Neonatus O2 en Hbneonatus.org/wp-content/uploads/2017/10/Progressive-ROP...2017-10-03 1 PROGRESSIVE ROP: ACCEPT OR TAKE ACTION FRANK KERKHOFF MD FRANK KERKHOFF MD PhD PhD MAXIMA MAXIMA

2017-10-03

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PROGRESSIVE ROP:PROGRESSIVE ROP:ACCEPT OR TAKE ACTIONACCEPT OR TAKE ACTION

FRANK KERKHOFF MD FRANK KERKHOFF MD PhDPhD

MAXIMA MAXIMA MEDICALMEDICAL CENTERCENTER

SEPTEMBER 29, 2017, NEONATUS, SEPTEMBER 29, 2017, NEONATUS, POSNANPOSNAN, POLAND, POLAND

ROP DEVELOPMENTROP DEVELOPMENT

General idea is thatGeneral idea is that

Incidence and severity of ROP is increased Incidence and severity of ROP is increased

byby

Extra oxygen Extra oxygen

ErytrocyteErytrocyte transfusionstransfusions


Retinal changes are always seen at the Retinal changes are always seen at the same moments in timesame moments in time


First signs of ROPFirst signs of ROP 32 32 wkn PMAwkn PMA

Laser treatment Laser treatment 3434--38 38 wkn PMAwkn PMA

Retinal DetachmentRetinal Detachment 40 40 wkn PMAwkn PMA

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ROP DEVELOPMENTROP DEVELOPMENT ROP DEVELOPMENTROP DEVELOPMENT

PHASE 1 ROP PHASE 1 ROP ANDAND OO22

From Birth to 32 From Birth to 32 wkswks PMAPMA

Increased SpO2Increased SpO2

��

HyperoxiaHyperoxia

��

Down regulation of the retinal angiogenesisDown regulation of the retinal angiogenesis


From 33 From 33 wkswks PMAPMA

Decreased SpODecreased SpO22

��

HypoxiaHypoxia

��

Increase in VEGF levels and low levels of IGFIncrease in VEGF levels and low levels of IGF--11

��

VasoproliferationVasoproliferation

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ROP and OROP and O22

ROP ROP ANDAND OO22

SpOSpO22 in Phase 1 or 2 in Phase 1 or 2

ROP ROP ANDAND OO22

Phase 1 Phase 1

ROP OROP O22

Phase 1 (birth Phase 1 (birth untilluntill 32 wkn PMA)32 wkn PMA)

VasoVaso--obliterativeobliterative

First 3 days after birth O2 most effect on the First 3 days after birth O2 most effect on the

development of ROPdevelopment of ROP

DoubleesDoublees the chance on Type1/Threshold ROP in the chance on Type1/Threshold ROP in

zone 1, 70% more chance getting plus signszone 1, 70% more chance getting plus signs

HauspurgHauspurg, Blood gases and ROP: the ELGAN study, Neonatology, 1104, Blood gases and ROP: the ELGAN study, Neonatology, 1104--11:99:201111:99:2011

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ROP OROP O22

WinnersWinners--MendazibalMendazibal, Hypoxia, Hypoxia--hyperoxiahyperoxia paradigms in the development of ROP of oxygenparadigms in the development of ROP of oxygen--induced induced

retinopathy in a rat pup model, J of retinopathy in a rat pup model, J of NeonatolNeonatol--PerinatolPerinatol Med 113Med 113--7:7:20147:7:2014

ROP OROP O22

Level of SpOLevel of SpO22

Recent 3 studiesRecent 3 studies

SUPPORT, COT en BOOST IISUPPORT, COT en BOOST II

Looks at the effect of high Looks at the effect of high (90(90--95%) 95%) and low and low (85(85--89%) 89%) levels of SpOlevels of SpO22 in Phase 1 (birthin Phase 1 (birth--

32wks PMA)32wks PMA)

Carlo, SUPPORT study group. Target ranges of oxygen saturation in extremely preterm infants, N Carlo, SUPPORT study group. Target ranges of oxygen saturation in extremely preterm infants, N EnglEngl J Med J Med 19591959--69:362:201069:362:2010

Schmidt, Canadian Oxygen Trail (COT) Group, JAMA 2111Schmidt, Canadian Oxygen Trail (COT) Group, JAMA 2111--20:309:201320:309:2013DarlowDarlow, Benefits of , Benefits of oxygensaturationoxygensaturation targeting (BOOST), J targeting (BOOST), J PediatrPediatr 3030--35:165:2014 35:165:2014

ROP OROP O22

Manja, Oxygen saturation target range for extremely preterm infants: a systematic review and metaManja, Oxygen saturation target range for extremely preterm infants: a systematic review and meta--analysis, JAMA analysis, JAMA

pediatrics 332pediatrics 332--40:169:201540:169:2015

ROP OROP O22

Manja, Oxygen saturation target range for extremely preterm infants: a systematic review and metaManja, Oxygen saturation target range for extremely preterm infants: a systematic review and meta--analysis, JAMA analysis, JAMA

pediatrics 332pediatrics 332--40:169:201540:169:2015

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ROP OROP O22

ManjaManja, , OxygenOxygen saturationsaturation target range target range forfor extremelyextremely pretermpreterm infantsinfants: a : a systematicsystematic review review andand metameta--

analysis, JAMA analysis, JAMA pediatricspediatrics 332332--40:169:201540:169:2015

MetaMeta--analysis showed that the quality of analysis showed that the quality of evidence is low for the estimate of effect of evidence is low for the estimate of effect of

low mortality before discharge with the higher low mortality before discharge with the higher

SpOSpO 22 target. target.

ROP OROP O22

ManjaManja, , OxygenOxygen saturationsaturation target range target range forfor extremelyextremely pretermpreterm infantsinfants: : andand outcomesoutcomes at 18at 18--24month; 24month;

asysthematicasysthematic review, review, PPediatricsediatrics 139;:2017139;:2017

The lower SpOThe lower SpO22 target group had a tendency target group had a tendency toward reduced severe ROP toward reduced severe ROP

ROP OROP O22

ManjaManja, , OxygenOxygen saturationsaturation target range target range forfor extremelyextremely pretermpreterm infantsinfants: a : a systematicsystematic review review andand metameta--

analysis, JAMA analysis, JAMA pediatricspediatrics 332332--40:169:201540:169:2015

Maxima Medical CenterMaxima Medical Center

Target SpOTarget SpO22 between 88between 88--95%95%

ROP OROP O22

Phase 1 Phase 1

The SpOThe SpO22 is dictated by the Neonatal is dictated by the Neonatal

literature at the present moment.literature at the present moment.

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ROP ROP ANDAND OO22

Phase 2 Phase 2

ROP OROP O22

Phase 2Phase 2

Retinal hypoxia leading to Retinal hypoxia leading to vasoprolifationvasoprolifation

..

ROP OROP O22

Phase 2Phase 2

Retinal hypoxia leading to Retinal hypoxia leading to vasoprolifationvasoprolifation

With adequate oxygenation abnormal vessel With adequate oxygenation abnormal vessel

growth regresses.growth regresses.

ROP OROP O22

STOPSTOP--ROP studyROP study

Objective:Objective:Can higher levels of SpOCan higher levels of SpO22 decrease the decrease the

progression of ROP and reduce the progression of ROP and reduce the

number of treated eyes.number of treated eyes.

STOPSTOP--ROP, a randomized controlled trail: 1 primary outcomes, Pediatrics 295ROP, a randomized controlled trail: 1 primary outcomes, Pediatrics 295--310:105:2000310:105:2000

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ROP OROP O22

STOPSTOP--ROP studyROP study

A trend but a significant decrease in the A trend but a significant decrease in the number of treated eyes in Type 1 ROP number of treated eyes in Type 1 ROP

except in eyes without plus signs. except in eyes without plus signs.

STOPSTOP--ROP, a randomized controlled trail: 1 primary outcomes, Pediatrics 295ROP, a randomized controlled trail: 1 primary outcomes, Pediatrics 295--310:105:2000310:105:2000

ROP OROP O22

SpOSpO22 9696--99%99%>32 wkn PMA>32 wkn PMA

ROP OROP O22

SpOSpO22 9696--99%99%>32 wkn PMA>32 wkn PMA

ROP OROP O22

SpOSpO22 9696--99% 99% >>32 wkn PMA32 wkn PMA

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ROP OROP O22

Progressive ROP and elevation of SpOProgressive ROP and elevation of SpO2 2

(>95%)(>95%)

Prevention of treatment in Prevention of treatment in progressieveprogressieve ROP ROP

without plus signswithout plus signs

ROP OROP O22


(>95%)(>95%)

Prevention of treatment in Prevention of treatment in progressieveprogressieve ROP ROP

without plus signswithout plus signs

Delay of treatment in progressive ROP with Delay of treatment in progressive ROP with

plus signsplus signs

ROP OROP O22


(>95%)(>95%)

Delay of treatment in progressive ROP with Delay of treatment in progressive ROP with

plus signsplus signs

Transfer for treatment neededTransfer for treatment needed

Sick infantsSick infantsDelay Delay �� older children older children �� anesthesia anesthesia

easiereasier



Increased SpOIncreased SpO22

��

Less tissue hypoxiaLess tissue hypoxia

��

Decrease in VEGF levels and low levels of IGFDecrease in VEGF levels and low levels of IGF--11

��

Less Less VasoproliferationVasoproliferation

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ROP OROP O22

Phase Phase 22

The SpOThe SpO22 is dictated by the is dictated by the OpthalmologistOpthalmologist

who who can observe can observe the progression the progression of ROPof ROP

ROP and ROP and HbHb

PProgressiverogressive ROP ROP withwith low low HbHb

PuckPuck

GestGest Age Age 2525+1+1 wkswks

BWBW 769 gr769 gr

ROP 1 in zone 2 ROP 1 in zone 2 forfor a long a long periodperiod, ,

howeverhowever in a in a twotwo weeks weeks windowwindow at 41at 41+5+5

severe severe ROPROP


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PProgressiverogressive ROP ROP withwith low low HbHb PProgressiverogressive ROP ROP withwith low low HbHb


PuckPuck

OxygenationOxygenation was was notnot changedchanged

AfterAfter discharge at the NICU 36 discharge at the NICU 36 wkswks

PMAPMA

High care center High care center acceptedaccepted forfor weeks a weeks a

HbHb of 5.2of 5.2--5.4mmol/l 5.4mmol/l andand was was onlyonly

treatedtreated withwith ferrofumaraatferrofumaraat

ROP ROP ANDAND HB HB

EnglertEnglert et al study on Anemia et al study on Anemia transfusions and ROPtransfusions and ROP

EnglertEnglert et al, Effect of anemia on ROP in et al, Effect of anemia on ROP in extreemextreem low birth weight infants, Journal of low birth weight infants, Journal of

Perinatology, 2001;21;121Perinatology, 2001;21;121--66

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ErdolErdol et al. study on distribution of et al. study on distribution of HbAHbAand and HbFHbF in term and premature infants in term and premature infants

and the effect on ROPand the effect on ROP


ErdolErdol et al, et al, InvestegationInvestegation of the effect of hemoglobin F an A levels on the development of of the effect of hemoglobin F an A levels on the development of

ROP, Journal of AAPOS, 2017;21;136ROP, Journal of AAPOS, 2017;21;136--4040

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Non of these studies made a Non of these studies made a differentiation in the moment that the differentiation in the moment that the

anemia is present or the anemia is present or the erytrocyteerytrocyte

transfusion is transfusion is given (given (wkswks PMA) PMA)

PHASE 1 ROP PHASE 1 ROP ANDAND HBHB

From Birth to 32 From Birth to 32 wkswks PMAPMA

Transfusion adult blood Transfusion adult blood

��

Increased Increased HbAHbA

��

HyperoxiaHyperoxia

��

Down regulation of the retinal angiogenesisDown regulation of the retinal angiogenesis

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PHASE 2 ROP PHASE 2 ROP ANDAND HB HB


AnemiaAnemia

��

Less tissue oxygenation Less tissue oxygenation

��

Increase in VEGFIncrease in VEGF

��

VasoproliferationVasoproliferation

PROGRESSIVE ROPPROGRESSIVE ROP

Something changed in oxygenation ?Something changed in oxygenation ?

Low Low HbHb levels ?levels ?

Systemic problems ?Systemic problems ?

PROGRESSIVE ROP PROGRESSIVE ROP IN THEIN THE

MMCMMC

Action Action �� Adjust Adjust SpOSpO22 >95>95%% Action Action �� Adjust Adjust SpOSpO22 >95>95%%

Effect Effect �� regression of ROPregression of ROP

vessel growth in vessel growth in avasculairavasculair

zonezone

(within 10 days)(within 10 days)


MMCMMC

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Action Action �� Adjust Adjust SpOSpO22 >95>95%%

Effect Effect �� regression of ROPregression of ROP

vessel growth in vessel growth in avasculairavasculair

zonezone

(within 10 days)(within 10 days)

Action Action �� Check Check HbHb


MMCMMCLASER TREATED ROPLASER TREATED ROP

After laser treatment After laser treatment untilluntill first checkfirst check

LASER TREATED ROPLASER TREATED ROP


VEGF down regulation take’s time after laser VEGF down regulation take’s time after laser

LASER TREATED ROPLASER TREATED ROP


VEGF down regulation take’s time after laser VEGF down regulation take’s time after laser

So So untilluntill first check after laser:first check after laser:

SpOSpO22 > 95%> 95%

HbHb > 7 > 7 mmolmmol/l/l

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Bedankt voor u aandachtThankThank youyou forfor youryour

attentionattention

Documents

Neonatus O2 en Hbneonatus.org/wp-content/uploads/2017/10/Progressive-ROP...2017-10-03 1 PROGRESSIVE ROP: ACCEPT OR TAKE ACTION FRANK KERKHOFF MD FRANK KERKHOFF MD PhD PhD MAXIMA MAXIMA