Histopathological studies of goats after prolonged ECLA with a heparin-bonded artificial lung]

A pathological study was performed on the effects of prolonged extracorporeal lung assist (ECLA) with a heparin-bonded artificial lung and circuit in goats. A veno-venous ECLA was carried out in 15 goats for 5 to 10 days. Ten of them (Group I) were subjected to heparin-bonded devices and the other 5 (Group II) were subjected to the usual devices as control. The activated clotting time during ECLA was maintained at 130 seconds in Group I vs 200 seconds in Group II. The dose of heparin used in Group I was a half of that in Group II. Thrombi were found only in the lungs and the right side of the heart. The incidence of thrombi formation was low, and it was not significantly different between the two groups. Thrombotic embolism could not be found in any of the vital organs. Except for congestion, histological examination in these groups failed to reveal any remarkable changes. Electron microscopic study showed that heparin-bonded ECLA could maintain the normal alveolar structure. Compared with a usual system, ECLA with a heparin-bonded bypass exerted no significantly different effects on the thrombi formation and tissue histology, in spite of less systemic heparin administration for a prolonged period.     

Experimental Results Using Nafamostat Mesilate as Anticoagulant During Extracorporeal Lung Assist for 24 Hours in Dogs

Abstract: We report on the experimental application of nafamostat mesilate (NM, 6-amidino-2-naphthyl p -guanidinobenzoate dimethanesulfonate, FUT®), a new anticoagulant, to extracorporeal lung assist (ECLA) with an artificial membrane lung. Venovenous ECLA, from the jugular vein to the femoral vein, was performed with a hollow-fiber membrane lung at a blood flow rate of approximate 82 ml kg^-1 min^-1 for 24 h in 7 dogs under anesthesia and hypoventilation. Heparin (10 U ml^-1 in a priming lactated Ringer solution of 140 ml, and 200 U kg^-1) was administered before blood access cannulation. After start of ECLA, however, no heparin was used, and nafamostat mesilate was continuously infused into the drainage line of the bypass circuit to control activated coagulation time (ACT) at about 150 to 200s. To maintain the prolonged ACT, 8:0 ± 1.7 mg kg^-1 h^-1 of NM was required. Arterial blood pressure and pulse rate decreased significantly. Though fibrin monomer test revealed hypercoagulability after 6 h of ECLA, platelet counts did not significantly decrease. Total blood loss remained less than 40 g. The artificial membrane lung sustained a good gas exchange and low flow resistance throughout ECLA. Macroscopic examination revealed small spotty thrombi in the artificial lung but no major pathologic changes of the visceral organs in the all dogs at autopsy. High-dose NM administration could control blood coagulation and decrease blood loss during ECLA for 24 h without deterioration of the artificial lung and systemic complication other than mild hypotension and bradycardia.     

A New Heparin-Bonded Dense Membrane Lung Combined with Minimal Systemic Heparinization Prolonged Extracorporeal Lung Assist in Goats

Heparin was covalently bonded to a new hollow-fiber dense membrane artificial lung and extracorporeal circuit using a silane coupling agent and polyethyleneimine. This study investigated whether prolonged, venoarterial bypass extracorporeal lung assist (V-A bypass ECLA) could be sustained in a goat by the combination of the new membrane lung and minimal systemic heparinization. We maintained ECLA with the hollow-fiber lungs (surface area, 0.8 m²) and circuits by titrating the activated clotting time (ACT) to below 150 s with minimal systemic heparinization in 5 goats. The outcome was assessed from the function of the artificial lung via macro and microscopic examinations after the experiments and the incidence of systemic complications. The 5 goats were maintained on ECLA for 6 to 27 days. The bypass flow rate, blood gases at the return and drainage sites, platelet counts, and platelet aggregation activity were well maintained. Although the hemoglobin concentration, hematocrit, and plasma protein at the start of the ECLA were significantly lower than the pre-ECLA values due to hemodilution, the values remained stable during ECLA. A cerebral infarction occurred in 1 goat. However, in the other 4 goats, no complications such as bleeding, thrombosis, or plasma leakage from the artificial lung were observed. Although several thrombi were observed in the stagnant area of the artificial lung, these local thrombi did not cause the function of the artificial lung to deteriorate. We found that this new type of highly biocompatible, dense membrane artificial lung, when combined with minimal systemic heparinization, prolonged ECLA without the deterioration of the artificial lung function and was suitable for prolonged ECLA.     

Antithrombin III substitution for optimization of the heparin effect during extracorporeal circulation in heart surgery

In a prospective randomised study 20 patients undergoing coronary bypass surgery were assigned to two groups. Patients in group I (n = 10) received initially 250 IU heparin X kg-1 before the start of extracorporeal circulation. Patients in group II (n = 10) were given the same amount of heparin and in addition 1 000 units of purified human antithrombin III (AT III) concentrate. A highly significant lower heparin coefficient [2.69 +/- 0.57 IU X kg-1 X min-1, which is a parameter of heparin consumption (units of heparin X kg-1 given per minute during the time of heparinisation)], was found in group II compared to group I (3.73 +/- 0.56 IU X kg-1 min-1). Heparin sensitivity, measured as an increase in the ratio of activated coagulation time (ACT) X IU heparin-1 X kg-1 as a response to initial heparin dose, was found to be significantly higher (1.22 +/- 0.30 sec X IU heparin-1 X kg-1) in patients receiving AT III as measured in the control group (0.95 +/- 0.23 s X IU heparin-1 X kg-1). Mean values of ACT during the period of heparinisation were comparable (group I: 533 +/- 81 s, group II: 512 +/- 62 s) in the two groups. The substitution of AT III led to an increase of plasma AT III activity of 1.4% per substituted unit AT III X kg-1. AT III plasma activity, corrected to initial haematocrit levels to avoid dilution dependency, decreased as a consequence of extracorporeal circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Veno-arterial ECLA (extracorporeal lung assist) for severe respiratory failure due to meconium aspiration

A full term newborn female, 3262g, aspirated meconium at birth and began to suffer from severe hypoxia and acidosis due to progressing pneumonitis, pneumothorax and pneumomediastinum. She also had severe hypotension and anuria. Venoarterial ECLA with a Kolobow membrane lung via the right internal jugular vein and the right common carotid artery was initiated. Blood gas parameters and blood pressure improved, and urine output increased to normal. ECLA permitted a reduction in FIO2 and airway pressure of mechanical ventilation, as well as frequent lavage of the lung. As the physical condition improved, the bypass flow was gradually decreased from 200 ml.kg-1.min-1 at the start to 130 ml.kg-1.min-1 for maintenance, then to 25 ml.kg-1.min-1 at the end. Bleeding throughout the ECLA for 69 hours could be minimized by a meticulous control of the activated coagulation time with a minimum dose of heparin and the transfusion of fresh frozen and platelet rich plasma. After ECLA, the carotid artery was simply ligated, and mechanical ventilatory support was carried out for 5 days. Her condition improved and she left the hospital without any neurological sequelae. ECLA will become an effective means of life support for a baby with severe MAS irresponsive to conventional ventilatory support.     

Comparison of a new heparin-coated dense membrane lung with nonheparin-coated dense membrane lung for prolonged extracorporeal lung assist in goats

Thrombosis and bleeding are major complications in cases of prolonged extracorporeal lung assist (ECLA) with an artificial-membrane lung. Antithrombogenic treatment of the artificial-membrane oxygenator and circuits is indispensable for safe ECLA. The efficacy of a new heparin-coated membrane lung with minimal systemic heparinization was evaluated for 7 days and compared with a nonheparin-coated membrane lung in goats. The animals were randomly assigned to either the heparin-coated membrane group (HM group, n = 5) or nonheparin-coated membrane group (NHM group, n = 5). Activated coagulation time (ACT) during ECLA was controlled to below 150 s in the HM group, and to near 200 s in the NHM group. All goats in the HM group were sustained on ECLA for 7 days, but two goats in the NHM group died on the 4th and 6th days, respectively. The mean systemic administration rate of heparin during ECLA was 22.4 +/- 4.4 U/kg/h in the HM group and 39.0 +/- 10.0 U/kg/h in the NHM group. There was a significant difference between the two groups (P < 0.05). The oxygen transfer rate, the Pco(2) difference, the perfusion resistance, and platelet counts showed no significant changes. There was no plasma leakage from the artificial lung. Although several clots were observed in the stagnant areas of the artificial lung, they did not lead to deterioration of the function of the artificial lung. The excellent antithrombogenicity, gas exchange ability, and durability of this new artificial lung with circuits might contribute to successful prolonged ECLA with minimal systemic heparinization.     

Heparin-coated Cardiopulmonary Bypass Circuits in Coronary Bypass Surgery

Abstract: Cardiopulmonary bypass (CPB) is a nonphysiologic environment for an organism. The damage of blood components may also lead to organ dysfunction, sometimes recognized as postperfusion syndrome. One possible way to diminish the risk of these complications would be to reduce the thorombogenicity and to improve the biocompatibility of the artificial surfaces by using a heparin-coated CPB circuit. In this study, we compared a heparin-coated CPB circuit with a noncoated CPB circuit in terms of biocompatibility in 20 patients undergoing elective coronary bypass surgery. We employed a Dura-flo II (n = 10) as a heparin-coated CPB circuit and a Univox IC (n = 10) as control subjects. Ten patients (Group C) were operated on using the heparin-coated CPB circuit. A total of 10 patients were given heparin in a reduced dose (2.0 mg/kg), and additional heparin was given if the activated clotting time (ACT) was below 400 s. The control group also included 10 patients (Group NC), who were operated on with noncoated devices. They received 2.5 mg/kg of heparin, and additional heparin was given if the ACT was below 450 s. All patients had normal coagulation parameters and did not receive blood transfusion. We measured complement activation levels (C3a, C4a), platelet count, thrombin-antithrombin III complex levels, D-dimer levels, and ACT during CPB and respiratory index postoperatively. The concentration of C3a in group NC was significantly higher than that in group C. Platelet reduction in group NC was significantly greater than that in group C. There were no significant differences in the remaining parameters between the 2 groups. We concluded that heparin-coated CPB circuits improved biocompatibility by reducing complement activation and platelet consumption and enabled us to reduce the dose of heparin required for systemic heparinization.     

Heparin resistance during cardiopulmonary bypass

A 74-year-old man was scheduled for coronary artery bypass graft surgery with cardiopulmonary bypass. After intravenous heparin (200 U.kg-1), the activated clotting time (ACT) increased from 124 to 436 sec. However, it decreased to 128 sec immediately after cardiopulmonary bypass. The bypass was discontinued because the addition of heparin (200 U.kg-1) proved heparin resistance. The coronary artery bypass procedure was completed uneventfully without cardiopulmonary bypass. Several recent articles have reported that heparin resistance was corrected with antithrombin III concentrates, fresh frozen plasma, or argatroban. In this case, these drugs could not be used because the mechanism of heparin resistance remains uncertain. Thus, the off-pump technique is useful for unknown heparin resistance.     

Heparin resistance associated with elevated factor VIII

An 84-year-old female patient was scheduled to undergo AVR, CABG, and Maze procedure. She had a history of hypertension, cerebral infarction, and branch retinal vein occlusion. Warfarin was administered preoperatively. Before the cardiopulmonary bypass (CPB), heparin 5,000 units was administered. Activated coagulation times (ACTs) before and after CPB were 123 sec and 157 sec, respectively. Additional heparin of 5,000 units extended ACT to 221 seconds, which was not enough for the CPB. Heparin 10,000 units was added, and ACT was 157 sec. AntithrombinIII (ATIII) and platelet counts were 75% and 270,000 mm(-3), respectively. ATIII 1,500 units was administered. ACT and ATIII became 133 sec and 123%, respectively. Because heparin resistance did not respond to ATIII, the operative method was changed to off-pump CABG. A postoperative examination revealed high factor VIII activity of 263%. Other results were as follows: protein C antigen, 40%; protein S antigen, 65%; factor VII, 50%; platelet factor 4, 12%; heparin cofactor II, 104%; von Willebrand factor antigen, 181%; heparin-PF4-IgG antibody, negative; factor VIII inhibitor, negative. The low values of protein C, protein S, and factor VII may have been caused by warfarin. Other values were normal, except for the von Willebrand factor antigen.     

Comparison of two protocols for heparin neutralization by protamine after cardiopulmonary bypass

Twenty patients undergoing cardiac operations were randomly assigned to two protocols for heparin neutralization by protamine after cardiopulmonary bypass. In all patients protamine chloride was given at a ratio of 1 unit of protamine to 1 unit of injected heparin. In Group I (10 patients) all protamine was infused within 10 minutes after termination of cardiopulmonary bypass. Group II (10 patients) received 75% of the calculated protamine dose within 10 minutes after termination of bypass and the remainder after transfusion of all blood in the heart-lung machine. Plasma heparin levels were significantly lower in Group II 5 minutes after transfusion of all blood in the heart-lung machine and were 0.13 units/ml (standard deviation 0.04) in Group I and 0.06 units/ml (standard deviation 0.05) in Group II (p less than 0.001) 60 minutes after bypass. Activated partial thromboplastin time mirrored the changes in plasma heparin, whereas activated clotting time (Hemochron) was too insensitive to detect these low plasma heparin levels. We conclude that the two-dose protocol resulted in more complete heparin neutralization than the one-dose protocol.     

A reevaluation of heparin requirements for cardiopulmonary bypass

We wished to determine if reduction in the standard heparin administration for cardiopulmonary bypass could be accomplished safely with the use of membrane oxygenators. An experimental study was designed to evaluate two different heparin administration protocols for cardiopulmonary bypass with hollow-fiber membrane oxygenators. Two groups of six pigs were submitted to hypothermic cardiopulmonary bypass (28 degrees C) for 3 hours, then rewarmed, decannulated, and reassessed after 1 hour. In group I (control) heparin was administered to maintain the activated clotting time in excess of 450 seconds; in group II activated clotting time was maintained between 250 and 300 seconds. The mean total heparin administered was 41,000 units in group I and 25,000 units in group II. Concentration of coagulation factors II, V, and VIII, fibrinogen, and platelet count were determined before, during, and 1 hour after bypass. No significant difference in any of these coagulation parameters was observed between the groups. The performance of the oxygenators was similar in both groups, with no evidence of thrombosis. Thus reduced heparin administration, enough to keep activated clotting time between 250 and 300 seconds, was not related either to major coagulation factors and platelet consumption or to derangements in the oxygenator's performance.     

Preoperative low molecular weight heparin reduces heparin responsiveness during cardiac surgery

PURPOSE: Cardiac surgery with cardiopulmonary bypass requires systemic anticoagulation, defined by an activated clotting time (ACT) of 400-480 sec. Patients with altered heparin responsiveness require disproportionately higher doses of heparin to achieve this target ACT. A common risk factor for heparin resistance is preoperative heparin therapy. Recently, therapy with low molecular weight heparin (LMWH) has become an acceptable substitute for prolonged heparin therapy. The current study examines the effect of preoperative LMWH therapy on subsequent heparin responsiveness during cardiac surgery. METHODS: Records of patients undergoing cardiac surgery with cardiopulmonary bypass over a period of four months were reviewed. We identified patients who, during the week preceding surgery, had received prolonged (>24 hr) therapy with either sc LMWH (LMWH group) or continuous iv unfractionated heparin (Heparin group). A Control group consisted of patients who received neither heparin nor LMWH preoperatively. The heparin sensitivity index (calculated as the first change in ACT from baseline divided by the first intraoperative heparin dose, normalized to body weight), was compared among groups using ANOVA. RESULTS: One hundred and thirty-nine patients were included in the analysis. The heparin sensitivity index was 33-45% higher in the Control group (1.6+/-0.7 sec.IU-1.kg-1; P<0.0001) compared to the LMWH (1.2+/-0.4 sec.IU-1.kg-1) and Heparin (1.1+/-0.5 sec.IU-1.kg-1) groups. In a multivariable model, the use of preoperative LMWH remained a significant predictor of reduced intraoperative heparin responsiveness (P=0.002). CONCLUSION: Prolonged preoperative LMWH therapy, similar to the known effect of prolonged unfractionated heparin infusion, reduces subsequent intraoperative response to heparin.     

The treatment of heparin resistance with Antithrombin III in cardiac surgery

PURPOSE: To report three patients who developed heparin resistance during cardiac surgery which was successfully managed with 1000 U Antithrombin III (AT III). CLINICAL FEATURES: We observed heparin resistance prior to cardiopulmonary bypass (CPB) in one patient and during the CPB in two patients. In the first patient who was scheduled for mitral valve replacement, although heparin was administered sequentially up to 500 U x kg(-1) prior the CPB, the ACT value was 354 sec. After 1,000 U ATIII were administered the ACT was 395 sec and CPB was initiated. The ACT remained between 496 and 599 sec throughout CPB and a total of 260 mg protamine sulfate was given. In the other two patients following 300 U x kg(-1) heparin, the ACT was up to 400 sec and CPB was initiated. During CPB, ACT were decreased 360 sec and 295 sec in patients II and III respectively. Although heparin was added 1,500 U, ACT increased to > or = 400 sec could not be achieved. In the second patient ATIII activity was found 10%. After the administration of 1,000 U ATIII, ATIII activity was found to be 67% 40 min later and ACT were increased up to 400 sec. There was no thrombosis within the extracorporeal circuit, additional heparin was not required, less protamine was administered (< or = 3 mg x kg(-1)) and no excessive postoperative bleeding was observed in all patients. CONCLUSION: We recommend that AT III supplementation should be considered to manage heparin resistance prior or during CPB in patients undergoing open heart surgery.     

Maintenance of blood heparin concentration rather than activated clotting time better preserves the coagulation system in hypothermic cardiopulmonary bypass

In cardiopulmonary bypass (CPB), despite heparin regimens in which the activated clotting time (ACT) is kept at more than 400 s, there is biochemical evidence of thrombin generation indicating activation of the coagulation system and increased fibrinolytic activity. Therefore, to reduce the coagulant activation has been one of the main issues in the improvement of CPB. The purpose of this study was to compare the heparin concentration with the ACT and to evaluate the effect of keeping higher heparin concentration on the coagulation and fibrinolytic systems during hypothermic CPB, employing moderate hypothermia (MHT) or deep hypothermic circulatory arrest (DHT). Heparin was either administered to maintain an ACT >400 s (ACT group) or to maintain a whole blood heparin concentration of 3 mg/kg (heparin group). At the lowest core temperature during CPB, the ACT and the heparinase ACT (unrelated to heparin concentration) were increased the most whereas the whole blood heparin concentration was less than half the initial concentration in both ACT groups of MHT and DHT. The thrombin-antithrombin III (TAT) content just after CPB in both MHT and DHT was significantly lower in the heparin group than in the ACT group. In conclusion, ACT does not reflect the whole blood heparin concentration during hypothermic CPB. Furthermore, maintenance of the higher heparin concentration during hypothermic CPB may suppress the activation of the coagulation system via thrombin inhibition. That effect was more remarkable in deep hypothermic CPB. Therefore, we believe that anticoagulation management during hypothermic CPB should be based on the maintenance of the higher blood heparin concentration.     

Low activated coagulation time during cardiopulmonary bypass does not increase postoperative bleeding

The activated coagulation time (ACT) is widely used to monitor adequacy of anticoagulation during cardiopulmonary bypass despite absence of data establishing an ACT below which adverse outcomes occur. For anticoagulation before cardiopulmonary bypass, we administered a single dose of heparin (300 U/kg) to 193 patients and measured ACT and heparin levels at intervals after administration. No additional heparin was administered to any patient. Clot formation in the cardiopulmonary bypass circuit and excessive postoperative chest tube drainage were considered outcomes indicating inadequate anticoagulation. Cardiopulmonary bypass averaged 59 +/- 23 minutes (range, 30 to 138 minutes). Activated coagulation time values at every sampling period were normally distributed. In 51 patients (26.4%) ACT values were less than 400 seconds, including 4 less than 300 seconds, at some sampling time after heparinization. Patients with low ACT values did not bleed more postoperatively than those with high ACT values, nor was bleeding related to heparin level. No clots were found in any perfusion circuit. We conclude that a minimum ACT value for adequacy of heparinization is not yet defined but that it is less than 400 seconds.     

Aggressive blood conservation in coronary artery surgery: impact on patient care

Data on 100 consecutive non-emergency coronary artery bypass (CABG) patients were analyzed retrospectively. Sixty-nine patients received no homologous blood (Group I). Thirty-one patients received a total of 118 units of blood products averaging 2.23 units of red cells (Group II). The average red cell transfusion rate for all patients was 0.7 units per patient. The median age for Group I was 61 and Group II was 68 years (p less than 0.05). The average number of grafts was the same for both (3 per patient) with 75% of Group I and 58% of Group II receiving internal mammary artery (IMA) grafts (p less than 0.05). Twelve of the Group II patients who received intraoperative transfusions on cardiopulmonary bypass to maintain adequate hemoglobin levels were older and had lower admission hematocrits: 36 +/- 0.8% compared to 41 +/- 0.5% for all other patients (p less than 0.05). Average postoperative blood loss was 889 +/- 38 ml for Group I and 1077 +/- 104 ml for Group II (p less than 0.05). Increased hemorrhage was correlated with bypass time and IMA use but not with preoperative heparin administration, pre-existing risk factors (diabetes, hypertension, etc.), bleeding time, post-bypass clotting time, age or number of grafts. Two patients in Group II and none in Group I required exploration for excessive postoperative hemorrhage. Mortality rate was 2% (both in Group II, neither transfusion related). Discharge hematocrits were the same for all at 29.4 +/- 0.4%. Among anemia-related postoperative symptoms, only sinus tachycardia was significantly higher in Group I (20%) compared to Group II (6.5%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Arterial versus venous sampling for activated coagulation time measurements during cardiac surgery: a comparative study

OBJECTIVE: Activated coagulation times (ACTs) are widely used for monitoring anticoagulation during cardiac surgery. Significant variability of this test is well known. Variability in test results was studied, which may arise from the sample drawing site. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Sixty-five patients scheduled for surgery requiring cardiopulmonary bypass were enrolled in the study. INTERVENTION: ACTs were assessed using the Hemochron 801 ACT machine. Samples were collected (1) baseline I from the arterial catheter before anesthetic induction, (2) baseline II from the arterial and venous collection sites after pulmonary artery catheterization, (3) after heparin administration, (4) 10 minutes after blood collection number 3, and (5) after protamine administration. MEASUREMENTS AND MAIN RESULTS: At the baseline II, the ACT measures using venous blood were significantly higher than that obtained using an arterial sample (p = 0.001). There was no significant difference in ACT measures obtained using either arterial or venous blood samples at the other time points. After heparin administration, the ACT variability in individual patients was quite striking, with ranges of up to 600 seconds in repeated measures. CONCLUSION: During the period of systemic anticoagulation, there is great individual variability between ACT measures obtained from venous and arterial samples. Further studies are required to analyze the cause of differences at the baseline and the source of variable coagulation times after heparin.     

Experimental evaluation of the V-point heparin-bonding system applied to a dense-membrane artificial lung during 24-hour extracorporeal circulation in beagles

Heparin was covalently bonded to a hollow-fiber dense-membrane artificial lung and circuit using a silane coupling agent and polyethyleneimine as a spacer. This study investigated whether the novel artificial lung could sustain prolonged extracorporeal lung assist (ECLA) by venoarterial bypass in beagles using minimal anticoagulants. We maintained ECLA for 24 h in 3 groups of minimal systemic heparinization, heparinization with the new anticoagulant nafamostat mesilate, and without any systemic anticoagulant. The results were assessed from the functional performance of the artificial lung and by macroscopic and microscopic examination after the experiments. Artificial lung function, hemodynamics, hemogram, and platelet aggregation activity were well maintained in all groups. There was no plasma leakage from the artificial lung. Although several clots were observed in stagnant areas of the artificial lungs and circuits, there was no clot formation inside the artificial lung in any group. This highly biocompatible, heparin-bonded dense-membrane artificial lung performed well and safely during prolonged ECLA with blood clotting times less than 120 s.     

The plasma supplemented modified activated clotting time for monitoring of heparinization during cardiopulmonary bypass: a pilot investigation

The standard celite or kaolin activated clotting time (ACT) correlates poorly with heparin levels during cardiopulmonary bypass (CPB). We compared a modified kaolin ACT, in which plasma was supplemented, to a standard undiluted kaolin ACT for monitoring heparin levels during CPB. Fifteen patients undergoing normothermic CPB were enrolled in this prospective study. Heparin management was performed according to the Hepcon HMS results (Medtronic, Minneapolis, MN). The ACTs were performed with the ACT II device (Medtronic). Hepcon HMS calculations, standard kaolin ACTs, and plasma supplemented modified ACTs (mACTs), prepared by diluting blood samples 1:1 with human plasma (Behring, Marburg, Germany), were measured every 30 min during CPB. The data obtained were correlated to the plasma chromogenic anti-Xa activity as a reference assay for heparin levels. A total of 64 samples were evaluated. The chromogenic anti-Xa activity ranged from 0.2 to 5.5 IU/mL. The Hepcon HMS calculations ranged from 2.7-8.2 IU/mL of heparin, the standard ACT ranged from 424 to >999 s, and the mACT ranged from 210 to 801 s. The correlation to the chromogenic anti-Xa method was r = 0.43 for the standard kaolin ACT and r = 0.69 for the plasma mACT. The plasma mACT provided an improved correlation to chromogenically measured levels of anti-Xa activity during CPB. The improved correlation most likely results from a correction of the effects of the impairment of the coagulation system caused by hemodilution and consumption of procoagulants on extracorporeal surfaces. IMPLICATIONS: During cardiopulmonary bypass, the plasma modified kaolin activated clotting time (ACT) provides a better correlation with heparin levels than the standard kaolin ACT.     

Cytokine Generation in Rabbits During Extracorporeal Lung Assist with a Mini Hollow Fiber Lung

Abstract: To examine host responses to extracorporeal lung assist (ECLA) in small animals, we developed a mini hollow fiber lung of nonmicroporous polyolefin and an extracorporeal bypass circuit with a priming volume of 25 ml. This circuit allowed ECLA of up to 72 h without blood transfusion in 20 rabbits. The ECLA procedure induced the appearance of tumor necrosis factor-a (TNF-a) and interleukin-1 (IL-1) receptor antagonist (IL-IRa) in plasma, but not IL-ip. However, these changes were observed only at the initial stage of ECLA, and the levels returned to pre-ECLA levels within 24 h. Although leukocytes adhering to the hollow fibers were immunohisto-chemically positive for IL-ip and IL-IRa, the plasma levels of these cytokines in response to ECLA were not different from those observed in rabbits given anesthesia and subjected to minor surgery but without ECLA. Thus, ECLA itself is a minor factor in the production of these cytokines.