Platelet Transfusion During Neonatal Open Heart Surgery
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 2
- 主要终点
- Amount of Blood Products Transfused
研究概览
简要总结
Hypothesis:
Dilutional thrombocytopenia after cardiopulmonary bypass (CPB) is universal and administration of donor apheresis platelets just prior to termination of bypass will assist in early correction of coagulopathy, early hemostasis and lesser donor exposure of blood products after cardiac surgery.
Background:
What is the Problem? - Bleeding, Transfusion and Outcomes
- Excessive bleeding after neonatal cardiac surgery has been independently associated with increased adverse events, morbidity and mortality.1,2 Bleeding after neonatal open-heart surgery has multiple etiologies such as immaturity of the building blocks of coagulation, effects of deep hypothermia, longer CPB times, altered flow states and dilutional state induced by being on CPB leading to low platelet count, low platelet function, low fibrinogen levels, altered fibrinogen polymerization, complement activation, etc.2,3 The strongest predictor of transfusion after cardiopulmonary bypass in children was deemed to be the CPB circuit volume and the effect of hemodilution.4
- The dilutional coagulopathy after neonatal CPB requires intense damage control resuscitation with massive transfusion of platelets, packed red blood cells (PRBC), cryoprecipitate, fresh frozen plasma (FFP) and supplemental factor concentrates. In a previous study at this institution (IRB# HSC-MS-13-0647), we have shown that in neonates undergoing open-heart surgery there was a significant drop in platelet counts after bypass (71% change, baseline= 268 ± 90, Post CPB= 76 ± 27, 109/L). Associated with this drop , the average intraoperative transfusion load in neonates undergoing cardiac surgery with CPB at our institution constitutes of PRBC= 63± 43 ml/kg, FFP=51± 21 ml/kg, cryoprecipitate =12+6 ml/kg, platelets = 28 +16 ml/kg and cell-saver =27± 10 ml/kg. In addition 72% of these patients were exposed to a 3-factor prothrombin complex concentrate (Bebulin®). Although this "throw the kitchen sink" approach is effective in achieving hemostasis, it comes with significant effects on post CPB hemodynamics, constantly changing hematocrit, variable blood volume with inability to achieve steady state inotropic state affecting cardiac output, oxygen delivery and adding to pulmonary hypertension.
Overall, having higher platelet counts at the time of weaning from cardiopulmonary bypass has distinct advantages of reducing transfusions and improving outcomes.
详细描述
What do we do at our institution? The vast majority of centers including ours continue to utilize a regimen for neonatal CPB prime that constitutes of PRBCs ( 20-30 ml/kg) added to achieve a hematocrit > 25 on CPB and FFP (20-30 ml/kg) to assist the lower antithrombin levels, improve heparin efficiency and improved suppression of the thrombin generation on CPB. Platelets are not added in the CPB prime at our institution. This regimen of avoiding donor apheresis platelets transfusion during early CPB is because of the known effects of CPB on native platelets resulting in decreases in count from hemodilution and mechanical damage. Donor apheresis platelets administered as an initial constituent of CPB prime also carry the risk of platelet activation during hypothermia and CPB with potential activation of the coagulation cascade. Fresh whole blood is also not used secondary to the difficulty and logistics pertaining to availability fresh whole blood makes this approach unattractive.
What is the advantage of adding platelet apheresis just prior to separation from CPB? We know that native platelets are significantly reduced in count and function with increasing duration of CPB and function diminishes independently of platelet count with hypothermia.11 The advantages of adding donor apheresis platelets just prior to separating from CPB are that the donor platelets don't get spalliated and deformed by the roller pumps for long durations, they are not subjected to the intense cooling and rewarming process and spared of the early reperfusion injury/inflammation. Furthermore, addition of 10 ml/kg of platelets would raise the platelet counts by at least 50% based on a previous study at this institution (IRB# HSC-MS-13-0647; post-CPB platelet transfusion of 28 ± 16 ml/kg resulted in elevation of platelet counts from 76 ± 27 to 223 ± 60 (109/L).
Effect of modified ultrafiltration (MUF): MUF is routinely performed immediately on termination of CPB and prior to protamine administration. During this stage, after successful weaning from CPB, 10-15% of the cardiac output from the arterial cannula along with residual volume from the venous reservoir of the CPB pump is pumped through a hemofilter placed under vacuum to allow rapid hemofiltration with the effluent returned via a single atrial venous cannula to the patient. This 15-minute rapid hemofiltration allows for removal of excess water, improvement in hematocrit with improved oxygen delivery, faster achievement of steady state inotrope levels with improved hemodynamics and removal of inflammatory mediators.12-14 While MUF improves hematocrit, it does not increase platelet count significantly, MUF has no effect on native platelet function.3 The biggest advantage of transfusion of apheresis platelets prior to termination of bypass versus standard practice of their transfusion after protamine is that the transfused fluid load of 10-15 ml/kg of platelets volume that would have diluted the red cell fraction (hematocrit) and impacted oxygen delivery and pulmonary dysfunction would now take the full benefit of modified ultrafiltration with excess fluid removal even prior to protamine administration with overall improved hemodynamics.
Institutional Blood transfusion Management for Neonatal CPB For the CPB prime: PRBCs (50ml/kg) are added to allow for a hematocrit >30 for the estimated blood volumes. FFP is added to the pump prime for all patients weighing less than 5 kilograms and in those who demonstrate heparin resistance on initial heparin dose response assays. Heparin is added in the CPB prime. Other constituents of the CPB prime are epsilon aminocaproic acid (50 mg/kg), cefazolin (30 mg/kg) and methylprednisolone.
Post CPB: Current practice in neonates is to administer a combination of cryoprecipitate, platelet and PRBC in a 1:1:1 ratio till hemostasis is achieved. 3PCC factor administration is based on diffuse clinical bleeding suggestive of coagulopathy that persists despite one round of cryoprecipitate and platelet transfusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 1 Day 至 3 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All neonates and infants less than 3 months of age under 4 kilograms undergoing open heart surgery and cardiopulmonary bypass
排除标准
- •Redo open heart surgery
- •Bleeding Disorders - such as von Willebrand Disease, Hemophilia
结局指标
主要结局
Amount of Blood Products Transfused
时间窗: 0-72 hours
All Blood products administered (PRBC, FFP, Cryo, Platelets) from termination of CPB to first 24 hours post op
次要结局
- Time From End of CPB to Sternal Closure (Chest Approximation)(0-72 hours)
- Number of Exposures of 4-PCC and Factor 7(0-72 hours)
- Number of Participants With Mortality at 30 Days(0-30 days)
- Chest Tube Output(0-24 hours)
- Inotropic Support at the Time of Entry to the Pediatric Intensive Care Unit (PICU) as Indicated by Inotrope Score(At the time of entry to the pediatric intensive care unit (PICU))
- Number of Participants With Arrhythmia(0-72 hours)
- Length of Mechanical Ventilation(from start of mechanical ventilation to end of mechanical ventilation (about 4-8 days))
- Number of Participants With Cardiopulmonary Resuscitation (CPR) Events(0-72 hours)
研究者
Nischal Krishamurthy Gautam
Associate Professor of Anesthesiology
The University of Texas Health Science Center, Houston