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1.
Eur J Anaesthesiol ; 41(7): 480-489, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38323332

RESUMO

BACKGROUND: Induction of general anaesthesia has many potential triggers for peri-operative myocardial ischaemia including the acute disturbance of blood gases that frequently follows alterations in breathing and ventilation patterns. Free-breathing oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) imaging may provide the opportunity to continuously quantify the impact of such triggers on myocardial oxygenation. OBJECTIVE: To investigate the impact of breathing patterns that simulate induction of general anaesthesia on myocardial oxygenation in awake healthy adults using continuous OS-CMR imaging. DESIGN: Prospective observational study. SETTING: Single-centre university hospital. Recruitment from August 2020 to January 2022. PARTICIPANTS: Thirty-two healthy volunteers younger than 45 years old were recruited. Data were analysed from n  = 29 (69% male individuals). INTERVENTION: Participants performed a simulated induction breathing manoeuvre consisting of 2.5 min paced breathing with a respiration rate of 14 breaths per minute, followed by 5 deep breaths, then apnoea for up to 60s inside a magnetic resonance imaging scanner (MRI). Cardiac images were acquired with the traditional OS-CMR sequence (OS bh-cine ), which requires apnoea for acquisition and with two free-breathing OS-CMR sequences: a high-resolution single-shot sequence (OS fb-ss ) and a real-time cine sequence (OS fb-rtcine ). MAIN OUTCOME MEASURES: Myocardial oxygenation response at the end of the paced breathing period and at the 30 s timepoint during the subsequent apnoea, reflecting the time of successful intubation in a clinical setting. RESULTS: The paced breathing followed by five deep breaths significantly reduced myocardial oxygenation, which was observed with all three techniques (OS bh-cine -6.0 ±â€Š2.6%, OS fb-ss -12.0 ±â€Š5.9%, OS fb-rtcine -5.4 ±â€Š7.0%, all P  < 0.05). The subsequent vasodilating stimulus of apnoea then significantly increased myocardial oxygenation (OS bh-cine 6.8 ±â€Š3.1%, OS fb-ss 8.4 ±â€Š5.6%, OS fb-rtcine 15.7 ±â€Š10.0%, all P  < 0.01). The free-breathing sequences were reproducible and were not inferior to the original sequence for any stage. CONCLUSION: Breathing manoeuvres simulating induction of general anaesthesia cause dynamic alterations of myocardial oxygenation in young volunteers, which can be quantified continuously with free-breathing OS-CMR. Introducing these new imaging techniques into peri-operative studies may throw new light into the mechanisms of peri-operative perturbations of myocardial tissue oxygenation and ischaemia. VISUAL ABSTRACT: http://links.lww.com/EJA/A922.


Assuntos
Imageamento por Ressonância Magnética , Humanos , Masculino , Adulto , Estudos Prospectivos , Feminino , Imageamento por Ressonância Magnética/métodos , Estudos de Coortes , Respiração , Miocárdio/metabolismo , Anestesia Geral/métodos , Voluntários Saudáveis , Oxigênio/sangue , Oxigênio/metabolismo , Adulto Jovem , Imagem Cinética por Ressonância Magnética/métodos
2.
Eur Radiol ; 33(10): 7226-7237, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37145149

RESUMO

OBJECTIVES: Atrial function can be assessed using advancing cardiovascular magnetic resonance (CMR) post-processing methods: atrial feature tracking (FT) strain analysis or a long-axis shortening (LAS) technique. This study aimed to first compare the two FT and LAS techniques in healthy individuals and cardiovascular patients and then investigated how left (LA) and right atrial (RA) measurements are related to the severity of diastolic dysfunction or atrial fibrillation. METHODS: Sixty healthy controls and 90 cardiovascular disease patients with coronary artery disease, heart failure, or atrial fibrillation, underwent CMR. LA and RA were analyzed for standard volumetry as well as for myocardial deformation using FT and LAS for the different functional phases (reservoir, conduit, booster). Additionally, ventricular shortening and valve excursion measurements were assessed with the LAS module. RESULTS: The measurements for each of the LA and RA phases were correlated (p < 0.05) between the two approaches, with the highest correlation coefficients occurring in the reservoir phase (LA: r = 0.83, p < 0.01, RA: r = 0.66, p < 0.01). Both methods demonstrated reduced LA (FT: 26 ± 13% vs 48 ± 12%, LAS: 25 ± 11% vs 42 ± 8%, p < 0.01) and RA reservoir function (FT: 28 ± 15% vs 42 ± 15%, LAS: 27 ± 12% vs 42 ± 10%, p < 0.01) in patients compared to controls. Atrial LAS and FT decreased with diastolic dysfunction and atrial fibrillation. This mirrored ventricular dysfunction measurements. CONCLUSION: Similar results were generated for bi-atrial function measurements between two CMR post-processing approaches of FT and LAS. Moreover, these methods allowed for the assessment of incremental deterioration of LA and RA function with increasing left ventricular diastolic dysfunction and atrial fibrillation. A CMR-based analysis of bi-atrial strain or shortening discriminates patients with early-stage diastolic dysfunction prior to the presence of compromised atrial and ventricular ejection fractions that occur with late-stage diastolic dysfunction and atrial fibrillation. KEY POINTS: • Assessing right and left atrial function with CMR feature tracking or long-axis shortening techniques yields similar measurements and could potentially be used interchangeably based on the software capabilities of individual sites. • Atrial deformation and/or long-axis shortening allow for early detection of subtle atrial myopathy in diastolic dysfunction, even when atrial enlargement is not yet apparent. • Using a CMR-based analysis to understand the individual atrial-ventricular interaction in addition to tissue characteristics allows for a comprehensive interrogation of all four heart chambers. In patients, this could add clinically meaningful information and potentially allow for optimal therapies to be chosen to better target the dysfunction.


Assuntos
Fibrilação Atrial , Cardiomiopatias , Disfunção Ventricular Esquerda , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Átrios do Coração/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função do Átrio Esquerdo
3.
J Card Surg ; 37(12): 5608-5612, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36378941

RESUMO

Red blood cell salvage plays an important role in reducing the use of allogeneic blood transfusion during cardiac surgery. While there is consensus as to the benefit of employing cell salvage systems, there are no clear recommendations on the anticoagulant used for salvaged blood. In eight patients undergoing elective cardiac surgery at our university hospital's cardiovascular center, the authors describe hemodynamic effects of salvaged autologous blood transfusion when either unfractionated heparin or acid citrate dextrose formula A was used as the anticoagulant. Mean arterial pressure, heart rate, central venous pressure and acid-base status of the autologous red blood cell concentrate were compared between patients receiving autologous blood anticoagulated with acid citrate dextrose formula A versus unfractionated heparin. A clinically relevant decrease in mean arterial pressure (median change, - 19 mmHg [min -29; max -1] and marked acidosis [group median <6.30 [<6.30; 6.49] was observed in group acid citrate dextrose formula A. Acid citrate dextrose formula A anticoagulant for autologous red blood cell salvage has the potential to cause major adverse hemodynamic events during free-flowing re-transfusion of autologous red blood cell concentrate. Acute ionized hypocalcemia and acidemia may ensue from residual citrate in the supernatant of red blood cell concentrate reconstituted in unbuffered saline.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Heparina , Humanos , Heparina/efeitos adversos , Anticoagulantes/efeitos adversos , Eritrócitos
4.
Acta Anaesthesiol Scand ; 65(5): 633-638, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33529359

RESUMO

BACKGROUND: Extracorporeal cardiopulmonary resuscitation has become a recommended treatment option for patients with severe hypothermia with cardiac arrest. Minimal invasive extracorporeal circulation (MiECC) may offer advantages over the current standard extracorporeal membrane oxygenation (ECMO). METHODS: Retrospective cohort analysis of hospital database for patients with accidental hypothermia and extracorporeal rewarming with MiECC admitted between 2010 and 2019. RESULTS: Overall, six of 17 patients survived to hospital discharge. Eleven patients suffered accidental hypothermia in an alpine and six in an urban setting. Sixteen patients arrived at the hospital under ongoing cardiopulmonary resuscitation (CPR). CPR time was 90 minutes (0-150). Four patients survived from an alpine setting and two from an urban setting with CPR duration of 90 minutes (0-150) and 85 minutes (25-100), respectively. Asphyctic patients tended to have lower survival (one of seven patients). Two patients of six with major trauma survived. CONCLUSION: MiECC for extracorporeal rewarming from severe accidental hypothermia is a feasible alternative to ECMO, with comparable survival rates.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca , Hipotermia , Circulação Extracorpórea , Parada Cardíaca/terapia , Humanos , Hipotermia/terapia , Estudos Retrospectivos , Reaquecimento
5.
Crit Care ; 23(1): 159, 2019 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060591

RESUMO

BACKGROUND: Recent evidence suggests that acetate-buffered infusions result in better hemodynamic stabilization than 0.9% saline in patients undergoing major surgery. The choice of buffer in balanced crystalloid solutions may modify their hemodynamic effects. We therefore compared the inopressor requirements of Ringer's acetate and lactate for perioperative fluid management in patients undergoing cardiac surgery. METHODS: Using a randomized controlled double-blind design, we compared Ringer's acetate (RA) to Ringer's lactate (RL) with respect to the average rate of inopressor administered until postoperative hemodynamic stabilization was achieved. Secondary outcomes were the cumulative dose of inopressors, the duration of inopressor administration, the total fluid volume administered, and the changes in acid-base homeostasis. Patients undergoing elective valvular cardiac surgery were included. Patients with severe cardiac, renal, or liver disease were excluded from the study. RESULTS: Seventy-five patients were randomly allocated to the RA arm, 73 to the RL. The hemodynamic profiles were comparable between the groups. The groups did not differ with respect to the average rate of inopressors (RA 2.1 mcg/kg/h, IQR 0.5-8.1 vs. RL 1.7 mcg/kg/h, IQR 0.7-8.2, p = 0.989). Cumulative doses of inopressors and time on individual and combined inopressors did not differ between the groups. No differences were found in acid-base parameters and their evolution over time. CONCLUSION: In this study, hemodynamic profiles of patients receiving Ringer's lactate and Ringer's acetate were comparable, and the evolution of acid-base parameters was similar. These study findings should be evaluated in larger, multi-center studies. TRIAL REGISTRATION: Clinicaltrials.gov NCT02895659 . Registered 16 September 2016.


Assuntos
Hidratação/normas , Hemodinâmica/efeitos dos fármacos , Soluções Isotônicas/farmacologia , Lactato de Ringer/farmacologia , Idoso , Gasometria , Soluções Tampão , Procedimentos Cirúrgicos Cardíacos/métodos , Procedimentos Cirúrgicos Cardíacos/normas , Método Duplo-Cego , Feminino , Hidratação/métodos , Humanos , Soluções Isotônicas/efeitos adversos , Soluções Isotônicas/uso terapêutico , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Monitorização Fisiológica/estatística & dados numéricos , Lactato de Ringer/efeitos adversos , Lactato de Ringer/uso terapêutico , Fatores de Tempo
6.
J Cardiovasc Magn Reson ; 20(1): 31, 2018 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-29730991

RESUMO

BACKGROUND: Hyperventilation with a subsequent breath-hold has been successfully used as a non-pharmacological vasoactive stimulus to induce changes in myocardial oxygenation. The purpose of this pilot study was to assess if this maneuver is feasible in patients with multi-vessel coronary artery disease (CAD), and if it is effective at detecting coronary artery stenosis > 50% determined by quantitative coronary angiography (QCA). METHODS: Twenty-six patients with coronary artery stenosis (QCA > 50% diameter stenosis) underwent a contrast-free cardiovascular magnetic resonance (CMR) exam in the time interval between their primary coronary angiography and a subsequent percutaneous coronary intervention (PCI, n = 24) or coronary artery bypass (CABG, n = 2) revascularization procedure. The CMR exam involved standard function imaging, myocardial strain analysis, T2 mapping, native T1 mapping and oxygenation-sensitive CMR (OS-CMR) imaging. During OS-CMR, participants performed a paced hyperventilation for 60s followed by a breath-hold to induce a vasoactive stimulus. Ten healthy subjects underwent the CMR protocol as the control group. RESULTS: All CAD patients completed the breathing maneuvers with an average breath-hold duration of 48 ± 23 s following hyperventilation and without any complications or adverse effects. In comparison to healthy subjects, CAD patients had a significantly attenuated global myocardial oxygenation response to both hyperventilation (- 9.6 ± 6.8% vs. -3.1 ± 6.5%, p = 0.012) and apnea (11.3 ± 6.1% vs. 2.1 ± 4.4%, p < 0.001). The breath-hold maneuver unmasked regional oxygenation differences in territories subtended by a stenotic coronary artery in comparison to remote territory within the same patient (0.5 ± 3.8 vs. 3.8 ± 5.3%, p = 0.011). CONCLUSION: Breathing maneuvers in conjunction with OS-CMR are clinically feasible in CAD patients. Furthermore, OS-CMR demonstrates myocardial oxygenation abnormalities in regional myocardium related to CAD without the use of pharmacologic vasodilators or contrast agents. A larger trial appears warranted for a better understanding of its diagnostic utility. TRIAL REGISTRATION: Clinical Trials Identifier: NCT02233634 , registered 8 September 2014.


Assuntos
Suspensão da Respiração , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Hemoglobinas/metabolismo , Hiperventilação/fisiopatologia , Imagem Cinética por Ressonância Magnética , Miocárdio/metabolismo , Oxigênio/metabolismo , Taxa Respiratória , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Estenose Coronária/sangue , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Vasodilatação
8.
Artif Organs ; 42(10): 1001-1009, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29726003

RESUMO

Cerebral oximetry using near-infrared spectroscopy (NIRS) allows for continuous monitoring of cerebral perfusion and immediate treatment of hemodynamic perturbations. In configurations used in current clinical practice, NIRS optodes are placed on the patient`s forehead and cerebral oxygen saturation (ScO2 ) is determined in bilateral frontal cortical samples. However, focal cerebral ischemic lesions outside of the NIRS field of view may remain undetected. The objective of this observational case-series study was to investigate ScO2 measurements in patients with acute iatrogenic stroke not located in the frontal cortical region. Adult patients undergoing cardiac surgery with cardiopulmonary bypass or interventional cardiology procedures and suffering stroke in the early postoperative period were identified from the Bernese Stroke Registry and analyzed for their intraoperative ScO2 values and brain imaging data. Main outcome measures were the ScO2 values, computed tomography and magnetic resonance imaging findings. In six patients, the infarct areas were localized in the vascular territories of the posterior and/or dorsal middle cerebral arteries. One patient had watershed stroke and another one excellent collaterals resulting in normal cerebral blood volume and only subtle decrease of cerebral blood flow in initially critically perfused watershed brain areas. Intraoperative ScO2 values were entirely unremarkable or nonindicative for brain damage. Our results indicate that uneventful intraoperative NIRS monitoring does not exclude severe cerebral ischemia due to the limited field of view of commercially available NIRS devices. False negative NIRS may occur as a consequence of stroke localized outside the frontal cortex.


Assuntos
Isquemia Encefálica/diagnóstico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Monitorização Intraoperatória/métodos , Oximetria/métodos , Complicações Pós-Operatórias/diagnóstico , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/irrigação sanguínea , Isquemia Encefálica/etiologia , Ponte Cardiopulmonar/métodos , Infarto Cerebral/diagnóstico , Infarto Cerebral/etiologia , Circulação Cerebrovascular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia
10.
Artif Organs ; 40(12): E280-E291, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27283935

RESUMO

To compare intraoperative cerebral microembolic load between minimally invasive extracorporeal circulation (MiECC) and conventional extracorporeal circulation (CECC) during isolated surgical aortic valve replacement (SAVR), we conducted a randomized trial in patients undergoing primary elective SAVR at a tertiary referral hospital. The primary outcome was the procedural phase-related rate of high-intensity transient signals (HITS) on transcranial Doppler ultrasound. HITS rate was used as a surrogate of cerebral microembolism in pre-defined procedural phases in SAVR using MiECC or CECC with (+F) or without (-F) an oxygenator with integrated arterial filter. Forty-eight patients were randomized in a 1:1 ratio to MiECC or CECC. Due to intraprocedural Doppler signal loss (n = 3), 45 patients were included in final analysis. MiECC perfusion regimen showed a significantly increased HITS rate compared to CECC (by a factor of 1.75; 95% confidence interval, 1.19-2.56). This was due to different HITS rates in procedural phases from aortic cross-clamping until declamping [phase 4] (P = 0.01), and from aortic declamping until stop of extracorporeal perfusion [phase 5] (P = 0.05). Post hoc analysis revealed that MiECC-F generated a higher HITS rate than CECC+F (P = 0.005), CECC-F (P = 0.05) in phase 4, and CECC-F (P = 0.03) in phase 5, respectively. In open-heart surgery, MiECC is not superior to CECC with regard to gaseous cerebral microembolism. When using MiECC for SAVR, the use of oxygenators with integrated arterial line filter appears highly advisable. Only with this precaution, MiECC confers a cerebral microembolic load comparable to CECC during this type of open heart surgery.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Circulação Extracorpórea/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Próteses Valvulares Cardíacas , Embolia Intracraniana/etiologia , Idoso , Circulação Extracorpórea/métodos , Feminino , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Embolia Intracraniana/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Perfusão/métodos , Ultrassonografia Doppler Transcraniana
11.
Eur J Anaesthesiol ; 33(6): 417-24, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26914224

RESUMO

BACKGROUND: Etomidate is perceived as preserving haemodynamic stability during induction of anaesthesia. It is also associated with adrenocortical dysfunction. The risk/benefit relationship is controversial. OBJECTIVES: We tested the hypotheses that single-dose etomidate increases cumulative vasopressor requirement, time to extubation and length of stay in the ICU. DESIGN: Double-blind randomised controlled trial. SETTING: Bern University Hospital, Switzerland, from November 2006 to December 2009. PATIENTS: There were 90 patients undergoing coronary artery bypass grafts (CABG) and 40 patients undergoing mitral valve surgery (MVS). Reasons for noninclusion were known adrenocortical insufficiency, use of etomidate or propofol within 1 week preoperatively, use of glucocorticoids within 6 months preoperatively, severe renal or liver dysfunction, or carotid stenosis. INTERVENTIONS: CABG patients were allocated randomly to receive either etomidate 0.15 mg kg with placebo, propofol 1.5 mg kg with placebo or etomidate 0.15 mg kg with hydrocortisone (n = 30 in each arm). Risk stratification (low vs. high) was achieved by block randomisation. MVS patients received either etomidate 0.15 mg kg or propofol 1.5 mg kg (n = 20 in each arm). MAIN OUTCOME MEASURES: Cumulative vasopressor requirements, incidence of adrenocortical insufficiency, length of time to extubation and length of stay in ICU. RESULTS: Cumulative vasopressor requirements 24 h after induction did not differ between treatments in patients who underwent CABG, whereas more noradrenaline was used in MVS patients following propofol induction (absolute mean difference 5.86 µg kg over 24 h P = 0.047). The incidence of relative adrenocortical insufficiency was higher after etomidate alone than propofol (CABG 83 vs. 37%, P < 0.001; MVS: 95 vs. 35%, P < 0.001). The time to extubation, length of stay in ICU and 30-day mortality did not differ among treatments. Within low and high-risk subgroups, no differences in vasopressor use or outcomes were found. CONCLUSION: In elective cardiac surgery, laboratory indicators of etomidate-induced adrenal insufficiency do not translate into increased vasopressor requirement or inferior early outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 00415701.


Assuntos
Anestesia/métodos , Procedimentos Cirúrgicos Cardíacos/métodos , Etomidato , Hipnóticos e Sedativos , Insuficiência Adrenal/induzido quimicamente , Insuficiência Adrenal/epidemiologia , Idoso , Anestésicos Intravenosos , Ponte de Artéria Coronária , Método Duplo-Cego , Feminino , Humanos , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Propofol , Medição de Risco , Resultado do Tratamento , Vasoconstritores/administração & dosagem , Vasoconstritores/uso terapêutico
12.
Perfusion ; 31(6): 489-94, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26929238

RESUMO

Current guidelines for the treatment of hypothermic cardiocirculatory arrest recommend extracorporeal life support and rewarming, using cardiopulmonary bypass or extracorporeal membrane oxygenation circuits. Both have design-related shortcomings which may result in prolonged reperfusion time or insufficient oxygen delivery to vital organs. This article describes clear advantages of minimally invasive extracorporeal circulation systems during emergency extracorporeal life support in hypothermic arrest. The technique of minimally invasive extracorporeal circulation for reperfusion and rewarming is represented by the case of a 59-year-old patient in hypothermic cardiocirculatory arrest at 25.3°C core temperature, with multiple trauma. With femoro-femoral cannulation performed under sonographic and echocardiographic guidance, extracorporeal life support was initiated using a minimally invasive extracorporeal circulation system. Perfusing rhythm was restored at 28°C. During rewarming on the mobile circuit, trauma surveys were completed and the treatment initiated. Normothermic weaning was successful on the first attempt, trauma surgery was completed and the patient survived neurologically intact. For extracorporeal resuscitation from hypothermic arrest, minimally invasive extracorporeal circulation offers all the advantages of conventional cardiopulmonary bypass and extracorporeal membrane oxygenation systems without their shortcomings.


Assuntos
Oxigenação por Membrana Extracorpórea , Parada Cardíaca/terapia , Hipotermia/complicações , Humanos , Masculino , Pessoa de Meia-Idade
15.
Anesth Analg ; 119(1): 16-25, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24722261

RESUMO

BACKGROUND: Antifibrinolytics have been used for 2 decades to reduce bleeding in cardiac surgery. MDCO-2010 is a novel, synthetic, serine protease inhibitor. We describe the first experience with this drug in patients. METHODS: In this phase II, double-blind, placebo-controlled study, 32 patients undergoing isolated primary coronary artery bypass grafting with cardiopulmonary bypass were randomly assigned to 1 of 5 increasing dosage groups of MDCO-2010. The primary aim was to evaluate pharmacokinetics (PK) with assessment of plasmatic concentrations of the drug, short-term safety, and tolerance of MDCO-2010. Secondary end points were influence on coagulation, chest tube drainage, and transfusion requirements. RESULTS: PK analysis showed linear dosage-proportional correlation between MDCO-2010 infusion rate and PK parameters. Blood loss was significantly reduced in the 3 highest dosage groups compared with control (P = 0.002, 0.004 and 0.011, respectively). The incidence of allogeneic blood product transfusions was lower with MDCO-2010 4/24 (17%) vs 4/8 (50%) in the control group. MDCO-2010 exhibited dosage-dependent antifibrinolytic effects through suppression of D-dimer generation and inhibition of tissue plasminogen activator-induced lysis in ROTEM analysis as well as anticoagulant effects demonstrated by prolongation of activated clotting time and activated partial thromboplastin time. No systematic differences in markers of end organ function were observed among treatment groups. Three patients in the MDCO-2010 groups experienced serious adverse events. One patient experienced intraoperative thrombosis of venous grafts considered possibly related to the study drug. No reexploration for mediastinal bleeding was required, and there were no deaths. CONCLUSIONS: This first-in-patient study demonstrated dosage-proportional PK for MDCO-2010 and reduction of chest tube drainage and transfusions in patients undergoing primary coronary artery bypass grafting. Antifibrinolytic and anticoagulant effects were demonstrated using various markers of coagulation. MDCO-2010 was well tolerated and showed an acceptable initial safety profile. Larger multi-institutional studies are warranted to further investigate the safety and efficacy of this compound.


Assuntos
Antifibrinolíticos/farmacocinética , Ponte Cardiopulmonar , Ponte de Artéria Coronária , Inibidores de Serina Proteinase/farmacocinética , Idoso , Coagulação Sanguínea , Transfusão de Sangue , Método Duplo-Cego , Feminino , Fibrinólise , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Serina Proteinase/efeitos adversos
18.
J Vasc Surg ; 57(4): 943-50, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23332983

RESUMO

OBJECTIVE: In acute traumatic bleeding, permissive arterial hypotension with delayed volume resuscitation is an established lifesaving concept as abridge to surgical control. This study investigated whether preoperatively administered volume also correlated inversely with survival after ruptured abdominal aortic aneurysm (rAAA). METHODS: This retrospective study analyzed prospectively collected and validated data of a consecutive cohort of patients with rAAAs (January 2001 to December 2010). Generally, fluid resuscitation was guided clinically by the patient's blood pressure and consciousness. All intravenous fluids (crystalloids, colloids, and blood products) administered before aortic clamping or endovascular sealing were abstracted from paramedic and anesthesia documentation and normalized to speed of administration (liters per hour). Logistic regression modeling, adjusted for suspected confounding covariates, was used to investigate whether total volume was independently associated with risk of death within 30 days of rAAA repair. RESULTS: A total of 248 patients with rAAAs were analyzed, of whom 237 (96%) underwent open repair. A median of 0.91 L of total volume per hour (interquartile range, 0.54-1.50 L/h) had been administered preoperatively to these patients. The postoperative 30-day mortality rate was 15.3% (38 deaths). The preoperative rate of fluid infusion correlated with 30-day mortality after adjustment for confounding factors, and the association persisted robustly through sensitivity analyses: each additional liter per hour increased the odds of perioperative death by 1.57-fold (95% confidence interval, 1.06-2.33; P = .026). CONCLUSIONS: Aggressive volume resuscitation of patients with rAAAs before proximal aortic control predicted an increased perioperative risk of death, which was independent of systolic blood pressure. Therefore, volume resuscitation should be delayed until surgical control of bleeding is achieved.


Assuntos
Aneurisma da Aorta Abdominal/terapia , Ruptura Aórtica/terapia , Volume Sanguíneo , Hidratação , Substitutos do Plasma/uso terapêutico , Ressuscitação/métodos , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/mortalidade , Aneurisma da Aorta Abdominal/fisiopatologia , Ruptura Aórtica/diagnóstico , Ruptura Aórtica/mortalidade , Ruptura Aórtica/fisiopatologia , Pressão Sanguínea , Implante de Prótese Vascular , Procedimentos Endovasculares , Feminino , Hidratação/efeitos adversos , Hidratação/mortalidade , Técnicas Hemostáticas , Humanos , Modelos Logísticos , Masculino , Substitutos do Plasma/efeitos adversos , Modelos de Riscos Proporcionais , Sistema de Registros , Ressuscitação/efeitos adversos , Ressuscitação/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
19.
BJA Open ; 6: 100135, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37588173

RESUMO

Background: There are no current recommendations for oxygen titration in patients with stable coronary artery disease. This study investigates the effect of iatrogenic hyperoxia on cardiac function in patients with coronary artery disease undergoing general anaesthesia. Methods: Patients scheduled for elective coronary artery bypass graft surgery were prospectively recruited into this randomised crossover clinical trial. All patients were exposed to inspired oxygen fractions of 0.3 (normoxaemia) and 0.8 (hyperoxia) in randomised order. A transoesophageal echocardiographic imaging protocol was performed during each exposure. Primary analysis investigated changes in 3D peak strain, whereas secondary analyses investigated other systolic and diastolic responses. Results: There was no statistical difference in systolic function between normoxaemia and hyperoxia. However, the response in systolic function to hyperoxia was dependent on ventricular function at normoxaemia. Patients with a normoxaemic left ventricular (LV) global longitudinal strain (GLS) poorer than the derived cut-off (>-15.4%) improved with hyperoxia (P<0.01), whereas in patients with normoxaemic LV-GLS <-15.4%, LV-GLS worsened with transition to hyperoxia (P<0.01). The same was seen for right ventricular GLS with a cut-off at -24.1%. Diastolic function worsened during hyperoxia indicated by a significant increase of averaged E/e' (8.6 [2.6]. vs 8.2 [2.4], P=0.01) and E/A ratio (1.4 (0.4) vs 1.3 (0.4), P=0.01). Conclusions: Although the response of biventricular systolic variables is dependent on systolic function at normoxaemia, diastolic function consistently worsens under hyperoxia. In coronary artery disease, intraoperative strain analysis may offer guidance for oxygen titration. Clinical trial registration: NCT04424433.

20.
Circ Heart Fail ; 15(4): e008903, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35038887

RESUMO

BACKGROUND: The pathophysiology of heart failure with preserved ejection fraction is not well understood, but evidence strongly suggests involvement of microvascular dysfunction. We studied the myocardial oxygenation reserve as a direct marker of coronary vascular function and its relation to myocardial deformation and tissue characteristics by cardiovascular magnetic resonance (CMR). METHODS: In a dual-center case-control study, patients with heart failure and preserved ejection fraction (>50%) and healthy controls older than 50 years underwent quantitative CMR for ventricular volumes and functional assessment with feature tracking, as well as tissue characterization (T1, T2, extracellular volume). Coronary vascular function was measured by oxygenation-sensitive (OS)-CMR of the myocardial oxygenation response to a vasoactive breathing maneuver. RESULTS: Twenty-nine patients completed the CMR exam. Compared with cutoffs derived from 12 control subjects, circumferential peak strain was attenuated in 97% of patients. Native T1 was elevated in 93%, extracellular volume was elevated in 83%. Sixty-six percent of patients revealed either regional or global myocardial edema, defined by an increased myocardial T2. An attenuated global myocardial oxygenation reserve (<4.4%) was observed in 96% of the patients (1.7±3.9% versus 9.1±5.3% in controls, P<0.001). This was correlated with septal wall thickness (r=-0.54, P=0.003), edema (myocardial T2; ß=-0.26% oxygenation-sensitive/ms [95% CI, -0.49 to -0.03], P=0.029), and reduced diastolic strain rate (ß=1.50% oxygenation-sensitive/s-1 [95% CI, 0.06-2.90], P=0.042). CONCLUSIONS: In patients with clinical heart failure with preserved ejection fraction, vascular dysfunction as measured by an attenuated myocardial oxygenation reserve is associated with myocardial edema, a thicker septum, and diastolic dysfunction. A quantitative comprehensive CMR exam including oxygenation-sensitive-CMR allows for comprehensive imaging-based phenotyping of heart failure with preserved ejection fraction.


Assuntos
Insuficiência Cardíaca , Biomarcadores , Estudos de Casos e Controles , Humanos , Imagem Cinética por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Miocárdio/patologia , Valor Preditivo dos Testes , Volume Sistólico/fisiologia , Função Ventricular Esquerda
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