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Biomedical subjects

R N Dickerson

Publications and source records attributed to R N Dickerson.

48 records · Page 3Linked to original sources

Pentobarbital improves nitrogen retention in sepsis.

Pentobarbital therapy has been associated with decreased urinary nitrogen excretion and resting energy expenditure in stressed patients. The metabolic effects of pentobarbital in sepsis were investigated in 29 well-nourished rats who underwent superior vena caval cannulation, cecal ligation, and puncture. Animals were randomly assigned to receive either a continuous infusion of 20 mg/kg/day of pentobarbital combined with parenteral nutrition (n = 13) or parenteral nutrition alone (n = 16). Both groups received isocaloric, isonitrogenous parenteral nutrition postoperatively for 24 hr. Mean nitrogen balance (+/- SEM) was better in the pentobarbital group (+169 +/- 76 mg/kg/day vs -190 +/- 66 mg/kg/day, p less than 0.01). No significant differences between the pentobarbital and control groups were noted for urinary 3-methylhistidine excretion (9 +/- 0.7 micrograms/kg/day vs 11 +/- 0.6 micrograms/kg/day, respectively) or 24 hr survival (77% vs 69%, respectively). Pentobarbital improves nitrogen retention without decreasing urinary 3-methylhistidine excretion in septic rats.

Animals↗

Antibiotic therapy of catheter infections in patients receiving home parenteral nutrition.

Fifty-eight episodes of catheter-related sepsis in 21 patients receiving home parenteral nutrition were retrospectively studied. Of 81 organisms isolated from the blood, 59% were Gram-positive cocci, 25% were Gram-negative bacilli, and 16% were yeast. Attempts to treat bacterial infections at home with antibiotic therapy while the catheter remained in place were made; fungal isolation resulted in immediate hospitalization and catheter removal. Gram-negative infections more often resulted in eventual hospitalization (92%) and catheter removal (50%) than Gram-positive infections (57% hospitalization and 23% catheter removal). Empiric therapy with 1 g of cefazolin intravenously every 12 hr was successful in only 33% of episodes caused by coagulase-negative staphylococci, whereas vancomycin was successful in 62%. Sensitivity testing was not a reliable guide for antibiotic choice for treatment of these infections. Cefazolin, 1 g, intravenously every 12 hr was successful in only 25% of Gram-negative episodes treated empirically with this regimen. We conclude that our home parenteral nutrition patients should be hospitalized for a few days upon presentation with a catheter infection for clinical evaluation and aggressive antibiotic therapy. Vancomycin is the preferred drug for treatment of catheter-related infections caused by coagulase-negative staphylococcus.

Bacterial Infections↗

Efficacy of thrombolytic therapy for occlusion of long-term catheters.

Nineteen ambulatory outpatients requiring a tunneled central venous access device with catheter occlusion were studied. Mean catheter life was 7.9 +/- 8.2 months (range, from 1-36 months) at the time of the occlusion. Urokinase (5000 units/ml) was injected in sufficient amount to fill the internal volume of the catheter and allowed to stay for 5 to 10 min before attempting to aspirate. Repeated aspiration attempts were performed every 5 to 10 min for a maximum of 30 to 60 min or patency. In the event catheter patency was not restored, the thrombolytic solution was aspirated from the catheter and a maximum of two additional trials were instituted. Results included clearance of four out of 15 withdrawal occlusions (27%) and two out of four resistance to infusion occlusions (50%). Overall, successful catheter clearance occurred in six out of 19 occlusions (32%). The efficacy rate of thrombolytic therapy for successfully clearing occluded catheters at our institution using conventional low-dose thrombolytic therapy is markedly lower than previously reported rates of 57 to 100%. The reasons for this discrepancy may reflect differences in dosage of thrombolytic agent, method of administration, frequency of monitoring of catheter patency, and catheter life.

Catheterization, Central Venous↗

Early nutrition support modifies immune function in patients sustaining severe head injury.

BACKGROUND: Immunosuppression after severe head injury has been characterized by a depressed CD4 (T-helper/inducer)-CD8 (T-suppressor/cytotoxic) ratio and decreased T-lymphocyte responsiveness. Some investigators propose that this immunocompromized state is the result of an injury-associated hypermetabolic response and inadequate nutrient delivery during the immediate postinjury recovery phase. Previous observations from our institution demonstrated a preserved CD4-CD8 ratio in severe closed-head injury (CHI) patients receiving early parenteral nutrition (PN). It was unclear whether early PN or other aspects of patient care eliminated the characteristic depression in cellular immunity. The purpose of this study was to further investigate the effect of early PN on the immune function of CHI patients. METHODS: Nine patients sustaining severe CHI were prospectively randomized to either early PN (n = 4) at day 1 or delayed PN (n = 5) at day 5. Total nutrient administration was delivered at 2 g of protein/kg per day and 40 nonprotein kcal/kg per day for at least the first 14 days of hospitalization. Analysis for T-lymphocyte expression of CD4 and CD8 cell surface antigens and interleukin-6 was performed on days 1, 3, 7, and 14 of hospitalization. T-lymphocyte activation in response to stimulation by concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogens (PWM) was also assessed on these days. RESULTS: Significant increases in total CD4 cell counts (2048 +/- 194 to 2809 +/- 129 vs 1728 +/- 347 to 1825 +/- 563, p < .05) and CD4% (42.6 +/- 4.4% to 56.2 +/- 2.6% vs 36.6 +/- 6.6% to 36.6 +/- 11.3%, p < .05) were observed at day 14 in patients receiving early vs delayed PN. An improved lymphocyte response from baseline to day 14 after Con A stimulation was demonstrated in the early PN group (3850 +/- 1596 to 16144 +/- 5024 cpm, p < .05). A significant rise in the CD4-CD8 ratio over baseline to day 14 was also noted in the early PN group (1.43 +/- 0.17 to 2.38 +/- 0.54, p < .05). CONCLUSIONS: The early aggressive nutrition support of CHI patients appears to modify immunologic function by increasing CD4 cells, CD4-CD8 ratios, and T-lymphocyte responsiveness to Con A.

Adolescent↗

Hyperkalemia secondary to concurrent pharmacotherapy in a patient receiving home parenteral nutrition.

We report a case of probable combined octreotide- and heparin-induced hyperkalemia. The patient had been receiving home parenteral nutrition, enoxaparin, and octreotide for 10 months. She required very little potassium in her PN solution to maintain serum potassium concentrations in the normal range. The patient reportedly did not receive other medications or have clinical conditions that, to our knowledge, cause hyperkalemia. She maintained normal renal function throughout the hospitalization and did not appear to have any significant acid-base disorders. Practitioners should be aware of the potential for octreotide and heparin to cause hyperkalemia. Regular monitoring of serum potassium concentrations should be done for patients receiving octreotide and heparin to avoid hyperkalemia.

Anticoagulants↗

Retinol-binding protein and prealbumin: useful measures of protein repletion in critically ill, malnourished infants.

Plasma prealbumin (PA) and retinol-binding protein (RBP) concentrations were serially measured in 25 critically ill, malnourished infants requiring parenteral nutrition to determine if these visceral protein markers are useful in assessing acute protein repletion. Significant increases in both proteins (p less than 0.05) were noted as early as 5 to 7 days after institution of parenteral nutrition and continued significantly above baseline values through 2 weeks of observation. Gestational development (in infants less than 4 weeks old) and mean protein intake influenced visceral protein responses. Appropriate for gestational age neonates had more rapid and quantitatively greater PA responses (p less than 0.05) than small for gestational age neonates. Small for gestational age neonates never exceeded baseline RBP responses. Average protein intake of less than or equal to 2 g/kg/day resulted in PA and RBP concentrations below baseline and significantly lower than infants on higher protein intakes (p less than 0.05), at the end of 2 weeks. Average calorie intake of greater than 100 cal/kg/day had no differential influence on PA or RBP when compared with infants on less calories. Prealbumin values correlated with RBP values observed simultaneously (r = 0.588, p less than 0.0001). We conclude that PA and RBP are useful measures of protein repletion in critically ill infants requiring parenteral nutrition.

Critical Care↗

A simple technique to reduce ventilator-dependent errors in oxygen consumption measurements.

To evaluate the efficacy of adding a volume reservoir to reduce variability in ventilator-induced fluctuation in inspired oxygen concentration (FiO2) and to reduce oxygen consumption measurement error, we evaluated two ventilators (Puritan-Bennett 7200 and Bear 2) at three inspired oxygen concentrations ranging from 35% to 60%. Continuous sampling of oxygen concentration was conducted for each ventilator. The maximum variability in oxygen concentration was recorded at each minute and oxygen consumption error sensitivity was calculated for both ventilators at three different oxygen concentrations, with and without the use of a baffled 3-L reservoir placed into the inspiratory circuit between the ventilator and test lung. The use of a baffled 3-L reservoir reduced oxygen consumption error sensitivity with the Puritan-Bennett 7200 ventilator at all three oxygen concentrations (p < 0.01). Similar results were found with the Bear 2 ventilator except at the highest FiO2, at which oxygen consumption error sensitivity was not altered. Use of a baffled volume reservoir can significantly reduce ventilator-dependent errors in measuring oxygen consumption via indirect calorimetry. However, when the FiO2 is widely variable, the reservoir is not helpful in reducing error at higher FiO2 concentrations.

Calorimetry, Indirect↗

Insulin-like growth factor 1 and endotoxin-mediated kidney dysfunction in critically ill, parenterally fed rats.

Endotoxemia is an important contributor to the pathogenesis of acute kidney failure in sepsis. Data suggest insulin-like growth factor 1 (IGF-1) can increase creatinine clearance in healthy humans. The influence of recombinant human IGF-1 on kidney function in endotoxemia was investigated in 34 male Sprague-Dawley rats. After venous cannulation and postoperative parenteral nutrition (PN), the animals were randomly assigned to receive PN only, PN plus Escherichia coli lipopolysaccharide (LPS), or PN plus LPS plus IGF-1. Urine output was significantly higher for the IGF-1 and control groups compared with the LPS group (18.9 +/- 5.7, 13.0 +/- 3.8, and 17.7 +/- 3.1 ml/day for control, LPS, and IGF-1 groups, respectively, analysis of variance, p < 0.05). Creatinine clearance was significantly higher in the IGF-1 group than the LPS group and exceeded the control group (0.49 +/- 0.27, 0.36 +/- 0.14, and 0.65 +/- 0.27 ml.min-1.100(-1) g body wt) for control, LPS, and IGF-1, respectively (analysis of variance, p < 0.05). IGF-1 ameliorates the effects of endotoxin on kidney function as measured by creatinine clearance and urine output in endotoxemic parenterally fed rats.

Acute Kidney Injury↗

Octreotide and potassium homeostasis.

Somatostatin infusion causes hyperkalemia in healthy subjects and in some animal models. The purpose of this investigation was to determine what effect octreotide has on potassium homeostasis during serious illness and if there is a dose-response relationship. Sixty-six male Sprague-Dawley rats (185-225 g) were randomized to receive parenteral nutrition (PN) only, PN plus continuous infusion of Escherichia coli lipopolysaccharide (LPS), or PN plus LPS plus octreotide 10, 100, or 1000 micrograms/kg/day for 48 hours. Before randomization all animals received isocaloric, isonitrogenous, isokalemic PN. A 24-hour urine was collected and a blood sample was taken at the end of the study immediately before euthanization. Data were analyzed by ANOVA and Duncan's multiple range test. Nonhemolyzed serum samples from 50 rats were available for study. Serum potassium concentrations were in the normal range for rats and did not differ significantly among the groups: 5.97 +/- 0.86, 5.96 +/- 1.58, 5.78 +/- 1.48, 5.79 +/- 1.67, 5.35 +/- 0.78 mEq/L, respectively. No differences among groups were found for fractional excretion of potassium or serum creatinine concentration. Octreotide administration in escalating dosages does not cause hyperkalemia in endotoxemic rats given intravenous potassium at a constant rate by PN.

Animals↗

Impact of a pharmacist-based consult service on nutritional rehabilitation of nonambulatory patients with severe developmental disabilities.

A pharmacist consult service was developed to evaluate the appropriateness of enteral feeding through a permanent ostomy in 24 nonambulatory patients with severe developmental disabilities. Several problems with enteral nutrition were identified. Policies to improve them were instituted, and several educational presentations were made. Pharmacists' actions were implemented, including assessment of energy needs by indirect calorimetry and rearrangement of enteral feeding schedules to achieve optimal nutrition support and pharmacotherapy administration. By the fourth month of the consult service, body weight in these patients increased from 101 +/- 6% of baseline to 109 +/- 7% (p<0.05). Weight continued to increase through the seventh month of the consult service to 116 +/- 12% of baseline (p<0.0001). Measured resting energy expenditure for the group was 889 +/- 170 kcal/day compared with the predicted 1055 +/- 163 kcal/day.

Adolescent↗

Effect of sustained endotoxemia on alpha1-adrenergic responsiveness in parenterally fed rats.

We investigated the effect of endotoxemia on alpha1-adrenergic receptor-mediated smooth muscle contraction as measured by mean arterial pressure (MAP) in response to incremental doses of a vasopressor. Twelve male Sprague-Dawley rats were randomized to receive parenteral nutrition alone (PN) or in combination with a continuous infusion of endotoxin (PN-LPS) for 48 hours. Incremental doses of phenylephrine were given and peak MAP response was recorded. The endotoxin group had a decreased rise in MAP with the same dose of phenylephrine compared with the control group (59 +/- 14 and 99 +/- 12 mm Hg, respectively, p<0.001). However, the baseline MAP was higher in the endotoxin group (102 +/- 18 and 71 +/- 7 mm Hg, respectively, p<0.002). The overall maximum effect was the same for both groups (161 +/- 16 and 170 +/- 8 mm Hg, respectively, p=NS). These data indicate that sustained endotoxemia does not result in desensitization of alpha1-adrenergic responsiveness. Other mechanisms are responsible for the ineffectiveness of vasopressors during advanced sepsis.

Adrenergic alpha-Agonists↗

Considerations in the use of lipid-based drug products.

The availability and use of intravenous lipid-based drug products is increasing. These products may have increased efficacy, decreased adverse effects, or both when compared with conventional formulations of the same drug. Lipid-based drug products have nutrition support implications when a substantial caloric dose is received during administration of the drug. They also may have unique toxicities and much greater costs than do traditional therapies. The rationale for the use of lipid-based drug products is presented, along with an overview of the proper use of current commercially available lipid-based amphotericin B, propofol, daunorubicin, and doxorubicin products.

Drug Carriers↗