Effect Of Intravenous Fat Emulsion Research Articles

Fatty acids antagonize bupivacaine - induced INa blockade

Theories regarding the mechanism of intravenous fat emulsion for bupivacaine cardiotoxicity include creation of an intravascular lipid sink into which the cardiotoxic drug is sequestered, an improvement of impaired cardiac metabolism, and restoration of cardiomyocyte function by increasing intracellular calcium. However, work in this area is inconclusive and a more mechanistic explanation is desirable. We used a heterologous expression system (HEK-293 cells) and voltage clamp techniques to study the electrophysiologic effects of bupivacaine, polyunsaturated, and saturated fatty acids on sodium current (INa) in stable cell lines expressing human cardiac sodium channels. Linolenic (polyunsaturated) and stearic (saturated) fatty acids were selected for study as they are components of commonly used lipid infusions. Bupivacaine - induced significant tonic and use dependent INa block, as expected. Linolenic and stearic fatty acids directly modulated INa, inducing primarily tonic block. Greater block was seen with linolenic acid as compared with stearic acid. Simultaneous exposure to bupivacaine and fatty acids reduced both the tonic and use dependent block compared with bupivacaine alone. Reduction of bupivacaine - induced INa block was greatest in cells treated with linolenic acid. These results suggest that the salutary effects of intravenous fat emulsion may be, in part, due to a direct modulatory effect of fatty acids on cardiac sodium channels.

Hemodynamic Effects of Intralipid after Verapamil Intoxication May Be Due to a Direct Effect of Fatty Acids on Myocardial Calcium Channels

Academic Emergency MedicineVolume 14, Issue 8 p. 761-761 Free Access Hemodynamic Effects of Intralipid after Verapamil Intoxication May Be Due to a Direct Effect of Fatty Acids on Myocardial Calcium Channels Gildas Gueret MD, Gildas Gueret MD Department of Anesthesiology and Critical Care, University Hospital Brest, Brest, FranceSearch for more papers by this authorJean Pierre Pennec PhD, Jean Pierre Pennec PhD Department of Anesthesiology and Critical Care, University Hospital Brest, Brest, FranceSearch for more papers by this authorCharles C. Arvieux MD, PhD, Corresponding Author Charles C. Arvieux MD, PhD Department of Anesthesiology and Critical Care, University Hospital Brest, Brest, France (Email: [email protected]).Search for more papers by this author Gildas Gueret MD, Gildas Gueret MD Department of Anesthesiology and Critical Care, University Hospital Brest, Brest, FranceSearch for more papers by this authorJean Pierre Pennec PhD, Jean Pierre Pennec PhD Department of Anesthesiology and Critical Care, University Hospital Brest, Brest, FranceSearch for more papers by this authorCharles C. Arvieux MD, PhD, Corresponding Author Charles C. Arvieux MD, PhD Department of Anesthesiology and Critical Care, University Hospital Brest, Brest, France (Email: [email protected]).Search for more papers by this author First published: 28 June 2008 https://doi.org/10.1197/j.aem.2007.04.006Citations: 18AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. References Tebbutt S, Harvey M, Nicholson T Cave G. Intralipid prolongs survival in a rat model of verapamil toxicity Acad Emerg Med 2006; 13: 134– 139. Bania TC, Chu J, Perez E, Su M, Hahn IH. Hemodynamic effects of intravenous fat emulsion in an animal model of severe verapamil toxicity resuscitated with atropine, calcium, and saline Acad Emerg Med 2007; 14: 105– 111. Weinberg GL, Ripper R, Murphy P, et al. Lipid infusion accelerates removal of bupivacaine and recovery from bupivacaine toxicity in the isolated rat heart Reg Anesth Pain Med 2006; 31: 296– 303. Huang JM, Xian H, Bacaner M. Long-chain fatty acids activate calcium channels in ventricular myocytes Proc Natl Acad Sci U S A 1992; 89: 6452– 6456. Citing Literature Volume14, Issue8August 2007Pages 761-761 ReferencesRelatedInformation

Hemodynamic Effects of Intravenous Fat Emulsion plus Standard Therapy in a Model of Severe Verapamil Toxicity

Hemodynamic Effects of Intravenous Fat Emulsion plus Standard Therapy in a Model of Severe Verapamil Toxicity

Hemodynamic Effects of Intravenous Fat Emulsion in an Animal Model of Severe Verapamil Toxicity Resuscitated with Atropine, Calcium, and Saline

Hemodynamic Effects of Intravenous Fat Emulsion in an Animal Model of Severe Verapamil Toxicity Resuscitated with Atropine, Calcium, and Saline

Hemodynamic Effects of Intravenous Fat Emulsion in an Animal Model of Severe Verapamil Toxicity Resuscitated with Atropine, Calcium, and Saline

Intravenous fat emulsion (IFE) decreases cardiotoxicity from several lipid-soluble drugs, including verapamil. To verify if the addition of IFE to the standard treatment of severe verapamil toxicity would improve hemodynamics and survival. Fourteen dogs were instrumented to measure systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), heart rate, cardiac output, central venous pressures, left ventricular pressure changes over time, mixed venous oxygen saturation, pH, and base excess. Verapamil toxicity, defined as a 50% decrease in MAP, was induced with verapamil at 6 mg/kg/hr and maintained for 30 minutes by titrating the verapamil infusion rate. Following verapamil toxicity, the verapamil infusion rate was changed to 2 mg/kg/hr and continued for 90 minutes. All dogs were resuscitated with atropine (0.04 mg/kg intravenously) and calcium chloride (15 mg/kg intravenously every 5 minutes for three doses) and then randomized to receive either IFE (7 mg/kg of 20%) intravenously or equivalent volumes of 0.9% normal saline over 30 minutes. Measurements were recorded for 120 minutes by investigators blinded to the treatment. Data were analyzed using analysis of variance, survival analysis, and log-rank test. Before the 30-minute IFE or normal saline infusion, there were no differences in hemodynamic parameters. After IFE or normal saline infusion, the IFE-treated group had higher MAP at 30 minutes (95% confidence interval [CI] = 5.6 to 44.7 mm Hg), 45 minutes (95% CI = 10.8 to 50.0 mm Hg), and 60 minutes (95% CI = 10.2 to 53.1 mm Hg). Kaplan-Meier 120-minute survival rate was 14% (95% CI = 0.5% to 53%) for the saline group as compared with 100% (95% CI = 59% to 100%) for the IFE group (p = 0.01). Standard resuscitation and IFE increase MAP and survival in an animal model of severe verapamil toxicity compared with standard resuscitation alone.

Effect of intravenous fat emulsion on lung function

Effect of intravenous fat emulsion on lung function

Effects of Intravenous Fat Emulsion on Respiratory Failure

The effects of intravenous fat emulsion on ventilated normal, diseased or distressed lungs were studied. Forty-eight patients with different types of respiratory failure were divided into four groups. Group A was composed of the patients with a normal lung condition; group B, patients with infectious pulmonary condition and respiratory failure; group C, patients with COPD and respiratory failure; and, group D was composed of the patients with ARDS due to various causes. Five hundred milliliters of 10 percent fat emulsion was infused within 4 h as partial parenteral nutritional support. We concluded that intravenous fat infusion decreased PaO2/FIO2 and increased P(A-a)O2 and intrapulmonary shunt in the patients with ARDS, while it had little effect on the patients with infectious pulmonary disease or COPD. The infusion of fat emulsion had positive effects on the patients with normal lung condition with increased PaO2/FIO2 and decreased P(A-a)O2 and shunt.

Intravenous Fat Emulsion Acutely Suppresses Neutrophil Chemiluminescence

The immediate effect of intravenous fat emulsion on neutrophil oxidant release was studied. Opsonized nonencapsulated S. aureus was used to stimulate neutrophil activity. Luminol enhanced chemiluminescence was followed over 15 min and recorded as peak output (P; mV), integral under the curve (I; V-sec) and rate of increase (R; mV/sec). Eighteen chronically ill patients receiving glucose based total parenteral nutrition were studied before and after a 4- to 6-hr test infusion of 500 ml of 10% fat emulsion. P decreased from 719 +/- 46 to 461 +/- 42 mV (p less than 0.001), I decreased from 169 +/- 17 to 111 +/- 12 V-sec (p less than 0.001) and R decreased from 6.9 +/- 1.0 to 4.0 +/- 0.6 mV/sec (p less than 0.001). Preincubation of normal whole blood with fat emulsion in vitro did not adversely affect chemiluminescence (11 studies), nor did incubation of normal neutrophils with patient postinfusion plasma (10 studies). We conclude that fat emulsion infusion acutely suppresses neutrophil chemiluminescence. The suppression is not a direct effect of the fat emulsion per se and is not due to inhibitory substances in the plasma following infusion.

Influence of intravenous fat therapy on tracheal effluent phospholipids and oxygenation in severe respiratory distress syndrome

T w o COMPLICATIONS related to intravenous fat infusion that are of particular importance in the very-low-birthweight infant with respiratory distress syndrome are delayed plasma clearance I and hypoxemia z during fat infusion. Conversely, essential fatty acid deficiency may be noted within the first week of life in these VLBW infants? '4 Recently Friedman and Rosenberg s reported an association between essential fatty acid deficiency and altered fatty acid composition of pulmonary surfactant phospholipids, suggesting that this alteration may diminish lung function and contribute to the pathophysiology of RDS. We assessed the effect of intravenous fat emulsions on the production of lung phospholipid and on oxygenation as related to serum lipid clearance in premature neonates with RDS.

Hemodynamic effects of intravenous 20% soy oil emulsion following coronary bypass surgery.

Because of its high caloric density, intravenous fat emulsions have been suggested as useful sources of calories and essential fatty acids in patients with serious heart disease in whom fluid restriction must be closely monitored. Previous studies in the experimental animal have suggested a myocardial depressant effect of intravenous fat emulsions at high infusion rates. In the present study, 19 adult patients, following uncomplicated isolated coronary artery bypass surgery, were divided into two groups. A constant infusion of 2 ml/min of soy oil emulsion (20% Intralipid) was administered to the first group. The second group received 20% Intralipid at 1 ml/min followed by a 2 ml/min infusion. In the group receiving the 2 ml/min infusion (averaging 5.25 mg/kg/min), significant decreases in cardiac output and increases in pulmonary capillary wedge pressure occurred. One patient suffered an adverse side effect which may have been related to myocardial ischemia. The second group of patients received an initial infusion of 1 ml/min (averaging 2.35 mg/kg/min) following which the rate was doubled. No significant hemodynamic changes or adverse side effects occurred in the second group. It is concluded that 20% soy oil emulsion can be administered safely to the recently postoperative cardiac surgical patient recovering from coronary bypass grafting, but the rate should not exceed the maximum clearance rate of 1 ml/min (2.67 mg/kg/min).

Effect of intravenous fat emulsion on experimental acute pancreatitis.

The known relationship of hyperlipidemia and pancreatitis raises the question whether intravenous fat emulsion is detrimental in acute pancreatitis. Pancreatitis was induced in 52 male Sprague-Dawley rats followed by placement of a jugular catheter which was anchored to the back with a Teflon button. The animals were placed NPO in metabolic cages and continuously infused, initially with normal saline. The 37 animals surviving 24 hr were randomly assigned to group I (mean iv intake: glucose 222 kcal/kg/day; amino acids 13.1 g/kg/day) or group II (glucose 191 kcal/kg/day; intravenous fat emulsion 10% 47 kcal/kg/day; amino acids 12.9 g/kg/day). Nine animals were eliminated from the study because of mechanical problems leaving 14 in each group for analysis. Per cent survival on days 3, 5, and 7 was 64, 50 and 36 in group I, and 50, 36 and 36 in group II. Mean urinary amylase excretion was 244 +/- 185 units/day in group I and 262 +/- 127 units/day in group II. There was no significant difference in survival or urine amylase excretion nor in pancreatic histology or gross appearance of the animals between the two groups. In this model of acute pancreatitis, intravenous fat emulsion was not detrimental as measured by survival, urinary amylase excretion, and pancreatic histology.

The effect of intravenous fat emulsions in patients with pancreatic fistula

The effect of intravenous fat emulsions in patients with pancreatic fistula

Effect of intravenous fat emulsion of pentobarbital-induced sleep time in rats.

SummaryA 10% soybean oil emulsion (Intralipid) when given intravenously was found to prolong pentobarbital-induced sleep time in rats. The prolongation of sleep time was dose and time dependent. Heparin increased the clearance of Intralipid emulsion from the plasma and decreased the amount of time by which sleep was prolonged. It was further demonstrated that pentobarbital anesthesia decreased the clearance of intravenously administered Intralipid emulsion from the plasma. Thus, a reciprocal interaction was observed whereby pentobarbital prolonged the half-life of Intralipid emulsion and Intralipid emulsion prolonged the narcosis induced by pentobarbital.

Acute hemodynamic effects of intravenous fat emulsion in dogs.

An intravenous infusion of Intralipid-10% was observed to exert a negative inotropic effect on left ventricular performance in a canine isovolumetric left heart preparation. There was no effect on diastolic compliance, however. Intravenous fat emulsion also produced significant decreases in systemic vascular resistance. The mechanism of these actions has not been elucidated, but it is postulated that free fatty acid (FFA) components or their metabolites directly affect the contractile properties of both myocardium and smooth muscle. These results suggest that until suitable clinical studies can be obtained, caution should be exercised in administering intravenous fat emulsions, particularly at maximum rates of infusion or in conjunction with sodium heparin in patients with known cardiac dysfunction.

Acute hemodynamic effects of intravenous fat emulsion in dogs

Acute hemodynamic effects of intravenous fat emulsion in dogs

Effect of free fatty acid on the oxygen consumption of perfused rat heart.

Effect of free fatty acid on the oxygen consumption of perfused rat heart.

Effect of Intravenous Fat Emulsions on Human Blood Viscosity

Because intravenous fat emulsions are now frequently employed as nutritional supplements and because a relationship between increased viscosity and thrombosis has been suggested, 1 it appeared important to determine whether these substances increase blood viscosity in human beings. Swank 2 has demonstrated marked changes in the viscosity of blood following intravenous administration of lipids to dogs and after ingestion of large quantities of fat by hamsters. 3 His studies were not extended to man. In order to assess the effect of injected fat emulsions on the viscosity of circulating blood, an in vivo technique of measuring viscosity 4 was utilized. Method The method of determining blood viscosity employed in the present study is based on Poiseuille's law that during laminar flow of a homogeneous fluid in a tube of constant diameter the frictional loss bears a linear relationship to the volumetric rate of flow and is independent of the vessel

Effect of intravenous fat emulsions on human blood viscosity

Because intravenous fat emulsions are now frequently employed as nutritional supplements and because a relationship between increased viscosity and thrombosis has been suggested, 1 it appeared important to determine whether these substances increase blood viscosity in human beings. Swank 2 has demonstrated marked changes in the viscosity of blood following intravenous administration of lipids to dogs and after ingestion of large quantities of fat by hamsters. 3 His studies were not extended to man. In order to assess the effect of injected fat emulsions on the viscosity of circulating blood, an in vivo technique of measuring viscosity 4 was utilized. Method The method of determining blood viscosity employed in the present study is based on Poiseuille's law that during laminar flow of a homogeneous fluid in a tube of constant diameter the frictional loss bears a linear relationship to the volumetric rate of flow and is independent of the vessel

Metabolic Effect of Fat Emulsion

The effect of intravenous fat emulsion on nitrogen, potassium, sodium, and chloride metabolism was studied in four subjects, using the balance technic. It is concluded that fat emulsion promotes nitrogen and potassium retention in some patients, but that in other patients administration of fat emulsion under similar circumstances may be associated with excess nitrogen losses. Comparison of oral and intravenous feeding failed to demonstrate any difference in nitrogen metabolism, and it is concluded that the two methods are equivalent. Attention is directed to the fact that sodium and chloride retention may be associated with administration of intravenous fat.

Intravenous fat as supportive therapy after severe injuries

A total of 302 units of a commercially prepared fat emulsion was given to twenty-eight patients. During five of the infusions, reactions such as nausea, chills and urticaria occurred. These were very minor and the patients showed no untoward effects when reinfused with fat emulsion on the following day. After eighteen infusions in various patients a benign rise in temperature to above 100.6 ° f. was noted. Only one patient showed a serious response. This consisted of jaundice after twenty-four infusions. At the present time it appears that moderate quantities of fat emulsion are safe for clinical use, but large quantities may evoke a severe response. Interference with liver function and the coagulation mechanism after intravenous fat emulsion infusions over a prolonged period is the primary problem requiring further study. Metabolic balance studies were carried out on several patients. Data on six typical patients show the protein-sparing effect of intravenous fat emulsion. This preparation appears to be a useful adjunct in injured patients and other patients who are unable to take adequate calories by mouth.