Frederick G. Mihm

Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates.

In vitro and in vivo studies have suggested that human complement component C5a plays a key role in neutrophil injury in the adult respiratory distress syndrome (ARDS). First, using leukocyte aggregometry, we demonstrated that the addition of a recently developed rabbit anti-human polyclonal antibody to C5a des arg to endotoxin-activated plasma prevented leukocyte aggregation in vitro. We then administered the anti-C5a des arg antibody to septic primates (Macaca fascicularis). Three groups of primates, control, septic, and anti-C5a antibody treated septic, were studied (n = 4 in each group). A 30-min infusion of Escherichia coli (1 X 10(10)/kg) resulted in severe sepsis and ARDS. Primates were killed 4 h after completion of the E. coli infusion. Septic animals not treated with anti-C5a antibody had 75% mortality (3/4), decreased oxygenation, severe pulmonary edema, and profound hypotension. Septic primates treated with anti-C5a antibodies did not die and did not develop decreased oxygenation (P less than 0.05) or increased extravascular lung water (P less than 0.05). They also had a marked recovery in their mean arterial blood pressure (P less than 0.05). This study demonstrates that treatment with rabbit anti-human C5a des arg antibodies attenuates ARDS and some of the systemic manifestations of sepsis in nonhuman primates.

Measurement of Extravascular Lung Water in Dogs Using the Thermal-Green Dye Indicator Dilution Method

The measurement of extravascular lung water by a double-indicator dilution technique using cold indocyanine green dye was evaluated in dogs. Pulmonary edema was induced in 11 animals by volume overload; 12 animals served as controls. For each measurement, the two indicators (cold dye) were injected into the superior vena cava and detected in the femoral artery. The extravascular thermal volume was calculated using the mean transit times of the two indicator curves. Pretermination measurements of extravascular thermal volume correlated closely with standard gravimetric analysis of pulmonary extravascular tissue weight (EVTV - 1.15 PEW + 2.1 ml/kg, n = 21, r = 0.97, P less than 0.001; where EVTV = extravascular thermal volume and PEW = pulmonary extravascular tissue weight). Throughout the experiment, the arterial oxygen tension and alveolar-arterial oxygen tension gradient, correlated poorly with EVTV (linear correlation: r = 0.47, 0.45, respectively). The intrapulmonary shunt correlated better with EVTV (r = 0.72). Nonlinear correlation of EVTV with intravascular pressures (left ventricular filling pressures, colloid oncotic pressures, and the pulmonary artery occlusion pressure-colloid oncotic pressure gradient) were more significant than linear relationships. The critical pressures at which lung water rapidly increased in this model occurred at left ventricular filling pressures of 22-27 mmHg and at pulmonary artery occlusion pressure-colloid oncotic pressure gradients of 25-30 mmHg. The thermal dye technique appears to provide an accurate measurement of lung water changes in this pressure edema model.

A multicenter evaluation of a new continuous cardiac output pulmonary artery catheter system.

OBJECTIVE To validate a new system of continuous cardiac output monitoring. DESIGN Multicenter, prospective, nonrandomized clinical study. SETTING Four university hospitals. PATIENTS Forty-seven adult intensive care unit patients. INTERVENTIONS Pulmonary artery catheterization. MEASUREMENTS AND MAIN RESULTS Continuous and bolus cardiac output measurements were obtained over 72 hrs. The 327 continuous cardiac output measurements compared favorably with bolus cardiac output measurements (bias = 0.12 L/min, precision = +/-0.84). The continuous cardiac measurement was not adversely affected by temperatures of <37 degrees C or >38 degrees C, high (>7.5 L/min) or low (<4.5 L/min) cardiac output values, or duration (72 hrs) of the study. CONCLUSIONS This continuous cardiac output system provides a reliable estimate of cardiac output for clinical use if applied in conditions similar to this study. The combination of a continuous measure of cardiac output with other continuous physiologic monitoring (arterial and mixed venous oxygen saturation, oxygen consumption, etc.) may provide important information that no single parameter could achieve.

Thermal dye double indicator dilution measurement of lung water in man: comparison with gravimetric measurements.

The thermal dye double indicator dilution technique for estimating lung water was compared with gravimetric analyses in nine human subjects who were organ donors. As observed in animal studies, the thermal dye measurement of extravascular thermal volume (EVTV) consistently overestimated gravimetric extravascular lung water (EVLW), the mean (SEM) difference being 3.43 (0.59) ml/kg. In eight of the nine subjects the EVTV -3.43 ml/kg would yield an estimate of EVLW that would be from 3.23 ml/kg under to 3.37 ml/kg over the actual value EVLW at the 95% confidence limits. Reproducibility, assessed with the standard error of the mean percentage, suggested that a 15% change in EVTV can be reliably detected with repeated measurements. One subject was excluded from analysis because the EVTV measurement grossly underestimated its actual EVLW. This error was associated with regional injury observed on gross examination of the lung. Experimental and clinical evidence suggest that the thermal dye measurement provides a reliable estimate of lung water in diffuse pulmonary oedema states.

Prolonged toxicity of organophosphate poisoning.

A case of poisoning with a new organophosphate (fenthion) is reported in which the initial cholinergic crisis was delayed 5 days and recurred 24 days after ingestion. Psychosis was a persistent and sometimes singular manifestation. Because of the high lipid solubility of this pesticide, toxin analysis of repeated fat biopsies was an essential component of the management of this patient.

An Integrated Circuit-Based Optical Sensor for In Vivo Measurement of Blood Oxygenation

The theory, design, and initial evaluation of an optkal sensor for the measurement of blood oxygen saturation (SO2) and hematocrit (Hct) are presented. A model based on the diffusion of light in an anisotropically scattering medium is developed and used to predict the effects of physiological parameters and the source/detector configuration on the diffuse reflectance of blood measured by the sensor. From model results, a ratiometric method is developed by which SO2 and Hct can be determined using a sensor comprised of three light sources and a detector. An implantable integrated circuit-based sensor was built to perform the blood reflectance measurements. The design of the monolithic signal processor is discussed, along with techniques for combining the chip with hybrid optoelectronics on the same glasscapped silicon substrate. Finally, preliminary results of an in vitro evaluation of prototype sensors are presented.

Measurement of cardiac output by transpulmonary arterial thermodilution using a long radial artery catheter. A comparison with intermittent pulmonary artery thermodilution

Cardiac output can be measured accurately by transpulmonary arterial thermodilution using the PiCCO® (Pulsion Medical Systems, Munich, Germany) system with a femoral artery catheter. We have investigated the accuracy of a new 50 cm 4 French gauge radial artery catheter and the ability to use the system with a shorter radial catheter. We studied 18 patients who had undergone coronary artery surgery and made three simultaneous measurements of cardiac output by arterial thermodilution and with a pulmonary artery catheter. The radial catheter was withdrawn in 5 cm increments and the measurements were repeated. We found close agreement between arterial thermodilution and pulmonary artery thermodilution with a mean (SD) bias of 0.38 (0.77) l.min−1. Arterial thermodilution became unreliable once the catheter had been withdrawn by more than 5 cm. We conclude that cardiac output measurement with arterial thermodilution with a radial catheter is interchangeable with that derived from a pulmonary artery catheter, and that a centrally sited arterial catheter is required for accurate determination of cardiac output by transpulmonary arterial thermodilution.

New methods for whole blood oximetry

New techniques for determining the hematocrit (Hct) and oxygen saturation (SO2) of whole blood from backscattered light measurements are described. First, theoretical and experimental results are presented which show that the empirical linear relationship between SO2and the infrared-red backscattered light intensity ratio on which previous instruments have been based is an inadequate description primarily because it does not account for the strong effects of Hct and transducer geometry. Then it is shown that the ratio of backscattered intensities from two appropriately positioned infrared sources can be plotted against the infrared-red intensity ratio to produce a family of calibration curves from which SO2and Hct can be independently determined. Finally, a practical implementation of an oximetry system which employs a microelectronic catheter-tip optical sensor and a microprocessor-based signal processor is proposed.

Determination of the site of tracheal tube impingement during nasotracheal fibreoptic intubation.

This study examines the incidence and site of tracheal tube impingement during nasotracheal fibreoptic intubation, and the efficacy of anticlockwise tube rotation to overcome the problem. Forty‐three patients underwent fibreoptic‐assisted nasotracheal intubation using a preformed nasal tube, and a second fibrescope was used to observe any obstruction to passage of the tracheal tube. Impingement occurred in 10 cases, with the most common site being the right arytenoid cartilage. Rotation resulted in successful intubation in all 10 cases, but proximal rotation did not always result in an equal degree of rotation at the tube tip. We conclude that the site of impingement for nasotracheal intubation with preformed nasal tubes is located at the posterior structures of the laryngeal inlet and that anticlockwise rotation is a simple and effective solution.

Pulmonary Effects of Crystalloid and Colloid Resuscitation From Hemorrhagic Shock in the Presence of Oleic Acid-induced Pulmonary Capillary Injury in the Dog

The effects of resuscitation with crystalloid and colloid solutions in the presence of increased pulmonary capillary permeability were studied. Twenty-four hours after oleic acid administration, dogs were anesthetized and bled to produce hemorrhagic shock. One hour later, resuscitation was performed with saline, 5% albumin, or 6% hydroxyethyl starch solution to restore and then maintain cardiac output at pre-oleic acid values for 6 h. Dogs were recovered and, 24 h later, were reanesthetized for final measurements. Oleic acid administration resulted in increases in pulmonary artery pressure, pulmonary vascular resistance, and extravascular lung water (EVLW). Resuscitation from hemorrhagic shock restored pulmonary hemodynamics to pre-hemorrhage levels and did not affect EVLW, Pao2, shunt fraction, dead-space-to-tidal-volume ratio, or pulmonary compliance. There were no differences in these parameters related to the choice of resuscitation fluid. Saline resuscitation markedly reduced plasma oncotic pressure and the plasma oncotic-pulmonary artery occlusion pressure gradient. Values for these two variables were markedly lower with saline than with colloid resuscitation. The authors conclude that the pulmonary effects of crystalloid and colloid solutions are similar in the presence of moderate increases in pulmonary capillary permeability.