Quanguang Wang

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 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.

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.

Effect of Ultrasound-guided Nerve Block With 0.75% Ropivacaine at the Mid-forearm on the Prevalence of Moderate to Severe Pain After Hand Surgery

PURPOSE This study tested the hypothesis that ultrasound-guided mid-forearm nerve block with 0.75% ropivacaine reduces the prevalence of moderate to severe pain after wrist and hand surgery, and provides prolonged postoperative analgesia with minimal motor blockade. METHODS Thirty patients undergoing elective wrist and hand surgery were randomly assigned to 1 of 2 groups: group R (n = 15) and group NS (n = 15). We combined an ultrasound-guided supraclavicular brachial plexus block with mid-forearm median, radial, and ulnar nerve block in all patients. The supraclavicular brachial plexus was blocked with 20 mL of 1.5% lidocaine, and the mid-forearm nerves were blocked with 15 mL of either 0.75% ropivacaine (group R) or normal saline (5 mL each nerve) (group NS). A blinded observer provided a numeric rating pain score at 1, 2, 6, 12, 24, and 48 hours after surgery. The durations of sensory and motor blockade, patient satisfaction, morphine requirement for postoperative pain rescue, and adverse events were recorded. FINDINGS The prevalence of moderate to severe pain in group R was significantly lower than that in group NS (33% vs 86%; P = 0.008). The highest mean (SD) numeric rating pain score (worst pain) in group R was lower than that in group NS (2.7 [1.9] vs 5.6 [2.9]; P = 0.004), and the median (Q1, Q3) amount of morphine required for postoperative pain rescue in group R was lower than that in group NS (0 [0, 6] vs 8 [6, 10]; P = 0.001]. Additionally, there were no differences in the durations of motor blockade between the 2 groups. IMPLICATIONS Based on the findings from this study, ultrasound-guided mid-forearm nerve block with 0.75% ropivacaine significantly reduces the prevalence of moderate to severe pain after wrist and hand surgery, provides long-term postoperative analgesia, and facilitates the return of motor function in the upper limb. Chinese Clinical Trial Registry identifier: ChiCTR-IOR-15007278 (October 2015).

Epinephrine Deteriorates Pulmonary Gas Exchange in a Rat Model of Bupivacaine-Induced Cardiotoxicity: A Threshold Dose of Epinephrine.

Background and Objective The study goal was to compare the effect of epinephrine in different doses on pulmonary gas exchange in a rat model of bupivacaine-induced cardiac depression. Methods Twenty-four adult male Sprague-Dawley rats were divided into 4 groups (n = 6), and each group received a bupivacaine infusion (2.5 mg/kg per minute, 6 minutes) via the left femoral vein to induce cardiac depression. At the end of the bupivacaine infusion, each group was immediately given either isotonic sodium chloride solution (normal saline; NS group), 5-&mgr;g/kg epinephrine (Epi5 group), 10-&mgr;g/kg epinephrine (Epi10 group), or 20 &mgr;g/kg epinephrine (Epi20 group). Left atrial pressures were monitored for 20 minutes after epinephrine was administered (as was the NS group). Arterial blood gas analyses were performed before bupivacaine infusion and at the end of the 20-minute monitoring period. Results The Epi10 and Epi20 groups had lower pH (P = 0.02 and P < 0.001, respectively) and PaO2 (P = 0.049 and P < 0.001, respectively), and a higher PaCO2 (P < 0.001 and P < 0.001, respectively) compared with the NS group. There were no statistical differences between the Epi5 and NS groups in pH, PaCO2, or PaO2. Left atrial systolic pressure was higher in the Epi10 group (P = 0.002) and the Epi20 group (P < 0.001) within 2 minutes of epinephrine administration. There was no statistical difference between the Epi5 and NS groups in left atrial systolic pressure. Conclusion A single injection of 10 &mgr;g/kg epinephrine or greater was associated with deterioration of pulmonary gas exchange in our rat model of bupivacaine induced cardiac depression.