Full Systemic Heparinization Research Articles

Preoperative Angiotensin System Inhibitor Use Attenuates Heparin-Induced Hypotension in Patients Undergoing Cardiac Surgery

Both angiotensin system inhibitor (ASI) use and heparin are associated with hypotension. This study attempted to determine whether preoperative ASI therapy affected the hemodynamic response to heparin administered to patients undergoing cardiac surgery. Sixty-two patients undergoing elective cardiac surgery requiring full (300 units/kg) systemic heparinization were studied prospectively. Thirty-three patients were receiving preoperative ASI therapy, whereas 29 patients were not. Anesthetic technique and mechanical ventilation parameters were standardized. Hemodynamics were recorded at 3 time points: baseline (just before the administration of heparin), 1-minute post-heparin administration, and 4-minute post-heparin administration. Single university hospital. Patients undergoing elective cardiac surgery. None. The 2 groups were similar regarding preoperative demographics and baseline hemodynamics. Baseline mean arterial pressure (MAP) in non-ASI patients was 82.0 mmHg, and it decreased significantly to 76.3 mmHg (1 min; p<0.05) and 70.7 mmHg (4 min; p<0.05) following heparin administration. MAP values in ASI patients were 81.9 mmHg, 81.8 mmHg, and 76.8 mmHg at baseline, 1-minute post-heparin, and 4-minute post-heparin administration, respectively (changes not significant).Within-group analysis revealed that non-ASI patients experienced significant decrease in MAP at 1-minute (-6.6%, p = 0.01) and 4-minute (-13.0%, p = 0.0011) post-heparin administration, whereas ASI patients did not (+1.9%, p = 0.52; -3.8%, p = 0.16, respectively). Between-group analysis revealed that differences in MAP values at 1 minute were significant (p = 0.03), whereas differences at 4 minutes were not significant (p = 0.05). This prospective clinical study indicated that preoperative ASI therapy until the day before surgery may attenuate heparin-induced hypotension. Definitive mechanistic insight requires further clinical study.

A simple bypass technique for superior vena cava reconstruction☆

Superior vena cava (SVC) clamping can be required during thoracic surgery for SVC replacement or repair. In such cases, bypass techniques can be necessary to avoid hemodynamic instability, cerebral venous hypertension and hypoperfusion. Here, we report a novel and simple SVC bypass technique which does not require full systemic heparinization, specialized cannulation techniques or pumping devices and which can be applied percutaneously in the preoperative phase or intraoperatively. The preoperative shunt consisted in two Swan-Ganz catheters inserted in the jugular and femoral veins and connected by perfusion tubing with a three way stopcock. The intraoperative shunt consisted of a Pruitt(®)-catheter inserted in the left innominate vein and connected to a femoral Swan-Ganz catheter by perfusion tubing. We validated our system in seven patients undergoing SVC reconstruction. We monitored the systemic arterial blood pressures, the heart rate and vasoactive peptide requirements throughout the procedure. We also determined the neurological status and the in-hospital morbidity and mortality for each patient. Using this bypass, SVC clamping caused no hemodynamic instability, no neurological impairments and no in-hospital complications or deaths. This simple temporary SVC bypass procedure is safe and avoids hemodynamic instability and cerebral venous hypertension.

Endovascular Treatment of Blunt Traumatic Thoracic Aortic Injury

Blunt traumatic thoracic aortic injury (BTTAI) is a lethal injury associated with a prehospital mortality of 80% to 90%. Patients arriving in the emergency room and considered appropriate to undergo emergency open surgical repair still have a mortality rate of 15% to 30% because of severe associated injuries. Conventional open surgical repair requires a left thoracotomy, single lung ventilation, aortic-cross clamping and unclamping, with or without the adjunct use of partial or full cardiopulmonary bypass and systemic heparinization. All this leads to significant physiological stress and surgical trauma resulting in perioperative complications such as major blood loss, coagulopathy, myocardial infarction, stroke, respiratory failure, renal failure, bowel infarction, and paraplegia. Despite advances in anesthesia, critical care medicine, and surgical techniques, a recent meta-analysis showed no definite improvement in operative mortality over the past decade, following open surgical repair in patients with BTTAI. Endovascular repair of BTTAI does not require a thoracotomy, single lung ventilation, aorticcross clamping and unclamping, or systemic heparinization. As a result, endovascular repair of BTTAI has emerged as an effective, minimally invasive treatment alternative, especially in patients with severe concomitant injuries, which may be prohibitive to open surgical repair. Recent published studies have shown that endovascular repair of BTTAI is associated with lower morbidity, mortality, stroke, and paraplegia/paraparesis rates, when compared with open surgical repair of BTTAI.

Adhesion of thrombotic components to the surface of a clinically used oxygenator is not affected by Trillium coating

The Trillium coating is designed to minimize adsorption of protein and the attachment of cells and other particles. The present study was undertaken to investigate the effect of surface coating on the adhesion of thrombotic components (activated platelets, white blood cells and fibrin) to the surface of a clinically used oxygenator. Twenty patients undergoing elective coronary artery bypass grafting (CABG) were randomized to one of the two oxygenator groups: non-coated (NC, n = 10) or Trillium-coated (TC, n = 10). Platelet and white blood cell counts and factor XIIa concentrations were determined prior to the induction of anesthesia and at the end of cardiopulmonary bypass (CPB). Binding of activated platelets, white blood cells and fibrin to the artificial surfaces was quantified by means of antibody binding and histological validation was achieved by scanning electron microscopy. Patient demographic and CPB data were similar for the two groups. No significant differences between the groups were found for any of the tested thrombotic components. However, observations from our scanning electron microscopy suggested a release of formed particles from the Trillium-coated surface. Primary adhesion of activated platelets, white blood cells and fibrin to the artificial surface of the venous blood inlet from an oxygenator is not affected by the Trillium surface coating under conditions of full systemic heparinization.

Use of Concomitant Glycoprotein IIb/IIIa Inhibitors with Catheter-directed Peripheral Arterial Thrombolysis

THROMBOSIS of a peripheral artery or bypass graft can result in severely compromised nutrient blood flow to the limb. If left untreated, gangrene can develop and amputation may be necessary. When peripheral arterial thrombosis is diagnosed, percutaneous delivery of thrombolytic agents offers the opportunity to restore circulation and expose any underlying culprit lesion responsible for the occlusion. All clinically available thrombolytic agents are plasminogen activators; they convert plasminogen to its active form plasmin. Fibrin-bound plasmin then cleaves the insoluble fibrin polymer, forming smaller, soluble fibrin degradation products. If all goes as planned, antegrade arterial blood flow is restored and limb perfusion is returned to normal. Thrombolytic agents were first discovered in the early 1930s, when Tillett and Garner (1) noted fibrinolytic properties of a product of the bacterium streptococcus. Of necessity, however, clinical use of this “streptococcal fibrinolysin” awaited the formulation of a suitably pure form of the agent. After investigation in animal models of vascular thrombosis (2) and after testing intrapleural administration of the newly renamed agent streptokinase in patients with loculated hemothoraces (3), Tillett and colleagues (4) infused the agent into the veins of a small number of volunteers; this seminal work was published in 1955. Just 1 year later, Cliffton and Grunnet (5) published a report on the administration of a streptokinase and plasminogen mixture to dissolve pathologic occlusive thrombi in peripheral vessels. Interestingly, some of Cliffton’s patients were treated through a primitive catheter-directed intraarterial approach (5,6). Unfortunately, innovation in the development of thrombolytic strategies slowed dramatically thereafter. Novel approaches to intraarterial thrombolytic therapy awaited the development of adequate guide wire and catheter technical armamentaria and the emergence of a cadre of interventionalists skillful in the use of percutaneous techniques. Although quantum leaps would not be realized for years to come, a group led by Dotter (7) popularized catheter-directed thrombolytic infusion in the 1970s with use of low-dose streptokinase in an effort to limit distant bleeding complications. A decade later, McNamara and Fischer (8) published excellent results with catheter-directed urokinase (UK) administered in very high doses for just a few hours, then in decreasing doses in a stepwise fashion over a period as long as 2 days. By the decade of the 1990s, UK was the most commonly employed peripheral thrombolytic agent. The Rochester (9), STILE (10), and TOPAS (11,12) randomized clinical trials established the utility of catheter-directed thrombolysis in comparison with primary operative therapy. Virtually all thrombolytic cases in the United States were performed with use of UK, an agent that became the workhorse of the peripheral interventionalist. Then, with little warning, the US Food and Drug Administration raised concerns about the manufacture of UK, and its manufacturer, Abbott Laboratories, voluntarily withdrew UK from the marketplace in early 1999 (13). Although the controversy over UK was at first greeted with gloom by interventional radiologists and vascular surgeons, the absence of this familiar agent prompted investigation into alternative thrombolytic agents and treatment strategies. Alteplase, reteplase, and tenecteplase were studied (14). Many practitioners became relatively comfortable with the alternate agents, although anecdotal impressions surfaced suggesting that these alternative agents may be associated with an increased risk of hemorrhage. So while clinicians were comfortable adding full systemic heparinization to a regimen of intraarterial UK, heparin was kept to minimal, almost homeopathic doses with the other agents (15). In this renewed era of investigation stimulated by the loss of UK from the marketplace, clinicians sought alternate treatment strategies to enhance the efficacy of thrombolytic therapy. These investigations arose after realFrom the Department of Vascular Surgery, Desk S40, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195. Received March 10, 2004; accepted March 10. Address correspondence to K.O.; E-mail: ourielk@ccf.org

Case 4—2002 Near-fatal pulmonary embolism in the immediate postoperative period after off-pump coronary artery bypass graft surgery

A 72-year-old man with known coronary artery disease (exertional angina and 2 previous myocardial infarctions) was admitted to the hospital with a new non–Q-wave myocardial infarction as evidenced by elevated serum troponin concentration and non–Q-wave electrocardiogram changes in the anteroseptal leads. Acute management included intravenous nitrate therapy and subcutaneous enoxaparin, 80 mg twice a day; and long-term cardiac medications, including aspirin, furosemide, isosorbide mononitrate, atenolol, and ramipril, were continued. Thrombolytic therapy was not administered on this occasion. Relevant medical history included noninsulin-dependent diabetes mellitus and a dual-chamber pacemaker (Pacesetter Paragon III; St Jude Medical, St. Paul, MN), which was inserted 5 years previously for symptomatic bradycardia. The patient underwent a subsequent exercise stress test using a modified Bruce protocol. Electrocardiogram changes showed anterior ST depression at 7 minutes. He was referred for coronary angiography, which revealed significant stenosis of the left mainstem (60%), proximal anterior descending (99%), and midcircumflex (60%) coronary arteries. The right coronary artery had minor plaques in the midvessel only. Left ventricular function was preserved on ventriculography. Two hours after coronary angiography, the patient suffered further episodes of angina pectoris that responded to intravenous nitrate therapy. This condition was associated with 2 episodes of collapse on standing. The attending physician noted symptomatic bradycardia and attributed it to the vasodilatory effects of nitrate therapy. In view of his further chest pain, an intravenous infusion of unfractionated heparin was started at 12 U/kg/h. The heparin was titrated to maintain an activated partial thromboplastin ratio of twice control and was continued until surgery. The patient’s pacemaker function was not tested preoperatively, and he did not undergo a preoperative transthoracic echocardiography examination. Off-pump coronary artery bypass graft (OP-CAB) surgery was done the next day using the Octopus (Medtronic Inc, Minneapolis, MN) stabilizing device. Monitoring included electrocardiogram, peripheral oxygen saturation, end-tidal gas composition, invasive blood pressure monitored through the right radial artery, and central venous pressure monitoring. During the performance of coronary anastomosis, full systemic heparinization with 240 mg of unfractionated heparin (300 U/kg) was used. Effectiveness of anticoagulation was monitored intraoperatively by the activated coagulation time (ACT), maintaining an ACT 400 seconds throughout coronary artery grafting. On completion of the anastomoses, the heparin was fully reversed using 240 mg of protamine sulfate (1:1 ratio). The left internal mammary artery was found unsuitable after harvesting, and a solitary saphenous vein graft was used from the aorta to the distal left anterior descending artery. The procedure was well tolerated without any hemodynamic compromise, and no inotropic support was required. After surgery, the patient was returned to the intensive care unit. The first 2 hours in the intensive care unit were complicated by persistent systolic hypotension of 75 mmHg, attributed to excessive bleeding from the left pleural tube. Approximately 750 mL of blood drained. This hypotension was unresponsive to transfusion of 6 U of packed red blood cells and 2,000 mL of colloid. Inotropic support (epinephrine, 0.28 g/kg/min) now was required. At this point, a sudden marked change in central venous pressure (from 7 to 20 mmHg) was noted, and transesophageal echocardiography (TEE) was performed immediately to exclude cardiac tamponade. TEE examination revealed preserved systolic function and an underfilled left ventricle. In contrast, the right ventricle was dilated and akinetic. Trivial tricuspid regurgitation was noted. The permanent pacing lead was also noted within the right ventricle. In addition to a dilated right ventricle, the main and right branches of the pulmonary artery were dilated There was no evidence of tamponade; however, a large collection of blood was seen *M.J. Platt, S. Davies, and B. Riedel

Duroflo II heparin bonding does not attenuate cytokine release or improve pulmonary function

Background. Comparison of the cytokine generation and leukocyte activation properties of Duroflo II heparin bonded bypass circuit (Baxter Healthcare Corp, Compton, UK) and the conventional cardiopulmonary bypass circuit. Attempt to correlate these to pulmonary dysfunction postoperatively. Methods. Forty patients undergoing elective, isolated coronary artery bypass grafting were randomly allocated to have either plain extracorporeal circuits (group C) or heparin bonded extracorporeal circuits (group H). Full systemic heparinization was used in all patients. The inflammatory response was assessed by measuring plasma levels of interleukin-6, interleukin-8, interleukin-10, and polymorphonuclear elastase. Gas exchange was assessed by measuring the Pa o 2/F io 2 ratio. Results. Significant impairment of oxygenation was seen in both groups with the lowest values at the end of the operation before a gradual return to normal during the next 6 hours. There were no differences between the groups in gas exchange or times to extubation. There were significant elevations in all the cytokines, with interleukin-6 levels peaking at 4 hours in group H and 24 hours in group C, before starting to return to normal at 48 hours. The patterns of interleukin-8 and interleukin-10 rise were identical in the two groups. Polymorphonuclear elastase reached a peak at the end of the operation in group H and remained elevated up to 24 hours, whereas levels continued to rise in group C up to 4 hours. There were no significant differences in levels between groups at any time. There were no differences between the groups in blood loss or blood product usage. Conclusions. Cardiopulmonary bypass induces a systemic inflammatory response with release of cytokines and activation of leukocytes. This correlates with the severe deterioration in pulmonary gas exchange from preoperative levels up to 6 hours postoperatively ( p < 0.05). In the presence of systemic heparinization, Duroflo II heparin bonding of the circuits has minor effects on the pattern of evolution of this inflammatory response.

The antithrombin III–saving effect of reduced systemic heparinization and heparin-coated circuits

Objective: To investigate the perioperative changes of antithrombin III (AT-III) activity using reduced systemic heparinization and the possible role of AT-III in determining a better postoperative outcome. Design: Prospective randomized study. Setting: University hospital. Participants: Patients undergoing elective coronary revascularization with cardiopulmonary bypass (n = 90). Interventions: Of patients, 30 were treated with heparin-coated circuits and reduced systemic heparinization; 30, with heparin-coated circuits and full systemic heparinization; 30, with conventional circuits and full systemic heparinization. Measurements and Main Results: Heparin-coated circuits with full systemic heparinization did not exert any effect on coagulation parameters. Low systemic heparinization resulted in a significantly (p < 0.01) higher hematocrit value on arrival in the intensive care unit and in significantly higher values of AT-III activity during cardiopulmonary bypass (66 ± 12% v 57.4 ± 13% and 59.1 ± 12% in the full systemic heparinization groups; p < 0.05), on arrival in the intensive care unit (69.7 ± 13% v 60.7 ± 13% and 60.8 ± 11% in the full systemic heparinization groups; p < 0.01), and on the first postoperative day (81.3 ± 15% v 67.4 ± 13% and 70.2 ± 12% in the full systemic heparinization groups; p < 0.01). No differences were observed in the clinical outcome. Conclusion: Reducing systemic heparinization determines an AT-III-saving effect that could be responsible for the decrease in thromboembolic complications already observed by other authors. It induces higher hematocrit levels immediately after the operation, probably reducing the unmeasurable intraoperative blood loss. Copyright 2002, Elsevier Science (USA). All rights reserved.

Heparin-coated circuits reduce myocardial injury in heart or heart-lung transplantation: a prospective, randomized study

Background. The effects of heparin-coated (HC) circuits have been primarily investigated in routine cardiac operations with limited duration of cardiopulmonary bypass (CPB) and ischemia. Their benefits have not been conclusively proven but could be more significant when CPB and ischemic times are longer, such as during heart transplantation (HTx) or heart-lung transplantation (HLTx). Methods. In a 22-month period, 29 patients undergoing HTx and HLTx were randomly divided into two groups using HC (Duraflo II, n = 14, 10 HTx and 4 HLTx) or uncoated but identical circuits (NHC group, n = 15, 10 HTx and 5 HLTx). All patients received full systemic heparinization (3 mg/kg) during CPB. Plasma endotoxin, interleukin (IL)-6, IL-8, IL-10, IL-12, and cardiac troponin-I were measured before heparin administration, immediately after aortic cross-clamping, 5, 30, 60, 90, 120 minutes, and 12 and 24 hours after aortic declamping. The intensive care unit (ICU) staff and the laboratory technologists were blinded as to the use of HC circuits. Results. No statistically significant differences between groups were found with respect to all baseline values, duration of CPB and aortic cross-clamping, graft ischemic time, doses of heparin, postoperative blood loss and transfusion, peak lactate and creatine kinase-MB isoenzyme values, duration of mechanical ventilation, or length of ICU stay. One patient in each group died during the hospital stay. Patients in the HC group needed more protamine sulfate after CPB. Although endotoxin levels were similar in the two groups, significantly lower IL-6, IL-8, and IL-10 levels were observed 1 hour after aortic declamping in the HC group. The release of cardiac troponin-I was also significantly reduced in the HC group 12 and 24 hours after reperfusion. Conclusions. The use of HC circuit limits both pro- and anti-inflammatory responses to CPB. It may also reduce myocardial injury after prolonged duration of CPB and ischemia.

Assessment of heparin anticoagulation: comparison of two commercially available methods

Background. The activated clotting time is a bedside method routinely used to monitor heparin anticoagulation during operations requiring cardiopulmonary bypass. The thrombolytic assessment system heparin management test is a new bedside method for monitoring heparin effect. We compared these methods with respect to their ability to reflect the actual heparin concentration in plasma determined by an anti-FXa method.Methods. Two studies were done, an ex vivo study on ten patients who had coronary artery bypass using nonheparin-coated cardiopulmonary bypass circuits and full systemic heparinization and an in vitro study on single donor plasma spiked with heparin 0 to 10 IU/mL.Results. Ex vivo study correlation coefficients of activated clotting time and the thrombolytic assessment system heparin management test clotting times versus anti-FXa-based heparin assay were low (r = 0.53, p = 0.002/r = 0.64, p < 0.001) in contrast with the corresponding correlation coefficients for the in vitro study (r = 0.98, p < 0.001/r = 0.99, p < 0.001). A substantial variability in duplicate activated clotting time determinations was noted, which was less pronounced with the thrombolytic assessment system heparin management test.Conclusions. The thrombolytic assessment system method does not correlate better to the actual amount of heparin during cardiopulmonary bypass procedures than the activated clotting time method, which should be performed in duplicate.

Ex Vivo Testing of Heparin-Coated Extracorporeal Circuits: Bovine Experiments

In this study the intrinsic thrombogenicity of the extracorporeal circuits and the benefit of heparin-bonded circuits in an extracorporeal life support system without full systemic heparinization and with minimal interference of the so called material-independent factors was tested in four calves. In two circuits (group A) all blood-contacting surfaces were coated with end-point-attached heparin and the other two were non-coated (group B). Under standardized conditions the calves were perfused at a blood flow rate of 2 L/min. After only one bolus injection of heparin (250 IU/kg body weight) before cannulation, plasma heparin activity rapidly decreased in both groups: half life of about 55 minutes. This decrease of the heparin activity was accompanied by a fall of the activated clotting time (ACT) level to baseline values. The experiments using a heparin-coated circuit, had a runtime of more than 360 minutes, whereas the experiments using a non-coated circuit had to be terminated after a runtime of 255 minutes, because massive fibrin formation was noticed in the circuit. This formation was accompanied by a rapid increase in the line pressure, measured just before the inlet of the oxygenator. The macroscopic inspections after terminating the experiments and rinsing the circuit showed a clean circuit in group A. The fibrinopeptide A (FPA) level increased faster during perfusion with the non-coated circuit than in the heparin coated circuit. Lung histopathological examinations of the lungs of the animals in group A showed no fibrin deposition, whereas most of the blood vessels of the lung preparations of the animals in group B were partially or completely occluded with fibrin. These results suggest that heparin-bonding greatly reduces the thrombogenicity of the extracorporeal circuit, and therefore it can reduce the need for systemic heparinization in an extracorporeal life support system.

Acute traumatic rupture of the thoracic aorta: Delayed treatment with endoluminal covered stent. A report of two cases

Acute traumatic rupture of the thoracic aorta: Delayed treatment with endoluminal covered stent. A report of two cases

Heparinized cardiopulmonary bypass and full heparin dose marginally improve clinical performance

The use of completely heparin coated cardiopulmonary bypass circuits in combination with a reduced systemic heparin dose has previously been shown to reduce postoperative bleeding after cardiac operations. However, it has remained unknown whether this effect was related to the improved biocompatibility of the heparin-treated surfaces per se or to the reduced exposure to circulating heparin. Therefore we investigated patients undergoing heparin-coated extracorporeal circulation and full systemic heparinization. Two hundred seventeen patients having first-time myocardial revascularization were prospectively randomized either to a group in which a completely ("tip-to-tip") heparin-coated circuit (Duraflo II) was used for perfusion (n = 107) or to a control group (n = 110) in which an uncoated, but otherwise identical, circuit was used. Full systemic heparinization was induced in both groups (activated clotting time, > 480 seconds). The postoperative blood loss, requirements for homologous blood transfusions, clinical performance, and complications were recorded. The amount of postoperative mediastinal drainage was nearly identical in the two groups. The mean 18-hour drainage was 694 +/- 313 mL in the heparin-coated group and 679 +/- 269 mL in the control group (p = not significant). Three patients in the heparin-coated group and 6 patients in the control group received homologous red blood cell transfusions (p = not significant). The incidence of postoperative atrial fibrillation was significantly lower in the heparin-coated group (21.8%) than in the control group (43.1%) (p = 0.002). Otherwise, there were no significant differences in the extubation times, the incidence of perioperative myocardial infarction, the creatinine concentration, the incidence of neurologic dysfunction, the progress in physical rehabilitation, or the hemoglobin concentration at discharge. The use of completely heparin coated cardiopulmonary bypass circuits and full systemic heparinization in patients undergoing coronary artery bypass procedures did not reduce postoperative bleeding or change clinical performance, except for a significant decrease in the incidence of postoperative atrial fibrillation.

Effects on Coagulation and Fibrinolysis With Reduced Versus Full Systemic Heparinization and Heparin-Coated Cardiopulmonary Bypass

Extracorporeal circulation with circuits coated with surface-bound heparin has allowed reduced levels of systemic heparinization. Clinical benefits have included reduced postoperative bleeding and less homologous blood usage. However, the effects on the hemostatic and fibrinolytic systems have remained in part unknown. Indications of thrombin generation, platelet activation, and fibrinolytic activity were investigated in patients undergoing coronary artery bypass surgery. Two groups were perfused with cardiopulmonary bypass (CPB) circuits completely coated with surface-bound heparin: one group with low systemic heparin dose (activated clotting time [ACT] > 250 seconds; n = 17) and a second group having a full heparin dose (ACT > 480 seconds; n = 18). A third control group was perfused with ordinary uncoated circuits and full heparin dose (n = 17). The plasma level of thrombin-antithrombin complex and prothrombin fragment 1.2 increased in all groups during bypass, and somewhat more in both the heparin-coated groups toward the end of CPB, compared with the control group (P < .01). However, the increase during CPB was minimal compared with the major elevation observed 2 hours after surgery in all groups. Platelet release of beta-thromboglobulin increased in all groups (P < .01) during CPB and significantly more in the high-dose group compared with the other two groups (P = .03). Fibrinolytic activities were similar in all groups, and there were no indications of major consumption of coagulation factors. Reduced systemic heparinization (ACT > 250 seconds) in patients having extracorporeal circulation with completely heparin-coated circuits did not lead to increased thrombogenicity. Thrombin formation remained within low ranges during CPB compared with patients receiving a full heparin dose and with the major elevations observed after surgery.

Reduced complement activation and improved postoperative performance after cardiopulmonary bypass with heparin-coated circuits

A randomized controlled trial that involved 30 patients undergoing elective coronary artery bypass grafting was done to determine the effect of heparin-coated circuits and full heparinization on complement activation, neutrophil-mediated inflammatory response, and postoperative clinical recovery. Peak concentrations of terminal complement complex were 38% lower ( p = 0.004) in 15 patients treated with heparin-coated circuits (median 775 μg/L, interquartile range 600 to 996) compared with those in 15 patients treated with uncoated circuits (median 1249 μg/L, interquartile range 988 to 1443). Although no significant intergroup differences in concentrations of polymorphonuclear neutrophil elastase were found, a positive correlation (r s = 0.74, p < 0.0007) was calculated between peak concentrations of terminal complement complex and polymorphonuclear neutrophil elastase. Differences in patient recovery were analyzed with use of a score composed of fluid balance, postoperative intubation time, and the difference between rectal temperature and skin temperature. The score was significantly lower in patients treated with heparin-coated circuits ( p = 0.03), whereas its components showed no intergroup significance. We conclude that the use of heparin-coated circuits with full systemic heparinization results in improved biocompatibility, as assessed by complement activation, and leads to an improved postoperative recovery of the patient. (J T HORAC C ARDIOVASC S URG 1995;110: 829-34)

Completely heparinized cardiopulmonary bypass and reduced systemic heparin: Clinical and hemostatic effects

When heparinized circuits are used for cardiopulmonary bypass, the amounts of heparin and protamine administered systemically can be reduced. However, it is not entirely known what effects this reduction in systemic anticoagulation has on clinical performance and on the coagulation and fibrinolytic systems. Two hundred three patients undergoing first-time elective myocardial revascularization were prospectively randomized either to a group in which a completely heparin-coated circuit was used for perfusion (group H; n = 101 patients) and in which a reduced heparin dose was given (activated clotting time, > 250 seconds) or to a control group (group C; n = 102 patients) in which an uncoated, but otherwise identical, circuit was used and in which full systemic heparinization was induced (activated clotting time, > 480 seconds). Indicators of thrombin generation, platelet activation, and fibrinolytic activity were studied in a subset of 34 patients. The total amount of postoperative mediastinal drainage was significantly reduced in group H (median, 575 mL) compared with that in group C (median, 635 mL; p = 0.002). Two patients in group C but none in group H received homologous red blood cell transfusions (p = not significant). The loss of hemoglobin in group H was a median of 21 g/L, and this was significantly lower than the 25 g/L noted in the control group (p = 0.006). During cardiopulmonary bypass, the plasma levels of thrombin-antithrombin complex and prothrombin fragment 1.2 increased in both groups. At the end of cardiopulmonary bypass the plasma levels of these markers of thrombin formation were significantly higher in group H, although the increase was modest compared with the major increase observed 2 hours after operation in both groups. There were no significant intergroup differences in the platelet counts, the concentration of beta-thromboglobulin, or the plasma levels of fibrinogen and D-dimer. No differences in perioperative morbidity, the postoperative kidney function, or the intubation time were observed, and there were no hospital deaths. The combination of complete heparin-coated cardiopulmonary bypass circuits and low systemic heparinization is safe for patients undergoing elective coronary artery bypass procedures and reduces the perioperative blood loss. There was no evidence of increased thrombogenicity, fibrinolytic activity, or consumption of coagulation factors. No clinical or technical side effects were observed.

Spinal cord protection in the absence of collateral circulation: meta-analysis of mortality and paraplegia.

A meta-analysis of paraplegia complicating aortic surgery on patients having neither intercostal nor spinal collaterals, epitomized by patients with acute traumatic aortic rupture, was done. Index Medicus and Medline were searched for all suitable English publications between 1972 and 1992. New paraplegia occurred in 9.9% of 1492 patients who underwent surgery. However, 19.2% of patients undergoing surgery with only simple aortic cross-clamping developed paraplegia, in contrast to 6.1% if distal aortic perfusion was augmented by either "passive" or "active" methods (p < 0.00001). The risk of paraplegia increased progressively as cross-clamp times lengthened if simple aortic cross-clamping was used (p < 0.00001), but only once did the cross-clamp time exceed 30 minutes (p < 0.05). Paraplegia occurred in 8.2% of patients with "passive" shunts from the ascending aorta (p < 0.001 vs simple cross-clamping). Shunts from the left ventricular apex, however, had an incidence of paraplegia of 26.1% and, therefore, did not decrease the risk of paraplegia. "Active" augmentation of distal perfusion had the lowest risk of paraplegia: 2.3% (p < 0.00001 vs simple cross-clamping or "passive" shunts). Mortality, however, was higher in these potentially polytraumatized patients when they were perfused distally using methods requiring full systemic heparinization (18.2%), compared to mortality with methods not requiring heparin (11.9%; p < 0.01). In conclusion, simple aortic cross-clamping has a high risk of paraplegia if the cross-clamp time extends beyond 30 minutes. "Active" modalities of augmenting distal perfusion provide optimal spinal protection.

Risk and benefit of low systemic heparinization during open heart operations

Heparin surface-coated perfusion equipment with improved thromboresistance was evaluated in 104 consecutive patients undergoing open heart operation in a prospective, randomized trial with low versus full systemic heparinization. Surgical procedures included coronary artery revascularization in 47 of 54 (87%) for low versus 44 of 50 patients (88%; not significant [NS]) for full, valve repair/replacement in 8 of 54 (15%) for low versus 5 of 50 patients (10%; NS) for full, left ventricular aneurysm repair in 1 of 54 (2%) for low versus 2 of 50 patients (4%; NS) for full, and other in 3 of 54 (6%) for low versus 3 of 50 patients (6%; NS) for full. Cross-clamp time was 39.2 ± 10.7 minutes for low versus 39.5 ± 10.5 minutes for full (NS). Cardiopulmonary bypass time was 68.6 ± 20.1 minutes for low versus 69.3 ± 16.6 minutes for full (NS). Lowest activated coagulation time during perfusion was 255 ± 75 seconds for low versus 537 ± 205 seconds for full ( p < 0.0005). In the low group, the target activated coagulation time of more than 180 seconds was not reached during perfusion in 4 of 54 patients (7%), the lowest value being 164 seconds. No oxygenator failure occurred. Hospital mortality was 0 of 54 (0%) for low versus 1 of 50 patients (2%) for full (NS). Bleeding required surgical revision in 0 of 54 (0%) for low versus 4 of 50 patients (8%) for full ( p = 0.05). Drainage (24 hours) was 790 ± 393 mL for low versus 1,039 ± 732 mL for full ( p < 0.025). Amount of packed homologous red cells transfused (24 hours) was 300 ± 354 mL for low versus 957 ± 596 mL for full ( p < 0.0005). Baseline hematocrit of 43.3% ± 3.7% for low versus 43.0% ± 3.9% (NS) for full before operation moved to 28.9% ± 3.2% for low versus 28.8% ± 3.2% for full (NS) at 24 hours. Low systemic heparinization during open heart operation results in reduced blood loss and transfusion requirements.

Improved distal circulatory support for repair of descending thoracic aortic aneurysms

Bleeding is a well-known problem when cardiopulmonary bypass with full systemic heparinization is used for distal support during aortic cross-clamping. The recent advent of heparin-coated cardiopulmonary bypass equipment prompted our review of 91 consecutive patients who underwent repair of descending thoracic and thoracoabdominal aortic aneurysms. Two different surgical techniques were used: 42 of 91 patients had simple aortic cross-clamping and rapid reanastomosis, whereas 49 of 91 had distal support using all heparin-coated perfusion equipment with low systemic heparinization (100 IU/kg body weight; activated coagulation time >180 seconds). Baseline parameters, location (thoracoabdominal: 28 / 91 ; 31%), and type of aneurysm (ruptured: 14 / 91 ; 15%) were similar in both groups. Cross-clamp time was 37 ± 22 minutes for support versus 29 ± 13 minutes for simple clamping ( p < 0.05). There were fewer revisions due to bleeding for support ( 1 / 49 patients; 2%) versus simple ( 4 / 42 ; 10%; p < 0.05) and fewer patients with impaired renal function requiring temporary hemofiltration for support ( 4 / 49 patients; 8%) versus simple ( 6 / 42 ; 14%). Hospital mortality was lower for support ( 5 / 49 ; 10%) versus simple ( 8 / 42 ; 19%). Transfusion requirements during operation were 3,732 ± 3,458 mL for simple versus 3,392 ± 2,058 mL for support (not significant). Chest tube drainage totaled 982 ± 1,102 mL for simple versus 720 ± 618 mL for support (not significant). The total volume requirements were 8,156 ± 4,753 mL for simple versus 7,495 ± 3,342 mL for support (not significant) during operation and 4,416 ± 2,422 mL for simple versus 3,380 ± 1,432 mL for support ( p < 0.025) during the 24 hours after operation. After declamping of the aorta the mean arterial pH dropped to 7.29 ± 0.10 for simple clamping as compared with 7.37 ± 0.08 for clamping supported with partial cardiopulmonary bypass ( p < 0.0005), partial arterial CO 2 pressures increased to 6.44 ± 1.21 kPa for simple as compared with 5.22 ± 1.09 kPa ( p < 0.0005), and mean negative base excess values increased to 4.9 ± 5.8 for simple as compared with 2.6 ± 3.9 ( p < 0.05). No device failure occurred. We conclude that proximal unloading and support of distal circulation during resection of descending thoracic and thoracoabdominal aortic aneurysms prevents declamping shock and can now be realized without risk of bleeding complications. This approach provides superior hemodynamics and oxygenation.

Use of an intravascular gas exchanger: is low systemic heparinization safe?

Extracorporeal membrane oxygenation (ECMO) is a cumbersome procedure. Alternatively, mechanical lung assist can be realized with an intravascular gas exchanger (IVOX). To assess the degree of initial anticoagulation required during intravascular lung assist, we evaluated two regimens of systemic heparinization in 10 bovine experiments. The animals were randomly assigned to two groups with either full systemic heparinization (heparin loading dose 300 IU/kg bodyweight; activated coagulation time (ACT) &gt; 480 s) or low systemic heparinization (heparin loading dose 100 IU/kg bodyweight; ACT &gt; 180 s). The surface heparinized intravascular gas exchanger was placed in the caval axis under fluoroscopic control, and a standard battery of blood samples was drawn before and at regular intervals during the procedure. After six hours of intravascular lung assist the device was explanted, drained, weighed, and carefully analysed. Preassist haematocrit was 25 ± 5% for full versus 24 ± 7% for low (NS) as compared with 23 ± 8% for full versus 26 ± 3% for low (NS) postassist. Platelet levels were 100 ± 25 for full versus 100 ± 21 % for low (NS) preassist as compared with 64 ± 22% for full versus 78 ± 22% for low (NS) postassist. Mean ACT was 157 ± 12 s for full versus 158 ± 18 for low (NS) preassist as compared with 800 ± 244 s versus 219 ± 25 for low (p &lt; 0.05) postassist. Thrombin time was 20 ± 2 s for full versus 23 ± 2 s for low (NS) as compared with &gt; 200 s for both groups after assist. Relative fibrinopeptide A levels were 7.3 ± 1.1 ng/ml for full versus 6.3 ± 1.6 ng/ml for low (NS) preassist as compared with 4.7 ± 4.1 ng/ml for full versus 5.8 ± 0.9 ng/ml for low (NS) postassist. CO2 transfer was 40 ± 10 ml/min for full versus 36 ± 10 ml/min for low (NS) at the begining as compared with 45 ± 25 ml/min for full versus 46 ± 15 for low (NS) at the end. Weight increase due to device deposits (clots) was 14 ± 11 g for full versus 13 ± 10 g for low systemic heparinization (NS). Intravascular lung assist with low versus full systemic heparinization appeared to result in similar activation of the coagulation system, device deposits and gas transfer rates. Considering our clinical experience we can say that application of the device with reduced systemic heparinization is useful in selected patients.