Further Observations Regarding Less Aggressive Management of the PDA

Joe Kaempf, MDProvidence St. Vincent Medical Center

Portland, OR3.14.12

PSVMC PDA Study in VLBWsIndomethacin use decreased from 79% to 26%

28 day total fluids decreased from 140 ml/kg/d to 130 ml/kg/d

Ligation rate decreased from 45% to 33%

No significant change in mortality, any single morbidity, or morbidity count

CLD + Death >7 days did increase from 40% to 54%

More infants sent home with PDAs (6% to 19%) but most closed spontaneously and no increase in ligation/coiling.

J Perinatology, in press

Era 1 05-07 Era 2 08-6.09

PSVMC 139 72

RCH 76 43

SAL 21 7

SCR 4 7

Total 240 129

Era 1 Era 2 P ValuePMA (wks) 27.4 +/- 2 27.3 +/- 2 0.54

BWT (g) 989 +/-229 951 +/-274 0.16

Fluids Day 1-28 142+/-11 132 +/-9 <.001 (ml/kg/d)Week 1 127 115 <.001

Week 2 144 134 <.001

Week 3 148 139 <.001

Week 4 151 141 <.001

Indomethacin 79% 26% <.001

Day 1st Dose 5/4 12/13 <.001 mean/median

Era 1 Era 2 P Value

Ligation 44% 38% .27

Day of Lig 15/11 24/21 <.001 mean/median

NCPAP Days 22/22 27/26 .02 mean/median

Ventilator Days 11/7 14/8 .29 mean/median

Era 1 Era 2 P Value

Grade 3-4 IVH 10% 8% .48

PVL 4% 2% .23

ROP Stage 1-2 31% 40%ROP Stage 3-4 10% 9% .26

NEC 8% 10% .48

SIP 4% 4% .95

Late Infxn 13% 15% .63

Era 1 Era 2 P Value

Hospital Days 68/68 73/73 .07 mean/median

D/C >/=40 wks 18% 28% .09

Number of Major 0.8 0.9 Morbidities/pt

Morbidities/Day .01 .01 .56 (LRT Poisson Count)

Era 1 Era 2 P Value

Mortality >Day7 9% 13% .23

CLD 34% 48% <.01

Mortality or CLD 42% 57% <.01

“Stoicism is very close to one of the most subtle tenets of Oriental wisdom, and of Tibetan Buddhism in particular: contrary to the commonplace idea that one “cannot live without hope”, hope is the greatest of misfortunes. For it is by nature an absence, a lack, a source of tension in our lives. For we live in terms of plans, chasing after objectives located in a more or less distant future, and believing that our happiness depends upon their accomplishment.”

Luc Ferry, A Brief History of Thought, 2010

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Logistic RegressionPredictors for CLD Odds Ratio (95%CI) P Value

PMA (by week) 0.81 (0.68, 0.97) .02

BWT (by 100 g) 0.76 (0.66, 0.87) <.001

Era 2 1.77 (1.07, 2.91) .03

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Poisson RegressionPredictors NICU Morbidities Rate Ratio (95% CI) P Value

PMA (by week) 0.90 (0.82, 0.99) .03

BWT (by 100g) 0.86 (0.80, .93) <.001

Male 1.31 (1.04, 1.67) .02

Era 2 0.97 (.76, 1.24) .81

CLD, SIVH, PVL, SROP, NEC, SIP, Any Late Infection

Which, if any, are associated with the largest negative impact on long

term health and neurologic function?

Should we try to prevent one at the risk of increasing another?

Era 1

Era 2What were the major practice changes Era 1 v. Era 2?

Diagnosing and treating a PDA is an intricate clinical assessment, a complex and nuanced decision path based upon weaving the presence or absence of multiple variables – there is no EBM protocol as yet that we might be hoping for. Don’t create a

problem where there is none.

The decision to treat or not treat a PDA should be based upon a thorough clinical history, serial physical exams, respiratory support

needs, cardiac exam, and echocardiography. Laboratory markers (e.g., BNP) do not yet have sufficient Sens/Spec/PPV/NPV.

Prophylactic COX inhibitors should never be prescribed.

Early use of COX inhibitors or ligation (~first 7-10 days of life) should generally be avoided unless a PDA is significant by

echocardiogram, the exam is impressive, cardiorespiratory problems are obvious, and the infant is ~ELGAN.

Echocardiographic Risks PDA diameter >/= 2-3 mm

LA and LV chamber enlargement left-to-right shunt

PDA/PA ratios?

Physical Exam Riskscardiac murmur that is full, holosystolic, spills into diastole

hyperdynamic precordiumeasily palpable, full-to-bounding pulses

wide pulse pressurelow diastolic pressure

*decreased skin and mucous membrane perfusion*

Respiratory Support RisksNCPAP (or HFNC >/= 3 l/min) and FiO2 >24%

any mechanical ventilationnot weaning

pulmonary edema/vascular congestion on CXR

Historical RisksELGAN (<29 weeks GA), male, no-antenatal steroids, yes-antenatal indomethacin…..

“Improve mankind? That is the last thing that I of all people will promise. Don’t expect new idols from me; let the old idols learn what it costs to have feet of clay. To overthrow idols – my word for ideals – that is my business. Reality has lost its value, its meaning, its veracity, and an ideal world has been fabricated to take its place. The lie of the ideal has hitherto been the curse on reality, through which mankind itself has become mendacious and false down to its deepest instincts.”

Friedrich NietzscheEcce Homo, 1888