Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disease characterized by increased pulmonary vascular resistance (PVR) leading to right ventricular (RV) failure. Autonomic nervous system involvement in the pathogenesis of PAH has been demonstrated several years ago, however the extent of this involvement is not fully understood. PAH is associated with increased sympathetic nervous system (SNS) activation, decreased heart rate variability, and presence of cardiac arrhythmias. There is also evidence for increased renin-angiotensin-aldosterone system (RAAS) activation in PAH patients associated with clinical worsening. Reduction of neurohormonal activation could be an effective therapeutic strategy for PAH. Although therapies targeting adrenergic receptors or RAAS signaling pathways have been shown to reverse cardiac remodeling and improve outcomes in experimental pulmonary hypertension (PH)-models, the effectiveness and safety of such treatments in clinical settings have been uncertain. Recently, novel direct methods such as cervical ganglion block, pulmonary artery denervation (PADN), and renal denervation have been employed to attenuate SNS activation in PAH. In this review, we intend to summarize the multiple aspects of autonomic nervous system involvement in PAH and overview the different pharmacological and invasive strategies used to target autonomic nervous system for the treatment of PAH.

Purpose of review The present review aims to address the feasibility of opioid free anesthesia (OFA). The use of opioids to provide adequate perioperative pain management has been a central practice of anesthesia, and only recently has been challenged. Understanding the goals and challenges of OFA is essential as the approach to intraoperative analgesia and postsurgical management of pain has shifted in response to the opioid epidemic in the United States. Recent findings OFA is an opioid sparing technique, which focuses on multimodal or balanced analgesia, relying on nonopioid adjuncts and regional anesthesia. Enhanced recovery after surgery protocols, often under the auspices of a perioperative pain service, can help guide and promote opioid reduced and OFA, without negatively impacting perioperative pain management or recovery. Summary The feasibility of OFA is evident. However, there are limitations of this approach that warrant discussion including the potential for adverse drug interactions with multimodal analgesics, the need for providers trained in regional anesthesia, and the management of pain expectations. Additionally, minimizing opioid use perioperatively also requires a change in current prescribing practices. Monitors that can reliably quantify nociception would be helpful in the titration of these analgesics and enable anesthesiologists to achieve the goal in providing personalized perioperative medicine.

Harmful blooms formed by species of the dinoflagellate Cochlodinium have caused massive fish kills and substantial economic losses in the Pacific Ocean. Recently, prominent blooms of Cochlodinium have occurred in central and southern California (2004-2008), and Cochlodinium cells are now routinely observed in microscopical analysis of algal assemblages from Californian coastal waters. The first documented economic loss due to a Cochlodinium bloom in California occurred in Monterey Bay and resulted in the mortality of commercially farmed abalone. Increasing occurrences of Cochlodinium blooms, the fact that these cells preserve poorly using standard techniques, and the difficulty of identifying preserved specimens using morphological criteria make Cochlodinium species prime candidates for the development of a quantitative real-time polymerase chain reaction (qPCR) approach. The 18S rDNA gene sequenced from Cochlodinium cells obtained from California coastal waters, as well as GenBank sequences of Cochlodinium, were used to design and test a Molecular Beacon(®) approach. The qPCR method developed in this study is species specific, sensitive for the detection of C. fulvescens that has given rise to the recent blooms in the eastern Pacific Ocean, and spans a dynamic abundance range of seven orders of magnitude. Initial application of the method to archived field samples collected during blooms in Monterey Bay revealed no statistically significant correlations between gene copy number and environmental parameters. However, the onset of Cochlodinium blooms in central California was consistent with previously reported findings of correlations to decreased surface temperature and increased inputs of nitrogenous nutrients.

RationalePulmonary hypertension (PH) is a rare but fatal disease characterized by elevated pulmonary pressures and vascular remodeling, leading to right ventricular failure and death. Recently, neuroinflammation has been suggested to be involved in the sympathetic activation in experimental PH. Whether PH is associated with neuroinflammation in the spinal cord has never been investigated.Methods/ResultsPH was well-established in adult male Wistar rats 3-week after pulmonary endothelial toxin Monocrotaline (MCT) injection. Using the thoracic segments of the spinal cord, we found a 5-fold increase for the glial fibrillary acidic protein (GFAP) in PH rats compared to controls (p < 0.05). To further determine the region of the spinal cord where GFAP was expressed, we performed immunofluorescence and found a 3 to 3.5-fold increase of GFAP marker in the gray matter, and a 2 to 3-fold increase in the white matter in the spinal cord of PH rats compared to controls. This increase was due to PH (MCT vs. Control; p < 0.01), and there was no difference between the dorsal versus ventral region. PH rats also had an increase in the pro-inflammatory marker chemokine (C-C motif) ligand 3 (CCL3) protein expression (∼ 3-fold) and (2.8 to 4-fold, p < 0.01) in the white matter. Finally, angiogenesis was increased in PH rat spinal cords assessed by the adhesion molecule CD31 expression (1.5 to 2.3-fold, p < 0.01).ConclusionWe report for the first time evidence for neuroinflammation in the thoracic spinal cord of pulmonary hypertensive rats. The impact of spinal cord inflammation on cardiopulmonary function in PH remains elusive.

reintroduced in the 2-mg unit dose. An interrupted time series analysis was performed using segmented Poisson regression with two change-points, the first representing the switch from a 2-mg to 1-mg unit dose, and the second representing the reintroduction of the 2-mg dose. results: The 2-mg to 1-mg unit dose change was associated with a 49% relative decrease in the probability of receiving a hydromorphone dose greater than 1 mg (risk ratio, 0.51; 95% CI, 0.40-0.66; P < 0.0001). The reintroduction of a 2-mg unit dose was associated with a 48% relative increase in the probability of administering a dose greater than 1 mg (risk ratio, 1.48; 95% CI, 1.11-1.98; P = 0.008). conclusions: This observational study using an interrupted time series analysis demonstrates that unit dose of hydromorphone (2 mg vs. 1 mg) is an independent determinant of the quantity of hydromorphone administered to patients in the intraoperative period.

Sugammadex is a modified gamma cyclodextrin used to reverse the steroidal neuromuscular blockade in the perioperative period. 1 Neuromuscular blocking agents (NMBs) are used perioperatively to achieve muscle relaxation for surgery, endotracheal intubation, and medical therapy in the intensive care unit and emergency department. The antagonism of a NMB is achieved by 2 possible mechanisms, one by inherent drug metabolism and the other by drug reversal. 1 Before its approval by the US Food and Drug Administration in 2015, the only option for reversal was acetylcholinesterase inhibitors such as neostigmine, edrophonium, and pyridostigmine. Since its introduc-

Introduction: Medication errors occur in around 0.75% to 5% of all anaesthesia related medication administrations. We developed the "Additional verification of intravenous drug (AVOID) -error System" to reduce medication-errors in Anaesthesia and tested the effect of this system on drug-administration time and end-user acceptance in a simulated environment. Materials and Methods: A randomized-controlled cross-over trial study on 20 anaesthesiologists from Singapore General Hospital was conducted in a simulated operating-room environment in September 2018. Participants were randomized to administer five 1 millilitre doses, from a prefilled pre-labelled syringe with and without the AVOID-error System, (intervention group and control group, respectively). The primary outcome recorded was time to complete a "drug administration". Additionally, all study participants were individually asked to give an opinion about the effect of the AVOID-error system on workload, medication error reduction and willingness to use in their routine practice using a five-point Likert scale. A Paired t-test was used for inter-group comparison and statistical significance was defined as p < 0.05. Results: Twenty Anaesthesiologists, (12 consultants and 8 trainees) with median 8.5 years (IQR, of experience participated in the study. The mean time to complete a drug administration in the intervention and control groups were, 18.2 (SD ± 5.3) and 12.6(SD ± 3.8) seconds (p =0.001), respectively. Conclusions: On an average, the use of the Avoid-error system increased the total drug-administration time by 5.6 (95% CI: 4.6 -6.5) seconds.

No abstract