Selective convective brain cooling during normothermic cardiopulmonary bypass in dogs

BACKGROUND: Neurologic complications, primarily resulting from ischemic insults, represent the leading cause of morbidity and disability, and the second most common source of death, after cardiac operations. Previous studies have reported that increases (as occur during the rewarming phase of cardiopulmonary bypass [CPB]) or decreases in brain temperature of a mere 0.5 degrees to 2 degrees C can significantly worsen or improve, respectively, postischemic neurologic outcome. The purpose of the present study was to evaluate a novel approach of selectively cooling the brain during hypothermic CPB and subsequent rewarming. METHODS: Sixteen dogs were anesthetized with either intravenous pentobarbital or inhaled halothane (n = 8 per group). Normocapnia (alpha stat technique) and a blood pressure near 75 mm Hg were maintained. Temperatures were monitored by placing thermistors in the esophagus (i.e., core), parietal epidural space, and brain parenchyma at depths of 1 and 2 cm beneath the dura. During CPB, core temperature was actively cycled from 38 degrees C to 28 degrees C, and then returned to 38 degrees C. Forced air pericranial cooling (air temperature of approximately 13 degrees C) was initiated simultaneous with the onset of CPB, and maintained throughout the bypass period. Brain-to-core temperature gradients were calculated by subtracting the core temperature from regional brain temperatures. RESULTS: In halothane-anesthetized dogs, brain temperatures at all monitoring sites were significantly less than core during all phases of CPB, with one exception (2 cm during systemic cooling). Brain cooling was most prominent during and after systemic rewarming. For example, during systemic rewarming, average temperatures in the parietal epidural space, and 1 and 2 cm beneath the dura, were 3.3 degrees +/- 1.3 degrees C (mean +/- standard deviation), 3.2+/-1.4 degrees C, and 1.6 degrees +/-1.0 degrees C, cooler than the core, respectively. Similar trends, but of a greater magnitude, were noted in pentobarbital-anesthetized dogs. For example, during systemic rewarming, corresponding brain temperatures were 6.5 degrees +/-1.7 degrees C, 6.3 degrees +/-1.6 degrees C, and 4.2+/-1.3 degrees C cooler than the core, respectively. CONCLUSIONS: The magnitude of selective brain cooling observed in both study groups typically exceeded the 0.5 degrees to 2.0 degrees C change previously reported to modulate ischemic injury, and was most prominent during the latter phases of CPB. When compared with previous research from our laboratory, application of cold forced air to the cranial surface resulted in brain temperatures that were cooler than those observed during hypothermic CPB without pericranial cooling. On the basis of the assumption that similar beneficial brain temperature changes can be induced in humans, we speculate that selective convective brain cooling may enable clinicians to improve neurologic outcome after hypothermic CPB.     

Deleterious effects of cardiopulmonary bypass on early graft function after single lung allotransplantation: evaluation of a heparin-coated bypass circuit

Clinical lung transplantation may necessitate the use of cardiopulmonary bypass during the procedure, resulting in increased morbidity with more severe early graft dysfunction and increased blood loss. A heparin surface-coated cardiopulmonary bypass circuit is now available with improved biocompatibility and reduced systemic heparin requirements and may offer advantages compared with standard uncoated cardiopulmonary bypass circuits. This study investigates in a canine model of single-lung allotransplantation whether cardiopulmonary bypass adversely affects early graft function and whether a heparin-coated cardiopulmonary bypass circuit with reduced systemic heparin dosage improves results compared with standard uncoated cardiopulmonary bypass systems. Fifteen dogs underwent left single-lung allotransplantation with occlusion of the contralateral pulmonary artery and bronchus 1 hour after reperfusion. In one group, five animals underwent the procedure without cardiopulmonary bypass. In the group with uncoated circuits, five animals underwent the procedure with the use of standard uncoated cardiopulmonary bypass circuits with full systemic heparin dosage. In the group with heparin-coated circuits, five animals underwent the procedure with the use of heparin-coated cardiopulmonary bypass circuits and reduced systemic heparin dosage. Early graft function was evaluated by arterial oxygenation, pulmonary mechanics, lung water measurements, and histologic analysis. Hemodynamics and postoperative blood loss were also measured. Two hours after reperfusion, partial pressure of oxygen in arterial blood on an inspired oxygen fraction = 1.0 was significantly greater (p < 0.001) in the group without cardiopulmonary bypass (467 +/- 58 mm Hg) than in the group with uncoated circuits (114 +/- 90 mm Hg) and the group with heparin-coated circuits (193 +/- 105 mm Hg), with no significant difference between the groups undergoing bypass procedures. Lung compliance decreased and lung water increased in all transplanted lungs without significant differences between groups. Histologic analysis did not differentiate between the groups. After reperfusion, cardiac index and mean arterial pressure were significantly reduced in the groups with uncoated circuits and with heparin-coated circuits compared with the group that did not undergo cardiopulmonary bypass (p < 0.001). Postoperative blood loss was significantly less (p < 0.002) in the group that did not undergo cardiopulmonary bypass (90 ml +/- 38 ml) compared with both the group with uncoated circuits (750 +/- 15 ml) and the group with heparin-coated circuits (690 +/- 387 ml), with no significant difference between the groups that underwent bypass. The use of cardiopulmonary bypass with systemic heparinization is detrimental to early graft function in this canine model of left single-lung allotransplantation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Reduced complement and granulocyte activation with heparin-coated cardiopulmonary bypass

Plasma concentrations of the complement activation products C3b, iC3b, and C3c; the terminal C5b-9 complement complex; and the granulocyte proteins calprotectin, myeloperoxidase, and lactoferrin were assessed in two groups of patients undergoing aortocoronary bypass procedures. In 10 patients operated on, the bypass circuits were coated by the Carmeda Bio-Active Surface and systemic heparinization was reduced to 1.5 mg/kg; in another 10, the systems were uncoated and the dosage of systemic heparinization was 4 mg/kg. In both groups, significant complement activation was observed after the onset of cardiopulmonary bypass, but the maximum levels of C3b, iC3b, and C3c and the terminal C5b-9 complement complex were significantly lower in the heparin-coated group. In both groups, a significant increase in calprotectin, myeloperoxidase, and lactoferrin release was observed by the end of operation. The maximum myeloperoxidase levels were significantly lower in the heparin-coated group than those in the uncoated group (p = 0.03). There was a correlation of borderline significance between the formation of terminal C5b-9 complement complex and lactoferrin release, as well as between the formation of terminal C5b-9 complement complex and myeloperoxidase release (p = 0.05). The postoperative blood loss did not differ significantly between the two groups. We conclude that coating by end point-attached and functionally active heparin allows a significant reduction in the amount of systemic heparinization, and significantly reduces complement and granulocyte activation.     

A heparin-coated circuit maintains platelet aggregability in response to shear stress in an in vitro model of cardiopulmonary bypass

PURPOSE: To report the authors' experience in treatment of ruptures complicating percutaneous transluminal angioplasty (PTA) of hemodialysis access with implantation of a Wallstent. MATERIALS AND METHODS: Between January 1, 1990, and October 1, 1995, the authors performed 2,414 PTAs of angioaccesses. A severe rupture occurred in 40 (1.7%) of these procedures and was treated by means of stent placement. Wallstents were implanted in 37 of these ruptures. The angioaccesses comprised 22 grafts and 15 fistulas. The indications for stent placement were four isolated pseudoaneurysms and 33 cases of bleeding: 15 major leaks, five moderate leaks that persisted despite prolonged inflation at low pressure, seven leaks associated with greater than 50% residual stenosis, four leaks associated with pseudoaneurysm, and two leaks associated with both greater than 50% residual stenosis and pseudoaneurysm. Seventeen ruptures were located on a vein, 19 on the venous anastomosis of a graft, and one on a graft itself. RESULTS: Stent placement stopped the bleeding immediately in 28 cases and after prolonged inflation within the stent in four cases. Residual bleeding required implantation of a covered Cragg stent within the Wallstent in one case. A pseudoaneurysm was still visible at the end of the intervention in 11 cases. Two complications occurred; one hematoma was drained surgically and one access occluded on day 2. Follow-up angiography showed a small pseudoaneurysm in only one patient with impaired platelet function. The primary and secondary patency of the angioaccesses were 48% and 86% at 1 year, respectively. CONCLUSION: Wallstent implantation is very effective for both immediate and long-term treatment of rupture of angioaccess during PTA.     

Surface-bound heparin fails to reduce thrombin formation during clinical cardiopulmonary bypass

The hypothesis that heparin-coated perfusion circuits reduce thrombin formation and activity; fibrinolysis; and platelet, complement, and neutrophil activation was tested in 20 consecutive, randomized adults who had cardiopulmonary bypass. Twenty identical perfusion systems were used; in 10, all blood-contacting surfaces were coated with partially degraded heparin (Carmeda process; Medtronic Cardiopulmonary, Anaheim, Calif.). All patients received a 300 U/kg dose of heparin. Activated clotting times were maintained longer than 400 seconds. Cardiopulmonary bypass lasted 36 to 244 minutes. Blood samples for platelet count, platelet response to adenosine diphosphate, plasma beta-thromboglobulin, inactivated complement 3b, neutrophil elastase, fibrinopeptide A, prothrombin fragment F1.2, thrombin-antithrombin complex, tissue plasminogen activator, plasminogen activator inhibitor-1, plasmin alpha 2-antiplasmin complex, and D-dimer were obtained at these times: after heparin was given, 5 and 30 minutes after cardiopulmonary bypass was started, within 5 minutes after bypass was stopped, and 15 minutes after protamine was given. After cardiopulmonary bypass, tubing segments were analyzed for surface-adsorbed anti-thrombin, fibrinogen, factor XII, and von Willebrand factor by radioimmunoassay. Heparin-coated circuits significantly (p < 0.001) reduced platelet adhesion and maintained platelet sensitivity to adenosine diphosphate (p = 0.015), but did not reduce release of beta-thromboglobulin. There were no significant differences between groups at any time for fibrinopeptide A, prothrombin fragment F1.2, or thrombin-antithrombin complex or in the markers for fibrinolysis: D-dimer, tissue plasminogen activator, plasminogen activator inhibitor-1, and alpha 2-antiplasmin complex. In both groups, concentrations of prothrombin fragment F1.2 and thrombin-antithrombin complex increased progressively and significantly during cardiopulmonary bypass and after protamine was given. Concentrations of D-dimer, alpha 2-antiplasmin complex, and plasminogen activator inhibitor-1 also increased significantly during bypass in both groups. Fibrinopeptide A levels did not increase during bypass but in both groups increased significantly after protamine was given. No significant differences were observed between groups for levels of inactivated complement 3b or neutrophil elastase. Radioimmunoassay showed a significant increase in surface-adsorbed antithrombin on coated circuits but no significant differences between groups for other proteins. We conclude that heparin-coated circuits used with standard doses of systemic heparin reduce platelet adhesion and improve platelet function but do not produce a meaningful anticoagulant effect during clinical cardiopulmonary bypass. The data do not support the practice of reducing systemic heparin doses during cardiac operations with heparin-coated extracorporeal perfusion circuitry.     

Management of postoperative heparin rebound following cardiopulmonary bypass

Postoperative heparin rebound was investigated in 50 adult patients undergoing cardiopulmonary bypass with the use of the Hepcon heparin analyzer. Prior to bypass each patient received 2 mg/kg of heparin. During bypass, the activated clotting time (ACT) was utilized to assess the need for additional heparin to maintain the value between 300 and 400 seconds. The average amount of heparin given was 160 mg. Once cardiopulmonary bypass was terminated the Hepcon unit was employed to determine the actual amount of active circulating heparin and to calculate the dose of protamine sulfate. The average amount of protamine administered intraoperatively was 200 mg. The overall mean ratio of protamine-to-heparin was 1.25 : 1. Once hemostasis was achieved, no circulating heparin was measured with the Hepcon unit, and the ACT value had returned to its baseline, the incisions were closed and the patients were transferred to the intensive care unit. One hour later a blood sample was obtained and analyzed by the Hepcon unit for any heparin rebound. We found that 26 patients (52%) had circulating heparin and required an additional dose of protamine, averaging 70 mg. Drainage from the thoracotomy tubes averaged 400 cc in the first 24 hours, and a mean of 2 units of packed cells was infused. Three patients (6%) did not require any blood transfusions. The use of the Hepcon unit has produced a safe and expedient method of analyzing and neutralizing active circulating heparin in patients following cardiopulmonary bypass. It is a useful adjunct in blood conservation because it reduces excessive postoperative blood loss associated with heparin rebound.     

Inflammatory response to cardiopulmonary bypass using two different types of heparin-coated extracorporeal circuits

Previous reports have highlighted the disparity in biocompatibility of two differently engineered heparin coatings during the cardiopulmonary bypass (CPB) procedure. The aim of this prospective study was to evaluate the impact of the difference in haemocompatibility provided by either the Duraflo II equipment or the Carmeda equipment in the terminal inflammatory response observed after coronary artery surgery. Thirty patients were randomly allocated to two groups to be operated on using either Duraflo II equipment (group I) or Carmeda equipment (group 2) for extracorporeal circulation (ECC). Initial inflammatory response was assessed by terminal complement complex activation (SC5b-9). The late inflammatory response observed in the postoperative period was assessed by measuring cytokine production (tumour factor necrosis (TNF alpha), interleukin IL-6, interleukin IL-8) and circulating concentrations of adhesion molecules (ELAM-1, ICAM-1). The release of SC5b-9 after CPB and after protamine administration was lower in group 2 than in group 1 (p = 0.0002 and p = 0.006, respectively). A significant production of cytokines was detected in both groups with peak values observed within the time range of 4-6 h after the start of CPB.     

Gut mucosal ischemia during normothermic cardiopulmonary bypass results from blood flow redistribution and increased oxygen demand

Impaired gut mucosal perfusion has been reported during cardiopulmonary bypass. To better define the adequacy of gut blood flow and oxygenation during cardiopulmonary bypass, we measured overall gut blood flow and ileal mucosal flow and their relationship to mucosal pH, mesenteric oxygen delivery and oxygen consumption in immature pigs (n = 8). Normothermic, noncross-clamped, right atrium-to-aorta cardiopulmonary bypass was maintained at 100 ml/kg per minute for 120 minutes. Animals were instrumented with an ultrasonic Doppler flow probe on the superior mesenteric artery, a mucosal laser Doppler flow probe in the ileum, and pH tonometers in the stomach, ileum, and rectum. Radioactive microspheres were injected before and at 5, 60, and 120 minutes of cardiopulmonary bypass for tissue blood flow measurements. Overall gut blood flow significantly increased during cardiopulmonary bypass as evidenced by increases in superior mesenteric arterial flow to 134.1% +/- 8.0%, 137.1% +/- 7.5%, 130.3% +/- 11.2%, and 130.2% +/- 12.7% of baseline values at 30, 60, 90, and 120 minutes of bypass, respectively. Conversely, ileal mucosal blood flow significantly decreased to 53.6% +/- 6.4%, 49.5% +/- 6.8%, 58.9% +/- 11.6%, and 47.8% +/- 10.0% of baseline values, respectively. Blood flow measured with microspheres was significantly increased to proximal portions of the gut, duodenum and jejunum, during cardiopulmonary bypass, whereas blood flow to distal portions, ileum and colon, was unchanged. Gut mucosal pH decreased progressively during cardiopulmonary bypass and paralleled the decrease in ileal mucosal blood flow. Mesenteric oxygen delivery decreased significantly from 67.0 +/- 10.0 ml/min per square meter at baseline to 42.4 +/- 4.6, 44.9 +/- 3.5, 46.0 +/- 3.6, and 42.9 +/- 3.9 ml/min per square meter at 30, 60, 90, and 120 minutes of bypass. Despite the decrease in mesenteric oxygen delivery, mesenteric oxygen consumption increased progressively from 10.8 +/- 1.4 ml/min per square meter at baseline to 13.4 +/- 1.2, 15.9 +/- 1.2, 16.7 +/- 1.4, and 16.6 +/- 1.54 ml/min per square meter, respectively. We conclude that gut mucosal ischemia during normothermic cardiopulmonary bypass results from a combination of redistribution of blood flow away from mucosa and an increased oxygen demand.     

Induction of monocyte tissue factor procoagulant activity during coronary artery bypass surgery is reduced with heparin-coated extracorporeal circuit

The possible activation of monocytes to express tissue factor procoagulant activity (TF-PCA) during CPB (cardiopulmonary bypass) was investigated. 22 patients undergoing myocardial revascularization were randomly assigned to two groups. In group C, heparin-coated circuits (Duraflo II) and reduced systemic heparinization (ACT > 250s) were used. In group NC, non-coated circuits and standard heparin administration (ACT > 480s) were used. Adherent monocytes retrieved from the oxygenators immediately after bypass arrest showed a 2-3-fold increase in TF-PCA when compared to circulating cells pre-CPB (P < 0.01). When cell PCA was expressed as percent change from pre-CPB (baseline) values, circulating monocytes in group NC at CPB-arrest showed a 2-fold increase in PCA compared to group C (P < 0.05). Moreover, the percent increase in PCA of oxygenator-retrieved monocytes was 7-fold in group NC and 2-fold in group C (P < 0.008 and P < 0.004, respectively). Thus, heparin-coating of the extracorporeal circuit reduced induction of adherent cell TF-PCA by 70% (P < 0.05). Thus, monocyte TF-PCA may cause activation of the extrinsic coagulation pathway during CPB surgery. It is apparent that heparin-coating enhanced biocompatibility of extracorporeal circuits. Reduced systemic heparinization in group C proved to be safe. However, further reduction of heparin administration may not be advisable, since monocytes were still activated in the coated oxygenator.     

Two-chain factor VIIa generated in the pericardium during surgery with cardiopulmonary bypass : relationship to increased thrombin generation and heparin concentration

The effect of changes in medullary extracellular tonicity on mRNA expression for aldose reductase (AR), sorbitol dehydrogenase (SDH), Na+/Cl-/betaine (BGT) and Na+/myo-inositol (SMIT) cotransporter in different kidney zones was studied using Northern blot analysis and non-radioactive in situ hybridization in four groups of rats: controls, acute diuresis (the loop diuretic furosemide was administered), chronic diuresis (5 days of diuresis), and antidiuresis [5 days of diuresis followed by 24 h deamino-Cys1, d-Arg8 vasopressin (dDAVP)]. Acute administration of the loop diuretic furosemide significantly reduced AR, SMIT and BGT gene expression in the inner and outer medulla compared with controls. Administration of dDAVP to chronically diuretic rats raised the expression of these three mRNAs in the inner but not the outer medulla compared with the chronically diuretic rats. None of these alterations in medullary tonicity significantly changed SDH expression. The in situ hybridization studies showed AR, BGT and SMIT mRNAs to be expressed in both epithelial and non-epithelial cells of the outer and inner medulla. The various cell types (epithelial, endothelial and interstitial cells) differed in their expression pattern and intensity of AR, SDH, BGT and SMIT mRNA, but the inner medullary cells responded uniformly to a decrease in extracellular tonicity with a reduction, and to an increase with enhancement of their AR, BGT and SMIT expression.     

Pulsatile versus nonpulsatile flow. No difference in cerebral blood flow or metabolism during normothermic cardiopulmonary bypass in rabbits

BACKGROUND: Although pulsatile and nonpulsatile cardiopulmonary bypass (CPB) do not differentially affect cerebral blood flow (CBF) or metabolism during hypothermia, studies suggest pulsatile CPB may result in greater CBF than nonpulsatile CPB under normothermic conditions. Consequently, nonpulsatile flow may contribute to poorer neurologic outcome observed in some studies of normothermic CPB. This study compared CBF and cerebral metabolic rate for oxygen (CMRO2) between pulsatile and nonpulsatile CPB at 37 degrees C. METHODS: In experiment A, 16 anesthetized New Zealand white rabbits were randomized to one of two pulsatile CPB groups based on pump systolic ejection period (100 and 140 ms, respectively). Each animal was perfused at 37 degrees C for 30 min at each of two pulse rates (150 and 250 pulse/min, respectively). This scheme created four different arterial pressure waveforms. At the end of each perfusion period, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (microspheres), and CMRO2 (Fick) were measured. In experiment B, 22 rabbits were randomized to pulsatile (100-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 37 degrees C. At 30 and 60 min of CPB, physiologic measurements were made as before. RESULTS: In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all four waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile CPB (72 +/- 6 vs. 77 +/- 9 ml.100 g-1.min-1, respectively (median +/- quartile deviation)). CMRO2 did not differ between pulsatile and nonpulsatile CPB (4.7 +/- 0.5 vs. 4.1 +/- 0.6 ml O2.100 g-1.min-1, respectively) and decreased slightly (0.4 +/- 0.4 ml O2.100 g-1.min-1) between measurements. CONCLUSIONS: During CPB in rabbits at 37 degrees C, neither CBF nor CMRO2 is affected by arterial pulsation. The absence of pulsation per se is not responsible for the small decreases in CMRO2 observed during CPB.     

Extracorporeal heparin adsorption following cardiopulmonary bypass with a heparin removal device--an alternative to protamine

OBJECTIVES: To evaluate the therapeutic efficacy and applicability of a heparin removal device (HRD) based on plasma separation and poly-L-lysine (PLL) affinity adsorption as an alternative to protamine in reversing systemic heparinization following cardiopulmonary bypass (CPB). DESIGN: A prospective study. SETTING: University research laboratory. SUBJECTS: Adult female swine (n=7). INTERVENTIONS: Female Yorkshire swine (n=7, 67.3+/-3.5 [SEM] kg) were subjected to 60 mins of right atrium-to-aortic, hypothermic (28 degrees C) CPB. After weaning from CPB, the right atrium was recannulated with a two-stage, dual-lumen cannula which was connected to an HRD via extracorporeal circulation. Blood flow was drained at 1431.2+/-25.4 mL/min from the inferior vena cava, through the plasma separation chamber of the HRD (where heparin was bound to PLL), and reinfused into the right atrium. The HRD run time was determined by a previously established mathematical model of first-order exponential depletion. MEASUREMENTS AND MAIN RESULTS: Heart rate, mean arterial pressure, pulmonary arterial pressure, central venous pressure, kaolin and celite activated clotting time (ACT), activated partial thromboplastin time (APTT), heparin concentration, and plasma free hemoglobin were obtained before, during, and after the use of the HRD. Pre-CPB ACT was 167+/-89 secs (kaolin) and 99+/-7 secs (celite), and APTT was 34+/-5 secs. The HRD run time averaged 27.4 +/-1.5 mins targeted to remove 90% total body heparin. Use of the HRD was not associated with any adverse hemodynamic reactions or increases in plasma free hemoglobin. The heparin concentration immediately following CPB was 4.85+/-0.24 units/mL, with ACT >1000 secs and APTT >150 secs in all animals. During heparin removal, total body heparin content followed first-order exponential depletion kinetics. At the end of the HRD run, heparin concentration decreased to 0.51+/-0.09 units/mL, with kaolin ACT returning to 177+/-22 secs, celite ACT returning to 179+/-17 secs, and APTT returning to 27+/-3 secs (p > .05 vs. pre-CPB baseline for all variables). CONCLUSIONS: The HRD is capable of reversal of anticoagulation following CPB without significant blood cell damage or changes in hemodynamics. The HRD, therefore, can serve as an alternative to achieve heparin clearance in clinical situations where use of protamine may be contraindicated.     

Autologous blood transfusion during cardiopulmonary bypass

Immediately prior to cardiopulmonary bypass, two units of blood were removed from each of 25 patients undergoing open-heart surgery, and the autologous blood was reinfused after cessation of support with the pump oxygenator. Pertinent data on blood balance and hematologic measurements were compared to a matched group of control subjects. There were no significant differences in the amount of operative or postoperative bleeding, the requirements for homologous blood and blood products, or the amount of protamine needed for neutralization of heparin.     

The activated clotting time loading dose response ratio (ACTLORR) as an indicator of heparin demand during cardiopulmonary bypass

PURPOSE: To develop a new technique, intraoperative high dose rate brachytherapy (IOHDR), to deliver localized radiation therapy intraoperatively to head and neck tumors at sites inaccessible to intraoperative electron beam radiotherapy (IOEBRT) in the skull base region. METHODS: After maximal surgical resection, afterloading catheters spaced 1 cm apart embedded in custom surface applicators made of foam or silicone were placed on resected tumor beds. IOHDR was delivered in a shielded operating room using preplanned dosimetry with a nominal 10 Ci iridium-192 source in an HDR micro-Selectron afterloader. Twenty-nine patients (20 males, 9 females) ranging in age from 9 to 80 years (median = 61) were irradiated intraoperatively for advanced head and neck tumors at sites inaccessible to IOEBRT. Six patients who had previously received external beam radiation (EBRT) ranging from 50 to 75 Gy, were given 15 Gy of IOHDR only. Twenty-three patients who had no prior radiation received 7.5 to 12.5 Gy IOHDR, and 45 to 50 Gy EBRT was planned post-operatively; however, six of these patients did not complete the planned EBRT. Doses to normal tissues were reduced whenever possible by shielding with lead or by displacement with gauze or retractors. Treatment time ranged from 3.8 to 23 min (median = 6.5 min). Five patients received concurrent cis-platinum based chemotherapy. RESULTS: Twenty-nine patients treated to 30 sites had local tumor control of 67% and crade survival of 72%, with the follow-up ranging from 3 to 33 months (median = 21 months). In the group of 17 previously unirradiated patients who had completed full treatment (IOHDR and EBRT) to 18 sites, the local tumor control was 89%, and all of these patients survived. Tumor control in the six previously unirradiated patients who did not complete EBRT was 50% with a crude survival of 50%. In the group of six previously irradiated patients treated by IOHDR only, the local tumor control was 17% with a crude survival of 17%. No intraoperative complications were noted. The delayed morbidity included cerebrospinal fluid (CSF) leak with bone exposure (1), chronic subdural hematoma (1), septicemia (1), otitis media (1), and severe xerostomia (1). We cannot comment on long-term morbidity due to the relatively short follow-up period of 21 months. CONCLUSIONS: It is feasible to deliver IOHDR, with acceptable toxicity, to skull base tumors at sites inaccessible to IOEBRT. The use of IOHDR as a pre-radiotherapy boost produced excellent local control and survival in the selected group of patients who had no previous radiation therapy. The use of exclusive IOHDR in the previously irradiated group resulted in poor outcome, possibly due to the limitations on re-irradiation doses and/or volumes determined by normal tissue tolerance or because these patients have inherently radioresistant tumors. Higher IOHDR doses, additional EBRT, and/or chemotherapy should be considered for this group. The use of IOHDR as a pre-EBRT boost to maximize local control has a promising future in the treatment of carefully selected patients with advanced skull base tumor.     

Cerebral oxygenation during warming after cardiopulmonary bypass

OBJECTIVES: To evaluate jugular venous oxygen saturation (SjVO2), measured with a fiberoptic oximetry catheter, and brain tissue oxygen saturation, measured by near-infrared spectroscopy (NIRSO2), as monitors of cerebral oxygenation during cardiopulmonary bypass surgery. DESIGN: Prospective, clinical study. SETTING: Operating room of a Veterans Administration Hospital. PATIENTS: Nineteen patients undergoing moderate hypothermic cardiopulmonary bypass surgery. INTERVENTIONS: SjvO2 and NIRSO2 were monitored in the patients during the surgical procedure. MEASUREMENTS AND MAIN RESULTS: Moderate hypothermic cardiopulmonary bypass surgery had two distinct cerebral hemodynamic phases. While the patients were hypothermic, SjvO2 averaged 80 +/- 7% and none of the patients had an increase in cerebral lactate production. During the rewarming period, however, reductions in SjvO2 to < 50% occurred in 16 (84%) patients and increased cerebral anaerobic metabolism developed in 11 (58%) patients. SjvO2 during rewarming was dependent on mean arterial pressure, with 60 mm Hg appearing to be a critical value. Two other factors appeared to also contribute to the jugular desaturation, a low hematocrit and a rapid warming time. The SjvO2 catheter had excellent performance during the surgery. The average difference between paired measurements of SjvO2 by the catheter and in blood samples was -0.4 +/- 4.25%, and the correlation between the two measurements was highly significant (r2 = .93; p < .001). The NIRSO2 trended with the SjvO2 in most patients (r2 = .63; p < .001). CONCLUSIONS: The study confirms other studies showing that jugular venous desaturation can occur during rewarming after cardiopulmonary bypass surgery. Presently, SjvO2 appears to be a better monitor of cerebral oxygenation than NIRSO2. However, NIRSO2 has promise as a noninvasive monitor of cerebral oxygenation if future developments allow more quantitative measurements of oxygen saturation.     

Cerebral oxygenation during cardiopulmonary bypass in children

OBJECTIVE: Previous work has found cerebral oxygen extraction to decrease during hypothermic cardiopulmonary bypass in children. To elucidate cardiopulmonary bypass factors controlling cerebral oxygen extraction, we examined the effect of perfusate temperature, pump flow rate, and hematocrit value on cerebral hemoglobin-oxygen saturation as measured by near infrared spectroscopy. METHODS: Forty children less than 7 years of age scheduled for cardiac operations with continuous cardiopulmonary bypass were randomly assigned to warm bypass, hypothermic bypass, hypothermic low-flow bypass, or hypothermic low-hematocrit bypass. For warm bypass, arterial perfusate was 37 degrees C, hematocrit value 23%, and pump flow 150 ml/kg per minute. Hypothermic bypass differed from warm bypass only in initial perfusate temperature (22 degrees C); hypothermic low-flow bypass and low-hematocrit bypass differed from hypothermic bypass only in pump flow (75 ml/kg per minute) and hematocrit value (16%), respectively. Cerebral oxygen saturation was recorded before bypass (baseline), during bypass, and for 15 minutes after bypass had been discontinued. RESULTS: In the warm bypass group, cerebral oxygen saturation remained at baseline levels during and after bypass. In the hypothermic bypass group, cerebral oxygen saturation increased 20% +/- 2% during bypass cooling (p < 0.001), returned to baseline during bypass rewarming, and remained at baseline after bypass. In the hypothermic low-flow and hypothermic low-hematocrit bypass groups, cerebral oxygen saturation remained at baseline levels during bypass but increased 6% +/- 2% (p = 0.05) and 10% +/- 2% (p < 0.03), respectively, after bypass was discontinued. CONCLUSIONS: In children, cortical oxygen extraction is maintained during warm cardiopulmonary bypass at full flow and moderate hemodilution. Bypass cooling can decrease cortical oxygen extraction but requires a certain pump flow and hematocrit value to do so. Low-hematocrit hypothermic bypass and low-flow hypothermic bypass can also alter cortical oxygen extraction after discontinuation of cardiopulmonary bypass.