Normalizing Anti-Thrombin III for heparin management during routine cardiopulmonary bypass for congenital cardiothoracic surgery: A single institution practice review.

INTRODUCTION: Over the past decade, there has been an increase in the use of recombinant Anti-Thrombin III (AT-III) administration during neonatal and pediatric short- and long-term mechanical support for the replacement of acquired deficiencies. Recombinant AT-III (Thrombate) administration is an FDA licensed drug indicated primarily for patients with hereditary deficiency to treat and prevent thromboembolism and secondarily to prevent peri-operative and peri-partum thromboembolism. Herein we propose further use of Thrombate for primary AT-III deficiency of the newborn as well as for acquired dilution and consumption secondary to cardiopulmonary bypass (CPB). METHODOLOGY: All patients undergoing CPB obtain a preoperative AT-III level. Patients with identified deficiencies are normalized in the OR using recombinant AT-III as a patient load, in the CPB prime, or both. Patient baseline Heparin Dose Response (HDR) is assessed using the Heparin Management System (HMS) before being exposed to AT-III. If a patient load of AT-III is given, a second HDR is obtained and this AT-III Corrected HDR is used as the primary goal during CPB. Once CPB is initiated, an AT-III level is obtained with the first patient blood analysis. A subtherapeutic level results in an additional dose of AT-III. During the rewarm period, a final AT-III level is obtained and AT-III treated once again if subtherapeutic. A retrospective, matched analysis review of practice analyzing two groups, a Study Group (Repeat HDR, May 2022 onward) and Matched Group (Without Repeat HDR, July 2019 to April 2022), for age (D), weight (Kg) and operation was conducted. The focus of the study was to determine any change in heparin sensitivity identified post AT-III patient bolus load in the HDR (U/mL), Slope (U/mL/s), ACT (s), and total amount of heparin on CPB (U) and protamine (mg) used in each group. RESULTS: No significance was seen in Baseline AT-III (%), post heparin load HDR (U/mL), first CPB ACT (s), first CPB HDR (U/mL), or total CPB heparin (u/Kg) between the two groups. Statistical significance was seen in Baseline ACT (s), Baseline HDR (U/mL), Baseline Slope (U/mL/s), Post Heparin Load ACT (s), first CPB AT-III (%), and Protamine (mg/Kg) (p < .05). No statistical significance was seen in the Study Intragroup between pre versus post AT-III patient load baseline sample in ACT (s), however significance was seen in HDR (U/mL) and Slope (U/mL/s) (p < .05). CONCLUSION: Implementation of AT-III monitoring and therapy before and during CPB in conjunction with the HMS allows patients to maintain a steady state of anticoagulation with overall less need for excessive heparin replacement and potentially thrombin activation. The result is obtaining a steady state of anticoagulation, a reduced fluctuation in the heparin and ACT levels and a potential for lower co-morbidities associated with prolonged CPB times.

A novel approach to retrograde autologous priming for infant, pediatric and adult populations undergoing congenital heart surgery.

INTRODUCTION: Retrograde Autologous Priming (RAP) of cardiopulmonary bypass (CPB) circuits is an effective way to reduce prime volume, commonly through the transfer of prime into separate reservoirs or circuit manipulation. We describe a simple and safe technique for RAP without the need for any circuit modifications or manipulations. METHODS: For this technique, a separate roller pump for ultrafiltration (UF) is used. After adequate heparinization and arterial cannulation, the UF pump is initiated slowly, removing prime through the effluent of the UF, replacing with the patient's blood from the aortic cannula. Once the arterial line and UF circuit are autologous primed, the arterial head displaces reservoir crystalloid toward the UF circuit at a flow rate equal to the UF pump, displacing the crystalloid prime with blood from the UF circuit, autologous priming the boot and oxygenator with blood, crystalloid again being removed by the effluent. After venous cannulation, the venous line prime is replaced with autologous blood, the crystalloid removed by the effluent of the UF circuit via the arterial head. During RAP, if the patient becomes hypovolemic, either autologous volume is transfused back to the patient, or CPB is initiated, without the need for circuitry modifications. RESULTS: The patient population in this sample consisted of 63 patients ranging between 6.1 kg and 115.6 kg. The smaller the patient, the less blood volume available for RAP and therefore the less prime volume able to be removed. Overall percent removal increases as our patients size increases compared to total circuit volume. CONCLUSION: This RAP technique is a safe and effective way to achieve a standardized asanguinous prime for many regardless of patient or circuit size in the absence of contraindications such as low starting hematocrit, emergency surgery or physiologic instability. Most importantly, this potentially reduces the amount of hemodilution patients see from CPB initiation and therefore the lowest nadir hematocrit and consequently the amount of required homologous blood products needed during surgery.

Sterility and performance of open and closed extracorporeal circuits after long-term dry-wet setups.

BACKGROUND: The timeframe for safely using previously setup dry, crystalloid, and blood-primed extracorporeal circuits has long been debated. This study was undertaken to determine a safe deviation from standardized recommendations. METHODS: Open (cardiopulmonary bypass) circuits and closed extracorporeal membrane oxygenation circuits were setup dry for up to 60 days and wet primed for up to 6 weeks with one control inoculated with Escherichia coli. Open circuits were cultured daily, closed circuits weekly. Circuits were primed with blood, albumin, heparin, NaHCO3, and CaCl2. Baseline pCO2, pO2, hemoglobin, lactate dehydrogenase, and plasma free hemoglobin were measured. Circuits were recirculated at a blood flow of 6 Liters/minute with a sweep gas of 1 Liter/minute at 100% FiO2 for 1 minute. Post oxygenator blood gases were collected at 8-, 16-, and 24-hour intervals. RESULTS: There was no observed compromise to the sterility of the circuits and no clinically significant gas exchange abnormalities observed over the duration of the study period. Statistical significance (p < 0.01) was seen in free hemoglobin and lactate dehydrogenase levels, most significant in between the 16- and 24-hour time point in the closed systems intentionally inoculated with E. coli. CONCLUSION: Open and closed circuits can be safely setup dry for up to 60 days. Open, wet-primed circuits can be used safely up to 5 days. Closed, wet-primed circuits can be used safely up to 6 weeks. Blood-primed circuits can be safely run up to 16 hours prior to patient use but should be validated in a randomized clinical study.

Successful use of venovenous extracorporeal membrane oxygenation for complicated H1N1 pneumonia refractory to mechanical ventilation.

In April 2009, novel H1N1 influenza A pneumonia was initially identified in young adults by the Mexican Health Ministry. Previously healthy patients progressing to multisystem organ failure were common. Worldwide, hospitals reported surges in intensive care admissions during the initial phase of the pandemic. In patients with H1N1 pneumonia refractory to mechanical ventilation, centers were initially reporting low survival rates despite the use of extracorporeal membrane oxygenation (ECMO). The initial poor outcomes and protracted ECMO treatment epochs resulted in centers limiting or withholding the use of ECMO in this population. With respect to children with H1N1 infection there was uncertainty concerning optimal incorporation of ECMO as a therapeutic option. In children with rapidly progressive pneumonia and hypoxia refractory to mechanical ventilation, venovenous (VV) ECMO has been successfully used with survival ranging from 40-60% depending on the etiology. We report the successful use of VV ECMO in two children with confirmed novel H1N1 complicated by bacterial pneumonia or morbid obesity. Our Institutional Review Board waived the need for consent. Prompt initiation of VV ECMO resulted in rapid clinical improvement, radiographic resolution of diffuse consolidation, and return of full neurocognitive function. For children with rapidly progressive respiratory distress on conventional ventilation, VV ECMO can be used to improve outcomes when initiated early in the disease process even in children with a significant co-morbidity.

Stage 1 palliation for hypoplastic left heart syndrome without the use of allogeneic tissue, with reduced allogeneic blood product exposure: a case report.

In the 30 years since Norwood described the palliative procedure for hypoplastic left heart syndrome (HLHS), many modifications have been described which have increased the survival rate of children born with this lesion. We describe further modifications which result in reduced cardiopulmonary bypass time, no cooling or circulatory arrest time, and decreased banked blood exposure. A 16-day-old infant with HLHS undiagnosed during pregnancy presented for stage 1 palliation incorporating the Mee modification, Sano right ventricle to pulmonary artery conduit, dual arterial cannulation of the innominate artery and descending aorta, single venous cannulation of the right atrium, and a bypass prime volume of 130 mL. Anticoagulation and hemostasis were monitored with the Hepcon HMS Plus Hemostasis Management System (Medtronic USA, Minneapolis, MN). Bypass commenced at normothermia. A 5.0 Gore-Tex shunt was placed for the Sano Shunt, and the aortic arch was repaired without use of homologous tissue or synthetic material using a modification of the Mee technique. Bypass time was 92 minutes with a 10 minutes cardiac ischemic time. Modified ultrafiltration (MUF) was performed for 12 minutes and heparinization was reversed with protamine. There was no significant bleeding and no indication to transfuse clotting factors. The patient's only allogeneic donor exposure was 350 mL of red blood cells during bypass necessary to achieve a post MUF hematocrit of 50% per our current institution policy for cyanotic infants. Using modified surgical and perfusion techniques along with low prime bypass circuits can result in reduced cross clamp and bypass times as well as a decrease in blood donor exposure. Hypothetical benefits include reduced operating room, ventilation, intensive care unit, and hospital times, improved neurodevelopmental outcomes, and an overall reduction in the cost of care for infants with HLHS.

Clinical evaluation of the Terumo Capiox FX05 hollow fiber oxygenator with integrated arterial line filter.

Perfusion techniques and equipment in pediatric open heart surgery have continued to focus on decreasing prime volumes and lowering surface areas of the cardiopulmonary bypass circuit. While this has improved drastically over the last 20 years, greater demand is being placed on the perfusionist to reduce the deleterious effects of bypass without compromising safety or efficiency. Specifically, manufacturers of disposable perfusion equipment have focused on providing pediatric perfusionists with oxygenators that provide the smallest prime and surface area possible while attempting to maximize performance. Recently,Terumo Cardiovascular has introduced the Capiox FX05, a neonatal hollow fiber oxygenator that includes an integrated arterial line filter. The FX05 provides a blood flow range of 0.1-1.5 L/min and a low priming volume of 43 mL. Additionally, it is coated with X Coating, a biocompatible, hydrophilic polymer surface coating that reduces platelet adhesion and protein denaturation. The purpose of this study was to test the FX05 for gas transfer, blood path resistance, and blood handling characteristics in a standardized clinical setting. Heat exchange coefficients were also calculated during the cooling and warming period. Other data analyzed includes bypass circuit prime volumes and initial patient hematocrit along with the total operative homologous blood donor exposures. In summary, the FX05 offers good gas exchange capabilities and a low pressure drop during normal cardiopulmonary bypass parameters along with the safety of an integrated arterial line filter. Furthermore, the FX05 with integrated filter allows a reduction in overall bypass prime volume and surface area while promoting the reduction of homologous blood transfusions, optimizing hemostasis.

Evaluation of biocompatible cardiopulmonary bypass circuit use during pediatric open heart surgery.

The contact of blood with nonbiological surfaces during cardiopulmonary bypass (CPB) induces a whole body inflammatory response and increases postoperative morbidity directly related to bleeding complications and end organ dysfunction. Methods to reduce these effects have included modification of extracorporeal circuits through biocompatible coating of disposables and the application of various pharmacological agents. Biocompatible coated surfaces are designed to mimic physiologic surfaces. This study was designed to ascertain the effects of using coated circuits during pediatric CPB. After Institutional Review Board approval and parent/guardian consent, patients undergoing CPB, weighing less than 15 kg, with target CPB temperatures more than 28 degrees C, were enrolled into the Coated Circuit Group using an entirely biocompatible CPB circuit with poly(2-methoxyethylacrylate) (PMEA) and a biocompatible coated oxygenator (n = 16). Those patients were retrospectively matched to control patients having the same congenital repair with respect to patient size, surgeon, anesthesiologist, bypass time, cross-clamp time, bypass temperature, and noncoated bypass disposables; (n = 16). CPB data collected included on-bypass platelet count, hematocrit (HCT), and CPB blood product use. Postprotamine data collected in the operating room included blood product use, time from initial protamine administration to chest closure, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR). Postoperative intensive care unit (ICU) data included blood product use, HCT, chest tube output, platelet count, PT, aPTT, INR, blood gases, lactate, and ventilator settings at 1, 2, 4, 6, 12, and 24 hours. Other data collected included intubation time, length of time to chest tube removal, and length of ICU stay. Statistical significance (p < .05) was seen in units of platelets transfused postprotamine, ventilator peak inflation pressure (PIP) on admission to the ICU, postoperative day 0 packed red blood cells (PRBC) and fresh frozen plasma (FFP) transfused, and lactate at 1, 2, 4, 6, and 12 hours postoperative. Several parameters approached statistical significance, including PRBC transfused postprotamine, time from protamine administration to chest closure, postoperative day 0 platelets transfused, and ICU stay. The data suggest that PMEA biocompatible CPB circuits can be used safely during pediatric heart surgery, resulting in a decrease in postoperative blood product use, improved postoperative lung function, and a reduction in the time spent in the ICU.

Modified ultrafiltration postextracorporeal membrane oxygenation.

Modified ultrafiltration (MUF) has been widely used for the removal of extracellular water in the immediate postcardiopulmonary bypass (CPB) period. The reported benefits of this technique are improved hematological status and hemodynamic stability post-CPB, as well as a decrease in blood utilization during the operation. MUF has also been associated with improved pulmonary status along with enhanced myocardial performance. With these benefits in mind, we have explored the possible advantages of using MUF following extracorporeal membrane oxygenation (ECMO). The theoretical advantages of using MUF post-ECMO are the reduction of blood use prior to removal from ECMO for optimization of hemoglobin levels, improved pulmonary compliance decreasing the duration of ventilatory support, improved myocardial function, as well as the other reported benefits described with MUF post-CPB. This report communicates the technique used to perform MUF post-ECMO, as well as a simple MUF circuit design for use in the intensive care unit setting.

Extended support with the Terumo Baby-RX oxygenator.

The Terumo Baby-RX, a new-generation low prime oxygenator, recently has entered the perfusion market in North America. This oxygenator is designed exclusively for neonates and infants and has the smallest priming volume of any clinically available oxygenator. The BABY-RX also is treated with X Coating, Terumo's biocompatible, hydrophilic polymer surface coating that reduces platelet adhesion and protein denaturation. The oxygenator has a blood flow range of 0.1 to 1500 mL/min and operates with a minimum reservoir volume of 15 mL. A 3.2-kg patient, status post-Stage 1 Norwood, Palliation was placed on cardiopulmonary support after thrombus formation within the modified Blalock-Taussig shunt during a general surgery procedure. The extended support circuit incorporated the Baby-RX oxygenator for 17.5 hours. The oxygenator performed well over this time period at flows of 600-800 mL/min, sweep rates of 100-300 mL/min, FiO2 of 30-40%, and ACTs of 140-200 seconds. There were no indices of oxygenator failure noted within the time frame of support. After placement of a new systemic to pulmonary shunt, the patient was removed from support and the oxygenator drained of residual blood. No evidence of fiber damage or clot formation was noted. The patient had a successful support run without complications related to cardiopulmonary support.

Alleviating heat loss associated with modified ultrafiltration.

Modified ultrafiltration (MUF) has been described and utilized for the removal of extracellular water in the immediate postcardiopulmonary bypass (CPB) period. This technique has been associated with improved hematological status and hemodynamic stability post cardiopulmonary bypass. Hypothermia during the MUF period has been described as a complication associated with this technique. Decreased patient temperature may be associated with increased bleeding causing an increase in time to sternal re-approximation, OR time, decreases in cardiac function, peripheral vascular perfusion, and an increase in blood product utilization. These complications may reduce some of the benefits described with the use of MUF. The purpose of this study was to evaluate the use of a heated MUF infusion line to reduce the heat loss associated with this technique in a pediatric population. After obtaining Committee for Protection of Human Subjects exemption, a retrospective review to evaluate the efficiency of the hot MUF infusion line was undertaken. Twenty patients under 10 kg who underwent MUF before the change to a heated infusion line were retrospectively identified and matched to patients undergoing MUF with a heated infusion line with regard to weight, lesion, procedure, surgical staff and technique, and disposable equipment. Groups were evaluated for temperature and hematocrit change during the MUF period, blood loss and transfusion postprotamine in the OR and 24 h, and time to sternal re-approximation postprotamine. Statistical significance was seen between the two groups in temperature (-0.24 +/- 0.72 vs. - 1.58 +/- 0.89 degrees C; p < .0001) with the HotLine group having little change post MUF. Significance was also seen in the last OR temperature recorded (37.0 +/- 1.2 vs. 36.0 +/- 1.0 degrees C; p = .01) with the HotLine group having the higher temperature. There were no significant differences in hematocrit levels at 24 hours, last in the OR, or the change after the MUF period. No significant difference was found in blood transfused postprotamine in the OR, 24-h blood transfused, 24-h chest tube loss, or sternal closure. The study suggests that the use of a heated MUF infusion line safely reduces the heat loss associated with MUF in the immediate post-operative period.

A technique for performing antegrade selective cerebral perfusion without interruption of forward flow or cannula relocation for pediatric aortic arch reconstruction.

New technology and advances in extracorporeal bypass circuitry and surgical techniques have drastically improved outcomes in infants with congenital heart defects. Hypothermia with circulatory arrest has fallen out of favor in many institutions over the last decade in part from data implicating even short circulatory arrest times to long-term neurologic sequelae. Implementing continuous cerebral perfusion techniques for aortic arch reconstruction is desirable in ameliorating neurologic complications because long-term survival of complex defects can be more routinely achieved. Many centers have implemented alternative means of alleviating cerebral ischemic periods by incorporating selective antegrade or retrograde cerebral perfusion techniques. The incidence of post-operative neurologic events is low when alternative cerebral perfusion techniques are used. Many techniques used to perform continuous cerebral perfusion involve brief periods of circulatory arrest, usually for perfusion cannula repositioning. Herein we describe a technique for performing continuous antegrade cerebral perfusion without a need to interrupt forward flow.

Newborn aortic arch reconstruction with descending aortic cannulation improves postoperative renal function.

BACKGROUND: A clinically driven transition in perfusion technique occurred at Children's Hospital and Medical Center, Omaha, Nebraska, from primarily selective cerebral perfusion bracketed by brief periods of deep hypothermic circulatory arrest to a technique of dual arterial perfusion including innominate artery and descending aortic cannulation (DAC), with continuous mildly hypothermic (>30 °C) full-flow cardiopulmonary bypass to the entire body. This study retrospectively compared outcomes in a recent cohort of neonates undergoing aortic arch reconstruction with the two techniques. METHODS: The clinical records of 142 consecutive neonates undergoing operations involving aortic arch reconstruction at a single institution between April 2004 and September 2012 were reviewed. Renal function changes were graded according to the pediatric RIFLE score (based on risk, injury, failure, loss, and end-stage kidney disease). Sixteen patients, 8 supported with selective cerebral perfusion bracketed by brief periods of deep hypothermic circulatory arrest and 8 with DAC, required immediate postoperative extracorporeal membrane oxygenation and were excluded from renal function analysis. Multivariable regression models evaluated predictors of pediatric RIFLE score. RESULTS: Patients with DAC had shorter median bypass support (113 versus 172 minutes; p < 0.001) and myocardial ischemic time (43 versus 81 minutes; p < 0.001). Patients with DAC had less median fluid gain at 24 hours (37 versus 69 mL/kg; p < 0.001), and lower incidence of acute kidney injury (5% versus 31%; p < 0.001). Fewer patients with DAC (31% versus 58%; p = 0.001) required open chest. Use of selective cerebral perfusion bracketed by brief periods of deep hypothermic circulatory arrest, single-ventricular physiology, and aortic cross-clamp time were found to be multivariable predictors of serious kidney dysfunction. CONCLUSIONS: Multisite arterial perfusion, including DAC, and maintenance of continuous mildly hypothermic full-flow cardiopulmonary bypass may offer advantages as a perfusion strategy for neonatal arch reconstruction. Prospective investigation of this technique is warranted.

Descending aortic and innominate artery cannulation for aortic arch repair with mildly hypothermic continuous cardiopulmonary bypass in infants and children.

A technique is described for exposure of the descending aorta, allowing separate arterial cannulation for perfusion of the upper and lower body during reconstruction of the aortic arch, maintaining continuous full-flow cardiopulmonary bypass to the entire body. This single technique is applicable to all aortic arch pathologies and allows an unhurried aortic reconstruction in an unobstructed field.

Anoxic ventilation improves systemic perfusion during extracorporeal circulation with uncontrolled systemic-to-pulmonary shunt.

Uncontrolled systemic-to-pulmonary shunt results in decreased systemic flow during extracorporeal life support (ECLS). Ligation of systemic-to-pulmonary shunts during ECLS is associated with poor outcome and is not always readily achieved. In ex vivo preparations, alveolar hypoxia results in pulmonary vasoconstriction despite normoxic pulmonary perfusate. We hypothesized that anoxic ventilation would result in reduced pulmonary shunting and increased systemic flow during ECLS in piglets with systemic-to-pulmonary shunt. Four piglets were placed on ECLS with right and left atrial drainage. A shunt was created between the bicarotid trunk and pulmonary artery, using 5-mm ePTFE tubing. Inspired oxygen was reduced to <1% for 10 minutes, then returned to room air; pH, hematocrit, temperature, ventilatory pressures, and total pump flow were maintained constant. Systemic arterial pressure and right atrial return volume and hemoglobin saturation were measured: All decreased significantly upon shunt unclamping. Anoxic ventilation caused increased systemic pressure (34 vs. 28 mm Hg, p < 0.05), flow (335 vs. 278 mL/min, p < 0.05), and systemic venous saturation (53% vs. 48%, p = 0.13) compared with room air ventilation. In conclusion, anoxic ventilation during normoxic ECLS in subjects with systemic-to-pulmonary shunts results in a significant and potentially clinically useful reduction in pulmonary shunting.