ENDORSED BY
CHIEFS OF EMERGENCY MEDICINE
CHIEFS OF MEDICINE
CHIEFS OF PULMONOLOGY
HOSPITAL BASED SPECIALISTS PEER GROUP

CLINICAL PRACTICE STATEMENT

MANAGEMENT OF ACUTE EXACERBATIONS of
CHRONIC OBSTRUCTIVE PULMONARY DISEASE

As described by the American Thoracic Society', an acute exacerbation of COPD is characterized by
an acute worsening of symptoms accompanied by worsened lung function in an individual with COPD.
In the most severe of instances, an acute exacerbation poses the risk of acute respiratory failure. Potential
precipitants of such acute exacerbations include: various infections (viral and bacterial), fluid
overload, thromboemboli, cardiac ischemia, aspiration, excessive sedation from medications,
and bronchospasm.

INITIAL EVALUATION and ADMISSION CRITERIA
KEY COMPONENTS of INITIAL EVALUATION
*  History: baseline respiratory status, sputum volume and characteristics,
duration and progression of symptoms, severity of dyspnea, exercise limitations,
sleep and eating difficulties, home care resources, failure of home regimen,
symptoms of co-morbid acute or chronic conditions, smoking history
*   Physical examination: respiratory rate, blood pressure, temperature, pulse,
bronchospasm, altered mentation, paradoxical abdominal retractions, use of
accessory respiratory muscles, acute morbid conditions
*   Laboratory: usually includes ABG, BUN/Cr, Lytes, Glu, CBC, Chest
radiograph if pneumonia is suspected, ECG, pulse oximetry, theophylline level if
outpatient theophylline is used

CONSIDERATION for ADMISSION
The severity of the condition (by the high association with near and long-term mortality
rates) should be factored in when considering admission for patients with an acute
exacerbation of COPD. The following variables are significant predictors of COPD short-term
mortality 4,5,6,7.
*   Age > 65
*   Alveolar arterial oxygen gradient > 41mm Hg
*  Ventricular arrhythmia
*  Atrial fibrillation
*  CHF
*  Presence of cor pulmonale
*  Prior functional status

Note: Other significant predictors of short term mortality included the APACHE III score (Abnormal
values over a 24 hr period of the following: Glasgow Coma score, heart rate, mean blood pressure,
temperature, hematocrit, WBC count, creatinine, urine output, serum urea nitrogen, sodium,
albumin, glucose, respiratory rate, pH, PaCO₂
PaO₂) and a low body mass index.

ADDITIONAL INDICATIONS for HOSPITALIZATION¹
*  Inadequate response of symptoms to outpatient management
*  Inability to eat or sleep due to dyspnea
*  Prolonged, progressive symptoms before emergency visit
*  Planned invasive surgical or diagnostic procedure requiring analgesics or sedatives
    that may worsen pulmonary function
* Co-morbid condition such as severe steroid myopathy or acute vertebral compression
   fractures, with worsening pulmonary function

POTENTIAL INDICATIONS for ICU ADMISSION¹
* Severe dyspnea that responds inadequately to initial emergency therapy
* Confusion, lethargy, or respiratory muscle fatigue (the last characterized by
   paradoxical diaphragmatic motion)
* Persistent or worsening hypoxemia despite supplemental oxygen or severe worsening of
   respiratory acidosis (pH < 7.30)
* Assisted mechanical ventilation is required

TREATMENT FOR AN ACUTE EXACERATION of COPD
The principal goal of COPD management is to achieve and maintain control of the disease.
This includes improving symptoms and quality of life and reducing the frequency and severity
of COPD exacerbations; improving lung function and reducing the accelerated decline
in lung function; preventing and effectively treating complications; reducing mortality;
and avoiding or minimizing treatment side effects. Based on review of recent literature the
guideline team recommends the following approach:

*  Oxygen therapy: The most important consequence of hypoxemia is tissue
hypoxia. Hence, the first responsibility of the physician is to correct or prevent life
threatening hypoxemia. Continued monitoring is highly advisable in the unstable patient. 
The goal of oxygen therapy is correction of hypoxemia to a PaO₂ > 60mm Hg or 0₂ Sat > 90%.

*  Combination therapy with a beta₂-agonist (albuterol) and anticholinergic aerosols
(AtroventÒ or its generic equivalent, ipratropium bromide) should be considered
the next step in the inpatient management of acute COPD exacerbations. There is evidence to suggest
that they may act synergistically with no increase in adverse effects due to combined
usage^8,9,10,11 Although data indicates that therapy given via nebulizer or with metered
dose inhaler (MDI) are equivalent^12,13 it is recommended that the initial dose of
combined therapy be given by nebulizer to ensure drug delivery to patients in acute
distress. Nebulized beta₂-agonist (albuterol) can be given every 15 minutes
or until the patient's clinical condition changes. In severe exacerbations,continuous 
nebulized beta₂-agonist (albuterol) can be given up to 15 mg/hr,
but the patient must be carefully monitored for cardiac arrhythmias and hypokalemia.
Subsequent doses of AtroventÒ can then be given every 6-8 hours. Patients can then be
switched to MDI (albuterol 2-4 puffs with spacer QID, AtroventÒ 4-8 puffs TID or
QID) once considered stable. Patients presenting to the clinic or emergency
department in mild respiratory distress can often be treated with an inhaled beta₂-
agonist (albuterol) MDI with spacer 4-6 puffs every 5 minutes for two to three
treatments combined with one treatment of 4-8 puffs Atrovent MDI with spacer. If there 
is no significant clinical improvement, the patient can then be given
an albuterol/AtroventÒ nebulizer therapy [Initial dose can be combined: I unit dose
AtroventÒ with 0.5 cc of 0.5% albuterol solution (2.5 mg)].

*  Oral or intravenous corticosteroids should be considered to decrease airway
inflammation. Studies^14,5,6,7 have shown patients treated with corticosteroids
have rapid improvement ofFEV₁, decreased rate of relapse, fewer treatment failures,
better spirometry, and shorter length of stay. The amount and duration of corticosteroids
given to patients with an acute exacerbation of COPD is unclear, and is currently under
clinical investigation. However, patients requiring hospitalization may benefit from
Methylprednisolone 1 mg/kg every 6 hours for 2-3 days and then followed by
prednisone 40-60 mg per day on a tapering schedule. Patients not requiring
hospitalization may also benefit from prednisone 40-60 mg/day on a tapering
schedule.

*  Purulent sputum usually provides rationale for a course of antibiotic therapy:
amoxicillin, trimethoprim-sulfa, cephalosporins, or macrolides may be
chosen. It has been shown that such agents may assist in resolving an exacerbation, but
they have more value in decreasing the risk of further deterioration^l8 More recently a
meta-analysis^l9 demonstrated a small but significant improvement in peak expiratory
flow due to antibiotic therapy in patients with exacerbations of COPD.

*  The roles of theophylline or intravenous aminophylline have diminished
significantly in the setting of an acute exacerbation of COPD because of their toxic
effects and little proof of efficacy when combined with other bronchodilators^20,21
and are not recommended in the management of acute COPD exacerbations.

Other treatment & evaluation considerations during the hospital phase may include:
*  Sedation and pain management
*  Ambulation or DVT prophylaxis as applicable
*  Respiratory Therapist evaluation
*  Non Invasive Ventilation per protocol
*  Implementing COPD pathway as applicable
*  Discharge care planning

DISCHARGE CRITERIA for PATIENTS WITH ACUTE EXACERBATIONS of
COPD

Insufficient clinical data exists to establish the duration of hospitalization in individual
patients to achieve maximal benefit. Consensus and limited data support the discharge criteria listed below: ¹

*  Inhaled bronchodilator therapy is required no more frequently than q 4 h

*  Patient, if  previously ambulatory, is able to walk across room
*  Patient is able to eat and sleep without frequent awakening by dyspnea
*  Reactive airway disease, if present, is stable
*  Patient has been clinically stable, off parenteral therapy, for 12-24 h
*  0₂ Sat > 88% with or without oxygen and no significant increase in PaCo₂
*  Patient (or home caregiver) fully understands correct use of medications
*  Follow-up and home care arrangements have been completed (e.g., checking and
updating immunization status; referral to COPD case manager as applicable; visiting
nurse; enrollment in smoking cessation program; oxygen delivery; meal provisions)
Note: A patient who does not fully meet criteria for home discharge may be considered for discharge to a 
nonacute care facility for observation during the final resolution of symptoms.

BACKGROUND
Chronic Obstructive Pulmonary Disease (COPD) is the fourth leading cause of death in
the United States. Affecting 16 million people each year it accounts for 13.8 million office
visits and 297,000 hospitalizations at a cost of 18 billion dollars'. Even more distressing is
the fact that mortality due to heart disease and stroke have decreased substantially over the
past 10 years, mortality from COPD has increased by 33%. Despite the fact that acute
exacerbations of COPD account for a relatively high proportion of hospital admissions in the
United States, indications for hospitalization and length of hospital stay have received very
little attention. Relatively few studies have investigated patient-specific, objective clinical
and laboratory features identifying patients with COPD who require hospitalization.

This led to the formulation of consensus guidelines for COPD management by various
specialty organizations, the American Thoracic Society', the British Thoracic Society, the
Canadian Thoracic Society, and the European Respiratory Society. A recent review³ shows that
these guidelines are substantially similar in nature. This review also emphasized that these
COPD guidelines are restricted by limited empirical evidence. With these considerations
in mind, physicians from Kaiser Permanente Northern California convened to develop a
systematic approach that would help physicians identify and treat high-risk patients
needing admission among those presenting with an acute exacerbation. While we
undertook an extensive literature search and critically reviewed available evidence
in developing this approach we acknowledge the lack of large, double blind, placebo-
controlled clinical trials addressing fundamental questions of management. It
is for the aforementioned reason TMPG has entitled this document as a Clinical Practice
Statement as opposed to a Clinical Practice Guideline.

REFERENCES
1.     Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. American
Thoracic Society. Am J Respir Crit Care Med
1995;152(5 Pt 2):S77-121. Items reprinted with permission.

2.    U.S. Department of Commerce. Bureau of the Census.
Statistical abstract of the United States 1997. Washington, DC: U.S. Department of Commerce,
November 1997.

3.    Fabbri L et al. Curr Opin Pulm Med 1998;4:78-84.

4.    Fuso L et al. Am J Med 1995; 98:272-7.

5.     The SUPPORT investigators.AmJRespir Crit Care Med 1996;154(4 Pt l):959-67 [published erratum
appears in Am J Respir Crit Car Med 1997 Jan;155(l):386].

6.     Seneff MG etal./AM 19951274:1852-7.

7.     MoranJL at al. Crit Care Med 1998;26:71-8.

8.     Shrestha M at al. Ann Emerg Med 1991120:1206-9.

9.   COMBIVENT Inhalation and Aerosol Study Group. Chest 1994;105:1411-9.

10.  Levin DC et al. Am J Med 1996;100(IA):40S-48S.

11.  Tashkin DP et al. Am J Med 1996;100(IA):62S-69S.

12.  Kuhl DA et al. Ann Pharmacother 1994;28:1379-88.

13. Turner MO et al. Arch  Intern Med 1997:157:1736-44.

14. Albert RK et al. Ann Intern Med 1980:92:753-8.

15. Murata WH et al. Chest 1990;98:845-9.

16. Thompson WH et al. Am J Respir Crit Care Med 1996;154(2 Pt l):407-12.

17.  SCCOPE Study Group. Control Clin Trials 1998;19:404-17. Results presented at the
International Conference for American Lung Association/American Thoracic Society, April 1998,
will be published in an upcoming issue of the New England Journal of Medicine.

18. Anthonisen NR et al. Ann Intern Med 1987:106:196-204.

19.  Saint S. et al. JAMA 1995;273:957-60.

20.  Rice KL et al. Ann Intern Med 1987;107:305-9.

21.  Wrenn K et al. Ann intern Med 1991:115:241-7.

CONTACT INFORIVIATION
Kaiser Pemianente Northern California
TPMG Department of Quality and Utilization
1800 Hamson Street, 4th Floor, Oakland, CA 94612
510-987-2950 or tie-line 8-427-2950

To obtain more information about KPNC Clinical Practice Guidelines, printed copies, or permission to
reproduce any portion, please contact the TPMG Dept. of Quality & Utilization, or send an e-mail message
to clinical.guidelines@ncal.kaiperm.org
KPNC Clinical Practice Guidelines can be viewed on-line on the Kaiser Permanente Northern California
intranet website at http://clinical-library.al.kp.org  This website is accessible only from the Kaiser
Permanente computer network.

This Permanente Medical Group (TPMG) Clinical Practice Statement has been developed to assist
clinicians by providing an analytical framework for the evaluation and treatment of selected common
problems encountered in patients. This statement is not intended to establish a protocol for all patients
with a particular condition. While the statement provides one approach to evaluating a problem,
clinical conditions may vary significantly from individual to individual. Therefore, the clinician must
exercise independent judgment and make decisions based upon the situation presented.While great care
has been taken to assure the accuracy of the information presented, the reader is advised that
TPMG cannot be responsible for continued currency of the information, for any errors or omissions in this
statement, or for any consequences arising from its use.

ACKNOWLEDGMENTS
CLINICAL LEADER
David Goya, DO, MBA, FCCP, FACP, Pulmonology; Santa Clara
CLINICAL PRACTICE GUIDELINE TEAM
Mark Clark, MD, HBS; Vallejo
Nada Ferns, NP, Medicine; Hayward
PROJECT MANAGEMENT
Jay Krishnaswamy, MBA, Department of Quality and Utilization (DOQU)
Linda Rogers, MPA, DOQU
EDITING
The Medical Editing Department,
Kaiser Foundation Research Institute
REVIEWERS
Joe Anderson, RT; Redwood City
Christine Angeles, MD, Pulmonology; South San Francisco
Richard Blohm, MD, Medicine; Sacramento
George Bulloch, MD, Emergency; Redwood City
Laura Butcher, MD, Medicine; San Jose
Tony Cantelmi, MD, Medicine; Roseville
Doug Chartier, MD, HBS; Oakland
Uli Chettipally, MD, Emergency; South San Francisco
John David, MD, Emergency; San Rafael
Paul Feigenbaum, MD, Medicine; San Francisco
Maurice Franco, MD, Medicine; Hayward
Eric Koscove, MD, Emergency; Santa Clara
Pansy Kwong, MD, Medicine; Oakland
Lewis Lehman, MD, HBS; San Franrisco
David Langkammer, MD, Medicine; Antioch
Susan Marantz, MD, Pulmonology; Santa Rosa
Tom Padgett, MD, Emergency; San Francisco
Bill Plautz, MD, Emergency; South San Francisco
Christina Shih, MD, Emergency; San Francisco
Kurt Swartout, MD, HBS; Sacramento
Christopher Tyier, MD, HBS; San Francisco
Tuan Tran, MD, HBS; Stockton
Abdul Wali, MD, HBS; Walnut Creek
GRAPHIC DESIGN
Gail Holan,Curvey Graphic Design