Fish Oil Emulsion Reduces Liver Injury and Liver Transplantation in Children with Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Study.

OBJECTIVE: To compare the aspartate aminotransferase to platelet ratio index, liver transplantation, and mortality rates between children with intestinal failure-associated liver disease who received fish oil lipid emulsion (FOLE) or soybean oil intravenous lipid emulsion (SOLE). STUDY DESIGN: In this multicenter integrated analysis, FOLE recipients (1 g/kg/d) (n = 189) were compared with historical controls administered SOLE (≤3 g/kg/d) (n = 73). RESULTS: Compared with SOLE, FOLE recipients had a higher direct bilirubin level at baseline (5.8 mg/dL vs 3.0 mg/dL; P < .0001). Among FOLE recipients, 65% experienced cholestasis resolution vs 16% of SOLE recipients (P < .0001). The aspartate aminotransferase to platelet ratio index scores improved in FOLE recipients (1.235 vs 0.810 and 0.758, P < .02) but worsened in SOLE recipients (0.540 vs 2.564 and 2.098; P ≤ .0003) when baseline scores were compared with cholestasis resolution and end of study, respectively. Liver transplantation was reduced in FOLE vs SOLE (4% vs 12%; P = .0245). The probability of liver transplantation in relation to baseline direct or conjugated bilirubin (DB) was lower in FOLE vs SOLE recipients (1% vs 9% at DB of 2 mg/dL; 8% vs 35% at DB of 12.87 mg/dL; P = .0022 for both). Death rates were similar (FOLE vs SOLE: 10% vs 14% at DB of 2 mg/dL; 17% vs 23% at a DB of 12.87 mg/dL; P = .36 for both). CONCLUSIONS: FOLE recipients experienced a higher rate of cholestasis resolution, lower aspartate aminotransferase to platelet ratio index, and fewer liver transplants compared with SOLE. This study demonstrates that FOLE may be the preferred parenteral lipid emulsion in children with intestinal failure-associated liver disease when DB reaches 2 mg/dL. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00910104 and NCT00738101.

High Early Parenteral Lipid in Very Preterm Infants: A Randomized-Controlled Trial.

OBJECTIVE: To determine whether high early parenteral soybean oil lipid intake in very low birth weight (VLBW) infants in the first week after birth decreases the proportion of weight loss and subsequently the incidence of extrauterine growth restriction (EUGR). STUDY DESIGN: This was a randomized controlled trial of appropriate for gestational- ge VLBW infants. Lipid intake in the control group started at 0.5-1 g/kg per day and increased daily by 0.5-1 g/kg per day till reaching 3 g/kg per day. The intervention group was started on 2 g/kg per day that increased to 3 g/kg per day the following day. RESULTS: Of the 176 infants assessed for eligibility, 83 were included in the trial. Infants in the intervention group were started on lipid sooner (13.8 ± 7.8 vs 17.5 ± 7.8 hour; P = .03) and had higher cumulative lipid intake in the first 7 days of age (13.5 ± 4.2 vs 10.9 ± 3.5 g/kg per day; P = .03). Infants in the intervention group had a lower percentage of weight loss (10.4 vs 12.7%; P = .02). The mean triglyceride level was higher in the intervention group (1.91 ± 0.79 vs 1.49 ± 0.54 mmol/L; P = .01), however, hypertriglyceridemia was similar between the 2 groups. The incidence of EUGR was lower in the intervention group (38.6% vs 67.6%; P = .01). Head circumference z score was higher in the intervention group (-1.09 ± 0.96 vs -1.59 ± 0.98; P = .04). CONCLUSIONS: In VLBW infants, provision of a high early dose of parenteral lipid in the first week of age results in less weight loss and lower incidence of EUGR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03594474.

Effect of pre-administered flurbiprofen axetil on the EC50 of propofol during anesthesia in unstimulated patients: a randomized clinical trial / Efeito da pré‐ administração de flurbiprofeno axetil na CE50 do propofol durante anestesia em pacientes não estimulados: estudo clínico randomizado

Abstract Background and objectives Preoperative use of flurbiprofen axetil (FA) is extensively adopted to modulate the effects of analgesia. However, the relationship between FA and sedation agents remains unclear. In this study, we aimed to investigate the effects of different doses of FA on the median Effective Concentration (EC50) of propofol. Methods Ninety-six patients (ASA I or II, aged 18-65 years) were randomly assigned into one of four groups in a 1:1:1:1 ratio. Group A (control group) received 10 mL of Intralipid, and groups B, C and D received 0.5 mg.kg−1, 0.75 mg.kg−1 and 1 mg.kg−1 of FA, respectively, 10 minutes before induction. The depth of anesthesia was measured by the Bispectral Index (BIS). The "up-and-down" method was used to calculate the EC50 of propofol. During the equilibration period, if BIS ≤ 50 (or BIS > 50), the next patient would receive a 0.5 µg.mL−1-lower (or -higher) propofol Target-Controlled Infusion (TCI) concentration. The hemodynamic data were recorded at baseline, 10 minutes after FA administration, after induction, after intubation and 15 minutes after intubation. Results The EC50 of propofol was lower in Group C (2.32 µg.mL−1, 95% Confidence Interval [95% CI] 1.85-2.75) and D (2.39 µg.mL−1, 95% CI 1.91-2.67) than in Group A (2.96 µg.mL−1, 95% CI 2.55-3.33) (p = 0.023, p = 0.048, respectively). There were no significant differences in the EC50 between Group B (2.53 µg.mL−1, 95% CI 2.33-2.71) and Group A (p > 0.05). There were no significant differences in Heart Rate (HR) among groups A, B and C. The HR was significantly lower in Group D than in Group A after intubation (66 ± 6 vs. 80 ± 10 bpm, p < 0.01) and 15 minutes after intubation (61 ± 4 vs. 70 ± 8 bpm, p < 0.01). There were no significant differences among the four groups in Mean Arterial Pressure (MAP) at any time point. The MAP of the four groups was significantly lower after induction, after intubation, and 15 minutes after intubation than at baseline (p < 0.05). Conclusion High-dose FA (0.75 mg.kg−1 or 1 mg.kg−1) reduces the EC50 of propofol, and 1 mg.kg−1 FA reduces the HR for adequate anesthesia in unstimulated patients. Although this result should be investigated in cases of surgical stimulation, we suggest that FA pre-administration may reduce the propofol requirement when the depth of anesthesia is measured by BIS.

Resumo Justificativa e objetivos A administração pré‐operatória de Flurbiprofeno Axetil (FA) é amplamente usada para a modulação da analgesia. No entanto, a relação entre FA e fármacos sedativos permanece obscura. Neste estudo, nosso objetivo foi investigar os efeitos de diferentes doses de FA na Concentração Efetiva mediana (CE50) do propofol. Métodos Noventa e seis pacientes (ASA I ou II, com idades de 18-65 anos) foram alocados aleatoriamente em quatro grupos na proporção de 1:1:1:1. Dez minutos antes da indução, o Grupo A (grupo controle) recebeu 10 mL de Intralipid, enquanto os grupos B, C e D receberam FA na dose de 0,5 mg.kg‐1; 0,75 mg.kg‐1 e 1 mg.kg‐1, respectivamente. A profundidade da anestesia foi medida pelo Índice Bispectral (BIS). O método up‐and‐down foi usado para calcular a CE50 do propofol. Durante o período de equilíbrio, se o valor do BIS fosse ≤ 50 ou BIS > 50, o próximo paciente tinha a infusão de propofol ajustada para uma concentração alvo‐controlada 0,5 µg.mL‐1 inferior ou superior, respectivamente. Os dados hemodinâmicos foram registrados no início do estudo, 10 minutos após a administração de FA, após a indução, após a intubação e 15 minutos após a intubação. Resultados A CE50 do propofol foi menor no Grupo C (2,32 µg.mL‐1, Intervalo de Confiança de 95% [95% IC] 1,85-2,75) e D (2,39 µg.mL‐1, 95% IC 1,91-2,67) do que no Grupo A (2,96 µg.mL‐1; 95% IC 2,55-3,33) (p = 0,023, p = 0,048, respectivamente). Não houve diferenças significantes na CE50 entre o Grupo B (2,53 µg.mL‐1, 95% IC 2,33-2,71) e o Grupo A (p > 0,05). Não houve diferenças significantes na Frequência Cardíaca (FC) entre os grupos A, B e C. A FC foi significantemente menor no grupo D do que no grupo A após a intubação (66 ± 6 vs. 80 ± 10 bpm, p < 0,01) e 15 minutos após a intubação (61 ± 4 vs. 70 ± 8 bpm, p < 0,01). Não houve diferenças significantes entre os quatro grupos na Pressão Arterial Média (PAM) em qualquer momento. A PAM dos quatro grupos foi significantemente menor após a indução, após a intubação e 15 minutos após a intubação do que na linha de base (p < 0,05). Conclusão FA em altas doses (0,75 mg.kg‐1 ou 1 mg.kg‐1) reduz a CE50 do propofol, e 1 mg.kg‐1 de FA reduz a FC durante níveis adequados de anestesia em pacientes não estimulados. Embora esse resultado deva ser investigado na presença de estimulação cirúrgica, sugerimos que a pré‐administração de FA pode reduzir a necessidade de propofol durante anestesia cuja profundidade seja monitorada pelo BIS.

[Effect of pre-administered flurbiprofen axetil on the EC50 of propofol during anesthesia in unstimulated patients: a randomized clinical trial]. / Efeito da pré­administração de flurbiprofeno axetil na CE50 do propofol durante anestesia em pacientes não estimulados: estudo clínico randomizado.

BACKGROUND AND OBJECTIVES: Preoperative use of flurbiprofen axetil (FA) is extensively adopted to modulate the effects of analgesia. However, the relationship between FA and sedation agents remains unclear. In this study, we aimed to investigate the effects of different doses of FA on the median Effective Concentration (EC50) of propofol. METHODS: Ninety-six patients (ASA I or II, aged 18-65 years) were randomly assigned into one of four groups in a 1:1:1:1 ratio. Group A (control group) received 10 mL of Intralipid, and groups B, C and D received 0.5 mg.kg-1, 0.75 mg.kg-1 and 1 mg.kg-1 of FA, respectively, 10 minutes before induction. The depth of anesthesia was measured by the Bispectral Index (BIS). The "up-and-down" method was used to calculate the EC50 of propofol. During the equilibration period, if BIS ≤ 50 (or BIS > 50), the next patient would receive a 0.5 µg.mL-1-lower (or-higher) propofol Target-Controlled Infusion (TCI) concentration. The hemodynamic data were recorded at baseline, 10 minutes after FA administration, after induction, after intubation, and 15 minutes after intubation. RESULTS: The EC50 of propofol was lower in Group C (2.32 µg.mL-1, 95% Confidence Interval [95% CI] 1.85-2.75) and D (2.39 µg.mL-1, 95% CI 1.91-2.67) than in Group A (2.96 µg.mL-1, 95% CI 2.55-3.33) (p = 0.023, p = 0.048, respectively). There were no significant differences in the EC50 between Group B (2.53 µg.mL-1, 95% CI 2.33-2.71) and Group A (p ˃ 0.05). There were no significant differences in Heart Rate (HR) among groups A, B and C. The HR was significantly lower in Group D than in Group A after intubation (66 ± 6 vs. 80 ± 10 bpm, p < 0.01) and 15 minutes after intubation (61 ± 4 vs. 70 ± 8 bpm, p < 0.01). There were no significant differences among the four groups in Mean Arterial Pressure (MAP) at any time point. The MAP of the four groups was significantly lower after induction, after intubation, and 15 minutes after intubation than at baseline (p < 0.05). CONCLUSION: High-dose FA (0.75 mg.kg-1 or 1 mg.kg-1) reduces the EC50 of propofol, and 1 mg.kg-1 FA reduces the HR for adequate anesthesia in unstimulated patients. Although this result should be investigated in cases of surgical stimulation, we suggest that FA pre-administration may reduce the propofol requirement when the depth of anesthesia is measured by BIS.

Detoxification effects of long-chain versus a mixture of medium- and long-chain triglyceride-based fat emulsion on propafenone poisoning.

In the present study, we aimed to compare the detoxifying effects of two fat emulsions containing either long-chain triglyceride or a mixture of medium-chain and long-chain triglycerides in the propafenone-poisoned rat model. Rats were randomly divided into 3 groups according to the fat emulsions used: long-chain triglyceride-based fat emulsion (LL) group; medium-chain and long-chain triglyceride-based fat emulsion (ML) group; normal saline (NS) group. Propafenone was continuously pumped (velocity=70 mg/kg per h) until the mean blood pressure dropped to 50% of basal level. Then, LL/ML fat emulsions or NS was intravenously infused instantly with a loading-dose (1.5 mL/kg) and a maintenance dose (0.25 mL/kg per min) for 1 h. Subsequently, the propafenone was added to plasma (3.5 µg/mL) in vitro, mixed with three doses of LL or ML (1, 2, or 4%). Finally, after centrifugation, the concentration of propafenone was measured. Rats treated with LL exhibited accelerated recovery, characterized by higher blood pressure and heart rate. Rats in both the LL and ML groups demonstrated decreased propafenone in plasma (time-points: 15, 25, and 60 min). However, rats that received LL showed lower propafenone in myocardial tissue at the end of detoxification treatment. Rats in the ML group had the lowest value of pH, the minimum content of HCO3-, and the highest production of lactic acid at the end. In the in vitro experiments, propafenone decreased more dramatically in the LL group compared to the ML group. Long-chain triglyceride fat emulsion had a better effect on treating propafenone poisoning in rats.

Detoxification effects of long-chain versus a mixture of medium- and long-chain triglyceride-based fat emulsion on propafenone poisoning

In the present study, we aimed to compare the detoxifying effects of two fat emulsions containing either long-chain triglyceride or a mixture of medium-chain and long-chain triglycerides in the propafenone-poisoned rat model. Rats were randomly divided into 3 groups according to the fat emulsions used: long-chain triglyceride-based fat emulsion (LL) group; medium-chain and long-chain triglyceride-based fat emulsion (ML) group; normal saline (NS) group. Propafenone was continuously pumped (velocity=70 mg/kg per h) until the mean blood pressure dropped to 50% of basal level. Then, LL/ML fat emulsions or NS was intravenously infused instantly with a loading-dose (1.5 mL/kg) and a maintenance dose (0.25 mL/kg per min) for 1 h. Subsequently, the propafenone was added to plasma (3.5 μg/mL) in vitro, mixed with three doses of LL or ML (1, 2, or 4%). Finally, after centrifugation, the concentration of propafenone was measured. Rats treated with LL exhibited accelerated recovery, characterized by higher blood pressure and heart rate. Rats in both the LL and ML groups demonstrated decreased propafenone in plasma (time-points: 15, 25, and 60 min). However, rats that received LL showed lower propafenone in myocardial tissue at the end of detoxification treatment. Rats in the ML group had the lowest value of pH, the minimum content of HCO3-, and the highest production of lactic acid at the end. In the in vitro experiments, propafenone decreased more dramatically in the LL group compared to the ML group. Long-chain triglyceride fat emulsion had a better effect on treating propafenone poisoning in rats.

Pilot clinical study of carmustine associated with a lipid nanoemulsion in combination with vincristine and prednisone for the treatment of canine lymphoma.

A lipid nanoemulsion (LDE) resembling low-density lipoprotein can target malignant tumours. In in vivo and clinical studies, association of chemotherapeutic agents to LDE decreased their toxicity and increased pharmacological action. Here, safety of LDE as carmustine carrier (50 mg m(-2) , intravenous) combined with vincristine and prednisone for the treatment of dogs with lymphoma was tested and compared with commercial carmustine with vincristine and prednisone. In five dogs from LDE-carmustine and six from commercial carmustine, complete remission was achieved (P > 0.05). Partial remission occurred in two dogs from each group. In both groups, the median progression-free intervals (119 and 199 days) and overall survival times (207 and 247 days) were equal. Neutropenia was observed in both groups, but no other major toxicities occurred. Therefore, no difference was observed between the treatments. LDE-carmustine was shown to be safe and effective in a drug combination protocol, which encourages larger studies to investigate the use of this novel formulation to treat canine lymphomas.

Randomized controlled trial of early enteral fat supplement and fish oil to promote intestinal adaptation in premature infants with an enterostomy.

OBJECTIVE: To test the hypothesis that early enteral supplementing fat and fish oil decreases the duration of parenteral nutrition (PN) and increases enteral nutrition (EN) before bowel reanastomosis in premature infants with an enterostomy. STUDY DESIGN: Premature infants (<2 months old) who had an enterostomy and tolerated enteral feeding at 20 mL/kg/day were randomized to usual care (control=18) or early supplementing enteral fat supplement and fish oil (treatment=18). Intravenous lipid was decreased as enteral fat intake was increased. Daily weight, clinical and nutrition data, and weekly length and head circumference were recorded. The primary outcomes were the duration of PN and volume of EN intake, and the secondary outcomes were weight gain (g/day), ostomy output (mL/kg/d), and serum conjugated bilirubin level (mg/dL) from initiating feeding to reanastomosis. Data were analyzed by Student t test or Wilcoxon rank sum test. RESULTS: There were no differences in the duration of PN, ostomy output, and weight gain between the 2 groups before reanastomosis. However, supplemented infants received less intravenous lipid, had greater EN intake, and lower conjugated bilirubin before reanastomosis, and they also received greater total calorie, had fewer sepsis evaluations and less exposure to antibiotics and central venous catheters before reanastomosis, and had greater weight and length gain after reanastomosis (all P<.05). CONCLUSION: Early enteral feeding of a fat supplement and fish oil was associated with decreased exposure to intravenous lipid, increased EN intake, and reduced conjugated bilirubin before reanastomosis and improved weight and length gain after reanastomosis in premature infants with an enterostomy.

Bedside to bench: The risk of bleeding with parenteral omega-3 lipid emulsion therapy.

Our clinical experience led us to reassess the effect of sole omega-3 lipid therapy on hemostasis. We compared thromboelastography platelet mapping in neonatal piglets given sole omega-3 lipid. We identified abnormalities in reaction time (P = .025) and the arachidonic acid pathway (P = .025). The potential for bleeding complications from parenteral omega-3 lipid emulsion therapy in high-risk infants with liver disease has been dismissed but, on the basis of this data, should be reconsidered.

Effects of propofol in lipid-based emulsion and in microemulsion on the incidence of endothelial lesion in rabbits.

PURPOSE: To compare the incidence of endothelial injury after single-dose or continuous propofol infusion in conventional lipid-based emulsion (LE) versus microemulsion (ME). METHODS: Forty-two rabbits (2.5-4.5 Kg) were randomly allocated into seven groups of six animals each: SHAM- surgical treatment alone; Bolus Control Group - 3 mL-intravenous (IV) bolus of saline; Continuous Infusion Control Group - 3 mL- IV bolus of saline followed by a continuous infusion of 0.2 ml/kg/min for 60 min; Bolus LE Propofol Group - IV bolus of LE propofol (3 mg/kg); Bolus ME Propofol Group - IV ME propofol bolus (3 mg/kg); Continuous LE Propofol Group - IV LE propofol bolus (3 mg/kg) followed by a continuous infusion of 0.2 ml/kg/min for 60 min; Continuous ME Propofol Group - IV ME propofol bolus (3 mg/kg) followed by a continuous infusion of 0.2 ml/kg/min for 60 min. RESULTS: There were no statistically significant differences between the studied groups in blood pressure, in central venous pressure and in the biochemical profile. No significant differences were found in inflammatory mediators and in tissue analysis between the two emulsions. CONCLUSION: Microemulsion and lipid-based emulsion propofol had similar inflammatory, biochemical and microscopy profiles. Thus, microemulsion propofol can be used as an alternative to lipid-based emulsion propofol.

Effects of propofol in lipid-based emulsion and in microemulsion on the incidence of endothelial lesion in rabbits

PURPOSE: To compare the incidence of endothelial injury after single-dose or continuous propofol infusion in conventional lipid-based emulsion (LE) versus microemulsion (ME). METHODS: Forty-two rabbits (2.5-4.5 Kg) were randomly allocated into seven groups of six animals each: SHAM- surgical treatment alone; Bolus Control Group - 3 mL-intravenous (IV) bolus of saline; Continuous Infusion Control Group - 3 mL- IV bolus of saline followed by a continuous infusion of 0.2 ml/kg/min for 60 min; Bolus LE Propofol Group - IV bolus of LE propofol (3 mg/kg); Bolus ME Propofol Group - IV ME propofol bolus (3 mg/kg); Continuous LE Propofol Group - IV LE propofol bolus (3 mg/kg) followed by a continuous infusion of 0.2 ml/kg/min for 60 min; Continuous ME Propofol Group - IV ME propofol bolus (3 mg/kg) followed by a continuous infusion of 0.2 ml/kg/min for 60 min. RESULTS: There were no statistically significant differences between the studied groups in blood pressure, in central venous pressure and in the biochemical profile. No significant differences were found in inflammatory mediators and in tissue analysis between the two emulsions. CONCLUSION: Microemulsion and lipid-based emulsion propofol had similar inflammatory, biochemical and microscopy profiles. Thus, microemulsion propofol can be used as an alternative to lipid-based emulsion propofol.

Early enteral fat supplement and fish oil increases fat absorption in the premature infant with an enterostomy.

OBJECTIVE: To test the hypothesis that in the premature infant with an enterostomy, early enteral supplementation with Microlipid (fat supplement) and fish oil increases enteral fat absorption and decreases the requirement for Intralipid (intravenous fat emulsion). STUDY DESIGN: Premature infants (<2 months old) with an enterostomy after surgical treatment for necrotizing enterocolitis or spontaneous intestinal perforation and tolerating enteral feeding at 20 mL/kg/day were randomized to usual care (control 18 infants) or early supplementing enteral fat and fish oil (treatment 18 infants). Intravenous fat emulsion was decreased as enteral fat intake was increased. Daily weight, ostomy output, and nutrition data were recorded. Weekly 24-hour ostomy effluent was collected until bowel reanastomosis, and fecal fat, fecal liquid, and dry feces were measured. Fat absorption (g/kg/d) was calculated by subtracting fecal fat from dietary fat. The fecal liquid and dry feces were reported as mg/g wet stool. Date were analyzed by using ANOVA and mixed-effects model. RESULTS: The interval from initial postoperative feeding to bowel reanastomosis varied from 2 to 10 weeks. The treatment group received more dietary fat and less intravenous fat emulsion and had higher enteral fat absorption, less fecal liquid, and drier feces than the control group. These effects were greater among infants with a high ostomy compared with those with a low ostomy. Enteral fat intake was significantly correlated with fat absorption. CONCLUSION: Early enteral fat supplement and fish oil increases fat absorption and decreases the requirement for intravenous fat emulsion. This approach could be used to promote bowel adaptation and reduce the use of intravenous fat emulsion in the premature infant with an enterostomy.

Lipoprotein metabolism in patients with type 1 diabetes under intensive insulin treatment.

BACKGROUND: Type 1 diabetes (T1DM) is frequently accompanied by dyslipidemia related with insulin-dependent steps of the intravascular lipoprotein metabolism. T1DM dyslipidemia may predispose to precocious cardiovascular disease and the lipid status in T1DM under intensive insulin treatment has not been sufficiently explored. The aim was to investigate the plasma lipids and the metabolism of LDL and HDL in insulin-treated T1DM patients with high glycemic levels. METHODS: Sixteen male patients with T1DM (26 ± 7 yrs) with glycated hemoglobin >7%, and 15 control subjects (28 ± 6 yrs) were injected with a lipid nanoemulsion (LDE) resembling LDL and labeled with (14)C-cholesteryl ester and (3)H-free-cholesterol for determination of fractional clearance rates (FCR, in h-1) and cholesterol esterification kinetics. Transfer of labeled lipids from LDE to HDL was assayed in vitro. RESULTS: LDL-cholesterol (83 ± 15 vs 100 ± 29 mg/dl, p=0.08) tended to be lower in T1DM than in controls; HDL-cholesterol and triglycerides were equal. LDE marker 14C-cholesteryl ester was removed faster from plasma in T1DM patients than in controls (FCR=0.059 ± 0.022 vs 0.039 ± 0.022h-1, p=0.019), which may account for their lower LDL-cholesterol levels. Cholesterol esterification kinetics and transfer of non-esterified and esterified cholesterol, phospholipids and triglycerides from LDE to HDL were also equal. CONCLUSION: T1DM patients under intensive insulin treatment but with poor glycemic control had lower LDL-cholesterol with higher LDE plasma clearance, indicating that LDL plasma removal was even more efficient than in controls. Furthermore, HDL-cholesterol and triglycerides, cholesterol esterification and transfer of lipids to HDL, an important step in reverse cholesterol transport, were all normal. Coexistence of high glycemia levels with normal intravascular lipid metabolism may be related to differences in exogenous insulin bioavailabity and different insulin mechanisms of action on glucose and lipids. Those findings may have important implications for prevention of macrovascular disease by intensive insulin treatment.

Parenteral fish oil as a pharmacological agent to modulate post-operative immune response: a randomized, double-blind, and controlled clinical trial in patients with gastrointestinal cancer.

BACKGROUND: Fish oil-based lipid emulsions (FOLEs) have shown post-operative immunological and clinical benefits in parenteral nutrition. AIM: To assess post-operative immune response after short-term pre-operative parenteral infusion of isolated FOLE in gastrointestinal cancer patients. METHODS: The patients (n = 63) received pre-operative peripheral infusion (0.2 g fat/kg body weight/d) of FOLE (Omegaven(®)) or control lipid emulsion (MCT/LCT; Lipovenos MCT(®)) for 3 days. Post-operative concentrations of inflammatory mediators, leukocyte functions, surface molecules, infections, and length of intensive care unit (ICU) and hospital stay were measured. RESULTS: FOLE patients had a significant increase of IL-10 levels on day 3, decrease of IL-6 and IL-10 levels on day 6, lower decrease in leukocyte oxidative burst, maintenance of monocyte percentage expressing HLA-DR and CD32, and increase of CD32 neutrophil expression compared to MCT/LCT patients. No changes were observed in the frequency of post-operative infections or length of ICU and hospital stay. CONCLUSIONS: Short-term pre-operative infusion of FO alone improves the post-operative immune response of gastrointestinal cancer patients without significantly changing post-operative infections or length of ICU and hospital stay. ID:NCT01218841.

High rates of resolution of cholestasis in parenteral nutrition-associated liver disease with fish oil-based lipid emulsion monotherapy.

OBJECTIVE: To determine factors leading to resolution of cholestasis in patients with parenteral nutrition-associated liver disease treated with fish oil-based lipid emulsion (FOLE). STUDY DESIGN: Prospective observational study of 57 infants <6 months of age with parenteral nutrition-associated liver disease who received parenteral FOLE as monotherapy. RESULTS: Median gestational age of subjects at birth was 28 weeks (range 22.7-39.5). Median conjugated bilirubin level at initiation of therapy with FOLE was 7.5 mg/dL (range 2.1-25). Resolution of hyperbilirubinemia (conjugated bilirubin <2.0 mg/dL) and survival to hospital discharge occurred in 47 (82.5%) infants. Median number of days to resolution of cholestasis was 35 (range 7-129). Ten infants (17.5%) died. Non-survivors showed a trend towards being more premature than survivors at birth (25.9 vs 29.1 weeks, P = .056). Infants with higher conjugated bilirubin at initiation of therapy (>10.0 compared with <5.0 mg/dL) had longer times to resolution (98 vs 56 days, P < .005). Time to resolution correlated inversely with gestational age at birth (r(2) = 0.14, P = .02) and directly with time to receive 100% calories enterally (r(2) = 0.12, P = .03). CONCLUSIONS: Younger gestational age infants demonstrated higher degree of cholestasis, longer time to resolution of cholestasis, and increased mortality. Higher levels of cholestasis were associated with longer time to resolution. FOLE monotherapy led to resolution of cholestasis in all surviving infants.

Docosahexaenoic and arachidonic acid levels in extremely low birth weight infants with prolonged exposure to intravenous lipids.

OBJECTIVE: To report changes in red blood cell long-chain polyunsaturated fatty acids levels in extremely low birth weight (ELBW) infants relative to duration of intravenous lipid emulsion. STUDY DESIGN: Serial blood samples were collected from 26 ELBW infants during the first 2 months of life in the neonatal intensive care unit using a prospective cohort study design. The primary outcome was the change in long-chain polyunsaturated fatty acids levels over the study period relative to a duration of intravenous lipid emulsion of either ≤ 28 days or >28 days. Secondary outcomes included parenteral and enteral nutritional exposures as well as prematurity-associated morbidities. Longitudinal regression estimated changes in fatty acid levels between the 2 exposure groups. RESULTS: Infants with >28 days intravenous lipid emulsion had 36 more days of intravenous lipid emulsion than did those with ≤ 28 days (P < .001). Docosahexaenoic acid significantly decreased over time in all infants and decreased significantly more in infants exposed to intravenous lipid emulsion for >28 days (P = .03). Arachidonic acid significantly decreased over the study period but the decrease was not related to intravenous lipid emulsion duration. Linoleic and α-linolenic acids had significantly larger increases over time in those with longer exposure to intravenous lipid emulsion (P < .01). CONCLUSION: Docosahexaenoic acid status of ELBW infants declined significantly in the first 2 months of life and the decline was significantly greater in those exposed to intravenous lipid emulsion >28 days compared with those exposed ≤ 28 days.

Pressão arterial, respostas metabólicas e autonômicas à insulina e infusão de intralipid® em pacientes chagásicos / Blood pressure, metabolic and autonomic responses to insulin and intralipid® infusion in chagasic patients / Presión arterial, respuestas metabólicas y autonómicas a la insulina e infusión de intralipid® en pacientes chagásicos

FUNDAMENTO: Infusão de intralipid e heparina resulta em aumento da pressão arterial e também em anormalidades autonômicas em indivíduos normais e hipertensos. OBJETIVO: Avaliar a sensibilidade a insulina e o impacto da infusão de intralipid e de heparina (ILH) sobre a resposta hemodinâmica, metabólica e autonômica em pacientes com a forma indeterminada da doença de Chagas. MÉTODOS: Doze pacientes com a forma indeterminada da doença de Chagas e 12 voluntários saudáveis foram avaliados. RESULTADOS: A pressão arterial basal e a frequência cardíaca foram semelhantes nos dois grupos. Os níveis plasmáticos de noradrenalina encontravam-se ligeiramente aumentados no grupo de pacientes chagásicos. Após o Teste de Tolerância a Insulina (TTI), houve um declínio significativo na glicose dos dois grupos. A Infusão de ILH resultou em aumento da pressão arterial em ambos os grupos, mas não houve nenhuma mudança significativa na noradrenalina plasmática. O componente de Baixa Frequência (BF) mostrou-se semelhante e aumentou de forma semelhante em ambos os grupos. O componente de Alta Frequência (AF) apresentou-se menor no grupo chagásico. CONCLUSÃO: Pacientes com forma indeterminada da doença de Chagas apresentaram aumento da atividade simpática no momento basal e uma resposta inadequada à insulina. Eles também tiveram um menor componente de alta frequência e sensibilidade barorreflexa prejudicada no momento basal e durante a infusão de intralipid e heparina.

BACKGROUND: Intralipid and heparin infusion results in increased blood pressure and autonomic abnormalities in normal and hypertensive individuals. OBJECTIVE: To evaluate insulin sensitivity and the impact of Intralipid and heparin (ILH) infusion on hemodynamic, metabolic, and autonomic response in patients with the indeterminate form of Chagas' disease. METHODS: Twelve patients with the indeterminate form of Chagas' disease and 12 healthy volunteers were evaluated. RESULTS: Baseline blood pressure and heart rate were similar in both groups. Plasma noradrenaline levels were slightly increased in the Chagas' group. After insulin tolerance testing (ITT), a significant decline was noted in glucose in both groups. ILH infusion resulted in increased blood pressure in both groups, but there was no significant change in plasma noradrenaline. The low-frequency component (LF) was similar and similarly increased in both groups. The high-frequency component (HF) was lower in the Chagas' group. CONCLUSION: Patients with the indeterminate form of Chagas' disease had increased sympathetic activity at baseline and impaired response to insulin. They also had a lower high-frequency component and impaired baroreflex sensitivity at baseline and during Intralipid and heparin infusion.

FUNDAMENTO: La Infusión de intralipid® y de heparina trae como resultado un aumento de la presión arterial y también de las anormalidades autonómicas en los individuos normales e hipertensos. OBJETIVO: Evaluar la sensibilidad a la insulina y el impacto de la infusión de intralipid® y de heparina (ILH) sobre la respuesta hemodinámica, metabólica y autonómica en pacientes con la forma indefinida de la Enfermedad de Chagas. MÉTODOS: Fueron evaluados doce pacientes con la forma indefinida de la Enfermedad de Chagas y 12 voluntarios sanos. RESULTADOS: La presión arterial basal y la frecuencia cardíaca fueron similares en los dos grupos. Los niveles plasmáticos de noradrenalina estaban ligeramente más elevados en el grupo de pacientes chagásicos. Después del Test de Tolerancia a la Insulina (TTI), se produjo una ostensible disminución en la glucosa de los dos grupos. La Infusión de ILH trajo como consecuencia el aumento de la presión arterial en ambos grupos, pero no hubo ningún cambio significativo en la noradrenalina plasmática. El componente de Baja Frecuencia (BF), fue similar y aumentó de forma parecida en ambos grupos. El componente de Alta Frecuencia (AF) se presentó con un menor nivel en el grupo chagásico. CONCLUSIONES: Los pacientes con una forma indeterminada de la Enfermedad de Chagas, presentaron un aumento en la actividad simpática al momento basal y una respuesta inadecuada a la insulina. También tuvieron un menor componente de alta frecuencia y de sensibilidad barorrefleja, que fue perjudicado en el momento basal y durante la infusión de intralipid® y heparina.