Western Carolina University

Research Grant

Effectiveness of Continuous Positive Airway Pressure in the Management of Prehospital Pulmonary Edema

April, 2004

Applicants: Dr. Michael W. Hubble, Department of Health Sciences

Roger Jarvis, Department of Health Sciences

Tori Millikan, Department of Health Sciences

Research Hypothesis

Utilization of continuous positive airway pressure (CPAP) has a positive effect on patients suffering from pulmonary edema as measured by mortality, hospital length-of-stay, endotracheal intubation rate, oxygen saturation, and patients’ subjective assessment of dyspnea.

Significance

Dyspnea is a frequently encountered complaint among patients treated by an Emergency Medical Services System. An estimated 400,000 new cases of congestive heart failure are diagnosed in the United States each year.¹ Dyspnea constitutes approximately 4% of the chief complaints of patients presenting to emergency departments² and approximately 13% of EMS responses, second only to minor trauma.³

Cardiogenic pulmonary edema is associated with significant morbidity in the prehospital setting.⁴ While many patients respond to prehospital therapy with oxygen, nitrates, morphine and furosemide, others do not and develop progressive respiratory failure requiring ventilatory support.^5-7 Traditionally, this has been provided by endotracheal intubation and mechanical ventilation in the hospital setting. Positive pressure ventilation via mechanical ventilation has been shown to decrease the work of breathing, decrease cardiac afterload, and enhance alveolar recruitment, thereby decreasing shunt and improving oxygenation.^8-11 However, the traditional treatment of positive pressure ventilation is associated with traumatic injury to the upper airway and an increased risk of ventilator-associated pneumonia.^12-15

In an effort to reduce the need for endotracheal intubation and the complications associated with mechanical ventilation, non-invasive approaches to treating pulmonary edema have become popular. Randomized controlled trials of continuous positive airway pressure (CPAP) have demonstrated a significant reduction in the need for endotracheal intubation and a trend towards reduction in mortality of hospitalized patients suffering from acute pulmonary edema.^9,11,15-17 Although it is suggested that the prehospital use of CPAP may be beneficial, to date only two studies have investigated this notion.^18,19 Kallio et al conducted a retrospective cohort study in Helsinki, Finland. In their series of 121 patients, CPAP was found to improve oxygenation and decrease respiratory rate, heart rate, and systolic blood pressure.¹⁸ In a prospective case-series analysis, Kosowsky et al described nineteen patients who received prehospital CPAP therapy.¹⁹ Oxygen saturations for these patients improved from an average of 83.3% to 95.4% following CPAP. None of the CPAP patients required field intubation; however two patients did not tolerate the CPAP mask and required intubation upon arriving in the emergency department. Although both of these studies show promising results of prehospital CPAP, they both suffer from a lack of a control group for comparison which limits the utility of their findings. It is for this reason that the current study is proposed.

Project Plan

Study Design

Quasi-experimental nonequivalent control group.

Setting

 Interventional cases are patients transported by Forsyth County EMS (FCEMS) suffering from acute pulmonary edema. FCEMS utilizes CPAP as part of its routine treatment protocol in the management of pulmonary edema. FCEMS is a 3rd service county-based EMS system providing EMS response to the 306,000 residents of Forsyth County who inhabit a 420 square mile response area. FCEMS responds to approximately 29,500 calls annually with an average emergency response time of eight minutes. Patients are transported to one of two hospitals within the county. Forsyth Memorial Hospital has 906 inpatient beds and a 45 bed emergency department with an annual volume of 80,000 ED visits. North Carolina Baptist Hospital is a level I trauma center with 801 inpatient beds and 38 emergency department beds with an annual volume of 64,000 ED visits.

Control cases are patients transported by Guilford County EMS (GCEMS) suffering from acute pulmonary edema. GCEMS does not include CPAP as part of its routine treatment protocol for pulmonary edema. GCEMS is also a 3^rd service county-based EMS system providing EMS response to 410,000 residents within a 651 square mile response area. The annual call volume is approximately 30,000 with an average emergency response time of * minutes. Patients are transported to one of four hospitals in the county. Moses Cone Hospital is a level II trauma center with 529 inpatient beds and treats 60,000 patients annually in its emergency department. High Point Regional Hospital has 368 inpatient beds and 50,000 emergency department visits annually. Wesley Long Hospital sees 44,000 patients in its emergency department each year and has a 220 inpatient bed capacity.

With the exception of CPAP, both GCEMS and FCEMS use the same treatment protocols for managing pulmonary edema. Protocols at each institution are approved by the North Carolina Office of EMS.

Patient Enrollment

All adult patients (≥ 18 years) transported to one of the participating hospitals during the study period with a field diagnosis of acute cardiogenic pulmonary edema are eligible for enrollment. Patients who are dialysis-dependent or who suffer from pulmonary edema of non-cardiac origin (e.g., toxic inhalation) will be excluded from the data set.

Sample Size

Power calculations for intubation rates were based on a 39% intubation rate for non-CPAP and 8% for CPAP patients using pooled data among hospitalized patients from Bersten⁶, Lin⁷, and Takeda.²⁰ Power calculations for oxygen saturation, respiratory rate, and heart rate are based on the findings of Kallio and are presented below.¹⁸ A sample of 120 subjects in the interventional and control groups will provide adequate power for all outcome variables of interest (see below).

Variable	Pre-CPAP	Post-CPAP	Difference
Oxygen saturation	77 (±11)	90 (±7)	13
Respiratory rate	34 (±8)	28 (±8)	-6
Heart rate	108 (±11)	100 (±20)	-8

Variable	Difference	Power* (N = 120)	Power* (N = 150)	Power* (N = 175)
Oxygen saturation	13	1.000	1.000	1.000
Respiratory rate	-6	0.999	1.000	1.000
Heart rate	-8	0.999	0.999	1.000
Intubation Rate	0.31	0.999	1.000	1.000

*α = 0.05

Treatment Protocol

Patients in the control group will be treated according to pre-existing patient treatment algorithms established by Guilford County EMS, including the administration of oxygen, intravenous access, nitroglycerine, morphine, and furosemide (appendix 1). Patients in the interventional group will be treated according to pre-existing patient treatment algorithms established by Forsyth County EMS (appendix 2). These patients will receive treatment similar to the control group, with the addition of CPAP when indicated. There will be no modification of existing treatment protocols for the purpose of this study.

Data Collection

The following data will be abstracted from the ambulance call reports and hospital records by the investigators:

Variable	Level of Measurement	Definition
Age	Interval	Patient age in years
Gender	Nominal	0 = male, 1 = female
Pre-CPAP respiratory rate	Interval	Breaths per minute before CPAP (experimental group) or derived from first set of recorded vital signs (control group)
Pre-CPAP heart rate	Interval	Beats per minute before CPAP (experimental group) or derived from first set of recorded vital signs (control group)
Pre-CPAP systolic blood pressure	Interval	mm Hg before CPAP (experimental group) or derived from first set of recorded vital signs (control group)
Pre-CPAP diastolic blood pressure	Interval	mm Hg before CPAP (experimental group) or derived from first set of recorded vital signs (control group)
Pre-CPAP oxygen saturation	Interval	Percent before CPAP (experimental group) or derived from first set of recorded vital signs (control group)
Pre-CPAP dyspnea rating	Ordinal	Subjective assessment by patient on an ordinal 0-10 scale before CPAP(experimental group) or derived from initial assessment (control group)
Post-CPAP respiratory rate	Interval	Last recorded breaths per minute in the field or the first recorded upon arrival at the emergency department (control and experimental groups)
Post-CPAP heart rate	Interval	Last recorded beats per minute in the field or the first recorded upon arrival at the emergency department (control and experimental groups)
Post-CPAP systolic blood pressure	Interval	Last recorded systolic blood pressure in the field or the first recorded upon arrival at the emergency department (control and experimental groups)
Post-CPAP diastolic blood pressure	Interval	Last recorded diastolic blood pressure in the field or the first recorded upon arrival at the emergency department (control and experimental groups)
Post-CPAP oxygen saturation	Interval	Last recorded oxygen saturation in the field or the first recorded upon arrival at the emergency department (control and experimental groups)
Post-CPAP dyspnea rating	Ordinal	Subjective assessment by patient on an ordinal 0-10 scale upon arrival at the emergency department (control and experimental groups)
Patient subjective improvement	Nominal	Subjective assessment by patient (1= yes or 0 = no) measured upon arrival at the emergency department and compared to level of dyspnea prior to treatment
ER diagnosis	Nominal	Nominal scale (1 = Cardiogenic pulmonary edema or 0 = other)
Hospital discharge diagnosis	Nominal	Nominal scale (1 = Cardiogenic pulmonary edema or 0 = other)
Field intubation	Nominal	Nominal scale (1= yes or 0 = no)
ER intubation	Nominal	Nominal scale (1= yes or 0 = no)
Inpatient intubation	Nominal	Nominal scale (1= yes or 0 = no)
Field Mortality	Nominal	Nominal scale (1= yes or 0 = no) for all-cause mortality
Hospital Mortality	Nominal	Nominal scale (1= yes or 0 = no) for all-cause mortality
Hospital length of stay	Interval	Total days between admission and discharge
Complication-mask intolerance	Nominal	Nominal scale (1= yes or 0 = no)
Complication-hypotension	Nominal	Nominal scale (1= yes or 0 = no)
Complication-gastric distension	Nominal	Nominal scale (1= yes or 0 = no)
Complication-vomiting	Nominal	Nominal scale (1= yes or 0 = no)
Time arrive at scene	Time	Time of arrival of EMS at the scene as recorded by 911 center
Time arrive at emergency department	Time	Time of arrival of ambulance at the emergency department as recorded by 911 communications center
Total prehospital time	Interval	Total minutes elapsed between scene arrival and arrival at emergency department
Time CPAP started	Time	Starting time of CPAP as measured by time logged on Lifepak-12 cardiac monitor
Total Prehospital CPAP time	Interval	Total minutes on CPAP as measured by difference in start CPAP time logged on Lifepak-12 cardiac monitor and time arrived at emergency department
Oxygen concentration	Interval	FiO2 of oxygen administered
Furosemide administered	Interval	Total mg of furosemide administered in prehospital setting
Furosemide time	Time	Time furosemide administered as measured by time logged on Lifepak-12 cardiac monitor
Morphine	Interval	Total mg of morphine administered in prehospital setting
Morphine time	Time	Time morphine administered as measured by time logged on Lifepak-12 cardiac monitor
Nitroglycerine	Interval	Total mg of nitroglycerine administered in prehospital setting
Nitroglycerine time	Time	Time nitroglycerine administered as measured by time logged on Lifepak-12 cardiac monitor

Statistical Analysis

All relevant variables will be tested for equivalency between the experimental and control groups using the t-test or Mann-Whitney rank sum test as appropriate.

The control variables of oxygen concentration, prehospital time, CPAP time, morphine administration, nitroglycerine administration, and furosemide administration will be compared between the interventional and control groups using the t-test. Sub-group analysis will be performed to identify confounding when indicated.

Post-CPAP variables (oxygen saturation, heart rate, respiratory rate, blood pressure, and dyspnea rating) will be compared to pre-CPAP variables using the paired t-test or Wilcoxon signed rank test as appropriate (interventional group only).

Post-CPAP variables (interventional group) will be compared to the first set of the same variables recorded upon arrival at the emergency department (control group) using the t-test or Mann-Whitney rank sum test as appropriate.

The outcome variables of field intubation, hospital intubation, field mortality, hospital mortality, and hospital length-of-stay will be compared using the chi square test, t-test, and/or odds ratio as appropriate.

The complication variables of gastric distension, vomiting, hypotension, and mask intolerance will be reported as frequencies.

Project Timeline

March, 2004– June, 2004	Develop Data Collection Procedures
March, 2004– June, 2004	IRB Approval
March, 2004 – June, 2004	Study Organization
July, 2004 – July 2005	Data Collection
July, 2004 – July 2005	Data Entry and Verification
August, 2005	Statistical Analysis
September, 2005	Manuscript Preparation
January, 2006	Abstract Presentation at NAEMSP Meeting

Budget and Justification

Salary
	Base	$6,000.00
	TIAA/CREFF (10.04%)	$602.40
	Social Security (7.65%)	$459.00
	Health Insurance	$357.40
	Total Salary		$7,418.80
Travel
	Mileage	2330
	Reimbursement ($0.36.5/mile)	$850.45
	Lodging (per diem)	$297.50
	Meals (per diem)	$147.50
	Total Travel		$1,295.45
Telephone			$50.00
Printing			$50.00
Total Direct Costs				$8,814.25
Indirect Costs (12.3% of Direct Costs)				$1,084.15
Total Budget					$9,898.40

Funds in the amount of $7,418.80 are requested for faculty salary and fringe benefit costs.

Travel funds are requested for travel to the study sites for the purpose of organizing the study and for data collection. We anticipate a total of 5 trips at 466 miles each trip for a total of $850.45 (2330 miles x $0.365).

Funds are also requested for printing data collection instruments for a total of $50 (500 copies at $0.10/copy) as well as $50 for telephone service for coordinating data collection with the study sites.

References

1. Wilkes MS, Middlekauff H, Hoffman JR. Heart failure: Part I. First hospitalization and post hospital care. West J Med. 1999;170:268-73.
2. Vital and Health Statistics of the Centers for Disease Control and Prevention/National Center for Health Statistics. Advance Data No. 304; May 6, 1999.
3. Maio RF, Garrison HG, Spaite DW, Desmond JS, Gregor MA, Cayten CG, Chew JL, et al. Emergency medical services outcomes project I (EMSOP I): Prioritizing conditions for outcomes research. Ann Emer Med. 1999;33:423-432.
4. Tresch DD, Dabrowski RC, Fioretti GP, Darin JC, Brooks HL. Out-of-hospital pulmonary edema: Diagnosis and treatment. Ann Emerg Med. 1983;12:533-7.
5. Rasanen J, Heikkila J, Downs J, Nikki P, Vaisanen I, Viitanen A. Continuous positive airway pressure by face mask in acute cardiogenic pulmonary edema. Am J Cardiol. 1985;55:296-300.
6. Bersten AD, Holt AW, Vedic AE, Skowronski GA, Baggoley CJ. Treatment of severe cardiogenic pulmonary edema with continous positive airway pressure delivered by face mask. N Engl J Med. 1991;325:1825-30.
7. Lin M, Yang YF, Chiang HT, Chang MS, Chiang BN, Cheitlin MD. Reappraisal of continuous positive airway pressure therapy in acute cardiogenic pulmonary edema. Short-term results and long-term follow up. Chest. 1995;107:1379-86.
8. Katz JA, Marks JD. Inspiratory work with and without continuous positive airway pressure in patients with acute respiratory failure. Anesthesiology 1985; 63:598-607
9. Naughton MT, Rahman A, Hara K, et al. Effect of continuous positive airway pressure on intrathoracic and left ventricular transmural pressures in patients with congestive heart failure. Circulation 1995; 91:1725-1731.
10. Ghereni S, Peters RM, Virgilio RW. Mechanical work on the lungs and work fo breathing with positive end-expiratory pressure and continuous positive airway pressure. Chest 1979; 76:251-256.
11. Pang D, Keenan SP, Cook DJ, Sibbald WJ: The effect of positive pressure airway support on mortality and the need for intubation in cardiogenic pulmonary edema: A systematic review. Chest. 1998;114:1185-1192.
12. Fagon JY, Chastre J, Hance AJ, et al. Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay. Am J Med 1993; 94:281-288.
13. Stauffer JL, Olson DE, Petty TL. Complications and consequences of endotracheal intubation and tracheoltomy: a prospective study of 150 critically ill adult patients. Am J Med. 1980;70:65-76.
14. Pingleton SK. Complications of acute respiratory failure. Am Rev Respir Dis. 1988;137:1463-1493.
15. Pang D, Keenan SP, Cook DJ, et al. The effect of positive pressure airway support on mortality and the need for intubation in Cardiogenic pulmonary edema. Chest. 1998;114:1185-92.
16. Rieck J, Garzman I, Or J, Schabar A. The routine use of continuous positive airway pressucre (CPAP) by face mask with positive end expiratory pressure (PEEP) for the treatment of Cardiogenic pulmonary edema in the emergency room reduces the need for intubation and artificial mechanical ventilation. Resuscitation. 1996;31:179-90.
17. Delclaux C, L’Her E, Alberti C, et al. Treatment of acute hypoxemic nonhypercapnic respiratory insufficiency with continuous positive airway pressure delivered by a face mask. JAMA. 2000;284:2352-60.
18. Kallio T, Kuisma M, Alaspaa A, Rosenberg. The use of prehospital continuous positive airway pressure treatment in presumed acute severe pulmonary edema. Prehosp Emer Care. 2003;7:209-213.
19. Kosowsky JM, Stephanides SL, Branson RD, Sayre MR. Prehospital use of continuous positive airway pressure (CPAP) for Presumed Pulmonary Edema: A preliminary case series. Prehospital Emergency Care. 2001;5:190-96.
20. Takeda S, Nejima J, Takano T, Nakanishi K, Takayama M, Sakamoto A, Ogawa R. Effect of nasal continuous positive airway pressure on pulmonary edema complicating acute myocardial infarction. Jpn Circ J. 1998 Aug;62(8):553-8.

APPENDIX 1

Forsyth County EMS Pulmonary Edema and CPAP Protocols

APPENDIX 2

Guilford County EMS Pulmonary Edema Protocol