Surgery
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The body clearance of 10 plasma amino acids (AA) was determined from the rate of compared muscle-released AA and AA administered by infusion of total parenteral nutrition (TPN) compared to their estimated extracellular (ECW) pool in patients with multiple trauma with (n = 10) or without (n = 16) sepsis at 8-hour intervals. In both nonseptic and septic trauma, increasing TPN increased the mean clearance rate of all infused AA. When the individual AA clearance rates were normalized by the total AA infusion rate, regression-covariance analysis revealed that patients with sepsis had relatively impaired clearances of alanine (p less than 0.01) and methionine, proline, phenylalanine, and tyrosine p less than 0.05 for all). ⋯ At any AA infusion rate, compared with surviving patients with sepsis (p less than 0.05), patients who developed fatal multiple organ failure syndrome (MOFS) showed increased clearances of all BCAA with further impaired clearance of tyrosine. The clearance ratio of leucine/tyrosine was increased in MOFS at any AA infusion rate (p less than 0.0001), was an indicator of severity, and, if persistent, was a manifestation of a fatal outcome. Because tyrosine metabolism occurs almost entirely in the liver while leucine can be utilized by viscera and muscle, these data suggest early and progressive septic impairment of the pattern of hepatic uptake and oxidation of AA with a greater body dependence on BCAA, especially leucine, as septic MOFS develops.
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The relative merits of adding a "pulsatile" component to flow during cardiopulmonary bypass (CPB) has long generated controversy, the resolution of which has been hampered by lack of quantification of the "pulsatility" delivered by different devices. The present experimental series had two goals: to quantify the "pulsatility" of blood flow during CPB in terms of pulse rate and pulsatility index (PI) and to examine which aspects of a "pulsed flow" provide clinical benefits. A flow waveform can be expressed in terms of its baseline rate and its PI, the sum of the square of its harmonics components divided by the square of the mean flow. ⋯ The results indicated that a combination of a minimum PI of 1.88 and a minimum rate of 80 bpm were necessary to significantly reduce lactate production as compared with roller pump perfusion. Thus the same mean flow can have very different physiologic effects depending on how it is delivered. This quantification method permits direct comparison of different "pulsatile waveforms" and provides a means for identification of optimal pulsatile flow.
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Complement activation by the alternate pathway has been implicated in the pathophysiology of cardiopulmonary bypass (CPB), and laboratory studies suggest that the complement cascade may be activated by the protamine-heparin complex. To determine if the administration of protamine to patients receiving heparin activates complement, we studied 100 patients undergoing CPB by assaying levels of C3a and C4a (classic pathway) at regular intervals before and after protamine administration. In group I (90 patients), protamine was given at the usual interval (median 5 minutes) after CPB. ⋯ Corresponding results from C3a analysis before and after protamine administration confirmed the activation of complement cascade. Our study provides the first clinical evidence that the protamine-heparin complex activates complement via the classic (C4a) pathway. The hemodynamic effects of protamine after CPB may be related to complement activation.