Enhancing Utilization of Non-Invasive Positive Pressure Ventilation in Critical Care

Project Focus The focus of this project is to improve the ventilatory management of patients
with acute respiratory failure in the critical care setting by enhancing the use of
non-invasive ventilation, a goal that should lead to improved outcomes and efficiency of
care. Within the framework of the funding agency, the Chest Foundation, this proposal aims to
promote the use of alternative therapies in treating patients with critical illness, educate
practitioners, and disseminate new knowledge regarding the therapy.

Background Non-invasive positive pressure ventilation (NPPV) provides mechanical ventilation
without the need for airway invasion through the use of either nasal or oronasal masks
(covering both the nose and mouth) attached to positive pressure ventilators. Published
evidence from randomized control trials has demonstrated the effectiveness of the technique
in avoiding intubation, reducing complications associated with intubation, shortening ICU and
hospital lengths of stay, and reducing mortality rates in selected patients with acute
respiratory failure. Randomized trials have demonstrated effectiveness in patients with acute
exacerbations of COPD (1-3), cardiogenic pulmonary edema (4), immunocompromised patients with
hypoxemic respiratory failure (5,6), facilitating the weaning process in patients ventilated
invasively (7), and in patients who develop respiratory insufficiency after lung resection
(8). In addition, evidence that is not quite as strong supports the use of NPPV in patients
with acute asthma (9), cystic fibrosis (10), community-acquired pneumonia if there is
underlying COPD (11), and patients with a do-not-intubate status (12).

Based on this evidence, consensus groups have recommended the use of NPPV in treating
patients with COPD exacerbations and for selected patients with other diagnoses (13).
However, NPPV is still underutilized at many medical centers throughout the world (14) and it
is fair to presume that many patients are being deprived of NPPV's advantages and that ICU
resources are being wasted. Similar surveys have not been performed in the US, and my firm
impression from polling audiences when I speak on this subject is that a similar proportion
of US centers are not using NPPV. The purposes of this project are to acquire this
information in a US setting, to identify reasons for underutilization, to implement
interventions that encourage more appropriate use of NPPV, and then to evaluate the
effectiveness of the intervention.

The successful implementation of this project may have a major impact on the practice of
critical care medicine. Reliable information on utilization of NPPV as well as analysis of
reasons for underutilization will provide insight into ways of enhancing utilization.
Educational programs designed to enhance practitioners' skills in implementing NPPV should
lead to greater utilization and improved success rates. Optimal utilization of NPPV should
lead to improved outcomes for patients with respiratory failure, more rational use of
resources, and lower ICU costs for our health care system.

Project A. Major Hypothesis: An educational intervention will increase utilization and
success rates of NPPV in hospitals that currently underutilizing it.

B. General Outline 1. Site selection

1. Select 8 sites that use NPPV in < 10% of patients receiving mechanical ventilatory
assistance, based on a survey mailed to acute care hospitals in Massachusetts and Rhode
Island during 2002. Sites will be selected based on: (i) willingness to participate (as
per request of Respiratory Therapy director), (ii) > 30 mechanical ventilation
initiations/month as reported in the survey, and (iii) n more than 90 minute drive from
Boston.

2. Perform prospective evaluation of use of NPPV that will determine rate of utilization,
technology used, patient diagnoses, duration of ventilator use and hospital stay, and
success rates as recorded on case report forms.

3. Intervention (or control) phase. After completion of survey, provide
education/in-servicing program to 5 randomly selected sites aimed at increasing
knowledge and skill of physicians, nurses, and respiratory therapists in the use and
implementation of NPPV.

C. Evaluation phase

1. Re-survey targeted institutions with regard to use of NPPV and patient outcomes.

Methods A. Prospective Survey at 8 Selected Institutions Underutilize NPPV

1. Random selection will be performed using computer-generated number sequence,
selecting sites based on alphabetical listing.

2. Data will be gathered on CRFs that will document utilization of mechanical
ventilation; number of NPPV starts; patient diagnoses; date, time, and location of
NPPV use; equipment and settings used to ventilate; success rate of NPPV; duration
of NPPV use; and eventual patient outcomes.

3. Data collectors from Tufts or respiratory therapists at each site will initiate CRF
use. Personal health information will be de-identified by using study code numbers.
The patient medical record number cross-referenced to the patient code will be kept
on a separate list kept in a locked area, so that the patient's medical record can
be located to retrieve missing data and recorded data can be verified.

B. Education and In-Servicing

Educational and in-servicing sessions will be provided to randomly selected
underutilizing sites and will review guidelines provided in the literature by the PI
(15,16) as well as other investigators (17). Grand rounds and other lecture venues for
the physicians working in emergency and critical care settings will describe the skills
needed to select patients who will benefit from the use of NPPV. Workshops for
respiratory therapists will review patient selection, proper use of equipment, and
monitoring and weaning techniques. In-servicing sessions for emergency and critical care
nurses will review the rationale behind NPPV use and how to monitor patients who are
placed on NPPV. At control sites, no intervention will be undertaken prior to the second
data survey.

C. Evaluation Phase

Mechanical ventilation and NPPV utilization will be tracked with the same data gathering
instruments used during the initial phase. Initial and follow-up data gathering will be
staggered. The follow-up evaluation in the control group will be timed to correspond
with follow-up in institutions receiving the intervention.

Main Outcome Variables

1. Rate of NPPV utilization.

2. NPPV success.

3. Compliance with guidelines.

Analysis The main outcome variables will be analyzed as categorical variables by chi
square analysis or the Mann-Whitney test as appropriate. Initial data will be compared
to follow-up data obtained during the follow-up phase using paired t-tests, Mann-Whitney
tests, as appropriate. Comparisons between the intervention and control groups at
baseline and follow-up will be made using unpaired t-tests or chi square analyses as
appropriate. Because randomization is by site, data will be clustered by institution,
although we will be limited by resources as to the number of sites in this study. Using
linear regression analysis, we will be able to determine risk ratios for failure for a
number of initial characteristics, including diagnosis, vital signs, blood gases,
presence of cough and airway secretions, body mass index, sedation, kind of equipment
used, in-hospital locations for NPPV implementation, and other characteristics.

Anticipated Results We anticipate that results from the sites selected to receive the
training intervention and control sites will be similar at baseline and that the
intervention will increase utilization and success rates of NPPV compared to baseline.
Utilization and training rates also may increase at control sites, because of an
increased trend toward NPPV use in acute care settings. However, the important
comparison will be between the intervention and control sites at follow-up. If
intervention is effective, NPPV utilization and success rates will be increased at
intervention sites compared to controls. Other key differences may be detectable, such
as shorter ICU lengths of stay and reduced mortality rates among respiratory failure
patients treated at the intervention sites.

Risk/Benefit Analysis This is a prospective observational trial that involves no patient
intervention. Patients are to be managed by their primary caregivers, and guidelines are
provided to randomly selected institutions. These guidelines, derived from standards in
the literature (15-17) aim to improve the outcomes of patients receiving NPPV. Because
the trial is observational, involves no direct patient intervention, and poses
essentially no direct risk to patients, we are requesting waiver of consent. The patient
data that we are collecting aims to track standard clinical information and will be
de-identified.

Protection of Personal Health Information CRFs will be de-identified for the purposes of
the study. CRFs will be kept in a locked office. A cross-referenced sheet containing
medical record numbers and patient code numbers will be kept in a locked file until
missing data are retrieved and data verified using chart review. Once the data set is
complete and validated, the cross-referenced sheet will be shredded and discarded.

Limitations, Potential Problems, and Strengths One limitation is that optimal
utilization rates for NPPV in the acute care setting have not been established. In
addition, overutilization (use in inappropriate candidates) at some centers is also a
concern, as noted in the European survey (14). Although this project will focus on
underutilization of NPPV, we will able to track evidence of inappropriate applications.
Another concern is that there can be no blinding as to study condition at individual
centers, introducing the possibility of center-based bias. Randomization of intervention
and control centers should minimize this concern.

The study also has several strengths. Compared to the European ICU survey that only
included selected centers that had volunteered to serve in a consortium, this project
will obtain information on NPPV use in all acute care centers in a geographic region,
giving a more accurate glimpse of actual usage rates. In addition, the survey will
provide information on reasons for under-utilization and the inclusion of an
intervention will shed light on the effectiveness of strategies to enhance utilization.
These results can then be applied to achieve more appropriate use of NPPV. The study
might also provide insight into techniques that could also be applied to other critical
care practices, such as use of particular ventilator settings for invasive mechanical
ventilation, or use of certain pharmacological agents.

References

1. Kramer N, Meyer TJ, Meharg J et al: Randomized, prospective trial of noninvasive
positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care
Med 1995; 151: 1799-1806.

2. Brochard L, Mancebo J, Wysocki M et al: Noninvasive ventilation for acute
exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1995; 333:
817-822.

3. Plant PK, Owen JL, and Elliott MW: Early use of noninvasive ventilation for acute
exacerbations of chronic obstructive pulmonary disease on general respiratory
wards: a multicenter randomized controlled trial. Lancet 2000; 355:1931-1935.

4. Masip J, Betbese AJ, Paez J, Vecilla F, Canizares R, Padro J, Paz Marco A, Otero J,
Bllus J: Non-invasive pressure support ventilation versus conventional oxygen
therapy in acute cardiogenic pulmonary oedema; a randomized study. Lancet 2000;
356:2126-2132.

5. Antonelli M, Conti G, Bufi M, Costa MG, Lappa A, Rocco M, Gasparetto M, Meduri GU:
Noninvasive ventilation for treatment of acute respiratory failure in patients
undergoing solid organ transplantation. JAMA 2000, 283: 235-241.

6. Hilbert G, Gruson D, Vargas F, Valentino R, Gbikpi-Benissan G, Dupon M, Reiffers J,
and Cardinaud JP. Noninvasive ventilation in Immunosuppressed patients with
pulmonary infiltrates, and acute respiratory failure. N Engl J Med 2001;
344:481-487.

7. Nava S, Ambrosino N, Clini E, Prato M, Orlando G, et al. Non-invasive mechanical
ventilation in the weaning of patients with respiratory failure due to chronic
obstructive pulmonary disease: a randomized study. Ann Intern Med 1998; 128:
721-728.

8. Auriant I, Jallot A, Herve P, et al. Noninvasive ventilation reduces mortality in
acute respiratory failure following lung resection. Am J Respir Crit Care Med 2001;
164: 1231-1235.

9. Meduri GU, Cook TR, Turner RE, Cohen M and Leeper KV. Noninvasive positive pressure
ventilation in status asthmaticus. Chest 1996; 110: 767-774

10. Hodson ME, Madden BP, Steven MH et al. Noninvasive mechanical ventilation for
cystic fibrosis patients - a potential bridge to transplantation. Eur Respir J
1991; 4: 524-527.

11. Confalonieri M, Potena A, Carbone G, Della Porta R, Tolley EA, and Meduri GU. Acute
respiratory failure in patients with severe community-acquired pneumonia. Am J
Respir Crit Care Med 1999, 160: 1585-1591.

12. Meduri GU, Fox RC, Abou-Shala N, et al. Noninvasive mechanical ventilation via face
mask in patients with acute respiratory failure who refused endotracheal
intubation. Crit Care Med 1994; 22: 1584-1590.

13. Bach JR, Brougher P, Hess DR et al. Consensus statement: Noninvasive positive
pressure ventilation. Respir Care 1997; 42: 365-369. 6. 6.

14. Carlucci A, Richard J-C, Wysocki M, Lepage E, Brochard L. Noninvasive versus
conventional mechanical ventilation: and epidemiological survey. Am J Respir Crit
Care Med 2001; 163:874-880.

15. Criner GJ, Kreimer DT, Tomaselli M, Pierson W, and Evans D. Financial implications
of noninvasive positive pressure ventilation (NPPV). Chest 1995; 108: 475-481.

16. Hill NS, ed. Noninvasive Positive Pressure Ventilation; Principles and
Applications. Futura, Armonk, NY, 2001.

17. Sinuff T, Cook DJ, Randall J, Allen CJ. Evaluation of a practice guideline for
noninvasive positive pressure ventilation for acute respiratory failure. Chest
2003; 123(6):2062-73.

Inclusion Criteria:

- Starting on mechanical ventilation (including: invasive, noninvasive, CPAP or BiPAP
for purpose of treatment of respiratory failure)

- 18 years of age or older

Exclusion Criteria:

- Use of home mechanical ventilation, including nocturnal ventilation, continuous
mechanical ventilation,BiPAP.

- Continuous use of CPAP or BiPAP for treatment of obstructive sleep apnea.

- Placed on mechanical ventilation for purposes of surgical anesthesia or use of
anesthesia for a diagnostic procedure.

- Patient has tracheostomy or was intubated endotracheally prior to admission.