A prospective pilot study assessing levels of preoperative physical activity and postoperative neurocognitive disorder among patients undergoing elective coronary artery bypass graft surgery

Physical inactivity and a sedentary lifestyle are associated with a chronic low-level inflammatory state which has been implicated in the pathogenesis of cardiovascular disease. There is growing interest in exercise programs as part of surgical 'prehabilitation'. We therefore studied preoperative physical activity levels of patients undergoing elective Coronary Artery Bypass Graft (CABG) surgery, and performed an exploratory analysis of the influence of physical activity on postoperative outcome. The Short Questionnaire to Assess Health (SQUASH) was used to assess physical activity among 100 patients, of mean (SD) age 65.4 (7.6) years. Additionally, handgrip strength was measured, and the get-up-and-go test was conducted. Anxiety, depression, and quality of life were assessed, and a computerised cognitive test battery was used to assess cognitive performance preoperatively, and three months after surgery. Preoperatively, 76% of patients met the recommended national guidelines for physical activity. The incidence of pre-existing medical conditions, and other pre-operative patient features were similar in active and inactive patients. Preoperative physical activity was significantly inversely related to the logistic EuroSCORE. The level of physical activity was also significantly inversely related with preoperative C-reactive protein (CRP) and peak postoperative CRP, but physical activity did not appear to be associated with any adverse postoperative outcomes or extended length of hospital stay. The incidence of postoperative neurocognitive disorder (PNCD) at 3 months postoperatively was 26%. Cognitive performance was not related with physical activity levels. In summary, this was the first study to assess activity levels of cardiac surgical patients with the SQUASH questionnaire. The majority of patients were physically active. Although physical activity was associated with lower levels of inflammation in this pilot study, it was not associated with an improved clinical or cognitive postoperative outcome

Platelet Function in Stored Heparinised Autologous Blood Is Not Superior to in Patient Platelet Function during Routine Cardiopulmonary Bypass

Background: In cardiac surgery, cardiopulmonary bypass (CPB) and unfractionated heparin have negative effects on blood platelet function. In acute normovolemic haemodilution autologous unfractionated heparinised blood is stored ex-vivo and retransfused at the end of the procedure to reduce (allogeneic) transfusion requirements. In this observational study we assessed whether platelet function is better preserved in ex vivo stored autologous blood compared to platelet function in the patient during CPB. Methodology/Principal Finding: We measured platelet aggregation responses pre-CPB, 5 min after the start of CPB, at the end of CPB, and after unfractionated heparin reversal, using multiple electrode aggregometry (MultiplateH) with adenosine diphosphate (ADP), thrombin receptor activating peptide (TRAP) and ristocetin activated test cells. We compared blood samples taken from the patient with samples taken from 100 ml ex-vivo stored blood, which we took to mimick blood storage during normovolemic haemodilution. Platelet function declined both in ex-vivo stored blood as well as in blood taken from the patient. At the end of CPB there were no differences in platelet aggregation responses between samples from the ex vivo stored blood and the patient. Conclusion/Significance: Ex vivo preservation of autologous blood in unfractionated heparin does not seem to b

Bivalirudin is inferior to heparin in preservation of intraoperative autologous blood

Introduction: Bivalirudin is used as an alternative to heparin in cardiac surgery, and may be superior to heparin with regard to platelet function. Bivalirudin however, is prone to cleavage by thrombin resulting in coagulation in areas of stasis. Material and Methods: We compared the preservation of platelet function and the quality of anticoagulation in autologous blood of 26 cardiac surgical patients collected intraoperatively and anticoagulated ex vivo with either bivalirudin or heparin, with supplementation of bivalirudin over time and prevention of stasis. Results: We found in both preservatives a reduction in ADP-induced platelet aggregation response over a period of 105 minutes (median, IQR: 73-141) as measured by Multiplate (R). Supplementation of additional bivalirudin (23 +/- 1.1 mu g/ml/hr) and prevention of stasis was not able to prevent thrombin generation. We found a 5-fold increase in levels of prothrombin fragment 1 + 2 in bivalirudin preserved autologous blood as compared to heparin preserved blood (F1+2 levels median 8.9 nM [quartile percentiles 4.2-12.4] vs 1.3 nM [0.6-2.1], P = 0.001 Mann-Whitney, n = 10). Conclusions: Our study suggests that preservation of platelet function in autologous blood anticoagulated with bivalirudin is not a suitable alternative to heparin. (C) 2011 Elsevier Ltd. All rights reserved

Comparison of three plasma expanders used as priming fluids in cardiopulmonary bypass patients

Ten per cent low molecular weight hydroxyethyl starch is a plasma substitute only recently used as priming solution in an extracorporeal circuit, in contrast to human albumin and gelatin. To evaluate the effect of priming solutions on haemodynamics and colloid osmotic pressure, we studied 36 patients elected for cardiopulmonary bypass (CPB). They were randomly assigned to 2.5% hydroxyethyl starch, 3% gelatin or 4% human albumin priming solution. Total blood loss (perioperative + intensive care unit period) was higher in the gelatin group than in the albumin and hydroxyethyl starch groups. During CPB, the colloid osmotic pressure was best preserved in the gelatin group, although no excessively low colloid osmotic pressures were measured in the other two groups. Due to the extended half-life and the additional postoperative colloid administration, the hydroxyethyl starch group had a higher colloid osmotic pressure in the postoperative phase. We conclude that, next to human albumin, 2.5% hydroxyethyl starch is a safe CPB priming solution additive and is effective as plasma substitute. Its somewhat longer half-life requires adaptation of the routine protocol for transfusion of colloids and blood products

Demographic data of the 26 patients studied.

<p>Values are mean ± standard deviation. CPB = cardiopulmonary bypass. CABG = only coronary artery bypass graft, valve = only valve, combin = combination of CABG+valve surgery. ASPI = arachidon acid activated platelet aggregation response, ExTEM = tissue factor initiated whole blood clotting measured with RoTEM (thromboelastometry), ct = clotting time, cft = clot formation time, mcf = maximum clot formation (mm), angle α = indicative for speed of clot generation.</p>**<p>intraoperative change (p<0.05).</p

Platelet activation in patients on CPB and in ex vivo stored unfractionated heparin-anticoagulated blood.

<p>CPB = cardiopulmonary bypass, ADP, TRAP, Ristocetin = platelet activators, see text. Values represent area under the curve in arbitrarily units (U) given as mean ± standard deviation. CI = 95% confidence interval. P values relate to the difference between samples taken from the patient or from the ex-vivo stored blood at the corresponding time points.</p

The effect of midazolam at two plasma concentrations on hemodynamics and sufentanil requirement in coronary artery surgery

Objectives: In this study, the hemodynamics and sufentanil requirement were compared at two midazolam target plasma concentrations in patients undergoing coronary artery bypass grafting (CABG). Design: Prospective, randomized study. Setting: University hospital, single institution. Participants: Patients undergoing CABG. Interventions: Patients were randomly assigned to receive midazolam at a target plasma concentration of 150 ng/mL (group 1; n = 10) or 300 ng/mL (group 2; n = 10). Sufentanil infusion was titrated to maintain hemodynamic stability, defined as mean arterial pressure within 15% of baseline values. All patients received preoperative beta-blocking agents. Arterial blood samples of midazolam and sufentanil were analyzed by high-performance liquid chromatography and radioimmunoassay, respectively. Measurements and Main Results: The mean dose of sufentanil (7.5 +/- 1.7 mu g/kg in group 1 v 7.2 +/- 2.5 mu g/kg in group 2) did not differ. There were no significant differences in hemodynamics between the groups in the period before or after cardiopulmonary bypass (CPB). Before CPB, in two patients in each group, hypertension was controlled with sufentanil only. One patient in group 1 required a vasodilator in addition to sufentanil. No ischemic events occurred before CPB. After CPB, one patient in group 2 required a vasodilator to control hypertension. Two patients in group 2 required treatment with nitroglycerin for myocardial ischemia. Stable plasma concentrations of sufentanil and midazolam were obtained during and after CPB. The midazolam infusion was continued in both groups at a rate of 1.25 mu g/kg/min during the first 4 postoperative hours. The time to awakening did not differ between the groups (100 +/- 58 minutes in group 1 v 173 +/- 147 minutes in group 2) nor did the plasma concentrations of midazolam (96 +/- 28 ng/mL v 108 +/- 42 ng/mL) at the time of awakening. Intraoperative awareness was not reported. Conclusion: In patients undergoing CABG, good hemodynamic control with a similar incidence of hemodynamic interventions was observed at midazolam target plasma concentrations of 150 and 300 ng/mL when coadministered with sufentanil. The sufentanil requirement was identical in both groups. This study suggests that a midazolam plasma concentration of 150 ng/mL is sufficient to provide satisfactory hemodynamic control and to avoid intraoperative awareness. Copyright (C) 1996 by W.B. Saunders Company

Effects of preemptive enoximone on left ventricular diastolic function after valve replacement for aortic stenosis

OBJECTIVE: Left ventricular (LV) hypertrophy is associated with increased diastolic chamber stiffness early after aortic valve replacement for valve stenosis. Enoximone, a phosphodiesterase III inhibitor, has been shown to improve myocardial contractility and relaxation when administered as a single dose after cardiac surgery. The present study investigated, by analysis of transmitral flow velocity patterns and end-diastolic pressure-area relations, whether enoximone administered before aortic valve surgery has an effect on LV diastolic properties. DESIGN: Prospective, randomized study. SETTING: Referral center for cardiothoracic surgery at a university hospital. PARTICIPANTS: Thirty-four patients undergoing aortic valve replacement for aortic stenosis. INTERVENTIONS: Patients in the enoximone group (n = 17) received a bolus dose of 0.35 mg/kg (0.15 mg/kg before aortic cross-clamping and 0.2 mg/kg added to the cardioplegic solution). Individual pressure-area relations (pulmonary capillary wedge pressure v left ventricular end-diastolic area) were obtained by using volume loading by leg elevation before and after surgery with closed chest. MEASUREMENTS AND MAIN RESULTS: The pressure-area relation on the pressure-area plot was shifted to the left after surgery, indicating decreased LV diastolic distensibility in the enoximone and control groups and providing evidence of decreased LV diastolic function. Indices of LV diastolic chamber stiffness, LV operating stiffness (K(LV)) derived from the deceleration time of early ventricular filling, and the constant of chamber stiffness (beta) derived from pressure-area relations were not different after enoximone treatment. Systolic LV function was unaltered after cardiac surgery in both groups. Analysis of changes in transmitral flow patterns identified an increased atrial filling fraction in enoximone-treated patients, suggesting increased atrial systolic function. The unaltered systolic pulmonary venous flow velocity compared with the decrease in the control group after volume loading further supports preservation of left atrial reservoir function with enoximone in the absence of evidence for decreased LV stiffness. CONCLUSION: Preemptive enoximone did not change LV diastolic function based on diastolic filling patterns or LV stiffness indices (K(LV) and beta) derived from Doppler early filling deceleration time and pressure-area relations. Doppler data suggested improvement of left atrial systolic function and preservation of left atrial reservoir function with enoximon