James A. Cullen

Utility of serial EEGs in neonates during extracorporeal membrane oxygenation

We found electroencephalographic (EEG) studies to be useful for monitoring cerebral function, for confirming seizure activity, and for limited prediction of short-term outcome in 145 neonates who required extra-corporeal membrane oxygenation (ECMO) of reversible respiratory failure. The EEG tracings were classified as normal or as mildly, moderately, or markedly abnormal; abnormal recordings were further classified as focal, diffuse, or predominantly lateralized. A significant decrease in frequency and degree of EEG abnormalities was observed in recordings obtained after ECMO compared to those obtained prior to (P = .001) or during ECMO (P = .001). There was no significant increase in marked EEG abnormalities when recordings obtained before and during ECMO were compared (P = 0.41). Of 11 infants with electrographic seizures during ECMO, 7 (64%) either died during their nursery courses or were developmentally handicapped at age 1 year which is a significantly greater adverse outcome than that observed in infants without EEG seizure activity (P less than .003). No consistently lateralized EEG abnormalities were observed during or after ECMO when compared to tracings obtained before cannulation of the right common carotid artery. There was no acute change in EEG rhythm or amplitude over the right cerebral hemisphere during right common carotid artery cannulation. Our observations support the value of serial EEG in the assessment of cerebral function in critically ill infants undergoing ECMO. They further suggest that, in this patient population, cannulation of the right common carotid artery is a safe procedure that does not result in lateralized abnormalities of cerebral electrical activity.

Sensitivity and specificity of the neonatal brain-stem auditory evoked potential for hearing and language deficits in survivors of extracorporeal membrane oxygenation.

OBJECTIVE We determined the sensitivity and specificity of neonatal brain-stem auditory evoked potentials (BAEP) as markers for subsequent hearing impairment and for developmental problems found later in infancy and childhood. METHODS BAEP studies were performed before discharge in infants treated with extracorporeal membrane oxygenation (ECMO), and two specific abnormalities were analyzed: elevated threshold and delayed central auditory conduction. Behavioral audiometry was repeated during periodic follow-up until reliable responses were obtained for all frequencies, and standardized developmental testing was also conducted. The sensitivity and specificity of an elevated threshold on the neonatal BAEP for detecting subsequent hearing loss, and the relationship of any neonatal BAEP abnormality to language or developmental disorders in infancy, were calculated. RESULTS Test results for 46 ECMO-treated infants (57.5%) were normal, and those for 34 infants (42.5%) were abnormal, with either elevated wave V threshold, prolonged wave I-V interval, or both on neonatal BAEP recordings. Most significantly, 7 (58%) of the 12 children with subsequent sensorineural hearing loss had left the hospital after showing normal results on threshold tests. There was no significant difference in the frequency of hearing loss between subjects with abnormal (5/21, or 24%) and those with normal BAEP thresholds (7/59, or 12%; Fisher Exact Test, p = 0.28). Therefore the sensitivity of neonatal BAEP testing for predicting subsequent hearing loss was only 42%. Neonatal BAEP specificity for excluding subsequent hearing loss was 76%. In contrast, on language development testing, 19 children demonstrated receptive language delay. Of these children, 12 (63%) had abnormal neonatal BAEP recordings and 7 (37%) had a normal BAEP threshold, normal central auditory conduction test results, or both (p = 0.04). CONCLUSIONS Neonatal BAEP threshold recordings were of limited value for predicting subsequent hearing loss common in ECMO-treated survivors. However, an abnormal neonatal BAEP significantly increased the probability of finding a receptive language delay during early childhood, even in those with subsequently normal audiometry findings. Because neonatal ECMO is associated with a high risk of hearing and receptive language disorders, parents should be counseled that audiologic and developmental follow-up evaluations in surviving children are essential regardless of the results of neonatal BAEP testing.

Developmental changes in renal artery blood flow velocity during the first three weeks of life in preterm neonates.

Changes in color Doppler imaging measurements of renal artery blood flow velocity have been reported previously during fetal life and during the first week postnatally in term and preterm infants. This study reports longitudinal, developmental changes in renal artery and aortic blood flow velocities occurring postnatally, from birth to day 1 of life, at 1 week, and at 2 to 3 weeks of age in 14 premature babies (mean gestation, 30 +/- 4 (SD) weeks; birth weight, 1.45 +/- 0.57 kg), and identified by means of color Doppler imaging and pulsed Doppler spectral analysis. Results indicate that a significant increase in renal artery systolic blood flow velocity occurs within the first week of life (from 40 +/- 3 (SEM) cm/sec at birth or on day 1, to 53 +/- 3 cm/sec on day 7, to 51 +/- 4 cm/sec on day 14 to 21; repeated-measures analysis of variance, p = 0.004), concurrently with a significant increase in abdominal aortic blood flow velocities, both systolic (from 40 +/- 4 at birth or on day 1, to 70 +/- 8 on day 7, to 76 +/- 8 cm/sec on day 14 to 21; p <0.001) and diastolic (from 4 +/- 2 at birth or on day 1, to 11 +/- 2 on day 7, to 11 +/- 2 cm/sec on day 14 to 21; p = 0.00 1). Systemic blood pressure did not increase concomitantly during the some period. Neither the presence of respiratory distress syndrome or patent ductus arteriosus nor treatment with indomethacin altered developmental increases in observed renal artery blood flow velocities. The presence of an umbilical artery catheter in the high thoracic position in five infants, however, created turbulence at the level of the renal arteries, significantly increasing renal artery systolic flow velocity from 32 +/- 4 to 44 +/- 5 cm/sec (p = 0.009) and increasing renal resistive index from 0.90 +/- 0.03 to 0.96 +/- 0.04 (p = 0.046). These results suggest that renal artery blood flow velocity increases during the first postnatal week in preterm infants and is likely related to increases in aortic blood flow velocity and reduction in renal vascular resistance.

Predictive value of neonatal electroencephalograms before and during extracorporeal membrane oxygenation

We studied the prognostic significance of electroencephalograms recorded serially at 2- to 4-day intervals during the acute neonatal course of 119 near-term infants with severe respiratory failure treated by venoarterial extracorporeal membrane oxygenation (ECMO). A poor prognosis was defined as early death (n = 27), an abnormally low developmental assessment score (n = 14), or cerebral palsy (n = 14) at 12 to 45 months of age. The only electroencephalographic abnormalities that were significantly related to a poor prognosis were burst suppression (B-S) and electrographic seizure (ES). The 30 infants with two or more recordings of B-S or ES, when compared with the 58 neonates without such electroencephalographic abnormalities, had an odds ratio for a poor prognosis of 6.6 (95% confidence limits, 2.2 to 20.2). The 31 infants with a single ES or B-S recording did not have a significantly increased risk for a poor prognosis. Cardiopulmonary resuscitation immediately before ECMO (n = 8) and the lowest systolic blood pressure before or during ECMO were significantly related to the occurrence of ES or B-S recordings. There was no significant predilection of ES for either cerebral hemisphere. We conclude that in near-term neonates with respiratory failure, serial electroencephalographic recordings are of predictive value, and may facilitate clinical care including the decision to initiate or to continue ECMO.

Pulmonary sequelae in infants treated with extracorporeal membrane oxygenation

The decision to place an infant on extracorporeal membrane oxygenation (ECMO) is based on predictions of expected morbidity and mortality. One unknown factor is the relationship between pre‐ECMO pulmonary dysfunction and on barotrauma and post‐ECMO pulmonary sequelae. To determine whether placement of infants on extracorporeal membrane oxygenation (ECMO) early is associated with less subsequent pulmonary dysfunction than placing infants on EMCO later, we evaluated pulmonary function in 25 neonates prior to ECMO, when the infants had come off EMCO, and at the time of nursery discharge. Pulmonary resistance (R) and compliance (CL) were determined by a pneumotachograph and esophageal manometry, and functional residual capacity (FRC) was determined by a helium dilution method. Maximal expiratory flow (VmaxFRC) was determined by thoracic compression at the time of discharge. Infants were assigned to an early ECMO group (<36 hours of age, n = 12), or a late ECMO group (>36 hours of age, n = 13). When first evaluated, the early group had a higher oxygenation index than the late group (mean value, 63 versus 48), but initial pulmonary function measurements were not different between the two groups. In the early group mean CL increase from 0.20 to 0.36 ml/cmH2O/kg, FRC increased from 7 to 20 ml/kg, and mean R decreased from 107 to 61 cmH2O/L/sec between the initial study and immediately after ECMO. In the late group, only FRC increased from a mean of 8 to 20 ml/kg. CL and FRC increased from post‐ECMO to discharge in both groups (mean CL from 0.36 to 0.76 ml/cmH2O/kg in the early group, and from 0.30 to 0.79 in the late group). Mean FRC increased from 20 to 26 ml/kg in the early group, and from 20 to 25 ml/kg in the late group. VmaxFRC was lower in the late than the early group at discharge (mean, 1.14 versus 1.58 L/sec; P < 0.05). While both groups of infants had minimal pulmonary dysfunction at discharge, the infants placed on ECMO early had evidence of slightly less airway dysfunction despite a higher initial oxygenation index than the infants placed on ECMO late. Pediatr Pulmonol. 1997; 23:31–38.

Adverse neurodevelopmental outcome after extracorporeal membrane oxygenation among neonates with bronchopulmonary dysplasia.

OBJECTIVE The relationship between bronchopulmonary dysplasia (BPD) and neurodevelopmental outcome after extracorporeal membrane oxygenation (ECMO) has not been extensively reported. We compared the outcomes in a large series of infants with and without BPD after ECMO. STUDY DESIGN Hospital charts and follow-up records of 145 infants treated with ECMO (1985 through 1990) were reviewed. Complete long-term respiratory and follow-up outcome data were available in 64 infants. BPD occurred in 17 survivors; the remaining 47 did not have BPD. RESULTS Babies with BPD were more likely to have had respiratory distress syndrome. Mean (+/- SD) age at ECMO initiation was later for the BPD group (127+/-66 vs 53+/-39 hours, p < 0.001), and the duration of ECMO treatment was longer (192+/-68 vs 119+/-53 hours, p < 0.001). Bayley Scales of Infant Development scores at <30 months were lower in infants with BPD (p < 0.001), as were three of four Mullen Scales of Early Learning scores (> or = 30 months, p < 0.001 or p = 0.01). At 57+/-16 months 11 (64%) patients with BPD had mild neurologic disabilities, and 3 (18%) had severe disabilities. At a similar age (53+/-16 months, p = NS) 16 (34%) patients without BPD had mild disabilities, whereas 2 (4%) had severe disabilities (p < 0.01). CONCLUSIONS The occurrence of BPD after ECMO is associated with adverse neurodevelopmental outcome. Patients with BPD after ECMO merit close long-term follow-up.

Documented Home Apnea Monitoring: Effect on Compliance, Duration of Monitoring, and Validation of Alarm Reporting

The objectives of this study were to: (1) measure patient compliance with monitoring, (2) validate parental reports of alarms at home, (3) examine monitoring duration, and (4) compare documented monitor records with the traditional pneumogram to evaluate patients for monitor discontinuation. During the 1-year period fromJanuary through December, 1992, 114 infants were followed up with documented monitoring. Simultaneously, 113 infants were followed up with conventional monitors. Infants were premature, or victims of apparent life-threatening episodes (ALTE), or siblings of SIDS victims. Monitors recorded all episodes of apnea greater than 15 seconds and bradycardia loss than 80 beats per minute. All families were contacted biweekly by telephone. Downloads were performed at regular intervals. Monitor downloads were compared with simultaneous pneumograms to assess the accuracy of a long-term, intermittent event-recording system versus short-term (6-to 12-hour) continuous recording. All families were highly compliant with the use of home monitoring. Although Caucasian families used the monitors more often than non-Caucasian families, all groups used the monitor >75% of the time. True episodes were verified in 38% of patients by monitor downloads. Only 7.4% of all recorded events were true events. Of the real events, 51.2% were apneas of 16-20 seconds. No significant differences were found in overall duration of monitoring between documented and nondocumented monitors. In the premature infants, the duration of monitoring was significantly reduced in those infants found to have no true episodes over those with real events at home. Readmission for ALTE was reduced in infants with documented monitors. Premature infants without events were monitored an average of 24 fewer days (P=0.03). Computerized monitor downloads were found to be equally, if not more, sensitive than pneumograms in evaluating infants for monitor discontinuation. Documented monitoring offers a viable alternative to traditional monitoring and pneumograms in assisting clinicians and families in evaluating their infants progress. By accurately assessing compliance, distinguishing true from false alarms, and decreasing the need for pneumograms, these devices provide valuable information to clinicians and families.

Setting roller pump occlusion with the transonic HT109 flowmeter.

Setting the occlusion of a roller pump may be facilitated using the Transonic HT109 Ultrasonic Flowmeter (Transonic Systems, Inc., Ithaca, NY) with non-invasive transducer. The process addresses the need to set occlusion quickly and accurately before initiation of extracorporeal membrane oxygenation (ECMO). This can be performed with the circuit tubing before blood prime and does not require opening the fluid filled ECMO apparatus to air. The principle is based on the fact that fluid flow through the tubing will change with roller occlusion. Using the Transonic flowmeter, a pre determined (partially occlusive) setting can be achieved by first determining the point of total occlusion, then decreasing occlusion a small percentage from this maximum (i.e., total) occlusion. Clinical application in 35 neonatal ECMO cases has shown the practice to be safe, reliable, and efficient.

Progression of pulmonary cystic disease during ECMO

Only one of the 65 ECMO patients treated at Thomas Jefferson University Hospital to date has shown progression of pulmonary parenchymal cystic change on serial portable chest radiographs while on ECMO. The radiographic and clinical findings of this unique case are presented.