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.

Continuous renal replacement therapy and extracorporeal membrane oxygenation: implications in the COVID-19 era.

The novel severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 (coronavirus Disease 19 (COVID-19)) was identified as the causative agent of viral pneumonias in Wuhan, China in December 2019, and has emerged as a pandemic causing acute respiratory distress syndrome (ARDS) and multiple organ dysfunction. Interim guidance by the World Health Organization states that extracorporeal membrane oxygenation (ECMO) should be considered as a rescue therapy in COVID-19-related ARDS. International registries tracking ECMO in COVID-19 patients reveal a 21%-70% incidence of acute renal injury requiring renal replacement therapy (RRT) during ECMO support. The indications for initiating RRT in patients on ECMO are similar to those for patients not requiring ECMO. RRT can be administered during ECMO via a temporary dialysis catheter, placement of a circuit in-line hemofilter, or direct connection of continuous RRT in-line with the ECMO circuit. Here we review methods for RRT during ECMO, RRT initiation and timing during ECMO, anticoagulation strategies, and novel cytokine filtration approaches to minimize COVID-19's pathophysiological impact.

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).

Contributing Factors to Operating Room Delays Identified from an Electronic Health Record: A Retrospective Study.

The operating room (OR) is considered a major cost center and revenue generator for hospitals. Multiple factors contribute to OR delays and impact patient safety, patient satisfaction scores, and hospital financial performance. Reducing OR delays allows better utilization of OR resources and staffing and improves patient satisfaction while decreasing operating costs. Accurate scheduling can be the basis to achieve these goals. The objective of this initial study was to identify factors not normally documented in the electronic health record (EHR) that may contribute to or be indicators of OR delays. Materials and Methods. A retrospective data analysis was performed analyzing 67,812 OR cases from 12 surgical specialties at a small university medical center from 2010 through the first quarter of 2017. Data from the hospital's EHR were exported and subjected to statistical analysis using Statistical Analysis System (SAS) software (SAS Institute, Cary, NC). Results. Statistical analysis of the extracted EHR data revealed factors that were associated with OR delays including, surgical specialty, preoperative assessment testing, patient body mass index, American Society of Anesthesiologists (ASA) physical status classification, daily procedure count, and calendar year. Conclusions. Delays hurt OR efficiency on many levels. Identifying those factors may reduce delays and better accommodate the needs of surgeons, staff, and patients thereby leading to improved patient's outcomes and patient satisfaction. Reducing delays can decrease operating costs and improve the financial position of the operating theater as well as that of the hospital. Anesthesiology teams can play a key role in identifying factors that cause delays and implementing mitigating efficiencies.

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.

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.

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.

The 2019-2020 Novel Coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2) Pandemic: A Joint American College of Academic International Medicine-World Academic Council of Emergency Medicine Multidisciplinary COVID-19 Working Group Consensus Paper.

What started as a cluster of patients with a mysterious respiratory illness in Wuhan, China, in December 2019, was later determined to be coronavirus disease 2019 (COVID-19). The pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel Betacoronavirus, was subsequently isolated as the causative agent. SARS-CoV-2 is transmitted by respiratory droplets and fomites and presents clinically with fever, fatigue, myalgias, conjunctivitis, anosmia, dysgeusia, sore throat, nasal congestion, cough, dyspnea, nausea, vomiting, and/or diarrhea. In most critical cases, symptoms can escalate into acute respiratory distress syndrome accompanied by a runaway inflammatory cytokine response and multiorgan failure. As of this article's publication date, COVID-19 has spread to approximately 200 countries and territories, with over 4.3 million infections and more than 290,000 deaths as it has escalated into a global pandemic. Public health concerns mount as the situation evolves with an increasing number of infection hotspots around the globe. New information about the virus is emerging just as rapidly. This has led to the prompt development of clinical patient risk stratification tools to aid in determining the need for testing, isolation, monitoring, ventilator support, and disposition. COVID-19 spread is rapid, including imported cases in travelers, cases among close contacts of known infected individuals, and community-acquired cases without a readily identifiable source of infection. Critical shortages of personal protective equipment and ventilators are compounding the stress on overburdened healthcare systems. The continued challenges of social distancing, containment, isolation, and surge capacity in already stressed hospitals, clinics, and emergency departments have led to a swell in technologically-assisted care delivery strategies, such as telemedicine and web-based triage. As the race to develop an effective vaccine intensifies, several clinical trials of antivirals and immune modulators are underway, though no reliable COVID-19-specific therapeutics (inclusive of some potentially effective single and multi-drug regimens) have been identified as of yet. With many nations and regions declaring a state of emergency, unprecedented quarantine, social distancing, and border closing efforts are underway. Implementation of social and physical isolation measures has caused sudden and profound economic hardship, with marked decreases in global trade and local small business activity alike, and full ramifications likely yet to be felt. Current state-of-science, mitigation strategies, possible therapies, ethical considerations for healthcare workers and policymakers, as well as lessons learned for this evolving global threat and the eventual return to a "new normal" are discussed in this article.

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.

COVID-19 Blind Spots: A Consensus Statement on the Importance of Competent Political Leadership and the Need for Public Health Cognizance.

As the COVID-19 pandemic continues, important discoveries and considerations emerge regarding the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pathogen; its biological and epidemiological characteristics; and the corresponding psychological, societal, and public health (PH) impacts. During the past year, the global community underwent a massive transformation, including the implementation of numerous nonpharmacological interventions; critical diversions or modifications across various spheres of our economic and public domains; and a transition from consumption-driven to conservation-based behaviors. Providing essential necessities such as food, water, health care, financial, and other services has become a formidable challenge, with significant threats to the existing supply chains and the shortage or reduction of workforce across many sectors of the global economy. Food and pharmaceutical supply chains constitute uniquely vulnerable and critically important areas that require high levels of safety and compliance. Many regional health-care systems faced at least one wave of overwhelming COVID-19 case surges, and still face the possibility of a new wave of infections on the horizon, potentially in combination with other endemic diseases such as influenza, dengue, tuberculosis, and malaria. In this context, the need for an effective and scientifically informed leadership to sustain and improve global capacity to ensure international health security is starkly apparent. Public health "blind spotting," promulgation of pseudoscience, and academic dishonesty emerged as significant threats to population health and stability during the pandemic. The goal of this consensus statement is to provide a focused summary of such "blind spots" identified during an expert group intense analysis of "missed opportunities" during the initial wave of the pandemic.

Palliative Use of Nitroglycerin to Improve Microvascular Circulation.

BACKGROUND: In the setting of critical illness, life preservation may come at the expense of limb as increasing concentration of vasopressors causes peripheral ischemia. When goals of care specify comfort measures, clinicians are faced with the difficult task of mitigating already present distal malperfusion while abiding to wishes of patient and patients' families. Physical changes post vasopressor use, such as mottling of appendages or cooling of skin, can limit meaningful physical interactions with grieving family members. CASE PRESENTATION: We describe a case series of successful utilization of intravenous nitroglycerin to improve postvasopressor digital ischemia for comfort care measures to assist patient's families in the grieving process. CONCLUSION: Following decision for comfort care measures, management for patient care goes beyond the realm of pain control. Dignified dying is an active process that requires clinicians to navigate care for both patient and patients' families. By reversing the digital ischemia associated with vasopressors, patients' families have the opportunity to give meaningful touch in setting of which it may be needed most.

An Artificial Neural Network-based Predictive Model to Support Optimization of Inpatient Glycemic Control.

Background: Achieving glycemic control in critical care patients is of paramount importance, and has been linked to reductions in mortality, intensive care unit (ICU) length of stay, and morbidities such as infection. The myriad of illnesses and patient conditions render maintenance of glycemic control very challenging in this setting. Materials and Methods: This study involved collection of continuous glucose monitoring (CGM) data, and other associated measures, from the electronic medical records of 127 patients for the first 72 h of ICU care who upon admission to the ICU had a diagnosis of type 1 (n = 8) or type 2 diabetes (n = 97) or a glucose value >150 mg/dL (n = 22). A neural network-based model was developed to predict a complete trajectory of glucose values up to 135 min ahead of time. Model accuracy was validated using data from 15 of the 127 patients who were not included in the model training set to simulate model performance in real-world health care settings. Results: Predictive models achieved an improved accuracy and performance compared with previous models that were reported by our research team. Model error, expressed as mean absolute difference percent, was 10.6% with respect to interstitial glucose values (CGM) and 15.9% with respect to serum blood glucose values collected 135 min in the future. A Clarke Error Grid Analysis of model predictions with respect to the reference CGM and blood glucose measurements revealed that >99% of model predictions could be regarded as clinically acceptable and would not lead to inaccurate insulin therapy or treatment recommendations. Conclusion: The noted clinical acceptability of these models illustrates their potential utility within a clinical decision support system to assist health care providers in the optimization of glycemic management in critical care patients.

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.