Vitamin K in human milk--still not enough.

The breastfed infant has limited sources of vitamin K, as it is transmitted poorly across the placenta and is present in very low concentrations in human milk. The author of this paper reports a concentration of vitamin K in human milk (0.517 +/- 1.521 microg/dl) that is about twice the average of earlier reports (0.25 microg/dl). About half of the increased concentration (0.235 +/- 0.144 microg/dl) is accounted for by vitamin K2 (menaquinone) rather than vitamin K1 (phylloquinone); the latter generally thought to be more important in human nutrition. The significance of these findings is discussed.

Disulfide bonds in merozoite surface protein 1 of the malaria parasite impede efficient antigen processing and affect the in vivo antibody response.

Vol. 34(3) 2004, DOI 10.1002/eji.200324514 Due to a technical error, the wrong affiliations were given for C. Moss and V. Lindo. These are correct as given above. See original article http://dx.doi.org/10.1002/eji.200324514.

Vitamin K status of premature infants: implications for current recommendations.

OBJECTIVE: Newborn infants are vitamin K deficient. Vitamin K status in full-term infants after intramuscular vitamin K supplementation at birth has been described. Similar information in growing premature infants has not been reported. The objective of this study was to assess vitamin K status in premature infants by measuring plasma vitamin K and plasma protein-induced in vitamin K absence (PIVKA II) from birth until 40 weeks' postconceptional age. METHODS: Premature infants (/=1000 g) via total parenteral nutrition. After hyperalimentation, most received vitamin K-fortified enteral feedings with the remainder receiving unfortified breast milk. Blood was obtained for PIVKA II in cord blood and for PIVKA II and vitamin K at 2 weeks and 6 weeks after birth and at 40 weeks' postconception. RESULTS: Of the 44 infants enrolled, 10 infants in each gestational age group completed the study. The patient characteristics for groups 1, 2, and 3 were as follows: gestational age, 26.3 +/- 1.7, 30.3 +/- 1.3, and 33.9 +/- 1.1 weeks; birth weight, 876 +/- 176, 1365 +/- 186, and 1906 +/- 163 g; and days of hyperalimentation, 28.9 +/- 16, 16.8 +/- 12, and 4.3 +/- 4 days, respectively. At 2 weeks of age, the vitamin K intake and plasma levels were highest in group 1 versus group 3 (intake: 71.2 +/- 39.6 vs 13.4 +/- 16.3 microg/kg/day; plasma levels: 130.7 +/- 125.6 vs 27.2 +/- 24.4 ng/mL). By 40 weeks' postconception, the vitamin K intake and plasma levels were similar in all 3 groups (group 1, 2, and 3: intake, 11.4 +/- 2.5, 15.4 +/- 6.0, and 10.0 +/- 7.0 microg/kg/day; plasma level, 5.4 +/- 3.8, 5.9 +/- 3.9, and 9.3 +/- 8.5 ng/mL). None of the postnatal plasma samples had any detectable PIVKA II. CONCLUSIONS: Premature infants at 2 weeks of age have high plasma vitamin K levels compared with those at 40 weeks' postconceptional age secondary to the parenteral administration of large amounts of vitamin K. By 40 weeks' postconception, these values are similar to those in term formula-fed infants. Confirming "adequate vitamin K status," PIVKA II was undetectable by 2 weeks of life in all of the premature infants. With the potential for unforeseen consequences of high vitamin K levels, consideration should be given to reducing the amount of parenteral vitamin K supplementation in the first few weeks of life in premature infants.vitamin K, PIVKA II, premature, total parenteral nutrition, enteral nutrition.

Caffeine ingestion decreases glucose disposal during a hyperinsulinemic-euglycemic clamp in sedentary humans.

The purpose of this investigation was to examine the effect of caffeine (an adenosine receptor antagonist) on whole-body insulin-mediated glucose disposal in resting humans. We hypothesized that glucose disposal would be lower after the administration of caffeine compared with placebo. Healthy, lean, sedentary (n = 9) men underwent two trial sessions, one after caffeine administration (5 mg/kg body wt) and one after placebo administration (dextrose) in a double-blind randomized design. Glucose disposal was assessed using a hyperinsulinemic-euglycemic clamp. Before the clamp, there were no differences in circulating levels of methylxanthines, catecholamines, or glucose. Euglycemia was maintained throughout the clamp with no difference in plasma glucose concentrations between trials. The insulin concentrations were also similar in the caffeine and placebo trials. After caffeine administration, glucose disposal was 6.38 +/- 0.76 mg/kg body wt compared with 8.42 +/- 0.63 mg/kg body wt after the placebo trial. This represents a significant (P < 0.05) decrease (24%) in glucose disposal after caffeine ingestion. In addition, carbohydrate storage was 35% lower (P < 0.05) in the caffeine trial than in the placebo trial. Furthermore, even when the difference in glucose disposal was normalized between the trials, there was a 23% difference in the amount of carbohydrate stored after caffeine administration compared with placebo administration. Caffeine ingestion also resulted in higher plasma epinephrine levels than placebo ingestion (P < 0.05). These data support our hypothesis that caffeine ingestion decreases glucose disposal and suggests that adenosine plays a role in regulating glucose disposal in resting humans.

Comparison of caloric intake and weight outcomes of an ad lib feeding regimen for preterm infants in two nurseries.

BACKGROUND: Effects on caloric intake and weight gain of an ad libitum (ad lib) feeding regimen for preterm infants may be specific to a special care nursery. OBJECTIVE: To explore across two nurseries the similarity of effect on caloric intake and weight gain of an ad lib feeding regimen compared with a prescribed regimen and the similarity of effect of caloric intake on weight gain. METHODS: All infants participating in the multi-site randomized clinical trial (RCT) of the ad lib feeding regimen were <35 weeks gestational age at birth and had birth weight appropriate for gestational age. Data on caloric intake and weight gain were collected at two nurseries (A, n=22; B, n=78) with the same feeding regimen protocols. Two strategies were used to explore similarity of regimen effect on caloric intake and weight gain. Repeated measures analysis of variance (ANOVA) was used to examine the effect on caloric intake and weight gain of time, feeding regimen, and time-by-regimen interaction for each nursery. RESULTS: In both nurseries, regimen effects were reasonably consistent for caloric intake and weight gain. Caloric intake was lower across nurseries for infants fed ad lib. After accounting for caloric intake, the ad lib regimen did not affect weight gain. The time-by-regimen interaction effect on caloric intake was significant in both nurseries. Caloric intake for infants fed ad lib increased significantly over 5 days. CONCLUSIONS: Despite differences between nurseries in infant characteristics and in protocol implementation, the feeding regimen effect was consistent for caloric intake and weight gain. Further support was found for the development of infant self-regulatory capacity.

Caffeine ingestion elevates plasma insulin response in humans during an oral glucose tolerance test.

We tested the hypothesis that caffeine ingestion results in an exaggerated response in blood glucose and (or) insulin during an oral glucose tolerance test (OGTT). Young, fit adult males (n = 18) underwent 2 OGTT. The subjects ingested caffeine (5 mg/kg) or placebo (double blind) and 1 h later ingested 75 g of dextrose. There were no differences between the fasted levels of serum insulin, C peptide, blood glucose, or lactate and there were no differences within or between trials in these measures prior to the OGTT. Following the OGTT, all of these parameters increased (P < or = 0.05) for the duration of the OGTT. Caffeine ingestion resulted in an increase (P < or = 0.05) in serum fatty acids, glycerol, and plasma epinephrine prior to the OGTT. During the OGTT, these parameters decreased to match those of the placebo trial. In the caffeine trial the serum insulin and C peptide concentrations were significantly greater (P < or = 0.001) than for placebo for the last 90 min of the OGTT and the area under the curve (AUC) for both measures were 60 and 37% greater (P < or = 0.001), respectively. This prolonged, increased elevation in insulin did not result in a lower blood glucose level; in fact, the AUC for blood glucose was 24% greater (P = 0.20) in the caffeine treatment group. The data support our hypothesis that caffeine ingestion results in a greater increase in insulin concentration during an OGTT. This, together with a trend towards a greater rather than a more modest response in blood glucose, suggests that caffeine ingestion may have resulted in insulin resistance.

Do breastfed infants need supplemental vitamins?

Table 2 shows that human milk will not meet the DRI for all vitamins in breastfeeding infants. The most glaring discrepancy between intake and the RDA is for vitamin D, although, as discussed, infants may synthesize this from sunlight exposure. Vitamin K must be given in the newborn period. Deficiencies of other vitamins are rare, especially if mothers are nourished adequately. If breastfeeding infants are to be supplemented with vitamin D or any other vitamins, the standard liquid preparations available all contain large amounts of the water-soluble and fat-soluble vitamins (except for vitamin K), which more than meets the RDA. The milk content of thiamin, pyridoxine, and niacin is correlated highly with maternal intake, and these vitamins are all present in relatively large amounts in standard multivitamin tablets given to lactating mothers. In conclusion, in healthy, breastfed infants of well-nourished mothers, there is little risk for vitamin deficiencies and the need for vitamin supplementation is rare. The exceptions to this are a need for vitamin K in the immediate newborn period and vitamin D in breastfed infants with dark skin or inadequate sunlight exposure.

Feeding the premature infant in the 20th century.

This article reviews the historical development of feeding the premature infant in the 20th century. It describes the early work determining the energy requirements of the preterm infant, the evolution of the use of human milk and its fortification for these infants, the development of special formulas for very-low-birth-weight infants and the various techniques/methods utilized including total parenteral nutrition.

Fat-soluble vitamin supplements for enterally fed preterm infants.

Fat-soluble vitamin requirements for the enterally fed premature infant are an important concern, both before and after discharge from the neonatal intensive care unit. Because preterm infants fed unsupplemented human milk receive deficient quantities of these vitamins (A, D, E, and K), supplements are very important for this population. Vitamin intakes with special formulas for low birth weight infants and human milk fortifiers are also reviewed.

Are breast-fed infants vitamin K deficient?

Hemorrhagic disease of the newborn is a disease of breast-fed infants. We have followed 119 exclusively breast-fed infants for up to 6 months of age, who received 1 mg of vitamin K, intramuscularly at birth. As vitamin K is undetectable in cord blood, the only other source in breast-fed infants is human milk. We found persistently low vitamin K1 plasma concentrations in these infants by 4 weeks, and vitamin K concentrations at 2, 4, 6, 8, 12, and 26 weeks averaged 1.18+/-0.99, 0.50+/-0.70, 0.16 +/-0.07, 0.20+/-0.20, 0.25+/-0.34, and 0.24+/-0.23 ng/mL, respectively (lower limit of adult normal = 0.5ng/mL). Vitamin K, in breast milk at 2, 6, 12, and 26 weeks was also very low, averaging 1.17+/-0.70, 0.95+/-0.50, 1.15+/-0.62, and 0.87+/-0.50 mg/mL, respectively. This may be secondary to low maternal vitamin K1 intakes or inability of vitamin K1 to penetrate human milk. We had previously reported a relatively high mean vitamin K intake of 316+/-548 microg in 20 lactating women during the first 6 months of lactation (mean of 60, 3-day dietary recalls) which greatly exceeded the recommended daily allowance of 1 microg/kg/day. The vitamin K content of foods was recently revised downward utilizing newer analytical methods (Booth et al. 1995). Recalculating maternal vitamin K intakes in this original cohort resulted in a dramatic decrease in intake to 74+/-57 microg/day, an amount closely approximating 1 microg/kg/day. We have completed 69 new dietary recalls in 23 lactating women and, combining these data with the previous study, determined a maternal vitamin K1 mean intake of 65+/-48 microg/day (0.8-1.3 microg/kg/day). Other than plasma vitamin K1 concentrations, PIVKA (undercarboxylated prothrombin produced in the absence of vitamin K) is a marker of vitamin K deficiency. We measured PIVKA in 156 cord bloods of full-term infants. Seventy-five (48%) had a significantly elevated PIVKA (> or =0.1 absorption units per milliliter). Seventy-seven of these infants who were exclusively breast-fed subsequently had no detectable PIVKA at 4 weeks, but by 8 weeks, 3 were again positive for PIVKA (prothrombin times were normal). Breast-fed infants may benefit from increased maternal vitamin K intakes (>1 microg/kg/day) during pregnancy and lactation. A supplement of 5 mg of vitamin K to lactating mothers will increase the concentration in human milk to 80.0+/-37.7 ng/mL and significantly increase infant plasma vitamin K (Greer et al. 1997).

Comparison of caffeine and theophylline ingestion: exercise metabolism and endurance.

This two-part investigation compared the ergogenic and metabolic effects of theophylline and caffeine. Initially (part A), the ergogenic potential of theophylline on endurance exercise was investigated. Eight men cycled at 80% maximum O(2) consumption to exhaustion 90 min after ingesting either placebo (dextrose), caffeine (6 mg/kg; Caff), or theophylline (4.5 mg/kg Theolair; Theo). There was a significant increase in time to exhaustion in both the Caff (41.2+/-4.8 min) and Theo (37.4+/-5.0 min) trials compared with placebo (32.6+/-3.4 min) (P<0.05). In part B, the effects of Theo on muscle metabolism were investigated and compared with Caff. Seven men cycled for 45 min at 70% maximum O(2) consumption (identical treatment protocol as in part A). Neither methylxanthines (MX) affected muscle glycogen utilization (P>0.05). Only Caff increased plasma epinephrine (P<0.05), but both MX increased blood glycerol levels (P<0.05). Muscle cAMP was increased (P<0.05) by both MX at 15 min and remained elevated at 45 min with Theo. This demonstrates that both MX are ergogenic and that this can be independent of muscle glycogen.

Urea production is increased in neonatal piglets infused with alanine at 25, 50, and 75% of resting energy needs .

To study the ability of neonatal piglets to metabolize a nitrogen load and excrete it as urea, 12 newborn piglets, 6 small (0.99 +/- 0. 16 kg; expt. 1) and 6 large (1.86 +/- 0.16 kg; expt. 2), were infused intravenously with alanine (n = 8; 4 large, 4 small; treatment) or glucose (n = 4; 2 large, 2 small; control) at equal ATP equivalents, supplying 25-75% of the resting energy requirements of the piglet over 18 h. To adjust for differences in the baseline urinary urea nitrogen excretion, blood urea nitrogen (BUN) and estimated urea production between groups, the absolute changes from baseline to maximum value for piglets infused with alanine, and from baseline to the 24-h value for piglets infused with glucose were evaluated statistically. There were no differences (0.1 < P < 0.3) in the absolute changes from baseline to maximum values of urinary urea nitrogen, BUN or estimated urea production between small [18.6 +/- 3.8 mg N/(h. kg(0.75)); 19.1 +/- 2.2 mmol N/L; 2.7 +/- 1.2 mmol N/(h. kg(0.75)), respectively] and large [23.6 +/- 7.6 mg N/(h. kg(0. 75)); 21.6 +/- 3.3 mmol N/L; 3.7 +/- 1.5 mmol N/(h. kg(0.75)), respectively] piglets infused with alanine. Differences in the changes from baseline were detected between alanine and glucose (P = 0.001) infusions. Small piglets required more time (P < 0.005) for BUN to maximize after initiation of the alanine infusion, suggesting that small piglets require more time to process a nitrogen load. Infusion of alanine resulted in at least a threefold increase from baseline in the rate of calculated urea production, suggesting that neonatal piglets, small or large, have reserve capacity to metabolize nitrogen and excrete it as urea.

Comparison of total body urea production potential with total body carbamoyl phosphate synthetase (CPS-1) activity in newborn piglets infused with alanine at 50% of resting energy expenditure for 36 hours.

The calculated rate of urea production [U(p); mmol urea/(h. kg(0. 75))], based on urinary urea-N (UUN) excretion and changes in total body urea-N, was compared with the calculated total body V(max) of carbamoyl phosphate synthetase (CPS-1) of 24 neonatal piglets from four treatments as follows: 6 h baseline control (n = 8), 18 h of alanine intravenously (IV) at 50% of resting energy expenditure (REE; n = 4), 36 h of alanine IV at 50% of REE (n = 6), or 36 h of glucose IV at 50% of REE (n = 6). The following significant increases from baseline were seen in piglets infused with alanine for 36 h: 1) UUN excretion [10.6 +/- 5.9 mg N/(h. kg(0.75)) to 53.2 +/- 11.1]; 2) BUN concentrations (9.1 +/- 3.0 mmol urea N/L to 51.2 +/- 7.0); 3) calculated urea production [0.34 +/- 0.21 mmol urea/(h. kg(0.75)) to 2.39 +/- 0.53]; and 4) CPS-1 V(max) [2.0 +/- 0.81 mmol citrulline/(h. kg (0.75)) to 4.4 +/- 1.5], (P < 0.05). With the exception of CPS-1 activity, significant decreases from baseline were seen in these values in piglets infused with glucose for 36 h (P < 0.05). Comparison of calculated urea production with calculated total body CPS-1 V(max) at baseline, 18 or 36 h after the start of infusion of alanine or glucose revealed a positive relationship (slope = 0.263; P < 0.002). At all enzyme activities, infusion of alanine resulted in a significant increase in the rate of urea production compared with controls (P < 0.001). Total body CPS-1 activity varied from 1.8 to 5.8 times that of urea production, suggesting that CPS-1 did not limit urea production.

Growth in human milk-Fed very low birth weight infants receiving a new human milk fortifier.

BACKGROUND/AIMS: Human milk fortification has been advocated to enhance premature infants' growth. We, therefore, undertook this study of a new human milk fortifier containing more protein than a reference one. METHODS: Open, randomized, controlled, multiclinic trial, with weekly growth parameters and safety evaluations in premature infants <1,500 g. RESULTS: The 2 groups did not differ in demographic and baseline characteristics. The adjusted daily milk intake was significantly higher in the infants fed reference human milk fortifier (n = 29; 154.2 +/- 2.1 vs. 144.4 +/- 2.5 ml/kg/day, mean +/- SE; p < 0.05). Both human milk fortifiers produced increases over baseline in weight, length, and head circumference, with greater gains observed in the new human milk fortifier-fed infants for the former two parameters (weight gain 26.8 +/- 1.3 and 20.4 +/- 1.2 g/day, p < 0.05; head circumference 1.0 +/- 0.1 and 0.8 +/- 0.1 cm/week; length 0.9 +/- 0.1 and 0.8 +/- 0.1 cm/week, respectively). Serum chemistries were normal and acceptable for age. Study events were typical for premature infants and similar in both groups. CONCLUSIONS: This new human milk fortifier had comparable safety to the reference human milk fortifier and promoted faster weight gain and head circumference growth.

Vitamin metabolism and requirements in the micropremie.

Vitamin metabolism and requirements are reviewed for the micropremie (1000 Pounds g birthweight), for parenteral and enteral feedings. Recommendations are presented in table format. Human milk fortifiers and special formulas for the preterm infant are reviewed. For parenteral nutrition, only MVI Pediatric is currently available in the United States. Two millimeters per kilogram is recommended for the micropremie as the most satisfactory method of providing supplemental vitamins in total parenteral nutrition solutions.

Vitamin K status of lactating mothers and their infants.

Vitamin K deficiency remains a world-wide problem in the newborn. Vitamin K traverses the placenta from mother to infant very poorly and is present only in very low concentrations in human milk. Thus, it is not surprising that the newborn infant has undetectable vitamin K serum levels with abnormal amounts of the coagulation proteins and undercarboxylated prothrombin. Hemorrhagic disease of the newborn, secondary to vitamin K deficiency, remains largely a disease of breastfed infants. Lactating mothers easily achieve the recommended dietary allowance for vitamin K (1 microg kg(-1) d(-1)) and the breast milk concentration is readily increased by increasing maternal vitamin K intake. Breastfed infants do not receive the recommended vitamin K intake via human milk. To prevent vitamin K deficiency in the newborn, intramuscular or oral vitamin K prophylaxis is necessary.

The effects of prescribed versus ad libitum feedings and formula caloric density on premature infant dietary intake and weight gain.

BACKGROUND: Although feedings that are organized on an ad lib basis (i.e., in response to infant cues of hunger and of satiation) could enhance an infant's self-regulatory capacities for feeding, ad lib feeding of fully nipple-fed premature infants in a special care nursery has not been examined. OBJECTIVE: To study whether the caloric and protein intake and weight change of fully nipple-fed preterm infants differed by the feeding regimen (prescribed or ad lib) and by the caloric density of the formula (20- or 24-kcalories per ounce). METHOD: The 78 infants who participated in the study were randomized to prescribed or ad lib feeding regimens and, within each regimen, were further randomized to receive either 20-calorie or 24-kcalorie per ounce formula. Dietary intake (volume/kg, caloric intake/kg) and weight change (grams/kg gained or lost) were assessed for each of the 5 study days. Multivariate data analysis was used to examine the effects of feeding regimen and caloric density on dietary intake and weight change, controlling biologic variables (infant gender, race, lung disease diagnosis, treatment with supplemental oxygen, gestational age and weight at birth, and weight on the day prior to full nipple-feeding). RESULTS: Overall, the ad lib feeding regimen had a negative effect on volume intake and caloric intake. Weight gain was influenced by caloric intake, but not by feeding regimen or the caloric density of the diet. With increased full nipple-feeding experience, caloric intake of ad lib feeders approached that of the infants fed on the prescribed regimen. CONCLUSIONS: Development of self-regulatory capacities through ad lib feeding experience was indicated by infant regulation of the volume of intake by the caloric density of the formula, an unexpected finding. Furthermore, the approach of the caloric intake of infants on the ad lib regimen to that of infants on the prescribed regimen suggests they had gained skill in regulating intake with experience. Whether or not the trend for similar intakes would continue beyond 5 days is a question for further study.

Caffeine, performance, and metabolism during repeated Wingate exercise tests.

Investigations examining the ergogenic and metabolic influence of caffeine during short-term high-intensity exercise are few in number and have produced inconsistent results. This study examined the effects of caffeine on repeated bouts of high-intensity exercise in recreationally active men. Subjects (n = 9) completed four 30-s Wingate (WG) sprints with 4 min of rest between each exercise bout on two separate occasions. One hour before exercise, either placebo (P1; dextrose) or caffeine (Caf; 6 mg/kg) capsules were ingested. Caf ingestion did not have any effect on power output (peak or average) in the first two WG tests and had a negative effect in the latter two exercise bouts. Plasma epinephrine concentration was significantly increased 60 min after Caf ingestion compared with P1; however, this treatment effect disappeared once exercise began. Caf ingestion had no significant effect on blood lactate, O2 consumption, or aerobic contribution at any time during the protocol. After the second Wingate test, plasma NH3 concentration increased significantly from the previous WG test and was significantly higher in the Caf trial compared with P1. These data demonstrate no ergogenic effect of caffeine on power output during repeated bouts of short-term, intense exercise. Furthermore, there was no indication of increased anaerobic metabolism after Caf ingestion with the exception of an increase in NH3 concentration.

Differential effects of serial hemodilution with hydroxyethyl starch, albumin, and 0.9% saline on whole blood coagulation.

STUDY OBJECTIVES: To determine by thrombelastography assessed coagulation, the effects of progressive hemodilution with three intravascular volume expanders. DESIGN: Prospective, controlled, whole blood, volumetric ex vivo hemodilution study. SETTING: University of Pennsylvania Medical Center Operating Rooms. PATIENTS: 60 ASA physical status I and II patients; phlebotomy prior to administration of IV fluids or medications. INTERVENTIONS: Analysis of whole blood clotting determined by six thrombelastographic channels for control and five volumetric hemodilutions (11%, 25%, 33%, 50%, and 75%) with 0.9% saline, 5% albumin, and 6% hydroxyethyl starch (n = 20 for each diluent group). MEASUREMENTS AND MAIN RESULTS: Thrombelastographic parameters R (minutes), angle alpha (degree), MA (mm), and lysis (%) were measured and compared to the sample control for each dilution of the same specimen. There was no significant difference between control groups in any thrombelastographic variable (R, angle alpha, MA, or lysis). No changes were seen in any variable from any diluent at 11% hemodilution. Seventy-five percent hemodilution caused significantly hypocoagulable changes from control for all thrombelastographic parameters for all three diluents. Thrombelastographic indices differed significantly from controls at intermediate hemodilutions. Both colloids caused decreases in measured angle alpha and MA at lower hemodilution than did 0.9% saline. Albumin 5% caused significant hypocoagulable changes from control values at lower hemodilution than did either 0.9% saline or 6% hydroxyethyl starch for all thrombelastographic parameters. Saline 0.9% increased angle alpha significantly at 50% hemodilution. Abnormal lysis did not occur at any dilution. Differing ex vivo effects of three different intravascular fluids thrombelastography assessed coagulation are found. CONCLUSION: No differences were found after 11% hemodilution with any volume expanders. Hemodilution with up to 50% saline maintained thrombelastographic indices. Albumin produced early and profound hypocoagulable effects. Significant hypocoagulability occurred for all three diluents at 75% hemodilution. The study supports the use of albumin in patients at risk for thrombosis, and saline in patients with a need for normal hemostasis.