Amino Acid Metabolism in Fed Surgical Critically Ill Patients

Introduction Sarcopenia is defined as progressive generalized loss of skeletal muscle mass, strength and function. Sarcopenia due to lack of physical activity is a known phenomenon and is usually observed as a normal part of aging or in certain diseases and pathogenic processes. Major associated factors causing development of sarcopenia may be summarized as interactions of environmental and hormonal factors, underlying diseases, activation of inflammatory pathways, mitochondrial dysfunction, reduced satellite cell numbers, and loss of neuromuscular junctions.

Intensive care acquired weakness (ICU-AW) known formerly as critical illness polyneuropathy, is a diagnosis that becomes more common as survival rates from long ICU hospitalization are more prevalent. It is characterized by a primary axonal degeneration, without demyelination, that typically affects motor nerves more than sensory nerves.

ICU-AW affects the limbs (particularly the lower extremities) in a symmetric pattern. Weakness is most notable in proximal neuromuscular areas (e.g., the shoulders and hip girdle). In addition, involvement of the respiratory muscles can occur and can impede weaning from mechanical ventilation.

The pathophysiological mechanisms of ICU-acquired weakness are believed to be multifactorial. Some suspected factors include dysfunctional microcirculation and hyperglycemia. It has been shown that tight glucose control in ICU patients reduces the risk for ICU-AW (although it has been associated with other adverse events). Sodium channels channelopathy is also a researched cause for ICU-AW. Muscle loss in the ICU are usually related to bedridden condition and lack of mobility, increase in ubiquitination and inadequate protein administration associated with large negative nitrogen balance. In addition mechanical ventilation contributes greatly to this problem. This has been particularly relevant in post trauma/surgical long stayer patients.

In the past years great progress was made in the investigation of protein balance, breakdown and synthesis using stable isotope tracers in various medical conditions. In a research performed in PICU (1-5) and ICU (6, 7) regarding the measurement of plasma amino acid during critical illness, stable phenylalanine, tyrosine leucine, arginine and citrulline isotope were used intravenously without any safety issue problem. Another study was performed on adults suffering from COPD with matched healthy adults, using stable isotopes of phenylalanine, tyrosine leucine, isoleucine and valine (8). During the study the isotopes were given parenterally as well as enterally. The study showed significant change in splanchnic extraction of various amino acids and higher turnover of BCAA in COPD patients. Using the theory that supplemental milk can compensate for the elevated turnover of BCAA in COPD patients, using the isotope analysis demonstrated that this theory was proven wrong and the conclusion was that alterations are present in BCAA metabolism despite normal plasma levels in normal weight COPD. Further research is needed to find a way to compensate for it. These studies and other recent studies (9-19) show us the safety regarding the use of stable isotope tracers whether IV or PO, while giving us the opportunity to assess the metabolism of amino acid in all sorts of pathological states.

Hypothesis \& Aim of the study We think that based on current literature, there are important differences between critically ill patients and healthy population in the amino acid profile and distribution in the body as well as synthesis and breakdown.

The aim of the study is to measure these differences in long ICU stayers (above 7 days) admitted in the ICU after surgical/trauma injury, and to try and help aiming future treatment and research in this field.