Effectiveness of general anaesthesia with remimazolam tosilate on intraoperative haemodynamics and postoperative recovery: study protocol for a randomised, positive-controlled, pragmatic clinical trial (GARTH trial).

INTRODUCTION: It is encouraged to estimate the effectiveness of components within the enhanced recovery after surgery (ERAS) protocol through patient-reported outcomes, alongside doctor-reported outcomes and length of hospital stay. At present, studies on the contributions of optimal anaesthetic drugs within the ERAS protocol to patient-reported and doctor-reported outcomes are limited. Therefore, this study aims to pragmatically evaluate the effectiveness and safety of general anaesthesia (GA) with remimazolam tosilate within the ERAS protocol on intraoperative haemodynamics and postoperative recovery in adults undergoing elective surgeries, compared with propofol. METHODS AND ANALYSIS: This study is a single-centre, randomised, blinded, positive-controlled, pragmatic clinical trial. A total of 900 patients, aged ≥18 years old, scheduled for an elective surgical procedure under GA will be included. Patients will be randomised in a 1:1 ratio to the remimazolam group (the GA with remimazolam tosilate within the ERAS protocol group) or propofol group (the GA with propofol within the ERAS protocol group), stratified by general surgery, thoracic surgery and other surgeries (including urological surgery and otolaryngology surgery). The primary outcomes include the 24-hour postoperative quality of recovery-40 score and the rate of intraoperative hypotension. Secondary endpoints include the rate of sedative hypotension requiring treatment, the haemodynamic profiles, the 72-hour postoperative quality of recovery-40 score, the functional anaesthetic capability, adverse events and complications, quality of life within 3 months as well as economic health outcomes. ETHICS AND DISSEMINATION: This study protocol has been approved by the ethics committee of Guangdong Provincial People's Hospital (KY-H-2022-005-03-08). Dissemination plans will be presented at scientific meetings and in scientific publications. TRIAL REGISTRATION NUMBER: ChiCTR2200062520.

A single dose of ketamine relieves fentanyl-induced-hyperalgesia by reducing inflammation initiated by the TLR4/NF-κB pathway in rat spinal cord neurons.

A large amount of clinical evidence has revealed that ketamine can relieve fentanyl-induced hyperalgesia. However, the underlying mechanism is still unclear. In the current study, a single dose of ketamine (5 mg/kg or 10 mg/kg), TAK-242 (3 mg/kg), or saline was intraperitoneally injected into rats 15 min before four subcutaneous injections of fentanyl. Results revealed that pre-administration of ketamine alleviated fentanyl-induced hyperalgesia according to hind paw-pressure and paw-withdrawal tests. High-dose ketamine can reverse the expression of toll-like receptor-dimer (d-TLR4), phospho- nuclear factor kappa-B (p-NF-κB, p-p65), cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) 1 d after fentanyl injection in the spinal cord. Moreover, fentany-linduced-hyperalgesia and changes in the expression of the aforementioned proteins can be attenuated by TAK-242, an inhibitor of TLR4, as well as ketamine. Importantly, TLR4, p-p65, COX-2, and IL-1ß were expressed in neurons but not in glial cells in the spinal cord 1 d after fentanyl injection. In conclusion, results suggested that a single dose of ketamine can relieve fentanyl-induced-hyperalgesia via the TLR4/NF-κB pathway in spinal cord neurons.

Effects of the costoclavicular block versus interscalene block in patients undergoing arthroscopic shoulder surgery under monitored anesthesia care: a randomized, prospective, non-inferiority study.

BACKGROUND: Recent studies have reported that costoclavicular blocks (CCBs) can consistently block almost all branches of the brachial plexus while sparing the phrenic nerve and provide effective analgesia after shoulder surgery. We aimed to compare the efficacy of the CCB with that of the interscalene block (ISB) as the sole blocking technique for shoulder surgery. METHODS: A total of 212 patients undergoing elective arthroscopic shoulder surgery were randomized to receive an ISB or CCB based on a non-inferiority design. All patients received titration sedation with propofol under monitored anesthesia during surgery. The primary outcomes were the proportion of patients with complete motor blockade of the suprascapular nerve (SSN) and incidence of hemidiaphragmatic paralysis (HDP). The secondary outcomes included block-related variables, complications, and postoperative pain scores. RESULTS: The proportion of patients with complete motor blockade of the SSN at 20 min between the CCB and ISB groups (53% vs. 66%) exceeded the predefined non-inferiority margin of -5%, but was comparable at 30 min (87% vs. 91%). The CCB resulted in a significantly lower incidence of HDP (7.55% vs. 92.45%), Horner's syndrome (0% vs. 18.87%), and dyspnea (0% vs. 10.38%) than the ISB. None of the patients experienced failed blocks or required conversion to general anesthesia. Pain scores were comparable between the groups. CONCLUSIONS: Ultrasound-guided CCBs may be comparable to ISBs, with fewer unfavorable complications in patients with impaired lung function undergoing arthroscopic shoulder surgery.

Effects of double vs triple injection on block dynamics for ultrasound-guided intertruncal approach to the supraclavicular brachial plexus block in patients undergoing upper limb arteriovenous access surgery: study protocol for a double-blinded, randomized controlled trial.

BACKGROUND: Ultrasound-guided intertruncal approach (IA) has been proposed to be an alternative and promising approach to the supraclavicular block (SCB), in which double injection (DI) of local anesthetics (LA) is sequentially administered between intertruncal planes. We would like to apply a refined injection technique, named triple injection (TI) technique, based on the 3 separate compartments visualized by ultrasound. The aim of this study is to compare the percentage of patients with complete sensory blockade at 20 min of DI vs TI technique, when they are applied in patients undergoing upper limb arteriovenous access surgery. METHODS: This study is a prospective parallel-group randomized controlled trial. A total of 86 end-stage renal disease patients will be randomly allocated to receive IA-SCB using either DI or TI technique with identical LA (0.5% ropivacaine 24 mL). The primary outcome is the percentage of patients with complete sensory blockade of all 4 terminal nerves (median, ulnar, radial, and musculocutaneous nerves) of the brachial plexus measured at 20 min after injection. The secondary outcomes will consist of the sensory or motor blockade of all individual nerves, onset times, performance time, diaphragmatic paralysis, surgical anesthesia, and adverse events. DISCUSSION: It is expected that ultrasound-guided IA-SCB with the TI technique results in better block dynamic in patients undergoing upper limb arteriovenous access surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100045075 .

Effects of pericapsular nerve group (PENG) block on postoperative recovery in elderly patients with hip fracture: study protocol for a randomised, parallel controlled, double-blind trial.

INTRODUCTION: Hip fracture is a common and serious emergency in the elderly, and it is associated with severe pain, significant morbidity and mortality. The use of peripheral nerve block can relieve pain effectively and reduce opioid requirements, which may accelerate patient's recovery. The pericapsular nerve group (PENG) block has been found to provide an effective blockade to the hip joint with a potential motor-sparing effect, so we hypothesised that the PENG block may be an effective tool to enhance the recovery in elderly patients after hip fracture surgery. METHODS AND ANALYSIS: This study is a single-centred, randomised, parallel controlled, double-blind trial. A total of 92 elderly patients scheduled for hip fracture surgery will be divided into two groups at random to receive either ultrasound-guided femoral nerve block or ultrasound-guided PENG block. The primary outcome will be to compare the Quality of Recovery-15 scores at 24 hours postoperatively between the two groups. The secondary outcomes will include measuring and comparing the strength of the quadriceps, the visual analogue scale at rest and on movement, the total morphine consumption, the rescue analgesic, the first time of postoperative out-of-bed mobilisation and complications. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of the Ethics Committee of The First Affiliated Hospital of Guangzhou University of Chinese Medicine on 15 December 2020 (reference K2020-110). The results of this study will be published in peer-reviewed international journals. TRIAL REGISTRATION NUMBER: ChiCTR2100042341.

Intertruncal versus classical approach to the ultrasound-guided supraclavicular brachial plexus block for upper extremity surgery: study protocol for a randomized non-inferiority trial.

BACKGROUND: Ultrasound-guided intertruncal approach (IA) to the supraclavicular block (SB) is recently proposed as a new approach for local anesthetic (LA) injection in terms of the classical approach (CA) at the level of the first rib. The CA-SB has been proven to result in satisfying sensorimotor block, but associate with a high risk of intraneural injection. The aim of this randomized non-inferiority study is to explore whether IA-SB can obtain similar block dynamics, as the CA-SB, but avoiding an intraneural injection during the whole nerve block procedure. METHODS: The total 122 patients undergoing elective upper extremity surgery will be randomly allocated to receive either an IA-SB or a CA-SB using a double-injection (DI) technique. In the IA-SB group, a portion of LA (15 mL) is injected accurately to the intertruncal plane between the middle and lower trunks under real-time ultrasound guidance; then, the remaining volume (10 mL) is carefully distributed to the other intertruncal plane between the upper and middle trunks. In the CA-SB group, the DI technique will be carried out as described in Tran's study. The primary outcome is the percentage of patients with a complete sensory blockade at 20 min with a predefined non-inferiority margin of - 5%. The secondary outcomes include the sensory-motor blockade of all 4 terminal nerves, onset times of the individual nerves within 30 min, block-related variables, and adverse events. DISCUSSION: The results will provide sensory-motor blockade-related parameters and safety of the ultrasound-guided intertruncal approach to the supraclavicular block, thereby promoting clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000040199 . Registered on 25 November 2020.

Ultrasound-guided quadratus lumborum block for perioperative analgesia in robot-assisted partial nephrectomy: a randomized controlled trial.

BACKGROUND: Recently, several case reports and limited randomized studies have shown that quadratus lumborum blocks (QLB) are effective in providing pain relief after intra-abdominal and retroperitoneal operations. Additionally, robot-assisted partial nephrectomy (RAPN) has been proposed as a promising operative treatment for renal carcinoma because it enables early recovery and ambulation. Therefore, we aimed to evaluate the analgesic and opioid-sparing effects of a single-injection QLB in patients undergoing RAPN to determine its role in an early recovery program. METHODS: Fifty-six patients undergoing elective RAPN under general anesthesia were randomized to two equally sized groups. Patients were randomly allocated to receive either a unilateral QLB (n = 28) with 0.375% bupivacaine 0.5 mL/kg (QLB group) or a conventional scheme (n = 28) (control group). The QLB technique, termed QLB2, was performed as first described by Blanco. The primary outcome was visual analog scale (VAS) scores with movement at 6 h postoperatively. The secondary endpoints were morphine consumption at different time periods after surgery, morphine-related side effects, and assessment of postoperative rehabilitation. RESULTS: Both the VAS pain scores and cumulative opioid consumption were significantly lower in the QLB group at 6 h after surgery as compared with results in the control group (all P < 0.05). There were significant differences in pain scores at all time points except at 4 h with movement and 48 h at rest. However, at 12-24 h no significant differences between the two groups were observed in cumulative opioid consumption or in the duration of PACU and hospital stays. The patient recovery scores were significantly higher in the QLB group. CONCLUSIONS: Single-injection pre-emptive QLB applied to RAPN was effective and provided satisfactory analgesia and opioid-sparing effects in combination with typical patient-controlled analgesia. In addition, it may provide an effective technique for early recovery in the perioperative period for RAPN.

Comparison of ultrasound-guided supraclavicular and costoclavicular brachial plexus block using a modified double-injection technique: a randomized non-inferiority trial.

Ultrasound-guided costoclavicular block (CC-approach) is a recently described brachial plexus block (BPB) and an alternative approach to the supraclavicular approach (SC-approach). The relevant sonoanatomy is analogous in terms of the brachial plexus and its adjacent artery for both approaches. In the present study, we hypothesized that the two approaches will result in similar block dynamics when used the modified double-injection (MDI) technique. One hundred and twelve patients were randomly allocated to receive either a SC- or CC-approach with MDI technique. In the CC group, half the volume was injected adjacent to the medial cord of the brachial plexus, the procedure was guided by ultrasound and verified by nerve stimulator, subsequently the second half was injected close to the lateral cord. In the SC group, the MDI technique was carried out as described in our previous study. Sensory and motor blockade of all four terminal nerves were assessed with a 3-point scale. The primary outcome was the proportion of complete sensory blockade at 15 min with a predefined non-inferiority margin of -13%. The proportion of subjects at 15 min was comparable between the SC group and the CC group (91 vs 87%, absolute difference: -3%). No significant differences were found for complete motor blockade and onset times of the individual nerves within 30 min, and block-related serious adverse events (all P>0.05). We conclude that the MDI technique applied to a costoclavicular and supraclavicular block resulted in similar block dynamics. In addition, it may provide a promising alternative technique when considering the use of multipoint injection.

Accidental awareness while under general anaesthesia.

Accidental awareness during general anaesthesia may cause many intraoperative discomforts and bring further moderate to severe long-term symptoms including flashbacks, nightmares, hyperarousal or post-traumatic stress disorder. The incidence of awareness varied from 0.017% to 4% among studies. The relatively reliable incidence of intraoperative awareness with postoperative recall is 0.02%. The reason causing awareness was unclear. Insufficient anaesthetic dosing was thought as the principal cause. Even awareness was not comprehensively understood, some endeavors have been raised to prevent or reduce it, including i) Reducing the insufficient anaesthetic dosing induced by negligence; ii) Providing close clinical observation and clinical parameters from the monitor such as bispectral index or electroencephalogram, as well as isolated forearm technique and passive brain-computer interface may bring some effects sometimes. Because current studies still have some flaws, further trials with new detecting approach, superior methodology and underlying aetiology are needed to unfasten the possible factors causing awareness.

Effects of three forms of local anesthesia on perioperative fentanyl-induced hyperalgesia.

Both local infiltration analgesia (LIA) and nerve block are common analgesic modalities for pain relief after surgery. The aim of the current study was to investigate the effects of those two modalities on pain behavior and the expression of pro-inflammatory cytokines such as interleukin (IL)-1ß and IL-6 and tumor necrosis factor-α (TNF-α) in the spinal cord and dorsal root ganglion (DRG) in a rat model of perioperative fentanyl induced hyperalgesia. Rats were injected with fentanyl (60 µg/kg) 4 times and received a plantar incision after the second injection or they received pre-incision LIA and sciatic nerve block (SNB) or post-incision LIA with levobupivacaine (0.5%, 0.2 mL). Mechanical and thermal nociceptive thresholds were assessed using the tail pressure test and paw withdrawal test on the day before drug injection, 1 and 4 hours after injection, and 1-7 days later. The lumbar spinal cord and dorsal root ganglia were collected from rats in each group to measure IL-1ß, IL-6, and TNF-α on the day before drug injection, 4 hours after injection, and 1, 3, 5, and 7 days later. Fentanyl and an incision induced a significantly delayed mechanical hyperalgesia in the tail and thermal hyperalgesia in both hind paws and up-regulation of pro-inflammatory cytokines in the spinal cord and dorsal root ganglia. Rats treated with pre-incision LIA and SNB or post-incision LIA had alleviated hyperalgesia and significantly reduced levels of IL-1ß, IL-6, and TNF-α compared to the control group. LIA and SNB partly prevented perioperative fentanyl-induced hyperalgesia and up-regulation of pro-inflammatory cytokines in the spinal cord and dorsal root ganglia.

Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats.

BACKGROUND: Perioperative fentanyl has been reported to induce hyperalgesia and increase postoperative pain. In this study, we tried to investigate behavioral hyperalgesia, the expression of proinflammatory cytokines, such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the activation of microglia in the spinal cord and dorsal root ganglion (DRG) in a rat model of surgical plantar incision with or without perioperative fentanyl. METHODS: Four groups of rats (n = 32 for each group) were subcutaneously injected with fentanyl at 60 µg/kg or normal saline for 4 times with 15-minute intervals. Plantar incisions were made to rats in 2 groups after the second drug injection. Mechanical and thermal nociceptive thresholds were assessed by the tail pressure test and paw withdrawal test on the day before, at 1, 2, 3, 4 hours, and on the days 1-7 after drug injection. The lumbar spinal cord, bilateral DRG, and cerebrospinal fluid of 4 rats in each group were collected to measure IL-1ß, IL-6, and TNF-α on the day before, at the fourth hour, and on the days 1, 3, 5, and 7 after drug injection. The lumbar spinal cord and bilateral DRG were removed to detect the ionized calcium-binding adapter molecule 1 on the day before and on the days 1 and 7 after drug injection. RESULTS: Rats injected with normal saline only demonstrated no significant mechanical or thermal hyperalgesia or any increases of IL-1ß, IL-6, and TNF-α in the spinal cord or DRG. However, injection of fentanyl induced analgesia within as early as 4 hours and a significant delayed tail mechanical and bilateral plantar thermal hyperalgesia after injections lasting for 2 days, while surgical plantar incision induced a significant mechanical and thermal hyperalgesia lasting for 1-4 days. The combination of fentanyl and incision further aggravated the hyperalgesia and prolonged the duration of hyperalgesia. The fentanyl or surgical incision upregulated the expression of IL-1ß, IL-6, and TNF-α in the spinal cord and bilateral DRG for more than 7 days and increase of ionized calcium-binding adapter molecule 1 in the spinal cord. The combination of fentanyl and incision resulted in higher increase of IL-1ß, IL-6, and TNF-α in the spinal cord and bilateral DRG. CONCLUSIONS: The surgical plantar incision with or without perioperative fentanyl induced significant mechanical and thermal hyperalgesia, an increased expression of IL-1ß, IL-6, TNF-α in the spinal cord and DRG, and activation of microglia in the spinal cord.

Double-injection technique assisted by a nerve stimulator for ultrasound-guided supraclavicular brachial plexus block results in better distal sensory-motor block: A randomised controlled trial.

BACKGROUND: To evaluate the efficacy of a nerve stimulator when used with ultrasound-guided double injection in supraclavicular brachial plexus block. OBJECTIVES: We hypothesised that targeting the inferior trunk of the plexus guided by a nerve stimulator would obtain a higher success rate of ulnar nerve blockade than the traditional double-injection technique. DESIGN: A blinded randomised controlled study. SETTING: Conducted at the University Hospital from October 2015 to January 2016. PATIENTS: Ninety patients undergoing upper extremity surgery were randomised into two equal groups. INTERVENTIONS: Patients were randomly allocated to a modified double-injection group (MDI group) or a traditional double-injection group (DI group). All patients received 23 ml of a 1 : 1 mixture of 2% lidocaine and 1% ropivacaine during ultrasound-guided supraclavicular brachial plexus block. In the MDI group (n = 45), half the volume was deposited within the brachial plexus sheath guided by ultrasound, next to the inferior trunk and verified by nerve stimulation; the remaining volume was deposited in the main neural cluster. In the double-injection group (n = 45), the first half volume was deposited on ultrasound guidance alone. Sensory-motor blockade of the musculocutaneous, median, radial, ulnar nerves and surgical anaesthesia, performance time, number of needle passes and complications were recorded. MAIN OUTCOME MEASURES: The success rate of complete sensory block of the ulnar nerve within 15 min after local anaesthetic injection. RESULTS: Compared with the DI group the MDI group had higher success rates of complete sensory block of the ulnar nerve (93 vs 67%, P = 0.002) and complete anaesthesia (80 vs 56%, P = 0.014) at 15 min, whereas the average performance time was significantly longer (5.08 ±â€Š1.41 vs 4.10 ±â€Š0.64 min, P < 0.001) and the number of needle passes was significantly higher (4.40 ±â€Š1.14 vs 2.87 ±â€Š0.79, P < 0.001). CONCLUSION: The MDI technique has a higher success rate for complete sensory block of the ulnar nerve within 15 min of local anaesthetic injection. The time needed to perform the block is about 1 min longer than the traditional technique. TRIAL REGISTRATION: http://www.chictr.org.cn with the registration number of ChiCTR-IOR-15007588.