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BACKGROUND: This study focuses on biomarkers in infants after open heart surgery, and examines the association of high-sensitive troponin T (hs-cTnT), interleukin-6 (IL-6), and interleukin-8 (IL-8) with postoperative acute kidney injury (AKI), ventilatory support time and need of vasoactive drugs. METHODS: Secondary exploratory study from a double-blinded clinical randomized trial (Mile-1) on 70 infants undergoing open heart surgery with cardiopulmonary bypass (CPB). In this sub-study, the entire study population was examined without considering the study drugs. The biomarkers' peak concentration (highest concentration at 2 or 6 h post-CPB) were used for statistical analyses. RESULTS: Peak IL-8, hs-cTnT, and IL-6 occurred at 2 h post-CPB for 96%, 79%, and 63% of the patients, respectively. The odds ratio of developing AKI2-3 for IL-6 > 293 pg/mL was 23.4 (95% CI 5.3;104.0), for IL-8 > 100 pg/mL it was 11.5 (3.0;44.2), and for hs-cTnT >5597 pg/mL it was 6.1 (1.5; 24.5). In more than two third of the patients with the highest peak concentrations of IL-8, IL-6, and hs-cTnT, there was a need for ventilatory support for >24 h and use of vasoactive drugs at 24 h post-CPB, while in less than one third of the patients with the lowest peak concentrations of IL-8 and hs-cTnT such requirements were observed. CONCLUSIONS: The peak biomarker concentrations and CPB-time strongly predicted AKI2-3, with IL-6 and IL-8 emerging as strongest predictors. Furthermore, our findings suggest that measuring hs-cTnT and IL-8 just 2 h post-CPB-weaning may assist in identifying infants suitable for early extubation and highlight those at risk of prolonged ventilation.
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Lesión Renal Aguda , Biomarcadores , Procedimientos Quirúrgicos Cardíacos , Puente Cardiopulmonar , Interleucina-6 , Interleucina-8 , Complicaciones Posoperatorias , Troponina T , Humanos , Interleucina-8/sangre , Interleucina-6/sangre , Troponina T/sangre , Masculino , Biomarcadores/sangre , Femenino , Lactante , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/epidemiología , Método Doble Ciego , Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Puente Cardiopulmonar/efectos adversos , Recién NacidoRESUMEN
OBJECTIVES: We compared the effect of two inodilators, levosimendan and milrinone, on the plasma levels of myocardial injury biomarkers, that is, high-sensitivity troponin T and heart-type fatty acid binding protein, and on N-terminal prohormone of brain natriuretic peptide as a biomarker of ventricular function. We hypothesized that levosimendan could attenuate the degree of myocardial injury when compared with milrinone. DESIGN: A post hoc, nonprespecified exploratory secondary analysis of the Milrinone versus Levosimendan-1 trial (ClinicalTrials.gov Identifier: NCT02232399). SETTING: Two pediatric tertiary university hospitals. PATIENTS: Infants 1-12 months old, diagnosed with ventricular septal defect, complete atrioventricular septal defect, or Tetralogy of Fallot undergoing corrective surgery with cardiopulmonary bypass. INTERVENTIONS: Seventy patients received a loading dose of either levosimendan or milrinone at the start of cardiopulmonary bypass followed by an infusion of the respective drug, which continued for 26 hours. MEASUREMENTS AND MAIN RESULTS: Plasma levels of the three cardiac biomarkers were measured prior to the initiation of cardiopulmonary bypass and 2, 6, and 24 hours after weaning from cardiopulmonary bypass. In both groups, the levels of high-sensitivity troponin T and heart-type fatty acid binding protein were highest at 2 hours post cardiopulmonary bypass, whereas the highest level of N-terminal prohormone of brain natriuretic peptide occurred at 24 hours post cardiopulmonary bypass. There was no significant difference in the biomarkers' plasma levels between the study groups over time. Neither was there a significant difference in the postoperative peak plasma levels of the cardiac biomarkers. CONCLUSIONS: In this post hoc analysis of the MiLe-1 trial, there was no demonstrable difference in the postoperative cardiac biomarker profile of myocardial injury and ventricular function when comparing infants managed in the perioperative period with levosimendan versus milrinone.
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Procedimientos Quirúrgicos Cardíacos , Milrinona , Simendán , Biomarcadores , Puente Cardiopulmonar , Cardiotónicos/efectos adversos , Cardiotónicos/uso terapéutico , Humanos , Lactante , Milrinona/efectos adversos , Milrinona/uso terapéutico , Simendán/efectos adversos , Simendán/uso terapéuticoRESUMEN
AIMS: To evaluate the long-term use of secondary prevention medications [statins, ß-blockers, renin-angiotensin-aldosterone system (RAAS) inhibitors, and platelet inhibitors] after coronary artery bypass grafting (CABG) and the association between medication use and mortality. METHODS AND RESULTS: All patients who underwent isolated CABG in Sweden from 2006 to 2015 and survived at least 6 months after discharge were included (n = 28 812). Individual patient data from SWEDEHEART and other mandatory nationwide registries were merged. Multivariable Cox regression models using time-updated data on dispensed prescriptions were used to assess associations between medication use and long-term mortality. Statins were dispensed to 93.9% of the patients 6 months after discharge and to 77.3% 8 years later. Corresponding figures for ß-blockers were 91.0% and 76.4%, for RAAS inhibitors 72.9% and 65.9%, and for platelet inhibitors 93.0% and 79.8%. All medications were dispensed less often to patients ≥75 years. Treatment with statins [hazard ratio (HR) 0.56, 95% confidence interval (95% CI) 0.52-0.60], RAAS inhibitors (HR 0.78, 95% CI 0.73-0.84), and platelet inhibitors (HR 0.74, 95% CI 0.69-0.81) were individually associated with lower mortality risk after adjustment for age, gender, comorbidities, and use of other secondary preventive drugs (all P < 0.001). There was no association between ß-blockers and mortality risk (HR 0.97, 95% CI 0.90-1.06; P = 0.54). CONCLUSION: The use of secondary prevention medications after CABG was high early after surgery but decreased significantly over time. The results of this observational study, with inherent risk of selection bias, suggest that treatment with statins, RAAS inhibitors, and platelet inhibitors is essential after CABG whereas the routine use of ß-blockers may be questioned.
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Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria , Enfermedad de la Arteria Coronaria/prevención & control , Enfermedad de la Arteria Coronaria/cirugía , Humanos , Estudios Longitudinales , Sistema de Registros , Estudios Retrospectivos , Prevención Secundaria , Suecia/epidemiología , Resultado del TratamientoRESUMEN
OBJECTIVE: The objectives of the present study were to determine whether there was any association between the grade of heart failure, as expressed by preoperative levels of brain natriuretic peptide and Ross score, and the preoperative coagulation status in patients with non-restrictive ventricular shunts and determine whether there were any postoperative disturbances of the coagulation system in these patients, as measured by thromboelastometry and standard laboratory analyses of coagulation. DESIGN: Perioperative coagulation was analysed with laboratory-based coagulation tests and thromboelastometry before, 8 hours after, and 18 hours after cardiac surgery. In addition, brain natriuretic peptide was analysed before and 18 hours after surgery. PATIENTS: 40 children less than 12 months old with non-restrictive congenital ventricular or atrio-ventricular shunts scheduled for elective repair of their heart defects. RESULTS: All coagulation parameters measured were within normal ranges preoperatively. There was a significant correlation between brain natriuretic peptide and plasma fibrinogen concentration preoperatively. There was no statistically significant correlation between brain natriuretic peptide and INTEM-MCF, FIBTEM-MCF, plasma fibrinogen, activated partial thromboplastin time, prothrombin time, or platelet count at any other time point, either preoperatively or postoperatively. Postoperatively, fibrinogen plasma concentration and FIBTEM-MCF decreased significantly at 8 hours, followed by a large increase at 18 hours to higher levels than preoperatively. CONCLUSIONS: There was no evidence of children with non-restrictive shunts having coagulation abnormalities before cardiac surgery. Brain natriuretic peptide levels or Ross score did not correlate with coagulation parameters in any clinically significant way.
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Procedimientos Quirúrgicos Cardíacos , Insuficiencia Cardíaca , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea , Niño , Humanos , Lactante , TromboelastografíaRESUMEN
OBJECTIVE: The present study aimed to determine the differential effects of intraoperative administration of milrinone versus levosimendan on myocardial function after pediatric cardiac surgery. Transthoracic echocardiography was used for myocardial function evaluation using biventricular longitudinal strain with 2-dimensional speckle tracking echocardiography in addition to conventional echocardiographic variables. DESIGN: A secondary analysis of a randomized, prospective, double-blinded clinical drug trial. SETTING: Two pediatric tertiary university hospitals. PARTICIPANTS: Infants between 1 and 12 months old diagnosed with ventricular septal defect, complete atrioventricular septal defect, or tetralogy of Fallot who were scheduled for corrective surgery with cardiopulmonary bypass. INTERVENTIONS: The patients were randomly assigned to receive an infusion of milrinone or levosimendan at the start of cardiopulmonary bypass and for 26 consecutive hours. MEASUREMENTS AND MAIN RESULTS: Biventricular longitudinal strain and conventional echocardiographic variables were measured preoperatively, on the first postoperative morning, and before hospital discharge. The association between perioperative parameters and postoperative myocardial function also was investigated. Images were analyzed for left ventricular (nâ¯=â¯67) and right ventricular (nâ¯=â¯44) function. The day after surgery, left ventricular longitudinal strain deteriorated in both the milrinone and levosimendan groups (33% and 39%, respectively). The difference was not significant. The corresponding deterioration in right ventricular longitudinal strain was 42% and 50% (nonsignificant difference). For both groups, biventricular longitudinal strain approached preoperative values at hospital discharge. Preoperative N-terminal pro-brain natriuretic peptide could predict the left ventricular strain on postoperative day 1 (pâ¯=â¯0.014). CONCLUSIONS: Levosimendan was comparable with milrinone for left and right ventricular inotropic support in pediatric cardiac surgery.
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Procedimientos Quirúrgicos Cardíacos , Piridazinas , Cardiotónicos/uso terapéutico , Niño , Humanos , Hidrazonas , Lactante , Milrinona , Estudios Prospectivos , SimendánRESUMEN
OBJECTIVES: It has been shown that, in contrast to other inotropic agents, levosimendan improves glomerular filtration rate after adult cardiac surgery. The aim of this study was to investigate the efficacy of levosimendan, compared with milrinone, in preventing acute kidney dysfunction in infants after open-heart surgery with cardiopulmonary bypass. DESIGN: Two-center, double-blinded, prospective, randomized clinical trial. SETTING: The study was performed in two tertiary pediatric centers, one in Sweden (Gothenburg) and one in Finland (Helsinki). PATIENTS: Infants between 1 and 12 months old, diagnosed with Tetralogy of Fallot, complete atrioventricular septal defect or nonrestrictive ventricular septal defect, undergoing total corrective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Seventy-two infants were randomized to receive a perioperative infusion of levosimendan (0.1 µg/kg/min) or milrinone (0.4 µg/kg/min). The infusion was initiated at the start of cardiopulmonary bypass and continued for 26 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was the absolute value of serum creatinine data on postoperative day 1. Secondary outcomes included the following: 1) acute kidney injury according to the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes; 2) acute kidney injury with serum creatinine corrected for fluid balance; 3) plasma neutrophil gelatinase-associated lipocalin; 4) cystatin C; 5) urea; 6) lactate; 7) hemodynamic variables; 8) use of diuretics in the PICU; 9) need of dialysis; 10) length of ventilator therapy; and 11) length of PICU stays. There was no significant difference in postoperative serum creatinine between the treatment groups over time (p = 0.65). The occurrence rate of acute kidney injury within 48 hours was 46.9% in the levosimendan group and 39.5% in the milrinone group (p = 0.70). There were no significant differences in other secondary outcome variables between the groups. CONCLUSIONS: Levosimendan compared with milrinone did not reduce the occurrence rate of acute kidney injury in infants after total corrective heart surgery for atrioventricular septal defect, ventricular septal defect, or Tetralogy of Fallot.
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Lesión Renal Aguda/prevención & control , Puente Cardiopulmonar/métodos , Cardiotónicos/administración & dosificación , Cardiopatías Congénitas/cirugía , Milrinona/administración & dosificación , Simendán/administración & dosificación , Lesión Renal Aguda/epidemiología , Procedimientos Quirúrgicos Cardíacos/métodos , Creatinina/sangre , Método Doble Ciego , Femenino , Finlandia , Cardiopatías Congénitas/tratamiento farmacológico , Defectos de los Tabiques Cardíacos/prevención & control , Defectos del Tabique Interventricular/prevención & control , Humanos , Lactante , Masculino , Estudios Prospectivos , Suecia , Tetralogía de Fallot/prevención & controlRESUMEN
OBJECTIVE: To report outcome and intensive care strategy in a 7-year-old girl with accidental profound hypothermia and drowning. DATA SOURCES AND EXTRACTION: Patient records and interviews with search-and-rescue personnel. STUDY SELECTION: Case report. DATA SYNTHESIS: The girl was rescued after an estimated submersion time of at least 83 minutes in icy sea water. She presented with cardiac arrest, ice in her upper airways, a first-documented nasopharyngeal temperature of 13.8°C, and a serum potassium of 11.3 mmol/L. The patient was slowly rewarmed with extracorporeal membrane oxygenation and made an exceptional recovery after intensive care and a long rehabilitation time. CONCLUSION: Excellent outcome is possible in children with body temperature and serum potassium reaching the far limits of previously reported human survival and prolonged submersion time.
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Reanimación Cardiopulmonar/métodos , Oxigenación por Membrana Extracorpórea/métodos , Hipotermia/terapia , Ahogamiento Inminente/terapia , Niño , Terapia Combinada , Servicio de Urgencia en Hospital , Femenino , Estudios de Seguimiento , Humanos , Hipotermia/etiología , Recalentamiento/métodos , Medición de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Although rotational thromboelastometry (ROTEM) is increasingly used to guide haemostatic therapy in a bleeding patient, there is a paucity of data guiding its use in the paediatric population. OBJECTIVE: The objective of this study is to develop an algorithm on the basis of ROTEM values obtained in our paediatric cardiac population to guide the management of the bleeding child. DESIGN: A retrospective analysis. SETTING: Department of Anaesthesiology, Queen Fabiola Children's University Hospital. Data were collected between September 2010 and January 2012. PATIENTS: All children who underwent elective cardiac surgery requiring cardiopulmonary bypass (CPB) were reviewed. INTERVENTION: None. MAIN OUTCOME MEASURES: Significant postoperative bleeding was defined as blood loss more than 10% of the child's estimated blood volume within the first six postoperative hours, dividing our population according to high blood loss (HBL) or low blood loss (LBL). Factors independently associated with postoperative bleeding determined the bleeding probability. Receiving operating characteristics (ROC) curves were constructed with the aim of determining relevant ROTEM parameters (including clot amplitude 10 min after administration of protamine [A10]) to be used in our algorithm. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were determined for the developed algorithm. RESULTS: One-hundred and fifty children were included in our study. Univariate and multivariate logistic regression analysis revealed that preoperative weight (kg), presence of a cyanotic disease (yes/no) and wound closure duration (min) were independent predictors of postoperative bleeding. Analysis of our ROTEM parameters revealed that clotting time (CT)â≥â111âs, A10 ≤â38âmm measured on the EXTEM and A10â≤â3âmm obtained on the FIBTEM tests were the three relevant parameters to guide haemostatic therapy. If the ROTEM-based algorithm was applied according to the bleeding risk (nâ=â65), 27 out of 29 of the HBL and 24 out of 36 of the LBL group would have been treated. CONCLUSION: This study describes an algorithm starting with the detection of abnormal bleeding in which ROTEM could be used to guide haemostatic therapy in bleeding children after CPB. Further studies are needed to test the efficacy of this specific algorithm-based approach.
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Algoritmos , Procedimientos Quirúrgicos Cardíacos/normas , Hemostáticos/administración & dosificación , Hemorragia Posoperatoria/prevención & control , Guías de Práctica Clínica como Asunto/normas , Tromboelastografía/normas , Adolescente , Adulto , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Puente Cardiopulmonar/efectos adversos , Puente Cardiopulmonar/normas , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hemorragia Posoperatoria/etiología , Estudios Retrospectivos , Tromboelastografía/métodos , Adulto JovenRESUMEN
OBJECTIVE: Earlier detection of coagulopathy in pediatric cardiac surgery patients. AIM: To determine whether thromboelastometry (TEM) analysis before weaning from cardiopulmonary bypass (CPB) and hemoconcentration is predictive of post-CPB results and whether analysis of clot firmness already after 10 min yields reliable results. BACKGROUND: Cardiac surgery with CPB induces a coagulopathy that may contribute to postoperative complications. Earlier detection increases the possibility of initiating countermeasures. METHODS/MATERIAL: Fifty-six pediatric cardiac surgery patients were included in a prospective observational study. HEPTEM and FIBTEM clotting time (CT), clot formation time (CFT), and clot firmness after 10 min (A10) and at maximum (MCF) were analyzed during CPB and after CPB and ultrafiltration with modified rotational thromboelastometry (ROTEM). The analyses were compared, and correlations and differences were calculated. RESULTS: Hemoconcentration with modified ultrafiltration increased hematocrit from 28 ± 3 to 37 ± 4% (P < 0.001). Correlation coefficients of the TEM variables during and after CPB ranged from 0.61 to 0.82 (all P < 0.001). HEPTEM-CT and HEPTEM-MCF differed significantly but the differences were marginal. Both HEPTEM and FIBTEM A10 measurements during CPB were significantly less than MCF (P < 0.001 for both), but the correlations were highly significant (HEPTEM: r = 0.95, P < 0.001; FIBTEM: r = 0.96, P < 0.001), and the differences were predictable, with narrow confidence intervals (HEPTEM: -8.2 mm (-8.9 to -7.5); FIBTEM: -0.5 mm (-0.7 to -0.3). CONCLUSION: The results suggest that intraoperative TEM analyses can be accelerated by analyzing HEPTEM/FIBTEM on CPB before hemoconcentration and by analyzing clot firmness already after 10 min.
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Trastornos de la Coagulación Sanguínea/diagnóstico , Procedimientos Quirúrgicos Cardíacos/métodos , Tromboelastografía/métodos , Anestesia General , Anticoagulantes/antagonistas & inhibidores , Anticoagulantes/uso terapéutico , Trastornos de la Coagulación Sanguínea/sangre , Puente Cardiopulmonar , Niño , Preescolar , Diagnóstico Precoz , Femenino , Hematócrito , Hemoglobinas/metabolismo , Humanos , Lactante , Recién Nacido , Complicaciones Intraoperatorias/diagnóstico , Complicaciones Intraoperatorias/terapia , Masculino , Monitoreo Intraoperatorio , Recuento de Plaquetas , Estudios Prospectivos , UltrafiltraciónRESUMEN
BACKGROUND: Shunt thrombosis after implantation of systemic-to-pulmonary shunts in paediatric patients is common. Acetyl salicylic acid is used for anti-thrombotic treatment; however, the effect is rarely monitored, although it is known that the response varies. The aim was to determine the effects of acetyl salicylic acid medication on platelet aggregation in children with systemic-to-pulmonary shunts. METHODS: A total of 14 children median age 12 days; ranging from 3 to 100 days were included in a prospective observational longitudinal study. All children were treated with oral acetyl salicylic acid (35 milligrams per kilogram once daily) after shunt implantation. Acetyl salicylic acid-dependent platelet aggregation in whole blood was analysed with impedance aggregometry (Multiplate®) after addition of arachidonic acid. Analyses were carried out before the primary operation, before and 5 and 24 hours after the first acetyl salicylic acid dose, and after 36 months of treatment. The therapeutic range for acetyl salicylic acid was defined as a test result less than 60 units. RESULTS: Acetyl salicylic acid reduced the arachidonic acid-induced platelet aggregation in all but one patient. Of the patients, 93% were in the therapeutic range 5 hours after acetyl salicylic acid intake, 86% were in the range after 24 hours, and 64% after 36 months. CONCLUSIONS: Acetyl salicylic acid reduces platelet aggregation after shunt implantation in paediatric patients, but a considerable percentage of the children are outside the therapeutic range. Monitoring of platelet aggregation has the potential to improve anti-platelet treatment after shunt implantation by identifying children with impaired acetyl salicylic acid response.
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Aspirina/farmacología , Cardiopatías Congénitas/cirugía , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Trombosis/prevención & control , Procedimiento de Blalock-Taussing , Ventrículo Derecho con Doble Salida/complicaciones , Ventrículo Derecho con Doble Salida/cirugía , Impedancia Eléctrica , Femenino , Cardiopatías Congénitas/complicaciones , Defectos de los Tabiques Cardíacos/complicaciones , Defectos de los Tabiques Cardíacos/cirugía , Humanos , Síndrome del Corazón Izquierdo Hipoplásico/complicaciones , Síndrome del Corazón Izquierdo Hipoplásico/cirugía , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Procedimientos de Norwood , Pruebas de Función Plaquetaria , Estudios Prospectivos , Falla de Prótesis , Atresia Pulmonar/complicaciones , Atresia Pulmonar/cirugía , Trombosis/complicacionesRESUMEN
BACKGROUND: The majority of pediatric cardiac surgery patients receive blood transfusions. We hypothesized that the routine use of intraoperative thromboelastometry to guide transfusion decisions would reduce the overall proportion of patients receiving transfusions in pediatric cardiac surgery. METHODS: One hundred pediatric cardiac surgery patients were included in the study. Fifty patients (study group) were prospectively included and compared with 50 procedure- and age-matched control patients (control group). In the study group, thromboelastometry, performed during cardiopulmonary bypass, guided intraoperative transfusions. Intraoperative and postoperative transfusions of packed red blood cells, fresh frozen plasma, platelets, and fibrinogen concentrates, and postoperative blood loss and hemoglobin levels were compared between the 2 groups. RESULTS: The proportion of patients receiving any intraoperative or postoperative transfusion of packed red blood cells, fresh frozen plasma, platelets, or fibrinogen concentrates was significantly lower in the study group than in the control group (32 of 50 [64%] vs 46 of 50 [92%], respectively; P < 0.001). Significantly fewer patients in the study group received transfusions of packed red blood cells (58% vs 78%, P = 0.032) and plasma (14% vs 78%, P < 0.001), whereas more patients in the study group received transfusions of platelets (38% vs 12%, P = 0.002) and fibrinogen concentrates (16% vs 2%, P = 0.015). Neither postoperative blood loss nor postoperative hemoglobin levels differed significantly between the study group and the control group. CONCLUSIONS: The results suggest that routine use of intraoperative thromboelastometry in pediatric cardiac surgery to guide transfusions is associated with a reduced proportion of patients receiving transfusions and an altered transfusion pattern.
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Transfusión Sanguínea/estadística & datos numéricos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Complicaciones Intraoperatorias/epidemiología , Complicaciones Intraoperatorias/prevención & control , Tromboelastografía/métodos , Adolescente , Transfusión Sanguínea/tendencias , Procedimientos Quirúrgicos Cardíacos/tendencias , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Prevalencia , Estudios ProspectivosRESUMEN
Importance: Guidelines recommend dual antiplatelet therapy after coronary artery bypass grafting (CABG) for patients with acute coronary syndrome (ACS). However, the evidence for these recommendations is weak. Objective: To compare midterm outcomes after CABG in patients with ACS treated postoperatively with acetylsalicylic acid (ASA) and ticagrelor or with ASA monotherapy. Design, Setting, and Participants: This cohort study used merged data from several national registries of Swedish patients who were diagnosed with ACS and subsequently underwent CABG. All included patients underwent isolated CABG in Sweden between 2012 and 2017 with an ACS diagnosis less than 6 weeks before the procedure, survived 14 days after discharge from hospital, and were treated postoperatively with ASA plus ticagrelor or ASA monotherapy. A multivariable Cox regression model was used for the main analysis, and propensity score-matched models were performed as sensitivity analysis. Data were analyzed between May and September 2020. Exposures: Postoperative antiplatelet treatment, defined as filled prescriptions, with either ASA and ticagrelor or ASA only. Main Outcomes and Measures: Major adverse cardiovascular events (MACE), defined as all-cause mortality, myocardial infarction, and stroke, and major bleeding, at 12 months and at the end of follow-up. Results: A total of 6558 patients (5281 [80.5%] men; mean [SD] age at surgery, 67.6 [9.3] years) were included; 1813 (27.6%) were treated with ASA plus ticagrelor and 4745 (72.4%) were treated with ASA monotherapy. Crude MACE rate was 3.0 per 100 person years (95% CI, 2.5-3.6 per 100 person years) in the ASA plus ticagrelor group and 3.8 per 100 person years (95% CI, 3.5-4.1 per 100 person years) in the ASA group. After adjustment, there was no significant difference in MACE risk between ASA plus ticagrelor vs ASA only, neither during the first 12 months (adjusted hazard ratio [aHR], 0.84; 95% CI, 0.58-1.21; P = .34) or during total follow-up (aHR, 0.89; 95% CI, 0.71-1.11; P = .29). The use of ASA plus ticagrelor was associated with a significantly increased risk for major bleeding during the first 12 months (aHR, 1.90; 95% CI, 1.16-3.13; P = .011). Sensitivity analyses confirmed the results. Conclusions and Relevance: In patients with ACS who survived 2 weeks after CABG, no significant difference in the risk of death or ischemic events could be demonstrated between ASA plus ticagrelor and patients treated with ASA only, while the risk for major bleeding was higher in patients treated with ASA plus ticagrelor. Sufficiently powered prospective randomized trials comparing different antiplatelet therapy strategies after CABG are warranted.
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Síndrome Coronario Agudo/cirugía , Aspirina/uso terapéutico , Puente de Arteria Coronaria/efectos adversos , Terapia Antiplaquetaria Doble/métodos , Hemorragia Posoperatoria/tratamiento farmacológico , Ticagrelor/uso terapéutico , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Prospectivos , SueciaRESUMEN
OBJECTIVES: Preoperative testing of platelet function predicts bleeding risk in cardiac surgery patients treated with dual antiplatelet therapy, but the value of postoperative platelet function testing, reflecting both preoperative antiplatelet therapy and perioperative changes in platelet function, has not been evaluated. METHODS: Seventy-four patients with acute coronary syndrome treated with acetylsalicylic acid and ticagrelor within 5 days before cardiac surgery were included in a prospective observational study. Platelet aggregation induced by adenosine diphosphate, arachidonic acid and thrombin receptor-activating peptide was assessed with multiple electrode impedance aggregometry immediately before surgery and 2 h after weaning off cardiopulmonary bypass. Receiver operating characteristic curves were used to determine any association between platelet aggregation and severe bleeding according to the universal definition of perioperative bleeding in adult cardiac surgery. RESULTS: Severe bleeding occurred in 25 of 74 patients (34%). Preoperative and postoperative adenosine diphosphate-induced platelet aggregations were associated with bleeding, with comparable areas under the receiver operating characteristic curve [0.77 (95% confidence interval 0.65-0.89) vs 0.75 (0.62-0.87)]. Postoperative arachidonic acid- and thrombin receptor-activating peptide-induced aggregation had markedly smaller areas under the curve. There were significant correlations between preoperative and postoperative platelet aggregation induced by adenosine diphosphate (r2 = 0.77, P < 0.001), arachidonic acid (r2 = 0.24, P < 0.001) and thrombin receptor-activating peptide (r2 = 0.21, P < 0.001) but with large interindividual variations. CONCLUSIONS: Poor postoperative platelet function was associated with severe bleeding, with accuracy comparable to that of preoperative platelet function. There was a correlation between preoperative and postoperative platelet function, but the predictability in an individual patient was limited.
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Síndrome Coronario Agudo/cirugía , Plaquetas/fisiología , Revascularización Miocárdica/efectos adversos , Hemorragia Posoperatoria/inducido químicamente , Ticagrelor/efectos adversos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/efectos adversos , Pruebas de Función Plaquetaria , Hemorragia Posoperatoria/sangre , Periodo Posoperatorio , Estudios ProspectivosRESUMEN
INTRODUCTION: Ticagrelor, a novel platelet inhibitor acting on the ADP-dependent P2Y12 receptor, is currently approved for treating adults with acute coronary syndrome. The effect of ticagrelor in children has not been explored. As a first step, we here evaluate if the in vitro anti-platelet potency of ticagrelor in blood samples from children of different age is different as compared with in blood samples from adults. MATERIALS AND METHODS: Blood samples from 36 healthy children grouped by age (0-2 months, n=6; 2-6 months, n=6; 6months-2years, n=6; 2-6 years, n=10; 6-12 years, n=8) and 13 adults were collected for in vitro analysis using vasodilator stimulated phosphoprotein phosphorylation (VASP) assay in whole blood and ADP-induced light transmission aggregometry (LTA) in platelet rich plasma. Ticagrelor (0.01 - 10µmol/L) was added in vitro and its potency was assessed by calculating the concentration that provided 50% inhibition of the maximum response (IC50). RESULTS: The in vitro potency of ticagrelor in blood from adults and in blood from children of any age group were comparable, both when analyzed with LTA and with VASP. CONCLUSIONS: These in vitro results are consistent with the hypothesis that ticagrelor would achieve a comparable anti-platelet effect in children of different ages as in adults at equal plasma exposure.