Phase lag entropy as a hypnotic depth indicator during propofol sedation.

Phase lag entropy, an electro-encephalography-based hypnotic depth indicator, calculates diversity in temporal patterns of phase relationship. We compared the performance of phase lag entropy with the bispectral index™ in 30 patients scheduled for elective surgery. We initiated a target-controlled infusion of propofol using the Schnider model, and assessed sedation levels using the Modified Observer's Assessment of Alertness/Sedation scale every 30 s with each stepwise increase in the effect-site propofol concentration. Phase lag entropy and bispectral index values were recorded. The correlation coefficient and prediction probability between phase lag entropy or bispectral index and the sedation level or effect-site propofol concentration were analysed. We calculated baseline variabilities of phase lag entropy and bispectral index. In addition, we applied a non-linear mixed-effects model to obtain the pharmacodynamic relationships among the effect-site propofol concentration, phase lag entropy or bispectral index and sedation level. As sedation increased, phase lag entropy and bispectral index both decreased. The prediction probability values of phase lag entropy and bispectral index for sedation levels were 0.697 and 0.700 (p = 0.261) and for the effect-site concentration of propofol were 0.646 and 0.630 (p = 0.091), respectively. Baseline variability in phase lag entropy and bispectral index was 3.3 and 5.7, respectively. The predicted propofol concentrations, using the Schnider pharmacokinetic model, producing a 50% probability of moderate and deep sedation were 1.96 and 3.01 µg.ml-1 , respectively. Phase lag entropy was found to be useful as a hypnotic depth indicator in patients receiving propofol sedation.

Population pharmacokinetic analysis of propofol in underweight patients under general anaesthesia.

BACKGROUND: The modified Marsh and Schnider pharmacokinetic models for propofol consistently produce negatively and positively biased predictions in underweight patients, respectively. We aimed to develop a new pharmacokinetic model of propofol in underweight patients. METHODS: Twenty underweight (BMI<18.5 kg m-2) patients aged 20-68 yr were given an i.v. bolus of propofol (2 mg kg-1) for induction of anaesthesia. Anaesthesia was maintained with a zero-order infusion (8 mg kg-1 h-1) of propofol and target-controlled infusion of remifentanil. Arterial blood was sampled at preset intervals. A population pharmacokinetic analysis was performed using non-linear mixed effects modelling. The time to peak effect (tpeak, maximally reduced bispectral index) was measured in 28 additional underweight patients receiving propofol 2 mg kg-1. RESULTS: In total, 455 plasma concentration measurements from the 20 patients were used to characterise the pharmacokinetics of propofol. A three-compartment mammillary model well described the propofol concentration time course. BMI and lean body mass (LBM) calculated using the Janmahasatian formula were significant covariates for the rapid peripheral volume of distribution and for the clearance of the final pharmacokinetic model of propofol, respectively. The parameter estimates were as follows: V1(L)=2.02, V2(L)=12.9(BMI/18.5), V3(L)=139, Cl (L⋅min-1)=1.66(LBM/40), Q1 (L⋅min-1)=1.44, Q2 (L⋅min-1)=0.87+0.0189×(LBM-40). The median tpeak of propofol was 1.32 min (n=48). CONCLUSIONS: A three-compartment mammillary model can be used to administer propofol via target effect-site concentration-controlled infusion of propofol in underweight patients. CLINICAL TRIAL REGISTRATION: KCT0001760.

Development of a new analgesic index using nasal photoplethysmography.

Although surrogate measures to quantify pain intensity have been commercialised, there is a need to develop a new index with improved accuracy. The aim of this study was to develop a new analgesic index using nasal photoplethysmography data. The specially designed sensor was placed between the columella and the nasal septum to acquire nasal photoplethysmography in surgical patients. Nasal photoplethysmography and Surgical Pleth Index® (GE Healthcare) data were obtained for 14 min both in the absence (pre-operatively) or presence (postoperatively) of pain in a group of surgical patients, each patient acting as their own control. Various dynamic photoplethysmography variables were extracted to quantify pain intensity; the most accurate index was selected using logistic regression as a classifier. The area under the curve of the receiver-operating characteristic curve was measured to evaluate the accuracy of final model predictions. In total, 12,012 heart beats from 89 patients were used to develop a new Nasal Photoplethysmography Index for analgesic depth quantification. The two-variable model (a combination of diastolic peak point variation and heart beat interval variation) was most accurate in discriminating between the presence and absence of pain (numerical rating scale (NRS) ≥ 3). The accuracy and area under the curve of the receiver-operating characteristic curve for the Nasal Photoplethysmography Index were 75.3% and 0.8018, respectively, and 64.8% and 0.7034, respectively, for the Surgical Pleth Index. The Nasal Photoplethysmography Index clearly distinguished pain (NRS ≥ 3) in awake surgical patients with postoperative pain. The Nasal Photoplethysmography Index performed better than the Surgical Pleth Index. Further validation studies are needed to evaluate its feasibility to quantify pain intensity during general anaesthesia.

Predictive performance of the modified Marsh and Schnider models for propofol in underweight patients undergoing general anaesthesia using target-controlled infusion.

BACKGROUND: : In our preliminary study, the modified Marsh (M-Marsh) model caused an inadvertent underdosing of propofol in underweight patients. However, the predictive performance of the M-Marsh and Schnider models incorporated in commercially available target-controlled infusion (TCI) pumps was not evaluated in underweight patients. METHODS: : Thirty underweight patients undergoing elective surgery were randomly allocated to receive propofol via TCI using the M-Marsh or Schnider models. The target effect-site concentrations (Ces) of propofol were, in order, 2.5, 3, 4, 5, 6 and 2 µg ml -1 . Arterial blood samples were obtained at least 7 min after achieving each pseudo-steady-state. RESULTS: A total of 172 plasma samples were used to determine the predictive performance of both models. The pooled median (95% confidence interval) biases and inaccuracies at a target Ce ≤ 3 µg ml -1 were -22.6 (-28.8 to -12.6) and 31.9 (24.8-36.8) for the M-Marsh model and 9.0 (1.7-16.4) and 28.5 (21.7-32.8) for the Schnider model, respectively. These values at Ce ≥ 4 µg ml -1 were -9.6 (-16.0 to -6.0) and 24.7 (21.1-27.9) for the M-Marsh model and 19.8 (12.9-25.7) and 36.2 (31.4-39.7) for the Schnider model, respectively. CONCLUSIONS: The pooled biases and inaccuracies of both models were clinically acceptable. However, the M-Marsh and Schnider models consistently produced negatively and positively biased predictions, respectively, in underweight patients. In particular, the M-Marsh model showed greater inaccuracy at target Ce ≤ 3 µg ml -1 and the Schnider model showed greater inaccuracy at target Ce ≥ 4 µg ml -1 . Therefore, it is necessary to develop a new pharmacokinetic model for propofol in underweight patients. CLINICAL TRIAL REGISTRATION: KCT0001502.

External validation of pharmacokinetic and pharmacodynamic models of microemulsion and long-chain triglyceride emulsion propofol in beagle dogs.

This study aimed at assessing the predictive performance of a target-controlled infusion (TCI) system, which incorporates canine PK-PD models for microemulsion and long-chain triglyceride emulsion (LCT) propofol and at investigating time independency of propofol effect on the observed electroencephalographic approximate entropy (ApEn) in TCI. Using a crossover design with a 7-day washout period, 28 healthy beagle dogs were randomized to receive TCI of both formulations in a stepwise or constant manner. Plasma propofol concentrations and ApEn were measured at preset intervals. Pooled biases, inaccuracies, divergences, and wobbles in pharmacokinetic and pharmacodynamic predictions were 2.1% (95% CI: -0.8 to 4.9), 18.1% (15.6-20.5), 1.9%/h, 7.3% (5.4-9.3), and -0.5% (-2.6 to 1.6), 8.7% (7.3-10.1), 2.5%/h, 6.0% (4.1-7.2) for microemulsion propofol, and -9.3% (-11.6 to -6.9), 20.1% (18.2-22.0), 5.1%/h, 7.6% (6.1-9.1) and 5.6% (4.1-7.1), 8.0% (6.9-9.3), 4.7%/h, 4.1% (3.1-5.1) for LCT propofol. Observed ApEn values over time were statistically not different across all time points in a TCI with constant manner. Canine PK-PD model of microemulsion propofol showed good predictive performances. Propofol effect (ApEn) was time independent as long as time is allowed for equilibration.

Effectiveness, safety, and pharmacokinetic and pharmacodynamic characteristics of microemulsion propofol in patients undergoing elective surgery under total intravenous anaesthesia.

BACKGROUND: The aims of this study were to investigate the effectiveness, safety, pharmacokinetics, and pharmacodynamics of microemulsion propofol, Aquafol (Daewon Pharmaceutical Co., Ltd, Seoul, Republic of Korea). METHODS: In total, 288 patients were randomized to receive 1% Aquafol or 1% Diprivan (AstraZeneca, London, UK) (n=144, respectively). A 30 mg test dose of propofol was administered i.v. over 2 s for assessing injection pain. Subsequently, a bolus of propofol 2 mg kg(-1) (-30 mg) was administered. Anaesthesia was maintained with a variable rate infusion of propofol and a target-controlled infusion of remifentanil. Mean infusion rates of both formulations and times to loss of consciousness (LOC) and recovery of consciousness (ROC) were recorded. Adverse events and pharmacokinetic and pharmacodynamic characteristics were evaluated. RESULTS: Mean infusion rate of Aquafol was not statistically different from that of Diprivan (median: 6.2 vs 6.3 mg kg(-1) h(-1)). Times to LOC and ROC were slightly prolonged in Aquafol (median: 21 vs 18 s, 12.3 vs 10.8 min). Aquafol showed similar incidence of adverse events to Diprivan. Aquafol (vs Diprivan caused more severe (median VAS: 72.0 vs 11.5 mm) and frequent (81.9 vs 29.2%) injection pain. The dose-normalized AUC(last) of Aquafol and Diprivan was 0.71 (0.19) and 0.74 (0.20) min litre(-1). The V(1) of both formulations were proportional to lean body mass. Sex was a significant covariate for k(12) and Ce(50) of Aquafol, and for k(e0) of Diprivan. CONCLUSIONS: Aquafol was as effective and safe as Diprivan, but caused more severe and frequent injection pain. Aquafol demonstrated similar pharmacokinetics to Diprivan.

Machine learning methods applied to pharmacokinetic modelling of remifentanil in healthy volunteers: a multi-method comparison.

This study compared the blood concentrations of remifentanil obtained in a previous clinical investigation with the predicted remifentanil concentrations produced by different pharmacokinetic models: a non-linear mixed effects model created by the software NONMEM; an artificial neural network (ANN) model; a support vector machine (SVM) model; and multi-method ensembles. The ensemble created from the mean of the ANN and the non-linear mixed effects model predictions achieved the smallest error and the highest correlation coefficient. The SVM model produced the highest error and the lowest correlation coefficient. Paired t-tests indicated that there was insufficient evidence that the predicted values of the ANN, SVM and two multi-method ensembles differed from the actual measured values at alpha = 0.05. The ensemble method combining the ANN and non-linear mixed effects model predictions outperformed either method alone. These results indicated a potential advantage of ensembles in improving the accuracy and reducing the variance of pharmacokinetic models.

Ionizing radiation potentiates the induction of nitric oxide synthase by interferon-gamma (Ifn-gamma) or Ifn-gamma and lipopolysaccharide in bnl cl.2 murine embryonic liver cells: role of hydrogen peroxide.

The effects of ionizing irradiation on the nitric oxide (NO) production in murine embryonic liver cell line, BNL CL.2 cells, were investigated. Various doses (5-40 Gy) of radiation made BNL CL.2 cells responsive to interferon-gamma alone for the production of NO in a dose-dependent manner. Small amounts of lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha) synergized with IFN-gamma in the production of NO from irradiated BNL CL.2 cells, even though LPS or TNF-alpha alone did not induce NO production from the same cells. Immunoblots showed parallel induction of inducible nitric oxide synthase (iNOS). NO production in irradiated BNL CL.2 cells by IFN-gamma or IFN-gamma plus LPS was decreased by the addition of catalase, suggesting that H(2)O(2) produced by ionizing irradiation primed the cells to trigger NO production in response to IFN-gamma or IFN-gamma plus LPS. Furthermore, the treatment of nongamma-irradiated BNL CL.2 cells with H(2)O(2) made the cells responsive to IFN-gamma or IFN-gamma plus LPS for the production of NO. This study shows that ionizing irradiation has the ability to induce iNOS gene expression in responsive to IFN-gamma via the formation of H(2)O(2) in BNL CL.2 murine embryonic liver cells.

20(S)-Protopanaxatriol, one of ginsenoside metabolites, inhibits inducible nitric oxide synthase and cyclooxygenase-2 expressions through inactivation of nuclear factor-kappaB in RAW 264.7 macrophages stimulated with lipopolysaccharide.

Ginsenosides from Panax ginseng are metabolized by human intestinal bacteria after oral administration of ginseng extract. 20(S)-Protopanaxatriol (PPT) is one of the major metabolites of ginsenosides. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important enzymes that mediate inflammatory processes. Improper up-regulation of iNOS and/or COX-2 has been associated with the pathogenesis of inflammatory diseases and certain types of human cancers. Here, we investigated whether PPT could modulate iNOS and COX-2 expressions in RAW 264.7 macrophages stimulated with the endotoxin lipopolysaccharide (LPS). We found that PPT blocked the increase in LPS-induced iNOS and COX-2 expressions through inactivation of nuclear factor-kappaB by preventing I-kappaBalpha phosphorylation and degradation. Thus, it may be possible to develop PPT as a useful agent for chemoprevention of cancer or inflammatory diseases.

Penta-O-galloyl-beta-D-glucose inhibits phorbol myristate acetate-induced interleukin-8 [correction of intereukin-8] gene expression in human monocytic U937 cells through its inactivation of nuclear factor-kappaB.

We investigated the effects of the gallotannin penta-O-galloyl-beta-d-glucose (PGG) on interleukin (IL)-8 gene expression and nuclear factor (NF)-kappaB activation. PGG inhibited IL-8 production and gene expression in human monocytic U937 cells stimulated with phorbol myristate acetate (PMA), as measured by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction analysis, respectively. PGG also inhibited PMA-mediated NF-kappaB activation, as measured by electromobility shift assay. Furthermore, PGG prevented PMA-mediated degradation of the NF-kappaB inhibitory protein I-kappaBalpha, as measured by Western blot analysis. PGG also inhibited both IL-8 production and NF-kappaB activation in the U937 cells stimulated with tumor necrosis factor-alpha. These results suggest that PGG, a major constituent of the root cortex of Paeonia suffruticosa ANDREWS, can inhibit IL-8 gene expression by a mechanism involving its inhibition of NF-kappaB activation, which is dependent on I-kappaBalpha degradation.

Inhibition of TNF-alpha, IL-1beta, and IL-6 productions and NF-kappa B activation in lipopolysaccharide-activated RAW 264.7 macrophages by catalposide, an iridoid glycoside isolated from Catalpa ovata G. Don (Bignoniaceae).

Catalposide, the major iridoid glycoside isolated from the stem bark of Catalpa ovata G. Don (Bignoniaceae), was found to inhibit the productions of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), and the activation of nuclear factor kappaB (NF-kappaB) in RAW 264.7 macrophages activated with lipopolysaccharide (LPS). Catalposide also inhibited the expressions of TNF-alpha, IL-1beta, and IL-6 genes and the nuclear translocation of p65 subunit of NF-kappaB in LPS-activated RAW 264.7 cells. Flow cytometric analysis revealed that catalposide suppressed the binding of FITC-conjugated LPS to CD14 on the surface of cells, probably resulting in the inhibitory effects on TNF-alpha, IL-1beta, and IL-6 productions and NF-kappaB activation. These findings suggest that catalposide could be an attractive candidate for adjunctive therapy in gram-negative bacterial infections.

Induction of apoptosis by 4-acetyl-12,13-epoxyl-9-trichothecene-3,15-diol from Isaria japonica Yasuda through intracellular reactive oxygen species formation and caspase-3 activation in human leukemia HL-60 cells.

Recently we have reported that the trichothecene mycotoxin 4-acetyl-12,13-epoxyl-9-trichothecene-3,15-diol (AETD) from the fruiting bodies of Isaria japonica Yasuda is a potent inducer of apoptosis in human promyelocytic HL-60 cells. The present study aims to characterize the molecular events leading to AETD-induced apoptosis in HL-60 cells. The percentage of apoptotic cells (annexin-V-positive cell population) increased dose- and time-dependently after AETD exposure. Apoptosis of HL-60 cells by AETD was associated with the formation of intracellular reactive oxygen species (ROS), the depletion of intracellular glutathione (GSH) and the activation of caspase-3. Pretreating the cells with the antioxidant N-acetyl-L-cystein (NAC) and the caspase-3 inhibitor Z-DEVD-fmk abrogated AETD-induced apoptosis and caspase-3 activation. NAC blocked intracellular ROS formation and GSH depletion, but Z-DEVD-fmk did not. These results indicate that AETD induces apoptosis in HL-60 cells by causing intracellular ROS formation and GSH depletion followed by the downstream event of caspase-3 activation.

Inhibition of nitric oxide synthesis by butanol fraction of the methanol extract of Ulmus davidiana in murine macrophages.

Since there is increasing evidence that nitric oxide (NO) plays a crucial role in the pathogenesis of inflammatory diseases, this study was undertaken to address whether the methanol (MeOH) extract and its fractions of the bark of Ulmus davidiana Planch (Ulmaceae) could modulate the expression of inducible NO synthase (iNOS) in thioglycollate-elicited murine peritoneal macrophages and murine macrophage cell line, RAW264.7 cells. Stimulation of the peritoneal macrophages and RAW264.7 cells with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) resulted in increased production of NO in the medium. However, the butanol (BuOH) fraction of the MeOH extract of U. davidiana barks showed marked inhibition of NO synthesis in a dose-dependent manner. The inhibition of NO synthesis was reflected in the decreased amount of iNOS protein, as determined by Western blotting. The BuOH fraction did not affect the viability of RAW264.7 cells, as assessed by methylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide (MTT) assay; rather, it reduced endogenous NO-induced apoptotic cell death via inhibition of NO synthesis in RAW264.7 cells. On the other hand, the BuOH fraction showed no inhibitory effect on the synthesis of NO by RAW264.7 cells, when iNOS was already expressed by the stimulation with IFN-gamma and LPS. Collectively, these results demonstrate that the BuOH fraction inhibits NO synthesis by inhibition of the induction of iNOS in murine macrophages.

Inhibitory effects of the stem bark of Catalpa ovata G. Don. (Bignoniaceae) on the productions of tumor necrosis factor-alpha and nitric oxide by the lipopolisaccharide-stimulated RAW 264.7 macrophages.

In order to validate the use of the stem bark of Catalpa ovata G. Don. (Bignoniaceae) as an anti-inflammatory drug in the traditional Korean medicine, we have investigated the effects of the methanol extract of this folk medicine on the productions of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) on RAW 264.7 macrophages activated with the endotoxin lipopolysaccharide. The extract inhibited the productions of TNF-alpha and NO with significant decreases in mRNA levels of TNF-alpha and inducible NO synthase, suggesting that the stem bark of Catalpa ovata may have therapeutic potential in the control of inflammatory disorders.

Inhibitory effects of the root cortex of Paeonia suffruticosa on interleukin-8 and macrophage chemoattractant protein-1 secretions in U937 cells.

In an effort to elucidate the mechanism of the anti-inflammatory effect of mudanpi, the root cortex of Paeonia suffruticosa Andrews (Ranunculaceae), we determined the effects of the methanolic extract of mudanpi (MEM) on the secretions of interleukin (IL)-8, a major mediator of acute neutrophil-mediated inflammation, and macrophage chemoattractant protein (MCP)-1, a major mediator of chronic macrophage-mediated inflammation, in human monocytic U937 cells stimulated with phorbol myristate acetate (PMA). MEM significantly inhibited PMA-induced secretions of IL-8 and MCP-1 proteins in a dose-dependent manner. The inhibition of these chemokines by MEM was due to its suppression of IL-8 and MCP-1 genes. In addition, 1,2,3,4,6-penta-O-galloyl-beta-D-glucose, one of major constituents isolated from MEM, inhibited PMA-induced secretions of IL-8 and MCP-1 proteins by its suppression of IL-8 and MCP-1 genes. Thus, one possible anti-inflammatory mechanism of mudanpi, an anti-inflammatory Chinese crude drug, may be to inhibit the secretions of inflammatory chemokines.

Delayed cutaneous hypersensitivity reactions in Qigong (chun do sun bup) trainees by multitest cell mediated immunity.

To determine the difference of cellular immunity between a Qigong trainee group and a normal healthy group, skin tests for delayed cutaneous hypersensitivity (DCH) were carried out with ubiquitous seven antigens. The maximal antigen response time was faster in Qigong trainee group (24 hr) and the response antigen number was also higher in the Qigong trainee group (6 antigens) than in normal healthy person (48 hr and 4 antigens). Qigong trainee also had a larger induration diameter (5.14 mm) than normal healthy person (3.79 mm) at 24 hr. Our results represent the difference in cell mediated immunity (CMI) between Qigong trainees and normal healthy subjects.

Effect of qigong training on proportions of T lymphocyte subsets in human peripheral blood.

The effect of Qigong training on proportions of T lymphocyte subsets was investigated in human peripheral blood. We observed that the ratio of CD4+/CD8+ T lymphocytes was increased as much as 50% in a trainee group who practiced Qigong training more than 5 months compared to a normal healthy group who did not practice. The absolute number of CD4+ T lymphocytes was also elevated in trainee group with 100 cells/mm3 more than in normal healthy group. The positive correlation between the ratio of CD4+/CD8+ T lymphocytes and the ratio of CD4+45RA-/CD4+CD45RA+ T lymphocytes was shown in the trainee group. In contrast, there was a negative correlation between the ratio of CD4+/CD8+ T lymphocytes and the ratio of CD8+CD57+/CD8+CD57- T lymphocytes in the trainee group. The data indicate that Qigong training affects the profile of lymphocyte subsets in human peripheral blood, especially the proportion of CD4+ T lymphocytes.

The population pharmacokinetics of fentanyl in patients undergoing living-donor liver transplantation.

Fentanyl, an opioid analgesic with a high hepatic extraction ratio, is frequently used to supplement general anesthesia during liver transplantation and is also continuously infused to provide postoperative analgesia. However, because fentanyl is metabolized mainly in the liver, the pharmacokinetics of fentanyl may vary widely during the different phases of the surgery, potentially leading to adverse events. Using nonlinear mixed-effects modeling, we characterized the pharmacokinetics of fentanyl in 15 patients (American Society of Anesthesiologists Physical Status Classification 2 or 3) undergoing living-donor liver transplantation (LDLT). Fentanyl was continuously infused at the rate of 200-400 µg/h throughout the operation. The time course of the fentanyl plasma concentration levels was best described in terms of a two-compartment model. Estimates were made of the pharmacokinetic parameters during the preanhepatic, anhepatic, and neohepatic phases: central volume of distribution (V(1)) (l): 59.0 + hourly volume infused by rapid infusion system (RIS) × 42.5, 113.0, and 189.0, respectively, × (body weight/69)(1.3); peripheral volume of distribution (V(2)) (l): 94.3, 412.0, and 427.0, respectively; intercompartmental clearance (Q) (l/h): 96.4 × (cardiac output (CO)/6.7)(2.5), 22.6, and 28.2, respectively; metabolic clearance (Cl) (l/h): 21.7 during the preanhepatic and neohepatic phases, and 0 during the anhepatic phase. The preanhepatic central volume of distribution was found to be markedly influenced by the massive infusion of fluids and blood products. The more hyperdynamic the circulation was during the preanhepatic phase, the higher the distributional clearance.

Albumin versus normal saline for dehydrated term infants with metabolic acidosis due to acute diarrhea.

UNLABELLED: To compare the efficacy of albumin to normal saline (NS) for initial hydration therapy for dehydrated term infants with severe metabolic acidosis due to acute diarrhea. STUDY DESIGN: We randomized 33 infants presenting with moderate-to-severe dehydration and metabolic acidosis (pH <7.25 or base excess (BE) <-15) into two groups, an albumin group (n=15) and a NS group (n=18). For initial hydration treatment, the albumin group received 5% albumin (10 ml kg(-1)), whereas the NS group received NS (10 ml kg(-1)). RESULT: After 3 h of treatment, both groups improved. However, the magnitude of improvement in the pH, BE and HCO(3)(-) levels were not different in comparisons between these two groups. In addition, there were no differences either in the body weight and weight gain 4 days after treatment or in the length of hospital stay. CONCLUSION: Albumin was not more effective than NS for initial hydration treatment of dehydrated term infants with metabolic acidosis due to acute diarrhea.