Heparin Dose Response in Pediatric Cardiopulmonary Bypass

Heparin dosing for cardiopulmonary bypass is frequently based on empirical loading doses. Most cite this heparin loading dose as 3 mg/kg (300 units/kg) for both adults and pediatric patients. The purpose of this study was to retrospectively evaluate the heparin dose response (HDR) in a pediatric population. The HDR of 268 pediatric patients presenting for repair of congenital heart defects at Children's Hospital, Columbus, Ohio, was gathered retrospectively from May 1992 to October 1993. The HDR was gathered for the entire population and divided into four groups based on patient weight: Group I ≤ 5.0 kg; Group II 5.1 to 10.0 kg; Group III 10.1 to 20.0 kg; Group IV > 20 kg. The HDR is reported as mean (SD, range) in mg/kg. For the entire population (n = 268) the HDR was 3.5 mg/kg (1.20, 1.0 to 7.3). For patients > 20 kg (group IV, n =58) the HDR was 3.0 mg/kg (0.8, 1.0 to 4.9); Group III (10.1 to 20.0 kg, n = 80) HDR was 3.5 mg/kg (1.1, 2.0 to 7.3). Group II (5.1 to 10.0 kg, n = 66) HDR was 3.8 mg/kg (1.2, 1.8 to 7.3). Group I(≤ 5.0 kg, n = 64) HDR was 3.9 mg/kg (1.3, 1.5 to 7.3). Twenty-seven percent of the total population had a HDR > 4.0 mg/kg. When compared by weight, 10% of the patients > 20.0 kg had a HDR > 4.0 mg/kg compared to 45% of the patients < 5.1 kg. The heparin dose required by children becomes greater as the patient weight (size) decreases with more patients requiring > 400 units/kg. The use of a fixed dose protocol of heparin in the pediatric patient becomes increasingly inadequate as the patient size decreases. Heparin administration in the pediatric patient should be specific to the individual patient with a heparin dose response calculated for each patient

Bloodless Extracorporeal Membrane Oxygenation in the Jehovah’s Witness Patient

The successful use of prolonged extracorporeal life support with a heart-lung machine was first performed in 1972, as described by Hill et al., on a young man with post-traumatic respiratory failure. The first successful use of extracorporeal membrane oxygenation (ECMO) was 1976 by Bartlett et al. Since this time, the use of ECMO for neonatal and pediatric pulmonary support has become a standard of care in many children’s hospitals. The use of ECMO, being a very invasive procedure, is not without risk. In our experience, most patients require multiple transfusions of the different blood components (packed red blood cells, plasma, platelets, and cryoprecipitate). Exposure to one or more blood products often occurs with connection to the ECMO circuit, as the circuit is generally primed with blood products or whole blood. Jehovah’s Witnesses (JWs) are known best in the medical community for their refusal of blood products, even at the risk of death, which presents challenges for health care providers. This belief stems from the biblical passages that have been quoted as forbidding transfusion: Genesis 9:3–4, Leviticus 17:13–14, and Acts 15:19–21. This refusal of blood poses even greater challenges when treating the pediatric JW population. When a blood product is deemed medically necessary for the JW patient, the healthcare provider must either seek legal intervention, or support the patient’s/family’s wishes and associated outcome. This ethical dilemma may be further complicated in the setting of therapies, which may pose additional risks and potentially less clear benefit such as with ECMO. Bloodless cardiac surgery with cardiopulmonary bypass has been reported in the JW population in adults and pediatrics, including neonates. After a thorough search of the literature, no published report of a JW patient being supported on ECMO without blood or blood component utilization was identified. This case report will present our experience with multiple day, bloodless ECMO support of a 17-year-old male patient of the JW faith

Perfusion Techniques Toward Bloodless Pediatric Open Heart Surgery

There continues to be evidence regarding the negative impact of blood transfusion on morbidity and mortality in the adult literature, including infection risk, increased hospital and intensive care length of stay, and costs. More effort has been put into reducing the use of blood components in adult surgical centers but blood transfusions continue to be used frequently in pediatric centers. From 2002 through 2005, we embarked on a mission of reduced prime volume in an effort toward bloodless cardiac surgery to meet the needs of the Jehovah’s Witness patient. The same bloodless surgical and perfusion techniques were applied to all patients undergoing cardiopulmonary bypass beginning in 2006. Circuit size was minimized and acute normovolemic hemodilution (ANH) was considered and attempted more often, especially if a re-operation. Retrograde arterial prime (RAP) and venous antegrade prime (VAP), dilutional or balanced ultrafiltration during cardiopulmonary bypass, modified arteriovenous ultrafiltration post bypass, and cell salvage of remaining circuit contents after flushing with crystalloid were recorded. ANH, RAP, and VAP, separately or in combination, were used less than 1% of the time prior to 2006. From 2006–2008 ANH was performed on 42% of the patients and RAP/VAP was performed on 70% of the patients. From 2006–2008, 43% (287 of 662) of the open heart surgeries were performed bloodless in the operating room versus 30% (193 of 633) from 2003–2005. Bloodless surgery more than doubled for the 0–6, 6–15, and 15–20 kg groups from 3.5%, 23%, and 23% respectively in 2003–2005 to 9%, 44%, and 58%, respectively in 2006–2008. With the cooperation of the entire cardiac surgical team, bloodless open heart surgery is achievable in a pediatric cardiac surgical center, including neonates

In-Vitro Quantification of Gaseous Microemboli in Two Extracorporeal Life Support Circuits

During the course of extracorporeal membrane oxygenation, patients are at constant risk of exposure to air emboli. Air emboli may enter the circuit during routine lab sampling, medication administration, air entrainment through the venous cannula, or via a circuit disruption. Circuit components have been designed and positioned to minimize the quantity of air that travels through the arterial line to the patient. The purpose of this study was to assess the air handling of a newer generation extracorporeal life support circuit. The extracorporeal life support circuit consisted of an open hard-shell venous reservoir, Better Bladder (BB14) or silicone bladder (R-14), and Quadrox D® oxygenator or 0800 silicone oxygenator. Air emboli detection sensors were placed in the extracorporeal life support circuit: post bladder, post oxygenator, and post heat exchanger if applicable. Air was injected as a 1 mL/min for 5 minutes injection or as a single 5 mL bolus. Emboli detection was recorded continuously during and for 3 minutes post air injection at two blood flow rates (Qb) (.5 and 1.2 L/min). All tests were performed in triplicate with each condition. All tested components reduced the embolic volume transmitted through the circuit. The quantity of this reduction was dependent on both the Qb and the air injection condition. During this in-vitro testing, air emboli passing through any of the components tested was decreased. Furthermore, the emboli delivery was reduced post component with the slower Qb (.5 L/min)

Clinical Gaseous Microemboli Assessment of an Oxygenator with Integral Arterial Filter in the Pediatric Population

The use of an arterial line filter (ALF) within the pediatric cardiopulmonary bypass (CPB) circuit is not a new concept. It has always presented the perfusionist with a circuit component that while valuable, increased prime volume. The purpose of this study was to evaluate the change in prime volume and emboli between a conventional oxygenator with separate ALF and a new generation oxygenator with integral arterial filter (AF). We performed a clinical, non-randomized retrospective evaluation of the Terumo Capiox® RX15 (Terumo Cardiovascular Systems Corporation, Ann Arbor, MI) (n = 10) in conjunction with the Terumo Capiox® AF125X ALF or the Capiox ® AF02 vs. the Terumo Capiox® FX15 oxygenator with integral AF (n = 10). The above circuit components, in combination with the LUNA EDAC® (emboli detection and classification) Quantifier (LUNA Innovations, Blacksburg, VA) were placed at various locations within each patient’s CPB circuit to establish and quantify the presence and volume of gaseous emboli during all phases of cardiopulmonary bypass. The EDAC® system is available/used for all patients undergoing CPB at this institution. When compared to a more conventional CPB circuit, the Capiox® FX15 primes more easily as it does not require a carbon dioxide flush while still providing a 32 μ AF. There was no statistical difference in air handling between the tested oxygenators and their associated circuits. During this review it was determined that use of the Capiox® FX15 simplifies the arterial limb of the pediatric CPB circuit. Removal of the separate ALF led to the removal of several, now unnecessary, arterial connectors and additional tubing (arterial line filter bypass). Removal of these components led to a reduction in prime volume and decreased the hemodilutional effect. The FX15 provided a safe, simplified pediatric CPB circuit and was as effective in gaseous microemboli removal as was the more traditional RX15 with separate ALF during this review

Use of a Low-Prime Circuit for Bloodless Heart Transplantation in Xenotransplant of 5—7 Kilogram Primates

There is a great effort to decrease blood product use during open-heart surgery in pediatrics. We were presented with a research challenge to accomplish heart xenotransplantation from donor cynomologous monkey (Macaca fascicularis) to recipient olive baboon (Papio anubis) of 5–7 kilograms without benefit of donor or banked blood products. The purpose of this study was to design and implement a practical, low-volume circuit to minimize hemodilution and avoid the use of blood products. A simple circuit was assembled using a low-volume oxygenator with hardshell venous reservoir, an 1/8-inch arterial line, an 1/4-inch venous line, and gravity drainage. Three xenotransplants were performed and evaluated. The mean recipient weights were 6.3 ± 0.7 kg. Circuit prime volume was 228 ± 5.8 mL, and bypass time was 85 ± 6.7 min. Blood flow rates were 585 ± 113 mL/min with postmembrane arterial line pressures of 344 ± 81 mmHg, and patient mean arterial pressures (MAP) of 51.4 ± 16.7 mmHg. Venous saturations were 63.7 ± 8.0%. The hematocrit prebypass was 37.4 ± 3.2, bypass 20.7 ± 0.9, post-MUF 27.8 ± 3.3, and 7 days postoperative 24.5 ± 7.5%. Platelet count was 289 ± 1.1 K/µL, 147 ± 37.1 K/µL, and 322 ± 292.7 K/µL prebypass, postbypass, and 7 days postoperative, respectively. Plasma-free hemoglobin prebypass was 7.5 ± 4.4 mg/dL and postbypass 22.2 ± 16.5 mg/dL with no noted hematuria during and after the procedure. All patients survived and were successfully weaned from cardiopulmonary bypass (CPB) with same day extubation. A low-prime circuit for bloodless heart surgery is possible. To achieve low reservoir levels, especially without the use of an arterial line filter (ALF), it is necessary to have a full armament of monitoring and alarm devices

Novoseven Use in a Non-Cardiac Pediatric ECMO Patient With Uncontrolled Bleeding

Despite the presence of normal coagulation values, refractory bleeding during extracorporeal membrane oxygenation (ECMO) is encountered. Occasionally, hemostasis is not achieved through traditional techniques including surgical exploration, anti-fibrinolytics, increasing fibrinogen level, increasing platelet counts, and decreasing activated clotting time (ACT). We report the case of an infant on veno-arterial ECMO for respiratory syncytial virus with severe bleeding and the use of recombinant activated factor VII (rFVIIa; NovoSeven; Novo Nordisk, Copenhagen, Denmark). This was a retrospective review of the patient’s medical records, laboratory values, and chest radiographs. rFVIIa was given to this patient on two separate occasions for bleeding unresponsive to traditional bleeding management. On both occasions, the patient’s blood loss returned to zero within 20 minutes of administration and remained there for a minimum of 4 days. Continued bleeding on ECMO unresponsive to current medical management may be an indication for rFVIIa. However, rFVIIa should not be administered without first considering the ECMO circuits conditions to include presence of clot, and documentation of circuit pressures, which, after rFVIIa, may be the first indication of intraoxygenator clot formation. Additionally, rFVIIa should not be a first-line treatment until continued studies allow for approved use in this patient population

Modified Surface Coatings and their Effect on Drug Adsorption within the Extracorporeal Life Support Circuit

A recently completed study quantified the percent of fentanyl or morphine sulfate lost to uncoated polyvinylchloride (PVC) tubing or to one of two hollow fiber oxygenators within the extracorporeal life support (ECLS) circuit. The results demonstrated the majority of drug loss was due to adsorption by the PVC tubing. The purpose of this study was to determine if a tubing coating process affects fentanyl or morphine Sulfate adsorption. The goal was to quantify fentanyl or morphine sulfate lost due to adhesion within surface modified tubing. The following surface modifications were studied: 1) Maquet Safeline® (synthetic immobilized albumin); 2) Maquet Softline® (a heparin free biopassive polymer); 3) Maquet Bioline® (recombinant human albumin + heparin) (Maquet Cardiopulmonary AG, Hirrlingen, Germany); 4) Terumo X Coating™ (poly2methoxylacrylate)) (Terumo Cardiovascular Systems Corporation, Ann Arbor, MI); 5) Medtronic Carmeda® (covalently bonded heparin); and 6) Medtronic Trillium® (covalently bonded heparin) (Medtronic, Minneapolis, MN). A total of 36 individual circuits were built from the above six available modified surface coatings, for a total of six individual circuits of each coating type. Blood samples were drawn at 5 minutes, 120 minutes, and 360 minutes followed by High-Performance Liquid Chromatography to determine available circulating levels of either fentanyl or morphine sulfate. Fentanyl concentrations decreased to an average final available concentration of 35% (±5%) within the 18 circuits. Morphine sulfate however, decreased to a final available concentration of 57% (±1%) in all Maquet tubing and the Medtronic Trillium tubing, while it decreased to a final concentration of 35% (±1%) in the Medtronic Carmeda coated tubing and in the Terumo X Coating tubing. Biocompatible ECLS circuit surface coatings affected drug-adsorption and availability. Further evaluation is necessary to understand the adsorptive loss of other drugs administered to our patients while on modified surface coated ECLS circuits