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Objectives: Endotracheal self-extubation (ESE) is a serious health care concern. We designed this study to test our hypothesis that not all patients with ESE are successful in spontaneous breathing and reintubation has negative impact on outcomes., Methods: Data on all 39 patients of ESE in our surgical and trauma intensive care unit (ICU) in 2012 were prospectively collected and retrospectively analyzed., Results: There were 42 episodes of ESE in 39 of 939 intubated patients (frequency, 4.0%), with 54% of events requiring reintubation. Pre-ESE positive end-expiratory pressure was higher and Pao2/fraction of inspired oxygen ratio was lower, and the post-ESE respiration rate was higher in the reintubated group. On univariate analysis, weaning and spontaneous breathing trial before ESE were favorable predictors for nonreintubation. Multivariate regression analysis demonstrated that agitation before ESE was an independent predictor of reintubation. The need for reintubation was associated with increased risk of pulmonary infectious complications, ventilator days, the need for tracheostomy, and ICU and hospital LOS. The financial costs for ventilator days and ICU rooms were significantly higher in patients with reintubation., Conclusion: Not all patients were fine after ESE. We have not decreased the frequency of ESE or improved outcomes if the patients were reintubated. The need for reintubation was not only associated with a high pulmonary complication rate but also prolonged duration on mechanical ventilation and hospital/ICU stay and increased the hospital costs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Group A streptococcus has emerged as a major cause of aggressive life-threatening deep-seated infections. In addition, toxic shock syndrome caused by Group A streptococcus was recognized in 1983. Group A streptococcus produces several potent exotoxins which explain the pathophysiology of these invasive infections. Other virulence factors such as M protein, which can impede phagocytosis, are associated with some Group A streptococcus. M protein and streptococcal pyrogenic exotoxins may act as super antigens. Host factors may influence the severity of infection. Blood purification techniques such as continuous renal replacement therapy and plasmapheresis can remove streptococcal exotoxins as well as inflammatory mediators. Replacement with fresh-frozen plasma corrects coagulopathy and may provide some antibody protection. Four patients with Group A streptococcus-toxic shock syndrome treated with continuous renal replacement therapy, plasmapheresis, or both showed dramatic, rapid improvement in cardiovascular dynamics and respiratory parameters. Two patients died. The mainstay of treatment for Group A streptococcus-toxic shock syndrome remains early diagnosis, aggressive surgical control of the infection, and appropriate antibiotics (i.e., penicillin and clindamycin). Flush resuscitation may rescue some patients from profound toxic shock. The mechanisms of action need to be delineated.

Metabolic complications from overfeeding critically ill patients are serious and sometimes fatal. Nutrition care is best provided through repeated evaluation of patients' responses to feeding. Nutrition support may need to be modified over time to maintain metabolic stability and promote recovery. This article describes the etiology of 10 metabolic complications of overfeeding. Guidelines for recommending macronutrients are discussed, as are factors that could increase the risk of overfeeding. Patients who are very small, very large, or very old are particularly vulnerable to overfeeding. Overfeeding protein has led to azotemia, hypertonic dehydration, and metabolic acidosis. Excessive carbohydrate infusion has resulted in hyperglycemia, hypertriglyceridemia, and hepatic steatosis. High-fat infusions have caused hypertriglyceridemia and fat-overload syndrome. Hypercapnia and refeeding syndrome have also been caused by aggressive overfeeding. Dietitians can prevent or curtail the metabolic complications of overfeeding by identifying patients at risk, providing adequate assessment, coordinating interdisciplinary care plans, and delivering timely and appropriate monitoring and intervention. Dietitians need to document complications, interventions, and the outcomes of their clinical care to evaluate the appropriateness of existing nutrition guidelines.

To assess preference for outcome-focused nutrition notes, two note formats were selected from the literature and tested against a modified, goal-oriented format. Focus charting and intervention, evaluation, and revision (IER) formats were compared with a charting-by-exception style that was modified to include goals and reassessment of risk. Notes were handwritten in each format and contained the same information. Physicians were asked to choose their preference and explain why that format was selected. Initially, focus charting was tested against the goal-oriented format. The more popular of the two was then tested against the IER format. Nineteen physicians were surveyed by a registered dietitian for each comparison. Physicians preferred the goal-oriented format over focus charting and IER formats 9:1 and 3:1, respectively. In the first survey, physicians preferred the goal-oriented format because the plan was clearly stated, thereby rendering the note easier to understand. The goal-oriented format was preferred in the second survey because the note was considered to be concise and easy to read and contained expected outcomes. Physicians want short communication that includes easily identifiable goals and plans. We recommend that experienced dietitians use the goal-oriented format developed for this study, and preferred by physicians, for follow-up nutrition notes.

Objective: To determine glucose balance during dextrose-free continuous hemodiafiltration with or without dextrose-containing ultrafiltrate replacement fluid and full nutritional support., Design: Prospective, nonrandomized, observational study., Setting: A 24-bed multiple trauma critical care unit in a level-I trauma center., Patients: Seventeen multiple trauma patients with multiple organ dysfunction syndrome requiring hemodialysis for acute renal failure., Interventions: Continuous hemodiafiltration effluent volume and glucose concentration were measured. Study days were classified according to whether dextrose was used in the ultrafiltrate replacement therapy. Use of dextrose in replacement therapy was determined clinically. Parenteral nutrition was not altered for potential glucose absorption from continuous hemodiafiltration. Ultrafiltrate replacement consisted of 5% dextrose in saline on 21 study days (D5YES) and dextrose-free solutions on 54 study days (D5NO)., Results: The D5YES group received 316 +/- 145 g glucose/day from the ultrafiltrate replacement fluid, in addition to glucose in total parenteral nutrition (total glucose intake = 942 +/- 229 g/day in D5YES, 682 +/- 154 g/day in D5NO) (p < 0.05). Glucose loss in continuous hemodiafiltration effluent was 82 +/- 61 g/day in D5YES and 57 +/- 22 g/day in D5NO (P < 0.05), for a net glucose uptake of 8.1 +/- 2.1 mg/kg per min in D5YES and 5.4 +/- 1.5 mg/kg per min in D5NO (p < 0.05). Glucose loss was predictable when dialysate and ultrafiltrate replacement fluids were dextrose-free (R2 = 0.77), but less so when dextrose was used as ultrafiltrate replacement (R2 = 0.47)., Conclusion: Dextrose-free dialysate promotes glucose loss during continuous hemodiafiltration, but the loss is small and predictable. Use of a dextrose-containing ultrafiltrate replacement fluid results in a significant increase in glucose intake without a commensurate increase in glucose loss, and makes glucose loss in effluent less predictable.

Embolization of metallic missiles into the cerebral circulation is a rare occurrence. Most of the cases reported were due to gunshot wounds and shotgun wounds to the neck and face. Embolization from injuries sustained to the chest are extremely rare. We report a case of delayed pellet embolization to the middle cerebral artery resulting from a shotgun injury to the left chest.

Objective: To quantify resting and total energy expenditure in patients who have suffered severe trauma and sepsis., Design: Prospective, unblinded, observational, nonrandomized study., Setting: Critical care unit of a Level I adult trauma center., Patients: Immediate posttrauma patients or trauma patients exhibiting signs of sepsis with multiple organ dysfunction., Interventions: An indirect calorimeter was used to measure energy expenditure at rest (resting energy expenditure) at 0700 and 1900 hrs. The energy expenditure measurement was then continued for up to 12 hrs (total energy expenditure). Clinical data were collected for computation of an illness severity score., Results: Thirteen trauma and 20 septic patients were studied 240 times. All patients were mechanically ventilated. Morphine or fentanyl was infused during 99% of studies. Neuromuscular blocking agents were used in 42% of septic studies. Both the trauma and septic groups were hypermetabolic (mean trauma resting energy expenditure, 36 +/- 6 kcal/kg; mean septic resting energy expenditure, 44 +/- 8 kcal/kg; p < .05). Total energy expenditure was similar to resting energy expenditure (trauma total energy expenditure = resting energy expenditure x 1.035 +/- 0.078, septic total energy expenditure = resting energy expenditure x 1.039 +/- 0.071). Total energy expenditure and resting energy expenditure were linearly related (r2 = .89, p < .0001)., Conclusions: Trauma and septic patients are hypermetabolic, even when heavily sedated or medically paralyzed. A measurement of resting energy expenditure is a close approximation of total energy expenditure in most patients.

Background: Indirect calorimetry is the preferred method for determining caloric requirements of patients, but availability of the device is limited by high cost. A study was therefore conducted to determine whether clinically obtainable variables could be used to predict metabolic rate., Methods: Patients with severe trauma or sepsis who required mechanical ventilation were measured by an open-circuit indirect calorimeter. Several clinical variables were obtained simultaneously. Measurements were repeated every 12 hours for up to 10 days., Results: Twenty-six trauma and 30 sepsis patients were measured 423 times. Mean resting energy expenditure was 36 +/- 7 kcal/kg (trauma) vs 45 +/- 8 kcal/kg (sepsis) (p < .0001). The single strongest correlate with resting energy expenditure was minute ventilation (R2 = 0.61, p < .0001). Doses of dopamine, dobutamine, morphine, fentanyl, and neuromuscular blocking agents each correlated positively with resting energy expenditure. In the case of the inotropics and neuromuscular blockers, there was a probable covariance with severity of illness. A multiple regression equation was developed using minute ventilation, predicted basal energy expenditure, and the presence or absence of sepsis: resting energy expenditure = -11000 + minute ventilation (100) + basal energy expenditure (1.5) + dobutamine dose (40) + body temperature (250) + diagnosis of sepsis (300) (R2 = 0.77, p < .0001)., Conclusion: Severe trauma and sepsis patients are hypermetabolic, but energy expenditure is predictable from clinical data. The regression equations probably apply only to severe trauma and sepsis. Other studies should be conducted to predict energy expenditure in other patient types.

Objective: To assess whether variables reflective of early metabolic responses to injury are predictors of outcome in critically ill trauma patients., Design: Clinical inception cohort study comparing conventional measures of injury severity with early host response markers for the correlation of each with outcome. These data are prospectively collected in a group of patients being evaluated in a nutritional support investigation., Setting: Intensive care unit (ICU) of a major Level I trauma center., Patients: Seventeen blunt trauma patients, aged 18 to 60 yrs with an Injury Severity Score of > or = 15, requiring early mechanical ventilation., Interventions: Blood and urine samples were routinely obtained from patients undergoing nutritional support by one of three routes., Measurements and Main Results: Conventional assessment was consistent with moderate severity and variation: Injury Severity Score, 41 +/- 15; Glasgow Coma Score, 11 +/- 4; admission circulating lactate concentration, 4.8 +/- 2.2 mmol/L; and first 24-hr transfusion requirement, 3.1 +/- 2.9 L. The mean concentrations of inflammatory marker during the first week were: cholesterol, 2.67 +/- 0.80 mmol/L (103.2 +/- 31 mg/dL); C-reactive protein, 23 +/- 11 mg/dL; transferrin, 1.44 +/- 0.47 g/L; glucose, 9.21 +/- 2.27 mmol/L (166 +/- 41 mg/dL); albumin, 26 +/- 5 g/L; and nitrogen loss, 24 +/- 9 g/d. Hospital outcome variables were: ventilator days, 17 +/- 7; ICU days, 26 +/- 10; hospital days, 38 +/- 15; occurrence rate of adult respiratory distress syndrome (ARDS), 35%; infections, 82%; multiple organ failure, 71%; and total of hospital plus professional charges, $125,000 +/- $56,000. A significant (p < .05), but weak, correlation existed between all seven outcome variables and the inflammatory markers: ventilator days with cholesterol and C-reactive protein; ICU days with transferrin; total stay with cholesterol; ARDS with C-reactive protein; infections with glucose, cholesterol, and nitrogen loss; multiple organ failure with albumin and C-reactive protein; and financial charges with glucose. However, a significant correlation existed between only two of seven outcome variables and conventional measures of severity: multiple organ failure with lactate and financial charges with transfusion requirement., Conclusion: Readily obtainable inflammatory marker measurements may better reflect the summation effects of the early perfusion deficit and tissue injury in the blunt trauma patient compared with conventional measures of injury severity.

Objective: To compare urea nitrogen removal by continuous hemodiafiltration vs. functional native kidneys in critically ill, septic patients receiving > 2 g of amino acids/kg body weight per day., Design: Prospective, comparative, unblinded study., Setting: Trauma critical care units of a Level I adult trauma hospital., Patients: Fifteen septic patients with multiple organ failure including renal failure who were receiving continuous hemodiafiltration; 11 septic patients with multiple organ failure without renal failure (control group). Ages of patients ranged from 18 to 60 yrs., Interventions: Collection of effluent (dialysate + ultrafiltrate) from hemodiafilters. Collection of urine from control patients., Measurements: Urea nitrogen and creatinine concentrations in blood, urine, and the hemodiafiltration effluent, measured every 24 hrs for 6 days. Effluent and urine volumes were measured., Main Results: Hemodiafilters were operational for 21.8 +/- 3.0 hrs/day. Mean urea nitrogen removal in the renal failure group was 28 +/- 10 g/day. Blood urea nitrogen was stable over the 6-day study period. In control subjects, urea nitrogen removal was 27 +/- 9 g/day, which was not significantly different from the continuous hemodiafiltration group. Blood urea nitrogen concentrations in control patients increased over the 6-day study period (p < .05). Urea nitrogen removal correlated moderately well with amino acid intake in the control group (r2 = .30), but not in the continuous hemodiafiltration group (r2 = .0004). In patients receiving continuous hemodiafiltration, effluent volume was most significantly correlated with urea nitrogen removal (r2 = .69)., Conclusions: The technique of continuous hemodiafiltration can remove substantial amounts of urea nitrogen, similar to that of normal native kidneys. In addition, at amino acid intake rates of > 2 g/kg body weight/day, urea nitrogen removal during continuous hemodiafiltration remains a function of effluent volume, so there is no need to restrict amino acid intake in acute renal failure patients supported with 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.

Three areas of particular importance in dealing with critical complications of trauma are pharmacology, monitoring, and nutritional support. This article deals with each of these from the perspective of the doctor or nurse at the bedside. This survey stands as a sampler and guidebook to these subjects as they pertain to the critically ill multiple trauma patient.

Objective: To document the efficacy of continuous arteriovenous hemofiltration with dialysis following renal failure, without protein restriction, and to explore the magnitude and clinical applications of total daily urea clearance., Design: A noncomparative, descriptive account of a case series. Data were collected prospectively and analyzed retrospectively., Setting: A tertiary care facility in a statewide emergency medical services system., Patients: Twenty-eight patients with renal failure were supported by continuous arteriovenous hemofiltration with dialysis in a critical care unit during a 14-month period (21 patients with multitrauma; three patients with soft tissue infections; and four patients with multisystem organ failure who had been transferred from other hospitals). Renal failure was most commonly due to multisystem organ failure or associated with adult respiratory distress syndrome., Results: Continuous arteriovenous hemofiltration with dialysis days totaled 308 (mean 10.9). All patients received full protein alimentation (mean protein load 131 g/day). The blood urea nitrogen concentration was controlled, generally to 40 to 75 mg/dL (14.3 to 26.7 mmol/L) within 3 to 5 days. Total daily urea clearance ranged from 15 to 21 g/day. Five (18%) of the 28 patients survived., Conclusion: Continuous arteriovenous hemofiltration with dialysis appears to be effective for the control of blood urea nitrogen and clearance of urea. This modality also permits full protein alimentation. Total daily urea clearance can be calculated easily and may have important clinical uses and implications.

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.

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.

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.

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.

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.

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.

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.

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.

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.