Prolonged hemorrhagic shock does not impair regeneration of plasma coagulant masses in the rabbit.

BACKGROUND AND METHODS: Twelve adult male albino rabbits were assigned alternately to normotensive and hypotensive groups to assess the effect of hypovolemic shock on spontaneous correction of dilutional coagulopathy. All animals underwent dilutional exchange transfusion with 200 mL of rabbit RBCs and 5% human albumin. Half the animals were then acutely hemorrhaged and subsequent aliquots of blood removed as needed to maintain the mean arterial pressure at 40 mm Hg. RESULTS: By 6 hr after production of dilutional coagulopathy, masses and plasma concentrations of fibrinogen and Factor II had increased modestly but significantly, and Factor VII mass and concentration and in vitro coagulation had returned almost to normal; plasma volume was unchanged in the normotensive animals. In the hypovolemic shock animals, where coagulant mass regeneration was as rapid as in the normotensive animals, a doubling of total plasma volume (p less than .01) prevented the concentrations of fibrinogen and Factor II, and hence the coagulation times, from improving. CONCLUSIONS: Dilutional coagulopathy corrects spontaneously within hours. Normovolemic shock prolongs dilutional coagulopathy not by impairment of factor regeneration but because of further (internal) dilution due to plasma expansion. Rapid correction of dilutional coagulopathy is likely to necessitate cryoprecipitate administration.

Coagulopathy related to dilution and hypotension during massive transfusion.

A retrospective review of 64 patients receiving more than 10 units of red cell concentrate plus crystalloid within 12 h revealed two consecutive patterns of elevation of the partial thromboplastin time (PTT). The PTT at 3 to 4 h (PTT3-4) correlated with the number of liters of crystalloid (LC) infused over the first 3 h (PTT3-4 = 37 + 7 LC, r = .7643, p less than .001); the PTT thereafter (PTT4+) correlated with the number of hours of closely antecedent hypotension (AH) (PTT4+ = 37 + 21AH, r = .8680, p less than .001). These data indicate a transient dilutional coagulopathy, followed by coagulopathy related to the duration of closely AH. Whether this latter is due to impaired production, disseminated intravascular coagulation, or dilution due to internal shifts of fluids and/or proteins, remains to be clarified. Therapeutic implications of these data are discussed.

Continuous airway pressure with oxygen minimizes the metabolic lesion of 'pump lung'.

Water distribution and energy status of the lung were measured in ten rabbits at two hours of hypothermic cardiopulmonary bypass (CPB) with left heart venting and incision of the parietal pleurae. During CPB, half the animals had their airways open to room air at ambient atmospheric pressure (ZEEP), and the remainder had their lungs inflated (CPAP) at a pressure of 5 cms H2O with the oxygen-enriched (70-75 per cent) gas mixture exiting from the disc oxygenator. In both the ZEEP and CPAP groups, there was more than doubling of the pulmonary extravascular sodium-free water (intracellular) space and reciprocal reduction of the pulmonary extravascular sodium (extracellular) space, compared with 12 control animals not undergoing CPB. In the ZEEP group, there was an 18-fold increase in the pulmonary lactate/pyruvate (L/P) ratio compared with controls, and the pulmonary energy charge (E.C.) was significantly less than in controls (0.74 +/- 0.02 vs. 0.89 +/- 0.01). In the CPAP group the pulmonary L/P ratio was 2 1/2 times control values and the pulmonary E.C. was virtually identical with that of the control group. These data suggest that CPB results in a shift of fluid from the pulmonary interstitium into the pulmonary intracellular compartment with no net increase in total pulmonary extravascular water. The data also suggest that pulmonary deflation during CPB results in a significant pulmonary energy deficit which can be prevented by keeping the lung inflated with an oxygen-enriched gas mixture during CPB.

Steady-state plasma fentanyl in the rabbit.

Linear pharmacokinetic models were obtained for fentanyl in anaesthetized rabbits. A composite model was used to predict the bolus dose and infusion rates necessary to achieve rapidly a steady-state concentration of fentanyl in plasma. When this was tested in a further six rabbits, steady-state concentrations were greater than predicted. The most likely reasons for this are imperfect mixing between plasma and the central compartment, and substantial uptake of fentanyl by the lung. These sources of error were allowed for in modifications to the model. On further testing, a 4-h infusion set to achieve a plasma fentanyl concentration of 10 ng ml-1 yielded actual concentrations ranging from a mean low of 8.7 ng ml-1 to a mean high of 18.0 ng ml-1. The second model described more precisely the disposition of fentanyl, although a tendency to overestimate dosing requirement remained. This tendency is probably a consequence of continuing lung uptake of fentanyl. The demonstrated ability to obtain rapidly and maintain for 4h "steady" blood fentanyl concentrations suggests that the methods merits further investigation with other drugs both in animals and man.

Medical student health: ten years after the GSA/CMSH report.

In 1969 a committee of the Association of American Medical Colleges made recommendations relating to health status determination and health care of medical students. In 1979 a survey of 82 U.S. and Canadian schools showed little changes from the methods being used in 1967. The implications of the survey are discussed and a prototype program is outlined.

Perfusion characteristics during cardiopulmonary bypass and subsequent changes in alveolar-arterial oxygen tension gradients.

In 11 elective coronary artery bypass graft (CABG) recipients, changes in alveolar-arterial O2 tension difference (deltaAaDO2) from 5 minutes before to 30 minutes after cardiopulmonary bypass (CPB) ranged from -54.9 to +63.1 torr and exhibited significant linear correlation (r = 0.77, p less than 0.01) with the mean arterial perfusion pressure (MAPP) during CPB multiplied by the duration (T) of CPB divided by the body surface area (BSA) of the patient. The regression equation (deltaAaDO2 = 0.015 MAPP divided by BSA X T -50) enables estimation of the delta AaDO2 to result from a given episode of CPB. Mural edema of airways and pulmonary vasculature, developing during CPB, may be a mechanism underlying this correlation.

Transalveolar metabolic protection to the lung.

Radioactive glucose was administered as an aerosol to isolated rabbit lungs in an artificial thorax in order to investigate the capacity of the lung tissue to metabolize substrate supplied via the airway rather than via the circulation. Comparisons were made with radioactive glucose to which insulin had been added, with aerosolized distilled water, and with lungs that were neither ventilated nor perfused. The lung tissue utilized the aerosolized glucose as substrate (linear production of 14CO2 incorporation into lipid, and maintenance of high-energy phosphate content). Addition of insulin to the glucose did not alter the values. Ventilation with aerosolized water instead of glucose significantly reduced high-energy phosphate content, and these values decreased significantly further when the lungs were not ventilated. These studies confirm the fact that substrate can be utilized from the airway side of the lung, and encourage the speculation that it might prove therapeutically useful in pulmonary failure.

"A spoonful of sugar" - trans-alveolar nutrition.

In this initial study, it has been postulated that even the simple bronchial administration of isotonic glucose and insulin can maintain alveolar cell metabolism as measured by A.T.P. activity; further studies, using aerosolized glucose solutions, will test the validity of the hypothesis that alveolar metabolism can be maintained by the administration of substrate in aerosolized form by the alveolar route and will determine whether this form of substrate administration has clinical potential.