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Ann Thorac Surg 1998;65:155-164
© 1998 The Society of Thoracic Surgeons


Original Articles: Cardiovascular

Effects of Oncotic Pressure and Hematocrit on Outcome After Hypothermic Circulatory Arrest

Toshiharu Shin’oka, MD, Dominique Shum-Tim, MD, Peter C. Laussen, MBBS, Sophia M. Zinkovsky, MD, Hart G. W. Lidov, MD, PhD, Adre du Plessis, MD, Richard A. Jonas, MD

Department of Cardiovascular Surgery, Children’s Hospital and Harvard Medical School, Boston, Massachusetts, USA,
Department of Anesthesia and Intensive Care, Children’s Hospital and Harvard Medical School, Boston, Massachusetts, USA,
Department of Pathology, Children’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
Department of Neurology, Children’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

Dr Jonas, Department of Cardiovascular Surgery, Children’s Hospital, 300 Longwood Ave, Boston, MA 02115.

Presented at the Poster Session of the Thirty-third Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Feb 3–5, 1997.


    Abstract
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 
Background. A recent study found that a higher-perfusate hematocrit was associated with improved neurologic recovery after deep hypothermic circulatory arrest. The current study examined the relative contributions of oxygen delivery and colloid oncotic pressure to this result, as well as the efficacy of different colloidal agents and modified ultrafiltration.

Methods. Twenty-six piglets were randomized into five groups (n = 5 or 6 animals per group): control group 1—blood and crystalloid prime, hematocrit of 20%; group 2—blood and hetastarch prime, hematocrit of 20%; group 3—blood and pentafraction prime, hematocrit of 20%; group 4—blood and crystalloid prime with 10 minutes of modified ultrafiltration; group 5—whole blood prime, hematocrit of 30%. All groups underwent 60 minutes of deep hypothermic circulatory arrest at 15°C.

Results. Groups 2 and 3 showed less body weight gain (analysis of variance, p = 0.001; group 2 versus group 1, p = 0.0009; group 3 versus group 1, p = 0.0009) and body water content after cardiopulmonary bypass (analysis of variance, p = 0.001; group 2 versus group 1, p = 0.003; group 3 versus group 1, p = 0.013). Group 5 showed more rapid recovery of phosphocreatine and intracellular acidosis, as measured by magnetic resonance spectroscopy, during rewarming than group 1 did (phosphocreatine, p = 0.0329; intracellular acidosis, p = 0.0462). Group 3 also showed accelerated recovery of intracellular acidosis (p = 0.0411). Cytochrome a,a3 recovery, determined by near-infrared spectroscopy, was significantly better in group 5 than in group 1 and worse in group 2 than in group 1 after rewarming. The neurologic deficit score and overall performance category score were best in group 5 (neurologic deficit score, p = 0.012; overall performance category score, p = 0.046) on the first postoperative day. Group 3 also had a better overall performance category score than group 1 did (p = 0.0068). Only group 1 and 2 animals showed histologic damage.

Conclusions. Both higher hematocrit and higher colloid oncotic pressure with pentafraction improve cerebral recovery after deep hypothermic circulatory arrest. The higher hematocrit improves cerebral oxygen delivery but does not reduce total body edema. Modified ultrafiltration after cardiopulmonary bypass is less effective than having a higher initial prime hematocrit or colloid oncotic pressure.


    Introduction
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 
A previous study performed in our laboratory showed that extreme hemodilution results in evidence of inadequate oxygen delivery during the initial cooling phase of cardiopulmonary bypass (CPB) and during deep hypothermic circulatory arrest (DHCA). Relative to hemodilution to 20%, whole blood priming, which maintains the normal pig hematocrit (Hct) of 30%, results in optimal preservation of the mitochondrial redox state and high-energy phosphates, and subsequently better early neurologic and histologic scores [1]. The improved cerebral recovery with a higher Hct after DHCA may in part be explained by greater oxygen availability and therefore the preservation of high-energy phosphate metabolism. However, the effects of cerebral edema, low perfusion pressure, and low colloid oncotic pressure (COP) secondary to hemodilution with a crystalloid solution could also be important. The purpose of this study was to examine the relative contributions of oxygen delivery and COP to the result of the previous study, as well as to determine the efficacy of different colloidal agents and modified ultrafiltration (MUF).


    Material and Methods
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 
Experimental Preparation
The details of the experimental preparation have been described previously [1]. Briefly, twenty-six 5-week-old Yorkshire piglets weighing 7.2 to 11.2 kg (mean, 8.8 ± 1.1 kg) were anesthetized with 45 mg/kg intraperitoneal methohexital and intubated. After an intravenous bolus of fentanyl (50 mg/kg) and pancuronium (0.5 mg/kg), anesthesia was maintained by a continuous infusion of fentanyl (25 µg · kg-1 · h-1), midazolam (0.2 mg · kg-1 · h-1), and pancuronium (0.2 mg/kg) throughout the entire experiment, except during the period of circulatory arrest. Before operation a 3.0-cm-diameter surface coil for magnetic resonance spectroscopy (MRS) was sutured onto the scalp overlying the cerebral hemispheres and a pair of fiberoptic optodes for near-infrared spectroscopy (NIRS) were applied to the head over the frontal lobes with an interoptode distance of 3 cm. The right femoral artery was exposed for the CPB arterial cannula. A right anterolateral thoracotomy was performed in the third intercostal space to expose the right atrium for venous cannulation. After cannulation the animal was placed in an MRS horizontal-bore, superconducting, 4.7-Tesla magnet (Oxford Research System, Oxford, England) and subjected to hypothermic CPB and circulatory arrest as determined by the protocol (Fig 1). After 45 minutes of rewarming the piglet was weaned from CPB and decannulated outside the MRS bore. Protamine (5 mg/kg) was administered intravenously. Immediately after decannulation the animal was repositioned in the bore for 3 hours for MRS and NIRS data collection. After that, all incisions were closed in a sterile fashion. The animal remained intubated for up to 12 hours postoperatively.



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Flow diagram depicting experimental protocol. (AST = aspartate aminotransferase; ALT = alanine aminotransferase; ALP = alkaline phosphatase; CK = creatine kinase; DHCA = deep hypothermic circulatory arrest; LDH = lactate dehydrogenase; MRS = magnetic resonance spectroscopy; NIRS = near-infrared spectroscopy; T.Bil = total bilirubin.)

 
All animals received humane care in compliance with the "Principles of Laboratory Animal Care" formulated for the National Society for Medical Research and the "Guide for the Care and Use of Laboratory Animals" (NIH publication 86-23, revised in 1985). Institutional Review Board approval for the study was obtained.

Experimental Groups
Piglets were randomized into five groups: group 1 (n = 6, control group) received blood and crystalloid priming to achieve an Hct of 20%. The prime consisted of 800 mL of Normosol R with a pH of 7.4 (Abbott Laboratories, North Chicago, IL) and 400 mL of blood. Group 2 (n = 5, hetastarch group) was primed with 400 mL of blood, 400 mL of 6% hetastarch (Hespan; Du Pont Pharmaceuticals, Wilmington, DE), and 400 mL of Normosol to achieve an Hct of 20%. Group 3 (n = 5, pentafraction group) was primed with 400 mL of blood, 400 mL of 6% pentafraction (Viastarch; Laevosan-Gesellschaft, Linz, Austria), and 400 mL of Normosol to achieve an Hct of 20%. Group 4 (n = 5, MUF group) was primed like group 1 and underwent MUF after weaning from CPB for 10 minutes, consistent with clinical practice. Group 5 (n = 5, nonhemodilution group) was perfused with 1,200 mL of whole blood prime, resulting in an Hct of 30%.

Cardiopulmonary Bypass Technique
Details of the CPB technique have been described previously [1]. The pump prime was determined by the experimental protocols already described. Cefazolin sodium (25 mg/kg), methylprednisolone sodium succinate (30 mg/kg), furosemide (0.25 mg/kg), and sodium bicarbonate (10 mL) were added to the prime. The full bypass flow rate used was 100 mL · kg-1 · min-1, which was consistent with flow rates used in our previously published protocols using this animal model, and is sufficient to meet the perfusion and metabolic requirements in piglets of this size. After placement of the animal in the magnet bore, CPB was commenced and animals were immediately cooled to an esophageal temperature of 15°C during 40 minutes using the pH stat strategy. Phentolamine mesylate (0.2 mg/kg) was administered before cooling. Ventilation was stopped after the establishment of CPB. All groups underwent 60 minutes of DHCA at 15°C.

Upon reperfusion, furosemide (0.25 mg/kg), mannitol (0.5 g/kg), and sodium bicarbonate (10 mL) were administered into the pump. The animal was warmed to 35°C over 45 minutes, maintaining a flow rate of 100 mL · kg-1 · min-1. The heart was defibrillated as necessary at 25°C. Fresh whole blood from a donor pig drawn on the day of operation was transfused into the pump as required to increase the Hct to 25% during rewarming, except in group 5. Ventilation with a fraction of inspired oxygen of 1.0 was restarted 10 minutes before weaning from CPB. The animal was then weaned from bypass outside the bore. In group 4, MUF using a hemoconcentrator (Hemocor HPH 400; Minntech Corporation, Minneapolis, MN) was performed for 10 minutes after weaning from CPB.

Postoperative Management
Postoperatively all animals remained sedated and paralyzed and were mechanically ventilated and monitored continuously for 6 hours, at which time chest tubes were removed, infusions discontinued, and the animals weanedfrom ventilation and extubated. Hemodynamic stability was observed in all animals, and none required inotrope or vasopressor support postoperatively.

Data Collection
Body Weight Change
Body weight was measured before anesthesia (baseline), 3 hours after CPB, on postoperative day (POD) 1, and on POD 4 and was expressed as the percentage of the baseline measurement.

Colloid Oncotic Pressure
Blood samples were taken from the pump prime and after CPB. The plasma COP was measured with a membrane Colloid Osmometer 4420 (Wescor, Inc., Logan, UT) with a membrane cutoff of 30,000 molecular weight calibrated with 5% albumin (COP, 19.3 mm Hg).

Total Body Water Estimation by Bioelectrical Impedance
The total body water content was estimated by bioelectrical impedance using a Weight Manager Analyzer (BIA-101Q; RJL Systems, Inc, Clinton Township, MI). The percentage change in the total body water content 3 hours after CPB was calculated using the baseline body weight before operation.

Magnetic Resonance Spectroscopy
Magnetic resonance spectroscopy was performed as described previously [2].

Near-Infrared Spectroscopy
Details of NIRS have been described previously [3]. Briefly, NIRS is a noninvasive optical method with the ability to measure changes in the relative concentrations of chromophores in tissues. With the use of appropriate wavelengths of light, NIRS can provide information on the relative concentrations of oxygenated chromophores and deoxygenated hemoglobin, as well as on the redox state of cytochrome a,a3, which is the last enzyme of the electron transport chain.

Biochemical Analysis
Blood samples were taken on the day after the operation. Aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, and creatine kinase activities, as well as the total bilirubin concentration, were measured.

Platelet Count and Fibrinogen Analysis
Blood samples were taken before and after CPB. The platelet count was performed and the fibrinogen concentration measured. The value after CPB was expressed as the percentage of the baseline value.

Neurologic and Behavioral Evaluations and Histologic Evaluations
Details of the histologic methods employed have been described previously. A blinded observer was responsible for determining the neurologic deficit and overall performance scores, as well as for performing the histologic assessment [4][5].

Statistical Analysis
All results were expressed as mean ± standard error of the mean and analyzed by a Statistical Analysis Software package (Stat-View version 4.5; SAS Institute, Cary, NC). Analysis of variance with Bonferroni correction was used to analyze the MRS and NIRS data, the enzyme activities, and neurologic deficit scores for among-group differences. The Kruskal-Wallis test and Mann-Whitney U test were used for analysis of the overall performance category and histologic scores. A p value of less than 0.05 was considered statistically significant.


    Results
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 
Experimental Conditions
The experimental conditions for each group are summarized in Table 1. Animals were similar in size, and there were no differences in the Hct value and COP among groups before operation. During the cooling, arrest, and rewarming phase on CPB, there were no statistical differences in the esophageal temperature among groups. During the cooling phase the Hct was set according to the protocol, though during rewarming the Hct was raised by transfusion in all groups except group 5, so that there was no difference in the Hct value among groups on POD 1. The mean perfusion pressure and calcium concentration varied with the Hct value and were both therefore highest in group 5 during cooling. The osmolarity of the pump prime was significantly higher in group 2 and 3, but there were no significant differences among the groups after rewarming and on POD 1.


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Experimental Conditions1

 
Operative Results
A severe tension pneumothorax developed in 1 of the 6 animals in group 1 (the control group) during transportation after operation, and the animal could not be resuscitated. All data from this animal were excluded from subsequent analysis. All other animals were extubated within 12 hours of operation and survived until POD 4, when they were sacrificed for histologic examination.

Body Weight Change
At 3 hours after CPB the body weight gain was significantly lower in group 2 and 3 than in group 1 (Fig 2). On POD 1 and 4 there were no significant differences among groups.



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Percentage change of body weight 3 hours after cardiopulmonary bypass (0POD), and on postoperative day 1 (1POD) and 4 (4POD). (Gp = group; Hct = hematocrit; Heta = hetastarch; MUF = modified ultrafiltration; Penta = pentafraction.)

 
Colloid Oncotic Pressure
The COP in the pump prime in group 3 was significantly higher than that in all other groups 3 hours after CPB (Fig 3). In addition, group 2 and 5 had significantly higher COPs than did group 1 and 4, but no difference was observed between group 2 and 5. After CPB the COP in group 2, 3, and 4 was also higher than that in group 1.



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Colloid oncotic pressure before and 3 hours after cardiopulmonary bypass (CPB). (Gp = group; Hct = hematocrit; Heta = hetastarch; MUF = modified ultrafiltration; Penta = pentafraction.)

 
Total Body Water Content Estimation by Bioelectrical Impedance
The calculated percentage increase in the total body water content after CPB was significantly less in group 2 and 3 (Fig 4).



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Percentage change in total body water content calculated by bioelectrical impedance. (Gp = group; Hct = hematocrit; Heta = hetastarch; MUF = modified ultrafiltration; Penta = pentafraction.)

 
Cerebral High-Energy Phosphates and Intracellular pH
During the cooling phase a significant increase in the intracellular pH was noted in group 5, whereas it was only slightly increased in the other groups (Fig 5C). During the circulatory arrest period, the adenosine triphosphate signal tended to be highest in group 5 and lowest in group 2 (Fig 5A). The phosphocreatine concentration and intracellular pH did not show any significant differences among the groups during DHCA (Fig 5B). During the rewarming phase, group 3 and 5 showed more rapid recovery of the adenosine triphosphate signal, phosphocreatine concentration, and intracellular pH than group 1 did (adenosine triphosphate, p = 0.042; phosphocreatine, p = 0.0329; intracellular pH, p = 0.0462). After the discontinuation of CPB, group 5 maintained a higher intracellular pH than group 1 did (p = 0.0104). However, 3 hours after bypass, there were no significant differences among groups with respect to the adenosine triphosphate signal group and intracellular pH, although group 4 showed a significantly higher phosphocreatine concentration than group 1 did.



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Results of magnetic resonance spectroscopy. (A) Cerebral adenosine triphosphate (ATP) level. (B) Cerebral phosphocreatine (PCr) level. (C) Cerebral intracellular pH. (DHCA = deep hypothermic circulatory arrest; Gp = group; Hct = hematocrit; Heta = hetastarch; microMxDPF = differential path length factor; MUF = modified ultrafiltration; Penta = pentafraction.)

 
Near-Infrared Spectroscopy
The oxyhemoglobin signal increased significantly during cooling in the whole blood prime in group 5 (p = 0.0161) (Fig 6A). During cooling the redox state of cytochrome a,a3 increased in group 5 but decreased significantly in groups 1, 2, 3, and 4 (p = 0.0017) (Fig 6D). From the onset of DHCA there was a decline in the oxyhemoglobin and cytochrome a,a3 signals in all groups, whereas the deoxyhemoglobin signal increased reciprocally (Fig 6B). During DHCA and the rewarming phase, cytochrome a,a3 recovery was significantly higher in group 5 and less in group 2 relative to group 1. Overall, the cytochrome a,a3 levels were far better preserved in group 5, with recovery to suprabaseline levels after rewarming. However, at 3 hours after CPB the final recovery tended to be better in group 5 and worse in group 2.



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Results of near-infrared spectroscopy. (A) Oxyhemoglobin level. (B) Deoxyhemoglobin level. (C) Total hemoglobin level. (D) Cytochrome a,a3 level. (DHCA = deep hypothermic circulatory arrest; Gp = group; Hct = hematocrit; Heta = hetastarch; microMxDPF = differential path length factor; MUF = modified ultrafiltration; Penta = pentafraction.)

 
Enzymes
There were no statistically significant differences among the five experimental groups (Table 2). Activities of creatine kinase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, and creatine kinase tended to be lowest in group 5.


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Enzymes, Platelet Count, and Fibrinogen Analysis

 
Platelet Count and Fibrinogen Analysis
There were no statistically significant differences in the platelet count and fibrinogen level among the five experimental groups, though the platelet count tended to be lower in group 4.

Neurologic Deficit Score
The neurological deficit score and overall performance category score showed a more rapid recovery in group 3 and 5 than in group 1 (Fig 7Fig 8). On POD 1 both the neurologic deficit and overall performance category scores in group 5 and the overall performance category score in group 3 were significantly better than those in group 1 (p < 0.05 by analysis of variance, Bonferroni correction). No statistical significance was achieved among other groups. By POD 3 and 4 most animals had recovered and showed normal performance with no neurologic deficit.



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Neurologic deficit (ND) score. (Gp = group; Hct = hematocrit; Heta = hetastarch; MUF = modified ultrafiltration; Penta = pentafraction; POD = postoperative day.)

 


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Overall performance categories (OPC). (Gp = group; Hct = hematocrit; Heta = hetastarch; MUF = modified ultrafiltration; Penta = pentafraction; POD = postoperative day.)

 
Neuropathologic Results
Neuropathologic damage was evaluated, as in previous studies, primarily by the presence of hypereosinophilic shrunken neurons with karyorrhectic nuclei, indicating recent hypoxic ischemic injury. The hypoxic-ischemic injury was most pronounced in group 1 and 2, although the injury was quite mild. There was negligible injury in groups 3, 4, and 5 (Fig 9).



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Histologic score for neocortex, hippocampus, and caudate nucleus. (Gp = group; Hct = hematocrit; Heta = hetastarch; MUF = modified ultrafiltration; Penta = pentafraction.)

 

    Comment
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 
This study demonstrates that early cerebral recovery after 1 hour of DHCA can be accelerated either by using a higher-perfusate Hct or by increasing the perfusate COP using pentafraction. Intraoperative NIRS and MRS monitoring indicated that the higher Hct may improve recovery by improving intracellular oxygen delivery to the brain, as indicated by the increased redox state of cytochrome a,a3, both during the cooling phase on bypass and during circulatory arrest, and by enhanced recovery of high-energy phosphates during the rewarming phase. However, a higher Hct does not decrease fluid accumulation during bypass. In contrast to a higher Hct, the improved recovery seen in response to pentafraction is not related to higher oxygen delivery during bypass but to decreased fluid accumulation after bypass. Neither MUF nor increasing the COP with hetastarch is as effective as pentafraction or a high-perfusate Hct in improving intraoperative variables or early postoperative recovery, as determined by the neurologic deficit score or the overall performance category score.

This study is an extension of our previous work in which we compared recovery after DHCA using three levels of hemodilution [1]. We found that severe hemodilution with a crystalloid-only prime resulting in an Hct of less than 10% was associated with evidence of inadequate oxygen delivery before and during circulatory arrest. In contrast, the use of a blood-only prime with an Hct of 30% was associated with improved oxygen delivery and accelerated recovery relative to the response to a standard crystalloid prime with an Hct of 20%. However, it was unclear from this previous study what role the dilution of plasma proteins with a resultant lower COP and subsequent edema played in this result or whether oxygen delivery was the entire explanation. Furthermore, various methods have been proposed to increase the low COP that results from crystalloid hemodilution, including the use of the colloidal agents hetastarch and pentafraction as well as the use of postbypass hemofiltration [6][7].

Edema After CPB in Infants and Neonates
Edema is one of the most obvious deleterious effects of CPB, with or without circulatory arrest, in neonates and young infants [8]. In the Boston Circulatory Arrest Study, the average positive fluid balance was 664 mL in neonates with an average age of 7 days and average body weight of 3.5 kg [9]. The development of edema necessitates that the sternum be left open in some neonates, and it contributes to the longer intensive care unit and total hospital stays of neonates as opposed to those in older children.

There are probably many reasons why neonates are more susceptible to edema after CPB relative to older children. For one reason, capillary permeability is naturally higher in younger people [10]. Although there have been major advances in hardware design resulting in the use of much smaller circuit prime volumes for neonatal bypass, there is still a relatively greater exposure of the neonate to the bypass circuit’s prosthetic surface area relative to the neonate’s endothelial surface area and a much larger ratio of prime volume to blood volume than that in older children or adults. Neonates are also exposed to greater extremes of temperature, as well as to low-flow or circulatory arrest, thereby increasing the risk of ischemia-reperfusion injury with associated endothelial injury and white blood cell activation [11].

Methods to Reduce Postbypass Edema
It has been known for many years that one of the factors contributing to postbypass edema is the reduced COP that results from a crystalloid prime [12][13]. Although concentrated (25%) human albumin has been used successfully by many groups to boost the COP, it is expensive. Furthermore, albumin is a relatively small molecule (69 kD), which under circumstances of increased capillary permeability readily leaks into the interstitium and can contribute to an ongoing capillary leak [14].

Various larger molecules have been evaluated as alternatives to albumin. Hydroxyethyl starch, for example, is a naturally occurring amylopectin derived from the sorghum plant in which hydroxyethyl ether groups have been introduced by exposure to ethylene oxide. The ratio of hydroxyethyl groups to glucose can be varied and results in different formulations, such as 0.7 for "hetastarch" and 0.5 for "pentastarch." Investigators in several studies have concluded that hydroxyethyl starch, whether as hetastarch or as pentastarch, is a reasonable and certainly inexpensive alternative to albumin as a prime constituent. However, there have been suggestions that hetastarch produces coagulation abnormalities and lower platelet counts [15][16]. In our study we did not observe lower platelet counts with the use of hetastarch, though fibrinogen levels tended to be lowest in this group. Saunders and associates [15] conducted a prospective randomized trial of hetastarch and 25% albumin and found that there was significantly greater red blood cell usage when hetastarch was used. We did not measure blood loss in our study.

Another problem with hetastarch is the wide range of sizes of starch molecules, varying from 10 to 5,000 kD. In situations in which capillary permeability is increased, smaller molecules can pass into the third space. An additional risk of the use of larger molecules is the potential for increased blood viscosity during deep hypothermia and for impaired microcirculatory flow. Pentafraction is a hydroxyethyl starch with a limited molecular weight range (50 to 1000 kD) produced by the ultrafiltration of pentastarch. It was specifically designed to minimize the escape of colloid from the vascular space under conditions of increased vascular permeability. It has been suggested that the branched shape of pentafraction molecules allows them to "plug" the endothelial gaps in capillaries present in states of increased permeability [17]. Yeh and colleagues [6] studied the effectiveness of pentafraction in reducing edema in a neonatal piglet model of CPB. After 2 hours of normothermic bypass, control animals receiving a saline prime had a 48% increase in weight whereas those receiving pentafraction had an 11% increase.

Our study confirms that pentafraction is effective in reducing edema, and in contrast to animals receiving hetastarch, those receiving pentafraction had a significantly more rapid behavioral recovery than those receiving a crystalloid prime. Although hetastarch use was associated with a significantly reduced cytochrome a,a3 level during rewarming, differences between hetastarch and pentafraction in terms of the recovery of the adenosine triphosphate and phosphocreatine levels and the cerebral intracellular pH were not demonstrated.

Modified Ultrafiltration
Another approach to reducing the postbypass total body water content has been reported by Naik and associates [18]. This group previously validated the use of bioelectrical impedance as a method for monitoring changes in the total body water content in children undergoing CPB [8][19]. They modified the usual technique of continuous ultrafiltration during CPB, such that ultrafiltration was carried out in the first 10 to 15 minutes after the cessation of bypass to achieve an Hct of 36% to 42% in patients. They demonstrated that use of the modified method led to a significant reduction in the usual increase in the water content after bypass, possibly in part related to the removal of various inflammatory mediators. Elliott [20] later showed an improvement in hemodynamic variables after MUF, including improved myocardial contractility. In our study, 10 minutes of MUF usually increased the Hct to 35% to 40%, although we were unable to demonstrate any beneficial effects of MUF. This is not surprising from the standpoint of the variables measured during CPB, because the protocols for the crystalloid group and the MUF group were identical until after bypass. However, the body water content measured by bioelectrical impedance 3 hours after MUF as well as the body weight gain did not demonstrate any improvement relative to those in the crystalloid prime group. There was also no improvement in the rate of neurologic recovery. It is possible that the advantages of MUF are overwhelmed by the third-space movement of fluid that occurs during bypass if a low COP prime is used. Although MUF can remove fluid from the vascular space and perhaps reduce ongoing fluid shifts, our data suggest that it is not effective in removing fluid that has already shifted into the third space.

Advantages of High Hematocrit Prime
Consistent with the results from our previous study of Hct, the present study confirms that an Hct of 30% improves oxygen delivery to cerebral cells during the cooling phase of bypass before circulatory arrest relative to an Hct of 20%. Interestingly, however, we were unable to demonstrate that there was any advantage to a higher Hct in terms of reducing postbypass edema or weight gain. It is possible that the transfused white blood cells play some role in interactions with capillary endothelial cells and hence in exaggerating the increase in capillary permeability, thereby offsetting any advantage of the higher COP associated with a higher Hct.

Finally, it is important to recognize that 1 hour of circulatory arrest at 15°C is a relatively mild insult for the young pig. Much of the morbidity that is seen in this model is transient and stems from the deleterious effects of bypass and hypothermia rather than from hypoxic-ischemic injury. We speculate that with greater extremes of hypoxia-ischemia, for example, that occurring during longer duration of circulatory arrest, the improved oxygen delivery with a higher Hct would be increasingly advantageous relative to the benefits of the raised COP and decreased capillary leak afforded by pentafraction.


    References
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

  1. Shinoka T, Shum-Tim D, Jonas RA, et al. Higher hematocrit improves cerebral outcome after deep hypothermic circulatory arrest. J Thorac Cardiovasc Surg 1996;112:1610-1621.[Abstract/Free Full Text]
  2. Kawata H, Fackler JC, Aoki M, et al. Recovery of cerebral blood flow and energy state after hypothermic circulatory arrest versus low flow bypass in piglets. J Thorac Cardiovasc Surg 1993;106:671-685.[Abstract]
  3. Hiramatsu T, Miura T, Forbess JM, et al. pH strategy and cerebral energetics before and after circulatory arrest. J Thorac Cardiovasc Surg 1995;109:948-958.[Abstract]
  4. Forbess JM, Ibla JC, Lidov H, et al. University of Wisconsin cerebroplegia in a piglet survival model of circulatory arrest. Ann Thorac Surg 1995;60:S494-S500.
  5. Miura T, Laussen PC, Lidov HGW, du Plessis A, Shinoka T, Jonas RA Intermittent whole body perfusion with somatoplegia versus blood perfusate to extend duration of circulatory arrest. Circulation 1996;94(Suppl 2):S56-S62.
  6. Yeh T, Jr, Parmar JM, Rebeyka IM, et al. Limiting edema in neonatal cardiopulmonary bypass with narrow range molecular weight hydroxyethyl starch. J Thorac Cardiovasc Surg 1992;104:659-665.[Abstract]
  7. Elliott MJ Ultrafiltration and modified ultrafiltration in pediatric open heart operations. Ann Thorac Surg 1993;56:1518-1522.[Abstract]
  8. Maehara T, Novak I, Wyse RKH, Elliott MJ Perioperative monitoring of total body water by bio-electrical impedance in children undergoing open heart surgery. Eur J Cardiothorac Surg 1991;5:258-264.[Abstract]
  9. Wernovsky G, Wypij D, Jonas RA, et al. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation 1995;92:2226-2235.[Abstract/Free Full Text]
  10. Rosenthal SM, LaJohn LA Effect of age on transvascular fluid movement. Am J Physiol 1975;228:134-140.[Abstract/Free Full Text]
  11. Edmunds LH Inflammatory and immunological response to cardiopulmonary bypass. In: Jonas RA, Elloitt MJ, eds. Cardiopulmonary bypass in neonate, infants and young children. Oxford: Butterworth-Heinemann, 1994:225-241.
  12. Webber CE, Garnett ES The relationship between colloid osmotic pressure and plasma proteins during and after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1973;65:234-237.[Medline]
  13. Hindman BJ, Funatsu N, Cheng DC, Bolles R, Todd MM, Tinker JH Differential effect of oncotic pressure on cerebral and extracerebral water content during cardiopulmonary bypass in rabbits. Anesthesiology 1990;73:951-957.[Medline]
  14. Beattie HW, Evans G, Garnett ES, Regoeczi E, Webber CE, Wang KL Albumin and water fluxes during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1974;67:926-931.[Medline]
  15. Saunders CR, Carlisle L, Bick RL Hydroxyethyl starch versus albumin in cardiopulmonary bypass prime solutions. Ann Thorac Surg 1983;36:532-539.[Abstract]
  16. Sade RM, Crawford F, Jr, Dearing JP, Stroud M Hydroxyethyl starch in priming fluid for cardiopulmonary bypass. J Thorac Cardiovasc Surg 1982;84:35-38.[Abstract]
  17. Zikria BA The hypothesis of biodegradable macromolecules as capillary sealants. In: Zikria BA, ed. Reperfusion injuries and clinical capillary leak syndrome. New York: Futura, 1994:583-600.
  18. Naik SK, Knight A, Elliott M A prospective randomized study of a modified technique of ultrafiltration during pediatric open-heart surgery. Circulation 1991;84:III422-III431.
  19. Gonzalez J, Morrissey T, Byrne T, Rizzo R, Wilmore D Bioelectric impedance detects fluid retention in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 1995;110:111-118.[Abstract/Free Full Text]
  20. Elliott MJ Ultrafiltration and modified ultrafiltration in pediatric open heart operations. Ann Thorac Surg 1993;56:1518-1522.



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