| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 1998;65:59-65
© 1998 The Society of Thoracic Surgeons
Department of Anesthesia, University of Manitoba, Winnipeg, Canada
Department of Surgery, University of Manitoba, Winnipeg, Canada
Accepted for publication June 25, 1997.
Dr Mutch, Department of Anesthesia, St. Boniface General Hospital, 409 Tache Ave, Winnipeg, Manitoba, Canada R2H 2A6 (e-mail: mutch@bldghsc.lan1.umanitoba.ca).
 |
Abstract |
|---|
 Top Abstract IntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
|---|
Methods. Pigs were placed on CPB for 3 hours using a membrane oxygenator with alpha-stat acid-base management and arterial filtration. After baseline measurements and normothermic CPB, the animals were randomized to apulsatile CPB (n = 12) or computer-controlled pulsatile CPB (roller pump speed adjusted by an average of 2.9 voltage output modulations/s; n = 12). The animals were then cooled to a nasopharyngeal temperature of 28°C. During rewarming to stable normothermic temperatures, SjvO2 was measured at 5-minute intervals. The mean and cumulative areas for an SjvO2 less than 50% were determined for all animals.
Results. No between-group differences in temperature were noted during hypothermic CPB or during rewarming. The rate of rewarming was not different between groups. Mean arterial pressure, partial pressure of oxygen in arterial blood, and partial pressure of carbon dioxide in arterial blood also did not differ between groups. The hemoglobin concentration was within 0.4 g/dL between groups at all time periods. Mean pulse pressure was 10.0 ± 4.8 mm Hg in the apulsatile CPB group and 20.7 ± 5.2 mm Hg in the pulsatile CPB group (p = 0.0002; unpaired t test). Markedly greater mean and cumulative areas under the curve for SjvO2 less than 50% were seen with apulsatile CPB (164 ± 209 versus 1.9 ± 3.6% · min, p = 0.021; and 1,796 ± 2,263 versus 23 ± 45% · min, p = 0.020, respectively).
Conclusions. Computer-controlled pulsatile CPB was associated with significantly greater SjvO2 during rewarming from hypothermic CPB. Both the mean and cumulative areas under the curve for SjvO2 less than 50% exceeded a ratio of 75:1 for apulsatile versus computer-controlled pulsatile CPB. These experiments suggest that cerebral oxygenation was better preserved during rewarming from moderate hypothermia with computer-controlled pulsatile CPB, which returned biologic variability to the flow pattern.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
|---|
Bypass techniques that decrease the incidence and severity of cerebral venous oxygen desaturation during rewarming appear to be a logical place to start in an attempt to limit the neurocognitive complications of CPB. In this study, we compared conventional roller pump CPB with computer-controlled pulsatile CPB, programmed for biologic variability [6], in a porcine model. Frequent determinations of SjvO2 were made during rewarming from moderate hypothermia.
We developed the computer-controlled roller pump in an attempt to recreate spontaneous biologic rhythms [7][8][9][10][11][12][13] during CPB. In humans, blood pressure undergoes spontaneous and broadly repetitive fluctuations with a typical period of 5 to 10 seconds. These fluctuations are in part a consequence of respiration. Additional vasomotor fluctuations are present at greater frequencies. Closer examination indicates that fluctuations exist for respiratory rate, systolic and diastolic blood pressures, and heart rate. These variable rates influence each other in an interactive manner and are a common feature in all mammals. During various therapeutic interventions, these spontaneous rhythms are eliminated. Elimination of these inherent spontaneous rhythms may be detrimental and may contribute to the morbidity and mortality associated with medical life-support systems. Elimination of spontaneous biologic rhythms is especially likely with CPB. Because CPB takes over the function of both the heart and lungs to permit operative repair of the heart or its great vessels, the intrinsic rhythms of respiration, heart rate, and blood pressure are all eliminated. With conventional roller pump CPB, these variable rhythms are replaced by a monotonously regular, minimally pulsatile waveform.
Brain oxygen saturation during rewarming from hypothermic CPB can be tracked accurately by frequent sampling of jugular venous blood. Area under the curve at which saturation is less than 50% is an index of cerebral hypoxia. We measured SjvO2 at 5-minute intervals during rewarming from hypothermic bypass to compare apulsatile and computer-controlled pulsatile CPB. With such a model, a significant difference in the area under the curve would suggest that the CPB technique with the lesser area would be superior for maintaining cerebral oxygenation.
|
Material and Methods |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
|---|
Surgical Preparation
After premedication (atropine, 0.6 mg, and ketamine, 10 mg/kg intramuscularly), 36 pigs (30 to 35 kg) were anesthetized with 2.0% end-tidal isoflurane in oxygen. We performed sternotomy to permit ascending aortic (6.5-mm Jostra) and right atrial (28F Polystan) cannulation, retrograde cannulation of the left internal jugular vein (after ligation of all extracranial branches) for cerebral venous blood sampling and hemodynamic measurements, and femoral arterial and venous cannulation for hemodynamic and blood gas measurements. Temperature was recorded from calibrated nasopharyngeal and jugular venous probes. During bypass, pump arterial inflow and venous outflow temperatures also were recorded. After operation, a 30-minute stabilization period ensued. Before beginning CPB, we administered 100 mg of sodium hydrocortisol succinate intravenously. The bypass circuit was primed with pentaspan, lactated Ringer’s, and mannitol (20%) to a total volume of 1.5 L.
After heparin administration (12,000 to 15,000 IU intravenously and 1,000 IU/h as needed to maintain activated clotting time >500 seconds), apulsatile CPB was begun with a Travenol roller pump, membrane oxygenator (Bentley Spiraloxy), and arterial filtration (Bentley Duraflo II 1040D; 40-µm mesh) with alpha-stat acid-base management. Shed blood was returned to a Bentley Duraflow 1900G venous reservoir. Norepinephrine 4 to 8 µg was administered if blood pressure required support with initiation of CPB. Normothermic bypass was maintained for approximately 30 minutes to ensure stable hemodynamic indices and hemoglobin. After these measurements, active cooling to 28°C was begun by heat exchanger. If ventricular fibrillation did not occur, the heart was arrested with 40 mEq of KCl. The aortic root was subsequently cross-clamped. The animals were randomized to either conventional apulsatile CPB (group AP) or computer-controlled pulsatile (group P) CPB (see later).
Hypothermic CPB was continued for 75 to 90 minutes. Three periods of measurement for hemodynamic indices and blood gases were performed during hypothermic CPB. Rewarming to baseline temperature then occurred over 30 to 45 minutes, with a maximal 8°C temperature gradient between arterial and jugular venous blood. When baseline temperature was reached, the temperature was kept stable for a further 30 minutes. Blood gas data were obtained in triplicate at baseline, at stable normothermic CPB, at 30-minute intervals during hypothermic CPB, at the end of hypothermia, after rewarming to baseline temperature, and after the animals were stable at this normothermic temperature for 30 minutes. Blood gases were measured using a Radiometer ABL3, and arterial and jugular venous oxygen content and hemoglobin were measured using a Radiometer OSM3 set for porcine blood. Bypass time was constant at 3 hours. At the completion of each experiment, the animal was injected with a lethal dose of sodium thiopental and the roller pump was stopped.
Computer-Controlled Pulsation
The computer controller and software for the roller pump are patent pending. Biologically variable pulsatile CPB was based on recreating the systolic variations observed from invasive arterial pressure measured in a lightly anesthetized, spontaneously breathing pig. The arterial blood pressure was recorded in a data acquisition system (Advanced Codas). A peak height analysis of systolic arterial pressure was performed using post-analysis software. The results of this analysis were saved to file. The software program developed read this edited data file directly.
Minimum, maximum, and mean values for peak systolic arterial pressure were calculated. The minimum pressure recorded was subtracted from each pressure, and the new minimum (0 mm Hg), maximum, and mean peak values were recalculated and displayed. After initiation of stable normothermic CPB, the target baseline blood pressure and the maximum amount of computer modulation during CPB were set. We assumed a baseline mean arterial pressure (MAP) of 80 mm Hg with a 20-mm Hg pulse variation generated by the computer controller. The roller pump flow rate was adjusted to achieve the baseline pressure of 80 mm Hg with the computer modulation level preset to zero. The modulation level was now adjusted until the increase in pump flow rate resulted in a blood pressure increase from 80 to 100 mm Hg—the maximal computer modulation level chosen. Computer control of the roller pump was now initiated. At all times, the pump rate (rpm) could be controlled independently using the rate control, if required.
A representative portion of the voltage modulation for this series of experiments is shown in Fig 1. The changes in MAP induced by changes in the rpm rate of the roller pump are superimposed on the voltage modulation. In this application, there were 6,654 modulations of output voltage to alter the roller pump rpm rate over a period of 2,315 seconds (38.6 minutes). The modulating voltage had a range between 0 and 5 V and could increase pump speed only from its baseline setting. The data stored in memory were converted into time steps and relative amplitudes from 0% to 100%. For each time step, the voltage output was held at the relative level until the next time step occurred. The data stored in memory were scanned initially in a forward direction from observation 1 to n. At this point, the data were "reverse played" continuously from observations n-1 to 1 and then forward from 2 to n, and so on, until the program was terminated. The "reverse play" method was devised to compensate for possible large step changes in voltage output due to trends in the control recording.
|
Statistical Analyses
Time-related changes for temperatures, hemodynamic indices, and blood gas data were evaluated by analysis of variance for repeated measures. When analysis of variance was significant, comparisons were made with the least-squares means test. Bonferroni’s correction was applied (p < 0.05/n; where n = number of comparisons) when multiple comparisons were made. The corrected p value was considered statistically significant. The area under the curve for SjvO2 less than 50% was determined as an index of cerebral hypoxia during the time from end hypothermia to rewarming measurement period two (30 minutes after nasopharyngeal temperature had returned to normothermic baseline). The SjvO2 was measured every 5 minutes during this period. For each experiment, the cumulative product when SjvO2 was less than 50% was 
. The mean value for 
over the entire measuring period was also determined for each group. If the SjvO2 at any time period was 50% or greater, then the saturation x time product was set to 0. For each experiment, the area under the curve for a saturation less than 50% was calculated by computer using the trapezoid rule. The mean and cumulative mean for each group were determined and compared by Student’s t test for unpaired data. Cerebral perfusion pressure was calculated as MAP - jugular venous pressure. Data are presented as mean ± standard deviation.
|
Results |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
|---|
Temperature and Hemodynamic Data
At the four measurement sites, temperature was very stable between groups at all time periods (Table 1).
Per design, significant decreases in temperature were seen during the period of hypothermic CPB. The mean temperature difference between groups at initial rewarming did not exceed 0.5°C at any measurement site. At stable rewarming, mean temperature did not differ by more than 0.1°C between groups at any measurement site. In addition, the rate of rewarming was not different between the groups. In group AP, the rate of rewarming was 0.20 ± 0.07°C/min, and in group P it was 0.20 ± 0.04°C/min. In both groups, MAP was increased during CPB from before CPB, but there were no differences in MAP between groups at any time. The jugular venous pressure was less in group P at rewarming with a mean difference between groups of approximately 2.2 mm Hg, but there was no difference in cerebral perfusion pressure between groups at any time. The central venous pressure was not different between groups.
|
|
The relation between SjvO2 and time during the period of rewarming in the experiments is shown in Fig 2. In both groups, jugular venous blood was sampled every 5 minutes from end hypothermia to a stable nasopharyngeal temperature, which was maintained for an additional 30 minutes. The cumulative area under the curve for an SjvO2 of less than 50% was compared for the two groups of animals. The ratio of the cumulative areas for the two experiments was 78:1, with the larger area associated with apulsatile CPB (1,796 ± 2,263 versus 23 ± 45% · min; p = 0.020 by unpaired t test for unequal variances). The range of cumulative values for group AP was 0 to 6,264% · min and for group P was 0 to 157% · min. The ratio of the mean area below an SjvO2 of 50% was 86:1 (164.3 ± 209.2 in group AP versus 1.9 ± 3.8% · min in group P; p = 0.021 by unpaired t test for unequal variances). The range of values was 0 to 570% · min in group AP and 0 to 13.1% · min in group P. There was no difference in the number of jugular venous blood samples obtained in the two groups: 11.1 ± 0.8 in group P and 11.3 ± 1.6 in group AP (p = 0.625).
|
|
Comment |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
|---|
In this study, 9 of 12 animals managed with conventional roller pump CPB demonstrated an SjvO2 less than 50% at steady-state normothermic nasopharyngeal temperature after hypothermic CPB (see Fig 2). In contrast, only 1 of 12 animals with computer-controlled pulsatile CPB had a venous saturation less than 50% at this time (p = 0.0014; Fisher’s exact test). Of greater importance was the magnitude and duration over which the oxygen saturation was less than 50% between the groups of animals. Only 4 of 12 animals had a saturation less than 50% at any time over the period of rewarming to steady-state temperature in the computer-controlled pulsatile CPB group (see Fig 2). In contrast, 10 of 12 animals on apulsatile CPB demonstrated an SjvO2 less than 50% at some time during rewarming, as assessed at 5-minute intervals. The mean and cumulative area under the curve below 50% saturation were markedly greater in group AP (ratios of at least 75:1). This indicates that animals in this group had greater cerebral hypoxia during the period of rewarming than animals managed with computer-controlled pulsation.
The 83% (10 of 12 animals) incidence of SjvO2 less than 50% seen with apulsatile CPB during rewarming in this porcine model exceeds the reported incidence in man of 17% to 23% [1]. This may merely reflect species differences, but is more likely due to the fact that we sampled jugular venous blood every 5 minutes during the period of rewarming, not just at a single measurement point at a stable rewarmed temperature, as in the clinical study. Variability of jugular venous saturation during rewarming is evident from the figure depicted in the study by Nakajima and colleagues [3]. They used on-line continuous near infra-red spectroscopy to measure SjvO2 in humans during CPB. A single sampling period may limit clear identification of the frequency and magnitude of jugular venous oxygen desaturation. A recent clinical study by Goto and associates [4] demonstrated that SjvO2 was less than 50% during the period of rewarming from hypothermic apulsatile CPB in more than 50% of patients studied (SjvO2 = 43.8 ± 12.4%; n = 54).
We have demonstrated previously a correlation between SjvO2 and cerebral oxygenation as assessed by magnetic resonance imaging [5]. With rewarming from hypothermic CPB, using the same porcine model as described here, we showed a decrease in cerebral parenchymal oxygenation as measured by T2-weighted imaging after rewarming to normothermic temperatures. Such a decrease in parenchymal oxygenation was correlated with a decrease in SjvO2. Others have reported similar findings [14]. Therefore, significantly greater desaturation with apulsatile bypass suggests greater cerebral parenchymal hypoxia in this group, placing the brain at greater risk of injury. Other explanations for possible changes in SjvO2 between the groups have been controlled carefully in these experiments. For instance, temperatures between the groups were similar at all times, and the rate of rewarming was comparable. Additionally, pump flow rates, cerebral perfusion pressure, PaO2, PaCO2, pH, and hemoglobin were very similar between groups at all times during the experiments.
With this experimental model, the microembolic load to the brain should have been minimal (nonatheromatous aorta, alpha-stat acid-base management, membrane oxygenation, arterial filtration, no aortic unclamping, and no cardiac ejection on rewarming [15][16][17]). Recent work by Lodge and associates [18] indicated no difference in cerebral blood flow between pulsatile and apulsatile CPB in a neonatal porcine model. This finding implies that the embolic load should have been similar in our two experimental groups [18].
Reperfusion of poorly oxygenated parenchyma must occur with rewarming because of the marked reduction in SjvO2 compared with that seen in the initial normothermic CPB period. Microemboli must be washed out of the vascular bed at the time of rewarming for such venous desaturation to occur. If the microembolic load to the brain is low in this model and is not expected to differ between groups, another mechanism is required to explain the differences in SjvO2 seen with rewarming in this experiment. Critical closure of collapsible vessels with tone [19] may offer an explanation for the results. The cerebral circulation has been modeled successfully using the concept of critical closure of vessels [20]. Small increases in the critical closing pressure of parenchymal arterioles during apulsatile CPB would decrease driving pressure across cerebral vessels while they remain continuously perfused (until critical closing pressure equals or exceeds inflow pressure) [19]. Thus, a pathologic increase in regional vascular tone secondary to apulsatile perfusion could contribute to ischemic microcirculatory blood flow. With hypothermia, the cerebral vascular tone is already increased and the leftward shift of the oxyhemoglobin dissociation curve predisposes to inadequate oxygen delivery [21]. Upon rewarming, cerebral vascular tone decreases as cerebral blood flow increases to meet metabolic requirements. This decrease in tone decreases critical closing pressure, resulting in an increased driving pressure across the vascular bed. Under such circumstances, accrued oxygen debt would be repaid more rapidly and would be manifest as a decreased SjvO2 during rewarming. In contrast, pulsatile perfusion has been associated with enhanced capillary bed patency and increased release of endothelial-derived relaxing factor from blood vessel walls [22], which would limit any pathologic increase in vascular tone. Therefore, if reperfusion after an accrued oxygen debt is the mechanism of jugular venous desaturation with rewarming, greater desaturation would be expected with apulsatile flow (as is seen in Fig 2).
Brain hypoxia, with possible neuronal damage, could explain in part the postoperative neuropsychological dysfunction seen in humans, which has been correlated with decreased SjvO2 during rewarming after hypothermic CPB [1]. Such parenchymal hypoxia is compatible with the observation that cerebral edema was present after CPB in all patients within 1 hour of the end of cardiac operations, as assessed by magnetic resonance imaging [23].
This laboratory recently demonstrated the efficacy of a computer-controlled mechanical ventilator programmed for biologic variability. Using the same fundamental concepts as applied to these experiments, biologically variable intermittent positive pressure ventilation increased PaO2 when compared with conventional intermittent positive-pressure ventilation in a porcine model of adult respiratory distress syndrome [6]. Analogies may exist between biologically variable mechanical ventilation and biologically variable pulsatile CPB. Monotonous ventilation may be similar to monotonous low-amplitude roller pump pulsation in the inability to recruit closed alveoli on the one hand and cerebral vessels that have collapsed secondary to increased vascular tone on the other.
We cannot say whether the greater SjvO2 seen with computer-controlled pulsatile CPB would also be present if clinical pulsatile CPB techniques had been used. Current techniques involve a monotonously regular pulsation without the marked variation in beat-to-beat flow seen with our approach. Two large clinical studies demonstrated a significant advantage for organ systems other than the brain of monotonously regular pulsatile CPB [24][25]. However, neither of these studies demonstrated any evidence of improved neurologic outcome with standard pulsatile CPB over that seen with apulsatile CPB.
In conclusion, in this porcine model, computer-controlled pulsatile bypass was associated with better cerebral oxygenation on rewarming from hypothermic bypass as compared with conventional apulsatile CPB. The computer-controlled pulsatile bypass pump as described could be used in the clinical environment. Whether similar results could be obtained in humans and whether improved cerebral oxygenation with such an approach would be associated with better-preserved cognitive function after bypass must await further study.
|
Acknowledgments |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
|---|
|
References |
|---|
|
TopAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  R. K. Singal, L. M. Docking, L. G. Girling, M. R. Graham, P. W. Nickerson, B. M. McManus, A. B. Magil, E. K.-Y. Walker, R. K. Warrian, M. S. Cheang, et al. Biologically variable bypass reduces enzymuria after deep hypothermic circulatory arrest. Ann. Thorac. Surg., October 1, 2006; 82(4): 1480 - 1488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Hogue Jr, C. A. Palin, and J. E. Arrowsmith Cardiopulmonary bypass management and neurologic outcomes: an evidence-based appraisal of current practices. Anesth. Analg., July 1, 2006; 103(1): 21 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. T. Kiziltan, M. Baltali, A. Bilen, G. Seydaoglu, M. Incesoz, A. Tasdelen, and S. Aslamaci Comparison of Alpha-Stat and pH-Stat Cardiopulmonary Bypass in Relation to Jugular Venous Oxygen Saturation and Cerebral Glucose-Oxygen Utilization Anesth. Analg., March 1, 2003; 96(3): 644 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. BOKER, M. RUTH GRAHAM, K. R. WALLEY, B. M. MCMANUS, L. G. GIRLING, E. WALKER, G. R. LEFEVRE, and W.A. C. MUTCH Improved Arterial Oxygenation with Biologically Variable or Fractal Ventilation Using Low Tidal Volumes in a Porcine Model of Acute Respiratory Distress Syndrome Am. J. Respir. Crit. Care Med., February 15, 2002; 165(4): 456 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Graham, R. K. Warrian, L. G. Girling, L. Doiron, G. R. Lefevre, M. Cheang, and W. A. C. Mutch Fractal or biologically variable delivery of cardioplegic solution prevents diastolic dysfunction after cardiopulmonary bypass J. Thorac. Cardiovasc. Surg., January 1, 2002; 123(1): 63 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Svedjeholm, E. Hakanson, Z. Szabo, and F. Vanky Neurological injury after surgery for ischemic heart disease: risk factors, outcome and role of metabolic interventions Eur. J. Cardiothorac. Surg., May 1, 2001; 19(5): 611 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. Pigula, R. D. Siewers, and E. M. Nemoto Hypothermic cardiopulmonary bypass alters oxygen/glucose uptake in the pediatric brain J. Thorac. Cardiovasc. Surg., February 1, 2001; 121(2): 0366 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. C. MUTCH, S. HARMS, M. RUTH GRAHAM, S. E. KOWALSKI, L. G. GIRLING, and G. R. LEFEVRE Biologically Variable or Naturally Noisy Mechanical Ventilation Recruits Atelectatic Lung Am. J. Respir. Crit. Care Med., July 1, 2000; 162(1): 319 - 323. [Abstract] [Full Text]
|
|
|
|
|
|
W. A. C. Mutch, R. K. Warrian, G. M. Eschun, L. G. Girling, L. Doiron, M. S. Cheang, and G. R. Lefevre Biologically variable pulsation improves jugular venous oxygen saturation during rewarming Ann. Thorac. Surg., February 1, 2000; 69(2): 491 - 497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Kawahara, Y. Kadoi, S. Saito, D. Yoshikawa, F. Goto, and N. Fujita BALLOON PUMP-INDUCED PULSATILE PERFUSION DURING CARDIOPULMONARY BYPASS DOES NOT IMPROVE BRAIN OXYGENATION J. Thorac. Cardiovasc. Surg., August 1, 1999; 118(2): 361 - 366. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
