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Eur J Cardiothorac Surg 2001;20:282-289
© 2001 Elsevier Science NL
a Department of Cardiovascular Surgery, German Heart Center Munich, Clinic of the Technical University of Munich, Lazarettstrasse 36, D-80636, Munich, Germany
b Institute of Anesthesiology, German Heart Center Munich, Clinic of the Technical University of Munich, Lazarettstrasse 36, D-80636, Munich, Germany
Received 10 October 2000; received in revised form 7 May 2001; accepted 15 May 2001.
Corresponding author. Tel.: +49-89-1218-4117; fax: +49-89-1218-4113
e-mail: eising{at}dhm.mhn.de
| Abstract |
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Key Words: Cardiopulmonary bypass prime Extravascular lung water Cardiopulmonary function
| 1. Introduction |
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Therefore we undertook the following study to evaluate whether a hyperoncotic ECC prime solution beneficially affects EVLW, pulmonary function (shunt flow, oxygenation) and cardiac output in patients undergoing elective coronary artery bypass graft surgery (CABG).
| 2. Materials and methods |
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5.55 mmol K+) and heparin 5000 IU (Ratiopharm, Ulm, Germany) (Table 1). The other patients (crystalloid group, n=10) served as control patients and instead of HES 10% Ringer's lactate of equal volume was used (Table 1). Patients showing the following characteristics were not included in the study: age >75 years; body weight ±30% of ideal body weight; left ventricular ejection fraction <40%; hemodynamic instability or emergency operations; additional valvular diseases; complete bundle branch block; third degree AV-block; impaired renal function (creatinine >1.3 mg%); hematocrit <30%.
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A pulmonary artery catheter (7.5 F, Baxter, Irvine, CA, USA) via the right internal jugular vein through an introducer-sheath (8.5 F, Arrow, Reading, MA, USA) and two large-bore intravenous catheters were placed. Additionally, a combined fiberoptic-thermistor catheter 4 F was inserted via an introducer sheath into the femoral artery and advanced 40 cm up to the thoracic aorta for measurement of EVLW by the double indicator technique [11]. Care was taken that the position of the catheters did not change during the study.
For hemodynamic measurements, a commercial monitoring system was used (Solar 8000, Marquette Electronics, Inc.). Measurements of standard hemodynamic variables included heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP) and cardiac output. Cardiac output was measured in triplicate by thermodilution technique using boli of 10 ml cold sodium chloride (0.9%). Cardiac index (CI), systemic vascular resistance index (SVRI) and pulmonary vascular resistance index (PVRI) were calculated by the Marquette system.
EVLW was measured in triplicate. A bolus of 12 ml ice-cold indocyanine green (1.25 mg/ml ICG) was injected into the right atrium. For the assessment of the aortic dilution curves of the dye and the temperature and calculation of EVLW from these curves, a commercial device (Pulsion-COLD system, Pulsion, Munich, Germany) was used, which is described in detail elsewhere [11].
All measurements for cardiac and pulmonary function as well as EVLW of the patients were performed during continuous mandatory ventilation with an FiO2 of 1.0 and zero positive end-expiratory pressure.
2.1. Pre-CPB fluid management
After induction of anesthesia until the skin incision, 500 ml of HES 6% 200;0.5 was infused. Ringer's lactate (500 ml) was given after skin incision until the onset of CPB.
2.2. Cardiopulmonary bypass technique
The CPB equipment consisted of roller pumps (Stöckert, München, Germany), a disposable membrane oxygenator in combination with the cardiotomy reservoir and a tubing set (Dideco, Mirandola, Italy). The ECC circuit was primed according to the patients group (Table 1). For CPB, standard cannulation of the ascending aorta and the right atrium (two-stage venous cannula) was performed. Cardiopulmonary bypass was instituted at a flow rate of 2.4 l/min per m2 body surface area (BSA) upon systemic heparinization. The body temperature was reduced to 32°C by cooling on bypass. After cross-clamping the aorta, 10001500 ml of ice-cold crystalloid cardioplegic solution (Bretschneider=Custodiol®, Köhler Chemie, Alsbach-Hähnlein, Germany) were initially administered into the aortic root and supplemented as necessary.
Crystalloid as well as non-crystalloid fluid balances at the end of CPB were calculated. The crystalloid fluid balance equals the sum of crystalloid infusions, the crystalloid portion of the priming volume and the cardioplegia minus the urine output; the non-crystalloid fluid balance equals the HES-volume given minus the residual blood volume of the venous reservoir.
2.3. Post-operative care
The physicians responsible for post-operative care of the patients were blinded with respect to the study group. In the intensive care unit, the patients were sedated using 0.25 µg/kg/h sufentanil and 0.01 mg/kg/h midazolam and artificial ventilation was maintained with an FiO2 of 1.0 for 4 h. The sedation was then stopped, if the following criteria were fulfilled: the patient is hemodynamic stable using dopamine and/or dobutamine <10 µg/kg/min; thoracic drainage <50 ml/h; PCWP <20 mmHg; rectal temperature, >36.5°C. Extubation was performed if the patient was awake and the arterial pO2 >80 mmHg, pCO2 <50 mmHg, tidal volume >7 ml/kg using spontaneous breathing at Y-piece with 6 l/min O2.
Colloidal fluids (HES 6% 200;0.5) were given to maintain a CVP of about 10 mmHg, non-colloidal fluids and furosemid were given to achieve a negative crystalloid fluid balance of about 1000 ml until the first post-operative day.
2.4. Blood analyses
Arterial and mixed venous blood samples were obtained for gas analyses (Ciba Corning, Medfield, MA, USA) and measurement of the COP. Plasma COP was determined by a commercial membrane osmometer (Osmomat 050, Gonotec, Berlin, FRG) using a membrane with molecular mass cut-off at 20 kDa. Mixed venous oxygen saturation was measured using an oxymeter (Radiometer, Copenhagen, Denmark). Alveolo-arterial oxygen difference (AaDO2) and pulmonary shunt (Qs/QT) were calculated using standard formulae, as described previously [12].
2.5. Study protocol
Blood samples were obtained: (1) after induction of anesthesia before skin incision; (2) 15 min after the onset of CPB following cardioplegic cardiac arrest; (3) before weaning from CPB; (4) 2 h after CPB and (5) 4 h after CPB. Hemodynamic measurements were performed before skin incision and 2 h as well as 4 h after CPB, when the hemodynamic conditions were stable.
2.6. Statistics
Data are presented as mean±SD. The data were subjected to the Friedman two-way ANOVA. Comparison within groups were assessed with the Wilcoxon-matched-pairs signed-rank test and comparisons between groups with the MannWhitney U-test using the statistic software SPSS® 10.1 for WindowsTM. Significant differences were accepted for a tailed P-value of <0.05.
| 3. Results |
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No differences between the two groups were seen for arterial and pulmonary artery pressures (PAP), PCWP and CVP (Table 4).
The post-operative administered dosage of dopamine was similar in the two groups (Table 4).
| 4. Discussion |
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In animal experiments, an isooncotic as compared to a crystalloidal prime of CPB attenuated an increase in water content of duodenum and skeletal muscle [19] and addition of hypertonic NaCl, hyperoncotic HES to an isotonic, hypooncotic prime of CPB prevented an increase in intracranial pressure and cerebellar water content [20].
An investigation using a hyperoncotic priming solution in a clinical study with patients undergoing CABG was performed by Jansen et al. [14]. To the best of our knowledge, this is the only study demonstrating an improved clinical performance score as well as a reduced post-operative hospital stay for patients treated with a colloidal CPB-prime. The clinical performance score included fluid balance, post-operative duration of intubation and the difference between the rectal temperature and skin temperature. Superior hemodynamic effects of the colloidal prime compared to the crystalloid prime, however, could not be demonstrated possibly due to the fact that inotropic support was guided by the cardiac index, which was not the case in our series. In the present study, the increase in cardiac index was significantly more pronounced, when a hyperoncotic CPB-prime was used (Fig. 3). A favourable effect on cardiac index could also be demonstrated by London et al. using pentastarch, but not by using albumin [17]. The reason for the positive effect on cardiac index in the HES-group is rather unclear. There is a slight, but insignificant trend to reduced systemic and pulmonary vascular resistance in the HES group. The filling pressures as well as the arterial and PAPs do not systematically differ among the groups.
Jansen et al. used 1650 ml of a priming solution with a COP of 32 mmHg [13]. In the present study, the CPB circuit was primed with 1617±129 ml showing a COP of 48 mmHg, which is about twice the physiological value. Whereas Jansen et al. could demonstrate an increase of COP with the onset of CPB, our data show a 20% reduction of COP during the ECC. The difference between the data, however, can be readily explained. The time points of blood sampling are different in the two studies. Jansen et al. measured COP 5 min before and 5 min after the onset of CPB. It is likely that the blood sampling was performed before the cardioplegia was given, though it was not mentioned in the paper. In the present study, COP was measured before skin incision and 15 min after the onset of CPB. Between these time points, 500 ml of Ringer's lactate was given and 10001500 ml of cardioplegic solution was infused. Moreover, Jansen only used 8001000 ml of cardioplegia instead of 10001500 ml used in our study.
During CPB, a significant difference of the COP between the crystalloid group and the colloidal group could be demonstrated in our study. In the HES-group, COP was reduced by 20%, while it fell by more than 50% in the crystalloid group. COP stayed significantly lower in the crystalloid group than in the HES-group but the difference between the two groups constantly decreased until 4 h post-CPB (Fig. 1 and Table 3). This phenomenon goes in line with the time course of the oncotic effect of HES, being maximal for 34 h after infusion and is then fading away.
In principle, we could prevent post-operative accumulation of EVLW in the early post-pump period. The pulmonary function, however, was surely not affected in the two groups because both the reduced EVLW-levels in the HES group as well as the elevated EVLW-levels in the crystalloid group still stayed within the normal range, which is 57 ml/kg BW. [11]. Therefore, it is quite plausible that no change in AaDO2 and pulmonary shunt fraction occurred in either group and it is also not surprising that the time of post-operative ventilation did not differ among the two groups (Table 2). This was also seen by Jansen et al. [14]. Low post-operative tissue water accumulation by minimizing the peri-operative crystalloid fluid balance and the fall of COP can be of benefit, however, in patients with pre-operative pulmonary and cardiac dysfunctions.
| 5. Summary and conclusions |
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Further research has to be done to evaluate a possible beneficial clinical effect of post-pump improved cardiac output and low EVLW-levels for high-risk patients with impaired cardiac or pulmonary function or both and pre-operative elevated levels of EVLW.
| Footnotes |
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| Appendix A. Conference discussion |
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Dr Eising: The outcome of the patients was similar in the two groups because we examined relatively healthy patients. We saw a statistically significant difference in the weight gain after the procedure. The control group gained weight of about 1.8 kg at the second post-operative day, while we could totally prevent this weight gain in the hydroxyethyl starch group.
Dr van der Linden: Did you look at the amount of diuretics you needed?
Dr Eising: We only used furosemide in the post-operative course, and there was no difference between the two groups regarding the amount of diuretics.
Dr van der Linden: So you actually expect a bigger difference if you had had worse patients?
Dr Eising: We did this study more or less as a preliminary study. We now have to focus on patients with impaired organ function. We indeed expect more pronounced differences in the clinical outcome of those patients.
Dr A. Corno (Lausanne, Switzerland): It is well known that the amount of extravascular ling water content is dependent on several other variables during bypass other than osmotic pressure, for instance, the way you contact the cardiopulmonary bypass, temperature, flow, hematocrit and so forth, like the maintenance of low frequency ventilation or the urinary output or the utilization of ultrafiltration. Can we presume then in both groups you maintained stable all these variables during cardiopulmonary bypass, yes or not?
And the second question is, as a result of your observation, do you suggest HES priming for all patients or only for high risk patients?
Dr Eising: As this is a clinical investigation, you can never be sure that everything is a hundred percent systematic, but we tried to have a very consistent anesthesiologic regimen. All of the patients were treated the same way in terms of fluid input.
In response to your second question, we have not yet decided whether we should change our priming solution to a hyperosmotic prime. We first have to look at the older patients and the patients with impaired organ function.
| References |
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