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QTc Interval Prolongation and Severe Apneas Associated With a Change in Infant Positioning

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Associated With a Change in Infant Positioning

abstract

For more than a decade there has been considerable interest in the role of QT interval prolongation in the pathogenesis of sudden infant death syndrome. It has been proposed that the QT interval is a surro-gate marker for autonomic instability and can be used to identify infants at risk for significant morbidity and mortality, including sudden infant death syndrome. We present the case of an infant that experi-enced a significant increase in his QTc, as detected by continuous QTc monitoring in the NICU after repositioning from a supine to prone po-sition. This increase from a 41366 millisecond baseline average to 500 milliseconds was sustained for 2 hours and associated with clinically relevant apnea that ultimately required repositioning of the infant back to the supine position. Repositioning resulted in an immediate decrease of the QTc back to the previous baseline and termination of the apneic events. This case demonstrates an example of how the use of continuous QTc monitoring in the NICU setting may be used to detect QTc-accentuating factors in real time and identify situations that cause perturbations in an infant’s autonomic nervous system.Pediatrics2013;132:e1690–e1693

AUTHORS:Marc A. Ellsworth, MD,aTimothy J. Ulrich, MD,a

William A. Carey, MD,a,bChristopher E. Colby, MD,a,band

Michael J. Ackerman, MD, PhDa,c

aDepartment of Pediatric and Adolescent Medicine, and Divisions

ofbNeonatal Medicine andcPediatric Cardiology, Mayo Clinic,

Rochester, Minnesota

KEY WORDS

electrocardiography, infants, apnea, autonomic nervous system, NICUs

ABBREVIATIONS

ANS—autonomic nervous system ECG—electrocardiogram

SIDS—sudden infant death syndrome

Dr Ellsworth drafted the initial manuscript; Dr Ulrich was the resident physician that cared for the patient described in the case and drafted the case presentation of the initial manuscript; Dr Carey was the attending physician caring for the patient and reviewed and revised the manuscript as submitted; Dr Colby was the attending physician mentor of the 2 training physicians (Drs Ellsworth and Ulrich) and reviewed and revised the manuscript; Dr Ackerman was the content expert for the case discussion and critically reviewed the manuscript; and all authors approved thefinal manuscript as submitted.

www.pediatrics.org/cgi/doi/10.1542/peds.2012-4005

doi:10.1542/peds.2012-4005

Accepted for publication Jun 26, 2013

Address correspondence to Marc A. Ellsworth, MD, Department of Pediatric and Adolescent Medicine, 200 1st St SW, Rochester, MN 55905. E-mail: ellsworth.marc@mayo.edu

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2013 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE:Dr Ackerman has received consulting fees/honoraria from Biotronik; Boston Scientific Corp; Medtronic, Inc; and St. Jude Medical; he has received royalty income from Transgenomic. The other authors have indicated they have nofinancial relationships relevant to this article to disclose.

FUNDING:No external funding.

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The areas in the brainstem that regulate cardiac repolarization are in close proximity to areas that control respi-ration and temperature, and instability in 1 system may affect other systems.1

The QT interval, a marker of cardiac repolarization, is highly dependent on autonomic nervous system (ANS) input in the lower brainstem and as such can serve as a surrogate for ANS function and maturation. Over the past decade, many questions have arisen concerning the QT interval and its role in identifying disturbances in the ANS, most notably infants at risk for sudden infant death syndrome (SIDS).2Recently, continuous

QTc monitoring in the NICU has become available and reliable.3Continuous QTc

monitoring in the NICU may help identify situations and infants in which ANS disturbances and instability are pres-ent. We demonstrate a case in which continuous QTc monitoring identified marked QTc prolongation and associ-ated apneic episodes in an infant posi-tioned from supine to prone.

CASE

A male infant with no significant family history was found to have a prenatally identified congenital heart defect. After an uneventful delivery at 32 weeks, 5 days estimated gestational age, he was admitted to the NICU wherein a post-natal echocardiogram confirmed con-genitally corrected transposition of the great arteries with a single ventricular, left-dominant morphology. The patient was monitored continuously by using the IntelliVue MP70 Neonatal monitor (Philips, Boeblingen, Germany) with continuous QTc monitoring activated, which displays real-time QTc values (calculated by using the Bazett cor-rection formula) that are automatically downloaded to the electronic medical record at 15-minute intervals. The pa-tient was started on prostaglandins, furosemide, and caffeine while awaiting hisfirst palliative heart surgery. Of note,

none of these medications have been associated with prolongation of the QT interval.

As of the fourth day of life, the patient remained stable with no occurrence of significant events since birth. Continuous QTc monitoring during the early part of that day showed stable and consistent QTc values averaging 413 66 milliseconds with the patient in the supine position (Fig 1). During this time, there were no apneic episodes or clinical changes re-quiring significant intervention. Later that morning, the patient was repositioned from a supine to prone position, which correlated with an immediate increase in his QTc to 500 milliseconds. He remained prone for∼2 hours, during which time his continuous QTc values averaged 495

6 8 milliseconds. Subsequently, while still prone, he had 4 apneic episodes that required significant nursing intervention. As a result of these episodes, he was repositioned back to the supine position, which precipitated an immediate de-crease in his QTc to 412 milliseconds. The QTc remained normal for the remainder of the day.

Subsequent serial 12-lead electro-cardiograms (ECGs) documented normal QTc values over the next days and weeks while supine. The remainder of the hos-pital stay was significant for medical necrotizing enterocolitis, sepsis, and eventual successful modified Blalock-Taussig shunt placement with patent ductus arteriosus ligation. He was dis-charged on day of life 53 with planned follow-up with cardiology for timing of future surgical interventions.

DISCUSSION

The case of this infant with transient, marked QT prolongation and apnea as-sociated with positional change illustrates how dynamic changes in this index of cardiac repolarization might provide a noninvasive barometer of autonomic health. In 1998, Schwartz et al published a groundbreaking article demonstrating

an increased frequency of QT prolongation among infants who subsequently died of SIDS.2 The authors included a

recom-mendation for routine newborn ECG screening in an attempt to identify infants with significant QT prolongation as pos-sible candidates for medical prophylaxis. These findings and subsequent recom-mendations sparked immediate debate in which many opposing arguments centered on a previous study that did not demonstrate this correlation.4 This

de-bate led many to revisit the literature regarding SIDS and its possible patho-physiologic origins as a terminal re-spiratory event as opposed to death resulting from a cardiac arrhythmia.510

What was lost during the debate was the idea that QT prolongation may be a marker of vulnerable infants with autonomic in-stability rather than denoting the nature or mechanism of the terminal event itself.7It

is well known that the brainstem is the major regulatory site for respiration, cardiovascular function, sleep, and arousal and that dysfunction in any 1 of these areas influences the other regula-tory systems.1 Our case demonstrates

how the use of continuous QTc monitoring in the NICU setting can detect this complex interplay and possibly be used as a sen-sitive marker of autonomic instability.

In our infant, simple repositioning was associated with a dramatic increase in QTc values with subsequent clinical instability as demonstrated by repeated apneic episodes. Although it cannot be proven from a single case report, we speculate that in this case, prone posi-tioning precipitated autonomic dysregu-lation and apnea that were demonstrated by the transient and almost immediate rise in the infant’s continuous QTc read-ings. Regardless, it is obvious that posi-tional changes induced in this infant a vulnerable state that was relieved with repositioning back to the supine position. Previous studies have investigated the role of sleep position on QTc values and have found virtually no or little difference

CASE REPORT

PEDIATRICS Volume 132, Number 6, December 2013 e1691

at Viet Nam:AAP Sponsored on August 27, 2020 www.aappublications.org/news

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among healthy infants.11,12 The

correla-tion of these events with the dramatic changes in the QTc of our infant is both fascinating and provocative.

The infant in our study had 3 normal ECGs during his early life. However, continuous QTc monitoring demonstrated an acute and dramatic change that correlated with clinically relevant deterioration. Al-though determining causation and the exact mechanism of this phenomenon is impossible at this time, the QTc served as a noninvasive barometer of the health and stability of the patient’s ANS. Auto-nomic stressors are often cumulative and only result in clinical significance in an infant at critical times of autonomic or clinical vulnerability. The goal is to use the QTc to be able to detect these vul-nerable states in an attempt to intervene

or investigate a possible cause earlier than has been previously able.

Currently there are many QTc-inciting factors in neonates. The use of the standard 12-lead ECG has demonstrated QT prolongation in the setting of various electrolyte derangements and drug ad-ministration.13Enhanced use of

continu-ous QTc monitoring in the NICU setting may alert us to other relevant QTc al-tering situations. Is there an association between sepsis and QTc values that might suggest acute QTc changes as a possible marker? Does exposure to hypoxia alter the QTc in neonates, a

finding already demonstrated in mice?14

Can the severity and clinical relevance of gastroesophageal reflux be better un-derstood by the effect it has on the QTc? These are a few of the many questions

that may be explored with continuous QTc monitoring.

Inherent to the proposed use of continuous QTc monitoring in the NICU is the unique challenge that neonates present in mea-suring such intervals and whichcorrection formula should be used.15It is well known

that high heart rates, low-amplitude T waves, artifact secondary to crying, res-pirations, and caregiver interventions makes interpreting the QTc in neonates difficult and often unreliable.13,16 The

monitors used in our NICU are designed to account for these difficulties and use a signal averaging and filter-based algo-rithm to measure the QTc more accu-rately and provide more stable trends.3,17

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CONCLUSIONS

With the clinical availability of contin-uous QTc monitoring, QTc-accentuating

factors now may be gleaned in real time and infants with perturbations in their ANS might be identified. It remains to be

determined whether continuous QTc monitoring will become the next vital sign.

REFERENCES

1. Filiano JJ, Kinney HC. Sudden infant death syndrome and brainstem research.Pediatr Ann. 1995;24(7):379–383

2. Schwartz PJ, Stramba-Badiale M, Segantini A, et al. Prolongation of the QT interval and the sudden infant death syndrome.N Engl J Med. 1998;338(24):1709–1714

3. Helfenbein ED, Ackerman MJ, Rautaharju PM, et al. An algorithm for QT interval monitoring in neonatal intensive care units.J Electro-cardiol. 2007;40(suppl 6):S103–S110 4. Southall DP, Arrowsmith WA, Stebbens V,

Alexander JR. QT interval measurements before sudden infant death syndrome.Arch Dis Child. 1986;61(4):327–333

5. Hoffman JI, Lister G. The implications of a relationship between prolonged QT in-terval and the sudden infant death syn-drome.Pediatrics. 1999;103(4 pt 1):815–817 6. Hodgman JE, Siassi B. Prolonged QTc as a risk factor for SIDS.Pediatrics. 1999;103 (4 pt 1):814–815

7. Van Norstrand DW, Ackerman MJ. Sudden infant death syndrome: do ion channels play a role?Heart Rhythm. 2009;6(2):272–278

8. Franco P, Groswasser J, Scaillet S, et al. QT interval prolongation in future SIDS vic-tims: a polysomnographic study. Sleep. 2008;31(12):1691–1699

9. Guntheroth WG, Spiers PS. The triple risk hypotheses in sudden infant death syndrome.

Pediatrics. 2002;110(5). Available at: www.pe-diatrics.org/cgi/content/full/110/5/e64

10. Schwartz PJ. The quest for the mecha-nisms of the sudden infant death syn-drome: doubts and progress. Circulation. 1987;75(4):677–683

11. Baker SS, Milazzo AS Jr, Valente AM, et al. Measures of cardiac repolarization and body position in infants. Clin Pediatr (Phila). 2003;42(1):67–70

12. Ariagno RL, Mirmiran M, Adams MM, Saporito AG, Dubin AM, Baldwin RB. Effect of posi-tion on sleep, heart rate variability, and QT interval in preterm infants at 1 and 3 months’corrected age.Pediatrics. 2003;111 (3):622–625

13. Schwartz PJ, Garson A Jr, Paul T, Stramba-Badiale M, Vetter VL, Wren C; European Society of Cardiology. Guidelines for the

interpretation of the neonatal electrocar-diogram. A task force of the European So-ciety of Cardiology. Eur Heart J. 2002;23 (17):1329–1344

14. Neary M, Mohun T, Breckenridge R. A mouse model to study the link between hypoxia, long QT interval and sudden infant death syndrome (SIDS). Dis Model Mech. 2013;6(2):503–507

15. Benatar A, Ramet J, Decraene T, Vandenplas Y. QT interval in normal infants during sleep with concurrent evaluation of QT correction formulae.Med Sci Monit. 2002;8 (5):CR351–CR356

16. De Groote K, Suys B, Deleeck A, De Wolf D, Matthys D, Van Overmeire B. How accu-rately can QT interval be measured in newborn infants? Eur J Pediatr. 2003;162 (12):875–879

17. Zhou SH, Helfenbein ED, Lindauer JM, Gregg RE, Feild DQ. Philips QT interval measure-ment algorithms for diagnostic, ambulatory, and patient monitoring ECG applications.

Ann Noninvasive Electrocardiol. 2009;14 (suppl 1):S3–S8

CASE REPORT

PEDIATRICS Volume 132, Number 6, December 2013 e1693

at Viet Nam:AAP Sponsored on August 27, 2020 www.aappublications.org/news

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DOI: 10.1542/peds.2012-4005 originally published online November 11, 2013;

2013;132;e1690

Pediatrics

Michael J. Ackerman

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(6)

DOI: 10.1542/peds.2012-4005 originally published online November 11, 2013;

2013;132;e1690

Pediatrics

Michael J. Ackerman

Marc A. Ellsworth, Timothy J. Ulrich, William A. Carey, Christopher E. Colby and

Infant Positioning

QTc Interval Prolongation and Severe Apneas Associated With a Change in

http://pediatrics.aappublications.org/content/132/6/e1690

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the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2013 has been published continuously since 1948. Pediatrics is owned, published, and trademarked by Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it

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