Research Spotlight

Glenister, R. T. and P. A. McCullough (2020). “Analysing risk in heart failure: a Kalium check.” Eur J Heart Fail May 10. [Epub ahead of print].

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This article refers to ‘Cardiovascular risk associated with serum potassium in the context of mineralocorticoid receptor antagonist use in patients with heart failure and left ventricular dysfunction’ by P. Rossignol et al ., published in this issue on pages xxx. [No abstract; excerpt from text].

Gan, T. J., K. G. Belani, S. Bergese, F. Chung, P. Diemunsch, A. S. Habib, Z. Jin, A. L. Kovac, T. A. Meyer, R. D. Urman, C. C. Apfel, S. Ayad, L. Beagley, K. Candiotti, M. Englesakis, T. L. Hedrick, P. Kranke, S. Lee, D. Lipman, H. S. Minkowitz, J. Morton and B. K. Philip (2020). “Fourth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting.” Anesth Analg May 27. [Epub ahead of print].

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This consensus statement presents a comprehensive and evidence-based set of guidelines for the care of postoperative nausea and vomiting (PONV) in both adult and pediatric populations. The guidelines are established by an international panel of experts under the auspices of the American Society of Enhanced Recovery and Society for Ambulatory Anesthesia based on a comprehensive search and review of literature up to September 2019. The guidelines provide recommendation on identifying high-risk patients, managing baseline PONV risks, choices for prophylaxis, and rescue treatment of PONV as well as recommendations for the institutional implementation of a PONV protocol. In addition, the current guidelines focus on the evidence for newer drugs (eg, second-generation 5-hydroxytryptamine 3 [5-HT3] receptor antagonists, neurokinin 1 (NK1) receptor antagonists, and dopamine antagonists), discussion regarding the use of general multimodal PONV prophylaxis, and PONV management as part of enhanced recovery pathways. This set of guidelines have been endorsed by 23 professional societies and organizations from different disciplines (Appendix 1). WHAT OTHER GUIDELINES ARE AVAILABLE ON THIS TOPIC?: Guidelines currently available include the 3 iterations of the consensus guideline we previously published, which was last updated 6 years ago; a guideline published by American Society of Health System Pharmacists in 1999; a brief discussion on PONV management as part of a comprehensive postoperative care guidelines; focused guidelines published by the Society of Obstetricians and Gynecologists of Canada, the Association of Paediatric Anaesthetists of Great Britain & Ireland and the Association of Perianesthesia Nursing; and several guidelines published in other languages. WHY WAS THIS GUIDELINE DEVELOPED?: The current guideline was developed to provide perioperative practitioners with a comprehensive and up-to-date, evidence-based guidance on the risk stratification, prevention, and treatment of PONV in both adults and children. The guideline also provides guidance on the management of PONV within enhanced recovery pathways. HOW DOES THIS GUIDELINE DIFFER FROM EXISTING GUIDELINES?: The previous consensus guideline was published 6 years ago with a literature search updated to October 2011. Several guidelines, which have been published since, are either limited to a specific populations or do not address all aspects of PONV management. The current guideline was developed based on a systematic review of the literature published up through September 2019. This includes recent studies of newer pharmacological agents such as the second-generation 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, a dopamine antagonist, neurokinin 1 (NK1) receptor antagonists as well as several novel combination therapies. In addition, it also contains an evidence-based discussion on the management of PONV in enhanced recovery pathways. We have also discussed the implementation of a general multimodal PONV prophylaxis in all at-risk surgical patients based on the consensus of the expert panel.

Fry, E., H. Bollempali, K. Suarez, J. Banchs and J. Michel (2020). “Watchman outcomes comparing post-implantation anticoagulation with warfarin versus direct oral anticoagulants.” J Interv Card Electrophysiol June 5. [Epub ahead of print].

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PURPOSE: As left atrial appendage occlusion devices (LAAO) implantation rates grow, continued evaluation on best patient practices is important. We report pooled Watchman outcomes at a multicenter Texas healthcare system with an emphasis on clinical outcomes and post-implantation anticoagulation with direct oral anticoagulants (DOACs) versus warfarin. METHODS: Data for 163 patients with atrial fibrillation (AF) undergoing Watchman implantation was collected via retrospective chart review between June 2016 and June 2018. A Fisher’s exact test was utilized to evaluate associations in bivariate comparisons of categorical data. Tests of non-inferiority, applied between DOACs and warfarin, utilized a ratio of 2. RESULTS: Outcomes were significant for similar rates of stroke, disabling stroke, major bleeds, and all-cause mortality when compared to published clinical trials. Most patients with cerebrovascular events were found to have >5 mm peri-device leaks (PDLs), were on warfarin at the time of the event (75%), and all occurred within the first 6 months post implant. A significant number of patients were discharged on DOACs (42%). DOACs were shown to be non-inferior to warfarin with respect to stroke (p = 0.0048), disabling stroke (p = 0.0383), gastrointestinal bleeding (p = 0.0287), mortality (p = 0.0165), and combined adverse outcomes (p = 0.0040). DOACs were associated with less combined adverse outcomes (p = 0.021). CONCLUSION: Our findings suggest that additional imaging or aggressive management of PDLs in Watchman recipients within the initial 6-month follow-up may aid in reducing stroke rates. Additionally, anticoagulation with DOACs’ post Watchman implantation was found non-inferior to warfarin, with some evidence of lower risk for adverse outcomes favoring DOACs.

Erhun, F., R. S. Kaplan, V. G. Narayanan, K. Brayton, M. Kalani, M. C. Mazza, C. Nguyen, T. Platchek, B. Mistry, R. Mann, D. Kazi, C. Pinnock, K. A. Schulman, J. Xue, D. Ballard, M. Mack, B. James, G. Poulsen, J. Punnen, D. Shetty and A. Milstein (2020). “Are cost advantages from a modern Indian hospital transferable to the United States?” Am Heart J 224: 148-155.

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BACKGROUND: Multiple modern Indian hospitals operate at very low cost while meeting US-equivalent quality accreditation standards. Though US hospitals face intensifying pressure to lower their cost, including proposals to extend Medicare payment rates to all admissions, the transferability of Indian hospitals’ cost advantages to US peers remains unclear. METHODS: Using time-driven activity-based costing methods, we estimate the average cost of personnel and space for an elective coronary artery bypass graft (CABG) surgery at two American hospitals and one Indian hospital (NH). All three hospitals are Joint Commission accredited and have reputations for use of modern performance management methods. Our case study applies several analytic steps to distinguish transferable from non-transferable sources of NH’s cost savings. RESULTS: After removing non-transferable sources of efficiency, NH’s residual cost advantage primarily rests on shifting tasks to less-credentialed and/or less-experienced personnel who are supervised by highly-skilled personnel when perceived risk of complications is low. NH’s high annual CABG volume facilitates such supervised work “downshifting.” The study is subject to limitations inherent in case studies, does not account for the younger age of NH’s patients, or capture savings attributable to NH’s negligible frequency of re-admission or post-acute care facility placement. CONCLUSIONS: Most transferable bases for a modern Indian hospital’s cost advantage would require more flexible American states’ hospital and health professional licensing regulations, greater family participation in inpatient care, and stronger support by hospital executives and clinicians for substantially lowering the cost of care via regionalization of complex surgeries and weekend use of costly operating rooms.

Ding, X., L. Zhou, X. Jiang, H. Liu, J. Yao, R. Zhang, D. Liang, F. Wang, M. Ma, B. Tang, E. Wu, J. Teng and X. Wang (2020). “Propagation of Pathological α-Synuclein from the Urogenital Tract to the Brain Initiates MSA-like Syndrome.” iScience May 15;23(6):101166. [Epub ahead of print].

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The neuropathological feature of multiple system atrophy (MSA), a fatal adult-onset disorder without effective therapy, is the accumulation of pathological α-synuclein (α-Syn) in the central nervous system (CNS). Here we show that pathological α-Syn exists in nerve terminals in detrusor and external urethral sphincter (EUS) of patients with MSA. Furthermore, α-Syn-preformed fibrils (PFFs) injected in the EUS or detrusor in TgM83(+/-) mice initiated the transmission of pathological α-Syn from the urogenital tract to brain via micturition reflex pathways, and these mice developed widespread phosphorylated α-Syn inclusion pathology together with phenotypes. In addition, urinary dysfunction and denervation-reinnervation of external anal sphincter were detected earlier in the mouse models with α-Syn PFFs inoculation before the behavioral manifestations. These results suggest that pathological α-Syn spreading through the micturition reflex pathways retrogradely from the urogenital tract to CNS may lead to urinary dysfunction in patients with MSA, which is different from the etiology of idiopathic Parkinson disease.