Intralipid Therapy Research Articles

Intralipid infusion therapy as an adjunct treatment in women experiencing adenomyosis-related infertility.

Currently, there is some evidence that adenomyosis patients using gonadotropin-releasing hormone (GnRH) agonist long downregulation (LDR) prior to embryo transfer may improve in vitro fertilization (IVF) success rate, but not to the baseline expected success where there is no adenomyosis. Given the association between adenomyosis and an aberrant endometrial immune environment, many physicians also use prednisolone or Intralipid adjuvant treatments in combination with GnRH agonist therapy, despite neither being of proven benefit. The purpose of this study was to investigate whether the addition of prednisolone or Intralipid immune therapy to GnRH agonist LDR improves fertility outcomes in patients with adenomyosis. This is a retrospective cohort study of 116 consecutive adenomyosis patients who underwent their first transfer of a genetically screened euploid embryo between January 2019 and December 2020 at a private IVF clinic. There was no difference in maternal age, body mass index, number of embryo's transferred and gravidity or parity among the three treatment groups. Patients who received Intralipid had a poorer prognosis with a longer duration of infertility (4 years) and a higher number of previous embryo transfers (ETs, 5 previous ETs) compared to the comparison groups. Logistic regression analysis adjustment for all covariates revealed that LDR plus Intralipid therapy produced significantly higher live birth rates (LBRs; 60%) compared to LDR alone (40% LBR); yet, the addition of prednisolone to GnRH agonist LDR (30% LBR) provided no additional live birth benefit. In this retrospective analysis, we showed Intralipid adjuvant treatment in combination with GnRH agonist therapy in adenomyosis patients undergoing IVF resulted in a LBR expected in women without adenomyosis using preimplantation genetic testing screened embryos. This benefit was not seen when using prednisolone as an adjuvant to GnRH agonist LDR. Future randomized clinical trials will be required to confirm the therapeutic benefit of Intralipid in combination with GnRH agonist therapy.

Efficiency of intravenous therapy with Intralipid fat emulsion in patients with early reproductive loss

BACKGROUND: Immune mechanisms play a leading role in the pathogenesis of early reproductive loss. Modern methods of regulating disorders of immune homeostasis to overcome infertility and recurrent miscarriage include immune-efferent therapies such as immunocytotherapy, plasmapheresis, and intravenous administration of immunoglobulins and fat emulsions. Intralipid is the gold standard of the first generation parenteral fat emulsion that reduces the cytotoxicity of NK cells. In the literature, there are opposite data on the effectiveness of Intralipid fat emulsion in repeated implantation failure. This may be due to indications for its appointment and the choice of criteria for evaluating the effectiveness of this therapy.
 AIM: The aim of this study was to evaluate the effect of Intralipid therapy on the onset of pregnancy in patients with a history of early reproductive loss.
 MATERIALS AND METHODS: This prospective cohort study was conducted in Saint Petersburg, Russia in 20182021 and included 97 patients with a history of early reproductive loss (recurrent pregnancy loss or repeated In Vitro Fertilization failures). Patients were randomized into two study groups. The first group consisted of 41 women with Intralipid therapy, and the second group comprised 56 women without this therapy. Patients of the first group received 200 ml of Intralipid 20% (intravenous fat emulsion) once a month for three consecutive months before pregnancy. Inclusion criteria were ages 18 to 40 years, two cases of reproductive failure (pregnancy loss up to 12 weeks and / or unsuccessful In Vitro Fertilization attempts), and normal spouse karyotypes. Exclusion criteria were miscarriage due to fetal chromosomal abnormalities diagnosed by curettage and histopathological examination of products of conception from miscarriages, anatomical anomalies in the development of the genital apparatus, abnormal spouse karyotypes, and soy protein allergy. We evaluated anamnesis data and immunological parameters (functional activity of NK cells in peripheral blood before and after treatment). The efficacy of therapy was judged by the onset of pregnancy.
 RESULTS: The Mann Whitney U-test showed the difference in the levels of NKT cells before and after treatment with fat emulsions (p = 0.0076), this parameter decreasing 1.846 times compared to control. Clinical pregnancy in patients treated with Intralipid occurred twice as often compared to patients who did not receive fat emulsion therapy: 59.3% (n = 19) vs. 27.6% (n = 13), respectively (p = 0.0048).
 CONCLUSIONS: Intralipid fat emulsion increases pregnancy rates by decreasing NKT cells in women with early reproductive loss.

KALİTELİ EMBRİYO TRANSFERİNE RAĞMEN BAŞARISIZ IVF SİKLUSU OLAN KADINLARDA İN VİTRO FERTİLİZASYON (IVF) TEDAVİSİ BOYUNCA İV LİPİD (SMOFLIPID®) KULLANIMININ ETKİSİ: VAKA KONTROL ÇALIŞMASI

Objectives: Since recurrent implantation failure (RIF) is a challenging fact, effects of different therapeutic immunomodulatory agents are being investigated to overcome this problem. This study aimed to evaluate the effect of intralipid on pregnancy outcomes of IVF patients with RIF.
 Methods: 116 of the participants who received only the short antagonist protocol allocated in the control group, whereas 106 patients were in intralipid group by additionally receiving intravenous lipid (SMOFlipid®). Intralipid was given on the day of embryo transfer, on the day of positive pregnancy test and continued weekly until the tenth week of pregnancy. Implantation rate, biochemical pregnancy rate, clinical pregnancy rate and live birth rate were evaluated.
 Results: The positive pregnancy test, clinical pregnancy rate and live birth rate were statistically significantly higher (p0.05).
 Conclusions: This study revealed that intralipid therapy has better pregnancy outcomes in patients with RIF compared to patients undergo standard IVF protocol only. Further prospective studies are needed to suggest the routine use of intralipid in patients with RIF.

Correlation of TNF-α, IFN-γ and TGF-β Expression with In-vitro Fertilization Success Rates in Women with Recurrent Implantation Failure Undergoing Treatment with Intra-lipid Infusion

This study aimed at assessing the correlations between gene expression of TNF-α, IFN-γ, TGF-β in peripheral lymphocytes from women suffering from repeated implantation failure before and after intravenous Intra-lipid (IL) therapy, and correlation between changes in gene expression with IL infusion and success rate of IVF cycles. Twenty-three women complaining of unexplained infertility without history of autoimmune disorders, or immunodeficient diseases were included. All women included aged <40 years, BMI <28 with history of recurrent IVF cycles failure, seeking medical advice for new IVF trial. All were average responders to induction of ovulation (≥5 oocytes in each cycle) with good quality embryos transferred to uterus at proper time. Included women received 200 ml of 10% IL slowly intravenous. Two venous blood samples were taken from all candidates, one before IL infusion and the second was at day of embryo transfer. The current study detected a significant reduction of expression in TNF-α and increased expression of TGF-β, while non-significant reduction in expression of IFN-γ after treatment. Significant associations between reduction of TNF-α, IFN-γ expression and positive clinical and ongoing pregnancy were observed, while increased TGF-β expression was associated with only positive ongoing pregnancy. In conclusion, IL therapy might have a positive impact on IVF pregnancy rates via alterations in peripheral cytokines expression mainly reduction of TNF-α mRNA expression and increased TGF-β mRNA expression.

P–375 Intralipid supplementation in women with unexplained recurrent implantation failure and elevated uterine natural killer cell levels - A randomized placebo controlled trial

Abstract Study question Does intralipid supplementation in women with unexplained recurrent implantation failure (RIF) with elevated uterine natural killer cell (uNK) levels improve pregnancy outcomes during IVF? Summary answer Intralipid supplementation appears to improve clinical pregnancy rate in women with unexplained RIF with elevated uNK cell levels. What is known already The increased numbers of uNK cells in peri-implantation endometrium have been reported in women with recurrent miscarriage (RM) and RIF after IVF. However, reports are contradictory when it comes to correlation of increased numbers of uNK cells with pregnancy outcome. Current opinion suggests there is a potential for intralipid therapy in improving reproductive outcome, although data on live birth rate is very limited. No studies have assessed the effect of intralipid on IVF outcomes in RIF women based on elevated uNK cells. Identified studies have all used pNK cell testing as preferred diagnostic tool for analysis of NK cell levels. Study design, size, duration A randomized placebo controlled trial was conducted at Division of Reproductive Medicine at tertiary care institute. Thirty women with RIF and fifty fertile controls with age <35 years having regular menstrual cycles and no hormonal treatment in last 3 months were enrolled in the study from January 2019 to December 2020 for uNK cell testing. Randomization was done using random numbers and sealed envelopes. Only the subjects were masked and allocation concealment was done. Participants/materials, setting, methods Subjects included RIF 20–35 years, normal ovarian reserve, unexplained and tubal factors, normal karyotype and normal uterine cavity. Cut off for uNK cells was derived from fertile controls by immunohistochemical staining of CD56+ cells from midluteal endometrial biopsy sample. Subjects with elevated uNK cell levels were randomized during IVF to group A (Intralipid) or group B ( saline ). The infusion was repeated within one week of positive pregnancy test and then every 2 weeks. Main results and the role of chance The mean age and BMI were comparable between fertile control and study group(29.45±3.3 vs 31.17±3.3 years, 22.97±1.89 vs 23.21±2.2 kg/m2 ;p>0.05). The median uNK cell levels was 7%(used as cut off) in fertile controls and 13.5% in RIF. 18 women (60%, 18/30) with RIF who had elevated uNK cell level (>7%) were randomized. Four women were lost to follow up. The median age, BMI, number of previous failed cycles and duration of infertility were comparable between Group A(n = 7) and Group B(n = 7){30(IQR:27–31) vs 33(IQR:30–34)years, 22.7(IQR:21.08–24.4) vs 22.6(IQR:21.37–24.2)kg/m2, 2(IQR:2–3) vs 2(IQR:2–3), 8(IQR:7–8) vs 8(IQR:7–10)years}. The median FSH, AMH and AFC were 5.86(IQR:5.13–7.67)mIU/l, 2.4(IQR:2.16–6.12)ng/ml, 10(IQR:8–12) in Group A which were comparable with Group B {6.2(IQR:4.78–6.5)mIU/l, 4.8(IQR:2.67–6.25)ng/ml, 12(IQR:12–16) }. All patients underwent antagonist protocol. The clinical pregnancy rate was 57.14%(4/7) in group A which was significantly higher as compared to 28.6%(2/7) in group B(p < 0.05). None of the patients reported any side effects due to intralipid. Limitations, reasons for caution The limitation of present study is its small sample size. However, the study is currently recruiting more RIF patients, and these are the interim results of the same. More RCTs with larger sample size are required to assess the efficacy of intralipid in this specific subset of population. Wider implications of the findings: The present study suggests the beneficial effect of intralipid in women with unexplained RIF with elevated uNK cell levels in increasing the chemical and clinical pregnancy rate. However, ongoing pregnancy rate and live birth rate should be investigated further in this subset of population. Trial registration number CTRI/2019/01/017213

Intralipid therapy and adverse reproductive outcome: is there any evidence?

Controversy exists regarding the benefits of intravenous intralipid therapy in patients with a poor reproductive history. It is frequently reported that there is no evidence to support the effectiveness, utility or safety for this treatment. While individual studies may be perceived as weak, a systematic review and meta-analysis were performed to determine if there is any advantage to patients. PubMed, Embase and Scopus searches were performed with the target populations being either recurrent pregnancy loss (RPL), or recurrent implantation failure (RIF) undergoing assisted reproductive technology (ART) and receiving intralipid infusions. These cohorts were compared with either placebo, no intervention or alternative treatments. The most relevant outcome measures were considered to be clinical pregnancy rate (CPR), live birth rate (LBR), implantation rate (IR) and miscarriage rate (MR). Twelve studies encompassing 2676 participants met the criteria for selection and were included and reviewed. Treatment of the target population with intralipid led to an improvement in IR (Odds Ratio (OR): 2.97, 2.05–4.29), pregnancy rate (OR: 1.64, 1.31–2.04), and LBR (OR: 2.36, 1.75–3.17), with a reduction in MR (OR: 0.2, 0.14–0.30). Although intravenous intralipid is not recommended as a routine treatment for recurrent miscarriage or implantation failure, there is enough data to suggest consideration in selected patients where routine testing is unremarkable, standard treatments have failed and immunological risk factors are present. The presence of abnormal uterine natural killer (uNK) cells needs more study as a target marker to determine those who could benefit.Lay summaryThere is controversy regarding the benefits and efficacy of intravenous intralipid therapy in patients with a poor reproductive history. It is frequently reported that there is no credible evidence to support their use. A situation we frequently face as medical professionals is patients asking us to consider immune therapy (such as intralipid) for reproductive failure where good quality embryos have been used. Intralipid infusions have been reported to improve pregnancy rates with IVF, and reduce the miscarriage risk in selected patient groups, but study results are not universally accepted. We have performed a detailed review and analysis of the literature to determine if there is any benefit to this immune treatment in specific patient groups. Our paper identified and analyzed 12 studies, finding that treatment with intravenous intralipid leads to an improvement in implantation, pregnancy and live birth rates, with a decrease in miscarriage rate. This study shows that there is evidence to suggest consideration of intralipid in certain patients where standard treatments have failed.

P61: Intralipid therapy for recurrent implantation failure and recurrent pregnancy loss patients with elevated NK cell activity

P61: Intralipid therapy for recurrent implantation failure and recurrent pregnancy loss patients with elevated NK cell activity

Intralipid therapy for unexplained recurrent miscarriage and implantation failure: Case-series and literature review

IntroductionIn retrospective cohort study of women with unexplained recurrent implantation failure (RIF) and miscarriage (RM), we analyzed the efficacy and safety of intralipid therapy to obtain a live birth. Patients and methodsWomen with unexplained RM and/or RIF were included from 2015 to 2018 from three French university hospitals. ResultsAmong 187 women treated for unexplained recurrent miscarriages and implantation failures, 26 women with median age of 36 years (29−43) received intralipid therapy. Among these 26 women, 10 women with a median age of 33 years (31−40) had a history of spontaneous recurrent miscarriages, with a median of 5 (4–8) previous miscarriages. Live births occurred in 7 (70 %) pregnancies under intralipids and were significantly more frequent than in women with recurrent miscarriages who did not receive intralipid therapy (n = 20, p = 0.02). Age, number of previous miscarriages, and additional therapies did not significantly differ between the two groups. Among the 26 included women, 16 had a history of recurrent implantation failures, with median age of 37 years (29−43) and median 9.5 (3–19) embryo transfers. Clinical pregnancy occurred in 9 (56 %) women receiving intralipids after embryo transfers under intralipids among which 5 (55 %) resulted in a live birth. Comparing successful pregnancies under intralipids with those with fetal loss, no significant differences have been noted. ConclusionIntralipids could be an effective and safe therapy in women with unexplained recurrent miscarriages and infertility.

Effect of empiric intravenous intralipid therapy on pregnancy outcome in women with unexplained recurrent implantation failure undergoing intracytoplasmic sperm injection-embryo transfer cycle: a randomized controlled trial

To evaluate the effect of empiric intralipid infusion therapy on pregnancy outcomes for patients with unexplained recurrent implantation failure (RIF) undergoing intracytoplasmic sperm injection (ICSI). A total of 142 patients with a history of unexplained RIF (3 or more cycles) were included in this randomized controlled trial. Patients were randomized into two groups, study group (n = 71) and control group (n = 71). The study group received intralipid 20% infusion on the day of embryo transfer (ET) and a second dose on the day of pregnancy test. The clinical pregnancy rate in the study group was 36.6% (n = 26) compared to 28.2% (n = 20) in the control group (OR 1.47, CI 0.72–2.98, p = .282). The live birth rate in the study group was 18.3% (n = 13) and 14.1% (n = 10) in the control group (OR 1.37, CI 0.55–3.36, p=.49). No side effects of intralipid therapy were reported in the study period. There was improvement in the pregnancy rate among women with unexplained RIF who received empiric intralipid infusion therapy; however, this improvement did not reach statistical significance.

Case Study: Local Anesthetic Toxicity After Bier Block. Was intralipid Therapy the Correct Remedy

Introduction: Intralipid therapy is recommended for patients with local anesthetics like bupivacaine, but it is not advisable for patients with short acting local anesthetic toxicity like lidocaine.

The Effect of Intradialytic Intralipid Therapy in Pediatric Hemodialysis Patients

Growth of children on maintenance hemodialysis is poor. Oral nutritional supplements are the preferred way to augment nutrition; however, many children have difficulties adhering to prescribed oral supplements. In our unit, we have been utilizing intralipid (IL) therapy as nutritional supplement during hemodialysis sessions. The aim of this study was to assess the safety, efficacy, and benefits of intradialytic IL therapy. A retrospective chart review. Fifteen pediatric hemodialysis patients receiving intradialytic IL therapy for at least 3months from July 2011 through July2014. For each patient, anthropometric measurements and laboratory nutritional parameters were compared prior to and at the end of IL therapy. Anthropometric measurements evaluated were dry weight, height, body mass index (BMI), and BMI corrected for height age. Laboratory nutritional parameters evaluated were albumin, normalized protein catabolic rate, predialysis blood urea nitrogen, transferrin, cholesterol, and triglyceride levels. Adverse events during therapy were also noted. Significant improvement was noted in albumin levels, predialysis blood urea nitrogen, and normalized protein catabolic rate during therapy (P=.02; P=.03; P=.03, respectively). Six patients (37.5%) improved their weight standard deviation score, and eight patients (50%) improved their BMI standard deviation score though not statistically significant (P=.59; P=.9, respectively). No significant side effects were noted. Administration of IL alone during hemodialysis is well tolerated with beneficial effects on nutritional parameters. The provision of IL alone is relatively cheap and does not require additional resources. In conjunction with other measures of nutritional support, it can help improve nutritional status of pediatric hemodialysis patients.

Comparison of the Effects of Intralipid 10% and 20% on Peripheral Catheter Ablation in a Pediatric Intensive Care Unit

Background: Energy deficit is a common and serious problem in pediatric intensive care units. Parenteral nutrition, either alone or in combination with enteral nutrition, can improve nutrient delivery in critically ill patients by preventing or correcting the energy deficit and improving the outcomes. Intralipid 10% and 20% are lipid emulsions, widely used in parenteral nutrition. Despite several clinical advantages, intravenous Intralipid therapy has been associated with several complications.In this study, we aimed to investigate the effects of Intralipid 10% and 20% on peripheral intravenous catheter ablation in children receiving Intralipid in a pediatric intensive care unit. Methods: In this observational study, 96 patients were recruited through simple non-random sampling over six months. In total, 48 patients received intravenous Intralipid 10%, while 48 patients were administered Intralipid 20% as part of their parenteral nutrition plan. Through separate peripheral intravenous catheters, 0.5-3 g/kg/day of Intralipid was administered at an infusion rate of 0.5 g/kg/h. Length of hospital stay and intravenous catheter ablation were compared between the two groups. Results: Age of the patients ranged between two days and eight years. Esophageal atresia was the most common condition among patients receiving intravenous Intralipid infusion (8.3%). The mean duration of catheter survival was significantly shorter in patients receiving Intralipid 20% (28.77 vs. 68.23 h, P<0.001), while length of hospital stay was not significantly different between the two groups (P=0.48). Conclusion: Based on the findings, concentration of Intralipid infusion in pediatric patients, receiving parenteral nutrition, might be associated with intravenous catheter ablation.

Intravenous intralipid therapy is not beneficial in having a live delivery in women aged 40-42 years with a previous history of miscarriage or failure to conceive despite embryo transfer undergoing in vitro fertilization-embryo transfer

Purpose: To evaluate the efficacy of intralipid intravenous infusion in achieving a live pregnancy following IVF – embryo transfer in women of advanced reproductive age (40-42 years). Materials and Methods: A matched control was performed. Women aged 40-42 with a previous history of miscarriage or who failed to conceive despite previous embryo transfer who entered an IVF program were offered intravenous intralipid therapy (four ml of 20% liposyn II in 100 ml normal saline over one hour) during the mid-follicular phase. Clinical pregnancy rates (eight weeks with viable gestation) and live delivered pregnancy rates were then determined and compared. Results: The results were evaluated after ten matched cycles. There were no clinical pregnancies in those receiving intralipid vs. a 40% clinical and a 30% live delivered pregnancy rate in the untreated controls (p = 0.087, Fisher’s exact test). The study was terminated because of these preliminary data. Conclusions: In the test tube, adding intralipid to natural killer cells can inhibit their cytolytic action. However, the use of intravenous intralipid to suppress natural killer cell activity does not seem to improve the chance of a live delivery in women aged 40-42 years with a previous history of miscarriage. In fact this therapy may actually be detrimental in this age group. Since efficacy of this therapy was not found in a group of advanced reproductive age, it is not clear why this should be effective for a younger population. A controlled study for the younger group is needed. Perhaps such a study could be limited to only those with miscarriage rather than also concluding failure to conceive despite embryo transfer. Intralipid failed to improve live delivered pregnancy rates in women with prior miscarriage or previous failure with embryo transfer.

Clinical applications of intravenous lipid emulsion therapy

Intravenous lipid emulsion (ILE; Intralipid) therapy, a standard treatment in local anesthetic toxicity, has demonstrated therapeutic efficacies for a number of different drug class-mediated toxicities. Some of these varied drug groups include antipsychotics, antidepressants, antiarrhythmics, and calcium channel blockers. To meet the objective of describing the growing number of indications for Intralipid therapy and any diverse effects and/or failures of Intralipid therapy in reversing multiple drug toxicities, we queried several Internet search engines with the key words "intravenous lipid emulsion therapy," "Intralipid," "lipid emulsion," and "local anesthetic systemic toxicity," resulting in the identification of 31 case reports for descriptive analysis. These case reports included 49 separate drug overdose cases involving ten separate drug classes which were successfully reversed with Intralipid. The education of clinicians regarding the beneficial and varied roles of Intralipid therapy in different clinical settings is warranted, particularly in terms of the potential for Intralipid therapy to reverse the toxicities of non-local anesthetic drugs.

Abstract #908: Intravenous Intralipid Therapy is Not Beneficial in Having a Live Delivery in Women Aged 40-42 with a Previous History of Miscarriage or Failure to Conceive Despite Embryo Transfer Undergoing in Vitro Fertilization-Embryo Transfer

Abstract #908: Intravenous Intralipid Therapy is Not Beneficial in Having a Live Delivery in Women Aged 40-42 with a Previous History of Miscarriage or Failure to Conceive Despite Embryo Transfer Undergoing in Vitro Fertilization-Embryo Transfer

Intralipid therapy for inadvertent peripheral nervous system blockade resulting from local anesthetic overdose.

Although local anesthetics have an acceptable safety profile, significant morbidity and mortality have been associated with their use. Inadvertent intravascular injection of local anesthetics and/or the use of excessive doses have been the most frequent causes of local anesthetic systemic toxicity (LAST). Furthermore, excessive doses of local anesthetics injected locally into the tissues may lead to inadvertent peripheral nerve infiltration and blockade. Successful treatment of LAST with intralipid has been reported. We describe a case of local anesthetic overdose that resulted in LAST and in unintentional blockade of peripheral nerves of the lower extremity; both effects completely resolved with administration of intralipid.

Abstract 287: 5-Hydroxydecanoate, a Mitochondrial Selective KATP Antagonist, Blocks the Rescue Action of Lipid Emulsion in Bupivacaine-Induced Cardiotoxicity

Introduction: Lipid emulsion (intralipid) rescues Bupivacaine-induced cardiac toxicity. We have shown previously that glibenclamide, a non selective ATP potassium channel blocker abolishes the rescue action of intralipid. Here we explored the role of 5-Hydroxydecanoate (5-HD), a mitochondrial selective KATP antagonist in the intralipid-mediated rescue of bupivacaine overdose. Methods: Young male Sprague-Dawley rats (300-350 g) were anesthetized intraperitoneally with a mixture of ketamine (80 mg/kg) and xylazine (8 mg/kg), and ventilated with a ventilator. M-mode echocardiography were acquired throughout the experiment. In protocol-1 (n=5), asystole was induced by a single injection of bupivacaine (10mg/kg over 20 seconds, intravenously) and resuscitation with Intralipid 20% (5ml/kg bolus, and 0.5ml/kg/min maintenance) with chest compression was started immediately. In protocol-2 (n=8) rats were pre-treated with 5-HD (5 mg/kg, IV) 30 minutes prior to inducing asystole with bupivacaine. In both protocols the heart rate (HR), ejection fraction (EF) and fractional shortening (FS) were measured before inducing asystole (baseline), and at 1, 5 and 10 min after lipid treatment. A two way repeated measure analysis of variance (ANOVA) model was used for comparison of means. Values are mean ± SEM, n=5 rats/group, p&lt;0.05 significant. Results: In protocol-1, the baseline HR and EF were 321±21 and 72.3±4.6%. Bupivacaine resulted in asystole and intralipid therapy improved the heart rate and cardiac function within 10 min(HR=86±13beats/min at 1min, 216±10beats/min at 5 min, and 228±14beats/min at 10 min). The left ventricular systolic function fully recovered in all rats within 5 min of intralipid treatment (EF=72±5%, FS=42±4%). In protocol-2, there were no significant differences between HR and EF before (HR=324.6±16.5 beats/min, EF=78.0±2.8%) and 30 min after (HR=340.9±15.6 beats/min, EF=83.3±2.0%) 5-HD adminstration. However, 5-HD (5mg/kg), prevented the intralipid-induced rescue of bupivacaine overdose, as there was no recovery within 10 min of intralipid therapy. Conclusions: Pre-treatment with 5-HD prevents the lipid rescue of bupivacaine-induced cardiotoxicity suggesting that mitochondrial KATP channels are involved.

Intralipid therapy does not improve level of consciousness in overdoses with sedating drugs: a case series.

To assess the effect of intralipid emulsion therapy (ILE) in sedating drugs presenting to an urban emergency department. Following the introduction of a clinical protocol for the use of ILE a retrospective chart review was undertaken, which describes the use of ILE in treating sedating drug overdose in a facility with a tertiary referral level clinical toxicology unit. Demographic data as well as details of drug ingested, physiological parameters and disposition were extracted from the medical record. Over a 7 month period nine cases were treated with intralipid, of which two were male and the median age was 33 years (17-52 years). Endotracheal intubation was required in seven cases and of the other two, one required a nasopharyngeal airway for several hours while being observed in a critical care area. One patient was managed in the intensive care unit without intubation. The median duration of ventilation in the seven patients was 31 h (22-82 h), and median length of stay for all nine cases was 63 h (24-133 h). This study does not support any clinically significant effect of intralipid in sedating drug overdose.

Abstract 220: Intralipid Fails to Rescue Bupivacaine-Induced Cardiotoxicity in the Presence of the Opioid Antagonist Naloxone

Introduction: Exogenous opioids such as morphine protect the heart against I/R injury. This action is mediated through opioid receptors as Naloxone, an opioid receptor antagonist, inhibits the cardioprotective effect of ischemic preconditioning. Here we explored the involvement of opioid receptors in lipid-mediated rescue of Bupivacaine-induced cardiac toxicity. Methods: Young male SD rats (300-350 g) were anesthetized with ketamine (80 mg/kg) and xylazine (8 mg/kg) and ventilated with a ventilator. The M-mode echocardiography and Electrocardiograms were acquired throughout the experiment. Asystole was achieved with a single injection of Bupivacaine (10mg/kg over 20 s, intravenously), and resuscitation with Intralipid (5ml/kg bolus, and 0.5ml/kg/min maintenance) along with cardiac massage was started immediately. Some rats were pre-treated with different doses of Naloxone (1 mg/kg, 10 µg/kg, 5 µg/kg and 1 µg/kg) 2 min prior to inducing asystole with Bupivacaine. Results: Administration of Bupivacaine resulted in asystole and Intralipid therapy improved the heart rate gradually within 10 min: 73.3±3.3 beats/min at 1min (23% recovery), 180±23 beats/min at 5 min (56% recovery), and 243±20 beats/min at 10 min (76% recovery, n=6). The left ventricular systolic function was also fully recovered in all rats within 5 min of lipid treatment as the ejection fraction (EF) and fractional shortening (FS) were similar to their baseline values (EF=70±3%, FS=40±3%, n=6)., Interestingly, Intralipid failed to rescue Bupivacaine overdose in rats pretreated with a high dose of Naloxone (1mg/kg) as there was no recovery of cardiac function within 10 min of lipid therapy (n=5). In rats pretreated with lower doses of Naloxone of 5 µg /kg and 10 µg /kg (n=4/group), the heart rate and cardiac function were partially recovered. Lowering the dose of Naloxone further to 1 µg /kg resulted in 76% recovery of the heart rate at 10 min. Complete recovery of the left ventricular systolic function was observed in this group within 10 min of lipid treatment as EF and FS were similar to their baseline values (EF= 73±3%, FS=43±3, n=4). . Conclusions: The opioid receptor antagonist Naloxone abolishes lipid rescue of Bupivacaine-induced cardiotoxicity in a dose-dependent manner.

Intralipid therapy for recurrent implantation failure: new hope or false dawn?

Recurrent embryo implantation failure (RIF) is a disorder with potentially devastating physiological and psychological manifestations for those affected. Although its prevalence is not uncommon, many of the mechanisms involved still require elucidation. Both organ-specific and systemic autoimmunity are associated with an increased prevalence of recurrent miscarriage and reproductive failure, rendering the role of the maternal immunological system in fertility a key concept. It is believed by some that central to this theme is the maternal cytokine profile, with particularly T-helper (Th) cells. Immune modulating therapies have therefore been mooted as potential therapeutic strategies. Recent reports of high pregnancy rates achievable in women with RIF have added fuel to the debate regarding the effectiveness of intralipid in modulating the immune system. We would like to assess if there is sufficient current evidence of acceptable quality to permit an assumption that intralipid therapy is an effective treatment for women undergoing repeated assisted reproduction cycles. We have concluded that appropriately controlled, large-scale, confirmatory studies are necessary to prove the efficacy of intralipid before it can be recommended for routine use.