J. Milic-Emili

Nutrition and the respiratory system

SUMMARYMalnutrition and weight loss are among the signs of a poor prognosis in the natural history of patients with COLD.123, 124 Patients whose only source of daily nutrition is 2–31 of 5% dextrose suffer malnutrition and weight loss. This has been documented to be detrimental.Currently, there are insufficient data to propose the optimum form and amount of nutritional intake. Thus, it is appropriate to suggest moderation in nutritional support of patients with compromised pulmonary reserve. Glucose infusions may be expected to replenish tissue glycogen and, hence, be associated with improved work performance; however, CO2 production is significantly increased. However, an increased RQ may provide a more favorable alveolar Po2 which could be important in patients with COLD during room air breathing. Fat emulsions are commercially available, can minimize CO2 production, and have been shown to be N sparing. However, serum hyperlipemia may compromise pulmonary diffusing capacity. Increasing nitrogen intake can increase ventilatory drive, but this may lead to a feeling of dyspnea and be detrimental in patients unable to increase minute ventilation.Parenteral nutrition should be guided by whether the goal is to: (a) preserve lean body mass in patients who are in satisfactory nutritional condition but whose return to oral intake is not imminent, or (b) restore lean body mass in patients who have lost greater than 10% of normal body weight. In patients where the intent is maintenance of lean body mass, nutritional support should be designed to attain calorie and nitrogen equilibrium. Practically speaking, this means: (1) energy intake of 1–1.2 χ energy expenditure; (2) nitrogen intake of 200–300 mg/kg. At this institution, 50% of the nonprotein calories are given as fat emulsions. In patients where the goal is restoration of lean body tissue, the nutritional regimen should be designed to achieve a distinctively positive calorie and nitrogen balance. Energy intake is set at 1.4–1.6 χ energy expenditure. Nitrogen intake is between 250–400 mg/kg body weight. One-half of the nonprotein calories are given as lipid.These recommendations are based upon limited data and indirect evidence. Further studies of nutrition and respiration are needed to construct more definitive guidelines in this important area of clinical care.

Amino Acids and Respiration

Parenteral nutrition containing glucose and amino acids may stimulate respiration. To ascertain the effects of these solutions on respiration, eight normal subjects received an infusion of 5% dextrose (100 mL/h) for 7 days followed by an infusion of 3.5% amino acids (125 mL/h) for 24 hours. Minute ventilation (VE), tidal volume, mean inspiratory flow (VT/VI), oxygen consumption, and carbon dioxide production were significantly depressed after 7 days of 5% dextrose infusion. Ventilation and metabolic rate increased within 4 hours after initiation of the amino acid infusion and returned to normal 24 hours after the infusion. The effects of the amino acids on (VE) was secondary to an increase in (VT/VI), which is an indicator of neuromuscular ventilatory drive. Thus, within 4 hours amino acids will restore depressed metabolic rate, minute ventilation, and ventilatory drive after prolonged infusion of 5% dextrose.

Effect of protein intake on ventilatory drive

Previous studies have demonstrated that if isotonic amino acid infusions were administered at a rate that approximated normal daily protein requirements, a leftward shift of the minute ventilation · PaCO2 relationship occurred. This study examined the effect of the administration of parenteral nutrition, at a fixed caloric intake and two levels of nitrogen (N) intake, on the ventilatory response to CO2 in nutritionally depleted patients. The intent was to determine whether increasing protein intake from normal to twice normal requirements would result in a further enhancement of the ventilatory response to CO2. Eight patients with nutritional depletion (greater than 10% weight loss) were studied. The resting energy expenditure (REE) was measured during administration of 5% dextrose, using principles of indirect calorimetry. Each patient received parenteral nutrition for a 2-week period. Two diets were examined for a 1-week period each: 1) a high N intake—15 mg nitrogen per kcal REE (approximately 21 g/day), or b) a low N intake—7.5 mg nitrogen per kcal REE (approximately 11 g/day). The initial diet was assigned randomly. Total energy intake was set at 1.35 X REE as measured during administration of 5% dextrose solution. Nonprotein calories were administered as 50% glucose and 50% fat. Breathing patterns at rest and during inhalations of 2 and 4% CO2 were analyzed using a canopy-computer-spirometer system. With an increased nitrogen intake there was a significant reduction in resting arterial PaCO2 from 39.9 to 37.6 mmHg (P < 0.05) with no significant change in pH. The relationship between VE and PaCO2 observed during inhalation of CO2 showed a marked leftward shift (P < 0.01), indicating an increased ventilatory sensitivity to CO2. These data indicate that increasing the protein component of a fixed caloric intake will enhance the ventilatory response to carbon dioxide.

Changes in respiratory control induced by amino acid infusions.

We compared the metabolic and respiratory responses to a 4-h infusion of an amino acid solution consisting primarily of branched-chain amino acids (BCAA) to those after a standard amino acid solution in healthy subjects. Both the BCAA solution and the standard amino acid solution increased minute ventilation (mean increase 22%, p less than .001, and 18%, p less than .01, respectively), mean inspiratory flow (19%, p less than .01, and 19%, p less than .05) and oxygen consumption (9%, p less than .02, and 5%, NS). PaCO2 decreased (mean decrease 6%, p less than .01); there was a major increase in the ventilatory response to CO2 inhalation during administration of the BCAA solution but not the standard amino acid solution. Increased plasma norepinephrine concentration (mean increase 75%, p less than .001) during the infusion of the standard amino acid solution but not the BCAA solution suggested increased sympathetic activity. The results demonstrate augmented respiratory effects of amino acid infusions by BCAA enrichment, and a dissociation between the respiratory stimulation, metabolic rate, and sympathetic activity.