zhong Xu

The analgesic efficacy of subcostal transversus abdominis plane block compared with thoracic epidural analgesia and intravenous opioid analgesia after radical gastrectomy.

BACKGROUND: The transversus abdominis plane (TAP) block has been shown to provide effective postoperative analgesia in lower abdominal surgery. Subcostal TAP block has also been proposed as a new technique to provide analgesia for the supraumbilical abdomen. We compared the analgesic and opioid-sparing effects of a single-injection subcostal TAP block with continuous thoracic epidural analgesia and IV opioid analgesia. METHODS: Ninety patients undergoing elective radical gastrectomy were randomized to receive either combined general–subcostal TAP anesthesia (group TAP), combined general–epidural anesthesia (group EA), or general anesthesia (group GA), and were analyzed on an intention-to-treat basis. In group TAP, a bilateral subcostal TAP block was performed after induction of general anesthesia using 20 mL of 0.375% ropivacaine. In group EA, a thoracic epidural was placed between T8 and T9 and bolused with 8 mL of 0.25% ropivacaine before induction of general anesthesia. The epidural was maintained with 5 mL/h of 0.25% ropivacaine during the surgery. Group GA received standard general anesthesia. In the postanesthesia care unit (PACU), all groups received IV morphine titration for visual analog scale (VAS) pain scores >3. All patients were started on IV patient-controlled analgesia with morphine after morphine titration in the PACU, while group EA also had their epidural maintained with 5 mL/h of 0.125% bupivacaine with 8 &mgr;g/mL morphine. Patients were assessed in the PACU and at 1, 3, 6, 24, 48, and 72 hours postoperatively. Primary outcomes measured were morphine consumption at 24 hours and all VAS pain scores. RESULTS: Data from 82 of 90 (91.1%) patients were included in the study. Group TAP demonstrated decreased cumulative morphine consumption at 24 hours (98.75% confidence intervals, −29 to −9 mg) and noninferiority on VAS pain scores at all measurement times, as compared with group GA with standard opioid analgesia. However, group EA was superior to group TAP regarding cumulative morphine consumption at 24 hours (98.75% confidence intervals, −23 to −4 mg) and noninferior to group TAP on VAS pain scores at all comparison points. Group TAP had reduced morphine consumption from PACU admission to 6 hours as compared with group GA, but increased morphine consumption for 6 to 24 hours as compared with group EA. CONCLUSION: Single-injection subcostal TAP block was more effective than IV opioid analgesia, while continuous thoracic epidural analgesia was more effective than the single-injection subcostal TAP block.

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

BACKGROUND The 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. METHODS The 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. RESULTS In 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). CONCLUSIONS LCT 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.

Veno-venous ECMO: a synopsis of nine key potential challenges, considerations, and controversies

BackgroundFollowing the 2009 H1N1 Influenza pandemic, extracorporeal membrane oxygenation (ECMO) emerged as a viable alternative in selected, severe cases of ARDS. Acute Respiratory Distress Syndrome (ARDS) is a major public health problem. Average medical costs for ARDS survivors on an annual basis are multiple times those dedicated to a healthy individual. Advances in medical and ventilatory management of severe lung injury and ARDS have improved outcomes in some patients, but these advances fail to consistently “rescue” a significant proportion of those affected.DiscussionHere we present a synopsis of the challenges, considerations, and potential controversies regarding veno-venous ECMO that will be of benefit to anesthesiologists, surgeons, and intensivists, especially those newly confronted with care of the ECMO patient. We outline a number of points related to ECMO, particularly regarding cannulation, pump/oxygenator design, anticoagulation, and intravascular fluid management of patients. We then address these challenges/considerations/controversies in the context of their potential future implications on clinical approaches to ECMO patients, focusing on the development and advancement of standardized ECMO clinical practices.SummarySince the 2009 H1N1 pandemic ECMO has gained a wider acceptance. There are challenges that still must be overcome. Further investigations of the benefits and effects of ECMO need to be undertaken in order to facilitate the implementation of this technology on a larger scale.

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.

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 6 h, 12 h, and 24 h. 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 24 h). 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.

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.

Anesthesia and postoperative analgesia during unilateral lower-extremity fracture surgeries using multiple injections through catheters beside the lumbar plexus or sciatic nerve.

Objective To compare the clinical effects of anesthesia and postoperative analgesia for patients with unilateral lower-extremity fracture between multiple injections through catheters beside the lumbar plexus or sciatic nerve and continuous epidural analgesia. Methods Seventy patients with unilateral lower-extremity fracture scheduled for internal fixation were randomly divided into group N (n = 35) and group E (n = 35). Patients in group N received combined lumbar plexus and sciatic nerve block, then a catheter was inserted into the psoas compartment or beside the sciatic nerve, according to the surgical site, and 25 mL 0.375% ropivacaine was injected into patients in group N through the peripheral nerve catheter 12 hours after operation. Patients in group E received combined spinal and epidural anesthesia, and when the operation was complete kept the epidural catheter and received patient-controlled epidural analgesia with an analgesia pump. Results The visual analog scores of patients at each time point in the two groups showed no significant difference (P > 0.05). Mean arterial pressure at 30 minutes after anesthesia and 4 hours postoperation in group E decreased significantly and was significantly lower than group N (P < 0.01). Group E had significantly higher rate of urinary retention than group N (P < 0.05), and the time of first food intake of patients in group N was significantly shorter than in group E (P < 0.001). Conclusion For patients with unilateral lower-extremity fracture receiving internal fixation, multiple injections through catheters beside the lumbar plexus or sciatic nerve can provide adequate postoperative analgesia, with very few adverse effects.