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Background: Beta-hydroxybuturate (ß-OHB) supplements are commonly utilized in sports by both recreational and professional athletes. In a recent study, we observed a drop in testosterone levels following the oral ingestion of racemic sodium-ß-OHB. In this investigation, we aim to determine whether a single oral dose of ketone ester (study I) and prolonged endogenous ketosis (study II) also reduces testosterone levels. Design: This investigation integrated samples from two distinct studies. Study I was a randomized, controlled, crossover trial with ten healthy, young male participants receiving either a weight-adjusted ketone ester or control (water, CTR) and vice versa following an overnight fast. Repeated blood sampling was used to monitor plasma ß-OHB and testosterone levels. Study II, another randomized, controlled, crossover trial, included 11 middle-aged participants (five males). They followed either a ketogenic diet (KD) characterized by low carbohydrates and high fat content or a standard diet (SDD) for three weeks. After each study period, participants underwent examination following an overnight fast, with repeated measures employed to analyze concentrations of plasma ß-OHB and sex hormone levels. Results: Study I: Testosterone decreased from 23.8 ± 2.4 nmol/l to 22.3 ± 2.5 nmol/l 300 minutes after the ketone ester and increased from 20.9 ± 2.1 nmol/l to 22.2 ± 1.9 300 minutes after CTR. This difference was not significant, p = 0.06. Study II. Total testosterone was unaffected after the KD compared to the SDD in men (20.2 ± 1.23 nmol/l vs. 18.2 ± 1.23 nmol/l (p = 0.1)) and was lower after KD in women (0.87 ± 0.06 vs. 1.1 ± 0.06 nmol/l (p < 0.0001)). Sex hormone-binding globulin (SHBG) increased in men after KD compared with SDD (31.2 ± 2.6 nmol/l vs 25.0 ± 2.6 nmol/l, p < 0.0001) and women (26.5 ± 3.05 nmol/l vs 24.2 ± 3.05 nmol/l, p = 0.003). The free androgen index decreased after KD in men (ratio: 0.65 ± 0.05 vs. ratio: 0.74 ± 0.05, p = 0.04) and in women (ratio: 0.036 ± 0.006 vs. SDD 0.05 ± 0.006, p = 0.0001). Free estradiol index was also found lower after KD in men (ratio: 3.1 ± 0.8 vs. ratio: 4.8 ± 0.8, p = 0.0003) and in women (ratio: 1.2 ± 2.2 vs. 9.8 ± 2.2, p = 0.0001). Conclusion: Our findings indicate that the acute ingestion of ketone ester may not reduce testosterone levels in healthy young males. However, a three-week exposure to KB from a KD results in an increase in SHBG in men and women with obesity as well as it lowers free testosterone and estradiol for men and women. We thus present evidence of crosstalk between alterations in a metabolite, ß-OHB, and the regulation of the hypothalamic-pituitary-gonadal axis from a KD. The clinical impact of this reduction remains to be investigated. This trial is registered with NCT04156477 and NCT05012748.
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BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality in patients with type 2 diabetes (T2DM). Acute increases in circulating levels of ketone body 3-hydroxybutyrate have beneficial acute hemodynamic effects in patients without T2DM with chronic heart failure with reduced ejection fraction. However, the cardiovascular effects of prolonged oral ketone ester (KE) treatment in patients with T2DM and HFpEF remain unknown. METHODS: A total of 24 patients with T2DM and HFpEF completed a 6-week randomized, double-blind crossover study. All patients received 2 weeks of KE treatment (25 g D-ß-hydroxybutyrate-(R)-1,3-butanediol × 4 daily) and isocaloric and isovolumic placebo, separated by a 2-week washout period. At the end of each treatment period, patients underwent right heart catheterization, echocardiography, and blood samples at trough levels of intervention, and then during a 4-hour resting period after a single dose. A subsequent second dose was administered, followed by an exercise test. The primary end point was cardiac output during the 4-hour rest period. RESULTS: During the 4-hour resting period, circulating 3-hydroxybutyrate levels were 10-fold higher after KE treatment (1010±56 µmol/L; P<0.001) compared with placebo (91±55 µmol/L). Compared with placebo, KE treatment increased cardiac output by 0.2 L/min (95% CI, 0.1 to 0.3) during the 4-hour period and decreased pulmonary capillary wedge pressure at rest by 1 mm Hg (95% CI, -2 to 0) and at peak exercise by 5 mm Hg (95% CI, -9 to -1). KE treatment decreased the pressure-flow relationship (∆ pulmonary capillary wedge pressure/∆ cardiac output) significantly during exercise (P<0.001) and increased stroke volume by 10 mL (95% CI, 0 to 20) at peak exercise. KE right-shifted the left ventricular end-diastolic pressure-volume relationship, suggestive of reduced left ventricular stiffness and improved compliance. Favorable hemodynamic responses of KE treatment were also observed in patients treated with sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 analogs. CONCLUSIONS: In patients with T2DM and HFpEF, a 2-week oral KE treatment increased cardiac output and reduced cardiac filling pressures and ventricular stiffness. At peak exercise, KE treatment markedly decreased pulmonary capillary wedge pressure and improved pressure-flow relationship. Modulation of circulating ketone levels is a potential new treatment modality for patients with T2DM and HFpEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05236335.
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BACKGROUND: Cardiogenic shock (CS) presents a medical challenge with limited treatment options. Positive end-expiratory pressure (PEEP) during mechanical ventilation has been linked with clinical benefits in patients with CS. We investigated if increasing PEEP levels could unload the left ventricle (LV) in CS in a large animal model of LV-CS. METHODS: LV-CS was induced in 26 female pigs (60 kg) by microsphere injections into the left main coronary artery. In one study protocol PEEP was increased (5, 10, and 15 cmH2O) and then reverted (15, 10, 5 cmH2O) in 3-minute intervals. In another protocol PEEP increments with higher granularity were conducted through 3-minute intervals (5, 8, 10, 13, and 15 cmH2O). Hemodynamic measurements were performed at all PEEP levels during the healthy state and LV-CS with LV pressure-volume loops. The primary endpoint was pressure-volume area (PVA). Secondary endpoints included other mechano-energetic parameters and estimates of LV preload and afterload. RESULTS: Cardiac output (CO) decreased significantly in LV-CS from 4.5±1.0 L/min to 3.1±0.9 L/min (P<0.001). Increasing PEEP resulted in lower PVA, demonstrating a 36±3% decrease in the healthy state (P<0.001) and 18±3% in LV-CS (P<0.001) at PEEP 15 cmH2O. These effects were highly reversible when PEEP was returned to 5 cmH2O. While mean arterial pressure declined with higher PEEP, CO remained preserved during LV-CS (P=0.339). Increasing PEEP caused reductions in key measures of LV preload and afterload during LV-CS. Right ventricular stroke work index was decreased with increased PEEP. Despite a minor increase in heart rate (HR) at PEEP levels of 15 cmH2O (71 bpm vs. 75 bpm, p<0.05), total mechanical power expenditure (PVA normalized to HR) decreased at higher PEEP. CONCLUSIONS: Applying higher PEEP levels reduced PVA, preserving CO while decreasing MAP. PEEP could be a viable LV unloading strategy if titrated optimally during LV-CS.
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BACKGROUND: The ketone body 3-hydroxybutyrate (3-OHB) increases cardiac output (CO) by 35% to 40% in healthy people and people with heart failure. The mechanisms underlying the effects of 3-OHB on myocardial contractility and loading conditions as well as the cardiovascular effects of its enantiomeric forms, D-3-OHB and L-3-OHB, remain undetermined. METHODS AND RESULTS: Three groups of 8 pigs each underwent a randomized, crossover study. The groups received 3-hour infusions of either D/L-3-OHB (racemic mixture), 100% L-3-OHB, 100% D-3-OHB, versus an isovolumic control. The animals were monitored with pulmonary artery catheter, left ventricle pressure-volume catheter, and arterial and coronary sinus blood samples. Myocardial biopsies were evaluated with high-resolution respirometry, coronary arteries with isometric myography, and myocardial kinetics with D-[11C]3-OHB and L-[11C]3-OHB positron emission tomography. All three 3-OHB infusions increased 3-OHB levels (P<0.001). D/L-3-OHB and L-3-OHB increased CO by 2.7 L/min (P<0.003). D-3-OHB increased CO nonsignificantly (P=0.2). Circulating 3-OHB levels correlated with CO for both enantiomers (P<0.001). The CO increase was mediated through arterial elastance (afterload) reduction, whereas contractility and preload were unchanged. Ex vivo, D- and L-3-OHB dilated coronary arteries equally. The mitochondrial respiratory capacity remained unaffected. The myocardial 3-OHB extraction increased only during the D- and D/L-3-OHB infusions. D-[11C]3-OHB showed rapid cardiac uptake and metabolism, whereas L-[11C]3-OHB demonstrated much slower pharmacokinetics. CONCLUSIONS: 3-OHB increased CO by reducing afterload. L-3-OHB exerted a stronger hemodynamic response than D-3-OHB due to higher circulating 3-OHB levels. There was a dissocitation between the myocardial metabolism and hemodynamic effects of the enantiomers, highlighting L-3-OHB as a potent cardiovascular agent with strong hemodynamic effects.
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Hidroxibutiratos , Tomografía Computarizada por Rayos X , Humanos , Porcinos , Animales , Ácido 3-Hidroxibutírico/farmacología , Estudios Cruzados , Hidroxibutiratos/farmacología , Corazón , Cuerpos Cetónicos/metabolismoRESUMEN
BACKGROUND: Lactate is traditionally recognized as a by-product of anaerobic metabolism. However, lactate is a preferred oxidative substrate for stressed myocardium. Exogenous lactate infusion increases cardiac output (CO). The exact mechanism underlying this mechanism has yet to be elucidated. The aim of this study was to investigate the cardiovascular mechanisms underlying the acute haemodynamic effects of exogenous lactate infusion in an experimental model of human-sized pigs. METHODS: In this randomised, blinded crossover study in eight 60-kg-pigs, the pigs received infusions with one molar sodium lactate and a control infusion of tonicity matched hypertonic saline in random order. We measured CO and pulmonary pressures using a pulmonary artery catheter. A pressure-volume admittance catheter in the left ventricle was used to measure contractility, afterload, preload and work-related parameters. RESULTS: Lactate infusion increased circulating lactate levels by 9.9 mmol/L (95% confidence interval (CI) 9.1 to 11.0) and CO by 2.0 L/min (95% CI 1.2 to 2.7). Afterload decreased as arterial elastance fell by -1.0 mmHg/ml (95% CI -2.0 to -0.1) and systemic vascular resistance decreased by -548 dynes/s/cm5 (95% CI -261 to -835). Mixed venous saturation increased by 11 percentage points (95% CI 6 to 16), whereas ejection fraction increased by 16.0 percentage points (95% CI 1.1 to 32.0) and heart rate by 21 bpm (95% CI 8 to 33). No significant changes in contractility nor preload were observed. CONCLUSION: Lactate infusion increased cardiac output by increasing heart rate and lowering afterload. No differences were observed in left ventricular contractility or preload. Lactate holds potential as a treatment in situations with lowered CO and should be investigated in future clinical studies.
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Hemodinámica , Ácido Láctico , Animales , Gasto Cardíaco/fisiología , Estudios Cruzados , Frecuencia Cardíaca , Porcinos , Resistencia VascularRESUMEN
BACKGROUND: Heart failure triggers a shift in myocardial metabolic substrate utilization, favoring the ketone body 3-hydroxybutyrate as energy source. We hypothesized that 14-day treatment with ketone ester (KE) would improve resting and exercise hemodynamics and exercise capacity in patients with heart failure with reduced ejection fraction. METHODS: In a randomized, double-blind cross-over study, nondiabetic patients with heart failure with reduced ejection fraction received 14-day KE and 14-day isocaloric non-KE comparator regimens of 4 daily doses separated by a 14-day washout period. After each treatment period, participants underwent right heart catheterization, echocardiography, and blood sampling at plasma trough levels and after dosing. Participants underwent an exercise hemodynamic assessment after a second dosing. The primary end point was resting cardiac output (CO). Secondary end points included resting and exercise pulmonary capillary wedge pressure and peak exercise CO and metabolic equivalents. RESULTS: We included 24 patients with heart failure with reduced ejection fraction (17 men; 65±9 years of age; all White). Resting CO at trough levels was higher after KE compared with isocaloric comparator (5.2±1.1 L/min versus 5.0±1.1 L/min; difference, 0.3 L/min [95% CI, 0.1-0.5), and pulmonary capillary wedge pressure was lower (8±3 mm Hg versus 11±3 mm Hg; difference, -2 mm Hg [95% CI, -4 to -1]). These changes were amplified after KE dosing. Across all exercise intensities, KE treatment was associated with lower mean exercise pulmonary capillary wedge pressure (-3 mm Hg [95% CI, -5 to -1] ) and higher mean CO (0.5 L/min [95% CI, 0.1-0.8]), significantly different at low to moderate steady-state exercise but not at peak. Metabolic equivalents remained similar between treatments. In exploratory analyses, KE treatment was associated with 18% lower NT-proBNP (N-terminal pro-B-type natriuretic peptide; difference, -98 ng/L [95% CI, -185 to -23]), higher left ventricular ejection fraction (37±5 versus 34±5%; P=0.01), and lower left atrial and ventricular volumes. CONCLUSIONS: KE treatment for 14 days was associated with higher CO at rest and lower filling pressures, cardiac volumes, and NT-proBNP levels compared with isocaloric comparator. These changes persisted during exercise and were achieved on top of optimal medical therapy. Sustained modulation of circulating ketone bodies is a potential treatment principle in patients with heart failure with reduced ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05161650.
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Insuficiencia Cardíaca , Volumen Sistólico , Humanos , Masculino , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Femenino , Método Doble Ciego , Anciano , Volumen Sistólico/efectos de los fármacos , Persona de Mediana Edad , Estudios Cruzados , Tolerancia al Ejercicio/efectos de los fármacos , Administración Oral , Función Ventricular Izquierda/efectos de los fármacos , Resultado del Tratamiento , Ésteres/administración & dosificación , Cetonas/administración & dosificaciónRESUMEN
Lactate may inhibit lipolysis and thus enhance insulin sensitivity, but there is a lack of metabolic human studies. This study aimed to determine how hyperlactatemia affects lipolysis, glucose- and protein metabolism, and insulin sensitivity in healthy men. In a single-blind, randomized, crossover design, eight healthy men were studied after an overnight fast on two occasions: 1) during a sodium-lactate infusion (LAC) and 2) during a sodium-matched NaCl infusion (CTR). Both days consisted of a 3-h postabsorptive period followed by a 3-h hyperinsulinemic-euglycemic clamp (HEC). Lipolysis rate, endogenous glucose production (EGP), and delta glucose rate of disappearance (ΔRdglu) were evaluated using [9,10-3H]palmitate and [3-3H]glucose tracers. In addition, whole body- and forearm protein metabolism was assessed using [15N]phenylalanine, [2H4]tyrosine, [15N]tyrosine, and [13C]urea tracers. In the postabsorptive period, plasma lactate increased to 2.7 ± 0.5 mmol/L during LAC vs. 0.6 ± 0.3 mmol/L during CTR (P < 0.001). In the postabsorptive period, palmitate flux was 30% lower during LAC compared with CTR (84 ± 32 µmol/min vs. 120 ± 35 µmol/min, P = 0.003). During the HEC, palmitate flux was suppressed similarly during both interventions (P = 0.7). EGP, ΔRdglu, and M value were similar during LAC and CTR. During HEC, LAC increased whole body phenylalanine flux (P = 0.02) and protein synthesis (P = 0.03) compared with CTR; LAC did not affect forearm protein metabolism compared with CTR. Lactate infusion inhibited lipolysis by 30% under postabsorptive conditions but did not affect glucose metabolism or improve insulin sensitivity. In addition, whole body phenylalanine flux was increased. Clinical trial registrations: NCT04710875.NEW & NOTEWORTHY Lactate is a decisive intermediary metabolite, serving as an energy substrate and a signaling molecule. The present study examines the effects of lactate on substrate metabolism and insulin sensitivity in healthy males. Hyperlactatemia reduces lipolysis by 30% without affecting insulin sensitivity and glucose metabolism. In addition, hyperlactatemia increases whole body amino acid turnover rate.
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Hiperlactatemia , Resistencia a la Insulina , Humanos , Masculino , Glucemia/metabolismo , Estudios Cruzados , Glucosa/metabolismo , Técnica de Clampeo de la Glucosa , Insulina , Ácido Láctico/farmacología , Palmitatos , Fenilalanina , Proteínas , Método Simple Ciego , Sodio , TirosinaRESUMEN
Evaluating right ventricular (RV) function remains a challenge. Recently, novel echocardiographic assessment of RV myocardial work (RVMW) by non-invasive pressure-strain loops was proposed. This enables evaluation of right ventriculoarterial coupling and quantifies RV dyssynchrony and post-systolic shortening. We aimed to assess RVMW in patients with different etiologies of RV dysfunction and healthy controls. We investigated healthy controls (n=17), patients with severe functional tricuspid regurgitation (FTR; n=22), and patients with precapillary pulmonary hypertension (PCPH; n=20). Echocardiography and right heart catheterization were performed to assess 1) RV global constructive work (RVGCW; work needed for systolic myocardial shortening and isovolumic relaxation), 2) RV global wasted work (RVGWW; myocardial shortening following pulmonic valve closure), and 3) RV global work efficiency (RVGWE; describes the relation between RV constructive and wasted work). RVGCW correlated with invasive RV stroke work index (r=0.66, P<0.001) and increased in tandem with higher afterload, i.e., was low in healthy controls (454±73 mmHg%), moderate in patients with FTR (687±203 mmHg%), and highest among patients with PCPH (881±255 mmHg%). RVGWE was lower and RVGWW was higher in patients with FTR (86±8% and 91 mmHg% [53-140]) or PCPH (86±10% and 110 mmHg% [66-159]) as compared with healthy controls (96±3% and 10 mmHg%). RVMW by echocardiography provides a promising index of RV function to discriminate between patients with RV volume or pressure overload. The prognostic value of this measure needs to be settled in future studies.
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Insuficiencia de la Válvula Tricúspide , Disfunción Ventricular Derecha , Humanos , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/etiología , Valor Predictivo de las Pruebas , Ecocardiografía , Sístole , Función Ventricular Derecha , Volumen SistólicoRESUMEN
BACKGROUND: Cardiogenic shock (CS) is a life-threatening condition with sparse treatment options. The ketone body 3-hydroxybutyrate has favorable hemodynamic effects in patients with stable chronic heart failure. Yet, the hemodynamic effects of exogenous ketone ester (KE) in patients with CS remain unknown. OBJECTIVES: The authors aimed to assess the hemodynamic effects of single-dose enteral treatment with KE in patients with CS. METHODS: In a double-blind, crossover study, 12 patients with CS were randomized to an enteral bolus of KE and isocaloric, isovolumic placebo containing maltodextrin. Patients were assessed with pulmonary artery catheterization, arterial blood samples, echocardiography, and near-infrared spectroscopy for 3 hours following each intervention separated by a 3-hour washout period. RESULTS: KE increased circulating 3-hydroxybutyrate (2.9 ± 0.3 mmol/L vs 0.2 ± 0.3 mmol/L, P < 0.001) and was associated with augmented cardiac output (area under the curve of relative change: 61 ± 22 L vs 1 ± 18 L, P = 0.044). Also, KE increased cardiac power output (0.07 W [95% CI: 0.01-0.14]; P = 0.037), mixed venous saturation (3 percentage points [95% CI: 1-5 percentage points]; P = 0.010), and forearm perfusion (3 percentage points [95% CI: 0-6 percentage points]; P = 0.026). Right (P = 0.048) and left (P = 0.017) ventricular filling pressures were reduced whereas heart rate and mean arterial and pulmonary arterial pressures remained similar. Left ventricular ejection fraction improved by 4 percentage points (95% CI: 2-6 percentage points; P = 0.005). Glucose levels decreased by 2.6 mmol/L (95% CI: -5.2 to 0.0; P = 0.047) whereas insulin levels remained unaltered. CONCLUSIONS: Treatment with KE improved cardiac output, biventricular function, tissue oxygenation, and glycemic control in patients with CS (Treatment With the Ketone Body 3-hydroxybutyrate in Patients With Cardiogenic Shock [KETO-SHOCK1]; NCT04642768).
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Insuficiencia Cardíaca , Choque Cardiogénico , Humanos , Choque Cardiogénico/terapia , Volumen Sistólico , Cetonas/farmacología , Cetonas/uso terapéutico , Ácido 3-Hidroxibutírico/farmacología , Ácido 3-Hidroxibutírico/uso terapéutico , Estudios Cruzados , Función Ventricular Izquierda , Hemodinámica , Cuerpos Cetónicos/farmacología , Cuerpos Cetónicos/uso terapéuticoRESUMEN
Background The ketone body 3-hydroxybutyrate (3-OHB) increases cardiac output (CO) in patients with heart failure through unknown mechanisms. 3-OHB activates the hydroxycarboxylic acid receptor 2 (HCA2), which increases prostaglandins and suppresses circulating free fatty acids. We investigated whether the cardiovascular effects of 3-OHB involved HCA2 activation and if the potent HCA2-stimulator niacin may increase CO. Methods and Results Twelve patients with heart failure with reduced ejection fraction were included in a randomized crossover study and examined by right heart catheterization, echocardiography, and blood sampling on 2 separate days. On study day 1, patients received aspirin to block the HCA2 downstream cyclooxygenase enzyme, followed by 3-OHB and placebo infusions in random order. We compared the results with those of a previous study in which patients received no aspirin. On study day 2, patients received niacin and placebo. The primary end point was CO. 3-OHB increased CO (2.3 L/min, P<0.01), stroke volume (19 mL, P<0.01), heart rate (10 bpm, P<0.01), and mixed venous saturation (5%, P<0.01) with preceding aspirin. 3-OHB did not change prostaglandin levels, neither in the ketone/placebo group receiving aspirin nor the previous study cohort. Aspirin did not block 3-OHB-induced changes in CO (P=0.43). 3-OHB decreased free fatty acids by 58% (P=0.01). Niacin increased prostaglandin D2 levels by 330% (P<0.02) and reduced free fatty acids by 75% (P<0.01) but did not affect CO. Conclusions The acute increase in CO during 3-OHB infusion was not modified by aspirin, and niacin had no hemodynamic effects. These findings show that HCA2 receptor-mediated effects were not involved in the hemodynamic response to 3-OHB. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04703361.
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Insuficiencia Cardíaca , Niacina , Humanos , Ácido 3-Hidroxibutírico , Niacina/farmacología , Niacina/uso terapéutico , Ácidos Grasos no Esterificados , Estudios Cruzados , Hidroxibutiratos , Cuerpos Cetónicos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , ProstaglandinasRESUMEN
Background Pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) are debilitating diseases with a high mortality. Despite emerging treatments, pulmonary vascular resistance frequently remains elevated. However, the ketone body 3-hydroxybutyrate (3-OHB) may reduce pulmonary vascular resistance in these patients. Hence, the aim was to assess the hemodynamic effects of 3-OHB in patients with PAH or CTEPH. Methods and Results We enrolled patients with PAH (n=10) or CTEPH (n=10) and residual pulmonary hypertension. They received 3-OHB infusion and placebo (saline) for 2 hours in a randomized crossover study. Invasive hemodynamic and echocardiography measurements were performed. Furthermore, we investigated the effects of 3-OHB on the right ventricle of isolated hearts and isolated pulmonary arteries from Sprague-Dawley rats. Ketone body infusion increased circulating 3-OHB levels from 0.5±0.5 to 3.4±0.7 mmol/L (P<0.001). Cardiac output improved by 1.2±0.1 L/min (27±3%, P<0.001), and right ventricular annular systolic velocity increased by 1.4±0.4 cm/s (13±4%, P=0.002). Pulmonary vascular resistance decreased by 1.3±0.3 Wood units (18%±4%, P<0.001) with no significant difference in response between patients with PAH and CTEPH. In the rat studies, 3-OHB administration was associated with decreased pulmonary arterial tension compared with saline administration (maximal relative tension difference: 12±2%, P<0.001) and had no effect on right ventricular systolic pressures (P=0.63), whereas pressures rose at a slower pace (dP/dtmax, P=0.02). Conclusions In patients with PAH or CTEPH, ketone body infusion improves cardiac output and decreases pulmonary vascular resistance. Experimental rat studies support that ketone bodies relax pulmonary arteries. Long-term studies are warranted to assess the clinical role of hyperketonemia. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04615754.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Embolia Pulmonar , Animales , Ratas , Enfermedad Crónica , Estudios Cruzados , Hipertensión Pulmonar Primaria Familiar , Hemodinámica/fisiología , Cuerpos Cetónicos/farmacología , Arteria Pulmonar , Embolia Pulmonar/complicaciones , Ratas Sprague-Dawley , HumanosRESUMEN
INTRODUCTION: The palpation technique is generally used for radial artery catheterisation, but is associated with a high rate of failure and complications. Dynamic needle tip positioning (DNTP) is a new ultrasound-guided technique. We aimed to compare the traditional palpation technique with DNTP performed by four anaesthesiology residents. METHODS: The study was a randomised, controlled, patient-blinded, crossover study. Fourty patients underwent bilateral radial artery catheterisation using both techniques. The primary endpoint was the first attempt success rate. The secondary endpoints were: 1) number of skin perforations, 2) number of needle retractions, 3) needle manipulation time, 4) total time, 5) attempts lasting >180 seconds, 6) number of catheters used, 7) frequency of aborted attempts or crossovers, and 8) pain scores (VAS). RESULTS: The first attempt success rate was significantly higher in the DNTP group compared with the palpation group (36/40 vs. 28/40, p = 0.022).The palpation technique group required a higher number of skin perforations (44 vs. 60, p = 0.016), needle retractions (p = 0.001) and catheters (42 vs. 52, p = 0.011) compared with the DNTP group. Neither the total time required for arterial catheterisation, the needle manipulation time nor the VAS scores were significantly different between the groups (all p>0.407). Aborted attempts were only seen in the palpation group (7/40, p = 0.016). CONCLUSIONS: Ultrasound-guided arterial catheterisation using the DNTP technique is superior to the standard palpation technique. This study favours the ultrasound-guided DNTP technique as the first choice rather than merely being viewed as a rescue procedure.
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Anestesiología/educación , Cateterismo Periférico/métodos , Educación de Postgrado en Medicina/métodos , Internado y Residencia , Arteria Radial/diagnóstico por imagen , Ultrasonografía Intervencional , Cateterismo Periférico/efectos adversos , Cateterismo Periférico/instrumentación , Estudios Cruzados , Humanos , Agujas , Dolor/diagnóstico , Dolor/etiología , Dimensión del Dolor , Palpación , Punciones , Factores de TiempoRESUMEN
BACKGROUND: Apheresis treatments can be performed with peripheral venous catheters (PVC), although central venous catheters (CVC) are inserted when PVCs fail or patient with history of difficult vascular access prior to the apheresis. Ultrasound guidance for PVC has shown promising results in other settings. PURPOSE: To investigate if ultrasound guidance for PVC could be implemented among apheresis nurses. Second, how implementation of ultrasound guidance affected the number of CVCs used for apheresis per patient. METHOD: Apheresis nurses completed a systematic training program for ultrasound-guided vascular access. All independent catheterizations were registered during the implementation stage. The number of CVCs in the pre- and postimplementation stages of the ultrasound guidance was compared. RESULTS: Six nurses completed the training program within a median of 48 days (range 38-83 days). In 77 patients, 485 independent ultrasound-guided PVC placements were performed during the implementation stage. All apheresis treatments (485/485) were accomplished using PVCs without requiring CVC as rescue. During the preimplementation stage, 125 of 273 (45.8%) procedures required a CVC for completion of apheresis procedures; during the postimplementation stage only 30 of 227 (13.2%) procedures required a CVC (p < 0.001). In the postimplementation stage, no CVCs were placed as rescue caused by failed PVCs but were only placed for patients where the ultrasound machine was unavailable. It indicates an effective success rate of 100% for ultrasound-guided PVC use. CONCLUSION: This study showed that ultrasound guidance could be implemented among apheresis nurses as a routine tool eliminating the need of CVC as a rescue.
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Eliminación de Componentes Sanguíneos/métodos , Cateterismo Venoso Central/estadística & datos numéricos , Cateterismo Periférico/estadística & datos numéricos , Ultrasonografía Intervencional/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Educación en Enfermería , Humanos , Masculino , Persona de Mediana Edad , Ultrasonografía Intervencional/enfermería , Adulto JovenRESUMEN
PURPOSE: Vein punctures are performed daily to sample blood. Ultrasound (US) offers an alternative to the blind landmark technique for difficult vascular access. A challenge for this procedure is the presence of US gel in the puncture area. We present a technique for US-guided puncture from extremity veins not palpable or visible to the human eye, while keeping the puncture area dry and gel-free. METHODS: Ten healthy volunteers underwent two US-guided vein punctures from veins that were neither palpable nor visible. One was drawn from an antebrachial vein and another from a brachial vein. A sterile barrier drape was made from a commercially available dressing and a piece of transparent sterile plastic. The barrier drape consists of an adhesive part placed on the skin designed for sonography and a free transparent flap constituting the barrier between the unsterile sonographic site and the sterile gel-free puncture site. RESULTS: The success rate for vein puncture was 100% in both locations. A total of 22 skin punctures were performed (11 antebrachial and 11 brachial). Gain output was increased 7% (4-12%), and 8% (4-15%), respectively, to compensate for attenuation of the US signal due to the drape. Alignment of the centre of the transducer with the long-axis of the target vein during the procedure was reported as a challenge. CONCLUSIONS: US-guided blood sampling from a brachial and antebrachial vein was possible with a 100% success rate, while ensuring a dry and gel-free venipuncture area on one side and the transducer on the other side of a sterile barrier.