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Protein-sparing therapy in the postoperative period

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Abstract

Surgical trauma leads to increased nitrogen loss which may result from increased protein breakdown, diminished protein synthesis, or both. Increased protein breakdown is predominant after surgical trauma, whereas protein synthesis has been reported to be either unchanged or increased. Attempts to improve nitrogen balance should be directed toward both mechanisms; protein breakdown is diminished by avoiding tissue damage, and by prevention of sepsis which results in release of catabolic peptides, e.g., of interleukin 1. Protein breakdown may also be diminished by avoidance of stress hormones, particularly of cortisol, and by providing energy substrates, i.e., glucose, long- or medium-chain fatty acids. Protein synthesis is enhanced by providing nutrition, including supply of energy and amino acids. Data obtained in human volunteers demonstrated that transient elevation of plasma cortisol to stress levels resulted in sustained elevation of plasma amino acids, indicating increased proteolysis. Four hours after plasma cortisol elevation, glucose “clamp” studies indicated insulin resistance of peripheral and hepatic glucose metabolism. In contrast, insulin action on plasma amino acids was unimpaired suggesting that hyperinsulinemia was capable of reverting the cortisol-induced protein breakdown. The effect of postoperative amino acid therapy was studied in 60 patients after major surgery who received either amino acids or carbohydrates, or both by peripheral venous administration. Postoperative nitrogen balance during 6 days was not significantly improved when amino acids were administered in spite of different plasma concentrations of glucose, insulin, and ketone bodies during the various nutrition regimens. Thus, measures to diminish protein breakdown and to increase protein synthesis should be integrated into the management of the postoperative patient, in order to diminish nitrogen loss and thus to decrease postoperative morbidity.

Résumé

Le traumatisme chirurgical aboutit à une perte azotée qui peut être le fait de la désintégration des protéines, de la diminution de la synthèse protéique ou des deux mécanismes. La désintégration protéique est constante alors que la synthèse protéique parfois reste normale ou augmente. Les mesures pour améliorer l'équilibre azoté doivent prendre en compte les deux mécanismes. La protéolyse est diminuée 1) en évitant les altérations tissulaires et en prévenant l'infection qui détermine la libération de peptides cataboliques; 2) en évitant la formation des hormones de stress, en particulier le Cortisol; 3) en apportant des éléments énergétiques comme le glucose, les acides gras à chaîne moyenne ou longue. La synthèse protéique est renforcée par l'apport d'agents nutritifs comprenant des éléments énergétiques et des amino-acides. Les données recueillies chez des volontaires ont permis de démontrer que l'élévation passagère du cortisol plasmatique sous l'effet du stress resultait d'une élévation des amino-acides plasmatiques témoignant d'une augmentation de la protéolyse. Quatre heures après ce phénomène les dosages du glucose témoignent d'une résistance à l'insuline du métabolisme du glucose hépatique et périphérique. En revanche l'action de l'insuline sur les amino-acides plasmatiques n'est pas altérée ce qui suggère que l'hyperinsulinémie est capable de contrôler la protéolyse provoquée par le Cortisol. Les effets du traitement postopératoire par des amino-acides ont été étudiés chez 60 sujets qui ont subi une intervention chirurgicale majeure et qui ont été soumis à une perfusion veineuse soit d'amino-acides, soit d'hydrates de carbone, soit des deux nutriments. L'équilibre azoté au cours des 6 jours suivant l'intervention ne fut pas nettement amélioré lorsque les amino-acides furent employés quelles qu'aient été les différentes concentrations plasmatiques du glucose, de l'insuline et des corps cétoniques en fonction des différents régimes nutritionnels. Par conséquent toutes les actions possibles pour diminuer la protéolyse et accroître la synthèse protéique doivent être employées en postopératoire de manière à diminuer la perte azotée et à diminuer la morbidité.

Resumen

El trauma quirúrgico da lugar a un aumento en las pérdidas de nitrógeno, fenómeno que puede ser el resultado de un incremento en la degradación proteica, de una disminución en la síntesis proteica, o de ambos factores combinados. El aumento en la degradación proteica es un fenómeno predominante después del trauma quirúrgico, en tanto que la síntesis proteica, según ha sido publicado, puede permanecer sin alteración o aparecer aumentada. Los esfuerzos destinados a mejorar el balance de nitrógeno deben estar dirigidos hacia la intervención sobre ambos mecanismos; la degradación proteica puede ser disminuída evitando daño tisular y mediante la prevención de la sepsis, la cual puede resultar en la liberación de péptidos catabólicos, por ejemplo la interleucina 1. La degradación proteica también puede ser disminuída evitando las hormonas del estrés, particularmente el cortisol, y mediante la provisión de sustratos energéticos, como lo son la glucosa o los ácidos grasos de cadenas largas o medias. Se puede estimular la síntesis proteica mediante la provisión de nutrientes, incluyendo sustratos energéticos y aminoacidos. La información obtenida en voluntarios humanos demuestra que la elevación transitoria en el cortisol plasmático para llegar a los niveles de estrés resulta en una elevación sostenida de los aminoácidos, lo cual indica proteolisis. Por varias horas después de que aparece la elevación plasmática de cortisol, estudios de “clamp” de glucosa indican la presencia de resistencia a la insulina por parte del metabolismo periférico y hepático de la glucosa. Por el contrario, la acción insulínica sobre los aminoácidos del plasma aparece sin alteraciones, lo cual sugiere que la hiperinsulinemia es capaz de revertir la degradación proteica inducida por el cortisol. El efecto de la terapia postoperatoria con aminoácidos fué estudiado en 60 pacientes sometidos a cirugía mayor, los cuales recibieron amionácidos o carbohidratos, o ambos nutrientes, por vía venosa periférica. El balance postoperatorio de nitrógeno en el curso de los primeros seis días no apareció significativamente incrementado cuando los aminoácidos fueron administrados, a pesar de concentraciones diversas de glucosa, insulina y cuerpos cetónicos, en el curso de los diversos régimenes nutricionales. Por ello, las medidas que se emprendan para disminuír la degradación proteica y para aumentar la síntesis de proteína deben ser integradas dentro del manejo postoperatorio del paciente, con el objeto de disminuir la pérdida de nitrógeno y lograr así minimizar la morbilidad postoperatoria.

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  1. Departments of Internal Medicine and Research, University of Basel, Switzerland

    Ulrich Keller M.D., Didier Clerc M.D., Marius Kränzlin M.D. & M. Heberer M.D.

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  1. Ulrich Keller M.D.
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  2. Didier Clerc M.D.
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  3. Marius Kränzlin M.D.
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Keller, U., Clerc, D., Kränzlin, M. et al. Protein-sparing therapy in the postoperative period. World J. Surg. 10, 12–19 (1986). https://doi.org/10.1007/BF01656085

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