Blood volume measurement by hemodilution: association with valve disease and re-evaluation of the Allen Formula.

BACKGROUND: Total blood volume (TBV) assessment is central to the management of cardiac surgical patients with cardiopulmonary bypass (CPB). The widely accepted Allen Formula lacks accuracy in estimating TBV in these patients. Moreover, the impact of commonly encountered cardiac disease states on TBV has not been systematically investigated. The aim of this study was to determine TBV by hemodilution (TBVHD) for patients with valve disease, compare TBVHD to algorithms frequently used during cardiac surgery and to modify the Allen Formula to better fit today's patient population. METHODS: TBVHD was prospectively measured upon initiation of CPB. Ninety-six patients were grouped into 4 cohorts by preoperative diagnosis and compared to Allen and weight-based formulae in a univariate analysis: mitral regurgitation (MR), coronary artery disease requiring bypass surgery (CABG) and aortic stenosis (AS) ± CABG. The independent effects of height and weight on TBV were correlated to the original Allen Formula by multiple linear regression. RESULTS: Patients with MR had significantly larger TBVHD compared to patients with AS, CABG or both. The smallest TBVHD was found in the patients with AS and CABG. The modified Allen Formula had an excellent model fit (R(2) = 0.88 and R(2) = 0.95 for males and females, respectively; p<0.001) while the classic formula overestimated TBV by 30% in males and females. For males, height impacted TBV calculations the most whereas weight was the predominant determinant in females. CONCLUSION: Blood volume assessment via the Allen Formula or bodyweight overestimated TBV in cardiac surgical patients, with potential implications on their management. The assumption that MR frequently presents with increased intravascular volume was confirmed whereas AS patients with coronary disease had a relatively smaller TBV. Lastly, a modified Allen Formula to better reflect today's patient population was derived to reproducibly improve accuracy in mathematical estimates of TBV.

Blood volumes in cardiac surgery with cardiopulmonary bypass.

PURPOSE: Total blood volume (TBV) estimation potentially impacts various aspects of cardiac surgical care, including pharmacological and transfusion interventions, hemodynamic and volume management and perfusion equipment selection. TBV is commonly computed during cardiopulmonary bypass (CPB), using standardized formulae. We hypothesized that these equations fail to accurately predict individual blood volume variability. The aim of this study was to determine TBV with a dilution technique and compare the results to commonly utilized TBV calculations. METHODS: After institutional review board approval, data was prospectively collected and analyzed for 101 patients undergoing open-heart surgery. Hematocrits (Hct) just prior to and immediately after the initiation of CPB were used to calculate the TBV. Results were compared to (1) the Allen formula and (2) weight-based standards (70 ml/kg for males (SM); 65 ml/kg for females (SF)). RESULTS: The average dilution TBV (male: 4684 ± 1641 ml; female: 3027 ± 1067 ml; total: 4175 ± 1617 ml) was significantly smaller (p<0.05) than TBV estimated by Allen's formula (male: 6328 ± 973 ml; female: 4167 ± 643 ml; total: 5665 ± 1134 ml) and weight-based standards (male: 6278 ± 1256 ml; female: 4924 ± 1064 ml; total: 5862 ± 1350 ml). Allen's formula and the weight-based standards correlated strongly (R(2) = 0.821, p<0.001), suggesting similar estimates of TBV when using these methods. In contrast, hemodilution correlated poorly with the estimates by Allen (R(2) = 0.221, p<0.001) and weight-based formulae (R(2) = 0.122, p<0.001), suggesting different TBV computation. CONCLUSIONS: The dilution method during CPB for TBV estimation is applicable and reproducible in the cardiac surgical arena and can be utilized to calculate TBV. Our results suggest that traditional TBV assessment in cardiac surgical patients by Allen's and weight-based formulae lacks the desired accuracy in estimating true TBV.

Treating pulmonary hypertension post cardiopulmonary bypass in pigs: milrinone vs. sildenafil analog.

Procedures using cardiopulmonary bypass (CPB) and aortic cross-clamping are associated with a variable degree of ischemia/reperfusion of the lungs, leading to acute pulmonary hypertension (PHT). The purpose of this study was to compare the effects of the sildenafil analog (UK343-664), a phosphodiesterase type V(PDEV) inhibitor, with milrinone, a PDE type III inhibitor, in a porcine model of acute PHT following CPB. After the pigs were anesthetized, pressure-tipped catheters were placed in the right ventricle and carotid and pulmonary arteries. Cardiac output was measured with an ultrasound probe on the ascending aorta. After heparinization and placement of aortic and right atrial cannulae, non-pulsatile CPB was instituted and cardioplegia administered following aortic cross-clamping. After 30 minutes, the clamp was removed and the animals re-warmed and separated from CPB in sinus rhythm. The animals were randomized to 3 groups, and 16 animals were studied to completion: milrinone (n=5) 50 microg/kg; sildenafil-analog (n=5) 500 microg/kg; and normal saline (NS) (n=6). Hemodynamic data were collected at baseline pre-CPB and, following termination of CPB, at baseline, 5, 10 and 30 minutes after administration of the drug. Pulmonary hypertension was present in all groups following CPB. After administration of the drugs, mean pulmonary artery pressure decreased in all 3 groups; however, only in the sildenafil-analog group did pulmonary vascular resistance(PVR) decrease by 35%, from 820 to 433 dynes . cm . sec(-5) at 5 minutes (p<0.05), and continued to be decreased at 10 minutes by 26% (P<0.05). Pulmonary selectivity was demonstrated with sildenafil-analog, because there were no similar changes in systemic vascular resistance(SVR) and no significant changes in systemic hemodynamics. Sildenafil-analog, a PDEV inhibitor, shows a promising role for managing the PVR increases that occur following CPB.

Administration of milrinone before ischemia, in the presence of beta-blockade, to treat metabolic impairment and myocardial stunning in pigs.

BACKGROUND: We examined effects of phosphodiesterase type III inhibition on regional myocardial metabolism and global left ventricular function, during ischemia, in the presence of beta-blockade. METHODS: Twenty-three pigs were randomized and studied to completion in four groups: C, did not receive drugs; M, received 50 microg/kg milrinone; E, received esmolol (150 microg/kg/min); E+M, received both. The left anterior descending artery (LADa) was then occluded for 15 min, followed by a 60-min reperfusion. Left ventricular (LV) function data obtained included LV pressures, cardiac output (CO), slope of end-systolic pressure-volume relationship (Emax), and dP/dT. Blood lactate concentrations were obtained from the aorta, LADa, and vein at baseline, end of occlusion, and during early (5 min) and late (1 h) reperfusion. RESULTS: During ischemia, occlusion produced significant depression in LV dP/dT, Emax and concomitant elevation of LVEDP that persisted over early reperfusion in groups not treated with milrinone. After ischemia, measurements of CO were higher, with lower LVEDP and SVR; LV dP/dT and the Emax were higher, with lower LVEDP in the E+M group vs. the E group. Ischemic region lactate extraction during ischemia was better with E group vs. C group. Esmolol without or with milrinone was associated with nonsignificant lactate ischemic production during early reperfusion from baseline values. CONCLUSION: We demonstrated that the pre-emptive administration of milrinone before ischemia was associated with less ischemic hemodynamic effects, without worsening the ischemic metabolic process. The combination E+M diminished ischemic metabolic impairment, and preserved left ventricular function and baseline hemodynamics.

Treatment of ischaemic left ventricular dysfunction with milrinone or dobutamine administered during coronary artery stenosis in the presence of beta blockade in pigs.

BACKGROUND: This study examines the effects of phosphodiesterase type III (PDEIII) inhibition vs beta stimulation on global function of the left ventricle (LV) and systemic haemodynamics in a porcine model of acute coronary stenosis with beta blockade. METHODS: A total of 18 adult swine were anaesthetized. Micromanometer-tipped catheters were placed in the ascending aorta and LV. Two pairs of ultrasonic dimension transducers were placed in the subendocardium on the short axis proximal to a left anterior descending (LAD) artery occluder and the long axis of the LV. Before ischaemia, i.v. esmolol was infused to decrease baseline heart rate (HR) by approximately 25%, and all animals received an esmolol infusion (150 microg kg(-1) min(-1)). Ischaemia was produced by reducing the flow in the LAD artery by approximately 80%, from 17(4) to 3(2) ml min(-1). Animals were randomized to receive (after esmolol) one of the following: no drug, sham only (Group 1, n=6), control (C); 50 microg kg(-1) i.v. milrinone (Group 2, n=6) followed by 0.375 microg kg(-1) min(-1) (M); or incremental doses of dobutamine (Group 3, n=6) every 10 min (5, 10 and 20 microg kg(-1) min(-1)) (D). Left ventricular function data obtained included HR, arterial and LV pressures, cardiac output (CO), Emax and dP/dT. Measurements were taken during five time periods: before ischaemia (at baseline, after esmolol) and every 10 min during ischaemia (at 10, 20 and 30 min). RESULTS: The effects of beta blockade and ischaemia had a significant impact on contractility (Emax) in Group M and myocardial performance (left ventricular end-diastolic pressure, LVEDP) in all groups. Left ventricular function (Emax, CO, LVEDP and SVR) was better preserved when milrinone was added in Group M. A moderate dose of dobutamine (10 microg kg(-1) min(-1)) increased CO. Only the high dose (20 microg kg(-1) min(-1)) improved contractility (Emax), but at the expense of increased SVR. Also, LVEDP with either dose of dobutamine remained high and unchanged. CONCLUSIONS: From our limited findings, it would appear that there may, theoretically, be some benefit for using milrinone in preference to other inotropic drugs in the presence of beta blockade. Milrinone administration should be considered in patients with acute ischaemic LV dysfunction and preexisting beta blockade before using other inotropic drugs such as beta stimulants.

Reduced activation of immunomodulatory transcription factors during positive end-expiratory pressure adjustment based on volume-dependent compliance in isolated perfused rabbit lungs.

BACKGROUND: Repeated alveolar collapse and cyclic alveolar overdistension with associated activation of inflammatory signalling cascades contribute to ventilator-induced lung injury (VILI). The appropriate positive end-expiratory pressure (PEEP) which prevents or ameliorates VILI is unknown. In the isolated perfused lung, repeated adjustments of PEEP based on the continuously analysed intratidal compliance-volume curve have previously been shown to result in full end-expiratory alveolar recruitment and low risk of cyclic alveolar overdistension. Accordingly, we tested the hypothesis that such ventilatory management reduces intrapulmonary activation of the immunomodulatory transcription factors nuclear factor kappaB (NF-kappaB), activator protein 1 (AP-1) and cAMP-responsive element binding protein (CREB) which induce the expression of various chemokines and cytokines. METHODS: Isolated perfused rabbit lungs were randomly allocated to one of three groups: zero end-expiratory pressure (ZEEP) to induce repeated alveolar collapse (n=6), high PEEP to induce cyclic alveolar overdistension (n=6) and repeated PEEP adjustments based on intratidal compliance-volume curve analysis by the slice method to minimize repeated alveolar collapse and overdistension (n=9). All lungs were ventilated with a tidal volume of 6 ml kg(-1) bodyweight for 120 min. Thereafter, activation of transcription factors NF-kappaB, AP-1 and CREB in lung tissue was analysed by electrophoretic mobility shift assay. RESULTS: High PEEP was associated with the highest activation of NF-kappaB and AP-1 and repeated PEEP adjustments with the lowest activation when compared with the other two study groups (P<0.001). In contrast, activation of CREB did not differ between groups. Activated NF-kappaB and AP-1 protein complexes consisted mainly of the transactivators p50/p65 and c-Fos/Jun, respectively. CONCLUSIONS: In isolated perfused rabbit lungs, repeated adjustments of PEEP based on the continuously analysed intratidal compliance-volume curve were associated with less activation of early steps of inflammatory signalling cascades than ventilation with ZEEP or high PEEP.