| JOURNAL HOME | CME HOME | THIS MONTH | PAST ISSUES | ETOC | COLLECTIONS |
| AUTHORS | REVIEWERS | EDITORIAL BOARD | FEEDBACK | RSS | HELP |
| ||||||||||||||
| ||||||||||||||
|
|
|
|
||||||||||||
|
||||||||||||||
From the *Department of Anaesthesiology and Intensive Care Medicine, Pediatric Anesthesia Research Unit, and Department of Cardiac and Vascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
Address correspondence and reprint requests to Dr. Patrick Meybohm, Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 21, 24105 Kiel, Germany. Address e-mail to meybohm{at}anaesthesie.uni-kiel.de.
Abstract
BACKGROUND: Neonates with complex congenital heart defects have traditionally undergone surgery during deep hypothermic cardiac arrest (HCA). Selective cerebral perfusion (SCP) is thought to minimize ischemic brain injury by providing adequate cerebral blood flow. We investigated SCP with different flow rates compared with HCA with respect to cerebral perfusion and tissue oxygenation as assessed by near-infrared spectroscopy.
METHODS: Twenty-one piglets were placed on cardiopulmonary bypass at 18°C, then underwent either HCA or SCP at 25 or 50 mL · kg–1 · min–1 for 90 min. The blood flow index (BFI) derived by indocyanine green and tissue oxygen index (TOI) were determined by near-infrared spectroscopy. Mean cerebral blood flow velocity (FVmean) was recorded by transcranial Doppler ultrasound.
RESULTS: Both BFI and FVmean increased significantly (126 ± 27% of baseline; 19 ± 2 cm/s) in the SCP 50 group compared with HCA (no flow) and SCP 25 (65 ± 24%; 10 ± 1 cm/s), respectively. TOI increased in the SCP 50 group compared with baseline (74 ± 4% vs 65 ± 4%), and was higher compared with HCA (52 ± 2%) and SCP 25 (59 ± 2%). Intracranial pressure increased nonsignificantly compared with baseline in the SCP 50 group.
CONCLUSIONS: Both BFI and FVmean suggested increased cerebral perfusion in the SCP 50 group compared with the HCA and SCP 25 groups. TOI was significantly higher in both the SCP 25 and SCP 50 groups compared with HCA. SCP at 25 mL · kg–1 · min–1 may be most appropriate for cerebral protection.
Neonates with complex congenital heart defects have traditionally undergone surgery during deep hypothermic cardiac arrest (HCA), but this technique has been shown to be associated with adverse neuro-developmental outcomes.1 Antegrade selective cerebral perfusion (SCP) during systemic circulatory arrest is thought to minimize ischemic brain injury and to decrease the incidence of neurological sequelae by providing adequate blood flow to the brain.2,3 However, the ideal strategy in terms of flow rate of SCP is unclear. In newborn and juvenile patients, mechanisms causing neurological damage during cardiopulmonary bypass (CPB) comprise complete or incomplete cerebral ischemia and hypoxia and, therefore, monitoring of cerebral blood flow (CBF) and oxygenation is warranted. Despite its clinical relevance, a reliable and suitable method for measuring CBF rapidly, repeatedly and noninvasively at the bedside is still lacking. Perfusion magnetic resonance and computed tomographic imaging, though offering a very high spatial resolution, are both limited because they are not suitable for point-of-care monitoring and, therefore, cannot provide repeated measurements.4 Transcranial Doppler ultrasound (TCD) has been advocated as a point-of-care monitor of estimation of CBF5 but, in fact, measures CBF velocity and is technically challenging.
Near-infrared spectroscopy (NIRS) facilitates noninvasive intraoperative monitoring and has therefore been applied to measure cerebral tissue oxygenation during CPB.6 NIRS also enables detection of the tracer dye indocyanine green (ICG) during its passage through the cerebral vasculature after IV injection. Rapid clearance from the blood by both hepatic uptake and biliary excretion allows for repetitive measurements, even at short time intervals. In a preliminary animal study, a blood flow index (BFI) derived from ICG kinetics was significantly correlated with cortical blood flow, but not with skin blood flow, and the BFI was therefore found to be suitable for noninvasive estimation of CBF.7 More recently, the BFI has been shown to allow for rapid and repeated measurements with good reproducibility at the bedside in pediatric patients in the intensive care unit8 and to determine cerebral perfusion during CPB.9
The purpose of this study was to investigate SCP with different flow rates compared with HCA with respect to cerebral perfusion and tissue oxygenation. We hypothesized that SCP 25 and SCP 50 mL · kg–1 · min–1 as opposed to HCA would maintain both cerebral oxygenation and perfusion as assessed by NIRS.
METHODS
Study Design
Twenty-one healthy piglets (German domestic pigs), ranging from 3 to 4 wk of age of either gender, weighing 6 to 10 kg, were randomly assigned to 1 of 3 study groups: HCA, for 90 min (n = 7); SCP 25, SCP for 90 min at a flow rate of 25 mL · kg–1 · min–1 (n = 7); and SCP 50, SCP for 90 min at a flow rate of 50 mL · kg–1 · min–1 (n = 7). The project was approved by the Animal Investigation Committee of the University Schleswig-Holstein, Campus Kiel, Germany, and the animals were managed in accordance with institutional guidelines. All animals received humane care in compliance with the "Guide for the Care and Use of Laboratory Animals" published by the National Institute of Health (NIH Publication No. 88.23, revised 1996).
Anesthesia and Hemodynamic Monitoring
The animals were fasted overnight but had free access to water. The pigs were premedicated with azaperone (butyrophone neuroleptic, 8 mg/kg) and atropine (0.05 mg/kg) IM 1 h before surgery, and anesthesia was induced with a bolus dose of propofol (1–2 mg/kg IV) and sufentanil (0.3 µg/kg IV). After endotracheal intubation during spontaneous respiration, the lungs were ventilated with a volume-controlled ventilator (Siemens SV 900C, Germany) with 40% oxygen at 25 breaths/min, and a tidal volume adjusted to maintain normocapnia (Pco2 35 to 45 mm Hg). Ventilation was monitored using an inspired/expired gas analyzer that measured end-tidal carbon dioxide (ETCO2; M-PRESTN, Datex-Ohmeda, Helsinki, Finland). Oxygen saturation was monitored continuously with a pulse oxymeter placed on the ear (M-CaiOV, Datex-Ohmeda). Anesthesia was maintained with a continuous infusion of propofol (6 to 8 mg · kg–1 · h–1) and sufentanil (0.3 µg · kg–1 · h–1); muscle relaxation was provided by a continuous infusion of pancuronium (0.2 mg · kg–1 · h–1). Lactated Ringer's solution (10 mL · kg–1 · h–1) was administered throughout the preparation phase. A standard lead II electrocardiogram was used to monitor cardiac rhythm; depth of anesthesia was judged according to arterial blood pressure and heart rate during the preparation phase. In our experience, piglets do not respond to painful or auditory stimuli under this anesthetic regimen when the paralyzing drug is withheld and the initial loading dose of ketamine and propofol subsides. If clinical assessment suggested a decreasing level of anesthesia, additional sufentanil and propofol were given.
A 4F saline-filled catheter was advanced via left femoral artery cannulation into the aorta for withdrawal of arterial blood samples. Mean arterial blood pressure in the head was recorded from the central ear artery (Pear) using a 22G catheter. A 5F catheter was inserted in the right internal jugular vein to measure central venous pressure. All catheters were flushed with normal saline containing 5 U/mL heparin at a rate of 3 mL/h to prevent obstruction during the preparation phase. The intravascular catheters were attached to pressure transducers (Smiths Medical, Kirchseeon, Germany) that were aligned to the level of the right atrium. Arterial blood gases for analyzing pH, partial pressure of oxygen (Po2), partial pressure of carbon dioxide (Pco2), hemoglobin and hematocrit were measured with a blood gas analyzer (ABL System 615, Radiometer, Copenhagen, Denmark).
Neuromonitoring
For brain parameter access, a multiluminal probe introducer (Licox IM3.STV, GMS, Kiel, Germany) was inserted via a 5.3 mm skull burr hole (10 mm paramedian and 10 mm cranial of the coronal suture) for measurement of brain temperature and intracranial pressure (ICP; Ventrix, Integra NeuroSciences, Plainsboro, NJ). Cerebral perfusion pressure (CPP) was defined as Pear – ICP.
NIRS (NIRO 300, Hamamatsu Photonics, Herrsching, Germany) was used to measure cerebral tissue oxygenation index (TOI) that is the ratio of oxygenated to total tissue hemoglobin and concentration changes of the intravascular dye ICG (Pulsion Medical Systems, Munich, Germany). Four wavelengths of light (775, 810, 850, and 910 nm, respectively) are delivered by 4 pulsed laser diodes, and scattered light is detected by three closely placed photodiodes. The specific extinction coefficient of ICG is applied to a modified Beer-Lambert law and absolute concentration changes are calculated by proprietary software (Hamamatsu Photonics). ICG was administered as bolus at a dose of 0.1 mg/kg and a concentration of 0.2 mg/mL through the central venous line during spontaneous circulation or into the arterial line of the bypass circuit during CPB, respectively. For each measurement, the rise time (defined as the time between 10% and 90% of the ICG maximum), and the percent change of BFI compared with baseline were calculated (Fig. 1). The BFI method, originally described by Perbeck et al.10 for blood flow determination in intestinal capillaries, was subsequently applied to ICG dye kinetics in the cerebral vasculature.7 BFI was calculated as described previously according to the algorithm:
|
BFI = maximal 
ICG absorption/rise time
BFI is proportional to blood flow, but the proportionality factor is unknown. This means that BFI measurements are comparable within a subject, but not between subjects, since the proportionality factor may vary considerably between subjects8 and, therefore, relative changes of BFI to baseline were calculated during spontaneous circulation in the present study. Because of the difference in ICG injection technique during CPB, relative changes of BFI to the full-flow CPB before SCP were calculated for bypass BFI data. NIRS optodes were placed on the skin covering the right cerebral hemisphere on a line 1 cm lateral to the mid-sagittal plane to avoid signal irritation by the sagittal sinus. Because increasing the interoptode distance decreases extracerebral contamination, we chose an interoptode distance of 3 cm for optimal spatial resolution. Path length was adjusted according to the manufacturer's instructions for measurements on an intact human skull and sampling rate was set to 6 Hz. The optodes were covered with opaque material and secured to the head with adhesive tape.
CBF velocity was determined by TCD (DWL, Sipplingen, Germany) using the temporal bone window. With a 2-MHz pulsed Doppler probe, the left middle cerebral artery was insonated at a depth of 20 to 28 mm, and mean blood flow velocity (FVmean) was recorded. The transducer was kept fixed in place by an elastic headband to ensure a stable position of vessel insonation.
Operative Technique
After instrumentation for cerebral and hemodynamic variables and a 60-min equilibration phase, a median sternotomy was performed, the pericardium was opened, and the heart and the great vessels were exposed. After heparinization (450 IU/kg), a 10F arterial and a 20F venous single stage cannula were inserted into the ascending aorta and the right atrium, respectively. Using 
-stat management, nonpulsatile CPB was initiated at a flow rate of 80 to 100 mL · kg–1 · min–1 (roller pump, Stöckert S1, Stöckert instruments, Munich, Germany; membrane oxygenator, Dideco Lilliput 1, Sorin Group, Modena, Italy; heat exchanger, Hemotherm CSZ400 MR, CincinnatiSubzero, Cincinnati). The circuit was primed with heparinized fresh blood from a donor pig. During CPB, arterial pH (7.35 to 7.45), Pco2 (35 to 45 mm Hg), Po2 (100 to 250 mm Hg), and hematocrit (>0.2) were carefully controlled. After 30 min of cooling to a brain temperature of 18°C, pump flow was shut off followed by a 90-min interval of HCA at 18°C, or SCP with the specified flow rate at 18°C, respectively. In all study groups, myocardial protection was achieved with cold crystalloid cardioplegia (Saint-Thomas-II solution; induction 25 mL/kg, maintenance 10 mL/kg). For SCP, both ascending and descending aorta were cross-clamped proximal and distal to the aortic cannula. Isolated perfusion of the brain was then established via the bi-carotid trunk at either 25 or 50 mL · kg–1 · min–1 according to the same protocol as described for global CPB. After 90 min, the aortic clamp was removed and global CPB was reconstituted at a flow rate of 100 mL · kg–1 · min–1 with warming to a brain temperature of 36°C over 30 min. Internal defibrillation was performed after reaching a blood temperature of 30°C. During weaning from CPB, inotropic support and control of vascular resistance was performed if necessary. At 37°C, CPB was discontinued. Heterologous blood was transfused to maintain adequate preload. Sodium bicarbonate was used to correct metabolic acidosis. The piglet was decannulated, and the wounds were reapproximated to minimize heat loss. Hemodynamic and cerebral variables and blood gases were measured at baseline before CPB (BL), after 10 min of cooling on CPB (Cool), after 10 and 60 min of HCA or SCP, respectively (HCA/LF-10; HCA/LF-60), after 10 min of re-warming on CPB (Rewarm), and after 15 min of weaning from CPB (End CPB).
After finishing the experimental protocol, the animals were euthanized with an overdose of propofol, sufentanil, and potassium chloride.
Statistical Analysis
Statistical comparisons were performed using commercially available statistics software (GraphPad Prism version 4.03 for Windows, GraphPad Software, San Diego, CA). A Kolmogorov-Smirnov test was used to test for Gaussian distribution. BFI data were transformed to normal distribution using logarithms for statistical comparison. Variables were analyzed with two way repeated measures analysis of variance factoring for time and treatment group followed by Bonferroni correction for multiple comparisons and Student's t-test, if applicable; values are expressed as mean ± sem. Correlation between FVmean and BFI was analyzed with Spearman's rank correlation. Statistical significance was considered at P < 0.05.
RESULTS
Systemic Hemodynamic Data and Blood Gases
Systemic hemodynamic data and blood gases are given in Table 1. Pear was significantly increased in the SCP 50 group compared with the HCA and SCP 25 groups during SCP (67 ± 4 vs 48 ± 2 and 13 ± 3 mm Hg, respectively; P < 0.01). Groups did not differ with respect to systemic blood gases at any time throughout the study period, except during rewarming when Pco2 of the HCA group was significantly lower compared with the SCP 25 and SCP 50 groups, respectively (22 ± 3, 36 ± 9, and 34 ± 5 mm Hg, respectively; P < 0.05). Five animals could not be weaned from bypass, while in the remaining animals, spontaneous circulation was achieved.
|
Brain Temperature, ICP, and CPP
The mean and standard errors for brain temperature, ICP, and CPP for each of the experimental groups are presented in Table 2. There was no difference among groups for brain temperature at the times measurements were recorded. ICP decreased significantly from baseline in the HCA group during the period of circulatory arrest but returned to baseline at the end of CPB (P < 0.001). ICP remained stable in the SCP 25 group. Measured ICP increased in the SCP 50 group during LF, but ICP at LF-60 was not significantly more than the baseline value for this group. ICP at the end of bypass was increased compared with baseline in the SCP 50 group, but the comparison was not significant (P = 0.25). ICP was lower in the SCP 25 group compared with the SCP 50 group at LF-10 (P < 0.01), LF-60 (P < 0.01) and during rewarming (P < 0.05).
|
CPP was unobtainable in the HCA group during the circulatory arrest period and is not shown (Table 2). CPP was significantly decreased in the SCP 25 group compared with baseline at LF-60 (P < 0.05), but CPP increased to values not significantly different from baseline by the end of CPB. CPP was stable across time points in the SCP 50 group. CPP was significantly greater at LF-10 and LF-60 in the SCP 50 group than in the SCP 25 group (P < 0.05; Table 2).
CBF
Cerebral BFI is related linearly to the maximum change in light absorption due to ICG and inversely related to rise time. The rise time values are shown in Table 2 and a representative set of absorption peaks are shown in Figure 1. The BFI values obtained during bypass for each animal were normalized to the BFI obtained during cooling. The relative BFI values are shown in Figure 2. As expected, BFI was zero for the HCA group during the circulatory arrest period, however, flow rebounded to above baseline during rewarming. BFI declined, but not significantly, in the SCP 25 group at LF-10 and LF-60 (82 ± 29% and 76 ± 24% of cooling; Fig. 2). Significant increases in BFI were noted in the SCP 50 group at LF-10 and LF-60 (158 ± 11% and 115 ± 17% of cooling values; P < 0.05). Thus, BFI was significantly higher in the SCP 50 group compared with the SCP 25 group (P < 0.01) during SCP. BFI data before and after CPB during spontaneous circulation were compared separately. After 15 min of weaning from CPB, BFI decreased to 48 ± 15%, 53 ± 16%, and 50 ± 14% of pre-bypass in the HCA, SCP 25 and SCP 50 groups, respectively. The mean and standard error for measured CBF velocity at the six time points is shown in Figure 3. The mean CBF velocity followed the same time-group pattern as the BFI.
|
|
The relationship between mean flow velocity and BFI during SCP is shown in Figure 4. FVmean was correlated with relative changes of BFI obtained during cooling at full-flow CPB in the SCP 25 and SCP 50 groups (r2 = 0.14; linear regression line; P < 0.05). Data from the HCA group and data from all groups at baseline, full-flow bypass and the end of bypass were excluded from correlation analysis.
|
Cerebral Oxygenation
TOI did not change significantly in any group during cooling. TOI decreased significantly in the HCA group during circulatory arrest (P < 0.01), but rebounded to cooling levels during rewarming. TOI was significantly higher at LF-10 and LF-60 in both the SCP 25 (P < 0.05, P < 0.001, respectively) and SCP 50 groups (P < 0.001 at both time points) compared with the HCA group. The TOI for the SCP 25 and SCP 50 groups differed significantly at LF-10 and LF-60 (P < 0.01; Fig. 5). At the end of CPB, TOI did not differ from baseline in the HCA group, but was significantly below the baseline in both the SCP 25 and SCP 50 groups (P < 0.05 in both groups).
|
DISCUSSION
The main findings of this study are as follows: First, both BFI and TCD suggested increased cerebral perfusion in the SCP 50 group compared with the HCA and SCP 25 groups. Second, TOI was significantly higher in both the SCP 25 and SCP 50 groups during SCP using -stat management compared with the HCA group. Third, TOI did not differ from baseline at the end of CPB in the HCA group, but was below baseline values in both the SCP 25 and SCP 50 groups. Fourth, ICP remained stable in the SCP 25 group but increased nonsignificantly in the SCP 50 group during SCP and tended to be higher compared with baseline at the end of bypass.
Selective low-flow cerebral perfusion has been used for more than a decade in congenital heart surgery in an attempt to reduce central nervous system injury that has been observed after HCA.3,11 The ideal strategy with respect to flow rate of SCP, however, remains to be elucidated. Therefore, the evaluation of different flow-rates in comparison to the historic technique with HCA is still of paramount importance.
TCD ultrasound is a sensitive indicator of CBF velocity12 that has been used in neonatal heart surgery to guide flow rate during global low-flow bypass.13,14 In a preliminary study, BFI assessed by NIRS has also been shown to allow for determination of cerebral perfusion during CPB.9
The results of the present study indicate that both TCD and BFI reflected the expected changes of cerebral perfusion and thus are very likely reflecting CBF during CPB and SCP. The decrease of FVmean after cooling may be most probably attributed to decreased brain oxygen demand and consequently reduced CBF since Pear and CPP did not change significantly compared with baseline. As expected, BFI was zero for the HCA group during the circulatory arrest period, however, flow rebounded to above baseline during rewarming. During SCP, both TCD and BFI suggested increased cerebral perfusion in the SCP 50 group compared with the HCA and SCP 25 groups. Moreover, BFI was nearly twice as much in the SCP 50 group compared with the SCP 25 group reflecting the different flow rates of SCP. Theoretically, comparison between subjects of absolute BFI values is hampered by the fact that flow is not determined in absolute values but with a proportionality factor. This factor may vary considerably among subjects dependent on layer thickness between NIRS optodes and the cerebral tissue interrogated. Consequently, Wagner et al.8 reported a large interindividual variability in a heterogeneous pediatric population in the intensive care unit. Accordingly, the BFI values obtained during bypass and SCP for each animal were normalized to the BFI obtained during cooling at full-flow bypass.
In the present study, TCD readings were correlated with BFI during SCP. Although data from the HCA group and data from all groups at baseline, full-flow bypass and at the end of bypass were excluded from correlation analysis, the relatively weak correlation (r2 = 0.14) may be explained, at least in part, by the fact that BFI represents blood flow in a small tissue sample whereas TCD measures global cerebral perfusion. Furthermore, TCD measures blood flow velocity rather than CBF, but blood flow velocity often correlates well with changes in CBF in the individual patient.
With respect to cerebral oxygenation during SCP, TOI was significantly higher in both the SCP 25 and SCP 50 groups during SCP compared with the HCA group. Moreover, TOI profoundly decreased in the HCA group compared with baseline, but rebounded to cooling levels during rewarming. TOI has been proposed to represent the regional, organ-specific balance of oxygen supply and demand. If cerebral arterial oxygen content and cerebral metabolic rate of oxygen are constant, changes in CBF will produce equal change in cerebral venous oxygen saturation. Because TOI mainly reflects volume-averaged oxygenation changes in the venous compartment of cerebral blood volume,15 it is expected to vary with CBF during hypothermic CPB. Since cerebral metabolic rate of oxygen is nearly constant during hypothermic CPB at 18°C, higher TOI values observed in the SCP 50 group likely reflected an increase of oxygen supply and luxury cerebral perfusion than a reduction in oxygen utilization, since brain temperature was comparable among study groups. Therefore, SCP at 50 mL · kg–1 · min–1 significantly increased BFI and TOI compared with baseline, but also resulted in an increased ICP relative to baseline that did not reach statistical significance. Moreover, ICP in the SCP 50 group was higher than in the SCP 25 group during SCP and rewarming. Consequently, this flow may cause cerebral edema and perhaps cerebral vascular injury, which raises concerns about this flow-rate and implies that an assessment of ICP might be evaluated in neonates undergoing SCP by the use of a pressure monitor placed over the fontanel.
By contrast, SCP at 25 mL · kg–1 · min–1 preserved cerebral oxygenation within the range of baseline values, and did not result in excessive cerebral perfusion. This flow rate is similar to that used by Pigula et al.,3 who demonstrated that regional perfusion had to be approximately 20 mL · kg–1 · min–1 in order to maintain cerebral saturation. Even lower acceptable limits of CBF at 20°C have been reported.16 In an experimental study by DeCampli et al.,17 only regional perfusion with 40 mL · kg–1 · min–1 preserved cortical Po2 during the period of selective perfusion compared with pre-bypass data, but this flow rate was excessive in that it was associated with upper torso edema, greater post-CPB acidosis, and an overall declining clinical course after CPB. In contrast, SCP at 20 mL · kg–1 · min–1 resulted in a lesser cortical Po2 and a relatively greater proportion of hypoxic tissue but, overall, recovery was better. However, Andropoulos et al.5 demonstrated that, in contrast to our results and those by Pigula et al.3 and DeCampli et al.,17 a mean SCP-flow at 63 mL · kg–1 · min–1 was required to maintain cerebral oxygen saturation and blood flow velocity within ±10% of full flow CPB values during SCP for neonatal aortic arch reconstruction. This is more sophisticated, since Andropoulos and coworkers used pH-stat acid-base management, compared with -stat used in our study and by both Pigula3 and DeCampli.17 pH-stat acid-base management per se has yet to be suggested to result in cerebral vasodilatation and pronounced cerebral perfusion. Thus, pH-stat strategy might have even been expected to result in further elevated ICP.
Interestingly, SCP at 50 mL · kg–1 · min–1 using - stat management resulted in decreasing BFI, FVmean, and TOI with time during SCP and rewarming suggesting increasing cerebral vascular resistance but not SCP at 25 mL · kg–1 · min–1. This is similar to the data reported by Hoffman et al.,18 demonstrating that cerebrovascular resistance was increased after deep hypothermic CPB, even with regional perfusion techniques, resulting in delayed decreases in brain oxygenation after stage 1 Norwood palliation of hypoplastic left heart syndrome. This may occur as a result of altered dynamic autoregulation from changes in Pco2 and pH as a result of impaired autoregulation,19 endothelial dysfunction,20 tissue edema, microvascular occlusion, or cerebral edema. However, a flow rate of 50 mL · kg–1 · min–1 during SCP has also been advocated on the basis of theoretical calculations,21 but the issue of optimal flow rate for SCP remains controversial. Our data indicate that a flow rate of 25 mL · kg–1 · min–1 using -stat management may be most appropriate for SCP, since sufficient cerebral oxygenation was achieved without impact on ICP during SCP.
Regarding cerebral oxygenation at the end of CPB, TOI did not differ from baseline in the HCA group, but was below baseline values in both the SCP 25 and SCP 50 group. Since BFI decreased to nearly half of pre-bypass values at the end of bypass in all groups, and CPP and FVmean barely reached baseline values. TOI, however, is also weighted to venous saturation. The most likely explanation for this is that other mechanisms are involved in the early postoperative period. First, reduced oxygen delivery due to reduced cerebral perfusion may result in a decreased TOI. Second, the cerebral tissue is in a state of increased oxygen extraction, perhaps due to some sort of injury or predisposition to injury.
With respect to achieving optimal cerebral protection, clinical and experimental data suggest that SCP is superior to HCA, but further questions remain, particularly concerning the optimal temperature, acid-base management and hematocrit. Regarding the optimal temperature for SCP, data from animal experiments suggest that SCP in deep hypothermia ranging from 18°C to 20°C will provide adequate brain protection by reducing cerebral metabolic activity and histopathological changes and maintaining energy stores,11,22,23 but the side effects related to deep hypothermia also pertain to this technique. Thus, several preliminary retrospective human studies gave evidence that SCP, with moderate temperatures such as 24°C to 30°C, may also provide sufficient cerebral protection.24,25 With respect to the controversial issue of acid-base management, several experimental studies have demonstrated an advantage for pH-stat strategy,26,27 but -stat management is often the method of choice in clinical practice to achieve optimal cerebral protection. Further, hemodilution during hypothermic CPB has been shown to improve cerebral microcirculation. However, the optimal degree of hemodilution remains unclear, but hematocrit should be maintained between 20 and 30 during SCP.28
Clinical evidence suggests a correlation between low cerebral oxygen saturations and adverse neurological outcome. A study by Austin et al.29 showed that 70% of pediatric patients experienced a significant change in one or more variables when multimodal neurological monitoring, NIRS, TCD, and qualitative electroencephalogram, was used during cardiac surgery. We have focused in this study on TOI and BFI, two NIRS-derived variables that differ fundamentally in the type of data provided. TOI has been shown to represent the cerebral balance of oxygen supply and demand, while BFI has been claimed as an at least minimally invasive procedure for determination of cerebral perfusion30 and an efficient additional tool for that purpose. Thereby, NIRS technology provides information about cerebral oxygenation, but also allows for calculation of BFI derived from ICG dilution curves that might add further information during bypass and SCP to allow for rapid and repeated evaluation of CBF changes.
This study has several limitations. First, we perfused both carotid arteries in our model, as opposed to the clinical situation in which only the right carotid artery is perfused and the left carotid artery is occluded. Second, the pig's bi-carotid trunk delivers blood partially to the brain, and partially to extracerebral tissue. Therefore, it cannot completely be excluded that extracerebral tissue has been perfused during SCP. However, this resembles a clinical situation where, by perfusion of the brachio-cephalic trunk, cerebral and extracerebral tissue is also perfused. Third, the path length of NIRS in the porcine head is unknown, and thus we used the published data derived from human experiments.31 Although there may be a difference between species, this does not interfere with the results of our study, since it was aimed at investigating changes over time rather than presenting absolute values. Further, NIRS technology may be influenced by extracerebral contamination. Moreover, ICG kinetics will be altered during CPB and SCP as a result of bolus passage through the extracorporeal circuit and, therefore, on principle differs to pre-CPB and post-CPB values. Finally, since we were unable to measure CBF using radioactive microspheres due to limitations posed by government regulations, we cannot comment on effects of drugs given throughout the study on CBF. Further studies should focus on the ideal strategy for cerebral protection, particularly comparing -stat versus pH-stat for different flow-rates. An analysis of cerebral metabolism, brain histology, and neurological function may further reveal the superiority of one strategy to the other.
In conclusion, the present study demonstrated that both BFI and TCD suggested increased cerebral perfusion in the SCP 50 group compared with the HCA and SCP 25 groups, respectively. Further, cerebral oxygenation was significantly higher in both the SCP 25 and SCP 50 groups during SCP using -stat strategy compared with the HCA group, and ICP tended to increase compared with baseline in the SCP 50 group. This suggests that SCP at 25 mL · kg–1 · min–1 may be most appropriate for cerebral protection using -stat strategy during congenital heart surgery in infants and newborns. However, our results should exclusively be transferred to neonates with normal cerebral circulation, but not to children with left-sided obstructive lesions, since impaired brain development, delayed brain myelination and disabled cerebral circulation have been reported in these patients.32,33
ACKNOWLEDGMENTS
The authors are indebted to Gunnar Kuschel, BS, and Marion Frahm for excellent technical assistance and logistic support, and to Juergen Hedderich, PhD, for statistical advice.
Footnotes
Accepted for publication November 1, 2007.
Funding was restricted to institutional and departmental sources. No author has a conflict of interest in regards of any device or drug being employed in this study.
REFERENCES
This article has been cited by other articles:
|
|
 |
|
  J. D. Salazar, R. D. Coleman, S. Griffith, J. D. McNeil, M. Steigelman, H. Young, B. Hensler, P. Dixon, J. Calhoon, F. Serrano, et al. Selective cerebral perfusion: real-time evidence of brain oxygen and energy metabolism preservation. Ann. Thorac. Surg., July 1, 2009; 88(1): 162 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Khadra, K. McConnell, R. VanDyke, V. Somers, M. Fenchel, S. Quadri, J. Jefferies, A. P. Cohen, M. Rutter, and R. Amin Determinants of Regional Cerebral Oxygenation in Children with Sleep-disordered Breathing Am. J. Respir. Crit. Care Med., October 15, 2008; 178(8): 870 - 875. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
P < 0.01 versus cooling; #P < 0.05 versus cooling; **P < 0.05 versus baseline. No statistical comparisons between groups were performed at the end of CPB due to problems with weaning from CPB resulting in different group sizes.
