Bupivacaine toxicity

Ropivacaine is a local anesthetic with similar potency but lower systemic toxicity than bupivacaine, the most commonly used spinal anesthetic. The present study concerns the development of a combined drug delivery system for ropivacaine, comprised of two types of liposomes: donor multivesicular vesicles containing 250 mM (NH4)2SO4 plus the anesthetic, and acceptor large unilamellar vesicles with internal pH of 5.5. Both kinds of liposomes were composed of hydrogenated soy-phosphatidylcholine:cholesterol (2:1 mol%) and were prepared at pH 7...

AIMS: In the field of anaesthesia and intensive care, the controlled release systems capable of delivering constantly local anaesthetics are of interest because of the advantages brought to pain management. In this paper we presented the release profiles by usage of siloxane matrices of two common local anaesthetics, lidocaine and bupivacaine, analysed in vitro. METHODS: The siloxane matrices were obtained in accordance with the methods described in the specialized literature, tetraethoxysilane (TEOS) and tetramethoxysilane (TMOS) were used as precursors...

BACKGROUND: Intraoperative periarticular injections (PAIs) with local anesthetic are an important component of multimodal pain control in total joint arthroplasty. Liposomal bupivacaine is an extended-release formulation of bupivacaine designed to provide extended pain relief, approved for use in a single surgical site. The systemic safety profile for use in simultaneous bilateral TKA (bTKA) with a full dose in each knee has not been evaluated. The purpose of this study was to determine the safety and pharmacokinetics of bilateral full-dose PAI liposomal bupivacaine in the blood collected in patients undergoing simultaneous bTKA...

Bupivacaine has been shown to induce neurotoxicity through inducing excessive reactive oxygen species (ROS), but the underlying mechanism remains unclear. NOX2 is one of the most important sources of ROS in the nervous system, and its activation requires the membrane translocation of subunit p47phox. However, the role of p47phox in bupivacaine-induced neurotoxicity has not been explored. In our in vitro study, cultured human SH-SY5Y neuroblastoma cells were treated with 1.5 mM bupivacaine to induce neurotoxicity...

Bupivacaine is the most used local anesthetic in surgical procedures, producing prolonged anesthesia. The major limiting factor for the clinical use of bupivacaine comes from its systemic toxicity. Nanostructured lipid carriers (NLC) are vehicles for sustained drug delivery that are able to minimize the toxicity and to increase the action time of lipophilic drugs. This work reports a 22 factorial design, which elucidate the role of the lipids mixture in the NLC, towards an optimized formulation. It also provides a new method for Bupivacaine S75:R25 (BVCS75) quantification in NLC...

BACKGROUND AND OBJECTIVES: A relatively new technique to reduce postoperative pain for total knee arthroplasty is to inject a mixture of 266 mg of liposomal bupivacaine and 125 mg of 0.25% bupivacaine HCl with epinephrine 1:300,000 around the knee joint at the time of surgery. Currently, no publications report serum bupivacaine concentrations over time after periarticular injection of liposomal mixed with free bupivacaine. This information is important to ensure safe serum bupivacaine concentrations are maintained especially when considering supplemental or rescue peripheral nerve blocks...

PURPOSE OF REVIEW: Enthusiasm for regional anesthesia has been driven by multimodal benefits to patient outcomes. Despite widespread awareness and improved techniques (including the increasing use of ultrasound guidance for block placement), intravascular sequestration and the attendant risk of local anesthetic systemic toxicity (LAST) remains. Intravenous lipid emulsion (ILE) for the treatment of LAST has been endorsed by anesthetic regulatory societies on the basis of animal study and human case report data...

INTRODUCTION: Brachial plexus blockade is a time-tested technique for upper limb surgeries. The classical approach using paresthesia technique is a blind technique and may be associated with a higher failure rate and injury to the nerves and surrounding structures. To avoid some of these problems, use of peripheral nerve stimulator and ultrasound techniques were started which allowed better localization of the nerve/plexus. Ultrasound for supraclavicular brachial plexus block has improved the success rate of the block with excellent localization as well as improved safety margin...

The short time of action and systemic toxicity of local anaesthetics limit their clinical application. Bupivacaine is the most frequently used local anaesthetic in surgical procedures worldwide. The discovery that its S(-) enantiomeric form is less toxic than the R(+) form led to the introduction of products with enantiomeric excess (S75:R25 bupivacaine) in the market. Nevertheless, the time of action of bupivacaine is still short; to overcome that, bupivacaine S75:R25 (BVCS75) was encapsulated in nanostructured lipid carriers (NLC)...

BACKGROUND: Continuous wound infiltration (CWI) has become increasingly popular in recent years as an alternative to epidural analgesia. As catheters are not placed until the end of surgery, more intraoperative opioid analgesics might be needed. We, therefore, added a single pre-peritoneal bolus of bupivacaine at the start of laparotomy, similar to the bolus given with epidural analgesia. METHODS: This was a comparative study within a randomized controlled trial (NTR4948)...

BACKGROUND: Transversus abdominis plane block is an effective method of post-cesarean analgesia. There are no data available about plasma bupivacaine levels after this block in adults. This study aimed to assess bupivacaine pharmacokinetic parameters after ultrasound-guided transversus abdominis plane blocks following cesarean delivery under spinal anesthesia. METHODS: A prospective observational study in parturients undergoing elective cesarean delivery under hyperbaric bupivacaine spinal anesthesia was conducted...

PURPOSE OF REVIEW: The decision to provide intravenous lipid emulsion (ILE) therapy as a treatment modality for the reversal of various drug toxicity was discovered in the last decade. Numerous publications, in both humans and animals attest to its clinical use, but current supporting evidence is inconsistent. RECENT FINDINGS: A recent systematic review reported evidence for benefit of ILE in bupivacaine toxicity. Human randomized trials, large observational studies as well as animal models of orogastric poisoning failed to report a clear benefit of ILE for nonlocal anesthetics poisoning...

BACKGROUND: To assess the effectiveness of continuous preperitoneal wound infusion of local anesthetic drug bupivacaine in providing pain relief, reducing opioid consumption, and enhancing postoperative recovery. METHODS: Eligible patients were randomly allocated to two groups (study group: bupivacaine and control group: normal saline). There were 47 patients in each group. The patients received continuous infusion of either 0.25% bupivacaine or 0.9% normal saline at 6 mL/h, for 48 h, based on their group allocation, through a multiholed wound infiltration catheter placed preperitoneally...

Unintentional intravascular administration of bupivacaine may cause local anesthetic systemic toxicity (LAST). Although many systems are affected in LAST, the cardiovascular effects can be life-threatening. Remifentanil is a selective, ultra-short-acting, µ-opioid receptor agonist opioid. This study assessed the effects of combined pretreatment with intravenous lipid emulsion (ILE) and remifentanil on the cardiotoxicity caused by bupivacaine in an experimental model of anesthetized rats. The rats were divided into three groups...

BACKGROUND: Local anesthetic systemic toxicity (last) is a rare life threatening complication usually from intra-arterial or intravenous injection leading to systemic absorption of regional anesthesia drug. the objective of this research was to statistically quantify the association between exparel (bupivacaine liposome) injectable suspension and last. METHODS: Adverse Event Reporting System database of FDA, which houses public and industry submitted adverse event case reports, was queried and analyzed to quantify the passive pharmacovigilance signal for Local Anesthetic Systemic Toxicity as associated with use of bupivacaine Liposome...

QX-314 has been shown to produce long-acting local anesthesia in vivo in animals; however, translation to humans has been impeded by concerns about toxicity. We investigated whether the newly emerged QX-OH molecule could confer long-lasting anesthesia with a low local toxicity in rats. In rat sciatic nerve block model, QX-OH 25mM produced a longer sensory block than QX-314 25mM (median [25th, 75th percentiles], 5.5 [4.25, 6] h vs. 3 [3, 4] h; P=0.03). QX-OH 35mM produced a longer sensory block than QX-314 35mM (8 [6, 12] h vs...

[This corrects the article DOI: 10.1371/journal.pone.0174421.].

We evaluated blood bupivacaine concentrations in children having a single-shot sciatic and continuous femoral blocks after anterior cruciate ligament repair. Dried blood spot samples were analyzed for bupivacaine levels at 0, 5, 15, 30, 60, and 120 minutes and 4, 24, and 48 hours. The highest 99% upper confidence interval limit was 135 ng/mL at the 4-hour evaluation point. The 99% upper confidence interval was below potentially toxic levels (1500 ng/mL) across all sampling times. The risk of local anesthetic toxicity in pediatric patients receiving single-shot sciatic and continuous femoral nerve blocks is very low...

BACKGROUND: Tumescent mastectomy refers to usage of a mixture of lidocaine and epinephrine in a diluting saline solution that makes flaps firm and tense, thus minimizing systemic drugs toxicity and making surgery possible with minimal bleeding. This technique is very useful in elder women and those with American Society of Anesthesiologists; score III and IV. The objective was to establish an alternative safe technique to general anesthesia in some selected mastectomy patients. PATIENTS AND METHODS: Twenty candidate women for total mastectomy and axillary dissection were enrolled and consented to participate...

INTRODUCTION: The Lipid Emulsion Therapy workgroup, organized by the American Academy of Clinical Toxicology, recently conducted a systematic review, which subjectively evaluated lipid emulsion as a treatment for local anesthetic toxicity. We re-extracted data and conducted a meta-analysis of survival in animal models. METHODS: We extracted survival data from 26 publications and conducted a random-effect meta-analysis based on odds ratio weighted by inverse variance...