Complement activation during cardiopulmonary bypass. Comparison of bubble and membrane oxygenators

A prospective randomized trial involving 91 patients undergoing cardiopulmonary bypass compared the effects of bubble oxygenators (with and without methylprednisolone sodium succinate) and membrane oxygenators on complement activation and transpulmonary sequestration of leukocytes. Patients were divided as follows: Group I, 30 patients, bubble oxygenator; Group II, 31 patients, bubble oxygenator and methylprednisolone sodium succinate (30 mg/kg); Group III, 30 patients, membrane oxygenator. In Group I, C3a increased from 323 +/- 171 ng/ml during cardiopulmonary bypass to 1,564 +/- 785 ng/ml at 25 minutes after bypass (p less than 0.0001). A significant decrease in C3a was found in Groups II and III compared to Group I (p less than 0.0001). C5a did not change significantly during cardiopulmonary bypass in any group. Reestablishment of pulmonary circulation at the end of bypass produced significant transpulmonary leukocyte sequestration in Group I; the median cell difference was 1,700/microliter. Transpulmonary sequestration was significantly (p less than 0.0001) less in Group II (median cell difference = 200/microliter) and in Group III (median cell difference = 400/microliter) than in Group I. We conclude that cardiopulmonary bypass with a bubble oxygenator alone initiates significantly (p less than 0.0001) more C3a activation and leukocyte sequestration than when methylprednisolone sodium succinate (30 mg/kg) is given 20 minutes before the start of cardiopulmonary bypass with a bubble oxygenator or when a silicone membrane oxygenator is used.     

Complement activation with bubble and membrane oxygenators in aortocoronary bypass grafting

Thirty-three patients admitted for coronary bypass grafting were randomized to cardiopulmonary bypass with a bubble oxygenator (Cobe or Polystan) or a membrane oxygenator (SciMed). Plasma concentrations of C3 activation products and the terminal complement complex were measured using enzyme immunoassays. Both variables increased almost linearly after onset of cardiopulmonary bypass, with maximal concentrations at closure of the sternum. From a baseline of 7.5 to 12.0 arbitrary units (AU)/mL (medians), the concentrations of C3 activation products increased by 117.5 AU/mL (Cobe), 120.5 AU/mL (Polystan), and 213.3 AU/mL (SciMed). The increase in the membrane group was significantly higher than in the two bubble oxygenator groups (p less than 0.01). From a baseline of 0.9 to 1.3 AU/mL, the concentrations of terminal complement complex increased by 5.4 AU/mL (Cobe), 6.6 AU/mL (Polystan), and 7.7 AU/mL (SciMed) (differences not significant). The higher C3 activation caused by the membrane oxygenator may be explained by differences in flow profile and surface area in contact with blood. The study cannot confirm the general assumption that membrane oxygenators lead to lower complement activation than do bubble oxygenators.     

Complement activation in cardiopulmonary bypass, with special reference to anaphylatoxin production in membrane and bubble oxygenators

Complement activation by cardiopulmonary bypass (CPB) was studied in 82 patients divided into membrane (MOG) and bubble oxygenator groups (BOG). The influence of primed homologous to circulating autologous blood volume (H/A) ratio was also evaluated. C4a increased very slowly during CPB in both groups, maintaining slightly higher levels in the BOG than in the MOG, with the exception of a marked initial rise in the BOG with a high H/A ratio (greater than or equal to 20%). Anaphylatoxin C3a levels increased more steeply in the BOG than in the MOG. An obvious rise in anaphylatoxin C5a production was observed in the BOG alone. The influence of high H/A ratio perfusion on complement activation was milder in the MOG than in the BOG. In 20 monkeys (Macaca fascicularis), continuous intraaortic infusion with bubbled autologous blood increased C4a and C3a levels, while autologous blood extracorporeally contacted with nylon increased C3a levels alone. In vitro studies revealed that human immunoglobulin fractions denatured by oxygen bubbling produced C4a, C3a, and C5a in a dose-dependent manner, although human albumin treated identically as human immunoglobulin did not produce these complements. It was thus inferred that (1) during CPB, complement is predominantly activated via the classical pathway in the BOG and via the alternative pathway in the MOG; (2) higher anaphylatoxin levels in the BOG than in the MOG are related to mode and grade of blood trauma; (3) anaphylatoxin level differences in both groups tend to increase with high H/A perfusion; and (4) immunoglobulin-free sera may reduced classical pathway activation.     

Washin and washout of isoflurane administered via bubble oxygenators during hypothermic cardiopulmonary bypass

Washin and washout of a volatile anesthetic given through the oxygenator during hypothermic (23.4 +/- 2.1 degrees C) cardiopulmonary bypass were studied in nine patients. The authors administered isoflurane and measured its partial pressure in arterial (Pa) and venous (Pv) blood and the gas exhausted from the oxygenator (PE) at 1, 2, 4, 8, 16, 32, and 48 min during washin. These measurements were repeated during washout, which coincided with rewarming. During washin, PE, Pa, and Pv progressively rose toward inlet gas partial pressure (PI). Equilibration of Pa with PI was 41% after 16 min, 51% after 32 min, and 57% after 48 min of washin. During washout, Pa declined to 24% of its peak after 16 min and to 13% after 32 min. Washin and washout were considerably slower in mixed venous blood. Washin of isoflurane appeared to occur more slowly during cardiopulmonary bypass than during administration via the lungs in normothermic patients, presumably because hypothermia increases tissue capacity, compensating for the effect of hemodilution that otherwise would decrease the blood/gas partition coefficient. During rewarming, washout appeared to occur as rapidly as from the lungs of normothermic patients. This may have resulted from the declining blood/gas partition coefficient (due to rewarming) and relatively limited tissue stores of isoflurane. The relationship between exhaust and arterial partial pressures was reasonably consistent; for clinical purposes, measurement of PE can be used to estimate Pa.     

Pressure drop, shear stress, and activation of leukocytes during cardiopulmonary bypass: a comparison between hollow fiber and flat sheet membrane oxygenators

The membrane oxygenator is known to be superior to the bubble oxygenator, but little information is available about the difference between the hollow fiber and flat sheet membrane oxygenators with regard to pressure drop, shear stress, and leukocyte activation. In this study, we compared these 2 types of membrane oxygenators in patients undergoing cardiopulmonary bypass (CPB) surgery with special focus on leukocyte activation and pressure drop across the oxygenators. Plasma concentration of elastase, a marker indicating leukocyte activation, increased to 593+/-68% in the flat sheet oxygenator group versus 197+/-42% in the hollow fiber oxygenator group (p<0.01) at the end of CPB compared to their respective baseline concentrations before CPB. Pressure drop across the oxygenator was significantly higher in the flat sheet group than in the hollow fiber group throughout the entire period of CPB (p<0.01). High pressure drop across the oxygenator as well as the calculated shear stress was positively correlated with the release of elastase at the end of CPB (r = 0.760, p<0.01, r = 0.692, p<0.01). However, this positive correlation existed in the flat sheet oxygenator but not in the hollow fiber oxygenator. Clinically, both membrane oxygenators have satisfactory performance in O2 and CO2 transfer. These results suggest that a higher pressure drop across the flat sheet oxygenator is associated with more pronounced activation of leukocytes in patients undergoing cardiopulmonary bypass.     

Cardiopulmonary bypass without systemic heparinization. Performance of heparin-coated oxygenators in comparison with classic membrane and bubble oxygenators

Performance characteristics of heparin-coated hollow-fiber membrane oxygenators (COATED HFMO, n = 5) were evaluated in an open-chest dog model without systemic heparinization. Four other oxygenators were evaluated with standard systemic heparinization (300 IU/kg, activated clotting time more than 400 seconds): a standard hollow-fiber membrane oxygenator (HFMO, n = 5), an inversed hollow-fiber membrane oxygenator (IHFMO, n = 5), a plate membrane oxygenator (PLATE MO, n = 5) and a bubble oxygenator (BUBBLE O, n = 5). The 25 dogs (36 +/- 12 kg) were perfused after cavo-aortic cannulation for 6 hours with a mean flow of 100 ml/kg body weight. At the end of perfusion without systemic heparin, heparin-coated equipment was replaced in three animals with standard uncoated equipment for control studies. Besides continuous hemodynamic evaluation with Mikro-Tip pressure transducers (Millar Instruments, Inc., Houston, Texas), a standard battery of analyses was performed before, after mixing, and every 30 minutes during bypass. All animals could be perfused in accordance with the protocol. Blood-gas values (pH, arterial oxygen tension, and arterial carbon dioxide tension) were maintained within physiologic ranges for all groups. After 6 hours of perfusion, plasma hemoglobin levels were as follows: 0.57 +/- 0.51 gm/L for COATED HFMO without systemic heparinization versus 2.65 +/- 1.02 gm/L for HFMO (p less than 0.05), 1.77 +/- 0.48 gm/L for IHFMO (p less than 0.05), 1.96 +/- 0.41 gm/L for PLATE O (p less than 0.05), and 1.5 +/- 0.40 gm/L for BUBBLE O (p less than 0.05) with systemic heparinization. Platelet levels were highest for COATED HFMO with 47% +/- 36% without systemic heparinization versus 33% +/- 9% for HFMO, 12% +/- 2% for IHFMO, 36% +/- 17% for PLATE O, and 19% +/- 12% for BUBBLE O with systemic heparinization. Activated clotting time for COATED HFMO without systemic heparinization was 135 +/- 75 seconds before bypass, 207 +/- 21 seconds after mixing, and 131 +/- 20 seconds after 4 hours of perfusion. There was no statistically significant increase of plasma heparin levels in the group perfused without systemic heparin. Determination of fibrin split products during perfusion without systemic heparinization did not show a significant increase. At the end of perfusion all devices were disconnected and gently rinsed with saline: There were no macroscopic clots in the COATED HFMO group perfused without systemic heparin. However, uncoated equipment introduced for control in animals perfused without systemic heparin showed major clotting.(ABSTRACT TRUNCATED AT 400 WORDS)     

The detection of microemboli in the middle cerebral artery during cardiopulmonary bypass: a transcranial Doppler ultrasound investigation using membrane and bubble oxygenators

Twenty-seven patients were examined who were undergoing cardiopulmonary bypass (CPB) surgery with either a bubble oxygenator or a capillary membrane oxygenator. The latter incorporated an arterial filter and bubble trap. A noninvasive Doppler ultrasound technique is described for monitoring irregularities in the Doppler flow signals attributable to gaseous microemboli detected in the middle cerebral artery during CPB. The ultrasound index for detecting gaseous microemboli (MEI) indicated the presence of such microemboli in 22 of the 27 patients during insertion of the aortic cannula. Measurements during CPB showed the MEI ranged from 4 to 39 in the 17 patients with a bubble oxygenator. However, all 10 patients with a membrane oxygenator had an MEI of 0. Varying the gas flow rates in 3 patients with bubble oxygenators showed a change in MEI from 4 +/- 4 (SD) at a flow rate of 2 L/min to 17 +/- 9 at a flow rate of 5 L/min. This observation supports the assumption that the MEI is providing quantitative information regarding the presence of gaseous emboli in the middle cerebral artery.     

Pulmonary reperfusion injury : A comparison of bubble and membrane oxygenators

Twenty cases of single valve replacement or atrial septal defect repair who underwent elective corrective surgery using either membrane (Capiox E) oxygenator (n=10) or bubble (Bentley 10™) oxygenator (n=10) were studied for the activation of cellular and humoral elements in blood. The bubble oxygenator was found to have more damaging effect of platelet sequestration and pulmonary sequestration of leucocytes. The C_3c and’ c₄ levels were found to be equally decreased in both groups. Both groups however showed no significant pneumocyte changes and there was no adverse effect on the postoperative clinical outcome in both groups.     

In vivo uptake and elimination of isoflurane by different membrane oxygenators during cardiopulmonary bypass

BACKGROUND: Volatile anesthetics are frequently used during cardiopulmonary bypass (CPB) to maintain anesthesia. Uptake and elimination of the volatile agent are dependent on the composition of the oxygenator. This study was designed to evaluate whether the in vivo uptake and elimination of isoflurane differs between microporous membrane oxygenators containing a conventional polypropylene (PPL) membrane and oxygenators with a new poly-(4-methyl-1-pentene) (PMP) membrane measuring isoflurane concentrations in blood. METHODS: Twenty-four patients undergoing elective coronary bypass surgery with the aid of CPB were randomly allocated to one of four groups, using either one of two different PPL-membrane oxygenators for CPB or one of two different PMP-membrane oxygenators. During hypothermic CPB, 1% isoflurane in an oxygen-air mixture was added to the oxygenator gas inflow line (gas flow, 3 l/min) for 15 min. Isoflurane concentration was measured in blood and in exhaust gas at the outflow port of the oxygenator. Between-group comparisons were performed for the area under the curve (AUC) during uptake and elimination of the isoflurane blood concentrations, the maximum isoflurane blood concentration (C(max)), and the exhausted isoflurane concentration (F(E)). RESULTS: The uptake of isoflurane, expressed as AUC of isoflurane blood concentration and a function of F(E), was significantly reduced in PMP oxygenators compared to PPL oxygenators (P < 0.01). C(max) was between 8.5 and 13 times lower in the PMP-membrane oxygenator groups compared to the conventional PPL-membrane oxygenator groups (P < 0.01). CONCLUSIONS: The uptake of isoflurane into blood via PMP oxygenators during CPB is severely limited. This should be taken into consideration in cases using such devices.     

Comparing oxygen transfer performance between three membrane oxygenators: effect of temperature changes during cardiopulmonary bypass

Recently, a new oxygenator (Dideco 903 [D903], Dideco, Mirandola, Italy) has been introduced to the perfusion community, and we set about testing its oxygen transfer performance and then comparing it to two other models. This evaluation was based on the comparison between oxygen transfer slope, gas phase arterial oxygen gradients, degree of blood shunting, maximum oxygen transfer, and diffusing capacity calculated for each membrane. Sixty patients were randomized into three groups of oxygenators (Dideco 703 [D703], Dideco; D903; and Quadrox, Jostra Medizintechnik AG, Hirrlingen, Germany) including 40/20 M/F of 68.6 +/- 11.3 years old, with a body weight of 71.5 +/- 12.1 kg, a body surface area (BSA) of 1.84 +/- 0.3 m(2), and a theoretical blood flow rate (index 2.4 times BSA) of 4.4 +/- 0.7 L/min. The maximum oxygen transfer (VO(2)) values were 313 mL O(2)/min (D703), 579 mL O(2)/min (D903), and 400 mL O(2)/min (Quadrox), with the D903 being the most superior (P < 0.05). Oxygen (O(2)) gradients were 320 mm Hg (D703), 235 mm Hg (D903), and 247 mm Hg (Quadrox), meaning D903 and Quadrox are more efficient versus the D703 (P < 0.05). Shunt fraction (Qs/Qt) and diffusing capacity (DmO(2)) were comparable (P = ns). Diffusing capacity values indexed to BSA (DmO(2)/m(2)) were 0.15 mL O(2)/min/mm Hg/m(2) (D703), 0.2 mL O(2)/min/mm Hg/m(2) (D903), and 0.18 mL O(2)/min/mm Hg/m(2) (Quadrox) with D903 outperforming D703 (P < 0.0005). During hypothermia (32.0 +/- 0.3 degrees C), there was a lower absolute and relative VO(2 )for all three oxygenators (P = ns). The O(2) gradients, DmO(2) and DmO(2)/m(2), were significantly lower for all oxygenators (P < 0.01). Also, Qs/Qt significantly rose for all oxygenators (P < 0.01). The oxygen transfer curve is characteristic to each oxygenator type and represents a tool to quantify oxygenator performance. Using this parameter, we demonstrated significant differences among commercially available oxygenators. However, all three oxygenators are considered to meet the oxygen needs of the patients.     

Should the gas outlet port on membrane oxygenators be routinely scavenged during cardiopulmonary bypass?

Elimination of a volatile anesthetic agent administered prior to the start of bypass through the oxygenator has not been previously described. The purpose of this study was to determine the contamination risk from enflurane used before but not during cardiopulmonary bypass. Enflurane concentration was measured from the gas outlet port of a membrane oxygenator using infrared gas analysis in 11 cardiac surgical patients. The mean peak concentration at the gas outlet port in patients who had a final end-tidal concentration of < or = 0.3% was 0.08 +/- 0.04%, compared to 0.18 +/- 0.05% in patients with a final end-tidal concentration of more than 0.3%, P < 0.001. The elapsed time to reach peak concentration was 8.3 +/- 8.4 minutes, whereas the elapsed time from the peak concentration to 50% of the peak level was 63.1 +/- 25.1 minutes. At the time of peak enflurane release, a concentration of less than 2 ppm was measured at distances of 10 cm or less from the oxygenator gas outlet port in patients with an end-tidal enflurane of < or = 0.3%. In one patient with a final end-tidal enflurane of 1.1%, a contaminant level of 2 ppm could be measured at 95 cm from the oxygenator gas outlet port. This demonstrates that there is a potential risk of contamination from volatile anesthetics used immediately prior to extracorporeal circulation. Minimizing this risk may necessitate routine scavenging of the oxygenator, or simply avoiding increased concentrations of inhalation anesthesia before initiating cardiopulmonary bypass.     

两种氧合器对心肺转流炎症反应的影响

目的动态监测室间隔缺损修补术患者在心肺转流(CPB)各时段血清可溶性细胞间粘附分子(sICAM-1)、可溶性E-选择素(sE-selection)及肿瘤坏死因子α(TNF-α)的变化规律,并比较西京-90鼓泡式氧合器和希健-Ⅱ膜式氧合器对其的影响。方法选择择期行室间隔缺损修补术的患者30例,随机均分为鼓泡式氧合器组(B组)和膜式氧合器组(M组)。所有患者分别在麻醉后CPB开始前(T1)、主动脉阻断开放前(T2)、CPB结束时(T3)、术后2h(T4)、6h(T5)、24h(T6)及48h(T7)取静脉血5ml用ELISA法测定sICAM-1、sE-selection及TNF-α的浓度。结果两组患者血清中的TNF-α于T2时开始显著升高,T4时达到峰值(P<0·01)。sICAM-1于T5时开始升高,T6时达峰值。sE-selection于T4时开始升高,T5时达峰值(P<0·01)。M组大部分时点TNF-α、sICAM-1、sE-selection的浓度均低于B组。结论希健-Ⅱ膜式氧合器引起的炎症反应较轻。     

A prospective comparison of bubble and membrane oxygenators in short and long perfusions

In operations with perfusion times longer than 90 min, a hollow-fibre membrane oxygenator causes less damage to red cells and platelets than a standard bubble oxygenator. There is also a trend towards less post-operative pulmonary shunting when a membrane oxygenator is employed.     

低温心肺转流中不同氧合器对儿童罗库溴铵药效动力学的影响

目的研究先天性心脏病学龄儿童心肺转流(CPB)中,不同氧合器对其罗库溴铵药效动力学的影响。方法选择6～12岁先天性心脏病患儿46例,随机分为膜式氧合器组(MO组,n=22)和鼓泡式氧合器组(BO组,n=24)。诱导后静脉给罗库溴铵600μg/kg行气管插管。CPB前、中、后三阶段,肌颤搐反应强度(T1)25%时,静注罗库溴铵200μg/kg。监测两组诱导期、CPB前、中、后期罗库溴铵的起效时间、无反应时间、T110%、T125%、T175%恢复时间及恢复指数等指标。结果两组患儿CPB前罗库溴铵肌松时效比较差异无统计学意义。CPB中,MO组和BO组的起效时间、无反应时间、T110%、T110%～25%、T125%分别为(3.72±2.10)、(29.45±7.67)、(46.36±7.26)、(14.12±2.62)、(60.57±6.31)和(3.62±1.78)、(24.95±6.93)、(43.07±7.99)、(13.04±2.46)、(56.68±6.82)min,组间比较差异无统计学意义。结论低温CPB中使用膜式氧合器与鼓泡式氧合器对罗库溴铵维持量的肌松时效影响差异无统计学意义。