Cerebral hemodynamics in neonates and infants undergoing cardiopulmonary bypass and profound hypothermic circulatory arrest: assessment by transcranial Doppler sonography

Profound hypothermic circulatory arrest (PHCA) is followed by a transient period of increased intracranial pressure and a longer period of neurophysiologic dysfunction. To investigate the effect of cardiopulmonary bypass (CPB) with PHCA on cerebral hemodynamics, we used transcranial Doppler sonography to measure cerebral blood flow velocity in 10 neonates and infants before and after PHCA. Cerebral blood flow velocity was compared before and after PHCA during normothermic cardiopulmonary bypass at the same mean arterial pressure, central venous pressure, hematocrit, and arterial carbon dioxide tension. Cerebral blood flow velocity decreased exponentially with decreasing nasopharyngeal temperature before PHCA (P less than 0.05) and remained decreased after PHCA during normothermic CPB, compared with values for normothermic CPB before PHCA (P less than 0.005). During normothermic CPB after PHCA, the modified cerebral vascular resistance (mm Hg.cm.s-1) was increased above values for normothermic CPB before PHCA (P less than 0.05). The results of this study suggest that the observed increase in intracranial pressure during PHCA is not caused by increased cerebral perfusion, but rather that cerebral perfusion is reduced in response to a decreased demand for cerebral metabolic oxygen.     

Pulsatile flow improves cerebral blood flow in pediatric cardiopulmonary bypass

The objective of this study was to evaluate the effect of pulsatile flow on cerebral blood flow (CBF) in infants with the use of a mild hypothermic cardiopulmonary bypass (CPB). Thirty infants scheduled for open heart surgery were randomized to the pulsatile group (Group P, n = 15) and nonpulsatile group (Group NP, n = 15). In Group P, pulsatile perfusion was applied during the aortic cross‐clamping period, whereas nonpulsatile perfusion was used in Group NP. The systolic peak velocity (Vs), the end of diastolic velocity (Vd), the mean velocity (Vm), and the pulsatility index (PI) and the resistance index (RI) of the middle cerebral artery were measured by a transcranial Doppler (TCD) ultrasound after anesthesia (T1; baseline), at the beginning of CPB (T2), 10 min after aortic cross‐clamping (T3), 3 min after declamping (T4), at the cessation of CPB (T5), and at the end of the operation (T6). During T3 and T4, the Vs in Group P was significantly higher than in Group NP. However, there were no statistically significant differences between Vd and Vm. The PI and RI in Group P were also higher than those in Group NP (both P < 0.05). During T5, Vd and Vm were higher in Group P (P < 0.05), whereas there was no difference in Vs. Additionally, PI and RI in Group P were significantly lower than those in Group NP (P < 0.05). However, there was no difference during T6. Pulsatile perfusion may increase CBF and decrease cerebral vascular resistance in the early period after mild hypothermic CPB.     

Cerebral pressure-flow velocity relationship during hypothermic cardiopulmonary bypass in neonates and infants.

To examine the effect of temperature on the relationship between cerebral perfusion pressure (CPP) and cerebral blood flow velocity (CBFV) and the effect of low-flow cardiopulmonary bypass (CPB) on cerebral perfusion, we studied 25 neonates and infants ranging from 3 to 210 days of age at three nasopharyngeal temperature (NPT) ranges during cardiopulmonary bypass. Pressure-flow velocity relationships were studied during normothermic (NPT = 36-37 degrees C), moderate hypothermic (NPT = 23-25 degrees C), and profound hypothermic (NPT = 14-20 degrees C) CPB. A transcranial Doppler monitor was used to obtain CBFV, which was measured in the M1 segment of the middle cerebral artery. The CBFV was used as an index of cerebral perfusion. Anterior fontanel pressure (AFP) was subtracted from mean arterial pressure (MAP) to calculate CPP in mm Hg. Nasopharyngeal temperature, PaCO2, and hematocrit were controlled during the study period. Arterial blood gases were analyzed at 37 degrees C, uncorrected for body temperature (alpha-stat acid-base management). The CBFV measurements were made over a range of CPP from 6 to 90 mm Hg. Using nonlinear regression analysis, we showed that cerebral pressure-flow velocity autoregulation was present during normothermic CPB (r2 = 0.68). Autoregulation became pressure-passive, using linear regression analysis, during moderate hypothermic CPB (r2 = 0.33) and profound hypothermic CPB (r2 = 0.69). Cerebral blood-flow velocity was not detectable at a mean (+/- SD) CPP of 9 (+/- 2) mm Hg induced by the low-flow CBP state but became apparent when CPP was increased to 13 (+/- 1) mm Hg (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodilution elevates cerebral blood flow and oxygen metabolism during cardiopulmonary bypass in piglets

BACKGROUND: Hemodilution continues to be widely used during cardiopulmonary bypass (CPB) for both adults and children. Previous studies with nonbypass models have suggested that an increase in cerebral blood flow (CBF) compensates for the reduced oxygen-carrying capacity; however, this increased CBF is achieved by an increase in cardiac output. We hypothesized that even with the fixed-flow perfusion of CPB, CBF would be increased during hemodilution. METHODS: Two experiments were conducted and analyzed separately. In each experiment, 10 piglets were randomized to two different groups, one with a total blood prime yielding a high hematocrit (25% or 30%), and the other with a crystalloid prime resulting in a low hematocrit (10% or 15%). Animals were cooled with pH-stat strategy at full flow (100 or 150 mL.kg(-1).min(-1)) to a nasopharyngeal temperature of 15 degrees C, a period of low flow (50 mL.kg(-1).min(-1)) preceding deep hypothermic circulatory arrest (45 or 60 minutes), and a period of rewarming at full flow. Cerebral blood flow was measured at the beginning of CPB, at the end of cooling, at the end of low flow, 5 minutes after the start of rewarming, and at the end of rewarming by injection of radioactive microspheres. RESULTS: Mean arterial pressure was significantly greater with higher hematocrit at each time point (p< 0.05). Cerebral blood flow and the cerebral metabolic rate of oxygen decreased during cooling and further during low flow bypass but were significantly greater with lower hematocrit during mild hypothermia and at the end of rewarming (p< 0.05). CONCLUSIONS: Hemodilution is associated with decreased perfusion pressure, increased CBF and increased the cerebral metabolic rate of oxygen during hypothermic CPB.     

Temperature monitoring during CPB in infants: does it predict efficient brain cooling?

We examined jugular venous oxygen saturation data in 17 pediatric patients less than 1 year of age undergoing hypothermic cardiopulmonary bypass (CPB). Jugular venous oxygen saturations (JvO2SATS) were measured before bypass and during the active core cooling portion of CPB. The study intervals during CPB included 1 minute after initiation of CPB, at a tympanic membrane temperature of 15 degrees C, and at a rectal temperature of 15 degrees C. During these measurement intervals, there were no significant changes in mean arterial pressure, pump flow rate, arterial oxygen saturation, mixed venous oxygen saturation, carbon dioxide tension, or hematocrit. Six of the 17 patients (29%) demonstrated a significantly lower JvO2SAT (87.1% +/- 6.3% versus 98.1% +/- 0.9%) at a tympanic membrane temperature of 15 degrees C. Patients demonstrating jugular venous desaturation could not be predicted from continuous monitoring of tympanic membrane and rectal temperatures or through on-line measurements of mixed venous oxygen saturation. Low JvO2SAT suggests higher levels of cerebral metabolism and cerebral uptake of oxygen. In the presence of deep hypothermic CPB and stable anesthetic levels, the most likely cause of a low JvO2SAT is inadequate cerebral cooling. We believe JvO2SAT monitoring may be an important adjunct to conventional temperature monitoring in the patient undergoing deep hypothermic CPB or total circulatory arrest.     

The effects of deep hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral blood flow in infants and children

Cardiopulmonary bypass management in infants and children involves extensive alterations in temperature, hemodilution, and perfusion pressure, with occasional periods of circulatory arrest. Despite the use of these biologic extremes of temperature and perfusion, their effects on cerebral blood flow are unknown. This study was designed to examine the relationship of mean arterial pressure and nasopharyngeal temperature to cerebral blood flow during deep hypothermic cardiopulmonary bypass (18 degrees to 22 degrees C) with and without periods of total circulatory arrest. Cerebral blood flow was measured before, during, and after deep hypothermic cardiopulmonary bypass using xenon clearance techniques in 25 children, aged 2 days to 60 months. Fourteen patients underwent repair with circulatory arrest. There was a highly significant correlation of cerebral blood flow with temperature during cardiopulmonary bypass (p = 0.007). During deep hypothermic bypass there was a significant association between cerebral blood flow and mean arterial pressure (p = 0.027). In infants undergoing repair with deep hypothermia alone, cerebral blood flow returned to prebypass levels in the rewarming phase of bypass. However, in patients undergoing repair with circulatory arrest, no significant increase in cerebral blood flow during rewarming or even after bypass was observed (p = 0.01). These data show that deep hypothermic cardiopulmonary bypass significantly decreases cerebral blood flow because of temperature reduction. Under conditions of deep hypothermia, cerebral pressure-flow autoregulation is lost. This study also demonstrates that cerebral reperfusion after deep hypothermia is impaired if the patient is exposed to a period of total circulatory arrest.     

Dissociation between cerebral autoregulation and carbon dioxide reactivity during nonpulsatile cardiopulmonary bypass

Five patients undergoing cardiopulmonary bypass (CPB) procedures were extensively monitored because of anticipated high risk for neurological complications. Arterial blood pressure (BP), central venous pressure, and epidural intracranial pressure (EDP) were continuously recorded throughout CPB; thus, information on the cerebral perfusion pressure (CPP) was also continuously available (CPP = BP - EDP). Cerebral electrical activity was recorded by a cerebral function monitor. The flow velocity in the middle cerebral artery (MCA) was recorded using a transcranial Doppler technique. During steady-state CPB (constant hematocrit, constant temperature, and constant flow from the heart-lung machine) partial pressure of arterial carbon dioxide (PaCO2) was repeatedly changed to study the effect of changes in this variable on MCA flow velocity during nonpulsatile bypass. During CPB with constant temperature, hematocrit, and PaCO2, the effect of changes in CPP on MCA flow velocity was recorded and analyzed. During nonpulsatile, moderately hypothermic (28 degrees to 32 degrees C), low-flow (1.5 L/min/m2) CPB, there was no evidence of cerebral autoregulation, with CPP levels ranging from 20 to 60 mm Hg. The CO2 reactivity, however, was clearly present and in the range of 1.9 to 4.1%/mm Hg, indicating that there was a dissociation between cerebral autoregulation and CO2 reactivity under these circumstances.     

Neurologic monitoring for special cardiopulmonary bypass techniques

Low flow hypothermic cardiopulmonary bypass, deep hypothermic circulatory arrest, and regional low-flow cerebral perfusion are special techniques used to facilitate complex intracardiac and aortic surgery in neonates and infants. Each carries a risk of cerebral hypoxia and neurologic morbidity. Neurologic monitoring in the form of near-infrared spectroscopy for cerebral oxygenation, transcranial Doppler ultrasound, and the bispectral index electroencephalogram can monitor the brain during these techniques to determine the minimum acceptable bypass flow rates or maximum acceptable duration of deep hypothermic circulatory arrest. The use of this monitoring has the potential to improve long-term neurologic and developmental outcome.     

Cerebral Oxygenation during Pediatric Cardiac Surgery Using Deep Hypothermic Circulatory Arrest

Background: Deep hypothermic circulatory arrest is a widely used technique in pediatric cardiac surgery that carries a risk of neurologic injury. Previous work in neonates identified distinct changes in cerebral oxygenation during surgery. This study sought to determine whether the intraoperative changes in cerebral oxygenation vary between neonates, infants, and children and whether the oxygenation changes are associated with postoperative cerebral dysfunction.

Methods: The study included eight neonates, ten infants, and eight children without preexisting neurologic disease. Cerebrovascular hemoglobin oxygen saturation (ScO2), an index of brain oxygenation, was monitored intraoperatively by near-infrared spectroscopy. Body temperature was reduced to 15 degrees Celsius during cardiopulmonary bypass (CPB) before commencing circulatory arrest. Postoperative neurologic status was judged as normal or abnormal (seizures, stroke, coma).

Results: Relative to preoperative levels, the age groups experienced similar changes in ScO2 during surgery: Sco sub 2 increased 30 plus/minus 4% during deep hypothermic CPB, it decreased 62 plus/minus 5% by the end of arrest, and it increased 20 plus/minus 5% during CPB recirculation (all P < 0.001); after rewarming and removal of CPB, ScO2 returned to preoperative levels. During arrest, the half-life of ScO2 was 9 plus/minus 1 min in neonates, 6 plus/minus 1 min in infants, and 4 plus/minus 1 min in children (P < 0.001). Postoperative neurologic status was abnormal in three (12%) patients. The ScO2 increase during deep hypothermic CPB was less in these patients than in the remaining study population (3 plus/minus 2% versus 33 plus/minus 4%, P < 0.00l). There were no other significant ScO2 differences between outcome groups.     

Pharmacologic EEG suppression during cardiopulmonary bypass: cerebral hemodynamic and metabolic effects of thiopental or isoflurane during hypothermia and normothermia

We have determined the effects of thiopental or isoflurane upon cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMRO2) when these agents are used in sufficient dose to attain a deep burst suppression pattern on the electroencephalogram (EEG) during hypothermic and normothermic cardiopulmonary bypass (CPB). Thirty-one patients undergoing coronary artery bypass graft surgery were anesthetized with fentanyl 0.1 mg X kg-1, and were randomly allocated to one of three groups: control (no further anesthetics during bypass and continuous EEG activity), thiopental treatment (EEG suppression), or isoflurane treatment (EEG suppression). Hypothermia (25-29 degrees C) was routinely induced at onset of nonpulsatile cardiopulmonary bypass. In the treatment groups, thiopental or isoflurane were used during bypass to achieve a deep burst suppression pattern. Cerebral blood flow and cerebral metabolic rate for oxygen were determined during hypothermia and upon rewarming to normothermia (37 degrees C). Pharmacologic EEG suppression with either isoflurane or thiopental was associated with lower cerebral metabolic rate than control values during both hypothermic and normothermic bypass. However, only thiopental-induced EEG suppression was associated with lower cerebral blood flow than control. Cerebral blood flow during isoflurane-induced EEG suppression was similar to control values in spite of the reduced cerebral metabolic rate.     

Coagulation defects in neonates during cardiopulmonary bypass.

We examined components of the coagulation system in 30 neonates (age, 1 to 30 days) undergoing deep hypothermic cardiopulmonary bypass (CPB). A coagulation profile consisting of activated clotting time; prothrombin time; partial thromboplastin time; factors II, V, VII, VIII, IX, X, and I (fibrinogen); antithrombin III; platelet count; and heparin levels was evaluated before bypass, at three intervals during bypass (1 minute after initiation of bypass, stable hypothermic CPB, warm CPB), after weaning from CPB and administration of protamine, and 2 to 3 hours after skin closure. The initiation of CPB resulted in a 50% decrease in circulating coagulation factors and antithrombin III levels. Platelet counts were reduced by 70% with CPB initiation. Neither deep hypothermic temperatures nor prolonged exposure to extracorporeal surfaces had any additional effect on the coagulation profiles. This suggests that the coagulation system of a neonate undergoing CPB is profoundly and globally effected by hemodilution. We believe that treatment of post-CPB coagulopathy in neonates must address these global deficits.     

Cerebral carbon dioxide reactivity during nonpulsatile cardiopulmonary bypass

Five patients undergoing extensive cerebral monitoring during cardiopulmonary bypass (CPB) procedures were subjected to studies on cerebral CO2 reactivity during nonpulsatile CPB. The cerebral monitoring included recording of arterial blood pressure (BP), central venous pressure (CVP), epidural intracranial pressure (EDP), cerebral electrical activity by a cerebral function monitor (CFM), and middle cerebral artery (MCA) flow velocity by transcranial Doppler technique. The cerebral perfusion pressure (CPP) was thus continuously recorded (CPP = BP - EDP). During steady-state CPB with constant hematocrit, temperature, and arterial carbon dioxide tension (PaCO2), MCA flow velocity varied with changing CPP in a pressure-passive manner, indicating that the cerebral autoregulation was not operative. During moderately hypothermic (28 to 32 degrees C), nonpulsatile CPB, with steady-state hematocrit, temperature, and pump flow, we deliberately and rapidly changed PaCO2 for periods of 1 or 2 minutes by increasing gas flow to the membrane oxygenator, thereby testing the cerebral CO2 reactivity. Nineteen CO2 reactivity tests, performed at CPP levels ranging from 17 to 75 mm Hg, disclosed that the cerebral CO2 reactivity decreased with CPP, especially with CPP levels below 35 mm Hg. In these patients, concomitant changes in CPP during the CO2 reactivity test could be compensated for by adjusting the observed change in MCA flow velocity. The corrected CO2 reactivity values obtained in this way ranged from below 1.0 (observed at CPP levels below 20 mm Hg) to a 3.0 to 4.5% X mm Hg-1 change in PaCO2 (observed at CPP levels above 35 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral blood flow response to changes in arterial carbon dioxide tension during hypothermic cardiopulmonary bypass in children

We examined the relationship of changes in partial pressure of carbon dioxide on cerebral blood flow responsiveness in 20 pediatric patients undergoing hypothermic cardiopulmonary bypass. Cerebral blood flow was measured during steady-state hypothermic cardiopulmonary bypass with the use of xenon 133 clearance methodology at two different arterial carbon dioxide tensions. During these measurements there was no significant change in mean arterial pressure, nasopharyngeal temperature, pump flow rate, or hematocrit value. Cerebral blood flow was found to be significantly greater at higher arterial carbon dioxide tensions (p less than 0.01), so that for every millimeter of mercury rise in arterial carbon dioxide tension there was a 1.2 ml.100 gm-1.min-1 increase in cerebral blood flow. Two factors, deep hypothermia (18 degrees to 22 degrees C) and reduced age (less than 1 year), diminished the effect carbon dioxide had on cerebral blood flow responsiveness but did not eliminate it. We conclude that cerebral blood flow remains responsive to changes in arterial carbon dioxide tension during hypothermic cardiopulmonary bypass in infants and children; that is, increasing arterial carbon dioxide tension will independently increase cerebral blood flow.     

婴儿心脏手术中脑氧饱和度的监测：与手术后早期预后的关系

背景我们对婴儿心脏手术中脑氧饱和度的变化及其与解剖学诊断和早期预后的关系进行了研究。方法将104例接受双心室修补无主动脉弓缩窄手术的先心病患儿随机分成两组,两组的红细胞比容分别稀释至25％和35％。用近红外光谱仪监测各时点每例患儿的局部脑氧饱和度（rSO2）。结果在心肺转流前,与右位型大动脉转位（D-TGA）和室间隔缺损患儿相比,法洛氏四联症（TOF）患儿局部脑氧饱和度较高（P〈0．001）。在心肺转流降温、低流量转流及心肺转流结束时,右位型大动脉转位患儿的局部脑氧饱和度最高（P〈0．001）。但各组间手术中局部脑氧饱和度和早期预后经校正诊断后并没有明显关系。39例接受≥5分钟深低温停循环[deephypothermiccirculatoryarrest（DHCA）]的右位型大动脉转位患儿中,停循环开始时的局部脑氧饱和度（91％±6％）及红细胞比容（29．2％±5．5％）与停循环中的局部脑氧饱和度下降速率没有明显关系。结论手术中局部脑氧饱和度随解剖学诊断不同而变化,但是与手术后早期预后无明显关系。正如使用额叶近红外线光谱探头测量局部脑氧饱和度所示,高红细胞比容与当今的灌注技术似乎可为深低温停循环在短期内提供足够的氧储备。     

Cerebral response to hemodilution during hypothermic cardiopulmonary bypass in adults.

We examined the cerebral response to changing hematocrit during hypothermic cardiopulmonary bypass (CPB) in 18 adults. Cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), and cerebral oxygen delivery (CDO2) were determined using the nitrous oxide saturation technique. Measurements were obtained before CPB at 36 degrees C, and twice during 27 degrees C CPB: first with a hemoglobin (Hgb) of 6.2 +/- 1.2 g/dL and then with a Hgb of 8.5 +/- 1.2 g/dL. During hypothermia, appropriate reductions in CMRO2 were demonstrated, but hemodilution-associated increases in CBF offset the reduction in CBF seen with hypothermia. At 27 degrees C CPB, as the Hgb concentration was increased from 6.2 to 8.5 g/ dL, CBF decreased. CDO2 and CMRO2 were no different whether the Hgb was 6.2 or 8.5 g/dL. In eight patients in whom the Hgb was less than 6 g/dL, CDO2 remained more than twice CMRO2. IMPLICATIONS: This study suggests that cerebral oxygen balance during cardiopulmonary bypass is well maintained at more pronounced levels of hemodilution than are typically practiced, because changes in cerebral blood flow compensate for changes in hemoglobin concentration.     

Changes in respiratory mechanics among infants undergoing heart surgery

Children with excessive pulmonary blood flow (PBF) from congenital heart disease have abnormal respiratory mechanics. Exposure to hypothermic cardiopulmonary bypass (CPB) adversely affects lung function. We designed this study of 106 patients to determine the changes in respiratory mechanics in infants younger than 1 yr undergoing heart surgery. Dynamic respiratory compliance (Cdyn) and total respiratory resistance (Rrs) were measured before surgical incision, after sternal closure in the operating room, and after arrival in the intensive care unit. The following data were recorded: age, weight, preoperative pulmonary infiltrates, preoperative mechanical ventilation, evidence of increased PBF before surgery, duration of CPB, duration of aortic cross-clamp, duration of deep hypothermic circulatory arrest, use of steroids, and volume of ultrafiltrate removed. Repeated-measures analysis of variance with covariate analysis was used to determine the effect of each covariate on Cdyn and Rrs at the three time periods. Rrs improved after cardiac surgery correcting increases in PBF, and this was most pronounced in neonates. Among infants with normal or reduced PBF, cardiac surgery with CPB led to a reduction in Cdyn. We consider that the benefits of surgical correction of pulmonary overcirculation outweigh the negative effects of CPB on respiratory mechanics. IMPLICATIONS: The benefits of surgical correction of pulmonary overcirculation outweigh the negative effects of cardiopulmonary bypass on respiratory mechanics in infants.     

The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants, and children

Cardiopulmonary bypass management in neonates, infants, and children often requires the use of deep hypothermia at 18 degrees C with occasional periods of circulatory arrest and represents marked physiologic extremes of temperature and perfusion. The safety of these techniques is largely dependent on the reduction of metabolism, particularly cerebral metabolism. We studied the effect of hypothermia on cerebral metabolism during cardiac surgery and quantified the changes. Cerebral metabolism was measured before, during, and after hypothermic cardiopulmonary bypass in 46 pediatric patients, aged 1 day to 14 years. Patients were grouped on the basis of the different bypass techniques commonly used in children: group A--moderate hypothermic bypass at 28 degrees C; group B--deep hypothermic bypass at 18 degrees to 20 degrees C with maintenance of continuous flow; and group C--deep hypothermic circulatory arrest at 18 degrees C. Cerebral metabolism significantly decreased under hypothermic conditions in all groups compared with control levels at normothermia, the data demonstrating an exponential relationship between temperature and cerebral metabolism and an average temperature coefficient of 3.65. There was no significant difference in the rate of metabolism reduction (temperature coefficient) in patients cooled to 28 degrees and 18 degrees C. From these data we were able to derive an equation that numerically expresses a hypothermic metabolic index, which quantitates duration of brain protection provided by reduction of cerebral metabolism owing to hypothermic bypass over any temperature range. Based on this index, patients cooled to 28 degrees C have a predicted ischemic tolerance of 11 to 19 minutes. The predicted duration that the brain can tolerate ischemia ("safe" period of deep hypothermic circulatory arrest) in patients cooled to 18 degrees C, based on our metabolic index, is 39 to 65 minutes, similar to the safe period of deep hypothermic circulatory arrest known to be tolerated clinically. In groups A and B (no circulatory arrest), cerebral metabolism returned to control in the rewarming phase of bypass and after bypass. In group C (circulatory arrest), cerebral metabolism and oxygen extraction remained significantly reduced during rewarming and after bypass, suggesting disordered cerebral metabolism and oxygen utilization after deep hypothermic circulatory arrest. The results of this study suggest that cerebral metabolism is exponentially related to temperature during hypothermic bypass with a temperature coefficient of 3.65 in neonates infants and children. Deep hypothermic circulatory arrest changes cerebral metabolism and blood flow after the arrest period despite adequate hypothermic suppression of metabolism.     

Pharmacologic cerebral capillary blood flow improvement after deep hypothermic circulatory arrest: an intravital fluorescence microscopy study in pigs

BACKGROUND: Despite meticulous investigation of bypass techniques for deep hypothermic circulatory arrest, unfavorable long-term neurologic deficits have been well documented. Our aim was to improve brain perfusion by reducing platelet plugging with a glycoprotein IIb/IIIa inhibitor (eptifibatide) in an experimental model of deep hypothermic circulatory arrest-reperfusion in pigs. METHODS: Two groups of 12 piglets each (eptifibatide group [eptifibatide + unfractionated heparin] vs UFH group [only unfractionated heparin]) underwent 10 minutes of normothermic bypass, 40 minutes of cooling during cardiopulmonary bypass (hematocrit, 30%; cardiopulmonary bypass flow, 100 mL x kg(-1) x min(-1)), 60 minutes of circulatory arrest at 15 degrees C, and a 40-minute rewarming period. Intravital fluorescence microscopy of pial vessels at set intervals was performed. RESULTS: During the cooling period, there was a tendency toward reduced functional capillary density values without statistical significance in both groups. During reperfusion, the eptifibatide group demonstrated a significantly decreased platelet adhesion and aggregation (at 30 minutes of reperfusion: functional capillary density, 104% +/- 3% vs 77% +/- 4% relative to baseline, P = .02; red blood cell velocity, 0.65 vs 0.30 mm/s, P < .004). A more rapid recovery of tissue oxygenation (P < .001) was documented. Furthermore, a significant microvascular permeability reduction was achieved compared with that seen in the UFH group (P < .02). The use of eptifibatide resulted in fewer ultrastructural changes in hippocampal tissue, which is demonstrated by histologic examination. CONCLUSIONS: Platelet plugging reduction with the glycoprotein IIb/IIIa inhibitor eptifibatide improves cerebral capillary blood flow and reduces cerebral ischemia in the setting of deep hypothermic circulatory arrest. Furthermore, significant endothelial cell injury and perivascular edema reduction can be achieved.     

Persistent low cerebral blood flow velocity following profound hypothermic circulatory arrest in infants

Acute neurological morbidity following repair of congenital heart disease (CHD) in infancy is well recognized, particularly with the modalities of hypothermic cardiopulmonary bypass (CPB) and profound hypothermic circulatory arrest (PHCA). Reduced O₂ delivery (perfusion defect) during rewarming following PHCA has been shown in the operating room. This reduction in cerebral blood flow coincides with disordered cerebral metabolism and oxygen utilisation after PHCA. The objective of this study was to extend the period of investigation of cerebral blood flow velocity (CBFV) behaviour in infants following PHCA to determine if hypoperfusion persisted in the paediatric intensive care unit (PICU). Ten patients undergoing CHD surgery were divided, based on the pump modality employed, into either mild hypothermic CPB or profound hypothermic CPB with circulatory arrest. Following admission to the PICU, sequential recordings of the mean CBFV in the middle cerebral artery, anterior fontanelle pressure, haemodynamic variables, tympanic membrane temperature, haematocrit and PaCO₂ were performed. The PHCA group had a consistently reduced CBFV compared with the control group (P < 0.05). The CBFV values at one, two and four hours were 60 ± 11, 51.8 ± 11.4 and 52.6 ± 11.9 respectively in the mild hypothermic CPB group. The CBFV values at one, two and four hours were 26.6 ± 6.8, 32.6 ± 10 and 34 ± 8 respectively in the PHCA group. There was no difference in cerebral perfusion pressure between both groups. Tympanic temperature, haematocrit and PaCO₂ did not vary between groups at any interval. This study demonstrates a sustained reduction in the CBFV pattern following PHCA into the postoperative period despite adequate cerebral perfusion pressures. This abnormality correlates with electroencephalographic aberrations documented after PHCA. It supports the concept of a prolonged unreactive cerebrovascular bed which could potentially contribute to the acute neurological morbidity following PHCA in neonates.     

A glial-derived protein,S100B,in neonates and infants with congenital heart disease: evidence for preexisting neurologic injury

The glial-derived protein S100B is a serum marker of cerebral ischemia and correlates with negative neurological outcome after cardiopulmonary bypass (CPB) in adults. We sought to characterize the S100B release pattern before and after CPB in neonates and infants with congenital heart disease and correlate it with surgical mortality. Serum was collected before surgery and at 24 postoperative h from 109 neonates and infants with congenital heart disease. All patients had presurgical transthoracic echocardiograms and CPB with or without hypothermic circulatory arrest. S100B concentrations were determined using a two-site immunoluminometric assay (Sangtec 100). Thirty-day surgical mortality was observed. All neonates had significantly increased S100B concentrations before surgery that decreased by 24 postoperative h. Preoperative S100B concentrations in 32 neonates with hypoplastic left heart syndrome correlated inversely with the forward flow and size of the ascending aorta and postoperative mortality (r(2) = -0.63; P = 0.03). Among infants, increased pulmonary blood flow was associated with higher S100B levels before surgery than cyanosis. There was no correlation with postoperative S100B and time on CPB, hypothermic circulatory arrest, or 30-day surgical mortality. In conclusion, preoperative S100B concentrations correlate inversely with the size of the ascending aorta in hypoplastic left heart syndrome and may serve as a marker for preexisting brain injury and mortality. IMPLICATIONS: Neonates with hypoplastic left heart syndrome and no forward flow in the ascending aorta may have brain injury at birth before heart surgery.