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Journal of Perinatology (2007) 27, 291–296
                                                                                           r 2007 Nature Publishing Group All rights reserved. 0743-8346/07 $30
                                                                                           www.nature.com/jp



ORIGINAL ARTICLE
Diagnosis of patent ductus arteriosus by a neonatologist
with a compact, portable ultrasound machine
HC Lee1, N Silverman2 and SR Hintz3
1
 Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University, Palo Alto, CA, USA; 2Department
of Pediatrics, Division of Pediatric Cardiology, Stanford University, Palo Alto, CA, USA and 3Department of Pediatrics, Division
of Neonatal and Developmental Medicine, Stanford University, Palo Alto, CA, USA

                                                                                                 hemorrhage, bronchopulmonary dysplasia and pulmonary
    Objectives: To conduct a pilot study assessing a neonatologist’s accuracy                    hemorrhage.1–5 In a review of periventricular leukomalacia in
    in diagnosing patent ductus arteriosus (PDA) using compact, portable                         preterm infants, PDA was associated with decreased cerebellar
    ultrasound after limited training.                                                           volume, area of the vermis and diameter of the pons.6 The
    Study design: Prospective study of premature infants scheduled for                           frequency of PDA is high in premature infants, ranging from
    echocardiography for suspected PDA. A neonatologist with limited training                    53% in infants born before 34-weeks gestation, up to 65% in
    performed study exams before scheduled exams. Sensitivity and specificity                     infants born before 26-weeks gestation.7,8 PDA in preterm
    were calculated, compared to the scheduled echocardiogram interpreted                        infants often requires pharmacologic or surgical closure.
    by a cardiologist.                                                                           Treatment of PDA has been shown to improve pulmonary function,
                                                                                                 including increase in dynamic compliance, tidal volume and
    Results: There were 24 exams. Compared to the scheduled exam, the
                                                                                                 minute ventilation.9 Early pharmacological treatment has also
    neonatologist’s exam had sensitivity 69% (95% confidence interval (CI),
                                                                                                 been shown to reverse low renal and splanchnic blood flow in
    41 to 89%) and specificity 88% (95% CI, 47 to 99%). When a cardiologist
                                                                                                 infants with PDA.10
    interpreted the study exams, the sensitivity was 87% (95% CI, 60 to 98%)
                                                                                                    Although there are clinical signs for diagnosis of PDA including
    and specificity 71% (95% CI, 29 to 96%).
                                                                                                 auscultation of a cardiac murmur, bounding pulses and wide pulse
    Conclusion: A neonatologist with limited training was able to detect PDA                     pressure, studies have shown that physical exam is inadequate in
    with moderate success. A more rigorous training process or real-time                         detecting significant PDAs in preterm infants.11–13 The current
    transmission with cardiologist interpretation may substantially improve                      standard of care for diagnosis of PDA is an echocardiogram, yet
    accuracy. Institutions with experienced technicians and on-site pediatric                    echocardiography is not routinely taught to neonatologists.
    cardiologists may not gain from intensive training of neonatologists, but                    Nevertheless, it has been suggested that patient care could be
    hospitals where diagnosis and treatment of PDA would be delayed may                          improved in the neonatal intensive care unit (NICU) if
    benefit from such processes.                                                                  neonatologists were trained in echocardiography.14
    Journal of Perinatology (2007) 27, 291–296. doi:10.1038/sj.jp.7211693;                          Advances in technology are allowing echocardiography to be
    published online 15 March 2007                                                               performed by nontraditional personnel in certain settings.
                                                                                                 Ultrasound technology has become more compact, allowing use as
    Keywords: patent ductus arteriosus; echocardiography; neonatologist;
    diagnosis                                                                                    a point-of-care diagnostic tool. A handheld ultrasound was found
                                                                                                 to be effective in the diagnosis of congenital heart disease,
                                                                                                 including PDA.15 In this series, the interpreters were experienced
                                                                                                 echocardiographers. Such devices are being utilized in settings
Introduction
                                                                                                 such as the emergency department and surgical ICUs where a
Patent ductus arteriosus (PDA) in premature infants is an                                        quick, focused evaluation could benefit the patient.16 Neonatal
associated factor in serious neonatal morbidities, associated                                    units may also benefit from small handheld ultrasound devices for
with increased risk of necrotizing enterocolitis, intraventricular                               assessment of umbilical line placement and cerebral blood flow.
Correspondence: Dr SR Hintz, Department of Pediatrics, Division of Neonatal and                     We performed a pilot study to assess the potential utility of a
Developmental Medicine, Stanford University, 750 Welch Road, Suite 315, Palo Alto,               limited training program to diagnose PDA for a neonatologist with
CA 94304, USA.                                                                                   no cardiology background. We used a portable ultrasound
E-mail: srhintz@stanford.edu
Received 5 September 2006; revised 18 December 2006; accepted 10 January 2007; published         machine, one which could potentially be used in small NICUs
online 15 March 2007                                                                             without ready access to a pediatric cardiologist.
Diagnosis of PDA by a Neonatologist
                                                         HC Lee et al
292

Methods                                                                 the treating physician decided that the patient should not be
This was a prospective, masked pilot study of the accuracy of PDA       enrolled for any reason, the scheduled echocardiogram would be
diagnosis by neonatologist-performed compact ultrasound exam            performed before the study exam could be completed, or if the
compared with routine echocardiography. This pilot study was            trained neonatologist was unavailable to perform the study exam.
approved by the Stanford University Institutional Review Board.         Informed consent was obtained for all patients who participated in
    The ‘routine echocardiogram’ was the exam ordered by the            the study.
medical team taking care of the patient for clinical indications.           On some occasions, an infant received more than one
This exam was performed by an experienced technologist or               echocardiogram to follow-up on the status of PDA. For these
pediatric cardiologist using the Acuson Sequoia (Siemens USA,           infants, the study exam could be repeated for a maximum of two
Malvern, PA, USA), the primary device used by the pediatric             times, before each routine echocardiogram.
cardiology service in our institution.
    The ‘study exam’ was performed by a neonatologist who               Procedure
underwent training in echocardiography, focusing on diagnosis of        Enrolled patients underwent the study exam consisting of a
PDA; no other neonatologists were trained. This exam was                compact, portable ultrasound exam (Acuson Cypress, Siemens USA)
performed with the Acuson Cypress (Siemens USA), a portable             by the study neonatologist before the routine echocardiogram
ultrasound machine, approximately the size of a briefcase, with         performed by pediatric cardiology. Using the information as
fewer advanced capabilities than the Sequoia, but with features         outlined previously, the neonatologist made a determination of
such as Doppler and M-mode. The standard Cypress neonatal probe         patent ductus if color Doppler views indicated shunting across
was used at a frequency of 7.5 MHz. The training process included       the ductus. A subjective determination of ductal size was made:
instruction on the working of the ultrasound machine, application       small, moderate or large. Results of the study exam were not
of the transducer to the various sites on the patient, addition of      revealed to caregivers, cardiologists or families and did not
Doppler techniques, and pulsed continuous wave to denote                influence treatment decisions. No clinical actions were based on
magnitude of shunting. Five factors were considered as criteria for     these study results. These results were noted on a dated and timed
diagnosis of a patent ductus: (1) left atrial size assessed from the    confidential study form immediately after the study exam, and sent
aortic root and the left atrial aortic root relation, (2) left          to two different confidential electronic email accounts, to assure
ventricular size and function, (3) Color Doppler estimate of ductus     they would not be amended. The neonatologist recorded the
size at the point of the vena contracta (the narrowest portion of the   patency of the ductus, and if patent, an interpretation of the size
flow jet), (4) the velocity and character of the ductus Doppler          of the ductus.
signal, and (5) the amount of retrograde abdominal flow. The                 The primary outcome variable to be measured was the accuracy
training included visualization of the parasternal long axis view,      of the diagnosis of PDA by the neonatologist using the compact,
the parasternal short axis view to visualize pulmonary arteries,        portable ultrasound machine. The routine exam performed by the
apical four-chamber view, subcostal view and suprasternal views,        pediatric cardiology service was considered the gold standard for
including the ductus cut.17 Using this information, the                 diagnosis. In general, this exam was performed by a skilled
neonatologist made a determination of patent ductus if the color        pediatric echocardiography technician or member of the pediatric
Doppler views indicated shunting across the ductus. Pulse wave          cardiology staff or faculty, and subsequently interpreted by a
Doppler in the descending aorta was used to augment the                 pediatric cardiologist. None of these practitioners knew the results
diagnosis. A subjective determination of ductal size was made           of the study exam.
(small, moderate or large) based on this information.                       The study exams were recorded on electronic media and later
    The total training experience consisted of 2 h of lecture           reviewed in a masked fashion by a cardiologist who was not
including recorded tapes, observation of eight exams by                 familiar with the patients in the study. This cardiologist knew
experienced technicians, and three practice exams with guidance         neither the study exam interpretation by the neonatologist, nor the
on real patients. Approximately 50% of these evaluations had PDA.       routine exam interpretation by the pediatric cardiologist. The study
The total training time was approximately 8 h. Midway through the       cardiologist interpreted the study exams and also graded the quality
study, the study cardiologist reviewed the study exams already done     of the exams in a subjective fashion. For some selected study exams
with the neonatologist for 1 h.                                         in which there were discrepancies between the study exam results
                                                                        and the routine exam, the study cardiologist also reviewed the
Subjects                                                                routine exam.
Patients in the NICU who were undergoing evaluation only for
suspected PDA, with birth weight 401 to 2000 g or <34-weeks             Data analysis
gestational age were eligible for this pilot study. The period of       Sensitivities and specificities with 95% confidence intervals of the
enrollment was from January to July 2005. Infants were excluded if      neonatologist’s study exam compared with the routine

Journal of Perinatology
Diagnosis of PDA by a Neonatologist
                                                                                           HC Lee et al
                                                                                                                                                                       293

echocardiogram were calculated. After the primary analysis, we also                        within six h of the cardiology exam for 20 of the studies. Two study
looked at the diagnosis of moderate or large PDAs as determined by                         exams occurred 9 h before (exam no. 2) and 23 h before (exam
the routine exam.                                                                          no. 10) the cardiology exam. The exact timing of the cardiology
   We also calculated sensitivity and specificity of the study                              exam for two of the studies was unable to be determined (exams
cardiologist’s interpretation of the study exam performed by the                           nos. 19 and 21). The study cardiologist did not routinely go over
neonatologist compared with the routine echocardiogram results,                            the routine exams by the pediatric cardiology service that correlated
again with the routine echocardiogram considered as the gold                               with the study exams. However, on one occasion, when the
standard. The study cardiologist was masked to both the                                    cardiologist saw a PDA in the study exam for which the cardiology
neonatologist’s interpretation of the study exam, and the formal                           service had reported no PDA, he reviewed both studies and his
interpretation of the routine echocardiogram performed by the                              interpretation of both the study exam and the routine exam was
pediatric cardiology service.                                                              the presence of a small PDA (exam no. 8).
                                                                                              Compared to the routine echocardiogram, the study exam as
                                                                                           interpreted by the neonatologist had 69% sensitivity (95% CI, 44 to
Results                                                                                    86%) and 88% specificity (95% CI, 53 to 98%) (Table 2). The
There were 24 exams performed on a total of 14 patients (Table 1).                         positive predictive value was 92%, whereas the negative predictive
All study exams were performed before the routine echocardiogram                           value was 58%. In the five cases where the neonatologist interpreted
performed by the cardiology service. Study exams were performed                            the study exam as negative when the routine cardiology evaluation



Table 1 Interpretation of study exams and routine exams
Exam no.        Birth weight      Gestational age        Age at time                                 Study exam                                     Routine exam
                  (grams)             (weeks)             of study
                                                                           Neo interpretation                 Cardiologist interpretation

                                                                           PDA Y/N        Size            PDA Y/N             Size          PDA Y/N       Size

 1                   860                 30                  78 h          Y              Small           Y                   Tiny          Y             Small-moderate
 2                  1390                 32                  67 h          Y              Small           Y                   Tiny          Y             Moderate
 3                  1390                 32                   5d           Y              Moderate        Y                   Small         Y             Moderate
 4                   647                 24                  13 d          Y              Small           N                                 N
 5                  1197                 28                   7d           N                              N                                 Y             Very small
 6                  1053                 29                  55 h          Y              Large           Y                   Big           Y             Large
 7                  1053                 29                 101 h          Y              Moderate        Y                   Moderate      Y             Moderate
 8                   820                 24                   7d           Y              Small           Y                   1 mm          Ya            Smalla
 9                  1146                 30                   5d           N                              Y                   Tiny          Y             Tiny
10                   820                 24                  13 d          N                              N                                 N
11                   968                 29                   6d           N                              N                                 N
12                   968                 29                  16 d          Y              Small           N                                 Y             Small-moderate
13                   866                 25                  42 h          N                              Y                   Large         Y             Large
14                   969                 26                  78 h          Y              Small           Y                   Small         Y             Large
15                   969                 26                   5d           Y              Small           Y                   Small         Y             Small
                                                                                                          b
16                   866                 25                   8d           N                                                                N
17                   969                 26                   8d           N                              Y                   Small         N
18                   740                 26                  11 d          N                              N                                 N
19                   740                 26                  17 d          N                              Y                   Tiny          N
20                  1125                 28                   5d           N                              N                                 N
21                  1470                 30                 106 h          N                              Y                   Large         Y             Moderate
22                  1743                 31                   5d           Y              Moderate        Y                   Small         Y             Small
23                  1743                 31                   7d           Y              Small           Y                   Tiny          Y             Small
                                                                                                          b
24                  1743                 31                  14 d          N                                                                Y             Tiny
Abbreviations: d, days; N, no; PDA, patent ductus arteriosus; Y, yes.
a
  Exam was initially noted to be negative by routine exam cardiologist, however upon secondary review, there was noted to be a small PDA.
b
  Exam was judged to be inadequate by study cardiologist.

                                                                                                                                                 Journal of Perinatology
Diagnosis of PDA by a Neonatologist
                                                                    HC Lee et al
294

Table 2 Results of routine exams and study exams interpreted by                    Table 3 Results of routine exams and study exams interpreted by
neonatologist                                                                      neonatologist, excluding small PDAs
                                   Routine                    Routine                                                 Routine                    Routine
                                  ECHO: PDA                ECHO: no PDA                                              ECHO: PDA                ECHO: no PDA

Study exam: PDA                        11                       1             12   Study exam: PDA                         7                       1          8
Study exam: no PDA                      5                       7             12   Study exam: no PDA                      2                       7          9
                                       16                       8             24                                           9                       8         17
Abbreviation: PDA, patent ductus arteriosus.                                       Abbreviation: PDA, patent ductus arteriosus.
Sensitivity ¼ 11/16 ¼ 0.69; positive predictive value ¼ 0.92.                      Sensitivity ¼ 7/9 ¼ 0.78; positive predictive value ¼ 0.88.
Specificity ¼ 7/8 ¼ 0.88; negative predictive value ¼ 0.58.                         Specificity ¼ 7/8 ¼ 0.88; negative predictive value ¼ 0.78.


was positive for PDA, three of those five cases had PDAs which were                 Table 4 Results of routine exams and study exams interpreted by study
considered small or tiny (Table 1).                                                cardiologist
   Six PDAs were considered to be small or tiny by echocardiogram                                                     Routine                    Routine
performed by the cardiology service; if these exams were excluded,                                                   ECHO: PDA                ECHO: no PDA
the sensitivity was 78% (45 to 94%) and specificity 88% (53 to 98%)
(Table 3). The sensitivity and specificity of the masked cardiologist               Study exam: PDA                        13                       2         15
interpretation of the study exam compared with the routine                         Study exam: no PDA                      2                       5          7
echocardiogram were also determined (Table 4). Two of the studies                                                         15                       7         22
were deemed uninterpretable owing to poor quality. The study                       Abbreviation: PDA, patent ductus arteriosus.
cardiologist interpretation of the remaining 22 studies had                        Sensitivity ¼ 13/15 ¼ 0.87; positive predictive value ¼ 0.87.
                                                                                   Specificity ¼ 5/7 ¼ 0.71; negative predictive value ¼ 0.71.
sensitivity of 87% (62 to 96%) and specificity 71% (36 to 92%).

                                                                                   increasingly by nontraditional practitioners, such as nurses in
Discussion                                                                         obstetrics, trauma surgeons and emergency physicians.20–23
In our pilot study, we found that a neonatologist with very limited                By using telephone lines, real-time transmission of
training in echocardiography was able to detect PDA in preterm                     echocardiography can be performed. Some NICUs are taking
infants with moderate sensitivitiy and specificity using a portable,                advantage of this technology, in which a cardiologist guides a
compact ultrasound device; accuracy improved further when                          technician to perform the study, then interprets the study from a
considering only moderate to large PDAs. A cardiologist interpreting               distance.24 In that series, 182 of the 500 exams performed were for
the study exams had slightly better success than the neonatologist.                suspected PDA. There may be practicing neonatologists who do
These preliminary findings in a small number of patients suggest                    perform echocardiography in their NICUs for the diagnosis of PDA,
that a more intensive training program, perhaps with integration                   particularly in situations when a cardiologist is not available.
of real-time evaluation techniques, could result in further                        However, we are not aware of any previous studies reporting
diagnostic improvement. Although such a program may not be                         training regimens, accuracy or reliability of neonatologist-
necessary in hospitals with pediatric cardiologists and technicians,               performed exams using a portable bedside device.
it may be an appropriate and feasible approach for institutions                        There were several limitations to this study. The methodology
without this consistent on-site availability.                                      included several factors, any or all of which may have effected the
    This is the first study describing the training of a neonatologist              study results: (1) the use of a smaller portable ultrasound device as
to interpret ultrasound for the diagnosis of PDA. A previous study                 compared to the more sophisticated machine used by the
looked at echocardiography by a neonatologist of infants suspected                 cardiology service, (2) the fact that only one neonatologist
to have congenital heart disease. In that study, the cardiologist                  performed the study exams, and (3) the training process. The
interpretation was not considered a true gold standard, and a                      images on the portable device were not as clear as the usual
Cohen’s kappa of 0.84 of overall agreement was reported.18 If the                  machine. However, it did feature the ability to perform Doppler
cardiologist interpretation had been considered the gold standard,                 ultrasound and the large majority of exams were considered
the sensitivity of the neonatologist’s exam would have been 75%.                   sufficient by the study cardiologist. We may have seen different
    Technological advancements have made ultrasound devices                        results had more than one neonatologist performed the study
more readily available and portable. A recent study found that a                   exams. However, the device was available for use on a limited
handheld ultrasound device had utility in diagnosing valvular                      basis and it was not practical for more than one person to
regurgitation in adults.19 Ultrasounds are being performed                         perform the studies. It may be the case that another neonatologist

Journal of Perinatology
Diagnosis of PDA by a Neonatologist
                                                                                           HC Lee et al
                                                                                                                                                                         295

with the same training and similar patients may have performed                              3 Tortorolo L, Vento G, Matassa PG, Zecca E, Romagnoli C. Early changes
differently.                                                                                   of pulmonary mechanics to predict the severity of bronchopulmonary
    We reviewed the two cases (nos. 13 and 21) in which the study                              dysplasia in ventilated preterm infants. J Matern Fetal Neonatal Med 2002;
neonatologist missed the diagnosis of a large PDA. Both study                                  12: 332–337.
exams by the neonatologist were technically competent with clear                            4 Redline RW, Wilson-Costello D, Hack M. Placental and other perinatal risk
                                                                                               factors for chronic lung disease in very low birth weight infants. Pediatr Res
views of the PDA on several views, retrograde abdominal aorta flow.
                                                                                               2002; 52: 713–719.
The study cardiologist (and in retrospect, the study neonatologist)
                                                                                            5 Lin TW, Su BH, Lin HC, Hu PS, Peng CT, Tsai CH et al. Risk factors of
visualized a large PDA in both studies. We attribute the missed                                pulmonary hemorrhage in very-low-birth-weight infants: a two-year
diagnoses to lack of experience and confidence on the part of a                                 retrospective study. Acta Paediatr Taiwan 2000; 41: 255–258.
novice interpreting the exams.                                                              6 Argyropoulou MI, Xydis V, Drougia A, Argyropoulou PI, Tzoufi M, Bassounas
    A longer training program may also have allowed for improved                               A et al. MRI measurements of the pons and cerebellum in children born
diagnosis of PDA. We tried to simulate a relatively short, 1–2 days                            preterm; associations with the severity of periventricular leukomalacia and
training program that would allow participation by a busy                                      perinatal risk factors. Neuroradiology 2003; 45: 730–734.
neonatologist, in a setting where direct supervision would likely be                        7 Costeloe K, Hennessy E, Gibson AT, Marlow N, Wilkinson AR. The EPICure
unavailable after the training program. The training involved                                  study: outcomes to discharge from hospital for infants born at the threshold
education in learning how to use the ultrasound device itself,                                 of viability. Pediatrics 2000; 106: 659–671.
learning the various views, and the nuances of the diagnosis of                             8 Hammoud MS, Elsori HA, Hanafi EA, Shalabi AA, Fouda IA, Devarajan LV.
                                                                                               Incidence and risk factors associated with the patency of ductus arteriosus in
PDA in a very small infant. We found that the neonatologist had
                                                                                               preterm infants with respiratory distress syndrome in Kuwait. Saudi Med J
room for improvement in both the technical skills of
                                                                                               2003; 24: 982–985.
echocardiography as well as interpretation of exams to diagnose                             9 Szymankiewicz M, Hodgman JE, Siassi B, Gadzinowski J. Mechanics
PDA.                                                                                           of breathing after surgical ligation of patent ductus arteriosus in
    There can also be some subjectivity in the interpretation of                               newborns with respiratory distress syndrome. Biol Neonate 2004; 85:
echocardiograms. In our study, we reviewed one particular patient                              32–36.
who had a PDA seen in the study exam by both the neonatologist                             10 Shimada S, Kasai T, Hoshi A, Murata A, Chida S. Cardiocirculatory
and study cardiologist (exam no. 8). Although the practicing                                  effects of patent ductus arteriosus in extremely low-birth-weight
cardiologist’s interpretation of the routine exam in that                                     infants with respiratory distress syndrome. Pediatr Int 2003; 45:
circumstance had been no PDA, the study cardiologist interpreted                              255–262.
the routine exam as positive for PDA. However, practically                                 11 Davis P, Turner-Gomes S, Cunningham K, Way C, Roberts R, Schmidt B.
speaking, most clinicians would consider that echocardiography is                             Precision and accuracy of clinical and radiological signs in premature
                                                                                              infants at risk of patent ductus arteriosus. Arch Pediatr Adolesc Med 1995;
the gold standard for diagnosis of PDA.
                                                                                              149: 1136–1141.
    In summary, we found that, even with extremely limited
                                                                                           12 Urquhart DS, Nicholl RM. How good is clinical examination at detecting a
training, a neonatologist was able to detect PDA with moderate                                significant patent ductus arteriosus in the preterm neonate? Arch Dis Child
success. A more rigorous training process or real-time transmission                           2003; 88: 85–86.
with cardiologist interpretation and guidance could improve                                13 Skelton R, Evans N, Smythe J. A blinded comparison of clinical and
accuracy and thus avoid inappropriate patient treatment.                                      echocardiographic evaluation of the preterm infant for patent ductus
                                                                                              arteriosus. J Paediatr Child Health 1994; 30: 406–411.
                                                                                           14 Skinner JR. Echocardiography on the neonatal unit: a job for the
Acknowledgments                                                                               neonatologist or the cardiologist? Arch Dis Child 1998; 78:
                                                                                              401–402.
Siemens Medical Solutions USA provided equipment for this study. Henry Lee is
                                                                                           15 Li X, Mack GK, Rusk RA, Dai XN, El-Sedfy GO, Davies CH et al. Will a
the recipient of a Fellowship Grant from Discovery Labs. Neither institution
                                                                                              handheld ultrasound scanner be applicable for screening for heart
participated in the design of the study, training of the study staff, or analysis of the
                                                                                              abnormalities in newborns and children? J Am Soc Echocardiogr 2003; 16:
results.
                                                                                              1007–1014.
                                                                                           16 Duvall WL, Croft LB, Goldman ME. Can hand-carried ultrasound devices
                                                                                              be extended for use by the noncardiology medical community?
References                                                                                    Echocardiography 2003; 20: 471–476.
 1 Wang YH, Su BH, Wu SF, Chen AC, Lin TW, Lin HC et al. Clinical analysis of              17 Smallhorn JF, Huhta JC, Anderson RH, Macartney FJ. Suprasternal
   necrotizing enterocolitis with intestinal perforation in premature infants.                cross-sectional echocardiography in assessment of patent ductus arteriosus.
   Acta Paediatr Taiwan 2002; 43: 199–203.                                                    Br Heart J 1982; 48: 321–330.
 2 Evans N, Kluckow M. Early ductal shunting and intraventricular                          18 Samson GR, Kumar SR. A study of congenital cardiac disease in a neonatal
   haemorrhage in ventilated preterm infants. Arch Dis Child Fetal Neonatal                   population – the validity of echocardiography undertaken by a
   Ed 1996; 75: F183–F186.                                                                    neonatologist. Cardiol Young 2004; 14: 585–593.

                                                                                                                                                   Journal of Perinatology
Diagnosis of PDA by a Neonatologist
                                                               HC Lee et al
296

19    Kobal SL, Tolstrup K, Luo H, Neuman Y, Miyamoto T, Mirocha J et al.           22   Kirkpatrick AW, Simons RK, Brown R, Nicolaou S, Dulchavsky S. The
      Usefulness of a hand-carried cardiac ultrasound device to detect clinically        hand-held FAST: experience with hand-held trauma sonography in a level-I
      significant valvular regurgitation in hospitalized patients. Am J Cardiol           urban trauma center. Injury 2002; 33: 303–308.
      2004; 93: 1069–1072.                                                          23   Holmes JF, Brant WE, Bond WF, Sokolove PE, Kuppermann N. Emergency
20    Gegor CL, Paine LL, Costigan K, Johnson TR. Interpretation of biophysical          department ultrasonography in the evaluation of hypotensive and
      profiles by nurses and physicians. J Obstet Gynecol Neonatal Nurs 1994;             normotensive children with blunt abdominal trauma. J Pediatr Surg 2001;
      23: 405–410.                                                                       36: 968–973.
21    Brooks A, Davies B, Smethhurst M, Connolly J. Prospective evaluation          24   Sable CA, Cummings SD, Pearson GD, Schratz LM, Cross RC, Quivers ES
      of non-radiologist performed emergency abdominal ultrasound for                    et al. Impact of telemedicine on the practice of pediatric cardiology in
      haemoperitoneum. Emerg Med J 2004; 21: e5.                                         community hospitals. Pediatrics 2002; 109: E3.




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Ecocardio y neo

  • 1. Journal of Perinatology (2007) 27, 291–296 r 2007 Nature Publishing Group All rights reserved. 0743-8346/07 $30 www.nature.com/jp ORIGINAL ARTICLE Diagnosis of patent ductus arteriosus by a neonatologist with a compact, portable ultrasound machine HC Lee1, N Silverman2 and SR Hintz3 1 Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University, Palo Alto, CA, USA; 2Department of Pediatrics, Division of Pediatric Cardiology, Stanford University, Palo Alto, CA, USA and 3Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University, Palo Alto, CA, USA hemorrhage, bronchopulmonary dysplasia and pulmonary Objectives: To conduct a pilot study assessing a neonatologist’s accuracy hemorrhage.1–5 In a review of periventricular leukomalacia in in diagnosing patent ductus arteriosus (PDA) using compact, portable preterm infants, PDA was associated with decreased cerebellar ultrasound after limited training. volume, area of the vermis and diameter of the pons.6 The Study design: Prospective study of premature infants scheduled for frequency of PDA is high in premature infants, ranging from echocardiography for suspected PDA. A neonatologist with limited training 53% in infants born before 34-weeks gestation, up to 65% in performed study exams before scheduled exams. Sensitivity and specificity infants born before 26-weeks gestation.7,8 PDA in preterm were calculated, compared to the scheduled echocardiogram interpreted infants often requires pharmacologic or surgical closure. by a cardiologist. Treatment of PDA has been shown to improve pulmonary function, including increase in dynamic compliance, tidal volume and Results: There were 24 exams. Compared to the scheduled exam, the minute ventilation.9 Early pharmacological treatment has also neonatologist’s exam had sensitivity 69% (95% confidence interval (CI), been shown to reverse low renal and splanchnic blood flow in 41 to 89%) and specificity 88% (95% CI, 47 to 99%). When a cardiologist infants with PDA.10 interpreted the study exams, the sensitivity was 87% (95% CI, 60 to 98%) Although there are clinical signs for diagnosis of PDA including and specificity 71% (95% CI, 29 to 96%). auscultation of a cardiac murmur, bounding pulses and wide pulse Conclusion: A neonatologist with limited training was able to detect PDA pressure, studies have shown that physical exam is inadequate in with moderate success. A more rigorous training process or real-time detecting significant PDAs in preterm infants.11–13 The current transmission with cardiologist interpretation may substantially improve standard of care for diagnosis of PDA is an echocardiogram, yet accuracy. Institutions with experienced technicians and on-site pediatric echocardiography is not routinely taught to neonatologists. cardiologists may not gain from intensive training of neonatologists, but Nevertheless, it has been suggested that patient care could be hospitals where diagnosis and treatment of PDA would be delayed may improved in the neonatal intensive care unit (NICU) if benefit from such processes. neonatologists were trained in echocardiography.14 Journal of Perinatology (2007) 27, 291–296. doi:10.1038/sj.jp.7211693; Advances in technology are allowing echocardiography to be published online 15 March 2007 performed by nontraditional personnel in certain settings. Ultrasound technology has become more compact, allowing use as Keywords: patent ductus arteriosus; echocardiography; neonatologist; diagnosis a point-of-care diagnostic tool. A handheld ultrasound was found to be effective in the diagnosis of congenital heart disease, including PDA.15 In this series, the interpreters were experienced echocardiographers. Such devices are being utilized in settings Introduction such as the emergency department and surgical ICUs where a Patent ductus arteriosus (PDA) in premature infants is an quick, focused evaluation could benefit the patient.16 Neonatal associated factor in serious neonatal morbidities, associated units may also benefit from small handheld ultrasound devices for with increased risk of necrotizing enterocolitis, intraventricular assessment of umbilical line placement and cerebral blood flow. Correspondence: Dr SR Hintz, Department of Pediatrics, Division of Neonatal and We performed a pilot study to assess the potential utility of a Developmental Medicine, Stanford University, 750 Welch Road, Suite 315, Palo Alto, limited training program to diagnose PDA for a neonatologist with CA 94304, USA. no cardiology background. We used a portable ultrasound E-mail: srhintz@stanford.edu Received 5 September 2006; revised 18 December 2006; accepted 10 January 2007; published machine, one which could potentially be used in small NICUs online 15 March 2007 without ready access to a pediatric cardiologist.
  • 2. Diagnosis of PDA by a Neonatologist HC Lee et al 292 Methods the treating physician decided that the patient should not be This was a prospective, masked pilot study of the accuracy of PDA enrolled for any reason, the scheduled echocardiogram would be diagnosis by neonatologist-performed compact ultrasound exam performed before the study exam could be completed, or if the compared with routine echocardiography. This pilot study was trained neonatologist was unavailable to perform the study exam. approved by the Stanford University Institutional Review Board. Informed consent was obtained for all patients who participated in The ‘routine echocardiogram’ was the exam ordered by the the study. medical team taking care of the patient for clinical indications. On some occasions, an infant received more than one This exam was performed by an experienced technologist or echocardiogram to follow-up on the status of PDA. For these pediatric cardiologist using the Acuson Sequoia (Siemens USA, infants, the study exam could be repeated for a maximum of two Malvern, PA, USA), the primary device used by the pediatric times, before each routine echocardiogram. cardiology service in our institution. The ‘study exam’ was performed by a neonatologist who Procedure underwent training in echocardiography, focusing on diagnosis of Enrolled patients underwent the study exam consisting of a PDA; no other neonatologists were trained. This exam was compact, portable ultrasound exam (Acuson Cypress, Siemens USA) performed with the Acuson Cypress (Siemens USA), a portable by the study neonatologist before the routine echocardiogram ultrasound machine, approximately the size of a briefcase, with performed by pediatric cardiology. Using the information as fewer advanced capabilities than the Sequoia, but with features outlined previously, the neonatologist made a determination of such as Doppler and M-mode. The standard Cypress neonatal probe patent ductus if color Doppler views indicated shunting across was used at a frequency of 7.5 MHz. The training process included the ductus. A subjective determination of ductal size was made: instruction on the working of the ultrasound machine, application small, moderate or large. Results of the study exam were not of the transducer to the various sites on the patient, addition of revealed to caregivers, cardiologists or families and did not Doppler techniques, and pulsed continuous wave to denote influence treatment decisions. No clinical actions were based on magnitude of shunting. Five factors were considered as criteria for these study results. These results were noted on a dated and timed diagnosis of a patent ductus: (1) left atrial size assessed from the confidential study form immediately after the study exam, and sent aortic root and the left atrial aortic root relation, (2) left to two different confidential electronic email accounts, to assure ventricular size and function, (3) Color Doppler estimate of ductus they would not be amended. The neonatologist recorded the size at the point of the vena contracta (the narrowest portion of the patency of the ductus, and if patent, an interpretation of the size flow jet), (4) the velocity and character of the ductus Doppler of the ductus. signal, and (5) the amount of retrograde abdominal flow. The The primary outcome variable to be measured was the accuracy training included visualization of the parasternal long axis view, of the diagnosis of PDA by the neonatologist using the compact, the parasternal short axis view to visualize pulmonary arteries, portable ultrasound machine. The routine exam performed by the apical four-chamber view, subcostal view and suprasternal views, pediatric cardiology service was considered the gold standard for including the ductus cut.17 Using this information, the diagnosis. In general, this exam was performed by a skilled neonatologist made a determination of patent ductus if the color pediatric echocardiography technician or member of the pediatric Doppler views indicated shunting across the ductus. Pulse wave cardiology staff or faculty, and subsequently interpreted by a Doppler in the descending aorta was used to augment the pediatric cardiologist. None of these practitioners knew the results diagnosis. A subjective determination of ductal size was made of the study exam. (small, moderate or large) based on this information. The study exams were recorded on electronic media and later The total training experience consisted of 2 h of lecture reviewed in a masked fashion by a cardiologist who was not including recorded tapes, observation of eight exams by familiar with the patients in the study. This cardiologist knew experienced technicians, and three practice exams with guidance neither the study exam interpretation by the neonatologist, nor the on real patients. Approximately 50% of these evaluations had PDA. routine exam interpretation by the pediatric cardiologist. The study The total training time was approximately 8 h. Midway through the cardiologist interpreted the study exams and also graded the quality study, the study cardiologist reviewed the study exams already done of the exams in a subjective fashion. For some selected study exams with the neonatologist for 1 h. in which there were discrepancies between the study exam results and the routine exam, the study cardiologist also reviewed the Subjects routine exam. Patients in the NICU who were undergoing evaluation only for suspected PDA, with birth weight 401 to 2000 g or <34-weeks Data analysis gestational age were eligible for this pilot study. The period of Sensitivities and specificities with 95% confidence intervals of the enrollment was from January to July 2005. Infants were excluded if neonatologist’s study exam compared with the routine Journal of Perinatology
  • 3. Diagnosis of PDA by a Neonatologist HC Lee et al 293 echocardiogram were calculated. After the primary analysis, we also within six h of the cardiology exam for 20 of the studies. Two study looked at the diagnosis of moderate or large PDAs as determined by exams occurred 9 h before (exam no. 2) and 23 h before (exam the routine exam. no. 10) the cardiology exam. The exact timing of the cardiology We also calculated sensitivity and specificity of the study exam for two of the studies was unable to be determined (exams cardiologist’s interpretation of the study exam performed by the nos. 19 and 21). The study cardiologist did not routinely go over neonatologist compared with the routine echocardiogram results, the routine exams by the pediatric cardiology service that correlated again with the routine echocardiogram considered as the gold with the study exams. However, on one occasion, when the standard. The study cardiologist was masked to both the cardiologist saw a PDA in the study exam for which the cardiology neonatologist’s interpretation of the study exam, and the formal service had reported no PDA, he reviewed both studies and his interpretation of the routine echocardiogram performed by the interpretation of both the study exam and the routine exam was pediatric cardiology service. the presence of a small PDA (exam no. 8). Compared to the routine echocardiogram, the study exam as interpreted by the neonatologist had 69% sensitivity (95% CI, 44 to Results 86%) and 88% specificity (95% CI, 53 to 98%) (Table 2). The There were 24 exams performed on a total of 14 patients (Table 1). positive predictive value was 92%, whereas the negative predictive All study exams were performed before the routine echocardiogram value was 58%. In the five cases where the neonatologist interpreted performed by the cardiology service. Study exams were performed the study exam as negative when the routine cardiology evaluation Table 1 Interpretation of study exams and routine exams Exam no. Birth weight Gestational age Age at time Study exam Routine exam (grams) (weeks) of study Neo interpretation Cardiologist interpretation PDA Y/N Size PDA Y/N Size PDA Y/N Size 1 860 30 78 h Y Small Y Tiny Y Small-moderate 2 1390 32 67 h Y Small Y Tiny Y Moderate 3 1390 32 5d Y Moderate Y Small Y Moderate 4 647 24 13 d Y Small N N 5 1197 28 7d N N Y Very small 6 1053 29 55 h Y Large Y Big Y Large 7 1053 29 101 h Y Moderate Y Moderate Y Moderate 8 820 24 7d Y Small Y 1 mm Ya Smalla 9 1146 30 5d N Y Tiny Y Tiny 10 820 24 13 d N N N 11 968 29 6d N N N 12 968 29 16 d Y Small N Y Small-moderate 13 866 25 42 h N Y Large Y Large 14 969 26 78 h Y Small Y Small Y Large 15 969 26 5d Y Small Y Small Y Small b 16 866 25 8d N N 17 969 26 8d N Y Small N 18 740 26 11 d N N N 19 740 26 17 d N Y Tiny N 20 1125 28 5d N N N 21 1470 30 106 h N Y Large Y Moderate 22 1743 31 5d Y Moderate Y Small Y Small 23 1743 31 7d Y Small Y Tiny Y Small b 24 1743 31 14 d N Y Tiny Abbreviations: d, days; N, no; PDA, patent ductus arteriosus; Y, yes. a Exam was initially noted to be negative by routine exam cardiologist, however upon secondary review, there was noted to be a small PDA. b Exam was judged to be inadequate by study cardiologist. Journal of Perinatology
  • 4. Diagnosis of PDA by a Neonatologist HC Lee et al 294 Table 2 Results of routine exams and study exams interpreted by Table 3 Results of routine exams and study exams interpreted by neonatologist neonatologist, excluding small PDAs Routine Routine Routine Routine ECHO: PDA ECHO: no PDA ECHO: PDA ECHO: no PDA Study exam: PDA 11 1 12 Study exam: PDA 7 1 8 Study exam: no PDA 5 7 12 Study exam: no PDA 2 7 9 16 8 24 9 8 17 Abbreviation: PDA, patent ductus arteriosus. Abbreviation: PDA, patent ductus arteriosus. Sensitivity ¼ 11/16 ¼ 0.69; positive predictive value ¼ 0.92. Sensitivity ¼ 7/9 ¼ 0.78; positive predictive value ¼ 0.88. Specificity ¼ 7/8 ¼ 0.88; negative predictive value ¼ 0.58. Specificity ¼ 7/8 ¼ 0.88; negative predictive value ¼ 0.78. was positive for PDA, three of those five cases had PDAs which were Table 4 Results of routine exams and study exams interpreted by study considered small or tiny (Table 1). cardiologist Six PDAs were considered to be small or tiny by echocardiogram Routine Routine performed by the cardiology service; if these exams were excluded, ECHO: PDA ECHO: no PDA the sensitivity was 78% (45 to 94%) and specificity 88% (53 to 98%) (Table 3). The sensitivity and specificity of the masked cardiologist Study exam: PDA 13 2 15 interpretation of the study exam compared with the routine Study exam: no PDA 2 5 7 echocardiogram were also determined (Table 4). Two of the studies 15 7 22 were deemed uninterpretable owing to poor quality. The study Abbreviation: PDA, patent ductus arteriosus. cardiologist interpretation of the remaining 22 studies had Sensitivity ¼ 13/15 ¼ 0.87; positive predictive value ¼ 0.87. Specificity ¼ 5/7 ¼ 0.71; negative predictive value ¼ 0.71. sensitivity of 87% (62 to 96%) and specificity 71% (36 to 92%). increasingly by nontraditional practitioners, such as nurses in Discussion obstetrics, trauma surgeons and emergency physicians.20–23 In our pilot study, we found that a neonatologist with very limited By using telephone lines, real-time transmission of training in echocardiography was able to detect PDA in preterm echocardiography can be performed. Some NICUs are taking infants with moderate sensitivitiy and specificity using a portable, advantage of this technology, in which a cardiologist guides a compact ultrasound device; accuracy improved further when technician to perform the study, then interprets the study from a considering only moderate to large PDAs. A cardiologist interpreting distance.24 In that series, 182 of the 500 exams performed were for the study exams had slightly better success than the neonatologist. suspected PDA. There may be practicing neonatologists who do These preliminary findings in a small number of patients suggest perform echocardiography in their NICUs for the diagnosis of PDA, that a more intensive training program, perhaps with integration particularly in situations when a cardiologist is not available. of real-time evaluation techniques, could result in further However, we are not aware of any previous studies reporting diagnostic improvement. Although such a program may not be training regimens, accuracy or reliability of neonatologist- necessary in hospitals with pediatric cardiologists and technicians, performed exams using a portable bedside device. it may be an appropriate and feasible approach for institutions There were several limitations to this study. The methodology without this consistent on-site availability. included several factors, any or all of which may have effected the This is the first study describing the training of a neonatologist study results: (1) the use of a smaller portable ultrasound device as to interpret ultrasound for the diagnosis of PDA. A previous study compared to the more sophisticated machine used by the looked at echocardiography by a neonatologist of infants suspected cardiology service, (2) the fact that only one neonatologist to have congenital heart disease. In that study, the cardiologist performed the study exams, and (3) the training process. The interpretation was not considered a true gold standard, and a images on the portable device were not as clear as the usual Cohen’s kappa of 0.84 of overall agreement was reported.18 If the machine. However, it did feature the ability to perform Doppler cardiologist interpretation had been considered the gold standard, ultrasound and the large majority of exams were considered the sensitivity of the neonatologist’s exam would have been 75%. sufficient by the study cardiologist. We may have seen different Technological advancements have made ultrasound devices results had more than one neonatologist performed the study more readily available and portable. A recent study found that a exams. However, the device was available for use on a limited handheld ultrasound device had utility in diagnosing valvular basis and it was not practical for more than one person to regurgitation in adults.19 Ultrasounds are being performed perform the studies. It may be the case that another neonatologist Journal of Perinatology
  • 5. Diagnosis of PDA by a Neonatologist HC Lee et al 295 with the same training and similar patients may have performed 3 Tortorolo L, Vento G, Matassa PG, Zecca E, Romagnoli C. Early changes differently. of pulmonary mechanics to predict the severity of bronchopulmonary We reviewed the two cases (nos. 13 and 21) in which the study dysplasia in ventilated preterm infants. J Matern Fetal Neonatal Med 2002; neonatologist missed the diagnosis of a large PDA. Both study 12: 332–337. exams by the neonatologist were technically competent with clear 4 Redline RW, Wilson-Costello D, Hack M. Placental and other perinatal risk factors for chronic lung disease in very low birth weight infants. Pediatr Res views of the PDA on several views, retrograde abdominal aorta flow. 2002; 52: 713–719. The study cardiologist (and in retrospect, the study neonatologist) 5 Lin TW, Su BH, Lin HC, Hu PS, Peng CT, Tsai CH et al. Risk factors of visualized a large PDA in both studies. We attribute the missed pulmonary hemorrhage in very-low-birth-weight infants: a two-year diagnoses to lack of experience and confidence on the part of a retrospective study. Acta Paediatr Taiwan 2000; 41: 255–258. novice interpreting the exams. 6 Argyropoulou MI, Xydis V, Drougia A, Argyropoulou PI, Tzoufi M, Bassounas A longer training program may also have allowed for improved A et al. MRI measurements of the pons and cerebellum in children born diagnosis of PDA. We tried to simulate a relatively short, 1–2 days preterm; associations with the severity of periventricular leukomalacia and training program that would allow participation by a busy perinatal risk factors. Neuroradiology 2003; 45: 730–734. neonatologist, in a setting where direct supervision would likely be 7 Costeloe K, Hennessy E, Gibson AT, Marlow N, Wilkinson AR. The EPICure unavailable after the training program. The training involved study: outcomes to discharge from hospital for infants born at the threshold education in learning how to use the ultrasound device itself, of viability. Pediatrics 2000; 106: 659–671. learning the various views, and the nuances of the diagnosis of 8 Hammoud MS, Elsori HA, Hanafi EA, Shalabi AA, Fouda IA, Devarajan LV. Incidence and risk factors associated with the patency of ductus arteriosus in PDA in a very small infant. We found that the neonatologist had preterm infants with respiratory distress syndrome in Kuwait. Saudi Med J room for improvement in both the technical skills of 2003; 24: 982–985. echocardiography as well as interpretation of exams to diagnose 9 Szymankiewicz M, Hodgman JE, Siassi B, Gadzinowski J. Mechanics PDA. of breathing after surgical ligation of patent ductus arteriosus in There can also be some subjectivity in the interpretation of newborns with respiratory distress syndrome. Biol Neonate 2004; 85: echocardiograms. In our study, we reviewed one particular patient 32–36. who had a PDA seen in the study exam by both the neonatologist 10 Shimada S, Kasai T, Hoshi A, Murata A, Chida S. Cardiocirculatory and study cardiologist (exam no. 8). Although the practicing effects of patent ductus arteriosus in extremely low-birth-weight cardiologist’s interpretation of the routine exam in that infants with respiratory distress syndrome. Pediatr Int 2003; 45: circumstance had been no PDA, the study cardiologist interpreted 255–262. the routine exam as positive for PDA. However, practically 11 Davis P, Turner-Gomes S, Cunningham K, Way C, Roberts R, Schmidt B. speaking, most clinicians would consider that echocardiography is Precision and accuracy of clinical and radiological signs in premature infants at risk of patent ductus arteriosus. Arch Pediatr Adolesc Med 1995; the gold standard for diagnosis of PDA. 149: 1136–1141. In summary, we found that, even with extremely limited 12 Urquhart DS, Nicholl RM. How good is clinical examination at detecting a training, a neonatologist was able to detect PDA with moderate significant patent ductus arteriosus in the preterm neonate? Arch Dis Child success. A more rigorous training process or real-time transmission 2003; 88: 85–86. with cardiologist interpretation and guidance could improve 13 Skelton R, Evans N, Smythe J. A blinded comparison of clinical and accuracy and thus avoid inappropriate patient treatment. echocardiographic evaluation of the preterm infant for patent ductus arteriosus. J Paediatr Child Health 1994; 30: 406–411. 14 Skinner JR. Echocardiography on the neonatal unit: a job for the Acknowledgments neonatologist or the cardiologist? Arch Dis Child 1998; 78: 401–402. Siemens Medical Solutions USA provided equipment for this study. Henry Lee is 15 Li X, Mack GK, Rusk RA, Dai XN, El-Sedfy GO, Davies CH et al. Will a the recipient of a Fellowship Grant from Discovery Labs. Neither institution handheld ultrasound scanner be applicable for screening for heart participated in the design of the study, training of the study staff, or analysis of the abnormalities in newborns and children? J Am Soc Echocardiogr 2003; 16: results. 1007–1014. 16 Duvall WL, Croft LB, Goldman ME. Can hand-carried ultrasound devices be extended for use by the noncardiology medical community? References Echocardiography 2003; 20: 471–476. 1 Wang YH, Su BH, Wu SF, Chen AC, Lin TW, Lin HC et al. Clinical analysis of 17 Smallhorn JF, Huhta JC, Anderson RH, Macartney FJ. Suprasternal necrotizing enterocolitis with intestinal perforation in premature infants. cross-sectional echocardiography in assessment of patent ductus arteriosus. Acta Paediatr Taiwan 2002; 43: 199–203. Br Heart J 1982; 48: 321–330. 2 Evans N, Kluckow M. Early ductal shunting and intraventricular 18 Samson GR, Kumar SR. A study of congenital cardiac disease in a neonatal haemorrhage in ventilated preterm infants. 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