Local Anesthetic Systemic Toxicity Research Articles

Focused ultrasound-induced inhibition of peripheral nerve fibers in an animal model of acute pain

BackgroundModerate-to-severe acute pain is prevalent in many healthcare settings and associated with adverse outcomes. Peripheral nerve blockade using traditional needle-based and local anesthetic-based techniques improves pain outcomes for some patient...

Serum concentrations of local anesthetics after unilateral interpectoral-pectoserratus plane block in breast cancer surgery: a pharmacokinetic study

IntroductionThe ultrasound-guided interpectoral-pectoserratus plane block is a fascial plane block for superficial surgery of the anterolateral chest wall. This technique involves injecting a relatively large volume of local anesthetics (typically...

Perioperative medical emergencies: The role of clinical pharmacists and a review of pharmacotherapy considerations

AbstractMedical emergencies arising in the perioperative period can have unique etiologies, medication management, and care complexities. Clinical pharmacists have established roles and demonstrated value in resuscitative efforts elsewhere within acute care settings, but very little published description of pharmacist participation in perioperative emergency response is currently available. Furthermore, specialized clinical and operational knowledge may be needed to effectively optimize medication use during a perioperative medical crisis. This narrative review offers recommended pharmacist roles, concise pharmacotherapeutic considerations, and key resources to support clinical pharmacists in all facets of perioperative medical emergency management and preparedness. Specific medical crises discussed include malignant hyperthermia, local anesthetic systemic toxicity, intraoperative cardiac arrest, anaphylaxis, carcinoid crisis, pheochromocytoma, and vasoplegia. Additional pharmacy practice studies are needed to validate clinical pharmacists as essential members of perioperative emergency response teams and delineate their associated impact on patient outcomes in this setting.

Regional Anesthesia for Orthobiologic Procedures.

Peripheral nerve blocks (PNB) can lessen procedural pain and eliminate the known detrimental effects of our local anesthetics on our orthobiologic target tissues. Local nerve damage and local anesthetic systemic toxicity are risks of PNBs that can be minimized with meticulous injection technique and an understanding of why these complications can occur. Herein, several PNB techniques are described in an effort to enhance procedural safety, efficacy, and comfort.

A randomized controlled study of Ropivacaine with adjuvants in ultra sound guided supraclavicular brachial plexus blockade.

Adjuvants in brachial plexus blockade can improve the patient care by prolonging postoperative analgesia and early mobilization of patient with stable hemodynamics. Brachial plexus block has possible complications like local anaesthetic systemic toxicity, pneumothorax, nerve injury etc. These limitations can be overcome by use of ultrasound guided block with adjuvants like dexmedetomidine and clonidine to prolong the duration of block and postoperative analgesia. Ropivacaine¹ has greater degree of motor differentiation and less cardiotoxicity. Setting and Design: A prospective double – blind randomized control trial comprising of 90 subjects posted for elective upper extremity surgeries. Aim: To compare the onset, duration of sensory blockade, motor blockade and analgesia of 0.5% ropivacaine with clonidine 1mg.kg-1 and 0.5% ropivacaine with dexmedetomidine 1mg.kg-1 in upper extremity surgeries. Methods: Ninety patients aged between 18 – 60yrs of American Society of Anaesthesiology (ASA) Physical Status Class 1 and 2, scheduled for various elective upper extremity surgeries were selected and randomly allocated into two groups of 45 patients each. Group A received 20mL of 0.5% Ropivacaine with dexmedetomidine 1mg.kg-1 and Group B received 20 ml of 0.5% Ropivacaine with clonidine 1mg.kg-1 in 2mL of distilled water. Parameters were compared between the study groups. Results: In Group A, 73.3% of the patients showed onset of sensory block of 8 minutes. And 26.7% of the patients showed onset of sensory block of 10 minutes. In Group B, 44.4% of the patients showed onset of sensory block of 8 minutes, and 26.7% of the patients showed onset of sensory block of 10 min. There was a statistically significant decrease in onset of block and increase in mean duration of sensory and motor block in Group A as compared to Group B. Conclusion: Dexmedetomidine added to 0.5 % ropivacaine in supraclavicular brachial plexus block decreased the time of onset of sensory and motor block and prolonged the postoperative analgesia.

Mechanisms underlying lipid emulsion resuscitation for drug toxicity: a narrative review.

Currently, lipid emulsion (LE) is widely used in the treatment of local anesthetic systemic toxicity (LAST). Additionally, LE has been shown to be effective to ameliorate intractable cardiovascular collapse evoked by toxicity of lipid soluble non-local anesthetic drug. The goal of this review focused on the underlying mechanism of LE treatment in the drug toxicity including LAST, LE treatment, and further research direction. We searched the relevant articles using following keywords: "local anesthetic systemic toxicity or LAST or toxicity or intoxication or poisoning" and "Intralipid or lipid emulsion". The underlying mechanism associated with LE treatment can be divided into indirect and direct effects. Lipid shuttle (indirect effect) of LE treatment is the commonly accepted mechanism: lipid phase of LE absorbs highly lipid soluble drugs ( bupivacaine) from heart and brain, and then LE containing lipid soluble drugs is delivered to muscle, adipose tissue, and liver for storage and detoxification. The direct effects are as follows: inotropic effects, supply of fatty acid, attenuation of mitochondrial dysfunction, glycogen synthase kinase-3β phosphorylation, and inhibition of nitric oxide. These mechanisms seem to synergistically act to alleviate drug toxicity. The recommended LE dosage for LAST is as follows: bolus administration of 20% LE 1.5 ml/kg over 2 to 3 min followed by 20% LE infusion 0.25 ml/kg/min. LAST most occurs via intravenous administration. However, as drug toxicity caused by non-local anesthetic drugs occurs via oral administration, further study is needed to examine the optimal dosing schedule of LE treatment for non-local anesthetic drug toxicity.

Best practices for interventional pain procedures in the setting of a local anesthetic shortage: A practice advisory from the Spine Intervention Society

Representatives from the Spine Intervention Society (SIS) Standards Division and Evidence Analysis Committee have developed the following best practice recommendations for the performance of interventional pain procedures in the setting of a local anesthetic shortage. The practice advisory has been endorsed by SIS, the American Academy of Pain Medicine, the American College of Radiology, the American Society of Neuroradiology, the American Society of Spine Radiology, the North American Neuromodulation Society, the North American Spine Society, and the Society of Interventional Radiology, who support the following best practice recommendations and statements for the performance of intra-articular, extra-articular, paraspinal, and epidural injections in the setting of a local anesthetic shortage.1.Use of preservative-containing local anesthetics is discouraged in the performance of neuraxial procedures where the injectate may enter the epidural (or intrathecal) spaces.2.When performing procedures with risk of arterial injection, ropivacaine should not be mixed with dexamethasone and injected due to the risk of crystallization and embolization.3.Physicians should not withdraw directly from vials of local anesthetic for multiple patients due to infection risk as per Centers for Disease Control and Prevention (CDC) and Joint Commission guidelines [1].4.Only pharmacists may repackage local anesthetic vials for multiple patients. This must be performed under strict, sterile conditions and only in times of critical need. In such situations, physicians must adhere to the beyond-use-date and storage conditions on the repackaged label [2,3].5.Joint, tendon, bursa, and/or ligament injections may be performed with local anesthetic with or without preservative.6.Interventional pain physicians should weigh the relative chondrotoxicity risks associated with each anesthetic when performing joint injections.7.Topical anesthetics, infiltration with diphenhydramine, and nonpharmacologic therapies (i.e., cognitive behavioral therapy, guided imagery, virtual reality, mechanodesensitization) may be used as alternatives to skin infiltration of local anesthetic for reducing procedural pain.8.Use of small-gauge needles (25 gauge or thinner) mitigates the need for local anesthetic prior to needle insertion.9.For local anesthetic infiltration prior to insertion of large bore needles or incision, 0.5% lidocaine may be as effective as 1%, and for that reason current supplies of lidocaine can be stretched by dilution with normal saline.10.If using an ester local anesthetic due to an amide local anesthetic shortage, interventional pain physicians should be aware (as always) of the potential for an allergic reaction and should be able to respond accordingly.11.Local anesthetic systemic toxicity (LAST) differs between the varying local anesthetics, and interventional pain physicians should be well acquainted with these differences when switching between local anesthetics.Physicians should carefully weigh the risks and benefits of performing procedures without local anesthetic or using an alternative agent in the context of each unique patient's situation and should involve patients in shared decision making before proceeding.Procedures should be performed following Spine Intervention Society Guidelines [4]. The physician should confirm placement of the needle in at least two imaging planes. Please refer to the SIS Practice Guidelines for the full details and standards related to each unique procedure [4].

Forensic medical assessment of lidocaine and bupivacaine systemic toxicity

Was to assess the lidocaine and bupivacaine systemic toxicity in forensic medical practice. The number of patients' clinical observations equal three with local anesthetic systemic toxicity (LAST) from the practice of forensic medical experts were studied, and a search of scientific publications for the last 5 years in PubMed database was conducted. The amount of publications, describing cases with LAST, equal four were selected. Differential diagnostic features between LAST and anaphylaxis were considered. The literature data about relationship between lidocaine's concentration in the blood serum and clinical features are shown. The forensic medical assessment of LAST is proposed.

Ultrasound guided regional anesthesia: What we know, what we think we know, what we don't know yet: Running title USGRA: Overview about facts and questions: An educational narrative review of literature

The introduction of ultrasound guidance over the last two decades brought progress, new blocks and new challenges to Regional Anesthesia. This narrative review addresses and discusses facts, frequent questions, beliefs, controversies, unsolved issues, open safety questions and existing knowledge gaps related to efficacy and safety of ultrasound guided regional anesthesia (USGRA), based on the available literature. We discuss evidence-based advantages and limitations of ultrasound guidance, as well as unresolved questions, with respect to successful anesthesia, undesired side effects and patient safety, like nerve injury and local anesthetic systemic toxicity (LAST). In an educational approach we also emphasize some practical aspects of our everyday experience as well as necessary structural requirements.

Safety and Efficacy of Rescue Nerve Blocks

Background: The overall incidence of complications following peripheral nerve blocks is very low. Peripheral nerve blocks performed under ultrasound guidance are widely thought to present a lower risk to direct needle trauma than paresthesia and nerve stimulation techniques and have been shown to decrease opioid consumption by providing analgesia directly to the site of injury. Currently, when a nerve block fails altogether or provides inadequate analgesia, pain and opioid consumption increases which in turn decrease patient satisfaction and increases healthcare costs. Concerns remain whether the benefits of opioid reduction outweigh the risk of inadvertent needle trauma and other potential complications when performing a nerve block replacement, or ‘rescue block’. Objective: Examine whether performing a rescue peripheral nerve block provides adequate analgesia to elicit a decrease in opioid consumption. Analyze the incidence of nerve injury following ultrasound-guided ‘rescue’ continuous peripheral nerve blocks. Methods: Data was retrospectively collected from patient electronic medical records from a Level 1 academic Trauma Center at Regional One Hospital in Memphis, Tennessee from March 1, 2019 to May 31 2021. Inclusion criteria was patients over 18-years of age at time of admission who received consecutive continuous peripheral nerve blocks in the same relative location during a time when the peripheral nerves were likely partially or fully anesthetized (a rescue block). The primary outcomes assessed were 24-hour opioid consumption prior to the initial continuous nerve block, just prior to and after the ‘rescue’ block. Adverse outcomes potentially due to performing a ‘rescue’ block were also examined, including direct needle trauma, nerve injury related to extended exposure to local anesthetics, and local anesthetic systemic toxicity. Types of nerve blocks performed, range and median number of catheter days, and reason for rescue block was recorded for all patients. All available electronic healthcare records were reviewed to identify potential injury. Nerve blocks were categorized into low and high-risk for direct needle trauma based on the incidence of needle trauma found in the literature and whether the needle was required to be adjacent to a discrete nerve or nerve bundle in order to perform the procedure. Results: Fifty-five (55) patients were examined. Of the 55 patients, 5 had multiple locations both blocked and rescued, bringing the total rescue procedures examined up to 60. Additionally, 10 patients had their rescue site re-blocked multiple times due to either multiple surgeries, displacements, or duration of analgesia required bringing the total number of rescue blocks performed to 74. Patients that received an initial continuous peripheral nerve block consumed significantly fewer opioids during the 24-hour period following the block than the 24-hour period before the block was performed (p=0.033). Continuous peripheral nerve blocks (CNPB) were replaced or ‘rescued’ for two general reasons: Failed or inadequate analgesia (21) and to extend the utilization of adequately functioning infusions (35). Once a rescue nerve block was performed, there was no significant change in opioid consumption than after the original block (p=0.64). Of the 60 rescue blocks that were recorded, there were 0 adverse outcomes that were attributed to the rescue block procedure. Conclusion: Following failed CPNB or when performed to extend the utilization of CPNB infusions, ultrasound-guided ’rescue’ nerve blocks result in reduced opioid consumption to a similar level as the initial peripheral nerve block, and do not result in an increase in the incidence direct needle trauma. Given the relatively low incidence of needle trauma and other nerve block-related complications, larger studies are needed to confirm these initial findings, however, ultrasound provides numerous clinical strategies that can be employed that may reduce the incidence of direct needle trauma compared with traditional nerve localization techniques.

Strategies to Prevent Local Anesthetic Systemic Toxicity.

Strategies to Prevent Local Anesthetic Systemic Toxicity.

Serratus Anterior Plane Block for Clinically Suspected Rib Fractures in Prehospital and Retrieval Medicine

Objective: To describe the use of the serratus anterior plane block (SAPB) in the prehospital and retrieval environment including the ability to accurately identify those patients with thoracic trauma and clinically suspected rib fractures who would benefit from this procedure. Methods: This is a retrospective case series of all patients with thoracic trauma and clinically suspected rib fractures who received SAPB by a prehospital and retrieval medical team in New South Wales, Australia, between 2018 and 2021. The primary outcome was to identify the proportion of patients who received appropriate blocks based on the criteria of reporting moderate pain after receiving adequate pre-block analgesia. Secondary outcomes included the proportions of patients with rib fractures identified on thoracic imaging, concomitant time-critical pathology, radiologist identification of fluid adjacent to the serratus anterior muscle, and local anesthetic systemic toxicity. Results: Of the 2004 patients who sustained thoracic trauma, only 13 received a SAPB. Nine (69.2%) met the predetermined definition of appropriate selection. Of the four patients who did not meet this criteria, three reported less than moderate pain and one did not receive adequate pre-block analgesia. There was no significant effect on median scene interval when compared to other thoracic trauma patients who did not receive a SAPB. Ten patients had rib fractures identified on in-patient imaging (chest x-ray or computed tomography (CT)) with a median (IQR) number of ribs fractured of 5 (interquartile range 2–10). Three of these patients had radiological flail segments. Prespecified time-critical pathology was identified in three patients (23.1%) on initial hospital imaging. Five out of eight patients with post-SAPB CT imaging (62.5%) available for radiologist review had fluid identified adjacent to the serratus anterior muscle. None of the 13 patients had local anesthetic systemic toxicity. Conclusion: The SAPB can be safely and successfully performed in the prehospital and retrieval environment, where clinicians can appropriately identify patients with thoracic trauma and clinically suspected rib fractures who would benefit from this technique. Further research is required to identify the ideal patient population to perform the SAPB upon and compare its performance to current analgesic options.

Complications and Technical Consideration of Ultrasound-Guided Rectus Sheath Blocks: A Retrospective Analysis of 4033 Patients.

Although the ultrasound-guided rectus sheath block (RSB) is usually regarded as an easy and safe procedure in clinical settings, there is currently no report on complications incidence. Therefore, the present study investigated complications in a large cohort and described the technical considerations to minimize complications of real-time ultrasound-guided RSBs. This was a retrospective cohort study of patients who underwent real-time ultrasound-guided RSBs for perioperative pain control in laparoscopic surgery with an umbilical port between February 1, 2017, and February 28, 2021, at the Asan Medical Center in South Korea. All RSBs were performed bilaterally using a 23-gauge Quincke needle, and a bilateral 2-block placement was regarded as 1 RSB. Patient data, including demographics, preoperative laboratory data, preoperative antiplatelet or anticoagulant medication with the duration of discontinuation, and type of surgery, were collected to show the study population characteristics and explore potential factors associated with adverse events such as hematoma. Ultrasound images of patients and adverse events of RSBs, including extrarectus sheath injections, vascular injuries, bowel injury, or local anesthetic systemic toxicity, were also analyzed accordingly. A total of 4033 procedures were analyzed. The mean body mass index of the patients was 24.1 (21.8-26.5) kg/m2. The preoperative laboratory data were within normal range in 4028 (99.9%) patients. Preoperative antiplatelets or anticoagulants were administered in 17.3% of the patients. Overall, 96 complications (2.4%) were observed. Among them, extrarectus sheath injection occurred in 88 cases (2.2%), which included preperitoneal injection (0.9%) and intraperitoneal injection (1.3%). Vascular injuries constituted 8 cases (0.2%) and all vascular injuries resulted in hematoma: 7 cases of inferior epigastric artery injury with rectus sheath hematoma and 1 of inferior mesenteric artery injury with retroperitoneal hematoma. Bowel injury or local anesthetic systemic toxicity was not reported. In this study of RSBs performed on 4033 patients using a 23-gauge Quincke needle in patients with low body mass index, there were 8 cases (0.2%) of vascular injury, all of which accompanied hematoma.

Assessment of Awareness of Local Anaesthetic Systemic Toxicity (LAST) among Postgraduate Trainees.

Although uncommon, local anaesthetic systemic toxicity (LAST) may impose fatal risk to the patients. We investigated the awareness of LAST and knowledge on local anaesthetics among our postgraduate trainees. A total of 134 postgraduate trainees from the departments of general surgery (Surgical), orthopaedic surgery (Ortho), otorhinolaryngology (ENT), obstetrics and gynaecology (OBGYN), as well as anaesthesiology and intensive care (Anaesth) were recruited. A validated questionnaire was used to assess awareness and knowledge. All participants attended a medical-education session and completed the questionnaire as preassessment and postassessment. Data were analysed, and comparisons between disciplines were conducted. The trainees' awareness of LAST was overall poor at preassessment which improved almost 6-folds at postassessment. Surprisingly, only 20 (45.5%) participants from the anaesthesiology group had awareness of LAST at preassessment, and none of the participants were from surgical, orthopaedic, and obstetrics and gynaecology departments. Preassessment scores were significantly higher in the anaesth group as compared to all other groups; with a difference in the average score for Anaesth vs Surgical of 3.46 (95%, CI:2.17, 4.74), Anaesth vs Ortho of 3.64 (95%, CI:2.64, 4.64), Anaesth vs ENT of 3.43 (95%, CI:2.20, 4.67), and Anaesth vs OBGYN of 6.93 (95%, CI:5.64, 8.21). However, there was no significant difference of awareness scores between all participants at postassessment scores. The overall level of awareness was poor. However, the implementation of an education session significantly improved the knowledge and awareness across all disciplines.

Efficacy of femoral periarterial block in preventing thigh tourniquet pain: a randomized controlled trial.

Tourniquet pain, described as a dull, tight, poorly localized aching sensation, is common in conscious patients. Although various pain-reduction methods have been implemented, none are completely effective. Femoral periarterial block (FAB) has been shown to attenuate tourniquet-induced hypertension in patients undergoing general anesthesia. We aimed to test the feasibility of FAB in inhibiting thigh tourniquet pain in orthopedic patients under conscious sedation. Forty-two patients (aged 18-64 years and ASA I-II) scheduled for below-knee orthopedic surgeries with an anticipated tourniquet duration of more than 40 min were recruited and received FAB (Group 1) or not (Group 2). The primary outcome was the occurrence of tourniquet pain. The onset time and severity of the tourniquet pain were recorded. Total doses of sedatives and analgesics administered intraoperatively and hemodynamic changes were documented. The occurrence of local anesthetic systemic toxicity was recorded. Kaplan-Meier time-to-event curves indicated an improved tourniquet tolerance and delayed pain onset. Tourniquet pain occurrence was lower in Group 1 than in Group 2 (30% vs. 95.5%, P=0.02). Tourniquet pain onset was delayed in Group 1 (80[67,84] min vs. 58[51.5,60] min, P<0.01). Fewer patients in Group 1 experienced severe pain (3(15%) vs. 18(81.8%), P<0.01), and less hemodynamic changes (2(10%) vs. 12(54.5%), P<0.01). Local anesthetic systemic toxicity was absent. FAB, applied with regional anesthesia in patients undergoing below-knee orthopedic surgeries, could reduce thigh tourniquet pain, stabilize blood pressure and heart rate, and prolong tourniquet duration.

Liberal use of local anaesthetic and the risk of toxicity in elective arthroplasties at a tertiary teaching hospital

Background Local anaesthetic systemic toxicity (LAST) is a life-threatening potential complication that may follow the administration of local anaesthetic (LA) drugs, and is cumulative across the drug class. Local anaesthetics are commonly administered via different routes for elective orthopaedic procedures – both by anaesthetists and surgeons. We hypothesized that total doses of LA may be routinely encroaching upon toxicity. Methods All total hip or knee arthroplasties (THAs and TKAs) performed within a 3 month period at the John Hunter Hospital (tertiary referral centre and teaching hospital) were audited to assess total administration of LA. Demographics, surgical characteristics, use of general anaesthesia or sedation, and use of local anaesthetic via any route of administration was recorded. For each patient, a weight-based theoretical maximum safe dose was calculated and compared against the dose they received. Data is presented as mean ± SD, percentages. Statistical significance was determined at p &lt; 0.05. Results 130 THAs and TKAs were identified within the audit period. 52 patients exceeded their drug-class theoretical maximum safe dose. 49 patients exceeded their weight-based maximum dose for a single LA agent, in all cases ropivacaine. Non-obese individuals receive significantly higher mean dose than obese individuals (119.4% [98.6–140.3] vs 78.82% [65.95–91.69], p = 0.001). No LAST events were identified. Conclusions Patients who received elective total hip or knee arthroplasties were exposed to concerningly high total doses of local anaesthetic, suggesting that greater awareness of the additive toxicity of drugs within this class is required.

Low-dose lipid emulsion for pediatric vasoplegic shock due to quetiapine and fluvoxamine overdose: a case report

Background: Intravenous lipid emulsion (ILE) therapy was originally used for treatment of for local anesthetic systemic toxicity. Over the last decade, it has been successfully used to treat severe toxicity of numerous lipophilic substances. The mechanism by which ILE therapy treats lipophilic drug toxicity was originally purported to be due to the lipid sink mechanism; however, further research suggests that several other factors likely play more substantial roles, including free fatty acid provision to cardiomyocytes, positive inotropic effect, ion channel modulation, and nitric oxide synthase inhibition. No standardized dosing recommendation exists for ILE treatment of pediatric lipophilic drug toxicity. Several case reports have documented successful resuscitation of such overdoses using much lower dosages of ILE than are used for local anesthetic toxicity.

Guy Weinberg, MD, to Present 2022 John W. Severinghaus Lecture on Translational Science

Article| October 2022 Guy Weinberg, MD, to Present 2022 John W. Severinghaus Lecture on Translational Science Roy A. Winkler Roy A. Winkler Search for other works by this author on: This Site PubMed Google Scholar ASA Monitor October 2022, Vol. 86, 34. https://doi.org/10.1097/01.ASM.0000890100.46213.01 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Search Site Citation Roy A. Winkler; Guy Weinberg, MD, to Present 2022 John W. Severinghaus Lecture on Translational Science. ASA Monitor 2022; 86:34 doi: https://doi.org/10.1097/01.ASM.0000890100.46213.01 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll PublicationsASA Monitor Search Advanced Search Topics: translational research For two decades, Guy Weinberg, MD, has been recognized worldwide as an authority on the rare but potentially devastating condition of local anesthetic systemic toxicity, or LAST. Many physicians will never treat an episode of LAST, but the ones who do will probably treat those patients with the therapies developed by Dr. Weinberg. His Severinghaus Lecture will explore lipophilic drug toxicity and his years of research on the subject, which began quite tangentially: “My interest in LAST stems from a single patient encounter, and my talk will trace the unexpected and very circuitous route of identifying, then explaining, the basis of lipid therapy,” Dr. Weinberg said. Guy Weinberg is currently a Full Professor in the Department of Anesthesiology at the University of Illinois, Chicago, and a physician at the Jesse Brown VA, where his lab was active until just last year. He has been a leading figure within the American... You do not currently have access to this content.

Local anesthetic systemic toxicity.

It results from supratherapeutic levels of local anesthetic in the bloodstream. Most cases occur in hospitals (61%), while fewer occur in outpatient settings (14%), primarily following upper or lower extremity nerve blocks (19%), naso-oropharyngeal infiltration (17%) or spinal and epidural blocks (

Levobupivacaine plasma concentrations following repeat caudal anesthetics.

A single caudal anesthetic at the start of lower abdominal surgery is unlikely to provide prolonged analgesia. A second caudal at the end of the procedure extends the analgesia duration but total plasma concentrations may be associated with toxicity. Our aim was to measure total plasma levobupivacaine concentrations after repeat caudal anesthesia in infants and to generate a pharmacokinetic model for prediction of plasma concentrations after repeat caudal anesthesia in neonates, infants and children. Infants undergoing definitive repair of anorectal malformations or Hirschsprung's disease received a second caudal anesthesia at the end of the procedure. Total levobupivacaine concentrations were assayed 3-4 times in the first 6h after the initial caudal. These data were pooled with data from four studies describing plasma concentrations after levobupivacaine caudal or spinal anesthesia. Population pharmacokinetic parameters were estimated using nonlinear mixed-effects models. Covariates included postmenstrual age and body weight. Parameter estimates were used to simulate concentrations after a repeat levobupivacaine 2.5mg kg-1 caudal at 3 or 4h following an initial levobupivacaine 2.5mg kg-1 caudal. Twenty-one infants (postnatal age 11-32 weeks, gestation 37-39 weeks, weight 5.2-8.6kg) were included. The measured peak plasma concentration after repeat caudal levobupivacaine 2.5mg kg-1 4 h after initial caudal was 1.38 mg L-1 (95% prediction interval 0.60-2.6mg L-1 ) and 3 h after initial caudal was 1.46 mg L-1 (0.60-2.80)mg L-1 . Simulation of total plasma concentrations in neonates (7kg, 57 weeks postmenstrual age) given caudal levobupivacaine 4 h after the initial caudal were 1.76 mg L-1 (0.68-3.50) mg L-1 if 2.5mg kg-1 levobupivacaine was used and 0.88 mg L-1 (0.34-1.73)mg L-1 if 1.25 mg kg-1 of 0.125% levobupivacaine was used. In simulated older children (20 kg, 6 years), the mean maximum concentration was 1.43 mg L-1 (0.60-2.70)mg L-1 if 2.5mg kg-1 levobupivacaine was repeated at 3h. Repeat caudal levobupivacaine 2.5mg kg-1 at 3h after an initial 2.5mg kg-1 dose does not exceed the concentration associated with systemic local anesthetic toxicity. In 2.5% of simulated neonates (weight 3.8kg, PMA 40 weeks), repeat caudal anesthesia demonstrates broaching of the lower concentration limit associated with toxicity at both 3 and 4 h after initial caudal.