Transcript NSAID in Europe 2009

5th International Workshop on Neonatology
The Future of European Neonatology
Cagliari, October 30-31, 2009
Non Steroids Anti-inflammatory Drugs in the
treatment of PDA in European Newborns
Hercília Guimarães
On the behalf of the Collaborative Study
NSAIDs to treat PDA in European Newborns
Introduction I
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PDA is a common cause of morbidity and mortality among
VLBW infants.
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The clinical decision of treating PDA should be carried out
on an individual basis, according to the clinical condition of
the newborn, its hemodynamic importance and potential
risks.
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Echocardiographic evaluation is necessary to establish the
diagnosis and to follow the treatment.
NSAIDs to treat PDA in European Newborns
Introduction II
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Indomethacin and ibuprofen, NSAIDs, used in the treatment
of PDA in preterm newborn infants have been shown to
produce closure in approximately 85% of patients.
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The choice for Indomethacin or Ibuprofen should be
established after evaluation of the clinical condition, costs
and local or regional availability
NSAIDs to treat PDA in European Newborns
Aim
To know the European reality on NSAIDs in the
treatment of PDA in preterm newborns.
NSAIDs to treat PDA in European Newborns
Material and Methods
A questionnaire to be filled was sent to:
• Presidents of the 24 European Societies of Neonatology/
Perinatology (UENPS)
and
• 3 representatives NICUs in Europe (UK, Belgium, Germany)
NSAIDs in the treatment of PDA in European newborns
Questionnaire
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Country and NICU
What drugs do you use in your country to treat PDA?
Ibuprofen (iv)
No ____Yes ____ Doses _________
Ibuprofen (oral)
No ____Yes ____ Doses _____________
Indomethacin (iv)
No ____Yes ____ Doses____________
Indomethacin (iv) Perfusion 30 min_____ 60 min__________ Others_________________
How many courses of treatment do you use? 1___ 2 ____3______
Do you use prolonged treatment? No __ Yes_____ Doses ____
How many days? ____ In which babies?______
Why do you prefer ibuprofen ? ______________________________
Why do you prefer indomethacin ? _____________________
When do you use NSAIDs?
Prophylactic treatment No________ Yes___________
PDA no hemodynamically significant No_______Yes ___________
PDA hemodynamically significant
No________ Yes __________
Do you use fluid restriction with NSAIDs ? No___ Yes __ If yes, how much (ml/kg) __________
Do you stop oral feeding during NSAIDs ? No_____ Yes ______
Do you use diuretics: No_____ Yes ____Which?_____
Do you diagnose PDA on a clinical basis only ? No________ Yes ________
Do you diagnose PDA by echocardiography ? No________ Yes ________
Which echocardiography criteria do you use to PDA hemodinamically significant:
Ductal diameter of >1.4mm
No___ Yes ________
Left atrial:aortic root >1.3:1
No________ Yes _______
Retrograde diastolic flow in descending aorta exceeding 30% of anterograde flow: No__Yes __
Other criteria_________________
Do you monitor PDA by echo ? No___ Yes____ Examinations during a course__________________
NSAIDs in the treatment of PDA in European newborns
Questionnaire
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What contra-indications do you consider to NSAIDs treatment?
Indomethacin
Platelets < 25.000
Creat. > 2.5 mg/dl (or >___)
Oliguria
NEC
HIV
Bleeding
Others
When do you propose surgical closure of PDA?
1. After failure of : 1___ 2__ 3 ___ 4______
courses of treatment
2 .After 3 weeks of life
No ___ Yes _____
3 .Before 3 weeks of life No ____ Yes___
4. In babies < 1000g
No ____ Yes ____
5. Contra-indications to medical treatment No_____ Yes___
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Please Indicate Ibuprofen solution__________________________________
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Are your choices influenced by Administration economical reasons?
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Number of babies with PDA / year in your NICU?__________________
Number of Admission / year in your Unit?__________________________
Number of Admission / year of VLBW in your Unit?_________________
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Comments
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Ibuprofen
NSAIDs to treat PDA in European Newborns
Results
45 NICUs from 19 countries filled the questionnaire:
1 (2 %) - North
26 (58 %) - South
12 (27 %) - East
6 (13 %) - West
Number of admissions, VLBW infants and PDA / year
n=45
Admissions
VLBW infants
PDA
% PDA/ admissions
% PDA/ VLBW infants
Mean  SD
Median (min – max)
441+234
372 (125–1300)
102+90
81 (4–550)
38+31
30 (2–150)
9+ 6
9 (0.4–25)
41+20
39 (3–100)
PDA=patent ductus arteriosus; VLBW infants
NSAIDs to treat PDA in the European newborns
n=45
n (%)
Number of doses †
Ibuprofen
intravenous
oral
rectal
16 (36)
13 (29)
1 (2)
3
3*
3*
Indomethacin
intravenous
intramuscular
32 (71)
1 (2)
3**
1 NICU does not use NSAIDs; † 2 NICUs use prolonged treatment in all cases;
* 2 NICUs use 2 doses; ** 3 NICUs use 4 and 5 doses
Indomethacin and Ibuprofen
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The perfusion of Indomethacin is done during :
30 minutes in 20 (63%) NICUs
60 minutes in 8 (25%)
20 minutes in one.
The number of treatment courses used is :
2 in 20 (45 %) NICUs
3 in 12 (27 %) NICUs
more than 3 courses in 2
1 NICU uses 2 courses of Ibuprofen + 1of Indomethacin
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Indomethacin and Ibuprofen
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Prolonged treatment (4-6 days) was mentioned
by 20 (45%) NICUs.
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The selected newborns to prolonged treatment are:
failure of 3 treatment courses in 7 (35 %)
< 1500g in 6 (30 %)
< 1000g in 3 (15 %)
all babies in 2
critical conditions in 1
Ibuprofen failure in 1
Indomethacin and Ibuprofen
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Prophylactic treatment is used in 2 NICUs
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11 (25%) treat no hemodynamically significant PDA
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43 (98%) treat hemodynamically significant PDA.
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1 NICU uses surgical closure as first line treatment.
Indomethacin and Ibuprofen
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Fluid restriction during NSAIDs treatment in 36 (80%) NICUs
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the percentage of restriction is 20% in 9 NICUs and 30% in 5.
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9 (20%) NICUs stop oral feeding during NSAIDs treatment.
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Diuretics are used in 22 (49%) NICUs:
furosemide in 19 (86%)
furosemide and/or spironolactone in 3 (+ NSAIDs)
Indomethacin and Ibuprofen
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The diagnosis of PDA is confirmed by echocardiography in all NICUs.
The echocardiographic criteria of hemodynamically significant PDA are:
ductal diameter >1.4mm in 28 (64%) NICUs;
left atrial:aortic root >1.3:1 in 31 (70%);
retrograde diastolic flow in desc. aorta>30% of anterograde flow in 24 (55%)
15 (34 %) use other criteria.
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37(82%) NICUs monitor PDA by echocardiography.
Indomethacin and Ibuprofen
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Surgical closure of PDA is proposed :
after failure of 1, in 2 (5 %), 2, in 20 (45 %), and >3, and 12 (27 %) NICUs
after 3 weeks of life in 24 (53 %)
before 3 weeks of life in 12 (27 %)
in babies < 1000g, in 17 (39%)
contra-indications to NSAIDs in 27 (61 %)
Indomethacin and Ibuprofen
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PedeaR is the iv Ibuprofen solution used
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Ibuprofen oral solution has a concentration of 20mg/ml.
Contra-indications for NSAIDs treatment
Indomethacin
(n=33), n (%)
Ibuprofen
(n=30), n (%
Platelets < 25.000
231* (94)
24* (80)
Creatinine ≥ 2.5 mg/dl
22** (67)
18*** (60)
Oligury
33 (100)
16 (53)
NEC
33 (100)
24 (80)
IVH
19 (58)
13 (43)
Bleeding (active)
30 (91)
22 (73)
1 (3)
1 (3)
1(3)
2 (7)
1 (3)
1 (3)
Others
ETcriteria
heart failure
infection
*1 NICU uses < 30.000; **3 NICUs use > 1.5 mg/dl and 1 NICU uses > 1.8 mg/dl; *** 2
NICUs use > 1.5 mg/dl
Indomethacin and Ibuprofen preference
Indomethacin
(n=33), n (%)
Ibuprofen
(n=30), n (%)
Safety
2 (6)
15 (50)
Effectiveness
4 (12)
3 (10)
Cost
10 (30)
6* (20)
12** (36)
4*** (13)
Experience
* oral Ibuprofen; ** only Indomethacin was available in 5 NICUs ;
*** only oral Ibuprofen was available
Indomethacin and Ibuprofen
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The choices are influenced by economical
reasons in 10 (22%) NICUs.
NSAIDs to treat PDA in European Newborns
Conclusion
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Our data show a wide variation among NICUs and
countries regarding the use of NSAIDs to treat
PDA and no general guidelines are followed.
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Guidelines or recommendations are necessary to
treat PDA in Europe, giving all newborns identical
health care opportunities.
Collaborators
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Belgium: B. van Overmeire, University of Antwerp.
Bósnia and Herzegovinia: S. Heljic, Clinical University Sarajevo; S. Bajic,
Cardiology, Clinical Centre Banja Luka.
Bulgary: N. Jekova, Neonatology, Specialized Hospital of Obstetrics and
Gynecology "Maichin dom", Sofia.
Croatia: Emilja Ejuretic,NICU Clinical Hospital Zagreb.
Estonia: Tuuli Metsvaht, Tartu Paediatric and Neonatal Intensive.
France: P-H. Jarreau, Port-Royal, Paris; J.C. Picaud, Hôpital de la Croix
Rouge, Lyon.
Germany: A.Franz, University of Tuebingen.
Greece: F. Anatolitou, Agia Sophia Children Hospital, Athens; K. Sarafidis,
Hippokration General Hospital, Thessaloniki; Andreou A Hippokration, General
Hospital Thessaloniki; Mitsiakos G. Papageorgiou, General Hospital
Thessaloniki; Mousafiris K, Interbalcan Medical Center Thessaloniki;
Galanopoulou A., Agios Andreas Hospital, Patras; Sigalas I, University
General Hospital Alexandroupolis; Andronikou S, University Hospital of
Ioannina; Papadimitriou M, Aglaia Kyraikou Children Hospital, Athens; Siokou
E, Lito Maternity Hospital Athens, Kostantinou D, Iaso Maternity Hospital,
Athens Gounaris A, Nikaia General Hospital, Piraeus.
Hungary: T. Kovacs, Medical and Health Science Center, Debrecen.
Collaborators
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Italy: V. Fanos, Neonatal Intensive Care Unit, University of Cagliari; M.
Pusceddu, Cesena.
Macedonia: K.Piperkova.
Netherlands: J.B. van Goudoever, Erasmus MC/Sophia Children's Hospital,
Rotterdam.
Portugal: A.Freitas, Hospital Senhora da Oliveira, Guimarães; E. Proença,
Maternidade Júlio Dinis, Porto; A. Pereira, Hospital de S. Marcos, Braga; A.
Salazar, Hospital S. Francisco Xavier, Lisboa; D. Virella, Hospital d. Estefânia,
Lisboa; H. Guimarães, G. Rocha, São João Hospital, Porto University; T.
Tomé, Maternidade Alfredo da Costa, Lisboa; S. Pedro Frutuoso, Hospital de
Santo António, Porto; G. Mimoso, Maternidade Bissaya Barreto, Coimbra.
Romania: S. Silvia, Bucharest; Tg- Mures; Iasi.
Spain: M. Sanchez-Luna, Gregorio Maragnon Hospital, Madrid; J. Pérez, La
Paz Hospital, Madrid.
Slovakia: F. Bauer, Nové Zámky; M. Zibolen, University Hospital Martin;
Slovenia: J. Babnik, University Medical Centre, Ljubjana.
Turkey: M. Yurdakok, Hacettepe University, Istanbul.
United Kingdom: N. Modi, Imperial College, London.
Thank you very much
for your atention
Porto and River Douro