutrophils during the first passage through the pulmonary circulation, their subsequent washout from the lungs, and the effect of local blood velocity on the number of neutrophils retained in each lung region. We observed no difference in these measurements between subjects who had never smoked (n = 6) and smokers who did not smoke during the study (n = 12). However, subjects who did smoke during the study (n = 12) had a significantly slower rate of washout of radiolabeled neutrophils from the lung (0.08 +/- 0.04 of the total per minute, as compared with 0.13 +/- 0.06 in smokers who did not smoke during the experiment and 0.14 +/- 0.08 in non-smokers) (P = 0.02). We also observed an increase in the regional retention of labeled neutrophils with respect to blood velocity in 5 of the 12 subjects who smoked during the study, but in none of the other subjects. We conclude that the presence of cigarette smoke in the lungs of some subjects increases the local concentration of neutrophils, and suggest that the lesions that characterize emphysema may be a result of the destruction of lung tissue by neutrophils that remain within pulmonary microvessels.

Increased concentrations of plasma lactate predict pathologic dependence of oxygen consumption on oxygen delivery in patients with adult respiratory distress syndrome

Abstract We asked whether increasing systemic oxygen delivery by blood transfusion could identify pathologic dependence of oxygen consumption on oxygen delivery in patients who have adult respiratory distress syndrome (ARDS) with and without increased concentrations of plasma lactate. Twenty-four ARDS patients were divided into normal (n = 11, lactate ≤ 1.8 mmol/L) and increased (n = 13, lactate > 1.8 mmol/L) plasma lactate groups. After transfusion of two units of packed red blood cells, oxygen delivery index increased significantly in both the normal and increased plasma lactate groups. In the increased plasma lactate group, this was associated with a significant increase in oxygen consumption index and an unchanged oxygen extraction ratio. In contrast, in the normal plasma lactate group, oxygen consumption index did not change from the baseline value and the oxygen extraction ratio decreased significantly. We conclude that increasing systemic oxygen delivery by blood transfusion identifies pathologic dependence of oxygen consumption on oxygen delivery in patients who have ARDS and increased concentrations of plasma lactate.

Pulmonary transit time and diffusion limitation during heavy exercise in athletes

To investigate relationships between pulmonary transit times (PTT) and pulmonary diffusion limitation during exercise, 10 high aerobic capacity athletes (VO2max = 5.15 +/- 0.52 l.min-1) who had multiple inert gas elimination analysis evidence suggestive of diffusion disequilibrium were studied at rest and maximal exercise. Diffusing capacity for oxygen (DLO2) was calculated from the inert gas data. First pass radionuclide angiography was performed using 99mTechnecium labeled erythrocytes and whole lung PTT and pulmonary blood volume (PBV) were calculated. PTT decreased from 9.32 +/- 1.41 sec at rest, to 2.91 +/- 0.30 sec during exercise and was correlated with diffusion limitation suggested by the inert gases (r = -0.58, P < 0.05). PBV increased during exercise to over 25% of whole blood volume and correlated with DLO2 (r = 0.82, P < 0.01). These data suggest that diffusion limitation is related to shortened PTT in athletes and that maximal recruitment of PBV may defend against diffusion limitation.

Ultrastructure and tensile properties of human tracheal cartilage.

The cartilage of the walls of the trachea and bronchi acts to keep these airways open despite intrathoracic pressure differences during breathing that would otherwise collapse them and limit air flow. Changes in biomechanical properties and composition of airway cartilage may contribute to altered lung function in obstructive lung diseases. To investigate the relationship between collagen organization and equilibrium tensile modulus within the structure of airway cartilage, we used scanning electron microscopy (SEM), histochemistry and equilibrium tensile testing to analyze tracheal cartilage from 10 humans aged 17-81 yr. We show that the surfaces of tracheal cartilage matrix are collagen-rich and surround a proteoglycan-rich core. Collagen fibrils in the superficial zones are oriented in the plane of the cartilage surface. In deeper layers of the cartilage, collagen fibrils are oriented less regularly. Equilibrium tensile modulus of 100 microm thick strips of cartilage was measured and was found to decrease with depth; from 13.6 +/- 1.5 MPa for the ablumenal superficial zone to 4.6 +/- 1.7 MPa in the middle zone (means +/- S.D., n = 10, p < 0.001). Stress-strain curves were linear for strains up to 10% with minimal residual strain. This is consistent with a model in which collagen fibres in the outer layers of the cartilage resist tensile forces, and hydrated proteoglycans in the central zone resist compression forces as the cartilage crescent bends.

Types, numbers, sizes, and distribution of mineral particles in the lungs of urban male cigarette smokers

We analyzed the exogenous mineral particle concentration, size, type, and distribution for particles larger than 0.1 micron in the left lungs of 10 long-term male cigarette smokers. The mean number of particles found was 465 +/- 295 X 10(6)/g dry lung, of which 80% were kaolinite, micas, feldspars, free silica, and talc. Lead particles were extremely rare, despite their ubiquity in urban air. Overall there were no differences in particle concentration in upper vs lower lobes or central vs peripheral sampling sites. However, a significant correlation was found for upper lobe (r = 0.68), but not lower lobe (r = 0.08), particle concentration and amount of cigarette smoking. Overall, the geometric mean particle size was 0.6 +/- 2.1 microns; 56% of the particles in the upper lobes were larger than 0.75 micron in diameter, compared to 17% in the lower lobes, and the mean upper lobe particle size was greater than the mean lower lobe particle size for all individual mineral types. There was a remarkable homogeneity of mean particle size from patient to patient (mean intercase arithmetic particle size +/- SD of 0.8 +/- 0.1 micron). Particle size was not affected by the amount of smoking. We conclude that contrary to some published acute deposition data, there are no long-term differences in upper vs lower lobe particle concentration; total upper lobe particle retention is influenced by the amount of smoking as measured by pack-years, whereas total lower lobe particle retention appears to be independent by the amount of smoking; particles retained in the upper lobe are somewhat larger than those retained in the lower lobe, but the amount of smoking does not appear to influence retained particle size; the size of long-term retained particles most likely reflects largely atmospheric particle burden; and in the absence of overwhelming dust loads, the lung is able to regulate retained particle concentration and size in a fairly narrow range.

Mucosal Folding in Biologic Vessels

A two-layer model is used to simulate the mechanical behavior of an airway or other biological vessel under external compressive stress or smooth muscle constriction sufficient to cause longitudinal mucosal buckling. Analytic andfinite element numerical methods are used to examine the onset of buckling. Post-buckling solutions are obtained by finite element analysis, then verified with large-scale physical model experiments. The two-layer model provides insight into how the stiffness of a vessel wall changes due to changes in the geometry and intrinsic material stiffnesses of the wall components. Specifically, it predicts that the number of mucosal folds in the buckled state is diminished most by increased thickness of the inner collagen-rich layer, and relatively little by increased thickness of the outer submucosal layer. An increase in the ratio of the inner to outer material stiffnesses causes an intermediate reduction in the number of folds. Results are cast in a simple form that can easily be used to predict buckling in a variety of vessels. The model quantitatively confirms that an increase in the thickness of the inner layer leads to a reduction in the number of mucosal folds, and further, that this can lead to increased vessel collapse at high levels of smooth muscle constriction.

Mineral particles, mineral fibers, and lung cancer

The total fibrous and nonfibrous mineral content of the lung has been analyzed in a series of 14 men with lung cancer but no history of occupational dust exposure, and in a series of 14 control men matched for age, smoking history, and general occupational class. The lung cancer patients had an average of 525 +/- 369 X 10(6) exogenous mineral particles and 17.4 +/- 19.6 X 10(6) exogenous mineral fibers/g dry lung, while the controls had averages of 261 +/- 175 mineral particles and 4.7 +/- 3.2 X 10(6) mineral fibers/g dry lung. These differences are statistically significant for both particles and fibers. Kaolinite, talc, mica, feldspars, and crystalline silica comprised the majority of particles of both groups. Approximately 90% of the particles were smaller than 2 micron in diameter and approximately 60% smaller than 1 micron; the mean particle size in the cancer group was 1.1 +/- 0.2 micron and in the control group 1.3 +/- 0.2 micron. In both groups, patients who had smoked more than 35 pack years had greater numbers of particles than patients who had smoked less than 35 pack years. It is concluded that, in this study, lungs from patients with lung cancer had statistically greater numbers of mineral particles and fibers than lungs from controls, and that smoking influences total long-term retention of particles from all sources.

Blood transfusion as a cause of leucocytosis in critically ill patients

The diagnosis of infection in the intensive care unit is confounded by the presence of non-infectious causes of leucocytosis. Unless such causes are recognised, time and effort will be spent on unnecessary investigations and treatments. In a prospective study we have shown that the transfusion of blood frequently (45/50 patients) causes an acute leucocytosis in such patients. This effect was not seen in 8 patients who received plasma. Blood transfusion should be added to the list of non-infectious causes of leucocytosis in the critically ill.

Leukocyte activation does not mediate myocardial leukocyte retention during endotoxemia in rabbits

Our goal was to determine whether coronary leukocyte retention after endotoxin infusion was due primarily to leukocyte activation. Leukocytes were activated by infusion of endotoxin into 12 blood donor rabbits. Separately, 12 isolated rabbit hearts were perfused with blood from an endotoxemic support rabbit to expose coronary endothelium to an inflammatory stimulus. During an infusion of 20 ml of donor blood into the isolated heart, the coronary transit time of leukocytes was determined by deconvolution of multiple measurements of injectate and collected leukocyte concentrations. With no leukocyte activation or inflammatory stimulation of endothelium, leukocyte transit time was 9.2 +/- 3.5 s, and 11.6 +/- 4.1 x 10(6) leukocytes were retained in the coronary circulation. Leukocyte activation alone did not alter transit time (9.8 +/- 3.2 s) or retention (9.3 +/- 4.6 x 10(6) leukocytes). Inflammatory stimulation of endothelium with and without leukocyte activation increased transit time (18.0 +/- 3.6 and 18.9 +/- 3.8 s, respectively; P < 0. 05) and retention (24.8 +/- 8.4 and 25.3 +/- 6.8 x 10(6) leukocytes, respectively; P < 0.05) to the same extent. Differential counts showed that neutrophils (but not lymphocytes) were slowed and retained. Inflammatory stimulation of endothelium caused coronary capillary endothelial swelling and pseudopod formation. Thus increased coronary neutrophil transit time and retention are due to structural changes of coronary endothelial cells or other effects of the inflammatory response occurring within coronary capillaries, not only due to activation of leukocytes.Our goal was to determine whether coronary leukocyte retention after endotoxin infusion was due primarily to leukocyte activation. Leukocytes were activated by infusion of endotoxin into 12 blood donor rabbits. Separately, 12 isolated rabbit hearts were perfused with blood from an endotoxemic support rabbit to expose coronary endothelium to an inflammatory stimulus. During an infusion of 20 ml of donor blood into the isolated heart, the coronary transit time of leukocytes was determined by deconvolution of multiple measurements of injectate and collected leukocyte concentrations. With no leukocyte activation or inflammatory stimulation of endothelium, leukocyte transit time was 9.2 ± 3.5 s, and 11.6 ± 4.1 × 106leukocytes were retained in the coronary circulation. Leukocyte activation alone did not alter transit time (9.8 ± 3.2 s) or retention (9.3 ± 4.6 × 106 leukocytes). Inflammatory stimulation of endothelium with and without leukocyte activation increased transit time (18.0 ± 3.6 and 18.9 ± 3.8 s, respectively; P < 0.05) and retention (24.8 ± 8.4 and 25.3 ± 6.8 × 106 leukocytes, respectively; P < 0.05) to the same extent. Differential counts showed that neutrophils (but not lymphocytes) were slowed and retained. Inflammatory stimulation of endothelium caused coronary capillary endothelial swelling and pseudopod formation. Thus increased coronary neutrophil transit time and retention are due to structural changes of coronary endothelial cells or other effects of the inflammatory response occurring within coronary capillaries, not only due to activation of leukocytes.