NiPPV in the Treatment of Acute Asthma Exacerbations

This study is a prospective and randomized clinical trial to investigate the utility of BiPAP
therapy for the pediatric patient in an acute moderate to severe asthma exacerbation. The
study will be conducted in the pediatric emergency department at Arkansas Children's
Hospital. Patients between 2-17 years old will be identified to participate based on the past
medical history, history of present illness and PAS and the consent process will begin
immediately. All patients will be started on standard of care therapies including continuous
albuterol and atrovent aerosols, intravenous corticosteroids, intravenous magnesium sulfate
and a normal saline fluid bolus. Additional therapies with subcutaneous epinephrine or
terbutaline will be given at the discretion of the treating physician in the first 20
minutes. Further escalation of asthma therapy, for example administration of IV
bronchodilators, ketamine, terbutaline and/or epinephrine will be at the discretion of the
treating physician. The history of present illness, past medical history, triage information
and initial physical exam information will be collected by the study investigator in the
first hour and marked on the data sheet.

Once consented, participants will be randomized to one of two groups by selection of an
opaque folder by the study investigator. A PAS will be assigned at 1 hour after only having
received traditional standard of care therapies and before placing the subject on the therapy
determined by the randomization. If the child receives a score of 7 or less, he/she will not
be placed on NIPPV; however, they will be analyzed in this group based on intention to treat.

i. Group #1: This group will receive all standard of care therapies as per the pediatric ED
Asthma Severity Protocol. Will be referred to as the control group.

ii. Group #2: This group will receive all standard of care therapies as per the pediatric ED
Asthma Severity Protocol. All nebulized treatments will be given via the NIPPV/BiPAP machine
via the Servo i Ventilator. The treating PED Attending and treating PED respiratory therapist
will be blinded to the BiPAP/NIPPV settings during the study period. The PED clinical trial
research assistant and in conjunction with one of the study investigators will adjust the
BiPAP settings in concert with the treating physician. The discussion will be about either
increasing or decreasing the IPAP or EPAP not the true number changes to keep it blinded,
will be as follows: The inspiratory positive airway pressure (IPAP) will be started at 10 cm
H2O for all patients. The patient will be observed clinically by a PED respiratory therapist
in conjunction with the treating pediatric ED attending and/or fellow. The IPAP will be
increased as needed by 2 cm H2O up to a maximum IPAP of 16 cm H2O for patients 2-6 years of
age, 20 cm H2O for patients 7-12 years of age, and 24 cm H2O for patients older than 12
years. The expiratory positive airway pressure (EPAP) will be set at 5 cm H2O. If the IPAP
settings are maximized based on age and the respiratory distress score continues to be 5 or
greater, the EPAP can be increased by 1 cm H2O to a maximum of 8 cm H2O for all patients less
than 12 years and 10 cm H2O for all patients older than 12 years. The I:E setting will be
1.75 seconds. Optimal settings for each participant should be achieved within 20 minutes of
initiation of BiPAP and respiratory distress scores should recorded at least every 5 minutes
or with every BiPAP settings change during this period. Pediatric asthma scores will continue
to be recorded at least every 30 minutes or with every physician suggested NIPPV ventilator
setting change for an 8 hour period. Furthermore, the NIPPV ventilator, Servo i ventilator,
has volumetric end tidal CO2 monitoring capabilities and will record ventilatory data in this
NIPPV/BiPAP group and will be compared to other study groups.

The subjects will remain in the study for minimum of 4 hrs NIPPV therapy and total of 8 hours
unless clinically still needing the NIPPV therapy. The first hour they will all receive the
same standard therapies, followed by 7 hours of the therapies from the group in which they
were randomized. Each 30 minutes in the study, the subject will be assessed by treating
PED/PICU attending as to whether to continue the patient on the study arm, switch to a rescue
arm or discontinue the patient from the study. This reassessment will be facilitated by the
study investigator via a direct discussion with the treating attending physician.
Furthermore, every 30 minutes the treating RT, treating PED attending or fellow, or study
investigator will perform a PAS. Based on the PAS, the treating PED attending will be asked
if patient needs further adjustment of the EnVe or continue present therapy. Once a subject
in the NIPPV arm reaches a PAS of less than or equal to 7, the NIPPV settings may be weaned
per the ACH PED NIPPV/BiPAP weaning protocol.

i. Rescue Arm A: If at any point during the treatment it is deemed medically necessary by the
treating PED attending that a subject from the control arm, Group 1, requires an escalation
of therapy, they may be moved from the group to the NIPPV/BiPAP group, Group 2, or be removed
from the study i.e. if intubated.

ii. Rescue Arm B: If at any point during the treatment it is deemed medically necessary by
the treating PED attending that a subject from a NIPPV/BiPAP group,Group 2, is not tolerating
NIPPV they may be removed from the study. Patients may not tolerate NIPPV due to agitation,
vomiting or need for escalation of care.

Additionally, in an attempt to better understand the physiology of NIPPV/BiPAP parameters of
cardiac output, aortic flow and pulmonary flow, will be measured using the USCOM. This will
assist us in understanding the physiological effects of the setting choices.

Subjects in Group 2 will be kept on the NIPPV machine for 4 hours minimum, unless the PED or
PICU treating attending deems the patient has dramatically improved to take off the machine.
The study investigator will collect information regarding medications given and any
complications. At the end of the 8 hour study period, a PAS score will be calculated, and the
study investigator will ask the PED or PICU treating attending whether to continue present
therapy or switch to another therapy.

After the study time has completed, the study investigator will collect information such as
PED/PICU diagnosis, disposition from PED/PICU and related information based on disposition,
length of hospital stay and 72 hour returns from PED and mark it on the data sheet.

VII. Selection and enrollment of subjects

Inclusion criteria

2-17 years old For subjects 3 years and older, a known history of asthma as diagnosed by the
PCP or per the ACH problem list For children ages 2-3 years, four or more episodes of
wheezing in the past year that lasted more than 1 day and affected sleep AND one of the
following: parental history of asthma, a physician diagnosis of atopic dermatitis, or
evidence of sensitization to aeroallergens Acute asthma exacerbation Pediatric Asthma Score
(PAS) ≥ 8 Parents willing and able to sign consent Children over the age of 6 willing to
provide assent

Exclusion criteria

History of congenital heart disease, chronic respiratory disease including bronchopulmonary
dysplasia, cystic fibrosis, pulmonary hypertension or any chronic lung disease other than
asthma History of sickle cell disease Recently diagnosed pneumonia Current tracheostomy, on
home ventilator or home oxygen requirement Recent diabetic ketoacidosis Requiring immediate
intubation Weight less than 5 kilograms Any contraindication to BiPAP use including altered
mental status, recent bowel surgery, intractable vomiting, inability to protect airway A
history of prematurity of ≤ 30 weeks gestation

Inclusion Criteria:

- 2-17 years old

- For subjects 3 years and older, a known history of asthma as diagnosed by the PCP or
per the ACH problem list

- For children ages 2-3 years, four or more episodes of wheezing in the past year that
lasted more than 1 day and affected sleep AND one of the following:

- parental history of asthma, a physician diagnosis of atopic dermatitis, or
evidence of sensitization to aeroallergens

- Acute asthma exacerbation

- Pediatric Asthma Score (PAS) ≥ 8

- Parents willing and able to sign consent

- Children over the age of 6 willing to provide assent

Exclusion Criteria:

- History of congenital heart disease, chronic respiratory disease including
bronchopulmonary dysplasia, cystic fibrosis, pulmonary hypertension or any chronic
lung disease other than asthma

- History of sickle cell disease

- Recently diagnosed pneumonia

- Current tracheostomy, on home ventilator or home oxygen requirement Recent diabetic
ketoacidosis

- Requiring immediate intubation