Browsing by Author "Manning, Michael W"
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Item Open Access Complex Role for E-Prostanoid 4 Receptors in Hypertension.(Journal of the American Heart Association, 2019-02) Herrera, Marcela; Yang, Ting; Sparks, Matthew A; Manning, Michael W; Koller, Beverly H; Coffman, Thomas MBackground Prostaglandin E2 ( PGE 2) is a major prostanoid with multiple actions that potentially affect blood pressure ( BP ). PGE 2 acts through 4 distinct E-prostanoid ( EP ) receptor isoforms: EP 1 to EP 4. The EP 4 receptor ( EP 4R) promotes PGE 2-dependent vasodilation, but its role in the pathogenesis of hypertension is not clear. Methods and Results To address this issue, we studied mice after temporal- and cell-specific deletion of EP 4R. First, using a mouse line with loss of EP 4 expression induced universally after birth, we confirm that EP 4R mediates a major portion of the acute vasodilatory effects of infused PGE 2. In addition, EP 4 contributes to control of resting BP , which was increased by 5±1 mm Hg in animals with generalized deficiency of this receptor. We also show that EP 4 is critical for limiting elevations in BP caused by high salt feeding and long-term infusion of angiotensin II . To more precisely identify the mechanism for these actions, we generated mice in which EP 4R loss is induced after birth and is limited to smooth muscle. In these mice, acute PGE 2-dependent vasodilation was attenuated, indicating that this response is mediated by EP 4R in vascular smooth muscle cells. However, absence of EP 4R only in this vascular compartment had a paradoxical effect of lowering resting BP , whereas the protective effect of EP 4R on limiting angiotensin II-dependent hypertension was unaffected. Conclusions Taken together, our findings support a complex role for EP 4R in regulation of BP and in hypertension, which appears to involve actions of the EP 4R in tissues beyond vascular smooth muscle cells.Item Open Access Conventional Ultrafiltration During Elective Cardiac Surgery and Postoperative Acute Kidney Injury.(Journal of cardiothoracic and vascular anesthesia, 2021-05) Manning, Michael W; Li, Yi-Ju; Linder, Dean; Haney, John C; Wu, Yi-Hung; Podgoreanu, Mihai V; Swaminathan, Madhav; Schroder, Jacob N; Milano, Carmelo A; Welsby, Ian J; Stafford-Smith, Mark; Ghadimi, KamrouzObjective
Conventional ultrafiltration (CUF) during cardiopulmonary bypass (CPB) serves to hemoconcentrate blood volume to avoid allogeneic blood transfusions. Previous studies have determined CUF volumes as a continuous variable are associated with postoperative acute kidney injury (AKI) after cardiac surgery, but optimal weight-indexed volumes that predict AKI have not been described.Design
Retrospective cohort.Setting
Single-center university hospital.Participants
A total of 1,641 consecutive patients who underwent elective cardiac surgery between June 2013 and December 2015.Interventions
The CUF volume was removed during CPB in all participants as part of routine practice. The authors investigated the association of dichotomized weight-indexed CUF volume removal with postoperative AKI development to provide pragmatic guidance for clinical practice at the authors' institution.Measurements and main results
Primary outcomes of postoperative AKI were defined by the Kidney Disease: Improving Global Outcomes staging criteria and dichotomized, weight-indexed CUF volumes (mL/kg) were defined by (1) extreme quartiles (Q3) and (2) Youden's criterion that best predicted AKI development. Multivariate logistic regression models were developed to test the association of these dichotomized indices with AKI status. Postoperative AKI occurred in 827 patients (50.4%). Higher CUF volumes were associated with AKI development by quartiles (CUF >Q3 = 32.6 v CUF < Q1 = 10.4 mL/kg; odds ratio [OR] = 1.68, 95% CI: 1.19-2.3) and Youden's criterion (CUF ≥ 32.9 v CUF <32.9 mL/kg; OR = 1.60, 95% CI: 1.21-2.13). Despite similar intraoperative nadir hematocrits among groups (p = 0.8), higher CUF volumes were associated with more allogeneic blood transfusions (p = 0.002) and longer lengths of stay (p < 0.001).Conclusions
Removal of weight-indexed CUF volumes > 32 mL/kg increased the risk for postoperative AKI development. Importantly, CUF volume removal of any amount did not mitigate allogeneic blood transfusion during elective cardiac surgery. Prospective studies are needed to validate these findings.Item Open Access Fluid Management in the Elderly(Current Anesthesiology Reports, 2017-12) Williams, David GA; Sandler, Aaron J; Koepke, Elena; Manning, Erin L; Miller, Timothy E; Manning, Michael WItem Open Access Impact of an enhanced recovery pathway on length of stay and complications in elective radical cystectomy: a before and after cohort study(Perioperative Medicine, 2019-12) Dunkman, W Jonathan; Manning, Michael W; Whittle, John; Hunting, John; Rampersaud, Edward N; Inman, Brant A; Thacker, Julie K; Miller, Timothy EItem Open Access Perioperative fluid and hemodynamic management within an enhanced recovery pathway.(Journal of surgical oncology, 2017-10) Manning, Michael W; Dunkman, William Jonathan; Miller, Timothy EGoal-directed fluid therapy (GDFT) seeks to improve outcomes through individualized optimization of oxygen delivery using IV fluid and vasoactive infusions. Trials of GDFT show clinical benefits over traditional liberal fluid administration, but fail to demonstrate benefits when compared to a restrictive strategy within an optimized enhanced recovery protocol. The ideal monitors, hemodynamic goals, and fluid administration strategy are not well established but may be less important than rational application of thoughtful fluid management strategies.Item Open Access Perioperative Quality Initiative (POQI) consensus statement on fundamental concepts in perioperative fluid management: fluid responsiveness and venous capacitance(Perioperative Medicine, 2020-12) Martin, Greg S; Kaufman, David A; Marik, Paul E; Shapiro, Nathan I; Levett, Denny ZH; Whittle, John; MacLeod, David B; Chappell, Desiree; Lacey, Jonathan; Woodcock, Tom; Mitchell, Kay; Malbrain, Manu LNG; Woodcock, Tom M; Martin, Daniel; Imray, Chris HE; Manning, Michael W; Howe, Henry; Grocott, Michael PW; Mythen, Monty G; Gan, Tong J; Miller, Timothy EItem Open Access The rising tide of opioid use and abuse: the role of the anesthesiologist.(Perioperative medicine (London, England), 2018-01) Koepke, Elena J; Manning, Erin L; Miller, Timothy E; Ganesh, Arun; Williams, David GA; Manning, Michael WOpioid use has risen dramatically in the past three decades. In the USA, opioid overdose has become a leading cause of unintentional death, surpassing motor vehicle accidents. A patient's first exposure to opioids may be during the perioperative period, a time where anesthesiologists have a significant role in pain management. Almost all patients in the USA receive opioids during a surgical encounter. Opioids have many undesirable side effects, including potential for misuse, or opioid use disorder. Anesthesiologists and surgeons employ several methods to decrease unnecessary opioid use, opioid-related adverse events, and side effects in the perioperative period. Multimodal analgesia, enhanced recovery pathways, and regional anesthesia are key tools as we work towards optimal opioid stewardship and the ideal of effective analgesia without undesirable sequelae.