Cardio Protective Effects of Lipid Emulsion against Ropivacaine-Induced Local Anesthetic Systemic Toxicity—An Experimental Study (original) (raw)
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Acta Marisiensis - Seria Medica
Introduction: Local Anesthetic Systemic Toxicity (LAST) is the most feared local anesthesia accident. As the cardiac arrest determined by LAST is mostly refractory to known resuscitation protocols, due local anesthetic blockade produced in the cardiac cells, the Lipid Emulsion (L.E) has been proved to be beneficial in resuscitating the cardiac arrest determined by local anesthetic. The aim for this presentation is to ease future studies on this topic, to ensure a starting point for next related research on LAST and LE mechanism of action. Method: Under genaral anesthesia we induced Local Anesthetic Systemic Toxicity to a rat model, by injecting Ropivacaine into the inferior vena cava. We monitored the cardiac activity of the subjects during the experiment. We used 4 groups of rats, control group- no intervention, lipid group- lipid emulsion was adminsitered, local anesthetic group- local anesthetic was administered and local anesthetic and lipid emulsion group- a dose of lipid emuls...
Lipid Emulsion for Local Anesthetic Systemic Toxicity
Anesthesiology Research and Practice, 2012
The accidental overdose of local anesthetics may prove fatal. The commonly used amide local anesthetics have varying adverse effects on the myocardium, and beyond a certain dose all are capable of causing death. Local anesthetics are the most frequently used drugs amongst anesthetists and although uncommon, local anaesthetic systemic toxicity accounts for a high proportion of mortality, with local anaesthetic-induced cardiac arrest particularly resistant to standard resuscitation methods. Over the last decade, there has been convincing evidence of intravenous lipid emulsions as a rescue in local anesthetic-cardiotoxicity, and anesthetic organisations, over the globe have developed guidelines on the use of this drug. Despite this, awareness amongst practitioners appears to be lacking. All who use local anesthetics in their practice should have an appreciation of patients at high risk of toxicity, early symptoms and signs of toxicity, preventative measures when using local anesthetics...
Systematic review of the effect of intravenous lipid emulsion therapy for local anesthetic toxicity
Clinical toxicology (Philadelphia, Pa.), 2016
Following national and regional recommendations, intravenous lipid emulsion (ILE) has become established in clinical practice as a treatment for acute local anesthetic (LA) toxicity, although evidence of efficacy is limited to animal studies and human case reports. A collaborative lipid emulsion workgroup was therefore established by the American Academy of Clinical Toxicology to review the evidence on the effect of ILE for LA toxicity. We performed a systematic review of the literature published through 15 December 2014. Relevant articles were determined based on pre-defined inclusion and exclusion criteria. Pre-treatment experiments, pharmacokinetic studies not involving toxicity and studies that did not address antidotal use of ILE were excluded. We included 113 studies and reports. Of these, 76 were human and 38 animal studies. One publication included both a human case report and an animal study. Human studies included one randomized controlled crossover trial involving 16 heal...
Lipid Emulsion for the Treatment of Local Anesthetic Toxicity: Patient Safety Implications
Anesthesia & Analgesia, 2008
is little question that the absolute, scientific "proof" of lipid emulsion's efficacy in reversing local anesthetic-induced cardiac arrest is yet lacking. Such a proof would require prospective, double-blind, placebo-controlled studies in humans, and such studies will thankfully never be performed, for obvious ethical reasons. However, when deciding on the patient safety implications of a novel, potentially life-saving, therapy, one must consider the tenuous and often unknown balance between the purported benefits and potential risks.
JA Clinical Reports, 2017
Background: A scalp block or wound infiltration of local anesthetic is thought to effectively control post-craniotomy pain. However, it can result in local anesthetic toxicity (LAST), which is difficult to distinguish from brain damage due to the surgical procedure when emergence from general anesthesia is delayed. Lipid rescue (infusion of a lipid emulsion) is a widely accepted treatment for LAST. Case presentation: A 64-year-old man underwent surgical resection of a glioma in the brainstem. While still under general anesthesia, and before suturing of the wound, he received a 20-mL scalp infusion of ropivacaine 0.75%. His emergence from anesthesia was delayed, his respiration was suppressed, and premature ventricular contractions occurred; all of which are symptoms of LAST. Injection of a 20% lipid emulsion rapidly alleviated these symptoms. Interestingly, the blood concentration of ropivacaine increased after lipid rescue. Conclusions: The increase in ropivacaine concentration in the blood after lipid rescue suggests that the intravenously administered lipid emulsion absorbed the ropivacaine from the intoxicated brain and heart tissue. This finding is consistent with the lipid sink theory as a mechanistic explanation of lipid rescue.
A review of local anesthetic cardiotoxicity and treatment with lipid emulsion
Local and Regional Anesthesia
Cardiovascular collapse from accidental local anesthetic toxicity is a rare but catastrophic complication of regional anesthesia. The long-acting amide local anesthetics bupivacaine, levobupivacaine and ropivacaine have differential cardiac toxicity, but all are capable of causing death with accidental overdose. In recent times, the chance discovery that lipid emulsion may improve the chance of successful resuscitation has lead to recommendations that it should be available in every location where regional anesthesia is performed. This review will outline the mechanisms of local anesthetic toxicity and the rationale for lipid emulsion therapy.
Use of lipid emulsion therapy in local anesthetic overdose
Saudi Medical Journal
The use of intravenous lipid emulsion (ILE) therapy as antidote in systemic toxicity of certain agents has gained widespread support. There are increasing data suggesting use of ILE in reversing from local anestheticinduced systemic toxicity severe, life-threatening cardiotoxicity, although findings are contradictory. Efficiency of ILE was demonstrated in animal studies in the treatment of severe impairment of cardiac functions, via a mechanism for trapping lipophilic drugs in an expanded plasma lipid compartment ("lipid sink"). In patients with hemodynamic compromise and/or cardiovascular collapse due to lipid-soluble agents, ILE may be considered for resuscitation in the acute setting by emergency physicians. The most common adverse effects from standard ILE include hypertriglyceridemia, fat embolism, infection, vein irritation, pancreatitis, electrolyte disturbances and allergic reactions. The advantages of ILE include an apparent wide margin of safety, relatively low cost, long shelf-life, and ease of administration.
Binding of Long-lasting Local Anesthetics to Lipid Emulsions
Anesthesiology, 2009
Background Rapid infusion of lipid emulsion has been proposed to treat local anesthetic toxicity. The authors wanted to test the buffering properties of two commercially available emulsions made of long- and of long- and medium-chain triglycerides. Methods Using the shake-flask method, the authors measured the solubility and binding of racemic bupivacaine, levobupivacaine, and ropivacaine to diluted Intralipid (Fresenius Kabi, Paris, France) and Medialipide (B-Braun, Boulogne, France). Results The apparent distribution coefficient expressed as the ratio of mole fraction was 823 +/- 198 and 320 +/- 65 for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively, at 500 mg in the Medialipide/buffer emulsion; and 1,870 +/- 92 and 1,240 +/- 14 for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively, in the Intralipid/buffer emulsion. Decreasing the pH from 7.40 to 7.00 of the Medialipide/buffer emulsion led to a decrease in ratio of molar concentration f...
Emergency Care Journal, 2014
Recently, although without a universal recognition, the use of lipid emulsions as a rescue therapy for the bupivacaine cardiac toxicity has been proposed. In this article we report a successful resuscitation of a patient after the injection of bupivacaine in emergency room and a commented review of the related literature. The patient is a 73 years old man that, after a subcutaneous injection of bupivacaine (0.5%, i.e. 0.5 mL/h), developed circulatory arrest. After the failure of the initial treatment based on the advanced life support protocol, we have successfully performed a therapy with lipid emulsion. The bupivacaine intravascular injection, together with its interaction with amitriptyline and carbamazepine, could lead to cardiac depression, severe arrhythmias, hypotension, and/or cardiac arrest. In the case of failure of traditional life support treatment, intravenous lipid emulsion proves to be the best therapy to treat bupivacaine systemic toxicity. This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0). ©Copyright M.
Journal of Pharmacy and Pharmacology, 2008
This study reports an investigation of the pharmacological activity, cytotoxicity and local effects of a liposomal formulation of the novel local anaesthetic ropivacaine (RVC) compared with its plain solution. RVC was encapsulated into large unilamellar vesicles (LUVs) composed of egg phosphatidylcholine, cholesterol and -tocopherol (4:3:0.07, mole %). Particle size, partition coefficient determination and in-vitro release studies were used to characterize the encapsulation process. Cytotoxicity was evaluated by the tetrazolium reduction test using sciatic nerve Schwann cells in culture. Local anaesthetic activity was assessed by mouse sciatic and rat infraorbital nerve blockades. Histological analysis was performed to verify the myotoxic effects evoked by RVC formulations. Plain (RVC PLAIN ) and liposomal RVC (RVC LUV ) samples were tested at 0.125%, 0.25% and 0.5% concentrations. Vesicle size distribution showed liposomal populations of 370 and 130 nm (85 and 15%, respectively), without changes after RVC encapsulation. The partition coefficient value was 132 26 and in-vitro release assays revealed a decrease in RVC release rate (1.5 fold, P 0.001) from liposomes. RVC LUV presented reduced cytotoxicity (P 0.001) when compared with RVC PLAIN . Treatment with RVC LUV increased the duration (P 0.001) and intensity of the analgesic effects either on sciatic nerve blockade (1.4-1.6 fold) and infraorbital nerve blockade tests (1.5 fold), in relation to RVC PLAIN . Regarding histological analysis, no morphological tissue changes were detected in the area of injection and sparse inflammatory cells were observed in only one of the animals treated with RVC PLAIN or RVC luv at 0.5%. Despite the differences between these preclinical studies and clinical conditions, we suggest RVC LUV as a potential new formulation, since RVC is a new and safe local anaesthetic agent.