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Biomedical subjects

C E Wiles

Publications and source records attributed to C E Wiles.

At least 37 records · Page 2Linked to original sources
PubMed1991

Leucine dose response in the reduction of urea production from septic proteolysis and in the stimulation of acute-phase proteins.

The administration of branched-chain amino acids (BCAAs) has been proved useful in reducing both urea nitrogen production and muscle proteolysis in trauma patients with sepsis, but the optimum infusion rate to achieve these effects is still in question. In this prospective randomized study, a group of 16 posttrauma patients with sepsis received a branched chain-enriched (BCAA = 49.4%) amino acid mixture (8 patients; 120 observations) or a standard amino acid infusion (BCAAs = 15.5%; 8 patients; 227 observations). Total calories, percent lipid calories, and amino acid nitrogen administration were not different in the two groups. Each patient was studied at 8-hour intervals for the plasma levels of amino acids, six hepatic acute-phase proteins, albumin, and other metabolic parameters, including urinary urea nitrogen and 3-methylhistidine excretion. The total intake of each amino acid and its clearance were calculated and the dose of leucine during each 8-hour period was related to the leucine clearance, plasma acute-phase protein levels, and the urinary production of urea and 3-methylhistidine, as an indicator of proteolysis. The results show a significant (r2 = 0.691; p less than 0.0001) reduction of urea nitrogen production and proteolysis as a function of the increase in leucine dose. The identification of a critical mean rate of leucine infusion has been derived from the analysis of the significant linear correlation between leucine intake and leucine clearance (r2 = 0.594; p less than 0.0001). Significant positive correlations between the leucine intake dose and the platelet count (r2 = 0.402; p less than 0.0001), the plasma fibrinogen level (r2 = 0.218; p less than 0.0001), and the regression-derived sum of six acute-phase proteins plus albumin (r2 = 0.696; p less than 0.0001) were found. The increase in leucine clearance was progressively less marked above a mean daily leucine intake rate of 1.4 mumol/kg/min, which also appeared to be the dose level that maximized the acute-phase protein and coagulation effects and reduced proteolysis and urea nitrogen production, suggesting that this is a critical BCAA infusion rate at which an optimum leucine effect occurs. From these data a BCAA (leucine) dose nomogram has been derived.

Acute-Phase Proteins↗
PubMed1989

Determinants of urea nitrogen production in sepsis. Muscle catabolism, total parenteral nutrition, and hepatic clearance of amino acids.

The major determinants of urea production were investigated in 26 patients with multiple trauma (300 studies). The body clearances (CLRs) of ten amino acids (AAs) were estimated as a ratio of muscle-released AAs plus total parenteral nutrition-infused AAs to their extracellular pool. While clinically septic trauma (ST) patients without multiple-organ failure syndrome (MOFS) had a higher level of urea nitrogen production (25.6 +/- 13.4 g of N per day) compared with nonseptic trauma (NST) patients (14 +/- 7.5 g of N per day) and with ST patients with MOFS (4.28 +/- 1.5 g of N per day), in all groups urea N production was found to be a function of muscle protein degradation (catabolism), total parenteral nutrition-administered AAs, and the ratio between leucine CLR and tyrosine CLR (L/T) (r2 = .82, P less than .0001). Since tyrosine is cleared almost exclusively by the liver, the L/T ratio may be regarded as an index of hepatic function. The significant differences between urea N production in ST and NST patients lay in an increased positive dependence on muscle catabolism and increased negative correlation with L/T in the ST group. At any L/T ratio, urea N production was increased in ST patients over NST patients, but in ST patients with MOFS, it fell to or below levels of NST patients. These data show that the ST process is associated with enhancement of ureagenesis, due to increased hepatic CLR of both exogenous and endogenous AAs. In sepsis with MOFS, a marked inhibition of urea synthesis occurs, partially explained by a decreased hepatic CLR of non-branched-chain AAs.

Adult↗
PubMed1989

Prospective evaluation of combined high-frequency ventilation in post-traumatic patients with adult respiratory distress syndrome refractory to optimized conventional ventilatory management.

This study explores the value of combined high-frequency ventilation (CHFV) in a prospective clinical trial of 35 patients suffering from severe post-traumatic and/or septic adult respiratory distress syndrome (ARDS) who were refractory to conventional controlled mechanical ventilatory (CMV) support. The severity of ARDS was quantified by lung mechanics and gas exchange variables and the patients were classified on clinical grounds as well as on the basis of their respiratory index/pulmonary shunt relationship [RI/(Qsp/Qt)]. During the same time period as the CHFV study, data from these patients were compared to those from 88 ARDS patients who had quantitatively similar degrees of respiratory insufficiency, but who were treated only with controlled mechanical ventilation (CMV). The use of CHFV in the 35 CMV refractory patients resulted in an increase in expired tidal volume (VTE) by reducing the CMV inspired tidal volume (VTI) while increasing the volume component derived from high-frequency ventilation (HFV). This procedure appeared to reveal potentially salvageable ARDS patients who were refractory to CMV. In these patients, CHFV significantly reduced pulmonary mean airway pressure (Paw). The RI also decreased significantly and it was possible to reduce significantly the FIO2. In surviving ARDS patients treated with CHFV, an improvement in blood gases at reduced FIO2, without decreased cardiac output, was produced. The CHFV technique was used for less than or equal to 25 days and resulted in 23% survival of patients who were clinically and physiologically indistinguishable from the patients in the ARDS nonsurvivor group who were treated by CMV only. In surviving CHFV patients the decrease in Paw permitted a sustained, or increased, cardiac output with a rise in the oxygen delivery/oxygen consumption ratio, thus allowing for a higher PaO2 for any given level of pulmonary shunt.

Adolescent↗
PubMed1989

Methodologic approach for a large functional trauma registry.

The utility of a clinical trauma registry (TR) is directly related to the constituents of the data base and to the accuracy of the data, which is contingent on a carefully constructed data collection system. A TR was developed by traumatologists at a busy Level I trauma facility that predominantly receives patients having incurred blunt injury. Four dedicated data collectors gather the AP information within 24 to 48 hours after admission, with prompt Attending Surgical review for verification. Examples of data output prove this is a functional system. Using a careful methodologic approach for design and implementation, clinicians can create a large, functional trauma registry with many potential applications.

Data Collection↗
PubMed1988

Inhibition of post-traumatic septic proteolysis and ureagenesis and stimulation of hepatic acute-phase protein production by branched-chain amino acid TPN.

Previous studies have shown that severe sepsis after major trauma results in the reprioritization of release of hepatic acute-phase proteins (APP). They suggest competition for leucine for nutritional utilization may be responsible. To test this hypothesis, a branched-chain enriched (46.6%) amino acid mixture (BCAA) was administered on a prospective randomized basis with standard TPN therapy to 16 septic post-trauma patients. After sepsis was diagnosed, a randomized therapy (control-TPN or BCAA-TPN) was given for 12 days, or until death occurred. Total calories and amino acid nitrogen (N) administered were not different in the two groups (t-test) and q 8 h (347 study periods) amino acid clearances, urinary urea nitrogen excretion, muscle proteolysis from 3-methyl-histidine (3-MH) excretion, and standard indices of sepsis severity and hepatic function were measured, as well as platelets (PLAT), leucocytes (WBC), albumin (ALB), and six acute-phase proteins: C-reactive protein (CRP), alpha-1-antitrypsin (A1TRIP), fibrinogen (FIBRIN), alpha-2-macroglobulin (AMACRO), ceruloplasmin (CERUL), and transferrin (TRANS). Using Scheffé analysis of all contrasts the data showed: BCAA resulted in a fall in 24-hour urea N excretion (24.0 to 20.0 gm/24 hr) and in proteolysis (138 to 126 gm/24 hr) (p less than 0.0001). Prestudy CRP levels were all elevated, but compared to control where APP reprioritization occurred, over the initial 10 days of therapy BCAA patients had a more rapid fall in CRP with a more rapid rise in FIBRIN, TRANS, CERUL, ALBUMIN, AMACRO, and A1TRIP (all p less than 0.0001) relative to CRP. Also, the sepsis-reduced clearances of glutamine and glutamate, alanine, and proline were increased (p less than 0.0001) during BCAA even though urea nitrogen production was reduced (p less than 0.0001). The increase in leucine clearance with BCAA-enriched TPN was positively correlated (r2 = 0.601; p less than 0.0001) with the increase in the sum of all APP and ALB and was also associated with an increase both in FIBRIN and in platelets (p less than 0.0001). The BCAA-related increase in FIBRIN (9.1 to 11.9 mg/ml) occurred at the same time as a fall in prothrombin time (p less than 0.0001). BCAA-enriched TPN reduced proteolysis and amino acid catabolism and appeared to increase the levels of the more rapidly appearing anti-inflammatory and nutritional hepatic APP and formed coagulation elements in post-traumatic sepsis.

Acute-Phase Proteins↗
PubMed1985

Reprioritization of hepatic plasma protein release in trauma and sepsis.

We studied the temporal pattern of seven hepatic synthesized plasma proteins in 26 severely injured patients beginning in the immediate posttrauma period. Clinical sepsis developed in ten patients between three and eight days after injury, and 16 patients had nonseptic courses. In the initial five days after injury, except for albumin, all acute-phase protein levels rose. However, if sepsis developed, C-reactive protein, fibrinogen, ceruloplasmin, and alpha 1-antitrypsin levels continued to be elevated after the initial five posttrauma days, while transferrin, albumin, and alpha 2-macroglobulin levels fell. This differential response became more extreme as sepsis progressed. Covariance analysis of the regression of the five true acute-phase hepatic proteins on C-reactive protein showed that, when sepsis occurred after major traumatic injury, the C-reactive protein rise was associated with a significant reprioritization of hepatic acute-phase plasma protein release. This reprioritization response seems to be both a predictor of sepsis as well as a measure of the adequacy of the host response to trauma and sepsis.

Acute-Phase Proteins↗
PubMed1985

Quantification of asymmetric lung pathophysiology as a guide to the use of simultaneous independent lung ventilation in posttraumatic and septic adult respiratory distress syndrome.

The management of impaired respiratory gas exchange in patients with nonuniform posttraumatic and septic adult respiratory distress syndrome (ARDS) contains its own therapeutic paradox, since the need for volume-controlled ventilation and PEEP in the lung with the most reduced compliance increases pulmonary barotrauma to the better lung. A computer-based system has been developed by which respiratory pressure-flow-volume relations and gas exchange characteristics can be obtained and respiratory dynamic and static compliance curves computed and displayed for each lung, as a means of evaluating the effectiveness of ventilation therapy in ARDS. Using these techniques, eight patients with asymmetrical posttraumatic or septic ARDS, or both, have been managed using simultaneous independent lung ventilation (SILV). The computer assessment technique allows quantification of the nonuniform ARDS pattern between the two lungs. This enabled SILV to be utilized using two synchronized servo-ventilators at different pressure-flow-volumes, inspiratory/expiratory ratios, and PEEP settings to optimize the ventilatory volumes and gas exchange of each lung, without inducing excess barotrauma in the better lung. In the patients with nonuniform ARDS, conventional ventilation was not effective in reducing shunt (QS/QT) or in permitting a lower FIO2 to be used for maintenance of an acceptable PaO2. SILV reduced per cent v-a shunt and permitted a higher PaO2 at lower FIO2. Also, there was x-ray evidence of ARDS improvement in the poorer lung. While the ultimate outcome was largely dependent on the patient's injury and the adequacy of the septic host defense, by utilizing the SILV technique to match the quantitative aspects of respiratory dysfunction in each lung at specific times in the clinical course, it was possible to optimize gas exchange, to reduce barotrauma, and often to reverse apparently fixed ARDS changes. In some instances, this type of physiologically directed ventilatory therapy appeared to contribute to a successful recovery.

Adolescent↗
PubMed1985

Increased dependence of leucine in posttraumatic sepsis: leucine/tyrosine clearance ratio as an indicator of hepatic impairment in septic multiple organ failure syndrome.

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). In contrast, the clearances of branched-chain AA (BCAA) valine and isoleucine were maintained, and the clearance of leucine was higher (p less than 0.05) in trauma patients with sepsis than in those without. 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.

Adolescent↗
PubMed1984

Computer-based evaluation of cardiopulmonary function for the optimization of ventilatory therapy in the adult respiratory distress syndrome.

A computer based evaluation system has been developed for the assessment of respiratory pressure flow dynamics, pulmonary gas exchange and ventilation perfusion interrelationships. This system is based on the acquisition of primary data on-line from intubated and ventilated patients consisting of airway pressures, ventilatory flows and mass spectrometric quantification of inspired and expired gas concentrations. The system has been applied to the study of patients with the adult respiratory distress syndrome (ARDS) following trauma and/or sepsis. The programs developed for evaluation of these data permit an interactive graphic capability to be used by the physician or the respiratory technician in a specific patient to determine the nature of the abnormalities in respiratory function. By use of this system for quantification of the extent and complications of the ARDS condition the specific ventilatory or cardiodynamic therapy can be tailored to meet the patient's physiologic needs. Techniques for optimization of conventional ventilator therapy are described and its application to the specific instances of combined high frequency ventilation or differential lung ventilation are presented. The clinical experience with this unit in a major trauma center suggests that quantitative analysis of an individual patients' respiratory dysfunction permits a precise, accurate and more effective approach to determining corrective therapy in ARDS.

Computers↗
PubMedDate not supplied

Amino acid loss and plasma concentration during continuous hemodiafiltration.

Amino acid loss, plasma concentration, and the relationship between amino acid intake and balance during continuous hemodiafiltration (CHD) were investigated in a prospective, nonrandomized study of trauma patients exhibiting the systemic inflammatory response with acute renal failure. Data were compared with those from a group of similar patients who had maintained renal function (control). Both groups received similar amounts of nonprotein calories (3015 +/- 753 nonprotein calories per day in the control group vs 3077 +/- 1018 nonprotein calories per day in the CHD group) and amino acids (2.24 +/- 0.36 g/kg per day in the control group vs 2.19 +/- 0.48 g/kg per day in the CHD group) via the parenteral route. Amino acid solutions were either 19% or 45% branched-chain amino acid enriched. Studies were performed every 12 hours for a maximum of 6 days. Amino acid loss was 2.5 +/- 2.3 g/12 h in the control group vs 6.6 +/- 2.4 g/12 h in the CHD group (p < .0001). Increasing the dialysate rate from 15 to 30 mL/min increased amino acid loss from 5.7 +/- 1.7 to 7.9 +/- 2.6 g/12 h (p < .0001). Amino acid loss was unrelated to amino acid intake but was directly related to plasma amino acid concentration, CHD effluent volume, and the efficiency of filtration as measured by the ratio of filtered urea nitrogen to blood urea nitrogen (R2 = .69). A linear relationship was found between amino acid intake and balance (R2 = .991). The patterns of plasma amino acid concentrations were consistent with metabolic changes wrought by a combination of sepsis and multiple organ dysfunction and type of amino acid intake but seemed unaffected by increased amino acid loss in CHD effluent. Amino acid losses were 2 to 3 times greater from CHD than from normal kidney. However, CHD amino acid losses may not be clinically significant unless amino acid intake is restricted to levels used typically in traditional hemodialysis.

Acute Kidney Injury↗