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.     

Cerebral proton magnetic resonance spectroscopy of neonates after extracorporeal membrane oxygenation

During venoarterial extracorporeal membrane oxygenation the right carotid artery is ligated in a hypoxic neonate. The aim of the present study was to compare the morphology and metabolism of the left and right basal ganglia in 10 neonates after extracorporeal membrane oxygenation, using proton magnetic resonance imaging and spectroscopy. Data could be obtained in 9 neonates. No significant metabolic differences were found between either the left or right basal ganglia, despite a small right-sided thalamic infarct in one child. Metabolism was normal in all cases. All the infants showed symmetrical neurodevelopment.

Conclusion: Ligation of the right carotid artery for venoarterial extracorporeal membrane oxygenation did not produce persistent changes in brain metabolism in the basal ganglia in this small group of patients.     

The natural history of direct hyperbilirubinemia associated with extracorporeal membrane oxygenation.

OBJECTIVE--To determine the incidence and natural history of direct hyperbilirubinemia in neonates treated with extracorporeal membrane oxygenation. DESIGN--A prospective series of patients. SETTING--A level 3 neonatal intensive care unit and center for extracorporeal membrane oxygenation in Ohio. PARTICIPANTS--Sixty-seven consecutive patients treated with extracorporeal membrane oxygenation in 33 months. INTERVENTION--None. MEASUREMENTS/RESULTS--Twenty-six (39%) developed direct hyperbilirubinemia. In 14 (54%), bilirubin levels were mildly elevated and occurred only during extracorporeal membrane oxygenation therapy. Levels were more severely elevated in the remaining 12 patients (46 +/- 10 mumol/L [2.7 +/- 0.6 mg/dL] vs 159 +/- 101 mumol/L [9.3 +/- 5.9 mg/dL], P less than .0001). Duration and severity of hyperbilirubinemia were correlated. Hyperbilirubinemia resolved in all patients by 9 weeks after extracorporeal membrane oxygenation therapy. No structural abnormalities or infectious agents were identified as causes. Aluminum levels were evaluated for 40 patients, were not in the toxic range, and did not correlate with hyperbilirubinemia. Multiple linear regression analysis suggested that hyperbilirubinemia in these cases resulted from interaction of injuries, with the primary contributor being hemolysis during extracorporeal membrane oxygenation. CONCLUSIONS--Direct hyperbilirubinemia occurs frequently in patients treated with extracorporeal membrane oxygenation and may be severe. However, direct hyperbilirubinemia typically resolves without short-term sequelae. Hemolysis may be an important contributing factor.     

Familial vocal cord dysfunction

Vocal cord paralysis is a common cause of neonatal stridor. Familial vocal cord dysfunction, however, is unusual. All three siblings in one family had neonatal stridor. Vocal cord dysfunction was confirmed after endoscopic examination in two of the children; a temporary tracheotomy was required by one child. Results of evaluation, including pulmonary function tests, suggest discrete dysfunction localized to the neuromuscular pathway responsible for vocal cord abduction. Endoscopy is of prime importance in the diagnosis of vocal cord dysfunction. In considering therapy, the physician must weigh both the potentially life-threatening nature of vocal cord paralysis, as well as the likelihood of eventual spontaneous resolution of many familial and idiopathic cases.     

Recombinant factor VII for severe bleeding during extracorporeal membrane oxygenation following open heart surgery.

OBJECTIVES: Severe bleeding is a recognized complication during mechanical cardiopulmonary support with extracorporeal membrane oxygenation. We present the use of recombinant activated factor VII (rFVIIa) for severe, refractory bleeding during extracorporeal membrane oxygenation support after open-heart surgery for congenital heart disease. DESIGN: Retrospective review of all patients receiving rFVIIa on extracorporeal membrane oxygenation. SETTING: A pediatric extracorporeal membrane oxygenation center located within the cardiac intensive care unit of a tertiary care children's hospital. PATIENTS: Four patients treated with rFVIIa for refractory bleeding on extracorporeal membrane oxygenation. INTERVENTIONS: The patients received rFVIIa for severe, refractory blood loss despite applying clotting products and aprotinin infusion and excluding surgical reasons. MEASUREMENTS AND MAIN RESULTS: rFVIIa was given 4-7 hrs after commencing extracorporeal membrane oxygenation; a second identical dose was administered 4 hrs later. Bleeding decreased significantly in all patients within 30 mins after the first dose of rFVIIa; no side effects were observed. CONCLUSIONS: rFVIIa is effective to achieve control of refractory hemorrhage in patients on extracorporeal membrane oxygenation. Now a randomized controlled trial to evaluate risks and benefits of rFVIIa on patients undergoing extracorporeal membrane oxygenation is required.     

Circle of Willis blood velocity and flow direction after common carotid artery ligation for neonatal extracorporeal membrane oxygenation

The velocity and direction of blood flow in the circle of Willis arteries were measured in three infants who underwent right common carotid artery ligation for extracorporeal membrane oxygenation treatment. Within 15 minutes of common carotid artery ligation, blood flow was detected in one infant's right middle cerebral artery; however, the velocity was reduced to 50% of the preextracorporeal membrane oxygenation level. The velocity remained 50% to 70% lower than normal during the 88 hours of extracorporeal membrane oxygenation therapy. In the other two infants, the velocity changes were less severe. By 2 to 10 weeks after weaning from extracorporeal membrane oxygenation, the velocities in the left cerebral arteries were increased to 116% to 217% of the corresponding right cerebral vessels. Following common carotid artery ligation, a retrograde direction of flow was noted in the first (A1) segment of the right anterior cerebral artery and in the right posterior communicating artery, whereas the direction of flow was normal in the corresponding vessels on the left. After common carotid artery ligation, the vertebrobasilar and the contralateral internal carotid systems appear to be the main sources of reperfusion of the right cerebral hemisphere via the circle of Willis. Furthermore, because of the known variants of the circle anatomy, a noninvasive pulsed Doppler method could be used to evaluate the flow patterns in the circle of Willis arteries, both before and after common carotid artery ligation for extracorporeal membrane oxygenation.     

Stridor: intracranial pathology causing postextubation vocal cord paralysis

During an 18-month period in a pediatric intensive care unit, nine patients with vocal cord paralysis were identified using flexible bronchoscopy. When tracheally extubated, each child was found to have stridor. The children ranged in age from 17 days to 5 1/2 years. Two patients had unilateral paralysis, but neither required tracheostomy. Seven patients displayed bilateral abductor vocal cord paralysis. Of these, six patients required tracheostomy. Surgical injury to the recurrent laryngeal nerve was the probable cause in two patients. The other seven patients had neurologic disorders with documented or suspected increases of intracranial pressure. Four of the seven patients with bilateral abductor vocal cord paralysis regained cord mobility within 4 months. Both children with unilateral cord paralysis have no stridor and vocalize well 1 year later. Cord paralysis in the setting of intracranial hypertension probably results from compression or ischemia of the vagus nerve before it exits the skull. Early visualization of the larynx should be done in patients who become stridulous when extubated, especially those with prior thoracic procedures or with neurologic disorders associated with intracranial hypertension.     

Long-term neurophysiologic outcome after neonatal extracorporeal membrane oxygenation

We examined clinical and neurophysiologic measures in 10 children 4 to 9 years after neonatal extracorporeal membrane oxygenation. Electroencephalograms did not correlate with clinical or other neurophysiologic measures of interhemispheric asymmetry. By ultrasound imaging, the right internal carotid artery velocity was approximately 62% of that on the left, and right internal carotid flow was reduced by 74% (p less than or equal to 0.01), whereas an age-matched control group showed no differences. A decrease in the amplitude of the long-latency auditory and somatosensory evoked potentials was noted over the right hemisphere after left-sided stimulation compared with the left hemispheric potentials after right-sided stimulation (p less than or equal to 0.005). No significant differences in hemispheric symmetry were noted in the amplitudes for wave V of the auditory brain-stem response or in the P30 component of the middle-latency auditory evoked potentials. Likewise, latency measures of the evoked potentials were symmetric. We conclude that (1) neonatal extracorporeal membrane oxygenation is associated with long-lasting decreased right internal carotid blood flow with compensatory increased flow through the left carotid system and (2) there is a consistent reduction in the amplitude of right hemispheric long-latency evoked potentials. These latter findings may reflect redirected cerebral blood flow patterns after extracorporeal membrane oxygenation.     

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.     

Vocal cord paralysis secondary to impacted esophageal foreign bodies in young children

Impacted foreign bodies in the esophagus can result in respiratory symptoms including stridor and aphonia. Several mechanisms have been proposed to explain these symptoms, but the possibility of vocal cord paralysis and its cause has not been adequately emphasized. Two cases of young children with esophageal foreign body are described; both presented with respiratory symptoms, 1 with aphonia and the other with stridor. In both cases, the symptoms were secondary to vocal cord paralysis. A possible mechanism of recurrent nerve injury is proposed.     

Reconstruction of the arteria carotis communis in newborn following extracorporeal membrane oxygenation (ECMO).

With the help of ECMO it is possible to save the lives of newborn infants suffering from severe respiratory distress syndrome not responding to conservative treatment. Using Bartlett's classic venous-arterial perfusion technique in ECMO the right arteria carotis communis had to be sacrificed. Thus, despite the life-saving character of this new method, the ligation of the carotid with all its possible complications had often been a major argument against using this therapy. We are now therefore trying to reconstruct the arteria carotis after decannulating the vessel after extracorporeal membrane oxygenation. In our 8 cases so far, post-op examinations showed no obstruction of blood flow in the vessel. No neurological deficiencies were recorded.     

Symmetric cerebral blood flow in newborns who have undergone successful extracorporeal membrane oxygenation.

Cerebral blood flow (CBF) was measured with positron emission tomography in 23 newborns following extracorporeal membrane oxygenation. In 9 newborns the common carotid artery was reanastomosed after extracorporeal membrane oxygenation and in 14 newborns the common carotid artery remained ligated. The ratio of right/left hemispheric CBF was not significantly different in the newborns with reanastomosed or occluded common carotid arteries (right/left CBF ratio was 0.98 in both groups). The maximum asymmetry was 8% and was observed in 2 newborns. All 9 newborns with reanastomosis of the carotid artery are normal at follow-up at 1 year or longer. Three newborns with ligation of the common carotid artery were lost to follow-up and 1 newborn died. Eight of 10 remaining newborns are normal at follow-up; the 2 other infants have developmental quotients of 60 and 64, respectively, and no other deficits. The data indicate (1) that hemispheric CBF is symmetric in newborns who have undergone extracorporeal membrane oxygenation and have no evidence of brain injury, and (2) that reanastomosis of the common carotid artery does not alter hemispheric CBF in the newborn period.     

Neonatal vocal cord paralysis-an early presentation of hereditary neuralgic amyotrophy due to a mutation in the SEPT9 gene

Hereditary neuralgic amyotrophy is a rare autosomal dominant disorder involving recurrent episodes of painful brachial plexus neuropathies. Involvement of other nerves has been described in some families. The age of onset is from infancy to adulthood. Mutations in the SEPT9 gene were identified in approximately half of the hereditary neuralgic amyotrophy families.We evaluated a family with six affected members from three generations with a point mutation in the SEPT9 gene. One of the patients presented in the neonatal period with vocal cord paralysis necessitating intubation and prolonged ventilation.The neonatal presentation of vocal cord paralysis broadens the phenotypic spectrum of hereditary neuralgic amyotrophy. The identification of a SEPT9 mutation in a neonate with respiratory distress due to vocal cord paralysis expands the differential diagnosis in these patients.     

Heparin-induced thrombocytopenia in a pediatric patient receiving extracorporeal support and treated with argatroban.

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is rare in the pediatric population, with a majority occurring in the pediatric intensive care unit setting. All reported cases have been associated with the use of unfractionated heparin. Because unfractionated heparin is the anticoagulant of choice for extracorporeal life support, the development of HIT in these patients can be devastating. We report a case of HIT with evidence of small-vessel arterial thromboembolism in a 17-month-old child receiving extracorporeal membrane oxygenation and continuous renal replacement therapy successfully treated with argatroban. CASE: The patient was a 17-month-old boy with severe respiratory failure secondary to asthma and mucus plugging that failed conventional and unconventional ventilation. Venovenous extracorporeal membrane oxygenation was initiated, and within 24 hrs, there was a precipitous decrease in the platelet count, with the development of cutaneous ischemia involving his lower limbs. Heparin-associated antibodies were positive. Argatroban was started, and the child maintained on extracorporeal membrane oxygenation and continuous renal replacement therapy, with resolution of the cutaneous ischemia and rebound of the thrombocytopenia. DISCUSSION: HIT is rare in the pediatric population. Recognition of HIT is vital because withdrawal of heparin is the first and most important therapy. For patients on extracorporeal membrane oxygenation or continuous renal replacement therapy who develop HIT, synthetic thrombin inhibitors (hirulogs) have been reported as an alternative. However, little information on their use in extracorporeal life support has been published, particularly in the pediatric population. CONCLUSION: This report documents a pediatric case of HIT successfully treated with argatroban, allowing continuation of the venovenous extracorporeal membrane oxygenation and continuous renal replacement therapy, with resolution of the thromboembolic ischemia and thrombocytopenia.     

One- to three-year outcome for 14 neonatal survivors of extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation, using venoarterial or venovenous perfusion, is a safe and effective procedure in the term of near-term infant with life-threatening respiratory failure. Without extracorporeal membrane oxygenation, due to the severity of their disease, these children are at high risk for neurologic damage, chronic lung disease, and death. Because survival is not expected without extracorporeal membrane oxygenation therapy, there is no corresponding control group to which these survivors may be compared. In this report, we reviewed the outcome at 1 to 3 years in the first 14 survivors of extracorporeal membrane oxygenation treated at our institution. Seven of 14 neonatal extracorporeal membrane oxygenation survivors (50%) were normal or near normal at between 1 and 3 years of age. Ten (71%) had normal mental ability. We conclude that in neonates with high mortality risk from respiratory failure, near-normal growth and development can be expected in the majority who survive with extracorporeal membrane oxygenation treatment.     

Use of extracorporeal membrane oxygenation for respiratory failure in term infants

Eight infants with intractable respiratory failure were treated with extracorporeal membrane oxygenation. Intractable respiratory failure was defined as alveolar-arterial oxygen gradient of more than 620 torr for six to 12 hours that did not respond to hyperventilation and the use of tolazoline. Infants with overt sepsis, CNS damage, or other debilitating conditions were not considered for extracorporeal membrane oxygenation. Six of the eight infants survived after a mean extracorporeal membrane oxygenation time of 164 hours. Five of the six survivors were normal neurologically and developmentally when examined at 1 year of age.     

Oxygenation and hemodynamics in left and right cerebral hemispheres during induction of veno-arterial extracorporeal membrane oxygenation

OBJECTIVE: Oxygenation and hemodynamics in the left and right cerebral hemispheres were measured during induction of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). STUDY DESIGN: Using near infrared spectrophotometry, effects of right common carotid artery (RCCA) and right internal jugular vein (RIJV) ligation and start of VA-ECMO on concentrations of oxyhemoglobin, deoxyhemoglobin, and cerebral blood volume (CBV) were evaluated in 10 newborn infants. Mean cerebral blood flow velocity (CBFV) in the major cerebral arteries was compared before and after the start of VA-ECMO (pulsed Doppler ultrasonography). RESULTS: RCCA ligation caused a decrease in oxyhemoglobin concentration and an increase in deoxyhemoglobin concentration. RIJV ligation caused no changes. Sixty minutes after the start of VA-ECMO, oxyhemoglobin concentration and CBV had increased, and deoxyhemoglobin concentration had decreased. There were no differences between the hemispheres. Mean CBFV had increased in the left internal carotid artery, and it increased equally in both middle cerebral arteries. Flow direction was reversed in the right internal carotid artery. Three patients had asymmetric cerebral lesions, not related to differences in the measurements between the cerebral hemispheres. CONCLUSION: The initiation of VA-ECMO causes changes in cerebral oxygenation and hemodynamics but without a difference in effect on left and right cerebral hemispheres.     

Respiratory obstruction and apnea in infants with bilateral abductor vocal cord paralysis, meningomyelocele, hydrocephalus, and Arnold-Chiari malformation

This report describes 21 infants and children with bilateral abductor vocal cord paralysis and associated meningomyelocele, Arnold-Chiari malformation, and hydrocephalus. Two life-threatening forms of respiratory distress are distinguished: (1) upper airway obstruction due to bilateral abductor cord paralysis and (2) apnea. Clinically significant episodes of apnea were documented in 13 infants. Ten infants had evidence of aspiration and dysphagia. Vocal cord paralysis, apnea, aspiration, and dysphagia were frequently temporally related to increased intracranial pressure.     

Ductus aneurysm as a rare cause of inspiratory stridor in the newborn infant

A paralysis of the left vocal cord was seen by laryngoscopy in a 3-days-old boy with inspiratory stridor. A ductus aneurysm was established by angiocardiography, which was believed to be the cause of the vocal cord paralysis. Within 8 days after the angiocardiography the aneurysm became smaller and the stridor disappeared. Twelfth months later the control-angiocardiography showed the total obliteration of the ductal aneurysm.     

Extracorporeal membrane oxygenation as rescue therapy for methadone-induced pulmonary edema

Opioid-induced pulmonary edema has been previously reported, but its mechanism remains unclear. The use of extracorporeal membrane oxygenation as rescue therapy for methadone-induced pulmonary edema has not been reported in the literature. We describe 2 cases of methadone ingestion complicated by pulmonary edema, acute respiratory distress syndrome, and circulatory failure successfully managed with venoarterial extracorporeal membrane oxygenation.