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Purpose Olprinone is a phosphodiesterase type III inhibitor that is often used to increase cardiac output after cardiopulmonary bypass (CPB). Hemodilution by CPB is likely to decrease total olprinone concentration, but it may also increase the free (unbound) concentration of olprinone due to reduced protein binding. The aim of this study was to investigate the effect of hemodilution on the protein binding of olprinone. Methods Eleven patients scheduled for elective cardiac surgery with CPB were enrolled in our study. Olprinone was continuously infused at a rate of 0.2 µg/kg/min from the time of the first surgical incision until the patient arrived at the recovery unit. Protein binding was evaluated twice, just before the start of CPB and at the beginning of withdrawal from CPB. Olprinone concentration and protein binding were determined with high-performance liquid chromatography and ultrafiltration methods, respectively. Olprinone protein binding was also evaluated in vitro. Results Olprinone protein binding to albumin was 63 % in vitro, but it did not bind to alpha-1 acid glycoprotein. Olprinone protein binding in patients before CPB was 81.5 ± 4.3 %, whereas protein binding at withdrawal from CPB was 63.3 ± 14.3 %. Conclusions Unbound olprinone concentration increased by 20 % during CPB, which suggests that the pharmacological effects of olprinone might be enhanced during and after CPB. Close hemodynamic monitoring is necessary to control the effects of olprinone after CPB, because CPB alters olprinone's pharmacokinetics. Keywords Olprinone * Cardiac surgery * Cardiopulmonary bypass * Protein binding * Albumin, Introduction Olprinone (Coretec®; Eisai, Tokyo, Japan) is a phosphodiesterase type III inhibitor (PDEI) with both strong inotropic and vasodilatory effects [1] that is often used in cardiac surgery for weaning [...]

Byline: Gregory M. T. Hare (1,2), Elaine Liu (1), Andrew J. Baker (1), C. David Mazer (1,2) Keywords: Hemoglobin based oxygen carrier; Hemodilution; Cerebral hypoxia; Lactate Abstract: Purpose To determine the oxygen affinity for optimal tissue oxygen delivery with a hemoglobin--hydroxyethyl starch conjugate (HRC 101). Methods Anesthetized rats were hemodiluted (180 ml kg.sup.-1) with low (P.sub.50 ~70 mmHg) or high affinity (P.sub.50 ~14 mmHg) HRC 101 at hemoglobin (Hb) concentrations near 100 or 70 g l.sup.-1 (n = 6--8). Hippocampal tissue oxygen tension ([P.sub.Br]O.sub.2), blood flow, arterial blood gases, Hb, hematocrit (Hct) and lactate were measured. Data (mean +- SD) were analyzed by two-way ANOVA. Results Hemodilution reduced the hematocrit to 1 +- 1% in all groups. [P.sub.Br]O.sub.2 was best maintained after hemodilution with low affinity HRC 101 at Hb 100 and 70 g l.sup.-1 (25.2 +- 7.6 and 16.6 +- 8.3 torr, respectively). [P.sub.Br]O.sub.2 decreased (9.5 +- 9.3 torr, P < 0.05) and serum lactate levels increased (5.0 +- 1.7 mmol l.sup.-1, P < 0.05) following hemodilution with the high affinity HRC 101 (Hb 100 g l.sup.-1). Conclusions HRC 101 with a lower oxygen affinity favored tissue perfusion and maintained [P.sub.Br]O.sub.2 after near complete blood volume exchange in rats. Author Affiliation: (1) Departments of Anesthesia and Critical Care, Cara Phelan Centre for Trauma Research, The Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada (2) Department of Physiology, University of Toronto, Toronto, ON, M5S 1A8, Canada Article History: Registration Date: 28/05/2009 Received Date: 29/12/2008 Accepted Date: 16/05/2009 Online Date: 10/07/2009 Article note: Preliminary results were presented at the meeting of 10th International Society of Blood Substitutes, Providence, Rhode Island, 13 June 2005. Dr. Hare is a recipient of the Bristol-Myers Squibb-CAS Career Scientist Award. Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1532-2) contains supplementary material, which is available to authorized users.

Byline: Thomas J. Morgan (1), Balasubramanian Venkatesh (2), Jonathan Hall (3) Keywords: Acid--base; Balanced crystalloid; Haemodilution; Strong ion difference Abstract: Objective To study the acid--base effects of crystalloid strong ion difference (SID) during haemodilution. Design Prospective in vivo study. Setting University laboratory. Subjects Anaesthetised, mechanically ventilated Sprague-Dawley rats. Interventions Rats were studied in seven groups of three. Each group underwent normovolaemic haemodilution with one of seven crystalloids, with SID values from 0 to 40 mEq/l. Six exchanges of 9 ml crystalloid for 3 ml blood were performed. Measurements and main results [Hb] fell from 142+-17 to 44+-10 g/l (p Conclusions There is a linear relationship between crystalloid SID and post-dilutional metabolic acid--base status. The SID of a crystalloid balanced for normovolaemic haemodilution is 24 mEq/l. These principles are applicable in designing fluids for volume resuscitation, acute normovolaemic haemodilution and cardio-pulmonary bypass. Author Affiliation: (1) Adult Intensive Care Unit, Mater Misericordiae Hospital, Raymond Terrace, 4101, South Brisbane, Queensland, Australia (2) The Princess Alexandra and Wesley Hospitals, Brisbane, Australia (3) Division of Anesthesiology and Intensive Care, Royal Brisbane Hospital, Brisbane, Queensland, Australia Article History: Registration Date: 09/01/2004 Received Date: 07/09/2003 Accepted Date: 06/01/2004 Online Date: 28/02/2004

Byline: A. Bacher (1), N. Mayer (1), A. M. Rajek (1), W. Haider (1) Keywords: Cardiopulmonary bypass; Hypothermic; Pulsatile; Heart, open heart surgery; Coronary artery bypass graft; Haematocrit; Haemoglobin, concentration; Oxygen, content; Perfusion, splanchnic; Tonometry, gastric; Gastric mucosal pH Abstract: Objective Acute normovolaemic haemodilution with subsequent autologous blood transfusion after surgery is widely used to reduce homologous blood requirements during cardiac surgery. The hypothesis tested was whether a low intraoperative haematocrit (Hct) resulting from haemodilution decreases gastric mucosal pH (pHi). Design Prospective clinical investigation. Setting University Hospital of Vienna, Austria. Patients 16 consecutive patients scheduled for elective cardiac surgery. Interventions The patients were randomly assigned to one of two groups: In 10 patients (group 1), 500 ml of blood was withdrawn and stored after anaesthesia induction. An equal amount of 6 % hydroxyethyl starch was simultaneously infused. After discontinuation of cardiopulmonary bypass (CPB), the autologous blood unit was transfused. Six patients (group 2), who were not subjected to haemodilution and autologous blood transfusion served as controls. In all patients, a gastric tonometry probe was inserted. Measurements and results Measurements of pHi and Hct were performed before and after acute normovolaemic haemodilution, during pulsatile hypothermic (30--32 degC) CPB, after rewarming, and 30 min after autologous blood transfusion in group 1, and at corresponding time intervals in group 2. Repeated measures analysis of variance and the Mann-Whitney U test were used for statistical analysis. Data are presented as means +- standard error of the mean. Haemodilution in group 1 caused a significant and persistent decrease in Hct (after haemodilution in group 1 34 +- 1 vs 40 +- 1 % in group 2). In both groups, pHi decreased during rewarming and after termination of CPB. However, in group 1, pHi was better preserved than in group 2 (rewarming: 7.44 +- 0.02 vs 7.34 +- 0.04 after CPB: 7.38 +- 0.03 vs 7.28 +- 0.02 p < 0.05). Conclusions Acute normovolaemic haemodilution does not aggravate gastric mucosal acidosis during cardiac surgery. Author Affiliation: (1) Department of Anesthesiology and General Intensive Care, University of Vienna, AKH, Wahringer Gurtel 18-20, A-1090, Vienna, Austria Article History: Registration Date: 23/03/2009 Received Date: 04/09/1997 Accepted Date: 17/12/1997 Article note: This study was performed at the Department of Anaesthesiology and General Intensive Care, University of Vienna, Austria. The study was financed with the department's own financial resources. The study was presented in part at the 26th Educational & Scientific Symposium of the Society of Critical Care Medicine, 6--10 February 1997, San Diego, California, USA