Local anaesthetic systemic toxicity

Christie, Linsey; Picard, John; Weinberg, Guy

doi:10.1093/bjaceaccp/mku027

Cited by 88 publications

(126 citation statements)

References 29 publications

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“…There are two main reasons for this finding. First, a fair number of patients in our study were infected with HBV or had a renal diseases and thus may be more susceptible to LAST [21]. Second, the lumbar plexus and sciatic nerves are difficult to visualize due to their depth.…”

Section: Discussionmentioning

confidence: 96%

“…liver diseases would have a decreased rate of LAs clearance due to a reduced AAG concentration, which may increase the incidence of LAST. However, even in patients with advanced liver dysfunction, the synthesis of AAG is still maintained [21,24]. In patients with hepatic dysfunction, single-dose blocks can usually be performed safely with a normal dose of LAs [25].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Combined Ultrasound and Nerve Stimulator-Guided Deep Nerve Block May Decrease the Rate of Local Anesthetics Systemic Toxicity: A Randomized Clinical Trial

Zhang

et al. 2019

Preprint

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Background: Ultrasound guidance might decrease the incidence of local anesthetics systemic toxicity (LAST) for many peripheral nerve blocks compared with nerve stimulator guidance. However, it remains uncertain whether ultrasound guidance is superior to nerve stimulator guidance for deep nerve block of the lower extremity. This study was designed to investigate whether deep nerve block with ultrasound guidance would decrease the incidence of LAST compared with that with nerve stimulator guidance and to identify associated risk factors of LAST. Methods: Three hundred patients undergoing elective lower limb surgery and desiring lumbar plexus blocks (LPBs) and sciatic nerve blocks (SNBs) were enrolled in this study. The patients were randomly assigned to receive LPBs and SNBs with ultrasound guidance (group U), nerve stimulator guidance (group N) or dual guidance (group M). The primary outcome was the incidence of LAST. The secondary outcomes were the number of needle redirections, motor and sensory block onset and nerve distribution restoration time, as well as associated risk factors. Results: There were 18 patients with LAST, including 12 in group U, 4 in group N and 2 in group M. By multiple comparisons among the three groups, we found that the incidence of LAST in group U (12%) was significantly higher than that in group N (4%) (P=0.037) and group M (2%) (P=0.006). The OR of LAST with hepatitis B (HBV) infection and the female sex was 3.352 (95% CI, 1.233-9.108, P=0.013) and 9.488 (95% CI, 2.142-42.093, P=0.0004), respectively. Conclusions: Ultrasound guidance, HBV infection and the female sex were risk factors of LAST with LPBs and SNBs. For patients infected with HBV or female patients receiving LPBs and SNBs, we recommended that combined ultrasound and nerve stimulator guidance should be used to improve the safety. Trial registration: This study was approved by the Ethical Committee of the First Affiliated Hospital of Army Medical University. The protocol was registered prospectively with the Chinese Clinical Trial Registry (ChiCTR-IOR-16008099) on March 15, 2016.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Combined Ultrasound and Nerve Stimulator-Guided Deep Nerve Block May Decrease the Rate of Local Anesthetics Systemic Toxicity: A Randomized Clinical Trial

Zhang

et al. 2019

Preprint

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“…improved the deterioration of cognitive function, indicating that ropivacaine protects against KA-induced cognitive deficit. It is known that high dose of ropivacaine produce central nervous system (CNS) and cardiac toxicity in patients [28,29] as well as in experimental animals [30,31]. The maximum recommended dose of ropivacaine is 3 mg/kg in a human clinical setting [32].…”

Section: Discussionmentioning

confidence: 99%

Ropivacaine Protects against Memory Impairment and Hippocampal Damage in a Rat Neurodegeneration Model

Chiu¹,

Lin²,

Lee

et al. 2018

Pharmacology

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Background: Ropivacaine, a long-acting amide local anesthetic agent, has been demonstrated to inhibit glutamatergic transmission. Glutamate neurotoxicity plays a pivotal role in the pathogenesis of brain disorders. The purpose of this study is to investigate the neuroprotective effect of ropivacaine against brain damage induced by kainic acid (KA), an analogue of glutamate. Methods: Rats were injected with ropivacaine (0.4 or 2 mg/kg, intraperitoneal) 30 min before KA treatment (15 mg/kg, intraperitoneal). KA-induced memory impairment was evaluated using the Morris water maze test. Extracellular hippocampal glutamate levels were assessed using high-performance liquid chromatography. Neuronal death was verified using Fluoro-Jade B and neutral red staining, and apoptosis was determined through terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Western blotting was conducted to assay the levels of activated (cleaved) caspase-3 and the phosphorylation of different mitogen-activated protein kinases (MAPKs). Results: Ropivacaine pretreatment effectively prevented KA-induced memory impairment. KA-induced elevations of glutamate release in rat hippocampi were inhibited by pretreatment with ropivacaine. Histopathological and TUNEL staining analyzes showed that ropivacaine inhibited KA-induced neuronal death and apoptosis in the hippocampal CA3 region. KA-induced caspase-3 activation and MAPKs phosphorylation in the hippocampus were also reduced by ropivacaine pretreatment. Conclusions: This study demonstrates that ropivacaine executes a protective action against KA-induced neuronal damage and apoptosis in vivo. Protective effects may be caused by glutamate level reduction, caspase-3 activation suppression, and MAPKs phosphorylation reduction. Our findings indicate that ropivacaine can benefit prevention or treatment of glutamate excitotoxicity-related neurodegenerative diseases.

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“…Ropivacaine has a lower potency than both levoand racemic bupivacaine and is approximately 10 times less lipophilic. At equipotent dose [19], it is uncertain whether there is really clinically relevant lower toxicity. Several cases in which intended epidural doses of ropivacaine were accidentally administered either intrathecally or intravenously resulted in severe complications [20,21].…”

Section: Article Highlightsmentioning

confidence: 99%

Safety of epidural drugs: a narrative review

Zuylen

Hoope

Bos

et al. 2019

Expert Opinion on Drug Safety

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Introduction: Epidural analgesia is a popular approach to postoperative and labor pain. Neurotoxicity and drug-specific systemic side effects can occur after epidural administration. As an increasing number of epidural drugs are studied and clinically applied, drug efficacy and safety evaluation are crucial. Areas covered: In this narrative review, the authors provide a thorough overview on the safety of the most widely used epidural drugs, focusing on potential neurotoxicity, side effects, and complications in the adult, non-pregnant population. A combined text and MeSH heading search strategy was used to identify relevant publications. Expert opinion: The search for the ideal epidural medication has resulted in a surplus of drug combinations with extensive heterogeneity amongst studies, while the value of investigating these is not always evident. Epidural drugs pose a potential threat of neurotoxicity and other side effects. Consequently, we should pursue safe epidural drug administration to patients and refrain from drugs with minimal proven benefit. Also, studies should compare epidural with systemic application. Because why use a drug epidurally, which can be safely used systemically? Future research should focus on providing solid evidence regarding efficacy of epidural analgesia compared to new and already existing modalities and optimizing presently used medicinal regimens.

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Local anaesthetic systemic toxicity

Cited by 88 publications

References 29 publications

Combined Ultrasound and Nerve Stimulator-Guided Deep Nerve Block May Decrease the Rate of Local Anesthetics Systemic Toxicity: A Randomized Clinical Trial

Combined Ultrasound and Nerve Stimulator-Guided Deep Nerve Block May Decrease the Rate of Local Anesthetics Systemic Toxicity: A Randomized Clinical Trial

Ropivacaine Protects against Memory Impairment and Hippocampal Damage in a Rat Neurodegeneration Model

Safety of epidural drugs: a narrative review

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