Malnutrition is common in critically ill patients, and it is associated with an increased risk of complications. Early enteral nutrition with adequate caloric and protein intake is critical nevertheless it is difficult to achieve. Peptide-based formulas have been shown to be beneficial in patients with feeding intolerance. However, there are limited studies showing the efficacy and safety of high-protein peptide-based formula in critically ill surgical patients.

To determine the effects of a high-protein peptide formulation on gastrointestinal tolerance, nutritional status, biochemical changes, and adverse events in patients in the surgery intensive care unit (SICU) compared to an isocaloric isonitrogenous standard polymeric formulation.

This study was a multi-center double-blind, randomized controlled trial. We enrolled adult patients in the surgical intensive care unit, age ≥ 15 years and expected to receive enteral feeding for at least 5-14 d post-operation. They were randomly assigned to receive either the high-protein peptide-based formula or the isocaloric isonitrogenous standard formula for 14 d. Gastric residual volume (GRV), nutritional status, body composition and biochemical parameters were assessed at baseline and on days 3, 5, 7, 9, 11, and 14.

A total of 19 patients were enrolled, 9 patients in the peptide-based formula group and 10 patients in the standard formula group. During the study period, there were no differences of the average GRV, body weight, body composition, nutritional status and biochemical parameters in the patients receiving peptide-based formula, compared to the standard regimen. However, participants in the standard formula lost their body weight, body mass index (BMI) and skeletal muscle mass significantly. While body weight, BMI and muscle mass were maintained in the peptide-based formula, from baseline to day 14. Moreover, the participants in the peptide-based formula tended to reach their caloric target faster than the standard formula.

The study emphasizes the importance of early nutritional support in the SICU and showed the efficacy and safety of a high-protein, peptide-based formula in meeting caloric and protein intake targets while maintaining body weight and muscle mass.

1. Fibronectins (FN) are believed to have a role in haemorheological perturbation associated with tissue damage. Fibronectins exist in two antigenically related forms, plasma (p) and cellular fibronectin, which has the extra domain sequences A (EDA) or B (EDB). The present study was designed to determine changes in plasma p-FN and EDA + FN under different types of surgical stress. 2. Sixty-two patients were divided into three groups: (i) group A, 33 patients undergoing hepato-pancreato-biliary surgery; (ii) group B, 19 patients undergoing laparoscopic cholecystectomy; and (iii) group C, 10 patients with postoperative complications. Plasma FN and EDA + FN levels were measured in these patients undergoing different types of surgical operation and either with or without liver cirrhosis using an enzyme-linked immunosorbent assay. 3. After surgery, a significant decrease in p-FN levels and a significant increase in EDA + FN levels was observed in all patient group compared with pre-operative levels. The duration of increased EDA + FN levels, but not p-FN levels, in group A patients was significantly longer than in group B patients. Although changes in p-FN levels between patients with and without liver cirrhosis were significantly different, there were no significant differences in the EDA + FN levels between these two patient groups. 4. In conclusions, EDA + FN and p-FN levels were found to exhibit opposite responses to surgical stress. Furthermore, with greater surgical stress, greater increases in EDA + FN levels were seen. The presence of liver cirrhosis had no significant effect on EDA + FN levels during the perioperative period; however, p-FN levels were significantly affected. 5. Thus, it is suggested that plasma EDA + FN levels reflect the magnitude of surgical stress more closely than do p-FN levels.

Plasma levels of the plasma protease inhibitor alpha-2-macroglobulin (alpha 2-M) were followed for 7 days in 90 patients subjected to various surgical procedures. Alpha 2-M was found to decrease strictly in parallel with the decrease seen for haemoglobin and albumin levels in all patients. Changes were most pronounced after extensive operations; total hip replacement (n = 7), pulmonary resection (n = 11), extensive colo-rectal resection (n = 15), and less pronounced after 'minor' operations; mastectomy (n = 23) proximal gastric vagotomy (n = 5) and moderate colo-rectal resection (n = 29). Levels were lowest on the second to third postoperative day, whereafter they slowly returned to normal, preoperative levels during the 7-day study period. Functional and quantitative alpha 2-M levels almost paralleled each other throughout the 7 days studied. Chromogenic peptide substrate assays indicated circulating plasmin-alpha 2-M complexes, while no protease-alpha 2-M complexes could be demonstrated using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) or isoelectric focusing (IEF) analyses. Local accumulation and consumption of proteins within wounded tissues, together with haemodilution, were probably the major factors responsible for the decreased plasma levels seen. It is concluded that the plasma levels of alpha 2-M decrease after major elective surgery strictly in parallel with the decrease seen in haemoglobin and albumin levels, and that circulating plasmin-alpha 2-M complexes are probable. The decrease seems to be graded, that is, proportional to the extent of the operative trauma, similar to the postoperative increase seen in positive acute-phase proteins. Thus, alpha 2-M cannot be used as an internal, unchanged plasma protein standard for other protein changes seen after trauma.

A randomized study of 30 patients undergoing uncomplicated surgery under spinal anesthesia was conducted to assess the influence of colloids on the kinetics of plasma fibronectin and complement. Both are opsonins of the reticuloendothelial system; moreover fibronectin is concerned with host resistance against septic complications following trauma and surgery. The patients were assigned to receive either Ringer's lactate (Group 1), gelatin (Group 2) or dextran 40 (Group 3). Blood samples were withdrawn before colloids or Ringer's infusion and during the 4 postoperative days. There was a reduction in plasma fibronectin throughout the study in groups 1 and 3, but an increase in group 2 by 24 h. The adhesion of plasma fibronectin to gelatin was maximal 1 h after infusion (44%) and remained significant up to day 2 in group 2. There was no relationship in groups 1 and 3. C3 and C4 components of complement exhibited a low value in the early post-operative period, due to hemodilution. This study shows an in vivo fibronectin-gelatin interaction, and suggests that gelatin infusion inhibits the increased shift of plasma fibronectin at the site of tissue injury after surgery.

The relationship between plasma fibronectin concentration and the regenerative process in liver remnants after hepatectomy was studied in 12 patients and in male Sprague-Dawley rats with and without cirrhosis. Plasma fibronectin levels were reduced immediately after hepatectomy in humans and rats. Patients and rats without cirrhosis displayed preoperative fibronectin levels within 1 mo and 1 wk, respectively, but low fibronectin levels persisted longer in those with cirrhosis. Plasma fibronectin levels correlated well with the degree of hepatic regeneration in the patients with cirrhosis (r = 0.4227; p less than 0.05) and without cirrhosis (r = 0.8148; p less than 0.001), and also with the percentage of change in liver weight during regeneration in the rat with thioacetamide-induced cirrhosis (r = 0.4905; p less than 0.01) or in the rat without cirrhosis (r = 0.6422; p less than 0.001). These results suggest that plasma fibronectin is a useful marker for the detection of regenerating liver.

The hypothesis that abnormal fibronectin metabolism in Crohn's disease could be an important mechanism leading to stricture formation or postoperative infection was tested in three related studies. (1) Lower concentrations of plasma fibronectin (p less than 0.05) were found in 20 patients with small and large bowel Crohn's disease (mean 0.24 g/l) compared with 13 patients with more limited disease confined to only small or only large bowel (mean 0.27 g/l) or 20 healthy controls (mean 0.29 g/l). (2) In 25 patients followed for 10 days after operation for Crohn's disease, there was a significant fall in fibronectin concentrations of 43% (p less than 0.01, Wilcoxon's rank-sum test). This fall was maximal on the second postoperative day and was more marked in patients undergoing more major operative procedures. (3) The predictive value of plasma fibronectin for subsequent stricture formation or progression was studied for one year; during which 10 patients developed strictures requiring operative treatment. Higher plasma fibronectin concentrations were related to stricture formation, although there was not a complete, predictive relationship. In this study we found that plasma fibronectin concentrations were low in patients with extensive or severe Crohn's disease, fall after operation and may be related to the risk of stricture formation. This relationship is unlikely to be of clinical value, although it shows the potential significance of fibronectin in the pathogenesis of strictures.

Severe sepsis leads to depression of the reticuloendothelial (RE) system with delayed bloodstream clearance of particulate matter and bacteria. Fibronectin may be an important opsonin of the RE system and low fibronectin levels often accompany severe sepsis in man. We have investigated the effect of prolonged intra-abdominal sepsis on plasma fibronectin concentrations and RE function. Serial plasma fibronectin concentrations were determined in rabbits for 2 weeks after either the induction of sepsis (appendix abscess) (n = 6) or laparotomy only (n = 6). RE function was measured at 2 weeks by determining the clearance kinetics and organ distribution of low dose technetium tin colloid (TTC). There was an early transient depression in plasma fibronectin values followed by elevated concentrations at 48-72 h which were more marked in the sepsis group. There was a delay in the blood clearance with reduced hepatic and increased bone uptake of TTC. We conclude that depletion of opsonic fibronectin is unlikely to be an important factor contributing to the impairment of RE function associated with intra-abdominal sepsis and that RE depression in septic animals is due to intrinsic Kupffer cell dysfunction.

Plasma fibronectin, an opsonic glycoprotein, is known to modulate the reticuloendothelial phagocytic clearance of nonbacterial and, possibly, bacterial particulates. The decreased plasma fibronectin levels seen after cardiac surgery have been considered to derive mainly from opsonic consumption. In the present study, we demonstrated that the administration of ulinastatin, a human urinary trypsin inhibitor, to patients after cardiac surgery not only inhibited the postoperative depression of plasma fibronectin levels, but also maintained the plasma fibronectin level within the normal range. This effect apparently resulted from the inhibitory activity of ulinastatin on the proteolytic enzymes released after operation. This result suggests that the decreased plasma fibronectin level noted after cardiac surgery may derive mostly from excessive proteolytic enzymes. Our observation also indicates that the prophylactic administration of ulinastatin to patients undergoing major operations will result in a favorably functional reticuloendothelial phagocytic system.

In the light of the recognition of Toxic Shock Syndrome occurring in burned children in our Unit, IgG subclass levels were monitored during the first week post burn in a group of 16 children. There were marked differences between some of the subclasses.

In summary, deficiency of plasma fibronectin has now been documented in a variety of clinical entities. Persistently low fibronectin may have prognostic value, and in certain patients may provide a clue to occult sepsis and potential organ failure. The clinical benefit of infusion of fibronectin-rich cryoprecipitate or purified human plasma fibronectin has yet to be determined in well-controlled randomized clinical trials. However, if such results become available then infusion of plasma fibronectin may provide a valuable therapeutic modality in the care of the critically-ill patient.