Multiple systems organ failure.
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Biomedical subjects
Publications and source records attributed to J R Border.
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Open reduction and internal fixation was performed on 50 displaced acetabular fractures in 49 patients by nine different attending surgeons over a 10-year period. At an average follow-up of 38 months, poor results were noted clinically in 38% and radiographically in 40%. The incidence of short- and long-term complications was greater than in other studies. Particularly distressing was the 58% incidence of heterotopic ossification (HO). Twenty-four percent had grade III or IV; five hips were autofused and the remainder had 40-60% loss of motion. There was no correlation of HO with age, sex, fracture type, degree of comminution, associated femoral head fracture or dislocation, delay to surgery, or operative time. However, 26 of 28 patients who had a trochanteric osteotomy as part of the operative exposure developed HO. Other complications included wound infection (12%), avascular necrosis of the femoral head (10%), nerve palsy (8%), and deep vein thrombosis/pulmonary embolism (8%). The data suggest formulation of specific treatment protocols, an awareness of surgical risks, and that staff specialization may reduce complications and improve outcome. Avoiding a trochanteric osteotomy at surgery and using prophylactic postoperative irradiation or indomethacin are suggested to reduce HO.
The mechanism by which simple hemorrhage profoundly impairs the proliferative response of T lymphocytes to mitogen and alloantigen, produces a defect in interleukin-2 generation, and increases the susceptibility to sepsis remains unknown. Since antigen presentation (AP) by the macrophage (M phi) plays a critical role in the antigen-specific activation of T-helper cells and lymphokine production, we investigated whether the function of the M phi as an AP cell is altered following hemorrhage. C3H/HEJ mice were bled to a mean BP of 35 mm Hg, maintained at that level for 1 hr, and then resuscitated. There was no mortality with this model. Control mice were not bled but otherwise treated identically. Immediately after resuscitation the mice were sacrificed and peritoneal M phi (PM phi) as well as splenic adherent cells (SAC) were harvested. AP function was tested by coculturing different numbers of PM phi and SAC with D10.G4.1 cells (2 x 10(4) cells/well) in the presence of conalbumin (300 micrograms/ml). This T-helper cell clone proliferates upon recognition of conalbumin in the context of Iak (a M phi surface membrane glycoprotein), thus directly reflecting M phi AP capability. After 72 hr of incubation, the cultures were pulsed with [3H]thymidine and harvested. D10.G4.1 proliferations induced via AP by PM phi and SAC from hemorrhaged-resuscitated mice were 29 and 24% of control, respectively (P less than 0.05). Thus, we conclude that AP by M phi following hemorrhage is defective despite adequate resuscitation, a mechanism which could explain the state of immunosuppression and enhanced susceptibility to sepsis.
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The association between support elements (ventilator days = Vd, enteral protein = EnP, number of antibiotics per day = AB/d) and the magnitude of the septic state (SSS) and its bacteriologic manifestations (bacti. log) in 66 patients with blunt multiple trauma (mean HTI-ISS = 40) over 1649 days have been studied retrospectively. SSS is measured by summing the standard deviation units of change in the septic direction for the 16 measurements taken every day in the intensive care unit. Increasing Vd is tightly associated with an increasing SSS (r = +0.52), after day 10 an increasing bacti. log (r = +0.21 to +0.32), and an increasing AB/d (r = +0.26) (all p less than 0.001, N = 1615 - 1626). The independent variables that best predicted Vd were delayed operations (DORS), day of rising EnP, and total positive blood cultures (TPC) (adj. R sq. = 0.84, F = 104, dF = 3/59). An increasing AB/d was associated with an increasing SSS (r = +0.38), increasing Vd (r = +0.26), and an increased bacti. log (r = +0.14 to +0.18) (all p less than 0.001, N = 1615). Only an increased EnP was consistently associated with a reduced SSS (r = -0.38) and a reduction in bacti. log (r = -0.10 to -0.21) (all p less than 0.001, N = 1626-1636). The independent variables Vd, EnP, AB/d, and TPC best predicted SSS for all surviving patients (adj. R sq. = 0.42, F = 268, dF = 4/1496). The patients who died of sepsis were not different in terms of bacti. log from those with equal Vd but were distinguished by zero EnP, high AB/d, and persistent ventilatory support. In conclusion, DORS is tightly associated with increased Vd, SSS, AB/d, and zero EnP. If Vd exceeds 10, there is an increasing bacti. log and evidence of infection probably from the gut. This responds only to increased EnP and not to AB/d. Death due to sepsis is not associated with increased bacti. log but with zero EnP and high AB/d and their consequences.
Fifty-six blunt multiple trauma patients (HTI-ISS 22-57) were studied for the effects of immediate versus delayed internal fixation of a femur or acetabular fracture on the pulmonary failure septic state. The pulmonary failure septic state may be defined as an alveolar arterial oxygen tension difference greater than 100, plus fever and leukocytosis. These patients were divided into four groups. Group I (N = 20) had immediate internal fixation, postoperative ventilatory support, and was sitting up at 30 hours. Group II (N = 20) had 10 days of femur traction and postoperative ventilatory support. Group III (N = 9) was immediately extubated after surgery and had 30 days of femur traction. Group IV (N = 7) had special circumstances that should increase the duration of the pulmonary failure septic state. These four groups of patients were statistically identical by 20 different criteria on admission except that Group I had more recognized chest injuries than Group II (12 vs. 9). Group I required 3.4 +/- 2.6 days of ventilator support and 7.5 +/- 3.8 intensive care unit (ICU) days; they had 12 +/- 8.8 elevated white counts, 3.8 +/- 4 febrile days, 0.05 positive blood cultures per patient, four fracture complications out of 93 fractures, 59 injections of narcotics, and 23 +/- 8.6 acute care days. Ten days of femur traction doubled the duration of the pulmonary failure septic state relative to Group I at a statistically significant level for nine out of 10 criteria, while increasing the number of positive blood cultures by a factor of 10, the number of fracture complications by a factor of 3.5, and the use of injectable narcotics by a factor of 2. Thirty days of femur traction increased the duration of the pulmonary failure septic state relative to Group I by a factor of 3 to 5 for all criteria at a statistically significant level, while increasing fracture complications by a factor of 17, positive blood cultures by a factor of 74, and the use of narcotics by a factor of 2. Group IV, which had four out of seven immediate internal fixations, behaved similarly to Group II. Femoral shaft traction should be avoided in the blunt multiple trauma patients because it greatly increases the cost of care and the risk of multiple systems organ failure.(ABSTRACT TRUNCATED AT 400 WORDS)
The monoglyceride of acetoacetate was prepared from diketene and glycerol. The resulting mixture was composed of nearly equal amounts of 1- and 2-monoacetoacetin. This mixture was tested as a parenteral energy substrate by continuous intravenous infusion into the rat. This glyceride provided 71% of the daily energy for 7 consecutive days. Other groups were either fed ad libitum or fed ad libitum and supplemented with intravenous glucose isoenergetic to monoacetoacetin. All three groups had similar daily non-protein energy intake, and the two supplemented groups ate less protein than normal rats. All three groups gained weight similarly although the glucose group tended to gain fastest and the monoacetoacetin group tended to gain slowest. The rates were not significantly different. At the end of 7 days, the glucose group was hyperglycemic and the monoacetoacetin group was hyperketonemic compared to normal fed rats. The only significant differences among the livers was the small size found for the glucose group. Hepatic compositions were similar. It was concluded from these data that intravenous monoacetoacetin can support weight gain in rats and is a potential alternative to glucose as an energy source in parenteral nutrition.
Proline metabolism was prospectively evaluated in patients with surgical sepsis, cirrhosis, and elective surgical procedures. Significant correlations were found in the septic patients. Proline levels were an excellent indicator of mortality and correlated positively with lactate levels. Lactate and proline were inversely related to total peripheral resistance and oxygen consumption. In septic patients who expired: the metabolites involved in the hepatic pathways of proline degradation were elevated in proportion to proline; lactate, glutamate and proline were directly related to pyruvate; lactate/pyruvate ratios were constant; proline, glutamate, ammonia, ornithine, lactate and pyruvate levels were inversely proportional to oxygen consumption and total peripheral resistance. The primary defects in sepsis seem to be metabolic; there are very strong correlations in time between physiology and metabolism; the metabolic abnormality seems to be a progressive energy-fuel deficit, possibly from a progressive inhibition of substrate entry into the Krebs cycle.
Simultaneous longitudinal hormonometabolic-physiologic (cardiopulmonary) profiles were measured in 14 nonseptic trauma/general surgery (T/GS) patients and in ten patients with Gram-negative abdominal surgical sepsis. The physiologic state classification system was used as the frame of reference. There were no response differences between the T and GS groups: they had A State responses. The sepsis (S) patients initially had exaggerated A State responses with significant changes in glucose, fat, amino acid, and glucagon plasma levels relative to T/GS. The S patients who survived (four) demonstrated profiles as in T/GS. The S patients who expired (six) progressively evolved an unbalanced, hyperdynamic B State response with progressive elevations of glucose, lactate, aromatic and branched-chain amino acids and glucagon, and low ketone bodies. There is definite correlation over time between metabolic and physiologic responses; the physiologic responses reflect the metabolic responses; the metabolic responses are consistent with a peripheral energy-fuel deficit.
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Preoperative and serial postoperative clinical, cardiovascular, physiologic, and metabolic studies were carried out on 86 patients undergoing coronary artery bypass surgery (CABG); and 48 patients undergoing abdominal general surgical procedures (GSEL). Multivariable statistical analysis of these data showed the patients to be in different physiologic states and to manifest several types of recovery trajectories that could not be discerned on clinical grounds alone. The CABG patients followed one of three types of cardiogenic recovery trajectories. In contrast, GSEL patients show a normal recovery trajectory different from all CABG types. When sepsis develops, and exaggerated stress response (A state) occurs, with increased oxygen consumption and a pattern of amino acids, fat, and glucose breakdown products, which is heightened but similar to the response of nonseptic GSEL patients. With progression of sepsis severity, an unbalanced hyperdynamic recovery trajectory (B state) develops in which a decrease in oxygen consumption is associated with increases in the aromatic amino acids tyrosine, tryptophane, and phenylalanine; and decreases in the branched-chain amino acids, leucine and isoleucine. Triglycerides rise as keto acids fall, but both lactate and pyruvate rise. Glucagon is persistently high, regardless of insulin levels. The quantifiably different physiologic recovery trajectories reflect altered hormone and metabolic states and imply different responses to therapy.
The septic response in man appears to be a disease in which the infecting agent induces a state of disordered metabolic control in the host. The abnormal regulation of metabolic pathways causes a diversion of substrate utilization toward gluconeogenesis and ketone body formation and a reduction in oxidative energy-producing metabolism. This state of metabolic insufficiency is reflected in the pattern of cardiorespiratory, vascular, and physiological compensation. The precise magnitude of the resultant physiological compensation and its rate and direction of change can be quantified by the use of physiological state trajectories which also reflect the magnitude of underlying metabolic derrangements. The prognostic and therapeutic implications of these changes are discussed.
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The plasma concentrations of substrates, together with transhepatic and transgut balances, have been studied in six control and eight septic awake fasted dogs. Four severely ill septic dogs (typically fluid in chest and/or abdomen, extensive peritonitis, respiratory difficulties) had high concentrations of threonine, glycine, tyrosine, lysine, histidine, tryptophan, and triglycerides (p less than or equal to 0.05). The other septic dogs (less severely ill) showed fewer and less pronounced alterations in the plasma substrates (aspartate and tryptophan were elevated, p less than or equal to 0.05). The infusion of glucose increased the concentration of glucose, lactate, and pyruvate and depressed the concentrations of most amino acids in both normal and septic dogs. Threonine, asparagine, glutamine, leucine, isoleucine, alpha-aminobutyrate, and tyrosine were significantly depressed in the severely ill septic dogs (p less than or equal to 0.05). In the normal dogs most amino acids were removed by the liver, with alanine accounting for approximately 40% of the total. Glutamine removal was negligible. In the septic dogs hepatic removal of amino acids was variable; livers of two severely ill septic dogs did not remove amino acids. In the control dogs glucose infusion (0.015--0.017 g/kg/min) tended to lower hepatic removal of amino acids. Hepatic dye removal in the septic dogs was always very poor. In the gut glutamine was removed and alanine, glutamate, glycine, and ammonia produced, but the overall sum of amino acid uptake was negligible in both the control and septic dogs. The ratio of tryptophan to the sum of valine, isoleucine, leucine, tyrosine, and phenylalanine concentrations was greatly elevated in all septic dogs in which it was measured. The free concentrations of amino acids in the liver, heart, and muscle tissues were grossly elevated in the low intravenous alimented septic state relative to the fasted normal state, whereas the tissue concentrative ability as measured by nonmetabolizable amino acids, alpha-aminoisobutyrate and cycloleucine, was not similarly increased. Sepsis clearly alters plasma and tissue concentrations, and in some instances hepatic uptake of amino acids.
Acetoacetic acid is oxidized independent of carnitine transport into the cell mitochondria and its monoglyceride is a water soluble compound. The latter was examined as an intravenous nutrient. The monoglyceride of acetoacetic acid was prepared from the acid anhydride, diketene, and glycerol and was found to be totally miscible with water. The nutritional properties of monoacetoacetin were investigated by continuous intravenous infusion of 25 or 50 g/kg body weight per day into ad libitum fed rats. The response of these animals was compared to normal and food restricted rats. All experimental animals survived the 7 day study period in good health and were free of detectable physiological and behavioral abnormalities. The test rats demonstrated weight gain dependent on the infusion rate while on an inadequate spontaneous oral food intake diet. Ketonuria, hyperketonemia and monoglyceride excretion in the urine accompanied the infusion of monoacetoacetin and were dependent on the infusion load. At 50 g/kg per day total plasma ketones were found to be comparable with the infusion load. At 50 g/kg per day total plasma ketones were found to be comparable with the maximum level obtained in fasted rats, but the acetoacetate concentration was relatively higher than in fasting. This was consistant with ketosis derived from the hydrolysis of the monoglyceride. It was concluded from these results that monoacetoacetin might be an asset for intravenous nutrition.
Repeated brief exposures to glucose in concentrations of 0.8 g/100 ml significantly depresses in vitro phagocytic ingestion of opsonized Gram-positive and Gram-negative bacteria by human peripheral polymorphonuclear granulocytes (PMN's), while the same concentration of L-aminoacid mixtures (Freamine) under the same conditions has no influence on it.
Intravenous nutrition was investigated using butyric acid because it is oxidized independent of carnitine transport into the cell mitochondria. This carnitine independent fatty acid, in the form of water soluble monobutyrin, was continuously infused into rats for seven days at 27 g monobutyrin per kilogram of body weight per day and provided half the daily energy requirement. All experimental animals survived the alimentation in good health and were free of detectable physiological and behavioral abnormalities. The intravenous infusion depressed the test animals spontaneous food intake to half their preinfusion level. These experimental rats still demonstrated continuous weight pain in contrast to weight loss by pair-fed controls. At decapitation, the monobutyrin infused rats had hepatic glycogen levels three times that of the controls, along with lower soluble hepatic protein, and normal lipid and water content. The plasma acetoacetate was also elevated in experimental rats. It was inferred from these results that monobutyrin was hydrolyzed, and the metabolites were oxidized by the rat. It is concluded from these observations that monobutyrin produces no obvious toxic affects during short infusion periods and provides calories for the rat when given intravenously.