Frank N. Konstantinides

Branched chain metabolic support. A prospective, randomized, double-blind trial in surgical stress.

A prospective, randomized, double-blind trial of the nutritional effects of branched chain modified amino acid solutions was undertaken in 23 surgical patients within 24 hours of the onset of major general surgery, polytrauma, or sepsis. The effects were evaluated in the absence of abnormalities of oxygen transport and perfusion in an isocaloric/isonitrogenous setting where the major difference between the groups was the amount of branched chain amino acids received. Both groups received balanced parenteral nutrition with 1.5 gm/kg/day of amino acids, 30 calories/kg/day of glucose, and 7 calories/kg/day of fat. At the end of the 7-day study interval, the group receiving the branched chain enriched therapy at 0.7 gm/kg/day of branched chain amino acids had improved nitrogen retention; an elevation of their absolute lymphocyte count from 800 to 1800/mm3, a reversal of anergy to recall skin test antigens in 60% of the patients, and improved plasma transferrin levels (p < 0.03). Nutritional support using the modified amino acid metabolic support solutions has beneficial effects during the stress interval that do not seem as achievable with current commercially available nutritional support regimens.

EARLY ENTERAL FEEDING DOES NOT ATTENUATE METABOLIC RESPONSE AFTER BLUNT TRAUMA

Enteral feeding very early after trauma has been hypothesized to attenuate the stress response and to improve patient outcome. We tested this hypothesis in a prospective, randomized clinical trial in patients with blunt trauma. Following resuscitation and control of bleeding, 52 patients were randomized to receive early feedings (target, < 24 hours) or late feedings (target, 72 hours). Feeding was given via nasoduodenal feeding tubes. A rapid advance technique was used to achieve full volume and strength within 24 hours (goal, 1.5 g protein/kg.day). Patients who underwent at least 5 days of therapy were considered to have completed the study: 38 in all, 19 in each feeding group. Patients were similar in age, gender, Injury Severity Score, and mean PaO2/FiO2 ratio. The early group, however, had more patients with a PaO2/FiO2 < 150. After feeding began, the amount fed per day was the same in both groups. We found no significant differences in metabolic responses as measured by plasma lactate and urinary total nitrogen, catecholamines, and cortisol. Both groups achieved nitrogen retention. In addition, we found no significant differences in intensive care unit (ICU) days, ventilator days, organ system failure, specific types of infections, or mortality, although the early group had a greater number of total infections. In this study, early enteral feeding after blunt trauma neither attenuated the stress response nor altered patient outcome.

Amino acid alterations and encephalopathy in the sepsis syndrome.

ObjectiveTo evaluate the role of amino acid profiles in septic encephalopathy. DesignRetrospective analysis. SettingMedical wards and medical ICU of a university hospital. PatientsPatients with infections and normal mental status were compared with patients with septic shock and altered sensorium. InterventionsPlasma amino acid levels and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were determined. Measurements and Main ResultsPatients with septic shock and altered sensorium had higher circulating concentrations of ammonia (425 ± 55 vs. 127 ± 7 mmol/L) and the aromatic amino acids phenylalanine (122 ± 19 vs. 74 ± 3 mmol/L) and tryptophan (97 ± 7 vs. 32 ± 13 mmol/L), and lower levels of the branch-chain amino acid isoleucine (48 ± 7 vs. 68 ± 5 mmol/L) than patients with infections and normal sensorium (p < .05). Aromatic amino acid levels correlated with APACHE II scores (r2 = .4, p < .001) and mortality. APACHE II scores were higher in the septic shock patients (30 < 2 vs. 8 < 1, p < .001), and these patients had a higher mortality rate (71% vs. 12%, p < .01). Patients with septic shock who died had higher levels of ammonia (524 ± 58 vs. 227 ± 40 mmol/L, p ± .05) and sulfur-containing amino acids (172 ± 31 vs. 61 ± 7 mmol/L, p < .05) than patients who survived. ConclusionsPlasma amino acid profiles appear to be important in septic encephalopathy and the severity of septic disease. (Crit Care Med 1991; 19:753)

Nitrogen retention in critically ill patients is proportional to the branched chain amino acid load.

The nitrogen retention effect of branched chain enriched parenteral nutrition (BcAA) during surgical stress and polytrauma was evaluated in a prospective, randomized, double blind study in 32 patients. The doses of BcAA were 0.16, 0.3, 0.5, and 0.7 g/kg·day with a total amino acid load of 1 or 1.3 g/kg·day. It was provided in a setting of 30 glucose cal/kg·day with 7 cal/kg·day of iv fat also given to 16 patients. After the 7-day study was completed, analysis of the 4 treatment groups of 8 patients each demonstrated that there was an increased nitrogen retention effect of BcAA, that the effect was proportionate to BcAA load, that the effect started at 0.5 g of BcAA/kg·day in a setting of balanced nutritional support, and that the effect was consistent with a BcAA influence on protein synthesis. There were no complications or side-effects from high dose BcAA. Metabolic support of the stress response in ICU patients has become a clinical reality.

Urinary urea nitrogen: too insensitive for calculating nitrogen balance studies in surgical clinical nutrition.

Urinary urea nitrogen (UUN) has been used as an estimate of total urinary nitrogen (TUN) when calculating nitrogen output for nitrogen balance (NB) studies. UUN is assumed to constitute 80 to 90% of the total nitrogen output; when estimating TUN from UUN, UUN values are multiplied by 1.25 to correct for non-urea nitrogen components. In order to evaluate the validity of estimating total urinary nitrogen output from measured UUN in a clinical setting, 491 UUN:TUN paired studies were performed on 24-hour urine collections in general surgical/trauma patients who had measured TUN outputs ranging from 0.04 to 54.0 g/d. Assessment of 315 NB studies was done to compare NB values of those calculated by using UUN as an estimate of TUN with those calculated from measured TUN. Patients in both studies were subdivided into four stress categories, using TUN/day as the index: less than 5 g, 5-10 g, 10-15 g, and greater than 15 g. On average, 80 to 90% of TUN is represented by the UUN. However, in our patient population the variability ranged from 12 to 112%. If these UUN values are used as estimates for TUN in calculating NB, variations of up to 12 g/d would result. Application of the correction factor of 1.25 is not consistent in correcting for nonurea nitrogen components in this clinical setting. The use of actual rather than estimated TUN may be a more accurate and appropriate method than UUN when calculating NB.

Paranasal sinusitis: a common complication of nasotracheal intubation in neurosurgical patients.

Sinusitis secondary to nasotracheal intubation has not been reported to occur in neurosurgical patients. Over a 1-year period, 11 patients admitted to the Intensive Care/Trauma Unit at St. Paul Ramsey Medical Center developed this entity. The mean age of these patients was 36 +/- 4 years; 7 were trauma victims, 3 had each had a subarachnoid hemorrhage, and 1 had suffered hypertensive hemorrhage. The patients presented with fever of unknown origin (FUO) and evidence of persistent hypermetabolism without an obvious cause. In 8 cases, the diagnosis was not suspected until mucopurulent nasal discharge was noted. Three additional cases were evaluated for suspected sinusitis before the occurrence of discharge. The mean duration of intubation before the diagnosis of sinusitis was 7.8 +/- 1.5 days. The diagnosis was confirmed by sinus films with a Waters view in 7 cases or by computed tomographic scanning in 4 cases and by bacteriological cultures. Two cases involved only the maxillary sinus on the side of intubation; the rest were polysinusites. The organisms involved included gram-positive and gram-negative species; all were polymicrobial with a single organism predominant. Secondary pulmonary involvement was common, and 4 patients revealed a bacteremia consistent with the major sinus organism. One patient developed septic shock. Treatment involved either orotracheal intubation or tracheostomy. This was curative in all cases. It is concluded that neurosurgical patients nasally intubated are at risk for sinusitis, which can have untoward effects such as septicemia or pulmonary infection. A high degree of suspicion will permit early diagnosis and treatment.

Does Modified Amino Acid Total Parenteral Nutrition Alter Immune-Response in High Level Surgical Stress

A randomized prospective double-blinded study was conducted in patients in moderate to high level surgical stress to ascertain the effect of high dose branched-chain (BcAA) hyperalimentation on skin test reactivity and lymphocyte count. Isocaloric, isonitrogenous balanced total parenteral nutrition solutions were administered to two treatment groups. The study group received the high dose (45% BcAA) solution while the control group received a standard amino acid solution (24.2% BcAA). All patients received 1 to 1.5 g/kg/day of amino acids and 30 nonprotein cal/kg/day, with 30% of them as fat. Immune function was assessed by absolute lymphocyte count and delayed cutaneous hypersensitivity on days 0 and 7 of therapy. Absolute lymphocyte count showed a marked improvement in patients receiving high dose aBcAA (p less than 0.03). All patients were anergic at baseline; a much greater percentage of skin test reactivity was observed in the BcAA group on day 7 (p less than 0.03). They were also in positive nitrogen balance. The data suggest that improved nitrogen retention and immune-competence is possible with branched-chain-enriched hyperalimentation in high level surgical stress.

Inaccuracy of nitrogen balance determinations in thermal injury with calculated total urinary nitrogen.

Many burn centers use nitrogen balance studies to estimate the adequacy of nutritional support. Nitrogen loss includes the sum of urinary urea nitrogen, nonurea urinary nitrogen, and losses from skin, wound, and stool. Urinary urea nitrogen is often used to calculate total urinary nitrogen by multiplying the urinary urea nitrogen by a factor of 1.25 to account for nonurea urinary nitrogen. This formula is appropriate when applied to a nonstressed individual who has fasted overnight but is not appropriate for patients who have undergone surgery or experienced trauma. We have undertaken this study to assess the predictability of this formula in patients with thermal injuries. Twenty-seven patients with major thermal injuries had random 24-hour urine collections, which were analyzed for both urinary urea nitrogen and total urinary nitrogen. In these patients with burns we found that urinary urea nitrogen represented approximately 65% of the directly measured total urinary nitrogen rather than 80% as assumed by the formula. This increase in the nonurea nitrogen loss is greater than that found after surgery or trauma. Individual measurements may underestimate losses by 20% to 60%. Directly measured total urinary nitrogen should replace calculated total urinary nitrogen as the index of urine nitrogen losses for nitrogen balance studies in patients with burns.

Decreased in vitro fluoroquinolone concentrations after admixture with an enteral feeding formulation

BACKGROUND The purpose of this study was to determine if mixing of fluoroquinolones with a common enteral feeding formulation, Ensure (Ross Products Division, Abbott Laboratories, Columbus, OH), would alter the measured in vitro quinolone concentrations over a 24-hour period. METHODS Tablets of ciprofloxacin (500 mg), levofloxacin (500 mg), and ofloxacin (300 mg) were crushed and mixed with 240 mL of Ensure, water and calcium chloride (500 mg/L), water and magnesium chloride (200 mg/L), water and calcium chloride and magnesium chloride, and water alone. Fluoroquinolone concentrations of the mixtures were measured, via high-performance liquid chromatography, at baseline and serially over 24 hours. Experiments were performed in duplicate, at three temperatures (5 degrees C, 25 degrees C, and 37 degrees C). RESULTS Average decreases of 82.5% +/- 1.5% for ciprofloxacin, 61.3% +/- 5.2% for levofloxacin, and 45.7% +/- 10.1% for ofloxacin (mean +/- 95% CI) were observed in vitro for Ensure over the two experimental sets at baseline. Serial analysis revealed no further significant change in any of the quinolone concentrations over the remaining 24-hour period. No significant decrease was noted with the quinolones when mixed in water and calcium, water and magnesium, water and calcium and magnesium, or water alone. This phenomenon appears to be unaffected by time and temperature. CONCLUSIONS These data suggest there is an immediate and significant loss of fluoroquinolone when mixed with Ensure. An explanation for the loss of fluoroquinolone remains unclear.

Growth hormone enables effective nutrition by peripheral vein in postoperative patients: a pilot study.

The purpose of this pilot study was to investigate the metabolic effects of growth hormone (GH) (Humatrope, Eli Lilly & Co., Indianapolis, IN) administration in postoperative (PO) patients receiving peripheral vein nutrition. Seven, well-nourished, nondiabetic patients undergoing elective surgical procedures were given either no drug (n = 3), GH 30 micrograms/kg/day (n = 2), or GH 60 micrograms/kg/day (n = 2) sub-Q daily until eating, up to 7 days PO. All the patients received 5% dextrose with electrolytes in the first 24 hours PO and then received calories at 80 +/- 5% of the measured resting energy expenditure (REE) and amino acid at 1 g/kg/day with electrolytes, vitamins, and minerals. There were no significant outcome differences between the 30 and 60 micrograms/kg/day groups and, therefore, these groups were analyzed together (n = 4). By day 6 of the study, the GH group had a significant reduction in the respiratory quotient (RQ) measured by indirect calorimetry; an increase in nitrogen retention; an increase in plasma transferrin concentrations; and an increase in plasma insulinlike growth factor (IGF1) concentration. There was no increase in blood glucose concentrations, or decrease in urinary 3-methylhistidine excretion; and no adverse effects occurred. We concluded that GH in PO patients on hypocaloric nutrition promoted protein synthesis, fat oxidation, and nitrogen retention. Effective parenteral nutritional support in postoperative adult patients can be achieved without the use of central vein access.