April 1980
TheJournalofPEDIATRICS
731
Auditory function in newborn intensive care unit patients revealed by auditory brain-stem potentials The relations between clinical illness and auditory response (as revealed by auditoey brain-stem potentials) were ~rospectively studied in a neonatal intensive care unit. Forty-nine tests were performed on 29 infants With gestational age 24 to L13 weeks and birth weight 530 io 3,380 gin. Auditory test results were classified as pass or fail, depending on the presence or absence o f wave V at a latency o f 7 to 11 ms in response to clicks 60 dB above the normal adult threshold. Six patients failed and 23 patients passed. The failures were not correlated with excessive noise exposure or ototoxic medication. Five of the patients who failed had intracranial hemorrhage. Routine screening o f infants in the NICU for auditory impairment is a clinically feasible and useful proceaure.
Richard E. Marshall, M.D.,* Timothy J. Reichert, M.D., Suzanne M. Kerley, B.S, and Hallowell Davis, M.D.,** St. Louis, Mo.
A SIMPLE METHOD of auditory screening of neonates by evoked brain-stem potentials has been described by Schulman-Galambos and Galambos. 1, 2 These authors report that about 20% of the infants leaving a neonatal intensive care unit have a significant auditory impairment. Two subsequent studies, by Despland and Galambos 3 and by Benitez et al, 4 have confirmed this surprisingly high incidence of impairment. We have replicated these studies in an exploratory proslJective study, evaluating auditoPy and neurologic function in 29 NICU patients by means of brain-stem electric response audiometry. We have incidentally tested certain hypotheses concerning risks to hearing in the NICU. Our specific questions, separate but related, were (1) Is the auditory screening of neowites in NICU by brain-stem evoked potentials a feasible procedure? (2) Do auditory brain=stem potentials offer a useful method of monitoring
From the Edward Mallinckrodt Department of Pediatrics and the Department of Otolaryngology, Washington University School of Medicine, and the Central Institute for the Deaf *Reprint address: St. Louis Children's Hospital, 500 S. Kingshighway, P.O. Box 14871, St. Louis, MO 63178. **Supported by a United States Public Health Service, Department of Health, Education and Welfare research grant NS03856 from the National Institute of Neurological and Communicative Disorders and Stroke to Central Institute for the Deaf
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the condition of critically ill neonates? (3) Do enough infants fail the auditory test to justify screening and f011ow-up testing as a routine procedure? (4) Are there identifiable special risks to hearing in the NICU, notably excessive noise exposure and/or medication with ototoxic drugs? (5) Among the infants who fail the test, can any common risk factor be identified? Abbreviations used NICU: neonatal intensive care unit nHL: normal hearing listeners ERA: electricresponse audiometry CAT: computerized axial tomography SPL: sound pressure levels INSTRUMENTS
AND METHODS
Auditory brain-stem potentials were recorded with a Nicolet CA 1800 unit that was temporarily available to us. Three Beckman miniature electrodes were placed on the head, one on each mastoid area and one in the middle of the forehead at the hairline. Wideband click stimuli were presented to each ear in turn at a rate of about 37/second. The infants were quiet during the test, ~with the head turne d sidewayS. The earphone rested lightly on or was hand-held Over the exposed ear. A total of 2,000 and sometimes 4,000 responses were averaged for each trial, and each trial was replicated at least once and often two or three times to ensure reproducibility. Each ear was tested
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The Journal of Pediatrics
April 1980
dt~ nHL
60
3O )
~0
30 9.16 10.3
E~2000 Figure. Brainstem responses of two babies, A and B. In each case,
the upper pair of tracings shows responses to 60 dB clicks, the lower pair to 30 dB clicks at 37.1/second. Duration of trace = 15.0 msec. The latencies were measured on line, using the cursor and digital read-out of the Nicolet CA 1800 instrument. Upward excursion indicates Scalp more negative relative to ear lobe. The downward excursions at about 8.8 msec in the upper traces and at 9.57 to 10.3 msec in the lower traces are identified as the Jewett V wave. The prominent earlier wave in the upper traces at about 6.0 msec is Jewett III. It is barely visible at about 7.5 msec in the lower tracings.
first at 60 dB nHL (i.e., relative to normal adult threshold, as determined by a jury of six otologically normal listeners). If the averaged response, illustrated in the Figure, viewed on the oscilloscope and written out on the X-Y plotter, was seen at 60 dB, the next trials were at 30 dB nHL and, often if necessary, at 40 dB. If no responses appeared at 60 dB, additional trials at 70 or 80 dB were usually added. This routine of testing generally follows that recommended by Schulman-Galambos and Galambos?' ~ Some minor practical difficulties from electrical interference from other NICU equipment and from failure of some infants to sleep quietly were encountered, but the
test routine proved to be feasible. It requires less than an hour to administer. A more complete analysis of the difficulties, of the responses of impaired ears to click stimuli, and of appropriate criteria for auditory screening will be published elsewhere when follow-up studies of some of the surviving infants who failed these screening tests are available. The present study centers on the infants who failed at the 60 dB level. The protocol to study auditory function in NICU patients was approved by the Human Experimentation Committee of Washington University School of Medicine. Informed consent was obtained from at least one parent for each subject. All infants were studied in the NICU at St. Louis Children's Hospital. Two major rooms comprise the NICU; the larger room has space for 20 patients and contains new admissions and acutely ill patients. A smaller area with space for nine beds is occupied by less acutely ill patients. Some-tests were conducted in an adjacent treatment room. Three types of beds are used within the unit: the Ohio Intensive Care Unit (known as :the open bed), the dosed Air Shields Isolettes, and the traditional open bassinet. All of the patients admitted to the NICU during the period from July 6, 1978, to July 25, 1978, for whom parental consent was obtained were tested by ERA. Each patient enrolled in the study was examined by the senior author (R. E. M.) who completed a data sheet that included the following information: birth weight, gesta tional age, clinical diagnosis, respiratory measurements (including gas values obtained closest to the time of the hearing test), and total antibiotics given by the time of the test. Data were also collected, between the first and second auditory tests, that included the highest and lowest values of pH, Paeo2 and Pao~ in the interval between tests. The clinical diagnosis of intracranial hemorrhage was confirmed by either CAT scan or autopsy in every case. Otoscopic examinations were not completed on every child. RESULTS B r a i n s t e m responses. Most of the infants gave clear brain-stem responses at 60 dB nHL (Figure). The peak (positive) latencies were noted, and were found c~mpatible with the limits given by Start et al 5 that relate peak latencies to gestational age and also t o intensity? The range was 7 to 11 msec for wave V. Ever~ if the latencies agreed with expectations, however, a response was not accepted as positive unless it was reasonably replicated on a second, third, or fourth trial. The responses at 30 dB nHL were smaller and latencies longer ( = 10 msec), and about half of the trials were judged negative. Increase of intensity to 40 dB nHL, however, often elicited a clear
Volume 96 Number 4 response. We attributed many of the failures at 30 dB to partial or complete masking of the clicks by the ambient noise in ICU. Reproducibility rather than a particular latency has been our major criterion, because of the strong dependence of latency on gestational age in the perinatal period. Scoring. About half of the tests were originally judged on line by the fourth author (H. D.). The others were judged on the basis of the write-out records, with only the gestafional age and click intensities as additional information. The final classification was made on a second review of all of the records. In a few of the borderline cases in which muscle or electrical artifacts had interfered, the original judgment was reversed, but because of the exploratory character of the study and frequent minor variations in routine in the early tests, we have not analyzed the scoring statistically. The test was scored as a screening test. "Pass" means at least a probable (but confirmed) response from one ear (and usually both), on the test administered at 60 dB nHL. Forty-nine technically satisfactory tests were performed on 29 infants. Among the 29, six were judged to have failed the test at least once. The other 23 infants were classified as having passed this auditory screening test. Clinical factors. The Table shows factors for the groups that passed and failed and the significance of any differences for these factors. Birth weight and gestational age, with standard deviations, are shown and were compared by means of a t test. Mortality, hyaline membrane disease, respiratory requirements, and presence of intracranial hemorrhage were compared by means of the Fisher exact test. As can be seen in the Table, the small, sicker infants failed the test in general, whereas the larger, healthier infants passed. However, many of the infants who failed the test were critically ill when they were studied. Prior to the testing it was thought that some infants might fail this test shortly after admission and pass as they recuperated. The data do not support that hypothesis. There were 21 repeat examinations and in all but one case the initial results were confirmed on the repeat examinations. However, the intervals between tests did not exceed one week except in two instances. Perhaps longer intervals would have revealed changes in test status. One patient did show a change in auditory function that apparently was related to an intracranial hemorrhage. She was the first of twins and weighed 960 gm, with an estimated gestational age of 26 weeks. She was apneic shortly after birth and was placed on the respirator. Sepsis was suspected and the patient was given ampicillin and kanamycin after blood, urine, and cerebrospinal fluid cultures had been obtained. On day 3 of life, bloody cerebrospinal fluid was obtained.
A uditory function in NICU
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Table
n Birth weight (gm) Gestational age (wk) Mortality Hyaline membrane disease Respirator required Intracranial hemorrhage
I
Fail
I
Pass
Significance of difference
6 830 _+ 177 25.6 _+ 1.7
23 2,260 _+ 760 35.0 _+ 4.0
P < 0.01 P < 0.01
67% (4/6) 83% (5/6)
4.4% (1/23) 70% (16/23)
P < 0.01 NS
83% (5/6)
26% (6/23)
P < 0.05
83% (5/6)
9% (2/23)
P < 0.001
On day 4, at 860 gm, she passed the initial screening test. A CAT scan, taken on day 5, revealed a mild intracranial hemorrhage. However, the baby was described as active and responsive with a flat anterior fontanel through days 3, 4, and 5. On day 7, at 760 gin, she failed a second auditory test. At the time of the second test, she was lethargic and within ten hours she had seizures and a dramatic fall in hematocrit, blood pressure, and blood pH. It was the clinical impression that the baby had sustained a major intracranial bleed. No association between hypoxia, hypercapnea, or acidosis and test passage or failure could be demonstrated. The relations between blood gas determinations and auditory evaluations in groups that passed and failed were examined. The results were compared by a t test and none was found significant (P = 0.05). This is contrary to the result reported by Despland and Galambos,3 who found an almost perfect correlation between asphyxia with acidosis (pH < 7.3) and failure on the screening test at 60 dB. Kanamycin. Kanamycin is a potentially ototoxic drug. The average kanamycin dosage (mg/kg body weight) was compared in those who passed (65.3 _+ 51.7) and those who failed (40.6 + 23.6). Those who passed the hearing evaluation had received significantly more kanamycin (P = 0.001) than those who failed, using a t test. Thus, kanamycin dosage could not be implicated as a factor in our test failures. Sound pressure levels. Measurements of sound pressure level were made with a Brtiel & Kjaer meter, model number 2203. There was little difference in sound pressure levels between the acute care area, where respirators were frequently employed (64-66 dBA), and the area where less ill patients were housed (60-62 dBA). The SPLs were remarkably constant throughout the month in which the study was performed. The SPLs were measured at ran-
734
Marshall et al.
dom throughout the day between 9 AM and 4 eM, as the ERA tests were performed. Nearly all readings were between 62 and 66 dBA SPL. The usual SPL inside the Isolettes was 60-62 dBA, whereas at the open cribs and bassinets it was 64-66 dBA. Note that these levels, expressed as dBA, were measured using the "A" filter network of the sound level meter. This network makes the instrument less sensitive to low-frequency and also to very high-frequency sounds than to middle-frequency sounds, so that its frequency response corresponds quite closely to the threshold sensitivity of the human ear. The frequency response also corresponds to the curve for equal risk of injury by sounds of different frequencies. The safety standards and recommendations of both the Environmental Protection Agency and the Occupational Safety and Health Administration are expressed in dBA. The sound level considered by EPA to involve no risk of injury to hearing, even for continuous exposure, is 75 dBA. 7 Our measurements indicate, therefore, that ambient noise is not a significant hazard in our ICU. DISCUSSION Why do the smaller, younger infants fail the test? At least two possibilities come directly to mind: physiologic immaturity of the small infants and the pathologic severity of the patients' diseases. Starr et aP recently reported studies on infants as young as 28 weeks of gestational age and believed that three brain-stem response wave complexes could be identified if the stimuli were sufficiently strong. Nevertheless, five of our infants who failed were tested also at a level of 80 dB nHL and did not display responses. The second possibility is a very long delay of the wave V complex in young infants who have an associated intracranial disease. For example, Starr et aP report an auditory brain-stem potential in a 1,360 gm infant with a gestational age of 32 weeks who had severe respiratory distress syndrome with intracranial hemorrhage on day 2. The infant developed hydrocephalus and sepsis and was tested on day 22. A response believed to be wave V appeared at 20 msec. Such a patient might have been reported as a test failure by us because our recording "window" was only 15 msec long. On the other hand, we should have detected wave III (see Figure). There may be a relation between abnormalities in auditory brain-stem potentials and intracranial hemorrhage. Five of six of our test failures had associated intracranial hemorrhages. Spector and associates ~recently reported the relation between respiratory distress and intracranial and inner ear hemorrhage. Spector examined consecutively the temporal bones on 52 infants who died either in utero or in the neonatal period. ~ Twenty-eight
The Journal of Pediatrics April 1980
infants died of respiratory distress and 24 of the 28 had central aaervous system hemorrhage. Twenty-three of the 28 also had hemorrhage into the inner ear. Such observations provide an anatomic explanation for our results if one assumes that our patients with intracranial hemorrhage had bleeding into their inner ears and failed the auditory test for that reason. The data in this study support the concept that the sick infants under 1,000 gm are at high risk for auditory impairment. One patient failed the hearing test shortly before clear evidence of a major intracranial hemorrhage became apparent. This observation is intriguing since it suggests that auditory brain-stem potentials may offer an early technique for detecting significant neurologic dysfunction before gross symptoms occur. We can now answer the specific questions posed in the introduction. (1) Auditory screening of neonates in NICU is a technically feasible procedure. (2) The auditory brain-stem potentials might offer a method of monitoring the condition of critically ill neonates. (3) The percentage of surviving infants who failed the auditory screening test (2 of 23 = 9%) justifies further trial of screening and follow-ups. (Actually one of the two surviving "failures" has now been retested at 10 months of age by complete ERA audiometry and found to have a sensorineural impairment sufficient to delay or prevent the development of speech.) (4) Neither noise exposure in ICU nor dosage with kanamycin can be implicated.as hazards to hearing in our series. (5) The only common risk factor to emerge among our infants who failed the test was intracranial hemorrhage: (Four of the six failures died in the ICt3.) We thank Drs. Robert Brouillette, Phillip Dodge, Gershon Spector, Bradley Thach, Joseph Volpe, and Suzanne Wilson for critical evaluation of the manuscript; Dr. Stuart Boxerman for statistical assistance, and Ms. Lois Price for assistance in preparation of the manuscript. REFERENCES
1. Schulman-Galambos C, and Galambos R: Brain stem evoked response audiometry in newborn hearing screening, Arch Otolaryngol 105:86, 1979. 2. Schulman-Galambos C, and Galambos R: Assessment of hearing, in Field T, Sostek M, Goldberg S and Shuman HH, editors: Infants born at risk, New York, 1979, Spectrum Publications, Inc., pp 91-120. 3. Despland P, and Galambo,s R: in Gerber SE and Mencher GT, editors: Early diagnosis of hearing loss, New York, 1978, Grune & Stratton, Inc. 4. Benitez L, Saloman R, and Martinez A: Deafness in high-risk babies; detection by BSER. XIV International Congress of Audiology (Acapulco, Mexico), November, 1978. 5. Starr A, Amlie R, Martin WH, and Sanders S: Develop-
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ment of auditory function in newborn infants revealed by auditory brain stem potential, Pediatrics 60:831, 1977. 6. Hecox K, and Galambos R: Brain stem auditory evoked responses in human infants and adults, Arch Otolaryngol 99:30, 1974. 7. Environmental Protection Agency: Report to the President
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and congress on noise. (In compliance with Title IV of Public Law 91-604: The Clean Air Act Amendments of 1970.) U.S. Government Printing Office, February, 1972. Spector G, Pettit W, Davis G, Strauss M, and Rauchbach E: Fetal respiratory distress causing CNS and inner ear hemorrhage, Laryngoscope 88:764, 1978.
Brief clinical and laboratory observations A new graph for insertion of umbilical artery catheters W. Rosenfeld, M.D.,* d. Biagtan, M.D., H. Sehaeffer, M.D., H. Evans, M.D., S. Flicker, M.D., D. Salazar, M.D., and R. Jhaveri, M.D., Brooklyn, N.Y.
THE LENGTH of insertion for umbilical artery catheters has been based on the graphs tabulated by Dunn 1 for total body length and shoulder umbilical length. Despite frequent use, these graphs have not been critically evaluated and have several potential limitations. They are based on the anatomic landmarks of the pathologist (the diaphragm) rather than those of the clinician (vertebrae). The original study included only eight of 25 patients with TBL _< 40 cm (fiftieth percentile for patients weighing 1,200 gin); and used only postmortem patients. Using live patients and including a larger number of low-birth-weight neonates, we re-evaluated Dunn's graphs. In addition, new graphs for catheterization were calculated and their accuracy determined. METHODS
Eighty-two infants consecutively admitted to our Neonatal Intensive Care Unit requiring umbilical artery catheterization from July, 1978, to December, 1978, were initially included Seven were eliminated because of an abnormal number of ribs (five had 11 ribs, two had 13 ribs). Eighty-eight percent of the patients were premature ~ and 49% had TBL _< 40 cm. All catheterizations were performed by housestaff and fellows using a previously From the Departments of Pediatrics and Radiology, The Jewish Hospital and Medical Center of Brooklyn, The Downstate University School of Medicine. *Reprint address: Department of Pediatrics, Jewish Hospital and Medical Center of Brooklyn, 555 Prospect Place, Brooklyn, NY 11238.
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described method? Standard polyvinyl arterial catheters (Argyle) were employed. Two clinicians performed the catheterization and independently measured TBL and SUL with a standard metric tape. Measurements differing by 0.5 cm or more were repeated until agreement was reached. All measurements were rechecked by one of the neonatologists. Abbreviations used TBL: total body length SUL: shoulder umbilical length The distance the catheter was to be inserted was calculated, using Dunn's graph for TBL and adding the length of the umbilical stump. The actual length of the inserted catheter was calculated by subtracting the distance from the abdominal wall to the first visible radiopaque marking on the catheter (5, 10, or 15 cm) or, if no markings were visible, from the end of the catheter (40.5 cm). The location of the catheter tip was determined by a radiograph of the chest and upper abdomen and verified by the neonatologists and radiologist. Catheters in improper position and catheters associated with complications such as blanching were changed or repositioned. As a result, 107 measurements were made in 75 patients. To determine if a new graph derived from this group of patients would result in more accurate catheter placements, new graphs for all catheters at T, in relation to TBL and SUL and the length of insertion were drawn. Both Dunn's graph and these new graphs for TBL and