Cardiopulmonary bypass (CPB) has been universally accepted in cardiac surgery and CPB physiological invasiveness is well documented. To minimize the risks of the operation and to stabilize the postoperative state, an attempt to regulate hemodynamic status during CPB should be considered.
During CPB, blood flow is redistributed even if perfusion pressure is maintained.1 Clinically, vasodilators and vasoconstrictors are used to decrease and increase, respectively, blood pressure during CPB at cardiac indices appropriate for the time point. This enables the patient to cope with temporary hyper- and/or hypotension that may induce systemic hypoperfusion. However, these agents may restore perfusion pressure without improving tissue perfusion,1 because they are a form of vasostimulation, whereas prostaglandin E2 remains elevated.2 Results of experimental reports suggest that vasoconstrictor administration during CPB may make tissue perfusion injury more severe and increase blood lactate levels despite changes in oxygen delivery, consumption, and extraction rate. In the present study, we clinically evaluated the influences on the whole body of vasodilators and vasoconstrictors administered during CPB.
Materials and Methods
The present study included 56 consecutive cases involving patients with valvular disease who received moderately hypothermic CPB without blood transfusion, all of whom were treated at a single institution. Another four patients were excluded for reasons such as surgical bleeding or infective endocarditis. The 56 patients were divided into four groups, depending upon whether a vasodilator (chlorpromazine) and/or a vasoconstrictor (norepinephrine or methoxamine hydrochloride) was administered. Postoperative data were compared between three agent-administered groups and one no-agent group: group 1, dilator (n = 6); group 2, dilator and constrictor (n = 10); group 3, constrictor (n = 19); group 4, no agent (n = 21).
The patients were anesthetized according to a protocol that included fentanyl for induction, and midazolam and low-dose fentanyl for maintenance. After the completion of CPB, neither midazolam nor fentanyl was administered. At the end of anesthesia, all patients were transferred to the intensive care unit with tracheal intubation.
Cardiopulmonary Bypass Management
Moderately hypothermic (blood temperature: 28–32°C) CPB was initiated with two venous cannulations and an ascending aortic perfusion. The CPB circuit with a roller pump was primed with lactated Ringer’s solution, sodium bicarbonate (7%), and D-mannitol (20%). Systemic heparinization was followed by subsequent administrations to maintain an activated clotting time (ACT) of > 4.00 seconds. The mean arterial pressure, central venous pressure, and blood flow calculated from revolutions per minute and output per revolution were recorded every 5 minutes during CPB. The blood-gas values, hematocrit levels, and ACT were also measured before and every 30 minutes during CPB.
Body temperature was allowed to drop naturally during CPB, but was restored, at almost fixed duration only, just before completion of the procedure. During CPB, bypass flow and systemic perfusion pressure were maintained at around 2.4 l/min/m2 and 50 to 90 mm Hg, respectively, by vasostimulator administration, and acidosis was treated with sodium bicarbonate administration. α-Stat management was performed.
The following data were compared between the three agent-administered groups and the no-agent group. Tracheal extubation criteria were revealed. With regard to SvO2 and ExO2, only cases where the FiO2 just after CPB was 1.0 were compared: group 1, dilator (n = 3); group 2, dilator and constrictor (n = 4); group 3, constrictor (n = 6); and group 4, no agent (n = 10). Most mathematical parameters are generally accepted as stated before2 except that for dilution stated in Table 1.
Tracheal Extubation Criteria
Extubation was performed when all of the following were present: patient responsive and cooperative, FiO 2 50%; positive end-expiratory pressure = 5 cm H2O; PaO2/ FiO2 > 150; hemodynamically stable, well perfused, urine output ≥ 0.5 ml/kg/h; chest tube drainage < 2 ml/kg in the last hour; absence of uncontrolled arrhythmia; rectal temperature. > 36.0°C.
All data are expressed as mean and standard error of the mean, and were analyzed and displayed by StatView (Version J 5.0, SAS Institute Inc., Cary, NC). We used a t test to compare the measured parameters among the three agent-administered groups and the no-agent group. A value of p < 0.05 was considered statistically significant.
Body weight, dilution, hematocrit levels, CPB duration, aortic clamp duration, blood temperature, perfusion pressure, and base excess levels during CPB were comparable between the agent-administered groups and the no-agent group (Table 1). Just a few cases were back-up-paced. After CPB, the cardiac index, PaO2/ FiO2, A-aDO2, and SvO2 were comparable between the agent-administered groups and the no-agent group (Figure 1). Systemic vascular resistance index before, during, and after CPB was also comparable between the agent-administered groups and the no-agent group (Figure 2). However, the time to extubation was longer (group 1, dilator 10.8 ± 3.7; group 2, dilator and constrictor 12.8 ± 3.9; group 3, constrictor 12.8 ± 5.4 vs. group 4, no agent 8.7 ± 5.1 hours; 2 vs. 4, p = 0.03; 3 vs. 4, p = 0.02) in the agent- administered groups than in the no-agent group, and blood lactate levels upon returning to the ward were higher (groups 1, 2, 3 vs. 4: 7.4 ± 0.9, 7.1 ± 1.7, 5.7 ± 1.9 vs. 5.6 ± 1.7 ml/kg; 1 vs. 4, p = 0.03, 2 vs. 4, p = 0.04), whereas blood lactate levels on extubation and blood creatinine levels on postoperative day 1 (and ExO2 after CPB) were comparable between the agent-administered groups and the no-agent group (Figure 3).
During CPB, hemodilution, reduced blood viscosity, dilution of circulating catecholamines, with lesser effects from hyperkalemia, complement activation, and a systemic inflammatory response to extracorporeal circulation frequently induce extraordinary changes.3 A previous report has demonstrated that significant gut mucosal ischemia occurs during CPB, despite normal systemic flow.4 Factors that cause mucosal ischemia include redistribution of blood flow away from the mucosa, possibly because of regional vasoconstriction, and increased total gut metabolism. It has also been reported that a decrease in pulmonary blood flow deprives a metabolic function through pulmonary circulation, and that the levels of some vasostimulators, such as prostaglandins (PGs), increase, which is related to tissue perfusion injury during CPB.1,2,5
In this study, our results have clarified the mechanism of injury during CPB to some extent. The clinical parameters (cardiac index, PaO2/ FiO2, A-aDO2, and SvO2 just after CPB) may imply the comparability of ischemic reperfusion injury in the heart and lungs. The differences in the duration to extubation and the blood lactate levels in intensive care unit, contrary to the comparable values of the other clinical parameters, may imply a difference in anaerobic metabolism that indicates blood flow redistribution during CPB.1,6
When vasodilators and/or vasoconstrictors are used to prevent hyper- and/or hypotension during CPB, their concentrations become much higher than usual, and the concentrations of other vasostimulators, unmetabolized during CPB (such as PGs), remain elevated. The peripheral tissues are then exposed to severe new vasostimulative effects in addition to the inflammatory effects of vasostimulators such as PGs.7 Therefore, a temporizing treatment, such as vasodilator and/or vasoconstrictor administration to restore normotension during CPB, may be more invasive to the body, although the time to reduce the concentration by half is generally very short.
In addition, the effect of PGs (e.g., PGE2) as a buffer8 cannot remain. For example, renal cortical blood flow is generally thought to directly correlate with perfusion pressure and administration of the vasoconstrictor. However, in a previous study,9 the use of vasoconstrictors during CPB did not improve renal perfusion abnormalities, despite the restoration of perfusion pressure. In other words, vasoconstrictors may be effective in maintaining renal circulation as long as appropriate concentrations of vasostimulators such as PGs are maintained. As in the kidney, blood flow in the brain during CPB has been said to be maintained by autoregulation.10–12 However, it is not clear whether a redistribution of blood flow occurs in the brain.13 Although the incidence of intraabdominal complications is not high,14 vasostimulator administration may cause more gut mucosal ischemia during CPB.
In the long run, perfusion pressure control by vasodilators and vasoconstrictors during CPB might worsen the complications induced by hypoperfusion in other organs during CPB.
Vasodilator and/or vasoconstrictor administration during CPB makes blood lactate levels higher and the time to extubation longer, which may imply deterioration of the body oxygen metabolism, even if both bypass flow and perfusion pressure are maintained.
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