Soft ferroelectret ultrasound receiver for targeted peripheral neuromodulation.

Bioelectronic medicine is a rapidly growing field where targeted electrical signals can act as an adjunct or alternative to drugs to treat neurological disorders and diseases via stimulating the peripheral nervous system on demand. However, current existing strategies are limited by external battery requirements, and the injury and inflammation caused by the mechanical mismatch between rigid electrodes and soft nerves. Here we report a wireless, leadless, and battery-free ferroelectret implant, termed NeuroRing, that wraps around the target peripheral nerve and demonstrates high mechanical conformability to dynamic motion nerve tissue. As-fabricated NeuroRing can act as an ultrasound receiver that converts ultrasound vibrations into electrostimulation pulses, thus stimulating the targeted peripheral nerve on demand. This capability is demonstrated by the precise modulation of the sacral splanchnic nerve to treat colitis, providing a framework for future bioelectronic medicines that offer an alternative to non-specific pharmacological approaches.

Expert consensus on difficult airway assessment.

Background: Identifying a potentially difficult airway is crucial both in anaesthesia in the operating room (OR) and non-operation room sites. There are no guidelines or expert consensus focused on the assessment of the difficult airway before, so this expert consensus is developed to provide guidance for airway assessment, making this process more standardized and accurate to reduce airway-related complications and improve safety. Methods: Seven members from the Airway Management Group of the Chinese Society of Anaesthesiology (CSA) met to discuss the first draft and then this was sent to 15 international experts for review, comment, and approval. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) is used to determine the level of evidence and grade the strength of recommendations. The recommendations were revised through a three-round Delphi survey from experts. Results: This expert consensus provides a comprehensive approach to airway assessment based on the medical history, physical examination, comprehensive scores, imaging, and new developments including transnasal endoscopy, virtual laryngoscopy, and 3D printing. In addition, this consensus also reviews some new technologies currently under development such as prediction from facial images and voice information with the aim of proposing new research directions for the assessment of difficult airway. Conclusions: This consensus applies to anesthesiologists, critical care, and emergency physicians refining the preoperative airway assessment and preparing an appropriate intubation strategy for patients with a potentially difficult airway.

Opioid MOP receptor agonists in late-stage development for the treatment of postoperative pain.

INTRODUCTION: Opioids remain important in postoperative analgesia although, the focus is on using them as part of multimodal regimens where it is not possible to avoid their use completely. The development of novel agents with more favorable adverse effect profiles may increase safety whilst maintaining efficacy. AREAS COVERED: This article reviews the clinical trials for opioids in late-stage development. The objective of this narrative review is to evaluate the pharmacokinetic properties, safety, tolerability, and analgesic efficacy of these agents in the management of postoperative pain. EXPERT OPINION: Oliceridine appears to be an effective and potentially safer µ opioid receptor agonist. Its main advantages are a relatively fast onset with reduced respiratory depression, nausea, and vomiting. Cebranopadol is an agonist at multiple opioid receptors, of which µ opioid and nociceptin/orphanin FQ peptide (NOP) receptor are most significant. It is an oral drug that appears to have efficacy in neuropathic pain, with reduced respiratory depression and abuse potential. Lastly, morphine-6-glucuronide is an active metabolite of morphine with a slower onset than its parent compound. It has failed to demonstrate appreciable benefit in the context of postoperative analgesia.

MicroRNA-503 Exacerbates Myocardial Ischemia/Reperfusion Injury via Inhibiting PI3K/Akt- and STAT3-Dependent Prosurvival Signaling Pathways.

Acute myocardial infarction is a leading cause of death worldwide, while restoration of blood flow to previously ischemic myocardium may lead to ischemia/reperfusion (I/R) injury. Accumulated evidence shows that microRNAs play important roles in cardiovascular diseases. However, the potential role of microRNA-503 (miR-503) in myocardial I/R injury is little known. Thus, this study is aimed at determining whether and how miR-503 affects myocardial I/R injury in vivo and in vitro. A mouse model of myocardial I/R injury and H9c2 cell model of hypoxia/reoxygenation (H/R) injury were established. The postischemic cardiac miR-503 was downregulated in vivo and in vitro. Mechanistically, PI3K p85 and Bcl-2 are miR-503 targets. The post-ischemic cardiac PI3K p85 protein level was decreased in vivo. Agomir-503 treatment exacerbated H/R-induced injuries manifested as decreased cell viability, increased lactate dehydrogenase activity, and cell apoptosis. Agomir-503 treatment reduced cell viability under normoxia as well and reduced both PI3K p85 and Bcl-2 protein levels under either normoxia or H/R condition. It reduced phosphorylation of Stat3 (p-Stat3-Y705) and Akt (T450) in cells subjected to H/R. In contrast, Antagomir-503 treatment attenuated H/R injury and increased p-Stat3 (Y705) under normoxia and increased p-Akt (T450) under either normoxia or H/R condition. It is concluded that miR-503 exacerbated I/R injury via inactivation of PI3K/Akt and STAT3 pathways and may become a therapeutic target in preventing myocardial I/R injury.

Comparison of the Efficiency and Usability of Aerosol Box and Intubation Tent on Intubation of a Manikin Using Personal Protective Equipment: A Randomized Crossover Study.

BACKGROUND: The aerosol box and intubation tent are improvised barrier-enclosure devices developed during the novel coronavirus pandemic to protect health care workers from aerosol transmission. OBJECTIVE: Using time to intubation as a crude proxy, we aimed to compare the efficiency and usability of the aerosol box and intubation tent in a simulated manikin. METHODS: This was a single-center, randomized, crossover manikin study involving 28 participants (9 anesthetists, 16 emergency physicians, and 3 intensivists). Each participant performed rapid sequence intubations in a random sequence of three different scenarios: 1) no device use; 2) aerosol box; 3) intubation tent. We compared the time to intubation between different scenarios. RESULTS: The median total intubation time with no device use, aerosol box, and intubation tent were 23.7 s (interquartile range [IQR] 19.4-28.4 s), 30.9 s (IQR 24.1-52.5 s), and 26.0 s (IQR 22.1-30.8 s), respectively. Post hoc analysis showed a significantly longer intubation time using the aerosol box compared with no device use (p < 0.001) and compared with the intubation tent (p < 0.001). The difference between the intubation tent and no device use was not significant. The first-pass intubation success rate did not differ between the groups. Only aerosol box use had resulted in breaches of personal protective equipment. Participants considered intubation with the intubation tent more favorable than the aerosol box. CONCLUSIONS: The intubation tent seems to have a better barrier-enclosure design than the aerosol box, with a reasonable balance between efficiency and usability. Further evaluation of its efficacy in preventing aerosol dispersal and in human studies are warranted prior to recommendation of widespread adoption.

Environmental Enrichment in Postoperative Pain and Surgical Care: Potential Synergism With the Enhanced Recovery After Surgery Pathway.

BACKGROUND: Holistic biopsychosocial care has been underemphasized in perioperative pathway designs. The importance and a cost-effective way of implementing biopsychosocial care to improve postoperative pain and facilitate surgical convalescence are not well established, despite the recent popularization of Enhanced Recovery After Surgery (ERAS) programs. OBJECTIVE: We have explored the evidence and rationale of environmental enrichment (EE) as a complementary multimodal psychosocial care pathway to reduce postoperative pain, optimize patient recovery and improve existing weaknesses in surgical care. METHODS: We conducted a database search to identify and grade potential EE techniques for their evidence quality and consistency in the management of acute postoperative pain, perioperative anxiety and the etiologically comparable acute procedural or experimental pain. FINDINGS AND CONCLUSIONS: The introduction of music, virtual reality, educational information, mobile apps, or elements of nature into the healthcare environment can likely improve patients' experience of surgery. Compared with traditional psychological interventions, EE modalities are voluntary, therapist-sparing and more economically sustainable. We have also discussed practical strategies to integrate EE within the perioperative workflow. Through a combination of sensory, motor, social and cognitive modalities, EE is an easily implementable patient-centered approach to alleviate pain and anxiety in surgical patients, create a more homelike recovery environment and improve quality of life.

Total Intravenous Anesthesia (TIVA) With Propofol for Acute Postoperative Pain: A Scoping Review of Randomized Controlled Trials.

Total intravenous anesthesia (TIVA) with propofol may improve acute postoperative pain control compared to inhalational anesthesia. The objective of this review was to comprehensively update and evaluate the existing literature on the analgesic efficacy of propofol TIVA. A systemized literature search for randomized controlled trials in adult patients was conducted in the PubMed and Cochrane CENTRAL (EMBASE source) databases up to August 2019. Clinical trials included compared propofol TIVA against inhalational isoflurane, sevoflurane, or desflurane. Only clinical trials that studied acute postoperative pain scores or analgesic consumption as a primary outcome were included. Sixteen randomized controlled trials were included. Surgical procedures evaluated included: radical gastrectomy, open vein stripping, breast cancer surgery, laparoscopic cholecystectomy, inguinal herniotomy, abdominoplasty, bariatric surgery, lumbar spine surgery, emergency neurosurgical operations, open and laparoscopic gynecological surgeries, and dental surgery. Propofol TIVA was associated with reduced postoperative pain scores and/or decreased opioid consumption in 9 out of 16 clinical trials. There was no difference in 5 clinical trials, and propofol TIVA was associated with worse analgesic outcomes in 2 trials. Propofol TIVA may improve acute postoperative analgesia after surgery, but different factors such as surgical procedures and anesthetic/analgesic techniques may influence its effectiveness.

Up-regulation of FoxO1 contributes to adverse vascular remodelling in type 1 diabetic rats.

Vascular complications from diabetes often result in poor outcomes for patients, even after optimized interventions. Forkhead box protein O1 (FoxO1) is a key regulator of cellular metabolism and plays an important role in vessel formation and maturation. Alterations of FoxO1 occur in the cardiovascular system in diabetes, yet the role of FoxO1 in diabetic vascular complications is poorly understood. In Streptozotocin (STZ)-induced type 1 diabetic rats, FoxO1 expression was up-regulated in carotid arteries at 8 weeks of diabetes that was accompanied with adverse vascular remodelling characterized as increased wall thickness, carotid medial cross-sectional area, media-to-lumen ratio and decreased carotid artery lumen area. This adverse vascular remodelling induced by hyperglycaemia in diabetic rats required FoxO1 activation as pharmacological inhibition of FoxO1 with 50mg/kg AS1842856 (AS) reversed vascular remodelling in type 1 diabetic rats. The adverse vascular remodelling in type 1 diabetes mellitus (T1DM) occurred concomitantly with increases in pro-inflammatory factors, adhesion factors, apoptosis, NOD-like receptor family protein-3 inflammasome activation and the phenotypic switch of arterial smooth muscle cells, which were all reversed by AS. In addition, FoxO1 inhibition counteracted the down-regulation of its upstream mediator PDK1 in T1DM. PDK1 activator reduced FoxO1 nuclear translocation, which serves as the basis for subsequent transcriptional regulation during hyperglycaemia. Taken together, our data suggest that FoxO1 is a critical trigger for type 1 diabetes-induced vascular remodelling in rats, and inhibition of FoxO1 thus offers a potential therapeutic option for diabetes-associated cardiovascular diseases.

Preoperative dexamethasone for pain relief after total knee arthroplasty: A randomised controlled trial.

BACKGROUND: Corticosteroids can reduce pain but the optimal dose and safety profiles are still uncertain. OBJECTIVE: This study aimed to evaluate two different doses of dexamethasone for pain management and their side effects after total knee arthroplasty. DESIGN: A prospective randomised, controlled trial. SETTING: A tertiary teaching hospital in Hong Kong. PATIENTS: One hundred and forty-six patients were randomly allocated to one of three study groups. INTERVENTIONS: Before operation, patients in group D8, D16 and P received dexamethasone 8 mg, dexamethasone 16 mg and placebo (0.9% saline), respectively. MAIN OUTCOME MEASURES: The primary outcome was postoperative pain score. Secondary outcomes were opioid consumption, physical parameters of the knees and side effects of dexamethasone. RESULTS: Compared with placebo, group D16 patients had significantly less pain during maximal active flexion on postoperative day 3 [-1.3 (95% CI, -2.2 to -0.31), P = 0.005]. There was also a significant dose-dependent trend between pain scores and dexamethasone dose (P = 0.002). Compared with placebo, patients in group D16 consumed significantly less opioid [-6.4 mg (95% CI, -11.6 to -1.2), P = 0.025] and had stronger quadriceps power on the first three postoperative days (all P < 0.05). They also had significantly longer walking distance on postoperative day 1 [7.8 m ([95% CI, 0.85 to 14.7), P = 0.023] with less assistance during walking on the first two postoperative days (all P < 0.029) and significantly better quality-of-recovery scores on postoperative day 1 (P = 0.018). There were significant dose-dependent trends between all the above parameters and dexamethasone dose (all P < 0.05). No significant differences were found in the incidence of chronic pain or knee function 3, 6 and 12 months postoperatively. CONCLUSION: Dexamethasone 16 mg given before total knee arthroplasty led to a reduction in postoperative pain, less opioid consumption, stronger quadriceps muscle power, better mobilisation and better overall quality-of-recovery after operation. No long-term improvement in reduction in pain and function of the knee was found. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02767882.

Adiponectin Facilitates Postconditioning Cardioprotection through Both AMPK-Dependent Nuclear and AMPK-Independent Mitochondrial STAT3 Activation.

Myocardial ischemic postconditioning- (IPo-) mediated cardioprotection against myocardial ischemia-reperfusion (IR) injury needs the activation of signal transducer and activator of transcription 3 (STAT3), which involves adiponectin (APN). APN confers its biological effects through AMP-activated protein kinase- (AMPK-) dependent and AMPK-independent pathways. However, the role of AMPK in APN-mediated STAT3 activation in IPo cardioprotection is unknown. We hypothesized that APN-mediated STAT3 activation in IPo is AMPK-independent and that APN through AMPK-dependent STAT3 activation facilitates IPo cardioprotection. Here, Sprague-Dawley rats were subjected to myocardial IR without or with IPo and/or APN. APN or IPo significantly improved postischemic cardiac function and reduced myocardial injury and oxidative stress, and their combination further attenuated postischemic myocardial injuries. APN or its combination with IPo but not IPo alone significantly increased AMPK activation and both nuclear and mitochondrial STAT3 activation, while IPo significantly enhanced mitochondrial but not nuclear STAT3 activation. In primarily isolated cardiomyocytes, recombined globular APN (gAd), hypoxic postconditioning (HPo), or their combination significantly attenuated hypoxia/reoxygenation-induced cell injury and increased nuclear and/or mitochondrial STAT3 activation. STAT3 inhibition had no impact on gAd or gAd in combination with HPo-induced AMPK activation but abolished their cellular protective effects. AMPK inhibition did not affect HPo cardioprotection but abolished gAd cardioprotection and disabled gAd to facilitate/enhance HPo cardioprotection and STAT3 activation. These results suggest that APN confers cardioprotection through AMPK-dependent and AMPK-independent STAT3 activation, while IPo confers cardioprotection through AMPK-independent mitochondrial STAT3 activation. Joint use of APN and IPo synergistically attenuated myocardial IR injury by activating STAT3 via distinct signaling pathways.

Anesthetic Management for Squamous Cell Carcinoma of the Esophagus.

While surgery plays a major role in the treatment and potential cure of esophageal cancers, esophagectomy remains a high-risk operation with significant perioperative morbidity and mortality compared to other oncosurgical procedures. Perioperative management for esophagectomy is complex, and close attention to detail in various areas of anesthetic and perioperative management is crucial to improve postoperative outcomes. Patients undergoing esophagectomy should be offered an evidence-based risk assessment for their postoperative outcomes to allow active participation and informed, shared-decision making. Novel perioperative risk scores have been developed to predict both short-term and long-term outcomes in patients with esophageal cancer, although independent validation of such scoring systems is still required. Apart from accurate preoperative risk assessment, further efforts to improve morbidity and mortality from esophagectomy is achieved through comprehensive Enhanced Recovery after Surgery (ERAS) protocols, which comprise an individualized bundle of care throughout the perioperative journey for each patient and should be implemented as a standard practice. Furthermore, anesthetic practice and perioperative anesthetic drug usage can potentially affect cancer progression and recurrence. This chapter reviews current evidence for various factors that contribute to the improvement of perioperative outcomes, including prehabilitation, preoperative optimization of anemia, thoracic epidural analgesia, intraoperative protective ventilatory strategies, goal-directed fluid therapy, as well as special attention to other perioperative issues that potentially reduce anastomotic and cardiopulmonary complications. In summary, it is difficult to show a measurable benefit from any one single intervention, and a multidisciplinary approach that encompasses multiple aspects of perioperative care is necessary to improve outcomes after esophagectomy.

Deletion of Rap1 protects against myocardial ischemia/reperfusion injury through suppressing cell apoptosis via activation of STAT3 signaling.

Ischemic heart disease is a leading cause of morbidity and mortality. Repressor activator protein 1 (Rap1), an established telomere-associated protein, is a novel modulator of hypoxia-induced apoptosis. This study aimed to explore the potential direct role of Rap1 in myocardial ischemia/reperfusion injury (I/RI) and to determine the underlying molecular mechanism. In a mouse model of myocardial I/RI (30-min of left descending coronary artery ligation followed by 2-h reperfusion), Rap1 deficiency significantly reduced myocardial infarct size (IS) and improved cardiac systolic/diastolic function. This was associated with a reduction in apoptosis in the post-ischemic myocardium. In H9C2 and primary cardiomyocytes, Rap1 knockdown or knockout significantly suppressed hypoxia/reoxygenation (H/R)-induced cell injury and apoptosis through increasing the phosphorylation/activation of STAT3 at site Ser727 and translocation of STAT3 to the nucleus. We surmise this since Stattic (selective STAT3 inhibitor) pretreatment canceled the abovementioned protective effect. Furthermore, co-immunoprecipitation assay revealed a direct interaction between Rap1 and STAT3, but not JAK2, suggesting that the association of Rap1 with STAT3 may contribute to the reduced activity of STAT3 (Ser727 ) upon H/R stimulation. In conclusion, Rap1 deficiency protects the heart from ischemic damage through STAT3-dependent reduction of cardiomyocyte apoptosis, which may yield viable target for pharmacological intervention in ischemic heart disease.

Allopurinol reduces oxidative stress and activates Nrf2/p62 to attenuate diabetic cardiomyopathy in rats.

Allopurinol (ALP) attenuates oxidative stress and diabetic cardiomyopathy (DCM), but the mechanism is unclear. Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) following the disassociation with its repressor Keap1 under oxidative stress can maintain inner redox homeostasis and attenuate DCM with concomitant attenuation of autophagy. We postulated that ALP treatment may activate Nrf2 to mitigate autophagy over-activation and consequently attenuate DCM. Streptozotocin-induced type 1 diabetic rats were untreated or treated with ALP (100 mg/kg/d) for 4 weeks and terminated after heart function measurements by echocardiography and pressure-volume conductance system. Cardiomyocyte H9C2 cells infected with Nrf2 siRNA or not were incubated with high glucose (HG, 25 mmol/L) concomitantly with ALP treatment. Cell viability, lactate dehydrogenase, 15-F2t-Isoprostane and superoxide dismutase (SOD) were measured with colorimetric enzyme-linked immunosorbent assays. ROS, apoptosis, was assessed by dihydroethidium staining and TUNEL, respectively. The Western blot and qRT-PCR were used to assess protein and mRNA variations. Diabetic rats showed significant reductions in heart rate (HR), left ventricular eject fraction (LVEF), stroke work (SW) and cardiac output (CO), left ventricular end-systolic volume (LVVs) as compared to non-diabetic control and ALP improved or normalized HR, LVEF, SW, CO and LVVs in diabetic rats (all P < .05). Hearts of diabetic rats displayed excessive oxidative stress manifested as increased levels of 15-F2t-Isoprostane and superoxide anion production, increased apoptotic cell death and cardiomyocytes autophagy that were concomitant with reduced expressions of Nrf2, heme oxygenase-1 (HO-1) and Keap1. ALP reverted all the above-mentioned diabetes-induced biochemical changes except that it did not affect the levels of Keap1. In vitro, ALP increased Nrf2 and reduced the hyperglycaemia-induced increases of H9C2 cardiomyocyte hypertrophy, oxidative stress, apoptosis and autophagy, and enhanced cellular viability. Nrf2 gene silence cancelled these protective effects of ALP in H9C2 cells. Activation of Nrf2 subsequent to the suppression of Keap1 and the mitigation of autophagy over-activation may represent major mechanisms whereby ALP attenuates DCM.

Hyperglycemia-Induced Oxidative Stress Abrogates Remifentanil Preconditioning-Mediated Cardioprotection in Diabetic Rats by Impairing Caveolin-3-Modulated PI3K/Akt and JAK2/STAT3 Signaling.

Diabetic hearts are more vulnerable to ischemia/reperfusion (I/R) injury and less responsive to remifentanil preconditioning (RPC), but the underlying mechanisms are incompletely understood. Caveolin-3 (Cav-3), the dominant isoform of cardiomyocyte caveolae, is reduced in diabetic hearts in which oxidative stress is increased. This study determined whether the compromised RPC in diabetes was an independent manifestation of hyperglycemia-induced oxidative stress or linked to impaired Cav-3 expression with associated signaling abnormality. RPC significantly attenuated postischemic infarction, cardiac dysfunction, myocardial apoptosis, and 15-F2t-isoprostane production (a specific marker of oxidative stress), accompanied with increased Cav-3 expression and enhanced Akt and STAT3 activation in control but not in diabetic rats. Pretreatment with the antioxidant N-acetylcysteine (NAC) attenuated hyperglycemia-induced reduction of Cav-3 expression and Akt and STAT3 activation and restored RPC-mediated cardioprotection in diabetes, which was abolished by cardiac-specific knockdown of Cav-3 by AAV9-shRNA-Cav-3, PI3K/Akt inhibitor wortmannin, or JAK2/STAT3 inhibitor AG490, respectively. Similarly, NAC could restore RPC protection from high glucose and hypoxia/reoxygenation-induced injury evidenced by decreased levels of LDH release, 15-F2t-isoprostane, O2 -, and JC-1 monomeric cells, which were reversed by caveolae disrupter methyl-ß-cyclodextrin, wortmannin, or AG490 in isolated primary cardiomyocytes or siRNAs of Cav-3, Akt, or STAT3 in H9C2 cells. Either methyl-ß-cyclodextrin or Cav-3 knockdown reduced Akt and STAT3 activation. Further, the inhibition of Akt activation by a selective inhibitor or siRNA reduced STAT3 activation and vice versa, but they had no effects on Cav-3 expression. Thus, hyperglycemia-induced oxidative stress abrogates RPC cardioprotection by impairing Cav-3-modulated PI3K/Akt and JAK2/STAT3 signaling. Antioxidant treatment with NAC could restore RPC-induced cardioprotection in diabetes by improving Cav-3-dependent Akt and STAT3 activation and by facilitating the cross talk between PI3K/Akt and JAK2/STAT3 signaling pathways.

Anaesthetic considerations in nonagenarians and centenarians.

PURPOSE OF REVIEW: The ageing population is a global public health issue and we can expect to encounter more and more older patients requiring anaesthetic care. Age itself is no longer the sole reason for declining a patient for anaesthesia and surgery. Undoubtedly, managing patients at the extremities of age is challenging and demanding, not only because of multiple comorbidities, but also the poorer functional status, frailty and decline in general well being that must be managed during the perioperative journey. In this article, we will focus on three important aspects of anaesthetic care for this patient group, namely, comorbidity, frailty and perioperative cognitive dysfunction; and give recommendations on how anaesthetists should tackle these aspects for the 'older old' and the 'oldest old', based on current best evidence. RECENT FINDINGS: The 'oldest old' (nonagerians and centenarians) are the fastest-growing geriatric population worldwide. Evidence has demonstrated that an enhanced care programme designed for elderly patients is safe, feasible and could diminish both complications and length of stay after surgery. Studies are emerging on frailty measurement and the association with outcomes of anaesthesia and surgery and have resulted in new recommendations on best practices for postoperative brain health and nomenclature of perioperative neurocognitive disorder. SUMMARY: Comorbidity, frailty and perioperative cognitive dysfunction are significant perioperative concerns specific to elderly patients and clearly associated with adverse outcomes after surgery. These anaesthetic concerns should be anticipated and properly managed through the perioperative pathway so that their potential complications can be mitigated.

Perioperative Quality Initiative consensus statement on the physiology of arterial blood pressure control in perioperative medicine.

BACKGROUND: Perioperative arterial blood pressure management is a physiologically complex challenge influenced by multiple factors. METHODS: A multidisciplinary, international working subgroup of the Third Perioperative Quality Initiative (POQI) consensus meeting reviewed the (patho)physiology and measurement of arterial pressure as applied to perioperative medicine. We addressed predefined questions by undertaking a modified Delphi analysis, in which primary clinical research and review articles were identified using MEDLINE. Strength of recommendations, where applicable, were graded by National Institute for Health and Care Excellence (NICE) guidelines. RESULTS: Multiple physiological factors contribute to the perioperative physiological importance of arterial pressure: (i) arterial pressure is the input pressure to organ blood flow, but is not the sole determinant of perfusion pressure; (ii) blood flow is often independent of changes in perfusion pressure because of autoregulatory changes in vascular resistance; (iii) microvascular dysfunction uncouples microvascular blood flow from arterial pressure (haemodynamic incoherence). From a practical clinical perspective, we identified that: (i) ambulatory measurement is the optimal method to establish baseline arterial pressure; (ii) automated and invasive arterial pressure measurements have inherent physiological and technical limitations; (iii) individualised arterial pressure targets may change over time, especially in the perioperative period. There remains a need for research in non-invasive, continuous arterial pressure measurements, macro- and micro-circulatory control, regional perfusion pressure measurement, and the development of sensitive, specific, and continuous measures of cellular function to evaluate blood pressure management in a physiologically coherent manner. CONCLUSION: The multivariable, complex physiology contributing to dynamic changes in perioperative arterial pressure may be underappreciated clinically. The frequently unrecognised dissociation between arterial pressure, organ blood flow, and microvascular and cellular function requires further research to develop a more refined, contextualised clinical approach to this routine perioperative measurement.

Vascular endothelial growth factor regulation of endothelial nitric oxide synthase phosphorylation is involved in isoflurane cardiac preconditioning.

Aims: Previous studies indicate that nitric oxide derived from endothelial nitric oxide synthase (eNOS) serves as both trigger and mediator in anaesthetic cardiac preconditioning. The mechanisms underlying regulation of eNOS by volatile anaesthetics have not been fully understood. Therefore, this study examined the role of vascular endothelial growth factor (VEGF) in isoflurane cardiac preconditioning. Methods and results: Wistar rats underwent 30 min of coronary artery occlusion followed by 2 h of reperfusion. Isoflurane given prior to ischaemia/reperfusion significantly decreased myocardial infarct size from 60 ± 1% in control to 40 ± 3% (n = 8 rats/group, P < 0.05). The beneficial effects of isoflurane were blocked by neutralizing antibody against VEGF (nVEGF). Coronary arterial endothelial cells (ECs) alone or together with cardiomyocytes (CMs) were subjected to hypoxia/reoxygenation injury. The expression of VEGF and eNOS was analysed by western blot, and nitric oxide was measured by ozone-based chemiluminescence. In co-cultured CMs and ECs, isoflurane administered before hypoxia/reoxygenation attenuated lactate dehydrogenase activity and increased the ratio of phosphorylated eNOS/eNOS and nitric oxide production. The protective effect of isoflurane on CMs was compromised by nVEGF and after VEGF in ECs was inhibited with hypoxia inducible factor-1α short hairpin RNA (shRNA). The negative effect of hypoxia inducible factor-1α shRNA was restored by recombinant VEGF. Conclusion: Isoflurane cardiac preconditioning is associated with VEGF regulation of phosphorylation of eNOS and nitric oxide production.

Anesthetic management of thoracoscopic resection of lung lesions in small children.

BACKGROUND: Video-assisted thoracoscopic surgery has dramatically increased over the last decade because of both medical and cosmetic benefits. Anesthesia for video-assisted thoracoscopic surgery in small children is more challenging compared to adults due to the considerable problems posed by small airway dimensions and ventilation. The optimal technique for one-lung ventilation has yet to be established and the use of remifentanil infusion in this setting is not well described. AIMS: This study investigated the use of extraluminal bronchial blocker placement for one-lung ventilation and the effect of infusion of remifentanil in infants and small children undergoing video-assisted thoracoscopic surgery. METHODS: We retrospectively reviewed the technique of one-lung ventilation and the hemodynamic effects of remifentanil infusion in 31 small children during elective video-assisted thoracoscopic surgery for congenital lung lesions under anesthesia with sevoflurane or isoflurane, oxygen, and air. Patients' heart rate, blood pressure, and endtidal carbon dioxide at baseline (after induction of anesthesia), immediately after one-lung ventilation, during carbon dioxide insufflation, and at the end of one-lung ventilation were extracted from the database and analyzed. The use of vasopressors or dexmedetomidine was also recorded and analyzed. RESULTS: Extraluminal placement of a bronchial blocker alongside the tracheal tube was successfully performed in 90.3% of cases (28 patients) without any serious complications or arterial oxygen desaturation. There was no significant rise in blood pressure or heart rate even with the rise of endtidal carbon dioxide concentration during video-assisted thoracoscopic surgery. In 58% of patients (18 patients), phenylephrine was administered to maintain the blood pressure within 20% of the baseline value. There was no significant change in the heart rate of all patients at each time point. CONCLUSION: One-lung ventilation with an extraluminal parallel blocker was used effectively in this series of young children undergoing thoracoscopic excision of congenital pulmonary lesions. Remifentanil infusion attenuated surgical stress effectively in infants and small children undergoing video-assisted thoracoscopic surgery.