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Respiratory and hemodynamic effects of three different sedative regimens for drug induced sleep endoscopy in sleep apnea patients. A prospective randomized study.
Elkalla, RS, El Mourad, MB
Minerva anestesiologica. 2020;(2):132-140
Abstract
BACKGROUND Drug induced sleep endoscopy (DISE) has emerged as a promising tool for customizing the adequate surgical approach to relieve airway obstruction in sleep apnea patients. We aimed to compare propofol, dexmedetomidine or ketofol with regards their efficacy and safety for sedation in patients with obstructive sleep apnea (OSA) undergoing DISE procedure. METHODS Sixty adult OSA patients scheduled for DISE procedure were randomly allocated into three equal groups to receive either propofol (group P), dexmedetomidine (group D), or ketofol (group K). Incidence of oxygen desaturation <90%, hemodynamic variables, time to achieve sufficient sedation level, recovery time, patients' and endoscopists' satisfaction, and incidence of adverse effects were recorded. RESULTS Higher incidence of oxygen desaturation <90% was observed in group P as compared to groups D and K (70%, 35%, and 30% respectively, P=0.021*). Group D showed a significantly longer time to reach target sedation level, prolonged recovery time with more consumption of rescue propofol as compared to group P and group K (P=0.000*, 0.000*, 0.000* respectively). Heart rate values were lower in group D after the loading dose till 30 min postoperative as compared to the other two groups, while blood pressure was lower in both P and D groups at five, 10, 15 min, and on reaching recovery room compared to K group. Two patients in the K group had psychomimetic symptoms with no difference between groups as regards other adverse events or patients' and endoscopist's satisfactions. CONCLUSIONS Dexmedetomidine and ketofol provided a safe respiratory profile compared to propofol during DISE without significant hemodynamic adverse events.
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Effect of nicorandil administration on cardiac burden and cardio-ankle vascular index after coronary intervention.
Sato, S, Takahashi, M, Mikamo, H, Kawazoe, M, Iizuka, T, Shimizu, K, Noro, M, Shirai, K
Heart and vessels. 2020;(12):1664-1671
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Abstract
Myocardial injury is a problem associated with percutaneous coronary intervention (PCI). This study aimed to clarify the role of nicorandil administration in preventing myocardial injury. This study included patients with stable angina who underwent PCI from November 2013 to June 2016. Of 58 consecutive patients, the first 20 patients received only saline infusion after PCI (control group); the other 38 patients received a continuous intravenous infusion of nicorandil and saline after PCI (nicorandil group). Troponin I and brain natriuretic peptide (BNP) levels were measured. Vascular parameters, such as blood pressure (BP), cardiac output, cardio-ankle vascular index (CAVI), and estimated systemic vascular resistance (eSVR), were measured. Troponin I of both groups increased 12 h after PCI. Changes in BNP levels between immediately after PCI and 12 h after PCI were significantly higher in the control than in the nicorandil group (10.8 ± 44.2 vs. - 2.6 ± 14.6 pg/ml, p = 0.04). In the nicorandil group, BP, eSVR, and CAVI decreased significantly at 12 h after PCI compared with those immediately after PCI (p < 0.0001), whereas no change was observed in the control group. In a single linear analysis, the change in BP (r = 0.36, p < 0.01) and nicorandil administration (r = - 0.47, p < 0.001) was significantly correlated with the change in CAVI, multiple regression analysis revealed that the changes in CO and eSVR were significant contributing factors for the changes in CAVI. PCI could result in myocardial injury and/or cardiac burden in patients with stable angina. Nicorandil administration after PCI may be effective in relieving the burden by decreasing arterial stiffness (CAVI).
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The Cardiorenal Syndrome in Heart Failure.
Costanzo, MR
Heart failure clinics. 2020;(1):81-97
Abstract
Abnormal fluid handling leads to physiologic abnormalities in multiple organ systems. Deranged hemodynamics, neurohormonal activation, excessive tubular sodium reabsorption, inflammation, oxidative stress, and nephrotoxic medications are important drivers of harmful cardiorenal interactions in patients with heart failure. Accurate quantitative measurement of fluid volume is vital to individualizing therapy for such patients. Blood volume analysis and pulmonary artery pressure monitoring seem the most reliable methods for assessing fluid volume and guiding decongestive therapies. Still the cornerstone of decongestive therapy, diuretics' effectiveness decreases with progression of heart failure. Extracorporeal ultrafiltration, an alternative to diuretics, has been shown to reduce heart-failure events.
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Metformin use in obese mothers is associated with improved cardiovascular profile in the offspring.
Panagiotopoulou, O, Syngelaki, A, Georgiopoulos, G, Simpson, J, Akolekar, R, Shehata, H, Nicolaides, K, Charakida, M
American journal of obstetrics and gynecology. 2020;(2):246.e1-246.e10
Abstract
BACKGROUND Maternal obesity increases the risk for pregnancy complications and adverse neonatal outcome and has been associated with long-lasting adverse effects in the offspring, including increased body fat mass, insulin resistance, and increased risk for premature cardiovascular disease. Lifestyle interventions in pregnancy have produced no or modest effects in the reduction of adverse pregnancy outcomes in obese mothers. The Metformin in Obese Pregnant Women trial was associated with reduced adverse pregnancy outcomes and had no effect on birthweight. However, the long-term implications of metformin on the health of offspring remain unknown. OBJECTIVE The purpose of this study was to assess whether prenatal exposure to metformin can improve the cardiovascular profile and body composition in the offspring of obese mothers. STUDY DESIGN In 151 children from the Metformin in Obese Pregnant Women trial, body composition, peripheral blood pressure, and arterial pulse wave velocity were measured. Central hemodynamics (central blood pressure and augmentation index) were estimated with the use of an oscillometric device. Left ventricular cardiac function and structure were assessed by echocardiography. RESULTS Children were 3.9±1.0 years old, and 77 of them had been exposed to metformin prenatally. There was no significant difference in peripheral blood pressure, arterial stiffness, and body composition apart from gluteal and tricep circumferences, which were lower in the metformin group (P<.05). The metformin group, compared with the placebo group, had lower central hemodynamics (mean adjusted decrease, -0.707 mm Hg for aortic systolic blood pressure, -1.65 mm Hg for aortic pulse pressure, and -2.68% for augmentation index; P<.05 for all) and lower left ventricular diastolic function (adjusted difference in left atrial area, -0.525 cm2, in isovolumic relaxation time, -0.324 msec, and in pulmonary venous systolic wave, 2.97 cm/s; P<.05 for all). There were no significant differences in metabolic profile between the groups. CONCLUSION Children of obese mothers who were exposed prenatally to metformin, compared with those who were exposed to placebo, had lower central hemodynamic and cardiac diastolic indices. These results suggest that the administration of metformin in obese pregnant women potentially may have a beneficial cardiovascular effect for their offspring.
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A randomized, controlled, double-blind crossover study on the effects of isoeffective and isovolumetric intravenous crystalloid and gelatin on blood volume, and renal and cardiac hemodynamics.
Bradley, CR, Bragg, DD, Cox, EF, El-Sharkawy, AM, Buchanan, CE, Chowdhury, AH, Macdonald, IA, Francis, ST, Lobo, DN
Clinical nutrition (Edinburgh, Scotland). 2020;(7):2070-2079
Abstract
BACKGROUND & AIMS Blood volume expanding properties of colloids are superior to crystalloids. In addition to oncotic/osmotic properties, the electrolyte composition of infusions may have important effects on visceral perfusion, with infusions containing supraphysiological chloride causing hyperchloremic acidosis and decreased renal blood flow. In this non-inferiority study, a validated healthy human subject model was used to compare effects of colloid (4% succinylated gelatin) and crystalloid fluid regimens on blood volume, renal function, and cardiac output. METHODS Healthy male participants were given infusions over 60 min > 7 days apart in a randomized, crossover manner. Reference arm (A): 1.5 L of Sterofundin ISO, isoeffective arm (B): 0.5 L of 4% Gelaspan®, isovolumetric arm (C): 0.5 L of 4% Gelaspan® and 1 L of Sterofundin ISO (all B. Braun, Melsungen, Germany). Participants were studied over 240 min. Changes in blood volume were calculated from changes in weight and hematocrit. Renal volume, renal artery blood flow (RABF), renal cortex perfusion and diffusion, and cardiac index were measured with magnetic resonance imaging. RESULTS Ten of 12 males [mean (SE) age 23.9 (0.8) years] recruited, completed the study. Increase in body weight and extracellular fluid volume were significantly less after infusion B than infusions A and C, but changes in blood volume did not significantly differ between infusions. All infusions increased renal volume, with no significant differences between infusions. There was no significant difference in RABF across the infusion time course or between infusion types. Renal cortex perfusion decreased during the infusion (mean 18% decrease from baseline), with no significant difference between infusions. There was a trend for increased renal cortex diffusion (4.2% increase from baseline) for the crystalloid infusion. All infusions led to significant increases in cardiac index. CONCLUSIONS A smaller volume of colloid (4% succinylated gelatin) was as effective as a larger volume of crystalloid at expanding blood volume, increasing cardiac output and changing renal function. Significantly less interstitial space expansion occurred with the colloid. TRIAL REGISTRATION The protocol was registered with the European Union Drug Regulating Authorities Clinical Trials Database (https://eudract.ema.europa.eu) (EudraCT No. 2013-003260-32).
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Investigating Physical and Nutritional Changes During Prolonged Intermittent Fasting in Hemodialysis Patients: A Prospective Cohort Study.
Adanan, NIH, Md Ali, MS, Lim, JH, Zakaria, NF, Lim, CTS, Yahya, R, Abdul Gafor, AH, Karupaiah, T, Daud, Z'M
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2020;(2):e15-e26
Abstract
OBJECTIVE Studies investigating the health effects of prolonged intermittent fasting during Ramadan among Muslim patients on hemodialysis (HD) are limited and reported heterogeneous findings. This study aimed to evaluate the effects of intermittent fasting during Ramadan on nutritional and functional status of patients on maintenance HD. DESIGN AND METHODS This was a 12-week, multicenter, prospective observational study. The study setting included three HD centers. Adult Muslim patients, who were undergoing HD session thrice weekly and planned to fast during Ramadan, were screened for eligibility and recruited. Nutritional and functional status assessments were carried out 2 weeks before (V0), at the fourth week of Ramadan (V1), and 4 weeks after Ramadan (V2). Nutritional status parameters included anthropometry (body mass index, interdialytic weight gain, waist circumference), body composition (mid-arm circumference, triceps skinfold, body fat percentage), blood biochemistry (albumin, renal profile, lipid profile, and inflammatory markers), blood pressure, dietary intake, and handgrip strength. Changes in nutritional and functional status parameters across study timepoints were analyzed using repeated-measures analysis of variance. RESULTS A total of 87 patients completed the study, with 68 patients (78.2%) reporting fasting ≥20 days. Ramadan fasting led to significant reductions (all P < .05) in body mass index, interdialytic weight gain, waist circumference, mid-arm circumference, fat tissue mass, and body fat percentage, but these were not accompanied by any significant change in lean tissue mass (P > .05). Significant improvement was observed in serum phosphate levels, but serum albumin, urea, and creatinine were also reduced significantly during Ramadan (P < .05). There were no significant changes in lipid profile and inflammatory markers. Interestingly, energy and protein intakes remain unchanged during Ramadan. Handgrip strength improved significantly during Ramadan and further improved after Ramadan. CONCLUSION Intermittent Ramadan fasting leads to temporary changes in nutritional status parameters and poses nondetrimental nutritional risk for patients on maintenance HD.
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A randomized-controlled trial of arginine infusion in severe sepsis on microcirculation and metabolism.
Luiking, YC, Poeze, M, Deutz, NE
Clinical nutrition (Edinburgh, Scotland). 2020;(6):1764-1773
Abstract
BACKGROUND & AIMS Sepsis is hypothesized as an arginine deficient state, with lack of nitric oxide (NO) for adequate microcirculation and local perfusion. This study aimed to investigate if prolonged (72-h) intravenous l-arginine administration in sepsis patients improves microcirculation. Secondly, effects on arginine and protein metabolism, and organ function were studied. METHODS Critically ill patients with a diagnosis of septic shock participated in a long-term (72 h) randomized double-blind placebo-controlled parallel-group study. l-arginine-HCl (1.2 μmol kg-1 min-1; n = 9) or l-alanine (isocaloric control: 2.4 μmol kg-1 min-1; n = 9) was continuously infused. Primary study outcome was microcirculation, assessed as gastric mucosal perfusion by gastric tonometry (Pr-aCO2 gap) and skin perfusion by Laser Doppler flowmetry. Secondary endpoints were whole body (WB) arginine and protein metabolism, organ function and clinical outcomes. We measured global hemodynamics continuously for safety monitoring. Statistical analyses were performed by mixed model for repeated measures with treatment by time interaction as estimate for between-group difference. RESULTS Pr-aCO2 increased only in the l-arginine group (p = 0.006), without a significant between-group difference (p = 0.17). We found no significant differences in skin perfusion parameters. l-arginine infusion resulted in a larger increase of plasma arginine and ornithine concentrations (p < 0.01), WB (endogenous) arginine appearance (p < 0.001), WB NO synthesis (p = 0.027) and WB arginine to urea conversion (p < 0.001) than infusion of l-alanine. We found no effect on global hemodynamics, and protein metabolism by l-arginine infusion. Organ function parameters were unaffected, except for a significant difference between groups in intra-abdominal pressure over time (p = 0.029). CONCLUSIONS Prolonged intravenous l-arginine administration does not improve local perfusion and organ function despite an increase in WB NO synthesis. Administration is safe with regard to global hemodynamics, but the observed increase in Pr-aCO2 and intra-abdominal pressure warrants careful application of l-arginine infusion and further research, especially in the early stage of septic shock.
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Omega-3 polyunsaturated fatty acid supplementation versus placebo on vascular health, glycaemic control, and metabolic parameters in people with type 1 diabetes: a randomised controlled preliminary trial.
O'Mahoney, LL, Dunseath, G, Churm, R, Holmes, M, Boesch, C, Stavropoulos-Kalinoglou, A, Ajjan, RA, Birch, KM, Orsi, NM, Mappa, G, et al
Cardiovascular diabetology. 2020;(1):127
Abstract
BACKGROUND The role of omega-3 polyunsaturated fatty acids (n-3PUFA), and the potential impact of n-3PUFA supplementation, in the treatment and management of type 1 diabetes (T1D) remains unclear and controversial. Therefore, this study aimed to examine the efficacy of daily high-dose-bolus n-3PUFA supplementation on vascular health, glycaemic control, and metabolic parameters in subjects with T1D. METHODS Twenty-seven adults with T1D were recruited to a 6-month randomised, double-blind, placebo-controlled trial. Subjects received either 3.3 g/day of encapsulated n-3PUFA or encapsulated 3.0 g/day corn oil placebo (PLA) for 6-months, with follow-up at 9-months after 3-month washout. Erythrocyte fatty acid composition was determined via gas chromatography. Endpoints included inflammation-associated endothelial biomarkers (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], E-selectin, P-selectin, pentraxin-3, vascular endothelial growth factor [VEGF]), and their mediator tumor necrosis factor alpha [TNFα] analysed via immunoassay, vascular structure (carotid intima-media thickness [CIMT]) and function (brachial artery flow mediated dilation [FMD]) determined via ultrasound technique, blood pressure, glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial metabolism. RESULTS Twenty subjects completed the trial in full. In the n-3PUFA group, the mean ± SD baseline n-3PUFA index of 4.93 ± 0.94% increased to 7.67 ± 1.86% (P < 0.001) after 3-months, and 8.29 ± 1.45% (P < 0.001) after 6-months. Total exposure to n-3PUFA over the 6-months (area under the curve) was 14.27 ± 3.05% per month under n-3PUFA, and 9.11 ± 2.74% per month under PLA (P < 0.001). VCAM-1, ICAM-1, E-selectin, P-selectin, pentraxin-3, VEGF, TNFα, CIMT, FMD, blood pressure, HbA1c, FPG, and postprandial metabolism did not differ between or within groups after treatment (P > 0.05). CONCLUSIONS This study indicates that daily high-dose-bolus of n-3PUFA supplementation for 6-months does not improve vascular health, glucose homeostasis, or metabolic parameters in subjects with T1D. The findings from this preliminary RCT do not support the use of therapeutic n-3PUFA supplementation in the treatment and management of T1D and its associated complications. Trial Registration ISRCTN, ISRCTN40811115. Registered 27 June 2017, http://www.isrctn.com/ISRCTN40811115 .
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Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam.
Forsyth, A, McMillan, R, Campbell, D, Malpas, G, Maxwell, E, Sleigh, J, Dukart, J, Hipp, J, Muthukumaraswamy, SD
Human brain mapping. 2020;(6):1472-1494
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Abstract
The pharmacological modulation of functional connectivity in the brain may underlie therapeutic efficacy for several neurological and psychiatric disorders. Functional magnetic resonance imaging (fMRI) provides a noninvasive method of assessing this modulation, however, the indirect nature of the blood-oxygen level dependent signal restricts the discrimination of neural from physiological contributions. Here we followed two approaches to assess the validity of fMRI functional connectivity in developing drug biomarkers, using simultaneous electroencephalography (EEG)/fMRI in a placebo-controlled, three-way crossover design with ketamine and midazolam. First, we compared seven different preprocessing pipelines to determine their impact on the connectivity of common resting-state networks. Independent components analysis (ICA)-denoising resulted in stronger reductions in connectivity after ketamine, and weaker increases after midazolam, than pipelines employing physiological noise modelling or averaged signals from cerebrospinal fluid or white matter. This suggests that pipeline decisions should reflect a drug's unique noise structure, and if this is unknown then accepting possible signal loss when choosing extensive ICA denoising pipelines could engender more confidence in the remaining results. We then compared the temporal correlation structure of fMRI to that derived from two connectivity metrics of EEG, which provides a direct measure of neural activity. While electrophysiological estimates based on the power envelope were more closely aligned to BOLD signal connectivity than those based on phase consistency, no significant relationship between the change in electrophysiological and hemodynamic correlation structures was found, implying caution should be used when making cross-modal comparisons of pharmacologically-modulated functional connectivity.
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Effects of intraoperative hemodynamic management on postoperative acute kidney injury in liver transplantation: An observational cohort study.
Carrier, FM, Sylvestre, MP, Massicotte, L, Bilodeau, M, Chassé, M
PloS one. 2020;(8):e0237503
Abstract
BACKGROUND Intraoperative restrictive fluid management strategies might improve postoperative outcomes in liver transplantation. Effects of vasopressors within any hemodynamic management strategy are unclear. METHODS We conducted an observational cohort study on adult liver transplant recipients between July 2008 and December 2017. We measured the effect of vasopressors infused at admission in the intensive care unit (ICU) and total intraoperative fluid balance. Our primary outcome was 48-hour acute kidney injury (AKI) and our secondary outcomes were 7-day AKI, need for postoperative renal replacement therapy (RRT), time to extubation in the ICU, time to ICU discharge and survival up to 1 year. We fitted models adjusted for confounders using generalized estimating equations or survival models using robust standard errors. We reported results with 95% confidence intervals. RESULTS We included 532 patients. Vasopressors use was not associated with 48-hour or 7-day AKI but modified the effects of fluid balance on RRT and mortality. A higher fluid balance was associated with a higher need for RRT (OR = 1.52 [1.15, 2.01], p<0.001 for interaction) and lower survival (HR = 1.71 [1.26, 2.34], p<0.01 for interaction) only among patients without vasopressors. In patients with vasopressors, higher doses of vasopressors were associated with a higher mortality (HR = 1.29 [1.13, 1.49] per 10 μg/min of norepinephrine). CONCLUSION The presence of any vasopressor at the end of surgery was not associated with AKI or RRT. The use of vasopressors might modify the harmful association between fluid balance and other postoperative outcomes. The liberal use of vasopressors to implement a restrictive fluid management strategy deserves further investigation.