Minutes Of Cardiopulmonary Bypass Research Articles

Influence of cardiopulmonary bypass on the erythrocyte membranes and the method of its protection

The damage to erythrocytes during cardiopulmonary bypass (CPB) remains a recent problem. The aim of this research was to study the effect of fructose-1,6-diphosphate on the state of the erythrocyte membrane during CPB and the level of phosphorus in blood as a marker of the energy potential in the cell. Patients were divided into two groups. The control group 1 (Gr 1) consisted of 75 individuals. The group 2 (Gr 2) included patients to whom fructose-1,6-diphosphate (FDP) was administrated according to the developed scheme as follows 10 g of the drug was diluted in 50 ml of a solvent, 5 g of the drug was injected intravenously with the use of perfusor immediately before initiation of CPB at a rate of 10 ml/min and 5 g at the 30th minute of CPB (before the stage of warming) the same way. When comparing two groups the best results in hemolysis (p<0.01), mechanical (p<0.01). osmotic resistance of erythrocytes (p<0.01), the time of acid hemolysis (p<0.01) and the permeability of the erythrocyte membrane in postperfusion period were in Gr 2. Вefore cardiac surgery hypophosphatemia was detected in 18% out of 150 and in 32% out of 150 patients – a lower limit of normal phosphorus content in the blood. After CPB in Gr 1 phosphorus content in blood was 0.85±0.32 mmol/l and hypophosphatemia was in 53% out of 75 patients. This indicates a pronounced energy deficit in this group. In Gr 2 phosphorus level was 1.7±0.31 mmol/l and there was no hypophosphatemia. As a result, FDP as an endogenous high-energy intermediate metabolite of the glycolytic pathway leads to resistance to hemolysis, protects the erythrocyte membrane from damage and increases the energy potential of the cell during CPB.

Does the roller pump adjustment in cardiopulmonary bypass settings influence hemolysis?

Roller pumps are widely used in procedures involving cardiopulmonary bypass (CPB) due to their ease of operation and maintenance, safety, and cost. Several studies in the literature have compared the use of roller pumps with centrifugal pumps, but the influence of the roller pump adjustment on hemolysis has been poorly explored. Measurements of hemolysis rates were carried out in 86 patients. The pump was adjusted by the dynamic calibration method, which was performed by an auxiliary device, and the patients were grouped according to the pump calibration: Group 1 (n = 20) 75 mmHg; Group 2 (n = 24) 150 mmHg; Group 3 (n = 22) 300 mmHg and Group 4 (n = 21) 450 mmHg. The hemolysis rates were measured at 4 different times during CPB (T0: before the surgical procedure; T1: 5 minutes after the start of CPB; T2: 30 minutes of CPB; and T3: 5 minutes after the CPB procedure). Hemolysis rates were calculated between the time intervals T0-T1, T1-T2, and T0-T3. No difference in hemolysis rates was observed between the groups (p>0.31). During the first 5 minutes of CPB, hemolysis represented 35.5% of the total hemolysis and no significant difference was found between groups (p>0.60). Calibration of roller pumps by the dynamic method did not influence the hemolysis rates. Additionally, the hemolysis during the first 5 minutes of CPB accounted for ~1/3 of the total hemolysis.

Etiology of Intraoperative Metabolic Acidosis upon Cardiopulmonary Bypass

Objective: Upon usage of cardiopulmonary bypass (CPB), intraoperative metabolic acidosis is frequently found. Its etiology has not been yet fully understood. In accordance with the traditional concept of dilution, the fast administration of large volumes with minor bicarbonate concentration into the patients' systemic circulation causes dilutional acidosis. During initiation of CPB, the priming volume is rapidly administered. Using crystalloid cardioplegia, additional volume is introduced within the first minutes of CPB. Usually, both the priming as well as the cardioplegic solution contain less than physiological bicarbonate concentration. Therefore, CPB constitutes an excellent model for studying dilutional metabolic acidosis. Although the lactic acidosis' severity is known to correlate with CPB duration, little is known about the contribution of dilutional acidosis. Aim of the study was to prove the general existence of dilutional acidosis and evaluate its impact on intraoperative metabolic acidosis upon CPB.

Utility of cerebral oxymetry for assessing cerebral arteriolar carbon dioxide reactivity during cardiopulmonary bypass.

Our study evaluated changes in cerebral arterial oxygen saturation (rSO2) during cardiopulmonary bypass (CPB) that were caused by changes in arterial carbon dioxide tension (PaCO2). A group of 126 patients undergoing routine, elective, first-time coronary artery bypass graft surgery (CABG) was entered into a prospective study using bilateral near-infrared spectroscopy (NIRS) before anesthetic induction (T1), after anesthetic induction (T2), and continuing at 5-minute intervals during moderate hypothermic (32°C) CPB. Pump flows were set at 2.5 L/min/m(2) and adjusted to maintain mean arterial pressure (MAP) within 10 mmHg of the MAP recorded at the initial fifth minute of CPB (T3). Thirty-two patients were excluded from data collection because MAP could not be stabilized within the target range of 60-90 mmHg. In the remaining 94 patients, after obtaining steady state flow, MAP, and oxygenation, a trial period of hypocarbia (mean PaCO2 of 30 mmHg) was induced by increasing oxygenator fresh gas flow rate (FGFR) to 2.5 L/min/m(2) (T4). A reciprocal period was then measured at reduced FGFR (0.75 L/min/m(2)) (T5). After 20 minutes of a higher (2.75 L/min/m(2)) (FGFR), mean PaCO2 decreased from a baseline of 38 ± 4 mmHg to 30 ± 2 mmHg. This was associated with a parallel decrease (-10 ± 9%) in mixed cerebral oxygen saturation without alteration of mean arterial oxygen tension (PaO2), lactate, MAP, CPB flow, or other parameters implying increased cerebral oxygen extraction. Parallel changes in PaCO2 and rSO2 occur during CPB when other variables remain constant, and are due to the effects of carbon dioxide on cerebral arterioles. Cerebral oxygen saturation measured by NIRS may be a useful indirect measure of PaCO2 when continuous blood gas analysis is not possible during open-heart surgery. Cerebral oximetry values may be useful measurements for setting an optimum gas flow rate through the oxygenator.

Active or passive bio-coating: does it matters in extracorporeal circulation?

Two types of surface coating for cardiopulmonary bypass (CPB) are used: bioactive (heparin, nitric oxide) and biopassive (albumin, polyethyleneoxide (PEO), phosphorylcholine). When haemocompatible coatings are combined with the separation of pleuro-pericardial aspiration, attenuation of both the coagulation and complement cascades, as well as better platelet preservation, has been demonstrated. This study wants to investigate if the combination of a bioactive with a biopassive coating (unfractionated heparin embedded in a phosphorylcholine matrix) combines the beneficial effects of both approaches. Thirty patients undergoing elective CABG were prospectively randomized into two groups of 15 patients. The sole exclusion criterion was an ejection fraction of less than 40%. In the control group (PC), the whole CPB circuit was coated with phosphorylcholine (PC). In the study group (XPC), unfractionated heparin was embedded in the PC matrix of the oxygenator and arterial line filter. No differences were found for haemolytic index, thrombin-anti-thrombin complex (TAT), IL-6, IL-10 and blood loss. PF4 plasma concentration increased from 27.6±22.0 IU/mL to 165.7±43.9 IU/mL (p<0.001) at 15 minutes of CPB in the PC and from 16.0±9.7 IU/mL to 150.9 ± 61.3 IU/mL (p<0.001) in the XPC group. Terminal complement complex (TCC) increased over time in both groups until the end of CPB (Figure 2A). Within each group, TCC generation was statistically significantly higher after the release of the aortic cross-clamp (p<0.001) and at the end of CPB (p<0.001). Total TCC generation was statistically significantly higher in the XPC group compared to the PC group (p=0.026). The difference was statistically significant after the release of the aortic cross-clamp (p=0.005) and at the end of CPB (p=0.001). Based on our results, there is no additional benefit in combining phosphorylcholine with unfractionated heparin in elective patients undergoing coronary artery bypass grafting (CABG). Massive haemodilution leads to enhanced complement activation.

Preceding unstable angina affects inflammatory response and hemodynamics after coronary artery bypass surgery

The authors set out to investigate the inflammatory response and its impact on the hemodynamic function in stable and unstable coronary artery bypass (CABG) patients. Nineteen stable and twenty unstable patients were included in this prospective study. Serum IL-6, IL-8, TNF-α, and IL-10 were measured before, during and after cardiopulmonary bypass (CPB). Hemodynamic data was also collected. TNF-α was detected more often in unstable patients than in stable patients before (p=0.03) and after CPB (p<0.01). TNF-α response after CPB was evident (p=0.03). Serum IL-6 and IL-8 level were significantly increased after 10 minutes of CPB, reaching the peak value at 6 hours after declamping. IL-10 level reached the highest, 6.8 × the baseline at 6 hours after declamping in the unstable, but 3.3 × of baseline on the first post-operative day (POD) in the stable patients (p=0.04). CI was better preserved in unstable patients (p=0.04). Serum TNF-α was more likely to be found in patients with recent unstable episodes. CPB induces a release of serum IL-6, IL-8 and IL-10. Recent unstable angina seems to modify the cytokine response and hemodynamic outcome.

Neutrophil Elastase Inhibitor, Sivelestat, Attenuates Acute Lung Injury After Cardiopulmonary Bypass in the Rabbit Endotoxemia Model

Neutrophil elastase probably contributes to the development of acute lung injury after cardiopulmonary bypass (CPB) in patients with infection or shock. We evaluated whether pretreatment with sivelestat sodium hydrate, a neutrophil elastase inhibitor (EI), can prevent acute lung injury caused by CPB. Rabbits were assigned four groups: CPB for 60 minutes, control CPB group; low-dose lipopolysaccharide (LPS) administration without CPB, LPS group; CPB after lipopolysaccharide administration, LPS+CPB group; or preparation with continuous infusion of sivelestat and CPBs after lipopolysaccharide administration, EI group. Blood samples to determine blood gas concentration, plasma elastase activity, and plasma interleukin-8 levels were obtained. Histopathologic examinations of the lung were performed. The decreased arterial oxygen pressure at the end of CPB was observed in the LPS+CPB group only, but was suppressed in the EI group (p < 0.01). Elastase activity was markedly elevated at 120 minutes after CPB, and interleukin-8 levels were markedly elevated at 180 minutes in the LPS+CPB group but were much lower (p < 0.05) in the EI group. Histopathology demonstrated accumulation of polymorphonuclear neutrophils in bronchoalveolar areas in the LPS+CPB group (p < 0.01). Pulmonary myeloperoxidase activity was significantly lower in the LPS+CPB group than in the other groups (p < 0.01). These changes were minimal in the EI group. The combination of low dose LPS+60 minutes of CPB, but neither intervention alone, produced evidence of acute lung injury in a rabbit model. This did not occur when the animals were pretreated with sivelestat.

Augmentation of Abdominal Organ Perfusion during Cardiopulmonary Bypass with a Novel Intra-aortic Pulsatile Catheter Pump

Current pulsatile pumps for cardiopulmonary bypass (CPB) are far from satisfactory because of the poor pulsatility. This study was undertaken to examine the efficiency of a novel pulsatile catheter pump on pulsatility and its effect on abdominal organ perfusion during CPB. Twelve pigs weighing 89+/-11 kg were randomly divided into a pulsatile group (n=6) and a non-pulsatile group (n=6). All animals had a CPB for 120 min, aorta clamped for 60 min, temperature down to 32 degrees C, and a perfusion flow of 60 ml/kg/min. In the pulsatile group, a 21 Fr intra-aortic pulsatile catheter, which was connected to a 40 mL membrane pump, was placed in the descending aorta and activated by a balloon pump driver during the first 90 minutes of CPB until aortic declamping. Hemodynamics, organ blood flow, body metabolism, and blood trauma were studied during experiments. Compared with the non-pulsatile group during CPB, the pulsatile group had a higher systolic blood pressure (p<0.01), higher mean arterial pressure (p<0.05), and higher blood flow to the superior mesenteric artery (p<0.05). The hemodynamic energy, indicated by the energy equivalent pressure (EEP) was higher in the gastrointestinal tract and kidney in the pulsatile group (p<0.01, p<0.01). Abdominal organ perfusion status, as indicated by SvO 2 in the inferior vena cava, was higher in the pulsatile group (p<0.05) 30 min after cessation of CPB. Hemolysis indicated by release of free hemoglobin during CPB was similar in the two groups. Applying the pulsatile catheter pump in the descending aorta is effective in supplying the pulsatile flow to the abdominal organs and results in improved abdominal organ perfusion during the ischemic phase of CPB.

Estimating the rate of thrombin and fibrin generation in vivo during cardiopulmonary bypass

Our objective was to estimate the in vivo rates of thrombin and fibrin generation to better understand how coagulation is regulated. Studied were 9 males undergoing cardiopulmonary bypass (CPB). The rates of thrombin, total fibrin, and soluble fibrin generation in vivo were based on measured levels of prothrombin activation peptide F1.2, thrombin-antithrombin complex, fibrinopeptide A, and soluble fibrin, combined with a computer model of the patient's vascular system that accounted for marker clearance, hemodilution, blood loss, and transfusion. Prior to surgery, the average thrombin generation rate was 0.24 +/- 0.11 pmol/s. Each thrombin molecule in turn generated about 100 fibrin molecules, of which 1% was soluble fibrin. The thrombin generation rate did not change after sternotomy or administration of heparin, then rapidly increased 20-fold to 5.60 +/- 6.65 pmol/s after 5 minutes of CPB (P =.000 05). Early in CPB each new thrombin generated only 4 fibrin molecules, of which 35% was soluble fibrin. The thrombin generation rate was 2.14 +/- 1.88 pmol/s during the remainder of CPB, increasing again to 5.47 +/- 4.08 pmol/s after reperfusion of the ischemic heart (P =.000 08). After heparin neutralization with protamine, thrombin generation remained high (5.34 +/- 4.01 pmol/s, P =.0002) and total fibrin generation increased, while soluble fibrin generation decreased. By 2 hours after surgery, thrombin and fibrin generation rates were returning to baseline levels. We conclude that cardiopulmonary bypass and reperfusion of the ischemic heart results in bursts of nonhemostatic thrombin generation and dysregulated fibrin formation, not just a steady increase in thrombin generation as suggested by previous studies.

Activation of the kallikrein-kinin system by cardiopulmonary bypass in humans.

We used cardiopulmonary bypass (CPB) as a model of activation of the contact system and investigated the involvement of the plasma and tissue kallikrein-kinin systems (KKS) in this process. Circulating levels of bradykinin and kallidin and their metabolites, plasma and tissue kallikrein, low and high molecular weight kininogen, and kallistatin were measured before, during, and 1, 4, and 10 h after CPB in subjects undergoing cardiac surgery. Bradykinin peptide levels increased 10- to 20-fold during the first 10 min, returned toward basal levels by 70 min of CPB, and remained 1.2- to 2.5-fold elevated after CPB. Kallidin peptide levels showed little change during CPB, but they were elevated 1.7- to 5.2-fold after CPB. There were reductions of 80 and 60% in plasma and tissue kallikrein levels, respectively, during the first minute of CPB. Kininogen and kallistatin levels were unchanged. Angiotensin-converting enzyme inhibition did not amplify the increase in bradykinin levels during CPB. Aprotinin administration prevented activation of the KKS. The changes in circulating kinin and kallikrein levels indicate activation of both the plasma and tissue KKS during activation of the contact system by CPB.

Substituição do arco aórtico sem parada circulatória total: técnicas, táticas e resultados

INTRODUCTION: Despite the development in cardiovascular techniques such as in cardiopulmonary bypass and cerebral protection the mortality in the correlations of the diseases of the aortic arch remains high. Deep hypothermic circulatory arrest and cardiopulmonary bypass times as well as neurological lesions are the major causes of morbi-mortality. OBJECTIVE: To show some techniques and tactics that allow the complete substitution of the aortic arch without the need of total circulatory arrest and deep hypothermia, and the results obtained in 10 consecutive patients. MATERIAL AND METHODS: Ten consecutive patients, all male, with a mean age of 48.7 years, had their aortic arch totally substituted using moderate hypothermia, selective cerebral perfusion via subclavian artery and an arch vessels anastomose performed isolatedly as the first stage. RESULTS: The mean selective cerebral perfusion time was 14.1 minutes with 39.6 minutes of myocardial ischaemia and 98.9 minutes of cardiopulmonary bypass. The mean esofagic temperature was 26.6o C (24o C to 30o C). The mean time of hospital stay was 18.4 days (8 to 40). There were no immediate or late deaths. Two patients had temporary cerebral dysfunction (confusion) and one had hemiparesis, completed recover with time. CONCLUSION: The combination of these techniques and tactics allowed an effective correction of the diseases in a wide and dry surgical field. They promoted an excellent cerebral protection without the need of deep hypothermia which decreasing substantially the postoperative complications and mortality.

Cytokines and pediatric open heart surgery with cardiopulmonary bypass.

It is well known that, subsequent to cardiopulmonary bypass, and particularly in children, an inflammatory response within the body can often result in a characteristic syndrome. Recently, it has been suggested that this phenomenon is due to a systemic inflammatory response, with significant involvement of cytokines. With this in mind, we investigated the behavior of tumour necrosis factor-alpha and interleukin-6 during the operative and in the immediate postoperative period in a group of children submitted to open heart surgery. We investigated any possible relation between the levels of these cytokines in the serum and the length of cardiopulmonary bypass, with the serum levels of lactate, and with the extent of use of inotropic drugs in postoperative period. The cytokines were measured in samples withdrawn after induction of anesthesia, after 10 minutes of cardiopulmonary bypass, after re-establishment of circulation, and then 2 and 24 hours after the end of cardiopulmonary bypass. The levels of tumour necrosis factor-alpha and interleukin-6 increased between the beginning and at two hours of the end of cardiopulmonary bypass. There was no correlation between the levels of these cytokines in the serum and the length of cardiopulmonary bypass, although there was a positive relation between levels of interleukin-6 and lactate in samples withdrawn at two hours of the end of bypass, and the measured levels of the cytokines correlated with the extent of inotropic drugs employed in the postoperative period.

Recombinant hirudin as an alternative for anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II: A 1-year experience in 57 patients

Recombinant hirudin as an alternative for anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II: A 1-year experience in 57 patients

Recombinant hirudin as an alternative for anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II: A 1-year experience in 57 patients

To explore the possible use of recombinant hirudin (r-hirudin) as an alternative to heparin for anticoagulation during cardiovascular surgery. Retrospective analysis. Two university hospitals. Fifty-seven patients with heparin-induced thrombocytopenia type II (HIT II) in whom r-hirudin was used during cardiovascular surgery with cardiopulmonary bypass (CPB). None. The r-hirudin concentration was monitored on-line, at the point of the patient's care using the ecarin clotting time and maintained in the range of 3 to 4 microg/mL. The r-hirudin elimination at the conclusion of CPB was augmented through modified zero-balanced ultrafiltration and forced diuresis. The duration of CPB was 63 to 246 minutes. The r-hirudin requirement per minute of CPB was 0.016 to 0.035 microg/kg/min, and the 24-hour blood drainage was 50 to 2,200 mL. Of the 57 patients, 54 fully recovered, including 9 patients who did not require any allogenic products. Four patients, all with impaired renal function, showed prolonged r-hirudin elimination and excessive bleeding and required surgical reexploration. Three patients died as a result of complications unrelated to the perioperative management. This study provides evidence that r-hirudin can be used safely and effectively for routine anticoagulation during CPB in patients diagnosed with HIT II. Almost 95% of the patients in whom it was used were discharged uneventfully. Patients with perioperative renal failure, however, showed increased bleeding.

Trillium™ Biopassive Surface: A New Biocompatible Treatment for Extracorporeal Circulation Circuits

139 patients undergoing cardiac surgery were included in a prospective, randomized trial. Patients were randomly allocated to receive cardiopulmonary bypass (CPB) with Trillium Biopassive Surface (TBS Group) coated oxygenators or conventional circuits (control group). 112 patients were studied with respect to postoperative biochemical profile; a subgroup of 27 patients was studied with respect to perioperative complement (C3a) activation. Patients in the TBS group demonstrated a significantly lower white blood cell count at the end of the operation (p=0.036) and a significantly higher platelet count the day after the operation (p=0.023) when compared to the control group. C3a was significantly higher (p=0.02) in the TBS group after 30 minutes of CPB, but the C3a increase after protamine administration was significantly less pronounced in the TBS group vs. the control group. Further studies involving platelet and leukocyte activation are required to better elucidate the action of this new coating in the setting of routine CPB.

Changes of the Serum Antibiotic Levels During Open Heart Surgery (ceftazidim, ciprofloxacin, clindamycin)

Wound, mediastinal and intracardiac infections are still very serious complications of open-heart surgery. The incidence of it is still in the range of 0.4%-5%. The aims of our study were to assess the adequacy of regimen using ceftazidim (CTZ), ciprofloxacin (CPF) and clindamycin (CLIN) as prophylactic antibiotics and to verify whether cardiopulmonary bypass (CPB) can modify the time of antibiotic serum concentrations. That is why the serum levels of them were measured during open heart procedures. The prospective study comprised 75 consequent coronary patients randomized in to three groups receiving 1 g of CTZ or 400 mg of CPF or 900 mg of CLIN i.v. with anesthesia induction. Routine coronary surgery with left internal mammary artery harvesting, moderate body hypothermic (30 degrees C) CPB with crystaloid cardioplegia was performed. Serum antibiotic levels were determined before application, with skin incision, prior CPB induction, after cardioplegia infusion, every 20 minutes of CPB, prior end of CPB, in time of chest closure. Conventional cylinder-plate microbiological assay was used for antibiotic level measurement. All serum antibiotic concentrations showed a sharp decrease immediately after starting CPB and lasted until CPB ended. After initiating of CPB after cardioplegia administration serum concentrations of CTZ (105 min after initial dose) decreased by, on average 55%, CPF (97 min) by 42% and CLIN (116 min) by 78%. CPB can modify the time course of antibiotic serum concentrations. The serum levels of CTZ at the end of the longest procedures were found to be below the MICs for some of the suspected pathogens. We recommend to use higher antibiotic doses for prophylaxis and to administer the second dose with protamin sulphate to obtain maximum concentration in newly formed blood clots.

Unilateral Antegrade Cerebral Perfusion Through the Right Axillary Artery Provides Uniform Flow Distribution to Both Hemispheres of the Brain

Background —Bilateral antegrade cerebral perfusion (ACP) has decreased in popularity over the past decade because of its complexity and the risk of cerebral embolism. We used magnetic resonance (MR) perfusion imaging to assess flow distribution in both hemispheres of the brain during unilateral ACP through the right carotid artery via a cannula placed in the right axillary artery in conjunction with hypothermic circulatory arrest. Methods and Results —Twelve pigs were randomly exposed to 120 minutes of either bilateral ACP through both carotid arteries (n=6) or unilateral ACP through the right axillary artery (n=6) at pressures of 60 to 65 mm Hg at 15°C, followed by 60 minutes of cardiopulmonary bypass at 37°C. MR perfusion images were acquired every 30 minutes before, during, and after ACP. The brain was perfusion fixed for histopathology. During initial normothermic cardiopulmonary bypass, MR perfusion imaging showed a uniform distribution of flow in the brain. In both the bilateral and unilateral ACP groups, the same pattern was maintained, with an increase in regional cerebral blood volume during ACP and reperfusion. The changes in regional cerebral blood volume and mean transit time were similar in both hemispheres during and after unilateral ACP. No difference was observed between the 2 groups. Histopathology showed normal morphology in all regions of the brain in both groups. Conclusions —Both bilateral ACP and unilateral ACP provide uniform blood distribution to both hemispheres of the brain and preserve normal morphology of the neurons after prolonged hypothermic circulatory arrest.

Do Different Heparin Brands Influence Activated Clotting Times?

A change in brand suppliers of heparin at our institution resulted in a number of anecdotal reports of possible differences in potency. Both products are marketed as heparin sodium extracted from porcine intestinal mucosa. Heparin Leo® is 1000 international units (British Pharmacopeia) per ml. while Hepalean® is 10000 United States Pharmacopeia (U.S.P) units per ml. Perfusion records were retrospectively reviewed for one month periods when Heparin Leo® (n=52) or Hepalean® (n=61) were used to provide anticoagulation therapy for cardiopulmonary bypass. Heparin Leo® was found to be less clinically potent than Hepalean®. While increasing the initial loading dose of Heparin Leo® by 5% (378 vs 395 units/kg−1), the initial post load activated clotting time (ACT) was 17% lower (556 vs 666 seconds). Heparin units required per kilogram per minute of cardiopulmonary bypass were 23% higher for Heparin Leo®. Additionally 8 of 52 Heparin Leo® patients did not achieve an initial post load ACT of greater than 400 sees while this occurred in 2 of 61 patients treated with Hepalean®. These results were statistically significant. British Pharmacopeia and United States Pharmacopeia heparin reference standards differences are insufficient to explain the discrepancies observed in this study.

Case 5—1996 thrombosis after the use of a heparin-coated cardiopulmonary bypass circuit in a patient with heparin-induced thrombocytopenia

A 64-year-old, 165-cm, 58-kg woman was admitted to the hospital with an inferior myocardial infarction. She underwent an emergent percutaneous transluminal coronary angioplasty (PTCA) complicated by an early reocclusion necessitating a second PTCA. The second PTCA complicated itself by the dissection of the right coronary artery (RCA), necessitating the placement of four stents in the RCA. The patient was then treated with porcine heparin (H) for 7 days. Warfarin was progressively titrated to a prothrombin time of 23% (international normalized ratio = 3.8), and heparin was then stopped. After 3 days of effectwe warfarin treatment, she suddenly developed cardiogenic shock with third-degree atrioventricular block, necessitating resuscitation maneuvers, intubation, placement of an intra-aortic balloon pump, and a pacemaker. After this resuscitation, she recovered well except for a right hemiparesis that was attributed to a prolonged hypotensive state. Coronary angiography disclosed a reocclusion of the RCA. Fibrinolytic therapy was then administered, and a continuous infusion of heparin was reintroduced. Forty-eight hours after her ischemic event, a cerebral computed tomography (CT) scan was normal, and she had no neurologic sequelae. Nine days later, despite receiving a continuous infusion of heparin, she became ischemic in the right coronary artery territory, and an emergent coronary revascularization was planned. While evaluating the patient's files, the attending anesthesiologist found that the platelet level was below 35,000/mm 3 from the beginning of the second heparin administration 10 days earlier (Fig 1), and he suspected a syndrome of heparin-induced thrombocytopenia (HIT). Because of the presence of four stents in the patient's RCA and owing to her history of the repetitive coronary occlusions, the cardiologists refused to stop the heparin infusion. This infusion was therefore stopped in the operating room. A central venous catheter was already in place, a radial arterial catheter was then placed under local anesthesia, and both were flushed with 0.9% saline without heparin. Anesthesia was induced with etomidate and sufentanil, and muscle paralysis achieved with pancuronium. Anesthesia was maintained with midazolam, and a continuous infusion of sufentanil, 2 Ixg/kg/hr. Iloprost is not available in Belgium; neither are the heparin substitutes proposed in the literature. The anesthesiologist had no experience with the use of low-molecularweight heparin (LMWH) during bypass. Therefore, he elected to use a heparin-coated cardiopulmonary bypass (CPB) circuit (HC-CPB) (Durafio II; Bentley [Englewood, CO], because of its theoretical advantages of biocompatibility and protection of platelets against activation caused by contact with the artificial surfaces. Only 50 IU/kg of porcine heparin were administered in place of the usual 300 IU/kg. Two saphenous grafts were sutured on the RCA. The procedure was performed under normothermia and intermittent antegrade warm blood cardioplegia. Aortic crossclamp time was 34 minutes, and CPB lasted 55 minutes. No pharmacologic support was needed to come off bypass. The platelet level was 34,000/mm 3 before surgery and 39,000/mm 3 after 50 IU/kg of H. It decreased to 22,000/ mm 3 after 7 minutes of CPB, possibly because of hemodilution, and returned to 39,000/mm 3 after discontinuation of CPB. Activated coagulation times with kaolin (ACT) (Hemotec; Medtronic [Uden, The Netherlands]) were 151 seconds before heparin administration, 231 seconds after 50 IU/kg of H, 445 and 443 seconds during CPB, and 295 seconds after CPB. Only 10 mg (2,000 IU) of protamine were then administered, and ACT returned to 148 seconds (Fig 2). After administration of another 1,000 IU of protamine, the ACT was 82 seconds. Despite this, the patient was still bleeding actwely. It was then judged that no more heparin was circulating at that time, and it was decided that it would

Effect of Thoracotomy and Cardiopulmonary Bypass on Activated Platelet and Neutrophil Dynamics and Platelet Emboli in a Pig Model.

The effects of thoracotomy and components of extracorporeal circuits on dynamics of platelets and neutrophils were quantified with autologous In-111-labeled platelets (INPLT) and neutrophils (INN) during cardiopulmonary bypass (CPB) operations in Yorkshire pigs. Cardiopulmonary bypass was carried out with a hollow-fiber oxygenator and an arterial filter in 48 pigs (30-35 kg; 12 unoperated controls for platelets and neutrophils; 12 sham operated controls; 12 with 180 minutes of CPB with platelets and neutrophils; 12 with 90 minutes of CPB and 90 minutes of reperfusion at 2.5-3.5 one/min. Platelets and neutrophils were labeled with In-111 tropolone and were injected intravenously: platelets at 24 hours and neutrophils at 15 minutes before CPB. All pigs were systemically heparinized [activated coagulation time (ACT) > 400 seconds]; CPB was instituted with a roller pump, oxygenator (OX; Bentley Univox, 1.8 m2), and arterial filter (AF; 0.025 m2) for durations of 180 minutes and 90 minutes of bypass, followed by 90 minutes of reperfusion. The kinetics and pooling of platelets and neutrophils were monitored by a Geiger probe. The adherent thrombi and neutrophils in the OX, AF, viscera, and brain were imaged with a gamma camera and were measured with an ion chamber and a gamma counter. The percentile distribution of labeled platelets and neutrophils expressed as the mean +/- standard deviation of injected dose in eight groups was calculated and statistical analyses were performed (ANOVA and paired t-test). Sham operation alone increased platelet retention in the lung, heart, and brain significantly (p < 0.001) over that of unoperated pigs. Neutrophil margination to lung immediately after injection was high; CPB and reperfusion altered the distribution in blood, viscera, and connective tissues. During CPB, an equilibrium among single platelets, platelet thrombi, and emboli was reached in the blood, oxygenator, arterial filter, perfused organs, and tissues. After CPB, the pulmonary neutrophil retention increased significantly (p < 0.001). Reperfusion of 90 minutes following 90 minutes of CPB decreased the level of neutrophils and increased the level of platelets in the lung. Only a small amount of platelets and neutrophils was retained in the oxygenator and arterial filter. Neutrophil retention in the OX and AF was higher than that of platelets. The small amount of retained neutrophils in the heart, kidneys, and brain suggested that cytokines, rather than marginated neutrophils alone, may play a major role in inflammatory insult to these organs during and after CPB. OX thrombi increased with the time of CPB; AF thrombus in both groups was almost similar. During CPB, AF functioned minimally as a thrombus trap with a small percent of retained thrombi; reperfusion post-CPB did not change the amount. Thoracotomy alone has a significant effect on platelet and neutrophil kinetics, and on the subsequent effect of thrombus formation, embolization, and neutrophil margination in organs during the CPB procedure.