CHANGES

OVER TIME IN

NEONATES

WITH HIE

Daphna Yasova Barbeau

FN3 2019

OBJECTIVES

Identify normal trends in laboratory values in neonates with HIE.

Define neonates who may need further evaluation for end-organ injury.

Understand how heart variability can predict inflammation and

neurological injury.

ACID BASE BALANCE

0-6

7-12

13-1

8

19-2

4

25-4

8

49-7

272

+0

5

10

15

20

Lactate over time

Time (hours)

lactate

(mmol/L)

0-6

7-12

13-1

8

19-2

4

25-4

8

49-7

272

+6.8

7.0

7.2

7.4

pH over time

Time (hours)

pH

TRANSAMINASES

0-6

7-12

19-2

4

25-4

8

49-7

2

72+

-200

-100

0

100

200

300

400

500

600

150

Aspartate Aminotransferase (AST) over time

Time (hours)

AST (IU/L)

0-6

7-12

19-2

4

25-4

8

49-7

272

+

-100

0

100

200

300

45

Alanine aminotransferase (ALT) over time

Time (hours)

ALT (U/L)

ALKALINE PHOSPHATASE AND BILIRUBIN

0-6

7-12

19-2

4

25-4

8

49-7

2

72+

0

2

4

6

8

10

Total Bilirubin over time

Time (hours)

0-6

7-12

19-2

4

25-4

8

49-7

2

72+

-100

0

100

200

300

400

500

Alkaline phosphatase over time

Time (hours)

IU/Lmg/dL

ELECTROLYTES

0-6

7-12

19-2

4

25-4

8

49-7

2

72+

0

1

2

3

4

magnesium over time

Time (hours)

0-6

7-12

19-2

4

25-4

8

49-7

2

72+

0

2

4

6

8

10

Phosphorus over time

Time (hours)

Mmol/L Mg/dL

ARE THERE DIFFERENCES IN THOSE BABIES

WHO DO AND WHO DO NOT

DEMONSTRATE INJURY ON THEIR MRI?

SARNAT SCORES

0-6

7-12

13-1

8

19-2

4

25-4

8

49-7

272

+

0

1

2

3

4

Sarnat Scores over time

Time (hours)

responders

nonresponders

Score

Moderate/severe injuryNo/mild injury

ACID BASE BALANCE

0-6

7-12

13-1

8

19-2

4

25-4

8

49-7

272

+

6.6

6.8

7.0

7.2

7.4

pH over time

Time (hours)

responders

nonresponders

pH

0-6

7-12

13-1

8

19-2

4

25-4

8

49-7

272

+

0

20

40

60

80

100

CO2 over time

Time (hours)

responders

nonresponders

CO2 (mmHg)

ACID BASE BALANCE

0-6

7-12

13-1

8

19-2

4

25-4

8

49-7

272

+

-5

0

5

10

15

20

25

lactate over time

Time (hours)

responders

nonresponders

Mmol/L

0-6

7-12

13-1

8

19-2

4

25-4

8

49-7

272

+

-30

-20

-10

0

10

Base deficit over time

Time (hours)

responders

nonresponders

BD mmol/L

No/ mild injuryModerate/severe injury

No/ mild injuryModerate/severe injury

MARKERS OF CARDIAC ISCHEMIA

resp

onders

nonresp

onders

0

2000

4000

6000

8000

10000

12000

Creatinine Kinase total

responders

nonresponders

CK (U/L)

resp

onders

nonresp

onders

0

100

200

300

CK-MB

responders

nonresponders

CK-MB (U/L)

resp

onders

nonresp

onders

0.0

0.5

1.0

1.5

2.0

Troponin I

responders

nonresponders

Troponin (ng/mL) *

resp

onders

nonresp

onders

0

2000

4000

6000

8000

10000

12000

Creatinine Kinase total

responders

nonresponders

CK (U/L)

No/ mild injuryModerate/severe injury

TRANSAMINASES

0-6

7-12

19-2

4

25-4

8

49-7

272

+

0

50

100

150

200

250

Alanine aminotransferase (ALT)

responders vs non responders

Time (hours)

responders

nonresponders

ALT (U/L)

Moderate/severe injury

No/ mild injury

No/mild injury vs moderate/severe injury No/mild injury vs moderate/severe injury

RENAL FUNCTION

0-6

7-12

19-2

4

25-4

8

49-7

272

+

0.0

0.5

1.0

1.5

CreatinineResponders vs Non Responders

Time (hours)

responders

nonresponders

Creatinine (mg/dL )

0.4

No/mild injury vs moderate/severe injury

No/ mild injuryModerate/severe injury

C- REACTIVE PROTEIN

24 48 72 960

20

40

60

80

Time (hours)

CRP

no/mild injury vs. moderate/severe injury

no/mild injury

moderate/severe injury

CRP

<24

WHAT ABOUT THE SEVERE BABIES?

1 2 3 4 5 6 70

5

10

15

20

Lactate over time in infants with

initial Sarnat of 3

Time points

responders

mild HIE

non responders

1 2 3 4 5 6 75.5

6.0

6.5

7.0

7.5

pH over time in infants

with initial Sarnat of 3

Time (hours)

pH

no injury

mild injury

significant injury

Time points

WHAT ABOUT THE SEVERE BABIES?

1 2 3 4 5 60

500

1000

sarnat 3 AST over time

no injury

mild injury

severe injury

1 2 3 4 50

100

200

300

400

sarnat 3 ALT over time

responders

mild HIE

non responders

LAB TREND KEY POINTS

Extremes of electrolytes, glucose or acid/base disturbance also

worsen prognosis, or are indicators of worse prognosis

Babies that do not follow the normal trends should be evaluated

for a different pathology

Still no definitive marker to predict injury

Could we combine markers?

Is there anything else?

HEART RATE VARIABILITY

HRV is the measurement of intervals between heartbeats and is

regulated by the branches of the autonomic nervous system.

First observed in the fetal heart rate, where changes (decrease) in

variability preceded actual heart rate abnormalities.

Since that time it has been linked to predicting:

autonomic neuropathy in patients with diabetes

predicting post-infarction morbidity in patients with heart attacks

Predicts brain injury and neuroinflammation

Predicts neonatal sepsis

FREQUENCY

High frequency

• Regulated by parasympathetic nervous

system (0.3 -1.0 Hz)

Low frequency

• Regulated by the sympathetic nervous system (0.04 - 0.20 Hz)

BENEFITS OF USING HRV AS A BEDSIDE MARKER

Non-invasive

Quick

Continuous information

Data in raw form is already being used

Simple conversion

HRV IN OTHER DISEASE STATES

Disease Process High frequency (HF) Low frequency (LF) LF/HF ratio

HIE (before cooling)

↑ ↓ -

Adults with sepsis - ↓ ↓

Children with

increased ICP

- ↓ ↓

Rheumatoid Arthritis/

Lupus

↓ ↓ ↑

PREVIOUS STUDIES

2014 Masaro et al. LF relative power was lower at nearly all time points and HF power was higher at all time points, in infants in the adverse outcome group compared to those with favorable outcome.

Particularly salient at 24 hours

PREVIOUS STUDIES

2017 Goulding et al. There is decreased HRV with increasing EEG

grade of HIE in both the pre-TH and TH groups and in infants with

moderate EEG grades undergoing TH, the HF feature of HRV was

increased with a resultant decrease in the LF/HF ratio

2017 Masaro et al. HRV did change as a result of temperature.

Demonstrated an overall decrease in variability as infants returned to

normothermia.

2017 Metzler et al. A decrease in relative LF power and an increase in

relative HF power was observed across brain injury pattern groups

there was a significant negative association between brain injury

pattern and relative LF power .

STUDY DESIGN

Infants undergoing

cooling identified

HRV measured

once during cooling and once after rewarming

ventilated infants

measured both on and off support

signal filtered and frequencies examined

HRV KEY POINTS

Neonates undergoing hypothermia with worse injury exhibit lower

LF power compared to neonates with moderate/severe injury.

During therapeutic hypothermia, neither mechanical ventilation or

pressor substantively impacted HRV.

There are differences in HRV between female and male neonates.

Continuous HRV monitoring may provide prognostic value.

ACKNOWLEDGEMENTS

Dr. Michael Weiss

Drs. Krueger and Weaver

Livia Sura

FN3 babies and families

FN3 hospitals- that’s you!

QUESTIONS