Yun Xia

Lipid resuscitation of bupivacaine toxicity: long-chain triglyceride emulsion provides benefits over long- and medium-chain triglyceride emulsion.

BACKGROUNDnThe superiority of Intralipid, a long-chain triglyceride (LCT) emulsion versus Lipovenoes, a long- and medium-chain triglyceride (LCT/MCT) emulsion, in reversing local anesthetic-induced cardiac arrest is poorly defined and needs to be determined.nnnMETHODSnThe study included two parts: in experiment A, bupivacaine (20 mg/kg) was injected to produce asystole. Either Intralipid 20% (LCT group, n = 30) or Lipovenoes 20% (LCT/MCT group, n = 30) with epinephrine was infused immediately. Return of spontaneous circulation and recurrence of asystole after resuscitation were recorded. In experiment B, 80 rats using the same model and resuscitation protocol were divided into 10 groups: LCT₀, LCT₁₅, LCT₃₀, LCT₆₀, and LCT₁₂₀ and LCT/MCT₀, LCT/MCT₁₅, LCT/MCT₃₀, LCT/MCT₆₀, and LCT/MCT₁₂₀ (n = 8 each; the subscripts represent respective observation period). LCT₁₅-LCT₁₂₀ and LCT/MCT₁₅-LCT/MCT₁₂₀ groups received Intralipid 20% or Lipovenoes 20%, respectively. Plasma and myocardial bupivacaine and triglyceride concentrations, as well as myocardial bioenergetics, were determined.nnnRESULTSnIn experiment A, 24 rats in LCT group and 23 in LCT/MCT group achieved return of spontaneous circulation (P = 0.754); among them, 2 (8.3%) and 8 (34.8%) rats suffered a repeated asystole, respectively (P = 0.027). In experiment B, plasma and myocardial bupivacaine concentrations in LCT₁₅ and LCT₆₀ groups were lower than LCT/MCT₁₅ and LCT/MCT₆₀ groups, respectively. Furthermore, the plasma bupivacaine level in LCT/MCT₆₀ group was higher than LCT/MCT₃₀ group (P = 0.003).nnnCONCLUSIONSnLCT emulsion may be superior to LCT/MCT emulsion in treating bupivacaine-related cardiotoxicity as it was associated with fewer recurrences of asystole after resuscitation and lower myocardial bupivacaine concentrations.

Lipid emulsion reverses bupivacaine-induced asystole in isolated rat hearts: concentration-response and time-response relationships.

Background:The concentration-response and time-response relationships of lipid emulsions used to reverse bupivacaine-induced asystole are poorly defined. Methods:Concentration response across a range of lipid concentrations (0–16%) to reverse bupivacaine-induced asystole were observed using isolated rat heart Langendorff preparation. Cardiac function parameters were recorded during infusion. Concentrations of bupivacaine in myocardial tissue were measured by liquid chromatography and tandem mass spectrometry at the end of the experiment. Results:Although all lipid-treated hearts recovered (cardiac recovery was defined as a rate-pressure product more than 10% baseline), no nonlipid-treated hearts (control group) did so. The ratio of the maximum rate pressure product during recovery to baseline value demonstrated a concentration-dependent relationship among lipid groups, with 0.25, 0.5, 1, 2, 4, 8, and 16%. Mean ± SD values for each corresponding group were 22 ± 4, 24 ± 5, 29 ± 6, 52 ± 11, 73 ± 18, 119 ± 22, and 112 ± 10%, respectively (n = 6, P < 0.01). Rate-pressure product in lipid groups with 4–16% concentrations was lower at 15–40 min than at 1 min, showing a decreasing tendency during recovery phase (P < 0.01). The concentration of myocardial bupivacaine in all lipid-treated groups was significantly lower than in the control group (P < 0.01). It was also lower in lipid groups with 2–16% concentrations than in those with concentrations at 0.25–1% (P < 0.05), with the 16% group lower than groups with 2–8% concentrations (P < 0.001). Conclusion:Lipid application in bupivacaine-induced asystole displays a concentration-dependent and time-response relationship in isolated rat hearts.

The effect of lipid emulsion on pharmacokinetics and tissue distribution of bupivacaine in rats.

BACKGROUND:While lipid emulsion may reverse the systemic toxicity of bupivacaine, the pharmacokinetics and tissue distribution of bupivacaine after lipid emulsion infusion are not clear. In this study, we assessed the influence of lipid emulsion administration on the pharmacokinetics and tissue distribution of bupivacaine. METHODS:Rats in the lipid group were administered IV bupivacaine at the rate of 2 mg·kg−1·min−1 for 4 minutes, and then were treated with an infusion of 30% lipid emulsion at the rate of 3 mL·kg−1·min−1 for 5 minutes; saline was substituted in the control group (n = 6 for pharmacokinetics). We then randomly assigned 100 rats into the lipid group and control group (n = 50 for distribution). The toxicity model and treatment were the same as the pharmacokinetic portion. Plasma and tissues including brain, heart, liver, spleen, lung, kidney, omentum, and muscle were collected. The plasma concentration and tissue content of bupivacaine were measured by a liquid chromatography-tandem mass spectrometric method. A 2-compartmental analysis was performed to calculate the pharmacokinetics of bupivacaine. RESULTS:All data are shown as mean ± SD. After treatment with the lipid emulsion, t1/2&bgr; of bupivacaine in the lipid group was significantly shorter (110 ± 25 minutes vs 199 ± 38 minutes, P = 0.001), the clearance was higher (14 ± 4 mL·mg−1·kg−1 vs 9 ± 4 mL·mg−1·kg−1, P = 0.038), and the t1/2&agr; was longer than that of the control group (4 ± 1 minutes vs 2 ± 1 minutes, P = 0.014); the K12 in the lipid group was less than that of the control group (0.13 ± 0.04 vs 0.32 ± 0.13, P = 0.011). In the lipid group, the bupivacaine content in heart, brain, lung, kidney, and spleen was lower than that in the control group, but higher in the liver at 20, 30, and 45 minutes. CONCLUSION:The lipid sink phenomenon was observed in this study. The use of a lipid emulsion accelerated the elimination of bupivacaine.

The Comparative Effects of Lipid, Epinephrine, and Their Combination in the Reversal of Bupivacaine-induced Asystole in the Isolated Rat Heart

BACKGROUND: It remains unclear whether lipid combined with epinephrine is superior or inferior to either drug alone in treating bupivacaine cardiotoxicity. We compared the effects of lipid, epinephrine, and the combination of the two in reversing bupivacaine-induced asystole in the isolated rat heart model. We also measured the effects of lipid, epinephrine, and the combination of the two on bupivacaine content in cardiac tissue. METHODS: Hearts from male Sprague–Dawley rats were excised and retrograde-perfused in a nonrecirculating Langendorff preparation. Bupivacaine 100 &mgr;mol/L was perfused until 3 minutes after asystole. Two percent lipid and 30 &mgr;mol/L bupivacaine mixture was then perfused in the lipid group; 0.15 &mgr;g/mL epinephrine and 30 &mgr;mol/L bupivacaine mixture in the epinephrine group; 2% lipid combined with 0.15 &mgr;g/mL epinephrine and 30 &mgr;mol/L bupivacaine in the combination group; and 30 &mgr;mol/L bupivacaine alone in the control group. Recovery of heartbeat was defined as unassisted regular rhythm with a rate-pressure product (RPP) >10% of baseline for >1 minute. We compared the time from the end of 100 &mgr;mol/L bupivacaine infusion to recovery of heartbeat (Trecovery) for each group. The variables of cardiac function were recorded for 40 minutes after recovery of heartbeat. The cardiac apex of each heart was taken for measurement of the bupivacaine content by liquid chromatography–tandem mass spectrometry at the end of the experiment. RESULTS: Time to recovery (Trecovery) in the lipid and combination groups was significantly shorter than that in the epinephrine and control groups (P < 0.001), and Trecovery in the epinephrine group was shorter than that in the control group (P < 0.05). The rank order of the mean RPP during the 40 minutes after recovery of heartbeat from highest to lowest was the combination group > the lipid and epinephrine groups > the control group (P < 0.01). The rank order of the highest RPP value during recovery (RPPmaximum) and the ratio of RPPmaximum to baseline value (RPPmaximum/RPPbaseline) from highest to lowest was the combination group > the lipid and epinephrine groups > the control group (P < 0.01). There was no significant difference between the lipid and epinephrine groups for RPP, RPPmaximum, and RPPmaximum/RPPbaseline. Cardiac tissue bupivacaine content in the epinephrine and control groups was higher than that in the lipid and combination groups (P < 0.001). CONCLUSIONS: Lipid combined with epinephrine resulted in better recovery of cardiac function than either drug alone in reversal of bupivacaine-induced asystole in the isolated rat heart model.

Epinephrine administration in lipid-based resuscitation in a rat model of bupivacaine-induced cardiac arrest: optimal timing.

Background and Objectives The medical community commonly uses lipid emulsion combined with epinephrine in local anesthetic–induced cardiac arrest, but the optimal timing of epinephrine administration relative to lipid emulsion is currently unknown and needs to be determined. Methods Thirty adult male Sprague-Dawley rats were subjected to bupivacaine-induced asystole and were then randomly divided into 3 groups. The temporal administration of epinephrine varied in each group: (1) immediately after the completion of the initial bolus of lipid emulsion therapy (postILE0); (2) immediately after cardiac arrest before the initial bolus of lipid emulsion (preILE); or (3) 1 minute after the completion of the initial bolus of lipid emulsion (postILE1). External chest compression was administered until the return of spontaneous circulation or the end of a 20-minute resuscitation period. Results The postILE0, preILE, and postILE1 groups displayed different survival rates (100%, 30%, and 40%; P = 0.003). After return of spontaneous circulation, the rate–pressure product of the postILE0 group was higher than that of the postILE1 group (P < 0.001). Wet-to-dry lung weight ratio of preILE and postILE1 groups was higher than that of the postILE0 group (P < 0.05). The rate of damaged alveoli of the postILE0 group was lower than those of the preILE (P = 0.001) and postILE1 (P < 0.001) groups. Concentrations of bupivacaine in the cardiac tissues of the postILE0 group were lower than that of the postILE1 group (P = 0.01). Conclusions In the rat model of bupivacaine-induced cardiac arrest, the optimal timing for the administration of epinephrine to produce best outcomes of successful cardiopulmonary resuscitation is immediately after the completion of the lipid emulsion bolus. This optimal timing/therapeutic window is of paramount importance.

Feasibility of ultrasound-guided capsule-sheath space block combined with anterior cervical cutaneous nerves block for thyroidectomy: an observational pilot study

BackgroundWe evaluated the efficacy of a new anesthetic technique termed ultrasound-guided capsule-sheath space block (CSSB) combined with anterior cervical cutaneous nerve block (CCNB) for thyroidectomy.MethodsThe study included two parts: Part one was an imaging study to determine technique feasibility. The CSSB was performed on five healthy volunteers by introducing the needle 0.5xa0cm lateral to the probe under in-plane needle ultrasound guidance. After puncture of the false capsule and its subsequent contraction with the true capsule of thyroid, 10xa0mL of contrast medium was deposited slowly in the capsule-sheath space. The CCNB was performed bilaterally as follows: Under ultrasound guidance, a subcutaneous injection was made along the sternocleidomastoid using 10xa0mL of contrast medium which was followed by a girdle-shaped picchu raised from the cricoid cartilage to supraclavicular region. The spreading pattern of contrast medium was imaged using computed tomographic scanning. In part two (a clinical case series) the technique efficacy was evaluated. Seventy-eight patients undergoing thyroidectomy had ultrasound-guided CSSB and CCNB with local anesthetics. The sensory onset of CCNB, intraoperative hemodynamic parameters, and analgesic effect were assessed and complications were noted.ResultsThe distribution of contrast medium was well defined. In part two the onset time of CCNB was 2.2u2009±u20090.7xa0min, and the hemodynamic parameters remained stable intraoperatively. The recall of visual analogue scale scores during surgery was 2 [1–4] for median (range). The patients’ and surgeons’ satisfaction scores were 2 [1–4] and 1 [1–3] for median (range). No serious complications occurred.ConclusionsCombining ultrasound-guided CSSB and CCNB is a feasible, effective and safe technique for thyroidectomy.Trial registrationCurrent Controlled Trials ChiCTR-ONC-12002025. Registered 19 March 2012.

The protective effect of lipid emulsion in preventing bupivacaine-induced mitochondrial injury and apoptosis of H9C2 cardiomyocytes

Abstract Lipid emulsion (LE) has been shown to be effective in the resuscitation of bupivacaine-induced cardiac arrest, but the precise mechanism of this action has not been fully elucidated. Pursuant to this lack of information on the mechanism in which LE protects the myocardium during bupivacaine-induced toxicity, we explored mitochondrial function and cell apoptosis. H9C2 cardiomyocytes were used in study. Cells were randomly divided in different groups and were cultivated 6u2009h, 12u2009h, and 24u2009h. The mitochondria were extracted and mitochondrial ATP content was measured, as was mitochondrial membrane potential, the concentration of calcium ion (Ca2+), and the activity of Ca2+-ATP enzyme (Ca2+-ATPase). Cells from groups Bup1000, LE group, and Bup1000LE were collected to determine cell viability, cell apoptosis, and electron microscopy scanning of mitochondrial ultrastructure (after 24u2009h). We found that LE can reverse the inhibition of the mitochondrial function induced by bupivacaine, regulate the concentration of calcium ion in mitochondria, resulting in the protection of myocardial cells from toxicity induced by bupivacaine.

Measurement of the efficacy of 2% lipid in reversing bupivacaine- induced asystole in isolated rat hearts

BackgroundThe reversal efficacy of 2% lipid emulsion in cardiac asystole induced by different concentrations of bupivacaine is poorly defined and needs to be determined.MethodsForty-two male Sprague–Dawley rats were randomly divided into seven groups: B40, B60, B80, B100, B120, B140 and B160, nu2009=u20096. The Langendorff isolated heart perfusion model was used, which consisted of a balanced perfusion with Krebs-Henseleit solution for 25xa0minutes and a continuous infusion of 100xa0μmol/L bupivacaine until asystole had been induced for 3xa0minutes. The hearts in the seven groups were perfused with Krebs-Henseleit solution containing a 2% lipid emulsion, and 40, 60, 80, 100, 120, 140 or 160xa0μmol/L bupivacaine, respectively. Cardiac recovery was defined as a spontaneous and regular rhythm with a rate-pressure productu2009>u200910% of the baseline value for more than 1xa0minute. Our primary outcome was the rate-pressure product 25xa0minutes after cardiac recovery. Other cardiac function parameters were also recorded.ResultsAll groups demonstrated cardiac recovery. During the recovery phase, heart rate, rate-pressure product, the maximum left ventricular pressure rise and decline in heart rate in the B120-B160 groups was significantly lower than those in the B40-B80 groups (Pu2009<u20090.05). The concentration of bupivacaine and the reversal effects of a 2% lipid emulsion showed a typical transoid S-shaped curve, R2u2009=u20090.9983, IC50 value was 102.5xa0μmol/L (95% CI: 92.44 - 113.6).ConclusionsThere is a concentration-response relationship between the concentrations of bupivacaine and the reversal effects of 2% lipid emulsion.

The Effect of Lipid Emulsion on Pharmacokinetics of Bupivacaine in Rats: Long-Chain Triglyceride Versus Long- and Medium-Chain Triglyceride.

BACKGROUND:Lipid infusions have been proposed to treat local anesthetic–induced cardiac toxicity. This study compared the effects of long-chain triglyceride (LCT) emulsions with those of long- and medium-chain triglyceride (LCT/MCT) emulsions on the pharmacokinetics of bupivacaine in a rat model. METHODS:After administration of intravenous infusion of bupivacaine at 2 mg·kg−1·min−1 for 5 minutes in Sprague–Dawley (SD) rats, either Intralipid 20%, an LCT emulsion (LCT group, n = 6), or Lipovenoes 20%, an LCT/MCT emulsion (LCT/MCT group, n = 6), was infused at 2mg·kg−1·min−1 for 5 minutes. The concentrations of total plasma bupivacaine and bupivacaine that were not bound by lipid (lipid unbound) were measured by a liquid chromatography–tandem mass spectrometric method. A 2-compartmental analysis was performed to calculate the lipid-bound percentage of bupivacaine and its pharmacokinetics. RESULTS:In the LCT group, the clearance (15 ± 2 vs 10 ± 1 mL·min−1·kg−1, P = .003) was higher; the volume of distribution (0.57 ± 0.10 vs 0.36 ± 0.11 L·kg−1, P = .007) and K21 (0.0100 ± 0.0018 vs 0.0070 ± 0.0020 min−1, P = .021, P′ = .032) were larger; and the area under the blood concentration–time curve 0 − t; (605 ± 82 vs 867 ± 110 mgL−1·min−1, P =.001) and the area under the blood concentration–time curve (0 − ∞) (697 ± 111 vs 991 ± 121 mgL−1·min−1, P =.001) were less, when compared with the LCT/MCT group. CONCLUSIONS:LCT emulsions are more effective than LCT/MCT emulsions in the metabolism of bupivacaine through demonstration of a superior pharmacokinetic profile.

The ultrasound-guided selective nerve block in the upper arm: an approach of retaining the motor function in elbow

BackgroundProximal brachial plexus blocks can lead to an extended period of motor paralysis and delay the return of motor function. This could influence patient satisfaction, and extend hospitalizations. The aim of the study is to compare a selective distal nerve block of the arm to a proximal axillary block, both ultrasound-guided, in terms of their motor block intensity of the elbow. Our hypothesis is that a selective nerve block of the arm would result in a different motor block of the elbow, compared to the axillary block.MethodsA sample size of 24 patients who were undergoing elective surgery (ASA I-III) of the wrist, hand or forearm was randomly divided into two groups: Arm Group (nu2009=u200912) and Axillary Group (nu2009=u200912). The Arm Group received ultrasound-guided block of the median, ulnar, and medial antebrachial cutaneous nerves at the level of upper-median 1/3 of the arm, and a block of the radial and musculocutaneous nerves at the level of low-median 1/3 of the arm, while the Axillary Group received ultrasound-guided axillary brachial plexus blocks. Both blocks used in combination with general anesthesia.ResultsOur results demonstrated that the incidence of motor block at the elbow in the Arm Group was lower than in the Axillary Group. Compared with the Axillary Group, the duration of motor block at the elbow and the onset time of sensory block in the Arm Group were shortened. The patient satisfaction was increased in the Arm Group. There were no differences in the duration of the sensory block, the effect on postoperative analgesia, or in the duration of the motor block at the shoulder between both groups.ConclusionOur study showed that ultrasound-guided selective nerve block in the upper arm allowed improved retention of motor function at the elbow compared to axillary block. Secondarily, the ultrasound-guided selective nerve block seemed to provide similar analgesia after surgery of the hand or forearm with an enhanced patient satisfaction.Trial registrationChinese Clinical Trial Registry, ChiCTR-IOR-16008769. Registered 3 July 2016.