Insulin and amino acid infusion after cardiac operations: effects on systemic and renal perfusion

OBJECTIVE: The purpose of this study was to answer two questions: (1) Does a mixed amino acid infusion enhance systemic and renal perfusion in the early postoperative period after heart operations? (2) Does the addition of insulin (glucose-insulin-potassium solution) provide additional effects to those of an amino acid infusion? METHODS: Thirty-three male patients undergoing coronary artery bypass grafting (mean age 65.9 +/- 1.2 years) were included in a prospective, controlled, randomized study. Eleven patients (AA group) received infusion of mixed amino acids (11.4 gm), 11 patients (AA + GIK group) received infusion of mixed amino acids (11.4 gm) and insulin solution (225 IU insulin, glucose with glucose clamp technique, and potassium), and 11 patients served as control subjects. RESULTS: Amino acid infusion alone had no effect on systemic vascular resistance or cardiac index but increased renal blood flow 51% +/- 11% (from 114 +/- 13 to 172 +/- 24 ml.min-1.m-2 in one kidney, p < 0.05 vs the control group). Insulin solution in addition to amino acid infusion reduced systemic vascular resistance 24% +/- 3% (from 1280 +/- 85 to 960 +/- 57 dyn.sec.cm-5, p < 0.05 vs the control and AA groups) and increased cardiac index 13% +/- 3% (from 2.3 +/- 0.2 to 2.6 +/- 0.2 L.min-1.m-2, p < 0.05 vs the control and AA groups). Insulin had no significant additive effect on renal blood flow. CONCLUSIONS: Our data imply that (1) infusion of mixed amino acids enhances renal blood flow after cardiac operations but has no effect on systemic perfusion and (2) the addition of insulin solution improves systemic perfusion. The combined treatment may potentially reduce the risk of renal hypoperfusion injury in the postoperative period after coronary artery bypass grafting.     

Randomised clinical trial of parenteral selenium supplementation in preterm infants

AIM: To determine whether selenium supplementation of parenteral nutrition with 3 micrograms/kg/day of selenious acid is safe and effective in improving the selenium status of preterm infants. METHODS: Thirty eight preterm infants with mean (SEM) birthweight of 1171 (38) g and gestational age 29 (0.3) weeks were randomly allocated to a non-supplemented (PN-selenium, n = 19) or supplemented (PN+selenium, n = 19) group. The study began at 2.8 (0.2) (range 1-5) days of age. Term breastfed (n = 23) and formula fed (n = 8) infants were used as a reference group. RESULTS: Initially there was no difference between the preterm groups in plasma or erythrocyte selenium or glutathione peroxidase activity. Plasma selenium declined by a mean (SEM) of -13.3 (3.2) micrograms/l from 28 (4) to 16 (3) micrograms/l over the first three weeks in the PN-selenium group, but there was no fall in the supplemented infants and no net change in either group over six weeks. Over six weeks, there was a net decline in erythrocyte selenium of -106 (27) ng/g haemoglobin in the PN-selenium group, but no change in the PN+selenium group, such that at week 6 erythrocyte selenium was lower in the PN-selenium group (401 (17) ng/g haemoglobin) than the PN+selenium group (493 (25) ng/g haemoglobin). Urinary selenium was substantially higher in the PN+selenium group at each week. Initially term and preterm plasma selenium concentrations were similar, but they increased in term breastfed infants (+17 (2) micrograms/l), with both groups of preterm infants having lower plasma selenium concentrations at week 6 compared with term breastfed infants (PN-selenium 22 (3) micrograms/l; PN+selenium 23 (4) micrograms/l and term breastfed 49 (2) micrograms/l). CONCLUSIONS: Selenium supplementation of PN at 3 g/kg/day prevented depletion in newborns, but was inadequate to achieve selenium concentrations equivalent to those of breastfed term infants. Whether higher doses are more effective remains to be determined, particularly in light of the high urinary selenium secretion in supplemented infants. Selenium supplementation of both parenteral nutrition and formulas is recommended, but the optimal form and dose remain unclear.     

Effect of a local nonsteroidal anti-inflammatory drug on postoperative irritation after squint surgeries. Prospective randomized double-blind study

BACKGROUND: Topical application of a nonsteroidal antiphlogistic drug (NSAD) is often recommended to minimize postoperative lid and conjunctival edema. However, the effectiveness of such therapy remains controversial. PATIENTS AND METHODS: The study presented included 100 patients aged 23.6 +/- 19.5 (5 to 77) years, who were randomly assigned to two treatment groups. Group 1 included 50 patients who underwent squint surgery, and who received Flurbiprofen ED twice a day from the first preoperative day to the third postoperative day. Group 2 served as a control group. These patients were treated with the same regimen using artificial tears. The extent of lid and conjunctival edema was assessed and scored from 1 to 4 on the fourth postoperative day. RESULTS: Squint surgery was performed on 129 eyes of 100 patients. In 32 eyes (24.8%) one muscle was operated on. In 79 eyes (61.2%) 2 muscles and in 18 eyes (14%) three muscles were operated on. The average postoperative conjunctival edema score was 2.08 +/- 0.62 (Flurbiprofen group) and 2.04 +/- 0.67 (control group), respectively. The scoring values for lid edema were 1.90 +/- 0.54 and 1.82 +/- 0.43. The differences between the two groups were not statistically significant (P = 0.21 and 0.39; Mann-Whitney test). No influence of the patient's age on the development of lid and conjunctival edema could be detected (P > 0.08). However, the number of muscles that were operated on had a significant influence on both parameters (P = 0.01 and 0.028). Single muscle operations revealed the lowest scaling values (P < 0.02 and P < 0.04). No difference was found whether 2 or 3 muscles were operated on (P = 0.24 and 0.12). CONCLUSIONS: No beneficial effect of topical application of NSAD on postoperative lid and conjunctival edema could be found in this controlled study.     

Exogenous insulin reduces proteolysis and protein synthesis in extremely low birth weight infants

OBJECTIVE: To determine the effect of a continuous insulin infusion on protein and glucose metabolism in extremely low birth weight (ELBW) infants. STUDY DESIGN: We measured the rate of appearance (Ra) of the essential amino acids leucine and phenylalanine (reflecting proteolysis), utilization of phenylalanine for protein synthesis, and glucose Ra using stable isotope tracers during a basal infusion of glucose (6 mg/kg/min) and in response to a continuous infusion of insulin (0.05 U/kg/hr) by means of the euglycemic hyperinsulinemic clamp technique. Four clinically stable, euglycemic ELBW infants (26 +/- 0 weeks' gestation, 894 +/- 44 gm birth weight, 2.8 +/- 0.8 days of age) were studied. RESULTS: In response to a greater than tenfold increase in insulin concentration (from 7 +/- 2 to 79 +/- 13 microU/ml), there was a 20% decrease in leucine Ra (Basal: 272 +/- 27 mumol/kg/hr; Insulin: 226 +/- 29 mumol/kg/hr; p < 0.01) and in phenylalanine Ra (Basal: 91 +/- 5 mumol/kg/hr; Insulin: 72 +/- 2 mumol/kg/hr; p < 0.05). Use of phenylalanine for protein synthesis also decreased by a similar magnitude (Basal: 77 +/- 4 mumol/kg/hr; Insulin: 62 +/- 1 mumol/kg/hr; p < 0.05). Glucose utilization doubled (from 8 +/- 0.9 to 15.7 +/- 1.1 mg/kg/min; p = 0.0003) and plasma lactate concentrations tripled (from 2.1 +/- 0.5 to 5.7 +/- 1.0 mmol/L; p < 0.05) during the insulin infusion. CONCLUSIONS: During an infusion of glucose alone, pharmacologic concentrations of insulin in ELBW infants produced no net protein anabolic effect. Furthermore, euglycemic hyperinsulinemia was accompanied by development of significant metabolic acidosis.     

Bone mineral density in pediatric patients with idiopathic hypercalciuria

Between October 1993 and April 1995, a total of 77 neonates requiring mechanical ventilation were enrolled in this study and were randomly divided into two groups. Group A consisted of 31 premature infants (mean birthweight 1.36 +/- 0.29 kg) with respiratory distress syndrome (RDS) and seven neonates (mean birthweight 3.2 +/- 0.5 kg) with meconium aspiration syndrome (MAS). Group B consisted of 31 premature infants (mean birthweight 1.31 +/- 0.3 kg) with RDS and eight neonates (mean birthweight 3.3 +/- 0.5 kg) with MAS. Infants in group A received synchronized intermittent mandatory ventilation (SIMV) and infants in group B received conventional intermittent mandatory ventilation (CIMV) therapy. In premature infants with RDS, our data showed: (i) the duration of ventilation was significantly shorter (P < 0.05) in the synchronized group (156 +/- 122 h) compared to the conventional group (242 +/- 175 h); (ii) significantly fewer (P < 0.05) patients required reintubation in the synchronized group than in the conventional group (three vs 11 patients); (iii) incidence of severe intraventricular hemorrhage (grades 3 and 4) was significantly lower (P < 0.05) in the synchronized group compared to the conventional group (one vs seven patients); (iv) incidence of bronchopulmonary dysplasia was significantly lower (P < 0.05) in the synchronized group than in the control group (one vs seven patients). In neonates with MAS, our data showed no significant difference (P < 0.05) on duration of ventilation, incidence of reintubation, incidence of pneumothorax or mortality rate between synchronized and control groups.     

Long-term follow-up after bowel resection for necrotizing enterocolitis: factors affecting outcome

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common surgical emergency among newborns and is associated with a high morbidity and mortality. This study evaluates the long-term survival of infants requiring surgical intervention for NEC and factors affecting outcome. METHODS: A retrospective review of infants requiring surgery for complications of NEC at a tertiary care, pediatric hospital over a 16-year period was performed. Patients were evaluated for early and late morbidity and mortality, length of intestinal resection, presence of the ileocecal valve (ICV), days of parenteral nutrition (PN), and growth. RESULTS: Two hundred forty-nine patients were included, with an average gestational age of 30 +/- 5 (+/- SD) weeks and birth weight of 1.50 +/- 0.89 kg. The surgical mortality rate was 45%, with survivors (137) being larger (P < .001) and older (P < .001) at time of birth than nonsurvivors. Mortality rates varied inversely with gestational age and birth weight. Surgical survivors had an average of 21 +/- 26 cm of intestinal length resected. The ileocecal valve was preserved in 45% of infants. Growth was similar between infants with or without an ICV. Stratification of length of intestine resected showed that infants with larger resections had greater requirements for parenteral nutrition, but this had no influence on long-term growth at follow-up. CONCLUSIONS: Survivors of NEC are characterized by greater gestational age, greater birth weight, and older postgestational age at surgery. Infants who underwent greater intestinal resections required longer periods of PN. The length of intestine resected or presence of the ileocecal valve had no overall bearing on long-term outcome.     

Alterations in glucose metabolism in patients with Alzheimer's disease

OBJECTIVE: To determine the alterations in glucose metabolism that occur in patients with Alzheimer's Disease (AD). DESIGN: Cross-sectional comparison of AD and healthy controls. SETTING: A University teaching hospital. PATIENTS: Healthy controls (n = 14, BMI: 24.9 +/- 0.5 kg/M2, age 73 +/- 1 years) and patients with AD (n = 12, BMI: 23.9 +/- 1.0 kg/M2, age 72 +/- 1 years). All controls and patients with AD had a normal history and physical examination, a negative family history of diabetes, and took no medications. MEASUREMENTS: All patients and controls underwent an assessment of their dietary intake and physical activity, a 3-hour oral glucose tolerance test (OGTT), and a 2-hour hyperglycemic glucose clamp study. RESULTS: Total caloric intake (AD: 27.1 +/- 1.3 kcal/kg/day; Control: 23.6 +/- 1.6 kcal/kg/day; P = ns) and intake of complex carbohydrates (AD: 5.9 +/- 0.4 kcal/kg/day; Control: 6.5 +/- 0.3 kcal/kg/day; P = ns) were not different between groups. Leisure time physical activity was greater in controls (AD: 2970 +/- 411 kcal/week; Control: 5229 +/- 864 kcal/week; P < 0.05). Patients with AD had higher fasting glucose (AD: 5.9 +/- 0.2 mmol/L; Control: 5.1 +/- 0.1 mmol/L; P < 0.01) and insulin (AD: 144 +/- 20 pmol/L; Control: 100 +/- 6 pmol/L; P < 0.05) values. In response to the OGTT, the area under the curve for glucose and insulin was similar in both groups. During the hyperglycemic clamp, steady-state glucose values were higher in the Alzheimer's patients (AD: 11.5 +/- 0.2 mmol/L; Control: 10.9 +/- 0.1 mmol/L, P < 0.01). First- and second-phase insulin responses were similar in each group. The insulin sensitivity index (units: mL/kg.min per pmol/L x 100), a measure of tissue sensitivity to insulin, was reduced in the patients with AD (AD: 0.59 +/- 0.06; Control: 0.79 +/- 0.07; P < 0.05). CONCLUSIONS: We conclude that early AD is characterized by alterations in peripheral glucose metabolism, which may relate, in part, to alterations in physical activity.     

Modified ultrafiltration improves left ventricular systolic function in infants after cardiopulmonary bypass

OBJECTIVE: Our objective was to test the hypothesis that use of modified ultrafiltration after cardiopulmonary bypass improves intrinsic left ventricular systolic function in children. METHODS: Twenty-one infants undergoing cardiopulmonary bypass were instrumented with ultrasonic dimension transducers, to measure the anteroposterior minor axis diameter, and a left ventricular micromanometer. Patients were randomized to modified ultrafiltration (n = 11, age 226 +/- 355 days, weight 6.7 +/- 3.1 kg) or control (n = 10, age 300 +/- 240 days, weight 7.0 +/- 2.5 kg) (all differences p > 0.05 between groups). Left ventricular systolic function was assessed by means of the slope of the preload-recruitable stroke work index. Myocardial cross-sectional area was measured by echocardiography. Data were acquired immediately after separation from bypass, at steady state, and during transient vena caval occlusion. Data acquisition was repeated after 13 +/- 5 minutes of modified ultrafiltration or after 12 +/- 5 minutes without modified ultrafiltration in the control group. Inotropic drug support was the same at both study points. RESULTS: In the modified ultrafiltration group, the filtrate volume was 363 +/- 262 ml. The hematocrit value increased from 26.0% +/- 2.7% to 36.7% +/- 9.5% (p = 0.018), myocardial cross-sectional area decreased from 3.72 +/- 0.35 cm2 to 3.63 +/- 0.36 cm2 (p = 0.04), end-diastolic length increased from 25.6 +/- 9.0 mm to 28.8 +/- 9.9 mm (p = 0.01), and end-diastolic pressure fell from 5.6 +/- 0.8 mm Hg to 4.2 +/- 0.8 mm Hg (p = 0.005), suggesting an improved diastolic compliance. In the control group, the hematocrit value, myocardial cross-sectional area, end-diastolic length, and pressure did not change (all p > 0.05). Mean ejection pressure increased in the ultrafiltration group (p = 0.001) but did not change in the control group (p = 0.22). The slope of the preload-recruitable stroke work index increased after ultrafiltration from 52.3 +/- 52.0 to 74.2 +/- 66.0 (10[3] erg/cm3) (p = 0.02) but did not change in the control group (p = 0.07). One patient from each group died in the postoperative period. Patients in the ultrafiltration group received less inotropic drug support in the first 24 hours after the operation (156.62 +/- 92.31 microg/kg in 24 hours) than patients in the control group (865.33 +/- 1772.26 microg/kg in 24 hours, p = 0.03). CONCLUSIONS: Use of modified ultrafiltration after cardiopulmonary bypass improves intrinsic left ventricular systolic function, improves diastolic compliance, increases blood pressure, and decreases inotropic drug use in the early postoperative period.     

Clinical experience with the video-assisted saphenectomy procedure for coronary bypass operations

BACKGROUND: Leg wound complications after saphenectomy are frequent after coronary bypass operations and have a detrimental effect on postoperative quality of life and treatment cost. To reduce morbidity, we evaluated a new technique of video-assisted vein harvest. METHODS: Between March 1996 and October 1996, 50 patients had video-assisted saphenectomy (VAS) and 40 patients had the standard open technique (control group). An additional 13 patients had both procedures (hybrid group). Level of pain, edema, and wound complications were evaluated at discharge and at 2, 4, and 6 weeks postoperatively. RESULTS: The mean operating time for VAS patients was slightly higher than for control (60.6+/-24.7 minutes versus 53.2+/-21.1 minutes; p > 0.05). The average incision length in VAS patients was 13.8+/-8.8 cm for an average of 3.3 grafts per patient. Three VAS procedures were aborted, two because of time constraints, and one because of bleeding, and a segment of vein was lost to injury. The VAS group had considerably less early postoperative pain than the control group (1.7+/-1.2 versus 4.1+/-1.4 [1 = mild, 10 = severe]; p < 0.005) and edema was similar for both groups. Patients in the hybrid group reported less pain in the VAS-operated leg. Serious wound infection occurred in 4 patients, with 2 patients in the control group requiring reoperation for drainage and flap reconstruction. CONCLUSIONS: Based on this initial experience, VAS harvesting, although initially more time consuming, is a rapidly mastered technique, results in shorter overall incision length, and is associated with considerably less postoperative pain than the standard open technique.     

Selective deimination of vimentin in calcium ionophore-induced apoptosis of mouse peritoneal macrophages

Amino acid infusions during general anesthesia induce thermogenesis and prevent postoperative hypothermia. The effects of increased heat production during anesthesia on postoperative nitrogen balance have not been examined. Therefore, we studied the effect of perioperative amino acid infusions on postoperative nitrogen excretion in 24 patients scheduled for hysterectomy. Seven volunteers not subjected to anesthesia or surgery were used as awake controls. During isoflurane anesthesia, 8 patients received acetated Ringer's solution, and 16 patients received an IV amino acid mixture, 240 kJ/h, before and during anesthesia. Rectal temperature and energy expenditure were measured. The urinary nitrogen content was calculated from urea, creatinine, and urate the day before surgery and for 4 days postoperatively. Diets were recorded. In anesthetized control patients, postoperative nitrogen excretion was less than preoperative levels. Those patients also experienced the largest decrease in core body temperature during anesthesia (1.7+/-0.1 degrees C). All had postoperative shivering. In the amino acid-treated patients, the temperature decrease during anesthesia was less pronounced (1.0+/-0.1 degrees C; P < 0.001) and postoperative shivering disappeared. In addition, the nitrogen excretion was unchanged postoperatively, perhaps indicating an increase in protein turnover known to generate heat. In conclusion, the increase in heat production induced by amino acids reduced hypothermia, abolished shivering, and attenuated/normalized the postoperative nitrogen saving that occurred in patients who did not receive amino acids. IMPLICATIONS: We compared nitrogen excretion before and after surgery in patients who received a saline or amino acid infusion during isoflurane anesthesia. The increase in heat production induced by amino acids reduced hypothermia, abolished shivering, and attenuated/normalized the postoperative nitrogen saving that occurred in patients who did not receive amino acids.     

Randomized long-term evaluation of bicarbonate-buffered CAPD solution

BACKGROUND: Over the past 15 years, lactate has been used successfully as a buffer in peritoneal dialysis solutions, although its effectiveness in the correction of uremic acidosis and its biocompatibility on peritoneal resident cells have been questioned. In addition, some investigators have suggested other potential adverse metabolic effects resulting from the unphysiologically high lactate flux into the body during CAPD. These potential problems associated with lactate-containing CAPD solution prompted the search for alternative buffer-containing solutions. Bicarbonate, the physiological buffer, was considered when the problem of calcium and magnesium carbonate solubility was solved by the use of a two-compartment bag system, allowing the mixing of bicarbonate and divalent cations immediately before infusion. The long-term tolerance, safety, efficacy and therapeutic value of a bicarbonate-buffered peritoneal dialysis solution were evaluated in this study. METHODS: This open, randomized, controlled, multicenter study comparing a 34 mmol/liter bicarbonate- with a 35 mmol/liter lactate-buffered peritoneal dialysis solution was performed in two consecutive 12-week-treatment phases. Fourteen Centers participated in this trial. RESULTS: A total of 69 out of initially 123 randomized patients completed the six-month study period (36 patients in the bicarbonate group and 33 in the lactate group). While the arterial acid base status of the total study population did not change during the study period and no significant difference was observed between the two treatment groups, the acid-base status of patients in the bicarbonate group entering the study with a metabolic acidosis significantly improved (mean +/- SD; blood pH: baseline = 7.361 +/- 0.05, week 12 = 7.380 +/- 0.04, P < 0.05; week 24 = 7.388 +/- 0.03 P < 0.05; plasma bicarbonate: baseline = 19.49 +/- 3.01 mmol/liter, week 12 = 21.16 +/- 2.63 mmol/liter, P < 0.01; week 24 = 21.51 +/- 2.42 mmol/liter, P < 0.01). No significant changes were recorded in acidotic patients treated with the conventional lactate-buffered solution. The changes in plasma bicarbonate from baseline during the study was significantly different between the groups (week 12: lactate = +0.11 +/- 2.21 mmol/liter, bicarbonate = +1.69 +/- 2.55 mmol/liter, P < 0.05, 95% confidence interval for the difference 0.21 to 2.94 mmol/liter; week 24: lactate = +0.03 +/- 2.48 mmol/liter, bicarbonate = +1.82 +/- 2. 96 mmol/liter, P < 0.05, 95% confidence interval for the difference 0.16 to 3.42 mmol/liter). The normalized protein catabolic rate (nPCR) slightly but significantly decreased in the lactate group (baseline -0.90 +/- 0.23 g/kg/day, week 24 -0.83 +/- 0.21 g/kg/day, P < 0.01) and increased in the bicarbonate group (baseline +0.89 +/- 0.28 g/kg/day, week 24 +0.92 +/- 0.26 g/kg/day, P < 0.05). Changes from baseline between groups were significant (week 24, lactate = -0. 099 +/- 0.15 g/kg/day, bicarbonate = 0.049 +/- 0.12 g/kg/day, P < 0. 01, 95% confidence interval for the difference 0.068 to 0.229 g/kg/day). Other evaluated parameters (biochemical profile, peritoneal function parameters, dialysate protein loss) did not differ significantly between the two groups. No adverse effects related to the study solution were recorded. CONCLUSIONS: These results support the efficacy and safety of bicarbonate-buffered peritoneal solutions in a controlled randomized comparison for up to six months. Peritoneal dialysis solutions containing the physiological buffer bicarbonate might effectively replace conventional lactate-buffered CAPD solutions.     

Effect of modified ultrafiltration in high-risk patients undergoing operations for congenital heart disease

BACKGROUND: Modified ultrafiltration (MUF) after cardiopulmonary bypass (CPB) in children decreases body water, removes inflammatory mediators, improves hemodynamics, and decreases transfusion requirements. The optimal target population for MUF needs to be defined. This prospective, randomized study attempted to identify the best candidates for MUF during operations for congenital heart disease. METHODS: Informed consent was obtained from 100 consecutive patients with complex congenital heart disease undergoing operations with CPB. They were randomized into a control group (n = 50) of conventional ultrafiltration during bypass and an experimental group using dilutional ultrafiltration during bypass and venovenous modified ultrafiltration after bypass (MUF group, n = 50). Postoperative arterial oxygenation, duration of ventilatory support, transfusion requirements, hematocrit, chest tube output, and time to chest tube removal were compared between the groups stratified by age and weight, CPB technique, existence of preoperative pulmonary hypertension, and diagnosis. RESULTS: There were no MUF-related complications. In patients with preoperative pulmonary hypertension, MUF significantly improved postoperative oxygenation (445 +/- 129 mm Hg versus control: 307 +/- 113 mm Hg, p = 0.002), shortened ventilatory support (42.9 +/- 29.5 hours versus control: 162.4 +/- 131.2 hours, p = 0.0005), decreased blood transfusion (red blood cells: 16.2 +/- 18.2 mL/kg versus control: 41.4 +/- 27.8 mL/kg, p = 0.01; coagulation factors: 5.3. +/- 6.9 mL/kg versus control: 32.3 +/- 15.5 mL/kg, p = 0.01), and led to earlier chest tube removal. In neonates (< or =30 days), MUF significantly reduced transfusion of coagulation factors (5.4 +/- 5.0 mL/kg versus control: 39.9 +/- 25.8 mL/kg, p = 0.007), and duration of ventilatory support (59.3 +/- 36.2 hours versus 242.1 +/- 143.1 hours, p = 0.0009). In patients with prolonged CPB (>120 minutes), MUF significantly reduced the duration of ventilatory support (44.7 +/- 37.0 hours versus 128.7 +/- 133.4 hours, p = 0.002). No significant differences were observed between MUF and control patients for any parameter in the presence of ventricular septal defect without pulmonary hypertension, tetralogy of Fallot, or aortic stenosis. CONCLUSIONS: Modified ultrafiltration after CPB is safe and decreases the need for homologous blood transfusion, the duration of ventilatory support, and chest tube placement in selected patients with complex congenital heart disease. The optimal use of MUF includes patients with preoperative pulmonary hypertension, neonates, and patients who require prolonged CPB.     

Randomised controlled trial of L-carnitine as a nutritional supplement in preterm infants

AIMS: To evaluate the effect of L-carnitine supplementation (25 mg/kg/d) on the growth and incidence of hypoglycaemia in preterm infants. METHODS: A double blind, placebo controlled randomised trial, stratified for gestational age, was conducted of 86 preterm infants between 28 and 34 gestational weeks. The median gestational ages in the carnitine group and placebo groups were 30.7 weeks (range 28.0 to 33.6) and 31.4 weeks (range 28.0 to 33.9), respectively. The median birthweights were 1.557 kg (range 0.944 to 2.275) and 1.645 kg (range 0.885 to 2.545), respectively. RESULTS: Mean plasma free carnitine concentrations were below values for normal term infants in both groups on day 1 (carnitine group 44.8 mumol/l, placebo group 25.5 mumol/l) in the placebo group on day 7 (50.7 mumol/l), but in neither group on days 14 and 28. Total, free, and acylcarnitine concentrations were significantly increased in both urine and blood in the L-carnitine group. There was no significant difference between the placebo and carnitine supplemented groups in growth rate, as assessed by weight, length, skinfold thickness and head circumference measurements, or in the incidence of episodes of hypoglycaemia. CONCLUSION: The addition of carnitine as a nutritional supplement at a dose of 25 mg/kg/day did not improve growth in our group of preterm infants nor protect them from episodes of hypoglycaemia.     

Intravenous glucose suppresses glucose production but not proteolysis in extremely premature newborns

To ascertain whether the inability to suppress glucose production and increase glucose utilization in response to glucose infusion is an inherent characteristic of immature individuals, we determined glucose rate of appearance (R(a)) in minimally stressed, clinically stable, extremely premature infants (approximately 26-wk gestation) at two glucose infusion rates (6.2 +/- 0.4 and 9.5 +/- 0.5 mg/kg per min). We also assessed whether an increase in glucose delivery suppresses proteolysis by measuring the R(a) of phenylalanine and leucine. Glucose R(a) (and utilization) increased significantly at the higher glucose infusion rate (7.9 +/- 0.5 vs. 9.8 +/- 0.6 mg/kg per min). Glucose production persisted at the lower glucose infusion rate but was suppressed to nearly zero at the higher rate (1.7 +/- 0.5 vs. 0.3 +/- 0.1 mg/kg per min). Proteolysis was unaffected by the higher glucose infusion rate as reflected by no change in the rates of appearance of either phenylalanine (96 +/- 5 vs. 95 +/- 3 mumol/kg per h) or leucine (285 +/- 20 vs. 283 +/- 14 mumol/kg per h). Thus, clinically stable, extremely premature infants suppress glucose production and increase glucose utilization in response to increased glucose infusion, demonstrating no inherent immaturity of these processes. In contrast, increasing the rate of glucose delivery results in no change in whole body proteolysis in these infants. The regulation of proteolysis in this population remains to be defined.     

Glutamine dipeptide attenuate mucosal atrophic changes and preservation of gut barrier function following 5-FU intervention

Traditional parenteral nutrition (PN) and chemotherapy may lead to changes mucosal morphology and gut barrier function. To investigate the effects of alanyl-glutamine on intestinal mucosal morphology and gut barrier function in PN-fed rats challenged with 5-FU male Wistar rats were central catheterized and randomily divided into two groups: PN group (n = 10) that received traditional parenteral nutrition solution only, and Ala-Gln group (n = 10) that received glutamine dipeptide enriched nutritional solution (3% Ala-Gln). The rats were maintained on their respective diets for 7 days. 5-FU (75 mg/kg) was injected intraperitoneally at 8 am on day 4. All rats were gavaged with lactulose (100 mg) and mannitol (50 mg) in 2ml before and three days after administration of 5-FU. Ala-Gln group maintained serum glutamine concentration, intestinal mucosal morphology. While bacterial translocation rates in ala-Gln group was 30%, in PN group was 90% (P < 0.05). Similar intestinal permeability was observed on day 3 in both groups. The control group had a significantly increased intestinal permeability on day 7 (P < 0.05), while Ala-Gln group maintained the intestinal permeability. It was suggested that alanyl-glutamine maintained intestinal morphology and gut barrier function in PN-fed rats challenged with 5-FU.     

Cerulein-induced changes in plasma amino acid concentrations are not a valid test for pancreatic insufficiency

OBJECTIVES: There is controversy about the cholecystokinin (CCK)-induced decrease of plasma amino acids for the diagnosis of pancreatic insufficiency in that it is unclear whether the conflicting results are due to different degrees of stimulation by CCK. We have therefore evaluated the amino acid consumption test by examining the dose-response relation among increasing doses of cerulein and plasma amino acids compared with the release of pancreatic polypeptide in six healthy volunteers and six patients with severe pancreatic insufficiency proven by a pathological para-aminobenzoic acid test. METHODS: Stepwise increasing doses of cerulein (10-80 pmol/kg/h) were given i.v., each for 60 min with a secretin background (1 CU/kg/h). In the volunteer group, an additional experiment with infusion of placebo (saline 0.9%) was performed. RESULTS: CCK-induced amino acid changes were small in volunteers (maximum decrease: 8.4 +/- 0.9%; mean +/- SEM), tended to be more pronounced in patients (maximum decrease: 13.8 +/- 2.8%; NS), and did not permit a distinction among volunteers and patients. There was no dose-response relationship between CCK and plasma amino acids in either group. In contrast, pancreatic polypeptide levels increased markedly and dose-dependently in volunteers and patients and tended to be lower in patients with pancreatic insufficiency. CONCLUSIONS: The decrease of plasma amino acid levels in response to cerulein does not reflect pancreatic function and does not permit the diagnosis of pancreatic insufficiency.     

Lack of effects of recombinant growth hormone on muscle function in patients requiring prolonged mechanical ventilation: a prospective, randomized, controlled study

OBJECTIVE: To evaluate the benefit of recombinant human growth hormone administration on muscle strength and duration of weaning in critically ill patients undergoing prolonged mechanical ventilation. DESIGN: Prospective, randomized, controlled, single-blind study. SETTING: Intensive care unit. Patients: Twenty patients requiring > or = 7 days of mechanical ventilation for acute respiratory failure. INTERVENTION: Random assignment to receive either 0.43 IU (approximately 0.14 mg) recombinant growth hormone/kg body weight/day (treated group), or saline (nontreated group) for 12 days. MEASUREMENTS AND MAIN RESULTS: Nutritional support was guided by indirect calorimetry. Cumulative nitrogen balance was positive throughout the study period in the treated group 17.3 (44.9 +/- 17.3[SEM] g/12 days) vs. the nontreated group (-65.8 +/- 11.8 g/12 days) (p<.0001). Despite similar initial plasma concentrations, recombinant growth hormone supplementation resulted in marked increases in growth hormone, insulin like growth factor-1, and insulin concentrations (p<.05, .02, and .0001, respectively, vs. nontreated group). Body impedance determined net fat-free mass increased in the treated group (0.8 +/- 0.6 kg) vs. the nontreated group (-1.1 +/- O.5 kg) (p<.03). Initial peripheral muscle function, assessed by computer-controlled electrical stimulation of the adductor pollicis, was similarly lower in treated and nontreated groups than sex and age-matched normal controls, and decreased further during the study period. Arterial blood gases, cumulative total mechanical ventilation time, and number of hrs/day of mechanical ventilation during weaning were similar in both patient groups. Only three of the ten patients in each group were weaned from mechanical ventilation by day 12. CONCLUSIONS: Daily administration of recombinant growth hormone in mechanically ventilated patients with acute respiratory failure promotes a marked nitrogen retention. However, this reaction is accompanied neither by an improvement in muscle strength nor by a shorter duration of ventilatory supports.     

Use of insulin-like growth factor I (IGF-I) and IGF-binding protein measurements to monitor feeding of premature infants

To determine whether peptides of the insulin-like growth factor (IGF) system might be useful indicators of nutritional adequacy in premature infants, we studied 50 premature (25-34 weeks gestation) infants prospectively to define the relationship between nutrient intake and serum concentrations of IGF-I, IGF-binding protein-2 (IGFBP-2), and IGFBP-3. Each infant was monitored for at least 2 weeks. Nutrient intake was quantified from daily logs; weight was determined daily, and measurements of IGF-I, IGFBP-2, and IGFBP-3 in serum were made twice weekly. Serum IGF-I correlated strongly with length of gestation, increasing 4.03 +/- 0.95 ng/mL for each additional week of gestation (P < 0.0001) and 0.36 +/- 0.07 ng/mL day each day since birth (P < 0.0001). A higher intake of calories increased IGF-I by 0.07 +/- 0.01 ng/mL for each calorie per kg ingested over the previous 3 days (P < 0.0001). IGF-I increased quadratically as protein intake increased. For each change of 1% in calories as protein squared, IGF-I increased 0.36 +/- 0.11 ng/mL (P < 0.0001). Serum IGFBP-3 concentrations also correlated with length of gestation, increasing 25.06 +/- 11.83 micrograms/L.wk (P = 0.035) and 4.14 +/- 1.33 micrograms/.day since birth (P = 0.003). Unlike IGF-I, variation in the amount of protein supplied did not change IGFBP-3. As calorie intake increased, IGFBP-3 increased by 0.54 +/- 0.17 microgram/L for each calorie per kg consumed over the previous 3 days (P = 0.0015). In contrast to IGF-I and IGFBP-3, IGFBP-2 declined as the length of gestation increased (56.12 +/- 16.92 ng/mL.week; P = 0.001) and with each additional day of life (7.57 +/- 2.44 ng/mL.day; P = 0.003). Dietary protein, the predominant regulator of IGFBP-2, caused a decrease of 33.22 +/- 9.00 ng/mL with each percent increase in dietary calories as protein (P < 0.0003). Calorie intake had less effect on IGFBP-2 than protein intake. These results indicate that each of the three peptides studied is regulated in premature infants by nutritional intake, and that their regulatory patterns are qualitatively similar to those observed in older individuals. Measurements of these peptides in premature infants may be useful indicators of nutritional status and adequacy of nutrient intake.     

In which neonates does early recombinant human erythropoietin treatment prevent anemia of prematurity? Results of a randomized, controlled study

To assess whether erythropoietin (EPO) treatment is safe and reduces the need for transfusion, we randomized 44 preterm infants to an EPO group and a comparable control (CON) group. EPO 150 U/kg was given s.c. twice weekly for 6 wk from the 1st wk of life. Hematologic parameters, transfusion requirements, and growth were followed during therapy and for 6 mo thereafter. To better assess in which neonates EPO treatment was effective, we classified retrospectively the EPO and CON groups into uncomplicated neonates (EPO A: n = 9, birth weight = 1247 +/- 126 g, gestational age = 29.8 +/- 1.5 wk; CON A: n = 7, birth weight = 1217 +/- 145 g, gestational age = 29.9 +/- 1.5 wk) and neonates requiring artificial ventilation (EPO B: n = 16, birth weight = 1169 +/- 249 g, gestational age = 28.1 +/- 2 wk; CON B: n = 12, birth weight = 1173 +/- 215 g, gestational age = 28.3 +/- 2 wk). There were significant differences in reticulocytes between both uncomplicated and ventilated neonates in the EPO group compared with respective control groups. However, the need for transfusion was significantly less in the uncomplicated EPO group (EPO A: 0.44 +/- 0.73 versus CON A: 1.28 +/- 0.75, p < 0.05) but not in the neonates on ventilation (EPO B: 8.25 +/- 5 versus CON B: 7.75 +/- 3.7). In conclusion, early EPO administration reduces the need for transfusion in uncomplicated premature neonates.(ABSTRACT TRUNCATED AT 250 WORDS)     

Urinary creatinine excretion in the ICU: low excretion does not mean inadequate collection

BACKGROUND: It has been assumed that a urinary creatinine excretion rate of less than 10 mg/kg per day means an inadequately collected urine sample. OBJECTIVE: To determine the frequency of a urinary creatinine excretion rate of less than 10 mg/kg per day in intensive care unit patients with an adequately collected urine sample. METHOD: In a prospective study of creatinine excretion rates, 24-hour urine samples were evaluated for urinary creatinine in 209 critically ill patients with indwelling Foley catheters. Patients from three adult intensive care units in New York City were divided into two groups. Group 1 patients excreted less than 10 mg/kg per day of urinary creatinine, and group 2 patients excreted at least 10 mg/kg per day. Groups 1 and 2 were first evaluated by dividing the creatinine excretion data by actual body weight. Since actual body weight may overestimate body weight in the critically ill patient, data from groups 1 and 2 were also evaluated using lean body weight. RESULTS: Urinary creatinine excretion was less than 10 mg/kg per day in 36.8% of patients using actual body weight and 29.7% of patients adjusted for lean body weight. The average age of patients in group 1 was 74 +/- 17 years for both actual body weight and lean body weight. The average age of group 2 patients was 60 +/- 19 years for actual body weight and 62 +/- 19 years for lean body weight. There was a significant difference in age between group 1 and group 2 patients for both actual body weight and lean body weight. The proportion of female vs male patients with reduced creatinine excretion was significantly greater, whether the actual body weight or lean body weight adjustment was used. CONCLUSIONS: A urinary creatinine excretion rate of less than 10 mg/kg per day occurs in about one third of critically ill patients, who are more likely to be elderly and female.