Lecture held at the International Arab Neonatal Care Conference, Dubai 1 Oct 2016.

1. Patent Ductus Arteriosus
- news and views on diagnosis and management
STEFAN JOHANSSON, MD PhD
Sachs Children’s Hospital
Karolinska institutet
Stockholm, Sweden

2. Get in touch!
stefan.johansson@ki.se
linkedin.com/in/johansson247
slideshare.com/stefanjohansson

3. www.99nicu.org

4. www.ebneo.org

5. PDA
PDA
PDA
PDA
PDA
PDA
PDA
PDA
PDA
PDA
PDA
PDA
PDA
PDA
PDA

6. ”Despite…research and clinical experience with thousands of
infants over nearly 6 decades, there is still uncertainty and
controversy about the significance, evaluation, and management
of patent ductus arteriosus in preterm infants…”
AAP Committee on Fetus and Newborn.
Pediatrics Dec 2015. doi: 10.1542/peds.2015-3730

7. You will still be confused
after this lecture

8. • What?
• Why?
• How?
• When?
• The Stockholm Way!

10. PDA – common clinical problem
0
20
40
60
80
100
22 w 23 w 24 w 25 w 26 w
PDA rate (%)
EXPRESS study (all live-born infants <27 weeks in Sweden 2004-2007)
EXPRESS Group. Acta Paediatrica 2010;99:978.

11. PDA – what is it?
☞ ”hemodynamically significant PDA”
• patophysiological consequences counts!

12. PDA – what it is really?
Clinical symtoms/signs
• murmur
• bounding pulses
• sBP >> dBP
• hypotension
• feeding intolerance
Echocardiographic signs
• patency of the duct
• left-right shunt
• large left atrium
• diastolic ”steal”
• diastolic flow in LPA

13. PDA – how is it defined?
let’s read Methods in papers

14. PDA – how is it defined?
• ”diastolic flow easily detectable… main
pulmonary artery”
• ”diastolic backflow in the aorta immediately
beneath the ductus”
• ”LA-to-Ao-ratio >1.6”
van Overmeire. New Engl J Med 2000;343:674

15. PDA – how is it really defined?
• ”left to right ductal shunting”
• ”increased LA-to-Ao-ratio”
• ”failure to wean from mechanical ventilation”
• ”PDA defined as the ICD code for PDA”
Richards. Pediatrics 2009;124:e287
Gudmundsdottir. Neonatology 2015:107:87

16. PDA – is there a definition?
Zonnenberg. Acta Paediatrica 2012;101:247

17. ”PDA” in randomized trials
Definition of a ”significant PDA” studies (n)
- not mentioned 3
- clinical only 7
- clinical and echocardiographic 44
- echocardiographic only 13
Zonnenberg. Acta Paediatrica 2012;101:247

18. So, how should we diagnose PDA?

19. • What?
• Why?
• How?
• When?
• The Stockholm Way!

21. Closing the PDA is rather easy…

22. … but what is the point doing it?

23. ”PDA increase the risk of…”
• mechanical ventilation
• pulmonary haemorrhage
• NEC
• IVH / PVL
• ROP
• BPD

24. Are these associations true?
• Conflicting results
• Treatment does not seem to reduce risks 

25. Causality or co-occurence?
PDA BPD
Short gestational age
PDA
BPD

26. Indomethacin prophylaxis and BPD
999 ELBW infants
49% had PDA
503 got placebo496 got indomethacin
21% had PDA
Schmidt. J Pediatr 2006;148:730
41% developed BPD45% developed BPD

27. Mandatory closure vs. no Tx
• Observational study of two time periods with
– mandatory treatment (indomethacin or surgery)
– fluid restriction only
• In total 178 infants born at 23-26 weeks
• BPD rate lower with non-Tx (58 vs. 38%)
• No other differences in other morbidities
Sung. J Pediatr 2016;177:66

28. Should PDAs be treated at all?
Benitz. Arch Dis Child FN Ed 2012;97:F80

29. I am still a Believer!
We have…
• plausible associations
• a heterogeneous patient population
(no clearly defined high-risk group)
We need…
• larger observational studies
• larger randomized trials, also with placebo

30. • What?
• Why?
• How?
• When?
• The Stockholm Way!

31. Medical treatment of PDA
• Ibuprofen or indomethacin
• Due to lower risk of NEC and transient renal
insufficiency, ibuprofen is ”drug of choice”
• Enteral and iv ibuprofen ”appears” as effective
Cochrane Database Syst Rev. 2015 Feb 18;(2):CD003481

32. ”What about paracetamol?”
• The jury is still out!
• 2 RCT and 14 observational studies
• Methodological quality judged as ”poor”
• Several studies ongoing / planned.
Terrin. Arch Dis Child FN Ed. 2016;101:F127

33. • What?
• Why?
• How?
• When?
• The Stockholm Way!

34. When is the shunt significant?
• ”…the shunt develops when the pulmonary
pressure drops during the first days in life”

35. When is the shunt significant?
It is not true that…
• ”…the shunt develops when the pulmonary
pressure drops during the first days in life”

36. Early ductal shunting
• First hours of life:
– large shunt volumes
– most pronounced
hemodynamic impact
Kluckow. Early Hum Dev 2005;81:429

37. When to treat?
• Prophylactic treatment?
• Early targeted treatment to high-risk infants?
• Treating the clinically apparent PDA?

38. Early targeted treatment
• 164 infants <29 weeks, echo within 12 hours
• 92 with PDA – indomethacin or placebo
• fewer with pulmonary hemorraghe (2 vs 21%)
• no effect on mortality or cranial ultrasound
but trend towards fewer IVH (4 vs 12%)
Kluckow. Arch Dis Child FN Ed. 2014;99:F99

39. Early diagnosis
• Screening before 3 days compared to
indicated echo later
– 605 ”paired” infants <29 weeks
– lower mortality (14 vs 18%), aOR 0.62
– fewer lung bleedings (6 vs 9%)
– no risk differences in NEC, BPD, CNS-lesions
Roze. JAMA 2015;313:2441

40. • What?
• Why?
• How?
• When?
• The Stockholm Way!

41. Current protocol in Stockholm
Echocardiography day 1-3
• < 27 weeks
• all preterm infants on mechanical ventilation
Echocardiography upon “clinical suspicion”
• preterms > 5-7 days on CPAP and “high” FiO2
• clinical signs

42. the ”Stockholm PDA definition”
Functional measurements
• Ductal blood flow pattern: pulsatile
• End-diastolic velocity in LPA: >0.3 m/s
• Diastolic flow in postductal aorta: reversed
Structural measurements
• LA:Ao-ratio >1.4
• Ductal diameter >2 mm

43. Our treatment options
• Ibuprofen if <14 days of age
• Surgery may be considered if:
– infant is ”stuck” on invasive ventilation
– late relapse
– heart failure and/or severe lung disease

44. Conservative strategy
In well infants on CPAP we wait and see!
• Repeated echo’s
• Wean CPAP slowly
• Fluid restriction at 160 ml/kg/d

45. Are you still confused?

46. Conclusions
• There is no universal PDA definition but…
use echocardiography to set your diagnosis
• You can close the PDA but…
noone knows exactly why you should
• Early management might have benefits but…
”more research is needed”