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Ann Thorac Surg 1995;60:544-549
© 1995 The Society of Thoracic Surgeons
Center for Cardiopulmonary Surgery Amsterdam and Departments of Anesthesiology and Surgery, Free University Hospital, Amsterdam, the Netherlands
Accepted for publication March 6, 1995.
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Abstract |
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 TopFootnotes Abstract IntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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Methods. Measurements were carried out at fixed time points before and after cardiopulmonary bypass (until 18 hours postoperatively) and include hematocrit, colloid oncotic pressure, fluid balance, and hemodynamic profile (mean of three measurements).
Results. The lower colloid oncotic pressure in the large prime group (16.2 ± 0.6 mm Hg versus 19.1 ± 1.1 mm Hg, p = 0.0002) was associated with a highly positive fluid balance (5.5 ± 0.9 L versus 2.8 ± 0.7 L, p = 0.0001). With the on-bypass hematocrit aimed at 22% to 23%, autologous blood was predonated by 16 patients in the small prime group but by none in the large prime group. Reinfusion of autologous blood resulted in a reduction in blood bank requirements (p = 0.03). Mean arterial pressure was 83 ± 4 mm Hg for small prime versus 76 ± 4 mm Hg for large prime (p = 0.01). Cardiac index was 2.9 ± 0.2 L • min-1 • m-2 for small prime versus 3.8 ± 0.3 L • min-1 • m-2 for large prime (p = 0.0001). Pulmonary vascular resistance index was 281 ± 40 dyne • s • cm5 • m-2 for small prime versus 188 ± 22 dyne • s • cm5 • m-2 for large prime (p = 0.0009). Oxygen delivery was 42 ± 5 mL • min-1 • m-2 for small prime versus 51 ± 3 mL • min-1 • m-2 for large prime (p = 0.004). Vasoactive medication was not different among groups.
Conclusions. Reduction in prime volume attenuates the hyperdynamic response after cardiopulmonary bypass. Furthermore, an important reduction in blood bank products can be obtained with small prime volumes.
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Introduction |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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Extracorporeal circulation is indispensable in daily practice of open heart operations, but the use of extracorporeal circuits is associated with postoperative organ dysfunction [1]. Apart from the activation of host defense mechanisms by the exposure of blood to the artificial surfaces of the circuit [2], a number of pathophysiologic changes occur with the institution of cardiopulmonary bypass (CPB). Hemodilution by the asanguineous pump prime and the crystalloid cardioplegia diminishes plasma colloid oncotic pressure (COP) with a concomitant expansion of the interstitial space [3, 4]. In addition, hypothermic, nonpulsatile CPB with reduced flow rates leads to redistribution of blood flow in favor of vital organs such as the brain, whereas perfusion of the digestive tract is reduced [5, 6]. The peripheral vasodilation during rewarming and the persistent hemodilution herald a hyperdynamic state after weaning from CPB, with elevated cardiac output, decreased vascular resistance, and excessive fluid requirements [6].
In an attempt to prevent the decrease in COP at the onset of CPB, many centers add colloids to the prime of the extracorporeal circuit, but the routine use of these substances remains controversial. There is no general agreement on the clinical benefit of colloid-containing prime in comparison with pure crystalloid prime, as demonstrated in various clinical studies [7–10]. However, with the large prime volumes used in these studies (ranging from 2 to 2.5 L), normooncotic perfusion was not achieved, whereas increasing the colloid content of the prime was associated with compromised hemostasis [11].
An alternative approach to modify the dilutional imbalance during CPB is reduction in the extracorporeal volume by using low prime volume oxygenators and ergonomically designed circuits. To determine the efficacy of low prime volume extracorporeal circuits, we performed a database study on patients who underwent elective coronary artery bypass grafting with either a standardly used extracorporeal circuit with a large prime volume or a modified extracorporeal circuit with a small prime volume. Measurements were carried out at fixed time points before and after CPB and include hematocrit, COP, hemodynamic profile, fluid balance, and thoracic electrical resistance; the latter as an estimate of changes in thoracic fluid contents [12, 13].
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Material and Methods |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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Anesthesia, Cardiopulmonary Bypass, and Postoperative Care
On the morning of operation, patients received their usual early morning dose of antianginal medication and 5 mg of lorazepam. Anesthesia was induced using 3 µg/kg of intravenous sufentanyl forte, 0.1 mg/kg of pancuronium bromide, and 0.1 mg/kg of midozalam and maintained by supplemental doses. After endotracheal intubation, patients were ventilated to normocapnia using an oxygen/air mixture. Radial artery and thermodilution pulmonary artery catheters were placed for hemodynamic measurements and procurement of blood samples. The extracorporeal circuit consisted of a soft-shell venous reservoir, roller pump, membrane oxygenator (large prime volume: Ultrox-1, Avecor, Plymouth, MN; small prime volume: Univox, Baxter Healthcare Corp, Irvine, CA), arterial line filter, cardiotomy reservoir, and polyvinyl tubing system. The large prime volume was 2,350 mL: 2,000 mL of lactated Ringer's solution, 200 mL of 20% human albumin (CLB, Amsterdam, the Netherlands), 100 mL of 20% mannitol, 50 mL of 8.4% sodium bicarbonate, and 5,000 IU of bovine lung heparin. The small prime volume was 1,400 mL: 1,250 mL of lactated Ringer's solution, 100 mL of 20% mannitol, 50 mL of 8.4% sodium bicarbonate, and 5,000 IU of bovine lung heparin. To perform subtotal CPB, a standard cannulation technique was used with cannulas placed in the ascending aorta and right atrium (two-stage venous cannula). After systemic heparinization (300 IE/kg), CPB was initiated, provided the activated clotting time was more than 400 seconds. The standardized perfusion protocol aimed at a hematocrit of 22% to 23% during CPB. Autologous blood was donated through the venous cannula before onset of CPB if the predicted ``on-bypass'' hematocrit was more than 24%. The predonated blood was replaced by an equal volume of normooncotic modified fluid gelatin (Gelofusine, NPBI, Emmer-Compascuum, the Netherlands). Nonpulsatile flow rate was maintained at 2.2 to 2.4 L • min-1 • m-2 and patients were cooled to 29° to 30°C nasopharyngeal temperature. After aortic cross-clamping, 800 to 1,000 mL of crystalloid cardioplegia was infused into the aortic root (16 mmol/L potassium chloride, 4°C). Blood from the pericardial cavity was collected in a cardiotomy reservoir and returned to the patient. After termination of CPB, heparin was neutralized using an equal dose of protamine sulfate (3 mg/kg). Postoperatively, all patients were transported to the intensive care unit (ICU) where they were ventilated with intermittent positive pressure breathing. Hemodynamic goals were heart rate, 70 to 80 beats/min; mean arterial blood pressure, 65 to 80 mm Hg; pulmonary artery wedge pressure, 8 to 12 mm Hg; and cardiac index, more than 2.5 L • min-1 • m-2. Red packed cells were infused if the hematocrit was less than 26%.
Hemodynamic Profile, Sampling, and Volume Management
The hemodynamic profile consisted of heart rate, mean arterial pressure, central venous pressure, mean pulmonary artery pressure, pulmonary artery wedge pressure, and cardiac output (thermodilution, mean of three subsequent measurements). In addition, the following variables were calculated: cardiac index = cardiac output/body surface area; systemic vascular resistance index = 80 x (mean arterial pressure - central venous pressure)/cardiac index; pulmonary vascular resistance index = 80 x (mean pulmonary artery pressure - pulmonary artery wedge pressure)/cardiac index; and oxygen delivery = (arterial oxygen saturation x hemoglobin concentration x 1.39 + arterial oxygen tension x 0.0031) x cardiac index. Measurements were recorded before onset of CPB (baseline), after weaning from CPB, and 1, 4, and 18 hours after arrival in the ICU.
All blood samples were drawn from the radial artery catheter or the arterial site of the extracorporeal circuit. Hematocrit and COP were determined before induction of anesthesia, after start of CPB, after weaning from CPB, and 1, 4, and 18 hours after arrival in the ICU. A membrane osmometer with a nominal molecular weight cut-off of 20,000 dalton (Onkometer BMT 921, BMT Messtechnik GmBH, Berlin, Germany) was used to measure COP in whole blood anticoagulated with ethylenedinitrotetraacetate.
Thoracic electrical resistance measurements were carried out to estimate changes in total thoracic fluid contents. For this purpose, a plethysmograph (model 101; RJL Systems, Mt Clemens, MI) was applied. Two electrodes placed diagonally across the thorax detected voltage that was transmitted by an 800-µA 50-kHz alternating current through two electrodes placed 20 cm peripherally from the detecting electrodes. Reduction in detected voltage is associated with increased fluid content [12–14].
Fluid balance was defined as fluid administration - (diuresis + blood loss) and was calculated from induction of anesthesia until 18 hours postoperatively. The distribution of insensible fluid losses was considered even among both groups and not included in the calculation. The use of blood bank products and colloids was registered separately.
Data Analysis
Data were stored and analyzed, using standard computer software (Statview 4.02; Abacus concepts, Berkeley, CA). Intergroup comparisons were assessed with unpaired two-tailed t tests. To analyze changes within each group, one-factor analysis of variance for repeated measures was applied, supplemented with the Scheffé's post hoc test. In addition, two-factor analysis of variance was used to assess intergroup comparisons and group-time interactions during ICU stay. A significant group-time interaction indicates that the difference for the main effect (the two groups) has no meaning as the difference would chance with time. Conversely, if the interaction is not significant, testing for group differences at different times is not appropriate as all differences are then assumed equal [15]. Ordinal variables were analyzed with the Mann-Whitney Usans-serif test and dichotomous variables with Fisher's exact test. Regression analysis was performed if appropriate. A two-tailed p value of less than 0.05 was considered to be statistically significant. Values are presented as mean ± 95% confidence interval of the mean, unless mentioned otherwise.
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Results |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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. No complications occurred and all patients survived and left the ICU on the first postoperative day. In both groups a sudden decline in hematocrit and COP was observed after initiation of CPB (Fig 1). In the small prime group COP increased during CPB and reached levels in the ICU that were not different from baseline levels. In the large prime group, COP remained low compared with baseline. In the ICU (mean of three measurements) COP was 19.1 ± 1.1 mm Hg in the small prime group versus 16.2 ± 0.6 mm Hg in the large prime group (p = 0.0002, no interaction with time).
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. None of these variables demonstrated intergroup differences before and after CPB. Although there was no significant intragroup difference, mean arterial pressure in the ICU was 83 ± 4 mm Hg for small prime versus 76 ± 4 mm Hg for large prime (p = 0.01, no interaction with time). In both groups cardiac index after CPB and in the ICU was increased compared with baseline. In the ICU, cardiac index was 2.9 ± 0.2 L • min-1 • m-2 in the small prime group versus 3.8 ± 0.3 L • min-1 • m-2 in the large prime group (p = 0.0001, no interaction with time). Both groups demonstrated decreased systemic vascular resistance indices after CPB and in the ICU. There was a significant group-time interaction on systemic vascular resistance index in the ICU (p = 0.04), therefore the intergroup difference during that period could not be explained by the difference in prime volume alone. Pulmonary vascular resistance index decreased after CPB in the large prime group but not in the small prime group. During ICU stay, pulmonary vascular resistance index was 281 ± 40 dyne • s • cm5 • m-2 in the small prime group versus 188 ± 22 dyne • s • cm5 • m-2 in the large prime group (p = 0.0009, no interaction with time). There were no intergroup differences in heart rate, central venous pressure, mean pulmonary artery pressure, pulmonary artery wedge pressure, and vasoactive medication.
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). In the ICU, oxygen delivery was 42 ± 5 mL • min-1 • m-2 in the small prime group versus 51 ± 3 mL • min-1 • m-2 in the large prime group (p = 0.004, no interaction with time). Thoracic electrical resistance decreased in both groups (Fig 3). In the ICU, thoracic electrical resistance was 80 ± 4% in the small prime group versus 72 ± 5% in the large prime group (p = 0.01, no interaction with time). Regression analysis demonstrated a weak correlation between thoracic electrical resistance and cardiac index in the ICU (r2 = 0.23).
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. Autologous blood was donated at the start of CPB by 16 of the 20 patients in the small prime group, but by none of the patients in the large prime group. Multiple comparison analysis of variance yielded that autologous donation determined the intergroup difference in blood bank requirements, whereas prime volume reduction accounted for all the other intergroup differences.
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Comment |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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If the extracorporeal circuit is primed with asanguineous or poor-colloidal solutions, the COP decreases precipitously at the onset of CPB. This pathophysiologic event jeopardizes the Starling law that governs transcapillary fluid exchange [16]. Beattie and colleagues [3] have demonstrated that during a CPB time of 80 minutes as much as 40% of the rapidly exchangeable extravascular albumin pool was transferred intravascularly to offset the decline in COP, with a concurrent increase in interstitial water of approximately 1 L. Because the perfusion protocol aimed at a hematocrit of 22% to 23% during CPB, the decrease in hematocrit and COP at the onset of CPB was similar in both groups. Because of this, in the majority (16 of 20) of patients in the small prime group autologous blood was donated just before CPB, whereas in the large prime group the predicted on-bypass hematocrit in none of the patients was sufficient to enable predonation. Retransfusion of predonated blood resulted in an important reduction in blood requirements in patients treated with small prime volumes. Therefore, predonation of autologous blood is an additional beneficial effect of reduced prime volumes.
Although the decrease in hematocrit and COP at the onset of CPB was similar in both groups, with the small prime volume oncotic reestablishment was already initiated during CPB and was completed 1 hour after arrival in the ICU. In contrast, with the large prime volume no oncotic reestablishment occurred during CPB or within 18 hours of ICU stay. Both albumin influx and infusion of colloids determine the increase in COP. With an equal amount of colloid infusion in both groups but a less expanded blood volume in the small prime group, the oncotic equilibrium also is achieved more rapidly in this group. In this context it is not surprising that by the end of CPB, COP in the small prime group was higher compared to COP in the large prime group.
The technique of electrical resistance measurements was applied to assess changes in fluid content of the thoracic cavity. Electrical resistance of a tissue compartment is related to its fluid content and changes in electrical resistance may reflect changes in fluid content. In the large prime group, a significantly lower electrical resistance across the thorax was measured in the ICU. In the same group, large fluid infusions were required to maintain an adequate intravascular filling state. The highly positive fluid balance and the decreased electrical resistance observed in the large prime group might represent a more pronounced extracellular fluid accumulation in this group. However, the highly positive fluid balance was well tolerated by this low-risk group, as all patients were extubated and left the ICU within 24 hours postoperatively.
In patients undergoing CPB, the circulating blood volume is expanded by the volume of the extracorporeal circuit. In fact, the extracorporeal circuit may be considered as a fixed ``fourth fluid compartment,'' apart from the intravascular fluid compartment, the intracellular fluid compartment, and the interstitial fluid compartment. Reducing the volume of the obligatory fourth fluid compartment in CPB was associated with an attenuation of the postoperative sepsislike syndrome with the typical pattern of low arterial pressure, high cardiac output, low vascular resistance, and increased oxygen supply [17, 18]. However, the effect of prime volume reduction on the release of inflammatory mediators during CPB and their interaction regarding the hemodynamic profile needs to be elaborated in future studies.
Colloid oncotic pressure in postoperative cardiac surgical patients and, more generally, in trauma patients, has been related to interstitial fluid accumulation [4, 19]. In a study on critically ill patients, COP and the transcapillary gradient (COP - pulmonary capillary wedge pressure) were proposed as useful indicators of pulmonary edema and mortality [20, 21]. The importance of oncotic re-establishment after CPB is emphasized by our findings that lower oncotic pressures in the large prime group were associated with a hyperdynamic response in the ICU.
Potential problems during CPB with minimized prime volumes include rapid loss of blood flow if venous return is compromised. At our institution, a soft-shell venous reservoir with an optical level controller is incorporated in the perfusion circuitry. The roller pump will stop automatically if shortage of volume in the venous reservoir is sensed by the level controller. Until venous return is restored, volume is provided immediately by infusion of crystalloids/colloids or, if available, reinfusion of predonated autologous blood. If venous return is compromised by rapid blood loss in the surgical field, immediate use of blood is effectuated with the cardiotomy suction device that is connected to the venous reservoir.
In the present study we have not incorporated measurements dealing with mechanical ventilatory support. In our postoperative coronary artery bypass grafting patients, extubation is merely a medical decision based on circumstantial criteria and only partly on pulmonary function, fluid state, and hemodynamic profile. The reason for this might be that in low-risk cardiac surgical patients the hyperdynamic response to CPB is an expected and early recognized phenomenon and subsequently, anticipated according to a standardized treatment protocol. In this setting, patients are usually extubated the morning after operation. However, the beneficial effects of small prime circuits justify a reconsideration of the actual criteria for extubation. With adjusted extubation criteria, early extubation might be attained after CPB with small prime circuits. The low budget modifications of the extracorporeal circuit leading to significant prime volume reduction are strongly recommended and might contribute positively to advanced patient recovery and cost containment in cardiac operations.
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Acknowledgments |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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Footnotes |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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–––). During intensive care unit (ICU) stay (
), two-factor analysis of variance yielded intergroup significance in colloid oncotic pressure. (CPB = cardiopulmonary bypass; *p < 0.05 compared with baseline; #p < 0.05 compared with previous sample.)
