A Multi-Center Study of High

Frequency Oscillatory
Ventilation in
Immunocompetent and
Immunocompromised Children
Claire A. Stewart MD
10th Annual Thomas F. Boat Lectures
March 29, 2016

Background

 High Frequency
Oscillatory Ventilation
(HFOV) is a form of
nonconventional
ventilatory support
employed for respiratory
failure
HFOV is commonly
used at our center for
refractory respiratory
failure
http://www.carefusion.com/Images/Respiratory/Ventilation/3100B-1.jpg

Arnold et al., 2000

First large, multi-center retrospective review of outcomes
for children needing HFOV support
Immunocompromised state and oxygenation index (OI)
were most powerful predictors of mortality
Arnold et al., 2015
Immunocompromised
patients had the highest
mortality risk
Oxygentation index
prior to HFOV used to
predict mortality

Arnold et al. High-frequency oscillatory ventilation in pediatric respiratory failure: A multicenter experience. Crit Care Med. 2000
Dec;28(12):3913-9.

Gupta et al. 2014

Propensity matched review of VPS database comparing
outcomes of children needing HFOV versus conventional
ventilation

Gupta et al. Comparison of High-Frequency Oscillatory Ventilation and Conventional Mechanical Ventilation in Pediatric Respiratory Failure.
JAMA Pediatr. 2014 Mar;168(3):243-9.

OSCAR Study
HFOV had no
significant effect on
30-day mortality in
patients undergoing
mechanical ventilation
for ARDS

Young et al. High-Frequency Oscillation for Acute Respiratory Distress Syndrome. N Engl J Med. 2013 Feb 28;368(9):806-13.

OSCILLATE Study
In ARDS, early
HFOV as
compared to low
TV, high PEEP
strategy, did not
reduce, and may
increase, in hospital
mortality.

Ferguson et al. High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome. N Engl J Med. 2013 Feb 28;368(9):795-805.

Improved Oxygenation may allow discrimination of Survivors

and Non-survivors amongst Immunocompromised
Children needing Non-Conventional Ventilation

Receiver operating characteristic (ROC) curves and associated calculated areas under
the curve (AUC) for oxygenation index (OI) and Pao2/Fio2 (PF) 24hr after transition to
high-frequency oscillatory ventilation (HFOV) as a fraction of pretransition values
(OI24/OIpre and PF24/PFpre).
Yehya et al. Pediatr Crit Care Med. 2014 May;15(4):e147-56.

Summary
Outcomes for HFOV in children in the current era
are not well known
Immunocompromised state and oxygenation trend
likely impact outcome for patients needing HFOV
Adult data suggests no benefit with HFOV use
while recent pediatric data question its utility

Aims
Determine survival and variables associated
with poor outcome for patients requiring HFOV
support at two large pediatric centers with a
large population of immunocompromised
patients
Test the performance of the ratio of oxygenation
index (OI) at 24h (OI24h) to oxygenation index
prior (OIPRE) in immunocompromised patients in
predicting outcome and/or determine the best
marker of oxygenation to predict outcome

Methods

Methods
Multi-center, retrospective review from January
2010 through December 2014
Inclusion criteria
Patients aged 1 month to 21 years of age
HFOV support for > 24h

Exclusion Criteria
HFOV support for <24h

Methods
Immunocompromised patients were defined as
those having a malignancy, primary
immunodeficiency, stem cell or solid organ
transplant
Immunocompromised patients were further split into
stem cell transplant and non-stem cell transplant
recipients

Results

Results
Over a five year period, 134 patients were supported with
HFOV for more than 24 hours.
51% (68/134) were immunocompromised, of these 51%
(35/68) were stem cell transplant recipients.
58% (78/134) survived to PICU discharge
Stem cell transplant (SCT) recipients had the lowest
survival rate of 21% (6/29).

80

Non-Survivor

Survivor

70
11

Number of Patients

60
50
40
30
20
10
0

29

16

55

17
6
SCT

Non-SCT

Non-Immunocompromised

Survivors vs. Non-Survivors

Survivors
n=78

Non-Survivors
n=56

Pvalue

6.9 [2.4,24]

13.5 [6, 43.5]

0.03

PRISM3

14 [8,21]

18 [10,24]

0.12

Immunocompromised

23 (34%)

45 (66%)

<.001

6 (17%)

29 (83%)

<.001

Mean Airway Pressure

21 [19,24]

22 [20,25]

0.13

PF Ratio

71 [60,95]

70 [54,86.5]

0.13

28.2 [21.6,35.4]

33.3 [23.8,40.8]

0.14

27.5 [25,30]

32 [28,35]

<.001

145 [105,250]

76.5 [60.7,132]

<.001

18.4 [10.3,26.7]

37.8 [23.8,51.3]

<.001

Total N= 134
Age (mos)

Stem cell transplant

Before HFOV

OI
At 24 hr of HFOV
Mean Airway Pressure
PF Ratio
OI

continuous data presented as median values with IQR (25th and 75th), categorical data presented as a
percentage

Results
OI pre and at 24 hours of HFOV
#

Multivariate Analysis for Mortality

Variable

POdds 95%
valu
Ratio CI
e

Immunocompromised
Status
Not
Refere
immunocompromis
nce
ed
Immunocompromis
4.9 1.7-14 0.003
ed, No SCT
4.8- <0.00
Immunocompromis
15.7
ed, SCT
51.1
1

*p<0.05 when compared OI pre in survivors; p<0.05

when compared to OI 24h in survivors
#

OI at 24 hrs of HFOV

1.05

1.020.001
1.08

For the entire cohort of patients

using OI at 24 hours of HFOV as
a predictor of mortality, the AUC
was 0.78 (0.7, 0.9).
The best cutoff value to predict
mortality for OI at 24 hours of
HFOV was 30.
Test Characteristics:
Sensitivity 0.70
Specificity 0.78
PPV 0.69
NPV 0.78

ROC curve for OI at 24 hours of HFOV as a Predictor

of Mortality

Conclusions
In this cohort of patients needing HFOV, PICU
survival was nearly 60%.
In keeping with published data, the presence of an
immunocompromised state had the strongest impact
on outcome with SCT recipients having the worst
outcome.
Survivors had a statistically significant improvement
in OI at 24h when compared to non-survivors.
Notably, OI at 24h was a significant predictor of
mortality.

Acknowledgments
Ranjit Chima, CCHMC
Hector Wong, CCHMC
Nadir Yehya, CHOP
Lin Fei, CCHMC