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.

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.

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.

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).

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.

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.

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.

Transmuscular quadratus lumborum block versus oblique subcostal transversus abdominis plane block for analgesia in laparoscopic hysterectomy: a randomised single-blind trial.

OBJECTIVE: The transmuscular quadratus lumborum (TQL) block and the oblique subcostal transversus abdominis plane (OSTAP) block both contribute to multimodal analgesia after laparoscopic surgery. The objective of this study was to compare the analgesic effects of the TQL block versus OSTAP block after laparoscopic hysterectomy. DESIGN: Prospective single-centre randomised single-blind trial. SETTING: University-affiliated hospital. PARTICIPANTS: Patients aged between 18 and 65 years scheduled for laparoscopic hysterectomy. INTERVENTIONS: Patients were randomised into two groups (1:1 ratio) and received bilateral TQL block or bilateral OSTAP block with 0.375% ropivacaine 20 mL on each side before surgery. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the cumulative morphine dose in the first 24 hours. The secondary outcome measures were the morphine consumption at each time interval after surgery, the time from the end of surgery to the first need for morphine, the Numerical Rating Scale (NRS) scores for visceral and incisional pain intensity, and the incidence of adverse events. RESULTS: The cumulative morphine dose was significantly lower in the TQL group than in the OSTAP group (17.2 (12.5) vs 26.1 (13.3) mg, p=0.010). Compared with the OSTAP group, the morphine doses from 6 to 12, 12 to 18, and 18 to 24 hours were significantly lower, the time of first need for morphine was significantly longer and the NRS scores for visceral pain intensity were significantly lower in the TQL group. CONCLUSION: Compared with the OSTAP block, the TQL block reduced morphine consumption and provided better visceral pain relief with a longer duration of effect after laparoscopic hysterectomy. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1800017995); pre-results.

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.

Single and Repeated Intrapleural Ropivacaine Administration: A Plasma Concentration and Pharmacodynamics Study.

BACKGROUND: Intrapleural analgesia has been increasingly recommended for postoperative analgesia after thoracic surgery. However, the analgesic effect provided by a single intrapleural administration is time limited. This study reports the efficacy and safety of repeated intrapleural 0.75% ropivacaine administration after thoracoscopic surgery. METHODS: Twenty patients were randomly divided into two groups: a single administration group receiving a single intrapleural injection of 0.75% ropivacaine 15 mL (single administration group, SA group), and a repeated administration group with an intrapleural injection of 0.75% ropivacaine 15 mL every 4h for 4 doses (repeated administration group, RA group). The primary outcomes of this study were the peak plasma concentration of ropivacaine and 24h morphine consumption. The secondary outcomes were pain score, patient satisfaction, extubation time, hospital length of stay, and adverse reactions. RESULTS: In SA group, the highest plasma concentration after intrapleural administration of 0.75% ropivacaine 15 mL was 1345±364 µg/L. The highest plasma concentration in RA group after the fourth administration was 1864±492 µg/L. The 24h morphine consumption in RA group was significantly less than that in SA group (9.0±5.66 vs 15.9±3.48 mg, P=0.004). The NRS scores at rest and while coughing of patients in RA group were significantly lower than those in SA group at 5, 9, 13, 17 and 24h after operation. The patients in RA group had higher satisfaction than those in SA group. There was no significant difference in postoperative adverse events, drainage tube placement days and hospital length of stay between the two groups. CONCLUSION: Repeated intrapleural administration with 0.75% ropivacaine, 15 mL every 4h for 4 doses after video-assisted thoracoscopic lobectomies, can provide a more durable and more effective analgesic effect than single intrapleural administration. Repeated intrapleural administration of ropivacaine is an effective postoperative method of analgesia resulting in higher patient satisfaction. Moreover, it was also able to keep the plasma concentration of ropivacaine within a possible safe range. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-IOR-17010560.

Omentin-1 attenuates glucocorticoid-induced cardiac injury by phosphorylating GSK3ß.

Glucocorticoid excess often causes a variety of cardiovascular complications, including hypertension, atherosclerosis, and cardiac hypertrophy. To abrogate its cardiac side effects, it is necessary to fully disclose the pathophysiological role of glucocorticoid in cardiac remodelling. Previous clinical and experimental studies have found that omentin-1, one of the adipokines, has beneficial effects in cardiovascular diseases, and is closely associated with metabolic disorders. However, there is no evidence to address the potential role of omentin-1 in glucocorticoid excess-induced cardiac injuries. To uncover the links, the present study utilized rat model with glucocorticoid-induced cardiac injuries and clinical patients with abnormal cardiac function. Chronic administration of glucocorticoid excess reduced rat serum omentin-1 concentration, which closely correlated with cardiac functional parameters. Intravenous administration of adeno-associated virus encoding omentin-1 upregulated the circulating omentin-1 level and attenuated glucocorticoid excess-induced cardiac hypertrophy and functional disorders. Overexpression of omentin-1 also improved cardiac mitochondrial function, including the reduction of lipid deposits, induction of mitochondrial biogenesis, and enhanced mitochondrial activities. Mechanistically, omentin-1 phosphorylated and activated the GSK3ß pathway in the heart. From a study of 28 patients with Cushing's syndrome and 23 healthy subjects, the plasma level of glucocorticoid was negatively correlated with omentin-1, and was positively associated with cardiac ejection fraction and fractional shortening. Collectively, the present study provided a novel role of omentin-1 in glucocorticoid excess-induced cardiac injuries and found that the omentin-1/GSK3ß pathway was a potential therapeutic target in combating the side effects of glucocorticoid.

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.

Comparison of Effectiveness of Ropivacaine Infusion Regimens for Continuous Femoral Nerve Block for Recovery After Total Knee Arthroplasty: A Randomized Double-Blind Trial.

PURPOSE: Continuous femoral nerve block (cFNB) is effective for analgesia after total knee arthroplasty (TKA). However, it is not clear which low-dose regimen of ropivacaine infusion for cFNB provides adequate analgesia and enables rapid recovery. The aim of this study was to compare the effects of different cFNB regimens on rehabilitation of patients after TKA. PATIENTS AND METHODS: Sixty patients scheduled for TKA were enrolled in this trial. After surgery, patients in the 0.1%, 0.15%, and 0.2% groups received infusion of 10 mL of 0.1%, 6.7 mL of 0.15%, and 5 mL of 0.2% ropivacaine per hour, respectively (n=20), at the dose of 10 mg/h for 48 h. The primary endpoint was time to readiness for discharge. The secondary endpoints were time to first walk, manual muscle testing (MMT) scores, numerical rating scale (NRS) scores at rest and movement, morphine consumption, rescue analgesia, and the incidence of adverse events. RESULTS: The time to readiness for discharge and the time to first walk of the 0.1% group were significantly longer than that of the 0.15% and 0.2% groups. MMT scores of the 0.2% group at 18 h after surgery were significantly lower than those of the 0.1% group. MMT scores of the 0.2% group at 24 and 48 h after surgery were also significantly lower than those of the 0.1% and 0.15% groups. NRS scores at rest and at movement in the 0.1% group were significantly higher than those in the 0.15% and 0.2% groups. CONCLUSION: Patients administered the regimens of 0.15% and 0.2% ropivacaine infusion for cFNB were ready for discharge earlier than the 0.1% group after TKA, at the dose of 10 mg/h for 48 h. The regimen of 0.15% ropivacaine, which is associated with less quadriceps muscle strength weakness than 0.2%, is recommended for postoperative analgesia after TKA.

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.

Comparison of programmed intermittent bolus infusion and continuous infusion for postoperative patient-controlled analgesia with thoracic paravertebral block catheter: a randomized, double-blind, controlled trial.

BACKGROUND AND OBJECTIVES: In this randomized, double-blind, controlled study, we hypothesized that programmed intermittent bolus infusion (PIBI) of local anesthetic for continuous paravertebral block (PVB), combined with patient-controlled analgesia (PCA), provided better pain control, better patient satisfaction, and decreased in local anesthetic consumption when compared with a continuous infusion (CI) combined with PCA, after video-assisted thoracoscopic unilateral lung resection surgery. METHODS: Preoperatively, patients undergoing video-assisted thoracoscopic unilateral lung resection surgery received ipsilateral paravertebral catheters inserted at the level of thoracic vertebrae 4 and 5. All the subjects received an initial bolus of 15 mL 0.375% ropivacaine via the catheters. Subjects were randomized to receive 0.2 % ropivacaine 8 mL/h as either PIBI (n=17) or CI (n=17) combined with a PCA pump. The pain scores, frequency of PCA, local anesthetic consumption, patient satisfaction, and the need for rescue analgesia with tramadol were recorded until 48 hours postoperative. RESULTS: The numeric rating scale scores in the PIBI group were significantly lower than the CI group at 4, 8, 12 hours and 4, 8, 12, 24 hours postoperatively, at rest, and during coughing, respectively. PCA local anesthetic consumption (30 mg (20-60 mg) vs 120 mg (70-155 mg), p=0.000) and frequency of PCA use over 48 hours (3 (2-6) vs 12 (7-15.5), p=0.000) was lower in the PIBI group as compared with the CI group. Additionally, the PIBI group showed greater patient satisfaction. The need for tramadol rescue was similar in the two groups. CONCLUSIONS: In PVBs, local anesthetic administered as a PIBI in conjunction with PCA provided superior postoperative analgesia to a CI combined with PCA in patients undergoing video-assisted thoracoscopic unilateral lung resection surgery. CLINICAL TRIAL REGISTRATION: ChiCTR-IOR-17011253.

Lipid Emulsion Pretreatment Decreased the Maximum Total and Free Plasma Concentration of Levobupivacaine for Femoral and Sciatic Nerve Block in Below-Knee Fracture Surgery.

BACKGROUND AND OBJECTIVES: Although intravenous lipid emulsion has been proved a powerful antidote for local anesthetic toxicity, there are few pharmacokinetic data on using lipid infusion as a pretreatment for other clinical applications. We assessed the influence of lipid pretreatment on the pharmacodynamics and pharmacokinetics of levobupivacaine. METHODS: Altogether, 12 patients undergoing below-knee surgery for a fracture were randomly assigned to 2 groups (6 patients per group): pretreatment with 1.5 mL/kg lipid infusion (lipid group) or saline infusion (control subjects) followed by complete femoral and sciatic nerve block with 0.375% levobupivacaine (2.5 mg/kg). Total and free (non-protein bound) plasma levobupivacaine concentrations and triglycerides in the lipid group were determined. RESULTS: Results were given as means ± SD. Total and free maximum plasma levobupivacaine concentrations were lower in the lipid group than in control subjects (865 ± 98 vs 1145 ± 177 µg/L and 56.8 ± 7.5 vs 78.2 ± 13.7 µg/L, respectively; P < 0.01). Apparent volume of distribution and clearance were higher in the lipid group than in control subjects (211 ± 35 vs 170 ± 21 L and 35.1 ± 8.0 vs 25.8 ± 2.6 L/h, respectively; P < 0.05). Triglyceride level was significantly higher at the end of lipid infusion than baseline values (7.59 ± 1.32 vs 1.34 ± 0.39 mmol/L; P < 0.01). CONCLUSIONS: Lipid pretreatment increased the apparent volume of distribution and clearance and decreased the maximum total and free levobupivacaine concentrations, thus offering a reasonable explanation for the effects of lipids on local anesthesia-related toxicity in humans. Rapid lipid infusion induced hypertriglyceridemia without other apparent risks in this study. CLINICAL TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry, identifier ChiCTR-TRC-14005203.

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).