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.

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.

Ultrasound-guided bilateral pudendal nerve blocks of nulliparous women with epidural labour analgesia in the second stage of labour: a randomised, double-blind, controlled trial.

OBJECTIVE: To explore whether an ultrasound-guided pudendal nerve block (PNB) could decrease anaesthetic use, thereby shortening the length of the second stage of labour in women undergoing epidural analgesia. DESIGN: Prospective, single-centre, randomised, double-blind, controlled trial. SETTING: An obstetric centre in a general hospital in China. PARTICIPANTS: 72 nulliparous women were randomised, and 71 women completed the study. INTERVENTION: An ultrasound-guided bilateral PNB was administered to all study participants; the PNB group were given 0.25% ropivacaine 10 mL, while the control group were given 10 mL saline. MAIN OUTCOME MEASURE: The primary outcome measure was the duration of the second stage of labour. Secondary outcomes included additional bolus administration, total hourly bupivacaine consumption, difference in thickness between the contracted and relaxed rectus abdominis muscle before (DRAM1) and 30 min after (DRAM2) PNB, urge to defecate, maternal cooperation, preservation of the lower limb motor function, tightness of the perineum, and Numeric Rating Scale (NRS) score for pain. RESULTS: The duration of the second stage of labour was shorter in the PNB group than in the control group (difference of 33.8 min (95% CI 15.6 to 52.0), p<0.001). Additional bolus administration and total hourly bupivacaine consumption were lower in the PNB group than in the control group (p<0.001). DRAM2 was greater (p<0.001), rate of parturient women with the urge to defecate was higher (p=0.014), maternal cooperation was superior (p=0.002), and lower limb motor function preservation was greater (p=0.004) in the PNB group relative to the control group. Tightness of the perineum was eliminated from the results due to the inconsistent application of the criteria by the nursing staff. There was no significant difference in NRS scores between the groups. CONCLUSIONS: Nulliparous women with epidural analgesia who received an ultrasound-guided bilateral PNB may reduce their need for bupivacaine and consequently shorten the length of the second stage of labour, therein indicating that a bilateral PNB may serve as an additional effective adjunct method of labour analgesia. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-16009121.

Effects of Ropivacaine Concentration on Analgesia After Ultrasound-Guided Serratus Anterior Plane Block: A Randomized Double-Blind Trial.

PURPOSE: Serratus anterior plane (SAP) block is effective for analgesia after breast surgery. Whether a higher local anesthetic concentration prolongs sensory block duration and improves postoperative analgesia remains unclear. The aim of this study was to compare the analgesic effects of SAP block with different concentrations of ropivacaine. PATIENTS AND METHODS: Sixty patients scheduled for breast surgery were enrolled in this randomized double-blind trial. SAP block was induced with 20 mL of 0.375%, 0.5%, or 0.75% ropivacaine in Group R0.375, Group R0.5, and Group R0.75, respectively. The primary endpoint was the area under the curve (AUC) of numerical rating scale (NRS) pain intensity scores at rest over time. The secondary endpoints were AUC of NRS pain intensity scores on movement over time, active sensory block duration, tramadol consumption, and the elapsed time between completion of surgery and the first administration of rescue analgesia. RESULTS: The AUC of NRS pain intensity scores at rest of Group R0.375 was significantly higher than that of Groups R0.5 and R0.75 (P=0.025, and P=0.001). The AUC of NRS pain intensity scores on movement of Group R0.375 was also significantly higher than that of Groups R0.5 and R0.75 (both P<0.001). At higher ropivacaine concentrations, the duration of SAP sensory block increased (P<0.001). Tramadol consumption and the elapsed time between completion of surgery and the first administration of rescue analgesia were similar in the three groups (P>0.05). CONCLUSION: A comparison of 0.5% and 0.75% ropivacaine showed no significant difference in postoperative analgesia, but both were superior to 0.375% ropivacaine, although higher ropivacaine concentration lengthened the duration of SAP block. Therefore, SAP block with 0.5% ropivacaine is recommended for postoperative analgesia in breast surgery.

Sensory assessment and block duration of transmuscular quadratus lumborum block at L2 versus L4 in volunteers: a randomized controlled trial.

BACKGROUND: The efficacy of an ultrasound guided transmuscular quadratus lumborum block (QLB) for perioperative analgesia of the upper and lower abdomen remain debatable. The purpose of this study was to compare the cutaneous sensory blocked area (CSBA) between QLB blocks performed at the L2 vs. L4 levels. METHODS: Twenty-two healthy volunteers were randomized 1:1 to receive an ultrasound guided right transmuscular QLB at the L2 level (group QL2) or L4 level (group QL4). A cold stimulus was applied for testing of the CSBA at 30 minutes after the blockade was performed. The CSBA was mapped and then calculated. Three hours after the QLB, a cold stimulus was applied once every hour until sensation returned normal and the effective block duration for each volunteer was determined and recorded. RESULTS: The maximum cephalad dermatome level reached was T7 in group QL2 vs. T11 in group QL4, respectively. Caudally, both groups reached the L2 dermatome level. The QL2 block primarily affected dermatomes T9 to L1, while the QL4 block affected T11 to L1. The total CSBA was larger in QL2 group than that in QL4 group (748 [171] cm2 vs. 501 [186] cm2, P=0.004). The effective duration of the QLB was significantly longer in group QL2 than in group QL4 (18.5 [2.0]h vs. 14.1 [4.7]h, P=0.012). The number of affected dermatomes assessed by cold test was significantly larger for the volunteers in groups QL2 (4.6 [0.81] vs. 2.1 [0.30], P<0.001). CONCLUSIONS: Ultrasound guided transmuscular QLB injection of 0.375% 20 mL ropivacaine at the L2 level produced a widespread cutaneous sensory blockade and a prolonged sensory block to cold sensation compared with the L4 level.

ω-3 fish oil fat emulsion preconditioning mitigates myocardial oxidative damage in rats through aldehydes stress.

ω-3 fish oil fat emulsions contain a considerable quantity of unsaturated carbon-carbon double bonds, which undergo lipid peroxidation to yield low-dose aldehydes. These aldehydes may stimulate the production of antioxidant enzymes, thereby mitigating myocardial oxidative damage. This study aims to (1) verify the cardioprotective effect of ω-3 fish oil fat emulsion in vivo and in vitro, and (2) determine whether aldehyde stress is a protective mechanism. For modeling purposes, we pretreated rats with 2 ml/kg of a 10% ω-3 fish oil fat emulsion for 5 days in order to generate a sufficient aldehyde stress response to trigger the production of antioxidant enzymes, and we obtained similar response with H9C2 cells that were pretreated with a 0.5% ω-3 fish oil fat emulsion for 24 h. ω-3 fish oil fat emulsion pretreatment in vivo reduced the myocardial infarct size, decreased the incidence of arrhythmias, and promoted the recovery of cardiac function after myocardial ischemia/reperfusion injury. Once the expression of nuclear factor E2-related factor 2 (Nrf2) was silenced in H9C2 cells, aldehydes no longer produced enough antioxidant enzymes to reverse the oxidative damage caused by tert-butyl hydroperoxide (TBHP). Our results demonstrated that ω-3 fish oil fat emulsion enhanced the inhibition of oxidation and production of free radicals, and alleviated myocardial oxidative injury via activation of the Nrf2 signaling pathway.

Optimal dose of ropivacaine for relieving cough-pain after video-assisted thoracoscopic lobectomy by single intrapleural injection: A randomized, double-blind, controlled study.

BACKGROUND: Pain due to coughing after thoracoscopic surgery remains a clinical problem, and its relief by intrapleural analgesia has not been extensively studied. This study attempts to determine the suitable volume of 0.75% ropivacaine needed for intrapleural analgesia after thoracoscopic surgery. METHODS: A double-blind, randomized, controlled trial was performed. Forty-five patients were randomly divided into three groups: R20, R15, and R10 (n = 15); 20 ml, 15 ml, or 10 ml of 0.75% ropivacaine was injected into the pleural cavity of each patient in the 3 groups, respectively, when the pain score from postoperative coughing was ≥4. The primary outcome was pain score upon coughing (C-NRS), and the secondary outcomes were pain score at rest (R-NRS), morphine consumption, time of onset, and duration of intrapleural analgesia. RESULTS: All patients in the R20 and R15 groups reported effective pain relief after intrapleural injection when postoperative coughing occurred. However, only 7 patients in the R10 group reported effective relief of pain. Compared with the patients in the R10 group, patients in the R20 and R15 groups had lower C-NRS scores, less morphine consumption at 8 h and 24 h, a shorter time to pain relief, and a longer duration of analgesia. There was no significant difference of R-NRS among the three groups. CONCLUSION: Intrapleural analgesia with 0.75% ropivacaine at a volume of 15 ml or 20 ml effectively relieved pain due to coughing after thoracoscopic surgery. TRIAL REGISTRATION: ChiCTR1800017515.

Luteolin protects against diabetic cardiomyopathy by inhibiting NF-κB-mediated inflammation and activating the Nrf2-mediated antioxidant responses.

BACKGROUND: Diabetes mellitus is a well-known risk factor for the development of heart failure. Inflammation and oxidative stress play a key role in the development of diabetic cardiomyopathy (DCM), and this nexus represents an attractive target to combat this disease. Naturally occurring flavonoid luteolin exhibits both anti-inflammatory and antioxidant activities in various systems. HYPOTHESIS/PURPOSE: In this study, we aimed to investigate potential cardioprotective effects of luteolin in cultured cardiomyocytes and in mice with type 1 diabetes. METHODS: C57BL/6 mice were intraperitoneal injection of streptozotocin (STZ) to induce DCM. High glucose (HG) was used to induce H9C2 cells injury in vitro. Cardiac fibrosis, hypertrophy, inflammation and oxidative stress were studied both in vitro and in vivo. RESULTS: Our studies show that luteolin significantly reduces HG-induced inflammatory phenotype and oxidative stress in H9C2 cardiomyocytes. We found that the mechanisms involved inhibition of nuclear factor-kappa B (NF-κB) pathway and the activation of antioxidant nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway. Modulation of these pathways resulted in reduced expression of matrix proteins and cellular hypertrophy. Luteolin also prevented cardiac fibrosis, hypertrophy, and dysfunction in STZ-induced diabetic mice. These readouts were also associated with reduced levels of inflammatory cytokines and oxidative stress biomarkers. CONCLUSION: Our results indicate that luteolin protects heart tissues in STZ-induced diabetic mice through modulating Nrf2-mediated oxidative stress and NF-κB-mediated inflammatory responses. These findings suggest that luteolin may be a potential therapeutic agent for DCM.

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.

Comparative Regimens of Lipid Rescue From Bupivacaine-Induced Asystole in a Rat Model.

BACKGROUND: It is currently unknown whether bupivacaine-induced asystole is better resuscitated with lipid emulsion (LE) administered peripherally or centrally, and whether different LE regimens administered peripherally demonstrated similar effects. In this study, we compared the effects of various regimens of lipid administration in a rat model of bupivacaine-induced asystole. METHODS: Forty-five adult male Sprague-Dawley rats were subjected to bupivacaine-induced asystole and randomly divided into 3 lipid regimens groups: (1) 20% LE was administered continuously via the internal jugular vein (CV-infusion group); (2) 20% LE was administered continuously via the tail vein (PV-infusion group); and (3) 20% LE was administered as divided boluses via the tail vein (PV-bolus group). The maximum dose of LE did not exceed 10 mL·kg(-1). External chest compressions were administered until the return of spontaneous circulation (ROSC) or the end of a 40-minute resuscitation period. RESULTS: The survival rate, rate of ROSC, systolic blood pressure, heart rate, heart rate-blood pressure product, and coronary perfusion pressure during 2-40 minutes in the CV-infusion and PV-bolus groups were significantly higher than those in the PV-infusion group (P < .01), and the plasma total bupivacaine concentration and myocardial bupivacaine content were significantly lower (P < .05). Time to heartbeat return and time to ROSC in the CV-infusion and PV-bolus groups were significantly shorter than those in the PV-infusion group (P < .05). CONCLUSIONS: In the rat model of bupivacaine-induced asystole, a divided LE bolus regimen administered peripherally provided a better resuscitation outcome than that of a continuous LE infusion regimen peripherally, and performed in a similar fashion as the continuous LE infusion regimen administered centrally.

Levosimendan is superior to epinephrine on coronary flow for lipid-base resuscitation of bupivacaine-induced asystole in the isolated rat heart.

BACKGROUND: Successful resuscitation from asystole induced by bupivacaine requires the reestablishment of a sufficient coronary flow (CF) quickly. This study was designed to test whether levosimendan was superior to epinephrine in the reestablishment of crucial coronary flows after bupivacaine-induced asystole. METHODS: The isolated, perfused, nonrecirculating, Langendorff rat heart preparation was used. Bupivacaine 100 µmol/L was perfused into rat hearts to induce asystole, and then for 3 min thereafter. Three experimental groups were assessed after asystole with infusions as follow: (1) a mixture of 2% lipid emulsion and 40 µmol/L bupivacaine (control group), (2) a mixture of 0.15 µg/mL epinephrine combined with 2% lipid emulsion and 40 µmol/L bupivacaine (epinephrine group), and (3) a mixture of 5 µmol/L levosimendan combined with a 2% lipid emulsion and 40 µmol/L bupivacaine mixture (levosimendan group). Coronary flow (CF), the time to recovery (Trecovery), the number of ventricular arrhythmias, and cardiac function parameters were recorded for 40 min after heartbeat recovery. RESULTS: All hearts in the control, epinephrine and levosimendan groups had heartbeat recovery. The rank order of the mean CF from highest to lowest was the levosimendan group > the epinepgrine group > the control group (P < 0.05). The rank order of Trecovery from shortest to longest was the levosimendan group < the epinephrine group < the control group (P < 0.01). During the recovery phase, isolated rat hearts developed more ventricular arrhythmias in the epinephrine group than in the levosimendan group (P = 0.01). CONCLUSION: Levosimendan is superior to epinephrine in producing higher CFs and faster recovery when reversing bupivacaine-induced asystole in the isolated rat hearts.

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

BACKGROUND: Proximal brachial plexus blocks can lead to an extended period of motor paralysis and delay the return of motor function. This could influence patient satisfaction, and extend hospitalizations. The aim of the study is to compare a selective distal nerve block of the arm to a proximal axillary block, both ultrasound-guided, in terms of their motor block intensity of the elbow. Our hypothesis is that a selective nerve block of the arm would result in a different motor block of the elbow, compared to the axillary block. METHODS: A sample size of 24 patients who were undergoing elective surgery (ASA I-III) of the wrist, hand or forearm was randomly divided into two groups: Arm Group (n = 12) and Axillary Group (n = 12). The Arm Group received ultrasound-guided block of the median, ulnar, and medial antebrachial cutaneous nerves at the level of upper-median 1/3 of the arm, and a block of the radial and musculocutaneous nerves at the level of low-median 1/3 of the arm, while the Axillary Group received ultrasound-guided axillary brachial plexus blocks. Both blocks used in combination with general anesthesia. RESULTS: Our results demonstrated that the incidence of motor block at the elbow in the Arm Group was lower than in the Axillary Group. Compared with the Axillary Group, the duration of motor block at the elbow and the onset time of sensory block in the Arm Group were shortened. The patient satisfaction was increased in the Arm Group. There were no differences in the duration of the sensory block, the effect on postoperative analgesia, or in the duration of the motor block at the shoulder between both groups. CONCLUSION: Our study showed that ultrasound-guided selective nerve block in the upper arm allowed improved retention of motor function at the elbow compared to axillary block. Secondarily, the ultrasound-guided selective nerve block seemed to provide similar analgesia after surgery of the hand or forearm with an enhanced patient satisfaction. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IOR-16008769 . Registered 3 July 2016.

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).

The ED95 of Nalbuphine in Outpatient-Induced Abortion Compared to Equivalent Sufentanil.

This prospective study evaluated the 95% effective dose (ED95 ) of nalbuphine in inhibiting body movement during outpatient-induced abortion and its clinical efficacy versus the equivalent of sufentanil. The study was divided into two parts. For the first part, voluntary first-trimester patients who needed induced abortions were recruited to measure the ED95 of nalbuphine in inhibiting body movement during induced abortion using the sequential method (the Dixon up-and-down method). In the second part, this was a double-blind, randomized study. Sixty cases of first-trimester patients were recruited and were randomly divided into two groups (n = 30), including group N (nalbuphine at the ED95 dose) and group S (sufentanil at an equivalent dose). Propofol was given to both groups as the sedative. The circulation, respiration and body movement of the two groups in surgery were observed. The amount of propofol, the awakening time, the time to leave the hospital and the analgesic effect were recorded. The ED95 of nalbuphine in inhibiting body movement during painless surgical abortion was 0.128 mg/kg (95% confidence intervals 0.098-0.483 mg/kg). Both nalbuphine and the equivalent dose of sufentanil provided a good intraoperative and post-operative analgesic effect in outpatient-induced abortion. However, the post-operative morbidity of dizziness for nalbuphine was less than for sufentanil (p < 0.05), and the awakening time and the time to leave the hospital were significantly shorter than those of sufentanil (p < 0.05). Nalbuphine at 0.128 mg/kg was used in outpatient-induced abortion as an intraoperative and post-operative analgesic and showed a better effect compared with sufentanil.

Sensory Assessment and Regression Rate of Bilateral Oblique Subcostal Transversus Abdominis Plane Block in Volunteers.

BACKGROUND AND OBJECTIVES: The analgesic effect and duration of a transversus abdominis plane (TAP) block remain controversial. Transversus abdominis plane blocks are effective for somatic/incisional pain but do not provide analgesia for visceral pain from intra-abdominal procedures. The purpose of this study was to assess the area and extent of cutaneous sensory blockade and the regression of dermatomal anesthesia after bilateral oblique subcostal TAP block. METHODS: This observational, prospective clinical study consisted of 12 healthy volunteers. All volunteers received a bilateral oblique subcostal TAP block under real-time ultrasound guidance with 20 mL of 0.375% ropivacaine. The anterior abdominal cutaneous area was divided into 3 parts (midabdomen, left-lateral abdomen, right-lateral abdomen) using 2 lines drawn in a parasagittal fashion 5 cm lateral to the midline. The area of cutaneous sensory blockade involving the anterior abdomen was assessed 30 minutes after institution of the block using a cold stimulus. This was followed by repeated measurements using a cold stimulus applied along parasagittal lines drawn 3 cm lateral to the midline at 0.5, 6, 10, 14, 18, 22, and 26 hours after blockade. RESULTS: The area of cutaneous sensory blockade of the abdomen was 332 (SD, 73) cm; that of the midabdomen was 253 (SD, 29) cm, which represented an average of 90% of the area of the midabdomen; and that of the lateral abdominal wall (combination of left-lateral abdomen and right-lateral abdomen) was 79 (SD, 62) cm, which represented an average of 26% of total lateral abdominal area. Dermatomes T7-T12 of the midabdomen were successfully blocked in all volunteers after using the bilateral oblique subcostal technique. However, T6 and L1 were only variably blocked. The area of cutaneous sensory block of the anterior abdomen regressed over the ensuing 22 hours in the following manner: 90%, 87%, 73%, 50%, 22%, 3%, and 0% at 0.5, 6, 10, 14, 18, 22, and 26 hours, respectively. CONCLUSIONS: Bilateral oblique subcostal TAP block produces a widespread cutaneous sensory blockade with a consistent dermatomal distribution in the midabdomen for a considerable effective duration.

Patient-controlled Intravenous Analgesia With Combination of Dexmedetomidine and Sufentanil on Patients After Abdominal Operation: A Prospective, Randomized, Controlled, Blinded, Multicenter Clinical Study.

OBJECTIVE: To investigate the effect of combination of dexmedetomidine and sufentanil on patient-controlled intravenous analgesia (PCIA) in patients after abdominal operation and to assess the safety and validity of this treatment. METHODS: This is a prospective, randomized controlled, blinded, multicenter clinical study. A total of 210 patients from 9 clinical research centers underwent selective abdominal operation with general anesthesia were enrolled in the study, including laparoscopic-assisted abdominal operation on stomach, intestines or open surgery on stomach, intestines, kidneys and liver, the American Society of Anesthesiologists status I to II. Patients were randomly assigned into 2 groups: control group (group C) sufentanil 100 µg+normal saline 100 mL in total and test group (group D) sufentanil 100 µg+ dexmedetomidine 200 µg+normal saline 100 mL in total. PCIA was set as follow: background infusion of sufentanil 2 µg/h, bolus dose of sufentanil 2 µg, lockout interval 5 minutes. Main measure indices were analgesic consumption, pressing times and effective pressing times of analgesic pump, usage count, and consumption of remedy drug. Validity indices were visual analog scale (VAS) scores and patient satisfaction. Drug safety indices were hemodynamic parameters, drug side effects, and anal exhaust time. RESULTS: In total, 203 cases were analyzed. Seven cases were eliminated for incomplete data record. The total consumption of sufentanil (µg) in 24 hours after operation of group C and group D were 56.9±21.5 and 49.8±15.5, respectively, and the difference was statistically significant (P<0.05). Pressing times of analgesic pump in 24 hours after operation of group C and group D were 9.47±16.07 and 5.02±5.56 times, respectively, and the difference was statistically significant (P<0.05). Effective pressing times of analgesic pump in 24 hours after operation of group C and group D were 7.8±9.7 and 4.57±5.02 times, respectively, and the difference was statistically significant (P<0.05). Resting VAS scores and movement VAS scores at 2, 4, 8, and 24 hours postoperatively were statistically different (P<0.05). Usage times of rescue drug (pethidine) of group C and group D were 9 and 1, mean rank 118.13 and 85.71, respectively, and the difference was statistically significant (P<0.05). Mean rank of general satisfaction of group C and group D were 98.99 and 105.04, respectively, and the difference was statistically significant (P<0.05). Incidence rate of nausea in group C and group D within 24 hours after surgery was 25% and 12.5%, and of vomiting 18.2% and 6.25%, respectively and of vomiting and the difference was statistically significant. CONCLUSIONS: Compared with sufentanil PCIA alone, the combination of dexmedetomidine and sufentanil for PCIA after abdominal operation could reduce sufentanil consumption, decrease VAS scores, lower the rate of nausea and vomiting, and improve patient satisfaction.

Levosimendan combined with epinephrine improves rescue outcomes in a rat model of lipid-based resuscitation from bupivacaine-induced cardiac arrest.

BACKGROUND: The effectiveness of a combination of a lipid emulsion with epinephrine in reversing local anesthetic-induced cardiac arrest has been confirmed. The combination of a lipid emulsion with levosimendan, was shown to be superior to administration of a lipid emulsion alone with regard to successful resuscitation. In this study, we compared the reversal effects of levosimendan, epinephrine, and a combination of the two agents in lipid-based resuscitation in a rat model of bupivacaine-induced cardiac arrest. METHODS: Fifty-four adult male Sprague-Dawley rats were subjected to bupivacaine (15 mg·kg-1) -induced asystole and were then randomly divided into 3 groups. A lipid emulsion was used as the basic treatment, and administration of drug combinations varied in each group as follows: (1) levosimendan combined with epinephrine (LiEL); (2) epinephrine (LiE); and (3) levosimendan (LiL). The resuscitation outcomes were recorded and included the rate of return of spontaneous circulation (ROSC) and survival at 40 min, time to first heartbeat, time to ROSC, and cumulative dose of epinephrine. We calculated the wet-to-dry ratio of the lung, blood gas values at 40 min and bupivacaine concentration of cardiac tissue and plasma. RESULTS: The rates of ROSC in LiEL and LiE groups were higher than LiL group (P < 0.001; LiEL vs LiL, P = 0.001; LiE vs LiL, P = 0.007). The survival rate in LiEL group was higher than LiE group (P = 0.003; LiEL vs LiE, P = 0.008; LiEL vs LiL, P = 0.001). The time to first heart beat in LiEL group was shorter than LiE, LiL groups. (P < 0.001; LiE vs LiEL, P = 0.001; LiL vs LiEL, P < 0.001). The time to ROSC in LiEL group was shorter than LiE, LiL groups (P < 0.001; LiEL vs LiE, P < 0.001; LiEL vs LiL, P < 0.001). The result was similar for the bupivacaine concentration of cardiac tissue and plasma (cardiac tissue: P = 0.002; plasma: P = 0.011). Furthermore, there were significant differences in the blood-gas values at 40 min, wet-to-dry lung weight ratio, and ratio of damaged alveoli among groups. The LiEL group had the best result for all parameters (P < 0.01, P = 0.008, P < 0.001, respectively). Additionally, significantly less epinephrine was used in the LiEL group (P < 0.001). CONCLUSIONS: Levosimendan combined with epinephrine may be superior to either drug alone for lipid-based resuscitation in a rat model of bupivacaine-induced cardiac arrest. The drug combination was associated with a higher survival rate as well as decreased epinephrine consumption and lung damage.