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Therapeutic Hypothermia for Neonatal Encephalopathy and ExtracorporealMembrane Oxygenation

An Massaro, MD, Khodayar Rais-Bahrami, MD, Taeun Chang, MD, Penny Glass, PhD, Billie Lou Short, MD,

and Stephen Baumgart, MD

This case series describes the clinical management of 5 infants who underwent whole-body cooling during extra-corporeal membrane oxygenation (ECMO). In all 5 infants, systemic hypothermia was maintained during ECMOwith acceptable clinical outcomes. (J Pediatr 2010;157:499-501)

Whole-body cooling according to the National Insti-tute of Child Health and Human Development(NICHD) protocol1 has been used to treat new-

borns with encephalopathy referred to the Childrens Na-tional Medical Center neonatal intensive care unit sinceMay 2006. Modified Sarnat criteria are used to define the

moderate to severe encephalopathy required for entry ontothe whole-body hypothermia therapeutic protocol.1 Todate, we have provided whole-bodycooling to 117 infants who met thesecriteria. The Childrens National Medi-

cal Center criteria for extracorporeal membrane oxygenation(ECMO) include persistent hypoxia (preductal peripheraloxygen saturation [SpO2]

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intervention. Four infants had hypotension requiring vaso-

pressor support that was discontinued after stabilization onECMO. Four infants had initial transient oliguria that re-solved by day 4 of life. All 5 infants had some evidence ofend-organ ischemia with either elevated liver or renal func-

tion tests (Table II; available at www.jpeds.com), althoughthese studies normalized in all infants before discharge.Likewise, all infants demonstrated prolonged coagulationstudies and thrombocytopenia during hypothermia. All 5infants received platelet transfusions (median number

during the 72-hour cooling period, 3; range, 2-4), 3 infantsreceived fresh frozen plasma (median, 2 transfusions;range, 1-6), and 2 infants received a single cryoprecipitatetransfusion. Three infants exhibited evidence of pulmonary

hemorrhage. Two were noted to be mild and resolved withincreased peak end-expiratory pressure on the ventilator.

One infant had more significant bleeding that resolved afteradministration of fresh frozen plasma and platelets. Threeinfants had intracranial hemorrhage, 1 with a small choroidplexus hemorrhage and 2 with subdural and

intraparenchymal hemorrhages.

Patient Outcomes

All 5 infants survived to hospital discharge (Table I). Threewere developmentally age-appropriate at follow-up(assessment interval, 6-21 months). Patient 2, seen at age 3

months, was noted to have tone abnormalities but wassubsequently lost to follow-up. Patient 5 developedprogressive hydrocephalus after discharge and underwentventriculoperitoneal shunt placement. Assessment at age 5-

1/2 months revealed significantly delayed motor andcognitive/play skills.

Discussion

Hypothermia has been increasingly adopted since beingdemonstrated to reduce adverse outcome (ie, death or neuro-developmental impairment at 18 months) in infants withmoderate to severe neonatal encephalopathy.1-3 We reportneonates treated with the established NICHD therapeutic hy-pothermia protocol1 who also received ECMO life support.

Although our experience is limited to whole-body cooling,these findings might be generalizable to infants undergoingselective head cooling, because adverse effect profiles appear

to be similar between both cooling modalities.3

It is knownthat intrauterine fetal distress and fetal asphyxia are associ-ated with stimulation of intestinal peristalsis and relaxationof the anal sphincter resulting in premature passage of meco-nium in compromised fetuses.4 Thus, it is not surprising thatasphyxiated infants manifesting encephalopathy also wouldbe at risk for developing meconium aspiration syndrome

and hypoxic respiratory failure necessitating ECMO. We re-port cases of infants who met the defined criteria for entryinto hypothermia before meeting our institutional criteriafor ECMO.

ECMO has been demonstrated to have adverse neurodeve-

lopmental impacts. Infants treated with ECMO in the

TableI.

DemographicandClinicalCharacteristicsofECMO/HypothermiaPatients

Pt

GA(wks)

BW

(kg)

Sex

Ageat

cooling

(hours)

Ageon

ECMO(hours)

InitialpH

Base

Deficit

1Min

Apgar

5Min

Apgar

Dx

ECMO

days

LOS

EEG

Seizures

PostECMOMRI

Findings(DOL)

OUTCOME

(AssessmentAge)

1

36

2.7

8

M

5:

43

64:53

6.6

6

n/a

4

3

Chorio

MAS

6

28

No

Normal

(DOL10)

MDI/PDInormal(21months)

2

38

3.0

8

M

5:

56

30:07

6.6

9

27

2

3

MAS

18

50

No

Choroidplexushemorrhage

(DOL31)

Increasedtone(3mo,

then

LFU)

3

39

3.1

1

F

3:

06

19:08

6.9

0

10

1

3

Chorio

MAS

8

31

No

Normal

(DOL16)

MDI/PDInormal(6mo)

4

39

3.1

5

F

4:

15

13:12

6.8

0

10

4

5

MAS

8

22

Yes

Parietal/SDH,

multifocal

signalabnl(DOL9)

MDI/PDInormal(9mo)

5

40

3.8

4

M

4:

55

7:08

6.8

0

22

4

7

MAS

11

45

No

Parietal/SDH,

basalganglia

edema(DOL16)

MDI/PDI