[Problems related to resuscitation in studies with contrast media]. / Problematiche di interesse rianimatorio nelle indagini contrastografiche.

This study has the purpose of describing indications and legal implications related to the intravascular use of contrast media (ICM) in order to provide useful guidelines to the intensivist, often involved in the treatment of adverse reactions. The structure of modern contrast media (CM), is a benzenic ring carrying steadily three iodine ions. Adverse reactions due to the use of ICM, are local or systemic ranging from skin rashes or flushes (urticaria et al.), to cardiovascular, respiratory and neurologic symptoms. The prevention of these reactions is mandatory in patients reporting a history of allergy or atopia disease. From a legal point of view, the contraindication to procedures involving i.v. use of CM are not clearly pointed out therefore several concerns have been expressed. The intensivist is not required to physically attend the procedure, in agreement with the circular #64 edited in 1979; on the other hand his prompt intervention should be granted if necessary. Furthermore every therapeutic supply suitable for any resuscitational intervention should be available in the area where the test is performed. In conclusion we would like to stress the financial and ethic implications related to the choice of ICM (ionic versus non-ionic). The use of non-ionic CM offers several advantages: among them the better tolerance for the patient and the lower incidence of adverse reactions. However non-ionic CM have a cost ten-fold higher and both groups of drugs have same incidence of fatal reactions, therefore the use of non-ionic ICM is recommended for high risk patients.

Effects of growth hormone administration on dehydroepiandrosterone sulphate, androstenedione, testosterone and cortisol metabolism during nutritional repletion.

This study evaluated whether pharmacological doses of recombinant human growth hormone (hGH) influences androgen or cortisol metabolism during nutritional repletion following prolonged illness. Stable hospitalized adults (three males, seven female) receiving constant calorie and protein intake were studied. An initial control week was followed by a treatment period during which hGH (10 mg/day s.c.) was administered daily. Prior to hGH treatment, serum and 24-h urinary concentrations of dehydroepiandrosterone sulphate (DS) were below the normal range; serum androstenedione and testosterone concentrations were within the lower limit of normal. In contrast, serum cortisol (F) and 24-h urinary F excretion were normal. During hGH treatment, nitrogen balance became positive and plasma insulin-like growth factor I (IGF-I) concentrations rose five to seven-fold. However, serum DS, androstenedione, testosterone and F, and urinary F excretion did not change, while 24-h urinary DS excretion fell significantly. Growth hormone administration markedly stimulated protein anabolism but did not increase the low concentrations of circulating androgens or alter the disassociation between adrenal androgen and F release in stable hospitalized males and females. Thus, hGH does not appear to function as a cortical adrenal androgen stimulating hormone (CASH) or regulate adrenal cortisol or gonadal androgen release in this clinical setting.

Use of human growth hormone combined with nutritional support in a critical care unit.

The administration of growth factors may potentially accelerate recovery during critical illness by reducing body protein catabolism, enhancing wound healing, and improving skeletal muscle function. The purpose of this phase 1 study was to evaluate the safety and initial efficacy of a recombinant growth factor, human growth hormone (GH), combined with nutritional support in a critical care unit. Following an initial control week, 11 individuals received GH (10 mg/day) daily for 1-6 consecutive weeks. Near constant nutrient intake was provided via parenteral and/or enteral feedings throughout the study period. Vital signs and other clinical parameters, blood values, and nutrient excretion were monitored daily. GH administration was not associated with clinically significant adverse effects. During the first 2 weeks of study, nitrogen excretion decreased from 1356 +/- 157 mmol/day (19.0 +/- 2.2 g/day) during control to 899 +/- 107 mmol/day (12.6 +/- 1.4 g/day) with growth hormone (p less than 0.002) in association with markedly reduced urea generation. Significant reductions in potassium excretion (control 100 +/- 11 mmol/day vs 69 +/- 6 with GH; p less than 0.01) and phosphorus excretion (31 +/- 5 mmol/day vs 18 +/- 3; p less than 0.025) also occurred during GH. The protein-conserving effects of GH were sustained during several weeks of treatment. Growth hormone enhanced the efficiency of administered protein and facilitated nitrogen retention without clinically significant adverse effects in this small patient group. Controlled trials are indicated to determine whether use of this anabolic hormone reduces hospitalization time and improves other clinical outcomes in severely injured patients when combined with appropriate nutritional support.

Safety and metabolic effects of L-glutamine administration in humans.

A series of dose-response studies was conducted to evaluate the clinical safety, pharmacokinetics, and metabolic effects of L-glutamine administered to humans. Initial studies in normal individuals evaluated the short-term response to oral loads of glutamine at doses of 0, 0.1, and 0.3 g/kg. A dose-related increase in blood glutamine occurred after oral loading and elevation of amino acids known to be end products of glutamine metabolism occurred (including alanine, citrulline, and arginine). No evidence of clinical toxicity or generation of toxic metabolites (ammonia and glutamate) was observed. Glutamine was infused intravenously in normal subjects over 4 hr at doses of 0.0125 and 0.025 g/kg/hr. In addition, glutamine was evaluated as a component of parenteral nutrition solutions (0.285 and 0.570 g/kg/day) administered for 5 days to normal subjects. Intravenous administration of glutamine was well tolerated without untoward clinical or biochemical effects. Subsequent studies in patients receiving glutamine-enriched parenteral nutrition for several weeks confirmed the clinical safety of this approach in a catabolic patient population. In addition, nitrogen retention appeared to be enhanced when glutamine was administered at a dose of 0.570 g/kg/day in a balanced nutritional solution providing adequate calories (145% of basal) and protein (1.5 g/kg/day). Nitrogen balance in patients receiving lower doses of glutamine (0.285 g/kg/day) was similar to that in patients receiving standard formulations. Further controlled clinical trials of the metabolic efficacy, tolerance, and dose response of glutamine in other patient groups are necessary to determine the appropriate use of glutamine enrichment of nutrient solutions.

Tumor necrosis factor induces adult respiratory distress syndrome in rats.

To evaluate the effect of tumor necrosis factor (TNF), a major mediator of sepsis, on lung structure and function, we infused 200-g male Wistar rats with TNF (0, 2 x 10(5), or 4 x 10(5) U/kg of TNF) for 24 hours. Volume-pressure measurements were determined in the excised lungs using both air and saline, which eliminated surface tension forces. Total lung wet and dry weight, nitrogen level, and DNA and protein content were measured. Lungs of the rats that received TNF accepted significantly smaller volumes of air and saline at all pressures compared with the control group. Both the lung wet and dry weights increased with TNF. Lung DNA and protein content also increased, suggesting increased cellularity in the TNF-infused lungs. Thus, the lungs of the TNF-treated rats were stiffer, with reduced compliance values, and heavier due to increased water content and increased cellularity. These data indicate that sublethal administration of TNF in this rat model induces the adult respiratory distress syndrome and increases the work potential of respiration.

[Effects of the nutritional status on the respiratory system]. / Influenza dello stato nutrizionale sull'apparato respiratorio.

Mechanically ventilated patients are at high risk for malnutrition, and it is now accepted that nutrition can influence the respiratory function. In particular, malnutrition can adversely affect lung function and the adverse effects of such malnutrition include: decreased ventilatory drive, decreased respiratory muscle function, alterations of lung parenchyma and depressed lung defense mechanisms. Therefore, nutrition support should be considered if a patients has a severe chronic pulmonary disease or an acute respiratory disease. Recent studies showed that malnourished patients have a reduced respiratory muscle strength and that nutritional intervention can return muscle ventilatory function to normal levels. Furthermore, it seems very likely that the ventilatory drive can be influenced by dietary intake of amino acids and glucose. The structure of the pulmonary parenchyma can be affected by starvation and the pulmonary defense mechanisms are depressed in malnourished patients. The incidence of post-operative pneumonia or atelectasis is higher in protein-depleted patients. in comparison with well-nourished patients. In conclusion, the importance of nutrition support in the management of patients with respiratory failure, particularly those mechanically ventilated, is stressed in the paper.