Effectiveness of activated factor VII in postoperative bleeding after cardiac surgery with extracorporeal membrane oxygenation

A 4-year-old girl suffered severe postoperative chest tube drainage bleeding after cardiac transplant surgery requiring extracorporeal membrane oxygenation. Transfusions of platelets and fresh frozen plasma failed to decrease the bleeding. At 2.5 hours a dose of 180 mcg/kg of recombinant activated Factor VII was administered. The hemorrhage decreased from 45 ml/kg/h in the first 2.5 hours to 17 ml/kg/h in the next 2.5 hours. The same dose of recombinant activated Factor VII was administered and the hemorrhage suddenly decreased to 1.5 ml/kg/h in the next 2.5 hours, with subsequent disappearance. No adverse events related to activated Factor VII were observed. Recombinant activated Factor VII may be useful in some cases of severe postoperative bleeding in children after cardiac surgery. Randomized controlled studies are needed to confirm its safety and efficacy, and to evaluate the most suitable dose.     

体外膜氧合成功救治新生儿心脏术后严重低心排综合征一例

目的 总结ECMO救治新生儿心脏术后严重低心排的成功经验.方法 2007年7月18日我们对一例患先天性大动脉转位(TGA)合并房间隔缺损(ASD)、动脉导管未闭(PDA)2.8 kg出生6 d的新生儿,进行了大动脉调转术(arteries switch)、ASD修补、PDA结扎术,畸形矫正后出现严重低心排综合征,低血压[＜39/30 mm Hg(1 mm Hg=0.133 kPa)]、高乳酸血症(Lac 8.8 mmol/L)、高左房压(LAP＞20 mm Hg)、血性痰、少尿[＜1 ml/(kg·h)],由于转流时间较长(263 min)且难以脱离体外循环,常规治疗无效后接V-A ECMO进行心肺辅助.结果 经87h ECMO辅助后,左心功能明显恢复,患儿顺利脱离ECMO,ECMO第1天LVEF 20%,第2天34%,第3天43%;ECMO第1天CKMB 41 μ/L,第2天恢复正常.脱离ECMO后,在较高浓度血管活性药支持下[肾上腺素0.2 μg/(kg·min),多巴胺/多巴酚丁胺8 μg/(kg·min),米力农0.56 μg/(kg·min)],循环基本稳定.ECMO撤离后第4天,关闭胸部切口.ECMO撤离后第22天,撤离呼吸机,术后30 d撤离血管活性药.术后58 d康复出院.出院时心肺、肝肾功能正常,神志清醒,四肢肌张力和运动正常.整个病程中多次头颅超声检查均未发现脑出血、梗死等病灶.ECMO并发症:(1)肺出血;(2)伤口出血和心包填塞;(3)溶血;(4)高胆红素血症.结论 ECMO对抢救新生儿心脏术后严重心功能不全有良好的疗效.     

Use of recombinant factor VIIa for refractory hemorrhage during extracorporeal membrane oxygenation.

OBJECTIVE: To describe the outcome and treatment of two patients with recombinant factor VIIa (rFVIIa) for severe hemorrhage associated with extracorporeal membrane oxygenation (ECMO). DESIGN: Case report. SETTING: A 38-bed pediatric intensive care unit and 20-bed pediatric cardiac intensive care unit at a tertiary care children's hospital. Patient: Two patients with life-threatening hemorrhagic complications associated with ECMO requiring massive transfusion of blood products. INTERVENTIONS: Administration of repeated doses of rFVIIa at 90 microg/kg/dose. MEASUREMENT AND MAIN RESULTS: Patient 1 was an 11-yr-old male with a dilated cardiomyopathy who had undergone an orthotopic heart transplant treated with venoarterial ECMO postoperatively for right ventricular dysfunction. Patient 2 was a 13-yr-old male treated with venoarterial ECMO for cardiopulmonary failure from necrotizing staphylococcal pneumonia. Both patients had severe hemorrhage from the cannulation sites and thoracostomy tubes requiring massive transfusion to maintain intravascular blood volume and replace clotting factors. Both patients were treated with rFVIIa every 2-4 hrs and attained hemostasis. Patient 1 was administered three doses and Patient 2 was administered ten doses. No evidence of abnormal thrombus formation was noted in their respective ECMO circuits. CONCLUSIONS: The efficacy of rFVIIa in reducing intractable bleeding postcardiac surgery and in other coagulopathic states is being investigated. Despite theoretical concerns of thrombosis, these cases illustrate that there may be a role for the cautious use of rFVIIa in treating severe and intractable hemorrhage associated with ECMO.     

Nitrogen balance during extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation (ECMO) has been used as a support system for neonates with pulmonary failure since 1975. During ECMO, thermal regulation, pulmonary gas exchange, and cardiac output can be partially or nearly completely provided by the circuit. The presumed resultant decrease in energy requirement has prompted the question of whether infants are in a catabolic or anabolic state of metabolism while on ECMO. Directly measuring the metabolic rate in babies on ECMO is difficult. However, studying the nitrogen balance in these infants may suggest an answer. Nitrogen balance was studied in 21 neonates spanning a single ECMO team's experience at two institutions. Children were studied at the Ochsner Clinic from 1986 to 1990 and at the University of Chicago Wyler Children's Hospital from 1990 to the present. The infants received total parenteral nutrition (TPN) as their only nutritional source during the entire ECMO course. During this time, 24-h urine collections were analyzed for urea nitrogen (UUN). The daily nitrogen balance was calculated by subtracting nitrogen output (estimated as the UUN) from nitrogen input (the measured amino acid content of the intravenous feeding). Fecal losses were not included in the nitrogen output since the infants were not enterally fed and rarely had stools while on ECMO. The kilojoules (1 kilocalorie = 4.2 kilojoules) and protein provided by the parenteral nutrition varied. Nitrogen intake exceeded nitrogen output by ECMO day 2 (the initial nitrogen balance determination). Infants receiving as little as 0.4 g/kg protein and 168 kJ/kg daily remained in positive nitrogen balance. Correspondence to: R. Arensmann     

Hemolysis during long-term extracorporeal membrane oxygenation

We studied the cause of hemolysis during extracorporeal membrane oxygenation (ECMO) by monitoring hematologic and coagulation profiles in seven consecutive infants treated with this procedure. A constrained vortex pump was used in all patients, and the average duration of ECMO was 224 +/- 111 (SD) hours. In all patients, plasma free hemoglobin was low during the first 48 hours after the initiation of ECMO. Later, when visible clots appeared in the ECMO circuit, plasma hemoglobin progressively rose. A rise in the level of fibrin degradation products and a fall in the fibrinogen level were observed concurrently with a rise in the plasma hemoglobin level. After complete circuit changes in six patients, plasma free hemoglobin, fibrin split products, and fibrinogen all returned to baseline values. Neither circuit component changes nor exchange transfusion was effective in normalizing the levels of plasma free hemoglobin, fibrin split products, and fibrinogen. We conclude that when ECMO is administered for prolonged periods, circuit thrombosis occurs and hemolysis ensues. Additional studies are needed to assess the contribution of the constrained vortex pump to this process.     

Carotid artery reconstruction following extracorporeal membrane oxygenation

Right hemispheric brain injury has been noted in surviving infants treated with venoarterial extracorporeal membrane oxygenation (ECMO). This phenomenon may be secondary to permanent ligation of the right carotid artery. At our institution, conventional ventilatory therapy failed in five neonates with respiratory insufficiency, and they were treated successfully with ECMO. In four of the five neonates, the right carotid artery was reconstructed at the time of decannulation. At discharge, all newborns with carotid artery repair showed no signs of unilateral brain injury and had excellent antegrade flow in the right carotid artery as assessed by both duplex and transcranial Doppler ultrasound scanning. Carotid artery reconstruction after ECMO is a technically simple procedure that may reduce the incidence of right hemispheric brain injury and long-term consequences of marginal cerebral perfusion.     

Neonatal vocal cord paralysis following extracorporeal membrane oxygenation

Five cases of unilateral vocal cord paralysis/paresis were diagnosed following extracorporeal membrane oxygenation for newborn respiratory failure. All were right sided and transient in nature. None of the five patients had other findings commonly associated with vocal cord palsy. The extracorporeal membrane oxygenation procedure requires surgical dissection in the carotid sheath on the right side of the neck, an area immediately adjacent to both the vagus and recurrent laryngeal nerve. It is speculated that vocal cord paralysis in these infants was acquired as a result of the extracorporeal membrane oxygenation cannulation. Although the vocal cord paralysis resolved in all cases, two patients had difficult courses after extracorporeal membrane oxygenation. Therefore, laryngoscopic examination should be considered for patients after extracorporeal membrane oxygenation.     

Perioperative extracorporeal membrane oxygenation support for critical pediatric airway surgery

Extracorporeal membrane oxygenation (ECMO) has been used for cardiopulmonary support in neonates, infants, and adults. We report the application of ECMO for critical airway surgery when mechanical ventilation cannot provide adequate gas exchange. Three pediatric patients underwent emergency ECMO establishment because of hypercapnia that could not be managed by conventional mechanical ventilation. The pathology included: (1) left pulmonary artery sling with long-segment tracheal stenosis; (2) absence of the right intermediate bronchus and abnormal origin of the right lower bronchus arising from the left main bronchus; (3) right-lung agenesis with long-segment tracheobronchial stenosis. Venoarterial ECMO was established. Before ECMO, the arterial pH values were 7.28, 7.0, and 7.08, and the PaCO₂ values were 111.8, 112.0, and 208.7 mmHg for each patient, respectively. After ECMO support, respiratory acidosis was reversed. The patients then underwent surgical intervention. The surgical procedures included: (1) slide tracheoplasty and reimplantation of the left pulmonary artery; (2) resection of the stenotic tracheal segment and reconstruction of the bronchial tree; (3) tracheal dilatation and stent implantation. The ECMO durations were 11, 5, and 16 h, respectively. All patients were successfully weaned off ECMO without complications. In conclusion, ECMO provided adequate ventilation support for patients undergoing critical tracheobronchial reconstruction when conventional mechanical ventilation could not maintain adequate gas exchange.     

Heart rate variability during extracorporeal membrane oxygenation and recovery in severe neonatal disease

BACKGROUND: Heart rate variability (HRV) reveals information on the functional state of the autonomic nervous system (ANS) in neonates. During severe illness, heart rate variability is impaired. AIM: This study was initiated to measure the changes in HRV in neonates during extracorporeal membrane oxygenation (ECMO) and recovery from severe respiratory and circulatory failure. Moreover, we compared our data with HRV data of healthy newborns and we investigated the differences in HRV parameters between ECMO-survivors and non-survivors. STUDY DESIGN: This study is of an observational character. We performed short-term recordings of heart rate variability in 14 neonates during ECMO and recovery. We computed time- and frequency-domain HRV parameters. RESULTS: ECMO significantly affects time-domain HRV parameters. Severe neonatal illness causes a significant reduction of all calculated HRV parameters; clinical recovery is accompanied by an increase of HRV. In comparison with normative data of healthy newborns, however, HRV remains impaired. The ECMO-development ratio separated the non-survivors from the survivors during ECMO therapy. CONCLUSIONS: During severe neonatal illness, HRV is impaired. It remains to be clarified whether the impairment of HRV during severe illness can predict the neurological outcome. The ability of the E/D ratio as an HRV parameter to serve as a predictive tool has to be corroborated in larger group of patients.     

Evaluation of the reconstructed carotid artery following extracorporeal membrane oxygenation.

Over a 12-month period, 28 neonatal patients in respiratory failure were supported with extracorporeal membrane oxygenation (ECMO), and 11 of these underwent successful repair of the right carotid artery post-ECMO. Nine of 11 were studied with duplex color-flow Doppler imaging between 14 and 109 days of age and again at 1 year of age. A velocity ratio (A/B) of the peak systolic velocity above the level of the anastomosis to the peak systolic velocity below the anastomosis was measured to assess the degree of stenosis, if any, at the repair site. Antegrade flow through the carotid was detected post-ECMO in 8 of 9 infants, and antegrade and retrograde flow was documented in 1 infant. A/B ratios ranged from 1.00 to 8.60 (A/B ratio of 1 is normal; 2.0 indicates at least a 50% obstruction to flow). Four of 9 patients had ratios greater than 2.0, and 8 of 9 exhibited some evidence of obstruction. Follow-up scans were performed on 8 of 9 infants between 12 and 18 months of age. All infants examined showed marked improvement in A/B ratio and patency of the vessel, documenting that initial narrowing of the vessel is reversible. No infant had evidence of embolic phenomena to the right side of the brain by magnetic resonance imaging. Repair of the common carotid artery post-ECMO is technically feasible without increasing the risk of brain injury.     

Right-sided brain lesions in infants following extracorporeal membrane oxygenation

In retrospective review of survivors of neonatal extracorporeal membrane oxygenation, eight patients with varying degrees of right hemispheric brain injury were identified. The extent of preextracorporeal membrane oxygenation hypoxia and ischemia was documented: five of eight patients had arterial PO2 values of less than 40 mm Hg, seven of eight required dopamine for blood pressure support, and five of eight required cardiopulmonary resuscitation. Two patients had proven neurologic abnormalities before extracorporeal membrane oxygenation. Postextracorporeal membrane oxygenation CT brain scans showed right hemispheric focal abnormalities in three patients. Seven infants had neuromotor abnormalities which were lateralizing in nature; all were left sided, suggesting right-sided brain injury. EEGs showed an increased incidence of slowing and attenuation over the right hemisphere. These findings indicate that right-sided brain abnormalities exist after extracorporeal membrane oxygenation and that carotid artery ligation for extracorporeal membrane oxygenation is not without risk.     

Applications of extracorporeal membrane oxygenation to pediatric cardiac surgery

The stability of the membrane oxygenator has led to its applicaton as a means of long-term cardiopulmonary support. The use of technology is neonates has led the process achieved in adylt respiratory support. In the infant and neonate with congenital heart disease, extracorporeal membrane oxygenation (ECMO) has been used for both cardiac, and pulmonary support, and in situations of unrecoverable cardiac failure as a bridge to transplantion. Significant progres has bee made, and valuable lessons have been learned. Indications, techniques, and results of the application of ECMO to children with congenital heart disease are summarized here.     

Intracranial hemorrhage during extracorporeal membrane oxygenation in neonates

Intracranial hemorrhage is a complication of extracorporeal membrane oxygenation for the treatment of neonatal respiratory failure. A retrospective review of 35 neonates treated with extracorporeal membrane oxygenation was performed; ten had intracranial hemorrhage. Infants with intracranial hemorrhage had lower birth weights and were gestationally younger than infants with intracranial hemorrhage. Eight of eight neonates of less than 35 weeks' gestational age sustained intracranial hemorrhage. Six died immediately after extracorporeal membrane oxygenation was stopped. Two lived less than 1 year. Two of 27 neonates older than 34 weeks' gestational age sustained intracranial hemorrhage. One child is normal, the other died at 18 months of age. Based on the results of this study, the risk of intracranial hemorrhage appears low in neonates of greater than 34 weeks' gestational age who undergo extracorporeal membrane oxygenation treatment for severe respiratory failure. The use of extracorporeal membrane oxygenation, as it is presently performed, is contraindicated in neonates of less than 35 weeks' gestational age because of the risk of intracranial hemorrhage.     

Emergent use of extracorporeal membrane oxygenation during pediatric cardiac catheterization.

OBJECTIVES: The goal of this study was to evaluate the utility of extracorporeal membrane oxygenation (ECMO) to resuscitate patients following critical cardiac events in the catheterization laboratory. DESIGN: Retrospective review of medical records. SETTING: Cardiac intensive care unit and cardiac catheterization laboratory at a tertiary care children's hospital. PATIENTS: Pediatric patients cannulated emergently for ECMO in the cardiac catheterization laboratory (n = 22). INTERVENTIONS: ECMO was initiated emergently in the cardiac catheterization laboratory for progressive hemodynamic deterioration due to low cardiac output syndrome or catheter-induced complications. MEASUREMENTS AND MAIN RESULTS: Twenty-two patients were cannulated for ECMO in the catheterization laboratory between 1996 and 2004. Median age was 33 months (range 0-192), median weight 14.8 kg (2.4-75), and median duration of ECMO 84 hrs (2-343). Indications included catheter-induced complication (n = 14), severe low cardiac output syndrome (n = 7), and hypoxemia (n = 1). Three patients (14%) were cannulated in the catheterization laboratory before catheterization for low cardiac output or hypoxemia. During cannulation, 19 patients (86%) were receiving chest compressions; median duration of cardiopulmonary resuscitation was 29 mins (20-57). Eighteen patients (82%) survived to discharge (five of whom underwent cardiac transplantation) and four (18%) died. Of 19 patients who received cardiopulmonary resuscitation during cannulation, 15 (79%) survived to discharge and nine (47%) sustained neurologic injury. There was no significant difference between survivors and nonsurvivors in age, weight, duration of cardiopulmonary resuscitation or ECMO support, pH, or lactate levels. CONCLUSIONS: ECMO is a technically feasible and highly successful tool in the resuscitation of pediatric patients following critical events in the cardiac catheterization laboratory.     

Effects of carotid artery repair following neonatal extracorporeal membrane oxygenation

Between 1 June 1991 and 30 June 1996, 62 neonates were placed on extracorporeal membrane oxygenation (ECMO). In 61 the right carotid artery was cannulated. At the time of decannulation, a decision was made regarding carotid artery repair (CAR) based on the condition of the vessel. Thirty-two patients underwent end-to-end CAR and 29 had artery ligation. There was no difference between groups in gestational age or birth weight, but the ligation group contained 11 patients with congenital diaphragmatic hernia, compared to 2 in the repair group. The time on ECMO was 148 h for the repair group and 297 h in the ligation group. Follow-up contrast-enhanced magnetic resonance imaging (MRI) studies and ultrasound (US) demonstrated 2 occluded vessels in the repair group (7%); 3 vessels appeared stenotic on MRI. Follow-up neurologic examination was normal or near-normal in 17 of 19 repair infants and 9 of 16 ligation patients. Two repair infants had slight delays in development, while 3 ligation patients had significant delays. Follow-up US showed 3 grade I changes in the repair group with 1 hydrocephalus. There was 1 grade I and 1 grade III change in the ligation group. Follow-up MRI showed 6 minimal changes in the repair group and 9 in the ligation group. CAR does not adversely affect neurologic outcome after neonatal ECMO. The early patency rate was 93%, although 12% of the vessels appeared stenotic. Long-term follow-up confirmed persistent patency. CAR, if technically feasible, should be encouraged following neonatal ECMO therapy. Accepted: 24 June 1999     

Patient complications during extracorporeal membrane oxygenation (ECMO).

Extracorporeal membrane oxygenation (ECMO) has rapidly become the treatment of choice for critically ill newborns with reversible pulmonary disease not responding to conventional treatment. Since 1987 ECMO has been available at our hospital and up to December 1989 11 patients were treated. Several patient complications were seen. The aim of this study was to register the incidence and treatment of these complications and to compare our results with international ECMO experience. It is concluded that many of the complications seen during ECMO can be successfully managed.     

Outcome in neonates with congenital heart disease referred for respiratory extracorporeal membrane oxygenation

AIM: To evaluate the proportion of neonates referred for extracorporeal membrane oxygenation (ECMO) support in the modern era of advanced conventional treatments for respiratory failure who actually had congenital heart disease (CHD), and to assess the impact of this diagnostic route on patient condition and outcome. METHODS: A retrospective case-note review of neonatal ECMO and cardiac admissions to a single, tertiary ECMO and cardiac intensive care unit (ICU) between March 1999 and February 2002. RESULTS: 287 symptomatic neonates presented to the ICU with previously undiagnosed cardiac or respiratory disease. Eighty-two with presumed respiratory failure were referred for ECMO, and 205 with suspected CHD were referred for cardiac evaluation. Eight (10%) ECMO referrals, all with presumed persistent pulmonary hypertension of the newborn (PPHN), were found to have CHD (transposition: 3; total anomalous pulmonary venous connection: 3; left heart obstructive lesions: 2). Mortality in this group was 50%, compared with 11% for correctly identified CHD patients (odds ratio 8.2, 95% CI 1.92, 35.4, p<0.01). For all neonates with CHD, the risk of death was increased by the presence of cardiovascular collapse and end-organ dysfunction at presentation to the ICU (p<0.01 for both). CONCLUSION: Neonates with CHD may present as severe "PPHN" via the ECMO service. Poor outcome in these patients relates to the high incidence of cardiovascular collapse and end-organ dysfunction. Early echocardiography is recommended for neonates with presumed PPHN. Neonatal ECMO support should be based in centres with cardiac surgical services.     

经中央循环体外膜氧合治疗儿童难治性脓毒性休克（摘要）

目的因脓毒症住院的患儿病死率很高,发生休克是导致死亡最重要的风险因素。对任何常规治疗均无效的脓毒性休克患儿,推荐使用体外膜氧合（ECMO）,但预期存活率仅为50％,且该技术的最佳应用方法尚不明确。近年来,我们尝试直接经胸腔置管（经中央循环,心房－主动脉ECMO）以期达到更高血流流速。