Facilitating Lung Collapse for Thoracoscopic Surgery Utilizing Endobronchial Airway Occlusion Preceded by Pleurotomy and One-minute Suspension of Two-lung Ventilation.

OBJECTIVES: To assess when and whether clamping the double-lumen endobronchial tube (DLT) limb of the non-ventilated lung is more conducive to a rapid and effective lung deflation than simply allowing the open limb of the DLT to communicate with the atmosphere. DESIGN: This was a single-center, single-blind, randomized, controlled trial. SETTING: The trial was performed in a single institutional setting. PARTICIPANTS: The participants were 60 patients undergoing elective video-assisted thoracoscopic surgery. INTERVENTIONS: Patients were randomized to the open-clamp airway technique (OCAT group) or control group. Patients in the control group had one-lung ventilation initiated upon being placed in the lateral decubitus position. The OCAT group had two-lung ventilation maintained until the pleural cavity was opened with the introduction of a planned thoracoscopic access port to allow the operated lung to fall away from the chest wall. Thereafter, ventilation was suspended (temporarily ceased) for 1 minute before the DLT lumen of the isolated lung was clamped. The primary outcome of the trial was the time to complete lung collapse scored as determined from video clips taken during surgery. The secondary outcomes were (1) lung collapse score at 30 minutes after pleural incision, (2) surgeon satisfaction with surgery, and (3) intraoperative hypoxemia. MEASUREMENTS AND MAIN RESULTS: The median time to reach complete lung collapse in the OCAT group was 10 minutes (odds ratio 10.0, 95% CI 6.3-13.7), which was much shorter than that of the control group (25 minutes [odds ratio 25.0, 95% CI 13.6-36.4]). The difference in complete lung collapse at 30 minutes between the 2 groups was significant (p < 0.001). The surgeon's satisfaction with surgery was higher in the OCAT group than in the control group (8.5 ± 0.2 vs 6.8 ± 0.2; p < 0.001). There was no difference regarding intraoperative hypoxemia. CONCLUSIONS: Suspending ventilation of both DLT limbs for 1 minute after pleural cavity opening and then clamping the DLT lumen of the isolated lung resulted in a more rapid deflation of the surgical lung. This open-clamp airway technique is an effective technique for rapid surgical lung collapse during thoracoscopic surgery.

Dexmedetomidine prolongs the duration of local anesthetics when used as an adjuvant through both perineural and systemic mechanisms: a prospective randomized double-blinded trial.

BACKGROUND: To study the respective peripheral and systemic mechanisms of action of dexmedetomidine, as adjuvant to regional anesthesia, we compared dexmedetomidine added to ropivacaine for mid-forearm nerve blocks, to either systemic-only dexmedetomidine, and to a control with no dexmedetomidine. METHODS: Sixty patients undergoing hand surgery were randomly divided into three groups (n = 20 per group). Each group underwent a triple-nerve (median, radial and ulnar) mid-forearm blocks with 0.75% ropivacaine. In the DexP group, 60 µg of dexmedetomidine were added to the anesthetic mixture, while in the DexIV group, they were intravenously infused. Normal saline as a placebo was used, either as adjuvant, or intravenously. All patients underwent also a supraclavicular block with 1.5% lidocaine for tourniquet pain. The main outcomes were the duration of analgesia and the duration of sensory blockade separately for each nerve termination of the upper limb, and the duration of motor blockade of the upper limb. Tolerance was assessed by blood pressure and heart rate, and the report of adverse events. RESULTS: Duration of analgesia was longer in the DexP group, in comparison to the two other groups (P < 0.001), while it was similar in the DexIV and the control group. For cutaneous territories targeted by the three mid-forearm blocks, the between-group differences behaved similarly. For the other cutaneous territories (musculocutaneous and posterior brachial cutaneous nerves), duration of sensory blockade was shorter in the control group than in the two dexmedetomidine groups. For duration of motor blockade, the between-group differences behaved similarly. Both blood pressure and heart rate were reduced in the DexP and the DexIV groups, compared to the control. CONCLUSIONS: Dexmedetomidine used as an adjuvant to regional anesthesia may act mostly though a perineural mechanism, especially for the sensory aspects of anesthesia. A systemic action might however explain other clinical effects. TRIAL REGISTRATION: ChiCTR-IOR-17011149 , date of registration: 16/04/2017.

Anterior Quadratus Lumborum block area comparison in the three different volumes of Ropivacaine: a double-blind, randomized controlled trial in healthy volunteers.

BACKGROUND: In abdominal surgery, ultrasound-guided anterior quadratus lumborum blocks (QLB) are performed to induce analgesia. However, no study reported suitable volumes of the anterior QLB for the different postoperative analgesia regions. Therefore, this prospective randomized controlled study assessed the dermatomal spread and analgesic effects of the three different volumes of a local anesthetic for anterior QLB. METHODS: Ultrasound-guided anterior QLB was performed at the L2 level on 30 healthy volunteers. The volunteers were randomized to receive 20 ml (n = 10), 30 ml (n = 10), and 40 mL (n = 10) of 0.375% ropivacaine. The cutaneous sensory blocked area (CSBA), the number of block dermatomes, and the block duration time were measured by determining the extent of the cold sensation. RESULTS: The CSBA was significantly larger in the 40 ml group than in the 30 (P = 0.001; 1350.6 ± 234.4 vs. 1009.5 ± 151.6 cm2) and 20 ml groups (P < 0.001; 1350.6 ± 234.4 vs. 808.1 ± 120.5 cm2). Similarly, the number of blocked dermatomes was significantly higher in the 40 ml group than in the 30- and 20-ml groups. However, no significant difference was observed in block duration among the groups. CONCLUSIONS: No difference was observed in block duration with the various volumes of 0.375% ropivacaine. However, the larger volume for anterior QLB contributed to a larger area of cutaneous sensory blockade. Appropriate volumes in anterior QLB can create suitable postoperative analgesia levels for the different operative sites. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registration Center on www.chictr.org.cn on 27th April 2018 (registration number: ChiCTR-IOR-17010853).

Evaluation of Recombinant CYP3A4 Variants on the Metabolism of Oxycodone In Vitro.

Cytochrome P450 3A4 is a highly polymorphic enzyme and metabolizes approximately 40%-60% of therapeutic drugs. Its genetic polymorphism may significantly affect the expression and function of CYP3A4 resulting in alterations of the pharmacokinetics and pharmacodynamics of the CYP3A4-mediated drugs. The purpose of this study was to evaluate the catalytic activities of 30 CYP3A4 nonsynonymous variants and wild type toward oxycodone in vitro. CYP3A4 proteins were incubated with oxycodone for 30 min at 37 °C and the reaction was terminated by cooling to -80 °C immediately. Ultraperformance liquid chromatography tandem mass-spectrometry was used to analyze noroxycodone, and kinetic parameters Km, Vmax, and intrinsic clearance (Vmax/Km) of noroxycodone were also determined. Compared with CYP3A4.1, 24 CYP3A4 variants (CYP3A4.2-.5, -.7-.16, -.18 and -.19, -.23 and -.24, -.28 and -.29, and -.31-.34) exhibited significantly decreased relative clearance values (from 4.82% ± 0.31% to 80.98% ± 5.08%), whereas CYP3A4.6, -.17, -.20, -.21, -.26, and -.30 displayed no detectable enzyme activity. As the first study of these alleles for oxycodone metabolism in vitro, results of this study may provide insight into establishing the genotype-phenotype relationship for oxycodone and serve as a reference for clinical administrators and advance the provision of personalized precision medicine.

Apelin-13 Reverses Bupivacaine-Induced Cardiotoxicity via the Adenosine Monophosphate-Activated Protein Kinase Pathway.

BACKGROUND: Cardiotoxicity can be induced by the commonly used amide local anesthetic, bupivacaine. Bupivacaine can inhibit protein kinase B (AKT) phosphorylation and activated adenosine monophosphate-activated protein kinase alpha (AMPKα). It can decouple mitochondrial oxidative phosphorylation and enhance reactive oxygen species (ROS) production. Apelin enhances the phosphatidylinositol 3-kinase (PI3K)/AKT and AMPK/acetyl-CoA carboxylase (ACC) pathways, promotes the complete fatty acid oxidation in the heart, and reduces the release of ROS. In this study, we examined whether exogenous (Pyr1) apelin-13 could reverse bupivacaine-induced cardiotoxicity. METHODS: We used the bupivacaine-induced inhibition model in adult male Sprague Dawley (SD) rats (n = 48) and H9c2 cardiomyocyte cell cultures to explore the role of apelin-13 in the reversal of bupivacaine cardiotoxicity, and its possible mechanism of action. AMPKα, ACC, carnitine palmitoyl transferase (CPT), PI3K, AKT, superoxide dismutase 1 (SOD1), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p47-phox) were quantified. Changes in mitochondrial ultrastructure were examined, and mitochondrial DNA, cell viability, ROS release, oxygen consumption rate (OCR) were determined. RESULTS: Apelin-13 reduced bupivacaine-induced mitochondrial DNA lesions in SD rats (P < .001), while increasing the expression of AMPKα (P = .007) and PI3K (P = .002). Furthermore, apelin-13 blocked bupivacaine-induced depolarization of the mitochondrial membrane potential (P = .019) and the bupivacaine-induced increases in ROS (P = .001). Also, the AMPK pathway was activated by bupivacaine as well as apelin-13 (P = .002) in H9c2 cardiomyocytes. Additionally, the reduction in the PI3K expression by bupivacaine was mitigated by apelin-13 in H9c2 cardiomyocytes (P = .001). While the aforementioned changes induced by bupivacaine were not abated by apelin-13 after pretreatment with AMPK inhibitor compound C; the bupivacaine-induced changes were still mitigated by apelin-13, even when pretreated with PI3K inhibitor-LY294002. CONCLUSIONS: Apelin-13 treatment reduced bupivacaine-induced oxidative stress, attenuated mitochondrial morphological changes and mitochondrial DNA damage, enhanced mitochondrial energy metabolism, and ultimately reversed bupivacaine-induced cardiotoxicity. Our results suggest a role for the AMPK in apelin-13 reversal of bupivacaine-induced cardiotoxicity.

The erector spinae plane block causes only cutaneous sensory loss on ipsilateral posterior thorax: a prospective observational volunteer study.

BACKGROUND: Ultrasound-guided erector spine plane (ESP) block is widely used in perioperative analgesia for back, chest and abdominal surgery. The extent and distribution of this block remain controversial. This study was performed to assess the analgesia range of an ultrasound-guided ESP block. METHODS: This prospective observational volunteer study consisted of 12 healthy volunteers. All volunteers received an erector spinae plane block at the left T5 transverse process using real-time ultrasound guidance. Measured the cutaneous sensory loss area (CSLA) and cutaneous sensory declination area (CSDA) using cold stimulation at different time points after blockade until its disappearance. The CSLA and CSDA were mapped and then calculated. The block range was described by spinous process level and lateral extension. The effective block duration for each volunteer was determined and recorded. RESULTS: The cold sensory loss concentrates at T6-T9. The decline concentrates primarily at T4-T11. The lateral diffusion of block to the left side did not cross the posterior axillary line, and reached the posterior median line on the right. The area of cutaneous sensory loss was (172 ± 57) cm2, and the area of cutaneous sensory decline was (414 ± 143) cm2. The duration of cutaneous sensory decline was (586 ± 28) minutes. CONCLUSION: Ultrasound-guided erector spine plane block with 20 mL of 0. 5% ropivacaine provided a widespread cutaneous sensory block in the posterior thorax, but did not reach the anterior chest, lateral chest, or abdominal walls. The range of the blockade suggested that the dorsal branch of spinal nerve was blocked. TRIAL REGISTRATION: Chinese Clinical Trial Registry, CHiCTR1800014438. Registered 13 January 2018.

Supplement of levosimendan to epinephrine improves initial resuscitation outcomes from asphyxial cardiac arrest.

BACKGROUND: Levosimendan exerted favorable effects on the initial outcome in the treatment of ventricular fibrillation cardiac arrest. This study investigated the efficacy of levosimendan in the treatment of asphyxia-induced cardiac arrest in rats. METHODS: Animals underwent asphyxial cardiac arrest/cardiopulmonary resuscitation, randomized to three treatment groups: epinephrine (10 µg/kg) supplemented with levosimendan (bolus 12 µg/kg and infusion for 1 h, EL group); epinephrine only (10 µg/kg, E group), or levosimendan only (bolus 12 µg/kg and infusion for 1 h, L group). The resuscitation success rate, wet-to-dry ratio of lung, and rate of alveolar and blood gas analysis were recorded. RESULTS: 10 rats in the EL group, 8 in the E group, and 2 in the L group showed an initial return of spontaneous circulation (P < 0.001); among them, 10, 4, and 2 rats survived at the end of a 60-min observation period from each group, respectively (P = 0.001). The coronary perfusion pressure in the EL group was higher than that of either the E or L group (P < 0.05). The lung wet-to-dry weight ratio and rate of damaged alveoli were lower in the EL group than the E group (P < 0.05). CONCLUSIONS: In the early stage of resuscitation for asphyxia-induced cardiac arrest in rats, levosimendan supplemented with epinephrine can significantly increase coronary perfusion pressure, reduce lung injury, and ultimately enhance the survival rate.

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·min 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·min 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·kg, P = .003) was higher; the volume of distribution (0.57 ± 0.10 vs 0.36 ± 0.11 L·kg, P = .007) and K21 (0.0100 ± 0.0018 vs 0.0070 ± 0.0020 min, P = .021, P' = .032) were larger; and the area under the blood concentration-time curve 0 - t; (605 ± 82 vs 867 ± 110 mgL·min, P =.001) and the area under the blood concentration-time curve (0 - ∞) (697 ± 111 vs 991 ± 121 mgL·min, 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.

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

BACKGROUND: We 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. METHODS: The 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 0.5 cm 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, 10 mL 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 10 mL 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. RESULTS: The distribution of contrast medium was well defined. In part two the onset time of CCNB was 2.2 ± 0.7 min, 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. CONCLUSIONS: Combining ultrasound-guided CSSB and CCNB is a feasible, effective and safe technique for thyroidectomy. TRIAL REGISTRATION: Current Controlled Trials ChiCTR-ONC-12002025. Registered 19 March 2012.

Comparison Between Intraoperative Two-Space Injection Thoracic Paravertebral Block and Wound Infiltration as a Component of Multimodal Analgesia for Postoperative Pain Management After Video-Assisted Thoracoscopic Lobectomy: A Randomized Controlled Trial.

OBJECTIVE: To compare paravertebral block under thoracoscopy with wound infiltration at an early stage after video-assisted thoracic lobectomy surgery. DESIGN: A prospective, randomized, triple-blinded, placebo-controlled trial. SETTING: A single-center university hospital. PARTICIPANTS: Patients scheduled for video-assisted thoracic lobectomy surgery between February 20, 2014 and June 1, 2014 randomly were allocated into paravertebral block (PVB) (n = 35) and infiltration (n = 35) groups. INTERVENTIONS: In the PVB group, 0.5% ropivacaine was injected into the paravertebral space by the surgeon under direct vision with placebo infiltration of saline in the wounds. In the infiltration group, the wounds were infiltrated with 0.5% ropivacaine by the surgeon with a placebo paravertebral block. Subsequently, patient-controlled intravenous morphine analgesia and paracoxib were administered. MEASUREMENTS AND MAIN RESULTS: The primary endpoints were visual analog scale (VAS) pain scores at rest and on cough 0, 2, 6, and 24 hours after surgery. The secondary endpoints were the total morphine during postoperative 0 hours to 24 hours, adverse events, and patient satisfaction with the analgesia. Sixty-one patients completed the study. VAS score on cough at each time point was significantly lower (p<0.05) and median (25th, 75th) morphine consumption was lower in the PVB group than in the infiltration group (26 [10, 35] mg and 42 [29, 58] mg, p<0.001, respectively). There was no difference in VAS score at rest. Patients in the PVB group had higher satisfaction with analgesia than in the infiltration group (p = 0.003). CONCLUSIONS: As part of the multimodal postoperative analgesia, intraoperative paravertebral block provided better dynamic pain relief and reduced morphine consumption compared with local wound infiltration.

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

BACKGROUND: The reversal efficacy of 2% lipid emulsion in cardiac asystole induced by different concentrations of bupivacaine is poorly defined and needs to be determined. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into seven groups: B40, B60, B80, B100, B120, B140 and B160, n = 6. The Langendorff isolated heart perfusion model was used, which consisted of a balanced perfusion with Krebs-Henseleit solution for 25 minutes and a continuous infusion of 100 µmol/L bupivacaine until asystole had been induced for 3 minutes. 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 160 µmol/L bupivacaine, respectively. Cardiac recovery was defined as a spontaneous and regular rhythm with a rate-pressure product > 10% of the baseline value for more than 1 minute. Our primary outcome was the rate-pressure product 25 minutes after cardiac recovery. Other cardiac function parameters were also recorded. RESULTS: All 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 (P < 0.05). The concentration of bupivacaine and the reversal effects of a 2% lipid emulsion showed a typical transoid S-shaped curve, R(2) = 0.9983, IC50 value was 102.5 µmol/L (95% CI: 92.44 - 113.6). CONCLUSIONS: There is a concentration-response relationship between the concentrations of bupivacaine and the reversal effects of 2% lipid emulsion.

Apelin-13 reverses bupivacaine-induced cardiotoxicity: an experimental study.

INTRODUCTION: Cardiac arrest or arrhythmia caused by bupivacaine may be refractory to treatment. Apelin has been reported to directly increase the frequency of spontaneous activation and the propagation of action potentials, ultimately promoting cardiac contractility. This study aimed to investigate the effects of apelin-13 in reversing cardiac suppression induced by bupivacaine in rats. METHODS: A rat model of cardiac suppression was established by a 3-min continuous intravenous infusion of bupivacaine at the rate of 5 mg.kg-1.min-1, and serial doses of apelin-13 (50, 150 and 450 µg.kg-1) were administered to rescue cardiac suppression to identify its dose-response relationship. We used F13A, an inhibitor of Angiotensin Receptor-Like 1 (APJ), and Protein Kinase C (PKC) inhibitor chelerythrine to reverse the effects of apelin-13. Moreover, the protein expressions of PKC, Nav1.5, and APJ in ventricular tissues were measured using Western blotting and immunofluorescence assay. RESULTS: Compared to the control rats, the rats subjected to continuous intravenous administration of bupivacaine had impaired hemodynamic stability. Administration of apelin-13, in a dose-dependent manner, significantly improved hemodynamic parameters in rats with bupivacaine-induced cardiac suppression (p < 0.05), and apelin-13 treatment also significantly upregulated the protein expressions of p-PKC and Nav1.5 (p < 0.05), these effects were abrogated by F13A or chelerythrine (p < 0.05). CONCLUSION: Exogenous apelin-13, at least in part, activates the PKC signaling pathway through the apelin/APJ system to improve cardiac function in a rat model of bupivacaine-induced cardiac suppression.

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, t1/2ß 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 t1/2α 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 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 µg/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.

Ultrasound-guided anterior quadratus lumborum block at the L2 level for postsurgical analgesia in patients undergoing laparoscopic gynaecological surgery: a single-centre, randomised, double-blinded trial at a university-affiliated hospital in China.

OBJECTIVE: This study aimed to investigate the analgesic effect of an ultrasound-guided anterior quadratus lumborum block (QLB) at the L2 level on postoperative pain after laparoscopic gynaecological surgery. DESIGN: Prospective single-centre randomised double-blind trial. SETTING: University-affiliated hospital. PARTICIPANTS: Sixty patients aged between 18 and 65 years scheduled for laparoscopic gynaecological surgery. INTERVENTIONS: Before surgery, bilateral anterior QLB was performed with 20 mL of 0.375% ropivacaine injected on each side in the QLB group, whereas equal amount of saline was administered in the placebo group. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the cumulative morphine dose in the first 24 hours, and the secondary endpoints were morphine consumption at each time interval, area under the curve (AUC) of the numeric rating scale (NRS) for pain, maximum pain intensity, incidence of moderate-to-severe pain (NRS>3), sedation score, adverse events, and time to home-readiness. RESULTS: Cumulative morphine consumption in the first 24 hours after surgery was significantly lower in the QLB group than in the placebo group (mean difference, 14.2; 95% CI 6.3 to 22.1; p<0.001). The AUCs of NRS pain intensity scores, including visceral and incisional pain at rest and on movement, were significantly lower in the QLB group than in the placebo group (all p<0.001). The time to home-readiness was significantly shorter in the QLB group than in the placebo group (p<0.05). CONCLUSION: Ultrasound-guided anterior QLB at the L2 level significantly reduced morphine consumption and relieved visceral and incision pain intensity after laparoscopic gynaecological surgery, which was beneficial for enhanced recovery. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR-IOR-17011960).

Efficacy of ultrasound-guided bilateral costal margin block in laparoscopy-assisted gastrectomy: A double-blind randomized trial.

BACKGROUND: Ultrasound-guided costal margin block (CMB) is a superficial and easily applicable technique. The current study aims to investigate its analgesic efficacy in patients undergoing laparoscopy-assisted gastrectomy and describe its feasibility. METHODS: Forty-two patients undergoing laparoscopy-assisted gastrectomy were enrolled in this prospective, double-blind, randomized clinical trial. Patients were randomized to receive standard general anesthesia with (block group, n = 21) or without (control group, n = 21) ultrasound-guided bilateral CMB. The primary outcome was 24-h intravenous morphine equivalents after surgery. Secondary outcomes included consumption of titrated morphine, 24-48 h morphine equivalents, consumption of intraoperative remifentanil, numerical pain rating scale scores, time to first opioid dose, patient satisfaction, adverse effects, and recovery events. RESULTS: The postoperative 24-h morphine equivalents in the block group were significantly reduced compared to the control group (14.4 ± 7.4 mg vs. 29.9 ± 9.8 mg, p < 0.001). Both the titrated morphine consumption in the post-anesthesia care unit (PACU) and intraoperative remifentanil consumption were lower in the block group than in the control group. Patients in the block group had relatively lower average pain scores in PACU and reported more satisfaction with pain relief. Adverse effects and hospital length of stay after surgery were comparable between the two groups (p > 0.05). CONCLUSION: As a novel and easily-performed technique, ultrasound-guided bilateral CMB can reduce opioid consumption in patients undergoing laparoscopy-assisted gastrectomy.

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 µmol/L was perfused until 3 minutes after asystole. Two percent lipid and 30 µmol/L bupivacaine mixture was then perfused in the lipid group; 0.15 µg/mL epinephrine and 30 µmol/L bupivacaine mixture in the epinephrine group; 2% lipid combined with 0.15 µg/mL epinephrine and 30 µmol/L bupivacaine in the combination group; and 30 µmol/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 µmol/L bupivacaine infusion to recovery of heartbeat (T(recovery)) 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 (T(recovery)) in the lipid and combination groups was significantly shorter than that in the epinephrine and control groups (P < 0.001), and T(recovery) 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 (RPP(maximum)) and the ratio of RPP(maximum) to baseline value (RPP(maximum)/RPP(baseline)) 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, RPP(maximum), and RPP(maximum)/RPP(baseline). 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.

KGF-2 Protects against Lung Ischemia-Reperfusion Injury by Inhibiting Inflammation-Induced Damage to Endothelial Barrier Function.

Lung ischemia-reperfusion injury (LIRI), which has a mortality rate of approximately 50%, is a popular topic in critical care research. Keratinocyte growth factor-2 (KGF-2) is secreted by mesenchymal cells, and it is effective in promoting the proliferation, migration, and differentiation of various epithelial cells. To date, however, only a few reports on KGF-2-related regulators in LIRI have been published. In the current study, an LIRI rat model is constructed, and the upregulation of the fibroblast growth factor receptor 2 (FGFR2) is observed in the LIRI rat model. In addition, LIRI induces NLRP1 inflammasome activation in vivo and in vitro, and KGF-2 inhibits LIRI-induced damage to pulmonary microvascular endothelial cells. Mechanistically, KGF-2 inhibits NLRP1 inflammasome and NF-κB activity. KGF-2 inhibition attenuates LIRI injury-induced damage to endothelial integrity. In conclusion, KGF-2 protects against LIRI by inhibiting inflammation-induced endothelial barrier damage.

[Evaluation of safety and anesthetic effect for ultrasound-guided cervical plexus block].

OBJECTIVE: To observe the influences upon the degree of diaphragmatic excursion during deep cervical plexus block at the third cervical vertebra (C3) and compare the safety and anesthetic effect of modified cervical plexus block by ultrasonic guidance and blocking of cervical plexus at one point. METHODS: Part I: 30 patients of ASA (American society of anesthesiologists) I-II scheduled for thyroid surgery were selected for bilateral cervical plexus block at C3 and bilateral skin nerve branches via ultrasonic guidance. Diaphragmatic excursion was recorded. Part II: 80 patients of ASAI-II scheduled for thyroid surgery were randomly divided into 2 groups: experimental group (Group U) and control group (Group C). In Group U, modified cervical plexus block was used to fix both sides of C3 and skin nerve branches. The anesthetic mixture with 2% lidocaine and 0.75% ropivacaine was injected. And anesthetic effects and complications were detected. In control group, traditional one-point method for blocking cervical plexus was employed. RESULTS: High-frequency Doppler sonography could clearly visualize important neck structures and precisely guide the injection of mixture to the transverse process of C3. Diaphragmatic excursion decreased significantly at 15 and 30 min post-blocking (P < 0.05). And no paralysis of diaphragmatic muscle occurred. Hoverer 3 cases had partial diaphragmatic paralysis. Both blood pressure and heart rate increased significantly post-blocking in both groups (P < 0.05 or 0.01). In comparison with Group C, the range of blood pressure was notably lower at 10 and 20 min in Group U. And heart rate was notably lower at 5, 10, 20 and 30 min (P < 0.05 or 0.01). Furthermore the onset time of skin nerve branches was significantly shorter in Group U (P < 0.01). And the anesthetic effect score was better than that in Group C (P < 0.01). The incidence of complications, such as hoarseness, was significantly lower in Group U (12 cases in Group C but none in Group U, P < 0.01) and Horner's syndrome (2 cases in Group C). The number of cases requiring hypotensor and heart rate control drug was significantly smaller in Group U than that in Group C (P < 0.01). CONCLUSION: The improving effect of ultrasound-guided cervical plexus block upon the degree of diaphragmatic movement is within the compensatory range of body. In comparison with the traditional one-point blocking of cervical plexus, the modified cervical plexus block with ultrasonic guidance offers better anesthetic effects, fewer complications and convenient anesthetic localization. Thus it may be clinically applicable.

Comparison of the effect of different volumes ropivacaine on deep serratus anterior plane block in patients undergoing breast surgery: a prospective randomized double-blinded trial.

BACKGROUND: A larger volume of local anesthetic provides a wider range of blocked sensory but carries a greater risk. The purpose of this trial was to compare the effect of different volumes of ropivacaine injected to deep serratus anterior plane in patients undergoing breast surgery. METHODS: In this randomized double-blind trial, 60 patients undergoing breast surgery were randomly allocated to R10, R20 and R30 groups (n=20), and received deep serratus anterior plane block with 10, 20 and 30 mL of 0.5% ropivacaine respectively. 30 minutes after block, the cutaneous sensory was tested by cold stimulus in the craniocaudal direction along the midaxillary line. We recorded the numerical rating scale pain scores over 24 h after surgery and estimated the area under curve by numerical rating scale pain scores. The cases of rescue analgesia and the prevalence of adverse events were also recorded. RESULTS: The blocked dermatomes were 3 [3, 4], 6 [5, 7] and 7 [6, 8] in the R10, R20 and R30 groups, respectively (R10 vs. R20, P<0.001; R10 vs. R30, P<0.001; R20 vs. R30, P=0.005). The area under curve of R10 group was significantly higher compared with the R20 and R30 groups (P=0.014, P=0.003, at rest; P<0.001, P<0.001, on movement). CONCLUSIONS: The blocked dermatomes increased with increasing volume when 10, 20 and 30 mL ropivacaine was used for deep serratus anterior plane block. The analgesic effects of 20 and 30 mL were similar to each other and better than 10 mL. Therefore, in breast surgery, volume of 20 mL ropivacaine is considered to be appropriate for deep serratus anterior plane block.