Biomedical subjects

Dennis C Gore

Publications and source records attributed to Dennis C Gore.

11 recordsLinked to original sources

PubMed2003

Increased tissue oxygen extraction and acidosis with progressive severity of sepsis.

BACKGROUND: Lactic acidosis and increased production of CO(2) are common in septic shock. Presumably, both acidosis and CO(2) enhance the release of oxygen from hemoglobin. The purpose of this study was to assess the relationship of oxygen utilization, CO(2) production, acidosis, and hemoglobin oxygen (Hgb-O(2)) dissociation with progressive severity of sepsis to shock. MATERIALS AND METHODS: Femoral arterial and vein, hepatic vein, portal vein, and pulmonary artery catheters were placed in 16 anesthetized swine. Organ blood flow was determined by timed injections of colored microspheres. After baseline measurements, Pseudomonas aeruginosa was infused in eight animals. This bacterial slurry was continued inciting a progression of sepsis to shock. Eight animals served as instrumented controls. RESULTS: With sepsis and shock, there was a progressive decrease in pH and an increase in pCO(2) in plasma with all sampling sites (P < 0.01 septic shock versus baseline versus control). Blood flow to the liver and intestines increased with sepsis (P < 0.01) but then returned to near baseline control values during shock. VO(2) and/or percent O(2) extraction increased with sepsis and septic shock for the whole body and for the liver, intestine and leg (P < 0.01). There was a strong correlation between venous O(2) saturation, acidosis, and pCO(2) to percent O(2) extraction (r > 60; P < 0.0001). However, calculated P(50) values for Hgb-O(2) dissociation remained unchanged. CONCLUSIONS: This study demonstrates that increased oxygen extraction in severe sepsis is related to a fall in tissue oxygen availability and not related to any allosteric change in Hgb-O(2) dissociation. Therefore, acidosis and hypercapnia do not have a demonstrable effect on altering oxygen availability during sepsis.

Acid-Base Equilibrium↗

PubMed2003

Influence of fever on the hypermetabolic response in burn-injured children.

BACKGROUND: Burn injury typically elicits a hypermetabolic response characterized by increased energy expenditure and muscle protein catabolism. HYPOTHESIS: Fever further increases energy expenditure and muscle loss in otherwise highly hypermetabolic burn patients. DESIGN: Retrospective analysis of experimental study. SETTING: University hospital. PATIENTS: Eighty-four children (aged 2-18 years) with burns covering 40% or more of total body surface area. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Simultaneous measurements of indirect calorimetry and leg net balance of phenylalanine (as an index of muscle protein catabolism) were obtained. Patients were stratified by their rectal temperature taken at the time of these metabolic measurements: afebrile (n = 28; temperature, <39.0 degrees C); mild fever (n = 26; temperature, 39.0 degrees C-39.4 degrees C); moderate fever (n = 18; temperature, 39.5 degrees C-39.9 degrees C); or severe fever (n = 12; temperature, > or =40.0 degrees C). RESULTS: Febrile and afebrile patients were similar in age, body weight, and extent of burn area. Severe fever was associated with significantly increased resting energy expenditure (mean +/- SD resting energy expenditure-predicted basal, 1.38 +/- 0.39 for afebrile patients vs 1.68 +/- 0.30 for patients with severe fever; P<.05) and a greater net loss of phenylalanine from the leg (net balance of phenylalanine, -6.0 +/- 6.2 mg/min per 100 mL of leg volume for afebrile patients vs -10.8 +/- 7.2 mg/min per 100 mL for patients with severe fever; P<.05). Patient groups were similar in plasma glucose concentration and extent of leukocytosis. CONCLUSIONS: These findings demonstrate the association of severe fever with further increase in energy expenditure and muscle protein catabolism in otherwise hypermetabolic burned children. This suggests a possible metabolic benefit in attenuating fever in such patients.

Body Temperature↗

PubMed2003

Exogenous nitric oxide increases basal leg glucose uptake in humans.

This study addressed the role of blood flow and nitric oxide in leg glucose uptake. Seven subjects (5 men, 2 women) were studied during conditions of resting blood flow and increased blood flow, achieved by infusion of the nitric oxide (NO) donor sodium nitroprusside (SNP) into the femoral artery. Femoral arterial and venous blood samples were obtained and blood flow was determined by infusion of indocyanine green dye. SNP infusion significantly increased leg blood flow (769 +/- 103 v 450 +/- 65 mL. min(-1). leg(-1), P <.001), but did not affect arterial (4.68 +/- 0.13 mmol/L control, 4.63 +/- 0.09 mmol/L SNP) or venous (4.60 +/- 0.14 mmol/L control, 4.54 +/- 0.10 mmol/L SNP) glucose concentrations. Glucose uptake was significantly (P <.01) higher during SNP infusion (65 +/- 6 micromol. min(-1). leg(-1)) than during the basal period (34 +/- 6 micromol. min(-1). leg(-1)), whereas lactate release was unaffected (rest, 45 +/- 11 micromol. min(-1). leg(-1); SNP, 42 +/- 14 micromol. min(-1). leg(-1)). We conclude that blood flow and/or NO increase basal leg glucose uptake.

Coloring Agents↗

PubMed2003

Metformin blunts stress-induced hyperglycemia after thermal injury.

BACKGROUND: Hyperglycemia is associated with detriments in immune function and impaired wound healing. The purpose of this study was to assess the effect of metformin, an oral antihyperglycemic agent approved for patients with diabetes mellitus, on glucose metabolism in severely burned patients. METHODS: Metformin was given in a double-blind, placebo-controlled fashion to 10 patients, all with burns > 60% body surface area (age, 36 +/- 4 years; weight, 92 +/- 3 kg; mean +/- SEM). After 8 days of metformin or placebo, glucose kinetics were quantitated using isotopic dilution with 6,6-d glucose and indirect calorimetry. Measurements were made during fasting; during an intravenous glucose infusion (30 micromol/kg/min); and during a hyperinsulinemic (500 mIU/m2/h), euglycemic clamp (mean plasma glucose concentration, 6.5 +/- 0.3 mmol/L). RESULTS: During fasting, metformin-treated subjects had a significantly lower rate of endogenous glucose production (met. 9.6) and glucose oxidation than placebo control subjects. With the administration of intravenous glucose, metformin treatment significantly accelerated glucose clearance, thereby attenuating hyperglycemia. During hyperinsulinemia, glucose uptake was significantly greater in metformin-treated patients. Patients receiving metformin also had a significantly higher plasma concentration of insulin. CONCLUSION: These findings suggest a potential clinical efficacy of metformin to reduce stress-induced hyperglycemia by increasing glucose clearance. This effect may be mediated by either a metformin-induced augmentation of insulin sensitivity or by increasing insulin availability.

Adult↗

PubMed2002

The use of abdominal computed tomography scan decreases the frequency of misdiagnosis in cases of suspected appendicitis.

BACKGROUND: Despite considerable experience the reported frequency of misdiagnosis in patients undergoing appendectomy continues in the range of 20% to 40% in some populations. METHODS: We developed a clinical guideline that recommended abdominal computed tomography (CT) for all nonpregnant adults in whom the diagnosis of appendicitis was suspected unless the diagnosis could be ruled out clinically. The records of adult patients that underwent appendectomy from July 1998 through October 2001 were reviewed. The clinical guideline was developed in July 2000. RESULTS: There were 194 appendectomies performed, 114 prior to the guideline and 80 after the development of the guideline. The rate of misdiagnosis decreased from 25% to 6% (P <0.05), the rate of CT use increased from 32% to 84% (P <0.05), and the perforation rate remained unchanged. CONCLUSIONS: These results support the effectiveness of a clinical guideline that encourage the use of abdominal CT in decreasing the frequency of misdiagnosis in cases of suspected appendicitis.

Adolescent↗

PubMed2002

Nutritional support.

Despite the increasing obesity of the American population, many chronically ill patients are malnourished. When this malnutrition is combined with the hypermetabolic response and protein catabolism of an acute event, such as an operation, nutritional support becomes an important facet for optimal critical care. This chapter reviews the basic tenants of nutritional support with special emphasis on patients with pulmonary compromise. Important aspects of caloric and protein support are discussed and enteral nutrition is emphasized because of its numerous advantages and documented improvement in outcome.

Critical Illness↗

PubMed2002

Hyperglycemia exacerbates muscle protein catabolism in burn-injured patients.

OBJECTIVE: The purpose of this study was to assess if hyperglycemia influences energy expenditure or the extent of muscle protein catabolism in severely burned adults. DESIGN: Retrospective study. SETTING: Burn intensive care unit at a university hospital. PATIENTS: Adults with burns on >/=40% of their body surface area. INTERVENTIONS: Simultaneous measurement of indirect calorimetry and leg net balance of phenylalanine (as an index of muscle protein catabolism). Patients were stratified by plasma glucose values at the time of metabolic measurements (i.e., normal, glucose at </=130 mg/dL; mild hyperglycemia, glucose at 130-200 mg/dL; severe hyperglycemia, glucose at >200 mg/dL). MEASUREMENTS AND MAIN RESULTS: Normal (n = 9; plasma glucose, 109 +/- 13 mg/dL [mean +/- sd]), mildly hyperglycemic (n = 13l plasma glucose, 156 +/- 17 mg/dL), and severely hyperglycemic subjects (n = 7, glucose 231 +/- 32 mg/dL) were similar in age, body weight, extent of burn area, and daily caloric intake. Severe hyperglycemia was associated with significantly higher arterial concentrations of phenylalanine (normal, 0.079 +/- 0.027 micromol/L; severe hyperglycemia, 0.116 +/- 0.028; p <.05) and a significantly greater net efflux of phenylalanine from the leg (normal, -0.067 +/- 0.072 micromol.min(-1).100 mL(-1) leg volume; severe hyperglycemia, -0.151 +/- 0.080 micromol.min(-1).100 mL(-1) leg volume; p <.05). Resting energy expenditure and respiratory quotient were similar between patient groups. CONCLUSIONS: These findings demonstrate an association between hyperglycemia and an increased rate of muscle protein catabolism in severely burned patients. This suggests a possible link between resistance of muscle to the action of insulin for both glucose clearance and muscle protein catabolism.

Adult↗

PubMed2002

Impact of discontinuing a hospital-based air ambulance service on trauma patient outcomes.

BACKGROUND: The clinical benefit of aeromedical transportation of injured patients in the civilian population has been debated. The purpose of this study was to examine the effects of discontinuing a hospital-based helicopter transport program on trauma patient outcomes, with the hypothesis that the loss of an air ambulance would result in increased transport time and increased mortality among severely injured patients. METHODS: Data on injury severity and patient outcomes were collected prospectively for the 12 months immediately preceding and 24 months following discontinuation of the helicopter ambulance service. Transport time, mortality rate, and hospital length of stay was compared. RESULTS: The number of trauma patient admissions decreased 12%, with a 17% decrease in admissions of severely injured patients. Transport time decreased, with no change in mortality. CONCLUSION: Discontinuation of a hospital-based air ambulance service did not increase transport time or increase mortality for trauma patients.

Air Ambulances↗

PubMedDate not supplied

Relative influence of glucose and insulin on peripheral amino acid metabolism in severely burned patients.

BACKGROUND: Protein catabolism and glucose intolerance are prominent in critically injured patients. The objective of this study was to assess if glucose or insulin availability influences the extent of protein catabolism in hypermetabolic patients. METHODS: Amino acid net balance from the leg was quantitated in 6 severe burn victims. Furthermore, whole body and leg protein kinetics were assessed with 2H5 phenylalanine and 15N alanine. Measurements were obtained after a 9-hour fast, during an IV glucose infusion (30 micromol/kg per minute), and during a hyperinsulinemic (500 mIU/kg per minute) euglycemic clamp. RESULTS: Compared with fasting values, the administration of glucose resulted in a significantly increased efflux of amino acids from the leg. In contrast, insulin administration significantly decreased the cumulative net efflux of amino acids. During hyperinsulinemia, isotopic measurements demonstrated a significant decrease in alanine appearance and an increase in phenylalanine disappearance into the leg. CONCLUSIONS: These findings demonstrate that in critically injured patients, acute hyperglycemia increases muscle catabolism despite an endogenous insulin response. In contrast, exogenous insulin given in sufficient amount impedes muscle protein loss. The mechanism for this anabolic effect of insulin may vary between different amino acids.

Adult↗

PubMedDate not supplied

Glutamine supplementation fails to affect muscle protein kinetics in critically ill patients.

BACKGROUND: In vitro work suggests that glutamine availability may be an important factor in controlling the rate of muscle protein synthesis. The objective of this study was to determine if enteral administration of glutamine affects muscle protein metabolism in critically ill patients. METHODS: Six postsurgical patients requiring prolonged mechanical ventilation for pneumonia (age, 51 +/- 12 years, Acute Physiology and Chronic Health Evaluation [APACHE] 22 +/- 6, mean +/- SEM) and 6 normal healthy volunteers (age, 33 +/- 4 years) underwent evaluation of whole body and muscle protein metabolism using an 8-hour infusion of d5-phenylalanine, 5(15)N glutamine, and d3-alanine with serial blood sampling from the femoral artery and vein and biopsies from the vastus lateralis muscle. Metabolic measurements were obtained while subjects received Peptamen enterally (Basal Period) and with glutamine supplementation (24 g/3 h; Glutamine Period). RESULTS: Glutamine concentration in muscle was significantly less in the critically ill patients. Glutamine supplementation increased the arterial plasma concentration of glutamine, yet with no demonstratable effect on muscle glutamine concentration or on the rate of muscle protein synthesis in either volunteers or patients. Furthermore, muscle glutamine kinetics (incorporation into muscle, release from muscle, and rate of de novo glutamine synthesis in muscle) were not affected by glutamine supplementation in the critically ill patients. In contrast, there was a significant decrease in these kinetic parameters with glutamine supplementation within the muscle of healthy subjects. Metabolism of alanine was unaffected by administration of glutamine in either group. CONCLUSIONS: Enteral glutamine supplementation to critically ill patients fails to alter muscle glutamine metabolism or muscle protein synthesis. This suggests a possible restriction in transport of glutamine into muscle of critically ill patients.

Adult↗

PubMedDate not supplied

Metabolic response of muscle to alanine, glutamine, and valine supplementation during severe illness.

BACKGROUND: Alanine and glutamine are released from muscle in response to critical illness. Subsequent depletion of glutamine from muscle is proposed as a principal factor in the limitation of muscle protein synthesis in severely ill patients. The objective of this study was to assess the peripheral metabolic response to enteral supplementation of alanine, glutamine, and valine in critically ill patients. METHODS: Isotopic tracers of alanine, glutamine, and phenylalanine were given IV to 6 critically ill patients and 6 healthy volunteers. Blood sampling from the femoral artery and vein along with muscle biopsies provided assessment of leg (ie, muscle) kinetics. Measurements were obtained during enteral nutrition alone and then with combined alanine (11.25 g), glutamine (7.5 g) and valine (11.25 g) supplementation for 3 hours. RESULTS: Compared with healthy volunteers, critically ill patients had significantly reduced concentrations of alanine and glutamine in arterial plasma (p < .05), which increased significantly with amino acid supplementation. Muscle glutamine concentrations were significantly less in the patients and were not significantly affected by supplementation. Alanine and glutamine transport into and out of muscle and the rates of alanine and glutamine incorporation into and production from muscle were not affected by supplementation. Phenylalanine kinetics, as a marker of muscle protein metabolism, were not significantly altered by alanine, glutamine, and valine intake. CONCLUSIONS: These results demonstrate that alanine, glutamine, and valine administration fails to significantly affect muscle glutamine availability or muscle protein metabolism. These findings suggest that accelerated muscle catabolism in critically ill patients is not in response to any deficiency in alanine or glutamine availability.

Adult↗