Replacement of aprotinin by ε-aminocaproic acid in infants undergoing cardiac surgery: consequences for blood loss and outcome.

BACKGROUND: Once aprotinin was no longer available for clinical use, ε-aminocaproic acid (EACA) and tranexamic acid became the only two options for antifibrinolytic therapy. We compared aprotinin and EACA with respect to their blood-sparing efficacy and other major clinical outcome criteria in infants undergoing cardiac surgery. METHODS: We retrospectively analysed data from a large consecutive cohort of infants (n=227) aged 31-365 days undergoing primary cardiac surgery requiring cardiopulmonary bypass encompassing the transition from aprotinin to EACA (aprotinin n=88, EACA n=139); all other aspects including the medical team and departmental protocols remained unchanged. The primary outcome was postoperative blood loss measured as chest tube output (CTO). Secondary outcome parameters were transfusion requirements, reoperation due to bleeding, renal, vascular, and neurological complications, and in-hospital mortality. RESULTS: CTO was significantly higher in the EACA patients {aprotinin 18 (13-27) ml kg(-1) 24 h(-1), EACA 23 (15-37) ml kg(-1) 24 h(-1) [mean (inter-quartile range)], P=0.001}, but transfusion requirements and donor exposures were not significantly different. A sensitivity analysis strengthened our finding that the increased blood loss in the EACA group was attributable to lower efficacy of EACA. There were no significant differences in the other clinical outcome measures. CONCLUSIONS: CTO was lower in aprotinin-treated patients. Nonetheless, EACA remains a suitable substitute without measurable differences in other clinical outcome criteria.

Switch from aprotinin to ε-aminocaproic acid: impact on blood loss, transfusion, and clinical outcome in neonates undergoing cardiac surgery.

BACKGROUND: With the withdrawal of aprotinin from worldwide marketing in November 2007, many institutions treating patients at high risk for hyperfibrinolysis had to update their therapeutic protocols. At our institution, the standard was switched from aprotinin to ε-aminocaproic acid (EACA) in all patients undergoing cardiac surgery with extracorporeal circulation including neonates. Although both antifibrinolytic medications have been used widely for many years, there are few data directly comparing their blood-sparing effect and their side-effects especially in neonates. METHODS: Perioperative data from 235 neonates aged up to 30 days undergoing primary cardiac surgery were analysed. Between July 1, 2006 and November 5, 2007, all patients (n=95) received aprotinin. Starting November 6, 2007 until December 31, 2009, all patients (n=140) were treated with EACA. The primary outcome criterion was blood loss; secondary outcome criteria were transfusion requirements, renal, vascular, and neurological complications and also in-hospital mortality. RESULTS: All descriptive and intraoperative data variable were similar. Blood loss was significantly higher in the EACA group (P=0.001), but there was no difference in the rate of re-operation for bleeding (P=0.218) nor the number of transfusions. There were no differences in the incidences of postoperative renal, neurological, and vascular events or in-hospital mortality. CONCLUSIONS: In neonatal patients undergoing cardiac surgery, the switch to EACA treatment led to a higher postoperative blood loss. However, there were no differences in transfusion requirements or major clinical outcomes.

Comparison of blood-sparing efficacy of ε-aminocaproic acid and tranexamic acid in newborns undergoing cardiac surgery.

BACKGROUND: ε-Aminocaproic acid (EACA) and tranexamic acid (TXA) are used for antifibrinolytic therapy in neonates undergoing cardiac surgery, although data directly comparing their blood-sparing efficacy are not yet available. We compared two consecutive cohorts of neonates for the effect of these two medications on perioperative blood loss and allogeneic transfusions. MATERIAL AND METHODS: Data from the EACA group (n = 77) were collected over a 12-month period; data from the tranexamic acid group (n = 28) were collected over a 5-month period. Blood loss, rate of reoperation due to bleeding, and transfusion requirements were measured. RESULTS: There was no significant difference in blood loss at 6 hours (EACA 24 [17-30] mL/kg [median (interquartile range)] vs. TXA 20 [11-34] mL/kg, P = 0.491), at 12 hours (EACA 31 [22-38] mL/kg vs. TXA 27 [19-43] ml/kg, P = 0.496) or at 24 hours postoperatively (EACA 41 [31-47] mL/kg vs. TXA 39 [27-60] mL/kg; P = 0.625) or transfusion of blood products. CONCLUSIONS: ε-Aminocaproic acid and tranexamic acid are equally effective with respect to perioperative blood loss and transfusion requirements in newborns undergoing cardiac surgery.

Cardiac surgery with deep hypothermic circulatory arrest produces less systemic inflammatory response than low-flow cardiopulmonary bypass in newborns.

OBJECTIVE: We sought to compare low-flow cardiopulmonary bypass with deep hypothermic circulatory arrest in respect to the influence on the systemic inflammatory response. METHODS: Twenty-three infants weighing less than 10 kg and scheduled for repair of congenital malformations were enrolled in a randomized, controlled study. Eleven patients underwent cardiac surgery with deep hypothermic circulatory arrest (the DHCA group). Low-flow cardiopulmonary bypass was used in another 12 patients (the LF group). Interleukin 6 and 8 and anaphylatoxin C3a levels were measured 6 times perioperatively. Also, perioperative weight gain and a radiologic soft-tissue index were compared. RESULTS: All patients had an uneventful clinical course. Duration of deep hypothermic circulatory arrest was 40 +/- 4 minutes; the bypass time was significantly shorter in the DHCA group (85 +/- 8 vs 130 +/- 19 minutes). However, the duration of the operation was similar in both groups (245 +/- 30 vs 246 +/- 30 minutes). During cardiopulmonary bypass (rewarming), the concentration of C3a (3751 +/- 388 vs 5761 +/- 1688 ng/mL, mean +/- SEM) was significantly lower in the DHCA group than in the LF group. The interleukin 8 level was significantly lower, and the interleukin 6 level had a tendency to be lower in the DHCA group compared with levels in the LF group. There was less weight gain on the first postoperative day in the DHCA group (65 +/- 61 vs 408 +/- 118 g). The soft-tissue index suggested reduced edema formation in the DHCA group. CONCLUSION: Deep hypothermic circulatory arrest produces less systemic inflammatory response than low-flow cardiopulmonary bypass. In addition, there is an indication of less fluid accumulation postoperatively.

Capillary leak syndrome after cardiopulmonary bypass in elective, uncomplicated coronary artery bypass grafting operations: does it exist?

OBJECTIVE: Operations coupled with cardiopulmonary bypass may provoke a systemic inflammatory response, and it has been suggested that this responses causes capillary leakage of proteins, edema formation, and even organ failure. However, capillary leak syndrome is mainly a clinical diagnosis and has not been verified as yet by actual demonstration of protein leakage from the circulation. We have therefore measured the disappearance of labeled plasma protein before and after cardiopulmonary bypass. METHODS: Sixteen patients scheduled for elective coronary artery bypass grafting were enrolled in a prospective controlled study. The cardiopulmonary bypass circuit was primed with crystalloids only. Tumor necrosis factor alpha, interleukin 6, interleukin 8, anaphylatoxin C3a, and terminal complement complex C5b9 levels were determined before, during, and 3 hours after cardiopulmonary bypass. The transvascular escape rate of plasma protein from the intravascular compartment was assessed by measuring the disappearance of intravenously injected Evans blue dye before and during the third hour after cardiopulmonary bypass. RESULTS: A significant inflammatory response could be demonstrated by means of the 5 measured mediators after bypass. The maximal increase, as compared with the baseline value, was found for interleukin 6 (36-fold). The transvascular escape rate of Evans blue dye was similar before and after bypass (7.6 +/- 0.6%/h vs 7.3 +/- 0.6%/h). CONCLUSIONS: The above data confirm the systemic inflammatory response induced by cardiopulmonary bypass. Contrary to expectations, the transvascular escape rate of Evans blue dye did not change when comparing values before and after bypass. The data do not support the concept of increased protein leakage in the exchange vessels after bypass. We were unable to demonstrate a capillary leak syndrome.

Effect of C1-esterase-inhibitor on capillary leak and inflammatory response syndrome during arterial switch operations in neonates.

OBJECTIVE: To determine if prophylactic administration of C1-esterase-inhibitor would have a beneficial effect on postoperative weight gain and the inflammatory response in neonates undergoing cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: Randomized, double-blinded study. SETTING: University-affiliated heart center. PARTICIPANTS: Twenty-four neonates with transposition of the great arteries. INTERVENTIONS: In group inhibitor (INH) patients (n = 12), 100 IU/kg of C1-esterase-inhibitor (Berinert) was given 30 minutes before CPB. In group placebo (P) patients (n = 12), placebo was administered instead. Interleukin (IL)-6, C3a anaphylatoxin, C1 activity, prekallikrein, Hageman factor, D-dimers, and clinical parameters were measured 6 times perioperatively. MEASUREMENTS AND MAIN RESULTS: All 24 patients had an uneventful clinical course. Mean arterial pressure and pulmonary oxygenation after CPB were superior in group INH patients. The weight gain on postoperative days 1 to 4 was significantly less in group INH patients compared with group P (55 +/- 59 g vs. 340 +/- 121 g, day 1). The concentration of IL-6 (76 +/- 17 pg/mL vs. 262 +/- 95 pg/mL during CPB) was significantly lower in group INH patients compared with group P patients. In contrast, no influence on C3a anaphylatoxin and coagulation factors was found. CONCLUSION: Prophylactic application of C1-esterase-inhibitor in neonates undergoing arterial switch operations produces less inflammatory response compared with placebo. This difference may have contributed to improved clinical parameters, including less weight gain postoperatively.

Does a hyperoncotic cardiopulmonary bypass prime affect extravascular lung water and cardiopulmonary function in patients undergoing coronary artery bypass surgery?

OBJECTIVE: Different types of colloidal priming for cardiopulmonary bypass (CPB) have been used to reduce fluid load and to avoid the fall of plasma colloid osmotic pressure (COP) that leads to edema formation and consequently can cause organ dysfunction. The discussion about the optimal priming composition, however, is still controversial. We investigated the effect of a hyperoncotic CPB-prime with hydroxyethyl starch (HES) 10% (200;0.5) on extravascular lung water (EVLW) and post-pump cardiac and pulmonary functions. METHODS: In 20 randomized patients undergoing elective coronary artery bypass graft surgery (CABG), a colloid prime (COP: 48 mmHg, HES-group, n = 10) and a crystalloid prime (Ringer's lactate, crystalloid group, n = 10) of equal volume were compared with respect to the effects on cardiopulmonary function. Cardiac index (CI), mean arterial pressure (MAP), pulmonary capillary wedge pressure (PCWP), systemic vascular resistance index (SVRI), pulmonary artery pressure (PAP), pulmonary vascular resistance index (PVRI), alveolo-arterial oxygen difference (AaDO(2)), pulmonary shunt fraction (Q(s)/Q(T)), EVLW (double-indicator dilution technique with ice-cold indocyanine green), COP, fluid balance and body weight were evaluated peri-operatively. RESULTS: Pre-operative demographic and clinical data, CPB-time, cross-clamp time and the number of anastomoses were comparable for both groups. During CPB, COP was reduced by 20% in the HES-group (18.9 +/- 3.7 vs. 23.7 +/- 2.2 mmHg, P < 0.05) while it was reduced by more than 50% of the pre-CPB value (9.8 +/- 2.0 vs. 21.4 +/- 2.1 mmHg, P < 0.05) in the crystalloid group (P < 0.05 HES- vs. crystalloid group). Post-CPB EVLW was unchanged in the HES-group but it was elevated by 22% in the crystalloid group (P < 0.05 HES- vs. crystalloid group), CI was higher in the HES-group (3.4 +/- 0.3 vs. 2.7 +/- 0.5l/min, P < 0.05). Fluid balance was less in the HES-group (813 +/- 619 vs. 2143 +/- 538, P < 0.05). Post-operative weight gain could be prevented in the HES-group but not in the crystalloid group (1.5 +/- 1.2 vs. -0.3 +/- 1.5, P < 0.05). No significant differences were seen for MAP, PAP, PCWP, SVRI, PVRI, AaDO(2) and (Q(s)/Q(T)) between the two groups at any time. CONCLUSIONS: Hyperoncotic CPB-prime using HES 10% improves CI and prevents EVLW accumulation in the early post-pump period, while pulmonary function is unchanged. This effect can be of benefit especially in patients with congestive heart failure.

Reduction of pro-inflammatory cytokine levels and cellular adhesion in CABG procedures with separated pulmonary and systemic extracorporeal circulation without an oxygenator.

OBJECTIVE: We have recently shown that a considerable amount of pro-inflammatory cytokines is released during pulmonary passage after aortic declamping in patients undergoing coronary artery bypass grafting. The present study was performed to investigate whether bilateral extracorporeal circulation with the lungs as oxygenators can reduce the inflammatory responses of the lungs. METHODS: Eighteen consecutive patients undergoing coronary artery bypass grafting were randomly assigned to routine extracorporeal circulation with cannulation of right atrium and aorta (routine circulation, ten patients) or to a bilateral extracorporeal circulation with additional cannulation of left atrium and pulmonary artery (bilateral circulation, eight patients). Blood was simultaneously drawn from right atrium and pulmonary vein at 1, 10 and 20 min reperfusion. The levels of interleukin (IL)-6 and IL-8 and the adhesion molecules CD41 and CD62 on platelets and CD11b and CD41 on leukocytes were determined. Because of considerable interindividual scatter, the pulmonary venous levels are normalized to percent of the respective right atrial value at each time point. RESULTS: At 1 min reperfusion pulmonary venous levels of IL-6 and IL-8 in routine circulation were +44+/-15% and +43+/-28% of the respective right atrial values. The respective values in bilateral circulation were -3+/-4% and -6+/-7% (P=0.02 and P=0.05 vs. respective right atrium). Similar increments were found after 10 and 20 min. Platelet-monocyte coaggregates were retained during pulmonary passage at 1 min reperfusion in routine circulation (-21+/-6%), but washed out in bilateral circulation (+5+/-8%, P=0. 007). At 20 min reperfusion, activated polymorphonuclear neutrophils (PMN) were retained in routine circulation (-16+/-9%) but washed out in bilateral circulation (+19+/-29%, P=0.05; all data given as mean+/-SEM). CONCLUSIONS: Bilateral extracorporeal circulation without an artificial oxygenator significantly reduces the inflammatory responses during pulmonary passage after aortic declamping.

Corticosteroids during operations using cardiopulmonary bypass.

Although corticosteroids have been used for more than 30 years in the context of extracorporeal circulation, there is an ongoing debate about the benefits of their routine application. Methylprednisolone was given as early as 1966 to reduce vasoconstriction during cardiopulmonary bypass (CPB) and to prevent low output syndrome thereafter. An explanation for these findings was recently published. Lipid mediators lead to vasoconstriction and inflammatory cytokine production during CPB. There is no doubt about the potential of corticosteroids to reduce inflammatory and enhance anti-inflammatory mediators, while their possible influence on clinical parameters and their side effects are controversial, as discussed in the literature. There have been contradictory results with respect to pulmonary oxygenation, while an increase in the patient's blood glucose levels, however clinically unimportant, could be demonstrated. The influence of other drugs affecting the inflammatory response has to be taken into account, leading to a patient-specific recommendation for the use of corticosteroids during operations requiring CPB.

Drew-Anderson technique attenuates systemic inflammatory response syndrome and improves respiratory function after coronary artery bypass grafting.

BACKGROUND: Cardiopulmonary bypass causes inflammatory reactions leading to organ dysfunction postoperatively. This study was undertaken to determine whether using patients' own lungs as oxygenator in a bilateral circuit (Drew-Anderson Technique) could reduce systemic inflammatory response to cardiopulmonary bypass, improving patients clinical outcome following coronary artery bypass grafting. METHODS: A prospective randomized controlled trial involving 30 patients, divided in two groups of 15 patients each, undergoing elective coronary artery bypass grafting, was undertaken. In the Drew-group bilateral extracorporeal circulation using patient's lung as oxygenator was performed. The other patients served as control group, where standard cardiopulmonary bypass procedure was used. RESULTS: Pro-inflammatory and anti-inflammatory mediators were measured. Peak concentrations of proinflammatory interleukin-6, interleukin-8, were significantly lower in 15 patients undergoing Drew-Anderson Technique compared with the concentrations measured in 15 patients treated with standard cardiopulmonary bypass technique. Differences in patient recovery were analyzed with respect to time of intubation, blood loss, intrapulmonary shunting, oxygenation, and respiratory index. In patients undergoing uncomplicated coronary artery bypass grafting procedures bilateral extracorporeal circulation using the patients' own lung as oxygenator provided significant biochemical and clinical benefit in comparison to the standard cardiopulmonary bypass procedure. CONCLUSIONS: This prospective randomized clinical study has demonstrated that exclusion of an artificial oxygenator from cardiopulmonary bypass circuit significantly decreases the activation of inflammatory reaction, and that interventions that attenuate this response may result in more favorable clinical outcome.

High-dose aprotinin modulates the balance between proinflammatory and anti-inflammatory responses during coronary artery bypass graft surgery.

OBJECTIVE: To rule out the effect of high-dose aprotinin in respect to the balance of proinflammatory and anti-inflammatory mediators induced by cardiopulmonary bypass (CPB). DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: University-affiliated cardiac center. PARTICIPANTS: Twenty patients scheduled for coronary artery bypass graft surgery. INTERVENTIONS: In group A patients (n = 10), high-dose aprotinin was administered (2 x 106 KIU pre-CPB, 2 x 10(6) KIU in prime, 500,000 KIU/hr during CPB). In group C patients (n = 10), placebo was used instead. Proinflammatory interleukin (IL)-6, anti-inflammatory IL-1-receptor antagonist, and clinical parameters were measured 8 times perioperatively. The values are presented as mean +/- SEM. MEASUREMENTS AND MAIN RESULTS: Four hours after CPB, IL-6 concentration reached the maximum value, being significantly lower in group A patients as compared with group C patients (615 +/- 62 pg/mL v 1,409 +/- 253 pg/mL; p = 0.019). On the first postoperative day, the concentration of IL-6 in group A patients remained lower (219 +/- 24 pg/mL v 526 +/- 123 pg/mL; p = 0.015). In contrast, IL-1-receptor antagonist concentration was higher in group A patients as compared with group C patients after CPB (13,857 +/- 4,264 pg/mL v 5,675 +/- 1,832 pg/mL; p = 0.03). Total postoperative blood loss was lower in group A patients as compared with group C patients (648 +/- 64 mL v 1,284 +/- 183 mL; p = 0.002). CONCLUSIONS: High-dose aprotinin treatment reduced the inflammatory reaction and postoperative blood loss. The anti-inflammatory reaction was significantly enhanced in these patients, which suggests that the physiologic reaction of the organism to reduce the deleterious effects from CPB is more pronounced by using high-dose aprotinin.

Influence of combined zero-balanced and modified ultrafiltration on the systemic inflammatory response during coronary artery bypass grafting.

OBJECTIVE: To evaluate whether combined zero-balanced and modified ultrafiltration affects the systemic inflammatory response in coronary artery bypass graft (CABG) patients. DESIGN: Randomized and controlled. SETTING: University-affiliated heart center. PARTICIPANTS: Forty-three patients scheduled for elective CABG. INTERVENTIONS: In the ultrafiltration group (UF group; n = 21), zero-balanced ultrafiltration was performed during rewarming and modified ultrafiltration immediately after the end of cardiopulmonary bypass (CPB). A control group of patients (n = 22) was treated identically to the treatment group except no ultrafiltration process was performed. MEASUREMENTS AND MAIN RESULTS: Immediately after CPB (ie, after zero-balanced ultrafiltration), and again after the modified ultrafiltration, the concentrations of interleukin-6 and interleukin-8 were significantly less (p < 0.05) in the UF group compared with the control group. Both proinflammatory cytokine levels peaked at 2 and 4 hours after CPB, at which time no difference between the two groups could be observed. The levels of measured anti-inflammatory mediators (interleukin-10 and interleukin-1 receptor antagonist) did not show any difference between the two groups. Intrapulmonary shunt fraction decreased in the course of the modified ultrafiltration from 31% +/- 1.2% to 25% +/- 1.3% (p < 0.01), whereas mean arterial pressure increased (69 +/- 1.8 to 80 +/- 2.8 mmHg; p < 0.01); neither parameter changed in the control group. Time to extubation was shorter in the UF group (6.1 +/- 0.5 v 8.6 +/- 0.7 hours; p < 0.05). CONCLUSION: It was concluded that the use of ultrafiltration diminished inflammatory response in a very limited time period immediately after CPB and, probably as a consequence, slightly improved clinical parameters.

Does high-dose methylprednisolone in aprotinin-treated patients attenuate the systemic inflammatory response during coronary artery bypass grafting procedures?

OBJECTIVE: To discover the possible effects of methylprednisolone on the systemic inflammatory response during aprotinin treatment. DESIGN: Randomized, double-blinded study. SETTING: University-affiliated heart center. PARTICIPANTS: Fifty-two patients scheduled for elective coronary artery bypass grafting. INTERVENTIONS: In the methylprednisolone group (n = 26), 1 g of methylprednisolone was administered 30 minutes before cardiopulmonary bypass (CPB). The 26 control patients received a placebo instead. High-dose aprotinin was administered to all participants. MEASUREMENTS AND MAIN RESULTS: After CPB, the concentration of the proinflammatory cytokines, interleukin-6 and interleukin-8, was significantly less in the methylprednisolone group. The anti-inflammatory interleukin-10 concentration was, in contrast, greater. After CPB, PaO2 was greater in the methylprednisolone group (245+/-17 v 195+/-16 mmHg). Dynamic pulmonary compliance was also greater, whereas the alveolar-arterial oxygen difference was less (376+/-17 v 428+/-16 mmHg). On arrival in the intensive care unit, the oxygen delivery index was greater in the methylprednisolone group (62+/-2.7 v 54+/-2.3 mL/min/m2) and the oxygen extraction rate was less (25%+/-0.02% v 30%+/-0.02%). After CPB, the cardiac index was significantly greater in the methylprednisolone group (4.1+/-0.2 v 3.6+/-0.2 L/min/m2). These patients had less blood loss postoperatively (616+/-52 v 833+/-71 mL; p = 0.017) and a greater urine output (8,015+/-542 v 6,417+/-423 mL/24 h; p = 0.024). CONCLUSION: The use of methylprednisolone attenuates the systemic inflammatory response during aprotinin treatment and improves clinical outcome parameters.

Induction of anesthesia by titration of eltanolone compared with thiopental and etomidate for coronary artery bypass grafting.

STUDY OBJECTIVE: To evaluate whether induction of anesthesia with eltanolone in coronary artery bypass graft (CABG) patients is associated with greater hemodynamic stability than either thiopental sodium or etomidate. DESIGN: Randomized, controlled study. SETTING: University hospital. PATIENTS: 75 ASA physical status III and IV patients scheduled for elective CABG over 18 years of age, with left ventricular ejection fraction over 30%. INTERVENTIONS: The participants were prospectively randomized into three groups, each group consisting of 25 patients. Anesthesia was induced by titration of either eltanolone, thiopental sodium, or etomidate. The end point was "loss of verbal contact." MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables were recorded in the awake state, 2 minutes after induction, after administration of fentanyl 0.01 mg/kg, and 2 and 5 minutes after intubation. After induction of anesthesia, cardiac index (CI) decreased from 2.6 +/- 0.5 to 2.2 +/- 0.5 Lxmin-1xm-2 in the eltanolone group and remained at this value throughout the study period in contrast to the control groups. After fentanyl was given, mean arterial pressure was significantly lower in the case of eltanolone (69 +/- 15 mmHg) compared with thiopental (81 +/- 19 mmHg) and etomidate (84 +/- 18 mmHg). Mean arterial pressure remained significantly lower at the points of measurement after intubation. Two minutes after intubation, CI was likewise significantly lower in the eltanolone group (2.2 +/- 0.4 Lxmin-1xm-2) compared with the thiopental group (2.7 +/- 0.7 Lxmin-1xm-2). CONCLUSIONS: Eltanolone produces more hemodynamic depression compared with etomidate and thiopental when administered in combination with fentanyl 10 micrograms/kg.

Transfusion of platelet-rich plasma from the organ donor during cardiac transplantation.

STUDY OBJECTIVE: To evaluate whether transfusion of platelet-rich plasma from the organ donor during cardiac transplantation can influence the amount of the needed homologous blood products. DESIGN: Randomized, controlled study. SETTING: University hospital. PATIENTS: 16 ASA physical status III patients undergoing orthotopic cardiac transplantation. INTERVENTIONS: Eight patients received donor plasma, while another 8 patients served as a control group. Blood from the organ donor was acquired during cardiac explantation. Thereafter platelet-rich plasma was separated by plasmapheresis (2400 turns per minute). The plasma was then transfused to the organ recipient at the end of the cardiac transplantation. The control group received a similar amount of albumin 5%. MEASUREMENTS AND MAIN RESULTS: In the patients who received donor plasma, the platelet count increased significantly from 98,000 +/- 49,000 mm-3 to 123,000 +/- 55,000 mm-3, the postoperative requirement of packed red blood cells (PRBCs) was 5.8 +/- 4.5 units, which was significantly lower as compared to the control group (10.8 +/- 5.9 units). CONCLUSIONS: Transfusion of platelet-rich plasma from the organ donor to the recipient was confirmed to be feasible, the number of postoperatively transfused PRBCs was reduced.

Bolus administration of eltanolone, thiopental, or etomidate does not affect systemic vascular resistance during cardiopulmonary bypass.

OBJECTIVE: To discover possible effects on systemic vascular resistance of the anesthetic induction agent eltanolone in comparison with thiopental and etomidate. The measurements were performed during cardiopulmonary bypass to maintain a constant cardiac output (approximately pump flow). DESIGN: The patients were prospectively randomized in three groups to receive either eltanolone, thiopental, or etomidate. SETTING: University hospital as a single center. PARTICIPANTS: Seventy-five patients scheduled for elective coronary artery bypass grafting. INTERVENTIONS: The anesthetic induction agents were repeated at the same dosage when cardiopulmonary bypass was instituted. The respective mean dosages were eltanolone, 0.41 +/- 0.1 mg/kg; thiopental, 2.88 +/- 0.62 mg/kg; etomidate, 0.26 +/- 0.06 mg/kg. MEASUREMENTS AND MAIN RESULTS: Systemic vascular resistance was calculated from the mean of a triple measurement (normal pump flow and +/- 20%). Points of measurement were before, and 2 and 5 minutes after injection of the hypnotic agent. None of the injected drugs made a significant change in the systemic vascular resistance. A small (not significant) decrease from 1,295 +/- 296 dyne/s/cm-5 to 1,196 +/- 323 dyne/s/cm-5 (mean +/- SD) was seen in the eltanolone group, whereas the other patients did not show any change during the study period. CONCLUSIONS: The reason for the significant reduction of the arterial pressure attributed to anesthetic induction by eltanolone may be more a cardiodepressive effect than a direct vasodilation.

[Hemodynamic effects of three different dosages of the induction hypnotic, eltanolone, in coronary surgery patients]. / Hämodynamische Wirkungen von 3 uterschiedlichen Dosierungen des Induktions-hypnotikums Eltanolon bei koronarchirurgischen Patienten.

UNLABELLED: Eltanolone is a new steroid anaesthetic agent that is 5-beta reduced derivative of progesterone. In the present study we investigated the haemodynamic effects of eltanolone or thiopentone in patients scheduled for coronary artery bypass grafting. METHODS: After obtaining approval of the institutional ethics committee and informed patient consent, 40 patients (age 45-70 years, ASA III and IV, ejection fraction > 50%, cardiac index > 2.5 l/min per m2) were randomly assigned to four groups, each containing 10 patients: After premedication with 2 mg flunitrazepam, anaesthesia was induced with 3 mg/kg thiopentone in group 1, 0.5 mg/kg eltanolone in group 2, 0.75 mg/kg eltanolone in group 3, 1.0 mg/kg eltanolone in group 4. Each patient additionally received 3 mirograms/kg fentanyl after induction and 0.1 mg/kg pancuronium. Heart rate, mean arterial pressure, pulmonary arterial pressure, central venous pressure, pulmonary artery occlusion pressure and cardiac output were recorded in the awake state, 2 min after induction of anaesthesia, and 1 and 5 min after intubation. Cardiac index and systemic vascular resistance were calculated. RESULTS: Two minutes after induction, mean arterial pressure was significantly lower than the baseline (P < 0.05) in each group. Mean arterial pressure changes were more prominent in the case of eltanolone, but intergroup tests did not reveal significant differences between the four groups. There was a fall in cardiac index in all groups, and these changes reached the level of significance only in the thiopentone patients. The most obvious difference between eltanolone and thiopentone was systemic vascular resistance. It dropped significantly 2 min after induction with eltanolone at all dosages. In contrast, there was an increase in systemic vascular resistance following induction of anaesthesia with thiopentone. Intergroup tests also showed significantly (P < 0.05) lower systemic vascular resistance 1 and 5 min after intubation with eltanolone compared to thiopentone. DISCUSSION: Mean arterial pressure reduction induced by eltanolone is most likely the result of the combination of a decrease in cardiac contractility and peripheral vasodilatation. In contrast, mean arterial pressure reduction in the case of thiopentone seems to be exclusively related to the negative inotropic properties of the drug. Results of a dosage finding study [5] with eltanolone revealed an AD50 of 0.33 mg/kg. In our study 0.5 mg/kg eltanolone brought all the patients to sleep within 2 minutes. The haemodynamic results do not show any significant difference up to twofold dosage. Therefore, the therapeutic margin seems to be large. Because of considerable interindividual variability additional studies in larger collectives are required for definitive evaluation of the drug.

Hemodynamic effects of anesthetic induction with eltanolone-fentanyl versus thiopental-fentanyl in coronary artery bypass patients.

We evaluated the hemodynamic profile of eltanolone and fentanyl versus thiopental and fentanyl anesthetic induction in patients with documented coronary artery disease. Fifty patients scheduled for coronary artery bypass grafting were randomly assigned to two treatment groups (25 patients each). Anesthesia was induced by eltanolone (0.5 mg/kg) or by thiopental (3 mg/kg). Each patient also received 3 micrograms/kg fentanyl and 0.1 mg/kg vecuronium. Heart rate, arterial, pulmonary arterial, central venous, and pulmonary capillary wedge pressures, and cardiac output were determined in the awake state, 2 min after induction of anesthesia, and at 1 and 5 min after intubation, which was performed 3 min after induction. Between-group statistics showed significantly (P < 0.05) lower mean arterial pressure and systemic vascular resistance for eltanolone-treated patients at all measuring points. Pulmonary capillary wedge pressure was lower at 1 min after intubation; left ventricular stroke work index was lower at 1 and 5 min after intubation in the eltanolone group. We conclude that the lower mean arterial pressure with eltanolone as compared to thiopental is a result of greater peripheral vasodilation.

Evaluation of right ventricular function by assessment of cardiac efficiency: influence of induction of anaesthesia in coronary artery bypass grafting patients.

Considering the heart as a physical pump cardiac efficiency is calculated from the ratio of cardiac work performed to the maximum level of energy of the heart. The aim of the study was to compare cardiac efficiency with cardiac output and right ventricular ejection fraction. Nine patients scheduled for coronary artery bypass grafting were investigated. A femoral arterial and a right ventricular ejection fraction pulmonary artery catheter were placed in the awake state. Anaesthesia was induced with eltanolone and fentanyl. Cardiac output, pulmonary artery and central venous pressures, and right ventricular ejection fraction were measured in the awake state (baseline), 2 min after induction of anaesthesia and 1 and 5 min after intubation. Cardiac efficiency was calculated by dividing the stroke work by the maximum energy of the heart as calculated from the pressure volume diagram. An analysis of variance was carried out for cardiac efficiency, cardiac output and right ventricular ejection fraction. Cardiac efficiency was significantly (p < 0.05) reduced 1 min after intubation from 28 +/- 11 to 14 +/- 5%. In contrast the right ventricular ejection fraction (from 48 +/- 10 to 35 +/- 13%) and cardiac output (from 6.5 +/- 1.5 to 5.3 +/- 1.2 L/min) did not change significantly during the induction of anaesthesia. Cardiac efficiency was found to be a more sensitive parameter to describe changes in the right ventricular function than the ejection fraction and cardiac output during induction of anaesthesia with eltanolone and fentanyl which was used as a model to vary cardiac performance and afterload.