Effects Of Intravenous Lipid Emulsion Research Articles

Survival following massive amitriptyline overdose: The use of intravenous lipid emulsion therapy and the occurrence of acute respiratory distress

While survival has been reported after ingestion of 4.25 g amitriptyline, for which intravenous lipid emulsion (ILE) therapy was administered, we recently managed a patient who made a full recovery after a 4.8 g amitriptyline overdose. Interesting features of the case were a marked response to ILE and the subsequent development of acute respiratory distress syndrome (ARDS). Our patient had taken 96 amitriptyline 50mg tablets (total 4.8 g or 80mg/kg), an uncertain amount of zopiclone, alcohol and venlafaxine. In the emergency department the patient was hypotensive and unresponsive (GCS 3), with a prolonged QTc identified on ECG. Rapid sequence induction was performed followed by transfer to the intensive care unit for full supportive therapy. Further management and key parameters are illustrated in Figure 1. Hypotension was unresponsive to fluid therapy, and noradrenaline therapy was required. Intravenous bicarbonate therapy and mild hyperventilation (with tidal volumes 6ml/kg) were utilised, aiming to achieve a pH of 7.55. Three grand mal seizures occurred which were treated with a midazolam bolus followed by an infusion. Approximately 12 h after the drug ingestion, with escalating noradrenaline requirements, ILE was administered. The subsequent improvement in blood pressure and reduction in noradrenaline can be seen in Figure 1. Case reports detailing the successful use of ILE for the treatment of toxicity of lipophilic drugs including tricyclic antidepressants are well documented. A recent prospective, randomised, controlled trial found no benefit of ILE compared to bicarbonate in a pig model of amitriptyline toxicity. A rabbit model found conflicting results. Various mechanisms have been suggested for the mechanism of action of ILE, but the lipid sink hypothesis describes how ILE may provide a large binding site for the drug, removing it from effective circulation. Given the pKa of amitriptyline of 9.4, prior alkalinisation, as was undertaken in this case, might be expected to augment the effect of ILE by decreasing the ionised portion of the drug. On day 3 of their care, our patient developed criteria of ARDS with a PaO2/FiO2 ratio of 70mmHg by day 5. Proning was required, tracheostomy was performed and a prolonged respiratory wean ensued with 40 days of invasive ventilation. There was no evidence of pulmonary aspiration at the scene of the overdose, during intubation or on the initial chest radiograph, though micro-aspiration cannot be excluded. Ultimately, Streptococcus pneumonia and mixed coliforms were grown from bronchoalveolar lavage of the patient’s lungs; however, concern was raised that ILE could have been linked to the ARDS. The patients subsequently made a full physical recovery. Acute respiratory distress syndrome has been reported in three patients in a case series of nine patients treated with ILE but, as the authors acknowledge, critically ill patients are at risk of ARDS. Furthermore, ARDS has been reported as a complication of tricyclic overdose. Nonetheless, case series into the use of lipid infusion in ARDS and septicaemia have linked it to worsening oxygenation. We believe this to be one of the highest reported overdoses of amitriptyline that has been survived and that the use of ILE contributed to this outcome. Our experience demonstrates the potential use of ILE outside the setting of cardiac arrest or cardiovascular collapse but highlights concerns regarding its potential association with ARDS.

Effect of Intravenous Lipid Emulsion Therapy on Serum Pseudocholinesterase in Experimental Model of Diazinon Intoxication

The aim of this study was to investigate the effect of intravenous lipid emulsion (20% lipid solution) on serum pseudocholinester ase in an toxication model of diazinon. Organophosphate poisoning has a different importance for individuals those admitted to the emergency service due to poisoning. The most commonly used organic phosphorus compounds are diazinon, malathion, and parathion. Intravenous lipid emulsion (ILE) treatment is used as a new treatment method in systemic toxicity cases caused by local anesthetics. Twenty-one male Wistar albino rats, (weighing 180–200 g) were randomly divided into three equal groups. Group I was control, while Group II was diazinon and Group III was diazinon + lipid emulsion treatment. Only 1 ml corn oil was given by gavage to the rats in Group I. A diazinon dose of 335 mg/kg was given by gavage to the rats in Group II. In addition to diazinon, a 20% lipid solution (3 ml/kg) was administered via tail vein to the rats in Group III. At the end of the experimental period, blood samples were taken from animals, and serum pseudocholinesterase levels were measured. When the pseudocholinesterase levels were analyzed, no significant difference was found between diazinon and diazinon + lipid emulsion treatment groups. However, a significant difference was found between control and the others (p < 0.05). In our study, there was no positive effect of lipid treatment detected on serum pseudocholinesterase. Toxication models with lower doses can be designed in future studies.

Evaluation of intravenous lipid emulsion on haloperidol-induced hypotension in rabbits

There are many reports on the effects of intravenous lipid emulsion (ILE) as an antidote in drug toxicity. Haloperidol (HAL) is a butyrophenone antipsychotic agent which is highly lipophilic. Hypotension is an important adverse effect of HAL administration and overdose. The aim of this study was to investigate the beneficial hemodynamic effects of ILE on acute HAL poisoning. We used six groups of five male rabbits. Two groups received aseptic distilled water intravenously followed by infusion of 18.6 ml/kg normal saline, as negative control group, or ILE 20% after 0.5 h. The third group received 18.6 ml/kg normal saline after HAL infusion (2.6 mg/kg). The other three groups received ILE 20% solution (6, 12, and 18.6 ml/kg) following HAL (2.6 mg/kg) administration. We measured blood pressure at 0, 0.5, 1, 2, 3, 4, 8, and 24 h after starting HAL administration, from left forelimb using a noninvasive method that was carried out automatically with a neonatal intensive care unit bedside monitor. ILE 20% at the dose of 18 ml/kg could return the reduced mean arterial pressure and diastolic blood pressure sooner than the other doses and normal saline. In conclusion, ILE could reverse HAL-induced hypotension same as the other lipophilic drugs. However, the clinical use of ILE for this purpose needs more evaluation to determine its exact indication and safety.

An in vitro analysis of the effects of intravenous lipid emulsion on free and total local anaesthetic concentrations in human blood and plasma.

Background. Intravenous lipid emulsion (ILE) is recommended as a “rescue” treatment for local anaesthetic (LA) toxicity. A purported mechanism of action suggests that lipophilic LAs are sequestered into an intravascular “lipid-sink,” thus reducing free drug concentration. There is limited data available correlating the effects of ILE on LAs. Aims. To compare the in vitro effect of ILE on LA concentrations in human blood/plasma and to correlate this reduction to LA lipophilicity. Method. One of four LAs (bupivacaine-most lipophilic-4 mg/L, ropivacaine-6 mg/L, lignocaine-14 mg/L, and prilocaine-least lipophilic-7 mg/L) was spiked into plasma or whole blood. ILE or control-buffer was added. Plasma was centrifuged to separate ILE and total-LA concentration assayed from the lipid-free fraction. Whole blood underwent equilibrium dialysis and free-LA concentration was measured. Percent reduction in LA concentration from control was compared between the LAs and correlated with lipophilicity. Results. ILE caused a significant reduction in total and free bupivacaine concentration compared with the other LAs. Ropivacaine had the least reduction in concentration, despite a lipophilicity similar to bupivacaine. The reduction in LA concentration correlated to increasing lipophilicity when ropivacaine was excluded from analysis. Conclusion. In this first in vitro model assessing both free- and total-LA concentrations exposed to ILE in human blood/plasma, ILE effect was linearly correlated with increasing lipophilicity for all but ropivacaine.

Evaluating the effects and safety of intravenous lipid emulsion on haloperidol-induced neurotoxicity in rabbit.

There are many reports on the effect of intravenous lipid emulsion (ILE) as an antidote in drugs related toxicities. We determined the effects of ILE on neurotoxicity of haloperidol (HA), a highly lipophilic antipsychotic, as a model of antipsychotics poisoning. We used six groups of five male rabbits. Two groups received distilled water intravenously followed by infusions of either 18 mL/kg of normal saline or ILE 20%, after 30 minutes. The third group received 18 mL/kg of normal saline after HA (2.6 mg/kg) administration. The three other groups received ILE 20% solution (6, 12, and 18 mL/kg) following HA injection. Catalepsy scores, temperature, pupil size, and mortality rate were measured at 0, 0.5, 1, 2, 3, 4, 8, and 24 hours after HA administration began. Blood and tissue samples were taken from all animals at 24 hours or at death time for biochemical, cell count, and pathological studies. ILE reversed cataleptic scores, miotic pupils, and hypothermia of HA intoxication much faster than normal saline (P < 0.001). Biochemical complications and mortality rate of the animals were significantly higher in the HA + 18 mL/Kg ILE group. ILE reversed sings of HA neurotoxicity; however, synergistic effect of high dose of ILE and HA increased complications and mortality.

Pretreatment With Intravenous Lipid Emulsion Reduces Mortality From Cocaine Toxicity in a Rat Model

We compare the effects of intravenous lipid emulsion and normal saline solution pretreatment on mortality and hemodynamic changes in a rat model of cocaine toxicity. We hypothesize that intravenous lipid emulsion will decrease mortality and hemodynamic changes caused by cocaine administration compared with saline solution. Twenty male Sprague-Dawley rats were sedated and randomized to receive intravenous lipid emulsion or normal saline solution, followed by a 10 mg/kg bolus of intravenous cocaine. Continuous monitoring included intra-arterial blood pressure, pulse rate and ECG tracing. Endpoints included a sustained undetectable mean arterial pressure (MAP) or return to baseline MAP for 5 minutes. The log-rank test was used to compare mortality. A mixed-effect repeated-measures ANOVA was used to estimate the effects of group (intravenous lipid emulsion versus saline solution), time, and survival on change in MAP, pulse rate, or pulse pressure. In the normal saline solution group, 7 of 10 animals died compared with 2 of 10 in the intravenous lipid emulsion group. The survival rate of 80% (95% confidence interval 55% to 100%) for the intravenous lipid emulsion rats and 30% (95% confidence interval 0.2% to 58%) for the normal saline solution group was statistically significant (P=.045). Intravenous lipid emulsion pretreatment decreased cocaine-induced cardiovascular collapse and blunted hypotensive effects compared with normal saline solution in this rat model of acute lethal cocaine intoxication. Intravenous lipid emulsion should be investigated further as a potential adjunct in the treatment of severe cocaine toxicity.

Promising effects of intravenous lipid emulsion as an antidote in acute tramadol poisoning

Promising effects of intravenous lipid emulsion as an antidote in acute tramadol poisoning

Effect of intravenous lipid emulsion in patients with acute glyphosate intoxication

Background. Although glyphosate intoxication has been considered minimally toxic in animals, severe toxicity has been observed in humans due to surfactant. We aimed to examine the potential therapeutic effects of intravenous lipid emulsion (ILE) on the patients with acute glyphosate intoxication. Methods. This study enrolled 64 glyphosate-intoxicated patients with allocation to two groups: those treated with ILE (ILE group, n = 22), and control patients treated with only supportive (conservative) care. Control patients were selected by matching for the amount ingested and time since ingestion. Twenty-two control patients were separately selected from the 42 patients receiving supportive care only. In ILE group, 20% lipid emulsion product was injected intravenously at the rate of 20 mL/h for the patients who ingested less than 100 ml of glyphosate. In the patients who ingested more than 100 ml of glyphosate, the loading dose was 500 ml for 2–3 h according to the status of the patients, followed by a maintenance dose of 1000 ml for the next 24 h. Results. Thirteen patients received high dose of ILE because the ingestion amount was more than 100 ml. None of the ILE group suffered from the complication of hypotension, while approximately 41% of the control group developed the complication. Additionally, arrhythmia was not observed in the ILE group. The incidence of mental change, respiratory failure, and acute kidney injury was similar between the two groups. Conclusions. ILE administration was associated with lower incidence of hypotension and arrhythmia in patients with acute glyphosate intoxication. ILE administration seems to be an effective treatment modality in patients who ingested sufficient amount of glyphosate herbicide that is expected to bring about significant toxicity.

Hypertonic sodium bicarbonate versus intravenous lipid emulsion in a rabbit model of intravenous flecainide toxicity: no difference, no sink

Context. The use of intravenous lipid emulsion (ILE) as an antidote in non-local, anaesthetic drug toxicity has generated considerable interest. Flecainide is a lipophilic anti-arrhythmic with a significant cardiotoxic profile, with blockade of sodium and potassium channels causing arrhythmias and shock in severe toxicity. ILE has been proposed as a treatment option in severe flecainide toxicity refractory to other modalities. Objective. We compared the effects of ILE and hypertonic sodium bicarbonate in a rabbit model of flecainide toxicity. Materials and methods. Twenty sedated and ventilated New Zealand White Rabbits received flecainide infusion titrated to a mean arterial pressure (MAP) of 60% baseline, which was defined as toxicity. The rabbits then received either sodium bicarbonate or ILE, and the flecainide infusion was reduced in an attempt to model ongoing enteric absorption. MAP and heart rate were recorded every minute for 15 min and plasma flecainide concentration was measured at toxicity and 15 min. ECG QRS duration was recorded at baseline, toxicity and at 5, 10 and 15 min post-toxicity. Results. No difference was observed in heart rate (p = 0.2804), MAP (p = 0.1802) or QRS duration (p = 0.7471) between groups. The immediate rate of rise in MAP was greatest in the bicarbonate group in the 5 min immediately post-toxicity. Conclusions. In this study, no differences were observed between an active control of hypertonic sodium bicarbonate and ILE for the primary endpoint of MAP at 15 min nor for QRS duration at any timepoint. There was a transient rapid increase in blood pressure seen in the sodium bicarbonate group that was not sustained. No increase was seen in blood concentration of flecainide in the ILE group, suggesting no ‘lipid sink’ for flecainide in this model. More research is warranted to define any role for ILE in flecainide toxicity.

An assessment of the in vivo effects of intravenous lipid emulsion on blood drug concentration and haemodynamics following oro-gastric amitriptyline overdose

Background. Overdose with lipophilic drugs, such as amitriptyline, may cause cardiotoxicity in overdose. Severe poisoning can be resistant to traditional treatments. Intravenous lipid emulsion (ILE) has been recommended as a novel therapy for the treatment of such overdoses; however, a little is known about the effects of ILE-infusion on drug concentration and haemodynamics in the early/absorptive phase after oral poisoning. Method. Thirty minutes after oro-gastric administration of amitriptyline (70 mg/kg), either 20% intravenous lipid emulsion (ILE), 8.4% sodium bicarbonate or Hartmann's solution was infused to anaesthetized and ventilated rodents (n = 10 per group). Heart rate, blood pressure, cutaneous ECG – QRS interval duration (QRS-d), and survival were serially recorded over 120 min. Blood drug concentrations were also collected during this period. Continuous variables were compared using one-way ANOVA. Results. ILE infusion significantly decreased the survival compared to other treatments (10% ILE vs 70% bicarbonate vs 70% Hartmann's solution, p = 0.005). There was a gradual prolongation of QRS-d and fall in blood pressure over time compared to baseline (T0) measurement for both ILE and Hartmann's solution treatments. This was associated with significantly increased blood AMI concentration with ILE treatment at T60, T90 and T120 min to the other treatments (p < 0.02). Conclusion. Administration of ILE early after oral amitriptyline overdose resulted in worse survival and no improvement in haemodynamics. In addition, blood amitriptyline concentrations were higher in the ILE-treated group. This suggests that either drug absorption from the gastrointestinal-tract was facilitated or drug redistribution was retarded when ILE was given early after oral poisoning.

Promising Effects of Intravenous Lipid Emulsion as an Antidote in Acute Tramadol Poisoning

In recent years, research has provided experimental and subjective evidence that intravenous lipid emulsions (ILEs) reverse some hemodynamically considerable poisonings with various drugs. The aim of this study was to investigate the possible antidotal effect of ILE on acute tramadol poisoning. Thirty male New Zealand rabbits weighing 2.5 to 3 kg were divided into 6 groups, 5 in each. Two groups were considered controls, and the rest were treated intravenously with a dose of 50 mg/kg of tramadol. Thirty minutes later, infusions of either ILE 20% (3 doses of 6, 12, and 18 mL/kg) or normal saline (dose of 18 mL/kg) were administered. The survival of animals, total seizure time, and hemodynamic parameters were monitored immediately after infusions and subsequently for 3 observations during 24 hours. Survival percentages at doses of 6 and 12 mL/kg of ILE were both 100% (P < 0.001), and 80% at a dose of 18 mL/kg (P < 0.01). Intravenous lipid emulsion reduced tramadol-induced tachycardia when administered within 30 minutes of poisoning (P < 0.01) and showed positive effects on normalizing mean arterial pressure and diastolic blood pressure (P < 0.05). However, ILE did not have major effect on systolic blood pressure. Intravenous lipid emulsion also prevented tramadol-related seizures in doses of 6 and 12 mL/kg (P < 0.001) and reduced elevated creatine phosphokinase levels with the 2 higher doses (P < 0.001). Intravenous lipid emulsion significantly reduced mortality due to acute toxicity with tramadol in rabbits, although increasing the ILE dose may cause reverse effects.

Effect of intravenous lipid emulsion on bupivacaine plasma concentration in humans

Intravenous lipid emulsion is the recommended treatment for severe local anaesthetic intoxication. Lipid emulsion may entrap lipid soluble drugs by functioning as a 'lipid sink', but its effect on bupivacaine pharmacokinetics remains unknown. In this randomised, double-blind, crossover study, eight healthy male volunteers were infused bupivacaine 0.5mg.kg(-1) intravenously over 20 min, followed by an infusion of either intravenous lipid emulsion or Hartmann's solution for 30 min. At 20 and 30 min after the start of the infusion, the total plasma bupivacaine concentration was lower while receiving lipid emulsion than Hartmann's solution (mean difference 111 (95% CI 55-167) μg.l(-1) and 75 (95% CI 26-124 μg.l(-1) at 20 and 30 min, respectively; p<0.02). However, there were no differences in un-entrapped (non-lipid bound) or free (non-protein bound) bupivacaine plasma concentrations during the infusion. Intravenous lipid emulsion infusion reduced the context-sensitive half-life of total plasma bupivacaine from 45 (95% CI 32-76)min to 25 (95% CI 20-33)min; p=0.01. We observed no significant adverse effects of lipid emulsion. In conclusion, lipid emulsion may slightly increase the rate of bupivacaine tissue distribution. No 'lipid sink' effect was observed with the non-toxic dose of bupivacaine used.

No Antidotal Effect of Intravenous Lipid Emulsion in Experimental Amitriptyline Intoxication Despite Significant Entrapment of Amitriptyline

Intravenous lipid emulsion has been used in the resuscitative treatment of intoxications caused by local anaesthetics and tricyclic antidepressants with seemingly beneficial results. We studied the effect of intravenous lipid emulsion on the plasma concentration of amitriptyline and haemodynamic recovery in a pig model of amitriptyline intoxication. Twenty pigs were anaesthetized (1% isoflurane in 21% O(2)) and given amitriptyline 15 mg/kg intravenously for 15 min. In random fashion immediately thereafter, either 20% lipid emulsion (ClinOleic(®), Lipid group) or Ringer's acetate (Control group) was infused for 30 min.; first 1.5 ml/kg for 1 min., followed by 0.25 ml/kg/min. for 29 min. The amitriptyline concentration in total and lipid-poor plasma and haemodynamic parameters were measured until 30 min. after the infusions. Lipid infusion prevented the decrease in plasma total amitriptyline concentration, resulting in a 90% higher (p < 0.001) total concentration and significantly (p = 0.014) lower free fraction of plasma amitriptyline in the Lipid group (1.1%) compared with the Control group (3.0%) at 30 min. Haemodynamic recovery from the intoxication as measured by heart rate, arterial pressure or cardiac output was similar in both groups. However, five pigs in the Lipid group and two pigs in the Control group died. In conclusion, a marked entrapment of amitriptyline by intravenous lipid emulsion was observed but this did not improve the pigs' haemodynamic recovery from severe amitriptyline intoxication. Care should be exercised in the antidotal use of lipid emulsion until controlled human studies indicate its efficacy and safety.

Local anaesthetic systemic toxicity treated with intravenous lipid emulsion: ineffective treatment or selection of an inadequate lipid rescue dose?

We thank Aveline et al.1 for their detailed account of central nervous system (CNS) toxicity following ultrasound-guided sciatic and saphenous nerve block using lidocaine and ropivacaine in a patient scheduled for hallux valgus surgery. They reported clinical signs compatible with systemic absorption of local anaesthetics and initiated treatment with 20% intralipid as 100 ml bolus doses 2 min apart. Unfortunately, this intervention was unsuccessful and general anaesthesia was required. The authors concluded that intralipid had been ineffective and suggested an interaction between local anaesthetic agents, intralipid, and carbamazepine treatment the patient was taking for trigeminal neuralgia, may have been a contributory factor. We agree that the patient exhibited local anaesthetic systemic toxicity (LAST) and wish to suggest possible explanations for the apparent failure of intralipid in this case. In their calculations of the local anaesthetic dose administered, the authors appear to have omitted the saphenous nerve component of their technique of 100 mg lidocaine, which, if included means the patient received a total dose of 400 mg or 7.02 mg kg−1 of plain lidocaine. The plasma lidocaine concentration of 2.3 μg ml−1, recorded 25 min after the block, is consistent with levels previously reported with injection of the same dose of lidocaine in the subcutaneous tissue of the abdominal wall.2 This would support the notion that LAST most likely represents systemic absorption from correctly placed peripheral nerve blocks rather than primarily from an intravascular injection. If the additive effect of the ropivacaine element of the block is taken into consideration in overall dose calculations,3 this may explain why CNS signs of LAST became apparent. Given the absence of significant cardiovascular, metabolic or electrolyte disturbance, all of which may have contributed to the severity of LAST, we agree that drug interaction may have been relevant in this case.4 All three drugs rely on protein binding of 75% or more for transport within the blood and all three are lipid soluble to varying degrees, with log P values for carbamazepine, lidocaine and ropivacaine of 2.73, 2.36 and 3.11, respectively. It is possible that competition for protein-binding sites between drugs resulted in a greater proportion of unbound local anaesthetics manifesting as systemic toxicity. Thus, for the lipid sink sequestration activity of intralipid to be fully effective, we consider this may have required administration of a proportionately larger volume of intralipid than usual. Previously intravenous lipid emulsion (ILE) has been reported to reverse LAST completely after presumed intravascular injection. We are aware of two published reports in which recovery from LAST occurred by early bolus administration of 20% intralipid followed by an infusion to a total volume of 500 ml.5,6 Although the time taken to restore a full level of consciousness did vary, in these cases the ILE reversed the LAST rapidly enough to avoid tracheal intubation. We advocate the early use of ILE but not as an alternative to safe local anaesthetic dosing and other appropriate resuscitation measures. Guidance for treatment of LAST has been posted on the Lipid Rescue website (http://www.LipidRescue.com) and elsewhere.7 For adults, these recommendations generally advocate an initial bolus dose of 100 ml (approximately 1.5 ml kg−1) 20% intralipid, followed by a rapid infusion of 400 ml over 20 min. Two further 100 ml boluses may be given and an infusion continued until signs of LAST have been reversed, if necessary continuing until a total volume of 12 ml kg−1 has been administered. We are curious as to why intravenous lipid treatment was suspended when only 200 ml had been given. Although we can only speculate at what might have happened had the volume of intralipid administered been bigger, this case is of value because it seems to confirm that the effects of ILE in the clinical setting are dose-dependent and perhaps the dose administered in this case was inadequate.

Effects of Intravenous Lipid Emulsions in Postoperative Patients

The essential nature of intravenous lipid emulsion (ILE) in preventing essential fatty acid deficiency in patients requiring parenteral nutrition (PN) is undisputed, and its role in providing a balanced caloric source is well recognized. These seemingly simple roles, however, mask the complex and competitive nature of fatty acid biochemistry. Different fat sources provide different fatty acid profiles and have the potential for distinct effects, both beneficial and adverse, throughout the body. Adverse effects attributed to the traditional soybean oil and soybean-safflower oil ILEs include hepatic, pulmonary, and immune system dysfunction. This has resulted in continued investigation into other fat sources

Evolution of Lipid Profile, Liver Function, and Pattern of Plasma Fatty Acids According to the Type of Lipid Emulsion Administered in Parenteral Nutrition in the Early Postoperative Period After Digestive Surgery

The metabolic effects of intravenous lipid emulsions (ILEs) used in parenteral nutrition (PN) depend on their fatty acid composition. Subjects in this prospective and randomized double-blind study were 28 adult patients post digestive surgery. PN was started after surgery and lasts for 5 days. Randomly, patients receive 1 of 4 different ILEs: medium-chain triglycerides/long-chain triglycerides (soybean oil; MCT/LCT), olive/soybean oil (oleic), long-chain triglycerides (soybean oil; LCT), and structured lipid. On days 0 and 6, serum liver function tests were analyzed for cholesterol, triglycerides, lipoproteins, and serum fatty acids. No differences were found in the 4 groups according to their gender, age, body mass index, diagnosis, baseline white blood cell, C-reactive protein, glucose levels, and other study parameters. Differential significant changes were not observed in any of the hepatic function parameters or plasmatic lipid levels between the groups. A significant decrease was observed in cis monounsaturated fatty acids (MUFAs) and a significant increase in omega-6 polyunsaturated fatty acids (PUFAs) and omega-3 PUFA values in LCT and structured groups compared with MCT/LCT and oleic groups, and a tendency for a decrease in trans fatty acids in the oleic and structured groups was found. All ILEs administered were safe and well tolerated. The changes in serum fatty acids reflected the pattern of fatty acids administered with different ILEs. The group receiving the olive oil emulsion achieved a fatty acid composition of serum lipids that could offer major therapeutic or biological advantages.

Effects of three intravenous lipid emulsions on the survival and mononuclear phagocyte function of septic rats

Objectives The immunosuppressive effects of intravenous lipid emulsions are a matter of great concern and debate. In a rat model of gram-negative bacteremia, we assessed whether the use of three intravenous lipid emulsions with different triacylglycerol compositions could influence mortality, bacterial clearance, and prostaglandin E 2 (PGE 2) levels and compared these groups with groups of orally fed rats and rats that received a small amount of calories in form of glucose without enteral feeding (starvation). Methods Rats were assigned to one of five groups: group 1 (control, n = 15) received rodent chow ad libitum and saline infusion; group 2 (starvation group, n = 12) had no access to chow and received an infusion of 5% glucose; group 3 ( n = 17) received total parenteral nutrition (TPN) with long-chain triacylglycerols; group 4 ( n = 12) received TPN with medium- and long-chain triacylglycerols; and group 5 ( n = 15) received TPN with its emulsion based on olive oil. Animals received isonitrogenous and isocaloric TPN. After 2 d of TPN, a dose of 10 8 colony-forming units of Escherichia coli was introduced via the venous catheter; 2 d later the animals were killed. Blood, spleen, liver, and lungs were cultured. Circulating levels of PGE 2 were measured. Results Bacterial growth in the liver and lungs were significantly higher in groups 3 and 4 than in group 1, with no differences among the other groups. Rates of bacteremia were significantly higher in groups 3 and 4 than in group 1, with no differences among the other groups. Plasma levels of PGE 2 did not differ, and mortality was unaffected. Conclusions Bacterial clearance clearly was preserved in orally fed, control rats when compared with rats on TPN with long-chain triacylglycerols or medium- plus long-chain triacylglycerols. However, the use of a lipid emulsion enriched intravenously with oleic acid was a valid way of reducing this disturbance, although plasma levels of PGE 2 and survival were not modified.

Effect of intravenous lipid emulsions on hepatic cholesterol metabolism.

Total parenteral nutrition offers the chance of survival to children who have had extensive gut resections or gut failure. However, in infants it is often associated with serious complications including cholestatic liver disease. The causes of these complications remain unclear, although it has been suggested that the lipid emulsions used in total parenteral nutrition may be responsible. An in vitro system was developed to study the effect of lipid emulsions on hepatic cholesterol metabolism using cultured hepatocytes. Incubations of Hep G2 cells with medium containing Intralipid (Pharmacia and Upjohn, Milton Keynes, UK) demonstrated that the fat emulsion mediated a powerful dose-dependent but reversible inhibition of cholesterol uptake. In addition Intralipid was shown to stimulate the efflux of cholesterol from Hep G2 cells. The component or components of the Intralipid responsible for these effects and the mechanism by which they act remain to be established. Intravenous lipid emulsions may interfere with hepatic cholesterol metabolism in vivo. This may have implications for the development of total parenteral nutrition-associated cholestasis in neonates.

Effect of intravenous lipid emulsions enriched with γ‐linolenic acid on plasma n‐6 fatty acids and prostaglandin biosynthesis after burn and endotoxin injury in rats MD KARLSTAD, SJ DEMICHELE, WD LEATHEM, ET AL University of Tennessee Medical Center, Knoxville, TN; Ross Products Division, Abbott Laboratories, Columbus, OH; New England Medical Center Hospitals, Tufts School of Medicine, Boston

Effect of intravenous lipid emulsions enriched with γ‐linolenic acid on plasma n‐6 fatty acids and prostaglandin biosynthesis after burn and endotoxin injury in rats MD KARLSTAD, SJ DEMICHELE, WD LEATHEM, ET AL University of Tennessee Medical Center, Knoxville, TN; Ross Products Division, Abbott Laboratories, Columbus, OH; New England Medical Center Hospitals, Tufts School of Medicine, Boston

A Historical Perspective and Review of the Safety of Lipid Emulsion in Pregnancy

Total parenteral nutrition for pregnant patients is essential to maintain or restore optimal nutritional status for both the mother and fetus when adequate protein and caloric intake by the oral or enteral route is not feasible. This report reviews the safety of intravenous lipid emulsions in total parenteral nutrition programs for pregnant patients. Controversy regarding the adverse effects of intravenous lipid emulsion when administered to pregnant patients is based on early reports of the use of cottonseed oil lipid emulsions. The adverse effects reported included infarction of the placenta, ketonemia, increased myometrial activity, and induction of labor. In 32 subsequent case reports in which soybean oil- or soybean/safflower oil-based emulsions were used in total parenteral nutrition programs for pregnant patients, there was no relationship apparent between onset of labor and harmful maternal or fetal effects associated with the administration of lipid emulsion. It appears that the currently available soybean and soybean/safflower lipid-based emulsions can be safely administered to pregnant patients.