464
Clinical and laboratory observations
direct calorimetry for subjects receiving ventilatory support is mostly flawed by an underestimation of minute ventilation and therefore of Vo2 and VQCO29;this happens because of leaks in the system, especially around the endotracheal tube. Our study results do not contradict the values reported by others, because Vo2 measured in the two sickcst infants, who later died, was comparable to published findings in patients with BPD who had a poor clinical outcome. 2 The period of observation was too short to evaluate the impact of this hypermetabolism on growth rate. This study documents the start of hypermetabolism early in the disease process in infants with BPD. The cause of this hypermetabolism remains to be explored. The relationship with the ventilatory index suggests a stress caused by mechanical ventilation that could induce the release of a factor stimulating energy metabolism. One could speculate that with levels of Vo2 so high, intervals of inadequate oxygen supply at the cellular level could stimulate catecholamine release. I~ It seems important to enlarge our understanding of the relationships among energy expenditure, oxygen supplementation, and growth in patients with BPD. REFERENCES
1. Weinstein MR, Oh W. Oxygen consumption in infants with bronchopulmonary dysplasia. J PEr)rATR 1981;99:958-61.
The Journal of Pediatrics March 1992
2. Kurzner SI, Garg M, Bautista DB, Sargent CW, Bowman MC, Keens TG. Growth failure in bronchopulmonary dysplasia: elevated metabolic rates and pulmonary mechanics. J PEDIATR 1988;112:73-80. 3. Kao LC, Durand D J, Nickerson BG. Improving pulmonary function does not decrease oxygen consumption in infants with bronchopulmonary dysplasia. J P~DIATR 1988;112:615-21. 4. Mayfield SR. Technical and clinical testing of a computerized indirect calorimeter for use in mechanically ventilated neonates. Am J Clin Nutr 1991;54:30-4. 5. Piedboeuf B, Chessex P, Hazan J, Pineault M, Lavoie JC. Total parenteral nutrition in the newborn infant: energy substrates and respiratory gas exchange. J PEDIATR1991;118:97102. 6. Merritt TA, Hallman M, Bloom BT, et al. Prophylactic treatment of very premature infants with human surfactant, N Engl J Med 1986;315:785-90. 7. Draper NR, Smith H. Applied regression analysis. 2nd ed. New York: Wiley & Sons, 1981:193-217. 8. Hazan J, Chessex P, Piedboeuf B, Bourgeois M, Bard H, Long W. Energy expenditure during synthetic surfactant replacement therapy for neonatal respiratory distress syndrome. J PEDIATR 1992;120:$29-33. 9. Dietrich KA, Romero MD, Conrad SA. Effects of gas leak around endotracheal tubes on indirect calorimetry measurement. JPEN J Parenter Enteral Nutr 1990;14:408-13. 10. Connett R J, Honing CR, Gayeski TEJ, Brooks GA. Defining hypoxia: a systems view of "V'o2,glycolysis, energetics, and intracellular Po 2. J Appl Physiol 1990;68:833-42.
Auditory brain-stem responses in neonates receiving extracorporeal membrane oxygenation Daniel C, P a c c i o r e t t i , MS, CCC-A, M e r e d i t h M a g a t h a n Haluschak, MS, CCC-A, Nell N. Finer, MD, FRCP(C), C. M. T. Robertson, MD, FRCP(C), K. S. Pain, PhD, a n d Marian Hagler, MS, CCC-A From the Audiology Centre, Vancouver Health Department, Vancouver, and the Departments of Audiology and Research Servicesand the Neonatal Follow-up Clinic, Glenrose Rehabilitation Hospital, the Royal Alexandra Hospital, and the Universityof Alberta, Edmonton, Alberta, Canada
Auditory brain-stem responses from 25 neonates treated with extracorporeal membrane oxygenation were c o m p a r e d with those of 11 control subjects. Results revealed no statistically significant differences for recorded responses, either between ears or between groups. We conclude that infants who receive extracorporeal membrane oxygenation, with or without carotid artery repair, are not at greater risk for auditory brain-stem dysfunction than similar infants who do not receive extracorporeal membrane oxygenation. (J PEDIATR 1992; 120:464-7) Supported by the Glenrose Rehabilitation and Royal Alexandra Hospitals and the Northern and Central Perinatal Program, Edmonton, Alberta, Canada. 9/24/34959
Submitted for publication Sept. 23, 1991; accepted Nov. 12, 1991. Reprint requests: Daniel Paccioretti, MS, CCC-A, Vancouver Health Department, Audiology Centre, Suite 250, 555 W. 12th Ave., Vancouver, British Columbia V5Z 3X7, Canada.
Volume 120 Number 3
ABR ECMO ECMO-n ECMO-r nHL non-ECMO PPHN
Clinical and laboratory observations
Auditory brain-stem response Extracorporeal membrane oxygenation ECMO-carotid artery not repaired ECMO-carotid artery repaired Normal hearing level Control group of infants not receiving ECMO Persistent pulmonary hypertension of the newborn
Ligation of the carotid artery and jugular vein poses a theoretic risk to the patient who requires extracorporeal membrane oxygenation. Neurologic injury, as well as sensorineural hearing loss, could occur as a result of the severe hypoxemia or altered blood supply, l, 2 Schumacher et al. 3 found that infants receiving ECMO had a significantly higher incidence of prolonged left ear III to V interpeak wave latencies (thought to originate from the right brain stem) than that found in the right ear on auditory brainstem response testing. They postulated that relative ischemia of the auditory nuclei occurs as a result of rightsided carotid artery ligation and a subsequent vascular "steal" from the vertebrobasilar system. Matsumoto et al. 4 demonstrated that, at the time of right common carotid artery ligation, collateral flow was immediately established in the right middle cerebral artery distribution and that, although there was some initial decrease, cerebral systolic velocity increased toward preligation levels within minutes. The purpose of this study was to evaluate the ABR of survivors of ECMO, with and without carotid artery repair. We hypothesized that survivors of neonatal ECMO would have a significant asymmetry between ears for the ABR and a higher incidence of prolonged interpeak wave latencies than that found in a control group of infants not receiving ECMO. We also hypothesized that infants who had carotid artery repair performed after decannulation would be distinguished from infants who had not had repair on evaluation of the right versus left ABR.
METHODS Study population. All neonates who received ECMO in the first 19 months of the program were included in this studyl The ABRs were measured in 25 infants receiving neonatal ECMO, 11 (8 male) with permanent ligation of the right common carotid artery and internal jugular vein, and 14 (8 female) who had carotid artery repair. The criteria for ECMO were as follows: gestational age >35 weeks, reversible eardiopulmonary disease, normal findings on a cranial ultrasonogram (no more than a grade I intraventricular hemorrhageS), three oxygen indexes of 40 or greater in a 2-hour interval,6 and parental consent. None of the subjects studied had any evidence of craniofacial anomalies or family history of neurosensory hearing loss. Diagnoses
4 65
included meconium aspiration (14), primary persistent pulmonary hypertension (11), congenital diaphragmatic hernia (5), asphyxia (4), septicemia (2), hydrops fetalis (2), pneumonia (1), streptococcal pneumonia (1), and shock (1). A non-ECMO control group of 11 infants (7 male) consecutively chosen was studied for comparison. These infants had adjusted postconceptional ages of 38 weeks or more, birth weight of 2 kg or greater, severe respiratory disease requiring mechanical ventilation for at least 48 hours, and the need for an inspired oxygen fraction of 1 and a mean airway pressure of at least 18 cm H20. These infants had at least one oxygen index >25 and did not have recognized severe hypoxic-ischemic encephalopathy (Sarnat stage III). 7 Principal diagnoses included meconium aspiration (6), hyaline membrane disease (2), congenital diaphragmatic hernia (1), persistent pulmonary hypertension of the newborn (1), and pneumonia (1). All subjects were evaluated for ABR before discharge. Test results were recorded by a Nicolet CA 1000 Clinical Averager (Nicolet Instruments, Madison, Wis.). The signal used to elicit the ABR was a 0.1 msec, alternating polarity, unfiltered click, which was presented at a rate of 31.1 clicks/sec. The click was delivered monaurally through insert tubephones (Nicolet TIP-300; Nicolet Instruments). Click intensity was calibrated in decibels with regard to normal bearing level (dB nHL). All responses were compared against this institution's clinical norms, which when compared against published norms s were not significantly different for a similar population. Data collection. Single-channel recordings were obtained from a three-electrode array: vertex to earlobe, with the contralateral earlobe serving as ground. Responses were averaged for 2000 sweeps with a 15 msec time base at 70 and 35 dB nHL. Each response measurement was replicated. The electroencephalographic input was band-pass filtered from 150 to 3000 Hz. Absolute and interpeak latencies for replicated responses were measured for waves I, III, and V. The responses were then compared for rightleft differences and for deviation from standardized clinical norms. Data analysis. The ABRs were analyzed first in the conventional manner, by measuring the response ipsilateral to the side of stimulation for peak and interpeak wave latencies for waves I, III, and V, and then by the method of Schumacher et al. 3 The latter method is based on the model in which waves I and II and at least part of wave III are generated ipsilateral to the stimulation by the auditory nerve and brain stem and waves IV and V are generated by the brain stem contralateral to the stimulation.9 Thus the interpeak wave latency of I to III is combined with the contralaterally stimulated ear's III to V interpeak latency to establish the I to V interpeak latency generated from the right or left brain stem.
466
Clinical and laboratory observations
The Journal of Pediatrics March 1992
T a b l e . Right versus left conventional and anatomic interpeak latencies for E C M O and n o n - E C M O groups C o n v e n t i o n a l ABR measurements Group
ECMO-n (n = 11) ECMO-r (n = 14) non-ECMO (n = l l)
Ear
R L R L R L
I-III
2.90 2.86 2.74 2.88 2.70 2.66
_+ 0.38 _+ 0.35 _+ 0.30 _+ 0.16 _+ 0.29 _+ 0.29
A n a t o m i c ABR m e a s u r e m e n t s
III-V
2.26 2.30 2.45 2.40 2.38 2.48
_+ 0.24 _+ 0.30 _+ 0.21 _+ 0.27 _+ 0.26 + 0.30
I-V
5.19 5.16 5.22 5.29 5.13 5.14
Left brain stem I-V (I-III L + III-V R)
Right brain stem I-V (I-III R + III-V L)
5.12 _+ 0.42
5.20 ___0.4l
5.34 _+ 0.31
5.14 +__0.49
5.08 _+ 0.33
5.19 ___0.44
_+ 0.45 + 0.39 _+ 0.36 _+ 0.38 _+ 0.39 _+ 0.35
All measurements in milliseconds. ECMO-n, Carotid artery not repaired; ECMO-r, carotid artery repaired; non-ECMO, control subjects.
The "pass" criteria used for analyzing the infants' ABRs were as follows: (1) for normal peripheral sensitivity, replicated response at 35 dB nHL; and (2) for normal brainstem transmission time, peak and interpeak latencies within 2 SD from the mean for adjusted chronologic age at 70 dB n H L for waves I, III, and V. Data were analyzed with a series of 2 x 3 (ear x group) analyses of variance, w i t h " e a r " used as a repeated measure. RESULTS Replicable responses with good waveforrn shape were recorded for all infants. Although minor differences were noted between ears for some infants in both the E C M O - n and E C M O - r groups, the differences did not reach statistical significance for any of the interpeak measures. There were no significant right versus left side differences for the n o n - E C M O control group (Table). The results of the anatomic right side versus left side model indicated no statistically significant differences between the right and left brain-stem transmission times. The interpeak latencies I to V, I to III, and III to V were scored as exceeding clinical norms if they were >_2 S D from the mean. To make a comparison with the study by Schumaeher et al., 3 we also evaluated results at 1 SD from the mean. The percentages of infants with values more than 1 and 2 S D of their age-appropriate comparison groups were determined for all three subgroups: Comparison at 1 SD indicated that values for 6 (54.5%) of the 11 E C M O - n subjects, 5 (35.7%) of the 14 E C M O - r subjects, and 5 (45.5%) of the 11 n o n - E C M O subjects exceeded clinical norms for at least one of the interpeak measures. Comparison at 2 S D indicated that values for 2 (18.2%) of the 11 E C M O - n subjects, 2 (14.3%) of the 14 E C M O - r subjects, and 1 (9.1%) of the 11 n o n - E C M O subjects exceeded clinical norms. Chi-square analysis indicated no statistical differences among the three subgroups. As determined by the established standards for peripheral sensitivity, 2 (18.2%) of the 11 E C M O - n subjects had
a unilaterally elevated sensitivity (one elevated in the right ear and one elevated in the left ear). The A B R test results for these two subjects at 70 dB n H L showed prolonged absolute wave latencies with normal interpeak wave latencies, consistent with a middle ear conductive component. Follow-up medical and audiologic evaluations subsequently indicated no chronic middle ear abnormality, and normal hearing sensitivity was found by behavioral audiometry. All other subjects in the study population met the peripheral sensitivity criterion. DISCUSSION In this study none of the infant groups had any significant differences in interpeak latencies between right and left ears, nor were there any significant differences among group means. There were no significant differences in the proportions of the groups that had interpeak wave latencies exceeding clinical norms by 1 or 2 SD. The percentages of infants with interpeak prolongations that were more than 1 and 2 SD from the norm are similar to those noted by Schumacher et al. 3 and are consistent with results of studies indicating prolonged interpeak latencies associated with perinatal asphyxia, a~ It would appear from the data, however, that the prolongations noted were associated with asphyxia common to all the groups rather than being the result of having undergone either the E C M O procedure or carotid artery ligation. This study did not show the prolongation of the III to V interpeak latency generated from the left ear or a I to V interpeak latency asymmetry for the anatomic A B R model reported by Schumacher et al, 3 As reported by Matsumoto et al., 4 collateral flow is established instantaneously at the moment of ligation and is further augmented shortly thereafter; it is therefore not surprising that no marked asymmetry wotild be shown by ABR. Although our findings do not agree with those of Schumacher et al., 3 those authors did state that their right-left differences should be viewed with caution and that the ef-
Volume 120 Number 3
fects of respiratory failure without E C M O on right-left differences in ABR require further study. The populations of these two studies may also differ in the causes of the conditions treated and the severity of the hypoxemia. The numbers of subjects both in this study and in the study by Schumacher et al. 3 are small; hence the power t o detect significant differences is low. To our knowledge, our study is the only one to investigate the differences in the ABR between infants who have had carotid artery repair and those who have not. At the time of the study all infants underwent Doppler studies indicating adequate carotid blood flow. Although the number of subjects was small, there were no significant differences or trends among the groups. We conclude that the E C M O procedure does not cause any significant asymmetry or prolongation of interpeak wave lateneies of the ABR. In addition, infants who undergo the E C M O procedure, with or without carotid artery repair, are not at greater risk for auditory brain-stem dysfunction than are control-group infants with lesser degrees of hypoxemia and hypotension. Our results do not provide support for vascular repair of the carotid artery at decannulation. Further long-term evaluations and controlled trials will be necessary to address this issue fully.
REFERENCES
1. Gerkin KP. The high-risk register for deafness. ASHA 1984;26:1%23.
Clinical and laboratory observations
467
2. MacDonald HM, Mulligan JC, Allen AC, Taylor PT. Neonatal asphyxia. I. Relationship of obstetric and neonatal complications to neonatal mortality in 38,405 consecutive deliveries. J PEDIATR1980;96:898-902. 3. Schurnacher RE, Spak C, Kileny PR. Asymmetric brain stem auditory evoked responses in infants treated with extracorporeal membrane oxygenation. Ear Hear 1990;11:359-62. 4. Matsumoto JS, Babcock DS, Brady AS, Weiss RG, Ryckman FG, Hiyama D. Right common carotid artery ligation for extracorporeal membrane oxygenation: cerebral blood flow velocity measurement with Doppler duplex US. Radiology 1990; 175:757-60. 5. Papile L, Burnstein J, Burnstein R, Koffler H. Incidence and evolution of subependymal and intraventricular haemorrhage: a study of infants with birth weight less than 1500 g. J PEDIATR 1978;92:529-34. 6. Bartlett RH, Gazzaniga AB, Huxtable RF, et al. Extracorporeal circulation (ECMO) in neonatal respirator), failure. J Thor Cardiovasc Surg 1977;74:826-33. 7. Sarnat HB, Sarnet MS. Neonatal encephalopathy following fetal distress: a clinical and electroencephalographic study. Arch Neurol 1976;33:696-705. 8. Gorga M, Reiland J, Beauchaine K, Worthington D, Jesteadt W. Auditory brainstem responses from graduates of an intensive care nursery: normal patterns of response. J Speech Hear Res 1987;30:311-8. 9. Moller AR, Janetta PJ. Neural generators of the auditory brainstem response. In: Jacobsen J, ed. The auditory brainstem response. San Diego: College Hill Press, 1984:13-31. 10. Kileny P, Robertson CMT. Neurological aspects of infant hearing assessment. J Otolaryngol 1985;14:34-9. 11. Murray AD. Newborn auditory brainstem evoked responses (ABRs): longitudinal correlates in the first year. Child Dev 1988;59:1542-54.
Clinical and laboratory observations
direct calorimetry for subjects receiving ventilatory support is mostly flawed by an underestimation of minute ventilation and therefore of Vo2 and VQCO29;this happens because of leaks in the system, especially around the endotracheal tube. Our study results do not contradict the values reported by others, because Vo2 measured in the two sickcst infants, who later died, was comparable to published findings in patients with BPD who had a poor clinical outcome. 2 The period of observation was too short to evaluate the impact of this hypermetabolism on growth rate. This study documents the start of hypermetabolism early in the disease process in infants with BPD. The cause of this hypermetabolism remains to be explored. The relationship with the ventilatory index suggests a stress caused by mechanical ventilation that could induce the release of a factor stimulating energy metabolism. One could speculate that with levels of Vo2 so high, intervals of inadequate oxygen supply at the cellular level could stimulate catecholamine release. I~ It seems important to enlarge our understanding of the relationships among energy expenditure, oxygen supplementation, and growth in patients with BPD. REFERENCES
1. Weinstein MR, Oh W. Oxygen consumption in infants with bronchopulmonary dysplasia. J PEr)rATR 1981;99:958-61.
The Journal of Pediatrics March 1992
2. Kurzner SI, Garg M, Bautista DB, Sargent CW, Bowman MC, Keens TG. Growth failure in bronchopulmonary dysplasia: elevated metabolic rates and pulmonary mechanics. J PEDIATR 1988;112:73-80. 3. Kao LC, Durand D J, Nickerson BG. Improving pulmonary function does not decrease oxygen consumption in infants with bronchopulmonary dysplasia. J P~DIATR 1988;112:615-21. 4. Mayfield SR. Technical and clinical testing of a computerized indirect calorimeter for use in mechanically ventilated neonates. Am J Clin Nutr 1991;54:30-4. 5. Piedboeuf B, Chessex P, Hazan J, Pineault M, Lavoie JC. Total parenteral nutrition in the newborn infant: energy substrates and respiratory gas exchange. J PEDIATR1991;118:97102. 6. Merritt TA, Hallman M, Bloom BT, et al. Prophylactic treatment of very premature infants with human surfactant, N Engl J Med 1986;315:785-90. 7. Draper NR, Smith H. Applied regression analysis. 2nd ed. New York: Wiley & Sons, 1981:193-217. 8. Hazan J, Chessex P, Piedboeuf B, Bourgeois M, Bard H, Long W. Energy expenditure during synthetic surfactant replacement therapy for neonatal respiratory distress syndrome. J PEDIATR 1992;120:$29-33. 9. Dietrich KA, Romero MD, Conrad SA. Effects of gas leak around endotracheal tubes on indirect calorimetry measurement. JPEN J Parenter Enteral Nutr 1990;14:408-13. 10. Connett R J, Honing CR, Gayeski TEJ, Brooks GA. Defining hypoxia: a systems view of "V'o2,glycolysis, energetics, and intracellular Po 2. J Appl Physiol 1990;68:833-42.
Auditory brain-stem responses in neonates receiving extracorporeal membrane oxygenation Daniel C, P a c c i o r e t t i , MS, CCC-A, M e r e d i t h M a g a t h a n Haluschak, MS, CCC-A, Nell N. Finer, MD, FRCP(C), C. M. T. Robertson, MD, FRCP(C), K. S. Pain, PhD, a n d Marian Hagler, MS, CCC-A From the Audiology Centre, Vancouver Health Department, Vancouver, and the Departments of Audiology and Research Servicesand the Neonatal Follow-up Clinic, Glenrose Rehabilitation Hospital, the Royal Alexandra Hospital, and the Universityof Alberta, Edmonton, Alberta, Canada
Auditory brain-stem responses from 25 neonates treated with extracorporeal membrane oxygenation were c o m p a r e d with those of 11 control subjects. Results revealed no statistically significant differences for recorded responses, either between ears or between groups. We conclude that infants who receive extracorporeal membrane oxygenation, with or without carotid artery repair, are not at greater risk for auditory brain-stem dysfunction than similar infants who do not receive extracorporeal membrane oxygenation. (J PEDIATR 1992; 120:464-7) Supported by the Glenrose Rehabilitation and Royal Alexandra Hospitals and the Northern and Central Perinatal Program, Edmonton, Alberta, Canada. 9/24/34959
Submitted for publication Sept. 23, 1991; accepted Nov. 12, 1991. Reprint requests: Daniel Paccioretti, MS, CCC-A, Vancouver Health Department, Audiology Centre, Suite 250, 555 W. 12th Ave., Vancouver, British Columbia V5Z 3X7, Canada.
Volume 120 Number 3
ABR ECMO ECMO-n ECMO-r nHL non-ECMO PPHN
Clinical and laboratory observations
Auditory brain-stem response Extracorporeal membrane oxygenation ECMO-carotid artery not repaired ECMO-carotid artery repaired Normal hearing level Control group of infants not receiving ECMO Persistent pulmonary hypertension of the newborn
Ligation of the carotid artery and jugular vein poses a theoretic risk to the patient who requires extracorporeal membrane oxygenation. Neurologic injury, as well as sensorineural hearing loss, could occur as a result of the severe hypoxemia or altered blood supply, l, 2 Schumacher et al. 3 found that infants receiving ECMO had a significantly higher incidence of prolonged left ear III to V interpeak wave latencies (thought to originate from the right brain stem) than that found in the right ear on auditory brainstem response testing. They postulated that relative ischemia of the auditory nuclei occurs as a result of rightsided carotid artery ligation and a subsequent vascular "steal" from the vertebrobasilar system. Matsumoto et al. 4 demonstrated that, at the time of right common carotid artery ligation, collateral flow was immediately established in the right middle cerebral artery distribution and that, although there was some initial decrease, cerebral systolic velocity increased toward preligation levels within minutes. The purpose of this study was to evaluate the ABR of survivors of ECMO, with and without carotid artery repair. We hypothesized that survivors of neonatal ECMO would have a significant asymmetry between ears for the ABR and a higher incidence of prolonged interpeak wave latencies than that found in a control group of infants not receiving ECMO. We also hypothesized that infants who had carotid artery repair performed after decannulation would be distinguished from infants who had not had repair on evaluation of the right versus left ABR.
METHODS Study population. All neonates who received ECMO in the first 19 months of the program were included in this studyl The ABRs were measured in 25 infants receiving neonatal ECMO, 11 (8 male) with permanent ligation of the right common carotid artery and internal jugular vein, and 14 (8 female) who had carotid artery repair. The criteria for ECMO were as follows: gestational age >35 weeks, reversible eardiopulmonary disease, normal findings on a cranial ultrasonogram (no more than a grade I intraventricular hemorrhageS), three oxygen indexes of 40 or greater in a 2-hour interval,6 and parental consent. None of the subjects studied had any evidence of craniofacial anomalies or family history of neurosensory hearing loss. Diagnoses
4 65
included meconium aspiration (14), primary persistent pulmonary hypertension (11), congenital diaphragmatic hernia (5), asphyxia (4), septicemia (2), hydrops fetalis (2), pneumonia (1), streptococcal pneumonia (1), and shock (1). A non-ECMO control group of 11 infants (7 male) consecutively chosen was studied for comparison. These infants had adjusted postconceptional ages of 38 weeks or more, birth weight of 2 kg or greater, severe respiratory disease requiring mechanical ventilation for at least 48 hours, and the need for an inspired oxygen fraction of 1 and a mean airway pressure of at least 18 cm H20. These infants had at least one oxygen index >25 and did not have recognized severe hypoxic-ischemic encephalopathy (Sarnat stage III). 7 Principal diagnoses included meconium aspiration (6), hyaline membrane disease (2), congenital diaphragmatic hernia (1), persistent pulmonary hypertension of the newborn (1), and pneumonia (1). All subjects were evaluated for ABR before discharge. Test results were recorded by a Nicolet CA 1000 Clinical Averager (Nicolet Instruments, Madison, Wis.). The signal used to elicit the ABR was a 0.1 msec, alternating polarity, unfiltered click, which was presented at a rate of 31.1 clicks/sec. The click was delivered monaurally through insert tubephones (Nicolet TIP-300; Nicolet Instruments). Click intensity was calibrated in decibels with regard to normal bearing level (dB nHL). All responses were compared against this institution's clinical norms, which when compared against published norms s were not significantly different for a similar population. Data collection. Single-channel recordings were obtained from a three-electrode array: vertex to earlobe, with the contralateral earlobe serving as ground. Responses were averaged for 2000 sweeps with a 15 msec time base at 70 and 35 dB nHL. Each response measurement was replicated. The electroencephalographic input was band-pass filtered from 150 to 3000 Hz. Absolute and interpeak latencies for replicated responses were measured for waves I, III, and V. The responses were then compared for rightleft differences and for deviation from standardized clinical norms. Data analysis. The ABRs were analyzed first in the conventional manner, by measuring the response ipsilateral to the side of stimulation for peak and interpeak wave latencies for waves I, III, and V, and then by the method of Schumacher et al. 3 The latter method is based on the model in which waves I and II and at least part of wave III are generated ipsilateral to the stimulation by the auditory nerve and brain stem and waves IV and V are generated by the brain stem contralateral to the stimulation.9 Thus the interpeak wave latency of I to III is combined with the contralaterally stimulated ear's III to V interpeak latency to establish the I to V interpeak latency generated from the right or left brain stem.
466
Clinical and laboratory observations
The Journal of Pediatrics March 1992
T a b l e . Right versus left conventional and anatomic interpeak latencies for E C M O and n o n - E C M O groups C o n v e n t i o n a l ABR measurements Group
ECMO-n (n = 11) ECMO-r (n = 14) non-ECMO (n = l l)
Ear
R L R L R L
I-III
2.90 2.86 2.74 2.88 2.70 2.66
_+ 0.38 _+ 0.35 _+ 0.30 _+ 0.16 _+ 0.29 _+ 0.29
A n a t o m i c ABR m e a s u r e m e n t s
III-V
2.26 2.30 2.45 2.40 2.38 2.48
_+ 0.24 _+ 0.30 _+ 0.21 _+ 0.27 _+ 0.26 + 0.30
I-V
5.19 5.16 5.22 5.29 5.13 5.14
Left brain stem I-V (I-III L + III-V R)
Right brain stem I-V (I-III R + III-V L)
5.12 _+ 0.42
5.20 ___0.4l
5.34 _+ 0.31
5.14 +__0.49
5.08 _+ 0.33
5.19 ___0.44
_+ 0.45 + 0.39 _+ 0.36 _+ 0.38 _+ 0.39 _+ 0.35
All measurements in milliseconds. ECMO-n, Carotid artery not repaired; ECMO-r, carotid artery repaired; non-ECMO, control subjects.
The "pass" criteria used for analyzing the infants' ABRs were as follows: (1) for normal peripheral sensitivity, replicated response at 35 dB nHL; and (2) for normal brainstem transmission time, peak and interpeak latencies within 2 SD from the mean for adjusted chronologic age at 70 dB n H L for waves I, III, and V. Data were analyzed with a series of 2 x 3 (ear x group) analyses of variance, w i t h " e a r " used as a repeated measure. RESULTS Replicable responses with good waveforrn shape were recorded for all infants. Although minor differences were noted between ears for some infants in both the E C M O - n and E C M O - r groups, the differences did not reach statistical significance for any of the interpeak measures. There were no significant right versus left side differences for the n o n - E C M O control group (Table). The results of the anatomic right side versus left side model indicated no statistically significant differences between the right and left brain-stem transmission times. The interpeak latencies I to V, I to III, and III to V were scored as exceeding clinical norms if they were >_2 S D from the mean. To make a comparison with the study by Schumaeher et al., 3 we also evaluated results at 1 SD from the mean. The percentages of infants with values more than 1 and 2 S D of their age-appropriate comparison groups were determined for all three subgroups: Comparison at 1 SD indicated that values for 6 (54.5%) of the 11 E C M O - n subjects, 5 (35.7%) of the 14 E C M O - r subjects, and 5 (45.5%) of the 11 n o n - E C M O subjects exceeded clinical norms for at least one of the interpeak measures. Comparison at 2 S D indicated that values for 2 (18.2%) of the 11 E C M O - n subjects, 2 (14.3%) of the 14 E C M O - r subjects, and 1 (9.1%) of the 11 n o n - E C M O subjects exceeded clinical norms. Chi-square analysis indicated no statistical differences among the three subgroups. As determined by the established standards for peripheral sensitivity, 2 (18.2%) of the 11 E C M O - n subjects had
a unilaterally elevated sensitivity (one elevated in the right ear and one elevated in the left ear). The A B R test results for these two subjects at 70 dB n H L showed prolonged absolute wave latencies with normal interpeak wave latencies, consistent with a middle ear conductive component. Follow-up medical and audiologic evaluations subsequently indicated no chronic middle ear abnormality, and normal hearing sensitivity was found by behavioral audiometry. All other subjects in the study population met the peripheral sensitivity criterion. DISCUSSION In this study none of the infant groups had any significant differences in interpeak latencies between right and left ears, nor were there any significant differences among group means. There were no significant differences in the proportions of the groups that had interpeak wave latencies exceeding clinical norms by 1 or 2 SD. The percentages of infants with interpeak prolongations that were more than 1 and 2 SD from the norm are similar to those noted by Schumacher et al. 3 and are consistent with results of studies indicating prolonged interpeak latencies associated with perinatal asphyxia, a~ It would appear from the data, however, that the prolongations noted were associated with asphyxia common to all the groups rather than being the result of having undergone either the E C M O procedure or carotid artery ligation. This study did not show the prolongation of the III to V interpeak latency generated from the left ear or a I to V interpeak latency asymmetry for the anatomic A B R model reported by Schumacher et al, 3 As reported by Matsumoto et al., 4 collateral flow is established instantaneously at the moment of ligation and is further augmented shortly thereafter; it is therefore not surprising that no marked asymmetry wotild be shown by ABR. Although our findings do not agree with those of Schumacher et al., 3 those authors did state that their right-left differences should be viewed with caution and that the ef-
Volume 120 Number 3
fects of respiratory failure without E C M O on right-left differences in ABR require further study. The populations of these two studies may also differ in the causes of the conditions treated and the severity of the hypoxemia. The numbers of subjects both in this study and in the study by Schumacher et al. 3 are small; hence the power t o detect significant differences is low. To our knowledge, our study is the only one to investigate the differences in the ABR between infants who have had carotid artery repair and those who have not. At the time of the study all infants underwent Doppler studies indicating adequate carotid blood flow. Although the number of subjects was small, there were no significant differences or trends among the groups. We conclude that the E C M O procedure does not cause any significant asymmetry or prolongation of interpeak wave lateneies of the ABR. In addition, infants who undergo the E C M O procedure, with or without carotid artery repair, are not at greater risk for auditory brain-stem dysfunction than are control-group infants with lesser degrees of hypoxemia and hypotension. Our results do not provide support for vascular repair of the carotid artery at decannulation. Further long-term evaluations and controlled trials will be necessary to address this issue fully.
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