Effect of pentoxifylline on nitrogen balance and 3-methylhistidine excretion in parenterally fed endotoxemic rats.

Pentoxifylline interrupts early gene activation for tumor necrosis factor, interleukin-1, and interleukin-6 production and improves survival from experimental sepsis. These effects can alter nitrogen loss during critical illness. To determine the dose-dependent influence of pentoxifylline on nitrogen loss, 44 male Sprague-Dawley rats (220 to 265 g) were randomized to receive parenteral nutrition only (PN), PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide (LPS) at 9 mg x kg(-1) x d(-1), or PN plus LPS plus a continuous infusion of pentoxifylline at either 25 (PEN25) or 100 mg x kg(-1) x d(-1) (PEN100) for 48 h. Before randomization, all animals underwent intravenous cannulation and 40 h of PN adaptation. All animals received isocaloric, isonitrogenous PN (160 kcal x kg(-1) x d(-1) and 1.0 gN x kg(-1) x d(-1)) and were kept nil per os except for water ad libitum. Administration of LPS significantly worsened nitrogen balance for all three groups compared with PN control; however, pentoxifylline only modestly improved nitrogen balance compared with LPS (206 +/- 255, -497 +/- 331, -332 +/- 329, and -310 +/- 383 mg/48hr for the PN, LPS, PEN25, and PEN100 groups, respectively; P < 0.001). Pentoxifylline did not significantly change 3-methylhistidine urinary excretion compared with LPS (573 +/- 180, 705 +/- 156, 780 +/- 326, and 683 +/- 266 microg/48 h for the PN, LPS, PEN25, and PEN100 groups, respectively, P not significant). Pentoxifylline, given in therapeutic doses after an endotoxin challenge, modestly, but not significantly, improved nitrogen balance. Urinary 3-methylhistidine excretion was not influenced by pentoxifylline. A dose-dependent effect by pentoxifylline on these markers was not evident.

A comparison of renal phosphorus regulation in thermally injured and multiple trauma patients receiving specialized nutrition support.

To compare phosphorus intake and renal phosphorus regulation between thermally injured patients and multiple trauma patients, 40 consecutive critically ill patients, 20 with thermal injury and 20 with multiple trauma, who required enteral tube feeding were evaluated. Phosphorus intakes were recorded for 14 days from the initiation of tube feeding which was started 1 to 3 days postinjury. Serum for determination of phosphorus concentrations was collected at days 1, 3, 7, and 14 of the study period. A 24-hour urine collection was obtained during the first and second weeks of nutrition support for urinary phosphorus excretion, fractional excretion of phosphorus, renal threshold phosphate concentration, and phosphorus clearance. Average total daily phosphorus intake during the 14-day study for thermally injured patients and multiple trauma patients was 0.99+/-0.26 mmol/kg/d vs 0.58+/-0.21 mmol/kg/d, respectively, p < .001. Serum phosphorus concentration on the third day of observation was significantly lower in the thermally injured group than those with multiple trauma (1.9+/-0.8 mg/dL vs 3.0+/-0.8 mg/dL, p < or = .01). A trend toward hypophosphatemia in the thermally injured group persisted by the seventh day of feeding (2.7+/-1.2 mg/dL vs 3.3+/-0.6 mg/dL, p < or = .04). Differences in urinary phosphorus excretion was not statistically significant between the thermally injured and multiple trauma groups (271+/-213 mg/d vs 171+/-181 mg/d for week 1, and 320+/-289 mg/d vs 258+/-184 mg/d for week 2, respectively). Urinary phosphorus clearance, fractional excretion of phosphorus, or renal threshold phosphate concentrations were also not significantly different between thermally injured and multiple trauma patients. During nutrition support, serum phosphorus concentrations are lower in thermally injured patients compared with multiple trauma patients despite receiving a significantly greater intake of phosphorus. Renal phosphorus regulation does not significantly contribute to the profound hypophosphatemia observed in thermally injured patients when compared with multiple trauma patients during nutrition support.

Oxandrolone in trauma patients.

STUDY OBJECTIVE: To determine the effect of oxandrolone administration on nutritional and clinical outcomes after multiple trauma. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Level 1 trauma center in a university teaching hospital. PATIENTS: Sixty-two patients requiring enteral nutrition, 60 of whom completed the study. INTERVENTION: Patients were randomized to receive either oxandrolone 10 mg or placebo twice/day for a maximum of 28 days. MEASUREMENTS AND MAIN RESULTS: Total urinary nitrogen, prealbumin, nitrogen balance, total body water, and body cell mass were measured on day 1 of enteral nutrition and then at day 7, day 10, and study exit. Patients were assessed daily for metabolic and infectious complications. The two groups were similar for demographics and dosage of enteral nutrition. Measurement of total urinary nitrogen at study entry showed both groups to be highly catabolic (oxandrolone 17.2 +/- 4.9, placebo 19.1 +/- 10.8 g/day, NS). On days 7 and 10, total urinary nitrogen increased in both groups; however, there was no significant difference between groups. Nitrogen balance was negative throughout the study in each group. Body cell mass decreased slightly in both groups over the study period. Prealbumin serum concentrations increased significantly in both groups at day 10 and study exit compared with study entry. The groups did not differ significantly for length of hospital stay (oxandrolone 30.8 +/- 17.9, placebo 27.0 +/- 25.7 days), length of intensive care unit stay (oxandrolone 17.1 +/- 7.8, placebo 15.5 +/- 9.7 days), and frequency of pneumonia or sepsis (oxandrolone 48, placebo 43 episodes). CONCLUSION: Oxandrolone 20 mg/day does not have obvious benefit in nutritional and clinical outcomes during the first month after multiple trauma.

Sequential single doses of cisapride, erythromycin, and metoclopramide in critically ill patients intolerant to enteral nutrition: a randomized, placebo-controlled, crossover study.

OBJECTIVE: To evaluate the comparative efficacy of enteral cisapride, metoclopramide, erythromycin, and placebo for promoting gastric emptying in critically ill patients with intolerance to gastric enteral nutrition (EN). DESIGN: A randomized, crossover study. SETTING: Adult medical intensive care unit at a university-affiliated private hospital and trauma intensive care unit at a university teaching hospital. PATIENTS: Ten adult, critically ill, mechanically ventilated patients not tolerating a fiber-containing EN product defined as a single aspirated gastric residual volume >150 mL or two aspirated gastric residual volumes >120 mL during a 12-hr period. INTERVENTIONS: Patients received 10 mg of cisapride, 200 mg of erythromycin ethylsuccinate, 10 mg of metoclopramide, and placebo as 20 mL of sterile water every 12 hrs over 48 hrs. Acetaminophen solution (1000 mg) was administered concurrently. Gastric residual volumes were assessed, and plasma acetaminophen concentrations were serially determined by TDx between 0 and 12 hrs to evaluate gastric emptying. MEASUREMENTS AND MAIN RESULTS: Gastric residual volumes during the study were not significantly different between agents. No differences in area under the concentration vs. time curve or elimination rate constant were identified between agents. Metoclopramide and cisapride had a significantly shorter mean residence time of absorption than erythromycin (6.3+/-4.5 [SEM] mins and 10.9+/-5.8 vs. 30.1+/-4.5 mins, respectively [p<.05]). Metoclopramide (9.7+/-15.3 mins) had a significantly shorter time to peak concentration compared with erythromycin and placebo (60.7+/-8.1 and 50.9+/-13.5 mins, respectively [p<.05]). The time to onset of absorption was significantly shorter for metoclopramide vs. cisapride (5.7+/-4.5 vs. 22.9+/-5.7 mins [p<.05]). CONCLUSION: In critically ill patients intolerant to EN, single enteral doses of metoclopramide or cisapride are effective for promoting gastric emptying in critically ill patients with gastric motility dysfunction. Additionally, metoclopramide may provide a quicker onset than cisapride.

Measured energy expenditure of tube-fed patients with severe neurodevelopmental disabilities.

OBJECTIVE: To determine measured resting energy expenditure (REE) of nonambulatory tube-fed patients with severe neurological neurodevelopmental disabilities. METHODS: Twenty patients were prospectively studied. Only steady state indirect calorimetry measurements were taken. All measurements were conducted using a canopy system. Nutritional needs were met entirely by enteral feedings via a permanent ostomy. RESULTS: REE was widely distributed from 16 kcals/kg/day to 39 kcals/kg/day. The mean REE (888+/-176 kcals/day) of the patients was significantly (p<0.01) lower than predicted as estimated by the Harris-Benedict equations (1081+/-155 kcals/day) and World Health Organization equations (1194+/-167 kcals/day). Fat-free mass (FFM) was the best parameter for predicting REE. Two predictive equations were developed that are not significantly biased and more precise (< or =15% error) than conventional predictive formulas. CONCLUSION: Conventional formulas for estimating energy expenditure are inaccurate and generally overestimate measured energy expenditure of nonambulatory patients with severe developmental disabilities.

Alterations in N-acetylation of 3-methylhistidine in endotoxemic parenterally fed rats.

N-methylhistidine (3-meH) is endogenously released during muscle catabolism and serves as a marker of protein turnover. In rats > 85% of 3-meH is excreted in the urine as the N-acetyl derivative. It has been reported that the percent of non-acetylated 3-meH (NA-3-meH) varies minimally with stress. To further evaluate these reports we randomized 39 male Sprague-Dawley rats (157-213 g) to receive parenteral nutrition only (PN) or PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 (LPS-6) or 12 (LPS-12) mg.kg-1.d-1 for 48 h. All animals received isocaloric and isonitrogenous PN 24 h before and throughout the study with water ad libitum. Total 3-meH excretion was significantly increased (P < 0.05) in the LPS-6 (470 +/- 136 micrograms/48 h) and LPS-12 (557 +/- 171 micrograms/48 h) groups versus the PN (331 +/- 126 micrograms/48 h) group. NA-3-meH differed significantly between the LPS-12 (218 /+- 89 micrograms/48 h, LPS-6 (94 +/- 48 micrograms/48 h), and PN (39 +/- 12 micrograms/48 h) groups (P < 0.05). Percent NA-3-meH increased significantly from 12.7 +/- 3.9% in the PN group to 19.8 +/- 8.0 and 39.9 +/- 12.8% in the LPS-6 and LPS-12 groups, respectively (P < 0.05). No significant changes in acetyl 3-meH were found between groups. These data suggest that either saturation or inhibition of acetylation pathways occurs with increasing levels of stress. Due to the disproportionate increases in NA-3-meH and percent NA-3-meH during endotoxemia, only total 3-meH should be used as an indicator of protein turnover in rats.

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.