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.

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.

Anti-diabetic drug canagliflozin hinders skeletal muscle regeneration in mice.

Canagliflozin is an antidiabetic medicine that inhibits sodium-glucose cotransporter 2 (SGLT2) in proximal tubules. Recently, it was reported to have several noncanonical effects other than SGLT2 inhibiting. However, the effects of canagliflozin on skeletal muscle regeneration remain largely unexplored. Thus, in vivo muscle contractile properties recovery in mice ischemic lower limbs following gliflozins treatment was evaluated. The C2C12 myoblast differentiation after gliflozins treatment was also assessed in vitro. As a result, both in vivo and in vitro data indicate that canagliflozin impairs intrinsic myogenic regeneration, thus hindering ischemic limb muscle contractile properties, fatigue resistance recovery, and tissue regeneration. Mitochondrial structure and activity are both disrupted by canagliflozin in myoblasts. Single-cell RNA sequencing of ischemic tibialis anterior reveals a decrease in leucyl-tRNA synthetase 2 (LARS2) in muscle stem cells attributable to canagliflozin. Further investigation explicates the noncanonical function of LARS2, which plays pivotal roles in regulating myoblast differentiation and muscle regeneration by affecting mitochondrial structure and activity. Enhanced expression of LARS2 restores the differentiation of canagliflozin-treated myoblasts, and accelerates ischemic skeletal muscle regeneration in canagliflozin-treated mice. Our data suggest that canagliflozin directly impairs ischemic skeletal muscle recovery in mice by downregulating LARS2 expression in muscle stem cells, and that LARS2 may be a promising therapeutic target for injured skeletal muscle regeneration.

Notch3 and its CADASIL mutants differentially regulate cellular phenotypes.

Notch3 is a member of the Notch family and its mutations are known to cause a hereditary human disorder called cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, the specific function and signaling cascade initiated by CADASIL mutants remain unknown. To gain further insight into mechanism of action of CADASIL mutants, the present study conducted several experiments on the effects of Notch3 mutants in multiple cell lines. The protein levels of Notch3, fibronectin, collagen, inducible nitric oxide synthase and DNA (cytosine-5)-methyltransferase 1 (DNMT1) were determined by western blotting. The mRNA levels of IL-1ß and TNF-α were measured by reverse transcription semi-quantitative PCR and DNMT1 mRNA levels were determined by quantitative PCR. Trypan blue staining was used for proliferation analysis and wound healing assays were performed to determine cell migration capability. The present study reported that R90C and R169C Notch3 mutants, and wild-type Notch3 had different effects on several cell lines. In T/GHA-VSMC cells, following the transfection of the two mutants, collagen and fibronectin expression increased, whereas expression decreased in IMR-90 cells. In BV2 cells, the two mutants resulted in decreased nitric oxide and iNOS production. In HeLa cells, proliferation and migration increased significantly following the transfection of the two mutants, whereas in the MCF-7 and HCC1937 cell lines, cell proliferation and migration decreased. In addition, the two mutants suppressed the expression of DNMT1 in HeLa and IMR-90 cells. Overall, the present study provided novel insights that further explored the underlying mechanisms of CADASIL.

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.

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.

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.

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).

Dexmedetomidine Added to Local Anesthetic Mixture of Lidocaine and Ropivacaine Enhances Onset and Prolongs Duration of a Popliteal Approach to Sciatic Nerve Blockade.

PURPOSE: A literature review of multiple clinical studies on mixing additives to improve pharmacologic limitation of local anesthetics during peripheral nerve blockade revealed inconsistency in success rates and various adverse effects. Animal research on dexmedetomidine as an adjuvant on the other hand has promising results, with evidence of minimum unwanted results. This randomized, double-blinded, contrastable observational study examined the efficacy of adding dexmedetomidine to a mixture of lidocaine plus ropivacaine during popliteal sciatic nerve blockade (PSNB). METHODS: Sixty patients undergoing varicose saphenous vein resection using ultrasonography-guided PSNB along with femoral and obturator nerve blocks as surgical anesthesia were enrolled. All received standardized femoral and obturator nerve blocks, and the PSNB group was randomized to receive either 0.5 mL (50 µg) of dexmedetomidine (DL group) or 0.5 mL of saline (SL group) together with 2% lidocaine (9.5 mL) plus 0.75% ropovacaine (10 mL). Sensory onset and duration of lateral sural cutaneous nerve, sural nerve, superficial peroneal nerve, deep peroneal nerve, lateral plantar nerve, and medial plantar nerve were recorded. Motor onset and duration of tibial nerve and common peroneal nerve were also examined. FINDINGS: Sensory onset of sural nerve, superficial peroneal nerve, lateral plantar nerve, and medial plantar nerve was significantly quicker in the DL group than in the SL group (P < 0.05). Sensory onset of lateral sural cutaneous nerve and deep peroneal nerve was not statistically different between the groups (P > 0.05). Motor onset of tibial nerve and common peroneal nerve was faster in the DL group than in in the SL group (P < 0.05). Duration of both sensory and motor blockade was significantly longer in the DL group than in the SL group (P < 0.05). IMPLICATIONS: Perineural dexmedetomidine added to lidocaine and ropivacaine enhanced efficacy of popliteal approach to sciatic nerve blockade with faster onset and longer duration.

Enhancement of cisplatin-induced colon cancer cells apoptosis by shikonin, a natural inducer of ROS in vitro and in vivo.

Cisplatin-based therapy is one of the most important chemotherapy treatments for cancers. However, its efficacy is greatly limited by drug resistance and undesirable side effects. Therefore, it is of great importance to develop effective chemosensitization agents to cisplatin. In the present study, we demonstrated the strategy to use shikonin, a natural product from the root of Lithospermum erythrorhizon, as a synergistic agent of cisplatin and elucidated their action mechanisms. The combination of shikonin and cisplatin exhibited synergistic anticancer efficacy and achieved greater selectivity between cancer cells and normal cells. By inducing intracellular oxidative stress, shikonin potentiated cisplatin-induced DNA damage, followed by increased activation of mitochondrial pathway. In addition, inhibition of ROS reversed the apoptosis induced by shikonin and cisplatin, and recovered the depletion of mitochondrial membrane potential, which revealed the vital role of ROS in the synergism. Moreover, HCT116 xenograft tumor growth in nude mice was more effectively inhibited by combined treatment with shikonin and cisplatin. Our findings suggest that the strategy to apply shikonin as a synergistic agent to cisplatin could be a highly efficient way to achieve anticancer synergism by inducing intracellular oxidative stress. Shikonin may be a promising candidate as a chemosensitizer to cisplatin-based therapy for cancer treatments.

Magnesium Sulfate Plus Lidocaine Reduces Propofol Injection Pain: A Double-blind, Randomized Study.

PURPOSE: Propofol injection can cause distressing pain, and no method can inhibit it completely. Neither lidocaine nor magnesium sulfate (MgSO4) was sufficient to prevent pain from the injection of propofol. This prospective, double-blind, placebo-controlled study was designed to investigate the efficacy of the MgSO4 plus lidocaine on suppressing propofol injection pain. METHODS: Three hundred women received 300 mg MgSO4 (Group M), 40 mg lidocaine (Group L), or 300 mg MgSO4 plus 40 mg lidocaine (Group M+L). This was followed by administration of 50 mg propofol. Pain scores, behavior-related responses, and diameter of the vein were recorded following the injection of propofol. FINDINGS: Patients in Group M + L had lower pain scores. Patients' behavior-related responses in Group M + L were also better compared with the other groups. There were no differences in pain scores between Group L and Group M. The target vein diameter change in Group M and Group M + L was more obvious than in Group L. IMPLICATIONS: Administration of 300 mg MgSO4 plus 40 mg lidocaine reduces propofol injection pain very well. No complications were observed in the treatment groups.

Activation of spinal NF-КB mediates pain behavior induced by plantar incision.

A growing body of evidence indicates that the activation of nuclear factor kappa B (NF-κB) pathway was involved in neuropathic and inflammatory pain, however, the role of NF-κB in incisional pain is still unclear. Therefore, in this study, we investigated whether the activation of NF-κB in the spinal cord is involved in pain hypersensitivity after a plantar incision in the rat hind paw. After rats received a plantar incision surgery, mechanical allodynia and thermal hyperalgesia were determined by von Frey filaments and radiant heat, respectively. Western blot was used to determineNF-κB activation at different time points after incision. The NF-κB inhibitor pyrrolidinedithiocarbamate (PDTC) was administered intrathecally 30 min before hind paw plantar incision to determine the role of NF-κB in incision-induced pain. Our results showed that the expression level of NF-κB was significantly increased in spinal cord dorsal horn from 30 min to 3 days after the incision. Intrathecal pretreatment of PDTC attenuated incision-induced mechanical allodynia and thermal hyperalgesia. Furthermore, PDTC significantly reduced the expression level of c-Fos in the dorsal horn after plantar incision. Taken together, plantar incision-induced pain behaviors can be prevented by the NF-κB inhibitor. Our results suggest that the blockage of the NF-КB signaling pathway might represent a valuable alternative for treating postoperative pain.

A comparison of epidural magnesium and/or morphine with bupivacaine for postoperative analgesia after cesarean section.

BACKGROUND: Magnesium can potentiate the antinociceptive effect of morphine. This prospective randomized double-blinded study was undertaken to establish the analgesic effect of adding magnesium to epidural morphine during cesarean section. METHODS: Two hundred patients undergoing cesarean section under combined spinal-epidural anesthesia were recruited. After administration of intrathecal bupivacaine 10mg, patients were randomly assigned to receive one of four epidural study solutions: 0.1% bupivacaine 10 mL (Group B); 0.1% bupivacaine 10 mL and morphine 1.5mg (Group B+Mor); 0.1% bupivacaine 10 mL and magnesium 500 mg (Group B+Mg); or 0.1% bupivacaine 10 mL morphine 1.5mg and magnesium 500 mg (Group B+Mor+Mg). The primary outcome was the area under the curve for visual analog scale pain scores during 36 h postoperatively. Secondary outcomes included time to the use of rescue analgesics, patient satisfaction and side effects. RESULTS: Patients in Group B+Mor+Mg had lower for pain scores and area under the curve pain scores both at rest and on movement, increased time for first analgesic request, and increased satisfaction score at 24h after surgery. CONCLUSION: Addition of magnesium 500 mg and morphine 1.5mg to epidural 0.1% bupivacaine 10 mL reduced postoperative pain compared with addition of morphine or magnesium alone or no additive.