Blood loss and transfusion requirements in cystic fibrosis patients undergoing heart-lung or lung transplantation.
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Biomedical subjects
Publications and source records attributed to T W Feeley.
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Respiratory depression has been studied in 21 patients anaesthetized with either halothane and nitrous oxide, or isoflurane and nitrous oxide while undergoing routine surgery. Spontaneous ventilation was preserved and the end-tidal concentrations of the two volatile anaesthetics were at approximately equal MAC-multiples. The minute volume of pulmonary ventilation was not significantly different for the two anaesthetics, but tidal volume was significantly greater and frequency significantly lower with isoflurane. Arterial and end-tidal PCO2 were consistently lower in the patients receiving isoflurane, the difference being significant in many of the sub-groups. There was no evidence of a progressive increase in PCO2 with either anaesthetic during surgery lasting up to 225 min. Mean values for PCO2, however, tended to be well above the normal reference range, with mean arterial PCO2 in the range 7.2-8.6 kPa.
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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.
A model of endotoxin-induced lung injury was developed in the rat. We found that 24 h after intravenously administered endotoxin (3 mg/kg) there was increased clearance of the isotope 99mTcDTPA from the lung to blood, increased neutrophils in the lung in bronchoalveolar lavage, and increased levels of products of peroxidation of lipids and nucleic acid in the serum. Using this model, we evaluated the effect of pretreatment of rats with a human monoclonal antibody specific to the core glycolipid that is common to all endotoxins. We found that pretreatment prevented the increased clearance of 99mTcDTPA from the lung, as well as the increase in lipid peroxidation products in the serum. The antibody did not prevent increased neutrophil accumulation in the lung. The findings suggest that the administration of human antiendotoxin monoclonal antibodies prior to endotoxemia may prevent some of the changes in the lung associated with endotoxin.
The in vivo cardiovascular effect of intravenous administration of monophosphoryl lipid A (mp-lipid A) and diphosphoryl lipid A (dp-lipid A) in awake New Zealand white rabbits was investigated. Observed changes were evaluated in comparison to a control group and an endotoxin-treated group. Rabbits given lipid A showed a significant depression in cardiac index (p less than .025), mean arterial pressure (p less than .025, dp-lipid A only), arterial carbon dioxide tension (p less than .025), and total leukocyte count (p less than .05) compared to controls. Animals receiving lipid A tended to respond overall in a manner closely matching that of the endotoxin group. Dosages of lipid A given were approximately 3.5 times larger than the endotoxin dosages with respect to actual number of molecules administered (1.25-2.0 times larger by mass). These results indicate that lipid A is active in producing the cardiovascular and leukopenic effects characteristic of experimental septic shock.
The peptide leukotrienes have been detected in animals that have received endotoxin injections and also have been associated with patients suffering from the adult respiratory distress syndrome (ARDS). The ability of leukotriene D4 (LTD4) to cause pulmonary capillary permeability changes was investigated in ten anesthetized mongrel dogs. Four dogs were used as controls and six dogs received intravenous LTD4 (0.25 microgram/kg). There was a variable response in that two treated animals showed no apparent effect of LTD4. Analysis of the results from the remaining four treated animals demonstrated a significant increase in extravascular lung water (EVLW) that peaked 3 hr after LTD4 from 5.4 +/- 0.6 to 10.3 +/- 0.5 ml/kg (P less than .01). In these four dogs, EVLW increased before slight, but statistically significant, rises in pulmonary artery wedge pressure (4 +/- 1 to 9 +/- 1 mm Hg, P less than .01) and mean pulmonary artery pressure (13 +/- 1 to 17 +/- 1 mm Hg, P less than .01) occurred. During the same period, cardiac output decreased 56 +/- 7% (P less than .01), but no change in airway resistance was observed. This study is the first in vivo demonstration that LTD4 directly alters pulmonary fluid balance in the dog. We conclude LTD4 can cause increases in EVLW and may be an important mediator of the permeability changes observed in various clinical events that lead to the adult respiratory distress syndrome.
The measurement of lung water by the thermal-dye double indicator dilution technique was evaluated in dogs with normal and edematous lungs during a state of reduced cardiac output. The technique used cold indocyanine green dye to measure extravascular thermal volume (EVTV) as an estimate of extravascular lung water (EVLW). Anesthesia was maintained with pentobarbital. In 15 of 21 animals, pulmonary edema was first induced with oleic acid (0.75 to 0.18 ml/kg). Cardiac output (CO) was then decreased by a combination of propranolol and slow exsanguination (mean CO reduction to 36% of baseline). Extravascular lung water produced in this model ranged from 1.4 to 30.2 ml/kg. Predetermination measurements of EVTV correlated closely with EVLW as determined by gravimetric analysis (EVTV = 1.1 EVLW + 4.7 ml/kg, n = 21, r = 0.93, P less than 0.001). Thermodilution cardiac output measured in the abdominal aorta (used in the calculation of the EVTV) correlated well with simultaneous measurements of cardiac output by both indocyanine green dye dilution and pulmonary artery thermodilution (r = 0.86 and r = 0.88, respectively, pretermination). The thermal-dye technique appears to provide an accurate reflection of lung water in normal and edematous lungs, even in the presence of a low cardiac output.
The effect of preserving the heart and lungs with hypothermia and Collins solution was studied in 13 mongrel dogs undergoing combined heart-lung transplantation. The five control animals who underwent an immediate transplant following Collins solution perfusion had small increases in extravascular lung water when measured 2.5 hours posttransplant as seen in a previous study. The eight animals who had hypothermic preservation following Collins solution perfusion had significantly higher extravascular lung water than controls (16.3 +/- 1.8 ml/kg in preserved animals; 11.2 +/- 1.7 ml/kg in controls p less than 0.05). The level of lung water reached at 2.5 hours postoperatively was similar to that reached with a previously reported, unacceptable preservation technique. Survival beyond this point was poor due to severe pulmonary edema. We conclude that the use of this solution, given under the experimental conditions which we describe, is not acceptable for hypothermic preservation of the heart and lungs for combined transplantation.
The effect of hypothermic preservation of the heart and lungs with a crystalloid solution was evaluated in 12 mongrel dogs receiving heart-lung allografts. Six animals served as controls and received an immediate heart-lung transplant. Six animals were in the experimental group and received a heart-lung transplant after 5 hours of preservation at 4 degrees C following perfusion of both organs with a crystalloid solution. Physiological function of the heart and lungs was studied for 20 hours after transplantation. While cardiac function was minimally depressed following preservation, pulmonary function testing demonstrated significantly greater increases in extravascular lung water in experimental animals, suggesting that an ischemic lung injury occurred with this preservation technique. The model allows for future evaluation of other methods of combined preservation of both the heart and lungs for transplantation.
Colloid oncotic pressure (COP), pulmonary artery wedge pressure (WP), and the COP-WP gradient were measured in seven critically ill adult patients and compared with extravascular lung water determined using the thermal-dye double-indicator dilution technique and a bedside lung water computer. Correlation coefficients for changes in extravascular lung water vs. COP, WP, and COP-WP were not significant, and in this patient population the COP-WP gradient did not predict changes in extravascular lung water.
The diagnosis of pulmonary edema is frequently made from characteristic findings on the chest roentgenogram that suggest an increase in lung water. Optimal radiographic technique depends on a cooperative upright patient, which is not possible with most critically ill patients. These patients may also have multiple radiographic abnormalities that make interpretation of the chest roentgenogram difficult. The ability of portable chest roentgenograms to accurately identify the presence of excess lung water and monitor changes in lung water has not previously been evaluated in critically ill adults who are intubated and ventilated and in the supine position when the films are exposed. In 12 patients the pulmonary edema seen on portable chest roentgenograms was given a score (0 to 390 points), which was then compared with a determination of extravascular lung water using the thermal-dye indicator dilution technique. A linear correlation was observed (r = 0.51; p less than 0.05; n = 73). Evaluation of a change in radiographic score vs a change in lung water showed no linear correlation (r = 0.1; p greater than 0.05). While portable chest roentgenograms exposed under the conditions described were a useful technique for demonstrating pulmonary edema, they were not accurate in monitoring modest changes in lung water in critically ill patients.
The end-tidal carbon dioxide tension (PetCO2) measured after a single, large tidal-volume breath (15 ml/kg body weight) was compared to simultaneous measurements of PaCO2 in 6 dogs with normal lungs who were receiving high-frequency jet ventilation (HFJV). There was an excellent linear correlation between PetCO2 and the PaCO2 over the entire range of CO2 tensions commonly encountered in clinical practice (PetCO2 = 0.9 PaCO2 + 2.2 torr; n = 51, r = .98, p less than .001, range of PaCO2 = 12-72 torr). We conclude that when lung function is normal, a simple system of measuring PetCO2 after a large breath is an accurate method of monitoring the effectiveness of CO2 elimination during HFJV.
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