[Show abstract][Hide abstract] ABSTRACT: Background:
Amiodarone is commonly used in the acute care setting. However the acute hemodynamic and echocardiographic effect of intravenous amiodarone administered intraoperatively on right ventricular (RV) systolic and diastolic function using transesophageal echocardiography (TEE) has not been described.
The study design was a randomized controlled trial in elective cardiac surgical patients undergoing valvular surgery. Patients received an intravenous loading dose of 300 mg of either amiodarone or placebo in the operating room, followed by an infusion of 15 mg/kg for two days. Hemodynamic profiles, echocardiographic measurement of RV and left ventricular (LV) dimensions, Doppler interrogation of tricuspid and mitral valve, hepatic and pulmonary venous flow combined with tissue Doppler imaging of the tricuspid and mitral valve annulus were obtained before and after bolus.
Although more patients in the placebo group had chronic obstructive lung disease (14 vs 6, p=0.05) and diabetes (14 vs 5; p=0.0244), there was no difference in terms of baseline hemodynamic, 2D and Doppler variables. After bolus, a significant increase in pulmonary artery pressure, central venous pressure and pulmonary vascular resistance index (p<0.05) was observed in the amiodarone group with reduction in systolic to diastolic (S/D) ratio of the hepatic (p=0.0247) and pulmonary venous (p=0.0052) velocity.
Acute administration of amiodarone is associated with alteration in RV diastolic properties and has minimal negative inotropic effect on RV systolic function in cardiac surgical patients with valvular disease.
European Heart Journal: Acute Cardiovascular Care 09/2014; 4(4). DOI:10.1177/2048872614549102
[Show abstract][Hide abstract] ABSTRACT: Objective: Whereas it is established that endothelin-1 elicits sustained deleterious effects on the cardiovascular system during cardiopulmonary bypass (CPB), presently it remains unknown whether the inhaled administration of the dual ETA and ETB antagonist tezosentan prevents the development of pulmonary endothelial dysfunction. Design: A prospective, randomized laboratory investigation. Setting: University research laboratory. Participants: Landrace swine. Interventions: Three groups of animals underwent a 90-minute period of full bypass followed by a 60-minute period of reperfusion. Among treated groups, one received tezosentan through inhalation prior to CPB, whereas the other one received it intravenously at weaning from CPB; the third group remained untreated. Pulmonary vascular reactivity studies, realized on a total of 285 rings, were performed in all groups, including 1 sham. Measurements and Main Results: The contractility of pulmonary arteries to prostaglandin F-2 alpha and to the thromboxane A(2) mimetic U46619 was preserved in animals submitted to CPB. By contrast, there were significant increases both in the maximal contraction to endothelin-1 and in the plasma levels of the peptide 60 minutes after reperfusion. Tezosentan administered by inhalation or intravenously did not prevent the development of pulmonary CPB-associated endothelial dysfunction. However, while hemodynamic disturbances were improved with both routes, the inhaled administration had a beneficial effect on oxygen parameters over intravenous administration. Conclusions: Despite the blockade of the endothelin-1 pathway with tezosentan, the development of the pulmonary endothelial dysfunction associated with CPB still occurred. However, only the inhalation route had a significant impact on gas exchange during CPB.
Journal of Cardiothoracic and Vascular Anesthesia 06/2014; 28(3):698-708. DOI:10.1053/j.jvca.2013.12.013 · 1.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Milrinone administered through inhalation is an emerging method aimed at specifically reducing pulmonary hypertension without affecting systemic pressures. Its administration has been shown useful both in patients undergoing cardiac surgery and for persistent pulmonary hypertension of the newborn. These populations are prone to receive many concomitant medications and/or blood sampling may require a low volume quantification method. In order to address these issues in view of pharmacokinetic studies, this paper aims to develop and validate a specific and sensitive analytical assay using HPLC and MS/MS detection for the quantification of milrinone plasma concentrations after inhalation in patients undergoing cardiac surgery.
Plasma samples (50 µL) were extracted using ethyl acetate. Milrinone was separated on a C18 analytical column at 50°C. The mobile phase consisted of methanol and 10 mM ammonium acetate (45:55 v/v). The electrospray was operated in the negative ionization mode and monitored the following mass transitions: m/z 212.1 → 140.0 at 36 eV for milrinone and m/z 252.1 → 156.1 at 32 eV for olprinone.
Calibration curves followed a quadratic regression in the concentration range of 0.3125-640 ng/mL. The lower limit of quantification is 0.3125 ng/mL and is based on a low plasma volume of 50 µL. Mean drug recovery and accuracy were ≥ 72.3% and 96.0%, respectively. Intra- and inter-day precision (CV%) was ≤ 7.4 % and ≤ 11.5%, respectively. The specificity allowed milrinone quantification in the multidrug administration conditions of cardiopulmonary bypass.
This validated micromethod proved to be highly sensitive and specific while using a low volume of plasma. Its low volume and its lower limit of quantification indicate that this approach is suitable for further characterisation of milrinone pharmacokinetics in both adults (inhalation) and neonates.
Therapeutic drug monitoring 03/2014; 36(5). DOI:10.1097/FTD.0000000000000072 · 2.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to determine the factors independently associated with septal curvature in patients with pulmonary arterial hypertension (PAH).
Eighty-five consecutive patients with PAH who had an echocardiogram and a right heart catheterization within 24 hours of each others were included in the study. Septal curvature was assessed at the mid-papillary level using the eccentricity index (EI). Marked early systolic septal anterior motion was defined as a change in EI > 0.2 between end-diastole and early systole. Inter-ventricular mechanical delay was calculated as the percent time difference between right ventricular (RV) to left ventricular (LV) end-ejection time normalized for the RR interval.
Average age was 45 ± 11 years and the majority of patients were women (75%). Mean right atrial pressure was 11 ± 7 mmHg, mean PAP was 52 ± 13 mmHg, relative RV area 1.8 ± 0.9, and RV fractional area change 24 ± 8%. End-diastolic EI was 1.6 ± 0.4 and systolic EI was 2.5 ± 0.8. On multivariate analysis relative pulmonary pressure, relative RV area, and inter-ventricular mechanical delay were independently associated with systolic EI (R(2) = 0.72, P < 0.001). Independent determinants of diastolic EI included relative RV area and mean PAP (R(2) = 0.69, P < 0.001). A systolic EI >1.08 differentiated patients with PAH from healthy controls with an AUC = 0.99. Patients with early systolic septal anterior motion (44% of subjects) had lower exercise capacity, more extensive ventricular remodeling, and worst ventricular function.
Septal curvature is a useful marker of structural, hemodynamic, and electromechanical ventricular interdependence in PAH.
[Show abstract][Hide abstract] ABSTRACT: To assess the usefulness of central venous pressure (CVP), diastolic right ventricular pressure, and pulmonary capillary wedge pressure (PCWP) waveform analysis in predicting fluid responsiveness.
A prospective observational study.
Tertiary care university hospital.
Forty-four patients undergoing coronary artery bypass grafting.
Analysis of the a/v wave ratio of the PCWP, CVP, and right ventricular dP/dt to predict an increase in stroke volume >15% after the administration of 500mL of colloid.
Forty-four patients were enrolled in this study and 7 were excluded. There were 24 responders and 13 nonresponders. No differences in mean CVP and PCWP values between the responders and the nonresponders were found. The only parameter associated with a significant response to volume infusion was the ratio of the a/v waves of the PCWP tracing (p = 0.0001). The performance of the a/v wave ratio>1 of the PCWP tracing in predicting fluid responsiveness was evaluated by constructing a receiver operating characteristic curve. The area under the receiver operating characteristic curve was 0.89 (95% confidence interval, 0.79-0.99; p<0.05).
The a/v ratio measured on the PCWP tracing is a predictor of fluid responsiveness in patients with preserved left ventricular function undergoing coronary artery bypass grafting.
Journal of cardiothoracic and vascular anesthesia 08/2013; 27(4):676-680. DOI:10.1053/j.jvca.2012.11.002 · 1.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the perioperative predictors of long-term mortality after aortic valve replacement (AVR). The authors hypothesized that perioperative variables are more important predictors of mortality than patient-prosthesis mismatch (PPM).
A retrospective study of prospectively collected data.
A tertiary care university hospital.
One-hundred-ninety-nine adult patients who underwent AVR.
After Research and Ethics Committee approval, the authors studied consecutive adult patients that underwent AVR in 1999 from the time of procedure to 5 years later. Demographic data, hemodynamic profile obtained after the induction of anesthesia, and perioperative data were analyzed. Primary endpoint was 5-year survival.
Actuarial survival rate was 95.98%, 91.46%, and 81.91% at 30 days, 1 year, and 5 years, respectively. On univariate analysis, patients who died were significantly older (p<0.0001), had pulmonary hypertension (PHT), longer cardiopulmonary bypass (CPB) (p = 0.0001) and cross-clamping duration (p = 0.003), more frequent return to CPB (p = 0.036), or the use of an intra-aortic balloon pump to wean from CPB (p = 0.015). PPM was not related to 5-year mortality (p = 0.0649). Using Cox survival analysis, the only independent risk factors related to 5-year mortality after AVR were PHT using the mean arterial pressure-to-mean pulmonary artery pressure ratio (HR: 1.39, 95% CI 1.01-1.92, p = 0.0413) and the presence of complex separation from CPB (HR: 2.66, 95% CI 1.08-6.50, p = 0.0324).
In patients undergoing AVR, 5-year survival was mostly related to the severity of PHT and intraoperative factors, mainly complexity of weaning from CPB.
Journal of cardiothoracic and vascular anesthesia 08/2013; 27(4):647-653. DOI:10.1053/j.jvca.2013.03.016 · 1.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aims:
To investigate the physiological correlates of indices of RV function in a model of chronic pressure overload.
Methods and results:
Chronic pulmonary hypertension (PH) was induced in piglets by ligation of the left pulmonary artery (PA) followed by weekly embolization of right lower lobe arteries for 5 weeks (the PH group, n = 11). These animals were compared with sham-operated animals (controls, n = 6). At 6 weeks, a subgroup of five PH pigs underwent surgical reperfusion of the left lung and four others were followed until 12 weeks without treatment. Right ventricular function was assessed using echocardiography and conductance catheter measurements. At 6 weeks, mean PA pressure was higher in PH group compared with controls (35 ± 9 vs. 14 ± 2 mmHg, P < 0.01). Although RV elastance (Ees) increased at 6 weeks in the PH group (0.55 ± 0.09 vs. 0.38 ± 0.05 mmHg/mL, P < 0.001), ventricular-arterial coupling measured by the ratio of Ees on PA elastance (Ea) was decreased (0.68 ± 0.17 vs. 1.18 ± 0.18, P < 0.001). There was a strong direct relationship between Ees/Ea and indices of RV function, while relationship between Ees and indices of RV function was moderate. Changes in indices of RV function with time and after left lung reperfusion were associated with changes in Ees/Ea.
Usual indices of RV function are associated with ventricular-arterial coupling rather than with ventricular contractility in a model of chronic pressure overload.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
In many pathological conditions, including high-risk surgery, the severity of the inflammatory response is related to the patient outcome. However, determining the patient inflammatory state presents difficulties, as markers are obtained intermittently through blood testing with long delay. RBC aggregation is a surrogate marker of inflammation that can be quantified with the ultrasound Structure Factor Size and Attenuation Estimator. The latter is proposed as a real-time inflammation monitoring technique for patient care.
Ten swine underwent a 90-minute cardiopulmonary bypass, and surveillance was maintained during 120 minutes in the postbypass period. To promote the inflammatory reaction, lipopolysaccharide was administrated two times prior to surgery in six of those swine (lipopolysaccharide group). During the whole procedure, the Structure Factor Size and Attenuation Estimator cellular imaging method displayed a RBC aggregation index (W) computed from images acquired within the pump circuit and the femoral vein. Interleukin-6, interleukin-10, C-reactive protein, haptoglobin, immunoglobulin G, and fibrinogen concentrations were measured at specific periods.
Compared with controls, the lipopolysaccharide group exhibited higher W within the pump circuit (p < 0.05). In the femoral vein, W was gradually amplified in the lipopolysaccharide group during cardiopulmonary bypass and the postbypass period (p < 0.05), whereas interleukin levels were higher in the lipopolysaccharide group but only at the end of cardiopulmonary bypass and beginning of postbypass (p < 0.05).
Continuous RBC aggregation monitoring can characterize the evolving inflammatory response during and after cardiopulmonary bypass. The Structure Factor Size and Attenuation Estimator is proposed as a real-time noninvasive monitoring technique to anticipate inflammation-related complications during high-risk surgery or critical care situations. Because RBC aggregation promotes vascular resistance and thrombosis, W could also provide early information on vascular disorders in those clinical situations.
Critical care medicine 05/2013; 41(8). DOI:10.1097/CCM.0b013e31828a2354 · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pulmonary vascular resistance (PVR) and pulmonary arterial compliance (PAC) are important determinants of right ventricular (RV) afterload. We compared the relationship between PVR and PAC and indices of systolic and diastolic RV function in PAH.Methods and MaterialsWe conducted a retrospective cohort study of adult patients with a diagnosis of PAH who underwent right heart catheterization and echocardiography within 24 hours between January 2000 and December 2010. RV function was assessed using indexed stroke volume, RV fractional area change (RVFAC), tricuspid annular systolic excursion, RV myocardial performance index, and RV myocardial isovolumetric acceleration and right atrial pressure. Regression analysis was performed to determine the association between PVR and PAC with several indices of systolic and diastolic function and Cox proportional hazard model was used to determine independent correlates of death or transplantation.ResultsA total of 85 patients with PAH were included. Average age was 45±11years and 75% were female. Mean pulmonary arterial pressure averaged 52±14 mmHg, indexed PVR was 13±7 WU and indexed PAC was 1.1±0.7 mL/ mmHg. A strong inverse relationship was observed between PAC and PVR (R2=0.84, p<0.001). A moderate association between PVR and PAC with indices of systolic function was found (r=-0.65, p<0.001 and r=0.73, p<0.001 for RVFAC), while a weaker association was observed with diastolic parameters (r=0.23, p=0.03 and r=−0.33, p=0.002 for right atrial pressure and indexed right atrial area respectively). On Cox proportional hazard regression, indices of RV size and function were strongly related. In contrast, PVR or PAC did not significantly relate to outcome.Conclusions
In patients with PAH, resistance and compliance are inversely related and are moderately associated with indices of RV function. Indices of RV function and remodeling are more strongly associated with outcome than PAC or PVR.
The Journal of Heart and Lung Transplantation 04/2013; 32(4):S63-S64. DOI:10.1016/j.healun.2013.01.972 · 6.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To evaluate the efficacy of tezosentan in reducing the incidence of right ventricular (RV) failure and associated mortality in patients with pre-existing pulmonary hypertension. The primary endpoint was the proportion of patients with RV failure during weaning from cardiopulmonary bypass (CPB), assessed 30 min after the end of CPB. DESIGN: Multicenter, double-blind, randomized, placebo-controlled trial. SETTING: Thirty-one cardiac surgical centers in 14 countries. PARTICIPANTS: Two hundred seventy-four patients with pulmonary hypertension aged≥18 years scheduled to undergo cardiac surgery. INTERVENTION: Intravenous tezosentan (5 mg/h) during surgery and up to 24 hours afterwards (1 mg/h), or matched placebo. MEASUREMENTS AND MAIN RESULTS: One-hundred and thirty-three patients received tezosentan and 141 placebo. RV failure occurred in 30 patients (10.9%), 37% of whom died. There was no difference in the incidence of RV failure between the two treatment groups (relative risk reduction: 0.07 [95% CI-0.83, 0.53; p = 0.8278]). CONCLUSION: A reduction in RV failure with tezosentan was not observed in this study.(Current Controlled Trials, identifier NCT00458276).
Journal of cardiothoracic and vascular anesthesia 03/2013; 27(6). DOI:10.1053/j.jvca.2013.01.023 · 1.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose of review:
To evaluate new information on the importance of right ventricular function, diagnosis and management in cardiac surgical patients.
There is growing evidence that right ventricular function is a key determinant in survival in cardiac surgery, particularly in patients with pulmonary hypertension. The diagnosis of this condition is helped by the use of specific hemodynamic parameters and echocardiography. In that regard, international consensus guidelines on the echocardiographic assessment of right ventricular function have been recently published. New monitoring modalities in cardiac surgery such as regional near-infrared spectroscopy can also assist management. Management of right ventricular failure will be influenced by the presence or absence of myocardial ischemia and left ventricular dysfunction. The differential diagnosis and management will be facilitated using a systematic approach.
The use of right ventricular pressure monitoring and the publications of guidelines for the echocardiographic assessment of right ventricular anatomy and function allow the early identification of right ventricular failure. The treatment success will be associated by optimization of the hemodynamic, echocardiographic and near-infrared spectroscopy parameters.
Current opinion in anaesthesiology 12/2012; 26(1). DOI:10.1097/ACO.0b013e32835b8be2 · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Orthotopic liver transplantation (OLT) has been associated with major blood loss and the need for blood product transfusions. During the last decade, improved surgical and anesthetic management has reduced intraoperative blood loss and blood product transfusions. A first report from our group published in 2005 described a mean intraoperative transfusion rate of 0.3 red blood cell (RBC) unit per patient for 61 consecutive OLTs. Of these patients, 80.3% did not receive any blood product. The interventions leading to those results were a combination of fluid restriction, phlebotomy, liberal use of vasopressor medications, and avoidance of preemptive transfusions of fresh frozen plasma. This is a follow-up observational study, covering 500 consecutive OLTs. METHODS: Five hundred consecutive OLTs were studied. The transfusion rate of the first 61 OLTs was compared with the last 439 OLTs. Furthermore, multivariate logistic regression was used to determine the main predictors of intraoperative blood transfusion. RESULTS: A mean (SD) of 0.5 (1.3) RBC unit was transfused per patient for the 500 OLTs, and 79.6% of them did not receive any blood product. There was no intergroup difference except for the final hemoglobin (Hb) value, which was higher for the last 439 OLTs compared with the previously reported smaller study (94  vs. 87  g/L). Two variables, starting Hb value and phlebotomy, correlated with OLT without transfusion. CONCLUSIONS: In our center, a low intraoperative transfusion rate could be maintained throughout 500 consecutive OLTs. Bleeding did not correlate with the severity of recipient's disease. The starting Hb value showed the strongest correlation with OLT without RBC transfusion.